[Biochemical aspects of protease treatment in chronic inflammation].
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Biomedical subjects
Publications and source records attributed to S Fujisaki.
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Nine cases of mixed mesodermal tumor of the uterus were reviewed cytologically. Abnormal cytologic findings were seen in all cases, but malignant cells were detected in only 17 of 30 cytologic smears sampled prior to the therapy (2 of 7 pool smears, 2 of 3 portio rubbing-smears, 6 of 8 endocervical smears and 7 of 12 tumor-rubbing smears). The most commonly encountered cellular components were epithelial malignant cells which showed a close resemblance to those derived from uterine carcinomas, but tended to have multiple nuclei. In other cytologic components, a rhabdomyosarcoma was characterized by large, isolated, round or strap-shaped malignant cells with granular cytoplasms, bizarre and eccentric nuclei and one or more prominent nucleoli. Another infrequent cellular component was a fibrogenic sarcomatous cell which had an illdefined lacy cytoplasm and single or multiple nuclei containing rather finely granular chromatin, and occasionally formed a cluster. In several cytologic specimens, there were also seen multinucleated giant cells which were not in keeping with their histologic origins.
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A pregnancy with placental sulfatase deficiency was suspected when a 31-year-old patient at 36 weeks of gestation was found to have extremely low urinary estriol excretion but an otherwise normal prenatal course. The maternal plasma level of estrogens was extremely low, whereas dehydroepiandrosterone sulfate (DHA-S) was normal. Following intravenous infusion of 100mg DHA-S, no rise in urinary or serum estrogens was noted. At 40 weeks of gestation, a male infant was delivered vaginally. In vitro incubation study confirmed the diagnosis of placental sulfatase deficiency. Arylsulfatase C activity was not demonstrated in sulfatase deficient placenta, whereas arylsulfatase C activity was detected in the cytoplasma of syncytiotrophoblast cells of all normal placentas, by light and electron microscopy.
The method for the preparation of zymosterol was improved (13 mg of zymosterol/g dry cells) by the aerobic adaptation of the cells in the presence of 1 mM DL-ethionine. Lanosterol was also found to accumulate (5.0 mg/g dry cells) when the cells were adapted aerobically in the presence of 10(-4) M buthiobate. Pure lanosterol could be obtained by separation of the unsaponifiable lipids on TLC. Pure [14C]lanosterol with a high specific radioactivity (56 Ci/mol) could be prepared by incubation of the desiccated cells with [14C]isopentenyl pyrophosphate, cofactors such as ATP and NADPH-generating system, and buthiobate in phosphate buffer. The method using desiccated cells may also be applicable to the preparation of other radioactive sterol intermediates.
Upon rehydration of lyophilized E. coli cells with phosphate buffer containing [14C]isopentenyl pyrophosphate, 14C was incorporated into the cells. Radioactivity was found in prenylquinones and some polyprenyl phosphate derivatives. Evidence was obtained suggesting that the latter compounds were interconverted to each other and that the "lipid cycle" operated in these cells.
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Fifty-four patients with carcinoma of the cervix uteri were treated with external irradiation and high-dose intracavitary irradiation according to their clinical stage. The 4-year relative survival rate was 86.6% in stage I patients, 77.9% in stage II, 55.4% in stage III and 0% in stage IV. The incidence of radiation injury was: perforation of the intestine, 2 cases; vesico-vaginal fistula, 2 cases; recto-vaginal fistula one case; stenosis of the rectum or sigmoid, 2 cases. This suggests that severe complications may occur in reirradiated cases or cases irradiated with more than 7 fractions of intracavitary irradiation. The optimal radiation dose seemed to be 2,400 to 3,000 rad at point A with a fraction dose of 600 rad a week, combined with whole pelvis irradiation of 3,000 to 4,000 rad.
