Biomedical subjects

H Sugimura

Publications and source records attributed to H Sugimura.

At least 55 records · Page 3Linked to original sources

PubMed1996

p53 accumulation in colorectal cancer with hepatic metastasis.

The prevalence of immunoreactive p53 and argyrophilic nucleolar organizer region (AgNOR) numbers were compared between colorectal cancers with (n=44) and without (n=51) hepatic metastasis for at least 5 years. At the same time, the distribution of p53-positive cells in primary, metastatic, and xenografted tumors from the same individuals were studied. Overall, p53 positivity was found more frequently in the cases with hepatic metastasis than in non-metastatic controls, regardless of the distribution pattern (P<0.05), whereas AgNOR counts were not different between the two groups. Significant heterogeneity in the distribution of p53 immunoreactivity was noted in both the primary and metastatic lesions. The intratumor distribution patterns of p53 immunoreactive cells in the primary (n=33), metastatic (n=33), and xenografted (n=7) tumors of the same individuals were consistent in the majority of cases. There were a few cases in which the p53 immunoreactive cells were more dominant in the metastatic tumor cells. Our observations suggest that p53 accumulation in colorectal cancer is associated with increased risk for hepatic metastasis, while cell proliferation as represented by AgNOR numbers is not. In addition, heterogeneity of abnormal p53 accumulation in the tumor is maintained during the course of metastasis and even after implantation in nude mouse. p53-Immunoreactive cells in the population of colorectal cancer cells do not necessarily have higher metastasizing potential.

Animals↗

PubMed1996

[The results of p53 immunostaining in colorectal adenomas, early cancers, advanced cancers and their hepatic metastasis].

Overexpression of the p53 protein was analyzed in colorectal adenomas, early cancers, advanced cancers and their hepatic metastasis by immunostaining using monoclonal antibody (DO-7). Positive staining for p53 was detected in 8 (22.9%) of 35 adenomas, 19 (82.6%) of 22 early cancers, and 59 (63.2%) of 95 advanced cancers. In adenomas, p53 immunoreactivity for severe dysplasia was higher than that for mild or moderate dysplasia (3/9.33.3% vs 2/16.12.5% or 3/10.33.3%), we found almost the same p53 immunoreactivity both in early cancers in adenoma (7/8.87.5%) and "de novo" cancers without an adenoma component (12/14. 85.7%). In 95 of advanced cancers, we found p53 positive cells in 33 (76.7%) of 43 cases with hepatic metastasis, against 26 (50.0%) of 52 cases without hepatic metastasis and surviving more than 5 years from the colorectal cancer resection. The former group had a significantly higher incidence of p53 overexpression (p < 0.05). In the 33 above mentioned cases, both primary and liver metastatic lesions were p53 positive, and the others were negative in both of them. In this series, it was suggested that p53 had important roles in the colorectal adenoma-carcinoma sequence from adenoma to advanced cancer and its metastatic potential, as well as in "de nove" carcinoma.

Adenoma↗

PubMed1995

A mutational hot spot in the p53 gene is associated with hepatoblastomas.

Hepatoblastomas generally appear in children aged 2 or 3 years old and arise from apparently normal, non-cirrhotic liver. To elucidate any possible role of p53 mutations in their genesis, we amplified and sequenced exons 5 to 8 of the p53 gene in 10 cases of hepatoblastoma. Somatic mutations were detected in 9 cases, in eight of which a common point mutation at the first-base position of codon 157 was found, resulting in an amino-acid substitution of phenylalanine for valine. Two missense mutations in codon 244, and one each in codons 273 and 279, were also found, with 3 hepatoblastomas having double mis-sense mutations. Out of the total of 12 mutations, 11 were G-to-T transversions. One was a G-to-A transition and guanines were always present on the transcribed strand. Furthermore, p53 over-expression was immunohistochemically observed in 7 out of 9 cases with p53 gene mutations, although the staining pattern was focal and heterogeneous. The findings suggest that particular environmental mutagens may be involved in mutagenesis of the p53 gene in some cases of hepatoblastomas and that p53 mutations at a specific site may play an important role in the genesis of this disease.

Base Sequence↗

PubMed1995

Expression of p53 and flow cytometric DNA analysis of isolated neoplastic glands of the stomach: an application of the gland isolation method.

