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Biomedical subjects

T Ohnishi

Publications and source records attributed to T Ohnishi.

At least 73 records · Page 4Linked to original sources
PubMed2001

[Proposal from space radiation biologists. Importance of Centrifuge Facility in the study of biological effect by space radiation].

In microgravity, astronauts were constantly exposed to space radiation containing various kinds of radiation with a low-dose rate during long-term stays in space. It is very difficult to define the relative biological effectiveness (RBE) of space radiation under microgravity. In order to understand correct the RBE of space radiation, therefore, utilization of Centrifuge Facility is desired as a control experiment at orbit for removing other factors such as microgravity except space radiation. Here, we summarized the importance of Centrifuge Facility in the study of biological effect of space radiation.

Aerospace Medicine↗
PubMed2001

Japanese red-bellied newts in Space--AstroNewt experiment on Space Shuttle IML-2 and Space Flyer Unit.

Biological effects of gravity was examined in embryonic development of Japanese red bellied newt. Two space newt missions were conducted in 1994 and 1995. The Second International Microgravity Laboratory was flown in 1994 as one of the SpaceLab missions. Space Flyer Unit, a Japanese space platform, was delivered to the earth orbit by the third launch of the H-II rocket and retrieved by Space Shuttle in 1996. Female newts were induced to lay eggs in orbit at these two space missions. Eggs were successfully obtained on both missions, and exposed to space environment from its early developmental stages. Morphology of the embryos was found not deviated from those developed on ground, as long as in the images taken in orbit or the examined specimen retrieved to ground. On the other hand, pathological changes were discovered in several organs of the adult newts that returned alive from their space flight.

Adaptation, Physiological↗
PubMed2001

Delayed aortic rupture caused by an implanted anterior spinal device. Case report.

The authors describe a case of delayed aortic rupture following the application of a smooth-rod Kaneda (SRK) instrument. This is a rare but critical complication of anterior spinal fusion in which instrumentation is placed, and the authors wish to draw attention to the possible complications arising from such surgery. A few cases of this complication were reported in 1986. No reports have been published since then; perhaps because techniques and implant design have improved. In this case, a 53-year-old man suffered a T-11 fracture and related paraparesis, and he underwent decompression and anterior fusion in which an iliac bone graft was placed using an SRK device. Although his neurological deficit resolved postoperatively, nonunion of the grafted bone caused progressive kyphosis of the thoracolumbar spine. Twenty months after surgery, he complained of progressive gastrointestinal symptoms, and a delayed aortic rupture with a pseudoaneurysm was found surrounding the implant. The aortic pseudoaneurysm was replaced with an artificial vessel, and the SRK device was removed immediately. Delayed aortic rupture associated with anterior instrumentation is extremely rare but can occur. Even if the design of the implants can be improved, the placement of implants near the aorta and subsequent changes in the close anatomical relationship between the aorta and the implant eventually may result in this life-threatening complication. Careful follow-up examination and early removal of the implant, if necessary, are important.

Aneurysm, False↗
PubMed2001

Polymorphism of the WAF1 gene is related to susceptibility to cervical cancer in Japanese women.

The WAF1 gene, located on chromosome 6p21.2, has been cloned and identified as a p53 mediator and an inhibitor of G1 cyclin-dependent kinases (CDKs). The present study was performed to investigate the possible role of the WAF1 gene in the pathogenesis of human cervical carcinoma. Matched venous blood and cancer tissues from 66 patients with cervical cancer were screened for WAF1 mutation by reverse transcription-polymerase chain reaction (RT-PCR) and DNA sequencing. A polymorphism in the WAF1 gene involving a cytosine (C) to an adenine (A) transversion at the third base of codon 31 was observed in 52 of 66 (78.8%) patients with cervical carcinoma and 68 of 108 (63%) normal individuals (P=0.02). A total of 7 patients (10.6%) were found to have a change of the WAF1 gene at codon 31 on comparison of blood and tumor specimens. An A-->C transversion in 5 tumors and a C-->A transversion in 2 tumors, that were not found in matching normal specimens, were observed. In addition, the presence of loss of heterozygosity (LOH) on chromosome 6p21.2 in tumor and normal tissue DNA were analyzed by PCR at three polymorphic microsatellite loci (D6S276, D6S1624, D6S1583). In two cases, there was a change of Arg/Ser in blood to Ser/Ser in the tumor, which did not involve LOH on 6p21.2. Therefore, somatic mutation of the WAF1 gene was detected in 3% (2 of 66) of patients with cervical cancer in this series. In conclusion, the increased frequency of WAF1 polymorphism in the patients studied implied that codon 31 Arg allele of the WAF1 gene may be associated with a tendency to develop cervical carcinoma. To our knowledge, this is the first report of WAF1 somatic mutations in primary human cervical cancer.

