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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 253 records · Page 14Linked to original sources
PubMed1997

Serum levels of IL-10, IL-15 and soluble tumour necrosis factor-alpha (TNF-alpha) receptors in type C chronic liver disease.

We previously reported that the number of TNF-alpha-producing cells was increased in the liver of patients with type C chronic liver disease. To understand further the pathophysiology of this change, we examined serum levels of two soluble TNF receptors, TNF-alphaRI (p55) and -alphaRII (p75), and IL-10, all of which act as TNF-alpha buffer, and IL-15, a novel cytokine sharing many immunological activities with IL-2, using ELISA methods. We studied control individuals and patients with type C chronic liver disease, including asymptomatic hepatitis C virus (HCV) carriers with persistently normal serum ALT values, and those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Both types of sTNF-alphaR closely correlated with disease progression. Patients with LC and HCC had significantly elevated levels for sTNF-alphaRII compared with the other patient groups and controls. Serum IL-10 levels were significantly greater in all chronic liver disease groups than in controls. With respect to IL-15, the values were high in CH, LC and HCC compared with those of controls. Notably, HCC patients showed highest values for both IL-10 and IL-15, with significant differences from the other patient groups. Serial determinations revealed that interferon (IFN) treatment for CH patients resulted in the suppression of circulating IL-10 and IL-15 levels along with decrease in serum aminotransferase values. Both cytokines remained at decreased levels after cessation of therapy in patients who went into clinical and virological remission. On the other hand, treatment did not affect serum levels of sTNF-alphaRs. These findings indicate that serum levels of these molecules correlated with disease progress in chronic HCV infection, and that IL-10 and IL-15 may reflect the degree of inflammation in the liver. It is also suggested that both cytokines may be related to the development of HCC.

Adult↗
PubMed1997

Induction of tumor necrosis factor-alpha in the mouse hippocampus following transient forebrain ischemia.

To assess the role of tumor necrosis factor-alpha (TNF-alpha) in modulating the process of cerebral ischemic injury, we identified TNF-alpha-producing cells and studied the time course of TNF-alpha expression. Immunoreactivity for TNF-alpha appeared in white matter of the mouse hippocampus as early as 1.5 h following a 30-min global ischemic insult. Double staining for TNF-alpha and glial fibrillary acidic protein (GFAP) suggested that the TNF-alpha-positive cells are most likely microglia, not astrocytes. TNF-alpha immunostaining decreased at 6 and 24 h but increased again at 3 days, when pyramidal neurons showed degeneration. Adjacent-section staining for microglia and double staining with GFAP suggested that TNF-alpha-positive cells in the pyramidal cell layer were microglia and those in the white matter were astrocytes. By 5 days TNF-alpha immunostaining disappeared from these glial cells, while a number of microglia were accumulated in the degenerated hippocampal pyramidal layer. Pyramidal neurons never expressed TNF-alpha immunoreactivity. Western blotting confirmed biphasic TNF-alpha expression. Our findings suggest that early production of TNF-alpha by microglia may activate a cytokine network in post-ischemic brain resulting in TNF-alpha synthesis by astrocytes.

Animals↗
PubMed1997

Long-term follow-up study of unruptured intracranial aneurysms.

OBJECTIVE: The purpose of this study was to clarify the risk of rupture of unruptured intracranial aneurysms among large groups of patients with various underlying diseases or conditions. METHODS: A long-term follow-up study of unruptured intracranial aneurysms was performed with 360 patients who were treated conservatively during the period from April 1969 to December 1992. RESULTS: Follow-up evaluation (between February and June 1994) could be performed for 234 (65%) of the patients. The underlying diseases included multiple aneurysms with subarachnoid hemorrhage for 60 patients, cerebral infarction for 108, intracerebral hemorrhage for 27, and other diseases for 39. Single aneurysms were present in 171 patients and multiple aneurysms in 63. The mean follow-up period was 75 months (range, 3-270 mo). Of the 234 patients, 132 (56.4%) survived, 59 (25.2%) died because of other diseases, 9 (3.8%) underwent surgery, and 34 (14.5%) showed bleeding from unruptured aneurysms, which was fatal for 18 of the patients. The average annual rupture rate for all patients was 2.3% (subarachnoid hemorrhage, 3.2%; cerebral infarction, 2.2%; intracerebral hemorrhage, 3.2%; other diseases, 3.6%). There were no significant differences among the patients according to underlying disease or aneurysm site. The cumulative rate of bleeding for all patients was 20% at 10 years after diagnosis and 35% at 15 years. The cumulative probability of rupture was significantly higher for the multiple aneurysms than the single aneurysms (P < 0.001). CONCLUSION: The risk of rupture of unruptured aneurysms is high, especially for multiple aneurysms, but there are no significant differences in the risk of rupture according to the underlying disease or the aneurysm location. Radical treatment should be considered for patients with unruptured intracranial aneurysms.

