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41.
TG Orsière MM Chauvet MH Dell''Amico MJ Bourdeaux 《Canadian Metallurgical Quarterly》1995,291(3):237-243
Hepatocyte growth factor (HGF) is a potent mitogen for the maturation of hepatocytes in vitro which plays a role in liver regeneration in vivo. In addition, transforming growth factor-beta 1 (TGF-beta 1) is also a potent regulator of liver regeneration. In attempting to clarify the mechanisms related to liver regeneration after partial hepatectomy, we investigated the expression of HGF and TGF-beta 1 in rats with liver cirrhosis (LC). A rat model of LC was prepared using carbon tetrachloride (CCl4). The expression of HGF mRNA in both the LC and control groups showed a similar time-course with the highest expression seen at 18h after a 70% hepatectomy. The expression of TGF-beta 1 mRNA peaked at 18h after partial hepatectomy in the LC group and at 48h in the control group. The 5-bromo-2'-deoxyuridine (BrdU) labeling index for the LC group at 24, 48, and 72 h after partial hepatectomy was 9.2%, 5.9%, and 1.8%, while for the control group it was 7.0%, 11.7%, and 6.8%, respectively. The BrdU labeling index in the LC group was thus suppressed earlier than that in the control group. We therefore postulate that regeneration of the remnant liver in the presence of LC accelerates immediately after partial hepatectomy, but the extent of regeneration is insufficient because of an early cessation due to an early expression of TGF-beta 1. 相似文献
42.
MJ Rosen 《Canadian Metallurgical Quarterly》1995,1(3):216-222
Pneumocystis carinii pneumonia has long been considered the predominant pulmonary disease in patients with HIV, but several factors are changing this perception. The population infected with HIV is increasingly composed of injection drug users, and racial and ethnic minorities, which represent groups that have a high incidence of bacterial pneumonia and tuberculosis. The increased longevity attributed to antiretroviral therapy and P. carinii pneumonia prophylaxis is accompanied by more profound immunosuppression, rendering patients susceptible to Pseudomonas, Aspergillus, and other opportunistic pneumonias. Trimetrexate and atovaquone are now available for the treatment of P. carinii pneumonia. Both are less effective than standard regimens of trimethoprim-sulfamethoxazole, but have fewer adverse effects. The diagnosis of respiratory infections complicating HIV usually depends on isolation of the pathogen. The routine use of transbronchial biopsy during bronchoscopy is controversial because the prevalence of P. carinii pneumonia is high in most centers caring for patients with AIDS, and bronchoalveolar lavage is usually diagnostic in this disease. However, biopsy enhances the yield of bronchoscopy, especially in the diagnosis of noninfectious pulmonary disorders and infections other than P. carinii pneumonia. 相似文献
43.
Dapsone has clinical utility as an anti-inflammatory agent but the mechanism of this action remains unknown. We have previously reported that dapsone inhibits beta2 integrin (CD11b/CD18)-mediated adherence of human neutrophils in vitro and now describe studies designed to discover how dapsone-mediated inhibition of this neutrophil function occurs. Results indicate that dapsone interferes with the activation or function of the G-protein (Gi type) that initiates the signal transduction cascade common to chemotactic stimuli. They also show that dapsone-mediated suppression of this pathway inhibits the generation of second messengers essential to the activation of beta2 integrin molecules, as well as respiratory and secretory functions of neutrophils exposed to chemoattractants. We propose that the inhibition of chemoattractant-induced signal transduction by dapsone suppresses neutrophil recruitment and local production of toxic respiratory and secretory products in the affected skin of dermatitis herpetiformis and other neutrophilic dermatoses. 相似文献
44.
SJ Mihic Q Ye MJ Wick VV Koltchine MD Krasowski SE Finn MP Mascia CF Valenzuela KK Hanson EP Greenblatt RA Harris NL Harrison 《Canadian Metallurgical Quarterly》1997,389(6649):385-389
Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics. 相似文献
45.
