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Biomedical subjects

M Kudo

Publications and source records attributed to M Kudo.

At least 127 records · Page 7Linked to original sources

High prevalence of anti-hepatitis B virus serological markers in patients with hepatitis C virus related chronic liver disease in Japan.

BACKGROUND/AIMS: Evidence is accumulating that hepatitis B virus (HBV) is present in patients who are hepatitis B surface antigen negative but have antibody to hepatitis B core antigen (anti-HBc). Furthermore, recent studies have shown that patients with hepatocellular carcinoma who have antibody to hepatitis C virus (HCV) often possess HBV related serological markers. Data on the seroprevalence of HBV infection in patients with HCV related chronic liver disease were collected to evaluate the significance of the presence of antibodies to HBV. METHODS: The prevalence of HBV related serological markers was analysed in a total of 2014 Japanese patients with HCV infection. The control group comprised 352 subjects without liver disorder. RESULTS: A large number of patients (49.9%) with HCV related chronic liver disease including hepatocellular carcinoma were positive for anti-HBc. In addition, the prevalence of anti-HBc closely correlated with the clinical stage of the liver disease. There was no relation between a past history of blood transfusion and the prevalence of anti-HBc. Notably, anti-HBc was the only serological marker for HBV infection in a significant number of patients with HCV related chronic liver disease (24.1%). CONCLUSIONS: Our data provide further evidence for the high prevalence of anti-HBc in patients with HCV related chronic liver disease, particularly those with hepatocellular carcinoma, suggesting that HBV infection, probably including latent infection, may play an important role in carcinogenesis in these patients.

Adult↗

Apolipoprotein E deficiency worsens outcome from global cerebral ischemia in the mouse.

BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) has been found relevant in a variety of central nervous system disorders. This experiment examined the effect of endogenous murine apoE on selective neuronal necrosis resulting from a transient forebrain ischemia insult. METHODS: ApoE deficient (n=16) and wild type (n=17) halothane-anesthetized mice were subjected to severe forebrain ischemia (10 minutes of bilateral carotid occlusion and systemic hypotension). After 3 days' recovery, brain injury was determined histologically. In other apoE-deficient and wild-type mice, regional cerebral blood flow (CBF) was determined by 14C-iodoantipyrine autoradiography 10 minutes before, 5 minutes after onset of, and 30 minutes after reperfusion from 10 minutes of forebrain ischemia. RESULTS: The percentage of dead hippocampal CA1 neurons (mean+/-SD) was greater in the apoE-deficient group (apoE deficient=67+/-30%; wild type=37+/-33%; P=0.011). A similar pattern was observed in the caudoputamen (P=0.002) and neocortex (P=0.014). Cerebral blood flow was similar between groups at each measurement interval. Marked hypoperfusion persisted in both groups at 30 minutes after ischemia. CONCLUSIONS: ApoE deficiency worsens ischemic outcome. This is not attributable to effects on CBF. A role of apoE in the cerebral response to global ischemia is consistent with prior reports that murine apoE deficiency increases infarct size resulting from focal cerebral ischemia.

Animals↗

Superoxide mediates cigarette smoke-induced infiltration of neutrophils into the airways through nuclear factor-kappaB activation and IL-8 mRNA expression in guinea pigs in vivo.

