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K Kitamura

Publications and source records attributed to K Kitamura.

At least 253 records · Page 14Linked to original sources

Increased plasma levels of mature form of adrenomedullin in patients with chronic renal failure.

BACKGROUND: Adrenomedullin (AM), a novel vasodilator peptide, is produced by C-terminal amidation reaction of AM-glycine. AM-glycine, an intermediate form of AM (iAM), is processed from pro AM. AM circulating in the human blood stream was found to consist of an amidated mature form (mAM) and iAM. Biological activity is exerted only by mAM. METHODS: To investigate the pathophysiological role of mAM in renal disease, we measured plasma concentrations of mAM as well as total AM (tAM), representing both mAM and iAM, in patients with various renal diseases. In addition, plasma ANP level was measured in all patients. RESULTS: The concentrations of plasma mAM in renal failure with dialysis (2.1 +/- 0.2 fmol/ml, mean +/- SEM) and without dialysis (1.2 +/- 0.2) were significantly (p < 0.05) higher than those in control group (0.5 +/- 0.1). However, the plasma ANP level was increased only in renal failure patients with dialysis. Plasma mAM levels were significantly correlated positively with serum creatinine levels and negatively with hematocrit. No significant difference was noted in the ratio of mAM/tAM between renal failure patients and healthy subjects. CONCLUSION: These results suggest that plasma mAM is increased in renal failure in relation to deterioration of renal function, while the amidation process of AM seems to be unaffected in patients with renal failure.

Adrenomedullin↗

[Combined chemotherapy with low-dose cisplatin, tegafur and uracil for head and neck squamous cell carcinomas].

The mechanism for the effect of cisplatin (CDDP) as a modulator for 5-fluorouracil (5-FU) has already been described. The effective AUC of serum 5-FU concentration with oral administration of tegafur and uracil (UFT) has been revealed. We administered a dose of 200-600 mg/body of UFT orally every day, and 3.5-10 mg/m2 of CDDP by drip infusion 5 days a week. Hospitalized patients were administered these agents for 2-5 weeks. Eleven patients were enrolled, including 4 with untreated pharyngeal squamous cell carcinoma (SCC), 5 with locoregional recurrent SCC, and 2 with pulmonary multiple metastases. The mean age of the patients was 71 years, and all patients had a PS 3. Of the 4 patients with untreated pharyngeal SCC, PR was noted in 3 and NC in one, for a response rate of 75%. Of the 11 patients with locoregional recurrent and pulmonary metastatic SCC, PR was noted in only one patient for a response rate of 14%. Although on average these patients died of the primary disease 150 days after chemotherapy, 4 patients later showed an improved PS stage, and could were able to leave the hospital. These 4 patients could stay home with a PS 0 or PS 1 for an average of 133 days, and survived with the disease for an average of 240 days after chemotherapy. No side effects were observed in any patients. In side of the low response rate for locoregional recurrent and pulmonary metastatic SCC, the present therapy was thought to be useful from the viewpoint of the quality of life.

Administration, Oral↗

[Clinical evaluation of weekly hepatic arterial infusion chemotherapy in patients with unresectable metastatic liver cancer].

Twenty-five cases with unresectable metastatic liver cancers were experienced in our hospital over the past five years who underwent weekly 24-hour continuous hepatic arterial infusion chemotherapy using 5-FU and CBDCA. The response rate was 20%, the median survival was 23 months, and the one/two year overall survival rates averaged 81.3/45.5%. In 77% of patients, this therapy prevented death from hepatic metastases. Moreover, since adverse effects were limited compared with bolus infusion, weekly 24-hour continuous hepatic arterial infusion chemotherapy was thought to be a favorable method.

Adult↗

[Cross matching test].

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Blood Grouping and Crossmatching↗

[Birth cohort analysis of obesity in an occupational setting].

PURPOSE: The purpose of this study was to analyze the transition of body mass index (BMI) by birth cohort and to determine the relationship between BMI and high blood pressure, for the health management of workers in an industry. SUBJECTS AND METHODS: The eligible study subjects were 3,043 male workers at printing and papermaking plants who were 20 to 49 years of age in 1986 and whose annual health checkup information was available for both 1991 and 1996. First, we analyzed the transition of BMI by 5-year birth cohort. Second, we analyzed the relationship between BMI and high blood pressure (systolic blood pressure > = 140 mmHg or diastolic blood pressure > = 90 mmHg) using multiple logistic regression models. In this analysis, we excluded 596 subjects who were diagnosed as having high blood pressure in 1986 and 17 subjects whose alcohol drinking habits were unknown. Consequently, we had 2,430 study subjects. RESULTS: (1) All the birth cohorts showed that the proportion of obese subjects (BMI > = 26.4) became higher as age advanced. The proportion was higher for younger cohort. (2) By multiple logistic regression models, age at the beginning of the study, BMI, change of BMI in 5 or 10 years, and alcohol drinking habits were related to the risk of having high blood pressure. CONCLUSION: In the health management of workers, it is necessary to evaluate the risk by birth cohort. Also, we consider that we need to initiate obesity counseling before the workers become 30 years of age.

