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Biomedical subjects

M Maegawa

Publications and source records attributed to M Maegawa.

At least 37 records · Page 2Linked to original sources

Enzymatic activation of immunoglobulin binding factor in female reproductive tract.

Human seminal plasma and cervical mucus contains an immunoglobulin binding factor (IgBF) which interacts with IgG as monomers under reducing condition. It may play a role in preventing antibody production against allogeneic sperms in the female reproductive tract. However, since IgBF is secreted as a homodimer that does not bind IgG, in vivo activation systems should be investigated. GSH reduces the inactive native dimer to the active monomer. Protein disulfide isomerase (PDI), a molecular chaperone, alters the configuration of dimers to active monomers. 20S proteasomes produced by activated T cells which cleave the dimers in the presence of GSH to active fragments. All these activating systems are widely distributed as cellular enzymes in vivo. Also PDI mRNAs are expressed in uterine cervix, endometrium and fallopian tube. Since these enzymes are produced upon stimulation by the immune system, we hypothesize that immunocompetent cells interact with allogeneic sperms, leading to the local production of these enzymes that will activate IgBF.

Cervix Mucus↗

IL-1 alpha induces inducible nitric oxide synthase in uterine smooth muscle.

In a previous report, we have identified interleukin-1 alpha (IL-1 alpha) in amniotic fluid of women with premature rupture of the amniotic membrane (PROM), and suggested that this cytokine may play a role in the development of the fetus. To clarify the functional role of amniotic IL-1 alpha, we studied its effect on the induction of nitric oxide (NO) synthesis in the uterus. IL-1 alpha administered intraperitoneally to rats induced an increase in the amount of mRNA encoding the macro-phage-type iNOS which was determined by reverse transcription-polymerase chain reaction. NO measurement by NO selective electrode revealed that NO production in the rat and human uterus treated with IL-1 alpha was promoted by the addition of 1 mM L-arginine to the culture medium. These findings suggest that in women with PROM, amniotic IL-1 alpha may reduce uterine contractions, in part, by inducing of iNOS.

Animals↗

[Clinical results of combination chemotherapy with cisplatin, vinblastine and bleomycin (pvb) for advanced testicular cancer: evaluation of risk criteria].

Between 1982 and 1991, 24 patients with advanced testicular germ cell tumor were treated by combination chemotherapy with cisplatin, vinblastine and bleomycin (PVB). Based on short-term efficacy of the PVB regimen and long-term prognosis in our patients, we evaluated 4 risk criteria proposed by Indiana University, National Cancer Institute (NCI), Memorial Sloan-Kettering Cancer Center (MSKCC) and European Organization for Research and Treatment of Cancer (EORTC). Clinical staging were IIA in 8 patients, IIB in 8, IIIA in 1, IIIB in 5 and IIIC in 2. Metastases included retroperitoneal lymph node in 20 cases (> 5 cm in 10), lung in 6, bone and liver in each 1. Complete response (CR) was obtained in 12 (50%) patients and partial response (PR) in 9 (38%). According to the stage and metastatic site, CR was achieved in 75%, 38% and 38%of the stage IIA, IIB and III tumors, respectively, and in 60% and 50% of retroperitoneal and pulmonary metastases, respectively. However, neither CR nor PR was recognized for live and bone metastases. Prognosis was assessed with a mean followup period of 88.5 months. Although all 12 patients with CR were alive, 4 of the 9 with PR and all patients on whom the drug was ineffective died of cancer. Accuracy in predicting prognosis was 82%, 75%, 74%, and 63% using the MSKCC, Indiana, NCI and EORTC risk criteria, respectively.

Adolescent↗

Effect of IL-1 in amniotic fluid on the fetal keratinocyte.

