Kiyoshi Uchide

Matrix metalloproteinase-9 and Tensile strength of fetal membranes in uncomplicated labor

Objective To analyze the relation between tensile strength and levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 at a number of sites in human fetal membranes. Methods Tensile strengths of fetal membranes from five women who delivered vaginally at term were measured by the method of modified force application. A piece of membrane at each measured site was then dissected, and the levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 were measured by sandwich enzyme immunoassay. The relationship between tensile strength and enzyme levels was evaluated by Scheffé F test at a total of 81 sites on the five membranes. Results The mean tensile strength of the membranes was 45.3 ± 19.8 (mean ± standard deviation) mmHg/0.3 mm2 (n = 81). When the measured sites were divided according to tensile strength into four groups (<25, 25–49, 50–74, and ≥75 mmHg/0.3 mm2), the level of matrix metalloproteinase-9 (0.72 ± 0.82 nmol/g protein, n = 12) in the less than 25 mmHg/0.3 mm2 group was significantly higher than the other groups (0.35 ± 0.22, 0.28 ± 0.15, and 0.15 ± 0.08 nmol/g protein; n = 39, 23, and 7, respectively). The significance level was still higher when the molar ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 was used for comparison. Conclusion An increased molar ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 might be related to decreased tensile strength of human fetal membranes in uncomplicated labor.

The Possible Effect of Pregnancy on Ménière’s Disease

There are few reports on the course of Ménières disease during pregnancy. We report here the clinical course of Ménières disease before, during and after pregnancy and discuss the possible effect of pregnancy on Ménières disease and the treatment of Ménières disease during pregnancy. In the present case, the vertigo attacks increased up to 10 times per month during early pregnancy, when the serum osmolality was significantly below normal at 268 mosm/kg. As the pregnancy proceeded, the serum osmolality normalized and the vertigo attacks decreased in frequency. The vertigo attacks were treated by oral isosorbide and intramuscular injection of low-dose diazepam. The coincidence of the decline in osmolality with the increase in vertigo attacks points to serum osmolality as a possible factor in the effect of pregnancy on Ménières disease.

Changes with aging of steroidal levels in the cerebrospinal fluid of women

OBJECTIVE Age-related changes of steroid levels in the central nervous system (CNS) are not well understood. To investigate whether steroidal conditions in the CNS of women change with aging and menopause, steroid levels have been measured in serum and cerebrospinal fluid (CSF), and examined correlations with aging. METHODS Serum and CSF concentrations of estradiol (E2), cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS) and albumin were measured in 80 female patients who underwent operations for benign gynecological diseases. They had no endocrinological or neurological disorders and were aged 17-71 years; 62 patients were in premenopause and 18 were in postmenopause. RESULTS Serum levels of E2 decreased markedly after menopause, while levels of DHEA and DHEAS decreased gradually with age. There was no significant change with age of serum cortisol levels. The CSF concentrations of E2 (0.2-3 pg/ml) decreased with age [correlation coefficient (r)= 0.31, P < 0.01]. The CSF DHEA levels (0.1-0.8 ng/ml) did not change with age although not significantly, but CSF cortisol levels (0.1-0.6 microg/dl) increased with age (r = 0.35, P < 0.01). The CSF DHEAS concentrations were below the sensitivity of the radioimmunoassay (RIA) (1 ng/ml). The CSF/serum ratios of cortisol increased with age (r = 0.30, P < 0.01), as did those of DHEA (r = 0.55, P < 0.01). Although serum albumin levels did not change throughout life, CSF albumin levels and CSF/serum albumin ratios increased gradually with age (r = 0.28, P = 0.052; r = 0.23, P = 0.114, respectively), but there was no significance. There were marked decreases of serum E2 and DHEA levels and CSF E2 levels in postmenopausal women (P < 0.05), but CSF cortisol levels increased (P < 0.05) and DHEA levels in CSF were maintained after menopause. CONCLUSION These results indicate that steroids in CSF become cortisol dominated and deficient in estrogens with aging, especially after menopause.