The expression of p53 was studied immunohistochemically in combination with the DNA ploidy pattern by gland isolation in 97 alcohol-fixed gastric lesions. A polyclonal antibody, CM-1, was applied to the paraffin-embedded sections in this study. Overexpression of the p53 protein was found in 73.2% of 41 well or moderately differentiated gastric carcinomas and 52.2% of 23 cases with poor differentiation (P < 0.05). Immunoreactivity of p53 was also detected in isolated cancerous glands. No p53 immunoreactivity was detected in benign gastric lesions including adenomas, hyperplastic polyps and regions of intestinal metaplasia. In addition, flow cytometric DNA analysis was performed on isolated glandular epithelium adjacent to the portions used for immunostaining. DNA aneuploidy (DA) was detected in 85.7% of the well or moderately differentiated carcinomas and 42.9% of those with poor differentiation (P < 0.05). There was a positive correlation between DA, p53 positivity and the presence of regional lymph node metastasis, but not with other clinicopathological variables. In spite of the limited applicability of this method to poorly differentiated gastric cancer, we found that immunostaining and flow cytometry in combination with the gland isolation method facilitates analysis of gastric carcinogenesis.

DNA, Neoplasm↗

PubMed1995

Intrasellar neuronal choristoma associated with growth hormone-producing pituitary adenoma containing amyloid deposits.

The histological, immunocytochemical, and ultrastructural features of an intrasellar neuronal choristoma associated with pituitary growth hormone (GH)-producing adenoma are reported. Immunohistochemistry studies and electron microscopy examination showed the adenoma cells to be positive for GH but negative for prolactin, and the neurons of the choristoma to have GH-releasing factor (GRF) neurosecretory activity. The adenoma also had many amyloid deposits in its extracellular space immunoreactive to GRF. This is the first report of the tumor containing amyloid deposits.

Adenoma↗

PubMed1995

Contrast-enhanced MR imaging of intrahepatic cholangiocarcinoma.

The unenhanced spin-echo T1-weighted images, contrast-enhanced (dynamic and conventional) T1-weighted images and spin-echo T2-weighted images of 19 patients with histologically proven intrahepatic cholangiocarcinoma were reviewed. The results showed that typical intrahepatic cholangiocarcinoma presented as a large mass of low signal intensity on T1-weighted images. On T2-weighted images tumours generally presented as high signal intensity masses. In five patients the tumours exhibited varying degrees of central hypointensity on T2-weighted images. On contrast-enhanced images, large tumours (diameter larger than 4 cm, n = 14) typically showed peripheral enhancement with delayed or incomplete central filling. This pattern was seen most commonly. Smaller tumours (diam. 2-4 cm, n = 5) typically exhibited homogenous enhancement. On dynamic studies, enhancement of the tumours showed a centripetal pattern. Complete enhancement was observed in the small tumours. Among the larger lesions central sparing of the tumours was seen. It is concluded that contrast-enhanced MR imaging is useful in the diagnosis of intrahepatic cholangiocarcinoma. The characteristic enhancing pattern of intrahepatic cholangiocarcinoma was seen less commonly in smaller tumours. Definite differentiation from other liver masses in this case could be less certain.

Adult↗

PubMed1995

Frequent co-occurrence of mutator phenotype in synchronous, independent multiple cancers of the stomach.

The prevalence of multiple independent primary cancer of the stomach is high in Japanese. We hypothesized that individuals with multiple, independent gastric cancers might have a greater genetic susceptibility than persons with solitary gastric cancer at the time of diagnosis. We therefore determined the frequency of mutator phenotypes in 20 persons with independent multiple gastric cancers and 42 persons with solitary primary lesions. The mutator phenotype was determined by examining dinucleotide CA repeats at the microsatellite loci D2S136 (chromosome 2), MSX2 (chromosome 5q34), D5S82 (chromosome 5q14-21) and TP53 (chromosome 17p13.1). Although there were no significant differences between the clinical and pathological features (stage or histopathological subtype) of the two groups, the prevalence of any one microsatellite instability in patients with multiple gastric cancer was greater (65% versus 24%; P = 0.003) than in those with solitary gastric cancer. The prevalence of co-occurrence of mutator phenotype in synchronous lesions was greater than expected based on their frequency in solitary gastric cancer (12% versus 9% x 9%). Persons with advanced-stage multiple primary lesions were more likely to exhibit the mutator phenotype (P = 0.10). These findings indicate that individual predisposition for qualitative or quantitative defects in DNA repair systems significantly contribute to the simultaneous occurrence of gastric cancer in Japanese.

