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Biomedical subjects

Y Aoki

Publications and source records attributed to Y Aoki.

At least 487 records · Page 27Linked to original sources

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↗

Blood grouping of minute samples using monoclonal anti-A,B antibody.

The availability of a monoclonal anti-A,B antibody (AB-E6E2) for blood grouping of blood and saliva stains was investigated. The antibody, which was reacted with A, B and AB antigens but not with O antigen, was produced from BALB/c mouse-mouse hybridoma raised to group AB red blood cells. AB-E6E2 had heat-elutability enough to detect ABO antigens in blood and saliva stains by absorption-elution test, whereas it had extremely weak double combining potency in mixed agglutination test. Application of elution-ELISA method will enable the detection of smaller amount of ABH antigens. The antibody, therefore, would be useful to segregate group O minute samples from the other blood group ones.

ABO Blood-Group System↗

Effects of serum bilirubin on determination of uric acid by the uricase-peroxidase coupled reaction.

We examined the possible effect of different bilirubin species, including unconjugated (Bu), sugar-conjugated (Bc), and authentic delta bilirubin (Bd) isolated from serum, on the direct enzymatic measurement of uric acid by using the uricase (EC 1.7.3.3) and peroxidase (EC 1.11.1.7) coupled reaction. Bc, isolated from human bile, produced the most interference with uric acid determination. Although the presence of human serum albumin reduced interference by Bu and Bc, albumin-bound Bc complex still produced greater interference than Bu. Interference with the peroxidase reaction by Bc covalently bound to serum albumin (Bd) was less than that by Bu. We examined this phenomenon by using serum-isolated Bd obtained by ammonium sulfate precipitation and ultrafiltration and by using commercially available ditaurobilirubin (DTB) and chemically synthesized Bd (via Woodward's reagent, WBd) as surrogates for bile-isolated Bc and natural Bd, respectively. DTB produced the same amount of interference as natural Bc, but the interference produced by DTB in the presence of serum albumin was not the same as that produced by natural Bc with albumin. Our synthetic Bd appears to be a reliable surrogate for natural Bd in testing for bilirubin interference.

Bilirubin↗

[Intra-arterial infusion chemotherapy for hepatocellular carcinoma using an implantable drug delivery system].

Intra-arterial chemotherapy and chemoembolization using implantable drug delivery system were performed in sixty-one cases of unresectable hepatocellular carcinoma (HCC). The following results were obtained. (1) The follow-up period was 253 days, and the administrations numbered 13.9 times on average. (2) Response rate was 31.1%. (3) AFP decreased in 80% cases, and PIVKA-II in 83.3% cases. (4) Tumor thrombus in the portal vein disappeared in 4 of 40 cases(10%). (5) Free-CDDP continued for 60 minutes after injection of cisplatin-phosphatidyl-choline-Lipiodol (CPL), and the response rate was 47%. (6) The survival rates were 56% in one year, 25% in two years, and 20% for three years. These results were significantly higher than those of one shot therapy. It is suggested that good therapeutic effects can be obtained by the implantable drug delivery system, and CPL was a useful anticancer agent for the therapy.

Biomarkers↗

In vivo and in vitro interaction between interleukin 6 and granulocyte colony-stimulating factor in the regulation of murine hematopoiesis.

The interaction both in vitro and in vivo between human recombinant interleukin 6 (IL-6) and human recombinant granulocyte colony-stimulating factor (G-CSF) in the regulation of mouse hematopoiesis was investigated. In the in vitro experiments, mouse bone marrow and spleen cells were cultured in semisolid medium containing 5 or 50 ng/ml of G-CSF and concentrations ranging from 0 to 20 ng/ml of IL-6. In vivo, mice were treated for 4 days with 15, 50, or 250 micrograms/kg body weight/day of G-CSF, or with similar doses of G-CSF plus 50 micrograms/kg/day of IL-6, and the numbers of stem (spleen colony-forming units, CFU-S) and progenitor (megakaryocyte colony-forming cells, Meg-CFC; granulocyte-macrophage colony-forming cells, GM-CFC) hematopoietic cells and mature circulating blood cells were evaluated. In vitro IL-6 caused dose-dependent suppression of the proliferation of GM-CFC, decreasing numbers of granulocyte-macrophage colonies in culture. The inhibitory effect of IL-6 decreased along with the increase of density of cultured cells, suggesting the influence of accessory, cytokine-producing cells. In vivo, the numbers of GM-CFC and Meg-CFC in mice treated with IL-6 plus G-CSF were significantly closer to the values observed in untreated animals than those in mice treated with G-CSF only. The other cell populations were unaffected by IL-6 treatment. Our results demonstrate antagonism between IL-6 and G-CSF in the in vitro stimulation of the proliferation of late granulocyte precursors, and they suggest a similar effect in the in vivo regulation of granulopoiesis and megakaryocytopoiesis at the progenitor cell level.

Animals↗

In vitro effects of light on serum bilirubin subfractions measured by high-performance liquid chromatography: comparison with four routine methods.

The effects of light on serum bilirubin subfractions in vitro were investigated by HPLC and four routine methods for bilirubin analysis. By HPLC, the rate of photodegradation of unconjugated bilirubin (Bu) was nearly twice that of monoconjugated bilirubin (mBc) and threefold that of diconjugated bilirubin (dBc); delta bilirubin (Bd) was most stable against photoirradiation. In the diazo method, the rate of photodegradation of direct bilirubin was almost the same as that of the sum of mBc, dBc, and Bd determined by the HPLC method. However, the rate of photodegradation of indirect bilirubin was significantly lower (P < 0.001) than that obtained by HPLC, because approximately 30% of the bilirubin photoproducts reacted with the diazo reagent as indirect bilirubin. The rate of photodegradation of total bilirubin determined by the direct spectrometric method was lower than that determined by the diazo method, but equal to that of the total peak areas of HPLC. In the Ektachem method, bilirubin photoproducts affected total bilirubin negligibly, and Bc and Bu positively, so that the value of Bd decreased. In the bilirubin oxidase method, bilirubin photoproducts were oxidized enzymatically by both the total and direct bilirubin reagents. We re-emphasize the importance of shielding serum from light to avoid generating bilirubin photoproducts that interfere with the accurate determination of serum bilirubin subfractions. We also recommend HPLC analysis as a standard method for bilirubin measurement.

Adult↗

[Cold agglutinin hemolytic anemia complicating mycoplasma pneumonia].

A case of Mycoplasma pneumonia complicated with severe hemolytic anemia, which occurred as a result of a high titer of cold agglutinin is presented. A 49 year-old male was admitted because of fever, jaundice and dyspnea. Chest x-ray showed diffuse small nodular infiltrates throughout both lung fields. Laboratory studies disclosed the following values: Hb 4.6 g/dl, Ht 13.9%, reticulocyte 11.5%, direct and indirect Coombs' test positive, haptoglobin 38 mg/dl, ESR 145 mm/hr, cold agglutinin titer 1:2,048 mycoplasma antibody titer 1:640, PPD negative. The diagnosis of autoimmune hemolytic anemia associated with Mycoplasma pneumonia was made, and treatment with minocycline and prednisolone observed striking clinical improvement. It was suggested that the cold exposure was possibly a major factor in the pathogenesis of hemolysis in this patient.

Anemia, Hemolytic, Autoimmune↗