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Biomedical subjects

T Hosokawa

Publications and source records attributed to T Hosokawa.

At least 37 records · Page 2Linked to original sources
PubMed2000

Diverse effect of tributyltin on apoptosis in PC12 cells.

It has not been fully elucidated how endocrine-disrupting chemicals disrupt hormone functions or how strong their effects are compared with natural hormones. There is little information concerning the effects of tributyltin (TBT), one of the endocrine disrupters on living organisms. Although TBT at high concentration induced apoptosis in PC12 cells, TBT at low concentration inhibited the DNA fragmentation in the cells cultured in serum-free medium or in medium containing 6-hydroxydopamine. The cell viability grown in both medium conditions increased after treatment with TBT. These findings suggest that TBT exerted a apoptosis-inducing and -inhibiting effect. These diverse effect of TBT on apoptosis would cause serious damages on cell differentiation.

Animals↗
PubMed2000

Effects of near-infrared low-level laser irradiation on microcirculation.

BACKGROUND AND OBJECTIVE: Recently, there has been an increase in the clinical application of low-level laser irradiation (LLLI) in various fields. The present study was conducted to explore the effects of LLLI on microcirculation. STUDY DESIGN/MATERIAL AND METHODS: We investigated the effects of LLLI on rat mesenteric microcirculation in vivo, and on cytosolic calcium concentration ([Ca2+]i) in rat vascular smooth muscle cells (VSMCs) in vitro. RESULTS: LLLI caused potent dilation in the laser-irradiated arteriole, which led to marked increases in the arteriolar blood flow. The changes were partly attenuated in the initial phase by the superfusion of 15 microM L-NAME, but they were not affected by local denervation. Furthermore, LLLI caused a power-dependent decrease in [Ca2+]i in VSMCs. CONCLUSION: The circulatory changes observed seemed to be mediated largely by LLLI-induced reduction of [Ca2+]i in VSMCs, in addition to the involvement of NO in the initial phase.

Animals↗
PubMed2000

Histochemical characterization of silver-induced metallothionein in rat kidney.

Histochemical characterizations of Ag-induced metallothionein (MT) in the kidney of the rat have been reported. Ag, Cu and Zn contents increased in kidney and liver after Ag injection. In particular, the Cu content in kidneys increased dramatically after three injections of Ag. Sephadex G-75 elution profiles of the renal cytosol of rats injected with Ag revealed that the accumulated Cu in the kidney was bound to MT as were Ag and Zn. In addition, localization of Cu- and Ag-MT in the kidney was studied using autofluorescent signals, which are dependent on Cu- or Ag-thiol clusters, and immunohistochemistry. Although the MT induced by Ag was predominantly observed in the cortex of the kidney, some MT signals were also detected in the outer stripe of the outer medulla, as well as in the kidneys of LEC rats, an animal model of Wilson disease (a hereditary disorder of Cu metabolism). In these LEC rats, the Cu-MT also accumulated in the outer stripe of the outer medulla of the kidney. From these results, one possibility could explain that the Cu-MT detected in the outer stripe of the outer medulla in the kidney of Ag-injected rat was associated with the Cu transporter affected by Ag.

Animals↗
PubMed2000

Troxipide, a novel antiulcer compound, has inhibitory effects on human neutrophil migration and activation induced by various stimulants.

BACKGROUND: Neutrophils are considered to be involved in the pathogenesis of Helicobacter pylori-associated gastroduodenal diseases on account of their potent biological functions as effector cells. Troxipide, a new antiulcer compound used for patients with gastric ulcer or gastritis, has been shown to inhibit migration and activation of guinea pig neutrophils, but little is known about the pharmacological effects on human neutrophils. AIMS: To study the effects of troxipide on chemotactic migration and superoxide generation by human neutrophils. METHODS: The chemotactic response of neutrophils was determined in a multi-well chamber with a polycarbonate filter and the generation of O2- by neutrophils was measured using a chemiluminescence method. Concentrations of troxipide in gastric mucosa were measured by high-performance liquid chromatography. RESULTS: Incubation of neutrophils with 10(-6) to 10(4) M troxipide caused inhibition of recombinant interleukin-8-induced migration. These concentrations of troxipide also inhibited superoxide generation by neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine or platelet activating factor. These phenomena were not simply due to the direct cytotoxic effects since the above concentrations of troxipide did not induce neutrophil apoptosis. The concentrations of troxipide detected in the gastric mucosa after oral administration were in the range able to inhibit chemotactic migration and superoxide generation by neutrophils in vitro. CONCLUSION: These results suggest that troxipide may exert its therapeutic effect in patients with gastric ulcer or gastritis by inhibiting inflammatory responses and mucosal injury mediated by neutrophils in gastric mucosa.

