Biomedical subjects
Publications and source records attributed to M Ueno.
A novel RNA component with oxidoreductase activity (diaphorase activity) has been purified from an RNA fraction of Torula yeast. The RNA component was obtained in a 0.05% yield by a series of steps, SDS-phenol extraction, nuclease P1 digestion, alkaline phosphatase digestion, anion exchange chromatography, and HPLC on an ODS-column.
The number of lymphocytes (especially T-lymphocytes) in peripheral blood decreases with aging. The decline is most evident in the thymus. In this study, total AN in the thymocytes of aged mice clearly decreases from that of young mice. The quantity of thymic hormones secreted by thymic cells decreases with the organism's thymus involution with age. After demonstrating the decrease in total AN (primarily ATP) levels within the thymocytes of aged mice, we attempted to reattain the levels of younger thymocytes by the administration of various thymic hormones. Examination of DNA in the thymocytes of 4 and 58-week-old mice, using flowcytometry, showed no differences in content. However, it is significant that aged mouse thymocytes's energy level can be returned to those of young mice with the application of Th-5.
The authors report an adult patient with an asymptomatic interhemispheric cyst demonstrated by computerized tomography (CT), magnetic resonance imaging (MRI) scan and angiography. Partial agenesis of the corpus callosum is associated.
58-year-old male with bladder cancer complicated acute myocardial infarction (aMI) were treated by 5-FU 300 mg/day orally for approximately one and a half months as single drug chemotherapy preoperatively. CT studies showed PR in bladder lesion and an improvement of bilateral hydronephrosis also. Biochemical evaluations as Thymidylate synthase inhibition and FdUMP were made on biopsy and operative specimens of urinary bladder. Clinical trials with 5-FU oral administration in bladder cancer were not held widely. Although its effectiveness and safety has been accepted in several fields. It was useful for a conservative operation case as single drug chemotherapy.
This study was performed in order to elucidate the mechanisms of systemic endotoxemia in liver cirrhosis. For this purpose, the method of measuring biliary endotoxin was established. Endotoxin levels between in the bile and in the plasma in cirrhosis were compared using a modified method of chromogenic quantitative endotoxin assay in an attempt to clarify liver function of clearing portal endotoxin originated from the gut. And functional activities of the reticuloendothelial system were also examined by radioassay with 59Fe-labelled iron-chondroitin sulfate colloid and by enzymohistochemistry of acid phosphatase. Both the plasma and biliary endotoxin levels in liver cirrhosis were significantly higher, compared to those in control. The functional activities of the reticuloendothelial system, particularly of the Kupffer cells, were decreased in liver cirrhosis. These data provide evidence that in liver cirrhosis systemic endotoxemia is mainly due to a decrease of functional activities of Kupffer cells. On the other hand, the excretion of endotoxin into the bile is increased, compensating the decreased functional activities of Kupffer cells. This implies that the uptake of endotoxin and its excretion into the bile by hepatocytes might be one of the mechanisms of clearing excess endotoxin in the plasma in liver cirrhosis. This study also draws the importance of measurements of endotoxin levels in the bile in liver diseases.
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We have used recombinant human erythropoietin (rEPO) in order to prevent patients from developing anemia following preoperative autologous blood preservation. Thereby, we have been able to reduce intraoperative homologous blood transfusion during cardiac operations. In June and July, 1989, six middle-aged selective patients received rEPO (200 IU/kg) intravenously every other day starting from fifteen days before the day of their operations. One unit (200 ml) of autologous blood was drawn and preserved every few days. However, no significant differences were observed in red cell counts, hematocrit, hemoglobin and serum protein levels between before and after preservation. Not only preoperative autologous blood preservation with provision of rEPO, but also using the intraoperative autotransfusion system enabled us to perform cardiac operations on 5 out of 6 patients without any homologous blood transfusion. None of the six patients exhibited any undesirable effects due to rEPO administration. Their postoperative courses were excellent.
The therapeutic result by tumorous site were evaluated in 76 cases of carcinoma of the colon and rectum with the confirmed presence of metastasis to the peri-aortic lymph nodes. The results revealed that significant good out-comes were noted in the relatively non-curative cases of carcinoma of the sigmoid colon, with particularly good prognosis being found in six cases with skip metastasis. There was a 26.1% (6/23) incidence of the skip metastasis in carcinoma of the sigmoid colon with the peri-aortic lymph nodes metastasis. We confirmed two lymphatic routes of the skip metastasis; one route was from the lymph nodes near the tumor to the para-aortic lymph nodes directly, and the other was from the lymph nodes near the tumor to the lymph nodes at the aortic diffract directly and finally to the para-aortic lymph nodes. In the all six cases, the peri-aortic lymph nodes metastasis occurred only in inferior site of the inferior mesenteric artery. The average number of the peri-aortic lymph nodes metastasis were as few as 1.7 in these cases. The prognosis was favorable with three of the six cases scoring a three-year survival and included a five-year survival case.
