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Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 325 records · Page 18Linked to original sources
PubMed1995

Clonal determination of uterine leiomyomas by analyzing differential inactivation of the X-chromosome-linked phosphoglycerokinase gene.

To investigate the clonality of uterine leiomyomas, we developed a PCR-based method involving the differential inactivation of the X-chromosome-linked phosphoglycerokinase (PGK) gene. Small DNA samples of 22 leiomyomas from 9 Japanese patients, showing heterozygosity at the BstXI site of the PGK gene, were digested with the methylation-sensitive restriction enzyme HpaII. Only the inactive (methylated) PGK gene allele was selectively amplified by PCR followed by digestion with BstXI and electrophoresis. All leiomyoma samples consisted of a single type of inactive allele, even though alleles were detected that were specific to each nodule. The results indicated that all leiomyoma nodules were unicellular in origin but independently generated in the uterus.

Adult↗
PubMed1995

A single missense mutation in codon 918 of the RET proto-oncogene in sporadic medullary thyroid carcinomas.

The RET proto-oncogene is expressed in human medullary thyroid carcinoma and pheochromocytoma. Recently germline mutations of the RET proto-oncogene were reported in four syndromes (MEN 2A, MEN 2B, familial medullary thyroid carcinoma and Hirschprung's disease) and somatic mutation was also found in sporadic medullary thyroid carcinoma. To determine the incidence of RET mutations in medullary thyroid carcinoma in Japan, we investigated 14 medullary thyroid carcinomas (comprising 1 case of MEN 2A, 1 case of MEN 2B, 2 cases of familial medullary thyroid carcinoma and 10 cases of sporadic). Tumors from all cases were screened by PCR-SSCP on exons 10 and 11. DNA sequencing on these exons was performed for the hereditary medullary thyroid carcinoma cases. The PCR products of exon 16 from tumor DNA were analyzed by means of Fok1 restriction enzyme digestion analysis and mutations confirmed by DNA sequencing. We found no structural abnormalities in either exon 10 or exon 11 in any of the cases examined, but in four of 10 sporadic cases we detected a common point mutation at codon 918 (ATG to ACG) in exon 16, where methionine was replaced with threonine. Our results support the theory that a point mutation of exon 16 of the RET proto-oncogene may be related to the oncogenesis of sporadic medullary thyroid carcinomas. However, further studies on the entire RET proto-oncogene are needed to clarify the relationship between its expression and thyroid tumorigenesis.

Base Sequence↗
PubMed1995

c-Kit proto-oncogene is more likely to lose expression in differentiated thyroid carcinoma than three thyroid-specific genes: thyroid peroxidase, thyroglobulin, and thyroid stimulating hormone receptor.

Although c-kit proto-oncogene product is known to be weakly expressed on normal thyrocytes, its function is unclear. In order to investigate the significance of thyroid c-kit, c-kit gene expression in 37 various thyroid tissues was analyzed by comparing c-kit gene expression with the mRNA expression of three thyroid-specific genes: thyroid peroxidase, thyroglobulin, and thyroid stimulating hormone receptor, c-kit mRNA was hardly detected by the usual northern blot method in 2 of 7 follicular carcinomas, 11 of 12 papillary carcinomas, and a medullary carcinoma. On the other hand, a high level of c-kit mRNA expression was found in all 17 benign thyroid tissues (4 normal thyroid tissues, 4 Graves' disease, 2 adenomatous goiters, and 7 follicular adenomas). This study found that c-kit proto-oncogene is more likely to lose expression in differentiated thyroid carcinoma than any thyroid-specific gene. Decreased c-kit gene expression may serve as an indicator for the de-differentiation of thyrocytes.

Blotting, Northern↗
PubMed1995

A case of acute exacerbation of chronic hepatitis B accompanied by antibody to HBeAg with remission of liver damage after long-term treatment with interferon.

The patient was a 47-year-old female with chronic hepatitis B having antibody to HBe antigen (HBeAg). She was admitted to our hospital in March, 1994, because of acute exacerbation of chronic hepatitis B. Laboratory data revealed the elevated serum transaminase and DNA-polymerase levels, and decreased prothrombin activity. The histological examination of the liver showed chronic active hepatitis with severe hepatic necrosis. Point mutation of the precore region of HBV-DNA (pre-C mutant) was observed in clones from this case by polymerase chain reaction method. The patient was treated with recombinant interferon alpha-2a 9 MU daily for 2 weeks and thereafter 3 times weekly for 6 months. After interferon therapy, the pre-C mutant disappeared with the improvement of transaminase levels and prothrombin activity. These findings suggest the possibility that long-term treatment with interferon therapy is effective for the acute exacerbation of chronic hepatitis B accompanied by antibody to HBeAg.

