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Biomedical subjects

Y Takagi

Publications and source records attributed to Y Takagi.

At least 451 records · Page 25Linked to original sources

A 63-kilodalton cytosolic polypeptide involved in superoxide generation in porcine neutrophils. Purification and characterization.

A cytosolic protein essential for activation of the O2(-)-generating system in neutrophil membrane was highly purified from porcine neutrophils using conventional methods and high performance liquid chromatography. The molecular mass of the protein was estimated as 180 kDa by high performance gel permeation chromatography, and that of subunit as 63 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Partial amino acid sequence analysis of the 63-kDa polypeptide revealed that it corresponded to a 65-kDa human neutrophil cytosolic factor whose amino acid sequence was recently predicted from the cDNA clone (Leto, T. L., Lomax, K. J., Volpp, B. D., Nunoi, H., Sechler, J. M. G., Nauseef, W. M., Clark, R. A., Gallin, J. I., and Malech, H. L. (1990) Science 248, 727-730). Antibody raised against the porcine 63-kDa polypeptide reacted with a 65-kDa polypeptide in human neutrophils. Neither heme nor flavin was detected in the protein, yet it induced O2- generation when combined with neutrophil membrane in the presence of other cytosolic factors. Furthermore, the antibody diminished the activating effect of cytosol on O2- generation in a cell-free system. Thus, the protein is essential to activate the O2(-)-generating system in neutrophils, acting as a modifier rather than as an electron transport component.

Amino Acid Sequence↗

Purification and identification of a growth factor produced by Paramecium tetraurelia.

We previously reported that the jumyo mutant of a cilate protozoan Paramecium tetraurelia excretes into the medium a factor which promotes its own cell division. Here, the factor was purified to electrophoretic homogeneity through a series of liquid chromatographic procedures. This substance is a protein with a molecular weight of 17,000 which at concentrations of 1 X 10(-9) M (17 ng/ml) or more results in the recovery of the cell division rate of the jumyo mutant to the level of the wild type. The factor is therefore considered to be a growth factor and was named Paramecium growth factor (ParGF). This is the first report of direct proof for the production of a growth factor in an organism other than vertebrates.

Animals↗

[Determination of the normal range of serum LH and FSH levels in normal adult males--comparison with IRMA and RIA].

To determine the normal range of serum LH and FSH levels, blood samples from 53 normal adult males were measured by a double antibody radioimmunoassay system and a new immunoradiometric assay (IRMA) system. It was necessary to evaluate the individual pulsatile secretion and the differences in measured values among laboratories to determine the normal range. Therefore, in 53 normal adult males lacking any evidence of hormonal abnormalities, blood was sampled at 9:00 a.m. daily for 3 days, and these samples were measured in 3 laboratories. The result of the hormone concentration of blood sample was not appropriate as the normal range because of the high amplitude of LH and FSH pulses. Coefficient values (CV) between the mean value of the first two samples and the mean value of all three samples were small. Therefore, the mean value of the first two samples was clinically accurate for use as the normal range. Significant differences in measured values were observed among the 3 laboratories. The normal range, which included individual pulsatile secretion, and the differences in measured values among the laboratories was as followings: LH (RIA): 7.6-13.7 mIU/ml, LH (IRMA): 2.1-4.7 mIU/ml, FSH (RIA): 4.7-9.5 mIU/ml, FSH (IRMA): 3.0-7.4 mIU/ml. The serum LH and FSH levels of 68 untreated male infertility patients tended to rate high with respect to our normal range. It was considered that the normal range determined in this study was useful for clinical management.

Adult↗

Autocrine effect of endothelin on DNA synthesis in human vascular endothelial cells.

To elucidate the role of endogenous endothelin on DNA synthesis in endothelial cells, we have investigated the effects of rabbit anti-ET gamma globulin on DNA synthesis in cultured human vascular endothelial cells. DNA synthesis was markedly inhibited by anti-ET gamma globulin in a concentration dependent manner in the presence of fetal calf serum(FCS) (x5000;34%, x2500;54%, x1000;70%), but not in the absence of FCS. These data suggest that endogenous ET modulates FCS-stimulated DNA synthesis in an autocrine fashion.

Animals↗

Rapid Ca2+ refilling system of intracellular store(s) in human vascular endothelial cells.

