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Biomedical subjects

H Shimizu

Publications and source records attributed to H Shimizu.

At least 181 records · Page 10Linked to original sources

Anti-inflammatory response in patients with obstructive jaundice caused by biliary malignancy.

BACKGROUND: Obstructive jaundice potentially modulates the host defense mechanism resulting in perioperative infection. It has been reported that a systemic inflammatory response occurs in patients with obstructive jaundice. An anti-inflammatory response was studied in 29 jaundiced patients undergoing biliary drainage. RESULTS: Plasma concentrations of interleukin (IL)-10, soluble tumor necrosis factor receptor (STNFR) p55, STNFR p75, IL-1 receptor antagonist (IL-1ra), IL-6 and soluble CD14 (sCD14) were measured by using immunoassay. Plasma concentrations of IL-10, STNFR p55, STNFR p75, IL-1ra, IL-6 and sCD14 were significantly higher in jaundiced patients than in the controls (P < 0.01). After biliary drainage, the concentrations of IL-10, the three cytokine antagonists, and IL-6 decreased significantly (P < 0.05). The sCD14 concentration did not decrease. At the time of drainage, the concentrations of STNFR p55 and STNFR p75 were significantly higher in 10 patients with positive bile cultures than in 19 patients with negative bile cultures (P < 0.05). Bile cultures became positive 14 days after drainage in 10 patients, and remained negative in nine. The concentration of STNFR p55 before drainage was significantly higher in the former group (P = 0.05). The plasma concentrations of IL-10 and STNFRs were significantly correlated with the IL-6 concentration, body temperature and the white blood cell count (P < 0.05). Serum total bilirubin levels did not affect plasma levels of anti-inflammatory mediators, and sCD14. CONCLUSION: Jaundiced patients exhibited an anti-inflammatory immune response that potentially modulates the host defense mechanism and results in anergy and increased susceptibility to infection. Biliary infection may be one of the major stimuli of the immune response.

Aged↗

Angiogenesis and phenotypic alteration of alveolar capillary endothelium in areas of neoplastic cell spread in primary lung adenocarcinoma.

Normal alveolar capillary endothelium is quiescent in nature and displays anticoagulant thrombomodulin (TM) on its surface. The cytoplasms of these endothelial cells are ultrastructurally non-fenestrated type, and they barely express von Willebrand factor (vWf). Alveolar fibrosis is accompanied by a capillary endothelium reactive for vWf, and a loss of TM expression. In primary lung adenocarcinoma, neovascularization occurs in association with alveolar fibrosis. In order to study basic factors related to angiogenesis and phenotypic changes of the capillaries located in tumor-bearing alveolar walls, we examined 37 primary lung adenocarcinomas with electron microscopy and confocal laser scanning microscopy with antibodies for TM, vWf, vascular endothelial growth factor (VEGF), and its receptors (KDR and Flt-1), and proliferating markers (Ki-67/proliferating cell nuclear antigen). Tissues microdissected specifically from alveolar walls were used for reverse transcription-polymerase chain reaction (RT-PCR) to assess expressions of mRNA isoforms of VEGF and its receptors. New capillary branching was found by ultrastructural study in the alveolar walls in 12% of the patients. Nuclei of the capillary endothelial cells were reactive for proliferating cell markers. Endothelial fenestrae were developed in 65% of the patients, TM reactivity was lost in the alveolar capillaries, and their cell cytoplasms obtained a reactivity for vWf through a transitional mosaic-like distribution pattern of both antigens. Besides cytoplasmic VEGF expression in neoplastic cells, tumor-bearing alveolar walls showed significant expression of mRNA of VEGF165 and KDR. These findings imply that angiogenesis and phenotypic changes of the alveolar capillaries are closely related to a higher expression of tumor-associated VEGF165 and of KDR in the alveolar walls in primary lung adenocarcinoma.

Adenocarcinoma↗

Surgical outcome of corpus callosotomy in patients with drop attacks.

