Role of caspases in apoptosis and disease.

Apoptosis, a genetically governed process of eliminating cells in response to a variety of stimuli provides protection against cancer and viral infections as well as maintains homeostasis. Recent studies using both molecular and cloning approaches, and in vitro systems have identified a class of highly specific proteases, termed caspases, that appear to have an important role in apoptotic execution. Caspases are synthesized as precursor molecules that require processing at specific aspartate residues to produce the active enzyme which in turn leads to the cleavage of various death substrates that lead to morphological changes typical of apoptosis. This review discusses caspases, their inhibitors and regulators. Since cytotoxic drugs used in chemotherapy of leukemia's and solid tumors cause apoptosis in target cells, elucidating the consequences of proteolytic activity occupies a central role for understanding of the molecular mechanism of apoptosis which can help us to use the caspase inhibitors as targets of therapy.     

Fibrous dysplasia of the mastoid

A rare case of fibrous dysplasia involving the mastoid bone is reported. Its histopathological characteristics are also described.     

Women's health as empowerment: towards a holistic experience

The Women's Health Programme of the nongovernmental organization Social Action for Rural and Tribal Inhabitants of India (SARTHI) serves women living in the Santrampur taluka of Panchmahals district in Gujarat State, India. The program, which has been operating since July 1988, addresses gynecological and psychological health and issues of violence and exploitation. It incorporates traditional health practices and modern allopathic health practices. SARTHI provides gynecologic services via illiterate women health workers (barefoot gynecologists). They also counsel the rural and tribal women and mobilize them for collective action. The 1st phase of the program was training local women in maternal and child health care which included nutrition education and aseptic deliveries. It moved into its 2nd phase due to the realization that it was imposing an external health system on the local women. So the program undertook a research project to verify locally used traditional medicines. Training of the barefoot gynecologists marked the beginning of the 3rd phase. These women health workers soon realized that their main objective was empowerment of the local women. The program provides women with information to empower them to deal with their problems. Training is the key to the program's success. it designed training in phases to build upon knowledge. It begins with an 8-day training program followed by 3-day modules each month. Training includes technical health information and empowerment and leadership building. Content depends on the current situation of the women. Methodologies include role playing, songs, question-answer sessions, and reviews.     

Factors involved in the differential response to ethanol,barbital and pentobarbital in rats selectively bred for ethanol sensitivity

Two lines of rats, least affected (LA) and most affected (MA), had been selectively bred for their differential sensitivity to ethanol. Both males and females of the LA strain were observed to be less sensitive than their MA counterparts to the acute hypnotic and motor-impairing effects of ethanol. However, a lower ethanol metabolic rate of the MA males suggests that both CNS and metabolic factors contribute to their enhanced sensitivity to ethanol. By contrast, no differences were observed between the LA and MA males with respect to the hypnotic and subhypnotic effects of pentobarbital or to the clearance of this drug. MA females were more sensitive only to the hypnotic effects of pentobarbital, probably because of a smaller apparent volume of distribution. No strain difference was observed in the hypnotic effect or clearance of barbital. These observations suggest that, in spite of a differential sensitivity to ethanol, the LA and MA lines do not differ in their response to the barbiturates tested.     

Sarcomas of the breast: Homogenous or heterogenous?

Eighteen cases of sarcomas of the breast are reported. Cases could be divided into two groups histogenetically. Group A, malignant cystosarcoma phylloides (14 cases); and Group B, pure sarcomas (4 cases). The malignant cystosarcoma phylloides occurred in the forth decade, had linger duration of illness invariably followed by sudden increase in the size of the tumor, had a striking mucoid and slimy look grossly, and showed discernible epithelial elements histologically. In the event of their recurrence the ductal elements were not seen microscopically. Contrarily, Group B cases presented in the sixth decade were rapidly growing from the beginning, and grossly were fleshy and haemorrhagic. Microscopically these did not reveal any epithelial component. There was poor correlation between cytologic malignancy and the biologic behavior in Group A. Mode of treatment seems more important in determining the subsequent course of the disease. Simple mastectomy with follow-up appears to be adequate in the majority of cases.     

