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Biomedical subjects

Y Noguchi

Publications and source records attributed to Y Noguchi.

At least 127 records · Page 7Linked to original sources

Soluble Fas in the serum of patients with non-Hodgkin's lymphoma: higher concentrations in angioimmunoblastic T-cell lymphoma.

The soluble form of Fas (sFas) can block apoptosis induced by the Fas ligand in vitro. A recent report demonstrated that mice injected with sFas displayed autoimmune features. Therefore, an elevated serum concentration of sFas may be associated with lymphoproliferation and autoimmune diseases. We measured the serum concentrations of sFas in 77 patients with non-Hodgkin's lymphoma (NHL) [8 angioimmunoblastic T-cell lymphoma (AIL), 12 T-cell NHL, 53 B-cell NHL, and 4 natural killer-cell NHL]. Elevated concentrations of sFas were detected only in AIL, which is frequently accompanied by autoimmune diseases (P < 0.005 compared with age-matched controls). A possible association of sFas and autoimmune features in AIL is discussed.

Aged↗

Regulation of IFN-gamma production in granulocyte-macrophage colony-stimulating factor-deficient mice.

Granulocyte-macrophage colony-stimulating factor-deficient (GM-CSF-/-) mice produce far lower serum levels of IFN-gamma in response to LPS than GM-CSF+/+ mice. CD4+ and CD8+ T cells from LPS-injected GM-CSF-/- mice showed a deficiency in IFN-gamma production and proliferative activity in response to IL-2 and IL-12, whereas IFN-gamma production by NK cells was not compromised. These defects of T cells were reversed by administration of GM-CSF in vivo, but not by supplementation with GM-CSF in vitro. GM-CSF-/- mice do not have an intrinsic defect in IFN-gamma production, because IL-12 injection induces the same high levels of IFN-gamma in GM-CSF-/- and GM-CSF+/+ mice. To investigate the inhibitory effect of LPS on GM-CSF-/- T cells and the indirect restorative activity of GM-CSF, we tested the action of supernatants from cultured dendritic cells (DC). A factor or factors in the DC supernatant normalized serum IFN-gamma levels and T cell responses in LPS-injected GM-CSF-/- mice. IL-18 reproduced some but not all of these in vivo and in vitro effects of DC supernatants. Our results indicate that GM-CSF is important in protecting T cells from inhibitory signals generated during immunization or exposure to LPS, and that this effect of GM-CSF is indirect and mediated by factors produced by DC.

Animals↗

Effects of lecithinized SOD on sequential change in SOD activity after cerebral contusion in rats.

To analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide accumulation after traumatic brain injury (TBI) in rats, we studied the SOD activity by NBT-reducing method and the expression of Cu,Zn-SOD mRNA by Northern blot analysis. As determined by the specific gravity method, the administration of lecithinized SOD decreased brain edema in the periphery of the lesion at 6 hr after contusion. SOD activity, without lecithinized SOD administration, increased at the peripheral portion at 30 min after contusion, but decreased to normal level at 6 hr after TBI. By administration of lecithinized SOD, the increase of SOD activity was preserved until 6 hr after TBI. The expression of Cu,Zn-SOD mRNA increased in the core lesion, peripheral portion, and contralateral hemisphere until 6 hr after TBI, then was suppressed in all three areas by lecithinized SOD. These results support the hypothesis that superoxide anions may play an important role in the development of brain edema after TBI, and that leciyhinized SOD appears to prevent brain edema through a protective effect against superoxide anions.

Animals↗

Successful operative treatment for acute triple-barreled aortic dissection in a patient with Marfan's syndrome: report of a case.

Triple-barreled aortic dissection is a rare form of aortic dissection associated with high mortality. We report herein the case of a 41-year-old woman with Marfan's syndrome who developed acute triple-barreled aortic dissection from a Stanford type B dissecting aneurysm. Successful graft replacement of the proximal third of the descending thoracic aorta was subsequently performed. To the best of our knowledge, this is the first case of successful operative treatment for an acute triple-barreled aortic dissection ever to be reported.

Adult↗

[Evaluation of the growth of a new pulmonary trunk after the reconstruction of right ventricular outflow tract without using an external conduit].