The partition equilibrium of an nonionic detergent, octyl glucoside, between the membrane phase and water and the effect of the detergent on the barrier efficiency of the vesicle membrane were studied. When the detergent concentration was lower than 4 mM in the water phase, or a mole fraction of 0.3 in the membrane phase, the partition coefficient of the detergent was independent of the detergent concentration and was 75 M-1. This value was about twice the value predicted from the critical micelle concentration. In this concentration region, the permeability of Cl- was relatively low [(2-5) x 10(-10) cm/s]. When the detergent in the membrane phase exceeded a mole fraction of 0.3, the apparent partition coefficient decreased, and the permeability of Cl- abruptly increased. These observations are explained by the following model: If the effective cross-sectional areas of phospholipid molecules and detergent molecules are similar to each other, a detergent molecule in the membrane phase will be surrounded only by phospholipid molecules as long as the mole fraction of the detergent in the membrane phase is below 0.3, and in this condition, the membrane barrier efficiency is high. At a mole fraction higher than 0.3, the detergent molecules come into contact with each other, and the membrane barrier efficiency decreases.
In a morphometric study, we investigated histopathologic changes in the ciliary body and retinal pigment epithelium in eyes with secondary glaucoma. Eyes with malignant melanoma served as controls. The mean thicknesses of the ciliary muscle and inner connective-tissue layer of the pars plicata were significantly lower (P less than 0.001) in glaucomatous than in melanomatous eyes, as was the mean width of the stromata of ciliary processes (P less than 0.001). With increasing age, the ciliary muscle in melanomatous eyes became significantly thinner (P less than 0.001). The width of the stroma at the base of the ciliary process was significantly correlated with the thickness of the inner connective-tissue layer of the pars plicata in both groups of eyes (P less than 0.001). The mean number of ciliary processes was significantly lower in glaucomatous than in melanomatous eyes (P less than 0.001), as was the mean height of pigment epithelial cells in the midperipheral retina P less than 0.05). The present study revealed quantitative glaucomatous tissue changes in the ciliary body and retinal pigment epithelium.
Immunologic and antitumor effects of human recombinant interleukin-2 was studied in patients with advanced renal cell carcinoma. Intravenous drip infusion for inpatients or subsequent subcutaneous injection for outpatients at a daily dose of 1 x 10(6) units of interleukin-2 was given over a period varying from twenty-one to two hundred forty days to 13 patients. Natural killer cell activity increased 20 percent or more in 11 of the 13 patients, and lymphokine-activated killer cell activity increased 40 percent or more in 9 of the patients tested. Interleukin-2-receptor positive cells and HLA-DR positive cells in peripheral blood lymphocytes increased in 12 and 11 patients, respectively. Two patients achieved complete response; 1 had a partial response; 6 had no change; and 2 had progressive disease. Two patients were not evaluated because the therapy had been discontinued in less than four weeks. We conclude that low-dose interleukin-2 enhances patients' immunity and has a potential antitumor activity against renal cell carcinoma.
The difference spectra obtained upon the addition of nucleotides to bovine kidney RNase, which shows 40% sequence homology with bovine pancreatic RNase, are markedly different from those of bovine pancreatic RNase. As one of the factors which possibly contribute to this difference, we examined the effect of the substitution of Phe120 in bovine pancreatic RNase by Leu in RNase K2 on the difference spectra.
We have presented a model for the role of external messenger substances in hypoxic stimulation of kidney production of erythropoietin. These autacoids probably act in concert to activate the adenylate cyclase system to enhance production and/or secretion of erythropoietin. The phosphoproteins generated in this system could act at the level of transcription and translation of erythropoietin as well as at the level of release of erythropoietin from the cell. Even though eicosanoids and beta-2-adrenergic agonists may be involved in mild to moderate hypoxia, it seems more likely that adenosine is more involved in erythropoietin production with increasing severity of hypoxia. Adenosine may play a very early role in hypoxia following the decrease in ATP to trigger erythropoietin production, and hydrogen peroxide may be generated from hypoxanthine, a metabolite of adenosine, during reoxygenation and regional changes in blood flow in the normal kidney and perhaps in certain renal and hepatic tumors. Further work is necessary in vivo to completely clarify the role of adenosine and oxygen free radicals in regulating kidney production of erythropoietin.
