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Biomedical subjects

H Yamaguchi

Publications and source records attributed to H Yamaguchi.

At least 757 records · Page 42Linked to original sources
PubMed1994

An in vitro model for T cell-independent induction of humoral immunity. A requirement for NK cells.

We previously established an in vitro polyclonal model for membrane Ig-mediated Ig secretion by B cells in response to T cell-independent type 2 (TI-2) Ags, by using dextran-conjugated anti-IgD Abs (alpha delta-dex). We demonstrated that resting B cells activated with alpha delta-dex plus IL-2 secreted large amounts of Ig only in the presence of NK cells. In this report we show that, in contrast to small B cell-enriched spleen cells that require activation with the combination of alpha delta-dex and IL-2 for induction of Ig secretion, large B cells were induced to secrete Ig in response to alpha delta-dex, alone. These responses were inhibited by previous depletion of asialo-Gm-1+ cells from the B cell-enriched population, and restored both by the addition of freshly explanted NK cells and by in vitro-activated NK cells, suggesting a requirement for NK cells. Small alpha delta-dex-activated B cells could, however, also be stimulated to secrete Ig in the absence of added cytokines but only after the addition of in vitro-activated NK cells and not freshly explanted splenic NK cells. When highly purified large B cells, obtained by electronic cell sorting, were cultured with in vitro-activated NK cells, Ig secretion was induced even in the absence of any other added B cell stimulus. Because the splenic marginal zone has been implicated in humoral immune responses to TI-2 Ags, we further fractionated large B cells into marginal zone (MZB) and follicular (FB) B cells by electronic cell sorting. In vitro-activated NK cells stimulated large MZB, but not FB, cells to secrete Ig in the absence of exogenous stimuli. These data establish a T cell-independent model for induction of Ig synthesis in the absence of any added cytokine and demonstrate a role for freshly explanted NK cells in stimulating Ab production in response to TI-2 Ags. Further, they show that pre-activated NK cells can induce Ig secretion from pre-activated B cells even in the absence of any added stimuli. These data also underscore a special role for the MZB cell in these responses.

Animals↗
PubMed1994

Flexible loop that is novel catalytic machinery in a ligase. Atomic structure and function of the loopless glutathione synthetase.

The catalytic mechanism of glutathione synthetase is proposed to proceed via phosphorylation of the dipeptide substrate to yield an acyl phosphate intermediate; this intermediate is subsequently attacked by glycine, followed by loss of inorganic phosphate, leading to glutathione formation. A flexible loop (Ile226-Gly242) in Escherichia coli B glutathione synthetase is proposed to stabilize the acyl phosphate intermediate by preventing its decomposition by hydrolysis with water [Tanaka, T., Kato, H., Nishioka, T., & Oda, J. (1992) Biochemistry 31, 2259-2265; Tanaka, T., Yamaguchi, H., Kato, H., Nishioka, T., Katsube, Y., & Oda, J. (1993) Biochemistry 32, 12398-12404]. To investigate the function of the loop in the E. coli enzyme definitely, a loopless mutant in which the loop (Ile226-Arg241) was replaced with three residues of glycine was constructed. The crystal structure of the loopless mutant enzyme was essentially identical with that of the wild-type enzyme. Kinetic measurements showed that the replacement of the loop led to increases in the Km values, especially for the glycine, and a 930-fold decrease in the k0 value. Hence, the loopless mutant was 3 x 10(4) less active in terms of its specificity constant (k0/Km) for glycine than the wild-type enzyme. Moreover, the loopless mutant showed gamma-L-glutamyl-L-cysteine-dependent ATP hydrolase activity to almost the same extent as its glutathione synthetase activity. These studies support the fact that the loop enhances the recognition of glycine as well as stabilizes the acyl phosphate intermediate so that the intermediate rapidly reacts with glycine.

Amino Acid Sequence↗
PubMed1994

Dibasic (amidinoaryl)propanoic acid derivatives as novel blood coagulation factor Xa inhibitors.

