In order to establish the cholera model of adult mice, the intestinal growth, colonization and toxin production of Vibrio cholerae 0:1 (V. c) in the mice treated with cimetidine and atropine sulfate were examined. Cimetidine, which is an inhibitor of histamine-stimulated gastric acid secretion, increased the susceptibility of mice to cholera toxin (CT) and made a condition to cause a high fluid accumulation by CT. The treatment with a combination of cimetidine and atropine sulfate enhanced the intestinal growth and colonization by V. c. Especially, the simultaneuos oral challenge with CT and V. c to the treated mice accelerated the intestinal growth and colonization of V. c significantly. In addition, the growth rate of V. c in the intestinal fluid of mice was equal to or higher than that in the enrichment culture medium for V. c. And 1 ng/ml of CT was produced by 3.7〜9.0×10^8CFU/ml of V. c in the intestinal fluid of mice after the cultivation for 20 h, 37℃.

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The study was undertaken to determine the daily hormonal changes during the pulsatile subcutaneous administration of human menopausal gonadotropin in 14 anovulatory patients. The hormonal changes in 15 pregnant cycles were compared with those found in non-pregnant cycles. The levels of serum luteinizing hormone, follicle-stimulating hormone, progesterone (P), and estradiol (E_2) up to the late luteal phase were significantly greater in the non-pregnant cycles than those found in the pregnant cycles. Especially, the levels of P and E_2 during pulsatile administration of hMG were significantly greater than those in normal spontaneous ovulatory cycles. However the P/E_2 ratio in the pregnant cycles was significantly greater than that in the non-pregnant cycles. These results demonstrate that the P/E_2 ratio, but not the levels of P and E_2, is an important factor for the process of implantation. Furthermore, pulsatile subcutaneous administration of hMG is effective in the induction of successful ovulation and establishment of singleton pregnancy in patients with various type of anovulatory infertility.

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The present study was undertaken to evaluate the role of X-ray CT (CT) for predicting the prognosis of cervical cancer. In 129 patients with cervical cancer, nine parameters were analyzed on the basis of the prognosis during 5 years-follow up period (75 cases of survivals, and 54 cases of deaths). (1) The incidence of abnormal CT findings in the patients with poor prognosis was significantly higher than that of the survivals in every 9 parameter. (2) CT score for prognostic discrimination of cervical cancer was prepared using multivariate analysis. The analysis revealed that four parameters (irregular and/or indistinct cervical margin, parametrial images, enlargement of the lymph nodes and extension toward the bladder) were valuable in estimation for the prognosis. The discrimination ratio for the prognosis of cervical cancer was 83.7 %. (3) The individual CT score obtained by the analysis showed the correlation with the survival months of the patients with poor prognosis (r=0.45, p<0.01). These results demonstrate that the CT findings of cervical cancer before treatment are very effective for predicting the prognosis as well as the clinical staging.

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As a series of studies of the arterial supply in the human muscle in our laboratory, flexor digitorum longus muscle (FDL) of ten Japanese adult bodies with twenty side cases are examined to explore the origin of nutrient arteries, the branching condition and the distribution area in this muscle in this paper. As this muscle is located at right inside of A. tibialis posterior propria (Tpp, SATO. '84), it is mainly supplied by Tpp. The branch of A. tibialis anterior (Ta. p) which ramifies just before it penetrats Membrana interossea cruris (mic), the branch of A. peronea (Pe) and A. tibialis communis (Tpc, SATO. '84) and Ramus perforans (Rpef) which branches off Ta, where Ta is going down in front of mic and is going through mic are distributed at a part of this muscle. 1) The following types are classified by the origin of the nutrient arteries and the distribution situation. Type I-a: only Tpp is distributed (30 %). Type I-b: Ta (Rpef) is added to type I-a (25 %). Type II-a: Ta. p is added to type I-a (20 %). Type II-b: Ta (Rpef) is added to type II-a (5 %). Type III-a: Pe is added to type I-a (5 %). Type III-b: Ta (Rpef) is added to type III-a (5%). Type IV-a: Tpc is added to type III-a (5 %). Type V-a: Tpc is added to type I-a (5 %). 2) The distribution area of nutrient arteries is as follows. Type I-a: Tpp (Rfdl) is 81.8 %, Tpp (om) 17.3 % and Tpp (Rco) 0.9 %. Type I-b: Tpp (Rfdl) is 69.6 %, Tpp (om) 21.1 % and Ta (Rpef) 9.3 %. Type II-a: Tpp (Rfdl) is 57.5 %, Tpp (om) 28.6 % and Ta 13.9 %. 3) Total numbers of nutrient artery were counted from 7 to 14 and the highest frequency of its appearance was 10 (35.0 %). 4) There are Type I and II: In the former the original tendon of this muscle does not cross over the insterted tendon of tibialis posterior, while in the latter the original tendon (Arcus tendineus inferior) of this muscle crosses over the inserted tendon of tibialis posterior like an arch and inserted by the lower end of Tibia. Each type shows 70.0 % (Male: 6 cases, Female: 8 cases) and 30.0 % (Male: 6 cases) in frequency, respectively.

