Search PubMed⌕ Search

Biomedical subjects

N Kinoshita

Publications and source records attributed to N Kinoshita.

At least 55 records · Page 3Linked to original sources
PubMed1999

brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes.

Growth and patterning of the Drosophila wing is controlled in part by the long-range organizing activities of the Decapentaplegic protein (Dpp). Dpp is synthesized by cells that line the anterior side of the anterior/posterior compartment border of the wing imaginal disc. From this source, Dpp is thought to generate a concentration gradient that patterns both anterior and posterior compartments. Among the gene targets that it regulates are optomotor blind (omb), spalt (sal), and daughters against dpp (dad). We report here the molecular cloning of brinker (brk), and show that brk expression is repressed by dpp. brk encodes, a protein that negatively regulates Dpp-dependent genes. Expression of brk in Xenopus embryos indicates that brk can also repress the targets of a vertebrate homologue of Dpp, bone morphogenetic protein 4 (BMP-4). The evolutionary conservation of Brk function underscores the importance of its negative role in proportioning Dpp activity.

Amino Acid Sequence↗
PubMed1999

Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly.

At least 11 complementation groups (CGs) have been identified for the peroxisome biogenesis disorders (PBDs) such as Zellweger syndrome, for which seven pathogenic genes have been elucidated. We have isolated a human PEX19 cDNA (HsPEX19) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary cell line, ZP119, defective in import of both matrix and membrane proteins. This cDNA encodes a hydrophilic protein (Pex19p) comprising 299 amino acids, with a prenylation motif, CAAX box, at the C terminus. Farnesylated Pex19p is partly, if not all, anchored in the peroxisomal membrane, exposing its N-terminal part to the cytosol. A stable transformant of ZP119 with HsPEX19 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX19 expression also restored peroxisomal protein import in fibroblasts from a patient (PBDJ-01) with Zellweger syndrome of CG-J. This patient (PBDJ-01) possessed a homozygous, inactivating mutation: a 1-base insertion, A764, in a codon for Met255, resulted in a frameshift, inducing a 24-aa sequence entirely distinct from normal Pex19p. These results demonstrate that PEX19 is the causative gene for CG-J PBD and suggest that the C-terminal part, including the CAAX homology box, is required for the biological function of Pex19p. Moreover, Pex19p is apparently involved at the initial stage in peroxisome membrane assembly, before the import of matrix protein.

Amino Acid Sequence↗
PubMed1999

CD36 deficiency has little influence on the pathophysiology of hypertrophic cardiomyopathy.

CD36 is homologous with myocardial long-chain fatty acid (LCFA) binding protein and has been suggested to relate to myocardial fatty acid metabolism. Myocardial scintigraphy with iodine-123 15-(p-iodophenyl)-3-(R, S)-methylpentadecanoic acid (BMIPP) revealed an impairment in LCFA metabolism chiefly in the hypertrophic myocardium in hypertrophic cardiomyopathy (HCM). Recently, the incidence of CD36 deficiency has been reported to be high in HCM patients, and CD36 deficiency was proposed as an etiology of hereditary HCM. However, the pathophysiological effect of CD36 deficiency on HCM has not been fully investigated. We analysed the expression of CD36 antigens on both platelets and monocytes obtained from 82 patients with HCM using two-color flow cytometry. Among the study patients, seven patients (8.5%) demonstrated type II CD36 deficiency, whereas type I CD36 deficiency was not detected. Two of 23 patients (8.7%) with a family history of HCM and five of 59 patients (8.5%) without a family history of HCM showed type II CD36 deficiency respectively. Contrary to the previous report, three of 53 patients with asymmetric septal hypertrophy (ASH) (5.7%) and four of 29 patients without ASH (13.8%) showed CD36 deficiency. Moreover, clinical characteristics, scintigraphic findings, echocardiographic data, and hemodynamic findings disclosed no significant differences between the HCM patients showing normal CD36 expression and those with CD36 deficiency. The incidence of CD36 deficiency in HCM patients is not higher than in the general population. Therefore, CD36 deficiency is not a characteristic factor of HCM and has little influence on the pathyphysiology of HCM.

