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Biomedical subjects

H Yoshida

Publications and source records attributed to H Yoshida.

At least 289 records · Page 16Linked to original sources

Hematocrit and risk for hypertension in middle-aged Japanese male office workers.

The association of hematocrit with development of hypertension over 9 years was studied in 784 hypertension-free Japanese men aged 40 to 59 years. The age-adjusted relative risk for hypertension above the borderline level and definite hypertension increased in a dose-dependent manner as hematocrit level increased (P for trend: 0.007 and 0.001, respectively). After controls for other potential factors of hypertension, the test for trend across increasing categories of hematocrit level remained as statistical significance for definite hypertension (P=0.015). The multivariate-adjusted relative risk for definite hypertension compared with less than 43.8% of hematocrit level was 1.29 [95% confidence interval (CI): 0.62-2.67] for 43.8 to 45.2% hematocrit level, 1.35 (95% CI: 0.62-2.95) for 45.3 to 46.3% hematocrit level, 1.96 (95% CI: 0.97-3.97) for 46.4 to 48.1% hematocrit level, and 2.06 (95% CI: 1.02-4.15) for 48.2% or more hematocrit level. These results suggest that hematocrit is closely associated with development of hypertension in middle-aged Japanese men.

Adult↗

Association of alcohol consumption with increase in aortic stiffness: a 9-year longitudinal study in middle-aged Japanese men.

A 9-year longitudinal study was performed to prospectively examine the association of alcohol consumption with development of aortic stiffness in 1121 aortic stiffness-free [aortic pulse wave velocity (PWV) of less than 8.0 m/sec] Japanese men aged 35 to 59 years without definite hypertension, hypercholesterolemia, or diabetes. 274 men developed aortic stiffness (aortic PWV of 8.0 m/sec or more) during 8872 person-years follow-up. After controlling for potential predictors of aortic stiffness, the relative risk for increased aortic stiffness compared with non-drinkers was 1.01 [95% confidence interval (CI): 0.62-1.64] for those who drank 0.1 to 22.9 g/day of ethanol, 1.71 (95% CI: 1.12-2.60) for those who drank 23.0 to 45.9 g/day of ethanol, 1.79 (95% CI: 1.18-2.71) for those who drank 46.0 to 68.9 g/day of ethanol, and 2.09 (95% CI: 1.35-3.26) for those who drank 69.0 or more g/day of ethanol (P for trend < 0.001). These results suggest that alcohol consumption is closely associated with development of aortic stiffness.

Adult↗

[The relationship between fall-related activity restriction and functional fitness in elderly women].

The purpose of this study was to assess the relationship between experiences of falls or fear of falling and functional fitness in the elderly. A total of 41 women, aged 66-88, who visited Fall Prevention Clinic in Tokyo Metropolitan Geriatric Hospital, underwent an interview and functional assessment. We used a questionnaire about falls, fear of falling, activity restriction, and twelve variables were used to assess functional fitness. Data were collected from June 2000 to November 2001. The subjects were classified into four subgroups: the faller group (n = 29) were subjects who had at least one or more experiences of falling accidents in the past one year; the non-faller group (n = 12) were subjects who did not have any falling accidents in the past one year; the activity restricted group (n = 12) were subjects who were restricted from going out because of fear of falling; the activity non-restricted group (n = 23) consisted of subjects who did not have any restriction concerning going out because of fear of falling. The results were: 1) Among all subjects, 85.4% had fear of falling. Among the subjects who had fear of falling. 34.3% had restricted outdoor activities due to the fear of falling. 2) Where 86.2% of the faller group responded that they had fear of falling. 83.3% of the non-faller group also responded as having fear of falling. Of the faller group, 44.0% had some restriction concerning going out because of fear of falling. In the non-faller group, 10.0% of them showed some restriction concerning going out because of fear of falling. The rate of activity restriction in the faller group was significantly higher (p < 0.05) than in the non-faller group. 3) The faller group had significantly reduced LNG with eyes open and closed, one-leg balance with eyes open, tandem walking, grip strength, and leg extension than the non-faller group. 4) The activity-restricted group exhibited significantly reduced one-leg balance with eyes open, Up & Go test, grip strength, and leg extension than the activity non-restricted group. In conclusion, lower leg strength and walking ability as well as history of falls are significant predictors of activity restriction in elderly women related to fear of falling.

