Successful birth in a hemodialysis patient with SLE.
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Biomedical subjects
Publications and source records attributed to T Toyota.
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The effect of niceritrol at an ordinary dose (1500 mg/day) on the serum lipoprotein(a) (Lp(a)) concentration was investigated in 25 normolipidemic patients with coronary artery disease. The serum Lp(a) level was reduced by approximately 21% after 3 months of treatment (before treatment, 30.3 +/- 4.1 mg/100 ml; during treatment, 22.6 +/- 2.4 mg/100 ml; p < 0.01). By one month after the drug was discontinued, the Lp(a) returned to a pretreatment level (30.8 +/- 2.8 mg/100 ml). The levels of LDL-cholesterol and apoB were decreased significantly by the drug therapy; LDL-cholesterol increased closely to a pretreatment level after withdrawal of the drug. The percentage reduction of Lp(a) was significantly correlated with that of fibrinogen (r = 0.763, p < 0.01). Plasma concentration of fibrinogen was decreased in the patients whose reduction rate of Lp(a) was 30% or more. These results indicate that niceritrol has Lp(a)-lowering effect; sufficient reduction of Lp(a) may improve dyscoagulopathy of patients with coronary artery disease.
The molecular species of hepatitis B virus (HBV)-DNA of 44 sera taken from 25 HBV carriers were examined by Southern blot hybridization with a biotin-labeled HBV-DNA probe and classified into three patterns. Type I consisted of two distinct bands of 4.0 kb and 3.2 kb. Type II consisted of the 4.0 kb and 3.2 kb bands and a smear between these two bands. Type III showed a broad band below 4.0 kb. With endogenous HBV-DNA polymerase reaction, the smear disappeared and 4.0 kb and 3.2 kb bands appeared. After EcoRI digestion, the 4.0 kb band disappeared to form a single band of 3.2 kb. These results suggest that the 4.0 kb and 3.2 kb forms are a relaxed circular, fully double-stranded DNA and a linear, fully double-stranded DNA, respectively, and that the smear between 4.0 kb and 3.2 kb is formed from the sum of relaxed circular, partially double-stranded DNAs with various length of plus strands. Comparison between histological diagnosis and Southern blot hybridization patterns of 25 HBV carriers indicates that these three patterns are closely related to the degree of hepatitis.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a recently isolated active peptide of the VIP (vasoactive intestinal peptide) family. Two bioactive forms, PACAP38 and PACAP27, a shorter N-terminal amidated peptide of PACAP38, have been identified. In this study, we explored the action of PACAP27 in rat dispersed pancreatic acini and the characteristics of its binding sites. PACAP27 stimulated amylase secretion and intracellular cAMP production in a dose-dependent manner. Adding 0.5 mM IBMX increased the potency of PACAP27 on the amylase secretion, but did not change the efficacy. The biological action of PACAP27 was mediated via intracellular cAMP as is also the case with PACAP38 or VIP. The time course study, however, revealed that PACAP stimulated the initial amylase secretion greater than VIP, suggesting an involvement of mechanisms other than intracellular cAMP. Binding studies using 125I-PACAP27 and 125I-VIP indicated that the binding sites for PACAP27 interacted with PACAP27 and VIP with a similar affinity. These observations suggested the presence of type II PACAP-binding sites in the normal acini of the rat pancreas which may be functionally coupled with acinar enzyme secretion.
Macrophages oxidatively modify low density lipoprotein (LDL). These cells then recognize and take up oxidized LDL (OxLDL) via the scavenger receptor. In the present study, we examined the effect of lipoprotein depleted serum (LPDS) on the oxidative modification of LDL and its uptake and degradation by human monocyte-derived macrophages. LPDS inhibited LDL oxidation in a concentration-dependent manner and the complete inhibition was observed in the concentration from 2.5 to 10.0%. In the presence of 5% of LPDS, cell-associated 125I-LDL was reduced by 70%, compared with that in the absence of LPDS. In contrast, 125I-LDL degradation increased in the presence of LPDS. The ratio of degradation products to cell-associated radioactivity in the presence of LPDS was five-fold greater than that in the absence of LPDS. In the presence of LPDS, unlabeled LDL competed for about 50% of cellular uptake and degradation of 125I-LDL. In the absence of LPDS, however, unlabeled LDL competed for only 20% of uptake and only 30% of degradation of 125I-LDL. Unlabeled OxLDL competed for about 80% of uptake and degradation in the absence of LPDS. These results suggest that LPDS inhibited the production of OxLDL which was taken up by macrophages via the pathway for the OxLDL.
