Biomedical subjects

M Noguchi

Publications and source records attributed to M Noguchi.

At least 163 records · Page 9Linked to original sources

PubMed1998

The Role of Hormonal Therapy in Breast Cancer.

This review reassesses the role of hormonal therapy in breast cancer specifically the sequential or concurrent use of endocrine therapy and the combined use of chemotherapy with endocrine therapy. In advanced disease the sequential use of hormone therapies is generally recommended rather than the combined use of various hormonal agents, though combination hormonal therapy offers advantages in certain subsets of patients. The efficacy of combined chemo-endocrine therapy is questionable. Chemotherapy with estrogenic recruitment is an attractive but still experimental concept. However, in an adjuvant setting there is evidence that combined chemo-endocrine therapy causes a significant increase in disease-free and/or overall survival, particularly in postmenopausal patients with estrogen receptor(ER)-positive tumors. While hormonal treatment strategies have clearly benefitted from randomized studies, data regarding optimal endocrine therapy are still insufficient.

Journal Article↗

PubMed1998

The Role of Internal Mammary Lymph Node Metastases in the Management of Breast Cancer.

We reviewed the literature regarding internal mammary lymph node metastasis in the management of breast cancer. Internal mammary dissection or radiotherapy provides no survival advantage in breast cancer patients. However, internal mammary nodal metastasis is an important independent prognostic factor. Patients with such metastases are candidates for systemic adjuvant hormonal therapy and/or chemotherapy. Moreover, in patients with histologically confirmed internal mammary metastases, irradiation of the nodes is appropriate for local control. Noninvasive techniques, such as internal mammary lymphoscintigraphy, parasternal sonography, computed tomography, and magnetic resonance imaging, are not satisfactory for the practical diagnosis of internal mammary metastasis. At present, biopsy of the internal mammary nodes in the first and second intercostal spaces is indicated for assessing nodal status and planning treatment.

Journal Article↗

PubMed1998

Changes in the gap junctional intercellular communication in renal tubular epithelial cells in vitro treated with renal carcinogens.

Gap junctional intercellular communications (GJIC) are known as the channels for the direct transfer of cytoplasmic molecules between neighboring cells and are lost during transformation of normal cells. To study the function and the molecular mechanism for the loss of GJIC, the effects of dimethylnitrosamine, KBrO3 and FeSO4 x 7H2O, which are known as chemical tumor promoters of the kidney on the GJIC function and the expression of connexin 43 of Madin-Darby canine kidney (MDCK) epithelial cells, were examined. These tumor promoters inhibited the GJIC in MDCK cells. The expression of connexin 43 mRNA and connexin 43 protein was not altered by these treatments, whereas immunocytochemical study revealed that the distribution of connexin 43 protein was changed from the cell surface to the cytoplasma. These data suggest that blockage of GJIC in MDCK cells treated with renal carcinogens support the hypothesis that loss of GJIC might be important in renal carcinogenesis.

Animals↗

PubMed1998

Therapeutic strategies and long-term results in differentiated thyroid cancer.

Differentiated thyroid carcinoma (DTC) is usually an indolent tumor associated with a low mortality. However, DTC, particularly papillary thyroid carcinoma, happens to be a multicentric tumor and tends to spread to the regional lymph nodes in the early stage of the disease; some patients with DTC do die from metastatic or recurrent disease. Despite the small number of these patients, therapeutic strategies designed to prevent such outcomes should be pursued. In this review, we attempt to evaluate the impact of different therapeutic strategies on survival and recurrence. Consequently, we conclude that the surgical approach to DIC should be individualized on the basis of the biologic behavior of the tumor, rather than on the extent of cancer involvement in the thyroid and regional lymph nodes. It is mandatory to expand our efforts to identify high-risk patients more accurately, thereby facilitating more rational approaches to treatment.

Combined Modality Therapy↗

PubMed1998

Effect of subtotal thyroidectomy on natural history of ophthalmopathy in Graves' disease.