We examined the hypothesis that superoxide mediates infiltration of neutrophils to the airways through nuclear factor (NF)-kappaB and interleukin-8 (IL-8) after acute exposure to cigarette smoke (CS) in vivo. Male Hartley strain guinea pigs were exposed to air or 20 puffs of CS and killed 5 h after the exposure. The differential cell count of bronchoalveolar lavage fluid and specific myeloperoxidase enzyme assay demonstrated that acute exposure to CS caused neutrophil accumulation to the airways and parenchyma, respectively. Acute exposure to CS increased DNA-binding activity of NF-kappaB in the lung. Acute exposure to CS also increased IL-8 messenger RNA (mRNA) expression in the lung. Pretreatment of guinea pigs with recombinant human superoxide dismutase (rhSOD) aerosols reduced the CS-induced neutrophil accumulation to the airways. Both activation of NF-kappaB and increased IL-8 mRNA expression were also inhibited by the pretreatment of rhSOD aerosols. Strong immunoreactivities for p65 and p50 were detected in the nuclei of alveolar macrophages after acute exposure to CS. The signal for IL-8 mRNA expression was demonstrated in the alveolar space after acute exposure to CS. Neither significant immunoreactivities for p65 and p50 nor IL-8 mRNA signals were observed in airway epithelium. These observations suggest that acute exposure to CS initiates superoxide-dependent mechanism that, through NF-kappaB activation and IL-8 mRNA expression, produces infiltration of neutrophils to the airways in vivo. It was also suggested that the alveolar macrophage is one potential source of NF-kappaB activation and IL-8 mRNA expression after acute exposure to CS.

Animals↗

Age-dependent increase of IgE-binding and FcepsilonRI expression on circulating basophils in children.

Peripheral blood basophils are sparse in the circulation, but they express high-affinity receptors for IgE (FCepsilonRI) and bind IgE efficiently. The present study was performed to elucidate the role of IgE bound on the basophil surface in the development of allergic responses during infancy and early childhood. IgE-binding and FcepsilonRI expression on basophils were evaluated by two-color flow cytometry. Basophil-bound IgE increased rapidly and reached adult levels during infancy in atopic patients, while it gradually increased with advancing age in parallel with serum IgE in normal controls. IgE-binding and FcepsilonRI expression in atopic children were higher than in normal controls among various age groups. They correlated with serum IgE levels but reached a plateau when serum IgE exceeded 300 ng/mL. A low, but significant level of FcepsilonRI expression was observed on cord blood basophils, although IgE-binding was usually undetectable. Incubation of cord blood with IgE rapidly saturated the preexisting IgE receptors and basophil-bound IgE levels increased. When neonatal basophils were cultured for 48 h with IgE, FcepsilonRI expression was upregulated dose-dependently and IgE-binding increased further. The up-regulation of FcepsilonRI was completely inhibited by cycloheximide, indicating that it was dependent on de novo protein synthesis. These results suggest that IgE-binding on basophils serves as a sensitive indicator of allergic sensitization, and that IgE functions as a positive regulator of FcepsilonRI expression in vivo.

Adolescent↗

[The effects of fish supplementation of platelet function, count and metabolism in healthy Japanese].

To investigate changes in platelet function, count and metabolism following fish intake among Japanese, we conducted an experimental intervention study of seven healthy Japanese volunteers (4 males and 3 females) aged 28-58 years. We supplemented their diets with an approximate daily intake of 200-400 g fish which is equivalent to about 10 g n3-polyunsaturated fatty acids (about 3.5 g eicosapentaenoic acid plus 5.0 g docosahexaenoic acid) during the 17 days. The study continued until the 23rd day after returning to an ad libitum diet. The proportion of serum n3-polyunsaturated fatty acids increased two-fold on 5th day and three-fold on 15th day of fish supplementation, but decreased to one and a half-fold on the 2nd day and returned to the level before fish supplementation on the 12th day after returning to an ad libitum diet. The proportion of serum n6-polyunsaturated fatty acids decreased by 17% to the level before fish supplementation on the 5th day, 33% on the 15th day of fish supplementation. However, the decrease was only 10% on the 2nd day and the proportion returned to the same level as before fish supplementation on the 12th day after returning to an ad libitum diet. As a result, the serum n3/n6 polyunsaturated fatty acid ratio increased four-fold on the 15th day of fish supplementation, and returned to the baseline level on the 12th day after returning to an ad libitum diet. Platelet counts decreased and the mean platelet volume increased during fish supplementation. Both parameters returned to the level before fish supplementation on the 12th day after returning to an ad libitum diet. The counts and proportion of large type platelets increased significantly during fish supplementation. Although platelet aggregation by ADP (adenosine 5'-diphosphate) did not change significantly, platelet aggregation by collagen tended to decrease during fish supplementation. Platelet factor 4, one of the indices of platelet activity, decreased significantly during fish supplementation. The mean serum triglyceride level declined during fish supplementation, but returned to the level just before fish supplementation on the 2nd day after returning to an ad libitum diet. The mean plasma fibrinogen level tended to decline during fish supplementation and remained lower until the 12th day after returning to an ad libitum diet. Habitual fish intake may attenuate the development of atherosclerosis and prevent ischemic heart disease through suppression of platelet activity, and by reducing platelet counts and serum triglyceride levels.

