Molecular comparison of soluble intercellular adhesion molecule (sICAM)-1 and sICAM-3 binding to lymphocyte function-associated antigen-1

The interactions of intercellular adhesion molecules-1 and -3 (ICAM-1 and ICAM-3) with lymphocyte function-associated antigen-1 (LFA-1) have been characterized and compared on the molecular and cellular level. Enzyme-linked immunosorbent-based molecular assays have been utilized to calculate the binding affinities of soluble ICAM-1 (sICAM-1) and soluble ICAM-3 (sICAM-3) for LFA-1. Consistent with previously published data, we found that sICAM-1 binds to LFA-1 with an affinity of approximately 60 nM. In contrast, sICAM-3 binds to LFA-1 with an affinity approximately 9 times weaker ( approximately 550 nM). Both sICAM-1 and sICAM-3 require divalent cations for binding. Specifically, both Mg2+ and Mn2+ support high affinity adhesion, although interestingly, high concentrations of Ca2+ decrease the affinity of each molecule for LFA-1 substantially. Furthermore, a panel of anti-LFA-1 monoclonal antibodies were characterized for their ability to block sICAM-1 and sICAM-3/LFA-1 interactions in molecular and cellular assays to help distinguish binding sites on LFA-1 for both molecules. Finally, molecular and cellular competition experiments demonstrate that sICAM-1 and sICAM-3 compete with each other for binding to LFA-1. The above data demonstrate that sICAM-1 and sICAM-3 share a common binding site or an overlapping binding site on LFA-1 and that the apparent differences in binding sites can be attributed to different affinities of sICAM-1 and sICAM-3 for LFA-1.     

Phenytoin blocks the reversal of a classically conditioned discriminative eyeblink response in rabbits

The aim of the present study was to assess the role of vascular alpha 1D-adrenoceptors in the sympathetic vasopressor response in vivo. Specifically, we evaluated the effect of a selective alpha 1D-adrenoceptor antagonist, BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4,5)dec ane-7,9- dione 2HCl), on the vasopressor response induced by preganglionic (T7-T9) sympathetic stimulation in the pithed rat. The vasopressor response was dose-dependently sensitive to inhibition by intravenous BMY 7378 (0.1, 0.31, 1 and 3.1 mg/kg), doses of 1 and 3.1 mg/kg being equally effective. Like BMY 7378, 5-methylurapidil (0.1, 0.31, 1 and 3.1 mg/kg) antagonized the vasopressor response to spinal stimulation; doses of 1 and 3.1 mg/kg were also equally effective. In combination experiments, BMY 7378 (1 mg/kg, i.v.) and the alpha 1A-adrenoceptor antagonist, 5-methylurapidil (1 mg/kg, i.v.), showed an additive effect. The present results demonstrate that the alpha 1D-adrenoceptor subtype plays an important role in the pressor response to sympathetic nerve stimulation in the pithed rat, and confirm the participation of the alpha 1A-adrenoceptor subtype in the same response.     

A mechanism for anterior transposition of the anal fin and its appendicular support in the western mosquitofish, gambusia affinis affinis

Labored breathing and irregularities in the breathing pattern may be assessed by capnography; and, an abnormal capnogram wave form may often be rectified with the help of capnogram biofeedback. Clinical experience suggests this may relieve dyspnea but to what degree, for how long and for what conditions have not been determined; the issue is complex and much remains to be discovered. The more that can be learned about the various capnogram irregularities, the more effectively such information will guide us in therapy and research. To this end a 15-category capnogram disordered breathing scale (Landis CDBS) was developed to provide a measure of disordered breathing. The CDBS score is the ratio of the total number of abnormal capnogram forms to the total number of capnogram configurations in the test sample, expressed as a percentage. The total score as well as an accounting of each abnormal scoring category was tabulated for each subject. In this retrospective and preliminary study, findings of a normal comparison group were compared with capnogram data for 3 clinical groups: asthma, anxiety/panic attacks, and patients with diverse stress-related somatic symptoms. Mean CDBS scores were: a low 14% for the Normal group compared with 64% for the Asthma group; 66% for the Anxiety patients; and 47% for the Somatic group. Each group was characterized by distinctive clusters of capnogram abnormalities. As there are methodological limitations to this small group study, the findings require validation. However, as an introduction to the scoring system and because of its potential clinical value we present this paper now.     

L-374,087, an efficacious, orally bioavailable, pyridinone acetamide thrombin inhibitor

The potential for transfer of Escherichia coli O157:H7 from contaminated ground beef to grinding equipment and the inactivation of attached cells during cleaning and sanitizing was examined. Chub-packed ground beef with lean:fat ratios of 75:25, 80:20 or 90:10 was inoculated with 6 log CFU/g or 2 log CFU/g E. coli O157:H7 strain FRIK 910. Samples were consecutively ground in a Hobart meat grinder with stainless steel (SS) chips (1 cm2) glued to the auger housing. Chips were harvested after grinding, detergent washing with or without manual scrubbing and rinsing, sanitizing in a chlorine or peroxyacetic acid sanitizer, and overnight storage. Survival of E. coli O157:H7 was evaluated both by plate count and enrichment in trypticase soy broth. Approximately 3 to 4 log CFU/cm2 were attached to the SS after grinding with all three fat contents. After washing and sanitizing in a chlorine or peroxyacetic acid sanitizer, viable bacteria were infrequently recovered by plate count. Enrichment of chips resulted in a higher survival rate with both sanitizing treatments, indicating that cell numbers below the limit of detection (5 CFU/cm2) or potentially injured organisms remained on the surface. Manual scrubbing during the washing step reduced the recovery rate. The scrubbing step also increased the number of passing scores assigned using an ATP bioluminescence assay of total residual soil on the chips sanitized in chlorine. The overall results indicate that plate counts alone may not be a reliable indicator of sanitation efficacy and may be validated by enrichment assay.     

Daily reports of posttraumatic nightmares and anxiety dreams in Dutch war victims

Numerous women are treated with a combination of oestrogen and progestogen for contraception and hormone replacement therapy worldwide. A possible increased risk of cancer in target organs has been discussed vividly for many years. While oestrogens are clearly mitogenic for breast epithelial cells, there has been considerable uncertainty about the effects of progestogens. This article reviews current knowledge on this field, including our own data. Oestrogen receptors are down-regulated during the luteal phase, while progesterone receptors remain at a high level throughout the menstrual cycle. According to most studies, in vivo proliferation of normal breast epithelial cells is higher during the luteal phase in the vast majority of women. Normal breast tissue can convert oestrone sulphate to oestradiol. A negative correlation between the levels of circulating oestradiol and the enzyme converting oestrone into oestradiol suggests a local regulatory mechanism of tissue oestradiol formation. Serum progesterone levels correlate positively with sulphatase activity while 19-norsteroid progestogens may be inhibitory. We found that long-term continuous combined hormonal treatment with conjugated equine oestrogens and medroxyprogesterone acetate induced a proliferative response in the breasts of surgically postmenopausal macaques. The effect of combined treatment was more pronounced than that of oestrogen treatment alone. Both endogenous progesterone and exogenous progestogens increase proliferation of breast epithelial cells. Exogenous progestogens down-regulate both oestrogen and progesterone receptors. Oestrogen and progestogens may have both direct and indirect stimulating effects on proliferation. The finding of a positive correlation between insulin-like growth factor I messenger RNA and proliferation found in hormonally treated women with low receptor levels suggests the possibility of nonreceptor-mediated effects of sex steroids on proliferation, which needs to be investigated further.