IL-1 alpha is predominantly increased in amniotic fluid of the patients with premature rupture of the membrane (PROM). In the present study we examined the effect of IL-1 on the fetal keratinocytes, one of the main tissue exposed to the increased IL-1. Exposure of IL-1 at over 0.1 pg/ml IL-1 significantly (p < 0.01) inhibited proliferation of the keratinocytes in low calcium keratinocyte growth medium obtained from the umbilical cord. Immunohistochemical analysis using antibodies to various cytokeratins revealed that the umbilical cord keratinocytes is more similar to the mucosal epithelium than the skin epithelium. These results suggest that IL-1 alpha increased in amniotic fluid in the PROM cases leads the immature proliferating mucosal epithelium to maturate for protection of the fetus against environment.

Amniotic Fluid↗

High implantation rate and consequently high pregnancy rate by in vitro fertilization-embryo transfer treatment in infertile women with antisperm antibody.

OBJECTIVE: To examine the effect of antisperm immunity on postfertilization steps, such as implantation of embryos and fetal growth in IVF-ET treatment of women with sperm-immobilizing antibodies. DESIGN: Retrospective analysis of clinical laboratory data. SETTING: The IVF-ET program of the Department of Obstetrics and Gynecology. The University of Tokushima, School of Medicine. PATIENTS: Eighteen women with sperm-immobilizing antibodies and 122 infertile patients with nonimmune etiology as controls. Infertile couples due to a male factor and with unknown etiology were excluded. INTERVENTIONS: All patients received the same IVF-ET program with GnRH agonist. MAIN OUTCOME MEASURES: Rates of fertilization and cleavage, implantation rate per embryo transferred and pregnancy rate (PR) in both test and comparison groups. RESULTS: The rate of fertilization in the antisperm group (61.3%) was significantly lower than that in the comparison group (76.8%). But the implantation rate per embryo transferred (23.5%) and consequently the modified PR per oocyte recovery procedure (34.4%) in immunologically infertile women were significantly higher than those in the comparison group (7.9% and 17.8%, respectively). CONCLUSIONS: Although sperm-immobilizing antibodies prevent sperm-egg interaction, they do not seem to have any adverse effects on achievement of pregnancy. Moreover, the existence of antisperm immunity in woman with antisperm antibodies is suggested to be favorable for successful pregnancy by the IVF-ET procedure.

Adult↗

Immunoglobulin binding factor: a new tumor marker for prostatic tumors.

Human seminal plasma contains an immunoglobulin gamma binding factor (IgBF) with an estimated molecular weight of 16 kD under reducing condition. IgBF was detected only in the prostate, including benign prostatic hypertrophy (BPH) and neoplasm. The present study was performed to determine whether IgBF is a useful prostatic marker. Serum IgBF levels were measured in patients with prostatic tumors and in control patients without tumor by radioimmunoassay. Serum prostatic-specific antigen (PSA), the standard prostatic marker, was also determined. Serum IgBF levels in patients with prostate cancer were significantly higher than those in age-matched controls (P < 0.05). Also, patients with BPH tended to have elevated IgBF levels than the controls, although the values were not statistically significant. In control patients, serum IgBF levels increased with advancing age. There was no correlation between serum levels of IgBF and PSA in patients with prostate cancer. Using cut-off level at 28.5 ng/ml (2 S.D. above the mean IgBF level of age-matched control), the sensitivities were 41.2% (7/17) for prostate cancer, 23.1% (6/26) for BPH, and 5.6% (1/18) for control patients. In conclusion, serum IgBF is a useful marker in the diagnosis of patients with prostatic tumor, and in evaluating the course of treatment.

Adolescent↗

[Evaluation of clinical efficacy and safety of cefpodoxime proxetil (CPDX-PR) in acute uncomplicated cystitis].

