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Biomedical subjects

S Tominaga

Publications and source records attributed to S Tominaga.

At least 19 recordsLinked to original sources

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

Induction of two major isoforms of metallothionein in crucian carp (Carassius cuvieri) by air-pumping stress, dexamethasone, and metals.

The induction of metallothionein (MT) by physical and chemical stress was assessed using the fresh-water fish, crucian carp (Carassius cuvieri Temminck et Schlegel). The fish exposed to violent air-pumping stress for 6 days revealed time-dependent induction of MT-like metal-binding proteins in both their livers and kidneys. Their hepatic contents after exposure to stress were elevated to twice the basal level with 24 h, resulting in more than a 3-fold increase at 144 h, whereas their renal contents gradually increased after 24 h and reached the same level as that in the liver around 96 h. Two major inducible proteins were purified from livers of fish exposed to stress and were shown to be MT based upon their chromatographic behavior, UV absorption spectra and their molecular weights. Consequently, they were termed ccMT-1 and ccMT-2, according to their elution sequence upon anion-exchange chromatography. Both proteins mainly bound zinc in their endogenous forms and showed different immunogenicity to rat and rabbit MTs. Dexamethasone, a potent inducer for MT synthesis in mammals, induced the production of both isoforms in crucian carp, whereas cadmium and zinc ions prominently induced the synthesis of ccMT-2. These results indicate that crucian carp have the ability to produce MTs in response to various kinds of environmental stress and that violent air-pumping stress in crucian carp may induce MT synthesis, in part, via the release of endogenous factor(s), such as glucocorticoids.

Air

Opposite regulation of the expression of cyclin-dependent kinase inhibitors during contact inhibition.

Contact inhibition is a well-known phenomenon, but the details of its mechanism are poorly understood. Recently, cyclin-dependent kinase inhibitors have been studied intensively with respect to their regulatory role in the cell cycle, and of them, p27(Kip1) is particularly involved in contact inhibition. p27(Kip1) is believed to be regulated primarily through posttranscriptional mechanisms. We now report that cyclin-dependent kinase inhibitors, including p27, are regulated differently at the mRNA level during contact inhibition in murine BALB/c-3T3 fibroblasts. The mRNA expression of p15, p16, and p27 was up-regulated as the cell density increased, but, on the contrary, the mRNA level of p21(Cip1/WAF1/Sdi1) markedly decreased when the cells became confluent. The protein levels of these genes were regulated in the same way as their mRNA levels, and cyclin-dependent kinase-2 activity was markedly inhibited on density-mediated growth arrest of the cells. These results indicate that the regulation of mRNA expression of cyclin-dependent kinase inhibitors appears to contribute to their protein levels and to the arrest of cell growth through contact inhibition.

3T3 Cells

Tea polyphenol intake and changes in serum pepsinogen levels.

Following a phase I study, a phase II study was conducted to evaluate the effects of two different doses of tea polyphenols on serum pepsinogen levels. Subjects were patients aged 40 to 69 years who had undergone gastroscopy between 1995 and 1997 at Aichi Cancer Center Hospital, and had been found to have no disease requiring medication. Those with pepsinogen I < 70 ng/ml and pepsinogen I/II ratio < 6 were included in this study. Capsules containing 100 mg of tea polyphenols were administered for 1 year: 1 capsule per day for 101 patients (42 males and 59 females), and 6 capsules (equivalent to 10 cups) per day for 83 patients (30 males and 53 females). The enrollment of the 1 capsule group preceded that of the 6 capsule group, in which re-participation was allowed. Blood samples were obtained 1 year after participation from 86 participants of the 1 capsule group and 77 participants (43 new participants and 34 re-participants) of the 6 capsule group. The compliance in polyphenol capsule intake ranged from 11.4 to 105.7% (87.6% on average) of the scheduled amount for the 1 capsule group and 3.2 to 112.3% (77.8% on average) for the 6 capsule group. No serious polyphenol-related adverse effects were reported. The difference in pepsinogen I between before and after 1 year intake of the polyphenol was 3.1 ng/ml for the 43 participants of the 6 capsule group, but 3.5 ng/ml for the 1 capsule group. The mean pepsinogen I/II ratio for the 43 participants increased from 2.37 by 0.08. This increase was not larger than that for the 1 capsule group (from 2.61 by 0.11). Among 34 participants in both interventions, no significant increase in pepsinogen I and I/II ratio for the 6 capsule intervention was observed. This result suggests that additional polyphenol intake for 1 year in Japanese does not improve pepsinogen levels, which are considered to reflect stomach atrophy, a high-risk condition for stomach cancer.

