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Biomedical subjects

N Kinoshita

Publications and source records attributed to N Kinoshita.

At least 19 recordsLinked to original sources
PubMed1992

Protein phosphatases and cell division cycle control.

Fission yeast has at least ten protein phosphatase genes that appear to play distinct roles in cell cycle control. Because of functional overlap, a clear lethal phenotype can be obtained only after multiple genetic alterations. Cells that have lost the protein phosphatase 1 (PP1)-like dis2/sds21 phosphatase activities prematurely enter mitosis and remain in a defective mitotic state with high H1 kinase activity and without sister chromatid disjunction. The same phenotype can be obtained in the presence of hydroxyurea. Overexpression of PP1-like phosphatase, on the other hand, delays the entry into mitosis. Cells that have lost PP2A-like ppa2 phosphatase activity also prematurely enter mitosis with a reduction in cell size. This semi-wee phenotype is enhanced in delta ppa2 mutants treated with the phosphatase inhibitor, okadaic acid. Genetic interactions between ppa2 and mitotic regulators suggest that ppa1/ppa2 phosphatase may directly or indirectly inhibit p34cdc2/cyclin kinase. Thus both PP1- and PP2A-like phosphatases in fission yeast may negatively regulate entry into mitosis. The major property of the dis2/sds21 mutant which is distinct from those of the ppa2/ppa1 mutant is its failure to inactivate the p34cdc2/cyclin complex after entry into mitosis. A novel phosphatase regulator encoded by sds22+ binds to dis2 phosphatase and controls the substrate specificity which appears to become essential in the progression from metaphase to anaphase.

Cell Division↗
PubMed1992

Nortriptyline response in elderly depressed patients.

1. Depressed geriatric patients were treated with nortriptyline (NT) for 6 weeks. The authors measured serum levels of NT and 10-hydroxynortriptyline (10-OH-NT) using a column-switching HPLC method, and examined aging effects on NT steady-state levels to NT doses (doses/kg) ratios and NT levels to 10-OH-NT levels ratios as well as clinical response and propensity for side effects. 2. There was no significant relationship between the ages and the NT serum levels to NT doses (doses/kg) ratios, the ages and the 10-OH-NT levels to NT levels ratios, or the ages and the clinical response or the %improvement of Hamilton Scores. 3. Then the authors divided the subjects into two groups: a younger group and an elderly group with the cut off age of 60. The elderly group received significantly smaller doses of NT and had significantly lower serum levels of NT. The elderly group had tendency to have lower serum levels of 10-OH-NT. However, no significant difference was found in the improvement scores or the %improvement of depression. The elderly patients did not have higher propensity for unnegligible side effects.

Adult↗
PubMed1992

Immunohistochemical characterization of cellular infiltrates in epidermal tumors induced by two-stage and complete chemical carcinogenesis in mouse skin.

We investigated the population and pattern of the infiltrated cells in both benign and malignant epidermal tumors which were induced chemically with benzo(a)pyrene (B(a)P) in murine skin. In benign papillomas, which were evolved by a two stage carcinogenesis regimen, a slight to mild inflammatory infiltration around the tumors was observed, and cells infiltrating into the tumor nests were rarely seen. In carcinomas, which were produced by a complete carcinogenesis regimen, a dense inflammatory infiltration was observed around the tumor nests. The infiltrated cells were characterized as T-lymphocytes, macrophages, and neutrophils. Natural killer (NK) cells were found around and in the tumor nests, but their number was small. Both T-lymphocytes and macrophages were found to invade the tumor nests in squamous cell carcinoma whose duration was more than four weeks. This experimental carcinogenesis animal model allows the detailed quantitative and functional analysis of the infiltration of immunocompetent cells into epidermal tumors.

Animals↗
PubMed1992

In vivo detection by microscopic chromocystoscopy of concurrent urothelial atypia in superficial bladder cancer.