One hundred and fifty female patients with acute uncomplicated cystitis were given 200 mg of CPDX-PR twice daily for 3-7 days to evaluate both its overall clinical efficacy and its adverse effects. In 82 cases (Group I) in which it was administered for 3 days, the overall clinical efficacy, evaluated by the criteria proposed by the Japanese UTI committee, was excellent in 64 cases, moderate in 17 and poor in one, with the effective rate being 98.8%. In 35 cases (Group II) in which it was administered for 4-7 days, the overall clinical efficacy was excellent in 18 cases, moderate in 15 and poor in 2, with the effective rate being 94.3%. The overall clinical evaluation was not performed in another 33 cases because they were given CPDX-PR for more than 8 days or 300 mg/day. Subjective adverse effects such as hoarseness and lingual inflammation were observed in only one of the 150 cases, but they disappeared spontaneously after the cessation of administration of CPDX-PR. These findings suggest that CPDX-PR is one of the most effective and safe antibiotic in the treatment of acute uncomplicated cystitis.

Acute Disease↗

Detection of immunoglobulin binding factor by enzyme-linked immunosorbent assay using two monoclonal antibodies.

Immunoglobulin binding factor (IgBF) found in human seminal plasma may be involved in suppressing antibody production against sperm in the female and male genital tracts. In the present study an enzyme-linked immunosorbent assay (ELISA) for IgBF was developed using monoclonal anti-IgBF antibodies. The sensitivity of the method was 20 pg/ml. The method was used to quantify IgBF in sera from women. In addition high levels of IgBF was found in cervical mucus of the uterus and in bronchial washings. The present results suggest that IgBF is found in tissues that are exposed to the external environment and may be a component of the local immunity system.

Adult↗

[Clinical evaluation on renal pelvic and ureteral tumors].

We report 82 patients with renal pelvic and ureteral tumors admitted to Kyoto Prefectural University of Medicine, Kyoto Second Red Cross Hospital and Shakai-Hoken Kyoto Hospital between January, 1981 and December, 1991. Sixty two were males and 24 were females, and they were between 47 and 93 years old (average: 68.2 years). The tumor occurred on the right side in 34 patients, on the left side in 51 patients and on both sides in one patient. There were 43 renal pelvic tumors, 37 ureteral tumors and 6 renal pelvic with ureteral tumors. The most frequent symptom was macrohematuria, which was seen in 54 patients (62.8%). Urinary cytology was performed in 76 patients and a positive result was obtained in 44 patients (57.9%). We performed surgical treatment on 71 patients. The most frequently adopted method was total nephroureterectomy with partial cystectomy which was performed on 51 patients (71.8%). Of the 73 specimens diagnosed histopathologically, 71 specimens were transitional cell carcinoma (TCC), one was a squamous cell carcinoma (SCC) and one was a mixed type of TCC and adenocarcinoma. As to grading, 6 specimens were G1, 28 G2, 38 G3 and one GX. As to staging, 8 specimens were pTa, 17 pT1, 21 pT2, 18 pT3, 8 pT4 and one pTX. The overall survival rate (by Kaplan-Meier's method) at 3 and 5 years was 47.0% and 39.5%, respectively. The patients with high grade tumors and those who had ureter preservation, the survival rate was lower than in the other patients.

Aged↗

[Clinical evaluation of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy for advanced urothelial cancer].

M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy was performed on 27 patients with advanced urothelial cancer. The patients included 20 with bladder cancer, 4 with upper urinary tract cancer and 3 with both lesions. Complete response (CR) was observed in 2 (7.4 +/- 9.9%) patients and partial response (PR) in 10 (37.0 +/- 18.2%) patients after the treatment, i.e., the overall objective response rate was 44.4 +/- 18.7%. The rate of relapse or recurrence in the patients with CR and PR was 100% and 90.0%, respectively. The mean duration of the response was 18.5 +/- 13.4 months and 10.7 +/- 10.9 months for CR and PR, respectively. The overall survival rate after one year was 30.2%. Bone marrow suppression was the most serious side effect. The white blood cell count became below 1,000/microliters in 10 patients (36.7%). Among them, 4 patients suffered from sepsis. In conclusion, M-VAC chemotherapy was effective for induction therapy against advanced urothelial cancer, although the effective duration was short. Further maintenance therapy should be established.

