Search PubMed⌕ Search

Biomedical subjects

M Tominaga

Publications and source records attributed to M Tominaga.

At least 91 records · Page 5Linked to original sources
PubMed1999

FK506 markedly enhances apoptosis of antigen-stimulated peripheral T cells by down-regulation of Bcl-xL.

BACKGROUND: FK506 is a clinically effective immunosuppressive agent and promoter of immunologic tolerance. However, limited information is available about the mechanism of FK506-induced immunosuppression. METHODS: In the present study, we investigated the molecular mechanism of FK506-mediated enhancement of apoptosis using in vivo activated T lymphocytes. We examined the effects of FK506 on apoptosis-related proteins in superantigen-stimulated peripheral T cells. RESULTS: Injection of staphylococcal enterotoxin B (SEB) into BALB/c mice resulted in a selective apoptosis of splenic Vbeta8-positive T cells after 48 hr. Injection of FK506 within 36 hr of SEB injection resulted in a marked enhancement of DNA fragmentation of splenic Vbeta8+ T cells. FK506 did not affect the expression of Fas antigen on SEB-activated Vbeta8+ T cells. As Bcl-2-related proteins are involved in apoptotic process, we also evaluated their role by examining the expression of Bcl-2, Bcl-X(L), and Bax on SEB-FK506-treated murine splenic T cells. Although SEB injection slightly increased the expressions of Bcl-2 and Bax on V138+ T cells, FK506 did not modulate Bcl-2 or Bax expression in these cells. In contrast, the expression of Bcl-x(L) on Vgamma8+ T cells, which was markedly induced by SEB, was abrogated by FK506. CONCLUSIONS: Our findings indicate FK506-induced enhancement of apoptosis of activated T cells is mediated by down-regulation of Bcl-X(L) expression on these cells. Our results also suggest that Bcl-x(L) is a critical determinant of apoptosis of activated T cell and may represent a potential target for new therapies designed to achieve immunological tolerance.

Animals↗
PubMed1999

Tin speciation in the femtogram range in open ocean seawater by gas chromatography/inductively coupled plasma mass spectrometry using a shield torch at normal plasma conditions.

A sensitive method for the determination of ultratrace organotin species in seawater is described. The merits and demerits of derivatization methods using Grignard reagent or sodium tetraethylborate (NaBEt4) were evaluated in terms of derivatization efficiency, applicability to the programmed temperature vaporization (PTV) method, and procedural blanks. The sensitivity of the gas chromatography/inductively coupled plasma mass spectrometry (GC/ICPMS) was improved by more than 100-fold by operating the shield torch at normal plasma conditions, compared with that obtained without using it. The absolute detection limit as tin reached subfemtogram (fg) levels. Furthermore, the detection limit in terms of relative concentration was improved 100-fold by using the PTV method, which enabled the injection of a large sample volume of as much as 100 microL without loss of analyte. When the organotin species in seawater were extracted into hexane with a preconcentration factor of 1000 after ethylation with NaBEt4 and a 100 microL aliquot of the extract was injected into the GC, the instrumental detection limit in relative concentration reached 0.01 pg/L in original seawater. Sources of contamination of organotin species during the sample preparation were examined, and a purification method of NaBEt4 was developed. Finally, the method was successfully applied to open ocean seawater samples containing organotin species at the level of 1-100 pg/L.

Borates↗
PubMed1999

A capsaicin-receptor homologue with a high threshold for noxious heat.

Pain-producing heat is detected by several classes of nociceptive sensory neuron that differ in their thermal response thresholds. The cloned capsaicin receptor, also known as the vanilloid receptor subtype 1 (VR1), is a heat-gated ion channel that has been proposed to mediate responses of small-diameter sensory neurons to moderate (43 degrees C) thermal stimuli. VR1 is also activated by protons, indicating that it may participate in the detection of noxious thermal and chemical stimuli in vivo. Here we identify a structurally related receptor, VRL-1, that does not respond to capsaicin, acid or moderate heat. Instead, VRL-1 is activated by high temperatures, with a threshold of approximately 52 degrees C. Within sensory ganglia, VRL-1 is most prominently expressed by a subset of medium- to large-diameter neurons, making it a candidate receptor for transducing high-threshold heat responses in this class of cells. VRL-1 transcripts are not restricted to the sensory nervous system, indicating that this channel may be activated by stimuli other than heat. We propose that responses to noxious heat involve these related, but distinct, ion-channel subtypes that together detect a range of stimulus intensities.