Adolescent↗
PubMed1999

Reverse redistribution of Tc-99m-tetrofosmin in patients with acute myocardial infarction.

We examined reverse redistribution (RR) of Tc-99m-tetrofosmin after a single injection in patients with acute myocardial infarction (AMI). Tc-99m-tetrofosmin myocardial SPECT was performed in 28 patients with AMI 10-14 days after the onset. Myocardial images were obtained 30 min and 180 min after the injection of 740 MBq of Tc-99m-tetrofosmin. The left ventricular wall was divided into 9 segments. Regional myocardial uptakes of Tc-99m-tetrofosmin were scored by 4-point scoring (0 = normal, 1 = mildly reduced, 2 = moderately reduced, and 3 = defect). RR was defined as an increase of more than 1 in the regional score in images at 180 min. RR of Tc-99m-tetrofosmin was observed in 17 of 20 patients with direct PTCA and 3 of 8 patients without reperfused therapy. RR was observed in 61 of all 252 segments. Coronary angiography performed 1 month later revealed that the infarct-related artery was patent in 19 of 20 patients (95%) with RR and in 3 of 8 patients (37.5%) with persistent defects (PD) (p < 0.05). In segment-by-segment analysis, the incidence of regional wall motion abnormality I month later was reduced in regions with RR compared to those with PD (p < 0.0001). In conclusion, RR of Tc-99m-tetrofosmin was frequently observed in patients with successful direct PTCA. As the segments with RR showed signs of preserved function 1 month later, this phenomenon may reflect a salvaged myocardium in AMI.

Adult↗
PubMed1999

Risk factors for breast cancer in Japan, with special attention to anthropometric measurements and reproductive history.

BACKGROUND: Breast cancer incidence has increased rapidly in Japan recently, but there have been only a few studies on the risk factors for breast cancer in Japan. A case-control study was conducted to evaluate the roles of anthropometric and reproductive factors in the etiology of breast cancer in Osaka. METHODS: Based on information from a self-administered questionnaire at Osaka Medical Center for Cancer and Cardiovascular Diseases, body mass index, body weight and height were compared between 376 cases and 430 controls, together with other factors such as age at menarche, age at first delivery and family history of breast cancer by menopausal status. Logistic regression analysis was employed for adjusting confounding factors and estimating odds ratios with their 95% confidence interval for breast cancer. RESULTS: A body mass index of >25 was significantly associated with the risk among post-menopausal women (age-adjusted odds ratio: 1.90, 95% confidence interval: 1.10-3.24) as compared with the risk for a body mass index of < or = 20. A weight of > or =58 kg showed significantly increased risk compared with a weight of < or = 47 kg among post-menopausal women (1.83, 1.10-3.01), while height of > or = 159 cm showed a significantly elevated risk than height of < or = 149 cm among pre-menopausal women (2.51, 1.17-5.39). Age at menarche of < or = 13 years resulted in a higher risk of breast cancer among post-menopausal women, while age at first delivery of > or = 28 years was associated with the risk among pre-menopausal women. Family history of breast cancer was associated with the risk for breast cancer. CONCLUSIONS: These results were all very consistent with findings observed in western countries.

Adult↗
PubMed1999

Suicide risk among cancer patients: experience at one medical center in Japan, 1978-1994.

