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Biomedical subjects

H Sugano

Publications and source records attributed to H Sugano.

At least 55 records · Page 3Linked to original sources

Allelotype of non-small cell lung carcinoma--comparison between loss of heterozygosity in squamous cell carcinoma and adenocarcinoma.

We examined loss of heterozygosity (LOH) on all autosomal chromosomes in 53 non-small cell lung carcinomas. Frequent LOH was observed on the long arms of chromosomes 1 (37%), 2 (31%), 5 (30%), 8 (31%), and 13 (32%), and the short arms of chromosomes 3 (54%) and 17 (62%). LOH on chromosomes 3p and 17p was observed in all informative cases of squamous cell carcinoma, but was significantly less frequent in adenocarcinomas (P = 0.003 and 0.001, respectively). Similarly, LOH on chromosome 13q was observed frequently in squamous cell carcinomas (5 of 9 informative cases, or 56%), but in only 5 of 26, or 19%, of adenocarcinomas. In contrast, LOH on chromosome 2q was observed only in adenocarcinomas. In addition, this chromosomal arm was lost more frequently in poorly differentiated, compared to well differentiated adenocarcinomas. Furthermore, a correlation between fractional allelic loss and pathohistological grade was identified. These results implicate the presence of several tumor suppressor genes associated with development and/or progression of non-small cell lung carcinomas.

Adenocarcinoma↗

Nephroblastomas in the Japanese eel, Anguilla japonica Temminck and Schlegel.

Nephroblastomas were observed in 50 Japanese eel reared at a farm for 5 to 9 months from 1989 after collection in the wild. The tumors, arising from the trunk kidney near the anus, were noted externally as abdominal swellings and varied in size from 30 to 75 mm in maximum diameter. Most were elastic, solid, and well encapsulated. Histologically, the nephroblastomas were composed of combinations of three main tissue elements. Spindle- or oval-shaped cells resembling human blastema cells were observed in most tumors to some larger or smaller degree. Although variation was evident from tumor to tumor, and even within the same tumor, the most common histological type was epithelial with formation of alveolar nests, the cells sometimes being arranged in tubular structures simulating normal renal tubules. A muscle tissue element with distinct cross-striations was also observed. Liver metastases were found in one case. Histological examination of apparently normal kidneys from 100 eels revealed one early-stage nephroblastoma. The cause of these tumors is unclear, although they have been discovered with increasing incidence after the spread of indoor eel culture with raised water temperatures (26-27 degrees C) in Japan. Environmental factor(s) associated with the new aquaculture method may thus play a role in their genesis.

Anguilla↗

Isolation and some properties of a 34-kDa-membrane protein that may be responsible for ribosome binding in rat liver rough microsomes.

We have isolated, by hydroxyapatite chromatography with a non ionic detergent and a high salt concentration, a non-glycosylated, membrane protein with a relative molecular weight of 34 kDa that had previously been found to be a major constituent of the membrane protein fraction showing ribosome-binding activity derived from rat liver rough microsomes (RM). The isolated 34 kDa protein (p34), when incorporated into a liposome model membrane, exhibited significant binding activity toward ribosomes, its binding properties being similar to those observed with intact RM. Immunochemical analyses using antibodies directed against p34 suggested that it is a membrane-embedded RM surface protein, which is specifically localized in ribosome-attached organelles and widely distributed among mammalian tissues. These results would constitute evidence that p34 is a likely candidate for an RM ribosome-binding protein.

Animals↗

Incidence of atypical bronchioloalveolar cell hyperplasia of the lung: relation to histological subtypes of lung cancer.

The incidence of atypical bronchioloalveolar cell hyperplasia (ABH) of the lung was investigated to evaluate the possibility of this lesion being a precancerous stage in the histogenesis of adneocarcinoma. Lobectomy and pneumonectomy specimens of 165 primary and 45 metastatic tumour cases were step-sectioned horizontally and examined histologically. An average of 51 blocks were taken in each case. Sixty-seven ABHs up to 10 mm in diameter were detected, only 2 lesions being associated with scar tissue. Age was one factor apparently related to ABH development, although not the major one. There was no correlation between smoking index and ABH occurrence. In males, the incidence was highest in association with adenocarcinoma (25.5% of cases, 0.8% of sections), followed by large cell carcinoma (25.0% of cases), squamous cell carcinoma (10.5% of cases) and metastatic tumours from other sites (4.8% of cases). In females, ABH was also more common together with adenocarcinoma (8.3% of cases) than with metastatic tumours (4.0% of cases). The differences in male incidences by case and by section between the adenocarcinoma and metastatic tumour categories were statistically significant (P less than 0.05, P less than 0.01 respectively) indicating that ABH may be a precancerous lesion capable of transformation of adenocarcinoma.