Adult↗

Immunosuppressive 30-kDa protein in urine of pregnant women and patients with trophoblastic diseases.

Urine samples obtained from normal pregnant women and patients with trophoblastic diseases contain 30-kDa protein that suppresses phytohemagglutinin-induced T cell proliferation. The immunosuppressive protein was measured by a newly developed radioimmunoassay. The 30-kDa protein was demonstrated in almost all urine samples examined, fluid from hydatid vesicles and chorionic extracts, but not in any serum samples except at low levels in some sera from patients with choriocarcinoma. During pregnancy, the level of urinary 30-kDa protein was higher in the first (1625.5 +/- 1212.0 ng/ml, mean +/- S.D.) and second (1457.4 +/- 1332.4 ng/ml) trimesters than in the third trimester (460.6 +/- 419.0 ng/ml). The urinary 30-kDa protein/hCG ratios in patients with choriocarcinoma (8.3 +/- 10.9) were significantly higher than those in patients with hydatidiform mole (0.67 +/- 1.00, P < 0.01) and in all trimesters than those of normal pregnant women (0.54 +/- 0.44 in first trimester, P < 0.05; 0.63 +/- 0.46 in the second trimester, P < 0.05; 0.24 +/- 0.17 in the third trimester, P < 0.01). There is no significant difference between the ratios in hydatidiform mole and normal pregnancy. These findings and the fast disappearance of the 30-kDa protein from the circulation suggest that the 30-kDa protein plays a part in proliferation of trophoblastic cells in, or their invasion into the host by locally suppressing the immune reaction of the host and that the increase in the urinary 30-kDa protein level, in cases of choriocarcinoma, may be due to the malignant transformation of trophoblastic cells resulting in their rapid invasion.

Female↗

Blocking of human fertilization by carbohydrates.

The zona penetration test and triple stain technique were used to elucidate the blocking effects of carbohydrates on human fertilization and their mechanisms. In the presence of D-mannose or D-fructose (final concentration, 50 mmol/l), sperm penetration through the human zona pellucida was completely blocked. The triple stain technique revealed that D-fructose (50 mmol/l) significantly (P < 0.01) suppressed the acrosome reaction of human spermatozoa, while D-mannose did not show a suppressive effect on the acrosome reaction. These results reinforce our hypothesis proposed previously, that a mandatory step in human fertilization is the binding of a D-mannose-binding constituent of the sperm surface to a D-mannose residue in the sperm receptor site on the zona pellucida. In addition, D-fructose may play an important role as an acrosome stabilizing factor in seminal fluid.

Acrosome↗

Difference of the hormonal profile at the periovulatory phase in pregnant and nonpregnant cycles of infertile women with unexplained etiology.

Ten women with unexplained infertility, who conceived by intrauterine insemination (IUI) or timed intercourse under controlled ovarian hyperstimulation, were analyzed to investigate the difference of hormonal environment at the periovulatory phase. Forty-two cycles were divided into three groups: the pregnant cycle group, the high luteinizing hormone (LH) group (LH > or = 60 mIU/ml on day -1: the day of human chorionic gonadotropin administration) of nonpregnant cycles and the low LH group (LH < 60 mIU/ml on day -1) of nonpregnant cycles. Progesterone (P4)/estradiol (E2) ratios of the high LH group on day -1 and day 0 were significantly higher than those of each corresponding day in the pregnant cycle. On the other hand, P4/E2 ratio of the low LH group on day +1 was significantly lower. P4/E2 ratio but absolute level of each hormone showed a high indicative value for the estimation of abnormal hormonal environment. It is concluded that the P4/E2 ratio at the periovulatory phase is a good parameter to estimate the efficacy of the method for ovulation induction.

Adult↗

Effective prophylaxis of thrombosis by antithrombin III concentrate in a pregnant woman with congenital antithrombin III deficiency: relations between plasma antithrombin III activity and the plasma levels of hemostatic molecular markers.

