M4M chat rooms: individual socialization and sexual autonomy.

This paper uses data from twenty-one online and in-person qualitative interviews to examine the meaning and use of chat rooms located on men for men (M4M) websites from the perspectives of men seeking men on the Internet. This research is inspired by recent public health and social sciences literature on gay websites and chat rooms. The data indicate that these online sites help expedite learning about sex and sexuality and, for men who are shy or geographically isolated, to interact with metropolitan gay communities. There is, however, a measure of stigma associated with use of these chat rooms, particularly by men who are older or in coupled relationships. Using these data, the paper argues that M4M chat rooms play a vital role in fostering the sexual autonomy of many men who frequent these venues and that sociologists should devote more study to the complexity of online social interaction.

4-Heterocyclohexanone-based inhibitors of the serine protease plasmin.

Three inhibitors that are based upon a 4-heterocyclohexanone nucleus were synthesized and evaluated for activity against the serine protease plasmin. Inhibitors of plasmin have potential as cancer chemotherapeutic agents that act by blocking both angiogenesis and metastasis. Inhibitor 1 has moderate activity against plasmin but shows good selectivity for this enzyme compared to other serine proteases including trypsin, thrombin, and kallikrein. Inhibitor 2 shows both good activity and selectivity for plasmin. Inhibitor 3, which does not incorporate an aminohexyl group that can interact with the S1 subsite, has poor activity. These results, along with previous work, demonstrate that the 4-heterocyclohexanone nucleus can effectively serve as the basis for designing inhibitors of both serine and cysteine proteases.

Inhibition of phosphatase activity by positively-charged cyclodextrins.

[formula: see text] Aminocyclodextrins are known to bind phosphate esters such as phosphotyrosine and p-nitrophenyl phosphate. This paper describes the inhibition of phosphate ester hydrolysis, as catalyzed by lambda-protein phosphatase and acid phosphatase, that is caused by such binding interactions. ROESY studies provide structural information about the cyclodextrin-aryl phosphate complexes. In addition, these experiments are used to generate approximations of the rates of dissociation of the noncovalent complexes.

Segmental vasodilatory effectiveness of inhaled NO in lungs from chronically hypoxic rats.

Inhaled nitric oxide (iNO) is being used to treat pulmonary hypertension in a variety of chronic lung diseases associated with pulmonary vascular remodeling. We hypothesized that chronic hypoxia (CH)-induced vascular remodeling decreases the vasodilatory effectiveness of iNO due to a thickened diffusional barrier. We therefore examined segmental vasodilatory responses to iNO in U-46619-constricted lungs isolated from control and CH (4 weeks at 0.5 atm) rats using double occlusion technique. We further measured lung fluid flux and vascular wall thickness in lungs from each group to provide an index of vascular permeability and vascular remodeling, respectively. CH was associated with decreased venous, but not arterial, responsiveness to iNO in saline-perfused lungs. In addition, the presence of red blood cells (RBC) within the perfusate greatly reduced venodilation in both groups of lungs, indicating that venous responsiveness to iNO in saline-perfused lungs is largely dependent upon transport of NO from an upstream site. In contrast, RBC had no effect on arterial dilation in control lungs, but attenuated arterial dilation to iNO in lungs from CH rats. Finally, fluid flux and arterial wall thickness were greater in lungs from CH rats. We conclude that arterial remodeling associated with CH may limit venous dilation to iNO. Furthermore, the decreased arterial responsiveness to iNO following CH is consistent with extravasation of hemoglobin within the arterial vasculature.

Selective upregulation of arterial endothelial nitric oxide synthase in pulmonary hypertension.

We have previously demonstrated that arterial, but not venous, vasodilatory responses to endothelium-derived nitric oxide (EDNO)-dependent agonists are enhanced in lungs isolated from rats with chronic hypoxia (CH)-induced pulmonary arterial hypertension. These data suggest that CH is associated with increased endothelial nitric oxide synthase (eNOS) activity within the pulmonary arterial vasculature. In addition, the correlation of increased pulmonary arterial pressure with selectively enhanced arterial responsiveness to EDNO-mediated agonists suggests that arterial hypertension, rather than hypoxia per se, is a contributing factor in this response. Therefore, we hypothesized that 1) CH selectively upregulates eNOS within the pulmonary arterial vasculature and 2) monocrotaline (MC)-induced pulmonary arterial hypertension selectively enhances pulmonary arterial dilation to EDNO-dependent dilators and upregulates arterial eNOS. We examined the responses to the EDNO-dependent dilators arginine vasopressin and ionomycin in U-46619-constricted isolated perfused lungs from control and MC-treated rats. Microvascular pressure was assessed by the double-occlusion technique, allowing calculation of segmental resistances. Lungs from MC-treated rats exhibited augmented arterial dilation to arginine vasopressin compared with control lungs. However, the responses to ionomycin were not different between the two groups. Quantitative immunocytochemistry was used to compare pulmonary eNOS immunoreactivity in vessels from control, CH, and MC-treated rats. eNOS staining was more intense in the arteries of CH and MC-treated rats compared with those of control animals, whereas CH and MC treatment had no effect on eNOS staining in veins. We conclude that pulmonary arterial hypertension, or altered vascular mechanical forces associated with hypertension, may be responsible for the augmented EDNO-dependent arterial dilation and upregulation of arterial eNOS in lungs from CH and MC-treated rats.

Autocatalytic processing of the potyvirus helper component proteinase in Escherichia coli and in vitro.

The virus-encoded proteins of tobacco etch virus (TEV), a plant potyvirus, arise by proteolytic processing of a large polyprotein precursor. The TEV genome codes for two proteinases, a 49-kilodalton proteinase and helper component proteinase (HC-Pro), which cleave the polyprotein at specific sites. The only known cleavage event catalyzed by HC-Pro occurs at the HC-Pro carboxyl terminus. The proteolytic activity of HC-Pro was analyzed by expression of the enzyme in bacterial and cell-free systems. The carboxyl-terminal domain of HC-Pro exhibited proteolytic activity in Escherichia coli with a processing half-time of approximately 100 s. The processing kinetics of HC-Pro expressed in vitro by cell-free transcription and translation was variable, depending on the presence or absence of TEV polypeptide sequences at the amino terminus of the proteolytic domain. Cleavage of the HC-Pro carboxyl terminus appeared to proceed exclusively by an autocatalytic mechanism; the proteinase synthesized in vitro exhibited little or no proteolytic activity when reacted with the HC-Pro cleavage site in trans or biomolecular reactions.