Amino Acid Sequence↗
PubMed1999

Gender of demented patients and specific family relationship of caregiver to patients influence mental fatigue and burdens on relatives as caregivers.

OBJECTIVES: To survey the burden and psychological problems of family caregivers of demented people. DESIGN: All scores were compared according to gender of the demented patients and which family members were the caregivers. SETTING: Outpatients clinic at the university hospital and the day service system for the elderly. PATIENTS: Sixty-two demented patients living at home and family members acting as caregivers. MEASURES: Cognitive function, activities of daily living (ADL) and behaviour of demented patients were rated using the Hasegawa scale, the ADL scale and the dementia behaviour disturbance (DBD) scale. Caregiver's burden and mental fatigue were rated using a burden scale and a general health questionnaire (GHQ). RESULTS: Caregiver burden correlated negatively with the Hasegawa score and positively with the GHQ and DBD scores. Caregiver burden, GHQ and DBD for male patients were significantly higher than for females. Little difference was evident for caregiver burden scale or patient DBD between spouses and offspring as caregiver, but the GHQ score for spouses was significantly worse than that for offspring. CONCLUSIONS: The difficulty of caregivers in supporting the daily life of demented family members correlated with patients' cognitive impairment, abnormal behaviour and ADL status, and caregivers' difficulty resulted in mental fatigue. Caregivers' relative isolation from friends, attributable to their caregiving responsibility, did not correlate with the demented person's cognitive impairment or ADL status.

Aged↗
PubMed1999

Successful treatment of rapidly progressive lupus nephritis associated with anti-MPO antibodies by intravenous immunoglobulins.

We report a case of systemic lupus erythematosus (SLE) associated with crescentic glomerulonephritis and myeloperoxidase-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA). A 34-year-old Japanese female patient diagnosed with SLE developed rapidly progressive renal failure and nephrotic syndrome. Haemodialysis was required to restore renal function. Methylprednisolone pulse therapy followed by plasmapheresis did not suppress the progression of renal failure, so she was treated with high-dose intravenous immunoglobulin (IV-IG) therapy, which was well tolerated and effectively prevented renal failure. A renal biopsy showed diffuse proliferative lupus nephritis (WHO classification IVc) with predominant crescent formation and scant subendothelial immune deposits. These findings indicate that, in addition to lupus nephritis, which usually results from the deposition of circulating or locally formed immune complexes, MPO-ANCA may be involved in the pathogenesis of crescentic glomerulonephritis. Furthermore, we propose that IV-IG is an effective therapy for MPO-ANCA-related renal crisis in lupus nephritis.

Acute Kidney Injury↗
PubMed1999

Kainic and domoic acids differentially affect NADPH-diaphorase neurons in the mouse hippocampal formation.

We investigated changes in numbers of nitric-oxide-producing cells in the hippocampal formation, striatum, and temporal cortex of mice 24 h after intraperitoneal administration of kainic acid (5, 10, 15, and 20 mg/kg) or domoic acid (1, 2, and 4 mg/kg). Nitric-oxide-producing cells were demonstrated histochemically by staining for nicotinamide adenine dinucleotide phosphate diaphorase. Nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in the dentate gyrus and the subiculum did not change in number following administration of kainic acid or domoic acid at any dose. Positive neurons in the CA3 region of mice treated with kainic acid or domoic acid at any dose were significantly fewer than in controls. Although the numbers of positive neurons in the CA1/CA2 regions did not differ from those of controls at any of the four doses of kainic acid, positive cells in the CA1/CA2 were significantly more numerous than in controls at any dose of domoic acid. Although no significant differences in the numbers of positive neurons in the striatum were apparent between controls and any of the four doses of kainic acid, domoic acid significantly decreased the numbers of such cells. These results suggest that systemically administered kainic acid and domoic acid affect differentially nitric-oxide-producing cells in the hippocampal formation.