Since activated factor X (FXa) is a coagulant enzyme that generates thrombin and participates in both intrinsic and extrinsic coagulation pathways, inhibition of FXa may be more effective than inactivation of thrombin for interrupting blood coagulation. To assess the possible effectiveness of FXa inhibition as an anticoagulant, we designed and synthesized 3-(amidinoaryl)-2-[4-[(3S)-3-pyrrolidinyloxy]phenyl]propanoi c acid derivatives as low molecular weight, nonpeptidic, orally active FXa inhibitors. These derivatives exhibited potent and highly selective anti-FXa activity in vitro and anticoagulant activity on oral administration. The most promising compound, (2S)-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]- 3-(7-amidino-2-naphthyl)propanoic acid hydrochloride pentahydrate (4,DX-9065a), inhibited 50% of FXa activity (IC50) at 0.07 microM, doubled plasma recalcification time (PRCT) at 0.5 microM, and significantly prolonged activated partial thromboplastin time (APTT) at a dose of 100 mg/kg on oral administration. In contrast with FXa inhibition, 4 showed no activity against thrombin (IC50 > 2000 microM).

Animals↗
PubMed1994

Esophageal carcinoma simultaneously associated with gastric carcinoma: analysis of clinicopathologic features and treatments.

Among 1,420 patients with thoracic esophageal carcinoma, 85 (6.1%) had synchronous gastric carcinoma. Seventy-two patients (84.7%) underwent esophagectomy. Their operative mortality and prognosis were similar to those without gastric carcinoma. Among them, 25 patients, of whom the majority had advanced gastric carcinoma, underwent transthoracic esophagectomy with total gastrectomy (group A); eight died of esophageal cancer and four of gastric cancer. Forty-six patients, of whom the majority had gastric carcinoma in an early stage, underwent esophagectomy and esophagogastric anastomosis following partial gastrectomy or local treatment for gastric carcinoma (group B). None of the group B patients had recurrent gastric carcinoma. The operative burden was larger in group A. The 5-year survival rate for groups A and B were 38.8% and 23.0%, respectively. Esophagectomy and esophagogastric anastomosis after limited treatment for gastric carcinoma is an adequate treatment for the majority. However, esophagectomy and total gastrectomy are recommended for patients with advanced gastric carcinoma.

Aged↗
PubMed1994

Presence of apolipoprotein E on extracellular neurofibrillary tangles and on meningeal blood vessels precedes the Alzheimer beta-amyloid deposition.

The localization of apolipoprotein E (ApoE) has been examined immunohistochemically in the autopsied brains of middle-aged and old-aged control subjects, with and without amyloid beta protein (A beta) deposits, and of Alzheimer's disease patients. Senile plaques were consistently labeled with ApoE antiserum even in the very early stage of senile plaque formation seen in the fifth decade. In the cerebellar molecular layer, small dots of ApoE immunoreactivity, which were prominent in the Alzheimer's disease subjects, were observed in addition to immunoreactivity in diffuse plaques. ApoE antisera labeled all of the extracellular neurofibrillary tangles (NFT), whereas only a small minority of extracellular NFT were positive for A beta. A punctate pattern of ApoE immunoreactivity was seen at the media of the meningeal vessels lacking amyloid, when senile plaques were present in the nearby cortex. In the early stage of amyloid angiopathy, the distribution of ApoE immunoreactivity was much more extensive than that of A beta positivity. These findings suggest that ApoE accumulates in the early stage of senile plaque formation and, furthermore, that ApoE accumulation precedes A beta deposition in extracellular NFT and amyloid angiopathy.

Aged↗
PubMed1994

Protective effects of gabexate mesilate on acute pancreatitis induced by tacrolimus (FK-506) in rats in which the pancreas was stimulated by caerulein.

We investigated the acute effects of the immunosuppressive agent, tacrolimus (FK-506), on the exocrine pancreas, in rats with or without stimulation of the pancreas, and evaluated the protective effects exerted by gabexate mesilate (FOY). While an intravenous injection of FK-506 did not change serum amylase levels during the 5-h observation period, this agent increased pancreatic amylase and protein content, and decreased the content of pancreatic DNA. Histologically, we observed intra-acinar vacuolization and individual cell necrosis. When the pancreas was stimulated by two intraperitoneal injections of caerulein (5 micrograms/kg) at 1-h intervals, however, which treatment did not induce any evident pancreatic change, FK-506 significantly increased serum amylase, pancreatic wet weight, and pancreatic amylase and protein, and decreased pancreatic DNA. Histologically, there were significant dose-related differences in the severity of intra-acinar vacuolization, interstitial edema, neutrophil infiltration, individual cell necrosis, and hemorrhage. Levels of intrapancreatic elastase were elevated and local pancreatic blood flow was reduced. Treatment with FOY improved the FK-506-induced acute pancreatitis, but did not increase the pancreatic blood flow. These findings indicate that FK-506 enhances abnormal pancreatic enzyme secretion and suggest that therapeutic doses of this agent can induce acute pancreatitis when the pancreas is stimulated. A protease inhibitor may protect the exocrine pancreas in patients who receive FK-506 after organ transplantation.

