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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 793 records · Page 44Linked to original sources

The synergistic effect of total-lymphoid irradiation with extracted donor alloantigen in inducing transplantation unresponsiveness.

The synergistic effect of total lymphoid irradiation with KCl-extracted donor type antigen (H-Ag) was examined in the rat cardiac graft model. TLI therapy alone of 10, 16, and 20 Gy achieved by a 2 Gy daily treatment of WFu recipients produced modest prolongation of BUF heart survival to median survival times (MST) of 11, 26, and 30 days, respectively, in comparison with normal control (MST = 6). The TLI immunosuppressive effect was significantly potentiated with donor H-Ag when combined with 16 (greater than 100 days) but not with 10 or 20 Gy TLI therapy. This effect was specific: 16 Gy TLI treated recipients of BUF hearts rejected their grafts in a MST of 27 days when treated with third-party BN H-Ag. The state of unresponsiveness was transferable to 6 Gy total-body-irradiated WFu recipients of BUF hearts with 60 x 10(6) purified T cells isolated from TLI/H-Ag-treated rats (greater than 100) but not from normal controls (MST = 6). In vitro analysis of nontransplanted WFu rats 1-4 weeks after completion of 16 Gy TLI therapy alone demonstrated a nonspecifically reduced MLR proliferative response as well as the presence of potent nonspecific suppressor cells (NSC). By 3 or even 6 months post-TLI, W3/25- NSC displayed persistent suppressive activity and inhibited normal proliferative response to alloantigens. Limiting dilution assay revealed that the frequency of T cytotoxic cells (fTc) was severely decreased to 1:63111 at one day and to 1:16488 at one week postirradiation in comparison with normal control (1:2551). At 3 and 6 months the fTc of 1:2301 and 1:2040, respectively, approximated normal levels. These combined in vivo and in vitro results demonstrate that 16 Gy TLI therapy induces an unresponsiveness mediated by NSC and that the administration of donor type H-Ag facilitates the generation of potent regulatory T cells capable of inducing prolonged heart allograft survival.

Animals↗

Is immunotherapy for habitual aborters an immunologically hazardous procedure for infants?

Physical development and tests of immunologic function are reported from the first year of life for 13 infants born to mothers who were habitual aborters and who had undergone subcutaneous vaccination with their husband's lymphocytes. The mean weight of the infants at birth was 2,975 +/- 540 g, including one infant who was small for dates. Physical development parameters for the first year were all within normal range. Immunologic studies were performed at ages 0, 1, 3, 6, 9, and 12 months. The studies included the following: (1) serum levels of immunoglobulins and complement components; (2) the number of peripheral blood lymphocytes (PBL) and their subpopulations; and (3) proliferative responses by PBL against unrelated lymphocytes and some mitogens (pokeweed, phytohemagglutinin, and concanavalin A). All were normal when compared with studies of infants of nonimmunized mothers. These observations suggested that subcutaneous vaccination of women with their husband's lymphocytes did not result in any adverse effects on their infants' physical or immunologic development.

Abortion, Habitual↗

Serological analysis of cell surface antigens in choriocarcinoma cell lines.

Major histocompatibility complex (MHC) antigens as well as blood group related antigens were investigated in four newly established gestational choriocarcinoma cell lines (NaUCC-1, -2, -3, and -4) using protein A and immune adherence assays. Antibodies to both monomorphic determinants of HLA class I antigens and beta 2 microglobulin reacted with all of the choriocarcinoma cell lines at levels equal to or much greater than SCH, which was teratoid choriocarcinoma cell line. Antibodies to polymorphic determinants not only of the patient's HLA type, but also of the husband's type, reacted to NaUCC-1 and -2. These results indicated that all four newly established choriocarcinoma cell lines express class I HLA antigens. However, we could not demonstrate expression of class II antigens. No expression of blood group A and B antigens could be established, and binding of antibody to Rho(D) antigens was only positive in the NaUCC-1 cell line. These results suggest that some choriocarcinoma cell lines actually express alloantigens and that choriocarcinomas have the character of transplanted tumors that have activities to induce transplantation immunity of the patients.

ABO Blood-Group System↗

Specific inhibitory substance to the husband's HLA allotype in sera from patients with gestational trophoblastic disease detected by lymphocytotoxicity testing.

The sera of nine patients with gestational trophoblastic disease were investigated for the inhibitory substance specific to the HLA allotypes of the patients' husbands by microcytotoxicity inhibition testing using monoclonal antibodies (anti-A2, A9, A10) and HLA-typing serum to Bw52. The specific inhibitory substance was present in three of three choriocarcinoma patients, in three of four invasive mole patients, and in one of two hydatidiform mole patients and seemed to change in titer parallel with tumor growth. These facts suggest that the inhibitory substance could have some relation to the patient's immunological response against the tumor; that is, this inhibitory substance could be the reason why patients could not induce graft rejection response to trophoblastic tumor cells.

