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Biomedical subjects

H Miyamoto

Publications and source records attributed to H Miyamoto.

At least 181 records · Page 10Linked to original sources

[Prognosis and prognostic factor after extended lymphadenectomy in lung cancer].

From 1984 to 1994, 418 patients were received surgery for the lung cancer in our center. Of them, 178 patients were underwent extended lymphadenectomy. Fifty six of the 178 were histologically proven N2 of N3 alpha disease after surgery. Extended lymphadenectomy means R2b lymphadenectomy including the left tracheobronchial node dissection for the right lung cancer and R3 (bilateral mediastinal lymphadenectomy through a median sternotomy) for the left. In the 56 patients, we examined the location and frequency of metastases to the mediastinal lymph nodes and the relationship between some clinical factors (pT, number of metastatic station, clinical staging of the lymph node (CN), histological type, contralateral mediastinal lymph nodes metastases) and prognosis. Most of the pN2 patients of the right lung cancer showed ipsilateral mediastinal lymph nodes metastases and 25 percent of the patients showed the spread to N2b mediastinal modes. The patients of the left lung cancer showed higher incidence of contralateral mediastinal lymph nodes metastases than the patients of the right lung cancer. The five years survival rate of all pN2 patients (N = 39) was 48%, and T1 or T2-N2 patients (N = 22) was 67%. On the other hand, all T4 N2 patients (N-9) died within 3 years after operation. There was no significant difference in postoperative survival between the patients with single station metastasis (N = 20) and multistation metastases (N = 30, including 11 cases with N3 alpha). The five years survival rate of all the patients with multistation metastases was 45%, and that of T1 or T2 multilevel (N = 20) was 65%. There was significant difference in postoperative survival between the patients with CN0-pN2 and CN2-pN2 (p < 0.05). The five years survival of CN0-pN2 patients (N = 14) was 85% and four years survival rate of CN2 pN2 patients (N = 19) was 30%. Among the patients with T1 or T2 tumor, however, there was no significant differences in postoperative survival between CN0-pN2 patients and CN2 pN2 patients. There was no difference in postoperative survival between adenocarcinoma and squamous cell carcinoma (5 years survival: 56%, 43%). In conclusion, extended lymphadenectomy has brought a good prognosis in the patient with T1 or T2 in spite of presence of CN2 or multistation N2. The patients with contralated mediastinal metastases (N3 alpha) showed good prognosis after R3 (5 years survival: 100%) in the patients with the left lung cancer (N = 6). But the N3 alpha patients of right lung cancer showed poorer prognosis (3 years survival: 30%) after R3 (N = 5) than the left. It suggested that R3 lymphadenectomy was significant and beneficial for the left lung cancer patients with N3 alpha but controversial for the right.

Aged↗

Analysis of p21Waf1/Cip1 expression in normal, premalignant, and malignant cells during the development of human lung adenocarcinoma.

Our studies suggested that adenocarcinoma of the peripheral lung mostly develops by several steps from atypical adenomatous hyperplasia through early adenocarcinoma to overt adenocarcinoma, and that some p53 abnormalities play an important role in this progression. In the present study, we examined by immunohistochemistry the expression of p53-inducible cyclin-dependent kinase inhibitor p21Waf1/Cip1 (p21) in the cells at various developmental stages of lung adenocarcinoma (32 lesions of adenomatous hyperplasia, 14 of early adenocarcinoma, 23 of well differentiated adenocarcinoma, and 17 of moderately or poorly differentiated adenocarcinoma) in comparison with 19 reactive proliferative lesions and analyzed the relationship between p53 and p21 expression. Bronchioalveolar cells in the normal lung expressed very little or no p21 and no p53 expression. In not only reactive but also neoplastic lesions regardless of their developmental stage, the cells expressed p21 at various frequencies. The average labeling indices ranged from 5.4 to 13.8%, and there was no significant difference between any of these categories. The expression of p21, however, tended to be relatively low in moderately and poorly differentiated adenocarcinomas (5.5%) compared to well differentiated adenocarcinomas (12.2%), and high-level p21 expressors (10% < or = positive cells) were more frequent in the latter group (1 of 17 (6%) versus 3 of 23 (35%), P < 0.05), suggesting that p21 expression is affected by the degree of differentiation of the neoplastic cells. Although the correlation was positive between the expression of p21 and p53 in reactive lesions (r = 0.88; P < 0.001), none was found in neoplastic lesions at any step or grade (-0.12 < or = r < or = 0.26). These results indicated that p21 expression depends upon p53 expression in reactive lung cells, whereas p21 expression is at least in part independent of that of p53 from the earliest to the most fully developed step of lung adenocarcinoma tumorigenesis. We concluded that disruption of the p53-dependent cell cycle regulation is a very early event in the tumorigenesis of lung adenocarcinoma.