Adult

DNA vaccination against HuD antigen elicits antitumor activity in a small-cell lung cancer murine model.

There is a clinically significant correlation between the presence of an antibody against the paraneoplastic encephalomyelitis antigen HuD and the limitation of tumor spread in patients with small-cell lung cancer (SCLC). This suggests that HuD is a possible target molecule for antitumor immunotherapy against SCLC. We have hypothesized that anti-HuD immunity suppresses in vivo growth of HuD-expressing tumor cells. In this study, Colon 26, a murine adenocarcinoma cell line, stably transfected with the HuD gene (Colon 26/HuD cell) was used as a target cell, and the immunity against HuD was evoked by intramuscular injection of a HuD-expressing plasmid, a technique of DNA vaccination previously used in BALB/c mice. Colon 26/HuD cells were injected subcutaneously and tumor size was calculated as a product of width and length. Antitumor activity was investigated by using two different lots of Colon26/HuD cells in two protocols: Protocol 1, in which either Colon 26/HuD or Colon 26 cells were injected in each side, and Protocol 2, in which Colon 26/HuD cells alone were injected. The size of Colon 26/HuD tumors obtained from mice vaccinated with HuD-expressing plasmid was significantly smaller than those from negative control plasmid-vaccinated mice (86.6 +/- 29.9 versus 195.3 +/- 48.1 mm2, P < 0.05 in Protocol 1; 107.7 +/- 12.8 versus 156.6 +/- 22.8 mm2, P < 0.05 in Protocol 2). Moreover, the de novo DNA synthesis of spleen cells obtained from HuD-vaccinated mice was significantly enhanced. In addition, anti-HuD antibody was found in individual sera obtained from HuD-vaccinated mice. DNA vaccination with mouse HuD antigen suppressed HuD-expressing tumor growth in a murine SCLC model.

3T3 Cells

Intracerebral cystic meningioma--case report.

A 46-year-old female presented with persistent bifrontal headache. Computed tomography revealed a large cystic tumor in the right temporoparietal area, which included a solid component. The tumor had no attachment to the dura. There was no peritumoral edema or mass effect usually found around cystic meningiomas. The solid component was totally removed. Histological examination indicated that the tumor was a fibrous meningioma. Intracerebral meningioma with a large cystic component without dural attachment should be considered in the differential diagnosis of cystic cerebral tumors.

Arachnoid Cysts

Effect of life styles on the risk of subsite-specific gastric cancer in those with and without family history.

To evaluate a combined effect of gastric cancer family history (GCFH) and selected living habits on the subsite-specific of gastric cancer, a hospital-based case-referent study was conducted in Tokai area of Japan. The study subjects were 850 newly diagnosed gastric cancer (GC) patients and 28,619 cancer-free first-visit outpatients. Odds ratios (ORs) of all subsites of GC in subjects with both GCFH and habitual smoking were significantly higher (OR = 4.22) compared with those with merely GCFH (OR = 1.81) or habitual smoking (OR = 2.83). When positive GCFH subjects frequently consumed raw vegetable, the risk of GC decreased in cardia (OR = 0.68), antrum (OR = 0.43) and all subsites (OR = 0.74). Our findings provided evidence that GCFH and habitual smoking increased the risk of GC with family history, while frequent intake of raw vegetable decreased the risk and it was modified by other environmental factors.

Adult

[CT diagnosis of hyperdense intracranial neoplasms: review of the literature].