Using a fura-2 method, cytosolic Ca2+ concentration [( Ca2+]i) was measured in endothelial cell monolayers from human umbilical vein. In the presence of 1.5 mM Ca2+, bradykinin (BK) induced a rapid (within 15 sec) and dose-dependent (10(-8)-10(-6) M) increase in [Ca2+]i, consisting of an initial peak and a subsequent sustained phase. The pretreatment with 3 mM EGTA for 1 min caused a significant reduction in [Ca2+]i levels both of the basal (p less than 0.05) and BK-stimulated initial peak (p less than 0.001). However, the BK-stimulated initial peak was retained in magnitude for at least 5 min under the treatment with EGTA. In contrast, the sustained phase was completely abolished by EGTA treatment. The BK-stimulated Ca2+ transient, once having been completely inhibited by ionomycin (10(-6) M) in the presence of EGTA, was rapidly (within 2 min) recovered to the untreated level by replacing it with fresh medium containing 1.5 mM Ca2+. The present results indicated that BK mobilized Ca2+ from both intracellular and extracellular space(s) and suggest the presence of an extracellular Ca2(+)-dependent rapid refilling system of intracellular Ca2+ store(s) in human vascular endothelial cells.

Benzofurans↗

Structural characterization of the human estrogen synthetase (aromatase) gene.

The estrogen synthetase (aromatase, cytochrome P-450AROM) gene has been isolated from human genomic libraries and characterized. The restriction map of 43 positive clones obtained indicated that this enzyme is present as a single copy gene. The aromatase gene is unexpectedly large compared with other forms of the cytochrome P-450 superfamily, spanning at least 70 kilobases. The gene consists of 10 exons and its 5'-untranslated region is divided into 2 exons by an intron of more than 35 kilobases long. This organization of the first exon in the aromatase gene is unique in the cytochrome P-450 superfamily. All the exon-intron junctional sequences conform to the canonical GT/AG rule. The sequences of a TATA box and a CAAT box are present 27 and 83 base pairs upstream from the transcriptional initiation site. Within 3 kilobases upstream from the initiation site, there are no typical consensus sequences of responsive elements for glucocorticoid and c-AMP, which regulate aromatase expression.

Aromatase↗

Zinc in clinical surgery--a research review.

Among the essential trace elements in mammals, zinc is somewhat unique in that it is a constituent of numerous metallo-enzymes having biologic significance in many respects. The discovery of zinc deficiency in man induced the remarkable progress of studies on its physiology and it is now recognized that zinc deficiency manifests itself differently in different areas of clinical medicine. It also appears reasonable to say that no trace elements have been more closely related to surgery than zinc. We discuss herein, its significance, implications and role in such areas as; (1) wound healing: where the usefulness of zinc for promoting wound healing in the presence of low plasma zinc levels has been firmly established; (2) total parenteral nutrition (TPN); zinc free TPN may cause skin eruptions associated with abdominal symptoms presenting a picture closely resembling that of acrodermatitis enteropathica; (3) specific pathological conditions: patients with Crohn's disease and other benign diseases accompanied by mal-digestion or -absorbtion are often predisposed to zinc deficiency, similar to those manifesting clinical signs in the early stage of TPN; and (4) surgical stress: which triggers the release of various mediators, possibly increasing hepatic zinc deposition and decreasing plasma and skin zinc levels.

Humans↗

Immunohistochemical localization of alpha 2HS glycoprotein in dentin.

Monoclonal antibody against bovine serum alpha 2HS glycoprotein was raised in mice and the localization of this glycoprotein in bovine and human teeth was examined by immunohistochemical techniques on undemineralized ground sections after surface etching with dilute HCl. Positive reactions were found in both bovine and human peritubular dentin, whereas virtually negative staining was detected in the intertubular dentin. When the ground section was examined without surface etching, no reaction was found in any area of mineralized dentin. These results suggest that alpha 2HS glycoprotein is present mainly in the peritubular dentin associated with the mineral phase. The presence of this component in dentin may not be due simply to nonspecific binding to calcium phosphate crystals.

Animals↗

The effect of metronidazole on TPN-associated liver dysfunction in neonates.

