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Biomedical subjects

K Isobe

Publications and source records attributed to K Isobe.

At least 127 records · Page 7Linked to original sources
PubMed1997

Radiotherapy for centrally recurrent cervical cancer of the vaginal stump following hysterectomy.

PURPOSE: This study was performed to establish the classification and the treatment modality for recurrent cervical cancer of the vaginal stump after hysterectomy. PATIENTS AND METHODS: Ninety patients with centrally recurrent cervical cancer of the vaginal stump following hysterectomy were treated with high-dose-rate intracavitary brachytherapy with or without external irradiation. The intervals between primary surgery and vaginal recurrences varied from 3 months to 36 years. Tumor size of the vaginal stump was determined by bimanual rectovaginal examination at the time of recurrence and was classified into three groups, i.e., small (no palpable tumor), medium (less than 3 cm), and large (3 cm or more). RESULTS: The 10-year survival rates for all patients were 52%. Survival was greatly influenced by the tumor sizes of the vaginal stump. The 10-year survival rates of patients with small, medium, and large size tumors were 72, 48, and 0%, respectively. All patients with large size tumors died within 5 years. Of 90 patients, 75 (83%) were determined by physical examination to be free of tumor on at least one visit within 2 months of the completion of treatment (CR). The remaining 15 patients (17%) had physical findings suggestive of residual tumor (Residual). The overall 10-year survival rate for all patients with CR was 63%, compared with 10% for the patients with Residual (P < 0.0001). The incidences of distant metastases of the patients with or without local failure were 55 and 13%, respectively (P < 0.0001). The patients with local failure had significantly higher incidence of metastases. Most patients with small size tumor were treated with brachytherapy alone, and the survival rates of these patients were not improved by combination with external irradiation. CONCLUSION: These results suggest that tumor size was a significant prognostic factor for recurrent cervical cancer of the vaginal stump. Patients with small size tumors were recommended to be treated with brachytherapy alone.

Adult↗
PubMed1997

The immunosuppressive effect of fresh allogeneic bone graft in mice.

We investigated the immunosuppressive effect of fresh bone allografts after donor specific spleen cell transfusion in mice. Allografts from major histocompatibility complex incompatible mice were performed one week after the transfusion. Cellular and humoral immune responses were recorded by measuring alloreactive cytotoxic T-lymphocyte activity and antibody activity. Survival in days of a second set skin graft was measured for determining clinical immunity. Alloreactive cytotoxic T-lymphocyte activity was stimulated at 17 days (10 days after bone grafting) and then suppressed at 31 days (24 days after bone grafting). The survival of the second set skin graft was not diminished at this time. This outcome indicates that the spleen cell stimulated cellular immune response was suppressed after fresh bone allografts, suggesting that these allografts have an immunosuppressive effect and induce immunosuppressive actions.

Animals↗
PubMed1997

Types of organic solvents used in small- to medium-scale industries in Japan; a nationwide field survey.

OBJECTIVE: The aim of the present survey is to identify organic solvents commonly used in various workplaces in Japan. METHODS: A total of 24 occupational health service institutions (OHSI) distributed nationwide in Japan offered data on types of solvent workplaces, types of solvents used therein, and the solvent concentrations surveyed in a 2-month period between April and May 1996 to form a data base (OHSI data base, consisting of 1597 cases). Separately, Kyoto Industrial Health Association (KIHA) offered information on 948 cases studied during a 1-year period ranging from April 1995 to March 1996 (KIHA data base). The two data bases were treated in parallel to examine the reproducibility of the results. RESULTS: Detection prevalence was very low (0-1%) for almost half of the 47 legally regulated solvents. Among the solvents in use, toluene was most frequently detected, although the prevalence appeared to be reduced as compared with that recorded for the early 1980s. The most frequently observed solvent combinations comprised toluene, xylenes, and ethyl acetate in the OHSI data base and toluene, xylenes, and methanol in the KIHA data base. Contrary to the case in the 1980s, dichloromethane was used more often than trichloroethylene as a degreasing agent in the present survey. No use was detected for carbon tetrachloride, chloroform, 1,2-dichloroethane, 1,2-dichloroethylene, or 1,1,2,2-tetrachloroethane except for research purposes. CONCLUSIONS: Toluene remained the most common solvent and was used in combination with xylenes, ethyl acetate, and methanol. There was an increase in the use of dichloromethane as a degreasing agent.

