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Biomedical subjects

S Tominaga

Publications and source records attributed to S Tominaga.

At least 55 records · Page 3Linked to original sources

Mucin histochemistry in primary adenocarcinoma of the urinary bladder (of urachal or vesicular origin) and metastatic adenocarcinoma originating in the colorectum.

In order to evaluate the mucin histochemistry of primary adenocarcinomas (PA) of the urinary bladder and metastatic adenocarcinoma (MA) originating in the colorectum, 52 PA and nine MA were examined. It was determined that the percentage of cases in which more than 25% of the tumor was stained by each of the following: (i) Alcian blue pH 2.5 periodic acid-Schiff (AB-PAS); (ii) high iron diamine-AB (HID-AB); (iii) periodic acid-sodium borohydride-potassium hydroxide-PAS (PA-SB-PH-PAS); (iv) galactose oxidase- Schiff (GOS); and (v) paradoxical concanavalin A stain (PCS). For PA, the values obtained were: 75% of cases (blue, AB-PAS), 85% (magenta, AB-PAS), 71% (black, HID-AB), 75% (blue, HID-AB), 0% (PA-SB-PH-PAS), 19% (GOS), 8% (class II concanavalin A (Con A)-reactive mucin)), and 0% (class III Con A-reactive mucin). For MA, the corresponding values were 33, 22, 0, 11, 0, 0, 11, and 0%, respectively. A higher percentage of PA than MA cases showed staining in AB-PAS for acidic and neutral mucins, in HID-AB for sialo- and sulfomucins, and in GOS for terminal beta-galactose and beta-N-acetylgalactosamine. PA and MA were significantly different in terms of both frequency of staining with AB-PAS and frequency of staining with HID-AB. However, the overlap was such that in practice, it might be difficult, if not impossible, to use mucin histochemistry to inform a differential diagnosis. In view of the differences in AB-PAS and HID-AB positivity between PA and MA, we speculate that MA (originating in the colorectum) may have undergone structural distortion affecting the production and/or secretion of neutral mucins and acidic mucins (sialo- and sulfomucins) during metastasis or invasion.

Adenocarcinoma↗

Osteopontin is induced by nitric oxide in RAW 264.7 cells.

Nitric oxide (NO) produced by macrophages is thought to contribute to various pathological conditions. Osteopontin (OPN) is a phosphorylated glycoprotein produced principally by macrophages. OPN inhibits inducible nitric oxide synthase (iNOS), which generates large amounts of NO production. However, the relationship between NO and endogenous OPN in activated macrophages has not yet been elucidated. We therefore examined expression of endogenous iNOS and OPN in a murine macrophage cell line, RAW 264.7 cells, by treating the cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Treatment of cells with LPS and IFN-gamma resulted in an increase of iNOS mRNA to maximum at 12 h after stimulation. In contrast, OPN mRNA was induced more slowly than iNOS mRNA. Induction of both iNOS and OPN mRNA in RAW 264.7 cells was markedly suppressed by addition of the specific iNOS inhibitor S-2-aminoethyl isothiourea dihydrobromide. The NOS inhibitor NG-methyl-L-arginine also suppressed induction of OPN mRNA but hardly affected iNOS mRNA expression. The NO-releasing agent spermine-NONOate but not peroxynitrite enhanced induction of OPN mRNA. These results suggest that NO directly up-regulates the endogenous OPN in macrophages stimulated with LPS and IFN-gamma. This up-regulation of endogenous OPN may represent a negative feedback system acting to reduce iNOS expression.

Animals↗

Molecular and biological analysis of carcinoma of the small intestine: beta-catenin gene mutation by interstitial deletion involving exon 3 and replication error phenotype.

