Malassezia pachydermatis: a review.

Malassezia pachydermatis is of importance in both veterinary and human medicine. Its taxonomic status and physiological characteristics are now better understood. Skin disease associated with this lipophilic yeast is now commonly recognized, especially in dogs.

Treatment with inverse agonists enhances baseline atrial contractility in transgenic mice with chronic beta2-adrenoceptor activation.

In this study, we investigate whether chronic treatment with beta-adrenoceptor (betaAR) ligands with inverse agonist activity enhances myocardial beta2AR-mediated atrial tension more than neutral antagonists in transgenic mice (TG35). These mice exhibit chronic adrenoceptor activation because they possess a greater number of constitutively active receptors than wild type mice due to cardiac-specific overexpression of human betaARs. TG35 and wild type mice were chronically treated for 90 h with three inverse agonists, ICI-118,551, propranolol, and carvedilol, and one neutral antagonist, alprenolol.

Crystal structure of farnesyl protein transferase complexed with a CaaX peptide and farnesyl diphosphate analogue.

The crystallographic structure of acetyl-Cys-Val-Ile-selenoMet-COOH and alpha-hydroxyfarnesylphosphonic acid (alphaHFP) complexed with rat farnesyl protein transferase (FPT) (space group P61, a = b = 174. 13 A, c = 69.71 A, alpha = beta = 90 degrees, gamma = 120 degrees, Rfactor = 21.

Humoral and cell-mediated responses to Malassezia pachydermatis in healthy dogs and dogs with Malassezia dermatitis.

The in vitro proliferative responses of peripheral blood mononuclear cells from seven healthy basset hounds exposed to Malassezia pachydermatis antigen (500 micrograms/ml) exceeded (P < 0.05) those of seborrhoeic basset hounds with high populations of M pachydermatis and eight Irish setters with gluten-sensitive enteropathy. The stimulation indices in the latter two groups and in eight healthy beagles were comparable.

The elusive nature of intrinsic efficacy.

In the discipline of pharmacology, drugs (ligands) are used as tools to elucidate the processes of biological systems. Because of this, pharmacologists strive to delineate all characteristics of drugs. Decades of research have resulted in the proposal that ligands possess two properties that are intrinsic to the ligand and are invariant of the system in which their effects are investigated.

Racial origin, sexual lifestyle, and genital infection among women attending a genitourinary medicine clinic in London (1992).

Objectives: To compare variables of sexual behaviour and incidence of genital infections among women of different racial origins and lifestyles.

Design: A prospective cross sectional study of sexual behaviour reported by a standardised self administered questionnaire in new patients who presented for screening and diagnosis.

Setting: A genitourinary medicine clinic in west London.

Racial origin, sexual behaviour, and genital infection among heterosexual men attending a genitourinary medicine clinic in London (1993-4).

Objectives: To compare variables of sexual behaviour and incidence of genital infections among heterosexual men of different racial origins.

Design: A prospective cross sectional study of sexual behaviour reported by a standardised self administered questionnaire in new patients who presented for screening and diagnosis.

Setting: A genitourinary medicine clinic in west London.

Sexual relationships, risk behaviour, and condom use in the spread of sexually transmitted infections to heterosexual men.

Objective: To examine the effect of patient defined non-regular sexual relationships and other risk behaviours on the incidence of sexually transmitted infections in heterosexual men and the role of condom use in the prevention of their spread.

Design: A prospective cross sectional study of sexual behaviour reported by a standardised self administered questionnaire in new patients who presented for screening and diagnosis.

Setting: A genitourinary medicine clinic in west London.

Heterosexual behaviour, risk factors and sexually transmitted infections among self-classified homosexual and bisexual men.

Our study of men presenting at a genitourinary medicine clinic shows that self-classification into homosexual or bisexual does not accurately define behaviour. We found that 8.5% of self-defined homosexual men had had heterosexual intercourse in the past year and that 26% of self-defined bisexual men had not.

Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma.

Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months' duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time.

Inverse agonism and the regulation of receptor number.

Inverse agonists are ligands that preferentially stabilize inactive conformations of G protein-coupled receptors. In a range of systems, sustained treatment with inverse agonists can produce substantially greater upregulation of receptor levels than antagonists. The use of constitutively active mutant receptors can exaggerate this effect but may also allow agonists and antagonists to mimic the effect by preventing denaturation of the mutant receptor polypeptide.

Field trauma triage: combining mechanism of injury with the prehospital index for an improved trauma triage tool.

Background: The objective of this study was to combine a physiologic triage score (prehospital index, PHI) with criteria regarding mechanism of injury (MOI) to increase the efficacy of trauma triage. The specific question being asked was: will the combined score improve the sensitivity and specificity over that of the individual scores?

