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Biomedical subjects

H Aoyama

Publications and source records attributed to H Aoyama.

At least 91 records · Page 5Linked to original sources

Isolation and conformational analysis of fragment peptide corresponding to the heparin-binding site of hepatocyte growth factor.

Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes. The mitogenic activity of HGF is mediated by its binding to a high-affinity receptor, c-Met. Heparan sulfate is an initial binding site for HGF, based on its relative abundance on the cell surface. The binding of HGF to heparin or heparin-like molecules may induce oligomerization of HGF and facilitate c-Met-dependent mitogenesis [Zioncheck et al. (1995) J. Biol.Chem. 270, 16871-16878]. Thus, heparin binding is important for the biological activity of HGF. To identify the heparin-binding site of HGF, we isolated fragment peptides corresponding to the site by limited proteolysis and chemical degradation of recombinant human HGF (rhHGF). The heparin-binding ability of the peptides was expressed as their elution positions on heparin-affinity column chromatography with NaCl gradient elution. Because all of the heparin-binding peptides obtained in this study were isolated from the N-terminal hairpin-loop region (PyrGlu32-Asn127) of HGF, the region was identified as the heparin-binding site of HGF. One of the isolated peptides, Phe42-Glu111, containing the N-terminal hairpin-loop structure, was considered a suitable model peptide for the heparin-binding site of HGF. From the observation using circular dichroism spectroscopy, it was indicated that the secondary structure of the peptide changed from a random structure to a beta-sheet-like structure upon heparin binding. In addition, oligomerization of HGF in the presence of heparin was observed by dynamic light scattering. Based on our evidence, it is considered that the conformational change in the heparin-binding site may induce the oligomerization of HGF.

Amino Acid Sequence↗

Bovine kidney low molecular weight acid phosphatase: FMN-dependent kinetics.

A low molecular weight bovine kidney acid phosphatase, electrophoretically homogeneous and with a relative molecular mass of 17.8 kDa, was used in this work. Among the various substrates tested, FMN was found to be the most effective, at pH 7.0. Distinct activation energy values were obtained for p-nitrophenyl phosphate- (45.44 kJ mol-1) and flavin mononucleotide- (28.60 kJ mol-1) hydrolysis reactions. The FMN hydrolysis was strongly inhibited by Cu2 and pCMB, but activated by guanosine. Pyridoxal-phosphate and vanadate were competitive inhibitors for the FMN-dependent reaction.

Acid Phosphatase↗

Specificity of antibodies against rodent transforming growth factor-alpha protein.

We found that the immunohistochemical distribution of TGF-alpha varied in rodent tissues depending on the antibody used, suggesting that the specificity of anti-TGF-alpha antibodies differs significantly. To address this issue, we compared the specificity of two representative antibodies that have been widely used to detect rodent TGF-alpha. In a competition study, the antibodies were preincubated with an excess of synthetic rat TGF-alpha 34-50 and were used for staining of rat and mouse kidneys and/or uterus. The results revealed that one of the antibodies, anti-rat TGF-alpha polyclonal antibody, was neutralized by the peptide, whereas the other, anti-human TGF-alpha monoclonal antibody, was not absorbed by the peptide up to an excess of 100-fold. Western blotting analysis showed that the anti-rat TGF-alpha polyclonal antibody recognized both human and rat purified TGF-alpha. However, the anti-human TGF-alpha monoclonal antibody did not detect purified rat TGF-alpha, although the antibody reacted with mouse proteins other than TGF-alpha from kidneys and uterus, purified human TGF-alpha, and mouse carbonic anhydrase II. These data indicate that the anti-human TGF-alpha monoclonal antibody does not recognize rodent TGF-alpha under our experimental conditions and suggest that distribution of TGF-alpha in rodent tissues may need to be reexamined.

Animals↗

Comparison of immune reactivity profiles against various environmental allergens between adult patients with atopic dermatitis and patients with allergic respiratory diseases.

To clarify the pathomechanisms underlying the involvement of different organs by atopic dermatitis (AD) and allergic respiratory disease (ARD), we compared the immune reactivities to various environmental allergens between 46 adult patients who suffered only from AD but were without any history of ARD and 41 patients who had only ARD, using a RAST FEIA (radioallergosorbent test/fluoroenzyme immunoassay) and a scarification patch test. We also studied 42 healthy adult subjects in a similar fashion. Total serum IgE antibody levels were found to be far higher in the AD group than in the ARD and healthy control group, and RAST revealed that the AD group was sensitized to far larger numbers of allergens such as food mix, cereal mix, fungus mix and Candida albicans than were the other groups. The ARD group displayed a high incidence in RAST, comparable to that of the AD group, only against Japanese cedar and grass pollen mix antigen. However, the most remarkable difference in the immune reactivity profiles was that the AD group showed a uniquely higher RAST score and a lower incidence of positive patch test reactions to C. albicans antigen than did the ARD group. The reactivities in the ARD group to C. albicans antigen did not differ from those in the control group. Our present data suggest that a more pronounced shift from Th1 to Th2 cells, reactive against various allergens, takes place in AD patients.