In order to identify the risks, methods and locations of suicide among Japanese cancer patients, we followed up 23,979 cancer patients aged 15 years and older, who were newly diagnosed at one medical center between 1978-94. Suicide risk was evaluated by comparing the observed number (O) with the expected number (E), which was calculated from the suicide mortality rate among Osaka residents. By the end of 1994, there were 48 suicide death among 109,374 person-years of follow-up. Suicide risk was significantly increased within the first five years following cancer diagnosis (male: O/E=1.62, 95% confidence interval (CI)=1.03-2.43, female: O/E=2.13, 95% CI=1.22-3.47), and decreased to unity after five years had elapsed following the cancer diagnosis. Patients in their fifties (O/E=1.93, 95% CI=1.48-4.37), diagnosed between 1978-85 (O/E=1.93, 95% CI=1.19-2.95), having remote metastasis at their initial diagnosis (O/E=4.66, 95% CI=2.12-8.84), the site being in the female genital organs (O/E=3.58, 95% CI=1.54-7.06) or in the male genital organs (O/E= 5.86, 95% CI=1.58-15.05), had a significantly higher suicide risk within five years following cancer diagnosis. The highest suicide mortality was observed between the third and fifth months after cancer diagnosis (O/E=4.35, 95% CI=1.87-8.58); most of these suicides (7/8) occurred soon after discharge from hospital. Among the 39 patients who committed suicide within five years after their diagnosis, the most common method among those who took their lives while in hospital was by jumping to their death (10/16), and that among those who committed suicide in other locations was by hanging (14/23). These findings indicate that Japanese patients with cancer run the highest risk of suicide soon after having been discharged from hospital. Clinicians should assess cancer patients' psychological distress and potential risk of suicide before approving discharge from hospital.

Adolescent↗
PubMed1999

Time trends of incidence for cutaneous melanoma among the Japanese population: an analysis of Osaka Cancer Registry data, 1964-95.

Cutaneous malignant melanoma occurs much less frequently among non-white populations than among white populations. Little is known of the descriptive epidemiology of melanoma among Japanese. We investigated time trends of incidence of invasive cutaneous malignant melanoma using data from the Osaka Cancer Registry (Japan) among 321 men and 313 women diagnosed between 1964-95. Average, annual, age-standardized incidence rates per 1,000,000 population were 2.45 (95% confidence interval (CI): 2.17-2.72) for men and 2.04 (95% CI: 1.81-2.28) for women. The age-standardized rate ratio among men from 1964-71 as a reference was almost constant during the study period, whereas that among women increased up to 1.8 fold (95% CI: 1.25-2.56) in 1980-87 and seems to have reached a plateau recently. Among men, the ratio for head and neck lesions decreased to 0.5 fold (95% CI: 0.26-0.99) in 1988-95. Among women, the ratio for lesions of the extremities steeply increased up to 4.7 fold (95% CI: 2.68-8.35) in 1980-87 from the reference period of 1964-71, whereas a slight increase for trunk lesions and no increase for head and neck lesions were noted during the same period. Possible explanations for the subsite-specific time trends are discussed.

Adolescent↗
PubMed1999

Decatromicins A and B, new antibiotics produced by Actinomadura sp. MK73-NF4. I. Taxonomy, isolation, physico-chemical properties and biological activities.

New antibiotics designated decatromicins A and B were isolated from the culture broth of Actinomadura sp. MK73-NF4. They were purified by butyl acetate extraction, silica gel column chromatography, silica gel TLC and Sephadex LH-20 column chromatography. Decatromicins A and B inhibited growth of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA).

Actinomycetales↗
PubMed1999

Vinylamycin, a new depsipeptide antibiotic, from Streptomyces sp.

A new depsipeptide antibiotic, vinylamycin, was isolated from the culture broth of an actinomycete strain. The producing organism, designated MI982-63F1, was identified as a member of Streptomyces. Vinylamycin was isolated from the culture broth by extraction with EtOAc and purified by crystallization from EtOAc. The structure of vinylamycin was determined by spectroscopic analysis and degradation studies. Vinylamycin showed antimicrobial activities against Gram-positive bacteria including MRSA.

Animals↗
PubMed1999

Serum carnitine concentrations in patients with idiopathic hypertrophic cardiomyopathy: relationship with impaired myocardial fatty acid metabolism.