PURPOSE: We examined presurgical factors that independently influence surgical outcome after corpus callosotomy. For adequate measurement of the surgical outcome, we analyzed seizure outcome of drop attacks, postoperative overall daily function, and family satisfaction. METHODS: At least 2 years after callosotomy (mean, 40.0 months), we retrospectively investigated 52 patients with drop attacks. As presurgical factors, we analyzed the age at surgery, age at seizure onset, age at drop attack onset, sex, hemiparesis, severe mental retardation, EEG abnormality, MRI abnormality, and extent of callosal section (total or partial callosotomy). Stepwise logistic regression was used for analysis. RESULTS: Satisfactory outcome (seizure cessation or >90% seizure reduction) was achieved in 85% of patients with drop attacks, 32% of those with generalized tonic seizures, and 31% of those with generalized tonic-clonic seizures. The families assessed the overall daily function as improved in 62% of patients, unchanged in 23%, and impaired in 15%. Family satisfaction with callosotomy was achieved in 83% of patients (definitely satisfied, 39%, somewhat satisfied, 44%). Total callosotomy is independently predictive of satisfactory reduction of drop attacks (p = 0.013). A younger age is independently predictive of improvement of overall daily function (impaired and improved: p = 0.004) and family satisfaction (unsatisfied and somewhat satisfied, p = 0.018; unsatisfied and definitely satisfied, p = 0.0006). CONCLUSIONS: In the present study, we found that total callosotomy is more effective for treatment of drop attacks than partial callosotomy and that children receive more benefit than adults after callosotomy.

Adolescent↗

Aerogenous spread of primary lung adenocarcinoma induces ultrastructural remodeling of the alveolar capillary endothelium.

To determine whether pulmonary alveolar capillaries manifest ultrastructural remodeling at areas of neoplastic invasion of primary lung adenocarcinomas, we examined 17 well-differentiated adenocarcinomas of lung (2 bronchioloalveolar and 15 papillary adenocarcinomas) by electron microscopy. The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was demonstrated by immunohistochemical stainings. VEGF messenger RNA (mRNA) isoforms were detected by reverse-transcription polymerase chain reaction (RT-PCR) in alveolar walls microdissected from normal and tumor-associated tissues. Cytoplasm of neoplastic cells expressed VEGF protein in all patients. Endothelial cell nuclei of alveolar capillaries showed positive reaction for PCNA. Alveolar capillary lumina were distended like venules, and some intercellular junctions remained open. The cytoplasm of the capillary endothelial cells was enlarged and developed numerous organelles such as Weibel-Palade bodies and vesiculovacuolar organelles, in contrast to marked attenuation in their normal counterpart. Capillary sprouting occurred from proper alveolar capillaries in 2 patients. Cytoplasmic segments became extremely attenuated and developed diaphragm-like fenestrae in 65% of the patients. A relatively higher expression of diffusable isoforms of VEGF mRNA was seen in the tumor-bearing alveolar walls than in normal walls. Expression of KDR (one of the VEGF receptors) mRNA in tumor exceeded that in normal tissues. These results suggest that diffusable isoforms of VEGF mRNA released from the neoplastic cells are deeply involved in the induction of growth activity of alveolar capillary endothelial cells as much as in the characterization of tumor-associated microvessels in primary lung adenocarcinomas.

Adenocarcinoma, Bronchiolo-Alveolar↗

Immunohistochemical study of age-dependent brain lesions in mice infected intracerebrally with Kasba (Chuzan) virus.

When Kasba (Chuzan) virus (an orbivirus) was injected intracerebrally into 1-, 2- or 4-week-old mice, non-purulent necrotizing encephalitis developed and the mice showed nervous symptoms and became moribund. The necrotic lesions were more severe in younger animals. In 1-week-old mice, viral titres rose until 7 days post-infection, while in 2- and 4-week-old animals the titres reached a peak on day 3 and then declined gradually. Glial fibrillary acidic protein-positive astrocytes increased in the white matter, hippocampus and subpial area of the cerebral cortex of infected animals, and lectin-RCA-1-positive cells, thought to be microglial cells, increased in the necrotic lesions. The number of these glial cells increased even after viral titres had declined. In this study there were no survivors in any age group, but survival time increased with age.