The genetic mechanisms of carcinomas of the small intestine are not well understood. We report the results of analysis of genetic alterations in a case of small intestinal carcinoma. A tumor in the terminal ileum was resected in a 59-yr-old woman. Histologically, the tumor was classified as well-differentiated adenocarcinoma. We screened for genetic alterations in adenomatous polyposis coli (APC), beta-catenin, K-ras, and p53 genes, as well as microsatellite instability, which are known to be involved in colorectal tumorigenesis. The tumor exhibited somatic interstitial deletion of 425-bp, which included the entire exon 3 in beta-catenin gene. Immunohistochemical staining confirmed accumulation of aberrant beta-catenin protein in the cytoplasm and nuclei of the malignant tissue. Furthermore, a frameshift mutation in the transforming growth factor beta receptor type II gene with replication error phenotype was detected in the tumor DNA. In contrast, no genetic alterations were found in the APC, K-ras, and p53 genes. Our results suggested that both beta-catenin gene mutation and replication error phenotype might contribute to carcinogenesis of the small intestinal tumor in our case. This is the first report that activation of beta-catenin gene by somatic gene mutation is involved in the development of carcinoma of the small intestine.

Amino Acid Sequence↗

Effects of dietary, drinking, and smoking habits on the prognosis of gastric cancer.

Although it has been clarified that dietary, drinking, and smoking habits contribute to the onset of gastric cancer, little is known about their impact on prognosis of gastric cancer. To examine this question, a prognostic analysis was conducted using data from Aichi Cancer Center Research Institute and Hospital. From January 1988 to December 1994, information on 877 gastric cancer patients (578 men and 299 women) regarding habitual smoking and drinking, food consumption, histological grade, and clinical stage of tumor as well as follow-up results were collected. Survival status of all patients was followed up until December 1998, and the survival function was estimated by the Kaplan-Meier method. Proportional hazard analysis was used to test the effect of each lifestyle item on gastric cancer death. After controlling for age, gender, histological grade, and stage of disease, hazard ratios (HR) were calculated. Values for consumption of raw vegetables [HR = 0.74, 95% confidence interval (CI) = 0.56-0.98], tofu (HR = 0.65, 95% CI = 0.42-0.99), and chicken meat (HR = 0.61, 95% CI = 0.39-0.95) more than three times per week demonstrated significantly decreased risk. However, the risk ratio was 2.53 (95% CI = 1.22-5.29) for habitual smokers, and an inverse dose-response relationship was also found between ever smoking and gastric cancer patient survival. Therefore, this study suggested that frequent intake of raw vegetables and tofu is favorable, whereas habitual smoking is an adverse prognostic factor for gastric cancer. Our study implies that an improvement of survival of Japanese gastric cancer might be achieved by lifestyle improvement.

Adenocarcinoma↗

Two metallothioneins in the fresh-water fish, crucian carp (Carassius cuvieri): cDNA cloning and assignment of their expression isoforms.

Two metallothionein cDNAs (MT-A and MT-B) in the fresh-water fish crucian carp (Carassius cuvieri Temminck et Schlegel) were cloned. Sequence analysis of both cDNAs gave the structure of a coding region corresponding to 60 amino acid residues. The homology of their deduced amino acid sequences was completely conserved at the positions of the cysteine residue, but a significant difference existed in the size of their 3'-untranslated regions (130 base pairs for MT-A and 280 base pairs for MT-B). Direct amino acid sequencing of the MT-II isoform purified by HPLC was accomplished for up to 30 residues and its sequence was identical to that deduced from MT-B cDNA. This is the first case in vertebrates that N-terminal methionine in crucian carp MT-II was not blocked. By northern blot analysis, basal and cadmium chloride- or dexamethasone-induced MT-B (MT-II) mRNAs were detected time dependently after treatment. On the other hand, the expression of MT-A mRNA was extremely low. These results indicate that the MT isoform II in crucian carp is coded by the MT-B gene, and that the MT-B-dominant expression of mRNA in crucian carp may be due to the difference in the 3'-untranslated regions of MT mRNAs.

Amino Acid Sequence↗

[Regional differences of in vivo proton MR spectroscopy in developing human brain].

The purpose of this study was to clarify regional differences in proton MR spectroscopy (1H-MRS) in the developing human brain. Proton MR spectra were obtained from 24 infants aged 0 to 24 months old. Proton MR spectroscopy was performed on a 1.5 Tesla clinical MR unit using a 3D-chemical shift imaging sequence (3D-CSI). MR spectra obtained from voxels in frontal white matter and those in parietal white matter were compared. The NAA/Cho ratios of the frontal region were lower than those of the parietal region at birth but increased rapidly during the first six months of life. The rate of increase was reduced in the second year of life. In contrast, NAA/Cho ratios in paracentral areas were already high at birth but increased slowly through the first two years of life. Cho/Cr ratios of the frontal region were stable during the first year of life and started to decrease in the second year of life. In the parietal region, Cho/Cr ratios were decreased throughout infancy. Regional differences in 1H-MRS spectra were apparent during infancy, and these differences were suggested to reflect regional differences in the maturation of the developing human brain.