Accidental Falls↗

Effect of dietary seal and fish oils on lipid metabolism in hamsters.

Eicosapentaenoic and docosahexaenoic acids were distributed mainly in the sn-1 and 3 positions of seal oil triacylglycerols and in the sn-2 position of fish oil triacylglycerols. Seal oil-rich or fish oil-rich fats having constant polyunsaturated (PUFAs)/monounsaturated/saturated fatty acids and n-6/n-3 PUFAs ratios were fed to hamsters for 3 weeks. The control fat contained linoleic acid as the sole PUFA. The concentration of triacylglycerols in the liver was significantly lower in the fish oil group than in the control group. Phospholipid concentration in serum was lower and that in the liver was higher in the seal oil group compared with the fish oil group. The activities of fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH), and the malic enzyme were significantly lower in both the fish and seal oil groups than in the control group. Dietary seal oil more effectively reduced arachidonic acid content in liver phosphatidylcholine and phosphatidylethanolamine and serum phosphatidylcholine than fish oil. These results showed that different intramolecular distribution of n-3 PUFAs influenced glycerolipid metabolism and arachidonic acid content in serum and liver phospholipids of hamsters.

Animals↗

CD71 antibody enhances iron uptake by mouse bone marrow cells and the survival potential of erythroid progenitor cells.

Transferrin has been shown to have cytoprotective functions. The aim of this study was to evaluate the effect of antibody against CD71 (transferrin receptor) on survival potential of erythroid progenitor cells. After anti-CD71 IgG or control IgG was reacted with cells for 20 min on ice, the uptake of transferrin-bound 59Fe by the MEL cells or the mouse bone marrow cells during 2-day incubation without erythropoietin was measured. Erythropoiesis was evaluated by addition of erythropoietin after 4-5 weeks' culture without erythropoietin or beta-mercaptoethanol, and production of cells containing hemoglobin was compared by immunocytological methods. MEL cells reacted with anti-CD71 IgG incorporated more transferrin-bound 59Fe than MEL cells reacted with control IgG. Uptake of transferrin-bound 59Fe by mouse bone marrow cells reacted with anti-CD71 IgG was also greater than by cells reacted with control IgG. Erythrocytes developed from cells reacted with anti-CD71 IgG and cultured for 4-5 weeks, but few erythrocytes developed from cells reacted with control IgG. Bone marrow cells depleted of TER119+ cells, CD34+ cells, or CD45+ cells and reacted with CD71 antibody did not differentiate into erythrocytes. Survival potential of erythroid progenitor cells were enhanced by reaction with anti-CD71 antibody.

Animals↗

Mouse erythroblast formation is inhibited by anemia-inducing substance from the plasma of a patient with a malignant neoplasm.

An anemia-inducing substance (AIS) was found as a protein, with a molecular weight of 50,000 on SDS electrophoresis gel, that decreased the osmotic resistance of erythrocytes. In this study, the plasma fraction containing AIS is shown to inhibit mouse erythroblast formation in vitro. The addition of the plasma fraction from a patient with an advanced malignant neoplasm to a liquid culture of mouse bone marrow cells with erythropoietin results in low numbers of erythroblast formation and low cellular yields of alpha- and beta-globin mRNAs. These inhibitions were not observed after immunoadsorption of the plasma fraction with an antiserum against AIS.

Animals↗

Expression of apoptosis regulatory proteins in the skeletal muscle of tumor-bearing rabbits compared with diet-restricted rabbits.