Adult↗
PubMed1997

Efficacy of lithium carbonate on public and compulsive masturbation: a female case with mild mental disability.

The efficacy of lithium carbonate in the first reported case of a female with mild mental disability who engaged in public and compulsive masturbation is described. The patient was born in 1975, and was 19 years old at first admission. A diagnosis of schizophrenia was initially suspected, therefore the patient was given medication including pimozide, haloperidol, carbamazepine, diazepam and levomepromazine. These medications, however, did not control the symptoms, and the patient showed several side effects, such as incontinence. Only lithium carbonate was efficacious among the medications administered; the patient's abnormal sexual behavior was significantly reduced and no conspicuous side effects were recognized. The mechanisms of lithium carbonate in controlling abnormal sexual behavior are discussed.

Adult↗
PubMed1997

Renal angiosarcoma: a case report.

We report the first case of angiosarcoma in the kidney occurring in a woman; the tumor was initially believed to be renal cell carcinoma. This malignant tumor was discovered in a patient with macrohematuria. The final diagnosis was confirmed by histologic and immunohistochemical findings. A review of the literature on this tumor is also included in the discussion.

Angiography↗
PubMed1997

CD95 (Fas) may control the expansion of activated T cells after elimination of bacteria in murine listeriosis.

CD95 (Fas) is known to mediate activation-induced T-cell death by apoptosis. To understand the role of CD95 during the course of bacterial infection, we examined the kinetics of alphabeta and gammadelta T cells in the peritoneal cavities and livers of 5-week-old CD95-defective MRL/lpr mice after an intraperitoneal infection with Listeria monocytogenes. The number of bacteria in the spleen decreased to an undetectable level by day 10 after infection with 7 x 10(3) Listeria cells similar to the number in MRL/+/+ mice. The number of alphabeta T cells expressing CD44 and CD95 reached a maximum in the peritoneal cavity on day 6 after listerial infection and thereafter decreased gradually in MRL/+/+ mice, whereas CD44+ alphabeta T cells without CD95 expression continued to increase throughout the course of listerial infection in MRL/lpr mice. Freshly isolated T cells from MRL/+/+ mice infected with L. monocytogenes 10 days previously showed DNA fragmentation with apoptosis, whereas such fragmentation was not prominent in T cells from infected MRL/lpr mice. In correlation with the increased number of CD44+ alphabeta T cells, Listeria-specific T-cell proliferation of peritoneal exudate cells was significantly greater in MRL/lpr mice than in MRL/+/+ mice on day 10 after listerial infection. In contrast to alphabeta T cells, gammadelta T cells increased in number only transiently in the peritoneal cavity and liver after listerial infection in both MRL/lpr mice and MRL/+/+ mice. These results suggest that CD95-mediated cell death with apoptosis may be involved in termination of the alphabeta-T-cell-mediated immune response after the battle against L. monocytogenes has been won, whereas gammadelta T cells may undergo apoptosis independently of CD95 during the course of listerial infection.

Animals↗
PubMed1997

Targeting deletion of angiotensin type 1B receptor gene in the mouse.

We null mutated the mouse angiotensin type 1B (AT1B) receptor gene (Agtr1b) by gene targeting. To identify the specific cell types carrying high Agtr1b gene transcriptional activities, the AT1B coding exon was replaced with a reporter gene, lacZ. In 6- to 8-wk-old Agtr1b -/- mice, high AT1B transcriptional activity was observed in adrenal zona glomerulosa cells and the testis, including mature and immature spermatic cells, whereas low activity was detected homogeneously in anterior pituitary cells and choroidal plexus vessel walls. A similar pattern was observed in Agtr1b +/- mice with less intensity. Microscopically, the anterior pituitary, heart, adrenal, zona glomerulosa, kidney, and the testis of Agtr1b -/- mice were intact and were indistinguishable from those of Agtr1b +/+ mice. Systemic blood pressure was comparable in Agtr1b -/- and Agtr1b +/+ mice. Moreover, plasma aldosterone level was comparable between the two mouse groups. No compensatory enhancement of AT1A mRNA was found in the kidney and adrenal gland of Agtr1b -/- mice. The observed absence of the abnormal phenotypes in Agtr1b -/- mice, which have been described for homozygous angiotensinogen null mutant mice, indicates that 1) AT1A receptors can take over the role of AT1B receptors in Agtr1b -/- mice or 2) functionally significant non-AT1, non-AT2 receptor(s) may exist for the action of angiotensin.

