Competitive binding to a charged leucine motif represses transformation by a papillomavirus E6 oncoprotein

E6 oncoproteins from HPV-16 and bovine papillomavirus type 1 (BPV-1) bind to similar leucine-rich peptides termed charged leucine motifs found on the cellular focal adhesion protein paxillin and the E3 ubiquitin ligase E6AP. BPV-1 E6 (BE6) mutants that do not bind to paxillin are defective at inducing cellular transformation. It is possible, however, that BE6 mutants that do not bind paxillin are defective for transformation for an unrelated reason than the ability to bind to charged leucine motifs. To address the role of BE6 interaction with charged leucine motifs, we fused a BE6-binding charged leucine motif to the amino terminus of BE6, thereby creating an autoinhibitory binding domain. We found that the fusion protein failed to bind to paxillin or transform murine C127 cells. Mutation of the amino terminal binding motif in the fusion protein restored both interaction with paxillin and transformation. This demonstrates that BE6 transformation requires binding to charged leucine motifs on particular cellular proteins and that transformation by papillomavirus oncoproteins can be repressed by competitive interactions with charged leucine motifs.     

Cystic duct and Heister's "valves"

The anatomy and physiology of the cystic duct have been relatively neglected by anatomists and the function of the spiral mucosal folds or "valves" of Heister, first described in 1732, remains obscure. The gross and microscopic anatomy of the cystic duct is reviewed together with results from laboratory investigations into the function of the cystic duct and its spirally arranged folds. The duct and spiral folds contain muscle fibers responsive to pharmacologic, hormonal, and neural stimuli. There is, however, no convincing evidence of a discrete muscular sphincter within the duct. Although the cystic duct is unlikely to play a major role in gallbladder filling and emptying, it appears to function as more than a passive conduit. Coordinated, graded muscular activity in the cystic duct in response to hormonal and neural stimuli may facilitate gallbladder emptying. The principal function of the internal spiral folds that are found in man and other animals may be to preserve patency of this narrow, tortuous tube rather than to regulate bile flow.     

Immunomodulation of autoimmune and inflammatory diseases with intravenous immunoglobulin

Abstract Intravenous immunoglobulin (IVIg) has been used in the treatment of primary and secondary antibody deficiencies for over two decades. Since the early 1980s, the therapeutic efficacy of IVIg has been established in idiopathic thrombocytopenic purpura, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, dermatomyositis and Kawasaki syndrome, and the prevention of graft versus host disease in recipients of allogeneic bone marrow transplants. Its use has also been reported in a large number of other autoimmune and systemic inflammatory conditions. In this review, we discuss the mechanisms by which IVIg exerts immunomodulatory effects in immune pathologies.     

Use of alkaline phosphatase to correct the underestimation of fosphenytoin concentration in serum measured by phenytoin immunoassays

The pharmacologic activity of fosphenytoin, a new phosphate ester pro-drug of phenytoin, is due to in vivo conversion to phenytoin. Fosphenytoin concentrations cannot be accurately estimated by phenytoin immunoassays (fluorescence polarization and chemiluminescence) owing to the nonlinear relation between fosphenytoin concentration and the observed cross-reactivity. The problem of slow conversion of fosphenytoin to phenytoin in serum in vitro can be circumvented by rapidly converting fosphenytoin to phenytoin in vitro by alkaline phosphatase. Drug-free serum, heparin, EDTA, or citrated plasma were supplemented with 2 concentrations of fosphenytoin. Then to 1-mL aliquots of specimen, no enzyme (control), 10 microL, or 25 microL of enzyme solution was added. The specimens were incubated, and phenytoin concentrations were measured by fluorescence polarization and chemiluminescent assays. In the absence of enzyme, we observed little conversion of fosphenytoin to phenytoin, but in the presence of only 10 microL of enzyme, the conversion of fosphenytoin to phenytoin was complete in 5 minutes. We also observed complete conversion of fosphenytoin to phenytoin by alkaline phosphatase in heparin, EDTA, and citrated plasma. If clinically indicated, the phenytoin concentration can be measured before and after addition of enzyme to roughly estimate the rate of conversion.     

Diagnostic role of fibreoptic bronchoscopy in pulmonary tuberculosis

Fibreoptic bronchoscopy with bronchial aspiration* washings and biopsy was performed in 104 patients suspected clinically and radio logically of having pulmonary tuberculosis diagnostic yield in 9230% (96/104) cases. Diagnostic yield for tuberculosis was in 69.22% (72/ 104) cases, it includes positive aspiration and washings smear in 38.46%(40/l04) patients,positive mycobacteriai culture alone in 26.92% (28/104) cases and positive biopsy in 3*84% (4/ 104) patients, Non-tuberculous conditions like pneumonia and bronchogenic carcinoma were diagnosed in 19.23% (20/104) cases and 3.84% (4/104) cases respectively. These results suggest that in areas with high prevalence of tuberculosis, bronchoscopy should be performed for early diagnosis and initiation of therapy in sputum smear-negative cases of pulmonary tuberculosis.     

In the footsteps of "Arundhati": Asian Indian women's experience of domestic violence in the United States

This study examined the ideologies and conditions that are creating women's vulnerability to spousal abuse in the Asian Indian community in the US. The study focused on the multiple factors involved in Asian Indian women's experiences of domestic violence in the US: their minority status, life as an immigrant, and pressures to preserve a flawless public image of their community. The data were collected from interviews with 12 highly educated women from India who had sought outside help due to spousal abuse. 10 of these women were foreign born, and 2 were brought up in the US. The study revealed that the most important factor in these women's lives seemed to be childhood indoctrination into the ideals of ?good? wife and mother that include sacrifice of personal freedom and autonomy. Although majority of the women worked as professionals, economic independence did not seem to provide them with a sense of empowerment. Furthermore, they felt responsible for the reputation of their families in India, were eager not to compromise their families' honor with a divorce, and operated under the added pressures of preserving traditions and presenting an ?unblemished? image of the community to the US mainstream.     

Relationship between body weight and the incidence of positive axillary nodes at mastectomy for breast cancer

The question, whether obesity is associated with an increased incidence of positive axillary nodes at mastectomy for breast cancer, was studied in two quite different hospital populations; one from a large urban teaching hospital (Montefiore) and one from a medium-sized Air Force medical center (Malcolm Grow). In the Montefiore population, the answer was "yes"; 67% of the node-positive patients, but only 31% of the node-negative patients were obese (20% or more above ideal weight) (p less than 0.05). In the Malcolm Grow population, the answer was "no"; 20% of the node-positive and 20% of the node-negative patients were obese. The different answers, we believe, are due to the biological differences between the populations; the Montefiore population was shorter (by an average of 1.7 inches), heavier (by an average of 20 lbs), and more obese. The incidence of obesity was about three times as high in the Montefiore population (52% versus 20%; p less than 0.02) and it contained a statistically distinct subpopulation of obese patients, while the few obese patients in the Malcolm Grow population constituted merely the upper tail of a unimodal log-normal distribution of weight in that population. We propose that it is possible to demonstrate a relationship of obesity to node-positivity in the Montefiore population but not in the Malcolm Grow population because obesity was highly prevalent in the former and almost nonexistent in the latter. It seems self-evident that it is not possible to demonstrate an effect of obesity in a population if that population manifests no significant obesity, statistically speaking, but disregarding this principle, we believe, may account for the controversy in the literature about whether obesity is a risk factor in breast cancer.