The effect of metronidazole (MNZ) on hepatic dysfunction associated with total parenteral nutrition (TPN) in neonates was investigated. Neonates receiving TPN for more than 2 weeks were divided into three groups. In group 1, TPN was given alone, in group 2, 25 mg/kg/d of MNZ was administered intravenously for the first 2 weeks of TPN, and in group 3, 50 mg/kg/d of MNZ was given for the first 3 weeks of TPN. Several parameters of liver function tests (LFTs) during the first 4 weeks of TPN were compared among these three groups. There was no significant difference of these parameters between group 1 and group 2. Although there was no significant difference of alkaline phosphatase, gamma-glutamyl transpeptidase, direct bilirubin, and total bile acid between groups 1 and 3, transaminase (glutamic oxaloacetic, glutamic pyruvic) of group 3 remained significantly lower than those of group 1. In conclusion, the administration of MNZ 50 mg/kg/d for 3 weeks, at least, prevented the elevation of transaminase during TPN in neonates, suggesting the possible involvement of intestinal anaerobic flora in the pathogenesis of TPN-associated liver dysfunction.

Cholestasis, Intrahepatic↗

The cellular mechanism of action by vasoconstrictor hormones in cultured rat vascular smooth muscle cells.

The effects of angiotensin (Ang) II, arginine vasopressin (AVP), and serotonin (5-HT) on inositol trisphosphate (IP3) production, cytosolic Ca2+ concentration [( Ca2+]i), and the phosphorylation of 20 kilodalton myosin light chain (MLC) were examined in cultured rat vascular smooth muscle cells (VSMC). These vasoconstrictors immediately induced dose-dependent and concomitant increases in IP3 production, [Ca2+]i, and phosphorylation of 20 kDa MLC. The agonist-induced increases in IP3 production, [Ca2+]i, and phosphorylation of 20 kDa MLC in VSMC were completely blocked by pretreatment with the receptor antagonists for Ang II, V1, and 5-HT2, respectively. These data suggest that receptor-mediated increases in IP3 production, [Ca2+]i, and phosphorylation of 20 kDa MLC by these vasoconstrictors are closely interrelated.

Angiotensin II↗

[Therapeutic evaluation of male infertility--the increase of seminal transferrin level and the improvement in sperm concentration following administration of clomiphene citrate].

This study was designed to evaluate the functional changes of Sertoli cells following the administration of clomiphene citrate for male infertility. Sperm count and seminal transferrin level were measured before and after the treatment in 22 cases of oligozoospermia (sperm count: less than 20 X 10(6)/ml) and 14 cases of subnormal sperm count group (sperm count: 20-30 X 10(6)/ml). Clomiphene citrate was administered per os for more than 3 months consecutively in a dose of 25 mg/day. Seminal transferrin concentration increased more than 1.5 times compared with pre-treatment level in 6 cases (16.7%). Among these patients, sperm count markedly increased (20 X 10(6)/ml or more than the pre-treatment level) in 3 cases (50%) and slightly increased (10 X 10(6)/ml or more than pre-treatment) in 1 case (16.7%). In 30 cases, in which seminal transferrin level did not increase, sperm count markedly increased in 6 cases (20%) and slightly increased in 6 cases (20%). Thus, sperm count was improved more frequently in the cases in which seminal transferrin level remained elevated than the cases with no elevation of serum transferrin level. Serum FSH level of patients whose seminal transferrin level remained elevated after the treatment was significantly higher than that of patients with no elevation of serum transferrin level (mean +/- SD = 32.8 +/- 18.0 mIU/ml v.s. 14.4 +/- 11.7 mIU/ml, respectively). These data suggested that the activation of Sertoli cells may contribute to the increase of sperm count following the administration of clomiphene citrate and the elevated seminal transferrin secretion may be related to the increase of serum FSH level following this treatment.

Clomiphene↗

[Statistical evaluation of determinants of progression of superficial bladder cancer by proportional hazards model].