Adenocarcinoma↗

Site-dependent development of complete and incomplete intestinal metaplasia types in the human stomach.

The topographical distribution of complete and incomplete types of intestinal metaplasia in human stomach samples was investigated in order to elucidate their mutual histogenetic relationship and significance in carcinogenesis. Subgross stereomicroscopic examination of alcian blue and hematoxylin-stained gastric mucosae allowed clear distinction of complete and incomplete intestinal metaplasia types as white (with or without purple hue) and purple foci, respectively, against the background magenta areas of non-intestinalized mucosa. Intestinal metaplasias which developed in the fundic area were predominantly of the complete type whereas those of the antrum were a mixture of both with a distinct predilection for expression of the incomplete type. Although there was some variation among foci regarding the hue of white or purple, the color feature was principally homogeneous within each individual intestinal metaplasia focus. Thus phenotypic analysis indicated intestinal metaplasia expression to be clearly influenced by intragastric topography. The study did not provide any evidence that a shift from incomplete to complete type intestinal metaplasia may occur with time or that the incomplete type may be more intimately associated with development of well-differentiated carcinomas.

Adult↗

Histopathological and immunohistochemical study of atypical lymphoid hyperplasia and benign lymphoid hyperplasia of the stomach.

We propose dividing histologically reactive lymphoid hyperplasia (RLH) of the stomach into two categories: atypical lymphoid hyperplasia (ALH), characterized by abnormal follicular architecture and infiltration of atypical lymphoid cells, and benign lymphoid hyperplasia (BLH), where normal follicular patterns are preserved and no atypical cells are found. Using twenty RLH cases (10 ALHs and 10 BLHs), both categories were compared from histopathological and immunohistochemical aspects. Macroscopic division into superficial, thick-walled and nodular types revealed most ALH (80%) to be superficial in character whereas in BLH superficial and thick-walled types were almost equally represented. Lesion size tended to be larger in ALH (greater than 6.1 cm) than in BLH (6.0 cm greater than) cases. As for prognosis after gastrectomy, both categories were favorable. On immunohistochemistry, ALH tended to be strongly labeled by B lymphocyte markers as compared to BLH, where only a weakly positive reaction was expressed. Infiltration of cells labeled by T lymphocyte markers was less conspicuous in ALH than in BLH. From these data, we concluded that ALH and BLH are two distinctive categories of lesion and that ALH has characteristics similar to these demonstrated by malignant lymphoma.

Female↗

[Effects of a specific thromboxane A2 synthetase inhibitor on lymphocyte and neutrophil functions in adult intractable asthmatics].

To clarify whether thromboxane A2 (TXA2) is involved in type III and IV allergy, or so called "cell-mediated allergy", we studied the effect of a specific TXA2 synthetase inhibitor, sodium ozagrel (OKY-046) on peripheral blood mononuclear cells and neutrophils in adult intractable asthmatics. The results revealed, firstly, that lymphocyte blastogenesis and interleukin-2 (IL-2) production from peripheral blood mononuclear cells stimulated by PHA and Candida antigen in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. Secondly, there was a tendency that neutrophil chemotactic factor (NCF) and eosinophil chemotactic factor (ECF) from peripheral blood mononuclear cells stimulated by Candida antigen in intractable asthmatics were suppressed by OKY-046. Thirdly, leukotriene (LTC4) and superoxide (O2-) production from peripheral blood neutrophils in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. That is, OKY-046 has a suppressive effect on type IV allergy caused by lymphocyte activation and on mediator release from neutrophils. These results suggest that TXA2 plays an important role in the development of bronchial asthma and OKY-046 might be a useful drug in the treatment of intractable asthmatics.

Adult↗

[The penetration of cefpiramide into the skin].

