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Biomedical subjects

N Kitamura

Publications and source records attributed to N Kitamura.

At least 397 records · Page 22Linked to original sources

Osteoclast-mediated osteolysis in bone metastasis from renal cell carcinoma.

Osteolytic characteristics of bone metastasis from renal cell carcinoma were morphologically and biochemically investigated. First, undecalcified ground sections of bone metastases were made from four patients with renal cell carcinoma. Second, renal cell carcinoma cell line (RCC-K1) was established from one of the four patients, and its effect on bone resorption in vitro was examined. Marked proliferation and activation of osteoclasts around the tumor cells was histologically demonstrated. Conditioned medium from the RCC-K1 cells contained potent bone-resorbing activity in vitro. The activity was reduced to basal level by calcitonin, but was not blocked by indomethacin. The activity was lost after dialysis (MW cutoff 3500), while it was retained after 2 weeks of storage. Levels of prostaglandin E2 and 1,25-dihydroxyvitamin D of the RCC-K1-conditioned medium were insufficient to cause bone resorption in vitro. The conditioned medium did not stimulate cAMP accumulation in rat osteoblastic cells. These results suggest that renal cell carcinoma causes bone destruction through the stimulation of osteoclasts by locally secreting an unknown humoral factor or factors.

Aged↗

Structure and chromosomal localization of the human renal kallikrein gene.

Glandular kallikreins are a family of proteases encoded by a variable number of genes in different mammalian species. In all species examined, however, one particular kallikrein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. This kallikrein is found in the kidney, pancreas, and salivary gland, showing a unique pattern of tissue-specific expression relative to other members of the family. We have isolated a genomic clone carrying the human renal kallikrein gene and compared the nucleotide sequence of its promoter region with those of the mouse renal kallikrein gene and another mouse kallikrein gene expressed in a distinct cell type. We find four sequence elements conserved between renal kallikrein genes from the two species. We have also shown that the human gene is localized to 19q13, a position analogous to that of the kallikrein gene family on mouse chromosome 7.

Amino Acid Sequence↗

Localization of DNA sequences governing alternative mRNA production of rat kininogen genes.

The two types of the rat kininogen genes show different modes of mRNA production. The K gene encodes two distinct mRNAs for high molecular weight (HMW) and low molecular weight (LMW) kininogens. These two mRNAs are generated by differential usage of the 3'-terminal exon (LMW exon) and the one next to this exon (HMW exon) through alternative polyadenylation and splicing. In contrast, the two T genes selectively generate the LMW form of the mRNA, although the T genes are extremely homologous to the K gene, including the sequence (psi HMW region) corresponding to the HMW exon of the K gene. In this study, we constructed a series of chimeric kininogen genes by exchanging equivalent restriction fragments of the K and T genes and examined the sequences and the mechanisms governing the different expression patterns of the kininogen genes by introducing the chimeric genes into heterologous COS cells. The results indicate that the formation of the two forms of the mRNA is controlled by two separate 3' sequences of the kininogen genes. One is located within the internal sequence of the HMW/psi HMW region, whereas the other is within the LMW exon and its preceding region. Our data also suggest that the different expression patterns of the kininogen genes are primarily governed by differing splicing efficiency.

Animals↗

Immunohistochemical study on the endocrine pancreas of cattle with special reference to coexistence of serotonin and glucagon or bovine pancreatic polypeptide.

Bovine pancreatic endocrine cells were investigated by light microscopic immunohistochemistry. Serotonin-immunoreactive cells as well as insulin-, glucagon-, somatostatin-, bovine pancreatic polypeptide (BPP)-immunoreactive cells were detected in the pancreatic islets. Generally, insulin-immunoreactive cells were distributed throughout the islet and the others took peripheral location. Since the distribution and shape of serotonin-immunoreactive cells were very similar to glucagon- and BPP-immunoreactive cells, serial sections were restained by using the elution method. All glucagon- and BPP-immunoreactive cells also showed serotonin immunoreactivity but glucagon and BPP immunoreactivities were never observed to be colocalized in the same cell. A small number of serotonin-immunoreactive cells were observed that showed serotonin immunoreactivity only.

Animals↗

Electron immunocytochemical co-localization of prochymosin and pepsinogen in chief cells, mucous neck cells and transitional mucous neck/chief cells of the calf fundic glands.

The electron immunocytochemical co-localization of prochymosin and pepsinogen in chief cells, mucous neck cells and transitional mucous neck/chief cells of calf fundic glands was studied using specific antisera for prochymosin and pepsinogen with a protein A-gold method. Prochymosin and pepsinogen immunoreactivities were detected in the same secretory granules of the chief, mucous neck and transitional cells, simultaneously using small and large colloidal gold particles. In chief cells, both immunoreactivities were distributed uniformly over the same zymogen granules showing a round, large, homogeneous and electron-dense appearance. In mucous neck cells, both immunoreactivities were found exclusively on the same electron-dense core located eccentrically in the mucous granule showing light or moderate electron density. In transitional mucous neck/chief cells, electron-dense cores became larger in size and some granules were occupied by the electron-dense core without a halo between the core and the limiting membrane. Both immunoreactivities were found uniformly over the electron-dense core. The granules having no halo in the transitional cells could not be distinguished from the typical zymogen granules in the chief cells.