Amylases↗
PubMed1994

Vasodilatory capacity of coronary resistance vessels in dilated cardiomyopathy.

Both the endothelium-dependent and endothelium-independent vasodilatory responses of coronary resistance vessels were studied in patients with dilated cardiomyopathy (DCM). A 3F coronary Doppler catheter was placed in the proximal left anterior descending artery in 14 patients with DCM and in 10 patients with chest pain syndrome and a normal heart (control subjects). The ratio of maximum mean coronary blood flow velocity after intracoronary administration of the endothelium-independent vasodilator papaverine (10 mg) to resting mean coronary blood flow velocity (Vp/Vo) in patients with DCM was diminished compared with that in control subjects (2.2 +/- 0.6 vs 4.1 +/- 0.9, p < 0.001). The ratio after administration of the endothelium-dependent vasodilator acetylcholine (40 micrograms) (Va/Vo) in 10 DCM patients was also diminished compared with that in seven control subjects (1.3 +/- 0.5 vs 2.4 +/- 0.8, p < 0.01). In DCM patients, Vp/Vo was correlated with left ventricular end-diastolic pressure (r = -0.48, p < 0.05), left ventricular end-diastolic volume index (r = -0.68, p < 0.01), ejection fraction (r = 0.75, p < 0.01), and left ventricular end-diastolic wall stress (r = -0.73, p < 0.01). However, Va/Vo was not correlated with any of these parameters. These results indicate that impairment of the vasodilatory capacity of coronary resistance vessels in DCM may be related to endothelial dysfunction and to an extravascular factor resulting from left ventricular dysfunction.

Acetylcholine↗
PubMed1994

Neck ultrasonography for thoracic esophageal carcinoma.

The value of ultrasonography for detecting positive cervical lymph nodes in patients with intrathoracic esophageal carcinoma was studied. Positive cervical lymph nodes were detected by palpation in 26 of 209 patients. In 83 patients without palpable nodes, the sensitivity and the accuracy of ultrasonography for cervical lymph node metastases were 78.9% and 94.0%, respectively. Ultrasonography was useful for detecting positive cervical nodes in patients with intrathoracic esophageal carcinoma. For the 16 patients with positive cervical nodes detected by ultrasonography who underwent esophagectomy and neck lymph node dissection, the median survival was 26 months (range, 3 to 70 months), and the 3-year survival rate was 43.8%. There was a significant difference between the postoperative survival curves of the 12 patients with palpable cervical nodes and that of the 16 patients with positive cervical nodes detected by ultrasonography. In patients with intrathoracic esophageal carcinoma in whom palpation reveals no positive nodes, we believe that even if positive cervical nodes are revealed by ultrasonography, surgical intervention cannot be ruled out, and neck lymph node dissection is recommended for cure.

Aged↗
PubMed1994

Effectiveness of LDL-apheresis in preventing restenosis after percutaneous transluminal coronary angioplasty (PTCA): LDL-apheresis angioplasty restenosis trial (L-ART).

To investigate the efficacy of reducing plasma lipoprotein(a) (Lp(a)) as well as low density lipoprotein cholesterol (LDL-C) levels on the prevention of restenosis after PTCA, LDL-apheresis was attempted on a total of 54 patients at six institutions. LDL-apheresis using a dextran sulfate cellulose column has been proven to be an effective method for reducing both plasma Lp(a) and LDL-C levels. As a subgroup (apheresis-drug combined group), 29 of the 54 patients were given Pravastatin (HMG CoA reductase inhibitor) and Niceritrol (Nicotinic Acid) in addition to LDL-apheresis to maintain low plasma levels of both Lp(a) and LDL-C through the follow-up period of 5 months after PTCA. Patients whose plasma Lp(a) levels were reduced by more than 50% showed a lower restenosis rate than those whose plasma Lp(a) levels were reduced by less than 50% (21.2% vs. 52.4%, P = 0.0179), especially in patients with high plasma Lp(a) levels above 30 mg/dl where a much lower restenosis rate (15.0%) was observed. Furthermore, in the apheresis-drug combined group, the restenosis rate was 11.8% regardless of baseline plasma Lp(a) levels, including even those below 30 mg/dl. In conclusion, in patients with high plasma Lp(a) levels, a greater than 50% reduction in Lp(a) levels by LDL-apheresis is effective in preventing restenosis after PTCA. If the plasma Lp(a) reduction rate is greater than 50%, LDL-apheresis combined with lipid-lowering drugs such as niceritrol and pravastatin seems to be more effective, even in patients with low plasma Lp(a) levels.