Antibodies, Monoclonal↗

MLR-blocking antibodies are directed against alloantigens expressed on syncytiotrophoblasts.

In this study, the reactivity of mixed lymphocyte reaction-blocking antibodies toward trophoblasts was investigated. Nineteen sera that had a significant level of MLR-blocking effect were obtained from normal pregnant women and from primary habitual aborters after immunotherapy. The blocking effects of these sera were studied before and after absorption with syncytiotrophoblast plasma membrane (STPM) from the respective mothers' placenta (autologous) as an experimental group and from unrelated mothers' placenta (allogeneic) as a control. The HLA types of cord blood lymphocytes corresponding to ten of these STPM were then determined. In the study with the 11 normal pregnancy sera, the blocking effect of every serum was partially removed by autologous STPM absorption. This revealed a significant difference between the preabsorption and postabsorption MLR-blocking effect. Nevertheless, absorption by the allogeneic STPM either partially removed or did not remove the blocking effect. Furthermore, there was a statistically significant difference in the elimination of the MLR-blocking effect between the autologous STPM and the allogeneic STPM. Studies with the sera from the immunized aborters revealed similar results. There was no statistically significant difference in the elimination of the antibodies between absorption with autologous and with allogeneic STPM. In these habitual aborters' sera, comparison of paternal stimulator and cord blood lymphocytes HLA types showed that the positive allogeneic STPM absorptions could not be explained sufficiently by coincidence of HLA types. Further studies are needed to determine whether the alloantigens are HLA-linked or not.

Abortion, Habitual↗

In vitro and in vivo activities of QA-241, a new tricyclic quinolone derivative.

The in vitro susceptibilities of 1,310 clinical isolates to QA-241, a novel tricyclic quinolone, were evaluated in comparison with susceptibilities to norfloxacin, ofloxacin, enoxacin, and ciprofloxacin. The MICs of QA-241 for 90% of staphylococci, Enterococcus faecalis isolates, and streptococcal species ranged from 1.56 to 6.25 micrograms/ml, and the activity of QA-241 was similar to those of norfloxacin and enoxacin but two to four times less potent than those of ofloxacin and ciprofloxacin. At the concentration of less than or equal to 1.56 micrograms/ml, QA-241 inhibited 90% of Haemophilus influenzae, Bordetella pertussis, Neisseria gonorrhoeae, and gram-negative enteric bacteria except for Serratia marcescens and Citrobacter freundii. QA-241 was moderately active (MIC for 90% of strains tested, 6.25 to 12.5 micrograms/ml) against S. marcescens, Pseudomonas aeruginosa, Xanthomonas maltophilia, and Bacteroides fragilis. The antibacterial activity of QA-241 was roughly comparable to that of enoxacin but two to four times less potent than that of ofloxacin. In systemic infections in mice with gram-positive cocci and gram-negative rods, the efficacy of QA-241 was generally greater than that of norfloxacin and similar to those of ofloxacin and ciprofloxacin. In urinary tract infections in mice with Escherichia coli or Pseudomonas aeruginosa, QA-241 was as active as ofloxacin and more active than norfloxacin but less active than ciprofloxacin. In pulmonary infections in mice with Klebsiella pneumoniae, the effectiveness of QA-241 was similar to that of ofloxacin.

4-Quinolones↗

Preparation and pharmacokinetic and pharmacodynamic evaluation of hydroxy propyl cellulose-ethyl cellulose microcapsules containing piretanide.

Hydroxy propyl cellulose (HPC)-ethyl cellulose (EC) microcapsules containing piretanide were newly by a solvent evaporation technique and their slow-release properties were evaluated on dissolution properties in vitro and pharmacokinetic and pharmacodynamic parameters in beagle dogs. The dissolution behavior of piretanide from the microcapsules in dissolution media of pH 1.2-6.8 and the plasma piretanide level in beagle dogs varied dependently on the contents of HPC and EC. As compared with ordinary piretanide tablet on the market, the HPC-EC10 (5:3) microcapsule showed the controlled dissolution behavior, sustained plasma piretanide level, almost same AUC (area under curve), slow urinary piretanide excretion, decreased urine excretion maximum rate, and no difference in the cumulative urine volume and cumulative urinary electrolytes (Na+, K+, Cl-) excretion. HPC-EC microcapsules containing piretanide sufficiently satisfied the conditions which slow-release preparations must have.

Animals↗

The effect of bile salts on the oral mucosal absorption of human calcitonin in rats.