The semen characteristics, before and after varicocelectomy, were studied in 220 husbands from infertile couples, whose wives had no significant abnormalities. All couples were followed for one year or until the wife became pregnant. Sperm density, vitality, motility and percent with normal morphology were analysed before surgery. Based on these results, subjects were divided into 2 groups according to whether their semen had normal or abnormal characteristics. The group with semen had normal or abnormal characteristics. The group with semen parameters within normal limits showed significantly less improvement after surgery, and the posttreatment pregnancy rate was independent of the effect of surgery on the characteristics of sperm. Between 71 and 84% of the subjects with abnormal semen characteristics showed improvement after surgery, and between 56 and 72% of those who improved, impregnated their wives. Subjects whose abnormal semen characteristics did not improve after surgery, had a very low pregnancy rate.
A number of studies have been reported providing indirect evidence of maternal immune response to fetus based on the data from peripheral blood of pregnant women, but little information is available on maternal local immune response at the endometrium involved in control of fetus rejection occurring around the time of implantation. Proliferative response of lymphocytes was measured in phytohemagglutinin (PHA)-stimulated cultures in the presence of prostaglandins of the E series (PGE). When present in the culture at concentration of 10(2) ng/ml, physiological level in the secretory endometrium, PGE inhibited H3-thymidine (H3-TdR) incorporation by 50% of the control. The inhibitory effect was found not to be antagonized by polyphloretin phosphate or di-4-phloretin phosphate. Thus, effects of PGE in the endometrium on lymphocytes and uterine smooth muscle appear to be independent processes. When PGE was added at the beginning of culture, H3-TdR incorporation was suppressed most markedly. However, when added late during the activation process, the suppression was reduced. When PGE was in culture for 12 h and was removed by washing the cells before the addition of PHA, the effect of PGE was negated. These data indicate that effect of PGE affect the early period of the inductive phase of the immune response and is reversible. The significance of such a effect of PGE is discussed in connection with the nonspecific immunosuppression in the secretory endometrium preceding nidation.
The nonspecific cell-mediated immunocompetence of 51 patients with gestational trophoblastic disease (GTD), including 16 patients with hydatid mole (HM), 24 with nonmetastatic trophoblastic neoplasia (NTN) and 15 with metastatic TN (MTN), was studied with the use of both in vitro and in vivo parameters of cell-mediated immunity (CMI) such as lymphocyte blastogenic response to phytohemagglutinin (PHA), subpopulation constitution, and delayed cutaneous hypersensitivity responses to 2,4-dinitrochlorobenzene (DNCB) and to purified protein derivative of tuberculin (PPD). The pretreatment cell-mediated immune status of patients with HM developing no malignant sequelae was shown to be essentially similar, in terms of both in vitro PHA and in vivo DNCB reactivities, to that of normal women and of patients with benign gynecological diseases. In patients with TN, however, there was a significant depression in the blastogenic lymphocyte response to PHA before evacuation of the mole, which was persistently demonstrated after uterine evacuation and more marked throughout the course of disease in patients with MTN, than in those with NTN, with a tendency to return to normal in remission. Moreover, patients with TN had a significant depletion of T lymphocytes as determined by rosette-forming cell procedures before treatment, which was most evident in patients with MTN. Plasma from the MTN patients was also shown to have an inhibitory effect on PHA responsiveness of lymphocytes from normal women. There was an increased incidence of impaired reactivity to DNCB in patients with TN (higher in MTN than in NTN), compared with HM and benign diseases, while no such difference in incidence was observed in response to PPD. On the basis of these findings, a preliminary characterization of altered immunocompetence in patients with TN and its mechanism are discussed.
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The function of thymus-dependent lymphocytes (T lymphocytes) was studied in women during pregnancy and labor and postpartum by evaluating the blastogenesis of peripheral lymphocytes, which were stimulated with phytohemagglutin-P (PHA-P) in both whole-blood semimicroculture and purifed lymphocyte culture. Data from 353 random samples (203 women) and 50 serial specimens from 10 women revealed that PHA-P induced-lymphocyte blastogenesis was significantly (p less than 0.005) reduced during pregnancy and labor but rapidly returned to normal several days after artificial termination in the early stage of pregnancy as well as after full-term delivery. These results indicate that the T-lymphocyte function in maternal peripheral blood is depressed by causes related to pregnancy. It seems very likely that depressed T-lymphocyte function during pregnancy is caused by inhibitory factors in the blood plasma derived from the feto-placental unit. Questions relating to the inhibitory factors in maternal plasma are discussed.
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