Amplification of the gene encoding the alpha-subunit of the mitochondrial ATP synthase complex in a human retinoblastoma cell line.

A cDNA clone encoding the precursor of the alpha-subunit of the human mitochondrial ATP synthase (F1-ATPS) complex was isolated from a library prepared from the poly(A)+ RNA present in a retinoblastoma (RB) cell line. Northern blot analysis of RNAs derived from a variety of transformed cell lines as well as from normal human fetal tissues indicated that RNA expression was significantly higher in two of the four RB cell lines analysed, Y79 (10- to 30-fold) and RB522A (3- to 8-fold), than in other cell lines or tissues. The increased mRNA level was apparently the result of gene amplification in Y79, but not in RB522A.

Inherent radiosensitivity testing of tumor biopsies obtained from patients with carcinoma of the cervix or endometrium.

The inherent radiosensitivity of tumor biopsies obtained from a series of patients with carcinoma of the uterine cervix or endometrium has been characterized. Early passage cell lines were irradiated and assayed for cell survival using a clonogenic assay system. Survival curves were generated using the alpha/beta model and the surviving fraction at 2 Gy (SF2) was estimated. A wide range of SF2 values was observed among histologically similar tumors. The mean (+/- SD) SF2 value was 0.29 +/- 0.12 (range = 0.11-0.59) for the cervical biopsies and 0.30 +/- 0.13 (range = 0.11-0.67) for the endometrial biopsies. No correlation between inherent radiosensitivity and tumor DNA index or histopathology was observed. Patient accrual continues with the expectation that these results may help to determine whether SF2 values are of clinical value in predicting the response of individual patients to treatment with radiotherapy.

Possible association between the hernia of Morgagni and trisomy 21.

Of the 5 liveborn infants with the hernia of Morgagni recorded in the California Birth Defects Monitoring Program, 3 had trisomy 21. This significant association (P < 10(-6)) between the hernia of Morgagni and trisomy 21 may reflect defective dorsoventral migration of rhabdomyoblasts from the paraxial myotomes, caused by increased cellular adhesiveness in trisomy 21.

Is there an association of Down syndrome and omphalocele?

The possible association of Down syndrome (DS) with omphalocele is controversial. We reviewed the 2,979 live births and stillbirths with DS born from 1983 to 1993 in the catchment area of the California Birth Defects Monitoring Program (CBDMP). We observed one infant with both defects, a number that did not differ significantly from what was expected (P < 0.40). We also reviewed the pathological reports of one of us (L.H.H.) from a series of 36 DS fetuses and neonatal deaths; none had an omphalocele. We then reviewed the literature for epidemiological studies of DS and for epidemiological, surgical, prenatal, and familial studies of omphalocele. Possible biases inherent in each type of study were evaluated. The majority of epidemiological studies showed no association of DS with omphalocele. In surgical series, the occasional infant with both defects was more likely to undergo surgery than infants with omphalocele and trisomies 13 and 18 or other severe birth defects. Inclusion of both omphalocele and umbilical hernia in the same ICD-9 code may explain some of the correlations with DS noticed in a few epidemiological studies. In conclusion, our data suggest that trisomy 21 does not predispose the fetus to an increased risk for an omphalocele.

Microscopic study of holoprosencephalic facial anomalies in trisomy 13 fetuses.

The cerebral and facial anatomy of four trisomy 13 fetuses was studied in order to delineate the varying degrees of expression of severity of holoprosencephaly. Fetal heads were serially sectioned and analyzed microscopically in the horizontal plane. Examples of cyclopia, cebocephaly, and a proposed new category, premaxillary dysgenesis, were studied. The last category represents the least severe end of the facial spectrum of holoprosencephaly in this series. In this condition, there are deficiencies or clefts within the premaxilla, in contrast to the usual site of clefting between the maxilla and the premaxilla. There is asymmetry of the defects in the anterior midface of all four cases.

Ovarian hilus cell heterotopia.

A systematic pathologic study was done of the paratubal and parametrial tissues, submitted along with distal tubal segments excised for sterilization and with uteri (with or without attached adnexa) removed for common gynecologic conditions. Heterotopic ovarian hilus cell rests were noted in 12 cases, giving an overall incidence of 0.52% (12/2299). These cell rests, confined exclusively to the endosalpinx and perisalpinx, were easily differentiated from pregnancy-related decidual nodules, Walthard rests, foci of paratubal endometriosis, and ectopic adrenal rests.

Invasive squamous cell carcinoma of the vagina during pregnancy.