To evaluate the growth of a pulmonary trunk reconstructed without an extracardiac conduit, the hemodynamics and diameter of a new pulmonary trunk were measured in 5 patients from the right ventriculogram and MRI at postoperative follow-up periods. There were tetralogy of Fallot with pulmonary atresia in two patients, tetralogy of Fallot with single coronary in one, truncus arteriosus type I in one and transposition of the great arteries with ventricular septal defect and pulmonary stenosis in one. The age at operation ranged from 26 days to 4.5 years. The posterior wall continuity of the right ventricle and pulmonary artery was established by the direct pulmonary-right ventricular anastomosis in three patients and by the interposition of the left atrial appendage in two. Postoperative follow-up periods ranged from 2 years and 6 months to 3 years and 10 months (median: 2 years and 11 months). In four of them, the postoperative right ventricular to aortic or left ventricular systolic pressure ratios were less than 0.4 without any significant systolic pressure gradients between pulmonary artery and right ventricle. In these four patients, the diameters of the reconstructed pulmonary trunks grew from 10-18 mm to 18-21 mm postoperatively. These diameters were more than 100% of normal values. In the remaining patient with tetralogy of Fallot and single coronary artery, the obstruction of the new pulmonary trunk by a bulged left atrial appendage, which was used as the posterior wall, was observed on the right ventricular outflow tract reconstruction without an extracardiac conduit has growth potential in the future.

Bioprosthesis↗

[Closed Brock operation for an infant case of double outlet right ventricle with pulmonary atresia].

One-month-old boy with double outlet right ventricle and pulmonary atresia was referred to us for surgical treatment. As he had a membranous obstruction of the pulmonary artery we chose closed Brock operation as an initial procedure. A 6.5 mm in diameter of Trocar was used to open the atretic valve. Postoperative course was uneventful and his oxygen saturation was maintained satisfactory. At the age of one year and nine months he underwent corrective surgery. The pulmonary valve was widely opened enough to perform the right ventricular outflow tract reconstruction with valvotomy and outflow patch. The boy got well and was followed in the outpatient clinic. Double outlet right ventricle with membranous pulmonary atresia is a rare combination and closed Brock operation is shown to be one of the most effective procedure for this type of anomaly.

Double Outlet Right Ventricle↗

Surgical treatment of a cardiac papillary fibroelastoma developing from the chordae of the tricuspid valve: report of a case.

Papillary fibroelastoma is a rare, benign cardiac tumor that can cause multiple emboli. We report herein a case of papillary fibroelastoma developing from the chordae of the tricuspid valve which was detected by echocardiography and confirmed by surgical resection. To our knowledge, this is only the fifth documented case of a tricuspid valve papillary fibroelastoma detected by echocardiography in a living patient.

Adult↗

Methylenetetrahydrofolate reductase and apolipoprotein E polymorphisms are independent risk factors for coronary heart disease in Japanese: a case-control study.

A missense variant of the C677T (Ala --> Val) polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR) (the T allele) may increase levels of plasma homocysteine. Apolipoprotein E4 increases plasma LDL-cholesterol levels. Increased levels of homocysteine and LDL-cholesterol have been recognized as risk factors for coronary heart disease (CHD). To examine whether the polymorphisms in the MTHFR gene and the APOE gene are associated with CHD in the Japanese, we analyzed 214 CHD patients with an onset age before 65 and 310 apparently healthy persons. In the controls, significantly higher plasma concentrations of homocysteine were observed in the MTHFR TT genotype (15.1+/-6.0 mmol/l) compared with the CT genotype (11.2+/-1.9 mmol/l) and the CC genotype (10.5+/-3.3 mmol/l). The MTHFR TT genotype was significantly more frequent in the CHD patients (28.5%) compared with the control subjects (13.5%); the odds ratio was 2.54 (P < 0.00003). Subjects with the apo E4 allele were significantly more frequent in the CHD group (22.9%) than in the control group (10.0%); the odds ratio was 2.74 (P < 0.00004). Multivariate analysis showed that the TT genotype of MTHFR and the apoE4 allele are independent risk factors for CHD in the Japanese.

Adult↗

The fate and acute toxicity of aflatoxin B1 in the mastomys and rat.

The fate and acute toxicity of aflatoxin B1 (AFB1) were studied in the mastomys (Praomys coucha) and compared with Fischer rats. The experiment regarding the fate of [3H]AFB1 showed that the radioactivity was excreted mainly through the feces, more rapidly in the mastomys than in the rat, regardless of whether [3H]AFB1 was given orally or intravenously. The levels of radioactivity bound to the liver DNA were lower in the mastomys than in the rat, indicating that the levels of AFB1 binding to the macromolecules in the liver were lower in the mastomys. Consistent with such differences in the fate of AFB1 between the two species, the mastomys were far more resistent to the acute effects of AFB1 than were the rats. Oral administration of AFB1 at a dose of 1.0 mg/kg to rats caused marked microscopic changes in the liver, involving hepatic necrosis and proliferation of bile ducts, but at a dose of 4.0 mg/kg to mastomys caused no pathological changes in the liver or kidneys, and at a dose of 10.0 mg/kg caused only glycogen deposition in hepatic cells in a limited area. The observed differences in susceptibility to the toxic effects of AFB1 and in the fate of AFB1 between the two species are in accord with our previous finding that liver cytosol in the mastomys inhibits microsome-mediated AFB1-DNA binding in vitro more strongly than in rat liver.