In contrast to typical astrocytic tumors that show hypodense areas on computed tomographic images, some intracranial tumors show hyperdense areas on CT images. The major reasons for hyperdensity on CT images are hypercellular lesions, intratumoral calcification, and intratumoral hemorrhage. Malignant lymphomas, germinomas, and medulloblastomas show homogeneous hyperdensity on CT images because of their hypercellularity. Tumorous lesions such as subependymal giant cell astrocytomas, oligodendrogliomas, ependymomas, central neurocytomas, craniopharyngiomas, and meningiomas often present with hyperdense calcified lesions on CT images. Intratumoral hemorrhage also causes hyperdensity on CT images, and is often associated with metastatic brain tumors, glioblastomas, pituitary adenomas, and rarely with any of the other intracranial tumors. Although magnetic resonance imaging is now the major diagnostic tool for diseases of the central nervous system, the first imaging studies for patients with neurologic symptoms are still CT scans. Hyperdense areas on CT images are a clue to making an accurate diagnosis of intracranial neoplasms.

Adult

Human papillomavirus as a risk factor for head and neck cancers--a case-control study.

A retrospective, case-control study was conducted to examine the relationship between the presence of human papillomavirus types 16 and 18 (HPV16/18) DNA and the risk of head and neck cancers. Twelve out of 74 (16.2%) head and neck cancers contained HPV16/18 DNA, while 3 out of 70 (4.2%) non-cancer controls showed HPV16/18 positivity by polymerase chain reaction. The presence of HPV16/18 DNA was associated with an increased risk of head and neck cancer formation, showing an odds ratio of 4.32, with a 95% confidence interval of 1.26-14.78. Although its epidemiological impact might be smaller than that of other factors like cigarette smoking, the presence of HPV16/18 DNA in the aerodigestive tract is suggested to be a risk factor for human head and neck cancers.

Carcinoma, Squamous Cell

Family history and subsite of gastric cancer: data from a case-referent study in Japan.

A comparative case-referent study was conducted using data from the Hospital-Based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) (Nagoya, Japan), with the aim of clarifying the effect of family history on gastric cancer by subsite. Our study comprised 995 histologically confirmed gastric cancer cases (180 cardia, 430 middle, 365 antrum and 20 unclassified) and a total of 43,846 non-cancer outpatients at Aichi Cancer Center Hospital between 1988 and 1995. Logistic regression was used to calculate odds ratios (ORs) for family history of gastric cancer and other cancers, adjusted for age, year and season at first hospital visit, habitual smoking, habitual alcohol drinking, regular physical exercise, preference for salty food and raw vegetable intake. In both genders, a positive family history of gastric cancer was associated with a moderate, but statistically significant increase in risk of gastric cancer [OR = 1.51, 95% confidence interval (95% CI) = 1.29-1.76], while no association was observed between the risk of gastric cancer and a family history of other cancers [OR = 0.97, 95% CI = 0.84-1.13]. OR increased for the middle and antrum parts of gastric cancer, but an increment for the cardiac part was observed only in those with a maternal history of gastric cancer. Our results suggest that the risk of gastric cancer in relation to family history varies by subsite and, furthermore, that the subsite-specific risk of gastric cancer is linked to a maternal history of gastric cancer.

Adult

Evaluation by ventilation and perfusion scintigraphy in patients who developed postural hypoxemia in the supine position.

Ventilation and pulmonary perfusion scintigraphy were performed in 7 patients in whom postural change from the sitting position to the supine position decreased partial oxygen pressure in arteries (PaO2) by 15 mmHg or more. Six of these 7 patients were obese. Five patients had organic pulmonary disease or space occupying lesions of the liver. On lateral supine-position images taken by using the continuous inhalation method for 81mKr ventilation scintigraphy, ventilation was reduced in the dorsal area corresponding to a gravity-dependent area, but on pulmonary perfusion scintigrams, there were no marked changes compared to normal adults. The mismatch of ventilation to perfusion may have caused hypoxemia. Reduced ventilation was correlated with reduced PaO2. The distribution of 81mKr bolus gas inhalation suggested closure of the airway in the dorsal area at functional residual capacity (FRC), which means the resting expiratory level, in the supine position.

Adult

Expression of bcl-2 oncoprotein in transitional cell carcinoma of the upper urinary tract.