Aldosterone↗
PubMed1997

Therapeutic effect of a newly developed antioxidative agent (OPC-15161) on experimental immune complex nephritis.

The effect of a newly developed free radical scavenger (OPC-15161) on the progression of nephrotoxic serum (NTS) nephritis was evaluated. NTS nephritis rats were sacrificed immediately before and 1, 2, 3, 6, and 24 h and 13 and 19 days after intravenous injection of NTS. The tissue content of phosphatidylcholine hydroperoxide, the activity of superoxide, the activity of superoxide dismutase in the renal cortex, and the serum malondialdehyde levels were measured. The phosphatidylcholine hydroperoxide content in the renal cortex of OPC-15161-treated NTS nephritis rats was lower than that in the control rats 24 h after NTS injection. The activity of superoxide dismutase in OPC-15161-treated rats was sustained in contrast to the decrease in this activity in the control rats 6 h after injection of NTS. The effects of OPC-15161, dipyridamole, and prednisolone on NTS nephritis rats were investigated. OPC-15161 (20 mg/kg p.o.) showed a potent inhibitory effect on the urinary protein excretion, whereas dipyridamole (30 and 100 mg/kg p.o.) and prednisolone (2 mg/kg p.o.) had less suppressive effects. In view of these results, we conclude that OPC-15161 notably ameliorated the urinary protein excretion by way of the suppression of lipid peroxidation in the renal tissue of NTS nephritis rats.

Animals↗
PubMed1997

Glucocorticoid regulation of leptin synthesis and secretion in humans: elevated plasma leptin levels in Cushing's syndrome.

Leptin, the obese (ob) gene product, is an adipocyte-derived satiety factor that is involved in the regulation of food ingestion and body weight. To investigate glucocorticoid regulation of leptin synthesis and secretion in humans, we measured plasma leptin levels in patients with Cushing's syndrome with adrenal or pituitary adenoma and in patients with iatrogenic Cushing's syndrome. Plasma leptin levels in patients with Cushing's syndrome were significantly elevated compared to those in nonobese healthy subjects and obese subjects without any metabolic or endocrine diseases at a given percentage of body fat by analysis of covariance. In patients with adrenal or pituitary adenoma, after the tumor resection, plasma leptin levels were reduced, with a concurrent decrease in plasma cortisol levels. With no significant changes in body weight, plasma leptin levels were also elevated significantly in lean healthy volunteers 24 h after the administration of 1 mg dexamethasone. Dexamethasone potently induced ob gene expression and leptin secretion in the organ culture of human adipose tissue. The data demonstrate that glucocorticoids act, at least in part, directly on the adipose tissue and increase leptin synthesis and secretion in humans.

Adenoma↗
PubMed1997

Suppression of ischemic edema in mice by manganese-hyaluronate conjugate.

Manganese-hyaluronate conjugate (Mn-HA) was synthesized from a diethylenetriaminepenta-acetic acid derivative of hyaluronic acid and manganese ion. The conjugate markedly scavenged super-oxide anion in vitro and exhibited much higher anti-inflammatory activity than superoxide dismutase in suppressing paw edema in mice when intravenously injected 30 min before the initiation of ischemia.

Animals↗
PubMed1997

Rhythmical discharges recorded from cervical and trunk muscle nerves produced by stimulation of mesencephalic locomotor region (MLR) in the decerebrated cat.

This experiment investigated the effects of mesencephalic locomotor region (MLR) stimulation on cervical and trunk motoneurons in decerebrated cats. The experiments were performed on 28 adult cats (2.1-3.9 kg) of either sex. Stimulation of MLR produced the rhythmical discharge of muscle nerves of the splenius (SP), the longissimus lumborum (LL) and the obliquus externus abdominis (OEA). There was a close relationship between rhythmical discharge of SP, LL or OEA muscle nerve and hindlimb muscle nerve. This fact suggests that rhythmical discharges of cervical and trunk muscle nerves relate to locomotion.

Animals↗
PubMed1997

Hsp70 protects macrophages infected with Salmonella choleraesuis against TNF-alpha-induced cell death.