Adult↗

External quality control study of lymphocyte subset tests in Japan.

We have evaluated external quality assurance of lymphocytes subset tests in Japan. The data suggest: 1) Values of lymphocyte subsets were variable at each medical laboratory in Japan. 2) Value of CD3 did not varied so much, but that of CD 19/20 or NK marker was widely varied. 3) Values of CD4 and CD8 varied in small extension. 4) CV of values was relatively low when analysis was carried out in commercial laboratories or when antibodies and instrument of Ortho-Clinical Diagnostics were used. 5) In some cases, CV was also relatively low if number of cell washing times was low or if self made lytic agents were used for cell lysing.

Antigens, CD↗

One-step direct assay for mature-type adrenomedullin with monoclonal antibodies.

Adrenomedullin (AM) is a potent hypotensive peptide. Plasma contains mature-type AM (m-AM), which is amidated at the carboxy terminus, and an intermediate, AM-Gly. We developed a one-step two-site IRMA specific for determining human m-AM with monoclonal antibodies. The detection limit was 0.5 pmol/L, and the working range (CV <15%) was 1-300 pmol/L. Dilution of plasma samples showed good linearity. The recovery of added AM was 91-118%. The intra- and interassay imprecision values (CVs) were 4.4-8.2% and 5.5-8.3%, respectively. The assay had no cross-reactivity with AM-Gly or other peptides similar to AM. The mean (+/- SD) plasma human m-AM concentration of 61 healthy subjects was 1.18 +/- 0.65 pmol/L. In conclusion, our IRMA makes it possible to specifically measure m-AM, using a small amount of plasma sample (0.2 mL) by a one-step overnight assay without prior extraction. Our simplified method would be suitable for clinical studies on AM, especially when large numbers of samples must be processed.

Adrenomedullin↗

Cardiovascular and sympathetic effects of proadrenomedullin NH2-terminal 20 peptide in conscious rats.

Proadrenomedullin NH2-terminal 20 peptide (PAMP) and adrenomedullin (AM), which are derived from the same gene, are novel vasodilative peptides and have been shown to exhibit hypotensive action in anesthetized animals. To avoid the modification via anesthesia, we investigated the effects of intravenously administered PAMP on mean arterial pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) relative to those of AM in conscious unrestrained rats. We also examined whether the arterial baroreceptor reflex was altered with the two peptides. Intravenous injection of rat PAMP (rPAMP) (10, 20 and 50 nmol/kg) and rat AM (rAM) (0.3, 1.0 and 3.0 nmol/kg) similarly elicited dose-related hypotension accompanied by increases in HR and RSNA. However, the responses to rPAMP were less potent in magnitude and shorter in duration than those to rAM. Moreover, rAM facilitated baroreflex control, whereas rPAMP attenuated it. These findings indicate that although PAMP, as well as AM, may play an important role as a circulating hormone in the systemic circulation of conscious rats, the two peptides derived from an identical origin might have different mechanisms responsible for their cardiovascular and RSNA actions.

Adrenomedullin↗

Proliferative activity of cancer cells in front and center areas of carcinoma in situ and invasive sites of esophageal squamous-cell carcinoma.

Intraepithelial carcinoma contiguous with invasive squamous-cell carcinoma is a conspicuous feature of esophageal cancer. However, whether the mechanism of intraepithelial spreading is due to cell proliferation or field carcinogenesis has yet to be clarified. This study investigated the mechanism of intraepithelial spreading by measuring the cell proliferative activity using argyrophilic nucleolar organizer region (AgNOR) and proliferating cell nuclear antigen (PCNA)-positive cell counting. We examined the AgNOR number and PCNA-positive ratio (PCNA ratio) in the center and outer edge of intraepithelial carcinoma and in the center and deep margin of invasive squamous-cell carcinoma of the esophagus in 50 specimens from 18 cases of esophageal squamous-cell carcinoma concomitant with contiguous intraepithelial carcinoma. The proliferative activity was thus found to differ between the normal epithelium and cancerous lesions (p < 0.001), between intraepithelial carcinoma and invasive cancer (p < 0.001) and between deep margin and center areas of invasive cancer (p < 0.005). On the other hand, such activity was observed to be similar in the center and outer edge of the intraepithelial spread. These findings suggest that cell proliferation is the main mechanism of tumor progression at the invasive site of cancer, whereas in intraepithelial carcinomatous areas, "field carcinogenesis" or a paracrine mechanism, and not cell proliferation, is thought to be the cause of intraepithelial spread of esophageal cancer. These results therefore support the concept of field carcinogenesis.

Carcinoma in Situ↗

Multifocal occurrence of gastric carcinoma in patients with a family history of gastric carcinoma.