M Eberstadt B Huang Z Chen RP Meadows SC Ng L Zheng MJ Lenardo SW Fesik 《Canadian Metallurgical Quarterly》1998,392(6679):941-945
When activated, membrane-bound receptors for Fas and tumour-necrosis factor initiate programmed cell death by recruiting the death domain of the adaptor protein FADD to the membrane. FADD then activates caspase 8 (also known as FLICE or MACH) through an interaction between the death-effector domains of FADD and caspase 8. This ultimately leads to the apoptotic response. Death-effector domains and homologous protein modules known as caspase-recruitment domains have been found in several proteins and are important regulators of caspase (FLICE) activity and of apoptosis. Here we describe the solution structure of a soluble, biologically active mutant of the FADD death-effector domain. The structure consists of six antiparallel, amphipathic alpha-helices and resembles the overall fold of the death domains of Fas and p75. Despite this structural similarity, mutations that inhibit protein-protein interactions involving the Fas death domain have no effect when introduced into the FADD death-effector domain. Instead, a hydrophobic region of the FADD death-effector domain that is not present in the death domains is vital for binding to FLICE and for apoptotic activity. 相似文献
46.
MJ Snowling 《Canadian Metallurgical Quarterly》1996,313(7065):1096-1097
47.
48.
49.
Familial hypokalemic periodic paralysis. Clinical, diagnostic and therapeutic aspects 总被引:1,自引:0,他引:1
TP Links AJ Smit WM Molenaar MJ Zwarts HJ Oosterhuis 《Canadian Metallurgical Quarterly》1994,122(1):33-43
A model of induced lactation was modified to examine the effects of bovine prolactin (bPRL) and bovine placental lactogen (bPL) on mammary growth and differentiation. Thirty-two peripubertal, non-pregnant Holstein heifers were given daily s.c. injections of oestradiol (0.05 mg/kg) and progesterone (0.25 mg/kg) for 7 days to initiate mammary growth. Treatment with bromocriptine (40 mg/3 days) reduced serum PRL concentrations to approximately 25% of pretreatment levels, for the duration of the study. On the day following the last steroid injection, groups of eight heifers were given twice daily s.c. injections of either saline (negative control), recombinant bPRL (rbPRL; 80 mg/day) or recombinant bPL (rbPL; 80 and 160 mg/day) for 7 days. At the end of this period (day 15), growth and differentiation of the mammary glands were assessed. Treatment with rbPL increased total mammary DNA above control value by 50 and 60% for the 80 and 160 mg/day doses respectively. However, total DNA was not different for the control and rbPRL-treated groups. The blood serum concentration of alpha-lactalbumin was measured daily throughout the study and used as an index of mammary differentiation. Both rbPRL and rbPL stimulated mammary differentiation (i.e. induction of milk synthesis), although rbPRL appeared to be more potent than rbPL. These results indicate that rbPL is lactogenic in vivo and strongly suggest that bPL is a mammary mitogen. 相似文献
50.
Responses of cytotoxic T-cells (Tc) to human cytomegalovirus (CMV) represent the predominant mechanism by which hosts resist CMV infection. The CMV major immediate-early protein (IE) is present throughout the virus replicative cycle. Studies were performed to determine whether Tc specific for IE effectively lyse CMV-infected targets and are thus capable of providing protective immunity against infection. After in vitro stimulation of peripheral blood mononuclear cells with CMV-infected autologous fibroblasts, Tc specific for IE were not readily detectable in CMV-reactive polyclonal Tc lines. However, after stimulation of peripheral blood mononuclear cells with cells selectively expressing IE, weak but detectable IE-specific Tc responses were observed. The frequency of IE-specific Tc clones derived from cultures stimulated with IE-expressing cells was 50 to 100 times lower than the frequency of Tc clones specific for other CMV proteins isolated from cultures stimulated with CMV-infected cells. All of the IE-specific Tc clones, which efficiently lysed targets selectively expressing IE, demonstrated minimal lysis of CMV-infected fibroblasts, despite abundant IE expression in these target cells. In contrast to these results with IE, other viral proteins were efficiently presented during all phases of CMV infection. These data suggest that CMV has evolved a unique mechanism for selectively limiting the presentation of the potentially immunogenic IE protein, which may preclude IE-specific Tc from providing protective immunity to CMV infection. 相似文献