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Biomedical subjects

T Mori

Publications and source records attributed to T Mori.

At least 199 records · Page 11Linked to original sources

Apoptosis of renal tubular cells in Shiga-toxin-mediated hemolytic uremic syndrome.

In order to clarify the mechanism of unusual renal tubular dysfunction seen in a child with Shiga toxin (Stx)-mediated hemolytic uremic syndrome (HUS), we studied the renal biopsy specimens for Stx binding and apoptosis of renal tubular cells. A 7-year-old boy with Stx-2-mediated HUS demonstrated extensive renal tubular damage characterized by nonoliguric acute renal failure, increased urinary tubular enzymes and defective urine-concentrating capacity. His renal biopsy specimens were analyzed for Stx binding and apoptotic cell death. Seven kidney tissue specimens obtained from patients without HUS served as controls. Detection of Stx binding to renal sections and apoptotic cells were performed using mouse monoclonal anti-Stx 2 antibody and the TUNEL method, respectively. Positive staining was observed predominantly in renal tubular cells, while the 7 kidney tissue specimens from control patients did not show positive staining. To the best of our knowledge, this is the first case to show Stx binding and apoptotic cell death in renal tubules on biopsy specimens obtained from a child with Stx-mediated HUS. In conclusion, this case suggests that vascular endothelial cells are not the sole nor the consistent target for Stx-mediated cell injury and that significant renal tubular damage other than glomerular damage might occur in some children with Stx-mediated HUS.

Apoptosis↗

Effects of zinc deficiency and corticosterone elevation on bone marrow in rats.

OBJECTIVE: The effects of zinc deficiency and serum corticosterone elevation, in a zinc-deficient state, on rat bone marrow were studied. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into the following four groups: zinc-adequate (ZA), restricted ZA (RZA), zinc-deficient (ZD) and ZD with the injection of Mifepristone (ZD+Mife). Platelet and reticulocyte counts, levels of serum zinc and corticosterone, bone marrow cellularity and morphological alterations of marrow were examined in all rats. RESULTS: Decreased marrow cellularity, decreased numbers of peripheral platelets and reticulocytes, and increased adipocytes in the marrow were observed in ZD rats. The injection of Mifepristone improved marrow cellularity, and increased the number of platelets, while decreasing adipocytes in the marrow in ZD rats. CONCLUSION: Both zinc deficiency itself and the associated serum corticosterone elevation induced bone marrow suppression in rats.

Adipocytes↗

Intracisternal increase of superoxide anion production in a canine subarachnoid hemorrhage model.

BACKGROUND AND PURPOSE: Reactive oxygen species (ROS) are thought to be primary in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). However, as direct evidence of ROS has not yet been demonstrated in cerebral vasospasm, we sought to substantiate superoxide anion (.O(2)(-)) generation in the subarachnoid space after SAH using a modification of Karnovsky's manganese/diaminobenzidine (Mn(2+)/DAB) technique. METHODS: SAH or sham operation was induced according to a 2-hemorrhage model in a total of 24 beagle dogs. On day 2 or 7 after SAH or sham operation, dogs were intrathecally infused with buffer containing Mn(2+) and DAB, and the brain stem was prepared for light and electron microscopy. Possible colocalization of ferrous (Fe(2+)) or ferric (Fe(3+)) iron ions with.O(2)(-) was also examined with the use of Turnbull blue or Berlin blue staining, respectively. RESULTS: Light microscopy revealed amorphous, amber deposits within the subarachnoid hematoma, the periarterial space, and the tunica adventitia of the basilar artery on days 2 and 7 after SAH.O(2)(-) deposits were eliminated by addition of superoxide dismutase or exclusion of either Mn(2+) or DAB from the perfusate, confirming the specificity of the reaction. These deposits were colocalized with blue reaction deposits indicating Fe(2+) and Fe(3+). Within the subarachnoid space,.O(2)(-) indicating electron-dense fine granules were preferentially located around degenerated erythrocytes and, secondarily, infiltrating macrophages and neutrophils. CONCLUSIONS: We show direct evidence for enhanced production of.O(2)(-) and Fe(2+)/Fe(3+) iron ions in the subarachnoid space after SAH, lending further support to the pathogenic role of ROS in cerebral vasospasm after SAH.