The mechanism of body weight loss in the tumor-bearing state is still unclear. In this study, we investigated expressions of apoptosis regulatory proteins in the skeletal muscle of tumor-bearing and diet-restricted rabbits, and tried to evaluate the differences between the two groups. The apoptotic index (AI) in the tumor-bearing group was 28.1+/-2.84 on day 10. By day 20, many more apoptotic cells were found (AI: 40.5+/-3.20), but then after day 20 their numbers gradually decreased (AI: 9.67+/-2.22 on day 30 and 0.93+/-0.96 on day 40). By contrast, no apoptotic cells were detected in the diet-restricted group at any of the times examined. Bcl-2 immunoreactivity was either not detected at all or only weakly observed in both groups. By contrast, Bax expression increased gradually after implantation in the tumor-bearing group. Bax expression in skeletal muscle cell was graded (moderate) 10 days after tumor implantation, and (high) by day 20, in 2 of the 5 tumor-bearing rabbits. After day 20, however, Bax immunoreactivity decreased continuously in the tumor-bearing group. By contrast, hardly any Bax-immuno-positive cells were detected in the diet-restricted group. These results suggest that loss of body weight in the tumor-bearing group is different from that in the diet-restricted group, and is related to apoptosis of skeletal muscles.

Adipose Tissue↗

Expression of cyclooxygenase-2 in ovarian mature cystic teratomas with malignant transformation.

Cyclooxygenase-2 (COX-2) has been reported to be associated with tumor progression and angiogenesis and we previously reported that an increase in COX-2 expression might be associated with malignant transformation and tumorigenesis of epithelial ovarian neoplasms. In this study, COX-2 expression of ovarian mature cystic teratomas with malignant transformation, a rare entity accounting for just 1.8% of all mature cystic teratomas, was investigated using immunohistochemical techniques. There were 89 cases of mature cystic teratomas treated with surgery as their initial therapy at Osaka City University Medical School Hospital between 1995 and 2001. Ten cases of these were selected for study; five cases of mature cystic teratoma with malignant transformation, and five cases of mature benign teratoma. Expressions of CD34, vascular endothelial growth factor (VEGF), and COX-2 were investigated. Expressions of VEGF and COX-2 were strong in tissues of mature cystic teratomas with squamous cell carcinoma; however, expressions of them were hardly apparent in mature benign teratomas and in mature cystic teratomas with adenocarcinomas. These results tend to suggest that COX-2 is associated with tumor growth and progression in mature cystic teratomas with squamous cell carcinoma, as opposed to mature benign teratomas and mature cystic teratomas with adenocarcinomas.

Adult↗

Angiogenesis in adipose tissues and skeletal muscles with rebound weight-gain after diet-restriction in rabbits.

The mechanisms of excessive body weight gain after diet-restriction are still unclear. In this study, we investigated expression of angiogenic factors in adipose tissue and skeletal muscle of rabbits which had rebound weight gains; trying to make inquiries into the mechanisms of this rebound weight gain. Ten rabbits were divided into two groups. One group had free food intake (group C), and the other group had restricted food intake until day 40 of the experiments and then had free food intake (group DR). Specimens of adipose tissue and skeletal muscle were collected from each rabbit on days 20, 40, and 60 after the initial examination, and expressions of CD34, vascular endothelial growth factor (VEGF), and platelet-derived endothelial cell growth factor (PD-ECGF) were investigated. Expression of VEGF was significantly strong in the adipose tissue of group DR at the recovery period of body weight. In conclusion, rebound weight gain after a restricted-diet may be associated with angiogenesis in adipose tissue, and the angiogenesis may be induced by VEGF.

Adipocytes↗

Involvement of angiogenesis in weight-loss in tumor-bearing and diet-restricted animals.

The body's weight loss mechanism while in a tumor-bearing state is still unclear. In this study, we investigated expressions of angiogenic factors in the adipose tissue of tumor-bearing and diet-restricted rabbits evaluating the differences between the two groups. We postulated that low nutrition induced vasculogenesis to transport nutrition in the adipose tissues of diet-restricted rabbits, unlike in tumor-bearing rabbits, and that vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) were related to angiogenesis of the adipose tissues. Although we investigated the expressions of VEGF and PD-ECGF immunohistochemically in tumor-bearing and diet-restricted rabbits, there was no significant difference between the two groups. Whether angiogenesis of the adipose tissue in the diet-restricted animals may be observed during the nutritional recovery period should be investigated.