Erythropoietin (Ep) levels in spent culture media of a Hep G2 human hepatoblastoma cell line were measured by radioimmunoassay (RIA), fetal mouse liver erythroid colony formation (FMLC), and the exhypoxic polycythemic mouse assay (EHPCMA). The Hep G2 cells at high density produced approximately 700 mU/ml Ep when measured with the RIA. On the other hand, the Ep levels when assayed in EHPCMA and FMLC were 50 and 2,600 mU/ml, respectively. The bioactivity in FMLC was completely neutralized by an antibody to purified human recombinant Ep, indicating that the erythropoietic activity in the Hep G2 spent culture medium was immunologically equivalent to Ep. Ep levels in the medium from low-density Hep G2 cells in 5% O2 and 1% O2 were 2.5- and 4-fold greater, respectively, than that of 20% O2. In contrast, hyperoxia (40% O2) significantly inhibited Ep production. A significant increase in Ep secretion was also observed when the cells were incubated with cobaltous chloride (2 X 10(-6) -2.5 X 10(-4) M). Tunicamycin (0.5 micrograms/ml), which inhibits N-linked glycosylation, significantly reduced the enhancement of Ep secretion induced by hypoxia (1% O2) without affecting cell growth. Forskolin and cholera toxin, each of which increased the levels of cyclic AMP in the Hep G2 cells by 40-fold, produced a significant (P less than 0.05) further increase in Ep secretion in the presence of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
The dissolution behavior of several acidic and basic drugs from kneaded mixtures with water-soluble gelatin have been studied in comparison with that of the drug alone. The results revealed a significant increase of dissolution rate of drugs from kneaded mixtures. The water-soluble gelatin showed little interaction with any of the drugs in solution or in the solid state. Interestingly, the contact angle of the kneaded mixture was remarkably decreased compared with that of the drug powder and was found to be almost the same as that of water-soluble gelatin powder. Thus, the enhanced dissolution rate of the drug caused by water-soluble gelatin was explained by the improvement of wettability of the drug by water.
Two kinds of soft gelatin capsules containing meclizine dihydrochloride (MZ) were prepared by using a medium-chain length triglyceride as a base. One is a self-emulsifying type, and the other is an oil dispersing type. The release of MZ from soft capsules and its in vivo absorption behavior were examined and compared with those of a commercial tablet. The release of MZ from the self-emulsifying soft capsule which was only slightly affected by pH was greater than those from the oil dispersing soft capsule and commercial tablet. The serum levels of MZ after the administration of preparations orally to beagle dogs increased in the order of self-emulsifying soft capsule, commercial tablet, oil dispersing soft capsule. This result suggests that the self-emulsifying soft capsule is useful for the increase of the bioavailability of the drug.
Effects of a single administration of captopril on plasma and urinary vasopressin (AVP) were examined in 8 normotensive (NT) female volunteers, 17 patients with essential hypertension (EHT) and 2 patients with primary aldosteronism (PA). Orally-administered captopril (25 mg) had no effect on plasma AVP levels in the three groups. However, urinary excretion of AVP decreased significantly after use of captopril in both NT and EHT subjects (-57% and -67%, respectively), and also in PA subjects. The magnitude of reduction in urinary AVP was significantly correlated with the pretreatment levels of plasma renin activity (r = 0.85) and plasma aldosterone concentration (r = 0.88) in NT subjects. Such correlation was not found in EHT subjects. These results suggest that captopril decreases AVP secretion in both normotensive and hypertensive subjects, but the relation of the magnitude in AVP reduction by captopril to the peripheral renin-angiotensin system might be different.
We investigated the effects of sodium depletion and orthostasis on the plasma concentration and urinary excretion of vasopressin (AVP) in eight normal female subjects. After 4 days on a sodium controlled diet (130 mEq/day), the subjects were placed on a low sodium diet (30 mEq/day) for 3 days and 120 mg of furosemide was administered orally on the first day of the low sodium regimen. Sodium depletion in the present study reduced body weight by 1.6 kg and increased hematocrit by 3.5%. A significant (p less than 0.05) increase in plasma AVP and a significant (p less than 0.05) decrease in 24-h urinary excretion of AVP were observed during sodium depletion. One-hour ambulation significantly increased plasma AVP in both control and sodium depleted phases (p less than 0.01). The percent change in plasma AVP tended to correlate with that in mean blood pressure in the control phase (r = 0.69, 0.05 less than p less than 0.1), and significantly correlated in the sodium depleted phase (r = 0.86, p less than 0.01). The present results suggest that AVP may play an important role in the maintenance of blood pressure during orthostasis in the sodium depleted state.