3,3'-Diaminobenzidine↗

Study of plasma factors associated with neutrophil activation and lipid peroxidation in preeclampsia.

Neutrophil activation occurs in women with preeclampsia and is resolved after delivery. The present study examined whether circulating factors in plasma of women with preeclampsia caused neutrophil activation and lipid peroxidation. Twenty-one women with proteinuric preeclampsia were matched for age and gestational age with 19 normal pregnant women. Plasma was collected from all subjects before delivery and at 6 weeks postpartum and incubated with autologous white-cell buffy coat collected at the postpartum visit. Neutrophil activation was assessed by level of CD11b and CD18 expression after incubation with autologous antepartum or postpartum plasma. Lipid peroxidation was assessed by measurement of F(2)-isoprostanes in plasma, plasma-white cell incubates, and urine. Neutrophil CD11b and CD18 expression was not differentially altered by incubation with plasma from either women with preeclampsia or normal pregnant women and was similar between groups when incubation was performed with plasma collected after delivery. In preeclampsia, plasma F(2)-isoprostanes were significantly increased before and after delivery compared with controls. Plasma F(2)-isoprostanes were increased 2-fold after incubation of plasma with buffy coat, but preeclamptic women had higher levels compared with those of controls when either pregnant or postpartum plasma was used. In pregnant preeclamptics, plasma F(2)-isoprostanes were positively correlated with lymphocyte count. Six weeks after delivery, plasma F(2)-isoprostanes in the preeclamptic women were significantly positively associated with lymphocyte count and cholesterol and negatively associated with albumin. In conclusion, the present study does not suggest that a stable circulating factor causes neutrophil activation in preeclampsia. However, lipid peroxidation is elevated before and after delivery in women with preeclampsia, which suggests that these women may have an underlying predisposition to increased oxidative stress that may be driven by or contribute to a persistent low-grade inflammatory response.

Adult↗

Suppression of the development of experimentally induced uterine adenomyosis by a novel matrix metalloproteinase inhibitor, ONO-4817, in mice.

The inhibitory effects of a novel, orally active matrix metalloproteinase (MMP) inhibitor, ONO-4817, on the development of uterine adenomyosis induced experimentally by pituitary grafting were examined in mice. Mice were given transplants of isologous anterior pituitary glands (PGs) into the right uterine lumen at 7 weeks of age and were fed chow containing 0.1% to 1.0% ONO-4817 from 8 to 14 weeks of age. Mice treated with 0.3% or 1.0% ONO-4817 showed a significantly lower incidence of the development of adenomyosis than vehicle-treated mice. To evaluate the inhibitory effects of ONO-4817 on the progression of the invasion of the adenomyotic tissues, mice receiving PG grafts at 7 weeks of age were treated with 1.0% ONO-4817 from 13 to 17 weeks of age. The degree of pathological progression of adenomyosis was graded from 1 to 5 in increments of 1. The degree of the progression of the lesion was less in the uteri exposed to ONO-4817 (2.71 +/- 0.93) than in the uteri not exposed to the inhibitor (4.33 +/- 0.75). Finally, the invasiveness of endometrial stromal cells obtained from adenomyotic uteri into Matrigel consisting mainly of type IV collagen and laminin was examined using an invasion assay. The assay showed that the treatment with ONO-4817 markedly suppressed the invasion of the stromal cells of the adenomyotic uteri into the gel. These results indicate that ONO-4817 may be an effective inhibitor of the development of adenomyosis.

