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Biomedical subjects

H Yoshida

Publications and source records attributed to H Yoshida.

At least 631 records · Page 35Linked to original sources

Characteristics of cardiovascular morphology and function in the high-normal subset of hypertension defined by JNC-VI recommendations.

A cross-sectional study was conducted to compare the morphological and functional characteristics of the cardiovascular system among subgroups of hypertension defined by the JNC-VI recommendations. One hundred and sixteen subjects (normotensives and unmedicated hypertensives: 49+/-10 yr) were classified into 4 groups based on the criteria of JNC-VI: normotensive (NOR: n = 38), high-normal blood pressure (HN: n = 16), stage 1 hypertensive (SI: n = 28), and stage 2 to 3 hypertensive (SII-III: n = 34). Ultrasonographic examinations of the heart and carotid artery were performed in all subjects, and the following parameters were obtained: left ventricular mass index (LVMI), relative wall thickness at end-diastole (RWTd), cardiac diastolic function (A/E), common carotid artery diameter (CAD), intimal media thickness of the common carotid artery (IMT), and distensibility of the common carotid artery (Distens). RWTd, A/E, and IMT in SI (RWTd, 0.41+/-0.07; A/E, 1.21+/-0.41; IMT, 0.69+/-0.17 mm) and SII-III patients (0.40+/-0.08, 1.38+/-0.33, 0.80+/-0.21 mm) were larger than those in NOR patients (0.33+/-0.03, 0.86+/-0.21, 0.56+/-0.10 mm) (p < .01). Furthermore, LVMI in SII-III (135.5+/-35.5 g/m2) patients was larger than that in NOR patients (99.4+/-17.5 g/m2) (p < .05). RWTd in HN patients (0.37+/-0.06) was significantly higher than that in NOR patients (p < .05). A/E tended to be larger in HN than in NOR patients (p < 0.1). In the normotensives, no significant difference in any of the parameters was detected between those with optimal (n = 19) and normal (n = 19) blood pressure. Thus, both morphological and functional changes were associated with elevation of blood pressure. Cardiac morphological adaptation and functional impairment were present even in subjects with high-normal blood pressure level, while there were no significant differences between the normal and optimal subsets.

Adult↗

Insulin resistance and angiotensin converting enzyme polymorphism in Japanese hypertensive subjects.

Renin-angiotensin system activity has been shown to affect insulin sensitivity. However, the relationship between I/D polymorphism and insulin resistance is controversial. Therefore, we examined the relationship between the ACE genotype and insulin sensitivity in 51 Japanese hypertensive patients using the glucose clamp technique. The ACE genotype distribution in the hypertensive subjects was: 7 subjects with DD, 20 subjects with ID, and 24 subjects with II. Insulin sensitivity in terms of the glucose disposal rate was not significantly different among the three ACE genotypes, although there was a tendency for insulin sensitivity to decrease in the order of II, ID and DD, DD being the lowest. These findings are contrary to previous reports that insulin sensitivity was increased in normotensive subjects with the DD genotype who were Caucasian or African-American. There might be a difference due to race and whether the subjects are hypertensive or obese. We concluded that insulin sensitivity was not different among the ACE genotypes in the Japanese hypertensive subjects, supporting a previous report on the Chinese population. To date, insulin sensitivity has not been found to differ with ACE genotypes in the oriental population.

Adult↗

Specific targeting immunotherapy of cancer with bispecific antibodies.