Acetates↗
PubMed1997

Differential display analysis of murine collagen-induced arthritis: cloning of the cDNA-encoding murine ATPase inhibitor.

We used the differential display technique in order to detect a new gene involved in murine type II collagen-induced arthritis (CIA). In this study, we have identified a novel gene, IF1, whose expression level is increased during the natural course of CIA. Northern blot analyses suggest that IF1 is involved in the natural course of CIA but is not involved as a trigger of CIA. IF1 is considered to be the murine ATPase inhibitor gene for several reasons. First, IF1 shows an extremely high homology to the rat ATPase inhibitor; the highly conserved region between rat and bovine amino acid residues 22-45, which is the minimum sequence showing ATPase inhibitory activities, is also highly conserved in IF1. Second, IF1 possesses a histidine-rich region in the same area, which is thought to be important for regulation of mammalian inhibitors. Third, the tissue distribution of IF1 is very suggestive. The expression of IF1 was very strong in energetic organs such as the heart, brain and kidney, and the development of arthritis requires great amounts of ATP. As arthritis develops rapidly, the cellular ATP pool may be decreased. Before the ATP pool is exhausted, the ATPase inhibitor may serve as a brake for ATP hydrolysis. If the supply of free energy can be reduced, the inflammation of arthritis may in turn be restored. Our hypothesis is that the ATPase inhibitor is involved in regulating the inflammatory responses.

Amino Acid Sequence↗
PubMed1997

A strong association between HLA-B*5101 and Behçet's disease in Greek patients.

Behçet's disease is known to be associated with HLA-B51, one of the split antigens of HLA-B5, among many different ethnic groups. In a Greek population, an increased incidence of HLA-B5 in the patient group has also been reported. Because the B51 antigen has been recently identified to comprise seven alleles, B*5101-B*5107, we performed HLA-B51 allele genotyping by the PCR-SSP method as well as serological HLA-A and -B typing among 31 Greek patients with Behçet's disease to investigate whether there is any correlation between one particular B51-associated allele and Behçet's disease. The frequency of B51 was remarkably high (80.6%) in the patient group as compared to the ethnically matched control group (26.7%). In addition, HLA-A26 was also increased in the patients (29.0%) as compared with the healthy controls (3.3%). B51 allele genotyping revealed that all these B51-positive patients carried B*5101. This study revealed a strong association of Behçet's disease in Greeks with one of the B51 subantigens, providing insight into the molecular mechanism underlying an HLA association with Behçet's disease.

Behcet Syndrome↗
PubMed1997

Antiphospholipid syndrome complicated by thrombosis of the superior mesenteric artery, co-existence of smooth muscle hyperplasia.

A 37-year-old woman underwent an emergency operation at our hospital because of severe abdominal pain and ileus. Most of her small intestine and ascending colon were observed to have become necrotic due to occlusion of her superior mesenteric artery (SMA). Pathological findings of the resected intestine revealed that her SMA was completely thrombosed 2 cm distal from its origin with smooth muscle proliferation. Post-surgical blood analysis of her pre-operative serum was positive for lupus anticoagulant and antinuclear antibodies. She noticed vaginal bleeding due to missed abortion on the 31st day after the operation. We diagnosed her acute abdominal pain to be that of antiphospholipid syndrome associated with her pregnancy.

Abdominal Pain↗
PubMed1997

[Comparison of three methods for quantitative measurement of hepatitis C virus].

Three assays for measuring hepatitis C virus(HCV) were compared with regard to sensitivity and correlations. The methods included were the Roche Amplicor HCV Monitor test(PCR), the branched DNA signal amplification assay(b-probe), and the serum concentration of HCV core protein measured by the sandwich FEIA (Core-Ag). Also, HCV serotypes were determined by the enzyme-linked immunosorbent assay. Testing 105 consecutive HCV-RNA positive samples showed that the PCR was the most sensitive assay(100% quantifiable), followed by the Core-Ag(82.4%) and the b-probe(75.3%). The values obtained by each method correlated well in serotype 1, whereas some discordance was noted in serotype 2 cases. Also, serotype 2 samples were less quantifiable particularly by b-probe assay than serotype 1 samples. These points have to be considered in quantification of serum HCV levels by currently available these three methods.