We evaluated the clinical significance of serum carnitine concentrations in determining the severity of impaired myocardial fatty acid metabolism in idiopathic hypertrophic cardiomyopathy (HCM). We studied 56 asymptomatic or mildly symptomatic patients with HCM. Serum levels of free carnitine and acylcarnitine were measured by the enzymic cycling method. Myocardial scintigraphy with (123)I-labelled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) was performed, and the images were analysed quantitatively and semi-quantitatively. Serum free carnitine levels were significantly higher in HCM patients than in normal subjects (52. 5+/-9.5 and 42.3+/-5.5 nmol/ml respectively; P<0.0001). On the other hand, serum acylcarnitine levels and acyl/free carnitine ratios were lower in HCM patients than in normal subjects (10.2+/-4.0 nmol/ml and 0.19+/-0.08, compared with 13.2+/-3.9 nmol/ml and 0.32+/-0.11 respectively; P<0.0001). Clinical characteristics were not significantly different between the patients showing high and normal free carnitine levels, although female patients with high free carnitine levels were few (P=0.02). Both quantitative and semi-quantitative analyses revealed that the severity of decreased myocardial BMIPP uptake was significantly correlated with serum free carnitine levels (quantitative analysis: r=-0.422, P<0.0012; semi-quantitative analysis: r=0.633, P<0.0001). In the presence of reduced carnitine uptake into the myocardium in HCM, there may also be reduced transport of acylcarnitines out of the myocardium into the plasma. Although inborn errors of fatty acid metabolism and carnitine deficiencies are reported to provoke secondary HCM and are associated with low serum carnitine concentrations, this study has revealed that the levels of carnitine are, in contrast, increased in idiopathic HCM. Moreover, serum carnitine concentrations are a sensitive indicator of the severity of impaired myocardial fatty acid metabolism even in asymptomatic patients with HCM.

Adolescent↗
PubMed1999

[Descriptive and analytical epidemiology of second primaries in Osaka, Japan].

With the improvement in survival of cancer patients, the incidence of second primaries has been increasing. Data from the Osaka Cancer Registry showed that the incidence of metachronous second primaries was associated with gender (male), age and calendar year at diagnosis of the first cancer. The 10-year cumulative risk was estimated at around 10% for those who developed their first cancer in their sixties in 1978-83. The observed number (O) of second primaries (including synchronous) was compared with the expected number (E). The O/E ratios among those who developed their first cancer at ages 0-14 and 15-29 years old were much higher than the ratios among all age groups. Patients who had developed cancer of the colon, larynx, lung, bladder, or breast (1978-86) showed a significantly higher than expected risk of developing second primaries during the 1-4 years after diagnosis of the first cancer. Based on the hospital cancer registry data from Osaka Medical Center for Cancer and Cardiovascular Diseases, associations between adjuvant chemo-immunotherapy and the risk of second primaries were examined among 1,925 gastric cancer patients who underwent curative gastrectomy. The sex-, age-, and stage-adjusted hazard rate ratio of second primaries was 1.04 for patients who underwent chemotherapy and 0.70 for patients who underwent chemo-immunotherapy, when compared with the risk for patients who did not receive adjuvant chemo-immunotherapy. Some chemotherapeutic agents appeared to increase the risk of second primaries. Second primaries among 2,824 breast cancer patients were examined and their associations with adjuvant chemo-immuno-radiotherapy were analyzed. The O/E ratio for cancers of all sites was 1.28, significantly higher than 1.0. Cancer of the stomach, colon, lung and ovary were frequently observed as a second primary among them. Among 117 patients who developed second primaries, 4 developed cancer of the corpus uteri. This corresponded to 1.89 times the expected, however, only one of the 4 patients underwent tamoxifen treatment. The O/E ratio for non-Hodgkin's lymphoma was 3.40, significantly higher than 1.0. These results suggest associations between the risk for non-Hodgkin's lymphoma and chemotherapy.

Adult↗
PubMed1998

Newly identified Chinese hamster ovary cell mutants are defective in biogenesis of peroxisomal membrane vesicles (Peroxisomal ghosts), representing a novel complementation group in mammals.

