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Biomedical subjects

E Kobayashi

Publications and source records attributed to E Kobayashi.

At least 109 records · Page 6Linked to original sources

Mapping and determination of the cDNA sequence of the Erc gene preferentially expressed in renal cell carcinoma in the Tsc2 gene mutant (Eker) rat model.

The Eker rat develops hereditary renal carcinomas (RCs) due to two hit mutations of the tumor suppressor gene, Tsc2. We previously identified using representational difference analysis (RDA), four genes that were expressed more abundantly in an Eker rat RC cell line than in normal kidney tissue. One gene, Erc (expressed in renal carcinoma) showed sequence homology to the mouse and human megakaryocyte potentiating factor (MPF)/mesothelin gene. The present study determines the full sequence of the cDNA and the exon-intron structure of the rat Erc gene and maps its locus in the chromosome by fluorescence in situ hybridization. Rat Erc and its human homologue were localized in chromosomes 10q12-21 and 16p13.3, respectively, both of which coincided with the locus of the Tsc2/TSC gene. We also found that Erc was expressed at higher levels in primary RCs compared with the normal kidney of the Eker rat. Erc may be related to carcinogenesis in the Tsc2 gene mutant (Eker) rat model.

Amino Acid Sequence↗

Direct immunization of malaria DNA vaccine into the liver by gene gun protects against lethal challenge of Plasmodium berghei sporozoite.

The liver is the first target organ for malaria parasites immediately after the bite of an infected mosquito. We studied local immunization of malaria DNA vaccines at the site of the liver using a gene gun as a useful tool for in vivo transfection of foreign genes. A malaria DNA vaccine consisting of the Plasmodium berghei circumsporozoite protein (PbCSP) gene plus the mouse IL-12 gene was bombarded directly by a gene gun into mouse liver once or into the skin twice. A marked protective effect was induced by gene bombardment into the liver (more than 71%) compared with that into the skin (less than 33%). A Th1-type immune response and high production of iNOS were observed in the hepatic lymphocytes from mice bombarded into the liver, resulting in more effective protection compared with those bombarded into the skin. These results provide an important implication on the development of efficient malaria vaccine strategies.

Amino Acid Sequence↗

Changes of lead levels in 24-h urine from 1985 to 1998 in Japanese adults.

To determine whether current environmental lead (Pb) levels are causing any progressive changes in urinary Pb levels, 24-h urine samples were collected from 277 subjects (159 men and 118 women) in 1985, 312 subjects (155 men and 157 women) in 1993, and 311 subjects (156 men and 155 women) in 1998. All of the subjects worked in the same factory. The urinary Pb concentration was analyzed by flameless atomic absorption spectrophotometry. The geometric means for men were 4.74, 2.67 and 1.31 microg/day; 3.17, 1.78 and 1.04 microg/g creatinine; and 3.18, 1.99 and 0.98 microg/l urine in 1985, 1993 and 1998, respectively. The values for women were 3.22, 2.14 and 0.97 microg/day; 3.35, 2.26 and 1.15 microg/g creatinine; and 2.49, 1.86 and 0.83 microg/l urine, respectively. These results demonstrated that Pb levels in 24-h urine decreased significantly in the 13-year period (P<0.01).

Adult↗

Analysis of all exons of TSC1 and TSC2 genes for germline mutations in Japanese patients with tuberous sclerosis: report of 10 mutations.

Twenty-seven Japanese patients with the tuberous sclerosis complex (TSC), consisting of 23 sporadic and 4 familial cases, were tested for mutations in the TSC1 and TSC2 genes, using single-strand conformational polymorphism analysis and direct sequencing. Four possible pathogenic mutations were found in the TSC1 gene, including three frame shifts and a nonsense mutation in a familial case. All mutations were expected to result in a truncated hamartin gene product. The TSC2 gene analysis identified six possible pathogenic mutations only in the sporadic cases, including two frame shifts, one in-frame deletion, and three missense mutations. Two of the TSC2 mutations were expected to result in a truncated tuberin gene product. These results of the Japanese TSC patients were compatible with the reports from Europe and the United States, i.e., (1) TSC1 mutations are rarer in sporadic cases than in familial cases, (2) substantial numbers of sporadic cases arise from mutations in the TSC2 gene, and (3) mutations of the TSC1 gene may cause premature truncation of hamartin.

Adolescent↗

Renal effects of cadmium exposure in cadmium nonpolluted areas in Japan.

