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Biomedical subjects

M Hosaka

Publications and source records attributed to M Hosaka.

At least 145 records · Page 8Linked to original sources

[Clinical analysis on 40 cases of primary aldosteronism--long-term follow-up of blood pressure].

Forty cases of primary aldosteronism after adrenalectomy were observed from 1975 to 1993 at Yokohama City University hospital. All of them had adrenocortical adenoma producing aldosterone. These cases are evaluated retrospectively on localization, surgical approach and long term follow up blood pressure. These patients were from 26 to 65 years old (average 46.6), and consisted of 11 males and 29 females. Fourteen adenomas were located on the right adrenal gland, 25 on left, and one case had adenomas on bilateral adrenal glands. On localization study, 39 cases had been correctly diagnosed by combined diagnostic method of selective adrenal venous sampling, selective adrenal venography, adrenal scintigraphy, X-ray CT, and MRI, with each diagnostic values being 65.8%, 69.0%, 72.5%, 96.9%, 100% respectively. This analysis suggests that, in almost cases, it is enough to diagnose the laterality by adrenal scintigraphy, X-ray CT and MRI. Selective venous catheterization is not always necessary to know the laterality of the tumor. For surgical approach to the adrenal gland, 16 adenomas were removed through anterior subcostal incision (transabdominal approach) from 1975 to 1988, and 24 cases through lumbar oblique incision or dorsal incision (extra peritoneal approach) from 1986 to 1993. This analysis reveals that lumbar oblique and dorsal incision provided us superior surgical approach to the adrenal gland. Thirty-eight cases had been followed after adrenalectomy for more than one year (average 57.6 months). Blood pressure had been normalized in 28 cases, but 10 cases had remained hypertensive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

[Molecular genetic analysis of a family with von Hippel-Lindau disease].

We analyzed germline mutations of the von Hippel-Lindau (VHL) gene located at chromosome 3p25 in a family of VHL disease by using single strand conformational polymorphism (SSCP) and Southern blot analyses. In 10 individuals including 2 patients with multiple renal cell carcinomas, multiple pancreatic cysts and cerebellar hemangioblastoma, there are no positive results in SSCP analysis. However, in 2 patients and one kindred, same abnormal band was observed in Southern blot analysis. Moreover, in this one kindred of 17 years old girl, multiple pancreatic cysts were found by computerized tomography (CT). These results shows the alteration in the VHL gene is a major rearrangement but not a small mutation and this alteration caused VHL disease in this family. Furthermore, presymptomatic diagnosis by direct mutation analysis seems to be very useful for early detection of this disease.

Adolescent↗

[Effect of caffeine and pentoxifylline on human sperm motility after one week storage at 3 degrees C].

The effect of caffeine (C) and pentoxifylline (P) on the sperm motility was examined after a 3 degrees C storage in a TEST yolk buffer for one week. Thus stored 24 semen samples from infertile patients were incubated with or without C or P at 37 degrees C. The motility was analysed for up to 240 minutes. The poststorage addition of C (1 mM) and P (1 mM) significantly increased the serum motility rate (p < 0.01). The stimulant effect of C and P was rather transient lasting no more than 2 hours. The prestorage addition of C and P in a preservant TEST yolk buffer was less effective than the poststorage administration. According to the time-related profiles of the sperm motility, 24 cases were divided into three groups. In group A (11 cases), the sperm motility rate increased from 30 to 90 minutes even without C or P. This group was responder of C and P. In group B (8 cases), the motility rate increased only in response to C and P and, in group C (5 cases), no such responses were observed. The prestorage semen qualities in terms of the sperm concentration, the motility rate, the velocity, the linearity, and the amplitude of the lateral head displacement were compared in these three groups. There was a significant difference between these 3 groups (p < 0.05) on the parameters in terms of the sperm concentration, motility rate and velocity. It was suggested that these prestorage parameters predict the sperm activity in response to C and P after a one week 3 degrees C storage.

