Biomedical subjects
Publications and source records attributed to M Okubo.
We report a case of reconstruction of the upper lip in the male using a prefabricated hair-bearing island flap. The flap was made by implantation of a superficial temporal vascular bundle with microvascular anastomoses to the facial vessels. We conclude that the technique is a useful alternative to other methods of reconstruction because of its reliable blood supply.
Pathogenetic factors that may be related to uremic hypertriglyceridemia were studied in 27 patients who had been undergoing chronic hemodialysis treatment for over two years. They were divided into two groups consisting of 14 hypertriglyceridemic (HTG) patients with fasting serum triglycerides (TG) of 170 mg/dL or higher, aged 45 +/- 11 yr (mean +/- SD) and 13 normotriglyceridemics (NTG) with serum TG less than 170 mg/dL aged 42 +/- 9 yr. Serum lipid, lipoprotein [low density lipoprotein (LDL) and very low density lipoprotein (VLDL)] and apoprotein (Apo) levels, as well as ultracentrifugally obtained VLDL apo subfractions and serum carnitine were compared between the two groups, which enabled us to rule out various factors inherent to uremic state and present in both groups. The HTG group of patients, who showed (by definition) significantly elevated TG (300 +/- 167 mg/dL v 123 +/- 30 mg/dL in NTG) and VLDL levels, concomitantly showed significantly increased serum total cholesterol (P less than .001) and LDL (P less than .001), and significantly decreased apo AI/apo B, or an index of risk of atherogenesis (P less than .05). Serum apo CII (7.3 +/- 3.3 mg/dL v 3.6 +/- 1.0 mg/dL in NTG), apo E (4.8 +/- 2.8 mg/dL v 2.9 +/- 1.3 mg/dL) and VLDL/serum apo CII (38 +/- 18 v 22 +/- 12), ie, the amount of VLDL covered by a unit of apo CII, were elevated in the HTG compared with the NTG group of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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The cell surface antigen associated with the transformed state of cells that could grow in an anchorage-independent manner was analyzed by use of techniques of DNA transfection and hybridomas secreting the monoclonal antibody (MoAb). Spleen cells of C57BL/6 mice immunized with a highly tumorigenic, chemically induced murine cultured colon 36 tumor (C-C36) of BALB/c origin were hybridized with NS-1, a hypoxanthine phosphoribosyltransferase-deficient myeloma line of BALB/c mice. Screening of hybridomas revealed an antibody that reacted with C-C36 and transformed Swiss 3T3 cells growing in soft agar after transfection of 3T3 cells with C-C36 DNA. The hybridomas that did not react with nontransformed 3T3 and the less tumorigenic BALB/c hemangioendothelioma line D10 were then selected. An MoAb was designated "#71295." This MoAb immunoprecipitated the antigen that consisted of 65,000- and 14,000-molecular-weight components with soluble C-C36 membrane antigens. It also reacted with 2 other chemically induced syngeneic colon tumor lines, cultured colon 26 tumor line and cultured colon 51 tumor line, and with fibrosarcoma Meth A. However, #71295 was not found in NS-1, D14, and BALB/c normal thymus, liver, colon, and kidney tissues. In addition, this MoAb could not inhibit the anchorage-independent growth of C-C36 and transformed 3T3 cells. These results suggest that although the molecule defined by #71295 might not be associated with the anchorage independence of cell growth, it could be a newly expressed determinant on the cell surface that is related to the events of cell transformation.