Animals↗

In vitro effects of environmental salinity and cortisol on chloride cell differentiation in embryos of Mozambique tilapia, Oreochromis mossambicus, measured using a newly developed 'yolk-ball' incubation system.

To examine the functional differentiation of chloride cells in the yolk-sac membrane of tilapia (Oreochromis mossambicus) embryos, we developed a 'yolk-ball' incubation system in which the yolk sac was separated from the embryonic body and subjected to incubation in vitro. The yolk-ball preparation consists of the yolk and the covering yolk-sac membrane, which contains a rich population of chloride cells. After appropriate cutting, the incision on the yolk ball healed during incubation in balanced salt solution for 3h, so that the yolk-sac membrane completely enclosed the yolk. Yolk balls prepared from freshwater-acclimated embryos were transferred either to fresh water or to sea water and incubated for 48 and 96 h to elucidate the morphological changes in the chloride cells in response to environmental salinity. The chloride cells in the yolk-sac membrane were larger in sea water than in fresh water. In yolk balls transferred to sea water, chloride cells often formed multicellular complexes characteristic of seawater-type chloride cells. In those transferred to fresh water, however, the cells were small and rarely formed such complexes. These responses of chloride cells were identical to those observed in intact embryos. Thus, chloride cells in the yolk-sac membrane could differentiate into the seawater type independent of the embryonic body. To examine the possible effects of exogenous cortisol on chloride cell differentiation, the yolk balls were incubated for 48 h in fresh water or sea water containing different doses of cortisol (0.1-10 microg x ml(-1)). Although chloride cells were consistently larger in sea water than in fresh water in all experimental groups, cortisol administration had no effect on chloride cell surface area in either medium. These findings indicate that the chloride cells in the yolk-sac membrane are equipped with an autonomous mechanism of functional differentiation that is independent of the embryonic endocrine and nervous systems. The yolk-ball incubation system established here is an excellent experimental model for further studies on chloride cell differentiation and function.

Animals↗

Rat small intestine muscle relaxation alkaloids from Orixa japonica leaves.

Two quinoline alkaloids, japonine (1) and eduline (2) were isolated from the methanol extract of the leaves of Orixa japonica as relaxants against rat small intestine muscle. The activity of these alkaloids was comparable to that of the typical muscle relaxant papaverine (4). This is also the first report of the isolation of eduline (2) from O. japonica.

Alkaloids↗

Pharmacokinetics of nimustine, cytosine arabinoside, and methotrexate in cerebrospinal fluid during cerebrospinal fluid perfusion chemotherapy.

This report investigates the pharmacokinetics of nimustine (ACNU), cytosine arabinoside (Ara-C), and methotrexate (MTX) in cerebrospinal fluid (CSF) during CSF perfusion chemotherapy. A 47-year-old Japanese man with spinal cord, cerebellum and brain stem dissemination of oligo-astrocytoma received nine courses of CSF perfusion chemotherapy with ACNU, Ara-C, and MTX. A CSF perfusion chemotherapy solution was perfused via an Ommaya reservoir in the ventricle, and was discharged by drainage though another Ommaya reservoir in the lumbar spinal canal. CSF samples via Ommaya reservoirs in the lumbar spinal canal were obtained during the fifth and eighth courses of treatment. The concentrations of ACNU and Ara-C in CSF were measured by HPLC, and the MTX concentrations by fluorescence polarization immunoassay. In the fifth course of treatment, a CSF injection chemotherapy solution, consisting of 5 mg of ACNU dissolved in 20 ml of artificial CSF, was injected over a few minutes using the Ommaya reservoir. Next, a CSF perfusion chemotherapy solution, consisting of 10 mg of Ara-C and 5 mg of MTX dissolved in 100 ml of artificial CSF, was perfused over 2 h. In the eighth course of treatment, a CSF perfusion chemotherapy solution, consisting of 5 mg of ACNU, 10 mg of Ara-C and 5 mg of MTX dissolved in 100 ml of artificial CSF, was perfused over 2 h. In both treatments, the highest concentrations of Ara-C and MTX in CSF were observed 1 or 2 h after the end of perfusion, with the values of each drug being similar. The CSF AUCs of Ara-C and MTX in each treatment were of similar values. Although the highest concentration of ACNU in CSF was observed in the fifth treatment 1 h after injection (an injection chemotherapy of ACNU plus a perfusion chemotherapy of Ara-C and MTX), the concentration of ACNU in CSF was undetectable in the eighth treatment (a perfusion chemotherapy of ACNU, Ara-C and MTX). We were successful in administering all anticancer drugs, and reaching a level of over 1.0 microg/ml concentration in CSF of the lumbar spinal canal, using an injection chemotherapy of ACNU plus a perfusion chemotherapy of Ara-C and MTX; this was done even though the drugs, in particular ACNU, underwent some perfusion-period dependent decomposition.