Chronic Disease↗
PubMed1995

Thyroid dysfunction induced by interferon therapy for the treatment of hepatitis type C. A report of 4 cases.

We describe 4 patients with onset or aggravation of thyroid dysfunction induced by interferon (IFN) treatment of hepatitis type C. All 4 patients were females; 2 had hyperthyroidism and 2 had hypothyroidism during or after IFN therapy. The onset or aggravation of thyroid dysfunction occurred during administration of IFN in 1 patient and 4 weeks after the end of IFN therapy in the remaining 3 patients. The 2 patients who demonstrated hyperthyroidism were euthyroid and negative for thyroid autoantibodies before receiving IFN therapy. The remaining 2 patients who demonstrated hypothyroidism were positive for thyroid autoantibodies before IFN therapy. One of these patients had a slight decrease in thyroid function before IFN therapy. Anti-thyroid stimulating hormone (TSH) receptor antibodies became positive in all 4 patients. Since there may have been a causal relationship between IFN therapy and the onset or aggravation of thyroid dysfunction, IFN therapy should be administered with caution.

Adult↗
PubMed1995

Immunologic type of thyroid lymphoma in an adult T-cell leukemia endemic area in Japan.

Our previous study showed that thyroid non-Hodgkin's lymphoma (TL) in an adult T-cell leukemia/lymphoma (ATL) non-endemic area were exclusively B-cell derived. The present study was carried out to examine whether TL in an ATL endemic area are also exclusively of B-cell type. Eight cases with TL admitted to the hospital situated in an ATL endemic area were studied: they were all female with an age range from 50 to 75 (median 67) years. Histologically four of the eight cases showed a follicular pattern. Immunophenotypic study revealed all but one case to be of B-cell nature: CD3-, 4-, 8-, 20+, 22+, 45RA+, 45RO-, L22-, L24+/-, L28+. Neoplastic cells in one case with the histology of diffuse large cell lymphoma showed a CD3+, 4+, 8-, 20-, 22-, 45RA-, 45RO+/-, L22-, L24-, L28-, indicating a helper T-cell phenotype. Genotypic study showed rearrangement of T-cell beta-chain receptor in this case. This case also had antibodies against HTLV-1 in the serum. This case shows that it is also possible to develop T-cell TL in an endemic ATL area.

Aged↗
PubMed1995

[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↗
PubMed1995

[Prognostic factors for metastatic renal cell cancer].

We examined various prognostic factors of metastatic renal cell carcinoma. Patients who had metastasis at nephrectomy (A group, 38 cases) and those who had metastasis as recurrent tumors after nephrectomy (B group, 38 cases) entered in this study. Five-year survival rate of total cases after confirmation of metastatic foci was 15% and there was no statistical significant difference between A and B groups. Several pathological factors were related to poorer prognosis and included large diameters of original tumors, positive lymph nodes, higher grade tumors and non-clear cell type tumors. Patients who have a solitary lung metastasis showed better prognosis compared to those with multiple lung metastases or metastases of other organs. Two factors related to treatment were shown to contribute to better prognosis. These were the response to interferon alfa (IFN alpha) and the possibility of total resection of visible metastatic tumors. Patients who belong to A group were shown to achieve markedly better therapeutic benefit from IFN alpha or IFN alpha plus anticancer drugs. Five-year survival rate for the responders was 40%, as compared to less than 5% for the non-responders. Ten-year survival rate for patients with metastasis who had undergone complete resection of visible tumor was 50%, and the for patients belonging to B group Showed 80%. We concluded that these prognostic factors should be considered to decide how to select patients with metastatic renal cell cancer.

Adult↗
PubMed1995

[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↗
PubMed1995

[Preparation and application of knock-out mice].

Mouse embryonic stem cells can be cultured in vitro and still retain their pluripotency. When reintroduced into mouse embryos, these cells can contribute to the germ line of the resultant chimeras. Homologous recombination between DNA sequences residing in the chromosome of embryonic stem cells and newly introduced DNA sequences allows the transfer of any modification of the cloned gene into the genome of a living mouse. This article discusses the current status of knock-out mice preparation, with emphasis on unsettled steps, during the knock-out procedure and introduces some of the newly developed gene targeting techniques by which more ideal animals can be prepared.

Animals↗
PubMed1995

[Prognostic factors for breast cancer].

Recently, a variety of new prognostic factors for breast cancer have been advocated, although most of these studies are still preliminary. Until the results of definitive studies to evaluate the clinical usefulness of these new factors are obtained, it is practically relevant to plan a treatment schedule of breast cancer patients through classical prognostic factors such as tumor size, axillary lymph node status, histological grade, and estrogen/progesterone receptor status.

