Monacolins J and L, new inhibitors of cholesterol biosynthesis produced by Monascus ruber.
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Biomedical subjects
Publications and source records attributed to K Hasumi.
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A sesquiterpene named koningic acid has been isolated from a strain of Trichoderma koningii as a potent inhibitor of ATP generation in the glycolytic pathway. From experiments with both cultured mouse carcinoma FM3A cells and isolated enzymes, it was shown that koningic acid is a specific inhibitor of glyceraldehyde 3-phosphate dehydrogenase that catalyzes the conversion of glyceraldehyde 3-phosphate to 3-phosphoglycerate.
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Since patients with endometrial carcinoma tend to be elderly, diabetic and hypertensive, individualization of treatment is very important. The therapy for each patient with endometrial carcinoma should be individualized and determined by the stage and factors predisposing to extrauterine spread of the tumor. Such risk factors include the grade of the tumor and depth of myometrial invasion. Unfortunately, staging based on pelvic examination is inaccurate in endometrial carcinoma and the depth of myometrial invasion cannot be assessed preoperatively. In order to assess its uses in the staging and treatment planning of endometrial cancer, CT was performed in 28 previously untreated patients with endometrial cancer. Twenty patients subsequently underwent surgery and the CT findings were correlated with the surgical and pathologic findings. CT proved to be useful in determining the depth of myometrial invasion and whether cervical involvement is present or not. Such information provided by CT helps to plan treatment more adequately and accurately for the individual patients.
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The prognosis and treatment of patients with endometrial carcinoma are dependent on the clinically established extent of the tumor (stage). The grade of the tumor and depth of myometrial invasion have the most significant prognostic and therapeutic value after the stage. Unfortunately, staging based on pelvic examination is inaccurate in endometrial carcinoma and the depth of myometrial invasion cannot be assessed preoperatively. To stage the disease precisely and to evaluate the extent of myometrial invasion preoperatively, computed tomography (CT) was performed in 20 untreated patients with endometrial carcinoma who subsequently underwent surgery. The CT findings were correlated with the surgical and pathological findings. The tumor appeared as areas of decreased attenuation on CT in comparison with the surrounding myometrium after contrast infusion. Thus, it was easy to evaluate the depth of myometrial invasion on enhanced CT. CT showed the tumor invading less than half the thickness of the myometrium in 13 patients and this was histologically confirmed in all. There were 7 patients with the tumor invading more than half the thickness of the myometrium but confined to the uterus on CT. The CT findings were also histologically confirmed in all patients. CT showed the tumor involving the cervix in 5 patients. This was histologically confirmed in all. No cervical involvement was demonstrated by CT in the remaining 15 patients. Subsequent pathological examination revealed microscopic invasion to the endocervix in 2 cases and no cervical involvement in the other 13. The present study has demonstrated that CT is useful to assess the extent of endometrial cancer; especially useful to evaluate the depth of myometrial involvement. Such information provided by CT helps to plan treatment more adequately and accurately for the individual patients.
Lately there is a tendency for an increase in the incidence of endometrial cancer both in this country and other industrialized countries such as the United States. The routine cervicovaginal smear method is generally poor for the detection of endometrial carcinoma as compared to that used for the diagnosis of early cervical neoplasms. The principal reason for the poor detection rate is that the cells are not obtained directly from the lesion as is the case with disease of the cervix. Various techniques for obtaining endometrial cells directly from the lesions have been described, but none has enjoyed wide acceptance by the clinicians. The patients for this study consisted of 138 women who were referred to us for diagnostic curettage. We employed the new disposable device, the Endocyte, and Masubuchi's endometrial aspiration and compared the results. After obtaining specimens with both methods curettage was performed on all patients. In addition, the Endocyte was employed on 8 patients with endometrial carcinoma in another hospital, and the following results were obtained. 1. With the Endocyte it is possible to obtain a larger volume of cells than by aspiration. 2. Although a certain amount of difficulty is encountered in the insertion of the Endocyte in some cases, it is much easier than the brush method used heretofore. 3. No significant difference in the amount of bleeding after insertion could be observed between the two methods. 4. In patients with bleeding in the endometrium and pyometra it is easier to obtain specimens from the endometrium with the Endocyte than by aspiration. 5. With the Endocyte contamination of the cells of the cervix was less than after aspiration. 6. Although pain during collection of cells with the Endocyte was somewhat stronger than during aspiration, analgesics were not necessary in any one of the cases. 7. The Endocyte was used on 13 patients with endometrial carcinoma, and all specimens were positive for carcinoma. From the results of our study we conclude that for endometrial cytology the Endocyte is as useful as the aspiration method. Furthermore, it should pose no difficulty to the gynecologists to use the Endocyte because the Endocyte resembles IUD structurally.
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The inhibitors of prostaglandin (PG) production (indomethacin, etc.) block ovulation. But little is known about how the inhibition of PG production effects cell function in the follicle. This study was done to clarify the morphological changes and steroidogenesis in the follicles treated with the inhibitor. Fifteen gilts treated with PMS and hCG were administered with indomethacin of 7.6 mg/kg (enough for a complete block) 24 hrs. after hCG. The morphological study of the follicles was done by serial section. The levels of estradiol-17 beta, testosterone, 17 alpha OH progesterone and progesterone were estimated by RIA in the follicular fluid, ovarian vein and peripheral blood. A histologic section of the treated follicles revealed the presence of entrapped oocytes surrounded by heavily luteinized granulosa-theca cells. No morphological changes were found in the luteal cells at any stage of the luteal phase except for retention of fluid in the central cavity of the corpus luteum. The life span of the corpus luteum (18 days) was not affected by indomethacin. No differences in steroid levels were detected in the peripheral and ovarian vein blood or in the follicular fluid at any time compared with the control. Inhibition of PG production results in the luteinized unruptured follicle without interference with steroidogenesis.