Aged↗
PubMed1994

Effects of bezafibrate therapy on subfractions of plasma low-density lipoprotein and high-density lipoprotein, and on activities of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in patients with hyperlipoproteinemia.

We investigated the effects of 12 weeks of bezafibrate treatment on plasma lipoprotein subfraction levels and on activities of LCAT and CETP in 25 patients with hyperlipoproteinemia. Bezafibrate reduced plasma levels of VLDL-TC and VLDL-TG by 69% and 66% (P < 0.001) and plasma levels of IDL-TC and IDL-TG were decreased by 37% and 31% (P < 0.01). Bezafibrate had no significant effects on plasma levels of LDL1 (1.019 < d < 1.045)-TC and LDL1-TG in the study population as a whole but significantly increased the plasma level of LDL1-TC in the subgroup of 9 patients with type IV hyperlipoproteinemia. Bezafibrate reduced plasma levels of LDL2 (1.045 < d < 1.063)-TC, LDL2-TG by 48% and 44% (P < 0.001) in both type II and type IV hyperlipoproteinemic patients. Gradient polyacrylamide gel electrophoresis revealed a decrease in small LDL particles. Bezafibrate did not affect the plasma level of HDL2-TC but reduced the HDL2-TG concentration significantly (P < 0.001). Bezafibrate increased the plasma level of HDL3-TC by 37% and reduced the HDL3-TG level significantly by 20% (P < 0.001). Gradient polyacrylamide gel electrophoresis revealed an increase in HDL3a and a decrease in HDL2a. Bezafibrate suppressed the activities of LCAT and CETP by 21% (P < 0.001) and 17% (P < 0.01), respectively. The bezafibrate-induced decrease in plasma levels of small, heavy LDL might be related to its inhibition of LCAT and CETP activities which resulted in suppression of heteroexchange of HDL-EC with triglyceride in large, light LDL. The bezafibrate-induced increase in large HDL3 (HDL3a) could not be explained solely by its suppression of LCAT and CETP activities. The decrease of plasma small, heavy LDL as well as TG-rich lipoproteins by bezafibrate seems to be beneficial for prevention of atherosclerotic diseases.

Adult↗
PubMed1994

Increased heparin-releasable platelet factor 4 and D dimer in patients one month after the onset of acute myocardial infarction: persistent activation of platelets and the coagulation/fibrinolytic system.

To evaluate the activity of platelets and the coagulation/fibrinolytic system 1 month after the onset of acute myocardial infarction, we measured the plasma levels of molecular markers, i.e. beta-thromboglobulin, platelet factor 4, thrombin-antithrombin III complex and D dimer, in 16 patients with acute myocardial infarction and in 11 normal subjects. Blood was drawn through a catheter placed in the pulmonary artery before heparin injection. The heparin-releasable platelet factor 4 was calculated by subtracting the level before the injection of 5000 U of heparin, from the level 5 min after injection. The plasma beta-thromboglobulin, thrombin-antithrombin III complex and the D dimer levels in the acute phase of myocardial infarction were 134.9 +/- 121.2, 11.2 +/- 7.1 and 164.4 +/- 115.3 ng/ml, respectively. These values were significantly higher than those in the normal subjects. The plasma levels of beta-thromboglobulin and thrombin-antithrombin III complex, 1 month after the onset (36.6 +/- 16.4 and 4.6 +/- 2.3 ng/ml, respectively) were not significantly different from those of the normal subjects. In contrast, D dimer and heparin-releasable platelet factor 4 were 216.9 +/- 176.9 and 80.5 +/- 29.3 ng/ml, respectively, and significantly higher than in the normal subjects. These findings suggest a latent but persistent activation of the platelets and the coagulation/fibrinolytic system 1 month after the onset of acute myocardial infarction.

Adult↗
PubMed1994

Experimental idiopathic dilated cardiomyopathy under low-calcium condition.

Administration of long-term, low-dose Na2EDTA leads to moderate or severe thinning of the right ventricular wall with or without rupture. These morphological manifestations are known to be site-dependent on the constriction of pulmonary arteries (Yamaguchi et al. 1993a). They sometimes ensue from aneurysmal dilatation and/or plexiform-like-lesion in a pulmonary artery (Yamaguchi et al. 1993b). The present contribution reports that experimental animals who survived for a longer period, maximum for 6 months, showed dilatation of the left ventricle with a mode-rately thin ventricular wall as well as right ventricular changes, which are similar to the morphological manifestations in idiopathic dilated cardiomyopathy.