Animals↗
PubMed1999

7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl ]-2,3,4,5-tetrahydro-1H-1-benzazepine (OPC-41061): a potent, orally active nonpeptide arginine vasopressin V2 receptor antagonist.

We previously reported a series of benzazepine derivatives as orally active nonpeptide arginine vasopressin (AVP) V2 receptor antagonists. After the lead structure OPC-31260 was structurally evaluated and optimized, the introduction of the 7-Cl moiety on the benzazepine and 2-CH3 on the aminobenzoyl moiety enhanced its oral activity. The new AVP-V2 selective antagonist OPC-41061 was determined to be a potent and orally active agent.

Animals↗
PubMed1999

Antiangiogenic and antitumor effects of 14-membered ring macrolides on mouse B16 melanoma cells.

We examined the effects of macrolide antibiotics on tumor angiogenesis, tumor growth and metastasis in the B 16BL6 mouse melanoma and C57BL mouse system. Two 14-membered ring macrolide antibiotics, roxithromycin and clarithromycin, significantly reduced the dense capillary network area in a mouse dorsal air sac angiogenesis model, whereas a 15-membered ring macrolide, azithromycin, and a 16-membered ring macrolide, josamycin, did not show any inhibitory effect on angiogenesis at the same dose. Intraperitoneal administration of roxithromycin and clarithromycin at 50 mg/kg/day reduced the tumor size of B 16BL6 melanoma to about 41% and 56%, respectively, of that of the control, and significantly suppressed pulmonary metastasis of B16BL6 cells in a spontaneous system. Azithromycin and josamycin, on the other hand, did not inhibit tumor growth or pulmonary metastasis of B16BL6 cells. Immunohistochemistry revealed that roxithromycin and clarithromycin reduced the tumor vascularity and increased apoptosis of the tumor cells in vivo. These results suggest that 14-membered ring macrolides have antiangiogenic and antitumor effects and might have possible therapeutic applications.

Angiogenesis Inhibitors↗
PubMed1999

Randomized clinical trial of ultrasonic dissector or conventional division in distal pancreatectomy for non-fibrotic pancreas.

BACKGROUND: Resection of the non-fibrotic pancreas is prone to postoperative pancreatic fistula because of well preserved exocrine secretions and easily crushed soft parenchyma. The purpose of this study was to evaluate ultrasonic dissection for division of the non-fibrotic pancreas in distal pancreatectomy. METHODS: All pancreata included in this study were soft on direct palpation and their main ducts had no dilatation, at least proximally from the transection line. Fifty-eight patients with gastric cancer or pancreatic disease were randomly assigned to the two groups. In the ultrasonic dissection (UD) group (n = 27), all pancreatic ducts were identified and ligated securely. The stump was left open without parenchymal suturing. In the conventional (CV) group (n = 31), the pancreas was cut with a knife and the stump was oversewn in mattress fashion. The main pancreatic duct was ligated in all patients in both groups. Pancreatic fistula was defined as a pancreatic fluid discharge for more than 7 days after operation diagnosed according to amylase concentration in the drainage fluid. RESULTS: In the UD group, approximately 20-30 tubes including a mean(s.d.) 5.2(0.8) (range 4-6) pancreatic ducts were skeletonized and ligated per patient. There were nine pancreatic fistulas (16 per cent); one in the UD group and eight in the CV group (P = 0.020). CONCLUSION: In distal pancreatectomy for the non-fibrotic pancreas, ultrasonic dissection without suture closure of the stump reduced the incidence of pancreatic fistula compared with conventional division and suture, in this randomized trial.

