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Biomedical subjects

Y Aoki

Publications and source records attributed to Y Aoki.

At least 19 recordsLinked to original sources

Topical antibiotics in cholecystectomy for gallstone diseases.

Efficacy of topical antibiotics in cholecystectomy for gallstone disease was evaluated. Forty-four patients who accepted topical single administration of 1 or 2 g each of latamoxef, cefmenoxime, cefotiam or cefamandole during operation were compared with 36 patients with systemic administration of cefem antibiotics by intravenous drip at a dose of 1 or 2 g, twice daily for postoperative 4 to 7 consecutive days. In topical administration group, concentration of each antibiotic in the gallbladder and common duct bile, gallbladder tissue, parietal peritonea and intra- and postoperative peripheral blood exceeded mostly MIC80 against bacteria usually existing in bile by biliary tract infection or bacteria by wound infection. There was no difference between the two groups in postoperative clinical course. Thus, an adequate prophylactic effect can be expected by topical use of antibiotic during cholecystectomy.

Administration, Topical

Enzyme-linked immunosorbent assay for the detection of cathepsin-kininogen complexes in human plasma.

A simple and sensitive enzyme-linked immunosorbent assay (ELISA) for the determination of cathepsins B-, H- and L-kininogen (B-KG, H-KG, and L-KG) complexes was constructed using a microtiter plate based sandwich technique. The assay range was 7.5-480 ng/ml with three cross-linked cathepsin-kinin-free low molecular weight KG (LMWKGf) complexes. The average within-run coefficients of variation (CV) using three concentrations were 7.5, 7.2 and 9.9% for B-LMWKGf, H-LMWKGf, and L-LMWKGf complexes, respectively. The between-run CV values indicated satisfactory reproducibility for the method. Recoveries of cross-linked B-LMWKGf, H-LMWKGf, and L-LMWKGf complexes from negative control plasma were 127 +/- 7.1, 112 +/- 5.8 and 102 +/- 8.8% (n = 10, mean +/- SD), respectively, whereas the average recovery from phosphate buffer (pH 7.2) containing 0.15 M NaCl, 0.05% Tween-20 and 0.1% bovine serum albumin was 93.1 +/- 8.2% (n = 10, mean +/- SD). It was possible to detect B-KG and H-KG complexes in the plasma of 5/280 and 14/280 patients manifesting acute phase responses. Levels in plasma from healthy individuals were negligible. This ELISA should permit the study of cathepsin metabolism in acute phase disorders.

Acute-Phase Reaction

Induction of glutathione S-transferase P-form in primary cultured rat liver parenchymal cells by co-planar polychlorinated biphenyl congeners.

Alterations in protein synthesis in primary cultured rat liver parenchymal cells were examined after their exposure to the potent carcinogens, polychlorinated biphenyl (PCB) congeners. Co-planar PCB congeners (3,4,5,3',4'-PCB and 3,4,5,3',4',5'-PCB) (10 nM) induced a protein, the Mr of which was 25,000 (25 k protein) under denaturing conditions. However, non-co-planar PCB congeners and several xenobiotics, which induce microsomal proteins, did not induce the 25 k protein. By using immunoblotting, the 25 k protein was identified as glutathione S-transferase P-form (GST-P, 7-7, EC 2.5.1.18).

Animals

Clinical and immunological evaluation of intraoperative radiation therapy for patients with unresectable pancreatic cancer.

The clinical efficacy of intraoperative radiation therapy (IORT) and the changes of immunological parameters were investigated. Nine patients with unresectable pancreatic cancer were treated with IORT (2,500-3,500 cGy) and the changes of various immunological parameters were compared with those in 11 patients with advanced cancer who received external beam irradiation therapy (XRT), 2,500-3,500 cGy. After IORT, 71% of patients obtained pain relief, two of the nine patients showed a partial response, and the serum CA 19-9 level decreased in six patients. However, the median survival was only 210 days. Natural killer activity, lymphokine-activated killer activity, and interferon gamma-activated killer activity were not inhibited by IORT, and phytohemagglutinin-induced blastogenesis was actually augmented after IORT, whereas all these parameters were inhibited by XRT. Thus, it is suggested that IORT may augment or at least stabilize systemic antitumor immunity.