Adult↗
PubMed2000

Distribution of zinc-binding metallothionein in cirrhotic liver of rats administered zinc.

This study was undertaken in order to investigate the effect of zinc (Zn) administration on induction of Zn-binding metallothionein in rat liver with thioacetamide-induced cirrhosis, and the localization of metallothionein in the liver. Normal and cirrhotic rats received intraperitoneal injections with or without Zn. Subsequently, metal analyses, purification of metallothionein by gel filtration and immunohistochemical assessments of metallothionein were carried out. Although in Zn-injected cirrhotic rats, the Zn contents in the liver and plasma increased significantly depending upon the dose of Zn, the Zn contents in the liver and plasma of the cirrhotic rats were lower than those of normal rats after the same dose of Zn. The results of gel filtration also showed that the levels of Zn-metallothionein in the cirrhotic liver were reduced in comparison with those of the normal liver. By the immunohistochemical method, the presence of metallothionein in the parenchymal areas but not in the fibrotic areas of the cirrhotic liver was confirmed. These results suggested that the induced metallothionein was only located in the parenchymal areas. The metallothionein induced in the parenchymal areas was considered to play a role in protecting the parenchymal cells against the progression of fibrosis, because metallothionein has been thought to be involved in the cellular defense against oxidative stress.

Animals↗
PubMed2000

Analysis of IgG subclasses in chronic active Epstein-Barr virus infection.

BACKGROUND: Although elevated serum levels of immunoglobulins are frequently observed in patients with chronic active Epstein-Barr virus (EBV) infection, there have been no reports concerning levels of IgG subclasses. METHODS: Serum levels of IgG subclasses were measured by the enzyme-linked immunosorbent assay (ELISA) in 30 children with severe chronic active EBV infection. RESULTS: Serum levels of IgG1 were elevated in most patients, except for one who showed an abnormally low level of IgG1 and progressive hypogammaglobulinemia. Serum levels of IgG2, IgG3 and IgG4 in the patients were comparable to those in control children, while abnormally low levels of IgG2, IgG3 and IgG4 were observed in six, three and four cases, respectively. CONCLUSION: Although not always susceptible to bacterial infections, low levels of IgG2 were frequently observed in patients with chronic active EBV infection and elevated IgG1 is responsible for the increase of serum IgG in these patients.

Adolescent↗
PubMed2000

Suppression of cellular immunity by surgical stress.

BACKGROUND: Suppression of cellular immunity is one of the host responses to surgical stress. In cancer patients this immunosuppression may accelerate the growth and metastasis of residual cancer cells, so it is desirable to restrict immunosuppression by surgical stress to a minimum. However, the extent and duration of immunosuppression caused by operations on gastrointestinal cancer, as well as the mechanisms involved, have not been determined. METHODS: To clarify these points, we investigated immunocyte function and measured the blood levels of hormones, cytokines, and acute phase reactants from before to after operation in 20 patients with stage I gastrointestinal cancer. RESULTS: In patients exposed to surgical stress, peripheral blood lymphocyte numbers and function were suppressed until at least 2 weeks postoperatively. This immunosuppression was mainly due to a decrease of helper-inducer T cells, cytotoxic T cells, natural killer cells, and interleukin-2 receptor-positive cells, as well as an increase of suppressor T cells. In addition, hypersecretion of cortisol and overproduction of immunosuppressive acidic protein were observed. CONCLUSIONS: Cellular immunosuppression by surgical stress was mainly due to an increase of lymphocyte subsets that depress cellular immunity coupled with a decrease of the subsets that promote it. Overproduction of cortisol and immunosuppressive acidic protein in response to surgical stress may play an important role in the development of immunosuppression.