Adenocarcinoma↗

[Six patients in whom exacerbation of asthma was complicated by mediastinal emphysema].

We encountered 6 patients with bronchial asthma complicated by mediastinal emphysema. Their average age was 21 years. All were atopic and had histories of asthma in childhood. In 5 of the 6, mediastinal emphysema developed when the patients had upper respiratory infections. In 3, the mediastinal emphysema worsened. After insertion of subcutaneous drains to decrease intramediastinal pressure, the conditions of those 3 patients improved remarkably. The conditions of the other 3 improved after medication only. During the period of this study, 1.24% of all patients treated at Hiroshima Asa Citizen's Hospital for exacerbations of asthma had mediastinal emphysema.

Adolescent↗

[Relationship between the presence of side-holes in bone marrow aspiration needle and the number of harvested bone marrow mononuclear cells].

The aim of this study was to evaluate the yield of nucleated cells in bone marrow harvested by means of Downs' Islam aspiration needles with or without side-holes. Twenty marrow donors for HLA identical sibling transplants were studied. Bone marrow nucleated cells were harvested 50 ml in the right iliac bone with a Downs' Islam aspiration needle with or without side-holes and 50 ml in the left with another kind of needle by means of 5 ml aspirations in each donor. There were no significant difference between the number of nucleated cells by means of Downs' Islam aspiration needles with and without side-holes by cross-over analysis. All nucleated cell counts were 33.06 +/- 12.93 x 10(3)/microliter (mean +/- standard deviation) by means of the needle with side-holes and 32.90 +/- 15.25 x 10(3)/microliter by means of the needle without side-holes. The Downs' Islam aspiration needle without side-holes seems to be better in bone marrow harvest from normal volunteers than that with side-holes, because the former may be stronger than the latter.

Adolescent↗

A carbonic anhydrase from the nacreous layer in oyster pearls.

It is believed that the polymorphism observed in calcium carbonate crystals, such as aragonite and calcite in mollusk shells, is controlled by organic matrix proteins secreted from the mantle epithelia. However, the fine structures of these proteins are still unknown, and to understand the molecular mechanisms of mineralization process, detailed structural analyses of the organic matrix proteins are essential. For this, we have carried out purification, characterization, and cDNA cloning of nacrein, which is a soluble organic matrix protein in the nacreous layer of oyster pearls. Northern blot analysis showed that the nacrein transcript was specifically expressed in mantle pallial. Analysis of the deduced amino acid sequence revealed that the protein contained two functional domains: one was a carbonic anhydrase and another was a Gly-Xaa-Asn (Xaa = Asp, Asn, or Glu) repeat domain; however, the carbonic anhydrase domain was split into two subdomains with insertion of the Gly-Xaa-Asn repeat domain between them. Our findings suggest that nacrein actually functions as a matrix protein whose repeated Gly-Xaa-Asn domain possibly binds calcium and as a carbonic anhydrase that catalyzes the HCO3- formation, thus participating in calcium carbonate crystal formation of the nacreous layer.

Amino Acid Sequence↗

Orally active, nonpeptide vasopressin V2 receptor antagonists: a novel series of 1-[4-(benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepines and related compounds.

This paper describes a novel series of nonpeptide vasopressin V2 receptor antagonists. It has been demonstrated that the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepines and 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-1,5-benzodiazepines show a high affinity for V2 (and V1a) receptors. Among the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepine series, compounds with an alkylamino group on the benzazepine ring have been shown to have oral activity. A lipophilic group at the ortho position on the terminal benzoyl ring is important for both high V2 receptor affinity and oral activity. On the basis of these favorable properties, clinical testing of 31b has begun for use as an oral and iv aquaretic agent.

