Pubertal and adult Leydig cell function in Mullerian inhibiting substance-deficient mice

Mullerian inhibiting substance (MIS) causes Mullerian duct regression during sexual differentiation and regulates postnatal Leydig cell development. MIS knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals, basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations were similar. In adults, basal LH, and both basal and human chorionic gonadotropin (hCG)-stimulated testosterone concentrations were similar. Purified Leydig cells from pubertal MIS-KO mice had lower testosterone but higher androstanediol and androstenedione production rates. In contrast, testosterone, androstanediol, and androstenedione production rates were all lower in adult MIS-KO Leydig cells. Steroidogenic acute regulatory protein expression was lower in pubertal MIS-KO mice compared with WT, whereas 17beta-hydroxy-steroid dehydrogenase and 5alpha-reductase were greater, and P450c17 and P450scc were similar. The expression of steroidogenic acute regulatory protein and 17beta-hydroxysteroid dehydrogenase was lower in adult MIS-KO mice, whereas that of 5alpha-reductase, P450c17, and P450scc was similar. Collectively, these results suggest that in the absence of MIS, Leydig cells remain less differentiated, causing an altered intratesticular androgen milieu that may contribute to the infertility of MIS-KO mice. In immature mice, this deficit in steroidogenic capacity appears to be mediated by a direct loss of MIS action in Leydig cells as well as by indirect effects via the hypothalamic-pituitary-gonadal axis.     

Survival in Persons With Traumatic Spinal Cord Injury Receiving Structured Follow-Up in South India

Objective

To assess the survival in persons with traumatic spinal cord injury (SCI) receiving structured follow-up in South India.

Design

Retrospective study.

Setting

Rehabilitation center.

Participants

Persons with traumatic SCI (N=490) residing within a 100-km radius of the institute who were managed and regularly followed up by the rehabilitation center between the years 1981 and 2011.

Interventions

Not applicable.

Main Outcome Measures

Survival rates and mortality risk factors. Measures were estimated using the product limit (Kaplan-Meier) method and the Cox model.

Results

The survival rate after SCI was 86% after 5 years, 71% after 15 years, and 58% after 25 years. Survival of persons with complete high cervical injury is substantially low compared with other levels of SCI. Level of injury and extent of lesion (Frankel classification and/or American Spinal Injury Association Impairment Scale) play a significant role in predicting survival of this population.

Conclusions

Survival rates of regularly followed-up persons with SCI from this study show promising results, though survival rates are lesser when compared with studies from developed countries. Better understanding of the predictors, causes of deaths, comprehensive rehabilitation, community integration, and regular follow-up could possibly assist in improving survival rates.     

Acrolein-Induced Toxicity—Defective Mitochondrial Function as a Possible Mechanism

Administration of acrolein (2.5 mg/kg body weight/day) to rats for 45 days depleted the glutathione level in liver, which triggered an imbalance in the antioxidant defense, resulting in lipid peroxidation. Enhanced lipid peroxidation damaged the membranous structure of mitochondria, which was indicated by the loss of lamellae, and increased the oxidation of exogenously added NADH. Loss in membrane integrity altered the activities of the tricarboxylic acid cycle enzymes and levels of cytochromes. Decreased rate of ADP—stimulated oxygen uptake, respiratory coupling ratio, and ATP synthesis—were also observed. We report that the acrolein-induced toxicity is mediated through the depletion of GSH leading to impairment of rat liver mitochondrial function. Received: 24 November 1998     

Severe dysplastic lesions in the colon – how aggressive should we be?

Introduction Biopsies of colonic lesions are often reported as showing dysplasia, though in reality some lesions may harbour invasive malignancy. Aim To assess the risk of underlying invasive malignancy in sessile polyps where biopsies had shown severe dysplasia and also to attempt to define a management strategy in such patients. Methods Between 1997 and 2001, 30 patients were diagnosed as having severe dysplasia using Morson's criteria in colonic lesions not amenable for endoscopic polypectomy. Severely dysplastic lesions were completely excised by appropriate surgical measures. Results Out of 30 patients, 15 had invasive cancers. Surgical intervention involved anterior resections, endoanal excisions, sigmoid colectomies, or abdomino‐perineal excisions as deemed appropriate. The lesions ranged in size from 0.5 cm to 13 cm (mean 3.4 cm). There were nine T₁ lesions (one of which was T₁N₁) and two each of T₂, T₃, T₄ lesions (10 Dukes' A, 3 Dukes' B, 2 Dukes' C). Complete resection was confirmed histologically in all cases. One patient had a leak following endoanal excision, which required intervention. There was no mortality. Discussion This study demonstrates that endoscopic sampling can be misleading and severely dysplastic sessile lesions should be managed along the same principles as followed for invasive cancers, rather than adopting a ‘wait and watch’ policy with repeated endoscopies, biopsies or piece‐meal polypectomies.     