Adult↗

Association between a focal spared area in the fatty liver and intrahepatic efferent blood flow from the gallbladder wall: evaluation with color Doppler sonography.

OBJECTIVE: The purpose of this study was to investigate whether fatty sparing adjacent to the gallbladder fossa is related to efferent blood flow from the gallbladder wall. SUBJECTS AND METHODS: Color and power Doppler sonography were performed in 80 patients with a fatty liver that appeared as a fine echogenic pattern with considerable deep attenuation on sonography. We analyzed whether color signal appeared around the spared area, the gallbladder wall, or both. Subsequently, when such signal was detected, pulse Doppler analysis of the signal was performed. RESULTS: Color signal indicating efferent blood flow from the gallbladder wall was detected in 25 (64%) of 39 patients with a focal spared area at the gallbladder fossa and in two (5%) of 41 patients without a focal spared area. This difference was statistically significant (p < .05). The waveform of efferent blood flow signals (n = 25) that were seen within spared areas was continuous in 23 (92%) of 25 patients and was pulsatile in the remaining two patients (8%). CONCLUSION: Blood flow from the gallbladder wall to areas of the spared liver was frequently revealed by color and power Doppler sonography; therefore, this blood flow may be associated with focal fatty sparing.

Adult↗

[A study on the role of the transmembrane V to VI regions of the human luteinizing hormone receptor in its constitutive activation].

Gonadotropin (luteinizing hormone: LH, and follicle stimulating hormone: FSH) receptors are members of the seven-transmembrane (TM) receptor family. Recently, point mutations have been identified in the LH receptor gene, leading to constitutive activation (ligand-independent activation) of the receptor in patients with familial male-limited precocious puberty. Most of such point mutations were found in the coding region consisting of TM V, VI and the intracellular loop 3 (i3). Because the primary structures of gonadotropin receptors are highly conserved, in vitro mutagenesis was performed to introduce the amino acid substitution in the i3 domain (Asp-->Gly) of FSH receptor, corresponding to the point mutation leading to constitutive activation in LH receptor. However, the FSH receptor mutant showed almost similar basal cAMP production to wild type counterpart. For investigation of this difference in constitutive activation between two receptors, the author designed chimeric LH/FSH receptors with or without an amino acid substitution in the i3 (Asp-->Gly) to identify the region in the LH receptor which is important for its constitutive activation. Introduction of the amino acid substitution into a chimeric receptor containing only TM V to VI from the LH receptor led to major increases in ligand-independent cAMP production. Furthermore, the chimeric receptor with only TM V and VI derived from the LH receptor was constitutively activated by the amino acid substitution in the i3 from the FSH receptor. These results that interactions between TM V and VI of the FSH receptor are essential for maintaining the receptor conformation constrained, whereas interactions between these domains of the LH receptor are required for constitutive activation by the amino acid substitution in the i3.

Animals↗

[Degranulation of eosinophils by IgG antibody to Candida antigen].