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Radical hysterectomy and pelvic lymphadenectomy were performed on 135 patients with Stage I epidermoid carcinoma of the uterine cervix invading less than 5 mm below the basement membrane. These cases were studied to determine the biological behavior of early invasive carcinoma and to establish diagnostic criteria for microinvasive carcinoma of the cervix (Stage IA). None of the 135 patients had metastasis to the parametrial tissue in the final surgical specimen. One (0.9%) of 106 patients with invasion up to 3 mm had lymph node metastasis, while 4 (13.9%) of 29 patients with invasion of 3.1-5 mm had nodal metastasis. Of the 106 patients with invasion up to 3 mm, 25 had confluent invasion. None of the 25 patients had lymph node metastasis. In view of our result, carcinomas with invasion less than 3 mm may be regarded as a separate diagnostic group because of their limited metastatic potential, and may be treated by conservative methods used for carcinoma in situ, even if there is a confluent pattern. For carcinoma with invasion of 3.1-5 mm, more extensive procedures as used for frankly invasive carcinomas are probably necessary.
A man with a mediastinal mass shadow detected on chest roentgenogram was diagnosed as having achalasia by barium swallowing study. Megaesophagus caused by achalasia produced airway obstruction. Maximum expiratory-inspiratory flow volume curve identified that peak flow rate decreased in early expiration, and the ratio of expired to inspired flow at 50 percent of vital capacity was below 0.9, aggravated by 250 ml water intake. Deformation of the tracheal shape was proved easily.
In the past all clear cell carcinomas of the female genital tract were thought to arise from mesonephric remnants. Recently increasing evidence has related their origin to müllerian rather than mesonephric epithelium. One of the main reasons that has been advanced to support their mesonephric origin has been their occurrence in the uterine cervix and vagina, sites of mesonephric remnants. However, no clear evidence for mesonephric origin of clear cell carcinoma of the cervix and vagina has been ever provided. In contrast, there is substantial evidence that diethylstilbestrol-related clear cell carcinomas of the cervix and vagina are müllerian in origin. We report here a case of an exophytic clear cell carcinoma with an in situ component, involving the endocervical epithelium. The in situ lesion clearly indicates müllerian origin of the tumor, which occurred in the absence of prenatal exposure to diethylstilbestrol. This supports the general agreement that clear cell carcinomas of the cervix are müllerian in origin, whether diethylstilbestrol-related or not.
Four cases of primary malignant melanoma of the vagina in women aged 23, 44, 51 and 65 years are presented. In these 4 cases, thorough clinical and postmortem examinations ruled out the possibility of a primary melanoma elsewhere. The primary tumors showed exophytic growth with superficial ulceration. Three of the melanomas arose from the middle third of the vagina and one from the upper third. Melanin was visible in sections stained with hematoxylin and eosin in 3 of the tumors. In the other one, the first biopsy failed to reveal melanin. However, the second biopsy performed following irradiation showed abundant melanin pigment. Electron microscopic examination of 3 tumors revealed premelanosomes and melanosomes in the tumor cells, thus confirming the diagnosis. Two neoplasms showed atypical histologic features, and only the presence of melanin enabled us to make diagnosis of malignant melanoma. One melanoma was associated with an adjacent widespread intraepithelial component of superficial spreading type indicating its probable mode of origin. All 4 patients died of widespread metastases within 13 months after initial treatment. These 4 cases, in which clinical diagnosis was confirmed by thorough autopsy, strongly indicate that malignant melanoma can arise directly from the vagina.
The present study was carried out to investigate a distinctive type of carcinoma of the uterine cervix categorized under the designation as circumscribed carcinoma with lymphocytic infiltration. Grossly this carcinoma is characterized by defined circumscription with a superficial ulceration. A microscropic feature characteristic of this tumor is the presence of a loose fibrillary stroma infiltrated densely and uniformly by lymphocytes throughout the tumor mass. The tumor is arranged in solid cords separated by a lymphoid stroma with evidence of minimal squamous differentiation. The authors picked up 709 patients with carcinoma of the uterine cervix who underwent radical hysterectomy and pelvic lymphadenectomy at the Cancer Institute Hospital, Tokyo, between 1956-1967, without preoperative radio- or chemotherapy. Among them, 39 or 5.5% were identified as this type of carcinoma. Patients with this types of carcinoma had a significantly better prognosis than those with other types of cervical carcinoma of the same stage (p less than 0.05). This favorable prognosis is probably due to the less regional node metastases found in the group. A proposal was made to segregate this particular type of carcinoma from other types of cervical carcinoma on the basis of its morphologic and prognostic distinctiveness.
The incorporation of thymidine into DNA in the presence of hydroxyurea (HU) by guinea pig pancreatic slices following exposure to N-nitrosomethylurethane (NMUT) was used to follow DNA repair synthesis. HU was used to suppress normal replicative DNA synthesis. Slices from the duodenal segment of the pancreas were exposed for periods of 15 to 90 min to NMUT at concentrations of 2 to 20 mM, then incubated in tritiated thymidine ([H3]-TdR) free of carcinogen, and radioactivity in DNA was determined. NMUT induced a a dose- and time-dependent increase in HU-insensitive thymidine incorporation. This stimulated incorporation, which could be attributed to repair synthesis, occurred immediately following the treatment and was largely complete within 3 h.