Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50.

Two human B-cell differentiation antigens, Bp35 and Bp50, apparently play distinct roles as signal receptors in B-cell activation. Monoclonal antibodies (mAbs) to either Bp35 or Bp50 deliver positive signals to B cells that stimulate their transition through the cell cycle. mAb to Bp35, like anti-immunoglobulin antibodies, functions principally to activate resting B cells to become competent to enter the G1 phase of the cell cycle. In contrast, mAb to Bp50, a 50-kDa polypeptide expressed on all B cells, functions to stimulate activated B cells to traverse the cell cycle. mAb to Bp35, like anti-immunoglobulin antibodies, activates tonsillar B cells and induces low levels of B-cell proliferation. In contrast, anti-Bp50 mAb alone neither activates B cells nor induces B cells to proliferate but, together with anti-Bp35 or anti-immunoglobulin, augments B-cell proliferation. In this respect the action of anti-Bp50 antibody resembles the activity of B-cell growth factor(s) (BCGF). As little as 0.05 microgram of anti-Bp50 per ml is needed to augment proliferation and, like BCGF, anti-Bp50 is effective even when added 12-24 hr after B cells are activated with anti-immunoglobulin or anti-Bp35. Without additional exogenous signals, anti-Bp35 and anti-Bp50 together induce strong proliferation of purified resting B cells. These results suggest that the Bp35 and Bp50 surface molecules function in the regulatory control of B-cell activation and progression through the cell cycle.     

Cerebral hemorrhagic risk of aspirin or heparin therapy with thrombolytic treatment in rabbits

We studied the incidence of cerebral hemorrhage in an animal model of embolic stroke to determine the safety of aspirin, heparin, and tissue plasminogen activator therapies. We occluded the middle cerebral arteries of rabbits with labeled blood clots and administered either tissue plasminogen activator, heparin, aspirin, tissue plasminogen activator plus aspirin, tissue plasminogen activator plus heparin, or saline at various times after stroke. Compared to saline controls, both the aspirin-only and the tissue plasminogen activator-plus-aspirin groups had a significantly higher incidence of cerebral hemorrhage, whereas the heparin and tissue plasminogen activator combination groups did not. We conclude that aspirin antiplatelet therapy alone may increase the risk of hemorrhagic infarction, whereas heparin or tissue plasminogen activator therapy appears to be relatively safe.     

Intramuscular hypoperfusion, adrenergic receptors, and chronic muscle pain.

Despite a high prevalence of chronic muscle pain disorders such as fibromyalgia and regional myofascial pain, there is still limited knowledge about the factors that initiate and perpetuate these pain states. Although there are also likely to be downstream neuropathic changes in the central nervous system and spinal cord that sustain and exacerbate the pain states known as fibromyalgia, the focus of this critical review is on studies that examined the connection between both fibromyalgia and regional myofascial pain and sympathetic function. Specifically, we looked at studies that described Raynaud-like symptoms, cardiovascular dysfunction and altered intramuscular perfusion in chronic muscle pain. Our analysis showed that although the first 2 phenomena were intermittently present, a prominent and consistent feature for regional myofascial pain and to a lesser degree for fibromyalgia was intramuscular hypoperfusion. Several hypotheses can be offered why this hypoperfusion exists, and additional studies comparing and contrasting these theories are needed. This review focuses on one of these theories, namely, agonist-induced beta-adrenergic receptor desensitization as an explanatory model for hypoperfusion. What cannot be done at this time and is needed in the future is to compare and contrast to what degree the regional muscle pain disorder (myofascial) is similar or different from the more generalized disorder (fibromyalgia).     

Nuclear estrogen receptor beta in lung cancer: expression and survival differences by sex.

PURPOSE: A role for estrogens in determining lung cancer risk and prognosis is suggested by reported sex differences in susceptibility and survival. Archival lung tissue was evaluated for the presence of nuclear estrogen receptor (ER)-alpha and ER-beta and the relationship between ER status, subject characteristics, and survival. EXPERIMENTAL DESIGN: Paraffin-embedded lung tumor samples were obtained from 214 women and 64 men from two population-based, case-control studies as were 10 normal lung autopsy samples from patients without cancer. Nuclear ER-alpha and ER-beta expression was determined by immunohistochemistry. Logistic regression was used to identify factors associated with ER positivity and Cox proportional hazards models were used to measure survival differences by ER status. RESULTS: Neither tumor (0 of 94) nor normal (0 of 10) lung tissue stained positive for ER-alpha. Nuclear ER-beta positivity was present in 61% of tumor tissue samples (170 of 278; 70.3% in men and 58.3% in women) and 20% of normal tissue samples (2 of 10; P = 0.01). In multivariate analyses, females were 46% less likely to have ER-beta-positive tumors than males (odds ratio, 0.54; 95% confidence interval, 0.27-1.08). This relationship was stronger and statistically significant in adenocarcinomas (odds ratio, 0.40; 95% confidence interval, 0.18-0.89). Women with ER-beta-positive tumors had a nonsignificant 73% (P = 0.1) increase in mortality, whereas men with ER-beta-positive tumors had a significant 55% (P = 0.04) reduction in mortality compared with those with ER-beta-negative tumors. CONCLUSIONS: This study suggests differential expression by sex and influence on survival in men of nuclear ER-beta in lung cancer, particularly in adenocarcinomas.