Adult↗

[Prevention of lung cancer--primary and secondary prevention].

Prevention consists of primary and secondary prevention. For primary prevention of lung cancer, smoking control is considered to be most important and effective. If the present level of smokers in adults Japanese (52.8% in males and 13.4% in females) is decreased to the 50% level of the present level as it was once planned in "the Healthy Japanese 21", 32.3% of lung cancer in males and 7.6% in females (25.5% in both genders) could be prevented. For secondary prevention of lung cancer, periodic lung cancer screening may be useful. If the coverage rate of lung cancer screening is elevated to 30-50%, 15-25% of lung cancer deaths will be prevented assuming the odds ratio of lung cancer death is 0.50 for those who received lung cancer screening. It was estimated that if both smoking control and lung cancer screening were promoted extensively in Japan, as much as 30 to 50% of lung cancer incidences/deaths could be prevented.

Adult↗

[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia and pleural effusion].

A 56-year-old man was admitted for further evaluation of mediastinal lymphadenopathy and left pleural effusion. A blood test revealed polyclonal hypergammaglobulinemia with an elevated erythrocyte sedimentation rate and level of C-reactive protein. Chest computed tomography disclosed bilateral hilar and multiple mediastinal lymph-node swelling and bilateral pleural thickening accompanied by a moderate amount of left pleural effusion. Biopsy specimens from mediastinal lymph nodes and the right pleura were obtained under video-assisted thoracoscopy. Histology on microscopic examination demonstrated mature plasma cells and lymphocyte infiltration in the conserved lymph-node structure and the pleura, suggesting a diagnosis of idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia. Interestingly, IL-6 was elevated in the pleural effusion but normal in serum. This was a rare and instructive case of IPL accompanied by pleural effusion that was considered to be an important determinant of the clinical spectrum of the disease.

Biomarkers↗

Effects of black current anthocyanoside intake on dark adaptation and VDT work-induced transient refractive alteration in healthy humans.

The effects of oral intake of a black currant anthocyanosides (BCA) concentrate on dark adaptation, video display terminal (VDT) work-induced transient refractive alteration, and subjective asthenopia symptoms (visual fatigue) were examined in a double-blind, placebo-controlled, crossover study with healthy human subjects. In a dark adaptation study, intake of BCA at three dose levels (12.5-, 20-, and 50 mg/subject, n = 12) appeared to bring about dose-dependent lowering of the dark adaptation threshold. Statistical analysis comparing the values before and after intake indicated there was a significant difference at the 50 mg dose (p= 0. 011). Comparing the refraction values for the dominant eye, BCA intake (50 mg/subject, n = 21) resulted in no decrease in the average value after the visual task; whereas, a placebo trial resulted in a large decrease in the average value, resulting in borderline significance (p = 0.064). In the assessment of subjective asthenopia symptoms by questionnaire, significant improvement was recognized on the basis of the statements regarding the eye and lower back after BCA intake.

Adult↗

Epidemiology and Prevention of Breast Cancer in the 21st Century.

The incidence and mortality of breast cancer are high in Western industrialized and relatively low Japan and other Asian countries. In Japan the incidence and mortality of breast cancer have gradually been increasing. Marrying later, having fewer children, a larger intake of fat, dairy products and meats and a larger body mass index in menopausal women may be related to the increased incidence of breast cancer in Japan. A review of risk factors identified from recent epidemio-logical studies in Japan indicates that obesity after 50 years of age is an important risk factor for post-menopausal breast cancer. Future estimations of cancer mortality and incidence predict that breast cancer will further increase to become a leading cancer in Japan in the 21st century.

Journal Article↗

Identification of Cancer Antigens in Breast Cancer by the SEREX Expression Cloning Method.