In order to enhance cell mediated cytotoxicity, bispecific antibodies (BsAbs), molecules combining two or more antibodies with different antigenic specificities, have been developed as new agents for immunotherapy. Our recent studies revealed that simultaneous administration of two kinds of BsAbs (anti-tumor x anti-CD3 plus anti-tumor x anti-CD28) together with lymphokine activated killer cells with a T cell phenotype (T-LAK cells) inhibited growth of human xenotransplanted tumors in severe combined immunodeficient (SCID) mice, while single BsAb was without effect. Three kinds of BsAbs (anti-tumor x anti-CD3, anti-tumor x anti-CD28, anti-tumor x anti-CD2) showed the highest cytotoxicity against tumor cells when given simultaneously with T-LAK cells or peripheral blood mononuclear cells in vitro and in vivo. BsAbs can be preserved for immediate application, while cytotoxic T lymphocytes (CTLs) must be made-to-order, and are time-consuming to prepare. Tumor associated antigens, such as MAGE antigens, SART antigens, MUC1 antigen, c-erbB 2 antigen or cancer/testis antigens can be served to target antigens for BsAb production. By conjugation with antibodies to effector cells (anti-CD3, anti-CD28, anti-CD16, anti-CD64, anti-CD89 or anti-CD2), many kinds of BsAbs can be produced to cover most types of cancers from different organs. Therefore this strategy might be ubiquitously applicable to most malignancies.

Animals↗

Pulse intravenous cyclophosphamide treatment for steroid-resistant interstitial pneumonitis associated with polymyositis.

Interstitial pneumonitis (IP) is a serious complication in polymyositis/dermatomyositis (PM/DM), leading to significant morbidity or mortality. Here, we report the successful treatment by pulse intravenous administration of cyclophosphamide in the early course of lung involvement in PM, and with subsequent low-dosage oral administration of azathioprine in a patient with steroid-resistant IP associated with PM/DM. Although the precise pharmacological mechanism induced by cyclophosphamide in this disease remains unclear, such a cytotoxic drug raises the possibility of control of steroid-resistant PM/DM-associated IP when used in the early course of IP.

Adult↗

pH-dependent fusion of synaptosomal membrane studied by fluorescence quenching method.

We have found that both the synaptic vesicles (SV) and synaptic plasma membrane vesicles (SPM) have an activity to fuse with phosphatidylcoline/phosphatidylserine liposomes in a pH-dependent manner. The activity increases with decreases in extravesicular pH. At a pH lower than 4.0, the activity is almost steady at its maximum value, and there was a rapid drop around pH 5.5. The pH-dependent fusion was inhibited by proteolysis with trypsin; hence, at least in part, some membrane proteins play an important role in these pH-dependent fusion processes. To find specific markers, we screened various protein modifiers and found that anion channel blockers, stilbene derivatives (DIDS and SITS) and glibenclamide, affected the fusion process. DIDS and SITS decreased the fusion activity with an IC50 of 180 and 300 microM, respectively, whereas glibenclamide, on the contrary, increased it. From the results of an autoradiogram using 3H-tagged DIDS, a 30 kDa DIDS-binding protein was identified in the synaptic plasma membrane, which is possible to be responsible for the pH-dependent fusion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Inhibition of Ca(2+) entry caused by depolarization in acetylcholine-stimulated antral mucous cells of guinea pig: G protein regulation of Ca(2+) permeable channels.

The effects of depolarizing conditions resulting from increasing extracellular K(+) concentration or nystatin treatment on intracellular Ca(2+) concentration ([Ca(2+)](i)) were studied in guinea pig antral mucous cells following acetylcholine (ACh) stimulation. ACh stimulation evoked a biphasic increase in [Ca(2+)](i), that is, an initial transient increase followed by a plateau. Depolarizing conditions reduced the [Ca(2+)](i) in the plateau phase during ACh stimulation. However, pertussis toxin (PTX, a G protein inhibitor) treatment caused [Ca(2+)](i) in the ACh-evoked plateau phase to increase under depolarizing conditions, while it had no effect on [Ca(2+)](i) under hyperpolarized conditions. Based on these observations, Ca(2+) permeable channels are regulated by a G protein which is activated by depolarized conditions and inhibited by hyperpolarized conditions and PTX; activation of the G protein (depolarization) causes Ca(2+) permeable channels to inhibit, and in turn, inhibition of the G protein (hyperpolarization) causes them to activate.

