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.     

Glutamate receptor antagonists block cocaine-induced convulsions and death.

The involvement of excitatory amino acid (EAA) receptors in mediation of the toxic effects of cocaine was studied in male ICR mice. Cocaine HCl (90 mg/kg, IP) induced seizures in 95% and death within 24 h in 68% (n = 135) of the animals. There was a significant correlation (r = .54) between the time to onset of convulsions and the time to death in mice which died within 30 min of injection (n = 84). Pretreatment with selected EAA receptor antagonists 15 min prior to cocaine differentially blocked cocaine toxicity. Selective N-methyl-D-aspartic acid (NMDA) receptor antagonists (MK-801, dextrorphan, CPP) decreased both the incidence of seizures and mortality. A nonselective EAA antagonist, kynurenic acid, decreased lethality in doses which did not reduce convulsions. A similar action was observed following pretreatment with the selective kainic acid/AMPA receptor antagonist, GDEE. Antagonists at EAA receptors can provide significant protection against cocaine-induced toxicity. Moreover, the data provide evidence for the involvement of both NMDA and non-NMDA receptor subtypes in aspects of cocaine toxicity.     

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.     

Plasma beta-endorphin immunoreactivity during graded cycle ergometry

The present study was undertaken to define the response of plasma beta-endorphin immunoreactivity (ir-BE) to exercise of increasing intensity. Nineteen healthy males performed continuous exercise for 32 min on a cycle ergometer, comprised of 8-min bouts at %VO2max approximating 25, 50, and 75% of maximal exercise. Venous blood samples were collected before exercise (T = -20 and 0 min), during exercise (T = 8, 16, 24, and 32 min), and in recovery (T = +15, +30 min). Ir-BE in plasma was measured by radioimmunoassay using Immuno Nuclear assay kits. Plasma ir-BE level (pg X ml-1) was not altered from pre-exercise (18.3 +/- 1.3) after 8 min of exercise at 25 and 50% VO2max intensity; however, ir-BE rose significantly after 8 min of 75% VO2max work intensity (27.1 +/- 2.4) and was further elevated at maximal exercise (74.1 +/- 8.6). Ir-BE level remained elevated 15 min (60.9 +/- 8.1) and 30 min (35.2 +/- 5.2) post-exercise. The response pattern was further characterized by a significant (P less than 0.05) inter-individual variation, both at rest and during exercise; also, regression analysis indicated the ir-Be levels attained at maximal exercise were inversely related to the relative VO2max (ml X kg-1 X min-1) of the subject (predicted ir-BE = 248.2 - 3.39 VO2max; r = -0.397, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

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).     

Percutaneous management of lymphatic fluid collections

Eight lymphatic fluid collections were drained percutaneously. There were no immediate or late complications. Seven patients had follow-up; 1 required surgical drainage of a residual or recurrent lymphocele, and another had reaccumulated fluid in a lymphocele which was detected on autopsy. The remaining lymphatic collections responded to percutaneous drainage. Percutaneous drainage is safe and can be an effective tool in the management of lymphatic collections.     

Changes in bone structure and mass with advancing age in the male C57BL/6J mouse.

To determine whether the mouse loses bone with aging and whether the changes mimic those observed in human aging, we examined the changes in the tibial metaphysis and diaphysis in the male C57BL/6J mouse over its life span using microcomputed tomography (microCT). Cancellous bone volume fraction (BV/TV) decreased 60% between 6 weeks and 24 months of age. Loss was characterized by decreased trabecular number (Tb.N), increased trabecular spacing (Tb.Sp), and decreased connectivity. Anisotropy decreased while the structure model index increased with age. Cortical bone thickness increased between 6 weeks and 6 months of age and then decreased continuously to 24 months (-12%). Cortical bone area (Ct.Ar) remained constant between 6 and 24 months. Fat-free weight reached a peak at 12 months and gradually declined to 24 months. Total mass lost between 12 and 24 months reached 10%. Overall, the age-related changes in skeletal mass and architecture in the mouse were remarkably similar to those seen in human aging. Furthermore, the rapid early loss of cancellous bone suggests that bone loss is not just associated with old age in the mouse but rather occurs as a continuum from early growth. We conclude that the C57BL/6J male mouse maybe a useful model to study at least some aspects of age-related bone loss in humans.     

Human osteoblasts' proliferative responses to strain and 17beta-estradiol are mediated by the estrogen receptor and the receptor for insulin-like growth factor I.

The mechanism by which mechanical strain and estrogen stimulate bone cell proliferation was investigated using monolayer cultures of human osteoblastic TE85 cells and female human primary (first-passage) osteoblasts (fHOBs). Both cell types showed small but statistically significant dose-dependent increases in [3H]thymidine incorporation in response to 17beta-estradiol and to a single 10-minute period of uniaxial cyclic strain (1 Hz). In both cell types, the peak response to 17beta-estradiol occurred at 10(-8) - 10(-7) M and the peak response to strain occurred at 3500 microstrain ((mu)epsilon). Both strain-related and 17beta-estradiol-related increases in [3H]thymidine incorporation were abolished by the estrogen receptor (ER) modulator ICI 182,780 (10-8 M). Tamoxifen (10(-9) - 10(-8) M) increased [3H]thymidine incorporation in both cell types but had no effect on their response to strain. In TE85 cells, tamoxifen reduced the increase in [3H]thymidine incorporation associated with 17beta-estradiol to that of tamoxifen alone but had no such effect in fHOBs. In TE85 cells, strain increased medium concentrations of insulin-like growth factor (IGF) II but not IGF-I, whereas 17beta-estradiol increased medium concentrations of IGF-I but not IGF-II. Neutralizing monoclonal antibody (MNAb) to IGF-I (3 microg/ml) blocked the effects of 17beta-estradiol and exogenous truncated IGF-I (tIGF-I; 50 ng/ml) but not those of strain or tIGF-II (50 ng/ml). Neutralizing antibody to IGF-II (3 microg/ml) blocked the effects of strain and tIGF-II but not those of 17beta-estradiol or tIGF-I. MAb aIR-3 (100 ng/ml) to the IGF-I receptor blocked the effects on [3H]thymidine incorporation of strain, tIGF-II, 17beta-estradiol, and tIGF-I. HOBs and TE85 cells, act similarly to rat primary osteoblasts and ROS 17/2.8 cells in their dose-related proliferative responses to strain and 17beta-estradiol, both of which can be blocked by the ER modulator ICI 182,780. In TE85 cells (as in rat primaries and ROS 17/2.8 cells), the response to 17beta-estradiol is mediated by IGF-I, and the response to strain is mediated by IGF-II. Human cells differ from rat cells in that tamoxifen does not block their response to strain and reduces the response to 17beta-estradiol in TE85s but not primaries. In both human cell types (unlike rat cells) the effects of strain and IGF-II as well as estradiol and IGF-I can be blocked at the IGF-I receptor.     

Endoscopic pterygopalatine space surgery

Although lesions of the pterygopalatine space are uncommon, there are instances in which this relatively inaccessible region must be entered for biopsy or excision of masses. Traditional open approaches to the pterygopalatine space, involving external or intraoral incisions, provide limited visualization and carry associated morbidities. The evolution and advancement of endoscopic sinus surgical technique in recent years has led to its application to anatomic areas outside the strict limits of the sinonasal cavities. Such minimally invasive approaches are safe, effective, and spare unnecessary discomfort to the patient. This article describes the authors' method for performing an endoscopic approach to the pterygopalatine space.