Biomedical subjects
Publications and source records attributed to K Kawano.
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The refolded products of reduced native lysozyme and reduced OX62 lysozyme, in which Trp62 is converted to oxindolealanine (OX62) during the renaturation of sulfhydryl-disulfide interchange reactions at pH 8 and 37 degrees C, were investigated. On gel-chromatography eluted with 10% aqueous acetic acid containing 4 M urea, two peaks appeared in the refolded product of reduced OX62 lysozyme while a single peak appeared in the refolded product of reduced native lysozyme. From the analyses of the activity and primary and the tertiary structures of the derivative, the structure of the derivative from reduced native lysozyme was confirmed to be identical to that of the untreated one. On the other hand, the refolded product from reduced OX62 lysozyme had the same primary structure but a different tertiary structure compared to the untreated one. The tertiary structure of the refolded product from the reduced OX62 lysozyme was changed to that of the untreated one by the denaturation-renaturation treatment under nonreduced conditions. However, the refolded species was barely changed to that of the untreated one by incubation under physiological conditions. Therefore, the refolded product from reduced OX62 lysozyme was suggested to be a metastable and kinetically trapped product in the renaturation process of reduced OX62 lysozyme. In addition, an interaction involving the folding process of reduced lysozyme was discussed on the basis of the NMR analyses of the metastable structure.
The expression of P-selectin was more upregulated following the exposure to nonionic low osmolar contrast agents than to ionic contrast agents. Exposure to nonionic contrast agents led to a marked adhesion of leukocytes to endothelial cells. Thrombomodulin activity of endothelial cells was decreased, and plasminogen activator inhibitor-1 (PAI-1) and tumor necrosis factor (TNF) alpha in the supernatant were increased when leukocyte adhesion occurred after exposure to nonionic contrast agents. Results suggest that the adhesion of leukocytes to the endothelium increases procoagulant activity.
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The differentiation of PC12 cells to a neuron-like morphology was induced by ionizing radiation in the presence of serum. This effect was detectable at 5 grays (Gy) and reached a maximum at 10-20 Gy. Increases in the DNA binding activity of nuclear factor kappa B (NF-kappa B) and increased Interleukin 6 (IL-6) mRNA levels were observed at a dose of 15 Gy. Neutralization of supernatant IL-6 by the addition of anti-IL-6 antibody inhibited the neuronal differentiation and decreased cellular redox. Ionizing radiation and serum may act synergistically as neurotropic factors.
The hemodynamic alterations in hepatic microvasculature during acute rejection of rat liver allografts was studied using in vivo fluorescence microscopy. ACI rat livers were transplanted into Lewis (allograft) or ACI (isograft) recipients. Microscopy was performed on days 3 (n = 7) and 6 (n = 7) in allografts, and on day 6 (n = 7) in isografts. Naive ACI livers (n = 7) served as nontransplant controls. Changes in sinusoidal blood perfusion, microvascular structure, and leukocyte-endothelial interactions were observed and quantitated. Six days after transplantation, acinar perfusion was markedly impaired in allografts and was accompanied by a lower percentage of perfused sinusoids (59 +/- 8%, mean +/- SEM, P < 0.01) relative to isografts (89 +/- 3%) and nontransplant controls (100 +/- 0%). The hepatic cord width in allografts was significantly greater than in isografts or in nontransplant controls, indicating swelling of parenchymal and sinusoidal lining cells. Furthermore, the number of leukocytes adhering to the sinusoidal endothelium significantly increased in allografts. Adherence to postsinusoidal venules was more prominent in allograft livers (4025 +/- 1400/mm2 of vascular endothelial surface) compared with that in isografts (574 +/- 77/mm2) and nontransplant controls (185 +/- 28/mm2). These microcirculatory alterations in allografts were significant even on day 3. The results show extensive abnormalities of the microcirculatory hemodynamics in rejecting liver allografts which were associated with increased leukocyte adherence to microvascular endothelium. Our findings may provide strategic information for the prevention and treatment of allograft rejection.
The pharmacological profile of a new surmountable angiotensin AT1 receptor antagonist, ME3221, 3-methoxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4- yl]methoxy]pyridine, was studied in several animal models, and was compared with that of losartan. EF2831, 3-hydroxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4- yl]methoxy]pyridine, a metabolite of ME3221, is also a surmountable angiotensin AT1 receptor antagonist, whose potency was 1/30 that of ME3221 in vitro, but equal to or 1/3 of that of ME3221 in in vivo experiments. In rats and marmosets, ME3221 antagonized angiotensin II-induced pressor responses, but did not affect bradykinin-induced depressor responses. ME3221 lowered the blood pressure in renal hypertensive rats and spontaneously hypertensive rats (SHR), and its ED25 value was 3 times that of losartan. Repeated administration of ME3221 to SHR had a stable and long-lasting antihypertensive effect without influencing heart rate. Thus ME3221, like losartan, may be useful in the treatment of renal and essential hypertension.
BACKGROUND: Granuloma induced by silicone plate is rare. We present a case of silicone plate-induced granuloma in the sellar and suprasellar region confirmed by histologic examination at surgery. CASE DESCRIPTION: A 31-year-old woman suddenly complained of severe headache, polyuria, and visual disturbance 8 years and 9 months after an initial transsphenoidal surgery for pituitary adenoma. At surgery, granuloma and hematoma around the dimethylpolysiloxan (silicone) plate, which had been placed on the sella floor at the initial surgery, were found. Postoperative course was uneventful. CONCLUSIONS: Our presented case showed one of the disadvantages for silicone placement for repairing the sella floor, and the diagnostic possibility of silicone-induced granuloma in the sellar region.