Microendoscopic observation of methylene blue-stained urothelial surfaces, so-called microscopic chromocystoscopy (MCC), was undertaken in 65 patients with superficial bladder cancer (Ta and T1) and its effectiveness in detecting concurrent urothelial dysplasia or carcinoma in situ was studied. A total of 166 biopsy samples were taken from 75 stained and 91 non-stained portions. Of 75 methylene blue-stained areas, 21 were judged to be abnormal (MCC-positive) by microscopic observation. Fourteen of these 21 MCC-positive areas (67%) were proven to be abnormal histologically, while 7 of 54 MCC-negative portions (13%) were histologically abnormal. Only 4 of 91 biopsies (4%) from non-stained mucosa were proven to have urothelial atypia. In per patient figures, 1 or more concurrent field changes were detected in 15 of 65 cases (23%). MCC contributed to the diagnosis in 10 of these 15 patients.

Aged↗
PubMed1992

Effects of concentration reduction and partial replacement of paraquat by diquat on human toxicity: a clinical survey.

Paraquat poisoning was studied in 174 patients over a 12-month period when a new, low concentration paraquat product (4.5% w/v paraquat ion mixed with 4.5% w/v diquat ion; 63 cases) replaced the original high concentration paraquat product (20% w/v paraquat ion only; 111 cases). In both groups approximately 60% of the patients died from circulatory failure accompanied by multiple organ failure within a week of ingesting the products. However, a remarkable reduction in late deaths from respiratory failure was noted in the new product group (17.1% vs 6.3%). This was reflected in this group's improved survival (23.4% vs 34.9%). The improvement in survival seems to be attributable to the dilution of paraquat with diquat which seems to have a different toxicological profile to paraquat.

Blood Urea Nitrogen↗
PubMed1992

Elevation of immunoreactive serum Mn-superoxide dismutase in patients with acute myocardial infarction.

Serum Mn-superoxide dismutase (Mn-SOD) levels were determined in patients with acute myocardial infarction by an enzyme-linked immunosorbent assay (ELISA). The serial determinations performed on 29 patients with acute myocardial infarction indicated that Mn-SOD appears in serum in a biphasic manner; an early small elevation was observed at approximately 16.2 (+/- 7.3) h and a high elevation at approximately 108 (+/- 20.6) h after the onset of symptoms. A negative correlation was found between the maximum value of the late elevation of Mn-SOD and left ventricular function. Plasma levels of tumor necrosis factor-alpha (TNF-alpha) were also elevated in acute myocardial infarction. These facts suggest that TNF-alpha secretion from the infarcted area resulted in the production of Mn-SOD and that the induced Mn-SOD was released from myocytes into serum through damaged membranes, resulting in the late elevation.

Adult↗
PubMed1992

[Assessment of the rate of successful transcranial Doppler recording through the temporal windows in Japanese with special reference to aging and sex].

Transcranial Doppler method (TCD), newly developed in 1982, is ultrasound technology that measures physiologic parameters of blood flow in the major intracranial arteries. A major limitation of TCD is that, in some individuals, satisfactory recording is not possible, especially through the temporal windows. The purpose of the present study is to assess the rate of successful recording in TCD through the temporal ultrasonic windows in Japanese with special reference to aging and sex. In 423 Japanese (244 males and 179 females) aged from 25 to 93 years, measurement of blood flow velocity in basal cerebral arteries was performed by transcranial Doppler velocimeter with a 2 MHz pulsed wave Doppler probe. The signal was successfully recorded in 299 of 423 Japanese (71%). In Japanese males, successful measurement was more frequent (206/244; 84%) than in Japanese females (93/179; 52%). The rate of successful recording was evaluated in every decade from the twenties to the eighties, and it was found to decrease significantly according to age (100%, 94%, 91%, 74%, 66%, 67%, and 46%, respectively). In females, it significantly decreased in those older than 50 years old (100%, 100%, 93%, 61%, 36% 43%, and 27%, respectively), but not in males (100%, 88%, 89%, 81%, 88%, 83%, and 69%, respectively). These findings suggest that this noninvasive method has clinical usefulness for evaluating intracranial circulation but has limitation for assessing the intracranial lesions of elderly Japanese women.

Adult↗
PubMed1992

["Dismembered spiral flap pyeloplasty" for uretero-pelvic junction obstruction].