To investigate the skin penetration of cefpiramide (CPM, SM-1652), a broad-spectrum and long acting cephem antibiotic, 1 g of CPM was administered by single bolus intravenous injection to patients under general anesthesia during operations for full-thickness skin grafting. The CPM levels in both the serum and the skin were determined by bioassay at specified time intervals, and the following results were obtained. 1. Peak CPM concentrations in the serum (mean: 292.78 micrograms/ml) were observed 10 minutes after administration, and declined very slowly thereafter. 2. Peak CPM concentrations in the skin (mean: 23.05 micrograms/g) were observed 2 hours after administration, and then also declined very slowly. 3. The ratio of skin to serum concentrations was 16% when the peak CPM concentrations in the skin were obtained (2 hours after the administration). These results show that effective CPM concentrations were maintained in the skin for a long period, indicating a good therapeutic action against skin infections.

Adult↗

[Studies on the mechanism of late asthmatic response by Candida antigen inhalation using bronchoalveolar lavage].

To elucidate the mechanism of late asthmatic response (LAR), which is related to intractable asthma attack, the cellular and humoral components of LAR were examined in bronchoalveolar lavage fluid (BALF) obtained after bronchial inhalation tests with Candida allergen on Candida-sensitive asthma patients. BAL examination was carried out 2 hours after remission of LAR, and differential cell counts and measurements of leukotrienes (LTs) by high performance liquid chromatography were investigated in BALF and peripheral blood. The number of neutrophils and basophils in circulating blood showed a peak before LAR, and then decreased markedly at LAR. And an increase in the percentage of eosinophils (p less than 0.01) and neutrophils was evident in BALF after LAR compared with the level in the non-attack state. The percentage of basophil-mast cells, however, did not change in the same manner. The serum level of LTC4 increased significantly at LAR in comparison with its level in the phase before LAR. And the level of LTC4 was also significantly higher in BALF after LAR (p less than 0.01). However, LTD4 and LTB4 were at almost undetectable levels in BALF in the non-attack state and after LAR. The results indicate that neutrophils as well as eosinophils may accumulate and release several kinds of leukotrienes at local sites in late asthmatic response provoked by the inhalation of Candida antigen; this gives clues as to the mechanism of severe and intractable asthma attacks.

Adult↗

Duct endoscopy and endoscopic biopsy in the evaluation of nipple discharge.

Microdochectomy is usually performed on patients with nipple discharge caused by intraductal proliferative lesions, such as intraductal papilloma and carcinoma. But this operation often sacrifices large amounts of normal mammary gland even when the lesion is a benign intraductal papilloma a few millimeters in diameter. We have developed duct endoscopy for the mammary duct system, and have reliably performed biopsies for intraductal proliferative lesions intraductally. From June 1989 to April 1990, we examined 22 cases by duct endoscopy, and performed endoscopic biopsy in 16 cases. The method of endoscopic biopsy is as follows. First, a bougie is inserted, without anesthesia other than Xylocaine jelly, into the orifice of the duct to enlarge it. Second, the outer cylinder and the inner needle are inserted; then the inner needle is removed, and the endoscope is inserted. After examination, the outer cylinder is moved up to the lesion to be biopsied and the endoscope is taken out. Then a sample is taken into the outer cylinder by aspiration. We diagnosed 10 cases of benign lesion and 5 cases of malignant lesion by cytological and/or histological examination. In conclusion, endoscopic biopsy, aided by duct endoscopy, is a useful and harmless diagnostic procedure in the evaluation of nipple discharge.

Biopsy↗

Pathology of breast cancer: present and prospect in Japan.

Breast cancer among Japanese females is characterized by its relatively low incidence and better prognosis than among Caucasian females. The annual mortality due to breast cancer among Japanese is about one-fifth that among Caucasians. Comparison of case distribution by histological type indicates that the ratio of well-differentiated carcinoma is slightly higher among Japanese, while the ratio of poorly differentiated carcinoma is slightly higher among Caucasian females. It is noteworthy that the incidence of in situ and invasive lobular carcinoma among Japanese is much lower than among Caucasian females. The age distribution shows that breast cancer is more frequent among middle-aged females in Japan, but more common among aged females in the West. Breast cancer among Japanese females shows a better prognosis than among Caucasian females as a whole, even with equal tumor size and lymph node metastasis. As mentioned above, the morbidity and mortality rates of breast cancer among Japanese females are very low, but recently, both morbidity and mortality rates in Japan have been steeply increasing. For example, the mortality rate of breast cancer in Japan almost doubled during the past 20 years. Moreover, biological behavior of breast cancer among Japanese females has been recently changing. Time-trend data clearly indicate that breast cancer in Japan in the future will be much more like that in the West, and nowadays it is already westernizing.