Breast Neoplasms↗
PubMed1995

[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↗
PubMed1995

[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↗
PubMed1995

Sarcoglycan complex is selectively lost in dystrophic hamster muscle.

We recently reported that the dystrophin-associated glycoprotein (DAG) complex is biochemically divided into two subcomplexes: one is the dystroglycan complex comprised of 156DAG and 43DAG and the other is the sarcoglycan complex comprised of 50DAG, A3b, and 35DAG. A3b is a novel dystrophin-associated glycoprotein with an approximate molecular mass of 43 kd but is distinct from 43DAG. In the present study, we examined the striated muscles of the dystrophic hamster with anti-A3b antibody in addition to anti-50DAG, anti-43DAG, anti-35DAG, anti-dystrophin, and anti-laminin antibodies by both immunohistochemistry and immunoblot analysis and found that 50DAG, A3b, and 35DAG are selectively lost. This selective defect of the sarcoglycan complex in dystrophic hamster muscles may give rise to dystrophic changes in striated muscles. Thus, the differentiation of the dystrophin-associated glycoprotein complex into the dystroglycan and sarcoglycan complexes is important not only from a biochemical standpoint but also in understanding the cause of muscular dystrophy in the hamster. Our findings further show that the dystrophic hamster may serve as an animal model for a human disease, severe childhood autosomal recessive muscular dystrophy, which has recently been shown to result from a selective defect in the sarcoglycan complex.

Animals↗
PubMed1994

Over-expression of membrane-bound cytochrome c-551 from thermophilic Bacillus PS3 in Bacillus stearothermophilus K1041.

Cytochrome c-551 is a lipoprotein of about 10500 Da, found in thermophilic Bacillus PS3 grown under air-limited conditions. An expression vector was constructed from a structural gene of PS3 cytochrome c-551, synthetic oligonucleotide as a promoter for Bacillus stearothermophilus and a shuttle vector for Escherichia coli and B. stearothermophilus. The transformed cells of B. stearothermophilus K1041 expressed cytochrome c-551 as much as 5 nmol/mg membrane protein. The effects of over-expression on the host cells are analyzed; a slightly slower growth rate and an increased synthesis of cytochrome oxidase (about twofold) occurred. Over-expressed (4-10-fold) cytochrome c-551 were purified and its properties were examined to know whether the protein is processed as in PS3 cells grown under air-limited conditions. The molecular mass determination and treatment with Rhizopus lipase suggested that the same processes, cleavage of signal peptidase, blocking of the N-terminal group and acylation of glycerol residue by two fatty acids, took place in the over-expression system. Fatty acylation seems useful for the cytochrome c to be effectively oxidized.

Acylation↗
PubMed1994

Characterization of the zona pellucida glycoproteins from bovine ovarian and fertilized eggs.

Bovine zona pellucida (ZP) glycoproteins from ovarian egg emerged as three bands with molecular mass of 78 kDa, 64 kDa and 21 kDa in SDS-PAGE under reducing conditions. Endo-beta-galactosidase (E beta G) digestion of the glycoproteins yielded five products with molecular mass of 76 kDa (E beta G-76), 68 kDa (E beta G-68), 63 kDa (E beta G-63), 47 kDa (E beta G-47) and 21 kDa (E beta G-21) under the same conditions. The N-terminal amino acid sequences of E beta G-76 and E beta G-21 were identical. This fact together with the results of diagonal SDS-PAGE indicated that E beta G-21 (N-terminal region) is linked to E beta G-63 (C-terminal region) through disulfide bond to form E beta G-76. Immunoblot analysis using anti-pig ZP protein antibodies revealed that bovine E beta G-76, E beta G-68 and E beta G-47 correspond to pig PZP2, PZP3 alpha and PZP3 beta glycoproteins, respectively. The E beta G-76 and E beta G-68 components were shown to be specifically cleaved during fertilization.

Amidohydrolases↗
PubMed1994

Selective defect of sarcoglycan complex in severe childhood autosomal recessive muscular dystrophy muscle.

Dystrophin-associated glycoprotein complex is classified into two subcomplexes: the dystroglycan complex (156DAG and 43DAG) and the sarcoglycan complex (50DAG, A3b, and 35DAG). Severe childhood autosomal recessive muscular dystrophy (SCARMD) was first reported to result from a deficiency of 50DAG. We examined muscles from five SCARMD patients and found that dystrophin and 43DAG were present in almost normal levels while 35DAG and the newly-identified protein A3b in addition to 50DAG were absent or greatly reduced. Therefore, SCARMD is the disease with a selective defect of the sarcoglycan complex.

Child↗