Acetylcholine↗

[Compliance concerning external protectors for hip fractures among the institutionalized elderly in Japan].

An external protector (EHP) which was developed in Europe to protect the femoral neck from direct impact on falling is available but has not been examined sufficiently in Japan. In order to explore the compliance of use of the EHP among the institutionalized elderly with in case of hip fracture who are at high risk of falling, we conducted the four-week intervention study using two types of a EHP. The subjects of a study consisted of 10 elderly people (2 men, 8 women) with a mean age 85.7 living in nursing home in a village. Informed consent was obtained from all participants. At the end of the study, rate of subjects who wore EHP was relatively high for the Finnish EHP (Safety Pants) group compared to the Danish EHP (Hip Protector) group. There were no significant differences between variables in age, sex, fall experience during the previous year, history of diseases etc. The reasons for dropout were first: difficult in wearing EHP and accompanying delay in toilet, secondly: taking much time to wear, thirdly: a sense of incongruity, too small or too tight'. If the EHP is redesigned to suit Japanese elderly, the compliance might increase. Thorough explanation to institutionalized elderly who may have cognitive impairment, physical problems, or both, is required.

Aged↗

[Compliance in use of external protectors for hip fractures among the community elderly in Japan].

To protect femoral neck fractures which are the most serious complication of osteoporosis and are increasing in frequency in Japan, an external hip protector (EHP) fixed in special underwear has been proven to absorb a direct impact to the greater trochanter during a fall from standing height. In this study, we investigated compliance concerning the use of EHPs, for six months using two types of EHP, i.e., hard pad type (Hip Protector, Sahvatex) from Denmark (Fig. 1) and soft pad type (Safety Pants, Rounomo Oy) from Finland. The subjects were 20 elderly women aged 70 years or more who had at least one experience of falling within the year preceding the baseline survey in September of 1997. The compliance rate is shown in Fig. 2. Though the soft type EHP had relatively better compliance than the hard type EHP, there was no significant difference between them. The main reason for early dropout (one or two weeks after base-line) was "difficulty to remove especially with regard to using the toilet". The main reason for later dropout was "too tight to wear in winter". There were no significant differences with regard to anthropometric measurements, physical activity, ADL, and rate of falls between compliers and dropouts except age (73.6 vs 78.5 yrs). Sufficient explanation at baseline and generatively good motivation for wearing the EHP will maintain a high compliance which may result in the effective prevention of hip fractures among the community elderly.

Aged↗

[Association of physical performance and falls among the community elderly in Japan in a five year follow-up study].

Since falling is one of the main causes of morbidity and mortality among the elderly, attention should be paid to prevention. The purpose of the present study was to investigate the risk factors for falls among the elderly by a 5-year longitudinal observation. The subjects were the elderly aged 65 years and over living in a rural community in the eastern part of Honshu, Japan. Of the 852 eligible subjects, 685 persons (278 males and 407 females) received the multidimensional medical examination including physical performance as the baseline of TMIG-LISA (Tokyo Metropolitan Institute of Gerontology, Longitudinal and Interdisciplinary Study on Aging) in 1992. From baseline medical examinations, the following variables were adopted to investigate risk factors for falls (2 or more times during the 5-year follow-up): self-rated health, experience of falling, TMIG-index of competence, visual deficit, anthropometric measurements (height, weight, BML total skinfold thickness), lumbar bone mineral density, and physical performance tests (grip strength, finger-tapping rate, one leg standing time with eyes open or closed, preferred and maximum speed walking for 5 meters). A total of 108 subjects experienced falls two or more times during the 5-year follow-up period (43 men and 65 women). There were significant differences in grip strength, preferred and maximum walking speeds between those who fell and those who did not. Multiple logistic regression analysis controlled for age, sex and other variables adopted in this study revealed the following variables were significantly and independently related to falling: experience of falling within one year preceding the baseline survey (directly, p < 0.0001), preferred walking speed (inversely, p < 0.005) and total skinfold thickness (inversely, p < 0.01). These results suggest that the walking test as well as the experience of falling have discriminant and predictive validity for assessing the future occurrence of falls among the elderly.