Animals↗
PubMed1994

Experimental study on the hyperplasia of juxtaglomerular cells under low-dose, long-term administration of calcium chelating agents. Similar to the morphological manifestation of Bartter's syndrome.

Bartter's syndrome is a genetic disorder which has very rarely been clinically encountered. However, it is of specific interest with respect to the hormonal layer of the kidney, including renin, angiotensin and aldosterone as well as biological alteration of the various electrolytes. The fundamental morphological manifestation of this disorder is known to be hyperplasia of juxtaglomerular cells, although, until now, no experimental studies on this condition have been reported. Demonstrated in this initial study is the remarkable hyperplasia of the juxtaglomerular cells in all terminal portions of the afferent glomerular arterioles situated near the hilum of the glomerular tuft, using a low-dose, long-term administration of calcium chelating agents. This hyperplasia reported in this paper may lead to a new procedure in the analysis of this syndrome.

Animals↗
PubMed1994

Peripolar cells in guinea pigs under experimental hyperplasia of juxtaglomerular cells induced by long-term, low-dose calcium condition.

The peripolar cell was described in the glomeruli of sheep by Ryan et al. in 1979 and these cells have subsequently been detected in many species (Ryan et al. 1982; Gall et al. 1986; Hanner et al. 1980). The peripolar cells are located at the junction between the podocytes of the glomerular capillaries and the epithelial lining of Bowmann's capsule, encircling the hilar region of the glomerular tuft. Functionally, the peripolar cells have been considered to be a part of the juxtaglomerular apparatus but the precise nature of the cells has not been identified (Gardiner et al. 1985). Recently, it has been found that an antibody against rat urinary kallikrein reacts positively with sheep peripolar cell (Gall et al. 1984). This finding has led to the suggestion that the peripolar cells may influence the renin secretion through the kallikrein-kinin system. In our experiments with long-term low-calcium condition accompanied with hyperplasia of juxtaglomerular cells the peripolar cells were easily detected. The results suggests that the increase in the number of peripolar cells is closely related to the hyperplasia of juxtaglomerular cells.

Animals↗
PubMed1994

Necklace-like detachment of endothelial cell layer from arterial wall under low-calcium condition.

The diversified morphological manifestations in various tissues and organs obtained by administration of differing amounts of calcium chelating agents were reported in previous papers (Yamaguchi et al 1981 a & b; 1982; 1990; 1993). In our recent research described here, administration of a moderate dose of Na2EDTA over the short term demonstrated necklace-like detachment from the arterial wall without disruption of the endothelial cell chain. Intercellular spaces in the media just beneath the detached endothelial cell layer was stained strongly with colloidal iron staining. Electron microscopic observation revealed that the detached endothelial cells showed a lot of elongated anchoring villi from the basal surface, usually seen at the luminal surface, adhered to the degenerative and thin flattened internal elastic lamellae. The alteration of the colloidal iron staining of the vascular wall under the low-calcium condition is suggested to be induced by loosening of the molecular structure of glycosaminoglycans (GAGs) as well as glycoproteins (GPs), comprising the important component of the intercellular matrix and elastic lamellae, which would induce a change in their pasty or viscous character. This would be an accelerative factor for detachment of endothelial cells. Moreover, the lack of the waving of the internal elastic lamellae, trapping of endothelial cytoplasmic processes among them, would play the decisive role in the total detachment of the endothelial cell layer. On the other hand, the low-calcium condition did not adversely influence the joining of endothelial cells. The pathognomatic mechanism will be discussed, with a comparison made to the angiolytic changes provoked by a large amount of Na2EDTA.

Animals↗
PubMed1994

Anti-tumour activity of low-toxicity lipopolysaccharide of Bordetella pertussis.

A lipopolysaccharide (BP-LPS) isolated from killed Bordetella pertussis (Tohama strain) was determined to have low toxicity based on the mortality and decrease in body weight of BP-LPS-injected mice. BP-LPS, administered intradermally or intraperitoneally, clearly inhibited the growth of an MM46 murine mammary carcinoma. When compared with a toxic Escherichia coli-derived LPS, BP-LPS displayed excellent anti-tumour activity against MH134 hepatoma and Meth A fibrosarcoma. As part of a combined chemotherapy/immunotherapy regimen, BP-LPS also seemed to prolong the lifespan of mice inoculated with Lewis lung carcinoma. BP-LPS thus appears to have valuable characteristics as an anti-tumour agent.

Animals↗