Adult↗

[Clinical investigation of grade-up superficial bladder cancer].

Between January 1977 and December 1993, 249 patients with grade 1 or grade 2 superficial bladder cancer were initially treated at Yokohama City University Hospital. Eighty-six patients (33%) had recurrent tumors after initial resection, and sixteen recurrent cases were so-called grade-up tumors that is, grade 3 originating from grade 1 or grade 2 tumor. The morphology of the grade-up tumors mostly showed non-papillary and invasive type. Positivity for urinary cytology of grade-up tumors was 88%. The five-year survival rate of the patients with grade-up tumors was 85% after initial resection of grade-up patients and 48% after treatment of grade-up tumors. The five-year survival rate of the patients with grade-up tumors who were treated by total cystectomy was 72%, whereas that in the patients who were treated by bladder preservation therapy showed a 13% five-year survival rate and all of the six patients died of cancer during the six-year follow-up period. These findings suggest that patients who have grade up tumors should be treated by radical treatment with radical cystectomy.

Adult↗

[Results of mutation analyses of von Hippel-Lindau disease gene in Japanese patients: comparison with results in United States and United Kingdom].

Recently the gene responsible for the von Hippel-Lindau (VHL) disease was identified as a tumor suppressor gene. Our ongoing studies on the mutation of the VHL gene in Japanese 28 VHL families with single strand conformational analyses of DNA and Southern blot analyses revealed 6 cases of insertion or deletion, 1 cases of splice site mutation and 9 cases of missense mutation, and 3 possible intragenic deletions. Our analytical findings are essentially similar to those observed in the western countries. The VHL families associated with pheochromocytoma had the same mutational hot spot as those in the western countries. Molecular analyses of the VHL gene in the Japanese VHL disease substantially improved the understanding of this disease and its inheritance character.

Blotting, Southern↗

Retinoblastoma gene mutation in primary human renal cell carcinoma.

We searched for possible mutations in the E2F-binding region of retinoblastoma gene in primary human renal cell carcinomas, using polymerase chain reaction and single-strand conformational polymorphism analysis of RNA. Retinoblastoma gene mutation was detected in 1 of 21 cases (5%). DNA sequencing of the polymerase chain reaction product verified that this case had a 6-base deletion at the beginning of exon 8. Our findings suggest that mutation of the retinoblastoma gene is involved in only a subgroup of sporadic human renal cell carcinomas.

Base Sequence↗

[Development and expression of p53 in superficial early colorectal carcinoma].

We evaluated the histopathological and immunohistochemical findings of 41 superficial early colorectal carcinomas within 20 mm in diameter and twice of normal mucosa in height for the development. These colorectal cancers were divided into intramucosal carcinoma (21 lesions) and submucosal invasive carcinoma (20 lesions), and classified into two groups: superficial elevated type (25 lesions) and superficial depressed type (16 lesions). The average maximum diameter of superficial elevated type was larger than it of superficial depressed type, furthermore the increase in tumor diameter and the pattern of the overexpression of p53 protein was correlated to the invasivity. On the other hand, we found the submucosal invasion and the overexpression of p53 protein in the smaller depressed type carcinoma. Considering the circumstances mentioned above, we recognized the different development between superficial elevated type and superficial depressed type in the superficial early colon cancer, and thought superficial depressed type was more invasive.

Adult↗

[Combination therapy with interferon-alpha and continuous infusion of 5-fluorouracil for advanced renal cell carcinoma].

Between May 1990 and April 1994, eleven patients with metastatic renal cell carcinoma received a combination therapy with interferon-alpha (IFN alpha) and 5-fluorouracil (5FU). IFN was administered intramuscularly six or ten million units three times per week for 4 weeks and 300 mg/m2 of 5FU was administered by continuous intravenous infusion daily for 4 weeks. Of 8 evaluable patients, two had a partial response (25%) two had a minor response (25%), and two had a stable disease (25%). The common side effects of the regimen were flu-like symptoms (91%), mucositis (64%) and leukopenia (75%). Three patients refused this therapy because of severe mucositis or stomatitis. Although the combination of IFN and 5FU in patients with metastatic renal cell carcinoma had some efficacy, this regimen had severe toxicity especially for the gastrointestinal (GI) tract. None of the patients could be administered the initially scheduled dosage of 500 mg/m2 of 5FU. The dose limiting factor of this regimen is considered to be GI symptoms.