Accidental Falls↗

Effect of dietary seal and fish oils on triacylglycerol metabolism in rats.

Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were distributed mainly in the sn-1 and 3 positions of seal oil triacylglycerol and in the sn-2 position of fish oil triacylglycerol. Seal oil or fish oil-rich fats having constant polyunsaturated/monounsaturated/saturated fatty acids and n-6/n-3 polyunsaturated fatty acid (PUFA) ratios were fed to rats for 3 wk. Control rats were fed on a fat containing linoleic acid as the sole PUFA. Seal oil more effectively lowered serum and liver triacylglycerol concentrations than fish oil. The activities of fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH) and hepatic triacylglycerol lipase (HTGL) were significantly lower in the seal oil group than in the control group, whereas the activity of HTGL was significantly lower and the hepatic peroxisomal beta-oxidation and activity of lipoprotein lipase (LPL) in adipose tissue were significantly higher in the fish oil group than in the control group. These observations suggest that the predominant hypotriacylglycerolemic effect of seal oil is caused by the suppression of fatty acid synthesis.

Adipose Tissue↗

Wild-type p53 gene transfer resulted in cell cycle arrest, but not apoptosis of newly established human malignant fibrous histiocytoma cell line.

We established a human malignant fibrous histiocytoma (MFH) cell line, MFH-ToE, from a tumor originally developed in the right thigh of a 78-year-old woman. The original tumor histologically consisted of histiocytic, fibroblastic and giant cells. The tumor cells showed immunoreactivity for vimentin and alpha-1-antichymotrypsin, and were positive for acid phosphatase and non-specific esterase, being compatible with MFH. Although the histology of the heterotransplanted tumor into nude mice was similar to that of the primary MFH, the population of giant cells gradually decreased along with the culture passages. Cytogenetic analysis revealed a highly aneuploid nature with varying numbers of chromosomes from 71 to 140. Chromosome 17 showed monosomy and exon 6 to 8 of p53 gene was not amplified by PCR, implying absence of p53 function. Adenovirus vector-mediated wild-type p53 gene was successfully transfected into the MFH-ToE, which showed up-regulation of P53 and P21, as well as gradual up-regulation of Bcl-2 protein. The transfection resulted in cell cycle arrest, but not apoptosis of the MFH-ToE cells. These results revealed unique properties of the MFH-ToE, which might be useful in further studies analyzing pathological and biological characteristics of MFH.

Aged↗

[Experience with surgery for congenital esophago-bronchial fistula with esophageal diverticulum in adult].

A 65-year-old female was admitted into our department with complaint of bloody sputum. An upper G-I series examinations and thoracic CT demonstrated an esophago-bronchial fistula with diverticulum located between the mid-esophagus and right B6. Following postero-lateral thoracostomy, the fistula was surgically removed and right lower lobectomy was carried out. No inflammatory changes were found in the surrounding tissues of the fistula and the diverticulum. Histological examination revealed that the fistula wall contained squamous epithelium and muscularis mucosa. These results suggested that this case was congenital esophago-bronchial fistula categorized as Braimbridge type I.

Aged↗

[Detection of Helicobacter pylori 23S rRNA gene mutation associated with clarithromycin resistance and its clinical applicability].

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. We confirmed that this finding applied to the isolates in Japan. 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). Compared with other conventional methods, these assays achieved above 95% sensitivity. It is also demonstrated that the eradication rates achieved by clarithromycin-based regimens significantly differed between mutant and wild type infections. By detecting of 23S rRNA gene mutations associated with clarithromycin resistance, patients can be treated with adequate antibiotics with information about resistance.

Anti-Bacterial Agents↗

[PCR-monitoring of gastric juice obtained with the capsuled string for the evaluation of H. pylori eradication].