The relationship between the inhibition of the degradation of human calcitonin (HCT) in the supernatant of the rat's oral mucosa homogenate and the promoting effect on the rat's oral mucosal absorption of HCT was investigated by using ten kinds of sodium bile salts. The promoting effects and the inhibition of the degradation by the dihydroxy bile salts were related to the hydrophobicity, respectively. The inhibition of the degradation of HCT was related to the promoting effect on the oral mucosal absorption of HCT in the presence of the dihydroxy bile salts and to the concentration of the bile salts. Furthermore, the micelle formed by the bile salts would be concerned with the inhibition of the degradation of HCT.

Absorption↗

Determination of acetaldehyde in human blood by high-performance liquid chromatography using fluorometry.

A method was developed for the measurement of acetaldehyde in human blood by high-performance liquid chromatography (HPLC). The method was based on a pre-column reaction; a fluorescent substance was formed by a coupling reaction between 2 mol of cyclohexan-1,3-dione and 1 mol of acetaldehyde with ammonium acetate. The coupling compound was analyzed by HPLC and the concentration of acetaldehyde was obtained from the calibration curve drawn from the results using standard solutions. The determination was sensitive and reproducible with a range of 0.2-10 microM and a precision (coefficient of variation) of 2.43%.

Acetaldehyde↗

Biopharmaceutical evaluation of sustained-release ethylcellulose microcapsules containing amoxicillin using beagle dogs.

A beta-lactam antibiotic, amoxicillin, was microencapsulated with ethylcellulose using a solvent evaporation process in liquid paraffin containing sorbitan tristearate as a dispersing agent, and the microcapsules obtained showed first-order drug release. Usage of the previous log-log relationship of cefadroxil between in vitro dissolution half-lives (T50) and the experimental release rate constants (k'r) of the drug in vivo, and the nomogram for the design of satisfactory sustained-release preparations resulted in the prediction that ethylcellulose microcapsules containing 60% amoxicillin would show the most effective sustained-release pattern. Prepared microcapsules containing various amounts of amoxicillin were administered to beagle dogs and it was found that above prediction was correct. In addition, a more precise log-log correlation concerning amoxicillin was also undertaken, good linearity was observed and the decline was very similar to that of cefadroxil.

Amoxicillin↗

Occupational asthma from cobalt sensitivity in workers exposed to hard metal dust.

Eight asthmatic patients who had no history of asthma before starting work in a hard-metal plant and eight control subjects (three atopic, three nonatopic asthmatic, and two normal volunteers) without a history of exposure to hard metal dust were subjected to provocation tests, skin tests, radioallergosorbent tests (RAST) and Farr test with cobalt. Four of the eight patients were atopic, and seven showed bronchial hyperresponsiveness to methacholine (BHR). Patch and intradermal skin tests with cobalt chloride (CoCl2) could not discriminate the patients from control subjects. All patients had positive reactions to CoCl2 in the provocation tests; two developed immediate asthmatic reaction (IAR), four late asthmatic reaction (LAR), and two dual asthmatic reaction (DAR), while the control subjects showed no reaction. Evidence of specific IgE antibodies to cobalt-conjugated human serum albumin (Co-HSA) was presented by four patients (RAST score greater than 2) based on comparison of serum samples from 60 asthmatic patients and 25 asymptomatic workers in the same plant. Positive serum samples selectively bound 57Co, and the test was blocked by nonlabled cobalt sulfate (CoSO4). These findings suggest the development of hard metal-induced asthma from cobalt sensitivity.

Adult↗

[Evaluation of the self-administered respiratory questionnaire recommended by the Japanese Labour Ministry based on the standardized interviewer-administered BMRC questionnaire].

The self-administered respiratory questionnaire on persistent cough or sputum prepared and recommended by the Japanese Labour Ministry to detect pneumoconiosis was evaluated and compared with the Japanese version of the standardized interviewer-administered respiratory questionnaire developed by the British Medical Research Council (BMRC). The two questionnaires were given to 800 subjects on the same day. Because the wording of the questions was similar, the two questionnaires yielded very similar results. In terms of the overall prevalence of persistent cough or sputum, no important differences could be demonstrated between the results of the two questionnaires. The results of this study indicate that the self-administered questionnaire has good concordance with the BMRC questionnaire. When compared to the BMRC questionnaire, the specificity of the self-administered questionnaire was found to be more than 99%, but the sensitivity was inferior to the specificity, being less than 80%. When confined to subjects with persistent cough or sputum for two years or more, the sensitivity was up to 84%. These findings suggest the responses of the subjects to the self-administered questionnaire tend to be negative. A validity of the self-administered questionnaire needs to be further studied among dust workers including pneumoconiotics.

Adult↗

[Pharmacokinetics of neocarzinostatin in patients with malignant glioma. Quantitative analysis of tissue concentration].