Hsp70 plays an important role in cytoprotection against tumor necrosis factor (TNF) alpha-mediated cytotoxicity. To investigate the role of Hsp70 in cytoprotection during Salmonella infection, we examined endogenous Hsp70 induction and TNF-alpha production in a monocyte/macrophage line, J774A.1, after infection with a virulent strain of Salm. choleraesuis RF-1 carrying a 50 kb virulent plasmid or the plasmid-cured avirulent strain 31N-1. Intracellular bacteria progressively increased in J774A.1 cells phagocytosing virulent RF-1 bacteria, whereas such progressive growth was not evident in J774A.1 cells phagocytosing avirulent 31N-1 bacteria. On the contrary, J774A.1 cells infected with virulent RF-1 bacteria expressed less Hsp70 than those infected with avirulent 31N-1 bacteria. The level of TNF-alpha production by J774A.1 infected with virulent RF-1 was much the same as that by J774A.1 infected with avirulent 31N-1. J774A.1 infected with virulent RF-1 died spontaneously; death was inhibited by the addition of anti-TNF-alpha mAb. Although the frequency of dead J774A.1 with hypodiploid DNA content increased only marginally after infection with avirulent 31N-1, treatment with Hsp70 anti-sense oligonucleotide resulted in a dramatic increase of dead cells in the infected macrophages. Taken together, these results suggest that Hsp70 induced in infected macrophages plays an important role in host defense against Salmonella infection by protecting the macrophages against TNF alpha-induced cell death. Furthermore, cell death due to impaired endogenous Hsp synthesis in the phagocytes implies a novel pathogenic mechanism for virulence of Salm. choleraesuis RF-1.

Animals↗
PubMed1997

Molecular screening of both the promoter and the protein coding regions in the human ob gene in Japanese obese subjects with non-insulin-dependent diabetes mellitus.

OBJECTIVE: Although the molecular mechanism of obesity has been poorly understood, recent studies indicate that leptin plays a critical role in regulating both food intake and body weight. Because obesity decreases the sensitivity to insulin, the human ob gene is presumed to be one of the candidate genes for non-insulin-dependent diabetes mellitus (NIDDM) associated with obesity. Although the protein coding region in the ob gene has been screened for mutations, the promoter region and the non-coding first exon have not yet been studied. We investigated the involvement of the human ob gene, especially mutations at the promoter region and the non-coding first exon, in the development of NIDDM associated with obesity. SUBJECTS: The study group comprised 60 Japanese obese subjects with NIDDM (body mass index (BMI) 43.6 > or = BMI > or = 26.4, 29.0+/-0.41 (mean+/-S.E.M.)) and 24 obese individuals with impaired glucose tolerance (IGT) (30 > or = BMI > or = 26.4, 27.1+/-0.22). METHODS: Mutations at both the promoter region and all three exons in the human ob gene were screened by the single-stranded conformational polymorphism analysis. When aberrantly migrated bands were recognized, the PCR-amplified DNA fragment was directly sequenced. RESULTS: In the protein coding region a silent mutation in the second exon was detected. The non-coding first exon and the about 100 bp 5'-flanking region of the gene which contains a proximal CCAAT/enhancer-binding protein site were screened, but no mutations were found. CONCLUSION: These results suggest that no mutations in either the promoter region at the about 100 bp 5'-flanking region of the gene, or in any of the three exons, are involved in the development of NIDDM or IGT associated with obesity.

Asian People↗
PubMed1997

Cross-reactivity of anti-yellowtail thymic lymphocyte monoclonal antibody (YeT-2) with lymphocytes from other fish species.

The monoclonal antibody YeT-2, generated in mice hyper-immunized with thymic lymphocytes of the yellowtail, Seriola quinqueradiata, reacts with the major population of peripheral blood lymphocytes, which might be putative T cells. In this study, we examined the cross-reactivity of YeT-2 with lymphocytes from various fish species. Flow cytometric analysis showed that YeT-2 reacts with 69.8% lymphocytes in the thymus, 89.7% in the peripheral blood, 87.5% in the spleen, and 59.7% in the head-kidney. Among the six fish species examined, only the red sea bream, Pagrus major, which is included in the same suborder Percoidei with the yellowtail, showed the presence of YeT-2 positive cells. Electron microscopic studies revealed that YeT-2 positive cells in the peripheral blood of the red sea bream were lymphocytes or unidentified leucocytes. Thymic lymphocytes of the red sea bream were also immunocytochemically stained with YeT-2. The molecular weight of the YeT-2 cross-reacting antigen on blood cells from the red sea bream was identical with that from the yellowtail, which was identified at approximately 115 kDa. These results suggest that the monoclonal antibody YeT-2 recognizes a conserved antigen on lymphocytes common to the red sea bream and yellowtail.

Animals↗
PubMed1997

Transient worsening of Parkinson's disease after cigarette smoking.

We report a patient with probable Parkinson's disease who experienced a temporary worsening of his symptoms and signs after cigarette smoking. Deterioration of tremor, rigidity, and writing disturbance began soon after the inhalation of cigarette smoke and persisted for 15 minutes. Chewing nicotine gum also induced a brief worsening of the patient's symptoms. Aggravation of parkinsonian symptoms after cigarette smoking appeared to be caused by nicotine alone, although the mechanism for this effect remains unclear.

Adult↗