Biomarkers↗
PubMed1996

Mutant mtDNA at 1555 A to G in 12S rRNA gene and hypersusceptibility of mitochondrial translation to streptomycin can be co-transferred to rho 0 HeLa cells.

Human skin fibroblast line 95-119, which had been isolated from the mother of a Japanese patient with aminoglycoside-induced deafness and a 1555 A to G mutation at 12S rRNA gene in mitochondrial DNA (mtDNA), was used to investigate the relationship between the 1555 mtDNA mutation and its pathogenicity. By the intercellular transfer of mtDNA with or without the 1555 mutation to mtDNA-less (rho 0) HeLa cells, we isolated cybrid clones and found that the mitochondrial translation in a cybrid clone repopulated with the homoplasmic 1555 mutation showed the highest susceptibility to streptomycin. These observations suggest that the genotype of the mutant mtDNA and the phenotype of hypersusceptibility to streptomycin observed in 95-119 fibroblasts were co-transferred simultaneously to rho 0 HeLa cells, supporting the idea that the homoplasmic 1555 mtDNA mutation is involved in the pathogenesis leading to aminoglycoside-induced hearing loss.

Aminoglycosides↗
PubMed1996

Entire hemithorax irradiation following complete resection in patients with stage II-III invasive thymoma.

PURPOSE: To evaluate the feasibility and efficacy of prophylactic entire hemithorax irradiation (EH) in addition to mediastinal irradiation (MRT) following a complete resection in Stage II-III invasive thymoma. METHODS AND MATERIALS: Forty-three patients with invasive thymoma treated with surgery and radiation therapy between 1978 and 1993 were analyzed retrospectively. All 43 patients underwent a complete surgical resection and were judged to have Masaoka's Stage II-III invasive thymoma. Of these, 23 patients received EH and MRT (EH-MRT) and the remaining 20 received MRT. Of the 23 patients with EH-MRT, 11 were Stage II and 12 Stage III. Of the 20 with MRT, 11 were Stage II and 9 Stage III. In most cases, EH was 15 Gy per 15 fractions over 3 weeks (without lung compensation calculation). In both the EH-MRT and MRT group, the total radiation doses to the mediastinum were similar with a median of 40 Gy. The median follow-up time after surgery was 63 months and no patients were lost to follow-up. RESULTS: Only one of the 23 patients with EH-MRT relapsed. On the other hand, eight of the 20 with MRT relapsed, six of whom died of disease. The pleura was the most common site of failure. At 5 years, the relapse-free rate was 100% for those receiving EH-MRT and 66% for those with MRT (p = 0.03); the overall survival rate was 96% for those with EH-MRT, and 74% for those with MRT (p: not significant). The only significant treatment-related complication was radiation pneumonitis requiring treatment, in one patient who received MRT and three who received EH-MRT, including one death of a 72-year-old man and one 68-year-old woman with severe lung fibrosis. CONCLUSION: Except for elderly patients, EH-MRT following a macroscopically complete resection appears to be safe and feasible, and can reduce intrathoracic relapses.

Adult↗
PubMed1996

Inhibitory effect of double transfection to xenoendothelial cells using both decay accelerating factor and homologous restriction factor 20 genes on complement dependent cytolysis.

Hyperacute rejection in discordant xenotransplantation occurs due to the complement activation via classical and/or alternative pathway. Regulator of complement activation (RCA) molecules inhibit species-specific complement dependent cytolysis. To confirm the effect of gene engineering using double RCA molecules on xenogeneic cells, the inhibitory effect on complement dependent cytolysis was compared between bovine aortic endothelial cells (BAEC) doubly transfected with both decay accelerating factor (DAF) and homologous restriction factor (HRF) 20 cDNA and BAEC singly transfected with DAF alone using retroviral vector. The positive percent expression of DAF and HRF20 antigen on double transfectant (BAEC/D+H) was 97.0% and 95.0%, respectively, whereas that of DAF antigen on single transfectant (BAEC/D) was 97.0%. After incubated with 25% human serum and anti-BAEC antibody, the viability of double transfectant (BAEC/ D+H) was significantly preserved, compared with that of single transfectant (BAEC/D). These findings demonstrated that xenoendothelial cells doubly transfected with both DAF and HRF20 cDNA could be protected from complement dependent cytolysis more effectively than those singly transfected with DAF alone in the presence of antixenoendothelial antibody.

