Differential expression of TGF-beta1 and TGF-beta3 in serosal tissues of human intraperitoneal organs and peritoneal adhesions

Elevated local expression of transforming growth factor (TGF-beta) has been associated with increased incidence of peritoneal adhesion formation. In this study we determine whether differences in basal expression of TGF-beta in serosal tissue of peritoneal organs correlate with incidence of adhesion formation. Serosal tissue of parietal peritoneum, uterus, oviduct, ovary, omentum, large and small bowels as well as adhesions, skin, fascia, subcutaneous tissue, peritoneal fluid and serum were collected from 57 subjects with/without adhesions who were undergoing abdominal/pelvic surgery. To determine TGF-beta1 and TGF-beta3 mRNA and protein expression, total RNA and protein were isolated from these tissues and along with the fluids, subjected to quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA) respectively. Tissue sections were immunostained for TGF-beta1 and TGF-beta3 protein. We found that TGF-beta1 and TGF-beta3 mRNA and protein are expressed in these tissues and present in peritoneal fluids and serum, with considerable variations in level of their expression. Comparatively, there was more variation in TGF-beta1 than TGF-beta3 expression without age or gender relation. Adhesions express a significantly higher TGF-beta1 mRNA and have the highest TGF-beta1:TGF-beta3 ratio, with lowest concentrations and ratio detected in omentum, small and large bowels; in contrast uterus expresses higher TGF-beta3, with lowest concentrations detected in subcutaneous tissue and large bowels (P < 0.05). A similar trend was also observed for total (active + latent) TGF-beta1 protein expression, with low active TGF-beta1 that was not significantly different among the tissue extracts and fluids. However, the lowest active:total TGF-beta1 ratio was found in adhesions and ovary. In subjects with adhesions, the adhesions express significantly more TGF-beta1 compared to parietal peritoneum (P < 0.05). Immunoreactive TGF-beta1 and TGF-beta3 protein were present in various cell types in these tissues with intensity reflecting their mRNA and protein expression. In conclusion, we provided evidence that serosal tissue of various peritoneal organs and adhesions express TGF-beta1 and TGF-beta3. Since TGF-beta is expressed differently in these tissues and tissue injury often alters the expression of TGF-beta, we propose that tissues with a higher basal expression of TGF-beta may become predisposed to develop more adhesions compared to others.     

Use of ECT to Treat Bipolar Depression in a Mental Retardate with Cerebral Palsy

We report the use of electroconvulsive therapy (ECT) for treatment of a bipolar episode in a mildly retarded young man with cerebral palsy. Difficulties in the diagnosis and treatment of affective disorders in the retarded are discussed.     

Provider-patient relations and treatment choice in the era of fiscal incentives: the case of the end-stage renal disease program

Debates about the extent to which patients can and should participate in medical decision making take on new urgency as cost-containment efforts give patients more financial incentives. The Health Care Financing Administration's recent proposal to enable dialysis patients to "price shop" aroused consternation among nephrologists. A working seminar elucidated their fears about professional incomes and about increased patient autonomy.     

Understanding the Link Between Adolescent Same-Gender Contact and Unintended Pregnancy: The Role of Early Adversity and Sexual Risk Behavior

Past research suggests an apparent paradox: Women who engage in same-gender sexual behavior show higher rates of unintended pregnancy than women with exclusive other-gender sexual behavior. Such women also have disproportionate rates of early adversity (both harshness, such as abuse or neglect, and unpredictability, such as father absence). We used the Add Health data (N?=?5,617 cisgender women) to examine the relative contributions of early adversity, adolescent same-gender sexual behavior, and general sexual risk behavior to women’s risks for adult unintended pregnancy. Women who engaged in adolescent same-gender sexual behavior were more likely to report childhood adversity, and both childhood adversity and adolescent same-gender behavior made independent contributions to subsequent rates of unintended pregnancy. The association between adolescent same-gender sexual behavior and adult unintended pregnancy was partially attributable to the fact that women with adolescent same-gender sexual behavior engaged in greater sexual risk behavior more broadly. These findings suggest that same-gender sexual behavior in adolescence may relate to a broader set of sexual risk behaviors that augment future risk for unintended pregnancy, independent of sexual identity. We draw on life history theory to explain this pattern of results and suggest directions for future research.

