Structure and function of epididymal protein cysteine-rich secretory protein-1

Cysteine-rich secretory protein-1 （CRISP-1） is a glycoprotein secreted by the epididymal epithelium. It is a member of a large family of proteins characterized by two conserved domains and a set of 16 conserved cysteine residues. In mammals, CRISP-1 inhibits sperm-egg fusion and can suppress sperm capacitation. The molecular mechanism of action of the mammalian CRISP proteins remains unknown, but certain non-mammalian CRISP proteins can block ion channels. In the rat, CRISP-1 comprises two forms referred to as Proteins D and E. Recent work in our laboratory demonstrates that the D form of CRISP-1 associates transiently with the sperm surface, whereas the E form binds tightly. When the spermatozoa are washed, the E form of CRISP-1 persists on the sperm surface after all D form has dissociated. Cross-linking studies demonstrate different protein-protein interaction patterns for D and E, although no binding partners for either protein have yet been identified. Mass spectrometric analyses revealed a potential post-translational modification on the E form that is not present on the D form. This is the only discernable difference between Proteins D and E, and presumably is responsible for the difference in behavior of these two forms of rat CRISP- 1. These studies demonstrate that the more abundant D form interacts with spermatozoa transiently, possibly with a specific receptor on the sperm surface, consistent with a capacitation-suppressing function during sperm transit and storage in the epididymis, and also confirm a tightly bound population of the E form that could act in the female reproductive tract. （Asian J Androl 2007 July; 9： 508-514）     

A feasibility study of a web-based performance improvement system for substance abuse treatment providers

We report here on the feasibility of implementing a semiautomated performance improvement system—Patient Feedback (PF)—that enables real-time monitoring of patient ratings of therapeutic alliance, treatment satisfaction, and drug/alcohol use in outpatient substance abuse treatment clinics. The study was conducted in six clinics within the National Institute on Drug Abuse Clinical Trials Network. It involved a total of 39 clinicians and 6 clinic supervisors. Throughout the course of the study (consisting of five phases: training period [4 weeks], baseline [4 weeks], intervention [12 weeks], postintervention assessment [4 weeks], sustainability [1 year]), there was an overall collection rate of 75.5% of the clinic patient census. In general, the clinicians in these clinics had very positive treatment satisfaction and alliance ratings throughout the study. However, one clinic had worse drug use scores at baseline than other participating clinics and showed a decrease in self-reported drug use at postintervention. Although the implementation of the PF system proved to be feasible in actual clinical settings, further modifications of the PF system are needed to enhance any potential clinical usefulness.     

3-week inhalation exposure to cigarette smoke and/or lipopolysaccharide in AKR/J mice

AKR/J mice were exposed to cigarette smoke (CS) and/or lipopolysaccharide (LPS) via inhalation for 3 wk and pulmonary responses were evaluated. The objective was to explore the feasibility of coexposing LPS with cigarette smoke under a subacute exposure, as a surrogate for viral or bacterial insults, that would mimic the pathogenesis of infection-related chronic obstructive pulmonary disease (COPD) exacerbations. The study was the first step in an effort to develop a rodent COPD model in which morphologic lesions of COPD develop in a shorter period of exposure and more closely simulate human COPD. Mice were exposed 6 h/day, 5 days/wk for 3 wk to one of the following: (1) sham control: filtered air; (2) CS: 250 microg/L wet total particulate matter (WTPM) for 5 h/day followed by 1 h/day air; (3) LPS: 0.5 microg/L LPS (055:B5 Escherichia coli; 3,000,000 EU/mg) for the last 1 h/day 2 day/wk (following 5 h/day of filtered air); and (4) CS/LPS: CS 5 h/day followed by air or LPS (2 days/wk) for 1 h/day. After the last exposure, animals were necropsied and subjected to bronchoalveolar lavage (BAL) or histopathology. The BAL neutrophil counts were highest in the LPS group, while macrophage counts were higher in the CS/LPS group than other exposed groups. The LPS group displayed the greatest increases in BAL cytokines, while KC (keratinocyte-derived chemokine) and TARC (thymus and activation-regulated chemokine) were highest in the CS group. The CS/LPS group had generally lower cytokine levels relative to the LPS or CS groups, except for the levels of RANTES and G-CSF (granulocyte-colony stimulating factor) comparable to the LPS group. At microscopic examination of lung sections, cellular inflammatory infiltrates were most notable in the CS/LPS group, which had a diffuse, predominantly macrophage infiltrate with fewer neutrophils. The LPS group had predominantly neutrophils in the pulmonary infiltrate and the CS group had a predominantly macrophage infiltrate in alveolar ducts and adjacent alveoli. Apoptotic labeling of lung cells was highest with the CS/LPS group. In summary, the CS/LPS group displayed greater cellular infiltration and apoptotic responses in the lung with an indication of immunosuppressive effects (lower BAL cytokines) than the CS or LPS group, suggesting that the CS/LPS model shows promise to be further explored as an animal model for studying pathogenesis of COPD exacerbations. A longer term study with interim assessments is needed to confirm that the subacute responses observed in the CS/LPS group will result in greater severity of COPD-related pulmonary lesions following prolonged exposures.     