Adipose Tissue↗

Comparison of expression of apoptosis regulatory proteins in the adipose tissue of tumor-bearing and diet-restricted rabbits.

We investigated the expression of apoptosis regulatory proteins in the adipose tissue of tumor-bearing and diet-restricted rabbits, and analyzed the differences between the two groups. The apoptotic index in the tumor-bearing group was 25.1+/-12.4 on day 10 and increased to 27.2+/-14.4 by day 20. Thereafter, however, it gradually decreased, falling to 11.2+/-7.8 on day 30 and 0.67+/-0.88 on day 40. By contrast, no apoptotic cells were detected in the diet-restricted group at any of the times examined. Bcl-2 immunoreactivity was either not detected at all, or was only weakly observed in both groups. Bax expression, on the other hand, gradually increased after implantation in the tumor-bearing group. In 2 of the 5 tumor-bearing rabbits, Bax expression in adipocytes was moderate 10 days after tumor implantation, and strong by day 20, but steadily decreased thereafter. By contrast, hardly any Bax-immunopositive cells were detected in the diet-restricted group. These results suggested that loss of body weight in the tumor-bearing group was different from that in the diet-restricted group, and that it was related to adipocyte apoptosis.

Adipocytes↗

Expression of apoptosis regulatory proteins in advanced cancer of the uterine cervix after cyclic balloon-occluded arterial infusion chemotherapy.

We have already reported satisfactory therapeutic results of cisplatin-based cyclic balloon-occluded arterial infusion chemotherapy (BOAI) because it enabled advanced cervical cancer of the uterus (cervical cancer) to be treated by simple total hysterectomy (STH). In the present study, we investigated the expression of apoptosis regulatory proteins in advanced cervical cancer treated by cyclic BOAI. The results showed that the proportion of Bax-positive cells was 75.2 +/- 5.6% after the first BOAI in the cases in which STH became possible (group C), and significantly lower, 11.6 +/- 11.7% (p=0.0001), in the cases in which STH remained impossible (group I). The proportion of Bax-positive cells was significantly higher in group C than in group I throughout the treatment period, but there was no significant difference in Bcl-2 expression between the two groups. The survival rate by the Kaplan-Meier method was significantly higher in group C than in group I. These results suggest that the antitumor effect of cyclic BOAI is closely associated with apoptotic cell death, which may in part be influenced by the expression of Bax.

Aged↗

Survivin, bcl-2 and matrix metalloproteinase-2 enhance progression of clear cell- and serous-type ovarian carcinomas.

Clear cell adenocarcinomas (CA), unlike serous adenocarcinomas (SA) of the ovary, are often at stage I, are resistant to platinum-based drugs and have a poor prognosis. The causes of these differences are unclear. In this study, the differences in progression between CA and SA were examined in terms of apoptosis-related and tumor invasion-related factors. The 16 cases of CA and the 16 cases of SA were reviewed. Excised tissues were classified into primary or metastatic loci, and the expressions of survivin, Bcl-2 and matrix metalloproteinase-2 (MMP-2) in each locus immunohistochemically assayed. Whether the expression of each protein was correlated to prognosis was investigated and additionally the invasion ability of cell strains established from CA and SA were examined using in vitro invasion assay. CA at stage I showed significantly higher survivin expression than SA (p<0.05). In CA, survivin tended to be expressed higher in primary locus than in metastatic locus (p=0.068), however, Bcl-2 was expressed relatively higher in the latter (p=0.087). SA did not have these tendencies. While MMP-2 was expressed significantly higher in SA than in CA (p<0.05), and more so in metastatic locus than in primary locus of SA (p<0.05). Invasion assay showed that the invasion of cells derived from SA was significantly inhibited by tissue inhibitors of metalloproteinase-2, an MMP inhibitor. The disease-free interval was significantly shorter when survivin expression was observed in the nucleus. These results suggest that the expression of apoptosis inhibiting factors and enhanced invasion ability affect progression of CA and SA, respectively.