The pathophysiological role of IgG antibody to fungi antigen widely distributed in environment such as Candida albicans in bronchial asthma has not been clarified. Wells of microtiter plate were coated with the extract of Candida albicans and then IgG antibody was immobilized on the wells by incubation with patient's serum. After cultivation of eosinophils on the well, degranulation of eosinophils, as assessed by quantitation of EPX in the supernatant, has been observed. Degranulation was completely abrogated after depletion of IgG in the serum and also decreased by incubation of the cells with anti-CD32 antibody, or anti-CD18 antibody, but not anti-CD23 antibody. Immune complex, which had been prepared by incubation of the extract of Candida albicans with patient's serum, also evoked degranulation of eosinophils. We have examined whether degranulation can be induced by two purified antigens of Candida albicans, i.e., mannan A and acid protease. IgG antibody to acid protease was detected at no or minimal levels in most sera and the antigen did not induce degranulation. On the other hand, mannan A induced degranulation. This observation may be due to response for the presence of IgG antibody to mannan A in the sera. These results suggest that immobilized IgG induced degranulation of eosinophils through Fc gamma RII (CD 32) on eosinophils and mannan A is a major allergen associated with IgG-induced eosinophil degranulation.

Allergens↗

[Emergency coronary artery bypass grafting for acute coronary syndrome].

Between 1987 and 1998, 22 patients underwent emergency coronary artery bypass grafting for the treatment of acute coronary syndrome. Overall hospital mortality was 22.7% (5/22) versus 1.8% (9/501) in patients operated on electively (p < 0.01). There were no hospital deaths in the unstable angina group. Three patients (37.5%) in the myocardial infarction group and two patients (40%) in the failed catheter intervention group died due to postoperative low cardiac output syndrome (LOS) or mediastinitis. As a complication of mechanical supports, lower extremity ischemia was a risk factor for mortality. Postoperatively six patients (27.3%) had LOS. Univariate analyses showed that age greater than 70 years, old myocardial infarction, poor ejection fraction, preoperative shock, and left main trunk or three vessel disease were significantly associated with increased LOS. To improve the surgical results, it is considered that improvement of intraoperative myocardial protection, effective combination with catheter interventional therapy and careful use of mechanical supports are needed for these compromised patients.

Adult↗

[Changes in 24-hour urinary excretion of sodium and potassium in a community-based heath education program on salt reduction].

PURPOSE: To examine changes in urinary excretion of sodium, potassium and sodium/potassium ratio in a community-based health education program on salt reduction. SUBJECTS AND METHODS: The surveyed community was Kyowa town (census population in 1985 = 16,792) where we have conducted a community-based blood pressure control program since 1981 and health education on reduction of salt intake since 1983 for primary prevention of hypertension. A 24-hour urine collection was conducted for systematically selected samples of the participants aged 40-69 in cardiovascular risk surveys in 1982-86 (early period) and in 1990-94 (later period) to estimate changes in urine excretion of sodium, potassium, and sodium/potassium ratio. RESULTS: A 24-hour urine collection was available for 565 persons (410 men and 155 women) in 1982-86 and 1,461 persons (571 men and 890 women) in 1990-94. A decline in mean sodium excretion was larger in ages 40-49 than in other age groups, and for ages 40-69 combined, the decline was 0.9-1.1 g per day for men and women. Mean sodium excretion declined to 10 g or less per day for men and women aged 60-69. Mean potassium excretion did not change except for men aged 60-69 with an increase in potassium. Sodium/potassium ratio tended to decline for women aged 40-49, and declined significantly for other sex-age groups. A larger reduction in sodium excretion was seen among persons with a history of hypertension compared to those without it. CONCLUSIONS: A significant reduction in urinary excretion of sodium and sodium/potassium ratio was observed in a community-based health education program. Men and women aged 60-69 reached a recommended level of 10 g or less in sodium intake.

Adult↗

Eradication of Helicobacter pylori using 30 mg or 60 mg lansoprazole combined with amoxicillin and metronidazole: one and two weeks of a new triple therapy.

