Search PubMed⌕ Search

Biomedical subjects

Y Numata

Publications and source records attributed to Y Numata.

At least 37 records · Page 2Linked to original sources

Identification of two closely related genes, inducible and noninducible carbonyl reductases in the rat ovary.

Two closely related cDNAs encoding carbonyl reductase (CR) were isolated from the rat ovary and testis. One (inducible CR, iCR) was rapidly and strongly induced in the ovary by pregnant mare serum gonadotropin (PMSG), whereas the other (non-inducible CR, nCR) was constitutively expressed in the ovary and was not induced by PMSG. Both genes were also expressed in the rat testis. The cDNAs of rat iCR and nCR encode highly homologous proteins (86% identity in amino acid) with 277 and 276 amino acid residues, respectively. However, the 5'-upstream regions flanking respective genes are completely unrelated to each other except for a short (38 bp) overlap. These results indicate the presence of two closely related but differently regulated CR genes in rat gonadal tissues. Strong induction of iCR by PMSG suggests the importance of the gene in the ovarian follicular development.

Alcohol Oxidoreductases↗

New sandwich ELISA for human urinary N-acetyl-beta-D-glucosaminidase isoenzyme B as a useful clinical test.

We have developed a new ELISA for quantifying N-acetyl-beta-D-glucosaminidase (NAG) isoenzyme B in human urine after raising monoclonal antibodies against the isoenzyme from human placenta. Though the obtained antibodies reacted not only to isoenzyme B but also to A, we could detect isoenzyme B selectively by a two-step sandwich ELISA with a pair of selected antibodies at low pH in the first reaction. The detected limit was 0.5 microgram/L for a sample volume of 25 microL. Within-run CVs ranged from 2.5% to 5.4% and between-run CVs ranged from 6.2% to 9.1%. Recoveries of NAG isoenzyme B added to each of three urine samples ranged from 91% to 114%. The dilution curves of urine samples showed good linearity. The cross-reactivity of NAG isoenzyme A was practically negligible (2-3%). The mean value for NAG isoenzyme B in spot urines from healthy adults was 2.9 micrograms/g creatinine. This ELISA method is rapid and precise enough for routine determination of NAG isoenzyme B in human urine.

Acetylglucosaminidase↗

Biotinylated hyaluronan: a versatile and highly sensitive probe capable of detecting nanogram levels of hyaluronan binding proteins (hyaladherins) on electroblots by a novel affinity detection procedure.

Hyaluronan influences cellular proliferation and migration in developing, regenerating and remodelling tissues and in tissues undergoing malignant tumour-cell invasion. The widespread occurrence of hyaluronan-binding proteins indicates that the recognition of hyaluronan is important to tissue organisation and the control of cellular behaviour. A number of extracellular matrix and cellular proteins, which have been termed the hyaladherins, have specific affinities for hyaluronan. These include cartilage link-protein, hyaluronectin, neurocan, versican and aggrecan, which all bind to HA within the extracellular matrix. Cellular receptors for hyaluronan such as CD44 and RHAMM (receptor for hyaluronate-mediated motility) have also been identified. In the present study biotinylated hyaluronan (bHA) was prepared by reacting adipic dihydrazide with a 170 kDa hyaluronan sample using the bifunctional reagent 1-ethyl-3-[3-(dimethylamino) propyl] carbodiimide. The resultant free amine moeity of the hydrazido-hyaluronan was then reacted with biotin succinimidyl ester (sulfo-NHS-biotin) to prepare the bHA. After 4-20% gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and electroblotting to nitrocellulose membranes, bHA and avidin alkaline phosphatase conjugate could be used in conjunction with nitroblue tetrazolium/5-bromo-4-chloro-3-indolyl phosphate substrates to specifically visualise with high sensitivity (> or = 2 ng), bovine nasal cartilage link-protein, aggrecan hyaluronan binding region, and human fibroblast hyaluronan receptors such as CD-44. Conventional Western blotting using specific monoclonal antibodies to these proteins was also used to confirm the identities of these proteins.

Aggrecans↗

Modulation of sensitivity to mitomycin C and a dithiol analogue by tempol in non-small-cell lung cancer cell lines under hypoxia.