Deoxyribonuclease I (DNase I) typing from semen stains : Low enzyme activity in vaginal fluids does not interfere with seminal DNase I typing from mixture stains

We describe the use of deoxyribonuclease I (DNase I) polymorphism for individualization of semen in body fluid stain mixtures, as a means of providing new and more useful information to practicing forensic biologists as a genetic marker. We have already reported that human DNase I isozyme patterns from different subjects are classifiable into ten groups. Isoelectric focusing of DNase I isozymes on polyacrylamide gel (IEF-PAGE, pH 3.5 to 5) was accomplished using a 0.5 mm thick gel. Pretreatment of semen samples with neuraminidase enhanced the isozyme band resolution and sensitivity. Activity detection using the dried agarose film overlay (DAFO) procedure was reliable, sensitive and simple, with high resolution, and the phenotypes of DNase I were determined in semen stains of about 0.3 microL stored at room temperature for up to a year in most of the samples tested. The DNase I types in semen stains were correlated with the types found in the corresponding blood and urine samples, although most of the vaginal fluid samples had no typable DNase I activity. This is considerably advantageous for seminal individualization from body fluid mixture stains in criminal cases. An evaluation of DNase I typing by IEF-PAGE and DAFO was also performed on casework samples submitted to our laboratory, and the results showed that DNase I was expected to be one of the most useful individualization marker of semen in practical application.

A follicular cyst during tamoxifen therapy in a premenopausal breast cancer woman.

A large ovarian follicular cyst developed on day 43 of low-dose tamoxifen adjuvant therapy for a premenopausal breast cancer (total drug intake: 860 mg). The serum estradiol level increased to almost ten times the pretreatment level. However, the FSH and LH decreased slightly, and the serum progesterone level remained almost unchanged. It is hypothesized that tamoxifen acted directly on the ovaries to provoke excessive proliferation of the granulosa cells in a follicular cyst, causing it to grow very large, and resulting in elevated E2 levels.

Intracervical fibrin instillation as an adjuvant to treatment for second trimester rupture of membranes

We describe a pregnancy complicated by premature rupture of the membranes at 24 weeks. Delivery with successful outcome was postponed till 31 weeks by cerclage, ritodrine and intracervical instillation of fibrin.

Effect of Testosterone on the Development of Bladder Tumors and Calculi in Female Rats

In order to study the effect of testosterone on bladder calculi and tumor formation in female rats, Wistar rats were administered testosterone for 12, 18 or 24 weeks. Testosterone was found to increase the incidence of both bladder calculi and tumors in intact, but not in oophorectomized rats. It is suggested that testosterone in combination with estrogen may contribute to hyperplasia formation, in turn leading to an increased incidence of bladder calculi and tumors.

Effects of Testosterone on the Development of Endometrial Tumors in Female Rats

Long-term treatment of mature virgin female rats with a high dose of testosterone (24 weeks at a total dose of 300 mg) was associated with the development of endometrial adenomatous hyperplasia and resulted in a high incidence of adenocarcinoma when administered in combination with 7,12-dimethyl-benz[a]anthracene (DMBA; 2 mg in 0.1 ml sesame oil) introduced into the uterine cavity. Adenomatous hyperplasia occurred in all testosterone-treated rats, both with and without ovaries. Testosterone may promote the induction of endometrial tumors by DMBA.

Partial Hydatidiform Mole in the Fallopian Tube

An extremely rare case of partial hydatidiform mole located in the right Fallopian tube was diagnosed by ultrasonography and computed tomography. The lesion was excised, and the human chorionic gonadotropin (HCG) level in early morning urine fell below 1,000 IU/ml on postoperative day 11, and the serum HCG-beta level normalized on postoperative day 46.

Induction of ductal carcinomas by intraductal administration of 7,12-dimethylbenz(a)anthracene in Wistar rats

SummaryPostpartum Wistar inbred rats (weaned on the 9th puerperal day) were injected intraductally in one mammary gland with 7,12-dimethylbenze (a) anthracene (DMBA) to selectively induce ductal carcinoma. The incidence of ductal hyperplasia increased with time until it peaked at 7 weeks (12/13 animals) and then decreased. Ductal carcinoma first developed at 9 weeks in 3/12 (2 non-invasive and 1 invasive lesion) and the incidence increased with time until invasive ductal tumors were observed in 9/11 at 20 weeks. Tumors developed only in the DMBA-treated mammary glands and no systemic effects of the carcinogen were observed. Degeneration and detachment of epithelioglandular cells were seen here and there in the ducts and terminal ducts, and epithelioglandular cells proliferated in terminal duct until 2 weeks. Residual trace DMBA powder was detected in terminal ducts and the epithelioglandular layer until 7 weeks. This trace DMBA was considered to be the cause of the development of atypical epithelial cells, inducing ductal carcinomas.