Abomasum↗

[3H]GBR-12935 binding sites in human striatal membranes: binding characteristics and changes in parkinsonians and schizophrenics.

The binding of the diphenyl-substituted piperazine derivative, [3H]GBR-12935, a selective dopamine uptake inhibitor, to the post-mortem human putamen was studied. Inhibition curves by dopamine uptake inhibitors suggested the existence of two populations of [3H]GBR-12935 binding sites: one is potently inhibited by mazindol and/or nomifensine, and the second binding site is benztropine- and/or GBR 12909-sensitive. In the human putamen, [3H]GBR-12935 labeled both these two distinct binding sites. The [3H]GBR-12935 binding displaced by mazindol was enriched in the mouse and rat striatum, but not in the cultured mouse neuroblastoma cell N1E-115. The mazindol-sensitive [3H]GBR-12935 binding site increased in the presence of sodium and markedly decreased in the putamen from parkinsonians (45% of controls). On the other hand, the [3H]GBR-12935 binding displaced by benztropine showed no sodium-dependent increase and was not decreased in the putamen from parkinsonians. In the putamen from schizophrenics, the [3H]GBR-12935 binding did not significantly change in the density, while that displaced by mazindol tended to increase. It is concluded that in the human putamen, [3H]GBR-12935 binds to two distinct sites. One site is partially sodium-dependent and appears to be associated with a high-affinity dopamine uptake system on dopaminergic nerve terminals. The second binding site shows no sodium-dependency and may be associated with a nondopaminergic and/or extraneuronal DA uptake system.

Aged↗

[Expanding the surgical indication to the cases with high risk valve diseases].

Four hundred and fifty eight cases of valve surgery were performed at this institution over the past 7 years, during which the surgical indication has been gradually expanded to cases of three types. The first type is serious disease complicated by cardiac cachexia; in these cases, in addition to the aggressive use of IABP, we also use the intrapulmonary artery balloon pumping (IPBP) technique we developed. IVH therapy for two months before surgery has been especially effective and given good results to cases with low liver function and low respiratory function. The second type consists of cases necessitating special surgical technique, for example, cases with very narrow valvular annuli and cases complicated by acute endocarditis. Good results have been obtained in the former with a new technique that we developed, called "Coupling Valve Grafting", and in the latter with a technique of "Collared Prosthesis". The third type is elderly patients aged 70 years or more. In particular, the greatest problem now seems to lie in low liver function of which ICG (15 min) is higher than 40% and total serum bilirubin is over 3 mg/dl; in these cases, progression to MOF is frequent and the patient's life is saved in only 40% of cases.

Heart Valve Diseases↗

[Clinical studies on S 6472 granule preparation (sustained-release cefaclor) in chronic respiratory tract infections].

S 6472 granule preparation (sustained-release cefaclor) was orally administered to 15 patients with chronic respiratory tract infections (2 acutely exacerbated cases of chronic bronchitis, 13 cases of secondary infections consisting of 1 case of bronchial asthma, 2 cases of bronchial asthma/pulmonary emphysema, and 10 cases of bronchiectasis) at a daily dose of 750 mg divided into 2 doses administered after breakfast and dinner, for a duration of 14 days. The drug was ineffective in 3 of the 10 cases of bronchiectasis but was effective in the other 12 cases, with a rate of efficacy of 80%. There were no side effects of abnormal laboratory findings due to administration of this drug.

Administration, Oral↗

[A study on pharmacokinetics, antimicrobial activity and clinical efficacy of sultamicillin in children].

Sultamicillin (SBTPC), a mutual prodrug for ampicillin (ABPC) and beta-lactamase inhibitor sulbactam (SBT), was evaluated for its antibacterial activity, pharmacokinetics and clinical efficacy. Pharmacokinetic studies were done in 2 subjects (a male and a female) following single oral administrations of 5 mg/kg and 10 mg/kg SBTPC fine granules after meal. Peak serum concentrations of ABPC and SBT in the 2 cases were 0.85 and 0.38 micrograms/ml and 3.74 and 3.79 micrograms/ml, respectively. Urinary excretion rates in 6 hours were 43.5-58.1% for ABPC and 33.6-53.6% for SBT. A total of 20 patients including 14 with respiratory infections, 1 with urinary tract infection and 5 with skin and soft tissue infections were treated with daily oral dose of 15.4-39.3 mg/kg SBTPC fine granules t.i.d. for 4 to 13 days. Responses were excellent in 5, good in 13 and fair in 2, hence the overall efficacy rate was 90.0%. Bacteriological responses were confirmed on 5 (62.5%) out of 8 strains which were eradicated by the treatment. SBTPC showed strong antibacterial activities against an ABPC-resistant strain of Escherichia coli. Side effects of the drug were observed in 3 patients: diarrhea in 2 and loose stool in 1. An abnormal laboratory test value, eosinophilia, was observed in only one patient.

Adolescent↗