Acute-Phase Proteins↗
PubMed2000

Immune response to gangliosides in a case of Guillain-Barré syndrome after varicella.

An 8 year old girl was admitted to hospital with the typical clinical features of Guillain-Barré syndrome (GBS) after recovering from varicella. Onset of the disease was just two weeks after the onset of varicella in her young sister. Examination of cerebrospinal fluid and nerve conduction studies showed typical findings of GBS. Although serum from both the patient and sister were analysed for autoantibodies to gangliosides and myelin P0 protein, IgM anti-GM1 antibody and anti-GD1b antibody were only detected in the patient. HLA DR haplotypes were quite different between the two subjects. This suggests that these autoantibodies may play an important role in the pathogenesis of GBS after varicella zoster virus infection.

Autoantibodies↗
PubMed2000

Helicobacter pylori-associated gastric ulcer exhibits enhanced mucosal chemokine activity at the ulcer site.

BACKGROUND AND AIM: Although mucosal alpha- and beta-chemokines are considered to be involved in the pathogenesis of Helicobacter pylori-associated gastritis, little is known how these chemokines are related to the ulcerogenesis in peptic ulcer patients. We examined the levels of interleukin (IL)-8 and macrophage inflammatory protein-1alpha (MIP-1alpha) in organ cultures and the numbers of inflammatory cells infiltrating the lamina propria by using the mucosal tissues obtained from gastric ulcer (GU) patients with and without H. pylori infection. METHODS: Levels of IL-8 and MIP-1alpha secreted in organ cultures were measured by an enzyme-linked immunosorbent assay. Numbers of myeloperoxidase-positive neutrophils, CD68-positive macrophages, and mononuclear cells were determined in tissue sections. RESULTS: The mucosal tissues of both the gastric antrum and the ulcer site obtained from patients with H. pylori-positive GU showed significantly higher levels of IL-8 and MIP-1alpha and increased numbers of inflammatory cells compared with the corresponding mucosal tissues from those with H. pylori-negative GU or the antral mucosal tissues from H. pylori-negative controls. When the values were compared between the mucosal tissues from the gastric antrum and those from the ulcer site, the latter group of tissues showed significantly higher levels of IL-8 and MIP-1alpha and increased numbers of neutrophils and macrophages than the former group regardless of its healing process in patients with H. pylori-positive GU. CONCLUSION: Mucosal alpha- and beta-chemokines may be important to the ulcerogenesis in H. pylori-associated GU disease.

Adult↗
PubMed2000

Strategies for reaching by individuals with mental retardation: empty and filled glasses.

The purpose of this study was to assess the reaching strategies of individuals with mental retardation under different conditions. Much about reaching has been studied from the points of view of the optimization of the reading performance and the adaptation to the object's attributes. Few studies, however, have concerned reaching among individuals with mental retardation. Eight right-handed individuals with mental retardation reached for two types of glasses, one empty and the other filled with water. We translated the position of the index finger into X-Y-Z coordinate values and examined movement time, length of trajectory, and tangential velocity under the empty and filled conditions. There was no difference between conditions on any of the variables thought in many studies for individuals without mental retardation to indicate differences between attributes. This suggests that the present individuals with mental retardation might have difficulty in using information or context for planning movement and in optimizing their reaching movement for different conditions.

Adult↗
PubMed2000

[Two cases of rheumatoid arthritis associated with IgA -type multiple myeloma].