Animals↗
PubMed1996

Nitric oxide releasing reagent, S-nitroso-N-acetylpenicillamine, enhances the expression of manganese superoxide dismutase mRNA in rat vascular smooth muscle cells.

Cultured rat vascular smooth muscle cells (VSMCs) produce nitric oxide (NO) under stimulation by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). NO synthase (NOS) and manganese superoxide dismutase (Mn-SOD) mRNA expressions are simultaneously induced by these stimulants in rat VSMCs. In VSMCs, S-nitroso-N-acetyl penicillamine (SNAP), one of the NO releasing reagents, induces Mn-SOD mRNA which may protect the VSMCs themselves. This suggests that NO itself may enhance the expression of Mn-SOD to protect the VSMC themselves against NO radicals in cultured rat VSMCs.

Animals↗
PubMed1996

Establishment of a human DAF/HRF20 double transgenic mouse line is not sufficient to suppress hyperacute rejection.

To solve the chronic donor organ shortage, the pig is considered to be a possible donor candidate for human transplantation. However, hyperacute rejection occurs due to the activation of the complement cascade. Therefore, the introduction of human complement inhibitors into animal cells has been proposed as a means to prevent such exologous complement activation. To investigate the extent to which complement inhibitors are resistant to human sera in discordant animals, we established transgenic mice lines which expressed either human decay-accelerating factor (DAF) and/or homologous restriction factor 20 (HRF20) using microinjection methods. Human sera were injected into (a) 10 control mice, (b) 10 DAF-transgenic mice, (c) 10 HRF20-transgenic mice, and (d) 10 DAF and HRF20-transgenic mice. The results showed that all the mice in groups a, b, and c died immediately after injection. Three of the mice in group d died, while seven survived but showed hyperpnea and low activity. The pathological findings of groups a, b, and c included severe coagulation; however, the survivors of group d showed less severe symptoms. The above findings thus suggest that both DAF and HRF20 tend to prevent complement activation to some extent; however, its effectiveness is not considered to be sufficient for clinical use in transplantation.

Animals↗
PubMed1996

Promotion of proliferation of murine hematopoietic stem cells by growth factors in murine amniotic fluid.

It has been shown that murine amniotic fluid (MAF) displays immunosuppressive activities. We examined the effect of MAF obtained from normal mice on a murine fetal liver cell (FLC) primary culture in vitro for the detection of the possible existence of cytokines that affect hematopoiesis. MAF promoted proliferation of murine FLC and adult bone marrow cells. Proliferation-promoting activity of MAF was observed throughout the period between days 12 and 15 of pregnancy, peaking at day 12. Pooled MAF was subjected to purification procedures to isolate the active molecule(s). After ion exchange and size exclusion chromatography, one of the active molecules was shown to react with anti-mouse stem cell growth factor (SCF) antibody and the molecular weight was determined as 40-45 kDa by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. The proliferation-promoting activity of MAF was partially neutralised by the anti-SCF antibody. These results provide evidence that MAF may contain multiple growth factors for FLC, one of which may be a unique molecule related to SCF.