Aged↗

[Complete response of lung metastasis from bladder cancer by combination chemotherapy with methotrexate, epirubicin and cisplatin: a case report].

We report a case of lung metastasis from bladder cancer effectively responding to a combination chemotherapy using methotrexate, epirubicin and cisplatin (MEC therapy). A 78-year-old man with high grade bladder cancer underwent total cystectomy on June 5, 1991. He was pointed out to have an abnormal shadow on the plain chest X-ray on August 14, 1992. Computed tomography demonstrated multiple lung metastasis. MEC combination chemotherapy was applied for this case. After 3 courses of MEC therapy, computed tomography showed marked regression of tumor. He has been alive for 12 months with no evidence of disease after chemotherapy. Toxicity of MEC therapy were moderate myelosuppression and mild anorexia and alopecia. These toxicity was adequately tolerable by the 78-year-old patient. This case suggests that MEC therapy is effective against advanced bladder cancer.

Aged↗

[mRNA expression and protein localization of placental tissue protein 11, 12, 19 in gynecologic malignant tumors].

In recent years, the localization and function of placental tissue proteins (PPs), extracted by Bohn et al., have been extensively studied, the genetic code has been identified for each of the PPs. The present study was carried out to clarify the mRNA expression and protein localization of PP11, PP12, PP19 at the cell level and also to define PP19 the nature of which has remained obscure. PP19 was said to be placenta-derived S-100P. PP11 mRNA was not expressed in cytotrophoblast-derived normal placental tissue or endometrium-derived normal cells, but was expressed in syncytiotrophoblast-derived normal placental tissue, and in choriocarcinoma and endometrial adenocarcinoma, suggesting its involvement in carcinogenesis. PP12 mRNA was expressed in cytotrophoblast-derived normal placental tissue or endometrium-derived normal cells, but was not expressed in syncytiotrophoblast-derived normal placental tissue, choriocarcinoma or endometrial adenocarcinoma, suggesting that this protein serves in the function of normal cells. PP19 mRNA was expressed in the squamous epithelial cells of the uterine cervix and the villous cells, PP19 was localized in more differentiated regions, where cells tended toward keratinization, in both normal and dysplastic uterine cervices. In squamous cell carcinoma, PP19 was localized in more differentiated cells with a large cytoplasm. PP19 mRNA was not expressed in normal endometrial glands, but was detected in endometrial adenocarcinoma, suggesting its involvement in cell differentiation in cervical epitherial cells.

Base Sequence↗

Infrequent somatic mutations of the p16 and p15 genes in human bladder cancer: p16 mutations occur only in low-grade and superficial bladder cancers.

A recently identified gene, p16, located on chromosome 9p21, has been shown to be deleted and/or mutated in various types of human cancers. To investigate structural alterations of p16 and a neighboring gene, p15, we examined human bladder cancers for mutations in the entire coding region of these genes using polymerase chain reaction and single-strand conformational polymorphism analysis. Of 50 samples obtained from patients with bladder cancer, 3 (6%), all low-grade and superficial tumors, were found to have p16 gene alterations. The alterations included 1 missense mutation and 2 single-base deletions. We found no p15 gene mutations in these 50 bladder cancers. Our results suggested that p16 gene mutations, although they occurred at low frequency, are involved in some low-grade and early stage bladder cancers.

Base Sequence↗

Somatic mutations of the von Hippel-Lindau tumor suppressor gene in sporadic central nervous system hemangioblastomas.