We report here two Japanese cases of rheumatoid arthritis (RA) associated with IgA [symbol: see text]-type multiple myeloma (MM). Case 1. The patient was a 68-year-old man with eight-years history of RA. The M-proteinemia (IgA 2838 mg/dl) in laboratory findings suggested a complication of MM which had been noticed since four years ago. On May 1997, he was referred and admitted to our hospital because of cough, right chest pain and dyspnea. Serum immunoelectrophoresis showed monoclonal IgA[symbol: see text]-type light chain. Bone marrow aspirate contained 6.5% atypical plasma cells. The X-ray findings revealed radiolucent myelomatous foci in the skull. From these findings, IgA[symbol: see text]-type MM was diagnosed. His condition was recovered by administration of antibiotics for bacterial pleuritis. Case 2. The patient was a 75-year-old woman with twelve-years history of RA. The laboratory findings of M-proteinemia (IgA 1215 mg/dl) with the decrease of other serum immunoglobulin level (IgG 611 mg/dl, IgM 60 mg/dl) and monoclonal IgA[symbol: see text]-type light chain in serum immunoelectrophoresis suggested MM four years ago. Bone marrow aspirate contained 5% plasma cells. From these findings, IgA[symbol: see text]-type MM was diagnosed. In the review of reported Japanese cases of RA associated with MM, it might be characteristic that IgA type MM was found more frequently in RA patients than other immunoglobulin types.

Aged↗
PubMed2000

[Therapeutic efficacy of amantadine hydrochloride in patients with epidemic influenza A virus infection].

A virus infection was studied using half of the normal oral dose of amantadine hydrochloride-100 mg/d instead of 200 mg/d. The patients in this study, who visited the clinics during January and February 1999, were confirmed within 48 hours to have influenza A virus infections by the Directigen FluA test. Using a quasi-randomized controlled trial, 26 patients were treated with amantadine hydrochloride in addition to the usual medication, while 23 were treated with only the ordinary medication. There were no significant differences in the mean age, 35.6 years old, or in clinical features between the two groups. The period of fever over 38 degrees C in the amantadine treated group was 1 day while that in the control group was 1.7 days, which shows a significant difference (p = 0.049). There was no significant difference in the duration of aching, such as arthralgia, or of general fatigue. There was no significant difference in the appearance of subsequent new symptoms after the onset of influenza A virus infection. In conclusion, it is expected that oral amantadine hydrochloride, 100 mg/d, together with the ordinary medication, will reduce the duration of the period of fever over 38 degrees C.

Adult↗
PubMed1999

Inhibitory effects of vesnarinone in the progression of myocardial damage in experimental autoimmune myocarditis in rats.

OBJECTIVES: Vesnarinone, a positive inotropic and immunomodulatory agent, diminishes nitric oxide (NO) levels by suppressing the induction of inducible NO synthase (iNOS) expressed in cytokine-stimulated macrophages and cardiomyocytes. We examined whether vesnarinone exerts inhibitory effects on the progression of myocardial damage in experimental autoimmune myocarditis in rats through suppression of iNOS. METHODS: Myocarditis was induced in 30 Lewis rats by injection of porcine cardiac myosin and vesnarinone was orally administered to 20 of the 30 rats. On day 21 after immunization (the climax of inflammation), the hemodynamics were examined and the severity of myocarditis was evaluated by determining the area ratio (%) [affected/entire area] of myocardial lesions in histological sections. Levels of serum CK-MB, NOx (NO2(-)+NO3-), TNF-alpha and IL-1 beta, and cyclic GMP, iNOS mRNA, TNF-alpha and IL-1 beta in heart tissues were determined. Expression of iNOS and TNF-alpha protein were examined by immunohistochemical methods. RESULTS: Histopathological examination revealed extensive myocardial destruction and massive infiltration of inflammatory cells in the vesnarinone-untreated rats. The area ratio of the lesions in the treated rats was significantly lower than that in the untreated ones. Levels of CK-MB, NOx, cyclic GMP, cytokines and iNOS mRNA were significantly lower in the vesnarinone-treated rats. Infiltrating macrophages and cardiomyocytes in the untreated rats showed much higher levels of expression of iNOS and TNF-alpha than those in the vesnarinone-treated rats. CONCLUSIONS: Vesnarinone may prove to be useful in the treatment of myocarditis by attenuating NO production through suppression of iNOS induced by cytokines.

Analysis of Variance↗
PubMed1999

Hepatic cytochrome P450 and flavin-containing monooxygenase in male Nts:Mini rat, a transgenic rat carrying antisense RNA transgene for rat growth hormone.