We have developed a highly sensitive semi-nested PCR assay, URA-PCR, for the detection of H. pylori ureA gene in gastric juice. The primers were designed according to nucleotide sequence analyses of clinical isolates. The PCR assay has higher sensitivity than conventional methods such as culture. Characteristics of culture-negative but PCR-positive patients were similar to those of culture-positive ones. The PCR assay, using gastric juice samples obtained with capsuled strings, detected 97% cases of relapsed infection within eight weeks after antimicrobial therapy.

Breath Tests↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1997). I. Susceptibility distribution].

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 560 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period of June 1997 to May 1998. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. Susceptibilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90s of 2 micrograms/ml. The others had low activities with the MIC90s of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM and arbekacin (ABK) showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90s of them were 1 microgram/ml. The others except minocycline (MINO) had low activities with the MIC90s of 32 micrograms/ml or above. More than a half of S. aureus strains (including MRSA) showed high susceptibilities to gentamicin (GM) and MINO, the MIC50s of 0.25 microgram/ml or 0.5 microgram/ml. 3. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. The MIC90s of ciprofloxacin (CPFX) and tosufloxacin (TFLX) were 1 microgram/ml, the MIC90s of amikacin (AMK) and ofloxacin (OFLX) were 4 micrograms/ml, the MIC90 of GM was 16 micrograms/ml. Among E. cloacae strains, those with low susceptibilities to quinolones have decreased in 1997, compared with those in 1996. But the other drugs were not so active in 1997 as 1996. 4. Escherichia coli All drugs except penicillins were active against E. coli with the MIC90s of 8 micrograms/ml or below. Particularly, flomoxef (FMOX), cefmenoxime (CMX), cefpirome (CPR), cefozopran (CZOP), IPM, CPFX and TFLX showed the highest activities against E. coli with the MIC90s of 0.125 microgram/ml or below. 5. Klebsiella pneumoniae K. pneumoniae was susceptible to almost all the drugs except penicillins. Carumonam (CRMN) had the strongest activity with the MICs for all strains equal to or lower than 0.125 microgram/ml. FMOX, CPR, CZOP, CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. The MIC90s of quinolones had changed into a better state in 1997, compared with those in 1996. 6. Proteus mirabilis Almost all the drugs except ABPC and MINO showed high activities against P. mirabilis. CMX, ceftazidime (CAZ), latamoxef (LMOX), CPR, cefixime (CFIX), cefpodoxime (CPDX) and CRMN showed the highest activities against P. mirabilis. The MICs of them for all strains were equal to or lower than 0.125 microgram/ml. CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. 7. Pseudomonas aeruginosa The MIC90 of GM was 8 micrograms/ml, the MIC90s of AMK, IPM and meropenem (MEPM) were 16 micrograms/ml. The others were not so active against P. aeruginosa with the MIC90s of 32 micrograms/ml or above. The MIC90s of quinolones had changed into a lower state in 1997, compared with those in 1996. 8. Serratia marcescens IPM showed the highest activity against S. marcescens. Its MIC90 was 2 micrograms/ml. GM was also active with the MIC90 of 4 micrograms/ml. The MIC90s of the others were 16 micrograms/ml or above. The MIC50s of CRMN was 0.125 microgram/ml or below, the MIC50s of CPR and CZOP were 0.25 microgram/ml.

Anti-Bacterial Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1997). II. Background of patients].