Aged

Protective effect of vitamin E supplementation on increased thermal stability of collagen in diabetic rats.

Products similar to non-enzymatic glycation end products are known to arise from the interactions between proteins and lipid peroxides in vitro. In this study, we assessed the effect of vitamin E, which possibly modifies lipid peroxide, on advanced glycation end products or similar products in vivo by measuring the fluorescence and thermal rupture time of tail tendon collagen in streptozotocin-induced diabetic rats. The diabetic rats and non-diabetic rats were fed a vitamin E supplemented diet, and a control diet starting 3 days after the streptozotocin injection. After the 4-week treatment, the serum lipid peroxide levels expressed as thiobarbituric acid reactants in the diabetic rats on control diet (15.9 +/- 2.6 mumol/l[SEM]) were significantly (p less than 0.05) higher than in the non-diabetic rats (7.9 +/- 1.3 mumol/l on control diet and 3.3 +/- 0.4 mumol/l on supplemented diet), but the levels in the diabetic rats on supplemented diet (7.9 +/- 2.3 mumol/l) were reduced to the normal levels. No significant differences were found in serum glucose and glycated haemoglobin levels within the diabetic rats on control and supplemented diets. Both the fluorescence and thermal rupture time of collagen were significantly (p less than 0.05) increased in the diabetic rats on both diets compared with those in the corresponding non-diabetic rats. Although there was no significant difference in the collagen-linked fluorescence within the diabetic rats on control and supplemented diets, the thermal rupture time was significantly (p less than 0.01) shortened with supplemented diet (10.8 +/- 0.7 min on supplemented diet vs 15.0 +/- 0.7 min on control diet).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Suppression of ischemia-reperfusion injury by liposomal superoxide dismutase in rats subjected to tourniquet shock.

To investigate the role of oxygen-derived free radicals in the pathogenesis of tourniquet shock, the authors present an experimental animal model. Two groups of rats were fastened with rubber tubes on both thighs (1.5 kg/cm2) for 6 h under pentobarbital anaesthesia. One group was administered liposomal superoxide dismutase (L-SOD 30,000 U/kg body weight), and the other liposome as a control 3 h prior to tourniquet removal. No rats in the control group (n = 20) survived more than 24 h after reperfusion, whereas 55% of animals treated with L-SOD (n = 20) survived for 24 h or more, and two recovered completely (P less than 0.005). Blood samples were obtained from the abdominal aorta after laparotomy of anaesthetized rats of both groups at different time intervals. Changes in the hematocrit value and blood urea nitrogen during the early periods after reperfusion were attenuated by prior administration of L-SOD, and the total plasma SOD activity of the control animals decreased promptly and continuously throughout the experimental period. This experimental model was very useful to study the pathogenesis of tourniquet shock with respect to reproducibility, induction of the shock stages and mortality. It is thought that oxygen-free radicals are involved in the induction of tourniquet shock, and L-SOD was, to a certain extent, effective against reperfusion injury in the early stages of shock.

Alanine Transaminase

ATP-dependent strontium uptake by basolateral membrane vesicles from rat renal cortex in the absence or presence of calcium.