Graves' ophthalmopathy is a complex disease whose pathogenesis is thought to be autoimmune. The treatment of Graves' disease is considered to be related to the progression of Graves' ophthalmopathy. There have been no long-term prospective studies on the natural course of Graves' ophthalmopathy. In this study we assessed the influence of subtotal thyroidectomy on the outcome of Graves' ophthalmopathy, comparing it with that of radioactive iodine treatment. Altogether 287 untreated patients with Graves' disease referred to Ito hospital in 1989 were followed prospectively for 5 years. A group of 67 patients were treated with radioactive iodine, and 18 patients underwent surgery. Proptosis of the eyes was measured in all patients using Hertel's exophthalmometer. The mean value of proptosis in patients with untreated Graves' disease was 14. 8 +/- 0.2 mm (mean +/- SEM), and after 5 years it increased slightly to 15.0 +/- 0.2 mm. The mean changes of proptosis in patients treated surgically and patients given radioactive iodine were -0.01 +/- 0.22 and 0.93 +/- 0.28 mm, respectively (p < 0.05). In patients treated by subtotal thyroidectomy, ophthalmopathy did not change in 77.8%; it progressed in 5.6% and was alleviated in 16.7%. In patients treated with radioactive iodine, the ophthalmopathy did not change in 86.6%, progressed in 10.4%, and was alleviated in 3.0%. These findings indicate that surgery can be a better treatment than radioactive iodine for Graves' patients with ophthalmopathy.

Adult↗

PubMed1998

Generation of mutant mice with large chromosomal deletion by use of irradiated ES cells--analysis of large deletion around hprt locus of ES cell.

A method of generating mice from embryonic stem (ES) cells with a large chromosomal deletion produced by X-ray irradiation has been developed. Fifty-two mutant ES clones were made that carried a nested set of chromosomal deletions up to approximately 10 cM in length around the hprt locus on the X Chromosome (Chr). Germline chimeras were generated from three ES clones with deletions ranging from 200 to 700 kb. In germline male mice from two independent clones, deletions around the hprt locus yielded a runty phenotype or caused death at birth. The runty mice had approximately 1/3 the body weight and size of wild littermates and did not survive more than 3 weeks after birth. The most plausible cause of these phenotypes is defects in regions flanking the hprt locus. This method of creating mutant mice with a large chromosomal deletion is very useful for the identification and understanding of gene functions.

Animals↗

PubMed1998

Conjugated linoleic acid modulates tissue levels of chemical mediators and immunoglobulins in rats.

The effects of conjugated linoleic acid (CLA) on the levels of chemical mediators in peritoneal exudate cells, spleen and lung, and the concentration of immunoglobulins in mesenteric lymph node and splenic lymphocytes and in serum were examined in rats. After feeding diets containing either 0 (control), 0.5 or 1.0% CLA for 3 wk, there was a trend toward a reduction in the release of leukotriene B4 (LTB4) from the exudate cells in response to the dietary CLA levels. However, CLA did not appear to affect the release of histamine. A similar dose-response pattern also was observed in splenic LTB4, lung LTC4 and serum prostaglandin E2 levels, and the differences in these indices between the control and 1.0% CLA groups were all statistically significant. The reduction by CLA of the proportions of n-6 polyunsaturated fatty acids in peritoneal exudate cells and splenic lymphocyte total lipids seems to be responsible at least in part for the reduced eicosanoid levels. Splenic levels of immunoglobulin A (IgA), IgG, and IgM increased while those of IgE decreased significantly in animals fed the 1.0% CLA diet. This was reflected in the serum levels of immunoglobulins. The levels of IgA, IgG, and IgM in mesenteric lymph node lymphocytes increased in a dose-dependent manner, while IgE was reduced in those fed the higher CLA intake. However, no differences were seen in the proportion of T-lymphocyte subsets of mesenteric lymph node. These results support the view that CLA mitigates the food-induced allergic reaction.

Animals↗

PubMed1998

Genetic risk factor for abdominal aortic aneurysm: HLA-DR2(15), a Japanese study.

PURPOSE: Autoimmunity has been proposed to play a role in the pathogenesis of the abdominal aortic aneurysm (AAA). Several autoimmune diseases are associated with specific HLA DR alleles. These experiments were carried out to determine whether the same HLA DR types that have been reported to be associated with AAA in a mixed North American population are similarly associated with AAA in a more homogeneous group of patients in Japan. METHOD: HLA DR typing was performed by a serologic method on samples of peripheral blood of patients with nonspecific infrarenal AAA in Nagasaki University Hospital in Japan. The frequencies of HLA DR antigens were compared with those of volunteers approximately matched for age and sex from the same referral area. RESULTS: HLA DR haplotypes were determined in 46 Japanese patients with AAA and in 50 patients in a control group. The HLA-DR2(15) antigen was observed in 27 (58.7%) patients (29 alleles 31.5%) with AAA and in 14 (28%) subjects (16 alleles 26.0%) in the control group (p < 0.005). CONCLUSIONS: The data suggest that HLA-DR2(15) has an important role as a genetic risk factor for AAA in Japanese patients, as previously reported in a mixed North American population.