Age Factors↗

Demonstration of chymotryptic and tryptic activities in mast cells of rodents: comparison of 17 species of the family Muridae.

On the basis of studies in laboratory rats, mast cells were originally classified into two subgroups, namely, mucosal mast cells (MMCs), which contained chymase, and connective tissue mast cells (CTMCs), which contained both tryptase and chymase. This classification has been applied to other animal species, despite the fact that the MMCs and CTMCs of such species sometimes consist of mixed populations of mast cells in terms of tryptase and chymase constitution. This report describes the protease constitution of mast cells in 17 species of nine genera (Acomys, Apodemus, Cricetulus, Meriones, Millardia, Mus, Rattus, Sigmodon and Vandeleuria) of the family Muridae. MMCs with negative tryptase activity were detected only in the intestinal mucosa of six subspecies of Mus musculus, two Rattus spp. and Vandeleuria oleacea, and only Apodemus sylvaticus possessed CTMCs with no tryptase activity. Since mast cells conforming to the conventional classification were observed only in three of the nine genera examined, we propose that mast cells of rodents of the family Muridae should be classified by their protease constitution rather than by their location.

Animals↗

Atrial fibrillation impairs endothelial function of forearm vessels in humans.

BACKGROUND: Although there have been many studies on the effects of atrial fibrillation (AF) on cardiac function, few studies have been done on its effects on endothelial function. The present study was designed to examine the effects of AF on endothelial function in human subjects. METHODS AND RESULTS: Changes in forearm blood flow (FBF) induced by acetylcholine and nitroglycerin were measured by using plethysmography in 14 patients with lone AF, 13 patients with AF and underlying heart disease, and 12 normal control subjects. In the patients, these measurements were repeated after cardioversion. Although baseline FBF was the same in the 3 groups, acetylcholine-induced increases in FBF were significantly smaller in both patient groups than in the control group, and FBF increases were particularly depressed in AF patients with underlying heart disease. After restoration of sinus rhythm by cardioversion, FBF response to the highest dose of acetylcholine increased by 46% in patients with lone AF (n = 10) and by 90% in AF patients with underlying heart disease (n = 11). Nitroglycerin-induced vasodilatation was the same in all 3 groups and was not affected by cardioversion. CONCLUSIONS: These findings suggest that endothelium-dependent vasodilatation is impaired by AF and improves after sinus rhythm is restored.

Acetylcholine↗

QT and JT dispersion in patients with monomorphic or polymorphic ventricular tachycardia/ventricular fibrillation.

The present study evaluates the repolarization abnormalities in patients with monomorphic sustained ventricular tachycardia (MVT) and polymorphic ventricular tachycardia/ventricular fibrillation (PMVT/VF) by measuring QT and JT dispersion on the surface electrocardiogram (ECG). QT dispersion is a predictor of ventricular arrhythmias in several clinical settings. However, the value of QT and JT dispersion in identifying patients at risk for PMVT/VF is controversial. Maximum QT (JT) interval duration and QT (JT) dispersion were compared between 20 healthy individuals, 12 patients with inducible MVT during programmed electrical stimulation and seven patients with PMVT/VF recorded during 24-hour ambulatory ECG or induced by programmed electrical stimulation. QT dispersion was 40 +/- 9 ms in the control group, 63 +/- 21 ms in the MVT group, and 79 +/- 31 ms in the PMVT/VF group. QT dispersion in both the MVT and PMVT/VF groups were significantly greater than in the control group (P <.001 and P <.0001, respectively); however, there was no significant difference between the MVT and PMVT/VF groups. JT dispersion was 41 +/- 14 ms in the control group, 69 +/- 14 ms in the MVT group and 103 +/- 37 ms in the PMVT/VF group. JT dispersion differed significantly between the study groups and was significantly increased in PMVT/VF group than in the control group or MVT groups (P <.0001 vs. the control group, P <.005 vs. the MVT group). Patients with PMVT/VF have a greater dispersion of ventricular repolarization time. Repolarization abnormalities are important for ventricular arrhythmogenesis and detectable on the surface ECG.