ATP-dependent Sr2+ transport was examined in vitro using basolateral membrane (BLM) vesicles isolated from rat renal cortex to clarify the discrimination mechanisms between strontium (Sr) and calcium (Ca) in renal tubules during reabsorption. ATP-dependent Sr2+ uptake and Ca2+ uptake were observed in renal BLM vesicles and were inhibited by vanadate. Hill plots indicate similar kinetic behavior for Ca2+ and Sr2+ uptake. The apparent Km and Vmax of ATP-dependent Sr2+ uptake were both higher than those for Ca2+ uptake. ATP-dependent Sr2+ uptake by BLM vesicles diminished in the presence of 0.1 microM Ca2+ and was more markedly inhibited by 1 microM Ca2+. Hill plots of Sr2+ uptake data with and without 0.1 microM Ca2+ showed that the cooperative behavior of Sr2+ uptake was not changed by Ca2+. In the presence of 0.1 microM Ca2+, the affinity of the transport system for Sr2+ and the velocity of Sr2+ uptake in the BLM were both decreased. However, the rate of Ca2+ uptake was not diminished by Sr2+ concentrations of less than 1.6 microM. These results suggest that Ca2+ is preferentially transported in the renal cortex BLM when Ca2+ and Sr2+ are present at the same time.

Adenosine Triphosphate

No significant effect of vitamin E deficiency or supplementation on collagen-linked fluorescence in skin of diabetic rats.

It is speculated that oxidative stress in vivo may have some influence on advanced, nonenzymatic, glycosylation end products. However, this has not been demonstrated yet. We assessed changes in collagen-linked fluorescence in the skin of nondiabetic and streptozotocin-induced diabetic rats fed three different diets for 4 weeks that could modify oxidative stress: vitamin E-deficient (D), vitamin E-supplemented (S), and control (C). The serum lipid peroxide level expressed as thiobarbituric acid (TBA) activity in diabetic rats on the S diet (9.6 +/- 1.0 [SE] nmol/L/mL) was significantly (P less than .01) lower than that in rats on the D diet (111.4 +/- 22.4), and similar to that in nondiabetic rats on the C diet (12.4 +/- 2.2). The collagen-linked fluorescence level was significantly (P less than .01) higher in diabetic rats than in nondiabetic rats, which corresponded to the serum glucose and glycosylated hemoglobin levels. However, there were no significant differences in the fluorescence levels among three groups classified by three different diets in both nondiabetic and diabetic rats (21.7 +/- 1.7 arbitrary U/mg collagen for D, 22.3 +/- 2.0 for C, and 22.8 +/- 2.5 for S in nondiabetic rats v 41.2 +/- 4.1 for D, 40.1 +/- 4.7 for C, and 39.3 +/- 3.5 for S in diabetic rats), despite significant changes in serum lipid peroxide levels. Consequently, there were no significant changes found in collagen-linked fluorescence levels in diabetic rats wherein oxidative stress was modified by vitamin E deficiency and supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Possible participation of a prostaglandin E1 analogue in the aggravation of diabetic nephropathy.

A relation between the progression of diabetic nephropathy and glomerular hyperfiltration has been speculated. We describe two cases of non-insulin-dependent diabetic males aged 55 and 59 years in whom diabetic nephropathy was aggravated during the administration of limaprost, a a prostaglandin E1 analogue with a vasodilatory action. We also observed a short-term effect of limaprost on renal hemodynamics in three cases with diabetic nephropathy. In case 1, one year after limaprost administration the serum albumin level fell from 3.6 to 2.6 g/dl and the serum creatinine level rose from 1.0 to 1.6 mg/dl. In case 2, 9 months after limaprost administration the serum albumin level fell from 3.6 to 2.9 g/dl and the serum creatinine level rose from 1.8 to 2.3 mg/dl. In the latter stages of limaprost administration, the downslopes of reciprocal serum creatinine against time appeared to be augmented in the two cases. After the 3-day administration of limaprost, the peripheral and renal blood flows, and the glomerular filtration rate (GFR) were observed to rise, but the filtration fraction (FF) and urinary protein output were elevated. Keeping in mind the pre-existing renal damage, the increases in GFR and FF suggested acceleration of compensatory glomerular hyperfiltration in less damaged surviving glomeruli. The sustained acceleration of hyperfiltration with long-term administration of limaprost as an exogenous vasodilatory prostaglandin was assumed to eventuate in the aggravation of diabetic nephropathy. Attention should be paid to drugs which increase GFR in patients with established diabetic nephropathy.