We examined the mechanisms involved in the bioactivation of mitomycin C (MMC) and a newly developed MMC analogue: 7-N-(2-([2-(gamma-L-glutamylamino)ethyl]dithio)ethyl)mitomycin C, KW-2149, in non-small-cell lung cancer (NSCLC) cell lines under aerobic and hypoxic conditions. To investigate these mechanisms, we used MMC-resistant non-small-cell lung cancer cell lines (PC-9/MC4) that had been established in our laboratory from the parent PC-9 cell line by continuous exposure to MMC. We previously reported that the MMC-resistant cell line (PC-9/MC4) was poor in NAD(P)H dehydrogenase (quinone) activity and approximately 6-fold more resistant than the parent cells (PC-9) to MMC on 2-h exposure under aerobic conditions. In this study, the subline PC-9/MC4 was 6.7-fold more resistant to MMC than PC-9, the parent cell line, under aerobic conditions, and 5.2-fold more resistant under hypoxic conditions after 2-h exposure to MMC. However, on co-incubation with tempol, an inhibitor of the one-electron reduction pathway, the sensitivity of PC-9/MC4 to MMC was impaired under hypoxic conditions, but the impairment was not evident under aerobic conditions. KW-2149, the newly developed MMC analogue, was cytotoxic for both PC-9/MC4 and PC-9 cells, and the sensitivity of both cell lines to KW-2149 was not changed by exposure to hypoxic conditions or by coincubation with tempol. There were no significant differences in the intracellular uptake of MMC and the activities of cytosolic detoxification enzymes between the PC-9 and PC-9/MC4 cell lines. These results support the hypothesis that the one-electron reduction pathway plays a partial role in the bioactivation of MMC, but not of KW-2149, and that KW-2149 is excellent at circumventing resistance to MMC in NSCLC.

Antineoplastic Agents↗

Hypothalamic-pituitary-adrenal axis in WBN/Kob rats with non-insulin dependent diabetes mellitus.

In an attempt to define the hypothalamic-pituitary-adrenal (HPA) axis in non-insulin dependent diabetic rats (WBN/Kob), we measured plasma corticotropin releasing factor (CRF), as well as arginine vasopressin (AVP), ACTH, and corticosterone (B), CRF concentrations in the median eminence (ME), the remainder of the hypothalamus (rHY) and the neurointermediate lobe of the pituitary (NIL). We also measured Iodine-125-labeled ovine CRF ([125I]oCRF) binding in the brain and peripheral tissues. Body and thymus weight in WBN/Kob rats were significantly lower than in control Wistar rats, but adrenal weight was higher in WBN/Kob rats. Plasma ACTH levels were significantly higher in WBN/Kob rats than in the control rats. However, plasma CRF, AVP and B levels in WBN/Kob rats were not different from those in the control rats. The CRF concentration was significantly decreased in the ME of the diabetic rats, compared with control rats, but CRF concentrations in the rHY and NIL were unchanged in the two groups. A significant reduction in [125I]oCRF binding in the anterior pituitary was demonstrated in WBN/Kob rats, but no significant difference between the diabetic and control rats in CRF binding was observed in the frontal cortex, spleen or adrenal gland. These findings suggest that the HPA axis is chronically stimulated in the non-insulin dependent diabetic rats.

Adrenal Glands↗

Secretion of anterior pituitary hormones in patients with insulin-dependent diabetes mellitus and polyglandular autoimmune syndrome.

We extracted gammaglobulins from the serum of 10 patients with insulin-dependent diabetes mellitus (IDDM) to investigate their effect on anterior pituitary hormone secretion using cultures of rat anterior pituitary cells. Three of the 10 patients also had the polyglandular autoimmune syndrome (PGA) type III with an isolated failure of anterior pituitary hormone secretion. The gammaglobulin from each of the 3 patients with PGA and an isolated failure of secretion of adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH) or gonadotropin inhibited the secretion of ACTH, TSH or gonadotropin in cultures of rat anterior pituitary cells. The gammaglobulins obtained from the other 7 patients with IDDM also showed an inhibitory or stimulatory effect on anterior pituitary hormone secretion in vitro. We postulate that some patients with IDDM, especially those with other endocrine autoimmune diseases, may have substances in their gammaglobulin fraction that can affect the secretion of anterior pituitary hormones.