Adolescent↗

Erythrinan alkaloids and isoflavonoids from Erythrina poeppigiana.

A new erythrinan alkaloid, 8-oxo-alpha-erythroidine epoxide, was isolated from wood of Erythrina poeppigiana together with the five known compounds, 8-oxo-alpha-erythroidine, erystagallin C, alpinumisoflavone, erythrinin C and eryvarin A. Their structures were elucidated on the basis of spectroscopic evidence.

Alkaloids↗

Carbon tetrachloride-induced acute liver injury in Mini and Wistar rats.

Acute liver injury induced by CCl4 injection (0.5 ml/kg b.w.) was compared between Mini and Wistar rats. Mini rats (Jcl:Wistar-TgN (ARGHGEN)1Nts strain) are Wistar-derived transgenic animals in which the expression of growth hormone (GH) gene is suppressed by the presence of an antisense transgene. The hepatic lesion appeared earlier and its recovery was delayed in Mini rats compared to in Wistar rats. The degree of the liver injury was more severe in Mini rats than in Wistar rats, and this corresponded well with the changes in serum AST level. Moreover, in accordance with the localization of CYP2E1-positive hepatocytes in the early stage after CCl4 treatment, the initial lesion characterized by ballooning of hepatocytes developed in the centrilobular zone in Wistar rats while it appeared in the middle zone in Mini rats. The changes in the percentage of PCNA-positive cells and the levels of HGF and TGF-beta1 mRNAs were clearly different between the two strains. These results indicate that the response of the liver to CCl4 is different between GH-suppressed Mini rats and Wistar rats.

Alkaline Phosphatase↗

Effect of multiple subpial transection on motor cortical excitability in cortical dysgenesis.

We report here a 12-year-old patient with unilateral cortical dysgenesis and intractable simple partial seizure in his left arm, who underwent multiple subpial transection (MST) in the right cerebral cortex including the primary motor cortex. We investigated motor cortical excitability using multimodal transcranial magnetic stimulation (TMS) before and 1 month after MST, in which surgical cortical incisions were made with strokes 5 mm apart and 4 mm deep. Preoperative TMS studies showed hyperexcitability in the affected motor cortex as abnormally prolonged muscle responses to TMS with a wide cortical motor map, which were markedly reduced following the operation. The preoperative motor evoked potentials were large and polyphasic, and consisted of early and late components. The late component was completely abolished after MST, suggesting that this component might be due to activation of the corticospinal tract neurones by long recurrent axon branches of dysplastic excitatory pyramidal neurones, which were cut by MST, or by delayed, polysynaptic intracortical conduction with marked temporal dispersion. Intracortical inhibition in the affected motor cortex was also disrupted preoperatively and improved after MST. Postoperative recruitment order of muscle responses to TMS was bilaterally symmetrical, indicating that MST did not interfere with the function of the corticospinal tract neurones. The patient showed fair motor recovery and good seizure control after the operation. These results of TMS studies demonstrated the remarkable effectiveness of MST not only on intractable seizure but also on abnormal motor cortical organization and hyperexcitability in cortical dysgenesis.

Cerebral Cortex↗

Prospective and randomized comparison of combined androgen blockade versus combination with oral UFT as an initial treatment for prostate cancer.