We report a new operative technique for plastic correction of uretero-pelvic junction (UPJ) obstruction: dismembered spiral flap pyeloplasty. It is similar to the method described by Culp & DeWeerd in that a flap is made spirally but different in that UPJ is detached. Relatively a long and wide spiral (oblique) flap, the apex of which directs cranioventrally or craniodorsally, is made using the dilated pelvis. The apex of the flap is reflected downward and anastomosed to the split ureteral end. Because the flap is made obliquely, one side of the flap base is approximated to the opposite pelvic margin; this helps to make gradual funnelling of pelvio-ureteric transition. The method seems to be fit for cases with considerably long stenosis of UPJ and with the UPJ locating relatively close to the medial margin of the renal parenchyma. Seven of 26 pyeloplasties were done by this method in our institute, and all the 7 cases had satisfactory results.

Adolescent↗
PubMed1992

Dethymicin, a novel immunosuppressant isolated from an Amycolatopsis. Fermentation, isolation, physico-chemical properties and biological activities.

In the course of screening for immunomodulators inhibiting the mixed lymphocyte culture reaction (MLCR), we found a novel immunosuppressant, dethymicin in mycelium of Amycolatopsis mediterranei MI710-51F6. From physico-chemical properties and biological activity it is different from immunosuppressants produced by microorganisms such as cyclosporins, FK506 and rapamycin. It inhibited immune responses in vitro and in vivo, and prolonged skin allograft in rats.

Actinomycetales↗
PubMed1992

[Platelet accumulation in abdominal aortic aneurysms and the effect of antiplatelet drugs: assessment by indium platelet scintigraphy].

A dual tracer technique using 111In labeled platelets and 99mTc labeled human serum albumin was applied to evaluate the in vivo thrombogenicity in 12 cases with abdominal aortic aneurysm (AAA) and the effect of antiplatelet drug on the thrombogenicity. The magnitude of platelet accumulation at AAA was expressed as the ratio of radioactivity of 111In platelets on the vascular wall to those in the blood pool (PAI; platelet accumulation index). Of the 12 patients with AAA, 11 had positive studies on baseline imaging and 1 had equivocally positive image. The PAI value (Mean +/- SD) over the AAA was 53.8 +/- 34.1% as compared to -8.6 +/- 4.4% in the control group (p less than 0.01). Seven patients with an AAA and positive baseline images were restudied during platelet active drug with 325 mg of aspirin. During treatment with aspirin, of 7 patients, 5 had positive images, of which 3 were decreased and others unchanged compared to baseline studies, 1 equivocally positive one and one negative one. The PAI value during treatment (21.9 +/- 18.6%) was significantly decreased compared to those in baseline study (52.1 +/- 23.9%). Our results suggest that the method used for platelet imaging in the present study may be useful for studying the in vivo thrombogenicity and the effect of platelet active drugs in AAA.

Aged↗
PubMed1991

Glycosylation at the Fab portion of myeloma immunoglobulin G and increased fucosylated biantennary sugar chains: structural analysis by high-performance liquid chromatography and antibody-lectin enzyme immunoassay using Lens culinaris agglutinin.

An antibody-lectin enzyme immunoassay technique which had been developed for the analysis of sugar chains of alpha-fetoprotein (N. Kinoshita et al., Clin. Chim. Acta, 179: 143-152, 1989) was used for analysis of sugar chains of myeloma immunoglobulin G (IgG). The IgG sugar chains of four of nine patients with myeloma were found to be highly reactive to Lens culinaris agglutinin as compared with those of six normal controls and 177 patients without myeloma. This reflected a high L. culinaris agglutinin/concanavalin A ratio. The IgGs of these patients were found to have highly sialylated, fucosylated, and bisected biantennary sugar chains at Fab portions as judged by the lectin-blotting technique as well as by high-performance liquid chromatography analysis. These results indicate that some of the myeloma IgG proteins undergo unusual glycosylation processes.

Carbohydrate Sequence↗
PubMed1991

Serum interleukin-6 in schizophrenic patients.