Cyclin-Dependent Kinase Inhibitor p21↗
PubMed2001

Mutation of the PTEN gene in advanced cervical cancer correlated with tumor progression and poor outcome after radiotherapy.

Improvement in management of advanced cervical cancer after radiotherapy requires a better understanding of its biological behavior. PTEN/MMAC/TEP(PTEN), a candidate tumor suppressor gene located at chromosome 10q23.3, was recently identified and found to be frequently mutated in several different types of human tumors. In contrast, rare mutations of the PTEN gene have been reported in cervical cancer. The aim of this study was to determine whether mutation of PTEN leads to increased genomic alteration in advanced cervical carcinoma, and to identify the correlation between mutation of PTEN and patient outcome after radiotherapy. We examined 50 primary advanced cervical carcinomas (37 patients of Stage IIIB, 13 patients of Stage IVA) treated with definitive radiotherapy using a PCR-based assay followed by SSCP and direct sequencing. The PTEN gene was mutated in 8 of the 50 (16%) patients (2 of Stage III, and 6 of Stage IV). There was a significant difference in Stage III versus IV between the wild-type PTEN patients and mutant PTEN patients (P=0.002). The tumor size was 6+/-2.1 cm in the wild-type PTEN tumors versus 8.5+/-2 cm in the mutant PTEN tumors (P=0.009). In addition, there was a significant difference in survival between the wild-type PTEN patients and mutant PTEN patients (P=0.009). The results of this study suggest that the PTEN gene mutation rate increases with tumor progression, and that the PTEN gene may play a role in both progression of cervical carcinoma and treatment outcome.

Adult↗
PubMed2001

[A randomized comparative study assessing once versus twice a day treatment of benign prostatic hyperplasia with terazosin].

We compared the efficacy of once a day administration of terazosin hydrochloride with that of twice a day administration for benign prostatic hyperplasia (BPH) patients. Forty-two patients with BPH were randomly assigned to receive a maximum dose of 2 mg terazosin either once (n = 21) or twice (n = 21) a day. International prostate symptom score (IPSS), uroflowmetry and side effect profile were determined before and 4 weeks after randomization. Both groups were similar with respect to patient age, baseline IPSS and prostate volume. After 4 weeks of treatment with terazosin, significant improvement in IPSS, maximum flow rate and mean flow rate were observed in both groups. However, these improvements did not differ significantly between them. In addition, there were no differences in side effects between the groups. In conclusion, once a day administration of terazosin hydrochloride is as effective and safe as twice a day administration in patients with BPH.

Adrenergic alpha-Antagonists↗
PubMed2001

[Effects of topical prostaglandin analogues on the aqueous flare intensity in rabbit eyes at an early phase of endotoxin-induced uveitis].

PURPOSE: We examined the effects of prostaglandin analogues on the blood-aqueous barrier(BAB) permeability in rabbit eyes at an early phase of endotoxin-induced uveitis(EIU). SUBJECTS AND METHODS: One drop of 0.005% latanoprost or 0.12% unoprostone were applied to rabbit eyes. Escherichia coli lipopolysaccharides were injected to induce uveitis. The changes in flare intensity in normal eyes and EIU eyes after application of eye drops were evaluated. The effect of cyclooxygenase inhibitor on the flare intensity changes caused by the application of unoprostone was also examined. RESULTS: Flare intensity increased significantly after a single instillation of unoprostone, and the increase was not prevented by pretreatment with cyclooxygenase inhibitor. In eyes with EIU, unoprostone caused an additional increase of flare intensity to uveitis induced flare change. Latanoprost had no effects on BAB in eyes with normal and with uveitic conditions. CONCLUSION: Latanoprost and unoprostone did not cause an excessive inflammatory reaction in rabbit eyes at an early phase of EIU.