Molecular species of serum hepatitis B virus (HBV)-DNA in HBV carriers were classified by Southern blot hybridization into three types; type I with two bands of 4.0 kb and 3.2 kb, type II with the two bands of type I plus the smear between 4.0 kb and 3.2 kb, and type III with a broad band below 4.0 kb. A total of 51 HBV carriers were classified into three groups (group I, n = 19 with type I; group II, n = 12 with type II; and group III, n = 20 with type III). Serum aminotransferase levels of group I were significantly lower than those of groups II and III. Liver pathology revealed that 18 of the 19 (94.7%) group I patients showed nonspecific reactive hepatitis (NSRH), while 11 of the 12 (91.7%) group II patients and 19 of the 20 (95.0%) group III patients showed chronic persistent hepatitis (CPH) or chronic active hepatitis (CAH). Immunohistochemical study showed that hepatitis B core antigen (HBcAg) was localized in the nucleus of hepatocytes in most of patients with type I while it was localized in both the nucleus and cytoplasm in those with types II and III. Since the smear between 4.0 kb and 3.2 kb is specifically found in groups II and III, HBV-DNA with this smear may be related to active hepatitis.
We have reported previously that chronic and systemic administration of a streptococcal preparation (OK-432), an inducer of TNF, or of recombinant hTNF prevented the development of IDDM in the two animal models of IDDM-NOD mice and BB rats. In this study, we examined the effect of LT, which is structurally and functionally related to TNF, on NOD mice with diabetes. The cumulative incidence of diabetes at 30 wk of age was 22 of 40 (55%) in nontreated female NOD mice and was 4 of 8 (50%; NS), 3 of 29 (10%; P < 0.001), and 0 of 8 (0%; P < 0.001) in female mice treated three times a week from 4 to 30 wk of age with 5, 50, or 500 U of recombinant hLT, respectively. Intensity of insulitis was slightly reduced in the long-term LT-treated mice. LT productivity by ConA-stimulated spleen cells was examined in vitro. Although no significant difference was found between NOD mice and the other mouse strains, female NOD mice were slightly but significantly (P < 0.01) lower producers of LT immunoreactivity than male NOD mice, the diabetes incidence of which is lower than that of females. The SMLR as a marker of normal immune response, which was reported to be impaired in autoimmune animals including NOD mice, was significantly lower in female than male NOD mice. However, the low SMLR in female NOD mice was significantly increased by the administration of LT, and the increase was mediated by the responder cells of the LT-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Insulin binding to its receptor has been known to induce hydrolysis of phosphatidylinositol-glycan and release inositol-glycan and diacylglycerol, two putative second messengers of insulin actions. We metabolically labeled and purified PIG in rat cultured adipocytes. The treatment of [3H]glycerol-labeled PIG with phosphatidylinositol-specific phospholipase C released [3H]glycerol-labeled DAG and [3H]glycerol-labeled 1-alkyl,2-acyl-glycerol, suggesting that PIG has not only PIG but also plasmanylinositol-glycan moiety. Insulin induced hydrolysis of PIG/PMIG and generation of IG, DAG, and AAG in a dose-dependent manner. This report shows the first demonstration of insulin-sensitive PMIG in rat adipocytes. These results provide evidence that insulin-induced generation of IG, DAG, and AAG might be early events in the insulin-signaling mechanism in rat adipocytes, and insulin-releasable AAG seems to mediate some actions of insulin.
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Activated phagocytes are involved in the pathogenesis of Crohn's disease (CD). To clarify the activation of polymorphonuclear leukocytes (PMN) from CD patients in relationship with the clinical status, we investigated not only the expression of Fc receptor for IgG (huFc gamma R) but also the ability of the PMN to produce free oxygen radicals on stimulation of these receptors by using chemiluminescent techniques. The PMN obtained from the patients with active disease showed an enhanced chemiluminescence (CL) in response to huFc gamma RI stimulation, and an increased expression of huFc gamma RI. Moreover, PMN with huFc gamma RI were recognized in the colonic inflammatory lesions. After a successful treatment, however, we could hardly detect both the CL production and the expression of huFc gamma RI. Thus, it is suggested that the measurement of CL production through huFc gamma RI and the evaluation of the expression of huFc gamma RI are useful to evaluate the clinical status of the CD patients in a more accurate manner. The involvement of huFc gamma RI positive PMN in tissue destruction has been discussed.
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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.