We isolated peroxisome biogenesis-defective mutants from Chinese hamster ovary cells by the 9-(1'-pyrene)nonanol/ultraviolet (P9OH/UV) method. Seven cell mutants, ZP116, ZP119, ZP160, ZP161, ZP162, ZP164, and ZP165, of 11 P9OH/UV-resistant cell clones showed cytosolic localization of catalase, a peroxisomal matrix enzyme, apparently indicating a defect of peroxisome biogenesis. By transfection of PEX cDNAs and cell fusion analysis, mutants ZP119 and ZP165 were found to belong to a novel complementation group (CG), distinct from earlier mutants. CG analysis by cell fusion with fibroblasts from patients with peroxisome biogenesis disorders such as Zellweger syndrome indicated that ZP119 and ZP165 were in the same CG as the most recently identified human CG-J. The peroxisomal matrix proteins examined, including PTS1 proteins as well as a PTS2 protein, 3-ketoacyl-CoA thiolase, were also found in the cytosol in ZP119 and ZP165. Furthermore, these mutants showed typical peroxisome assembly-defective phenotype such as severe loss of resistance to 12-(1'-pyrene)dodecanoic acid/UV treatment. Most strikingly, peroxisomal reminiscent vesicular structures, so-called peroxisomal ghosts noted in all CGs of earlier Chinese hamster ovary cell mutants as well as in eight CGs of patients' fibroblasts, were not discernible in ZP119 and ZP165, despite normal synthesis of peroxisomal membrane proteins. Accordingly, ZP119 and ZP165 are the first cell mutants defective in import of both soluble and membrane proteins, representing the 14th peroxisome-deficient CG in mammals, including humans.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1998

Adenovirus-mediated transfer of human acid maltase gene reduces glycogen accumulation in skeletal muscle of Japanese quail with acid maltase deficiency.

Acid maltase deficiency (AMD) causes a lysosomal glycogenosis inherited as an autosomal recessive trait. The infantile type of AMD (Pompe disease) leads to early death due to severe dysfunction of cardiac and respiratory muscles and no effective therapy is available. Replication-defective adenovirus vectors offer a promising tool for in vivo gene delivery and gene therapy. We constructed a recombinant adenovirus containing the human acid maltase (AM) cDNA downstream of the CAG promoter, composed of modified chicken beta-actin promoter and CMV IE enhancer (AxCANAM). Japanese quail with AMD was used for this study as an animal model for human AMD. When cultured fibroblasts from AMD quail were infected with AxCANAM, AM activity in the cells increased in proportion to the multiplicity of infection (MOI). When AxCANAM (4.5 x 10(8) PFU) was injected into unilateral superficial pectoral muscle of AMD quail, PAS staining showed that glycogenosomes disappeared and stainability of acid phosphatase was reduced in the injected area as compared with the contralateral muscle of the same birds. Biochemically, AM activity increased and glycogen content decreased in the injected muscle. Western blot analysis showed that AMD quail muscle injected with AxCANAM expressed human AM protein processed to active forms. These results suggest that the human AM cDNA transferred by an adenovirus vector was sufficiently expressed, leading to a marked reduction of the glycogen accumulation in the skeletal muscle of AMD quail.

Adenoviridae↗
PubMed1998

Effect of exercise-induced activation of sympathetic nerve activity on clearance of 123I-MIBG from the myocardium.

The effect of exercise on the cardiac kinetics of 123I-MIBG was investigated in the present study. 123I-MIBG was administered intravenously at rest in 6 healthy male volunteers, and anterior planar and SPECT images were obtained 15 minutes, and 2 and 4 hours after administration (protocol A). After 4 weeks, 123I-MIBG was again administered intravenously at rest, and images were obtained 15 minutes later. After imaging, the subjects ran 10 km in approximately 1 hour, and anterior planar and SPECT images were obtained 2 and 4 hours after administration of 123I-MIBG (protocol B). The heart-to-mediastinum uptake ratio (H/M) was calculated from each anterior planar image, and the mean 123I-MIBG clearance from 15 minutes to 2 hours, and from 2 hours to 4 hours was calculated with a bull's eye display. The H/M was much lower after exercise. The mean clearance rate between 15 minutes and 2 hours in protocol B was significantly higher than that between 2 hours and 4 hours, and that between 15 minutes and 2 hours in protocol A. It was concluded that the clearance rate of 123I-MIBG may be a useful index of cardiac sympathetic nerve activity.