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To assess the alterations of plasma prostaglandin F_2α during a normal menstrual cycle, plasma concentrations of 13, 14-dihydro-15-keto-prostaglandin F_2α (PGFM) were measured daily in the groups of 10 normally menstruating women without dysmenorrhea (A group) and 3 women with severe dysmenorrhea (B group) at least for one menstrual cycle. Plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E_2), progesterone (P) and prolactin (PRL) were measured and the endometria were observed by ultrasonography. The result obtained were as follows: 1. Changes in the concentrations of FSH, LH, E_2, P and PRL in the 13 women were normal, consistent with previous reports. 2. The concentrations of PGFM in the B group were about 5 times higher than those of the A group throughout menstrual cycle. The average levels of PGFM were slightly higher in the late follicullar phase and at the beginning of the menstruation than in the other stages of the menstrual cycle. In a woman of the B group soon after the use of indomethacin just prior to the onset of menstruation, the concentration of PGFM became as low as those in the A group. 3. There were no significant differences between the endometria in the A and B groups as observed by ultrasound. Ultrasonically the movement of the endometrium was seen to be remarkably active in the late follicular phase and at the beginning of the menstruation. In conclusion, our study suggests that the endometrium has a close relationship with the production of PGFM.

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Interleukin-1 (IL-1) and tumor necrosis factor (TNF) are one of the cytokines produced mainly by activated macrophages and play an important role as a mediater of inflamation. In recent years, it has also become clear that these cytokines activate the hypothalamic-pituitary-adrenal axis and increase the secretion of glucocorticoid. However, little is known about the effects of these cytokines on mineralcorticoid secretion. Therefore, the effects of IL-1 and TNF on the aldosterone secretion were investigated by the incubation of rat adrenal glomerulosa cells. Basal secretion of aldosterone was suppressed by IL-1, but not by TNF. This suppressive effect of IL-1 was potentiated by addition of TNF. The stimulative effect of angiotensin II (AII) on aldosterone secretion was not affected by IL-1 or TNF alone. However, when IL-1 and TNF were added simultaneously, AII induced aldosterone secretion was suppressed significantly. These observations indicate that through the direct effect on adrenal glomerulosa, IL-1 and TNF may play a role in the pathogenesis of hyperreninemic hypoaldosteronism cooperatively.

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Effects of intra-arterial injection of rat-atrial natriuretic peptide on hepatic tissue blood flow (HTBF) and mean blood pressure (MBP) were evaluated in normal and cirrhotic rats. HTBF was measured by the electrolytic hydrogen clearance method at, 0, 1, 10 and 20 min after bolus injection of ANP into the femoral artery. In normal rats, no significant changes was observed after injection of 10, 100 and 1000 μg/kg of ANP on HTBF. However, MBP fell significantly for 20 min after injection of 1000 μg/kg of ANP, while no significant change was observed with 10, or 100 μg/kg of ANP. In cirrhotic rats, HTBF increased by 20 % at 1 min after injection of 100 μg/kg of ANP (p<0.05), whereas it decreased by 17 % at 1 min after injection of 1000 μg/kg of ANP. No significant change was observed with 10 μg/kg of ANP. MBP fell significantly at 1 min after injection of 100 μg/kg of ANP and 20 min after injection of 1000 μg/kg of ANP respectively (p<0.01, p<0.01), while no significant change was observed with 10 μg/kg of ANP. These results indicate that the effect of ANP on HTBF is more prominent in cirrhotic than normal rats, and that the injection of ANP in a case of optimal dose induces an increase of HTBF in cirrhotic rats. Concerning THBF, ANP may be benefit in the therapy of patients with cirrhosis.