Adult↗
PubMed1999

Induction of cyclooxygenase-2 in human synovial cells by beta 2-microglobulin.

BACKGROUND: Prostaglandins (PGs) are important mediators of inflammation in arthritis. We evaluated the role of the cycloxygenase-2 (COX-2) enzyme, which regulates PG biosynthesis, in osteoarthropathy associated with hemodialysis-associated amyloidosis (HAA) by characterizing COX-2 expression in beta 2-microglobulin-treated human synovial cells. METHODS: We examined the effects of beta 2-microglobulin (beta 2m), a major constituent protein of amyloid fibrils in HAA, on the COX-2 protein and mRNA expression in human synovial cells using Western blot and reverse transcriptase-polymerase chain reaction. RESULTS: beta 2m selectively increased the biosynthesis of COX-2 protein and induction of COX-2 mRNA in a dose-dependent manner. Immunoabsorption of beta 2m-containing media by anti-beta 2m-specific antibody abrogated beta 2m-mediated COX-2 expression on synovial cells. On the other hand, dexamethasone markedly suppressed the induction of COX-2 protein and mRNA in beta 2m-stimulated synovial cells. CONCLUSIONS: Our results suggest that induction of COX-2 expression by beta 2m may be an important component of the inflammatory process in hemodialysis-associated osteoarthropathy.

Blotting, Western↗
PubMed1999

Aminoguanidine has both an anti-inflammatory effect on experimental colitis and a proliferative effect on colonic mucosal cells.

BACKGROUND: The aim of this study was to assess the effect of aminoguanidine (AG) on developed colitis and cell proliferation. METHODS: Colitis was induced by means of trinitrobenzene sulphonic acid (TNB) in male Wistar rats weighing about 250 g. Seven days after induction of TNB colitis the rats were divided into two groups at random, and one group was orally treated with 1.5 micromol/kg AG each day. We assessed the effect of AG by measuring the mucosal damage, the ulcer area, myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOs) activity, and nitrogen oxide in serum 7 days after the beginning of treatment. RESULTS: AG significantly ameliorated the macroscopic damage score (AG versus control, 5.25 +/- 0.80 versus 7.50 +/- 0.50), the microscopic damage score (5.88 +/- 1.13 versus 9.25 +/- 0.31), ulcer area (0.57 +/- 0.14 versus 1.24 +/- 0.17 cm2), decreased MPO activity (51.5 +/- 9.4 versus 192.2 +/- 60 units/g tissue), and nitrogen oxide in serum (27.2 +/- 1.4 versus 32.3 +/- 1.8 microM) but did not decrease iNOs activity (8732 +/- 435 versus 8672 +/- 357 cpm/g tissue). Moreover, AG accelerated T84 cell proliferation in a dose-dependent manner. CONCLUSIONS: These results suggest that AG ameliorates TNB colitis not only by its anti-inflammatory effect but also by accelerating the proliferation of colonic mucosal cells. AG, accordingly, might well be a useful new medicine to ameliorate inflammatory bowel disease.

Analysis of Variance↗
PubMed1999

Stimulation of haematogenous liver metastases by ischaemia-reperfusion in rats.

OBJECTIVE: To find out whether hepatic ischaemia-reperfusion stimulates hepatic tumour metastases using a cell line of rat ascitic hepatoma (AH130). DESIGN: Prospective experimental study. SETTING: University laboratories, Japan. MATERIALS: 118 male Donryu rats. INTERVENTION: After laparotomy alone (group 1, n = 35) or laparotomy and 20-minutes ischaemia (group 2, n = 34) or laparotomy and 30-minutes ischaemia (group 3, n = 34) of the median and left hepatic lobes, the animals were given either an intraportal injection of 1 x 10(5) or an intravenous injection of 1 x 10(6) viable AH130 cells. MAIN OUTCOME MEASURES: 10 days after inoculation of tumour cells the number of nodules on the surface of the right lobe and of the median plus left lobes were separately counted for each liver. RESULTS: Irrespective of the route of tumour inoculation in group 1, there was no significant difference in the number of tumours/g liver between the right and the median plus left lobes. However, in groups 2 and 3, the number of tumours/g liver in the median plus left lobes was significantly higher than in the right lobe (p < 0.05). Furthermore, in the median plus left lobes, animals who had had 30 minutes of ischaemia had significantly more tumours than those in the other two groups (p < 0.01). CONCLUSION: Hepatic ischaemia-reperfusion may increase the risk of development of haematogenous liver metastases, by stimulating tumour cell-endothelial cell interactions.