Aged↗

PubMed1998

14q11 abnormality and trisomy 8q are not common in Japanese T-cell prolymphocytic leukemia.

We studied ten cases of Japanese T-cell prolymphocytic leukemia (T-PLL) collected over the last 9 years. Median age was 61 years with a male predominance (M:F, 8:2). The main disease features were splenomegaly, lymphadenopathy, hepatomegaly, skin lesions and serous effusions. The clinical course was progressive with a median survival of 10 months. Immunophenotyping showed that the prolymphocytes had a post-thymic phenotype (TdT-, CD1a-, CD2+, CD3+, CD5+, CD7+) with a predominant CD4+ immunophenotype. Cytogenetic analysis showed no consistent abnormalities. 14q abnormality and trisomy 8q, which are frequently seen in T-PLL of Western countries, were found in only two and zero cases, respectively. We conclude that the clinical and biological characteristics of T-PLL in Japan are almost the same as those in Western countries. However, the cytogenetic findings of T-PLL in Japan might be different.

Adult↗

PubMed1998

Overexpression of CAF1 encoding a novel Ca2+-binding protein stimulates the transition of Dictyostelium cells from growth to differentiation.

Among the expressed genes associated with the switch-over of Dictyostelium cells from cell proliferation to differentiation, the Calfumirin-1 (CAF1) gene has been shown to be preferentially expressed at the initial step of differentiation, encoding a novel Ca2+-binding protein (Abe & Maeda 1995). To analyze precisely the function of CAF1, transformants overexpressing the CAF1 mRNA at the vegetative growth phase and also CAF1-null mutants were prepared, and their developmental features were compared with those of parental wild-type cells. As a result, the CAF1-overexpression was found to promote cell differentiation, possibly through prompt induction of the cAMP receptor 1 (CAR1) gene expression. In addition, the CAF1-overexpressing cells were able to differentiate even under low external Ca2+ ([Ca2+]e) conditions around 10(-6) mol/L at which non-transformed wild-type cells never differentiated. Unexpectedly, however, the CAF1-null mutant produced by homologous recombination exhibited apparently normal development to form fruiting bodies on non-nutrient agar. These results seem to indicate that CAF1-overexpression has a stimulatory effect on differentiation, but that the CAF1 protein is not necessarily required for the phase-shift of cells from growth to differentiation.

Animals↗

PubMed1998

Analysis of loss of heterozygosity in small adenocarcinomas of the lung.

BACKGROUND: Despite the many studies of genetic alterations in advanced lung carcinomas, few reports have analyzed early stage adenocarcinoma of the lung. METHODS: We focused on small pulmonary adenocarcinomas, classified according to recently proposed histological criteria (Noguchi M., et al. Cancer 1995;75:2844-52) which divided adenocarcinomas 2 cm or less in diameter into two groups; one showing replacing growth of the pulmonary alveolar structure [A, localized bronchioloalveolar carcinoma (LBAC); B, LBAC with alveolar collapse; C, LBAC with active fibroblastic proliferation] and the other showing non-replacing growth (D, poorly differentiated adenocarcinoma). Ninety-four small pulmonary adenocarcinomas, including 40 of type A and B, 30 of type C and 24 of type D, were examined for loss of heterozygosity (LOH) using microsatellite markers. RESULTS: The frequencies of LOH were 19.8% in types A and B, 26.8% in type C and 32.7% in type D tumors. There were no significant differences in the frequency of LOH on chromosomes 2p, 3p, 9p and 17q among tumor types. However, on 17p, the frequency of LOH was significantly lower for types A and B than for type C or D. Three out of six type C tumors which were positive for LOH at several loci showed different LOH patterns in two areas (central and peripheral regions). CONCLUSIONS: Allelic losses were detected in very early adenocarcinomas and the frequency of LOHs on chromosome 17p increased during malignant progression of the tumor. Heterogeneous genetic alterations were demonstrated even in small pulmonary adenocarcinomas.

Adenocarcinoma↗

PubMed1998

Microsatellite instability and frameshift mutations in the Bax gene in hereditary nonpolyposis colorectal carcinoma.