The Otsuka Long-Evans Tokushima Fatty (OLETF) rat develops hyperglycemia, hyperinsulinemia and mild obesity, features that closely resemble those in human non-insulin-dependent diabetes mellitus (NIDDM). Here, we report a gene involved in the development of diabetes in OLETF rats. Segregation studies using OLETF and an unrelated strain, F344 showed that no diabetes was observed in F1 progeny and less than 12.5% of the F2 progeny developed diabetes, suggesting that multiple recessive genes are involved in the disease. Interestingly, diabetes was observed in approximately 40% of (OLETF female x LETO male) F1 male rats, whereas less than 4% of males were diabetic in the reverse F1 mating. This suggested that the LETO rat which has been established from the same original colony as the OLETF rat shares some, but not all, diabetogenic genes with the OLETF, and that one of the responsible genes locates on the X-chromosome. Linkage study using (OLETF female x F344 male)F2 progeny has confirmed that one of the diabetogenic loci in the OLETF rats locates on the X-chromosome 14 cM distant from the AR gene (LOD = 2.598) and has been designated as ODB-1.
Five high molecular weight glycolipids capable of stimulating human peripheral whole-blood cell cultures to cause interleukin 6 (IL-6) and tumor necrosis factor (TNF)-alpha induction were isolated from one of the lipoteichoic acid fractions (LTA-2) extracted from Enterococcus hirae ATCC 9790 (Tsutsui et al., (1991) FEMS Microbiol. Immunol. 76, 211-218) by a combination of hydrophobic interaction and anion-exchange chromatographies. This purification procedure resulted in a remarkable increase in the cytokine-inducing activities on the weight basis of isolated glycolipids (a maximum of 36- and 17-fold increases of IL-6 and TNF-alpha induction, respectively). The total yield of these bioactive glycolipids amounted to 6 wt% of the parent LTA-2 fraction, while the recovery rate in terms of the cytokine-inducing activities was estimated to be sufficient. The chemical composition and the profile, using SDS-PAGE, revealed that all of the isolated bioactive components were high molecular weight glycolipids, which were distinct from each other and from the parent LTA-2 fraction. These findings suggest that the IL-6 and TNF-alpha-inducing activities previously noted in the parent LTA-2 fraction are not attributable to a chemical entity, the structure of which had been proposed elsewhere (Fischer, W. (1990) in Glycolipids, Phosphoglycolipids and Sulfoglycolipids (Kates, M. ed.) pp. 123-234, Plenum Press, New York), but to the other high molecular weight glycolipids described here.
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A 42-year-old female presented with recurrent primary central nervous system lymphoma mimicking the roentgenographic appearance of diffuse brain degeneration. Betamethazone was administered, but her condition worsened. Biopsy of a swollen neck lymph node demonstrated lymphoma cells. Computed tomography and magnetic resonance (MR) imaging showed no contrast-enhanced lesions. T2-weighted MR imaging revealed diffuse, high intensity areas in the white matter of the bilateral cerebrum, basal ganglia, and brainstem. Despite chemotherapy for systemic lymphoma, she died of respiratory arrest. Histological examination of autopsy specimens showed diffuse infiltration of lymphoma cells in the perivascular space of the cerebral cortex, but little neovascularization. The absence of contrast enhancement may have been due to preservation of the blood-brain barrier. Histological confirmation of roentgenographic findings of brain degeneration is important in patients treated for primary central nervous system lymphoma.
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Seventy-five surgically treated patients with hepatocellular carcinoma (HCC) of Stage III or IV-A were divided into two groups: group I, control without postoperative adjuvant infusion (PAI); group II, patients treated with PAI. In the PAI group, 29 patients (mean diameter of tumors = 71 mm) prophylactically underwent PAI after hepatic resection. Chemotherapeutic agents, (5-FU, ADM, MMC, CDDP and Lipiodol) were administered 4 times a year via the hepatic artery through Infuse A port. The remaining 46 patients (mean diameter of tumors = 70 mm) served as the historical control without PAI. The 4-year cumulative survival rate was higher in the PAI group (45.6%) than in the control (25.4%, p = 0.0424). The 4-year disease-free survival rate was also improved in the PAI group (37.0%) compared with that in the control (14.4%, p = 0.0096). Intrahepatic multiple recurrence was recognized in 8 out of 29 patients in the PAI group (28%) and in 24 out of 46 in the control (53%, p = 0.036) within 1 year after surgery. Extrahepatic recurrence without diseases in the remnant liver tended to occur with higher frequency in the PAI group than in the control. Based on our data, we suggest that PAI is effective in alleviating intrahepatic multiple recurrence within 1 year after hepatic resection for advanced HCC and that systemic chemotherapy may be necessary for preventing extrahepatic recurrence.
FUT-187 was orally administered to 38 patients with postgastrectomy reflux esophagitis for 4 weeks. The drug reduced the chief subjective symptoms of reflux esophagitis, such as heartburn, chest pain, precordial pain, and dysphagia for solids in 78.1% of patients. Redness, edema and erosion were also reduced in 53.3% of patients as determined endoscopically. Overall, FUT-187 exhibited an excellent therapeutic effect on the reflux esophagitis which was refractory to conventional treatments.