Early postnatal methoxychlor exposure inhibits folliculogenesis and stimulates anti-Mullerian hormone production in the rat ovary

Methoxychlor [1,1,1-trichloro-2,2-bis(4-methoxyphenyl) ethane; MXC] is a chlorinated hydrocarbon pesticide commonly used in the United States as a replacement for DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane]. While MXC is a weak estrogenic compound, its more active, major metabolite [2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane; HPTE] shows estrogenic, anti-estrogenic, or anti-androgenic properties depending on the receptor subtype with which it interacts. Anti-Mullerian hormone (AMH) is a paracrine factor that suppresses initial follicle recruitment in the ovary. Studies have shown the effects of exposure to MXC on adult ovarian morphology and function. However, the effect of exposure to MXC at an early postnatal stage on pre-pubertal follicular development and ovarian AMH production has not been studied. Around postnatal day (P) 4, most of the primordial follicular assembly in rats is complete, and a large number of primordial follicles transition into the primary follicle stage, a process that is inhibited by estrogen. The objective of this study was to examine the effect of early postnatal (P3-P10) MXC exposure on ovarian morphology and size, follicle number, and AMH production in the pre-pubertal (P20) rat ovary and to investigate the effect of HPTE on AMH production in immature rat granulosa cells in vitro. Female rats were injected (s.c.) daily with vehicle (control) or 1, 10, 50, 100, or 500 mg MXC/kg per day (referred to here as 1MXC, 10MXC, and so forth.) between P3 and P10. On P20, uterine and ovarian weights were determined, ovarian histology was examined, and follicles were counted and classified into primordial, primary, secondary, pre-antral, or antral stages using the two largest serial sections at the center of the ovary. Ovarian AMH production was examined using immunohistochemistry and western blot analysis. The effect of HPTE (0.5-25 microM) on AMH production in cultured immature rat granulosa cells was determined by western blot analysis. Ovarian weight was reduced by 50, 100, and 500MXC (P < 0.01). MXC treatment inhibited folliculogenesis. Both 100 and 500MXC had a reduced number of antral follicles (P < 0.05) with a concomitant increase in pre-antral follicles (P < 0.05). Follicle numbers were not significantly affected by 1, 10, or 50MXC. Total follicle number and the number of primordial, primary, or secondary stage follicles were not significantly different in all treatment groups. Immunohistochemistry showed that MXC-treated ovaries had more AMH-positive follicles with stronger AMH immunostaining. Western blot analysis showed that AMH production was 1.6 +/- 0.2, 1.85 +/- 0.6, and 2.2 +/- 0.5 times higher in the 50, 100, and 500MXC ovaries as compared with the control ovaries respectively (P < 0.05). Granulosa cells treated with 1 or 5 microM HPTE had significantly greater AMH production (P < 0.05). These results demonstrate that MXC inhibits early ovarian development and stimulates AMH production directly in the rat ovary. In addition, HPTE was shown to stimulate AMH production in rat granulosa cells. Endocrine disruptors are widespread in the environment, and MXC represents a model endocrine disruptor due to the multiple actions of its metabolites. This study confirms that the endocrine disruptor MXC inhibits follicular development and demonstrates for the first time that MXC and HPTE directly stimulate AMH production in the ovary. This novel finding suggests that elevated AMH may play a role in MXC's inhibitory effect in the ovary.     

Molecular cloning of the cDNA for human erythrocyte beta-spectrin

Overlapping cDNA clones, totaling 3.3 kilobases (kb) in length, which encode over 50% of the human erythrocyte beta-spectrin subunit, were isolated by antibody screening of a lambda gt11 expression library constructed from human fetal liver mRNA. The amino acid sequence of the C-terminus of beta-spectrin was derived. The size of beta-spectrin mRNA in human erythroleukemia cells was found to be 7.5 kb. Erythrocyte beta- spectrin is encoded by a gene located on human chromosome 14, as determined by cDNA hybridization to human X mouse somatic cell hybrids.     

Acute esophageal hemorrhage from a vagal neurilemoma.

A man with known systemic neurofibromatosis developed an acute upper gastrointestinal hemorrhage while hospitalized after a neurosurgical procedure. Endoscopic evaluation showed a vascular lesion with an appearance consistent with a Dieulafoy-type lesion in the distal esophagus. Despite multiple endoscopic procedures with attempted coagulation of the bleeding lesion, the patient continued to have life-threatening hemorrhaging. At thoractomy, a tumor was found to arise from the vagus nerve at the site of bleeding. This tumor was resected and histologically determined to be a neurilemoma. Acute bleeding into the esophagus associated with this type of tumor has not been previously reported.     

Flow as a regulator of the activation of factor X by tissue factor

A novel enzyme reactor for phospholipid-dependent reactions was used to study the effects of flow on tissue factor-initiated coagulation. Microcapillaries were coated with a phospholipid bilayer containing tissue factor, a transmembrane protein that is an essential cofactor for a plasma procoagulant enzyme, factor VII. We show that, in contrast to static, closed systems, the steady-state catalytic activity is independent of enzyme concentration and the time to steady state becomes a function of the enzyme concentration.     

Effects of maternal hypervitaminosis A on perinatal rat lung histology

Retinyl acetate (160,000 USP/day in corn oil) was administered orally to pregnant Long-Evans rats during the last third of gestation. Postnatal evaluation of this treatment was assessed by examination of histologic sections of lung taken from stillborns and from pups that survived several hours. In all sections from treated litters, expansion of lung either did not appear to have occurred, or was not uniform. Control lung sections were uniformly expanded in all cases. It appears that hypervitaminosis A during the fetal period alters normal lung maturation. These data provide additional supporting evidence that the fetal period is susceptible to teratogens.     

Bilateral rupture of extensor pollicis longus. A case report

Bilateral rupture of the extensor pollicis longus tendon is a rare entity. Most case studies in the literature have been reported in patients with an underlying systemic condition such as rheumatoid arthritis or following an episode of trauma. An interesting and unusual case is presented and theories concerning etiology, various operative techniques, and recent cases in the literature are discussed.     

Nutrition, pregnancy, and transplantation.

One benefit of transplantation, along with the restoration of health, is the opportunity for successful pregnancies. A growing number of pregnancies have been reported among all types of solid-organ recipients. There is an increasing need for practice guidelines that include nutrition information in order to assist practitioners caring for and counseling these high-risk patients. In the transplant community, guidelines for managing pregnancies in transplant recipients have been evolving but lack specific nutrition recommendations. As for all pregnancies, there is a need to optimize nutrition for the mother and her infant, with additional consideration given to the transplant recipient's graft. This article reviews outcomes of posttransplant pregnancies and management guidelines, with special emphasis on nutrition in this unique population.