To evaluate clinical and pathological factors present at the initial consultation which affect disease progression, we reviewed data from 223 patients with superficial bladder cancer (pTa and pT1) who were initially treated at Nagoya University Hospital between January 1973 and December 1987. The factors included in the present analysis were age, sex, symptoms, interval between initial symptoms and first consultation, location of tumor, size, number, endoscopic shape, histological pattern of growth, grade and stage. The median duration of the follow-up after initial treatment was 46 months. Of the 223 patients, 17 died: 8 (3.6%) of bladder cancer and the remaining 9 (4.0%) of unrelated causes. Disease progression developed in 12 patients (5.4%): muscle invasion of the bladder wall in 11 and lung metastasis in one. The interval between initial treatment and progression ranged from 4 to 108 months, with a median of 11.5 months. Of the 12 patients, 9 (75%) had disease progression within 2 years. Progression was significantly associated with poor prognosis (p less than 0.001): the 5-year actuarial survival rates were 47.1% and 92.8% in patients with and without progression, respectively. Univariate analysis by Cox's proportional hazards model demonstrated that characteristics such as irritative bladder symptoms, higher-grade tumors, invasion into lamina propria, and nonpapillary growth seen at initial consultation were significantly related to disease progression. Cox's proportional hazards model produced hazard ratios of 10.2 in irritative bladder symptoms (yes vs. no), 6.3 in histological grade (grade 3 vs. grades 0-2), 4.9 in stage (pT1 vs. pTa), and 4.7 in pattern of growth (papillary vs. nonpapillary).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Hypertension and cardiovascular diseases in an epidemiological study in Hokkaido, Japan.

The present study describes the results from the 10-year follow-up data of a prospective epidemiological study for hypertension and cardiovascular diseases in two communities of rural agricultural districts in Hokkaido, Japan. The number of incidences of cerebrovascular accidents (CVAs) in persons who were normotensive, borderline hypertensive (BHT), untreated hypertensive (HT), well-controlled HT [blood pressure (BP) less than 150/90 mm Hg], and poorly controlled HT (BP greater than or equal to 150/90 mm Hg) were 0.46, 3.24, 4.17, 3.49, and 12.76 per 1,000 person-years. respectively: CVAs were markedly high in poorly controlled HT persons. The winter-summer mean BP differences in the first year were significantly and positively correlated with the differences in mean BP between the tenth and the first year, and were significantly higher in the progression to hypertension group than in the nonprogression group in both towns. Multivariate analysis indicated that the winter-summer mean BP difference was a significant variable for indication of progression to hypertension. From these results, we concluded that (a) good control of hypertension could considerably prevent CVA, (b) cold environment may contribute to the progression to hypertension, and (c) winter-summer variation in BP may predict the future course of BP.

Acute Disease↗

[Effects of prostaglandin E1 on cerebral blood flow, cerebrospinal fluid pressure, and spinal subarachnoidal compliance].

In enflurane-anesthetized subjects, controlled hypotension was induced by the intravenous administration of prostaglandin E1 (PGE1), and its effects on the cerebral blood flow (CBF) and intracranial pressure (ICP) were investigated by using changes in the flow velocity of the ophthalmic artery (OPA) and cerebrospinal fluid pressure (CSFP) as indices, respectively. After measurements of these hemodynamic variables, the spinal subarachnoidal compliance was also determined, and its relationship with the flow velocity in the ophthalmic artery and CSFP was investigated. The results of the study suggest that PGE1 causes no significant changes in CSFP and that cerebral blood flow is well-maintained despite a reduction in cerebral perfusion pressure.

Alprostadil↗

[Intra-arterial infusion of cisplatin and caffeine for a recurrent malignant fibrous histiocytoma].

We treated a 43-year-old man with recurrent malignant fibrous histiocytoma in right distal femur with intra-arterial infusion of cisplatin and caffeine 5 years after wide excision and chemotherapy. At the time of the first recurrence in the lateral aspect of thigh, intra-arterial infusion of CDDP (120 mg/m2) was ineffective. We treated him with radiation (7000 rad), and there was no evidence of tumor by radiological evaluation. The second local recurrence was treated with intra-arterial infusion of CDDP (120 mg/m2/1 hour) and caffeine (1.2 g/m2/24 hours x 3 days), and the tumor disappeared, radiologically and histologically. Caffeine did not increase the nephrotoxicity of CDDP, and no insomnia nor palpitation was seen. Intra-arterial infusion of CDDP and caffeine could be useful to increase the effect of CDDP for regional chemotherapy.

Adult↗