OBJECTIVE: This prospective and randomized clinical study was initiated to compare the efficacy and safety of combined androgen blockade with combination with UFT in patients with untreated prostate cancer. METHODS: A total of 142 patients were entered in this study between April 1990 and December 1992. All patients received bilateral orchiectomy and 200 mg/day of diethylstilbestrol diphosphate. Of these patients, 70 patients were administered an additional 400 mg/day of UFT after randomization. Either treatment was continued for at least 1 year or until objective progression occurred if the initial response was equal to or better than no change. The endpoints of this study were progression-free survival, cancer-specific survival and change of QOL scores. RESULTS: A total of 136 patients were evaluable and 131 patients (96.3%) could be followed up with a median follow-up period of 1469 days. Both groups showed similar initial treatment response at 12 weeks, adverse effect and change of quality of life score during the first year after initiation of the treatment. There was a significantly longer progression-free survival and better but not significant cancer-specific survival in the endocrine chemotherapy group. The patients with earlier stage and initial serum prostate-specific antigen values <40 ng/ml showed a good indication for this endocrine chemotherapy. CONCLUSION: This endocrine chemotherapy was confirmed to be tolerable and significantly effective in the delay of disease progression, which leads to longer survival in patients with prostate cancer.

Aged↗

Induction of micronuclei in mice exposed to static magnetic fields.

The aim of this experiment was to investigate whether static magnetic fields (SMFs) have cytogenetic effects in mouse bone marrow cells. The frequency of micronuclei was significantly increased by exposure of mice to 3.0 T for 48 and 72 h and 4.7 T for 24, 48 and 72 h. The increase in micronucleus frequency was dose dependent at all times. Micronucleus frequency at 4.7 T was higher than at 3.0 T. We consider that the increased numbers of micronuclei may be attributable to a stress reaction caused by SMFs or a direct clastogenic/spindle disturbance effect of SMFs.

Animals↗

Characterization of DNA, RNA and DNA/RNA duplexes containing an L-nucleotide.

In order to investigate the duplex structure of DNA and RNA containing an L-nucleotide residue, we carried out the UV-melting and CD experiments. Although the introduction of an L-nucleotide into DNA/DNA, DNA/RNA and RNA/RNA duplexes reduced their Tm values, the typical two-state transitions were observed for all of the duplexes. The incorporation of an L-nucleotide into the RNA strand caused more remarkable decreases of the Tm value than that into the DNA strand. The CD spectra of the DNA/DNA and RNA/RNA duplexes containing an L-nucleotide are similar to those of unmodified duplexes. On the other hand, the spectra of the heterochiral DNA/RNA hybrid duplexes are significantly different from those of the homochiral DNA/RNA hybrid duplexes, which are generally thought to adopt the A-form.

Base Sequence↗

How is the liver primed or sensitized for alcoholic liver disease?

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hidekazu Tsukamoto and Yoshiyuki Takei. The presentations were (1) Tribute to Professor Rajendar K. Chawla, by Craig J. McClain; (2) Dysregulated TNF signaling in alcoholic liver disease, by Craig J. McClain, S. Joshi-Barve, D. Hill, J Schmidt, I. Deaciuc, and S. Barve; (3) The role of mitochondria in ethanol-mediated sensitization of the liver, by Anna Colell, Carmen Garcia-Ruiz, Neil Kaplowitz, and Jose C. Fernandez-Checa; (4) A peroxisome proliferator (bezafibrate) can prevent superoxide anion release into hepatic sinusoid after acute ethanol administration, by Hirokazu Yokoyama, Yukishige Okamura, Yuji Nakamura, and Hiromasa Ishii; (5) S-adenosylmethionine affects tumor necrosis factor-alpha gene expression in macrophages, by Rajendar K. Chawla, S. Barve, S. Joshi-Barve, W. Watson, W. Nelson, and C. McClain; (6) Iron, retinoic acid and hepatic macrophage TNFalpha gene expression in ALD, by Hidekazu Tsukamoto, Min Lin, Mitsuru Ohata, and Kenta Motomura; and (7) Role of Kupffer cells and gut-derived endotoxin in alcoholic liver injury, by N. Enomoto, K. Ikejima, T. Kitamura, H. Oide, Y. Takei, M. Hirose, B. U. Bradford, C. A. Rivera, H. Kono, S. Peter, S. Yamashina, A. Konno, M. Ishikawa, H. Shimizu, N. Sato, and R. Thurman.