Alprostadil

Enzyme-linked immunoassay of haptocorrin: analysis of milk and granulocytes.

An enzyme-linked, sandwich-type immunoassay method was described for quantitive assay of haptocorrin. The ranges of haptocorrin concentrations measurable by the method were comparable with those by radioimmunoassay. Using the method, the mean +/- SD of haptocorrin was 4.83 +/- 1.23 micrograms/ml in the colostrum (4th and 5th days after parturition), 3.17 +/- 1.77 micrograms/ml in the mature milk, and 21 ng/10(4) granulocytes (634 ng/mg protein). Haptocorrin from milk showed a homogeneous band at 66 kDa on SDS polyacrylamide electrophoresis followed by immunoblotting, while that from the granulocytes exhibited several closely aligned bands at 80 kDa and one or two bands at around 20 kDa.

Colostrum

Solid-phase anti-CD3 antibody activation and cryopreservation of human tumor-infiltrating lymphocytes derived from epithelial ovarian cancer.

The effect of solid-phase anti-CD3 antibody activation and cryopreservation was evaluated on thirteen samples of tumor-infiltrating lymphocytes (TILs) derived from epithelial ovarian cancer. Seven preparations of TILs were cultured with or without solid-phase anti-CD3 antibody in addition to 100 units/ml of recombinant interleukin-2 (rIL-2). The proliferation rate of all of the seven TIL preparations stimulated by anti-CD3 antibody on the fourth or fifth day of culture was 3.4 to 9.8 times greater than that of lymphocytes cultured with rIL-2 alone. Furthermore, in an experiment with five TIL samples activated with anti-CD3 antibody, three of them showed augmented cytotoxic activity against autologous fresh tumor cells. The population of CD3+/CD8+ TILs was increased after 4-5 weeks of cultivation and CD8+ lymphocytes amounted to over 70% in all of seven preparations tested, whereas two of seven preparations not activated by anti-CD3 antibody were CD3+/CD4(+)-dominant. In addition, nine preparations of TILs cultured with rIL-2 were cryopreserved for several weeks; after recovery from cryopreservation, no major change was observed in cell surface markers, in growth rate or in cytotoxic activity. These results suggest that cryopreserved and/or anti-CD3 antibody-activated lymphocytes could conveniently be employed in a clinical trial of adoptive immunotherapy employing TIL.

Antibodies

Biliary obstruction: evaluation with three-dimensional MR cholangiography.

Three-dimensional (3D) magnetic resonance (MR) projection imaging was evaluated as a noninvasive alternative to direct cholangiography in 12 patients with malignancy-related obstructive jaundice. The 3D images of the bile ducts were formed by subjecting consecutive coronal MR images obtained with a fast imaging method to a maximum-intensity projection algorithm. Dilatation and obstruction of the biliary system were well documented in all cases, and good correlation between findings at 3D MR cholangiography and percutaneous transhepatic biliary drainage performed 0-21 days later was observed.

Adult

The effect of OK-432 upon erythropoietic recovery in sub-lethally irradiated mice: a preliminary report.

OK-432, a multicytokine inducer and clinically used as an immunopotentiating anti-cancer agent, is known to induce IL-1 and TNF-alpha. The suppressive effect of IL-1 and TNF-alpha on erythropoiesis could limit the clinical use of OK-432 in cancer treatment, especially when combined with radiotherapy. In this study, the effect of OK-432 on normal and X-ray impaired erythropoiesis was examined. C57BL/6J mice were injected with a single dose of OK-432 (5.0 KE). Erythropoietic activity was measured by 59Fe incorporation into circulating erythrocytes and the heme iron fraction of erythropoietic tissue. When irradiated with 662 cGy of X-rays, OK-432 prolonged the survival of mice. No significant change in erythropoiesis was observed when normal mice were treated with OK-432. When treated with OK-432, the recovery of erythropoiesis after irradiation was promoted as judged by the uptake of 59Fe into erythrocytes. This promotion was observed when OK-432 was injected within 1 day before or within 3 hours after the irradiation with 284 cGy of X-rays. This promoting effect, however, appeared to be limited to the spleen. Whether the combination of OK-432 with radiotherapy has the potential to improve the treatment of malignant tumors is still a subject of controversy. The present results, nevertheless, suggest that when combined with radiotherapy, OK-432, at the very least, may have no adverse effects on erythropoiesis.