Adolescent↗

The relationship between job stress and mental health at work.

In order to evaluate the relationship between job stress and mental health, a cross-sectional study was conducted using a questionnaire relating to demographics, subjective job stress and mental health state. The questionnaire consisted of a 30-item Japanese version of the General Health Questionnaire (GHQ) developed by Goldberg in addition to questions about subjective job stress, to measure mental health and job stress conditions, respectively. All subjects were employees of an electronic company in Japan. Among 782 workers, 763 workers responded to the questionnaire satisfactorily (response rate was 97.6%). People whose GHQ score was more than 7 were classified as having psychiatric problems, while the remaining respondents were considered as having no mental health problems. We employed a multiple logistic regression analysis to estimate the relationship between subjective job stress and mental health, adjusting for gender, age, marital state, familial stress, and physical health state. Subjective job stress was significantly associated with the state of mental health. In particular, the items of "too much trouble at work," "too much responsibility," "are not allowed to make mistakes," "poor relationship with superiors," and "cannot keep up with technology" were significantly related to mental health.

Adult↗

[A comparative study of the effects of granisetron alone and a combination of granisetron plus steroids on CDDP-based combination chemotherapy-induced emesis--outcomes of a multicenter randomized comparative study using the central registration method. Nara Medical University Kytril Study Group].

The present investigation was conducted to examine the effects of granisetron alone and a combination of granisetron plus steroids on CDDP-based combination chemotherapy-induced emesis by multi-institutional randomized comparative trial using a central registration method. A total of 62 patients with urological cancer enrolled this study were randomized into two groups: granisetron (40 micrograms/kg) only group and granisetron (40 micrograms/kg) plus steroids (500 mg of methylprednisolone or 8 mg of dexamethasone) group. There were 31 patients eligible in the granisetron only group and 28 in the combination group. The same anti-emetic treatments were given in the recycling courses of chemotherapeutic regimens. Therefore, eligible patients of the second and the third cycle numbered 31 (17 in the granisetron only group, 14 in the combination group) and 21 (11 in the granisetron only group and 10 in the combination group). Significant inhibition of acute emesis in combination group was observed when compared with the granisetron only group in each cycle. Delayed emesis was also significantly inhibited in the combination group on Day 2 and 3 of the first cycle and on Day 2 of the second and third cycle. In addition, appetite loss was significantly reduced in the combination group on Day 2 and 3 of the first and second cycle. No adverse events were seen in either group. These results suggested that a combination of granisetron and steroids was useful for preventing CDDP-based combination chemotherapy-induced emesis.

Adult↗

[Tc-99m labeled leukocyte scintigraphy and CT for the evaluation of patients with inflammatory bowel disease].

Seventeen cases (11 patients) of inflammatory bowel disease (IBD) were studied to define the intensity and extent of disease by 99mTc-HMPAO-labeled leukocytes scintigraphy (TLLS), and 10 cases underwent CT examination to evaluate the bowel wall, lymph-nodes, and mesenteric surroundings. Serial TLLS were obtained up to 4 hours and CT was carried out within one week before or after TLLS. The sensitivities of early (1 hour) and delayed (4 hours) TLLS were 91% and 100%, respectively. The respective specificities were 100% and 33%. However, it appeared that mild IBD may yield false negative results in early TLLS while non-specific bowel activity and migration of white cells may cause false positive results in delayed imaging. By setting the diagnostic criteria for labeled leukocyte accumulation on visualization of the small bowel regardless of uptake or activity of the large bowel similar to or greater than lumbar bone marrow, the sensitivity and specificity of delayed TLLS changed to 91% and 83%, respectively. On CT examination, mesenteric lymph-node swelling, periintestinal blurring and dilatation of mesenteric vasa recta were observed in all five patients with active Crohn's disease, while wall thickening and enhancement were seen in four of them. None of the other three cases of inflammatory disease showed positive findings of dilatation of the mesenteric vasa recta, and they revealed relatively low uptake of labeled leukocytes in TLLS. A "scintigram score" was calculated by comparing uptake of tracer in five bowel segments with lumbar bone marrow activity, and a "CT score" was calculated by adding abnormalities of the intestine and mesenteric surroundings. The scintigram score correlated closely with CT score and clinical disease activity. Combined use of CT and TLLS for the evaluation of patients with IBD was an excellent means to obtain the findings of intensity and extent of disease of the bowel wall and mesenteric surroundings and provided useful information in determining the patient management.