Long-term exposure to cadmium (Cd) causes renal damage in the general population. The maximum allowable urinary Cd concentration, which was calculated from our previous study performed in a Cd-polluted area, was almost the same as the mean urinary Cd concentration of people living in nonpolluted areas. We assessed whether environmental Cd exposure is related to renal dysfunction of people in nonpolluted areas in Japan. Blood and urine samples were collected from 2753 subjects (1105 men and 1648 women) ages over 50 years old in three nonpolluted areas. Blood was analyzed for Cd and urine was analyzed for Cd, total protein, beta(2)-microglobulin (beta(2)-mg), and N-acetyl-beta-D-glucosaminidase (NAG). Cd in blood or urine was employed as indicators of internal dose; and urinary total protein, beta(2)-mg, and NAG were used as an indicator of renal dysfunction. Multiple regression analysis and logistic regression analysis were performed to clarify the dose-effect and dose-response relationship between blood or urinary Cd concentration and indicators of renal dysfunction. Multiple regression analysis demonstrated a significant dose-effect relationship between Cd in blood and urine and indicators of renal dysfunction. Logistic regression analysis also showed that the probability that individual subjects would have abnormal values of the renal variables was significantly related to Cd in blood and urine.

Acetylglucosaminidase↗

Interhemispheric subdural hematoma caused by a ruptured internal carotid artery aneurysm: case report.

BACKGROUND: Interhemispheric subdural hematoma (ISH) usually occurs after head trauma; nontraumatic ISH is extremely rare. CASE DESCRIPTION: The authors describe a 62-year-old male presenting with severe headache and ptosis on the left side. Computed tomography (CT) and magnetic resonance imaging disclosed a hematoma in the interhemispheric subdural space without subarachnoid hemorrhage. Cerebral angiography revealed an aneurysm arising from the left internal carotid-posterior communicating artery (IC-PC) junction. The patient underwent emergency clipping of the aneurysm and was discharged without neurological deficit. CONCLUSION: Ruptured aneurysms resulting in ISH without subarachnoid hemorrhage have been reported in only a few cases; this is the second case to describe the association of a ruptured IC-PC aneurysm with an ISH. The etiology of ISH formation due to ruptured aneurysms and the diagnosis are discussed.

Aneurysm, Ruptured↗

Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole compounds bearing beta-(5',6',7'-trimethoxy-2'-indolyl)acryloyl group.

A series of A-ring pyrrole derivatives of duocarmycin bearing beta-(5',6',7'-trimethoxy-2'-indolyl)acryloyl group were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. New Seg-B analogues bearing beta-(5',6',7'-trimethoxy-2'-indolyl)acryloyl group containing double bond as spacer had lower peripheral blood toxicity than the derivatives bearing 5',6',7'-trimethoxyindole-2'-carboxyl group in Seg-B of the natural type. Moreover, most of them exhibited potent antitumor activity against in vivo murine tumor models.

Animals↗

Synthesis and antitumor activity of duocarmycin derivatives: modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups.

A series of the 8-O-substituted A-ring pyrrole derivatives of duocarmycin bearing the simplified DNA-binding moieties such as cinnamoyl or heteroarylacryloyl groups were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. In addition, the stability of the 8-O-substituted analogues in aqueous solution and the conversion to their active form (cyclopropane compound) from the 8-O-substituted analogues in mice or human serum were examined. The 8-O-substituted A-ring pyrrole derivatives bearing the simplified DNA-binding moieties showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the 8-O-substituted A-ring pyrrole derivatives having the trimethoxyindole skeleton in segment-B (Seg-B), which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates and 4'-methoxy-beta-heteroarylacrylates. Moreover, among 8-O-substituted analogues, several compounds can be chemically or enzymatically converted to their active form in human serum. This result indicated that new 8-O-substituted derivatives were different prodrugs from KW-2189 and 8-O-substituted analogues being the same type of prodrug as KW-2189.

Animals↗

Stress transmission through Ti-Ni alloy, titanium and stainless steel in impact compression test.

