[Studies on the mechanism of human parturition].
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Biomedical subjects
Publications and source records attributed to H Okamura.
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A 59-year-old woman with recurrent malignant melanoma of the vulva has well responded to a combination of immunotherapy and chemotherapy. As an immunotherapy, 10KE OK-432 were injected into the tumor twice a week. Chemotherapeutic regimen consisted of intravenous push of 1 mg vincristine on day 1,100 mg dacarbazine from day 1 through 5 and 50 mg nitrosourea (ACNU) on day 5. This treatment was repeated with 4 week intervals. Before treatment, the patient had a 3 X 3 X 5 cm subcutaneous mass on the left vaginal wall near the introitus. Fifty percent objective reduction of the tumor was achieved 6 weeks after commencement of intralegional immunotherapy and chemotherapy, and the tumor almost disappeared 8 months later. At this time, the treatment was changed to a supportive immunotherapy with intramuscular injection of 1KE OK-432 twice a week. But the tumor began to enlarge 2 months later and the patient is now being treated with the same combination therapy. Major side effects were febrile episodes on the day of intratumor injection of OK-432 and nausea, vomiting during the interval of chemotherapy. Anemia was the main hematologic side effect, but leukocytopenia and thrombocytopenia were not severe. The combination of intratumor injection of OK-432 and chemotherapy seems to be effective for the treatment of malignant melanoma.
Respiratory distress syndrome (RDS) is believed to be caused by a deficiency of pulmonary surfactant. The surfactant, secreted by fetal lung into amnionic fluid, has been analyzed by a variety of methods, but none of these methods have been found accurate enough to be widely used. Dipalmitoylphosphatidylcholine (DP-PC), the major surface-active component of the surfactant, occupies more than 50% of the surfactant phospholipids. In this study, DP-PC isolated from amnionic fluid, was determined enzymatically. DP-PC started to increase gradually in amnionic fluid from 22nd week of gestation, showed rather rapid increase after 35th week of pregnancy, and reached to a value of 6.97 +/- 0.56 mg/dl (Mean +/- SEM, n = 117) between 38 and 42nd week of gestation. This increase of DP-PC during gestation was found to be quite similar to that of L/S ratio reported previously. Eight out of 10 infants with RDS had less than 1.0 mg/dl of DP-PC in the amnionic fluid, whereas 137 infants without any sign of RDS had more than 1.0 mg/dl of DP-PC except 5 cases. These results demonstrated that if more than 1.0 mg/dl of DP-PC was found in amnionic fluid before birth, the fetus could be judged to have mature lung with 96% accuracy. In addition the enzymic determination of DP-PC requires less time, rather easy and reliable method to be done in most general clinical laboratories with less cost. Therefore we believe this method will be widely used in near future for the detection of RDS before birth.
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In the previous study, using carbon tracer, we reported the ultrastructural evidences which suggested the increased capillary permeability of preovulatory rabbit ovarian follicles. In the present study, another tracer, horseradish peroxidase (HRP 50 A in diameter, mw. 40,000), being smaller than carbon particle, was used to examine the permeability of perifollicular capillaries. HRP left capillaries and appeared in the follicular cavity immediately after the injection into aorta, through all stages of follicular development. In the capillaries, the narrow interendothelial clefts (about 100-200 A in width) were observed through preovulatory stages. Fenestrations were noted at 3,4,6 hours after the hCG injection, and interendothelial gaps (about 1,000-10,000 A in width) were seen at 10, 12 hours. HRP passed through these structures and infiltrated the capillary basal lamina and the basal lamina of the follicle and went through the intercellular spaces between granulosa cells. Therefore, the increased permeability of perifollicular capillaries, just prior to ovulation, were not so obvious as when carbon particles were used. On the other hand, carbon particles, injected via marginal ear vein, were incorporated in the endothelial vesicles 15 min. after its administration and retained beneath the basal lamina outside the follicle within 60 min. These observations indicated that "blood follicle barrier" consisting of capillary endothelium, basal lamina, basal lamina of the follicle and granulosa layer played an inhibitory role to large molecules but not to small molecules.
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The microvasculature of rabbit ovarian follicles was investigated three dimensionally with resin casting/SEM technique. Characteristic vascular patterns were revealed around the follicles of various developing stages. It is suggested that increased capillary permeability and congestion of the blood stream occurred just prior to ovulation.
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A total of 20 hospitalized patients underwent orthopedic surgery in the Tokyo Metropolitan Police Hospital during the period from December 1981 to March 1982. These patients were treated with cefoxitin, mainly, for the prevention of postoperative infections. The following clinical findings were obtained. 1. Out of the 20 patients, 14 were judged 'good' and 6 'fair'. 2. No side effects were reported by the patients or were evident in the clinical data. 3. These clinical results indicated that cefoxitin is a very effective antibiotic for the prevention of postoperative infections in orthopedic surgery.