Enormous strides in cancer immunology have been made during the past decade. This is largely due to the development of methodologies capable of defining the antigenic targets on cancer cells that elicit a host immune response. The molecular cloning of antigens recognized by cytotoxic T cells by Boon and his colleagues has provided a growing list of tumor antigens, particularly for melanoma, that allows detailed monitoring of T cell responses to these antigens and offers promising targets for cancer vaccine development. An alternative new method, SEREX, for the serological identification of cancer antigens has been developed by Pfreundschuh and his colleagues. SEREX can be applied to all types of cancer including breast cancer that have been unapproachable by using cytotoxic T cells and thus offers an opportunity to define a vast range of cancer antigens. Toward thedevelopment of a vaccine for breast cancer, we have begun using SEREX to study breast cancer and have identified a few promising cancer antigens. Each antigen is now being critically evaluated as a possible vaccine target.

Journal Article↗

Influence of habitual smoking on gastric cancer by histologic subtype.

A comparative case-referent study was conducted using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), with the aim of clarifying whether histologic subtypes of gastric cancer exhibit different risk-factor patterns of habitual smoking. Our study comprised 995 histologically confirmed gastric-cancer cases [460 differentiated (intestinal type), 527 non-differentiated (diffuse type) and 8 unclassified], identified via hospital cancer registry and surgical records, and 43,846 non-cancer outpatients at Aichi Cancer Center Hospital over the years 1988-1995. Odds ratios (ORs) were estimated by gender using logistic regression and adjusted for potential confounding factors. In males, a significantly increased OR of gastric cancer was observed for habitual smokers, and this was higher in the differentiated type than the non-differentiated type and in younger than in older age groups. Risk patterns were less clear in females. Our results suggest that habitual smoking is associated more likely with the differentiated type of gastric cancer, particularly in younger cases.

Adult↗

Experimental small bowel transplantation using newborn intestine in rats: II. Revascularization of newborn intestine is independent of vascular endothelial growth factor.

BACKGROUND: Fetal and newborn intestine often are revascularized after subcutaneous transplantation without surgical vascular anastomosis. However, the mechanism of this ability remains unclear. METHODS: First, the ability of natural revascularization in newborn organs was tested. Newborn organs in whole (liver, kidney, heart, intestine, spleen, and pancreas) were grafted i nto the subcuta neous tissue of the adult rat and evaluated histopathologically 2 weeks after transplantation. Second, expression of vascular endothelial growth factor (VEGF) mRNA in the intestinal graft was determined before and after transplantation. Finally, we tested whether the free graft survival of newborn intestine was interrupted by TNP-470, an antiangiogenic agent. RESULTS: Spleen and intestine were revascularized at a higher rate (91.6%, 75%, respectively), and kidney and heart grafts survived at a lower rate (41.7%, 25%, respectively). But all of liver and pancreas grafts failed to be revascularized. VEGF mRNA was not induced in the course of revascularizing. Furthermore, TNP-470 did not interfere with neovascularization of the newborn intestinal graft in vivo. CONCLUSIONS: Each organ had an organ-specific angiogenic activity. Neovascularization of intestinal graft was not dependent on VEGF expression.

Angiogenesis Inhibitors↗

Major avoidable risk factors of cancer.

With an aim of promoting primary prevention of cancer, major avoidable risk factors as well as protective factors of cancer are reviewed based on previous epidemiological studies. Among various risk factors of cancer, tobacco is the most important avoidable risk factor for cancers of the oral cavity, larynx, lung, pharynx, esophagus, stomach, liver, pancreas, kidney (pelvis), ureter, bladder, and cervix. Tobacco accounts for some 20-30% of all sites of cancer. Betel quid and tobacco chewing is an important risk factor for cancer of the oro-pharynx in some parts of South-East Asia. Diet also plays an important role in the etiology of cancer, but its relation to cancer is complicated. An excess or insufficient intake of some food components elevates risk of cancer of several sites. Eating habits, available foods, methods of food processing may vary from country to country. Infection of oncogenic viruses (especially, HBV, HVC, HPVs) is an important avoidable risk factor of cancer where liver cancer and cervical cancer are common. Infection of Helicobacter pylori could also be an important risk factor of stomach cancer. Attributable risks of other avoidable risk factors, such as occupation, environmental pollution, sun light, radiation, food additives, pesticides, drugs, etc. are relatively small compared to those of tobacco, diet and infection. Exercise and stress are also manageable risk factor of cancer.

Alcohol Drinking↗