Aflatoxin B1↗

A cross-validation of the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) for Japanese with lung cancer.

The EORTC QLQ-C30 was developed in English-speaking cultures. To determine if this instrument could cross a broad cultural divide and be used in Japan, the cross-cultural validity of its Japanese version was estimated. In evaluating psychometric testing, internal consistency by Cronbach's alpha, item-discrimination by multitrait scaling analysis, and validity analysis with ECOG performance score (PS) and Karnofsky Performance Status Scale (KPS) were performed. The QLQ-C30 (version 1.0) was given to 105 patients with lung cancer. Although the response rate was low in patients with PS 4, the questionnaire was well accepted by patients with PS 0-3. The Japanese QLQ-C30 has a weak scale of role functioning in terms of item discriminative validity. It also has a weak scale of cognitive functioning in items of discriminative validity and internal consistency. However, known-groups comparison showed the expected clinical validity with PS for all the scales except for financial impact, and longitudinally clinical validity with KPS was shown in scales of cognitive functioning, fatigue, and nausea and vomiting. Multitrait scaling analysis showed that the predicted scales constituting quality of life (QOL) in the English-speaking culture were extracted from the Japanese QLQ-C30, and found to be valid in Japan, indicating its possible usefulness as an instrument that is universally applicable across cultures.

Cross-Cultural Comparison↗

Circulating interleukin 6 concentrations and insulin resistance in patients with cancer.

BACKGROUND: The mechanism of insulin resistance in patients with cancer is not clear. This study was conducted to evaluate the possible role of circulating cytokines in inducing insulin resistance in patients with cancer. METHODS: Twenty-three patients with a variety of cancers were studied, including one patient with oesophageal cancer, 12 with gastric cancer, four with colon cancer and six with lung cancer. Six normal volunteers served as controls. Insulin resistance was evaluated by euglycaemic hyperinsulinaemic glucose clamp with a high physiological insulin concentration of 100 microunits/ml. Metabolized glucose, the M value, was compared between patients with cancer and controls. Serum concentrations of interleukin (IL) 6 and other cytokines (tumour necrosis factor (TNF) alpha, IL-8 and IL-10) were measured by enzyme-linked immunosorbent assay. RESULTS: The mean(s.d.) M value for patients with cancer (5.47(1.59) mg per kg per min) was significantly lower than that for controls (8.23(0.79) mg per kg per min) (P< 0.001). There was no relationship between the M value and degree of body-weight loss. Serum IL-6 concentration was measurable in eight of 23 patients: four with lung cancer, two with gastric cancer, and one each with oesophageal and colon cancer. None of the controls had a measurable serum IL-6 concentration. There was no significant relationship between serum IL-6 concentration and body-weight loss. TNF-alpha was undetectable in the serum of both patients with cancer and controls. Serum IL-8 and IL-10 were detected in seven and one of 23 patients respectively. These cytokines were not detected in the serum of controls. The M value was significantly smaller in those with measurable serum IL-6 (4.01(1.22) mg per kg per min) than in those with no measurable IL-6 (6.26(1.16) mg per kg per min) (P< 0.001). IL-6 and IL-8 levels were raised more frequently in the same patient but there was no significant relationship between IL-8 and M values. CONCLUSION: These results may suggest that IL-6 is related to insulin resistance in patients with cancer.

Aged↗

Alteration in immunoexpression of glucose transporter 2 in liver of tumour-bearing rats.