The relationship between acute rejection and chronic rejection is highly dependent on specific MHC matching: a multi-strain rat heterotopic heart transplant study

BACKGROUND: The impact of acute rejection, immunosuppression, and infection, specifically cytomegalovirus infection, on the development of chronic rejection in the cardiac allograft, has been the subject of a large number of investigations. One of the difficulties in finding associations has been the marked immunologic heterogeneity of the patient population coupled with the lack of the ability to HLA match. Furthermore, the ideal animal model, which duplicates as well as controls for this immunologic heterogeneity, is lacking. METHODS: To try to simulate differences in HLA matching, immunosuppression regiments and cytomegalovirus infection, heterotopic heart transplantation was performed in two separate, complete MHC mismatch, rat strain combinations (WF-LEW, BN-LEW) requiring chronic immunosuppression and employing four separate immunosuppression/infection protocols. Animals were followed for 6 months, killed, and rejection and vascular changes were scored blinded to the group. RESULTS: The mean vascular and acute rejection scores were not significantly different between treatment regiments for either specific strain combination. There was a trend for the subtherapeutic groups to have higher vascular scores. Overall, there were no significant differences in vascular scores between the WF-LEW and BN-LEW groups (1.25+/-0.18 vs. 1.13+/-0.20, P=NS). Similar numbers of WF-LEW and BN-LEW exhibited cellular infiltration and necrosis of the allograft, but the intensity of the response (rejection score) was more severe in the WF-LEW combination (4.54+/-0.22 vs. 3.92+/-0.21, P=0.052) when limiting the analysis to those with myocyte necrosis. There was no significant correlation between acute rejection and vascular lesion severity in the WF-LEW combination (r=0.22, P=NS) but a high correlation between these parameters in the BN-LEW combination (r=0.74, P<0.0001). CONCLUSIONS: These data suggest that, although acute rejection and chronic rejection are related, MHC matching may influence their interdependence. These data also may explain why the clinical association between acute and chronic rejection is difficult to demonstrate.     

Transforming growth factor-beta1 increases albumin permeability of isolated rat glomeruli via hydroxyl radicals

BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine. Glomerular cells and tubular epithelial cells secrete and respond to TGF-beta1. A close association between elevated levels of TGF-beta1 and the development of glomerulonephritis, glomerulosclerosis, and tubular hypertrophy has been documented. The role of TGF-beta1 in proteinuria is not well understood. METHODS: Isolated rat glomeruli were incubated in medium alone or with TGF-beta1 (1 to 10 ng/mL) and TGF-beta1 + 200 U/mL of superoxide dismutase (SOD) or 1 mmol/L of dimethylthiourea (DMTU) scavengers of superoxide and hydroxyl radicals, respectively, for up to 60 minutes at 37 degrees C. Glomerular albumin permeability (Palb) was calculated from the volumetric response of glomeruli to an oncotic gradient using videomicroscopy. RESULTS: One or 2.5 ng/mL of TGF-beta1 had no effect on Palb (0.18 +/- 0.08, N = 17; 0.18 +/- 0. 079, N = 20 vs. control 0.00 +/- 0.06, N = 25), whereas 5 or 10 ng/mL of TGF-beta1 caused a significant increase in Palb (0.31 +/- 0. 09, N = 20; 0.33 +/- 0.06, N = 23) within 15 minutes. The effect of 10 ng/mL of TGF-beta1 on Palb increased further after 30, 45, or 60 minutes of incubation (0.43 +/- 0.06, N = 24; 0.53 +/- 0.06, N = 25; 0.74 +/- 0.075, N = 21). The TGF-beta1-induced increase in Palb (0. 75 +/- 0.065, N = 15) was blocked by SOD (0.07 +/- 0.14 N = 15) or by DMTU (0.04 +/- 0.13, N = 15). Incubation of glomeruli with the carrier medium (4N HCl) in which TGF-beta1 is dissolved and SOD or DMTU alone did not affect Palb. CONCLUSION: Elevated levels of TGF-beta1 derived from glomerular or extraglomerular sources are capable of increasing glomerular Palb via superoxide and hydroxyl radicals and may lead to proteinuria in vivo.     

Reflex sympathetic dystrophy in a 12-year-old twin with comorbid conversion disorder in both twins

A case of reflex sympathetic dystrophy is presented in a 12-year-old girl with comorbid conversion disorder. Her identical twin also had a conversion disorder. This is the first reported case of coexistence of reflex sympathetic dystrophy and conversion disorder. It is important for clinicians to be aware that these conditions may coexist since the presentation of symptoms differ, even though there are shared features of treatment.