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Biomedical subjects

Y Kakehi

Publications and source records attributed to Y Kakehi.

122 records · Page 7Linked to original sources
PubMed1990

Generation of transgenic mice with elevated blood pressure by introduction of the rat renin and angiotensinogen genes.

The role of the renin-angiotensin system in blood pressure control and in the development of hypertension was investigated by generating transgenic mice carrying the rat renin or angiotensinogen gene or both genes under the control of the mouse metallothionein I promoter. The systolic blood pressure was significantly elevated in transgenic mice carrying both transgenes but was maintained normally in those bearing either of the transgenes. The transgene was effectively and properly transcribed to form the mature mRNA in the transgenic mice. The production of rat renin and angiotensinogen in the transgenic mice carrying the corresponding transgene was also verified by immunoanalyses of these proteins. Furthermore, the specific angiotensin-converting enzyme inhibitor captopril was effective in reducing the elevated blood pressure of the hypertensive transgenic mice. These results indicate that the combined action of the exogenous rat renin and angiotensinogen is responsible and necessary for elevation of blood pressure in the hypertensive transgenic mice.

Angiotensinogen↗
PubMed1989

P-glycoprotein gene (MDR1) cDNA from human adrenal: normal P-glycoprotein carries Gly185 with an altered pattern of multidrug resistance.

We isolated a full-length MDR1 cDNA from human adrenal where P-glycoprotein is expressed at high level. The deduced amino acid sequence shows two amino acid differences from the sequence of P-glycoprotein obtained from colchicine-selected multidrug resistant cultured cells. The amino acid substitution Gly----Val at codon 185 in P-glycoprotein from colchicine resistant cells occurred during selection of cells in colchicine. As previously reported, cells transfected with the MDR1 cDNA carrying Val185 acquire increased resistance to colchicine compared to other drugs. The other amino acid substitution Ser----Ala at codon 893 probably reflects genetic polymorphism. The MDR1 gene, the major member of the P-glycoprotein gene family expressed in human adrenal, is sufficient to confer multidrug-resistance on culture cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

MDR1 RNA levels in human renal cell carcinomas: correlation with grade and prediction of reversal of doxorubicin resistance by quinidine in tumor explants.

We examined the distribution of RNA levels expressed by the multidrug-resistance gene (MDR1, also known as PGY1) in 42 renal cell carcinoma (RCC) samples (38 primary and four metastatic lesions). The median MDR1 RNA level for the 38 primary lesions, expressed relative to the level for KB-3-1 cells, was approximately one-half of the level in multidrug-resistant KB-8-5 cells. Elevated MDR1 RNA levels were also observed in three of the four metastatic lesions. The mean MDR1 RNA level was higher in well-differentiated RCCs than in those that were poorly differentiated, suggesting that the increased expression of the MDR1 gene in RCCs originates from the increased expression in renal proximal tubule cells. To clarify the association of the MDR1 protein product P-glycoprotein with natural resistance to doxorubicin (ADR) in RCCs, we evaluated the effects of quinidine on in vitro sensitivity to ADR in 16 RCC samples, using a [3H]thymidine incorporation assay. The enhancing effect of quinidine (7.5 micrograms/mL) on sensitivity to ADR was statistically significant only in the group with high MDR1 RNA levels. Similar enhancement by quinidine of sensitivity to ADR was also observed in the established RCC cell lines in which MDR1 RNA levels were high. These results suggest that P-glycoprotein is active in the natural resistance of RCCs to ADR.

Adult↗
PubMed1989

Restriction fragment length polymorphism of the L-myc gene and susceptibility to metastasis in renal cancer patients.

We examined Southern blot analyses of normal and tumor DNAs from 50 patients with sporadic renal cancer, using the human L-myc oncogene fragment as a hybridization probe. Our purpose was to study the relationship between the restriction fragment length polymorphism (RFLP) of the L-myc and the frequencies of metastases. There was no individual difference in patterns of L-myc RFLP between normal and tumor-tissue DNAs digested with EcoRI. The patients were classified into 3 genetic types according to the polymorphic patterns defined by the 2 alleles [10-kilobase (kb) and 6.6-kb fragments]. The relative ratios of the 3 genotypes in the renal cancer patients were similar to those seen in healthy Japanese. However, of 16 patients who exhibited distant organ metastases at the time of surgery, only one was a 10-kb fragment homozygote. The incidence of distant metastases in 10-kb homozygotes was significantly lower than that in 6.6-kb homozygotes plus heterozygotes (p = 0.06). These results basically correspond to the previous findings in the lung cancer patients, and suggest that L-myc RFLP is a widely applicable genetic marker to predict prognosis in cancer patients.