A new triple therapy using a proton pump inhibitor and two antibiotics shows high efficiency against Helicobacter pylori infection. The aim of this study was to determine the optimal dose and duration of lansoprazole (LA) administration in combination with amoxicillin (AMPC) and metronidazole (MNZ). A total of 91 patients were enrolled in this study. They were divided into four groups: group A, 2 weeks of 30mg LA once daily, 500mg AMPC tid, and 250mg MNZ tid; group B, 2 weeks of 30mg LA bid, 500mg AMPC tid, and 250mg MNZ tid; group C, 1 week of 30mg LA once daily, 500mg AMPC tid, and 250mg MNZ tid; group D, 1 week of 30mg LA bid, 500mg AMPC tid, and 250mg MNZ tid. H. pylori status was determined by the rapid urease test, culture, histology, and 13C-urea breath test before and at least 4 weeks after the end of therapy. The cure rates in a per-protocol analysis and the incidence of adverse events in the evaluated patients were, respectively, 89.5% and 21.1% in group A, 100% and 20.0% in group B, 96.8% and 12.9% in group C, and 92.3% and 26.9% in group D. Most of the adverse events were tolerated. All four regimens in this study showed the same cure rates, and they were effective and well tolerated. One week of triple therapy using once-daily administration of 30mg LA is a good alternative.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Hepatocellular carcinomas infected with the novel TT DNA virus lack viral integration.

A novel DNA virus designated TT virus (TTV) was cloned from a patient with posttransfusion hepatitis and is thought to be a new hepatitis virus. At present, hepatitis B virus (HBV) and hepatitis C virus (HCV) are known to induce hepatocellular carcinoma (HCC). But, actually, in Japan approximately 5 to 10% of HCCs are in HBV-negative and HCV-negative (NBNC) patients. In order to study the possible role of TTV in hepatocarcinogenesis, we investigated the frequency of the TTV genome in liver tissue of 20 HCC patients. As a result, 3 of 8 NBNC HCC patients and 5 of 12 HBV- or HCV-associated HCC patients were TTV positive, and TTV was shown not to be specific for NBNC HCC. For all TTV-positive patients, we also confirmed that the TTV genome was not integrated into host hepatocyte DNA.

Aged↗

Potential role of kallikrein in diurnal rhythms and perivascular distribution in rat pineal glands.

Kallikrein hydrolyzes various biologically active peptides, other than kininogens, such as vasoactive intestinal polypeptide (VIP), in vitro. Since kallikrein and VIP have been immunohistochemically shown to be present in the perivascular areas of the pineal gland, this study was designed to determine their topographic proximity in these glands, using immunohistochemical and immunoelectron microscopic double staining methods. Furthermore, since this gland is well-known to have a circadian rhythm, the kallikrein content was measured every 4 h, using a synthetic substrate, Pro-Phe-Arg-MCA, and an enzyme-linked immunosorbent assay (ELISA) to determine whether kallikrein has a circadian rhythm. The immunoreactivities of kallikrein and VIP were highly localized in the perivascular extracellular spaces and were virtually identical in distribution. The kallikrein content changed every 4 h and was high under light and low under dark conditions. The change was more evident when the synthetic substrate was used, and this rhythm was subtle on ELISA. VIP is also said to have a circadian rhythm in the pineal glands, being low under light and high under dark conditions, i.e., opposite to that of kallikrein. Since kallikrein degrades VIP in vitro, it is reasonable to speculate that pineal gland kallikrein is involved in the processing of VIP and possibly other biologically active peptides in the perivascular areas with a discernible circadian rhythm.

Animals↗

Molecular cloning of ssd-form neural cell adhesion molecules (N-CAMs) as the major form in Xenopus heart.