Animals↗
PubMed2001

[Clinical significance of micrometastasis to lymph nodes in gastrointestinal tract cancers].

Surgery is the main therapy for malignancies of the gastrointestinal tract. Lymph node metastasis is one of the major factors in predicting patients' clinical course and choosing appropriate adjuvant therapy after surgery. The concept of micrometastasis to regional lymph nodes emerged over 10 years ago, but its significance has been controversial. To clarify the relevance of micrometastasis of gastrointestinal tract cancers, we have established RT-PCT based-diagnostic methods using multi-markers such as CEA, CK20, and Mage 3. Prospective studies have shown that not a few micrometastasis-positive patients with carcinoma of the colon, stomach, and esophagus suffered disease recurrence, even though they did not show histologically positive lymph node metastasis. They were initially diagnosed as node-negative, and thus predicted to be disease free. A retrospective study of 62 patients with stage II node-negative colorectal cancer showed that 5-year overall survival was 78.2% among micrometastasis-positive patients, against 95.3% micrometastasis-negative patients. Moreover, there was a marked difference in 5-year disease-free survival, with 61.4% versus 88.4%, respectively. These data warrant further prospective study with a large population since RT-PCR based detection systems for micrometastasis appear to have the potential to improve conventional diagnosis and therapy for colorectal cancer.

Biomarkers, Tumor↗
PubMed2001

A new strategy for cancer therapy based on a predictive indicator.

Tumor-associated genes have been analyzed at the molecular level in recent years, and using the analyses of these genes as a predictive indicator for cancer therapy has attracted attention. Among such genes, the actions of a tumor suppressor gene p53 are focused on the cancer therapy, and it is suggested that p53 genotypes can be used as a predictive indicator for radiotherapy, thermotherapy and chemotherapy. Transfection of wtp53 to p53-null cells increased radiation- or thermo-sensitivity and stimulated apoptosis induced by these therapies. Although therapy-induced apoptosis is suppressed in mp53 cells, apoptosis can be stimulated by glycerol treatment as a chemical chaperone. Therefore, a new strategy of combining p53-targeted gene therapy or chemical chaperone therapies is expected to improve the outcome and efficiency of cancer therapy in the future.

Apoptosis↗
PubMed2001

Early full donor myeloid chimerism after reduced-intensity stem cell transplantation using a combination of fludarabine and busulfan.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate lineage-specific chimerism reconstitution after reduced-intensity allogeneic stem cell transplantation (RIST) using a combination of fludarabine (30 mg/m2 for 6 days) and busulfan (4 mg/kg for 2 days). DESIGN AND METHODS: We prospectively enrolled 8 consecutive patients with hematologic malignancies who were not candidates for conventional transplantation because of either high age or organ dysfunction. Host-donor chimerism was evaluated using polymerase chain reaction-based amplification of a polymorphic short tandem repeat region. RESULTS: All of our patients achieved engraftment within a median of 11 days after transplantation. On day 30, full donor myeloid cell chimerism (>90%) was achieved in 7 patients whereas full donor T-cell chimerism was achieved in only one patient. Thus, in contrast to other reported results, full donor chimerism was achieved earlier in the myeloid lineage than the T-cell lineage. On day 60, however, T-cell chimerism caught up with myeloid chimerism. Two patients developed grade II-IV acute graft-versus-host disease (GVHD) before the detection of full donor T-cell chimerism. INTERPRETATION AND CONCLUSIONS: Our findings suggest that the kinetics of lineage-specific chimerism depend on the agents used in the conditioning regimen, and may provide insight into the chimerism kinetics and pathogenesis of GVHD. Thus, the strategy for controlling immunosuppression after RIST should be modified according to the type of conditioning regimen applied.

Adult↗
PubMed2001

Changes in brain morphology in Alzheimer disease and normal aging: is Alzheimer disease an exaggerated aging process?