The influence of sex, body composition, and nonesterified fatty acids on serum adipokine concentrations

Serum adiponectin concentrations are higher in women than men. The sexual dimorphism for adiponectin has been attributed to the direct effects of testosterone on adipose tissue adiponectin secretion. However, serum testosterone and adiponectin concentrations are generally lower in obese men than lean men, suggesting that sex steroids may not be the only factor that contributes to sex differences in serum adiponectin. The primary objective of this study was to examine the influence of sex, body composition, and nonesterified fatty acids (NEFAs) on serum adiponectin concentrations. Women and men between the ages of 18 and 35 years were consecutively accrued into the study. Sixty-one participants were partitioned into normal-weight (15 female and 16 male) or obese (14 female and 16 male) groups. Blood samples were obtained after a 12-hour fast. Differences between groups were determined by analysis of variance with Tukey-Kramer post hoc testing. Serum adiponectin was 26% higher in women compared with men. Body mass index was associated with total serum adiponectin in men (r = −0.63, P < .05) but not women. Adiponectin was correlated with the homeostasis model assessment index in women (r = −0.56, P < .05) and men (r = −0.58, P < .05) and with NEFAs (r = −0.68, P < .05) in men only. After partitioning men and women into normal-weight and obese groups, serum adiponectin was lower and NEFAs were higher in obese men only. Homeostasis model assessment was similar between obese women and men despite higher NEFAs in the obese men. Leptin and plasminogen activator inhibitor–1 were higher in obese participants but were not associated with serum NEFAs. These results suggest that serum NEFAs may reduce adiponectin concentrations independent of their effects on insulin sensitivity in obese young men.     

Development of a Pediatric Cardiology Quality Improvement Collaborative: From Inception to Implementation. From the Joint Council on Congenital Heart Disease Quality Improvement Task Force

While clinical outcomes in pediatric cardiac disease have improved in recent years, marked institutional and individual cardiology practice variability exists. Quality improvement science has demonstrated that reducing process variation leads to more favorable outcomes, safer practices, cost savings, and improved operating efficiency. This report describes the process undertaken to develop the first collaborative quality improvement project of the Joint Council on Congenital Heart Disease. The project chosen aims to reduce mortality and improve the quality of life of infants with hypoplastic left heart syndrome during the interstage period between discharge from the Norwood procedure and admission for the bidirectional Glenn procedure. The objective of this special article is to inform the pediatric cardiology and cardiac surgery communities of the project to help ensure that the early work by the project pilot participants will spread to clinicians caring for children with cardiovascular disease. It is anticipated that this project will add to our understanding of care for this challenging group of children with hypoplastic left heart syndrome, identifying clinical care changes with the potential to lead to improvements in outcome. It will also introduce the field of pediatric cardiology to the science of collaborative quality improvement and assist in reducing clinical process variation and improving patient outcomes across centers. Finally, it will establish an ongoing network of pediatric cardiologists and their teams linked through a longitudinal data set and collaboration for improvement and research.     

Promoting adherence to medical and lifestyle interventions for women with cardiovascular disease

The prevalence of cardiovascular disease (CVD) in American women is staggering. In 2008, the American Heart Association reported that one in three women had some form of CVD. An estimated 7.3 million women alive today have had a heart attack or are living with angina pectoris. This year, almost 500,000 new and recurrent myocardial infarctions are expected in women. Education and counseling focusing on the acquisition of healthy lifestyle behaviors will help to protect women against the development of atherosclerosis. It is the responsibility of health care professionals to develop skills to facilitate lifestyle change and CVD risk reduction. This change can be accomplished only through a partnership with women that is based on careful risk evaluation, trust, open communication, skill building for behavioral change, and follow-up care. This article identifies educational and counseling approaches that have been shown to effect behavioral change in women.     

Differential strain and velocity generation along the right ventricular free wall in pulmonary hypertension

BACKGROUND:

In contrast to the homogeneously distributed deformation properties within the left ventricle, the right ventricular (RV) free wall (RVFW) shows a more inhomogeneous distribution. It has been demonstrated that pulmonary hypertension (PH) results in significant RVFW mechanical delay.

OBJECTIVE:

To assess the effect of the degree of pulmonary arterial systolic pressure on the RVFW strain gradient and on myocardial velocity generation.

METHODS:

Peak longitudinal strain and velocity data were collected from three different segments (basal, mid- and apical) of the RVFW in 17 normal individuals and 31 PH patients.

RESULTS:

A total of 144 RV wall segments were analyzed. RVFW strain values in individuals without PH were higher in the mid and apical segments than in the basal segment. In contrast, RVFW strain in PH patients was higher in basal segments and diminished toward the apex. In terms of RVFW velocities, both groups showed decremental values from basal to apical segments. Basal and mid-RVFW velocities were significantly lower in PH patients than in individuals without PH.

CONCLUSIONS:

PH results in significant alterations of strain and velocity generation that occurs along the RVFW. Of these abnormalities, the reduction in strain from the mid and apical RVFW segments was most predictive of PH. It is important to be aware of these differences in strain generation when studying the effect of PH on the right ventricle. Additional studies are required to determine whether these differences are due to RV remodelling.