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Biomedical subjects

H Sugano

Publications and source records attributed to H Sugano.

At least 19 recordsLinked to original sources

Frequent development of pancreatic carcinomas in the Rana nigromaculata group.

In 1979, 2 species of pond frogs (Rana nigromaculata and Rana plancyi plancyi) were imported from China, and hybrids were made between these and Japanese, Korean, and Taiwanese pond frogs (R. nigromaculata, Rana plancyi fukienensis and Rana brevipoda) that had been kept for a number of years in the Laboratory for Amphibian Biology of Hiroshima University. From 1982, development of tumors, especially in the peritoneal cavity, was noticed frequently in the hybrids and also later, although rarely, in the Japanese pond frogs. Such tumors had never previously been observed among pond frogs in the laboratory. Histological and immunohistochemical studies identified the i.p. tumors to be pancreatic carcinomas with occasional production of insulin and/or somatostatin. Ultrastructural investigation revealed both endocrine and exocrine secretion granules together with C-type retrovirus particles in the carcinoma cells. Other tumors included a retroperitoneal rhabdomyosarcoma, liver adenomas, and an unclassifiable mesenchymal tumor of the foot pad.

Animals

High K-ras mutation rates in goblet-cell-type adenocarcinomas of the lungs.

Adenocarcinomas of the lungs show a variable histology. We have subclassified such lesions into five cell types: hobnail, columnar, polygonal, mixed and goblet cell types, and investigated their relationships with K-ras mutations. Codons 12, 13 and 61 of the K-ras gene in 120 surgically resected pulmonary adenocarcinomas were examined by the mutation-allele-specific amplification method. Point mutations were observed in 10% of the adenocarcinomas limited to K-ras codon 12 and the commonest base substitution (nine cases) was a G to T transversion. Of the five types, goblet cell lesions demonstrated the highest mutation index, which at 100% (6/6) was significantly different from that of all other cell types. No relationship between K-ras mutation and cigarette smoking was observed. From these findings, it appears that development of goblet-cell-type adenocarcinomas of the lung may involve different carcinogenic mechanisms from adenocarcinomas of other subtypes.

Adenocarcinoma

[Endoscopic placement of self-expandable metallic stents (Wallstent) for malignant biliary stenosis, with special reference to preventive endoscopic nasal bile drainage against acute obstruction after stenting].

From December 1993 to December 1994, we inserted 14 biliary endoprostheses (Wallstent) endoscopically in 12 consecutive patients (5 men and 7 women; 55-91 years [mean 69.8 years] of age) with malignant biliary stenosis. Successful placement of Wallstent was achieved in all 12 patients. Procedure related death was encountered in one patient (8.3%) who was complicated with emphysematous cholecystitis, combined with a slipping migration of the stent. In 11 of the 12 patients, serum bilirubin levels reduced to less than 2.0 mg/dl. Acute obstruction, which was defined as the obstruction of the stent within 24 hours after the stent placement, occurred in 2 patients (16.7%). Endoscopic nasal bile drainage (ENBD) following stent placement was performed in 4 patients and acute obstruction was not developed in these cases. After endoprosthesis 8 patients were discharged with 6-47 hospital days and the average hospitalized period excluding a case with cerebral infarction was 12.7 days. Excluding one procedure related death, 6 patients died of primary malignancy 39-189 days (average 90.7 days) after endoprosthesis and in 2 cases recurrence of jaundice was observed. The other 4 patients have been alive for 60-174 days (average 102.5 days) without jaundice. The survival rate of the all patients was 64% for 3 months and 32% for 6 months, respectively. In conclusion, we suggested that the endoscopic Wallstent placement would contribute to the improvement of the quality of life for patients with malignant biliary stenosis. However, acute obstruction may be developed in some cases. For the purpose of managing acute obstruction, we recommend ENBD for a few days following the placement of a Wallstent.

Acute Disease

[The relationship between genotypes of HLA-DRB1 alleles and progression of bony destruction changes of rheumatoid arthritis].

The relationship between genotypes of HLA-DRB 1 alleles and the progression of bone destruction of RA patients was assessed. The genotypes of the HLA-DRB 1 alleles were determined in 329 Japanese patients with seropositive RNA by polymerase chain reaction and allele-specific oligonucleotide probe techniques. We regarded HLA-DRB 1* 0101, 0401, 0404, 0405, 1001 and 1402 as susceptible alleles of RA and classified the patients into three groups. The s/s group consisted of those with susceptible factors in both of the HLA-DRB 1 alleles. The s/n group was made up of those having one susceptible factor and one non-susceptible factor. The n/n group consisted of those possessing two non-susceptible factors. The grading of radiographic change that was evaluated by Larsen's criteria compared with the genotyped results. In the result, the median years taken to development to grade III, IV and V were significantly shorter in the s/s groups compared with that in the s/n and n/n groups. Thus, genotyping of HLA-DRB 1 can be a useful prognostic market in the progression of bone destruction of RA.

Adult

Ribosome-binding protein p34 is a member of the leucine-rich-repeat-protein superfamily.

Protein p34 is a non-glycosylated membrane protein characteristic of rough microsomes and is believed to play a role in the ribosome-membrane association. In the present study we isolated cDNA encoding p34 from a rat liver cDNA library and determined its complete amino acid sequence. p34 mRNA is 3.2 kb long and encodes a polypeptide of 307 amino acids with a molecular mass of about 34.9 kDa. Primary sequence analysis, coupled with biochemical studies on the topology, suggested that p34 is a type II signal-anchor protein; it is composed of a large cytoplasmic domain, a membrane-spanning segment and a 38-amino-acid-long luminally disposed C-terminus. The cytoplasmic domain of p34 has several noteworthy structural features, including a region of 4.5 tandem repeats of 23-24 amino acids. The repeated motif shows structural similarity to the leucine-rich repeat which is found in a variety of proteins widely distributed among eukaryotic cells and which potentially functions in mediating protein-protein interactions. The cytoplasmic domain also contains a characteristic hydrophilic region with abundant charged amino acids. These structural regions may be important for the observed ribosome-binding activity of the p34 protein.

Amino Acid Sequence

Lung cancers associated with thorotrast exposure: high incidence of small-cell carcinoma and implications for estimation of radon risk.

The widely accepted concept that the alpha-emitting radionuclide radon (222Rn, 220Rn) induces lung cancers in humans has been based on the excess of lung tumours observed in underground miners extracting uranium or other substances. However, this poses the important question of whether radon is the only carcinogenic factor because such miners are also heavily exposed to mine dusts including silicates, diesel exhaust, etc. in their working environment. Patients to whom Thorotrast was administered continuously exhale radon (220Rn) derived from 232Th deposits in the body and therefore provide a good model for lung carcinogenesis by radon without concomitant dust exposure. We therefore investigated lung-cancer incidence in our epidemiological follow-up series, analysing the histological types of 11 lung cancers which were found among 359 Thorotrast autopsy cases and measuring radioactivity in the breath of living Thorotrast patients. The study revealed that, while the proportion of small-cell lung cancers considered to be related to alpha-particles was significantly increased, the overall lung cancer incidence was not significantly higher than in controls, in spite of the high level of 220Rn in the patients' breath. This result suggests that radon in the lung does induce cancers (particularly small-cell carcinomas) but that the induction rate is not as high as expected from risk factors associated with mining. Thus, excess lung cancers among the miners might be related to the combined effects of exposure to radon and mine dusts, and not solely to radon.

Aged

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