Analysis of Variance↗
PubMed1999

Evaluating the reported prevalence of type 2 diabetes mellitus by the Oguni diabetes registry using a two-sample method of capture-recapture.

BACKGROUND: Capture-recapture methods have been widely employed in the study of wildlife populations and have recently been applied to count various human diseases and conditions. We have estimated the prevalence of type 2 diabetes mellitus by adjusting for the degree of undercount using a two-sample model of capture-recapture among men and women aged 50-69 in Oguni town, Japan. METHODS: Oguni town diabetes registry data were utilized as the first source. In the registry, only those who had experienced fasting plasma glucose of > or = 7.8 mmol/l (140 mg/dl) or 2 h plasma glucose after a 75 g oral glucose tolerance test (OGTT) of > or = 11.1 mmol/l (200 mg/dl) were counted as having diabetes. A second source was a sample study selecting 200 men and 200 women aged 50-69 randomly, which was conducted in August 1991. A 75 g OGTT was done in the morning. The 1985 World Health Organization criteria were used to classify the diabetes status of the participants. A two-sample model of capture-recapture methods was employed to estimate the total number of cases of diabetes and determine the ascertainment rates of the registry. RESULTS: The prevalence estimated by the diabetes registry was 7.1%. The prevalence from the sample study was 8.8% with a participation rate of 74%. Estimated prevalence employing the capture-recapture method was 13.1%. The ascertainment rate of the registry was 53.8%. CONCLUSIONS: Little is known about the prevalence of type 2 diabetes in local areas in Japan, the US and the world. Capture-recapture methods are likely to provide a means to accurately assess the prevalence of diabetes.

Aged↗
PubMed1999

HTLV-I associated Sjögren's syndrome is aetiologically distinct from anti-centromere antibodies positive Sjögren's syndrome.

OBJECTIVE: To investigate whether Sjögren's syndrome (SS) with anti-HTLV-I antibodies is aetiopathologically distinguishable from SS without these antibodies, the study compared prevalence of autoantibodies in serum samples of SS patients with or without anti-HTLV-I antibodies. METHODS: The test group included 135 patients with primary SS and 97 patients with secondary SS. Serum samples of the patients were examined for the presence of anti-nuclear antibodies (ANA), anti-SS-A/Ro antibodies, anti-SS-B/La antibodies, anti-centromere antibodies (ACA), and anti-HTLV-I antibodies. RESULTS: Anti-HTLV-I antibodies were detected in 25.0% of primary SS patients and in 29.2% of secondary SS patients. There were no significant differences in the mean age, sex, values of asparate aminotransferase, alanine aminotransferase, alkaline phosphatase, serum complements and IgG between HTLV-I seropositive and seronegative SS patients. The rheumatoid factor, ANA, anti-SS-A/Ro, and anti-SS-B/La antibodies in serum samples of SS patients were detected in 60.0%, 84.0%, 51.9%, and 12.0%, respectively. There was no significant difference in the prevalence of these antibodies between HTLV-I seropositive and seronegative SS patients. Using the indirect immunofluorescence test, 14.2% showed a discrete speckled staining pattern. All serum samples contained significant amounts of ACA determined by enzyme linked immunosorbent assay. These antibodies were detected in only 4% of HTLV-I seropositive SS patients but were present in 19.9% of HTLV-I seronegative SS patients. Furthermore, the prevalences of anti-SS-A/Ro and anti-SS-B/La antibodies in serum samples of ACA positive patients were significantly lower than those in ACA negative SS patients. CONCLUSION: These results suggest that SS patients with anti-SS-A/Ro or anti-SS-B/La antibodies, or both, might be aetiopathologically distinct from SS patients with ACA. HTLV-I might be involved in the pathogenesis of SS in a subset of patients with anti-SS-A/Ro or anti-SS-B/La antibodies, or both, but not SS patients with ACA.