Administration, Oral↗

Apoptosis occurs in granulosa cells but not cumulus cells in the atretic antral follicles in pig ovaries.

The porcine antral follicles, 3-6 mm in diameter, were dissected from the ovaries of mature pigs, and then granulosa and cumulus cells were isolated from each follicle. In atretic follicles, high activity of neutral Ca2+/Mg2+-dependent endonuclease and DNA ladder formation, estimated by electrophoresis, were noted in granulosa cells but not in cumulus cells. Extremely low activity of the endonuclease and no DNA ladder formation were observed in both types of cells obtained from healthy follicles. Moreover, apoptotic cells were observed histochemically among granulosa cells only. A good correlation (r = 0.987) between the endonuclease activity of granulosa cells and the progesterone/estradiol ratio of follicular fluid in each follicle was found. These results suggest that apoptosis occurs in granulosa cells but not cumulus cells in the atretic antral follicles in pigs.

Animals↗

[Legionella infection in occupational and environmental health].

Air condition systems are indispensable for amenity in the work environment. It is known that Legionella species are widely distributed in the water of cooling towers, and that the bacteria are responsible for community-acquired pneumonia (Legionnaires' disease) and for influenza-like symptoms (Pontiac fever). Furthermore, Legionella species are associated with building-related illness. In Japan, however, prevention and countermeasures are inadequate against legionellosis compared to those of Europe and the USA. This is because occupational and environmental medicine in Japan has not been based on a microbiological point of view, and that workplace inspections have not covered cooling towers. Therefore, Legionella species in the water of coolig towers have not been routinely monitored in the work environment. This review describes the microbiological characteristics of Legionella species, their habits in the environment, the source and route of infection, the pathogenesis, the symptoms and treatment of legionellosis, outbreaks of this disease throughout the world, and how to deal with this organism in the work environment to prevent legionellosis.

Environmental Health↗

DNA polymerase beta gene mutations in human bladder cancer.

We examined 24 human bladder cancer tissues for possible mutations in the entire coding region of the human DNA polymerase beta gene using polymerase chain reaction analysis, single-strand conformational polymorphism analysis of RNA, and sequence analysis. DNA polymerase beta gene mutations were observed in four of the 24 cases (16.7%) and included three missense point mutations and a single base insertion. The single base insertion was also observed in our previous study of human prostate cancer, suggesting that this region may be a hot spot for mutation of the DNA polymerase beta gene. No clinical or pathological association was found among the four cases that contained the mutation. Three of the four cases with DNA polymerase beta gene mutation had mutations of the p16 or RB genes or loss of heterozygosity of the p53 and APC gene loci. The results of the study presented here suggest that DNA polymerase beta gene mutations, in combination with mutations of tumor suppressor genes, may be involved in certain cases of human bladder cancer.

Base Sequence↗

The effect and pharmacokinetics of nafamostat mesilate adjunct to cold nondepolarizing cardioplegia in a canine model of cardiac preservation.

We examined the effects of nafamostat mesilate (NM) on myocardial, biochemical, and functional changes in canine hearts. An isolated heart was preserved for 6 h at 5 degrees C and then reperfused for 2 h at 37 degrees C. NM wa added to the cardioplegic solution. At concentrations of both 10(-7) M (n = 8) and 10(-6) M (n = 6), NM was able to maintain myocardial cyclic adenosine monophosphate (cAMP) at a normal level and to reduce guanosine monophosphate (cGMP) concentrations at the end of both preservation and reperfusion. The serum N-acetyl-b-D-glucosaminidase (NAG) concentration during reperfusion was lower in hearts treated with NM 10(-6) or 10(-7) M than in those without NM (P < 0.05). Although NM failed to preserve myocardial concentrations of adenine nucleotide compounds, NM 10(-7) M maintained the +/- dp/dt of the left ventricle after reperfusion at the same level as in the nonischemic control group and better than NM 10(-6) M or no NM (P < 0.05). Myocardial uptake of NM 10(-5) M (higher concentration) was 55% +/- 8% (6-h preservation) and 29% +/- 15% (2-h reperfusion). We conclude that NM 10(-7) M adjunct to non-depolarizing solution does not preserve myocardial adenine nucleotide concentrations but does facilitate the recovery of left ventricular function. NM 10(-5) M (higher concentration) seems to have a high affinity for the myocardium and may depress the recovery of left ventricular function.