We investigated the characteristics of hepatic cytochrome P450s and flavin-containing monooxygenase 1 (FMO1) in male Nts:Mini rats, a Wistar/Jcl-derived transgenic rat strain showing less plasma GH concentration than the parental strain. The total hepatic P450 contents of Mini rats were significantly reduced. A suppression was observed in the activities and protein expression of male-specific P450s (CYP3A and CYP2C11) and was speculated to be a potential cause of the reduction in total P450 contents. The activity and protein expression of CYP2B1 were suppressed and those of CYP2E1 and CYP2B2 were enhanced. With the exception of our data on CYP2B1, these results largely agreed with previous reports concerning GH-depletion rat models (hypophysectomized rats, rats neonatally treated with glutamate, and dwarf rats), implying that the changes in Mini rats were caused by GH insufficiency. The liver FMO1 protein expression in Mini rats was higher than that in Wistar rats but the activity was comparable, suggesting that GH is not a positive regulator of FMO expression. With their insufficient but not depleted levels of plasma GH, Mini rats may thus become another candidate for use in the investigation of GH regulation of hepatic mixed-function monooxygenases.

Animals↗
PubMed1999

Immunohistochemical determination of the Wilson Copper-transporting P-type ATPase in the brain tissues of the rat.

Immunohistochemical localization of Copper-transporting P-type ATPase (ATP7B), a gene product responsible for Wilson disease, was visualized in the brain tissues of the Long-Evans agouti rat in detail using tissue-blotting technique and confocal laser microscopy. The ATP7B was intensely detected in neuronal cells of the hippocampal formation, olfactory bulbs, cerebellum, cerebral cortex and nuclei in the brainstem in which high amounts of copper and cuproenzymes, dopamine beta hydroxylase and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) were detected. The present results suggest that ATP7B plays key roles in neurotransmissions of catecholamine pathway and preventing brain tissues from injury by superoxide radicals to regulate the cellular Cu concentration and/or activities of cuproenzymes related to neurotransmissions and a free radical metabolism. Furthermore, it is reasonable to assume that neurotoxicity due to abnormal copper accumulation or irregular regulation of cuproenzymes in the critical brain regions by mutation of the ATP7B gene leads to neurological failures of Wilson disease.

Adenosine Triphosphatases↗
PubMed1999

Troglitazone can prevent development of type 1 diabetes induced by multiple low-dose streptozotocin in mice.

Recent investigations suggest that cytotoxic cytokines such as tumor necrosis factor (TNF)alpha and interleukin (IL)-1beta or free radicals play an essential role in destruction of pancreatic beta cells in Type 1 diabetes and that, therefore, anti-oxidant or anti-TNF alpha and IL-1beta therapy could prevent the development of Type I diabetes. Troglitazone belongs to a novel class of antidiabetic agent possessing the ability to enhance insulin action provably through activating PPAR gamma and to scavenge free radicals. In the present study, we examined whether troglitazone can prevent the development of Type 1 diabetes in multiple, low-dose streptozotocin (MLDSTZ)-injected mice. In addition, effects of troglitazone on cytokine-induced pancreatic beta cell damage were examined in vitro. Type 1 diabetes was induced by MLDSTZ injection to DBA/2 mice (40 mg/kg/day for 5 days). Troglitazone was administered as a 0.2% food admixture (240 mg/kg/day) for 4 weeks from the start of or immediately after STZ injection. MLDSTZ injection elevated plasma glucose to 615 +/- 8 mg/dl 4 weeks after final STZ injection and was accompanied by infiltration of leukocytes to pancreatic islets (insulitis). Troglitazone treatment with MLDSTZ injection prevented hyperglycemia (230 +/- 30 mg/dl) and, suppressed insulitis and TNF alpha production from intraperitoneal exudate cells. TNF alpha (10 pg/ml) and IL-1beta (1 pg/ml) addition to hamster insulinoma cell line HIT-T15 for 7 days in vitro decreased insulin secretion and cell viability. Simultaneous troglitazone addition (0.03 to approximately 3 microM) significantly improved cytokine-induced decrease in insulin secretion and in cell viability. These findings suggest that troglitazone prevents the development of Type 1 diabetes in the MLDSTZ model by suppressing insulitis associated with decreasing TNF alpha production from intraperitoneal exudate cells and the subsequent TNF alpha and IL-1beta-induced beta cell damage.

Animals↗