Adrenocorticotropic Hormone↗

Angiotensin converting enzyme as a genetic risk factor for coronary artery spasm. Implication in the pathogenesis of myocardial infarction.

It has been reported that individuals with the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene are at greater risk for myocardial infarction (MI), especially among subjects normally considered to be at low risk. However, little is known about the mechanism by which the ACE polymorphism affects the risk of MI. Coronary artery spasm (CAS) is considered to be one possible mechanism for developing MI. We therefore examined the ACE polymorphism relation to CAS to determine if this was the mechanism by which the DD genotype influences MI. We studied 150 angiographically assessed Japanese males, all more than 60 yr old. CASs were detected using intracoronary injection of ergonovine maleate. Subjects were divided into three groups: those with CAS (group 1), those without CAS, but with fixed organic stenosis (group 2); and those without CAS and no organic stenosis (group 3). DD subjects were significantly represented in group 1 when compared with groups 2 (P = 0.002) and 3 (P = 0.026). These results suggest that the DD genotype relates to the greater risk for MI in the patients with CAS.

Aged↗

Effect of the initial bolus volume of recombinant tissue-type plasminogen activator on coronary recanalization and infarct size in Japanese acute myocardial infarction patients. Kumamoto University Myocardial Infarction Study (KUMIS) Group.

Coronary recanalization rate and infarct size were compared between 2 different methods of intravenously administering recombinant tissue-type plasminogen activator (rt-PA) 41.4 mg; 1) an initial bolus dose of 30% followed by infusion of the remainder over 60 min (30% group), and an initial bolus dose of 10% followed by infusion of the remainder over 60 min (10% group). Thirty min after beginning rt-PA infusion, the coronary recanalization rate was higher in the 30% group than in the 10% group (82.9% (34/41) vs 53.7% (22/41), p < 0.01). The peak creatine kinase and peak creatine kinase-MB levels were lower in the 30% group than in the 10% group. We conclude that a higher initial bolus dose of rt-PA gives a higher rate of recanalization of the infarct-related artery at the very early phase, and probably leads to a smaller infarct size.

Aged↗

Abrupt-onset diabetes mellitus in the elderly.

We present three elderly Japanese patients with abrupt onset of diabetes mellitus: a 61-year-old male with a complete defect of insulin secretion without insulin resistance, a 60-year-old male with an incomplete defect of insulin secretion associated with insulin resistance, and a 69-year-old female with a complete defect of insulin secretion and insulin resistance. The findings in these cases indicate the heterogeneity in insulin secretion and sensitivity of abrupt onset diabetes mellitus in the elderly. The changes in insulin secretion and sensitivity over time due to glucose toxicity may at least partially explain the heterogeneity.

Aged↗

[The relationship between the improvement of cardiac function and the myocardial uptake of I-123 metaiodobenzylguanidine in patients with dilated cardiomyopathy treated by beta-blocker].

Chronic beta-blocker therapy improves hemodynamics and cardiac function in patients with idiopathic dilated cardiomyopathy. However, the change in myocardial uptake of I-123 metaiodobenzylguanidine (123I-MIBG) before and after treatment has not been determined. Myocardial imaging with 123I-MIBG was performed before and 2 or 3 months after beta-blocker (bisoprolol) therapy in 11 patients with dilated cardiomyopathy. The following parameters were compared before and after the treatment: 1) New York Heart Association functional class, 2) X-ray cardiothoracic ratio, 3) heart rate and blood pressure, 4) echocardiographic data (left ventricular end-diastolic and end-systolic diameters, and left ventricular ejection fraction), 5) plasma concentrations of epinephrine, norepinephrine and human atrial natriuretic peptide (HANP), and 6) exercise tolerance time by treadmill. The heart-to-mediastinum ratio of 123I-MIBG activities obtained 3 hours after intravenous injection (late H/M) and washout rate improved significantly after beta-blocker therapy. Cardiothoracic ratio, heart rate, echocardiographic parameters, HANP and exercise tolerance also improved significantly. Late H/M had no significant relationship with any of the clinical parameters, but washout rate was significantly related to left ventricular ejection fraction. These findings suggest that washout rate may be useful to assess the effect of short-term beta-blocker therapy in dilated cardiomyopathy patients.