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Immunohistochemical analyses have shown the presence of T lymphocytes (T-cells) in atherosclerotic places in addition to macrophages and smooth muscle cells. To elucidate the role of T-cells in the formation of atherosclerotic lesions, we studied whether T-cells can stimulate the scavenger pathway and promote esterified cholesterol (EC) synthesis by [14C]oleate incorporation in macrophages. Macrophages and T-cells were co-cultured in two ways. In one culture, macrophages were in direct contact with T-cells (direct contact form). In the other, macrophages and T-cells were separated by Transwell membrane, but shared the same culture medium via the membrane (indirect contact form). Based on the incorporation of [14C]oleate into EC, macrophages strikingly increased EC synthesis in both forms of co-culture. This increase was proportional to the number of T-cells present and was inhibited by cyclosporin A. When macrophages were co-cultured indirectly in contact with T-cells in the presence of AcLDL for 24 h, and the T-cells were subsequently removed, EC synthesis in macrophages increased. However, this increase was not observed in macrophages that were rinsed twice with PBS. When macrophages, previously incubated with AcLDL for 24 h, were co-cultured indirectly in contact with T-cells for 24 h, the medium were prepared as activated T-cell-conditioned medium (aTCM). EC synthesis in macrophages cultured with aTCM increased. The ability of aTCM to increase EC synthesis disappeared upon repeated freezing/thawing, boiling and trypsin treatment. T-cells (indirect contact form) and aTCM similarly increased AcLDL-binding and -degradation in macrophages. These results indicated that T-cells secreted an active substance(s), protein in nature, which could activate the scavenger pathway and increase EC synthesis in macrophages. These observations suggest that T-cells can promote the uptake of modified lipoproteins by macrophages to induce foam cell-formation.
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Lansoprazole is a newly developed proton pump inhibitor. The purpose of this study was to determine whether morning or evening dosage gave better control of 24-hr intragastric pH. In this study, we examined the antisecretory effect of lansoprazole by repeated intragastric pH monitoring on four occasions in eight normal subjects and compared median 24-hr pH values and pH threshold time of pH greater than or equal to 4 between morning and evening dosing, following the administration of lansoprazole 30 mg once daily in either the morning or evening for seven days. Intragastric pH was monitored before and after seven days of treatment. Both morning and evening dosing caused a rise in the intragastric pH. Median pH for 24 hr was 4.3 and 1.6 with and without lansoprazole morning dosing and 4.6 and 2.1 for evening dosing, respectively. The pH threshold curve shifted to the right with lansoprazole treatment in either case. However, no differences were found between morning and evening dosing in terms of median 24-hr pH values or pH threshold time of pH greater than or equal to 4. These results indicate that lansoprazole can be given once daily in either the morning or evening because of its potent and long-lasting antisecretory activity.
Galanin, the newly discovered 29 amino acid-residue peptide, has been shown to suppress glucose-induced insulin secretion in experimental animals, but its presence and physiological role in the human pancreas have not been established. In this study, the occurrence and distribution of galanin immunoreactivity in the human pancreas was investigated by immunohistochemistry. In addition, the possible coexistence of galanin and vasoactive intestinal peptide immunoreactivity in neural elements of the pancreas was examined. In the human pancreas, galanin immunoreactivity was localized in numerous nerve fibers around glandular acini, ductules and blood vessels, and in a few nerve fibers within islets. Nerve cells with galanin immunoreactivity were frequently noticed. Immunostainings for galanin and for vasoactive intestinal peptide on serial adjacent sections of intrapancreatic ganglia showed the coexistence of the two immunoreactivities in a large proportion (73.3%) of nerve cells. These observations may provide a morphological basis for the possible neurotransmitter or neuromodulator role of galanin in the human pancreas.
We have recently reported that chronic and systemic administration of tumor necrosis factor alpha (TNF) inhibits development of autoimmune diabetes in NOD mice and BB rats, animal models of insulin-dependent diabetes mellitus (IDDM). During these experiments, we unexpectedly found that in vivo production of TNF stimulated by a single injection of lipopolysaccharide was enhanced approximately 10 times in the long-term diabetic BB rats (P less than 0.0001), whose mean duration of diabetes with more than 16.8 mM (300 mg/dl) of nonfasting blood glucose level was 26.2 +/- 2.1 days, as compared to that in the rats of nondiabetes and in the rats at the onset of diabetes, whose mean duration of diabetes was 1.4 +/- 0.6 days. The long-term diabetic, but not short-term-diabetic, rats were also associated with increased levels of serum fructosamine/albumin (P less than 0.01) and triglyceride (P less than 0.01) and with a decreased level of serum albumin (P less than 0.01). The in vivo TNF productivity in the diabetic rats, including the short-term- and long-term-diabetic rats, was correlated positively with the level of fructosamine/albumin (P less than 0.05) and negatively with the level of serum albumin (P less than 0.05), but not with levels of blood glucose. None of these correlations were observed in nondiabetic rats. The increased LPS-induced serum TNF activity in the long-term diabetic state was observed not only in BB rats but also in NOD mice and GK rats, a model of non-IDDM, irrespective of sexes and ages, indicating that the enhancement of in vivo TNF production was a result of long-term diabetes. These findings indicate that some factor(s) associated with the long-term-diabetic state may prime macrophages in vivo to produce TNF. Further study is needed to reveal a mechanism of the enhanced TNF production and its possible relevance to various abnormalities associated with the chronic hyperglycemic state.