Adult↗

PubMed1995

A novel allelic variant of serum amyloid A, SAA1 gamma: genomic evidence, evolution, frequency, and implication as a risk factor for reactive systemic AA-amyloidosis.

Reactive systemic amyloidosis, also called AA-amyloidosis is a rare fatal complication of common chronic inflammatory diseases such as rheumatoid arthritis. It has been proposed that as yet undefined factors other than persistent elevation of serum level of the precursor protein, serum amyloid A (SAA), are also important for the development of AA-amyloidosis. In this work we show genomic evidence for a novel allelic variant of human SAA, SAA1 gamma, which we have recently identified at the protein level. The SAA1 gamma [Ala52(GCC), Ala57(GCG)] differed from SAA1 alpha [Val52(GTC), Ala57(GCG)] only at one base, indicating a single point mutation. On the other hand, SAA1 beta [Ala52(GCC), Val57(GTG)] had not only one, but additional differences in a nearby intron and this portion was identical to the SAA2 gene, suggesting a crossing-over between the SAA1 and SAA2 genes. Furthermore, we report that there was a significant difference in the observed numbers of SAA1 alleles between rheumatoid arthritis patients with AA-amyloidosis and the control population (chi 2(2) = 11.59, p = 0.003) with a higher frequency of gamma-allele in the AA-amyloid group (0.70 vs. 0.37). There was also a notable difference in the distribution of SAA1 genotypes (chi 5(2) = 14.63, p = 0.012) with an increased frequency of gamma/gamma-homozygotes in the AA-amyloid group (0.60 vs. 0.18). Thus our findings indicate that this novel allelic variant may be an important risk factor for the development of AA-amyloidosis.

Adult↗

PubMed1995

CYP1A1 and CYP2E1 polymorphism and lung cancer, case-control study in Rio de Janeiro, Brazil.

Msp I polymorphism and exon 7 Ile-Val polymorphism of CYP1A1, and Rsa I polymorphism of CYP2E1 were studied in lung cancer patients and controls in Rio de Janeiro, Brazil. Of the three polymorphisms studied, only the exon 7 polymorphism of CYP1A1 (Val-containing genotypes) had a distribution which was statistically significant in the patients and controls. The contribution of Val containing genotypes of CYP1A1 exon 7 was greater in the subpopulation of squamous cell carcinoma patients with a lower life-time smoking consumption (OR, 2.92 vs 1.97). This association is consistent with the previous findings by Kawajiri et al. and the first observation of the positive association of this locus with lung cancer in a Western population (Kawajiri K, Nakachi K, Imai K, Yoshii A, Shimada N, Watanabe J. FEBS Let 1990; 263, 131-133). Furthermore, together with the lack of association of Msp I polymorphism in the non-coding region of CYP1A1, the locus truly responsible for lung cancer risk among pleural polymorphisms of CYP1A1 appeared to be exon 7 Ile-Val polymorphism. In the future, investigations of multiple markers in different ethnic populations may reveal cancer risk markers common to all mankind.

Base Sequence↗

PubMed1995

Primary osteosarcoma arising from cirrhotic liver.

An autopsy case of a 67 year old man with primary osteosarcoma arising in cirrhotic liver is reported. His son had von Recklinghausen disease and he had had a history of hepatitis C virus infection for 10 years. A large tumor, about 10 cm in diameter, was found in the right liver lobe. This tumor showed marked central necrosis and hemorrhage, and histologically diffuse sarcomatous cell proliferation associated with extensive osteoid formation and calcification of the periphery. Examination of the whole tumor and the cirrhotic liver (155 tissue blocks) showed that the tumor consisted of sarcoma cells mixed with osteoid with no region resembling hepatocellular carcinoma or hepatoblastoma. Minute hepatocellular carcinomas were found in the cirrhotic liver distant from the sarcomatous area. On immunohistochemical examination, the main tumor gave a distinct positive reaction for vimentin, but not for keratin or other epithelial markers. These findings indicate that the tumor was a true primary osteosarcoma, not an osteoid metaplasia of hepatocellular carcinoma.

Aged↗

PubMed1995

Efficient and specific induction of esophageal tumors in rats by precursors of N-nitrososarcosine ethyl ester.