Toxic shock syndrome toxin-1 (TSST-1) is an exotoxin produced by Staphylococcus aureus isolated from patients with toxic shock syndrome. We investigated the proliferative response of human lymphocytes and their interleukin 2 (IL-2) production after stimulation with TSST-1 in vitro. Human cord blood mononuclear cells (HCBM) and human peripheral blood mononuclear cells (HPBM) could proliferate with TSST-1 stimulation. T cell-depleted HPBM showed only a marginal response to this toxin. A IL-2-like factor with a molecular weight of 15-18 kD was obtained from the supernatants of TSST-1-stimulated HPBM cultures. The factor was absorbed by CTLL-2 cells but not by T cell-depleted murine spleen cells, indicating that it is IL-2. HPBM are very sensitive to TSST-1: a low concentration of TSST-1 (0.01 ng/ml in 36 h stimulation) and a short period of stimulation (8 h at 10 ng/ml of the toxin) were fully effective for HPBM to produce substantial amounts of IL-2. Removal of T cells abrogated the TSST-1-induced IL-2 production by HPBM. Reconstituted cell cultures of nylon wool column-passed T cells and macrophages produced IL-2 by TSST-1 stimulation and, furthermore, the accessory activity of the macrophages could be partially replaced by a macrophage-derived factor containing interleukin 1. These findings indicate that T cells require macrophages or IL-1 for TSST-1-induced production of IL-2. The roles of lymphokines, including IL-2, in the development of this illness are discussed.
Clinical efficiency and side effects of cefoperazone (CPZ) against 40 infectious diseases in the field of internal medicine were studied. In addition, relationship between clinical efficiency and the value of area under the time concentration curve (AUC) was evaluated. It was possible to evaluate clinical responses in 36 cases of 40 infections; Responses were excellent in 15, good in 16, fair in 3 and poor in 2. An overall efficacy rate was 86.1%. A high dose of CPZ (2 g X 2/day) produced a higher efficacy rate than a low dose of the drug (1 g X 2/day) [95.8% (23/24 cases) vs. 66.7% (8/12 cases)] but the difference was not statistically significant. It was possible to evaluate bacteriological efficacy in 32 cases. Bacteria were eradicated in 29 (90.6%) and decreased in 3. The value of AUC in the high dose group was significantly higher than that in the low dose group. Values of AUC in cases of excellent or good clinical responses tended to be higher than values in cases of fair or poor responses. Side effects were noted in 4 cases, but they were not serious and improvements were observed without withdrawal of the drug except 1 case.
Making use of trinitrophenyl-Brucella abortus (TNP-Ba), a T-independent antigen, the mechanism of antibody production in vitro by human lymphocytes was studied, focusing on the accessory role played by macrophages (m phi). Human tonsillar cells and peripheral blood lymphocytes (PBL), and their fractions which were depleted of T cells, M phi, or both by rosetting with sheep erythrocytes and glass adherence plus passage through a Sephadex G-10 column, were stimulated in vitro with TNP-Ba under optimal culture conditions. Substantial antibody response against the antigen was induced in the whole tonsillar cells, while no appreciable level of response was induced in the whole PBL. The level of response observed after T-cell depletion was not different from that of the whole cells. In contrast, the response was significantly enhanced both in tonsillar cells and in PBL by depleting M phi to a low level, such as 1-2% of the cultured cells. It was further shown that a small amount of M phi added back to the M phi-depleted fraction activity suppressed the response again to the level seen in the whole cells. If allogenic M phi were substituted for autologous ones, the same degree of suppressor function was observed irrespective of the difference seen in the HLA types.
We report the usefulness of scar flaps and secondary flaps in the surgical repair of extensively burned patients. Burn scar contractures repaired with scarred axial pattern flaps, scarred musculocutaneous flaps and scarred fasciocutaneous flaps are described. However, it is our contention that their application should be strictly limited. An example of the use of scarred secondary axial pattern and musculocutaneous flaps for reconstruction of a burned ear is shown.
The mode of action of mizoribine (MZR) as a B cell inhibitor was studied using DBA/2 mice. Its in vitro administration significantly delayed the primary response in hemagglutinin production against sheep erythrocytes by suppressing the IgM antibody formation. In vitro plaque-forming cell (PFC) response against both T-dependent and T-independent antigens, such as TNP-SRBC and TNP-Brucella abortus, was dose-dependently suppressed by MZR. Since PFC formation by the T-depleted fraction of splenocytes was likewise suppressed, MZR may inhibit humoral antibody response by directly affecting the B cells (and/or macrophages) as well as by modulating the regulatory T cells. MZR may only act on a certain stage of the cell cycle of B lymphocytes following antigenic stimulation. It may not interfere with the initial antigen recognition or with mature B cells.