Adult↗

Stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil in rabbits.

We have estimated the pharmacokinetic and pharmacodynamic interactions of verapamil (VP) enantiomers and also the interaction between VP and its metabolite, norverapamil (NVP). ECGs of conscious rabbits were studied to determine the pharmacokinetics of VP enantiomers and racemic NVP in relation to their prolongation effect on PR intervals, which were used as an index of VP's antiarrhythmic effect. Plasma free fractions of VP enantiomers showed constant values at concentrations ranging from 0.022 to 1.10 microm. There were no interactions between enantiomers or between VP and NVP. The pharmacological effect of the S-enantiomer (S-VP), which was determined by linear regression analysis, showed it was about 20 times more potent than that of the R-enantiomer (R-VP). The effect of racemic VP was the simple sum of those elicited by both enantiomers. These relationships were not significantly different between intravenous infusion and bolus injection. Simultaneous intravenous infusion of NVP had no influence on the PR intervals. In conclusion, we demonstrated that the relationship between plasma unbound concentration of VP enantiomers and their pharmacological effect was the simple sum of two enantiomers.

Animals↗

Immediate-Type allergy against human insulin associated with marked eosinophilia in type 2 diabetic patient.

We describe a type 2 diabetic patient who showed immediate-type allergy against human insulin associated with marked eosinophilia at initial insulin therapy. Three months after initiation of insulin therapy, he noticed itchy skin wheals at the site of the insulin injection. Laboratory data at that time showed marked eosinophilia (2,512 /mm3) and progression of renal dysfunction. Skin test with semisynthetic human insulin and protamine sulfate resulted in local immediate skin reactions such as itchy erythema and wheals. Histopathology of the biopsy specimen from skin showed perivascular infiltration of lymphocytes and numerous eosinophils in the dermis and subcutaneous fat. Although the titer of total IgE antibody was within normal range, that of insulin-specific IgE antibody was high. Insulin administration was discontinued to preserve his insulin secretion, and stable control of his hyperglycemia was obtained by initiating nateglinide treatment (360 mg/day). His itchy skin lesions disappeared within two weeks after cessation of the insulin therapy and both eosinophilia and renal dysfunction gradually improved. Although the widespread use of human insulin in diabetic patients has greatly reduced the incidence of insulin allergy, the possibility of human insulin allergy should be kept in mind when initiating such therapy.

Aged↗

Elevated level of soluble HLA class I antigens in serum and bronchoalveolar lavage fluid in patients with sarcoidosis.