Cancers and precancerous lesions of the esophagus were efficiently induced in rats by the simulation of a clinico-epidemiological setting; that is, the administration of precursors of nitrosamine. Six week old non-inbred male Wistar rats were given 2g/kg bodyweight of sarcosine ethyl ester hydrochloride (SEEH) and concurrently 0.3g/kg bodyweight of sodium nitrite (NaNO2), precursors of N-nitrososarcosine ethyl ester (NSEE), in 2% sucrose as drinking water. Group 1 received the precursors twice a week for 6 weeks followed by 8 weeks observation, and group 2, once every 3 days for 7 weeks followed by 26 weeks observation. At the end of treatment, no tumor had developed in the esophagus of rats in group 1, but the [3H]-thymidine labeling indices in both basal and superficial layer cells were higher than in the control group. On subsequent observation, papillomas appeared in group 1 (33.3%), and carcinomas in group 2 (33.3%), within 4 weeks. The tumors induced in group 1 were mostly papillomas and rarely carcinomas. When the observation was prolonged in group 2, 100% of the animals had cancer in week 20. The pathological changes of the lesions paralleled the sequential development of human squamous cell carcinoma of the esophagus. Our system has the advantages in that papillomas and cancers can be induced in rats in a short time and the agents used are less toxic than preformed nitrosamines administered previously by gastric intubation. It would serve as a useful experimental tool to study premalignant lesions and cancers of the esophagus.

Animals↗

PubMed1995

Monoclonality of normal human colonic crypts.

The monoclonality of human colonic crypts was demonstrated by human androgen receptor (HUMARA) gene assay following application of the crypt isolation method. DNA was extracted from an isolated single crypt, Hpa II digestion was performed before polymerase chain reaction (PCR) by primers spanning the HUMARA exon 1 region. The PCR product of a single crypt clearly showed allelic exclusion based on methylation status, while PCR product from a mixture of 40 crypts or colonic mucosa as a whole that included epitheliums and interstitial connective tissue had two bands. This method will facilitate the non-isotopic analysis not only of tumor clonality, but also of the normal structures derived from a single progenitor cell.

Base Sequence↗

PubMed1995

Cytophotometric and flow cytometric DNA content of isolated glands in gastric neoplasia.

The gland isolation method was applied to various gastric lesions to measure DNA content by cytophotometry and flow cytometry for the first time. By incubating and agitating fresh specimens from surgically resected stomachs in calcium-magnesium free Hanks's balanced salt solution (CMFH) containing EDTA, many neoplastic glandular epithelial cells were successfully isolated from the stroma, and their characteristic three dimensional features were seen morphologically. The DNA content of pure nuclear suspensions of isolated glands was obtained by cytophotometry and flow cytometry staining with 4',6-diamino-2-phenylindole dihydrochloride (DAPI) and propidium iodide, respectively. Compared with histological grading, the frequency of the DNA aneuploidy of cancer with moderate or poor differentiation by cytophotometry (75%) was significantly higher than that of well differentiated cancer (25%), but the histological typing of gastric cancer DNA frequency were not correlated. This method allowed us to detect small aneuploid peaks by flow cytometry, which were previously masked by contaminating interstitial cells. The frequency of DNA aneuploidy detected by flow cytometry (87.5%) was higher than detected by cytophotometry (58.3%). The results of these studies shows the feasibility of this technique for analysing the DNA content of various lesions of the stomach.

Adenocarcinoma↗

PubMed1995

Magnetic resonance angiographic findings in vertiginous patients with slow vertebrobasilar blood flow.

To investigate arterial lesions underlying slow vertebrobasilar blood flow (SBF) which appears as a high intravascular signal on proton-density images, we examined 35 vertiginous patients, 15 with SBF and 20 without, using magnetic resonance angiography. Vertebrobasilar dolichoectasia, segmental stenosis with elongation and diffuse narrowing of the vertebrobasilar arteries (VBA) were found in 4, 4 and 2 patients with SBF, respectively. In one patient with SBF, the thrombi that induced SBF seemed to have embolized to distal arteries. These abnormalities were not detected in patients without SBF, although 2 patients demonstrated aneurysm in the VBA. Because SBF is frequently associated with atherosclerotic arterial lesions, patients with SBF should be treated to prevent more severe ischemic brain disease.

Aged↗

PubMed1995

[A case of localized fibrous mesothelioma arising from visceral pleura of the right lower lobe].