Animals↗

Kupffer cell sensitization by alcohol involves increased permeability to gut-derived endotoxin.

BACKGROUND: Studies with gut sterilization and Kupffer cell inactivation support the hypothesis that endotoxin and Kupffer cells are involved in mechanisms of alcohol-induced liver injury. Recently, we found that Kupffer cells isolated from rats treated only once with ethanol were sensitized to endotoxin 24 hr later. Moreover, we established a new, simple animal model of ethanol hepatotoxicity based on Kupffer cell sensitization. The purpose of this study was to determine the mechanisms by which alcohol sensitizes Kupffer cells to lipopolysaccharide (LPS). METHODS: Female Wistar rats were given ethanol (5 g/kg body weight) once every 24 hr intragastrically, and ethanol concentration, ethanol elimination, and portal vein endotoxin were measured. Gut permeability was measured in isolated segments of ileum by translocation of horseradish peroxidase. Kupffer cells were isolated 24 hr after ethanol administration in vivo and were cultured in RPMI 1640 with 10% fetal bovine serum. After the addition of LPS, intracellular Ca2+ was measured by using a microspectrofluorometer with the fluorescent indicator fura-2, and tumor necrosis factor (TNF)-alpha was measured by enzyme-linked immunosorbent assay. CD14 was evaluated by Western analysis. RESULTS: Ethanol levels exhibited a cyclic pattern in ethanol-treated rats. Similar results were obtained in groups given ethanol and antibiotics for 4 weeks. Rates of alcohol elimination were around 3.5 mmol/kg/hr in control rats. After 4 weeks of ethanol treatment with or without antibiotics, elimination rates were not changed. Translocation of horseradish peroxidase was increased about 3-fold in gut segments by treatment with ethanol. This increase was not altered by treatment with antibiotics. Moreover, portal vein endotoxin levels were increased from nearly undetectable levels to 80 pg/ml in plasma of rats treated with ethanol. As expected, this increase was prevented (<20 pg/ml) by antibiotics. In isolated Kupffer cells from rats treated with ethanol for 4 weeks, CD14, LPS-induced intracellular Ca2+, and TNF-alpha all were increased. These phenomena were blocked by antibiotics. CONCLUSIONS: Kupffer cells isolated from rats treated with ethanol for 4 weeks exhibit sensitization to LPS. It is likely that increased permeability of the gut is a prominent event that leads to alcoholic liver injury.

Animals↗

Decrement of N20 amplitude of the median nerve somatosensory evoked potential in Creutzfeldt-Jakob disease patients.

We studied somatosensory evoked potentials (SSEPs) in eight Creutzfeldt-Jakob disease (CJD) patients presenting with subacute progressive dementia, generalized myoclonus, and characteristic periodic sharp wave complexes in EEG. Somatosensory evoked potentials were elicited by median nerve stimulation at the wrist. We compared SSEP findings with EEG and the clinical stage proposed by the Japanese Slow Virus Infection Research Committee (stage 1: early stage to stage 5: terminal stage). Until clinical stage 3, short-latency SSEPs showed normal findings despite the severely abnormal EEG. With the progression to clinical stages 4 and 5, however, the amplitude of N20 began to decrease and finally disappeared without prolongation of the latency of N20, whereas other short-latency components were preserved. We recorded giant SSEPs in two of three patients in stage 4, when the periodic sharp wave complex in EEG began to decrease in amplitude. The giant SSEPs decreased in amplitude with the progression of the illness. These findings suggest that the short-latency SSEP is relatively preserved until the middle phase of the disease but that it is eventually affected in the terminal phase. We conclude that our results are compatible with the CJD pathologic findings and that the amplitude of N20 reflects the extent of cortical damage in CJD patients.

Aged↗