Aged↗
PubMed1999

Contribution of carotid chemoreceptors to mesenteric venoconstriction during acute hypercapnia in rabbits.

The contribution of carotid chemoreceptors to hypercapnia-induced mesenteric venoconstriction was examined in 12 alpha-chloralose-anesthetized rabbits (1.0-1.6 kg). Surgical preparation consisted of a tracheotomy, femoral arterial and venous cannulation, and a midline laparotomy through which a 13-cm loop of ileum was exteriorized and superfused with physiological salt solution. Mesenteric vein diameter and intravenous pressure (using a servo-null measurement system) were measured in 500- to 1,000-micron mesenteric veins during 40-s periods of 15%, 20%, and 25% CO2 inhalation. Measurements were then repeated following bilateral ablation of the carotid chemoreceptors. Before denervation, mesenteric vein diameter constricted 6.5 +/- 1.1%, 11.9 +/- 1.1%, and 17.9 +/- 2.2% during the 15%, 20%, and 25% CO2 inhalation, respectively. After denervation, these values were reduced to 5.0 +/- 0.9%, 6.9 +/- 1.2%, and 8.4 +/- 1.3%, respectively. We conclude that activation of the carotid chemoreceptors by hypercapnia induces active mesenteric venoconstriction. After denervation of the carotid baroreceptors and chemoreceptors, there was also a small decrease in venule diameter proportional to the level of inspired CO2. We further conclude that noncarotid body chemoreceptor activation contributes to mesenteric venular constriction.

Animals↗
PubMed1999

Minimal-change nephrotic syndrome and acute renal failure in a patient with aged onset insulin-dependent diabetes mellitus and autoimmune thyroiditis.

A 61-year-old woman with a 2-year history of insulin-dependent diabetes mellitus (IDDM) developed nephrotic syndrome. Renal biopsy showed minimal-change nephrotic syndrome (MCNS), and no evidence of diabetic glomerulosclerosis. Although steroid therapy was initiated, plasma urea and creatinine rose and hemodialysis was required. After 4 weeks, she responded to steroids and her renal function returned to normal. MCNS, which is not associated with diabetic glomerulosclerosis, has rarely been seen in IDDM patients with nephrotic syndrome. Her human leukocyte antigen typing was A24, BW52, BW61, DR2 and DR9. This typing has been reported to be associated with both IDDM and renal disease.

Acute Kidney Injury↗
PubMed1999

Waist to hip ratio, body mass index, and glucose intolerance from Funagata population-based diabetes survey in Japan.

To examine the association of body mass index (BMI) and waist-to-hip ratio (WHR) with glucose intolerance among adults age 45 and over, we conducted a population-based study using an oral glucose tolerance test as a primary examination in two areas of Funagata, Japan, in 1990 and 1992. The number of eligible subjects was 1673. The participation rate was 84% (1408/1673). Glucose tolerance was assessed by the 1985 World Health Organization criteria as having diabetes (DM), impaired glucose tolerance (IGT), or normal glucose tolerance (NGT). Analyses by the generalized linear model revealed that both BMI and WHR were higher in the subjects with DM and IGT than those with NGT in both men and women after controlling for age. Analyses employing multiple logistic regression indicated that BMI and WHR were independently associated with IGT and DM in both men and women, except for BMI with IGT for men. The odds ratios for IGT associated with BMI were 1.06 (p=0.19) for men and 1.11 (p<0.01) for women. Those associated with WHR were 2.14 (p<0.01) for men and 1.35 (p<0.01) for women. These results imply that WHR plays an important role for developing DM independent of BMI.

Aged↗