Adult↗
PubMed1989

Detection of multidrug resistance (MDR1) gene RNA expression in human tumors by a sensitive ribonuclease protection assay.

The human MDR1 gene encoding P-glycoprotein, an energy-dependent drug-efflux pump, was initially isolated from a multidrug-resistant KB carcinoma cell. When a 3 kb genomic sequence isolated from normal human tissue including the major downstream promoter and the first and second exons of the MDR1 gene was compared to the equivalent fragment from KB cells, the MDR1 gene from KB carcinoma cells was found to have a point mutation in the first exon. Although this mutation does not affect the downstream promoter sequence or the coding sequence of the MDR1 gene, it creates a single base mismatch between the 5' KB genomic fragment previously used for RNase protection analysis of MDR1 RNA expression in normal tissues and thereby reduces the sensitivity of this assay. Using the DNA fragment from normal tissues rather than KB cells, we have reanalyzed MDR1 mRNA levels in 12 renal carcinomas and 4 colon adenocarcinomas. By this RNase protection assay, MDR1 RNA levels are as high in these tumors as in the multidrug-resistant cell line, KB-8-5. The ribonuclease protection assay indicated that the major downstream promoter was mainly used in these clinical samples including two samples of RNA from metastatic renal cancer. This assay appears to be a very sensitive and specific assay for detecting MDR1 mRNA levels and mRNA initiation sites in clinical samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

[Testicular cancer].

A dramatic improvement in the survival of patients with testicular cancer has been witnessed in the 1970s. These advances are in the areas of diagnosis, staging, and monitoring of patients with this disease. The thrust of improvement includes the finding of sensitive and specific markers, the introduction of CDDP, and utilization of CT. Also, the finding of the efficacy of multidisciplinary treatment consisting of intensive chemotherapy and surgery has played a decisive role in the management of patients. This paper is devoted of a discussion of the basic sciences related to testicular cancer and the diagnosis and management of this tumor.

Adolescent↗
PubMed1988

Measurement of multidrug-resistance messenger RNA in urogenital cancers; elevated expression in renal cell carcinoma is associated with intrinsic drug resistance.

We measured the levels of messenger RNA of the human multidrug-resistance gene (MDR1) in 25 urogenital tumors before chemotherapy. Many of the renal cell carcinomas continued to express MDR1 gene at high levels, reflecting the increased expression of MDR1 RNA in normal kidneys. In other urogenital tumors, the MDR1 RNA levels were low reflecting low MDR1 RNA levels in normal bladder, prostate and testis. For comparative purposes, we performed in vitro chemosensitivity testing on many tumor samples using soft agar culture techniques. Vinblastine sensitivity in vitro inversely correlated with MDR1 RNA levels (p less than 0.01). Moreover, mean sensitivity of seven renal cell carcinomas to vinblastin was significantly lower than that of the other seven cancers (p less than 0.05). As for doxorubicin, mean sensitivity of six renal cell carcinomas was lower than the others (p less than 0.1). These results suggest that the high MDR1 RNA levels in renal cell carcinomas are associated with intrinsic multidrug-resistance.

Carcinoma, Renal Cell↗
PubMed1988

[In vitro chemosensitivity test by human tumor colony forming assay].

In vitro chemosensitivity of urological cancers was assessed by a human tumor colony forming assay (HTCA) and a 3H-thymidine incorporation assay. Primary tumor cells from 160 of 253 (63%) urological cancers showed adequate colony growth (greater than 30 colonies per well), and there was a 57% true positive and 100% true negative rate for predicting clinical response of anticancer agents. On the other hand, cells from 37 of 45 (82%) urologic cancers incorporated a sufficient amount of 3H-thymidine (greater than 300 cpm). However, when the positive control drug (chromomycin A3 100 micrograms/ml) was used for the assay quality control, the successful assay rate of the HTCA (38%) was lower than that of the 3H-thymidine incorporation assay (75%), while there was a significant correlation in drug sensitivities between the two assays. Thus, the 3H-thymidine incorporation assay seemed to be more useful than the HTCA for evaluating the chemosensitivity of urologic cancers.