To elucidate interactions between the glucose transport system and hepatic glucose production in the tumour-bearing state, glycogen storage, expression of glucose transporter isoform 2 (Glut 2) and activities of glucose-6-phosphatase (G-6-Pase) and hexokinase were histochemically examined in hepatocytes of tumour-bearing rats. Five male F344 rats, subcutaneously inoculated with methylcholanthrene (MCA)-induced sarcoma cells were compared with five pair-fed animals and four ad libitum fed controls. Glycogen storage was markedly decreased in liver cells of tumour-bearing rats compared to in those of control animals. Glut 2 immunoreactivity was uniformly seen in the cellular membrane of hepatocytes from control animals. In rats bearing sarcoma, the staining intensity was significantly decreased, suggesting that Glut 2 with its bi-directional transport capacity was down-regulated in the tumour-bearing state. Positive staining for hexokinase activity was located in the perivenous area in livers from control animals and was more diffusely located and more intense in livers from tumour-bearing animals. G-6-Pase activity, limited to the peripheral area in livers from controls, extended to the intermediate area and had stronger reactivity in livers from tumour-bearing animals. In the tumour-bearing cachectic condition, glucose may be partially consumed by a futile cycle, hepatic metabolic zonation was disturbed, and the release of glucose from the liver may not be mediated by a facilitative glucose transporter-2.

Animals↗

Early phase tumor accumulation of macromolecules: a great difference in clearance rate between tumor and normal tissues.

The objective of this study was to investigate the molecular weight (MW) and time-dependence of the phenomenon termed "the enhanced permeability and retention" (EPR) effect in solid tumor, in particular to determine and define the early phase accumulation of macromolecules in tumor and normal tissues and the relationship between blood concentration and tissue clearance. As a model, radioiodinated N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers of MW ranging from 4.5 K to 800 K were administered i.v. to mice bearing sarcoma 180 tumor. Within 10 min all HPMA copolymers accumulated effectively in the tumor regardless of MW (1.0-1.5% of injected dose per g of tumor). However, higher MW copolymers (> 50 K) showed significantly increased tumor accumulation after 6 h, while the lower MW copolymers (< 40 K) were cleared rapidly from tumor tissue due to rapid diffusion back into the bloodstream. Blood clearance was also MW-dependent; the lower MW copolymers displayed rapid clearance, with kidney radioactivity of the copolymers of MW < 20 K representing 24% of injected dose per g kidney at 1 min after i.v. administration. Within 10 min these copolymers passed through the kidney and were excreted in the urine. Higher MW copolymers consistently showed kidney levels of 3-5% dose per g kidney in the early phase with no time-dependent accumulation in kidney. There was also no progressive accumulation in muscle or liver, regardless of polymer MW. These results suggest the "EPR effect" in solid tumor primarily arises from in the difference in clearance rate between the solid tumor and the normal tissues after initial penetration of the polymers into these tissues.

Animals↗

Myasthenia gravis with alopecia totalis.

Myasthenia gravis was diagnosed on the basis of a positive Tensilon test in a 4-year-old male child with alopecia totalis. His scalp hair and eyebrows had began to disappear at the age of 10 months. No other physical abnormalities such as motor paralysis, were seen except for left ptosis and alopecia totalis. His serum titer of anti-acetylcholine receptor antibody was elevated. No immune system abnormalities (C3, C4, CH50, C-reactive protein, antinuclear antibody or lymphocyte function disorders) were detected. Although alopecia areata and alopecia totalis are sometimes present in adults with autoimmune diseases and myasthenia gravis, this association is rare in children. The present case represents the youngest patient with myasthenia gravis associated with alopecia totalis.

Alopecia↗

[Shigella dysenteriae strains possessing a new serovar (204/96) isolated from imported diarrheal cases in Japan].

Five Shigella strains isolated from stool cultures of imported diarrheal cases in Japan, did not react to any antisera of the established Shigella serovars. These strains had the typical biochemical characteristics of Shigella dysenteriae, and were biochemically identical. All strains were positive in the Sereny test and other tests for invasivness; these indicate that they can cause shigellosis in humans. The results of antigenic analysis revealed that they did not belong to any of the recognized or provisional serovars, and were serologically indistinguishable. They had the same drug-resistance pattern (CP.TC.SM.ABPC.ST) and plasmid-profile. Strain 96-204 is designated as the test strain for this new serovar.

Anti-Bacterial Agents↗

Enterohemorrhagic Escherichia coli O157:H7 present in radish sprouts.

Using cultivation, immunofluorescence microscopy, and scanning electron microscopy, we demonstrated the presence of viable enterohemorrhagic Escherichia coli O157:H7 not only on the outer surfaces but also in the inner tissues and stomata of cotyledons of radish sprouts grown from seeds experimentally contaminated with the bacterium. HgCl2 treatment of the outer surface of the hypocotyl did not kill the contaminating bacteria, which emphasized the importance of either using seeds free from E. coli O157:H7 in the production of radish sprouts or heating the sprouts before they are eaten.

Cotyledon↗