3-Iodobenzylguanidine↗

[A case of successful treatment of chronic sternal osteomyelitis and mediastinitis after ascending aorta and hemiarch reconstruction].

Mediastinitis is one of severe and fatal complications after cardiac surgery, especially in the presence of a prosthetic graft. A 70-year-old male, who was suffered from chronic sternal osteomyelitis and mediastinitis after ascending aorta and hemiarch reconstruction was reported. He developed high fever and leucocytosis on the 16th postoperative day. Wound culture was positive for Grampositive organisms. He was diagnosed as having sternal osteomyelitis and mediastinitis and treated by sternal bone debridement and irrigation with dilute povidone iodine solution with no effects. Total excision of the infected sternum, irrigation with non-diluted solution of povidone iodine and omental transfer were performed successfully. The literature regarding omental transfer for mediastinitis and infected prosthetic grafts was briefly reviewed.

Aged↗

DT-diaphorase as a determinant of sensitivity to adriamycin in non-small-cell lung-cancer cell lines.

We have reported the establishment of a mitomycin-C (MMC)-resistant non-small-cell lung-cancer cell line, PC-9/MC4. As determined by an MTT assay, this resistant cell line was found to be 4 times more sensitive to adriamycin (ADM) than was the parental PC-9. There were no significant differences in sensitivity to etoposide, mitoxantrone, daunomycin, epirubicin, pirarubicin, 9-aminoanthracycline or 3'-deamino-3'-morpholino-13-deoxo-10-hydroxy carminomycin. These data suggest that neither qualitative or quantitative changes in DNA topoisomerase II nor the enhanced repair of DNA can explain the differing sensitivity to ADM observed. No significant differences were found in the accumulation of ADM and glutathione (GSH) in these cell lines. Although total glutathione-S-transferase (GST) activity in PC-9/MC4 cells was lower than that observed in PC-9 cells and treatment with ethacrynic acid (EA) reduced sensitivity to ADM in both cell lines, relative resistance was unaffected. NADH-cytochrome b5 reductase (B5R) activity in PC-9/MC4 cells showed a 3-fold greater decrease than that in PC-9 cells, and DT-diaphorase (DTD) activity in PC-9/MC4 cells showed an approximately 200-fold greater decrease than that in PC-9 cells. Addition of dicumarol, an inhibitor of DTD, decreased the sensitivity of ADM of PC-9 but not of PC-9/MC4. DTD activity in the PC-9 cell line was inhibited by treatment with dicumarol while in PC-9/MC4 it remained unchanged. These data suggest that DT-diaphorase is a determinant of sensitivity to ADM in the 2 cell lines.

Adenocarcinoma↗

The effects of orally administered calcium pentosan polysulfate on inflammation and cartilage degradation produced in rabbit joints by intraarticular injection of a hyaluronate-polylysine complex.

OBJECTIVE: To determine the antiinflammatory and cartilage-protecting activities of orally administered calcium pentosan polysulfate (CaPPS) in a rabbit model of inflammatory arthritis. METHODS: A single intraarticular injection of a preformed polycation complex (PC) of poly-D-lysine and hyaluronan was used to induce joint inflammation; saline was injected into the contralateral joint as a control. Animals were killed 1, 4, 7, or 10 days post-PC injection. CaPPS, at 5 mg/kg, 10 mg/kg, or 75 mg/kg, was given every 48 hours commencing 7 days prior to PC injection. Serum interleukin-6 (IL-6), synovial fluid (SF) prostaglandin E2, cell numbers, and cartilage proteoglycan (PG) content, composition, and biosynthesis were determined for PC- and saline-injected joints. RESULTS: In PC-injected, non-drug-treated animals, serum IL-6 activity, SF leukocyte numbers, and prostaglandin E2 levels were elevated, while cartilage PG content and biosynthesis were reduced. CaPPS at 10 mg/kg, but not at 5 mg/kg, decreased serum IL-6 levels but maintained cartilage PG concentration and biosynthesis. However, SF leukocyte counts and prostaglandin E2 levels (except on day 1) were not reduced. CONCLUSION: The ability of CaPPS to attenuate serum IL-6 levels and preserve cartilage PGs in inflamed rabbit joints suggests that this substance could be of value as an effective orally administered chondroprotective, antiarthritic drug.