Antineoplastic Agents↗
PubMed1985

[Metastatic ureteral tumor: a case report].

Among the secondary ureteral tumors, there have been a few true metastases to the ureters. We report a case of metastatic ureteral tumor from the pancreas, and review and discuss 60 cases collected from the Japanese literature.

Adenocarcinoma↗
PubMed1984

[Metastatic penile tumors: report of three cases].

Metastatic tumor of the penis is uncommon in spite of its rich blood supply, abundant vascular space and the proximity of the pelvic organs which have a high incidence of malignant neoplasms. We report three cases of metastatic penile tumors. The primary sites of these cases were the left ureter, the right kidney and the rectum. We review and discuss sixty two cases collected from the Japanese literature, including our cases.

Adenocarcinoma↗
PubMed1984

[20 cases of hypercalcemia associated with urogenital malignancies].

Twenty cases (3.3%) of hypercalcemia of more than 11.0 mg/dl associated with urogenital malignancy were observed in 610 inpatients during the past 5 years and 6 months (Jan. 1978-June 1983). Incidences were 10 (16.1%) out of 62 cases of renal cell carcinoma, 6 (1.9%) out of 321 cases of bladder cancer, 3 (6.7%) out of 45 cases of renal pelvic and ureteral cancer, and one (1.1%) out of 95 cases of prostatic cancer. As treatment, surgery (radical nephrectomy) and anti-cancer chemotherapy were effective in 3 cases (2 renal cell carcinomas and one renal pelvic cancer). Conservative therapy with hydration combined with either indomethacin, steroid or eel calcitonin was effective in 11 cases, and s-Ca level was decreased by 3.7 mg/dl on the average. Eighteen patients were in the terminal stage of malignancy when hypercalcemia was observed, and died 5 days to 9 months (mean; 2 months) after the onset of hypercalcemia.

Adenocarcinoma↗
PubMed1984

[A case of renal oncocytoma].

We report a case of renal oncocytoma and review 158 cases in the literature. The patient was a 75-year-old woman whose chief complaint was epigastric discomfort without any urological symptoms. The right renal tumor was incidentally discovered by ultrasonography. Its angiographic patterns such as spoke-wheel appearance and homogeneous nephrogram were "characteristic" of renal oncocytoma. We diagnosed it as oncocytoma by microscopical and ultrastructural observation.

Adenoma↗
PubMed1983

[The effect of prostaglandin F2 alpha on the gastrointestinal movement after urological surgery].

To facilitate postoperative flatus, Prostaglandin F2 alpha (PGF2 alpha) was given intravenously to 23 patients who underwent urological operations. The patients were 14 males and 6 females aged from 20 to 77 years old. Patients with hypertension or cardiovascular disease were not included. Twelve operations were performed under general anesthesia, and 8 under epidural anesthesia. Thirteen operations were performed for the upper urinary tract or adrenal gland, and 5 were for the lower urinary tract. In 2 cases, the peritoneal cavity was opened and operations were performed on the intestines. PGF2 alpha 2000 micrograms was added to the postoperative drip infusion and administered in 2 to 3 hours. Until the first flatus was recognized, PGF2 alpha was given once a day in the same manner. Twenty-six patients, 10 of whom were given either vagostigmine or pantothen postoperatively, served as the control group. PGF2 alpha accelerated the postoperative flatus by 8.7 hours (mean) compared with the control group, but it was not significant. The onset of flatus was significantly promoted under epidural anesthesia. Gastrointestinal movement tended to be facilitated in the PGF2 alpha group after lower urinary tract surgery and in the patients over 50 years old. Three patients complained of severe abdominal pain as a side effect; and, injection of PGF2 alpha was stopped. In 7 patients, mild stomachache , vascular pain, nausea, vomiting or elevation of blood pressure were observed.

Adult↗