Clinical background was investigated on patients with urinary tract infections (UTIs) from whom 603 bacterial strains were isolated in 9 hospitals during the period from June, 1997 through May, 1998. 1. Distribution of age and sex of patients and type of infections Among males, those with ages less than 50 years were only 12.5%, and those in the 70's were most frequent (33.3%). Among females, those with ages less than 20 years were only 3.4%, and those in the 60's were the most frequent (22.9%). With regard to type of infections, more than a half of infections among males with ages 50 years or older were of complicated types, but most of infections among females were of uncomplicated types, especially those of ages less than 50 years. 2. Ages of patients and types of pathogens Escherichia coli was the most frequently isolated in uncomplicated and complicated UTIs without indwelling catheters. In complicated UTIs with indwelling catheters, Pseudomonas aeruginosa and Enterococcus faecalis had mainly detected, they had no relationship with ages. 3. Effect of antibiotic use on isolation frequencies of pathogens Use of antibiotics decreased pathogens isolated from patients with uncomplicated UTIs drastically (183 isolates before antibiotics compared to 13 after). Even isolated pathogens from patients with complicated UTIs decreased drastically with the use of antibiotics when indwelling catheters were not in use (175 isolates before antibiotics compared to 53 after), but when indwelling catheters were in use, antibiotics slightly decreased (109 isolates before antibiotics compared to 70 after). 4. Surgical procedures and types of causative organisms for UTIs E. faecalis were more isolated when a surgical procedures were used, and E. coli were more isolated when, they were not used in uncomplicated and complicated UTIs without indwelling catheters. In complicated UTIs with indwelling catheters, E. coli and E. faecalis were more isolated when a surgical procedures were used, and P. aeruginosa and Staphylococcus aureus were more isolated when they were not used.

Adult↗

Compensated endocytosis of LDL by hamster cells co-expressing the two distinct mutant LDL receptors defective in endocytosis and ligand binding.

The low density lipoprotein receptor (LDLR) regulates the plasma cholesterol level by mediating endocytosis of LDL. We established stable hamster cell lines expressing two LDLRs with distinct functional defects, i.e., endocytosis and ligand binding. In the cell line expressing only I189D h/r (human-rat chimeric) LDLR, defective in LDL binding, very little amount of LDL was internalized, although the receptor was endocytosed efficiently. In the cell line expressing Y807C LDLR solely, very few receptors were located in coated pits or endocytosed, while LDL binding to the receptor was not disrupted. In striking contrast, in the cells co-expressing both receptors, a much larger number of Y807C LDLR were internalized and co-located with I189D h/r LDLR in the perinuclear region. In these cells, LDL was bound exclusively to Y807C LDLR and its uptake was enhanced by 80% as compared to the cell expressing Y807C LDLR solely, whereas LDL binding affinity was not changed. These results suggest that a defect of the essential motif for endocytosis, cysteine 807, could be compensated by co-expression of I189D h/r LDLR, but the LDL binding was not affected.

Animals↗

[Prevalence of upper urinary tract stones in Tajima, north Hyogo, Japan].

Toyooka Hospital is a central hospital in Tajima, a rural area in the northern part of Hyogo Prefecture. Because we possess the sole lithotripter in this area, almost all urolithiasis patients requiring treatment have been referred to our department. Based on the number of urolithiasis patients treated in our institution, we estimated the annual prevalence and incidence of upper urinary tract stones in the Tajima area. The mean annual prevalence of urolithiasis and incidence during the 1991-1993 period were 141 and 93 per 100,000, respectively. The male to female ratio was 2.0 to 1 in prevalence and 2.2 to 1.0 in incidence. Prevalence was highest in the sixties (245) and fifties (235), followed by the forties (205), seventies (162) and thirties (160). The incidence was highest in the fifties (169), followed by the forties (147), sixties (145) and thirties (118). In consideration of sex, the incidence was highest in males in the fifties and the forties. Of the patients with upper urinary calculi, 23.1% were treated by extracorporeal shock wave lithotripsy, while in 23.8% stones passed spontaneously and 50.9% were followed up without treatment. On stone analysis, calcium oxalate and/or calcium phosphate was present in 75.6%, uric acid in 16.4%, struvite and/or carbonate apatite in 5.6% and cystine in 1.4%. In summary, the prevalence and incidence of upper urinary tract calculi in the Tajima area were considerably higher than those in the nationwide survey on urolithiasis in Japan conducted in 1985.

Adult↗