BACKGROUND AND PURPOSE: Whether Alzheimer disease (AD) represents exaggerated aging rather than a disease is controversial. Data about the effects of normal aging on the human brain are essential for clarifying this issue; however, whether coherent common patterns of regional morphologic brain changes emerge in the normal aged brain is unclear. Clarification of regional morphologic changes in the brain associated with normal aging and AD was sought using MR imaging. METHODS: Ninety-two healthy volunteers and 26 mildly to moderately impaired patients with AD participated. Images were anatomically normalized, and voxel-by-voxel analyses were done. RESULTS: In healthy volunteers, an age-related decline in the volume of the prefrontal cortex, insula, anterior cingulate gyrus, superior temporal gyrus, inferior parietal lobule, and precuneus was found. These decreases might contribute to the cognitive changes during normal aging. In patients with AD, a significant reduction of gray matter volume in the hippocampal formation and entorhinal cortex bilaterally was noted. CONCLUSION: Morphologic changes associated with normal aging are clearly different from those seen with AD.

Adolescent↗
PubMed2001

Tumor suppressor p53 response is blunted by low-dose radiation.

To estimate the effects of space radiation on health of space crews, we aimed to clarify whether g-ray-irradiation at a low-dose-rate interferes in a p53 centered signal transduction pathway induced by radiation in human cultured cells and CB-17 Icr+/+ mice. In vitro experiments, the human cultured squamous cell carcinoma cells (SAS/neo) were examined for cellular levels of p53 and Bax, and the incidence of apoptosis after irradiation at a low-dose-rate (1 mGy/min) or a high-dose-rate (1 Gy/min). It was found that challenging irradiation-induced apoptosis was depressed by chronic irradiation at 1.5 Gy for 25 h with the depression of p53 and Bax accumulation. In vivo experiments, a significant suppression of Bax and apoptosis induced by challenging irradiation at 3.0 Gy was observed when the mice were pre-irradiated chronically at 1.5 Gy for 25 h in the spleen of CB-17 Icr+/+ mice. These findings suggest that chronic pre-irradiation suppressed p53 function through radiation-induced signaling and/or p53 stability.

Animals↗
PubMed2001

Biological effects of space radiation.

To determine the effects of space radiation on human health for long-term stays in space, we performed 21 space experiments on radiation biology. Two main characteristics of space are microgravity and space radiation that consists of low dose, chronic exposure at low dose-rates, and heavy particles. Through space experiments, we demonstrated the formation of DNA strand breaks, induced mutations, abnormal cell differentiation and the inducible gene expression of a tumor suppressor gene product, p53, in various kinds of organisms. In addition, we investigated the influence of microgravity on radiation-induced biological effects in in vitro biochemical reaction systems and in vivo cell culture systems of bacteria and lower eukaryotes. We review here the importance of radiation biology studies on space radiation from the viewpoints of human health and biological evolution, from the beginning of life until today, in the context of environmental genotoxic radiation.

Aerospace Medicine↗
PubMed2001

[Space radiation biology].

Astronauts were constantly exposed to space radiation containing various kinds of energy with a low-dose rate during long-term stays in space. Therefore, it is important to judge correctly the biological effect of space radiation for human health. In addition, research for space radiation might give us useful information concerning birth and evolution of lives on the earth. Here, we described a view of the future about space experiments at an International Space Station. Therefore, we desire to educate the space researcher of the next generation for importance of research for space radiation.

Cosmic Radiation↗
PubMed2000

Wortmannin sensitizes human glioblastoma cell lines carrying mutant and wild type TP53 gene to radiation.

The purpose of this paper is to investigate the effect of wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), on TP53 (formerly known as p53) signal transduction initiated by ionizing radiation and radiosensitization in isogenic derivatives of human glioblastoma cells differing in TP53 status. Wortmannin inhibited the accumulation of TP53 and CDKN1A (formerly known as WAF1) after 6 Gy irradiation in A-172/neo cells bearing wild-type TP53. In A-172/Trp248 cells carrying mutant TP53, X-rays induced no significant accumulation of TP53 and slight increase of CDKN1A. There were, consequently, little differences in the expression of TP53 and CDKN1A between A-172/Trp248 cells exposed to 6 Gy alone and wortmannin plus 6 Gy. However, wortmannin sensitized both A-172/neo and A-172/Trp248 cells to radiation. These studies indicate that wortmannin inhibits TP53 upregulation, but this suppression does not account for the radiosensitization by this drug. These results indicate that inhibitors of PI3K-related kinases may present a new class of radiosensitizers, regardless of the TP53 status of tumor cells.

Androstadienes↗