Adenine Nucleotides↗

The characterization of tyrosine phosphorylation of 78 and 92 kDa proteins in rat basophilic RBL-2H3 cells.

Previously, we have demonstrated that tyrosine phosphorylation of 78 and 92 kDa proteins in rat basophilic leukemia cells (RBL-2H3) is involved in a signal transduction system for high-affinity IgE receptor (Fc epsilon RI)-mediated histamine secretion. However, it is not clarified whether the tyrosine phosphorylation of 78 and 92 kDa proteins in RBL-2H3 cells is regulated by activation of protein kinase C (PKC) or phosphatidylinositol 3-kinase (PI3-kinase). In this study, therefore, the effect of depletion of PKC in RBL-2H3 cells, or the influence of PKC, PI3-kinase and tyrosine kinase inhibitors on histamine release from RBL-2H3 cells was examined. The elimination of PKC in RBL-2H3 cells induced significant suppression of histamine release, although the tyrosine phosphorylation of 78 and 92 kDa proteins was not inhibited. The inhibition of histamine release was also observed by the treatment with a PKC inhibitor such as H-7, calphostin C, a PI3-kinase inhibitor such as wortmannin or a tyrosine kinase inhibitor such as ST638, genistein, hervimycin A, although the tyrosine phosphorylation of both proteins was inhibited by only ST638. These results suggest that the 78 kDa protein in RBL-2H3 cells is not identical to the protein-tyrosine kinase PTK72 and the tyrosine phosphorylation of 78 and 92 kDa proteins in RBL-2H3 cells occurs upstream of PKC and PI3-kinase activation or is regulated independently of the PKC- and PI3-kinase-dependent signaling pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Bilateral adrenocortical carcinoma showing loss of heterozygosity at the p53 and RB gene loci.

Presented is a rare case of nonfamilial, hormonally nonfunctional adrenocortical carcinoma with synchronous bilateral adrenal involvement. We investigated adrenal and metastatic tumors for loss of heterozygosity affecting four genetic loci containing the tumor suppressor genes p53, RB, DCC, and APC, using polymerase chain reaction and restriction fragment length polymorphism assay. Allelic losses at the p53 and RB loci were detected in all tumor samples, suggesting that the p53 and RB genes are involved in the tumorigenesis of adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗

Effects of long term stimulation of ACTH and angiotensin II-secretions on the rat adrenal cortex.

In the rat adrenal cortex, aldosterone synthase cytochrome P450 (P450aldo), a mineralocorticoid synthesizing enzyme, localizes in the zona glomerulosa (zG), while cytochrome P45011 beta (P45011 beta), a glucocorticoid synthesizing enzyme, localizes in the zonae fasciculata-reticularis (zFR). In between zG and zF, a cell-layer which contains neither P450aldo nor P45011 beta is present, where replicating cells were abundant as judged by the incorporation of bromodeoxyuridine (BrdU) and/or by detecting PCNA in their nuclei. When plasma ACTH level of the rat was raised 3-fold for 2-3 weeks by the administration of metyrapone, a potent inhibitor of glucocorticoid formation, most of zG cells containing P450aldo disappeared, while zF cells with P45011 beta increased. Under the conditions, the cell-layer without P450aldo and P45011 beta became very thin, and replicating cells were mainly in the outermost portion of zF. When angiotensin II secretion was also stimulated for 2-3 weeks by feeding the rats on Na-deficient diet, the P450aldo-containing cells proliferated to form a thicker zG (7-8 cells-thick from 1-2), while the width of zF containing P45011 beta decreased slightly. Coincidently the cell-layer devoid of P450aldo and P45011 beta became thin, though slightly, and numbers of replicating cells significantly increased in and around the inner edge of the proliferated zG. When both ACTH and angiotensin II secretions were stimulated simultaneously, the cell-layer without P450aldo and P45011 beta almost disappeared and replicating cells were around the boundary of zG and zF. Based on these results we propose that the cell-layer between zG and zF devoid of P450aldo and P45011 beta is the stem cell layer of rat adrenal cortex.

Adrenal Cortex↗