BACKGROUND: Smoking and alcoholic beverage drinking habits as well as a family history of cancer are well known risk factors for the multifocal occurrence of squamous cell carcinoma of the esophagus and the head and neck region. However, the role of these risk factors in multiple gastric carcinoma remains to be clarified. The purpose of this study was to examine the risk factors for multiple gastric carcinoma. METHODS: The smoking and drinking habits as well as the family history of 157 patients with synchronous multiple gastric carcinoma and 157 patients with solitary gastric carcinoma who were similar with regard to gender, age, stage of the tumor, and year of admission were investigated. The risk of a multiple occurrence of gastric carcinoma also was elevated using the odds ratio (OR). RESULTS: The ORs of a multifocal occurrence of gastric carcinoma in patients who currently smoked and drank alcoholic beverages were 1.1 and 0.8, respectively, although the ORs were not related to the quantity of smoking or drinking. In patients with a close relative with gastric carcinoma the OR was 2.1 (95% confidence interval [CI], 1.3-3.7). In those patients with > or =2 close relatives with gastric carcinoma, the OR increased to 5.1 (95% CI, 1.2-21.1). Conversely, no significant elevation in the ORs was recognized regarding a family history of other cancers. CONCLUSIONS: In this study, a family history of gastric carcinoma was found to be clearly associated with the multifocal occurrence of gastric carcinoma; however, no significant correlation between the multifocal occurrence of gastric carcinoma in these patients and their smoking and drinking habits was recognized.

Alcohol Drinking↗

Effect of a newly developed bisphosphonate, YH529, on osteolytic bone metastases in nude mice.

YH529, [1-hydroxy-2-(imidazo [1,2-a] pyridin-3-yl) ethylidene]-bisphosphonic acid monohydrate, is a newly developed third-generation bisphosphonate with a potent inhibitory activity toward osteoclastic bone resorption. The primary cellular mechanism of osteolysis associated with metastatic cancer is osteoclast-mediated. It is likely that bisphosphonates would be efficacious in this situation. In the present study, we examined the effect of YH529 in a nude mice bone metastasis model, in which the intracardiac injection of a human breast cancer cell line, MDA-MB-231 (MDA-231), leads to osteolytic bone metastases. To examine whether YH529 would prevent such bone metastasis, we administered YH529 s.c. to nude mice simultaneously with cancer cell inoculation through the entire experimental period (protocol 1) or performed short-term prophylactic administration before inoculation of the MDA-231 cells (protocol 2). In addition, to examine the possible therapeutic effects of the drug on established bone metastases, we injected YH529 after radiographically small but distinct osteolytic bone metastases had been detected (protocol 3). In all protocols, YH529 (2 microg/mouse/day) markedly inhibited bone metastases as well as the progression of established metastatic foci that were quantified on the radiographs. Histological examination and histomorphometrical analysis revealed that YH529 markedly reduced the number of osteoclasts and the size of the tumor at the metastatic bone sites. Our results suggest that YH529 may suppress metastasis formation and tumor growth in bone through inhibition of osteoclastic bone resorption.

Animals↗

Identification of a novel casein kinase-1 homolog in fission yeast Schizosaccharomyces pombe.

Fission yeast cells lacking either the ste9+- or rum1+ function cannot enter the cell differentiation pathway upon nutritional starvation. Sterility in both mutants is suppressed by the srs1-S41 mutation. A gene encoding a novel casein kinase-1 (CK1) isoform, cki3+, was isolated as a high-copy-number suppressor gene of the srs1 mutation. Cki3 protein is structurally more related to the Cki/Yck subfamily proteins than those of the Hhp/Hrr25 subfamily. A mutant cki3 gene in which a highly conserved lysine residue in the kinase subdomain II was substituted to arginine lost the ability to recover the growth defect in the srs1 mutant, indicating that catalytic activity was necessary for suppression. Gene disruption revealed that cki3+ was dispensable for cell viability, and cells lacking functional cki3+ exhibited no characteristic phenotype. Thus, S. pombe has three highly related CK1 isoforms (Cki1, Cki2 and Cki3), but none of them has an essential function.

Amino Acid Sequence↗

Family aggregation of carcinoma of the hypopharynx and cervical esophagus: special reference to multiplicity of cancer in upper aerodigestive tract.

The role of family history in the multiple occurrence of cancer in the upper aerodigestive tract (UADT) remains unclear. The family histories of close relatives were examined in 167 patients with either hypopharyngeal or cervical esophageal cancer (PhCe cancer) and in 167 control subjects with benign diseases. The odds ratio for PhCe cancer was 2.6 in relation to family history of UADT cancers. Based on the family histories of close relatives, 167 cases with PhCe cancer were divided into 3 groups (Group I, 18 cases with a family history of UADT cancer; Group II, 37 cases with a family history of other cancers; Group III, 112 cases with no family history of any cancers). The mean age of the cases in group I was 59.4, which was younger than in group III (64.2). Second primary squamous-cell carcinomas in the UADT were more frequently recognized in group I (39%) than in group III (11%). However, no differences were observed in the smoking and drinking habits of male patients between each group. These results thus suggest that a family history of UADT cancers appears to be associated with the multiple occurrence of UADT cancers as well as the development of PhCe cancer.

Aged↗