The value of antithrombin III (AT III) concentrate and a standard criterion for its use were examined in a pregnant woman with congenital AT III deficiency by continuous monitoring of plasma AT III activity and the plasma levels of hemostatic molecular markers. The rates of improvement of various markers after AT III administration (frequency of improvement/frequency of administration) were as follows: fibrinopeptide A (FPA) 82%, D-dimer 70%, fibrinopeptide B beta 15-42 73%, beta-thromboglobulin 60%, and platelet factor 4 50%. There was no significant correlation between the plasma AT III activity and all plasma FPA values, but FPA values of over 3.9 ng/ml showed a significant negative correlation with AT III activity: AT III activity (%) = -6.59 x FPA (ng/ml) + 125, r = -0.851, p less than 0.02. We therefore recommend continuous monitoring of the plasma FPA level and administration of AT III concentrate when the FPA level is elevated. According to the regression line shown above, plasma AT III activity should be raised to 100% to keep the FPA level below 6.0 ng/ml with 95% confidence limit.

Adult↗

[PVB therapy for advanced testicular cancer].

Twelve cases of advanced testicular cancer, including 5 cases of seminoma, 3 cases of teratocarcinoma, 1 case of yolk sac tumor, 1 case of embryonal carcinoma and 2 cases of mixed cell type, were treated with cisplatin-vinblastine-bleomycin (PVB) therapy. Among them, 10 cases had measurable metastatic lesions and the objective response rate was 80%. Three cases showed complete response. Ten cases showed nonexistent disease after PVB therapy and salvage operation. Though PVB therapy was useful for the treatment of advanced testicular cancer, a few cases having poor prognostic factors showed no response to the therapy.

Adult↗

Immunohistochemical evidence of serotoninergic regulation of vasoactive intestinal polypeptide (VIP) in the rat suprachiasmatic nucleus.

By applying a double-immunolabeling technique to preembedded tissue preparations, we demonstrated the existence of serotoninergic innervation to neurons containing vasoactive intestinal polypeptide (VIP) in the rat suprachiasmatic nucleus (SCN). Immunoreactivity for serotonin and VIP was revealed by the presence of diaminobenzidine (DAB) reaction products and silver-intensified DAB reaction products, respectively; in a further stage, the silver grains were substituted with gold particles. DAB reaction products were precipitated on the surface of vesicular structures, while gold particles were scattered diffusely throughout the neuroplasma at various densities. Serotoninergic axons were numerous and closely packed together, occasionally forming synaptic junctions with gold-labeled VIP-containing neurons. At these synaptic junctions, small vesicular structures accumulated to form a coat under the presynaptic membrane, and the postsynaptic membrane was lined with a homogeneous accumulation of fine deposits. This postsynaptic apparatus varied in appearance; some parts were flat and thin, while others were of irregular thickness. Serotoninergic fibers also formed synaptic junctions with unidentified neurons, in which postsynaptic membrane specialization was also observable. As VIP-containing neurons are known to be synapsed by somatostatin (SRIH)-containing neurons, their regulation must involve both serotonin and SRIH at least.

3,3'-Diaminobenzidine↗

Differential immunolabeling for electron microscopy of diverse peptidergic neurons.

We describe a simple and reliable method for differential immunolabeling of pre- and post-synaptic signal peptides at the ultrastructural level. Hypothalamic tissues of rats, including the suprachiasmatic nucleus, were cut on a Vibratome. Visualization of the immunolabeling of somatostatin (SRIH) and vasoactive intestinal polypeptide (VIP) was performed with avidin-biotin-peroxidase-diaminobenzidine (DAB). The end product of the DAB to VIP was further silver-intensified in a physical processing using silver nitrate, and the silver grains were finally substituted for gold. DAB-labeled SRIH fibers synapse on gold-labeled VIP perikarya and dendrites in the suprachiasmatic nucleus.

Animals↗