A 56-year-old male who had been followed for chronic hepatitis had cough and hemosputum. Chest X-ray and CT films showed an abnormal mass shadow in the right thorax. On suspicion of intrathoracic tumor, resection was performed. The tumor, which was on the diaphragm without invasion, was pedunculated and arose from the bottom surface of visceral pleura of the right lower lobe. From the microscopic findings and immunohistochemical staining, the tumor was diagnosed as localized fibrous mesothelioma. Some localized fibrous mesothelioma exhibit as malignant tumor. Therefore, complete resection and intensive follow-up should be done.

Humans↗

PubMed1995

[Efficacy of video thoracoscopic lung biopsy in diffuse lung diseases: comparison with open lung biopsy].

The efficacy and safety of video thoracoscopic lung biopsy (VTLB) and of open lung biopsy (OLB) were compared in patients with diffuse lung diseases. Thirty-three patients who had undergone VTLB were retrospectively studied and compared with 67 patients who had undergone OLB. There were no significant differences in age (52.8 +/- 10.9 vs 53.4 +/- 10.3), in the number of biopsies per patient (2.6 +/- 0.6 vs 2.7 +/- 0.6), or in the rate of diagnosis (94% vs 93%) between the two groups. However, the rate of diagnosis was low when the number of VTLB or OLB performed per patient was low. The patients undergoing VTLB had significantly shorter operative times (VTLB, 100.2 +/- 27.2 min. vs OLB, 119.8 +/- 42.6 min; p < 0.01) and less blood loss (VTLB, 4.7 +/- 14.6 ml vs OLB, 65.7 +/- 77.0 ml; p < 0.001). Complications occurred in 3 of the 33 who underwent VTLB, and in 18 of the 67 who underwent OLB. These results indicate that VTLB is an effective and safe alternative in the diagnosis of diffuse lung diseases.

Adult↗

PubMed1995

Glycosylation of nucleoside bases with 2,3-dideoxy-1-thio-D-glycero-pento-2-enofuranosides.

Both intermolecular and intramolecular glycosylation of thymine using phenyl 2,3-dideoxy-1-thio-D-glycero-pent-2-enofuranoside as a glycosyl donor was investigated. When the reaction was carried out intermolecularly in the presence of NBS as the promoter, the corresponding 2',3'-unsaturated beta-nucleosides were obtained stereoselectively. On the other hand, the intramolecular glycosylation employing a 5-O-(2-pyrimidyl) derivative of similar thioglycoside afforded an unexpected product, in which thymine was incorporated at the C-3' position.

Glycosylation↗

PubMed1994

High prevalence of p53 protein overexpression in patients with esophageal cancer in Linxian, China and its relationship to progression and prognosis.

BACKGROUND: Linxian is the highest endemic area of esophageal squamous cell carcinoma (ESCC) in China and one of the highest incidence areas in the world. The relationship of p53 protein accumulation to geographic variation, pathologic findings, and prognosis has not been investigated extensively. METHODS: Formalin fixed, paraffin embedded ESCC tissues from 100 patients who underwent esophagectomy between 1973 and 1983 were immunostained by using monoclonal antibody pAB1801. RESULTS: p53 overexpression was observed in 41 (87.2%) of 47 tumors of patients in Linxian and in 16 (64%) of 25 additional patients outside Linxian. Its prevalence in the noncancerous epithelium (11/72, 15.3%) and carcinoma in situ (1/7, 14.3%) was lower than that in invasive lesions (64/93, 68.8%). Its immunostaining intensity increased with the depth of cancer invasion. Of 30 primary carcinomas with lymph node metastasis, 29 (96.7%) were positive. However, only 36 (51.4%) of 70 primary lesions without metastasis were positive, and a higher intensity was noticed in the metastases. There was a lower expression rate in tumors of patients surviving more than 10 years (25/52, 48.1%) than in those surviving less than 3 years (40/48, 83.3%). Overall and nonadvanced or metastasis-free cumulative survival rates were both significantly different in patients with and without p53 protein overexpression. CONCLUSIONS: There is a higher expression rate of p53 protein in ESCC in tumors of patients from Linxian than in those from the surrounding area. The accumulation of p53 protein is related to the invasiveness and capability for metastases of cancer cells and appears to be a useful prognostic factor for patients with ESCC.

Adult↗