Hemangioblastoma is one of the benign tumors in the central nervous system. It is often associated with the von Hippel-Lindau (VHL) disease, a well known hereditary tumor syndrome. It is believed that inactivation of both alleles of VHL tumor suppressor gene is essential in the tumorigenic processes in hemangioblastomas associated with VHL disease. The molecular basis for the development of sporadic hemangioblastomas is not known. Here, we analyzed 13 cases of primary sporadic hemangioblastomas for somatic mutations of VHL gene with single strand conformational polymorphism analyses of the tumor DNAs. We detected abnormal single strand conformational polymorphism pattern in 7 tumors (54%). Of these 7 possibly mutated tumors, we successfully characterized 3 tumors by direct sequencing. We were unable to sequence 4 tumors because of the poor quality of DNA obtained from paraffin blocks. Somatic mutations in the 3 tumors were 2 missense mutations and 1 microdeletion. These mutations were observed in 1 tumor in exon 1 and 2 tumors in exon 2. Our results suggest that mutations of VHL tumor suppressor gene are involved in the development of at least 20% of sporadic central nervous system hemangioblastomas.

Base Sequence↗

Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas.

We analyzed 47 primary sporadic human renal cell carcinomas (39 clear cell and 8 non-clear cell) for mutations of the von Hippel-Lindau (VHL) tumor suppressor gene using the polymerase chain reaction and single strand conformational polymorphism analysis of DNA. All of the positive cases in single strand conformational polymorphism analyses were further characterized by direct sequencing. Somatic mutations were detected in 22 (56%) of 39 clear cell renal carcinomas including 15 deletions, 3 insertions, 3 missense mutations, and 1 nonsense mutation. Nineteen of these mutations predicted to produce truncation of the VHL protein. These mutations mainly occurred in the last one-third region of exons 1, 2, and 3. In addition, loss of heterozygosity of the VHL gene was observed in 16 (84%) of 19 informative clear cell renal carcinomas. No somatic mutations were detected in 8 non-clear cell carcinomas. These results show that the VHL tumor suppressor gene is one of the major tumor suppressor genes in human renal cell carcinomas, especially in the clear cell subtype renal cell carcinoma. Clear cell carcinoma might be distinguished from other pathological types of renal cell carcinomas by molecular genetic techniques.

Base Sequence↗

Differential expression of protooncogenes in human germ cell tumors of the testis.

BACKGROUND: It has been suggested that tumorigenesis of the germ cell tumor of the testis includes abnormal and developmentlike differentiation of primordial germ cells to several mature type tumors. METHODS: To clarify roles of protooncogenes in the unique tumorigenic mechanism in the human germ cell tumor, the authors examined the expression of 15 protooncogenes in human primary germ cell tumors of the testis with Northern blot analyses. RESULTS: Fifteen (94%) of 16 seminomas and 5 (83%) of 6 embryonal carcinomas had a significant levels of N-myc expression, whereas they did not express two receptor type protooncogenes, c-erbB-1 and c-erbB-2. In contrast, some immature teratomas had a high level of c-erbB-1 expression, and an advanced case showed a significant level of c-erbB-2 expression. Immature teratomas did not show N-myc expression. Higher levels of c-mos expression were observed in several cases of seminomas and embryonal carcinomas. Expression of c-Ki-ras or N-ras was observed in all histologic subgroups and normal testes. CONCLUSION: A significant level of N-myc expression may be essential for undifferentiated tumors including seminoma and embryonal carcinoma, whereas c-erbB-1 and possibly c-erbB-2 may have important roles in the differentiated tumors such as immature teratoma. These results suggest that some of the protooncogene expression may be switched critically during the differentiation from seminomas or embryonal carcinomas to the more differentiated-type tumor.

Biomarkers, Tumor↗

Histological evaluation of benign prostatic hyperplasia treated by long-term administration of chlormadinone acetate (CMA).