We investigated the immunoreactivity for bcl-2 oncoprotein in 154 cases of transitional cell carcinoma of the upper urinary tract (TCC-UUT) and its relation with the immunoreactivity for p53 oncoprotein and proliferating cell nuclear antigen (PCNA) immunoreactivity. Immunohistochemically, bcl-2 oncoprotein was recognized as positive in 29.2% of the samples. The immunoreactivity for bcl-2 oncoprotein was significantly (P < 0.05) correlated only with stage, though there was a borderline correlation (P = 0.050) with PCNA immunoreactivity. Furthermore, in invasive TCC the immunoreactivity for bcl-2 oncoprotein was associated with PCNA immunoreactivity (P < 0.041). The 5-year disease-free and overall survival rates were 55.7% and 71.5%, respectively. A univariate analysis of survival revealed that stage, grade, pattern of growth, immunoreactivity for p53 oncoprotein, and PCNA immunoreactivity each had a significant effect on disease-free and overall survival rates, whereas the immunoreactivity for bcl-2 oncoprotein had no significant effect on either rate. In the final models of the multivariate analysis, stage was found to be the only prognostic factor for disease-free survival and for overall survival. Detection of immunoreactivity for bcl-2 oncoprotein appears to be of no real value in deciding the prognosis of TCC-UUT.

Adult

Cerebral revascularization using omentum and muscle free flap for ischemic cerebrovascular disease.

BACKGROUND: Indirect cerebral revascularization has been generally accepted in the management of brain ischemia in moyamoya disease. We performed indirect cerebral revascularization by using omental flap and muscle flap techniques for the treatment of ischemic cerebrovascular disease. METHODS: Ten patients with ischemic cerebrovascular disease including three with adult moyamoya disease underwent this procedure (omental flap on eight sides and muscle flap on five sides). The muscle used for the flap was the serratus anterior muscle on two sides and shaved latissimus dorsi muscle on three sides. Angiography and cerebral blood flow studies were performed in all patients preoperatively and postoperatively. All patients demonstrated severely impaired cerebrovascular reserve capacity due to occlusive disease. RESULTS: There was one patient each with perioperative death and intracranial infection following omental flap loss, and two patients had perioperative strokes. The average follow-up period was 23.2 months. Of the nine surviving patients, all eight except for the one with flap loss had good outcome with complete resolution of neurologic episodes. CONCLUSIONS: It is concluded that this method seems to be effective in selected patients with ischemic cerebrovascular disease.

Adult

Bronchiolitis obliterans after bone marrow transplantation: evaluation with lung scintigraphy.

Bronchiolitis obliterans (BO) has been described as a main pulmonary complication following allogeneic bone marrow transplantation (BMT). Diagnosis of BO is usually based on clinical findings, pulmonary function tests, and computed tomography scan. However, histological examination of an open-lung biopsy specimen may sometimes be necessary to confirm the diagnosis, despite its relative invasiveness. The ventilation lung scan is another useful but non-invasive diagnostic method. In this study, we present two post-transplant BO cases, each showing different clinical conditions, characterized by delayed wash-out on 133Xe gas and airway depositions on radioaerosol inhalation scans. These methods succeeded in revealing pulmonary obstruction in cases where the pulmonary function tests were within normal range and the high-resolution CT scans (HR-CT) of the chest were only minimally abnormal, suggesting their usefulness as an additional tool in the diagnosis of post-transplant BO, as well as in the follow-up to pulmonary obstruction.

Adult

Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan.

OBJECTIVES: The purpose of this study was to examine the hypothesis that tea and coffee consumption have a protective effect against development of digestive tract cancers. METHODS: A comparative case-referent study was conducted using Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) data from 1990 to 1995 in Nagoya, Japan. This study comprised 1,706 histologically diagnosed cases of digestive tract cancers (185 esophagus, 893 stomach, 362 colon, 266 rectum) and a total of 21,128 non-cancer outpatients aged 40 years and over. Logistic regression was used to analyze the data, adjusting for gender; age; year and season at hospital-visit; habitual smoking and alcohol drinking; regular physical exercise; fruit, rice, and beef intake; and beverage intake. RESULTS: The odds ratio (OR) of stomach cancer decreased to 0.69 (95 percent confidence interval [CI] = 0.48-1.00) with high intake of green tea (seven cups or more per day). A decreased risk was also observed for rectal cancer with three cups or more daily intake of coffee (OR = 0.46, CI = 0.26-0.81). CONCLUSIONS: The results suggest the potential for protective effect against site-specific digestive tract cancer by consumption of green tea and coffee, although most associations are limited only to the upper category of intake and have no clear explanation for site-specificity.