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The present study was undertaken to evaluate the significance of coagulation-fibrinolytic system on the prediction of the onset of toxemia of pregnancy. Coagulation-fibrinolysis kinetics in 40 patients with toxemia of pregnancy was compared with that of 128 normal pregnant women during the entire period of pregnancy. In normal group, serum levels of thrombin-antithrombin III complex (TAT) and FDP, and urine levels of plasmin-α_2-PI complex (PAP) increased as the pregnancy progressed, while serum α_2-PI activity decreased. Although these results indicated the acceleration of coagulation and fibrinolytic activities, serum levels of PAP showed no change during the entire period. In toxemic group, serum levels of PAP became higher than those of normal group prior to the onset of toxemia of pregnancy. Especially, the PAP levels in the second trimester increased significantly (p<0.05) as compared to those in the normal group. We tried to predict the onset of toxemia of pregnancy according to the positive serum levels of PAP (≧0.5 μg/ml). The accuracies were 61.8 % at the first trimester, and 72.4 % at the second trimester, respectively.

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We designed a new plethysmograph called "the electric impedance-cuff" for the indirect measurement of blood pressure and volume elastic modulus (Ev) in human finger arteries. This comprises a compression chamber filled with electrolyte solution and a tetrapolar electric impedance plethysmograph whose electrodes are placed inside the chamber; the former for controlling the transmural arterial pressure (Pt), and the latter for detecting its pulsatile volume variation (ΔVa). Systolic, mean, and diastolic arterial pressure and pulse pressure (ΔP) were simultaneously determined by this device. Ev was defined as ΔPI (ΔVa/V^^-a); where Va was mean arterial volume at a desired Pt level. Ranges of Ev values were statistically determined from the data collected in 194 healthy subjects (18-97 years old), 44 hypertensive, and 50 diabetic patients with respect to (1) Pt, (2) sex, and (3) age. Ev values significantly increased with Pt and age. There was a tendency that men showed a larger Ev than women, and arteriosclerotic patients showed a larger Ev than healthy subjects.

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Relationships between obesity or underweight and endocrine profile were assessed in 358 patients with ovulatory disorders; 83 cases with short luteal phase, 50 cases with anovulatory cycle, 91 cases with oligomenorrhea, 53 cases with secondary amenorrhea who showed uterine bleeding after progesterone administration (Ist grade Am), 71 cases with secondary amenorrhea who showed no uterine bleeding after progesterone administration (IInd grade Am), and 10 cases with primary amenorrhea. The results were as follows: 1. The onset of menarche significantly delayed in patients with ovulatory disorders compared with women with normal ovulatory cycle. 2. The incidence of obesity was the most frequent in the patients with Ist grade Am, whereas that of underweight was the most frequent in the patients with IInd grade Am. 3. The patients with Ist grade Am and the patients with anovulatory cycle were classified into two different groups based on the degree of obesity. However, there was no significant difference of basal levels of serum FSH, LH and PRL between the two groups. 4. The patients with IInd grade Am were classified into two different groups based on the degree of obesity. Significantly elevated basal levels of serum FSH, LH and PRL were seen in the group of obesity. 5. The patients with elevated basal levels of serum LH and PRL had a tendency of obesity. 6. The degree of obesity in women with normal ovulatory cycle was composed of one group with logarithmic normal distribution.

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We described a case of germanium dioxide (GeO_2)-induced nephropathy and polyneuropathy. A 20-year-old female had been taking the GeO_2-containing preparation to maintain her health for about 32 months (Ge intake, about 37 grams in total). She became to complain of epigastralgia, vomiting, dysesthesia on her lip and difficulty in walking from February 1987. In November 1987, she admitted to the Hachioji Medical Center of Tokyo Medical College and was diagnosed as having GeO_2-induced nephropathy. She was treated by hemodialysis, but her gait disturbance was not improved. She was transffered to our hospital on account of a close medical examination for her gait disturbance in February 1988. On admission, she had normocytic-normochromic anemia, chronic renal failure without significant abnormal findings in the urinalysis and pain on grasping of muscles. Neurological examination showed a sensory dominant polyneuropathy, ataxic gait and mild proximal dominant muscular weakness. Electromyogram showed almost normal recording. Motor nerve conduction velocities of the right median, ulnar, tibial and peroneal nerve were slowed. Sensory action potentials of the right median, ulnar and sural nerve could not be elicited. The content of Ge in her hair was 23 ppm. Biopsy study of the right gastrocnemius and sural nerve disclosed a neurogenic muscular atrophy, reduction in the large myelinated fiber, segmental demyelination and axonal degeneration. Severe infiltration of lymphocytes was observed around an arteriole in the perineurium of the right sural nerve. Her pain on grasping of muscles was improved by oral administration of prednisolone (30 mg/day). All of the reported cases of the GeO_2-intoxication are Japanese in the literature. We recommend to ascertain a history of intake of GeO_2-containing preparation in cases with renal dysfunction without urinary abnormarities accompanied by neurological disorders of unknown origin.

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