Animals

Insulin-dependent diabetes mellitus showing microangiopathic hemolytic anemia and chronic disseminated intravascular coagulation.

It has been reported that microangiopathic hemolytic anemia occasionally occurs in patients with severe diabetic microangiopathy. We report a case of insulin-dependent diabetes mellitus in whom microangiopathic hemolytic anemia and chronic disseminated intravascular coagulation (DIC) were thought to be complicated. The patient showed fragmentation hemolytic anemia and progressive diabetic microangiopathy, together with a mild elevation of serum fibrin(ogen) degradation products. Considering the state of chronic DIC, heparin therapy was started, but mild hemolysis persisted. It is possible that microangiopathic hemolytic anemia and chronic DIC cause a vicious cycle in patients with severe diabetic microangiopathy, leading to rapid progression of diabetic microangiopathy.

Adult

Hospital-onset tuberculosis in compromised host.

A total of 21 patients developed active tuberculosis (TB) during hospitalization. Active TB was identified by bacteria-positive, biopsy or autopsy. Infection was confirmed to the lung, pleura, lymph node and miliary lesions and 7 patients had open tuberculosis. In half of the patients, chest X-ray films demonstrated unusual findings in adult tuberculosis: lower lung field pneumonia and miliary pattern. All the patients suffered from severe underlying diseases and an intensive therapy with steroid, immunosuppressive agents, antitumor drugs, radiation and operation was found as predisposing factors for TB occurrence. Nine patients recovered from current infection with anti-tuberculosis drugs; 14 patients died and TB directly caused death in 8 patients. These data strongly suggest that TB is one of the most important infections in compromised hosts. We emphasize that this infection presents a serious clinical problem in a general hospital today.

Aged

A new series of natural antifungals that inhibit P450 lanosterol C-14 demethylase. II. Mode of action.

From a Penicillium sp. we identified a new series of antifungals having a tetrahydropyran skeleton with an alkenyl side chain. We elucidated the mode of action of Ro 09-1470, the most active compound of the series. Treatment of Candida albicans with the compound caused an accumulation of C-14 methyl intermediates of ergosterol at concentrations of which no significant interference with the biosyntheses of other macromolecules and respiration was observed. P450 lanosterol C-14 demethylase (P450(14DM)) activity was inhibited and furthermore, the binding of Ro 09-1470 to the heme of the enzyme was demonstrated by a difference spectrum. We conclude that Ro 09-1470 is the first natural antifungal that inhibits the P450(14DM) of fungi.

Candida albicans

[A case of cardiac sarcoidosis associated with various clinical symptoms and thrombocytopenia].

A 29-year-old man presented with acute onset of high fever, chest pain and dyspnea. Chest X-ray film showed diffuse interstitial shadows, a cavitary lesion in the left upper lung field and cardiomegaly, but no lymphadenopathy. Abdominal CT scan showed hepatosplenomegaly and multiple small low density areas in the liver and spleen. Electrocardiogram demonstrated multifocal ventricular premature beats and ventricular tachycardia. Cardiac catheterization revealed left ventricular aneurysms. Sarcoidosis was confirmed by lung and liver biopsy. Drug therapy of prednisolone and mexiletine resulted in clinical improvement of symptoms, signs and chest X-ray film, but platelet count decreased gradually. It is suggested that an immune mechanism of sarcoidosis may have been the cause of this thrombocytopenia.

Adult