Adult

Evaluation of the death certificate follow-up method for the analysis of survival rate: data from Aichi Prefecture, Japan.

To evaluate the use, for studies on survival, of death certificates from population-based cancer registries in Japan, we compared 5-year survival rates by two different methods: passive, derived from death certificates, and active, using family register systems. Registered cancer cases from Aichi Prefectural Cancer Registry were used as a model. The study subjects comprised 9244 cancer patients (3830 males and 5414 females) newly diagnosed at the Aichi Cancer Center Hospital and recorded in the Aichi Prefectural Cancer Registry between 1983 and 1991. The passive follow-up method, using death certificates, identified 87-89% of deaths among the study subjects. The proportion of deaths which were not identified by the passive follow-up method did not vary greatly with age or gender, but was higher among patients in the earlier rather than the later stages of cancer. Overall, the absolute and relative effects of unregistered deaths on apparent survival rate vary with the absolute survival rate. The absolute and relative differences between the survival rates calculated by the two methods are explained more clearly when data are analyzed by cancer site. The results of the present study provide useful information for interpreting the survival rate following diagnosis of cancer estimated by the passive follow-up method, i.e. using death certificates from a population-based cancer registry.

Aged

Nested consent design for clinical trials.

BACKGROUND: Since random treatment allocation is hardly understood by the majority of patients, a new 'nested consent design' for clinical trials is proposed. PROPOSED DESIGN: The design consists of a two-step enrollment of study subjects. The first step is the enrollment of participants into a follow-up study, where consent to be subjects involved in the follow-up is obtained. The second step is the enrollment of randomly sampled eligible participants into a new treatment group. After the explanation of (1) treatment mode, (2) additional burdens associated with the proposed treatment and (3) expected effects and possible adverse events, written informed consent is obtained. Those who reject participation and those who are not allocated into the new treatment are treated by standard care. Endpoints are set to be the same for all follow-up study participants whether allocated into the new treatment or not, and follow-up is carried out in the same manner. Analyses are performed between those allocated to the new treatment and those non-allocated on an intent-to-treat basis. EXAMPLE: Although not a clinical trial, this design was applied in a smoking cessation program at Aichi Cancer Center Hospital for first-visit patients who answered in a questionnaire survey that they were smokers. Out of 1330 necessary participants, 324 were enrolled in the follow-up study during the first three months of enrollment. CONCLUSIONS: The design was found to be feasible for prevention trials, and possibly for clinical trials to compare a new treatment with a standard treatment. There seems to be no ethical difference between this design and the one-arm study design.

Clinical Trials as Topic

Cerebral revascularization using muscle free flap for ischemic cerebrovascular disease in adult patients.

The efficacy of encephalo-myo-synangiosis (EMS) using muscle free flap was evaluated for the treatment of ischemic cerebrovascular disease in adult patients. Three patients with adult moyamoya disease and three patients with atherosclerotic ischemic cerebrovascular disease were treated. EMS used four latissimus dorsi muscles and two serratus anterior muscles. Postoperative selective angiography showed collateral circulation from the transferred muscle to the brain in four of the six patients. The other two patients showed patent nutrient artery of the transferred muscle flap. Cerebral blood flow study disclosed postoperative improvement of perfusion reserve capacity in all sides. One patient suffered a perioperative stroke by hemoconcentration due to poor control of diabetes mellitus. The mean follow-up period was 23 months. EMS using muscle free flap is a possible procedure in selected patients with impaired cerebral perfusion reserve capacity due to multiple stenosis or occlusion of cerebral arteries including moyamoya disease or who required cerebral blood flow augmentation in the anterior and/or posterior cerebral artery territories due to internal carotid artery occlusion.

Adult