We examined serum interleukin-6 (IL-6) in 90 schizophrenic patients in remission and 90 normal controls using enzyme-linked immuno-sorbent assay (ELISA). We found a significant difference in variation between the schizophrenic and the control groups (F = 10.9, P less than .002). The difference in distribution was also statistically significant by Kolmogorov-Smirnov (chi-square = 45.0, P less than .001). Eight patients had aberrantly high serum levels of interleukin-6. Since the higher levels of IL-6 are characteristically found in several autoimmune disorders, our finding suggests a link between schizophrenia and immune response, which could be either autoimmune or a process induced by reactivation of viruses.

Adolescent↗
PubMed1991

The fission yeast dis3+ gene encodes a 110-kDa essential protein implicated in mitotic control.

The fission yeast mutant dis3-54 is defective in mitosis and fails in chromosome disjunction. Its phenotype is similar to that of dis2-11, a mutant with a mutation in the type 1 protein phosphatase gene. We cloned the dis3+ gene by transformation. Nucleotide sequencing predicts a coding region of 970 amino acids interrupted by a 164-bp intron at the 65th codon. The predicted dis3+ protein shares a weak but significant similarity with the budding yeast SSD1 or SRK1 gene product, the gene for which is a suppressor for the absence of a protein phosphatase SIT4 gene or the BCY1 regulatory subunit of cyclic AMP-dependent protein kinase. Anti-dis3 antibodies recognized the 110-kDa dis3+ gene product, which is part of a 250- to 350-kDa oligomer and is enriched in the nucleus. The cellular localization of the dis3+ protein is reminiscent of that of the dis2+ protein, but these two proteins do not form a complex. A type 1 protein phosphatase activity in the dis3-54 mutant extracts is apparently not affected. The dis3+ gene is essential for growth; gene disruptant cells do not germinate and fail in cell division. Increased dis3+ gene dosage reverses the Ts+ phenotype of a cdc25 wee1 strain, as does increased type 1 protein phosphatase gene dosage. Double mutant dis3 dis2 is lethal even at the permissive temperature, suggesting that the dis2+ and dis3+ genes may be functionally overlapped. The role of the dis3+ gene product in mitosis is unknown, but this gene product may be directly or indirectly involved in the regulation of mitosis.

Amino Acid Sequence↗
PubMed1991

Double fluorescent labeling method used for a study on liposomes.

Carboxyfluorescein (CF) and Calcein (CAL) have almost the same fluorescent spectrum. However, only CAL forms a nonfluorescent chelate with the Co2+ ion. It was proven that this phenomenon can be used for the fractional determination of CF and CAL. And this fractional determination method was available for a study on liposomes.

Animals↗
PubMed1991

Protein phosphatases in cell division: how vital are they?

In contrast to the wealth of information on cellular function of protein kinases, many of which are known to be the products of proto-oncogenes, little is known about how protein dephosphorylation is involved in growth control of normal and malignant cells. In the present study, roles of protein phosphatases in cell division cycle control were examined by molecular genetic approaches using a lower eukaryote, the fission yeast Schizosaccharomyces pombe. Nine protein phosphatase genes have been so far identified and characterized in this organism. Each of two (dis2+, sds21+, and ppa1+, ppa2+) gene products is highly similar to mammalian type 1 and 2A ser/thr phosphatases, respectively. The ppx1+ product is an intermediate of type 1 and 2A, while the ppb1+ product is similar to Ca(2+)-dependent type 2B. At least two protein tyrosine phosphatase genes (pyp1+ and pyp2+) exist. The cdc25 protein is now established to be a tyrosine phosphatase that activates cdc2 kinase. Some of these phosphatase genes are interrelated but have distinct, essential functions in cell cycle control. Missense mutations, deletions or high dosage expression of these phosphatase genes affect entry into and exit from mitosis, mitotic chromosome disjunction, cell size and cell shape. They seem to interact with the main regulators of mitosis, cdc2, cdc13/cyclin, cdc25 and weel, or with mitotic structural components, such as condensed chromosomes or the spindle apparatus. We show that the product of an essential gene, sds22+, is an important, positive factor in controlling the expression and modulating the activity of dis2 phosphatase.

Amino Acid Sequence↗