We studied microsatellite instability (MI) and bax gene abnormalities in colorectal carcinomas from 36 patients diagnosed as having hereditary nonpolyposis colorectal cancers (HNPCC) according to the clinical criteria (12 with confirmed HNPCC in group A and 24 at high risk of HNPCC in group B) and from 20 randomly selected patients with other colorectal cancers. MI was examined at 4 dinucleotide microsatellite loci and one mononucleotide locus. Frameshift mutations in the bax gene were detected by polymerase chain reaction-single strand conformation polymorphism analysis. MI was detected in 7 of the 12 patients in group A and 12 of the 24 in group B. Three MI patterns were identified: type 1, MI in both mono- and dinucleotide repeats; type 2, MI only in mononucleotide repeats and type 3, MI only in dinucleotide repeats. Most MI-positive patients in group A showed type 1 MI, whereas in group B, 5 showed type 1, 3 showed type 2 and 4 showed type 3. Frameshift mutations in the bax gene correlated strongly with type 1 and type 2 MI. These results indicate that mutations of different DNA mismatch repair genes may cause several types of MI and result in several different clinical phenotypes of HNPCC. The bax gene may be one of the target genes which play a role in the tumorigenesis of HNPCC.

Colorectal Neoplasms↗

PubMed1998

The implication of anthracosis in the development of pulmonary adenocarcinoma.

The relationship between anthracosis, which is the deposition of black dust matter in the lung parenchyma, and the development of pulmonary adenocarcinoma has not been fully characterized. In order to clarify whether background black dust matter deposition could be implicated in the development of pulmonary adenocarcinoma, we measured the level of anthracosis at autopsy in 47 patients who had died of pulmonary adenocarcinoma. Both lungs of all 47 cadavers were examined. Twenty-micrometer sections were cut from formalin-fixed, paraffin-embedded blocks of the largest cut surface of each lung. Black dust matter was extracted from the sections and blotted onto a nitrocellulose membrane. The density of the blotted black dust matter was then analyzed using an imaging densitometer. There were no significant differences in the density of black dust matter deposition between lungs affected by pulmonary adenocarcinoma and control lungs. However, well differentiated adenocarcinomas tended to develop more frequently than poorly differentiated ones in lungs showing less deposition. We found a very strong correlation between the degree of black dust matter deposition and smoking history. Patients with severe anthracosis tended to have a poorer prognosis than those with mild anthracosis.

Adenocarcinoma↗

PubMed1998

Lung cancer patients have increased 8-hydroxydeoxyguanosine levels in peripheral lung tissue DNA.

The 8-hydroxydeoxyguanosine (8-OH-dG) levels in the peripheral parts of human lung tissues were compared between lung cancer patients (n=70) and non-cancer patient controls (n=15). An increased level of 8-OH-dG was observed in the lung cancer group, in both the adenocarcinoma and non-adenocarcinoma (mainly squamous cell carcinoma) groups, as compared to the non-cancer control group. This result suggests that reactive oxygen species are partly involved in the induction of lung carcinomas (both adenocarcinoma and non-adenocarcinoma).

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1998

A case of double primary adenocarcinoma of the lung with multiple atypical adenomatous hyperplasia.

A case of double primary adenocarcinoma of the lung with multiple atypical adenomatous hyperplasia (AAH) in a 77-year-old woman is reported. Histopathologically, in the resected left upper lobe of the lung, both cancers were diagnosed as well-differentiated papillary adenocarcinoma, and 161 lesions of AAH were also found. Both the cancer lesions and six AAH (greater than 3 mm in diameter) were examined with regard to immunoreactivity of carcinoembryonic antigen (CEA) and p53 gene product, microsatellite instability (MI) and loss of heterozygosity (LOH) on chromosome 9q and 17q by polymerase chain reaction (PCR). Although both cancers expressed CEA, they did not show clonal immunoreactivity for the p53 gene product. Atypical adenomatous hyperplasia expressed CEA weakly and showed no immunoreactivity for p53 gene protein. Both carcinomas showed LOH on chromosome 17q, and one of them showed LOH on chromosome 9q. In six AAH, LOH on chromosome 17q was detected in two tumors, and one of them also showed LOH on chromosome 9q. One AAH, which was negative for LOH on chromosome 17q and 9q, showed MI at D17S791. These results indicated that AAH is a clonal neoplastic lesion with genetic abnormalities and should be called intraepithelial pneumocyte neoplasia, and that each of the numerous papillary lesions in this case was considered to be an independent lesion.