Different forms of neural cell adhesion molecule (N-CAM) are generated by alternative splicing of primary transcripts and considered to have distinct biological functions. We cloned cDNAs encoding a new form of N-CAMs from the Xenopus heart cDNA library. Comparison of the sequences with chicken and mouse N-CAMs revealed that these clones code for ssd-form N-CAM. We demonstrate by Northern blot analysis that the ssd form is the major form expressed in the Xenopus adult heart. We obtained two types of ssd-form N-CAM, which are transcripts from N-CAM 1 and N-CAM 2 genes. Both types contain muscle specific domain (MSD) but not pi domain. Northern blot analysis also indicated that this form is not expressed in adult brain, in which ld-form N-CAM is the main N-CAM expressed. It is possible that high levels of specific expression of ssd-form N-CAM are related with the differentiation of cardiac muscles.

Amino Acid Sequence↗

Role of O-linked carbohydrate of human urinary trypsin inhibitor on its lysosomal membrane-stabilizing property.

Human urinary trypsin inhibitor (UTI) was digested with various enzymes to obtain O-glycoside linked N-terminal glycopeptide (UTIm1), N-glycoside linked C-terminal tandem Kunitz-domains (domain I and II, UTIm2), UTI lacking O-glycoside (UTIc), asialo UTI (UTIa) and UTI lacking N-glycoside (UTIn). We investigated the membrane stabilizing effect of these UTI derivatives on rat renal lysosome by measurement of lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG) release after hypotonic treatment. Intact UTI suppressed NAG release, but aprotinin, gabexate mesilate (FOY), nafamostat mesilate (FUT) and recombinant domain II of UTI (R-020) had no effect, indicating that inhibition of serine proteases was not involved and the carbohydrate moiety of UTI might be necessary for this property. Among UTI derivatives, UTIm1, UTIm2, UTIm1+ UTIm2, and UTIc had no effect. In contrast, UTIa or UTIn suppressed NAG release. From these results, we conclude that O-glycoside linked core protein without N-glycoside is essential to the lysosomal membrane-stabilizing property of UTI.

Acetylglucosaminidase↗

Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes.

Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO2), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimer's type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO2 and rCBV were determined using C15O2, 15O2 and C15O, respectively. rCBF and CMRO2 were significantly decreased in the frontal, parietal and temporal cortex (P < 0.05) in patients with SDAT, and showed a significant correlation with the severity of dementia (P < 0.05). In patients with DWMH rCBF was significantly decreased in the parietal cortex and in the frontal white matter in nondemented patients, and in the cerebral cortex and white matter of most regions studied in demented patients (P < 0.05), whereas rCMRO2 was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. These results suggest that rOEF is increased in both SDAT and patients with DWMH. The increase in rOEF in patients with SDAT may be accounted for by reduction in rCBV resulting from decreased activity in the vasodilatory cholinergic system, impairment of glucose metabolism and white matter changes; the rOEF increase in patients with DWMH suggests relative preservation of oxidative metabolism compared to disturbed perfusion.

Aged↗

Triterpenoid saponins and sapogenins from Vaccaria segetalis.

Four new triterpenoid saponins, vaccarosides E, F, G and H were isolated from the seeds of Vaccaria segatalis and were respectively defined to be 3-O-beta-D-galactopyranosyl(1-->2)-beta-D-glucuronopyranosyl] quillaic acid 28-O-beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L-arabinofuranosyl-(1-->3)]-beta-D-4-O-acetylfucopyranoside; 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] 3beta,4chi,16chi-trihydroxy-23-norolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L-arabinofuranosyl-(1-->3)]-beta-D-4-O-acetylfucopyranoside; 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] gypsogenin 28-O-beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L-arabinofuranosyl (1-->3)]-beta-D-4-O-acetylfucopyranoside; and 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] 3beta,4chi-dihydroxy-23norolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2) -chi-L-arabinofuranosyl-(1-->3)]-beta-D-4-O-acetyfucopyranoside. Their structures were established on the basis of extensive NMR (DEPT, COSY, HOHAHA, HETCOR, HMBC AND NOESY), FAB-MS and ESI-MS studies as well as chemical strategies and enzymatic degradation. The new aglycones of two of the saponins have been designated as segetalic acid and vaccaric acid, respectively.

Carbohydrate Conformation↗