Adult↗

The morphologic feature of mucus leakage appearing in low papillary carcinoma of the breast.

This report summarizes the clinicopathologic findings in 11 cases of low papillary carcinoma of the breast accompanied by the morphologic feature of mucus leakage into the mammary stroma. These cases were characterized by two morphologic findings. First, abundant mucus produced by the tumor cells filled the intraductal spaces where neoplastic epithelium formed very low papillary projections, ie, a feature of mucinous-producing low papillary carcinoma in situ. Second, there was expansive leakage of mucus into the mammary stroma occasionally accompanied by a few epithelial cells. All the cases showed a high level of mucus production and contained no elements of invasive ductal carcinoma or ordinary invasive mucinous carcinoma. These cases have no evidence of direct invasion of the mammary stroma by malignant cells. The average age of the 11 patients was 41 years. Foci of microcalcification were seen in some tumors (seven cases; 64%). There were no cases with lymph node metastases. All the patients underwent mastectomy with no adjuvant therapy, and they are currently alive and well.

Adenocarcinoma, Mucinous↗

Characterization of the hydrophobic region of heat shock protein 90.

The modes of binding of heat shock protein 90 with phenyl-Sepharose, myristoylated AE-cellulose, and monomyristoylated lysozyme were studied to characterize a hydrophobic region(s) on the surface of the heat shock protein 90 molecule and the following results were obtained. (1) The binding of heat shock protein 90 with phenyl-Sepharose was inhibited by the addition of 30% ethylene glycol. This indicates that the binding involves a hydrophobic interaction. (2) The binding was strengthened by the addition of 10 mM Mg2+, Ca2+, Sr2+, and Ba2+ ions, but not by K+ or Na+ ions. (3) The binding of hsp 90 with phenyl-Sepharose decreased initially and then increased as the temperature was increased from 0 to 50 degrees C, with a minimum at around 35 degrees C. (4) Lowering the pH stimulated the binding of hsp 90 with phenyl-Sepharose. (5) Heat shock protein 90 bound to myristoylated AE-cellulose, which has aliphatic hydrophobic residues, but not to acetylated AE-cellulose. (6) Heat shock protein 90 bound to monomyristoylated lysozyme, but not to control unmodified lysozyme. Based on these results, the possible function of the hydrophobic region(s) of heat shock protein 90 in the interaction with hydrophobic proteins is discussed.

Amino Acid Sequence↗

c-Ki-ras point mutations in ductectatic-type mucinous cystic neoplasms of the pancreas.

Ductectatic-type mucinous cystic neoplasms of the pancreas constitute a recently recognized new human pancreatic tumor entity. Examination for the presence of point mutations at codon 12 of K-ras by oligonucleotide hybridization in 5 adenomas and 3 carcinomas revealed alteration in 3 and 2, respectively. In 4 of these positive cases, the transition was GGT----GAT (Gly----Asp) with the remaining one, found in a cancer, being GGT----GTT (Gly----Val). In two carcinoma cases, the same point mutation was detected both in the carcinoma area and in a coexisting adenoma component. Thus K-ras point mutation appears to be associated with this particular type of neoplasm in the same manner as observed for typical exocrine pancreas carcinomas. Our study also indicates the possible existence of an adenoma-carcinoma sequence in the evolution of this type of neoplasm and we suggest that K-ras activation may be an important event in the phase of adenoma development.

Adenoma↗

Widespread distribution of the 14-3-3 protein in vertebrate brains and bovine tissues: correlation with the distributions of calcium-dependent protein kinases.