The Association of Anovulation and Endometriosis in the Infertile Female

Summary: Ninety-six infertile patients with endometriosis were studied and their endometriosis staged according to the Revised American Fertility Society Classification. Anovulation was detected in 19% of the 32 patients with Stage 1 disease but in only 3% in the remaining 64 patients with Stage II, III and IV disease. These results show that contrary to traditional belief, anovulation does occur in a significant number of patients with endometriosis, especially in minimal or mild disease.     

Exercise stress alters the percentage of splenic lymphocyte subsets in response to mitogen but not in response to interleukin-1

Results of previous work from this laboratory demonstrated that reduced murine splenic lymphocyte proliferation in response to Concanavalin A (Con A) is associated with acute exercise stress. The present study was conducted to determine whether the stress of physical work further affects the expression of splenic lymphocyte phenotypes following in vitro stimulation by the T-cell mitogen, Con A, and also by interleukin-1 (IL1). Mice in this study were assigned to one of five treatment conditions. Two groups of mice were exposed only to the noise and vibration of a treadmill for 8 weeks; one of these groups was given an acute exhaustive run. Three groups of mice were exposed to 8 weeks of treadmill training: one group was sacrificed immediately after training, a second group was sacrificed 72 h after training, and a third group was rested for 72 h and then given an acute exhaustive run. There was a significant effect of stimulation by Con A on the percentage of splenic lymphocytes positive for Thy1.2, Lyt-2, L3T4, and goat anti-mouse Ig, regardless of treatment condition. Acute exercise, however, affected the magnitude of the response. There was a significantly greater increase in the percentage of Thy1.2+ and, especially of, Lyt-2+ cells in stimulated splenic lymphocytes from untrained mice given an exhaustive exercise session compared with controls and with trained mice. There was no significant effect of the addition of IL1 to any culture, irrespective of treatment condition. These results suggest that reduced mitogenesis after acute exercise stress exposure may be related to the increased appearance of Lyt-2+ (T suppressor) cells.     

Quantification and visualization of three-dimensional inconsistency of the globus pallidus internus in the Schaltenbrand-Wahren brain atlas

The major shortcomings of the Schaltenbrand-Wahren (SW) brain atlas include 3-dimensional (3D) inconsistency and spatial sparseness. This work quantifies and visualizes 3D inconsistency of the globus pallidus internus (GPi), a stereotactic target for the treatment of Parkinson's disease, dystonia and Huntington disease. The GPi 3D models 3D-A, 3D-C and 3D-S are reconstructed from the SW axial, coronal and sagittal microseries, respectively, by applying a shape-based (Nonuniform Rational B Splines) method. All three 3D models, placed in the SW coordinate system, are compared quantitatively in terms of location (centroids), size (volumes), shape (normalized eigen values), orientation (eigen vectors) and mutual spatial relationships (overlaps and inclusions). The analysis is done in 3D within each orientation and across them. The reconstructed 3D GPi models substantially differ in location, size and inclusion rate. The centroid of 3D-C is located more medially (15.6 mm) than those of 3D-A (17.5 mm) and 3D-S (18.2 mm), and that of 3D-A more ventrally (-2.3 mm) than those of 3D-C (-0.1 mm) and 3D-S (-0.4 mm). 3D-S has the smallest volume (347.3 mm3); 3D-A is 1.18 and 3D-C 1.85 times larger. The highest inclusion rate is for 3D-S (54.3 and 56.3%) and the lowest for 3D-C (28.8 and 30.6%). A smaller variability is observed in shape, orientation and overlap size (196.8, 196.1 and 185.5 mm3). To get a better correspondence between 3D-C and 3D-S, the coronal microseries were scaled laterally by 1.1667. This results in a substantial improvement of the inclusion rate of 3D-S (87.9%), though raising the volume mismatch to 2.16. The GPi in the SW atlas has a substantial 3D inaccuracy within each orientation and across them. Therefore, absolute and direct reliance on the original atlas is unsafe, and this atlas has to be used with great care and understanding of its limitations. As matching various SW microseries by global scaling is not feasible, we propose the target-dependent scaling based on structure centroid matching.