BACKGROUND: Squamous cell carcinoma of the vagina in pregnancy is rare. CASE: A 28-year-old primigravida with antepartum bleeding at 20 weeks' gestation was diagnosed with squamous cell carcinoma after biopsy of a vaginal mass. The histology revealed an invasive grade 3 squamous cell carcinoma of large-cell, nonkeratinizing type. The patient declined pregnancy termination and immediate radiation treatment. She continued to have episodes of vaginal bleeding and was admitted at 30 weeks' gestation. A decision was made in consultation with the neonatal unit to deliver her at 32 weeks' gestation. After corticosteroid treatment, she was delivered by cesarean delivery. Positive pelvic lymph nodes were noted at surgery. Postoperatively, she received external beam radiation and brachytherapy and concurrent cisplatin chemotherapy. She is disease free 3 years from her original diagnosis. CONCLUSION: This case emphasizes the importance of a thorough pelvic examination to assess the vaginal walls and cervix at the first prenatal visit and with any antepartum bleeding episode.

Cholesterol cholelithiasis in adolescent females: its connection with obestiy, parity, and oral contraceptive use--a retrospective study of 31 cases.

Thirty-one adolescent females, aged 14 to 20 years, underwent cholecystectomy for pathologically documented cholesterol gallstones. A retrospective study, using the Mantel-Haenzel method of statistical analysis, showed a strong association between cholesterol cholelithiasis and obesity and parity. The patients with gallstones had a higher rate of oral contraceptive use, which just failed to attain statistical significance. These findings indicate that adolescent cholelithiasis is largely preventable. Dietary obesity can be controlled by balanced diets and physical exercise. Early pregnancy should be discourgaed, espeically if there is a strong family history of cholelithiasis and if weight control is unsuccessful. Oral contraceptives should be used cautiously in the presence of other predisposing factors.

Nonspecific peritesticular fibrosis manifested as testicular enlargement.

Nine cases of peritesticular fibrosis initially appeared to be enlargement of the testes. Seven patients under went orchiectomy and two had biopsy specimens taken of the grossly thickened tunica albuginea. In six patients, a hydrocele was present with intramural fibrosis and minimal chronic inflammation. Active epididymitis and chronic interstitial orchitis were present in two patients, with some spread of the inflammation into the fibrotic peritesticular tissues. One case, without associated hydrocele or epididymitis, showed dense fibrosis of the peritesticular tissues with focal edema, lymphangiectasis, and minimal perivascular round cell infiltration. This clinicopathological entity of diffuse peritesticular fibrosis is an unrecognized cause of benign testicular enlargement. The hypothesis is advanced that the primary process is a congenital hypoplasia of the peritesticular lymphatics progressing at various speeds into a state of chronic lymphedema and end stage noninflammatory fibrosis.

Unilateral anorchism. Report of 11 cases with discussion of etiology and pathogenesis.

Eleven cases of unilateral anorchism are presented. The patients, aged two to thirty-nine years, were explored for cryptorchism but, though ducts could be identified operatively in most cases, there was doubt regarding the presence of the testis. These tissues, including the putative testes, were excised and pathologically the excurrent ducts, consisting of vas deferens with or without epididymis, were seen in all cases. No tunica albuginea or testicular parenchyma was identified and the structures, submitted as possibly testicular, were nonencapsulated, well-circumscribed, subserosal foci of highly vascularized fibrous tissue with few small nerves and smooth muscle bundles. Dystrophic calcific deposits were seen in 2 cases and microfoci of poorly developed Leydig cells in 2 cases. A vascular hypothesis is proposed for the etiology and pathogenesis of unilateral anorchism.

Hypernephroma with perirenal hemorrhage.

Two cases of hypernephroma with rupture of the renal capsule and localized perirenal hemorrhage are reported. This unusual complication of hypernephroma exhibited a subacute clinical presentation with pain as the major presenting symptom.

The influence of anatomical site and hormonal status on the copper and zinc levels of human uterine smooth muscle.

Copper and zinc levels were measured in smooth muscle from 47 uteri. Results were obtained for myocervix, isthmus and corpus in the secretory and proliferative phases and also from post-menopausal subjects. The levels were found to vary both with site sampled and the physiological state of the uterus.

Salpingitis isthmica nodosa in female infertility and ectopic tubal pregnancy.

Salpingitis isthmica nodosa has been studied in relation to female infertility and tubal ectopic pregnancy. The incidence of this lesion in a control Caucasian population was 0.6%, as compared with incidences of 2.86% in an ectopic group and 50% in a small infertility group undergoing tuboplasty. It is suggested that salpingitis isthmica nodosa should be considered as an etiologic factor in these reproductive disorders. Chronic tubal spasm is suggested as the underlying process.

A significant association between spontaneous abortion and tubal ectopic pregnancy.

A retrospective study of 83 patients with pathologically documented tubal ectopic pregnancy demonstrated a statistically significant association (P less than 0.005) between prior spontaneous abortion and ectopic pregnancy. In this population with a low incidence of chronic salpingitis, it is suggested that delayed (post-midcycle) ovulation, causing preovulatory over-ripeness of the ovum, may be the common underlying etiologic factor. The clinical significance of this finding is also briefly discussed.