OBJECTIVE: Soluble HLA class I antigens (sHLAs) in human serum have been reported to be associated with allografts and autoimmune disease and could modify immunological reactions induced by membrane type HLAs. To investigate the clinical significance of sHLAs in sarcoidosis, we assessed concentrations of sHLAs in both serum and bronchoalveolar lavage fluid (BALF) and also examined their production by peripheral blood mononuclear cells (PBMCs) and BALF cells. METHODS: Concentrations of sHLAs were determined by enzyme-linked immunosorbent assay, using a monoclonal antibody against HLA class I (W6/32) and an enzyme-labeled polyclonal antibody to human beta2-microglobulin. PBMCs and BALF cells were cultured in the presence or absence of either LPS or PHA. PATIENTS: Serum levels of sHLAs were assessed in 96 patients with sarcoidosis and in 32 healthy control subjects. sHLAs concentrations in BALF were also investigated in 17 active sarcoidosis patients and in 13 control subjects. RESULTS: sHLAs levels in both serum and BALF were higher in sarcoidosis cases than in control subjects (p<0.05, in both). In the patients, values were significantly higher in active than in inactive stages (p<0.001) and significantly correlated with angiotensin-converting enzyme (ACE) levels. Both PBMCs and BALF cells produced enhanced amounts of sHLAs in patients with active sarcoidosis compared with those in control subjects. CONCLUSION: These results demonstrated that the level of sHLAs in serum is a useful index of disease activity of sarcoidosis, partly reflecting production by PBMCs and BALF cells.

Adult↗

Heterochronous development of intrahepatic cholangiocellular carcinoma following hepatocellular carcinoma in a hepatitis B virus carrier.

A 68-year-old Japanese woman was admitted to our hospital in September 1995, because of a mass detected by ultrasonography during a follow-up examination for chronic hepatitis B. Hepatocellular carcinoma (HCC) in the right liver lobe was diagnosed based on imaging studies and elevated alpha-fetoprotein (AFP). Percutaneous ethanol injection therapy (PEIT) was performed. PEIT was repeated in November 1998, because the tumor had enlarged and serum AFP was re-elevated. Follow-up ultrasonography (US) demonstrated low echoic mass in the left liver lobe in August 1999; serum AFP was normal, but serum carbohydrate antigen 19-9 (CA19-9) was elevated to 420 U/ml. In October 1999, radiofrequency interstitial tissue ablation (RITA) was performed after tumor biopsy. Pathological findings revealed adenocarcinoma and pathological diagnosis was made as intrahepatic cholangiocellular carcinoma (ICC). Three weeks later, her serum CA19-9 was remarkably decreased (180 U/ml). The patient has been well for 5 months. Her latest AFP and CA19-9 in the serum were 2 ng/ml and 89 U/ml, respectively. The incidence of double cancer in the liver is rare. This is also the first case report to discuss ICC treated with RITA.

Aged↗

An operated case of lung cancer with pleural plaques: its asbestos bodies, fiber analysis and asbestos exposure.

This case was a 79-year-old man with pleural plaques, which had been pointed out in the left lung field on chest X-ray six years ago. A new shadow in the right chest appeared in 1999 and was closely examined. Cytological class IV carcinoma was detected in his lung tissue obtained by broncho-fiberscope. Lobectomy of the right upper lobe was performed, and calcified pleural plaques were found on the chest wall. The clinical diagnosis was poorly differentiated squamous cell carcinoma, T1N0M0. In World War II when he was 26 years old, he had worked as a boiler man on a battle cruiser for one year. The amount of asbestos bodies (AB) was 3,348 per gram dry lung tissue. The cores of AB and asbestos fibers were examined and showed that amosite was the most prevalent and crocidolite, tremolite and chrysotile were present in that order. After leaving the navy, he had worked as a farmer throughout his life, suggesting that he had never contacted asbestos occupationally after being a boiler man. It is strongly suggested that he had been exposed to asbestos during his work as a boiler man and that produced pleural plaques and lung cancer 50 years' later.

Aged↗

Active roles of caspase-3 in human gastric carcinoma cell death by apoptosis inducing nucleosides from CD57+HLA-DRbright natural suppressor cell line.