Uterine vascular architecture through estrus cycle of the rat was investigated by the microcorrosion casting/scanning electron microscopy method. Arterial system in the uterine horn was divided into two types, one of which consisted of circumferential artery with its branches extending to both side walls and an antimesometrial wall. The other system consisted of arterioles which turned into the vascular congromerate in the mesometrial triangle and then distributed their branches to the mesometrial wall. Both of two kinds of arterioles, the terminal arteriole in the myoendometrium and the larger arteriole composing the vascular congromerate, showed the circular impressions around them. Arteriovenous anastomosis was not observed in the uterus. During proestrus and estrus, uterine blood vessels were lengthened except for arterioles in the vascular congromerate, and the subepitherial capillary network became to be filled completely with resin and showed the signs of leakage. These changes reached the maximum in estrus, then subsided during the later part of the cycle. These observations suggest that different types of arterioles in the uterus have their own sphinctors, and maximum enlargement of the uterine vascular bed occurs in estrus concomitantly with increased capillary permeability.
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In order to examine the pathogenesis and histogenesis of leiomyomatosis peritonealis disseminata (LPD), guinea pigs were treated with various doses of estradiol benzoate (E) (40, 80, 100, and 200 microgram/day, three times a week, by intramuscular injection). After treatment for 3 months, each dose of E produced lesions simulating the disseminated pattern of LPD. Ultrastructurally, the nodules were considered to be composed of cells resembling those of fibroblast. In guinea pigs, pretreatment with estradiol benzoate (100 microgram/day, three times a week intramuscularly for 3 months followed by combination treatment with E and progesterone (P) (0.5 and 1.0 mg/day, once a week, intramuscularly) for 1 to 3 months produced nodules similar to those with estrogen alone. Ultrastructurally, these nodules were composed of cells resembling smooth muscle and decidual cells. According to these results, we conjectured that estrogen differentiates and proliferates cells with the features of fibroblast-like cells from the subcoelomic totipotential mesenchyme, and these cells are differentiated into smooth muscle-like cells and decidua-like cells under the influence of both estrogen and progesterone, resulting in the production of multiple subperitoneal nodules.
Collagenolytic enzyme activities presumed to play an important role in ovulation were investigated in the human follicular apex, base, and granulosa cell layer throughout the ovarian cycle. Those analyzed were human ovarian collagenase, 2,4-dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg-OH peptidase, N-carbobenzoxy-Gly-Pro-Gly-Gly-Pro-Ala peptidase, and alpha-N-benzoyl-DL-arginine beta-naphthylamide hydrolase. Collagenase activity was also measured in human granulosa cell cultures. The activities of all four enzymes showed a marked preovulatory decrease in the apex. The activities in the apex were slightly higher than those in the base throughout the ovarian cycle. However, the activities in the granulosa cell layer and collagenase activity in the granulosa cell cultures increased toward preovulation and decreased after ovulation. These findings suggest that collagenase is synthesized in the granulosa cells maximally at preovulation and is consumed in the follicular apex at the same time, resulting in collagen degradation and disruption of the follicular wall in collaboration with other collagenolytic enzymes investigated here.
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To obtain more exact knowledge of the adrenergic innervation around ovarian follicles at various stages, a combination of fluorescence and light microscopic observations of the same specimen was applied to the bovine ovary in the breeding season. We found no fluorescent nerve fibers in the membrana granulosa at any stages of follicular development. The sparse nerve fibers found in the theca interna of Graafian follicles were apparently those accompanying blood vessels, and such were considered not to play a significant role in the vasomotor control of follicular blood flow. The fluorescent fibers in the theca externa increased in density and intensity in the course of follicular development. This increase appears to coincide with the increasing contractility of the follicular wall around the time of ovulation.
Morphological and endocrinological studies were performed on a 19-year-old case of an arrhenoblastoma with marked virilization. The tumor was an intermediate type of Meyer's classification. Histochemically, 3 beta-HSD and G-6-PDH activities were demonstrated in Leydig cells. These cells also had ultrastructures typical of steroid-producing cells. Basal blood cells of pregnenolone, dehydroepiandrosterone, testosterone (T), androstenedione (A), progesterone, estradiol, estrone, LH, and FSH were determined pre- and postoperatively. T and A showed a very high level preoperatively, and were markedly decreased immediately after removal of the tumor. Stimulation of tumor cells by HMG-HCG did not show any significant changes in their main products of T and A. These findings suggest that Leydig cells of the present tumor produced mainly A and T independently on gonadotropins, and these hormones had virilized the patient.
To examine the possible roles of collagenolytic enzymes in the follicular wall at ovulation, we measured in rabbit ovaries collagenolytic enzymes by using synthetic substrates, DNP-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg OH supposed to be specific for vertebrate collagenase. Our results clearly demonstrated that DNP-peptidase activity existed, with its optimal pH7.6-pH7.8 in rabbit ovarian follicles. DNP-peptidase activity steadily increased for nine hours following the hCG injection. After nine hours of enzyme activity decreased sharply until about the tenth hour, at which time ovulation had occurred. This pattern of enzyme activities indicates that the DNP-peptidase was consumed for degradation of collagen fibers. After collagen fibers have been completely degraded, this enzyme was increased again. These changes of DNP-peptidase activities at ovulation were similar to cathepsin B1 activities with its optimal pH6.0. It is concluded that DNP-peptidase could be one of ovulatory enzymes in the rabbit.