Amniotic Fluid↗
PubMed1996

Pituitary adenylate cyclase-activating polypeptide induces gene expression of the catecholamine synthesizing enzymes, tyrosine hydroxylase and dopamine beta hydroxylase, through 3',5'-cyclic adenosine monophosphate- and protein kinase C-dependent mechanisms in cultured porcine adrenal medullary chromaffin cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP)i a potent stimulant of catecholamine secretion, increased catecholamine production in cultured porcine adrenal medullary chromaffin cells. PACAP induced dose-and time-dependent increases in mRNAs for the catecholamine synthesizing enzymes, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), with maximal 6- and 4-fold increases occurring at 8-16 h, respectively. The half-maximally and maximally effective PACAP concentrations for stimulation of TH and DBH gene expression were 0.5 and 3 nM, respectively. The TH protein level also showed an increase over the unstimulated basal level at 16-24 h in PACAP-stimulate cells. We previously demonstrated that PACAP activates both phospholipase C and adenylate cyclase in adrenal medullary cells. Addition of forskolin alone induced increases in mRNA expression of both TH and DBH. The phosphodiesterase inhibitor 3- isobutyl-1-methylxanthine potentiated the induction of TH and DBH mRNAs by PACAP. Addition of the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) also caused increases in TH and DBH mRNA levels. In protein kinase C-downregulated cells pretreated with PMA for 24 h, the stimulatory effect of PACAP on TH and DBH gene expression was diminished. These results suggest that cAMP and protein kinase C mediate the PACAP-induced TH and DBH gene expression. Removal of extracellular Ca2+ with EGTA enhanced the PACAP-induced increases in both cellular cAMP and mRNA levels of TH and DBH, suggesting that Ca2+ has an inhibitory effect on the induction of TH and DBH mRNAs. In conclusion, the present study indicates that PACAP coordinately upregulates the gene expression of both TH and DBH by activating the cAMP and protein kinase C signaling pathways, leading to simulation of cate-cholamine synthesis, while Ca2+ negatively regulates TH and DBH gene expression in porcine adrenal medullary cells.

Adrenal Medulla↗
PubMed1996

Characterization of the growth factor activity of amniotic fluid on cells from hematopoietic and lymphoid organs of different life stages.

We investigated the proliferation-promoting effects of murine amniotic fluid (MAF) on in vitro cultured cells originally obtained from murine hematopoietic and lymphoid organs at different life stages. MAF promoted proliferation of the fetal liver cells (FLC), newborn spleen cells and adult bone marrow cells. The proliferation-promoting activity of MAF was extended to liver cells and spleen cells from mice younger than 2 weeks old. MAF did not, however, promote the proliferation of newborn or adult thymocytes, or of spleen cells, liver cells or peritoneal cells, liver cells or peritoneal cells from 2-week-old or older mice. Rather, it partially inhibited the proliferation of spleen cells, thymocytes and peritoneal cells from 1-year-old mice. These results suggest that MAF contains growth factors for hematopoietic stem cells but not for either mature or immature T lymphocytes. Supporting this view, the MAF activity was partially neutralized by a polyclonal anti-mouse stem cell factor (SCF) antibody. Moreover, the immunoblotting of MAF against anti-mouse SCF antibody revealed a band at 30-32 kDa corresponding to the previously reported SCF. Interestingly, MAF was able to maintain FLC and adult bone marrow cells alive in culture for a relatively long time (2 weeks). The MAF activity was further shown to be partially and cell type-dependently antagonized by TNF-alpha and TGF-beta. These results provided evidence that MAF contains potentially multiple growth factors preferentially affecting the early stage of hematopoiesis, one of which is SCF.

Age Factors↗
PubMed1996

Cerebral energy metabolism in insulin induced hypoglycemia in newborn piglets: in vivo 31P-nuclear magnetic resonance spectroscopy.

The effect of insulin induced hypoglycemia on cerebral energy metabolism was examined in four newborn piglets. Cerebral energy metabolism was assessed using in vivo 31P-nuclear magnetic resonance spectroscopy. It was demonstrated that the normal level of phosphocreatine/inorganic phosphate (PCr/Pi), an indicator of phosphorylation potential, was maintained at a blood glucose level of 40 mg/dL or above, whereas when blood glucose was reduced to less than 40 mg/dL, PCr/Pi rapidly decreased in parallel with this. Below the critical blood glucose level of 40 mg/dL, a positive correlation (y = 0.02x + 0.632; r = 0.668; P < 0.001) existed between blood glucose and PCr/Pi. In the present investigation, a reduction of blood glucose level to 20 mg/dL or lower resulted in a PCr/Pi of less than 1, indicating a state of cerebral energy failure. The intracellular pH (pHi) was 7.08 +/- 0.05 at the onset and 7.15 +/- 0.07 in the hypoglycemic state, indicating no significant difference between the two groups. The present study has clarified that cerebral energy failure occurs when the blood glucose level is about 20 mg/dL or lower. The critical point of blood glucose exists to maintain brain energy metabolism.

Animals↗