Although the clinical effects of attempted nonsurgical treatment of benign prostatic hyperplasia have been well documented, detailed histological evaluation of the effects of treatment appears to be limited. The effect of long-term administration of an antiandrogen, chlormadinone acetate (CMA), on benign prostatic hyperplasia was evaluated with histological comparison of two biopsy specimens, one before treatment and one after treatment. Secretory epithelium showed obvious regressive changes with occasional basal cell prominence after CMA treatment. Stromal elements, however, did not show any marked changes, except for occasional edematous loosening. Scores of multiple epithelial parameters tended to be correlated with clinical improvement in urinary obstructive symptoms, especially in patients with predominant glandular hyperplasia. These results suggest that long-term administration of the potent antiandrogen CMA to inhibit dihydrotestosterone-receptor binding might be a useful therapeutic maneuver in patients with glandular hyperplasia, without any deterioration of the stromal component.

Aged↗

A phase II study of prophylactic intravesical chemotherapy with 4'-epirubicin in recurrent superficial bladder cancer: comparison of 4'-epirubicin and adriamycin.

Since intravesical recurrence of superficial bladder cancer (Ta, T1) after transurethral resection (TUR) is frequent, adjuvant therapy to reduce the recurrence rate has been extensively investigated. Although intravesical chemotherapy has been employed for 30 years or more, neither the exact effect on the bladder epithelium nor the optimal dose and administration schedule has yet been clarified. In recent years, several derivatives of Adriamycin (ADR) have been developed, and 4'-epirubicin (FARM) is one of them. This drug has been shown to have antitumor effects almost equal to those of ADR and to produce less toxicity when given systemically as chemotherapy. In an attempt to clarify the effect of intravesical FARM in the prevention of recurrence of superficial bladder cancer, we conducted a prospective randomized trial to compare the effects of equal doses of FARM and ADR given by intravesical instillation after TUR in cases of highly recurrent superficial bladder cancer. A total of 73 patients with recurrent superficial bladder cancer were randomized to receive TUR and either 30 mg FARM or 30 mg ADR by intravesical instillation every 2-4 weeks for 1 year. The prophylactic effect on recurrence and the toxic effects of these drugs were investigated. The current results show that FARM provides efficacy almost equal to that of ADR in the prevention of recurrence in these patients. However, FARM also caused almost the same local toxic effects (bladder irritation, among others) as ADR. On the basis of these preliminary results, FARM is surmised to be one of the agents as beneficial as ADR in the prevention of recurrence of superficial bladder cancer.

Administration, Intravesical↗

Neuroblastoma of parotid gland: report of a case and immunohistochemical characteristics.

A case of a parotid mass in a 2-year-old boy, postoperatively diagnosed as neuroblastoma, a rare tumour not previously reported in the parotid gland is presented. The neoplasm developed within the parotid gland as a painless mass without regional lymphadenopathy. Histopathologically, the tumour showed primitive nerve cells-neuroblasts-with round or oval dark basophilic nuclei and scanty cytoplasm. The cells were arranged in circular rosettes around an eosinophilic mass consisting of very fine filaments originating in the tumour cells or papillary configuration and sometimes scattered in the poorly developed stroma. Immunohistochemical evaluation of the tumour showed a positive immunoreactivity for vimentin, alpha and beta subunits of S-100 protein, neurone-specific enolase (NSE), substance P, met-enkephalin and chromogranin but cytokeratins, desmin, actin, myosin, glial fibrillary acidic protein (GFAP) and calcitonin gene related peptide (CGRP) were negative. The histopathological and immunohistochemical findings conclude a diagnosis of neuroblastoma of the parotid gland.

Child, Preschool↗

Spontaneous rupture of adrenal pheochromocytoma: a case report.

We report a case of retroperitoneal hemorrhage due to spontaneous rupture of a right adrenal pheochromocytoma, presenting as an acute abdominal emergency with symptoms of peripheral vasoconstriction. An elective operation was successfully performed on day 7 after sufficient volume replacement with continuous administration of an alpha and beta-adrenergic blocking agent.

Adrenal Gland Neoplasms↗