Methods: In this prospective study, 3,147 injury patients (all adults > or = 14 years) were reviewed. Each patient received a PHI score and a MOI score in the field, which were compared with their Injury Severity Score (ISS) at separation.

An efficacy-dependent effect of cardiac overexpression of beta2-adrenoceptor on ligand affinity in transgenic mice.

In previous studies, it was shown that the overexpression of beta2-adrenoceptor (beta2AR) in the hearts of transgenic mice (Tg) leads to agonist-independent activation of adenylate cyclase and enhanced myocardial function. Here, we measured the physical coupling of beta2AR and Gs by evaluating the coimmunoprecipitation of beta2AR and Gs and the ligand binding properties of beta2AR in the hearts of Tg mice to investigate the details of the interaction among ligand, receptor, and G protein. The following results were obtained: (i) coimmunoprecipitation of beta2AR and Gs was increased in the absence of agonist in Tg mice compared with the control animals.

Thrombocytopenia following timber rattlesnake envenomation.

Study Objective: To better characterize timer rattlesnake venom--induced thrombocytopenia and coagulopathy and the response to therapy with Antivenin (Crotalidae) Polyvalent.

Methods: We conducted a retrospective multicenter review of timber rattlesnake envenomation.

Results: We reviewed 18 cases at two institutions.

Skin and mucosal populations of Malassezia pachydermatis in healthy and seborrhoeic Basset Hounds.

Quantitative and semiquantitative cultural techniques were used to study skin and mucosal carriage of Malassezia pachydermatis in 20 healthy mixed-breed dogs, 13 healthy Basset Hounds and 33 seborrhoeic Basset Hounds. The frequencies of isolation and population sizes from the axilla, nose, mouth and vulva were significantly greater (P < 0.01) in both groups of Basset Hounds when compared with the healthy mixed-breed dogs.

Do recent operational studies indicate that a single state model is no longer applicable to G protein-coupled receptors?

Recent evidence suggests that unliganded G protein-coupled receptors exist in at least two states, an inactive conformation and an active conformation possessing affinity for the G protein even in the absence of agonist. The data accumulated so far for wild-type receptors imply that this is true for receptors for several hormones and receptor subtypes, and theoretically for all G protein-coupled receptors. The data now consist of studies implicating not only spontaneous receptor-G protein coupling, but also effector mechanisms and, in the case of transgenic mice over-expressing the human beta 2-adrenoceptor, physiologic responses at the level of the isolated tissue and in vivo.

Characterization of Ha-ras, N-ras, Ki-Ras4A, and Ki-Ras4B as in vitro substrates for farnesyl protein transferase and geranylgeranyl protein transferase type I.

Ras proteins are small GTP-binding proteins which are critical for cell signaling and proliferation. Four Ras isoforms exist: Ha-Ras, N-Ras, Ki-Ras4A, and Ki-Ras4B. The carboxyl termini of all four isoforms are post-translationally modified by farnesyl protein transferase (FPT).

Calcium-activated potassium channel-mediated arteriolar relaxation during endotoxic shock.

The role of calcium-activated potassium (KCa) channels in the in vivo relaxation of arterioles was investigated before endotoxin shock (Pre-ENDT) and during endotoxin shock at 180 min (Post-ENDT). Diameters of 2nd and 3rd order (A2 and A3) arterioles in the left cremaster muscle of male Sprague-Dawley rats anesthetized with pentobarbital sodium were measured using videomicroscopy. Adenosine (ADO) at 534 micrograms intraarterially, topical ADO at 10(-3) M, and the endothelium-dependent agonist topical acetylcholine (ACH) at 10(-4) M significantly dilated both A2 and A3 arterioles Pre-ENDT and Post-ENDT.

Ligand-induced overexpression of a constitutively active beta2-adrenergic receptor: pharmacological creation of a phenotype in transgenic mice.

Transgenic overexpression (40- to 100-fold) of the wild-type human beta2-adrenergic receptor in the hearts of mice leads to a marked increase in cardiac contractility, which is apparently due to the low level of spontaneous (i.e., agonist-independent) activity inherent in the receptor.

Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function.

The beta-adrenergic receptor kinase 1 (beta ARK1) is a member of the G protein-coupled receptor kinase (GRK) family that mediates the agonist-dependent phosphorylation and desensitization of G protein-coupled receptors. We have cloned and disrupted the beta ARK1 gene in mice by homologous recombination. No homozygote beta ARK1-/- embryos survive beyond gestational day 15.