Failed tubal sterilization as an etiologic factor in ectopic tubal pregnancy.

An indirect statistical method was used to demonstrate that failed tubal sterilization must be considered as a significant etiologic factor in tubal ectopic pregnancy. Since the exact incidence of poststerilization pregnancies was unknown in our population, a "theoretical" incidence of a 0.71% failure rate was used as the most realistic estimate on the basis of published reports of failed tubal sterilizations. From this figure the "expected" number of poststerilization conceptions, both total and tubal, was computed. The observed incidence of poststerilization ectopic tubal pregnancy was found to be 20 times the "expected" incidence in our population.

The late luteal phase in infertile women: comparison of simultaneous endometrial biopsy and progesterone levels.

Endometrial biopsy specimens were obtained from 107 normally menstruating infertile women 2 to 3 days before the anticipated onset of menses and were day-dated according to histologic criteria. A simultaneous blood sample was obtained for measurement of progesterone (P) and beta-subunit of human chorionic gonadotropin. Of 98 biopsies which could be accurately dated, 56 were in-phase (IP) and 42 were out-of-phase (OOP). Mean serum P levels were significantly lower in women with OOP biopsies undertaken more than 4 days before the onset of menses. A sharp decline in serum P levels was observed in women with IP but not OOP biopsies, so that on the final premenstrual day serum P levels were significantly higher than normal in women with OOP biopsies. Pregnancy continued without interruption in two of six patients who underwent biopsy in the cycle of conception. One patient had an ectopic pregnancy; and the three remaining pregnant patients, all with subnormal P values, aborted. The study suggests that there is a high frequency of minor abnormalities in luteal function in normally menstruating, infertile women for whom tubal and male factors were normal. The frequency of subclinical pregnancy (2 of 107) was lower than anticipated from earlier studies.

Hyperplacentosis: a novel cause of hyperthyroidism.

Human chorionic gonadotropin (hCG), which is capable of thyrotropic activity, is believed responsible for the hyperthyroidism of gestational trophoblastic disease and hyperemesis gravidarum. Hyperplacentosis is a condition of heightened trophoblastic activity characterized by increased placental weight and circulating hCG levels higher than those associated with normal pregnancy. We report the first case of hyperthyroidism associated with hyperplacentosis. Correction of the hyperthyroidism occurred after hysterotomy and correlated with declining hCG levels. Hyperplacentosis should be included among the causes of hCG-mediated hyperthyroidism.

The effect of the intrauterine contraceptive device on the prevalence of morphologic abnormalities in human spontaneous abortions.

Spontaneously aborted conceptuses from IUD-wearing patients and prior IUD users were examined pathologically to determine the prevalence of morphologic abnormalities, which had previously been shown to correlate with cytogenetically proven heteroploidy in the conceptus. These abnormalities were never seen in the IUD-associated abortuses while occurring with the same frequency in abortuses obtained from prior IUD users and from non-users. It is concluded that the IUD by itself is responsible for the absence of heteroploidy-correlated structural abnormalities in spontaneous abortuses conceived with the IUD in situ. Relevant mechanisms underlying this IUD effect are discussed.

The negative effect of the IUCD on the occurrence of heteroploidy--correlated abnormalities in spontaneous abortions: an update.

Two prior studies done in the seventies had shown that spontaneous abortions in current IUCD-wearers were never associated with morphologic abnormalities, previously demonstrated to correlate significantly with cytogenetically proven heteroploidy. This study, carried out in the early eighties and based on 45 IUCD-associated and 882 IUCD-unrelated non-molar spontaneous abortions, confirmed this negative effect of the IUCD with a difference. Structural abnormalities, suggestive of heteroploidy, were seen for the first time in IUCD-associated spontaneous abortions but their prevalence (9.8%) was significantly lower than that observed in the IUCD-unrelated abortions (54.1%). The clinical relevance of this finding is briefly discussed.

The intrauterine contraceptive device and hydatidiform mole: a negative association.

None of the 135 hydatidiform moles studied (40 complete and 95 partial) occurred in women currently wearing the IUCD. In the control series of 1,244 non-molar spontaneous abortions, conception took place with the IUCD in situ in 48 women (3.87%). The difference between the observed number of molar pregnancies with the IUCD in situ, i.e., 0, and the "expected" number, i.e., 4.64 (3.87%) was statistically different (p less than 0.05). This difference could not be explained by such uncontrolled confounding variables as maternal age, menstrual age of the abortions, prior pregnancy loss, gravidity, ethnicity or contraceptive practices. It is suggested that the IUCD selectively suppresses the development of molar pregnancies. The theoretical and practical implications of this observation are discussed.