Adenocarcinoma, Papillary↗

PubMed1998

Leukocyte removal filter-passed lymphocytes produce large amounts of interleukin-4 in immunotherapy for inflammatory bowel disease: role of bystander suppression.

To determine immunosuppression by leukocytapheresis, we studied the immune profiles of filter-passed lymphocytes (FPLs) in patients with ulcerative colitis. These patients were treated with a leukocytapheresis (LCAP) filter of granulocyte apheresis (GCAP) column. Cytokine profiles or FPLs and peripheral blood mononuclear cells (PBMCs) were examined using interleukin (IL)-4 and interferon-gamma (IFN-gamma) immunoassay with lectin stimulation. The IL-4 production of LCAP FPLs was significantly higher than in prefilter PBMCs and GCAP column-passed lymphocytes (median: 540 pg/ml x 10(6) cells versus 4.7 and 2.9, respectively, p = 0.001). IL-4 production in PBMCs was increased after LCAP. IFN-gamma production was not increased in the FPLs. The IL-4 immune deviation was not shown in the patients treated with GCAP. LCAP FPLs showed increased CD4+DR- cells and decreases CD4+DR+ cells in comparison to PBMCs. LCAP FPLs could produce IL-4 and may lead to bystander suppression.

Adult↗

PubMed1998

[Clinical efficacy of fosfomycin in combination with sulbactam/cefoperazone in the treatment of severe infections complicated to blood dyscrasia. Working Group of Kanto Combination Therapy for FOM + SBT/CPZ].

In the treatment of severe infections complicated to blood dyscrasia, the efficacy and usefulness of fosfomycin (FOM) in combination with sulbactam (SBT)/cefoperazone (CPZ) were compared between patients receiving FOM in the first followed by SBT/CPZ (Group A) and those receiving both drugs simultaneously (Group B). The following results were obtained. 1. The efficacy rate was 56.3% for Group A and 47.9% for Group B, with no significant difference. 2. The efficacy for patients suspected of the presence of septicemia, the efficacy rate was 57.9% for Group A and 54.3% for Group B, with no significant difference. 3. As for underlying disease, patients with acute myelogenous leukemia were most prevailing. In these patients, the efficacy rate was 57.1% for Group A and 27.3% for Group B, with no statistically significant difference. However, the efficacy rate tended to be higher in Group A. 4. The administration of antibiotics was effective to restore the neutrophil count to 501/microliters or higher in 77.8% and 45.5% of the cases for Groups A and B, respectively, with significantly higher efficacy for Group A. 5. In the safety evaluation a total of 115 cases were included. Side effects and laboratory abnormalities were seen in 3 cases each, but none of them were serious in degree. From these results, it was confirmed that the combination therapy consisting of administration of FOM followed by SBT/CPZ with some interval is effective for severe infections complicated to blood dyscrasia.

Anti-Bacterial Agents↗

PubMed1998

Secretion imbalance between tumour necrosis factor and its inhibitor in inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor (TNF) alpha and TNF-beta are soluble ligands binding to TNF receptors with similar activities; soluble TNF receptors neutralise TNF activity by acting as inhibitors. Little is known about the cytokine/soluble receptor role in inflammatory bowel disease (IBD). AIMS: To test the hypothesis that an imbalance in secretion between TNF and TNF inhibitors plays a role in gut inflammation in patients with IBD. METHODS: The secretion of TNF-alpha, TNF-beta, and soluble TNF receptors was compared in the culture supernatants of colonic biopsy specimens and isolated lamina propria mononuclear cells from patients with active colonic IBD. RESULTS: Spontaneous secretion of TNF-alpha in involved IBD mucosa was higher than in normal control and self limited colitis mucosa. Secretion of TNF-beta was higher in patients with Crohn's disease than in those with ulcerative colitis. Soluble TNF receptor in IBD mucosa inhibited TNF activity. Type 2 soluble receptor release from IBD mucosa was increased in active inflammation; release from lamina propria cells was not increased. Mucosal TNF-alpha production correlated with severity of disease. CONCLUSIONS: Results showed enhanced secretion of TNF-alpha but failure to release enhanced amounts of soluble TNF receptor in lamina propria mononuclear cells of patients with IBD. An imbalance in secretion between TNF and TNF inhibitor may be implicated in the pathogenesis of IBD.

Adolescent↗