Adolescent↗

[Anti-HCV antibody and hemolytic complement activity in sera from alcoholic patients].

We examined the association of complement activation at a low temperature in vitro with hepatitis C virus infection in alcoholic patients. The incidence of cold activation among these patients was 4.1%, which was higher than the reported incidence of 1.7% among general patients consulting a hospital, and that of 0.5% among donors for blood transfusion. In any population, most cases that showed cold activation were HCV antibody positive. The difference between the incidence of cold activation among HCV antibody positive cases in alcohol high consumers (6/21) and that in control patients (42/103) was regarded as nonsignificant. The higher incidence of cold activation among alcoholic patients may not directly associate with high alcohol consumption and may associate with higher incidence of HCV infection among the group.

Alcoholism↗

[Arterial infusion chemotherapy in pelvic space for advanced rectal cancer].

Three rectal cancer patients were treated with arterial infusion chemotherapy through the internal iliac artery. Two patients with pelvic recurrences unresectable after APRA were treated with intensive chemotherapy and the other patient with neoadjuvant chemotherapy. In all cases, 5-FU (500 mg/ body/day) was administered continuously for 5 days or 14 days. We attempted three methods for this procedure which were a bilateral catheterization to the internal iliac artery, a single catheterization with an embolization to the other internal iliac artery and a single catheterization without the embolization. As the result of this treatment, in the resected specimen with neoadjuvant case, histological necrosis was found in 50% in the main tumor and the metastatic lymph nodes. One patient with pelvic recurrence showed a partial response in CT imaging, but died one year later of the recurrence around the external iliac artery. The other patient with pelvic recurrence treated with the bilateral catheterization had no efficacy on CT imaging, but his CEA level has decreased at present. It was concluded that arterial infusion chemotherapy was effective for advanced rectal cancer and the pelvic recurrences. However, the efficacy of this treatment is limited to the area to which the drugs are delivered. Thus, it is important that the method and the location of the catheterization are determined adequately for each case.

Antidotes↗

[Evaluation of CTA for arterial infusion chemotherapy for liver metastasis from colorectal cancer].

To compare between the arterial blood supply of metastatic liver tumor and effects of intrahepatic arterial infusion chemotherapy (IHAC), we examined 8 patients with 27 liver metastasis from colorectal cancer. They were treated with ADM/lipiodol/5-FU/LV (19 nodules) or 5-FU/LV (8 nodules). To evaluate the arterial blood supply, CT arteriography (CTA) was performed, which classified tumors into 3 grades. Grade (Gr) 0; almost no enhancement, Gr1: less than one-third of tumor, Gr 2; less than two-thirds; Gr 3 over two-thirds (no case). As a result, 3 of NCs and 3 of PDs were Gr 0, 7 of MRs, 3 of NCs and 2 of PDs were Gr 1, and CR, PR and 7 of MRs were Gr 2. These results suggest that the arterial blood supply is necessary for a better response of IHAC and CTA is effective to forecast the response to IHAC.

Antineoplastic Combined Chemotherapy Protocols↗

Purification and characterization of a low-molecular-weight bovine kidney acid phosphatase.

A relative low molecular mass bovine kidney acid phosphatase was purified 1,640-fold to homogeneity, with 7% recovery. The purified enzyme (specific activity 100 mumol min-1 mg-1) was electrophoretically homogeneous with a relative molecular mass of 17.8 kDa, as determined by SDS-polyacrylamide gel electrophoresis. A broad pH optimum of 4.0-5.5 and a maximal enzyme activity at 60 degrees C were determined for the p-nitrophenyl phosphate hydrolysis. Apparent Km values of 0.14 mM, 0.4 mM, 0.3 mM and 7.9 mM were obtained, at 37 degrees C and pH 5.0, for the best substrates p-nitrophenyl phosphate, beta-naphtyl-phosphate, flavin mononucleotide and tyrosine-phosphate, respectively. The enzyme activity was enhanced by guanosine but inhibited by ZnCl2 and CuSO4, p-cloromercuribenzoate and ammonium molybdate. Vanadate (Ki 0.47 microM), pyridoxal 5'-phosphate (Ki 2.2 microM), inorganic phosphate (Ki 0.77 microM) are competitive inhibitors. Both glycerol and methanol increased significantly the acid phosphatase activity, acting as good phosphate acceptors in the transphosphorylation reaction.