Because of technical difficulties, the pharmacokinetics of neocarzinostatin (NCS) have not been thoroughly evaluated in patients with malignant glioma. The authors produced anti-NCS antibody by immunizing rabbits with NCS and established a means of quantifying tissue levels of NCS with enzyme-linked immunosorbent assay. In one patient given a bolus injection of 1 mg of NCS intra-arterially, the concentration of drug in neoplastic tissue at 25 minutes (0.1136 micrograms/g) was higher than that in blood at 20 minutes and was retained for a longer period. Rapid entry of NCS into the tumor cavity was observed at 5 minutes. In two postoperative cases, NCS applied topically to the tumor site (50 and 100 micrograms) was retained at high levels (0.2941 and 3.33 micrograms/ml) even after 48 hours, although no NCS was detected in blood after 60 minutes. NCS concentrations as low as 1 microgram/ml demonstrated cytocidal effects, and a delay in tumor growth was observed even at an NCS level of 0.1 microgram/ml, despite the fact that the half-life of NCS is extremely short (3 seconds in serum). Because its cytotoxic effect seems to be very rapid, it appears more important to obtain a high initial NCS concentration than to maintain a constant blood level.

Animals↗

[Uptake and localization of neocarzinostatin in malignant glioma. Experimental study by immunofluorescent staining method].

The authors studied the localization of neocarzinostatin (NCS) in cultured cells and in tumor-bearing rats by means of immunofluorescent staining. Anti-NCS antibody was obtained through immunization of rabbits with NCS. Cellular uptake of NCS was dose-dependent (1.0 to 1000 micrograms/ml) in 9L rat gliosarcoma cells in monolayer. In monolayer cells of 9L, KMG-4 (derived from human glioblastoma), and KMS II (human ependymoma) treated with 1 mg/ml of NCS, drug uptake occurred within a few seconds. Accumulation was much higher in the cytoplasm than in the nucleus and, although nuclear uptake increased slightly over time, there appeared to be no increase in total cellular uptake. Mitotic cells, which were spherical in culture, showed greater intracellular accumulation than other cells. There was no significant difference in uptake among non-mitotic cells. Cells surviving 20 hours of treatment retained accumulation as high as that in killed cells. In KMG-4 monolayers, cytoplasmic and nuclear NCS distribution still differed, whereas 9L monolayers exhibited more even intracellular distribution. In 9L spheroid models treated with 1 mg/ml of NCS, the drug permeated almost all layers within 10 minutes, and at 120 minutes had heavily accumulated in the central necrotic areas. In rats with transplanted brain tumors, NCS selectively accumulated in neoplastic tissues following intra-arterial administration. However, NCS uptake by arterial endothelium was also seen, which suggests the potential for vascular toxicity. The therapeutic value of NCS is discussed in terms of its pharmacokinetic characteristics.

Animals↗

[Salvage chemotherapy with a combination of VP-16, ifosfamide, procarbazine, prednisolone, bleomycin and methotrexate (VIPP-BM) for refractory malignant lymphoma].

Twenty patients with refractory malignant lymphoma were treated with a combination of VP-16, ifosfamide, procarbazine, prednisolone, bleomycin and methotrexate (VIPP-BM) as salvage chemotherapy. These patients were either resistant to front-line therapy or refractory in their relapses. Two patients (10%) achieved a complete remission and eleven patients (55%) attained a partial remission. An overall response rate was 65%. Major toxicities were myelosuppression, nausea and vomiting, and mucositis. However they were well tolerated. This regimen has been effective in the treatment for the patients with refractory lymphoma.

Adolescent↗

[Statistical analyses of clinical observations made on outpatients visiting the Department of Oral Diagnosis, Meikai University School of Dentistry Hospital, for the past 16 years].

Statistical analyses of clinical observations made on outpatients visiting the Department of Oral Diagnosis, Meikai University School of Dentistry Hospital from June, 1970, to August 1986 were carried out. The total number of new outpatients during this period was 73,708. The results were as follows: 1) The largest number of patients was found in 1978. 2) There was a tendency for the number of new patients to increase in March, June, and August of every year. The smallest number of patients came in December. 3) The greatest number of new patients visiting the hospital was in the 0-9 age category, followed by those in the 20-29 and 30-39 age categories. 4) The greatest chief complaint of patients visiting the hospital was pain, followed by masticatory disturbance and swelling. 5) The number of outpatients coming to the hospital for cosmetic and temporomandibular joint problems has been increasing on a yearly basis over the past 16 years.

Adult↗

A method for differentiating between monozygotic and dizygotic twins.

It has become possible to accurately differentiate monozygotic from dizygotic twins. In this study DNA fingerprinting was performed with new mini-satellite DNA as a probe. Identical DNA fingerprints from each twin indicate a monozygotic relationship and different fingerprints indicate a dizygotic relationship. In a case of dizygotic twins, the DNA fingerprints digested with HinfI indicated a monozygotic relationship, whereas the DNA fingerprints digested with MboI showed a dizygotic relationship.

DNA↗