Impact stress transmission of Ti-Ni alloy was evaluated for biomedical stress shielding. Transformation temperatures of the alloy were investigated by means of DSC. An impact compression test was carried out with use of split-Hopkinson pressure-bar technique with cylindrical specimens of Ti-Ni alloy, titanium and stainless steel. As a result, the transmitted pulse through Ti-Ni alloy was considerably depressed as compared with those through titanium and stainless steel. The initial stress reduction was large through Ti-Ni alloy and titanium, but the stress reduction through Ti-Ni alloy was more continuous than titanium. The maximum value in the stress difference between incident and transmitted pulses through Ti-Ni alloy or titanium was higher than that through stainless steel, while the stress reduction in the maximum stress through Ti-Ni alloy was statistically larger than that through titanium or stainless steel. Ti-Ni alloy transmitted less impact stress than titanium or stainless steel, which suggested that the loading stress to adjacent tissues could be decreased with use of Ti-Ni alloy as a component material in an implant system.

Journal Article↗

Quantitative trait loci (QTL) analysis in a Meishan x Göttingen cross population.

In order to locate the genetic regions in the swine genome that are responsible for economically important traits, a resource population has been constructed by mating two female Meishan pigs with a male Göttingen miniature pig. In subsequent generations, 265 F2 offspring were produced from two F1 males and 19 F1 females. The F2 offspring were scored for eight traits including growth rate, teat number, vertebra number and backfat thickness, and genotyped for 318 genetic markers spanning the swine genome. Least-square analysis revealed quantitative trait loci (QTL) effects for vertebra number on chromosomes 1 and 2; for teat number on chromosomes 1 and 7; for birth weight on chromosome 1; for average daily gain between 4 and 13 weeks of age on chromosomes 9 and 10; for backfat thickness on chromosome 7; and for backskin thickness on chromosome 3.

Animals↗

Enhanced responsiveness of circulatory neutrophils after cardiopulmonary bypass: increased aggregability and superoxide producing capacity.

Cardiac surgery with cardiopulmonary bypass (CPB) induces a whole body inflammatory response that sometimes leads to postoperative organ dysfunction, and neutrophil activation plays an important role in this reaction. Neutrophil priming has been described as a change in neutrophil status such that neutrophils show enhanced responsiveness to a second activating stimulus. We hypothesized that neutrophil priming occurs by cardiac surgery with CPB and is temporally related to the neutrophilia after surgery. To evaluate primed circulatory neutrophil status, we measured aggregation activity stimulated by N-formyl-methyl-leucyl-phenyl-alanine (FMLP) and free radical producing activity by tumor necrosing factor (TNF) alpha in peripheral blood samples. Eleven adult patients undergoing elective cardiac surgery with CPB were studied. Blood samples were taken before surgery, at the end of bypass, 12 h after surgery, and 7 days after surgery. Aggregation activity and superoxide generation were significantly elevated 12 h after surgery when compared to presurgery values, indicating that cardiac surgery is associated with circulatory neutrophil priming. The number of neutrophils markedly increased at the end of cardiopulmonary bypass and reached a peak 12 h after surgery. The circulatory neutrophils of cardiac surgical patients become primed after surgery, coincident with the peak neutrophil count. These results suggest that circulatory neutrophils after cardiac surgery with CPB have enhanced responsiveness and are predisposed to systemic inflammation.

Adult↗

Hepatic lymphocyte transplantation in hyperbilirubinemic gunn rats.

Hepatic lymphomyeloid cells (HLCs) are thought to contain liver stem cells. We investigated whether HLCs generated enzyme-producing cells in vivo. HLCs from normal Wistar/Shi rats and rats in which liver ischemia was induced using a portal clamp 4 days previously were studied histopathologically and characterized using flow cytometry. Splenic lymphocytes obtained from these animals were compared as a control. The proliferative activity of HLCs and splenic cells from both groups was also tested by stimulation with concanavalin A. HLCs contained a significantly higher number of NK-T cells and OV6+ cells compared with the splenic cells. The HLCs from rats in which liver ischemia was induced tended to have greater proliferative activity than those from normal rats, while the proliferative activity of splenic lymphocytes was impaired by liver ischemia. The HLCs obtained from Wistar/Shi rats with liver ischemia were then injected into hereditary hyperbilirubinemic Gunn rats to determine whether the HLCs generated enzyme-producing cells. After injection of these stimulated HLCs, the titer of serum bilirubin in the recipient rats was markedly reduced over a long time course (6.80+/-0.93 to 4.87+/-0.22 mg/dl after 1 month and 3.52+/-1.33 mg/dl after 6 months). The results of the present study indicate that HLCs have different populations than splenic cells, and ischemia-reperfusion of the liver increased their proliferative activity. HLC transplantation successfully reduced high bilirubin levels over a long time course.

Animals↗