The six apoptosis inducing nucleosides (AINs), which were isolated by high performance liquid chromatography from CD57+HLA-DRbright natural suppressor (57.DR-NS) cell cultures, induced apoptosis in human gastric carcinoma (GCIY) cells demonstrating the accumulation of sub-G1 DNA content and morphological changes. By means of DNA unwinding assay, it has been revealed that DNA strand breaks were initially involved in the apoptotic cell death of GCIY cells treated with AINs followed by activation of caspase cascades, especially caspase-3. Actually, the cleavage of fluorogenic substrate for caspase-3 was identified in the reaction. Whereas, the addition of caspase-3 inhibitor into the reaction prevented the cleavage of fluorogenic substrate for caspase-3 and resulted in the blockage of the sub-G1 DNA accumulation and DNA fragmentation as apoptotic signals. Thus, it was definitely elucidated that the activation of caspase-3 displayed a key feature during AIN-induced apoptosis in GCIY cells.

Apoptosis↗

Human esophageal cancer cell death mediated by apoptosis-inducing nucleosides from CD57+HLA-DRbright natural suppressor cell line.

We approached the induction of apoptosis in human esophageal cancer cells (T.Tn) by apoptosis-inducing nucleosides (AINs) from CD57+HLA-DRbright-natural suppressor (57.DR-NS) cell line originated in decidua. The 57.DR-NS cells generated apoptosis in T.Tn cells by AINs released into the cultures. We isolated a series of AINs by high performance liquid chromatography (HPLC) from 57.DR-NS cell culture fluids. Each AIN and its mixture induced apoptotic cell death in T.Tn cells, detected by DNA fragmentation in agarose gels, terminal deoxynucleotide transferase mediated dUTP-nick end labeling (TUNEL) method and accumulation of sub-G1 DNA content with flow cytometry. Furthermore, we found the occurrence of DNA strand breaks followed by the activation of caspase-3 during AINs-induced apoptosis in T.Tn cells. Thus, we validated that AINs could induce apoptosis in T.Tn cells mediated through DNA strand breaks and activation of caspase-3.

Apoptosis↗

Determination of elastic modulus of dentin by small spherical diamond indenters.

A nano-indentation test was applied to determine elastic modulus (E) and hardness (H) of dentin. Three spherical indenters with nominal radii of 20, 5 and 1 microns were used and load/partial-unload cycles were repeated. Each cycle provided E and contact pressure or Meyer's hardness. The plot of contact pressure versus penetration depth was converted into a normalized indentation stress-strain relationship, which was used to select the optimum maximum indentation force for each indenter. The results were compared with those determined by the conventional triangular pyramidal (Berkovich) indenter technique. The comparable E value, irrespective of radius, was 19.5-20.9 GPa and the 1 micron indenter was able to provide E values of peritubular (28.0 GPa) and intertubular dentin (14.9 GPa). The H values generated with the Berkovich indentation technique were comparable to those determined by the spherical indenter technique at indentation strains of 0.9 and 0.5 for the 1 and 5 microns indenters.

Adolescent↗

Gender difference in delays to diagnosis and health care seeking behaviour in a rural area of Nepal.

SETTING: Directly observed treatment for tuberculosis using a short-course regimen (DOTS) was introduced in a rural area of Nepal. All new patients assigned to DOTS from mid-December 1997 to mid-June 1999 were eligible for the study. OBJECTIVE: To examine delays in tuberculosis (TB) diagnosis and compare health care seeking behaviour between men and women. DESIGN: A cross-sectional analysis of patient interviews. RESULTS: Women were found to have a significantly longer total delay before diagnosis of tuberculosis (median 2.3 months for men, 3.3 months for women). When they visited traditional healers first, women had a significantly longer delay than men from the first visit to health care providers to diagnosis (median 1.5 months for men, 3.0 months for women). More women (35%) visited traditional healers before diagnosis than men (18%), and were more likely to receive more complicated charms from traditional healers. Men tended to visit the government medical establishment first if they knew that free TB treatment was available, but women did not. CONCLUSION: Women were more likely to visit and to believe in traditional healers; this might lead to the longer delays experienced before TB diagnosis.

Adolescent↗