Adenocarcinoma, Clear Cell↗

Angiogenesis in the adipose tissue of tumor-bearing rabbits treated by cyclic plasma perfusion.

The mechanisms of cancer cachexia have not been elucidated. We previously reported that cyclic plasma perfusion using non-coated charcoal was effective in cancer cachexia. In the present study we investigated the angiogenic effect of cyclic plasma perfusion on adipose tissue. Twenty rabbits were divided into two groups, i.e., tumor-bearing rabbits subjected to cyclic plasma perfusion (n=10, PP group), and tumor-bearing rabbits subjected to sham-perfusion (n=10, SP group). The changes in body weight, total body fat, and expression of angiogenic factors were investigated. Loss of body weight and total body fat was significantly suppressed in the PP group. Apoptosis of adipocytes was seen in both groups only in the early stage of tumor bearing. Lipolytic activity in the PP group showed a lower ratio than that in the SP group. In the PP group, increased microvessel density and expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) were seen at 40 days after transplantation. Similar findings were not seen in the SP group. These results suggest that cyclic plasma perfusion not only decreased lipolytic activity but induced angiogenesis in the adipose tissue.

Adipose Tissue↗

Dihydropyrimidine dehydrogenase mRNA level correlates with the response to 5-fluorouracil-based chemo-immuno-radiation therapy in human oral squamous cell cancer.

The measurement of the intra-tumoral level of thymidylate synthetase (TS), and dihydropyrimidine dehydrogenase (DPD), may be useful in predicting tumor sensitivity to 5-fluorouracil (5-FU). In this study, we examined the mRNA levels of DPD and TS in 28 oral squamous cell carcinomas (SCC), and 22 salivary gland tumors by semi-quantitative reverse transcription polymerase chain reaction. Then we examined the correlation of the responsiveness of the patients with oral SCC to 5-FU with the intra-tumoral levels of DPD and TS mRNA. All specimens were obtained at the biopsy before treatment, and then the patients were treated by oral administration of a 5-FU compound (UFT), the irradiation of cobalt-60 (upto 60 Gy) and injection of an immuno-potentiator (OK-432). Intra-tumoral levels of DPD mRNA in the patients who showed CR (complete response) and PR (partial response) were significantly lower than those in the patients who showed NC (no change). However, intra-tumoral levels of DPD mRNA did not correlate with the local recurrence of the tumor during the observation period after initial treatment with or without surgical resection of the residual tumors. On the other hand, TS mRNA levels in the tumors did not correlate with any clinico-pathological parameters. These observations suggest that intra-tumoral levels of DPD mRNA may predict the tumor response to 5-FU-based chemo-immuno-radiation therapy in the patients with oral SCC.

Antimetabolites, Antineoplastic↗

Expression of vascular endothelial growth factor in human monocyte/macrophages stimulated with lipopolysaccharide.

Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells. We have studied the production of VEGF by human macrophages in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS expressed VEGF mRNA and protein in concentration- and time-dependent manners. The LPS-induced expression of VEGF was inhibited by cycloheximide pretreatment, which suggested that synthesis of certain factor(s) is required for the LPS activity. The induction of VEGF was also suppressed by SB203580, an inhibitor of p38 mitogen-activated protein (MAP) kinase. These results suggest that the LPS-induced VEGF expression depends on the p38-mediated expression of c-Jun, which constitutes the AP-1 complex and binds to the AP-1 site in the VEGF promoter. Pretreatment of the cells with dexamethasone did not affect the LPS-induced upregulation of VEGF mRNA but strongly inhibited VEGF protein production, and the involvement of posttranscriptional regulation on VEGF expression by dexamethasone was suggested. The conditioned medium of LPS-stimulated macrophages enhanced the growth of cultured endothelial cells and it was inhibited by an antibody against VEGF. We conclude that macrophages produce VEGF in response to the stimulation with LPS, which may be partly mediated by the p38 MAP kinase pathway.