Acid Phosphatase↗

MR lmaging of the Primary Breast Lymphoma: A Case Report.

Recently magnetic resonance (MR) imaging has been investigated for the detection and differentiation of benign and malignant breast lesions. Dynamic scan using the contrast material has been shown to increase the specificity of breast MR imaging. Primary breast lymphoma (PBL) is a rare disease and its MR imaging finding has not been described before. We recently experienced a case of PBL that was demonstrated on MR imaging as an early enhancing mass similar to common carcinomas. Other imaging findings including sonography, mammography were also non-specific. Furthermore, lymphoma cells had spread beyond the early enhanced area. Thus the precise delineation of the tumor extent was impossible. However, features such as a quite unclear border on pre-contrast T2-weighted image, and increased uptake of gallium-67-citrate may allow diagnosis of such lesions as malignant lymphoma.

Journal Article↗

The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 A.

The crystal structure of bovine heart cytochrome c oxidase at 2.8 A resolution with an R value of 19.9 percent reveals 13 subunits, each different from the other, five phosphatidyl ethanolamines, three phosphatidyl glycerols and two cholates, two hemes A, and three copper, one magnesium, and one zinc. Of 3606 amino acid residues in the dimer, 3560 have been converged to a reasonable structure by refinement. A hydrogen-bonded system, including a propionate of a heme A (heme a), part of peptide backbone, and an imidazole ligand of CuA, could provide an electron transfer pathway between CuA and heme a. Two possible proton pathways for pumping, each spanning from the matrix to the cytosolic surfaces, were identified, including hydrogen bonds, internal cavities likely to contain water molecules, and structures that could form hydrogen bonds with small possible conformational change of amino acid side chains. Possible channels for chemical protons to produce H2O, for removing the produced water, and for O2, respectively, were identified.

Amino Acid Sequence↗

Distribution of D-aspartate oxidase and free D-glutamate and D-aspartate in chicken and pigeon tissues.

The presence of D-aspartate oxidase activity and D-glutamate was demonstrated for the first time in several tissues of chicken and pigeon. 2. The identification of the enzyme was based on substrate and inhibitors specificity of the activity as well as other requirements for the activity, and the amino acid was identified with HPLC analysis. 3. In each animal, the highest activity was found in the kidney. In chicken, the hepatic, renal and pancreatic activities were significantly higher in male than female. In pigeon, however, any significant gender difference was not observed. 4. A substantial amount of D-glutamate, as well as D-aspartate, was detected in each tissue, irrespective of species. 5. The contents of the free D-enantiomers were significantly different between two genders in the chicken kidney, heart and pancreas and pigeon liver and kidney. However, any common relationship was not observed between the contents and the D-aspartate oxidase activity.

Amino Acid Oxidoreductases↗

A late phase II study of RP56976 (docetaxel) in patients with advanced or recurrent breast cancer.

A late phase II clinical trial of RP56976 (docetaxel), derived from Taxus baccata was performed to evaluate anti-tumour activity, time to progression and clinical toxicity in patients with advanced or recurrent breast cancer. The patients, between 15 and 80 years old with performance status (PS) of 0-2, received at least two cycles of docetaxel 60 mg m-2 intravenously at 3-4 week intervals. Of the 81 patients enrolled, the 72 eligible for the study were given a total of 327 cycles, with a median of four cycles each. Five patients obtained a complete response (CR) and 27 a partial response (PR); the response rate (RR) was 44.4% (95% confidence interval 32.7-56.6%). A relatively high RR of 9/28 (32.1%) was observed in patients who had received prior chemotherapy involving anthracyclines. The dose-limiting toxicity was grade 3-4 leucocytopenia or neutropenia, found in 78.9% and 85.9% patients respectively. Other severe (grade > 3) toxicities included alopecia (38%), anorexia (18.3%), nausea/vomiting (11.3%), and fatigue (9.9%). Hypersensitivity reactions, oedema and skin toxicity were not severe and were reversible. One therapy-related death occurred 10 days after the initial dose was given. These findings indicate that docetaxel has potent activity against metastatic breast cancer, and that the dose of 60 mg m-2 is safe.

Adenocarcinoma↗

[Background and prospects of the Community Health Act].