3-Iodobenzylguanidine↗
PubMed1998

Early and delayed Tc-99m-tetrofosmin myocardial SPECT in patients with left bundle branch block.

UNLABELLED: To determine the utility of the myocardial tracer Tc-99m-tetrofosmin in the examination of patients with left bundle branch block (LBBB) and to investigate Tc-99m-tetrofosmin uptake and retention in the myocardium, early and delayed Tc-99m-tetrofosmin SPECT was performed in 10 patients having LBBB without coronary stenosis. METHODS: After 740 MBq of Tc-99m-tetrofosmin injection in the resting state, the early and delayed SPECT imaging was done at 30 min and 180 min, respectively. RESULTS: Decreased Tc-99m-tetrofosmin uptake in the septal segments was observed in 4 patients (40%) at 30 min and in 9 (90%) at 180 min. Reverse redistribution was seen in 9 of 10 patients. In patients with LBBB, the septal-to-lateral uptake ratio was lower in the delayed images than in the early images (0.80 +/- 0.09 vs. 0.89 +/- 0.09, p < 0.001). In patients with LBBB, the washout rate of Tc-99m-tetrofosmin was higher in the septal segments than in the lateral segments (28.3 +/- 4.3% vs. 22.8 +/- 3.3%, p < 0.001). CONCLUSION: The SPECT data indicate that in LBBB without coronary stenosis, the uptake of Tc-99m-tetrofosmin is decreased in the septal wall, and that reverse redistribution occurs frequently. Our results contribute to the elucidation of both the cellular biokinetics of Tc-99m-tetrofosmin in the myocardium and the hemodynamics of the septum in LBBB, and indicate the possible clinical utility of Tc-99m-tetrofosmin.

Adult↗
PubMed1998

Reverse redistribution of Tc-99m-tetrofosmin in exercise myocardial SPECT in patients with hypertrophic cardiomyopathy.

We examined the usefulness of Tc-99m-tetrofosmin in detecting exercise induced perfusion abnormalities in patients with hypertrophic cardiomyopathy (HCM) and to clarify time-related changes in myocardial distribution of Tc-99m-tetrofosmin after a single injection. We studied 44 consecutive patients with HCM by means of exercise/rest Tc-99m-tetrofosmin single photon emission computed tomography (SPECT). After injecting 370 MBq of Tc-99m-tetrofosmin at the peak exercise, the early SPECT imaging was performed at 30 min (EX-30) and the delayed imaging at 180 min (EX- 180). Immediately after the delayed imaging, 740 MBq of Tc-99m-tetrofosmin was injected in the resting state, and the rest SPECT imaging was performed 30 min later. Exercise-induced regional perfusion defects and/or apparent reversible left ventricular cavity dilation were identified in 26 (68.2%) of the 44 patients. When EX-30 images and EX-180 images were compared, reverse redistribution was confirmed in 36 patients (81.8%). Reverse redistribution was detected most frequently in the septal portion of the anterior wall, followed by the septal portion of the posterior wall and the septum. Exercise/rest Tc-99m-tetrofosmin myocardial imaging was a useful method for assessing myocardial perfusion abnormalities in patients with HCM. Reverse redistribution was detected very frequently on early and delayed images of exercise. We assumed that reverse redistribution may reflect a retention disorder of Tc-99m-tetrofosmin caused by some metabolic dysfunction of myocytes.

Cardiomyopathy, Hypertrophic↗