Cells, Cultured↗

[Mechanism of drug resistance in Helicobacter pylori].

Clarithromycin is one of the most important antibiotics for H. pylori eradication. However, 5-10% was reported to be resistant. It has been shown that one point mutation in the 23S rRNA gene is associated with resistance to clarithromycin. To detect H. pylori infection and the mutation simultaneously, we have designed PCR primers specific for H. pylori, and established assays of PCR-RFLP and PCR-preferential homo-duplex formation (PHFA). Using this assay, we can detect mixed infections with wild and mutant-strains. The prevalence of mutant infection increased through clarithromycin-based eradication. However, the existence of mutant strains had been confirmed before therapy in most cases who 'converted' to mutant after therapy. Metronidazole is also one of the most important antibiotics for eradication. However, 5-50% was reported to be resistant. It has been shown that rdx gene mutation is associated with resistance. It is reported that inactivation of the rdx gene is frequently, but not always, associated with resistance to metronidazole. Amoxicillin resistant strains were rare (1.2% in Japanese strains). It is reported that penicillin-binding protein might play a role in the resistance. By detecting of the resistance based on the molecular mechanism, patients can be treated with adequate antibiotics with information about resistance.

Clarithromycin↗

[Analyses of preanalytical issues on samplings and samples].

To obtain "exact" laboratory data which show or reflect the pathophysiological conditions of patients, preanalytical, analytical and postanalytical processes should be checked. However, it is difficult to know the preanalytical situation or out of laboratories. We realize preanalytical issue is one of the weak points in current laboratory medicine. I reported the results of analyses on the issues concerning abnormal laboratory data produced by inadequate handling of samples and sample collection. Five issues are described as follows: 1) The effect of detergents on fecal occult blood test. Immunological methods were affected markedly to moderately by various sanitizers and detergents tested. In collecting feces for immunological fecal occult blood test, contact of feces with toilet flush water dissolving sanitizers should be inhibited. 2) Blood storage and potassium(K) release. Causes of slight elevation of K in serum are sometimes unknown. Addition of injection drugs in vitro showed that various drugs induced K release from erythrocytes. Cold storage of blood is well-known to bring elevation of K level, however, the detailed mechanism is still unknown. We developed a simple method to measure K flux activity of erythrocytes and the decreased activity was shown in patients with chronic renal insufficiency and the aged as well as the aged erythrocytes. 3) Thawed serum and concentration difference. Frozen serum samples were thawed without mixing and various layers contained different concentrations in 60 items tested. Comparing the concentration before freezing, the upper layer contained 1/2 and the bottom 2 times more. T3 and FT4 showed exceptionally smaller difference, significance of which is unknown. 4) Two syringe method in blood collection. Blood samples drawn in the first half and the latter half were comparatively measured for APTT, PT and TT. Blood amount of 1 ml or more showed no differences. TT showed elevation in the first half in 0.5 ml-sample. The effects of local treatment by warming, tapping and congestion were examined. In some cases, tissue factor level elevated by such physical pretreatment. However, in usual blood collection in human, two syringe method is not necessarily employed. 5) Heat-inactivation and cold storage of serum. Preheating sera at 56 degrees C for 30 min reduced markedly the levels of ALT, ALP, CK, ChE, ATIII and alpha 2-PI. In seroimmunology, some complement components are markedly affected and rheumatoid factor of IgM classes was also affected. In about a half of HCV-Ab positive sera, CH50 levels were decreased by the cold storage(cold activation). We reported previously the non-participation of C1q in this phenomenon. In such sera, temperature management is important. Scientific data on the storage and collection of samples should be informed not only to laboratory staffs but to nurses and doctors in order to provide "exact" data.

Blood Preservation↗