     

Manifestations of diabeters mellitus on mouse preimplantation developement: effect of elevated concentration of metabolic intemediated

The metabolic derangements of pregnancies complicated by diabetesmellitus, specifically hyperglycaemia and hyper-ketonaemia,are known to be teratogenic during the period of organogenesisin animals. We have shown previously that poorly controled diabetesmellitus impairs in-vivo and in-vitro mouse preimplantationembryo growth, and that culturing embryos in elevated glucoseconcentrations only partially recreated this developmental dealy.To extend this observation we examined the effect on mouse preimplantationembryo growth of elevated concentrations of other metabolicintermediates, which may be deranged in diabetes mellitys, namelylipids, lactate, glycerol, amino acids, and ketones. Two-cellembryos from ovulation-induced B₆C₃F₁ mice were cultured for72 h in the presence of added lipids (250 mg/dl), lactate (5mM), glycerol (160 µM) or mixed amino acids (8.5% travosol,7 mM) and showed no significant difference in growth over 72h verus their control groups. However, growth of preimplantationembryos in acetoacetate (10 mM) or in the racemic micture ofDL--hydroxybutyrate (16 and 32mM) revealed marked retardationversus controls when assessed either by distribution of developmentalstages over time (24, 48, 72 h, P <0.001) or by the differencein the average rank of sums indicating a delay in maturation(P<0.0001). We conclude that elevated ketone concentrationsadversely affect preimplantation embryo development. These findingsextend previous studies which correlate uncontrolled diabetesmellitus as well as hyperglycaemia with abnormal organogenesis,and demonstrate tht exposure to metabolic derangements may alsohinder reproductive performane at even earlier stages in gestation.     

The nuclear jet and counterjet region of the radio galaxy Cygnus A

Very-long-baseline interferometry images of the nuclear region of the radio galaxy Cygnus A reveal a pronounced "core" and a knotty jet and counterjet. The knots are moving away from the core at apparent speeds which are subluminal for h = 1 [h = H0/100 km.s-1.Mpc-1;1 parsec (pc) = 3.09 x 10(16)m] and about c for h = 0.5. The jet is aligned with the outer, kiloparsec-scale jet to within 2 degrees. The counterjet has a total flux density at 5 GHz of about one-fifth of that of the jet. In the context of the twin relativistic jet model for active galactic nuclei, the jet in Cygnus A is oriented at an angle to our line of sight of 35-80 degrees and 55-85 degrees, and the intrinsic velocity of the jet fluid is 0.4-0.6c and 0.6-1c for h = 1 and h = 0.5, respectively.     

Tissue plasminogen activator (tPA) inhibits plasmin degradation of fibrin. A mechanism that slows tPA-mediated fibrinolysis but does not require alpha 2-antiplasmin or leakage of intrinsic plasminogen.

Thrombolysis is dramatically slower when high concentrations of lytic agent are used. This paradoxical observation, first described as "plasminogen steal," was originally believed to be due to depletion of extrinsic plasminogen and consequent leaching of clot-bound plasminogen. We report that administration of increasing concentrations of recombinant human tissue plasminogen activator (tPA) to fibrin gels resulted in lysis rates that displayed a maximum, with significantly slower rates found at higher tPA, regardless of whether plasminogen was supplied extrinsically or intrinsically. A similar maximum in lysis rates was observed in a system lacking an extrinsic phase when plasminogen was added to fibrin suspensions preincubated with increasing tPA. Thus, intrinsic plasminogen leakage and alpha 2-antiplasmin were not required for the decreased lysis at high tPA. No maximum was observed for increasing concentrations of urokinase. Using fibrin suspensions or gels preincubated with tPA before addition of plasmin, we report that tPA, but not urokinase, caused a dose-dependent inhibition of the fibronolytic action of plasmin. With respect to optimal dosage schemes and the design of novel lytic agents, these findings indicate that (a) there exists a biochemical mechanism against minimizing reperfusion time with increasing tPA dosages and (b) the fibrin affinity of tPA may cause reduced fibrinolysis by plasmin.     

Ocular manifestations of genetic and development diseases

Significant advances were reported this year in the identification of the chromosomal location of mutated genes on the 13 and 6 chromosomes which cause forms of autosomal dominant Stargardt's macular dystrophy. Observations in monozygotic twins with age-related macular dystrophy were described. Mitochondrial DNA mutations in Cubans with optic and peripheral neuropathy were reported. A new autosomal dominant proximal myotonic myopathy was described. Persistence of the tunica vasculosa lentis was suggested as a helpful sign of congenital myotonic dystrophy. The panoply of ocular findings in acromesomelic dysplasia were presented. Genetic characterization of the ocular findings in Duchenne type and Becker's muscular dystrophy was reported. Finally, a new syndrome of autosomal dominant cerebellar ataxia with retinal degeneration was described.