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In order to know the role of hydrolytic enzymes in various immunological disturbances, we compared the enzymatic changes in the spleens of nude mice and NZB/W mice relative to their respective controls. In spite of the different immunological features of these models, multivariate analysis demonstrated that there is some commonness in enzymatic changes between the two models. The enzymes related to such commonness included glycosidases, alkaline phosphatase, fMet-AP, and esterase. These enzymes may play some important roles in immunologic dysregulation , especially in relation to B-cell dominance in these disease models.
Blood concentration of water-soluble vitamins were measured in patients with mild chronic renal insufficiency, uremic undialyzed and dialyzed patients and control subjects. The whole blood concentration of B1 was significantly lower in dialyzed patients. Plasma levels of B2 were elevated in uremic and dialyzed patients and plasma B6 was significantly increased in dialyzed patients. Serum levels of B12 and folic acid were elevated in uremic and dialyzed patients. The results of this study differ from those reported from Europe and the U.S.A. These geographical differences may arise primarily from differences in staple food, vegetable intake, and traditional methods of food preparation.
The effects of bombesin and gastrin releasing peptide (GRP) on the release of catecholamine were investigated by using isolated rat adrenal gland. Bombesin and GRP stimulated an epinephrine (E) release with dose-dependency. A half maximal effect of bombesin was observed at 1.2 X 10(-9) M, and a maximal release of E occurred at 1 X 10(-6) M of bombesin. The stimulatory effect of GRP on the E release was very similar to that of bombesin. Although both these peptides also stimulated a norepinephrine (NE) release, a significant effect was detected at concentrations of bombesin and GRP above 1 X 10(-7) M. Nicotine and pilocarpine stimulated both E and NE releases dose dependently, but the effect of pilocarpine on E and NE release was 1/100 or less potent than that of nicotine. Bombesin-induced catecholamine releases were not inhibited by hexamethonium or atropine that fully impeded the stimulatory effects of nicotine or pilocarpine. In addition, bombesin had additive effects on the nicotine- or pilocarpine-induced E and NE releases. These data strongly suggest that bombesin or GRP plays a physiological role as one of the important regulators in catecholamine secretion in the adrenal gland.
Therapeutic trials with mizoribine (MZR), an imidazole nucleoside immunosuppressant, on experimental lupus nephropathy of NZB/W F1 mice resulted in the following. The MZR treatment, 20 mg per kilogram of body weight every other day, starting at 14 weeks of age, caused a significantly prolonged survival time of mice with a mean life span of 54.3 +/- 4.2 weeks, compared with the untreated controls, who had a mean survival time of 38.1 +/- 2.9 weeks (P less than 0.01). In addition, MZR suppressed the elevation of serum anti-DNA antibody titers, the spontaneous development of splenomegaly, and the histological development and progression of glomerulonephritis observed in untreated animals. Although no definite explanation is available at present to explain how MZR caused decreased anti-DNA antibody production and delay in the development of glomerulonephritis in these animals, it is suggested that it acts by directly suppressing the hyperfunctioning B cells of lupus mice. MZR may prove to be a promising immunosuppressant for the treatment of human lupus, in view of its lesser side effects such as bone marrow suppression or hepatotoxicity.
To evaluate the humoral immune system in patients with chronic renal failure, a cytological approach was taken. The uremic lymphocytes and their subsets in the peripheral blood were quantitated and their functions studied. In order to exclude the possible effects of extra-uremic factors, the lymphocytes were obtained from the uremic patients with serum creatinine levels of 8 mg/dl or more, and who had been submitted neither to blood transfusions nor dialysis therapy. Absolute numbers of PBL, T cells, B cells, null cells and double marker cells were decreased in uremic patients compared to healthy controls (p less than 0.001), although the percentages of each cell subset of the patients were the same as with the healthy controls. In vitro plaque forming cell responses and DNA synthesis by uremic lymphocytes, stimulated with pokeweed mitogen, were significantly lower than those of the healthy controls. These data point to B lymphocyte as well as T lymphocyte dysfunction in uremia, which may be causally related to the uremic state itself.