A highly specific antiserum was prepared against bovine brain 14-3-3 protein, a protein kinase-dependent activator of tyrosine and tryptophan hydroxylases. The immunoassay using this antiserum proved the presence of 14-3-3 protein in various bovine tissues and in brains of various vertebrate species. The quantitative analysis indicated that the tissue distribution of 14-3-3 protein is more closely related to the known distributions of the Ca2(+)-dependent protein kinases, i.e., Ca2+/calmodulin- and Ca2+/phospholipid-dependent protein kinases, rather than those of tyrosine and tryptophan hydroxylases. This result, together with the available data on this protein, suggests potential roles of the 14-3-3 protein in more diverse kinase-mediated processes than the predicted role in monoamine synthesis.

14-3-3 Proteins↗

[A case of rush dust (IGUSA-SENDO) pneumoconiosis with a large conglomerate mass shadow].

A 61-year-old woman, who had engaged in "tatami" mat production for 20 years, showed a gradually increasing large conglomerate mass shadow associated with small irregular opacities on chest X-ray film. Transbronchial lung biopsy revealed findings consistent with pneumoconiosis, with no suggestion of pulmonary tuberculosis or lung cancer. After 6 years' observation, right upper lobectomy was performed because the mass shadow was still increasing in size. Histological examination revealed a well-defined large mass composed of numerous macrophages containing abundant silicate minerals and fibroblasts proliferating in storiform fashion. No evidence of tuberculosis or malignancy has ever been detected. These findings are compatible with the previously reported pathological findings of "IGUSA-SENDO" pneumoconiosis; however, PR4 type "IGUSA-SENDO" pneumoconiosis has never been previously reported. This is the first reported case of PR4 type "IGUSA-SENDO" pneumoconiosis.

Female↗

Identification of a membrane protein responsible for ribosome binding in rough microsomal membranes.

A membrane protein fraction was obtained from rat liver rough microsomes by affinity chromatography on a concanavalin A-Sepharose column and then a chelating-Sepharose column. This protein fraction comprised about 2% of the total membrane proteins of rough microsomes and the ribosome-binding activity of ribosome-stripped rough microsomes was predominantly found in this protein fraction, as determined with a liposome assay system. To identify the essential components responsible for the ribosome binding, two approaches were employed. Trypsin treatment of liposomes reconstituted with this protein fraction resulted in the loss of the ribosome-binding activity in parallel with the loss of a dominant band, estimated Mr 34,000, in SDS-polyacrylamide gels. Next, the direct interaction between the binding sites on the membrane of reconstituted liposomes and 60S ribosomal subunits was investigated by photocrosslinking using sulfosuccinimidyl 2-(m-azido-o-nitrobenzamido)-ethyl-1,3'-dithiopropionate (SAND). The photocrosslinked complex was formed between 60S ribosomal subunits pretreated with SAND and binding-site proteins on the membrane of the liposomes. Then, after the liposomes were solubilized, the complex was isolated by sucrose gradient centrifugation of the binding mixture. The crosslinked proteins were released from 60S ribosomal subunits by cleavage of of crosslinks with beta-ME and analyzed by SDS-polyacrylamide gel electrophoresis and 125I-autoradiography. The 34-kDa protein (p34) was the predominant component that crosslinked to the 60S ribosomal subunits and was found in proportion to the amount of 60S ribosomal subunits added to the system. The p34 was distinguishable by immunoblot analysis from urate oxidase, which is the 34-kDa protein of peroxisomal cores contaminating rough microsomes. These results suggest that the present p34 is a likely candidate molecule for the ribosome-binding activity of rough microsomes.

Animals↗

Reconstitution of the 9 S estrogen receptor with heat shock protein 90.

As a first step in the investigation of the reconstitution of steroid hormone receptor systems, we studied the reconstitution of 9 S estrogen receptor (ER) from purified vero ER, which is the estradiol binding subunit, and heat shock protein 90 (hsp 90). By using a phosphate buffer containing molybdate, thiocyanate, dimethylformamide, glycerol, etc., vero ER could be converted to 9 S ER with hsp 90, but not with the control protein, ovalbumin. Inactivation of ER during the reconstitution was suppressed partially by hsp 90, but not by ovalbumin. Like native 8 S ER, the reconstituted ER was sedimented at about 8.9 S and 4.6 S on glycerol gradient centrifugation in low and high salt buffers, respectively.

Animals↗