Administration, Oral↗

Gelatinases and metalloproteinase inhibitor secreted by murine colonic carcinoma cells with differing metastatic potential.

Gelatinase activity and inhibitory activity against collagenase were measured in serum-free medium conditioned by murine colonic carcinoma cells with different spontaneous metastatic potentials to the lung. The medium conditioned with poorly metastatic NM11 cells gave higher inhibitory activity than that conditioned with highly metastatic LuM1 cells, while the level of secreted gelatinases in the same medium was lower in NM11 medium than in LuM1 case. Northern analysis showed the higher gene expression of both tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 in NM11 cells than in LuM1 cells, suggesting that both TIMPs are responsible for the increase of inhibitory activity in NM11 conditioned medium. Examination of the balance of gelatinases and inhibitor revealed that the amount of inhibitor exceeded that of gelatinases in the medium conditioned with NM11 cells. In contrast, the medium conditioned with LuM1 cells contained excess amounts of gelatinases. The results indicated a close correlation between the balance of gelatinases and inhibitors and the metastatic behavior of murine tumor cells.

Animals↗

Plasma CRH response to water immersion-restraint stress in rats bearing a hypothalamic knife cut.

We reported earlier that the plasma level of corticotropin-releasing hormone (CRH) remained high 120 min after the onset of such strong sustained stress as ether-laparotomy or water immersion-restraint, which reflected the persistent secretion of CRH from the hypothalamic median eminence (ME). We investigated the change in plasma CRH during water immersion-restraint stress in rats bearing an anterolateral cut around the medial basal hypothalamus (MBH) which cuts the CRH neurons from the PVN to the ME. Concentrations of CRH in the hypothalamus, extrahypothalamic tissues and peripheral blood were measured by radioimmunoassay. Plasma ACTH was measured with an immunoradiometric assay kit. Plasma baseline ACTH and CRH concentrations did not differ significantly in the sham vs. cut groups. At 120 min after the onset of stress, plasma ACTH concentrations were definitely higher in both groups. In the cut group, plasma CRH at 120 min after stress did not differ significantly from the baseline level, whereas plasma CRH at 120 min was definitely higher in the sham group. Baseline CRH concentrations in the ME did not differ greatly in the two groups. CRH concentrations in the ME of both groups had decreased appreciably 120 min after the onset of stress as compared with baseline CRH, and the CRH decrease was greater in the cut group than in the sham group. CRH in the neurointermediate lobe (NIL) and adrenal gland of both groups showed no significant change at 120 min, compared with the control. These findings confirm that the continuous CRH increase in plasma during sustained stress is derived mainly from the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Four patients with polyendocrinopathy with associated pituitary hormone deficiency.

Four cases of polyglandular endocrine disorders associated with pituitary hormone secretion failure are reported. Three of them had both insulin dependent diabetes mellitus (IDDM) and Hashimoto's disease. Each of these patients (cases 1-3) showed isolated deficiency of ACTH, TSH or gonadotropin, respectively. Another patient (case 4) had both Hashimoto's disease and isolated ACTH deficiency. Anti-pituitary antibody to AtT-20 cells was detected in case 1. Serum gamma-globulins from patients 1 and 4 attenuated corticotropin releasing hormone-induced ACTH release in monolayer cultured rat anterior pituitary cells. Gamma-globulins from patients 1 and 2 decreased baseline TSH release but stimulated baseline prolactin release in pituitary cell cultures. It is possible that pituitary hormone deficiency in these patients may be caused by autoimmune disorders.

Adrenocorticotropic Hormone↗

Alexithymia and defense mechanisms in myocardial infarction.

The relationship between alexithymia and defense mechanisms was examined among 66 patients with myocardial infarction. Alexithymia was greater among patients with acute myocardial infarction than among those with old myocardial infarction. Alexithymia was correlated with scores on measures of the defense mechanisms of denial, negation, repression, and reaction formation. The results suggest the possibility that alexithymia may be evident when effective coping mechanisms are employed to minimize the severity of perceived threats or conflicts.

Adaptation, Psychological↗