Japan was defeated in World War II and almost all of the nation was demoralized by the destruction and damage to much of the nation. The medical and health care system during and before World War II needed to be reformed radically and fundamentally since almost all medical and health institutes were destroyed. On the other hand, many health personnel came back from overseas after the war. Japanese modern medicine had developed on the basis of German medicine; however, many aspects of American medicine, including public health and democracy, were rapidly introduced following the end of World War II. The American type of health center was established and many laws concerning medical and health care were enacted in 1947-1948. One of them was "The Health Center Law." The National Health Insurance Act was enacted in 1958 and the total population has been covered by health insurance plans since 1961. Many physicians quit the health centers and they have worked as clinicians under the National Health Insurance scheme, because health centers were introduced before adequate education and research existed in the field of public health. On the other hand, the health insurance scheme was in its golden age during the high economic growth period of the 1960s. Japan has succeeded in all forms of modern technology and economy for the past 30 years and is now one of the top nations in the field of medical and health care, such as the numbers of clinics and hospitals and beds, the frequency of consulting with a doctor, length of hospital stay, examinee rates in mass health examinations in the community and workplace and so on. Health conditions have changed drastically from the 1950s to the present. Therefore, health centers do not fit current health needs. For example, mortality from tuberculosis, acute infections diseases and also stomach and uterus cancers and apoplexy have decreased rapidly while mortality from chronic diseases, especially lung, breast and rectal cancers, and myocardial infarction have increased gradually. Changes of life style resulting from rapid economic growth are suspected to be important causes of the change in the prevalence of these diseases. Mass health examination was important and effective as a preventive measure against tuberculosis, especially as a means of early detection and early treatment. However, it is not now effective against chronic diseases. The screening examination has resulted in identifying many patients suspected of being ill. Every examiner must be able to distinguish pathologic findings from physiologic changes of aging. Every patient must, therefore, understand his/her individuality and evaluate the result of his/her efforts to improve life style by receiving a health examination. Accordingly, the aim of health examination has changed from early detection to health support for the examinee. During the decades when life expectancy was less than 50 years of age, it was not necessary for people to plan for retirement. Moreover, there was little burden on younger generations to provide care for the aged people because there were few old people more than 70 years of age and the birth rate was high. Nowadays, elderly people face many years of life after retirement and there are too many aged people in relation to the number of younger persons. As for medical care services, many new medical needs have emerged in recent years, including "quality of life," "palliative medicine in terminal care," "establishment of a primary care system" and "comprehensive care connecting health and medical care with welfare" etc. Improved living standards resulting from economic growth, called the "economic miracle" internationally, have helped to bring about a rapid and wide range of change in daily lifestyle, such as eating habits, working conditions and environment. The Ministry of Health and Welfare has made every effort to revise the laws in relation to health and medical care systems, in order to adjust to recent

Community Health Centers↗

Transfer of male or female primordial germ cells of quail into chick embryonic gonads.

Blood from an individual quail embryo at stages 13-16, when primordial germ cells (PGCs) were in circulation, was taken from its marginal vein and transfused into the marginal vein of a chick embryo at stages 13-16. Both donor and recipient embryos were cultured in vitro until day 8 of development and their sex was determined by morphological and histological observations of the gonads. Sections of recipient gonads were stained immunohistochemically with QCR1 monoclonal antibody positive for quail PGCs but negative for chick PGCs. Donor and recipient embryos were sexed in 17 pairs which included all four sex combinations. Transferred PGCs, either female-derived ZW type or male-derived ZZ type, were observed in the gonads of both sexes of 15 recipient embryos. The population of donor PGCs ranged from 20 to over 2500. In all four sex combinations, there was a higher population in the left than the right gonad of the embryos.

Animals↗

Relation between the instrumental activities of daily living and physical fitness tests in elderly women.

A cross-sectional study was conducted to quantitatively evaluate the relationship between the instrumental activities of daily living (IADL) and various physical fitness tests in elderly women living at home. The study focused on the total population of those women aged 65 years and over living in Y Town, Hyogo Prefecture, Japan, who visited a nursing home for day services. A total of 128 subjects were divided into two groups: dependent in IADL group (n = 49) and independent in IADL group (n = 79). The magnitude of the relation was evaluated by the odds ratio (OR). The following tests showed a significant decrease in IADL: knee-raising test [age-adjusted OR = 4.23, 95% confidence interval (CI) 1.81-9.87], height (age-adjusted OR = 4.09, 95% CI 1.75-9.56), grip strength (age-adjusted OR = 3.68, 95% CI 1.57-8.60), sit-and-reach test (age-adjusted OR = 2.76, 95% CI 1.20-6.34), and standing on one leg with closed eyes (age-adjusted OR = 2.56, 95% CI 1.09-5.97). Multivariate analysis using Hayashi's quantification method I indicated that knee-raising was the test most highly correlated with decreased IADL. These results suggest that measurement of knee-raising ability, muscle strength of the lower extremities and flexibility of hip joint could be the most useful factors to assess the level of instrumental self-support ability.

Activities of Daily Living↗