Higher-level snake phylogeny inferred from mitochondrial DNA sequences of 12S rRNA and 16S rRNA genes

N-Nitrosomethylbenzylamine (NMBA) is a potent esophagus-specific carcinogen that has been utilized extensively in the study of esophageal carcinogenesis in rats. While many studies have focused on the pathogenesis of NMBA-induced esophageal tumors, the tumorigenicity of NMBA itself has not been thoroughly investigated in any single, systematic dose-response study. Therefore, in this study we evaluated NMBA tumorigenicity in rats following various short-term s.c. treatment regimens with the aim of developing an abbreviated treatment protocol which could be used in future studies. To assess the possible correlation of basal cell proliferation with NMBA tumorigenicity, we evaluated the expression of proliferating cell nuclear antigen (PCNA) in both control and NMBA-treated rats. In rats which received a cumulative NMBA dosage of 7.5 mg/kg over the course of 5 weeks, tumor incidence and multiplicity were as follows: 40% with 0.4 +/- 0.3 tumors/rat at week 10; 100% with 2.2 +/- 1.0 tumors/rat at week 20; and 100% with 2.3 +/- 1.0 tumors/rat at week 30. These rats exhibited marked increases in basal cell labeling, with indices that were 1.5- to 1.8-fold higher than controls. NMBA treatment regimens of shorter duration with equivalent or higher cumulative dosages were generally ineffective in producing esophageal tumors, even though significantly elevated levels of basal cell proliferation occurred. Together, these findings indicate that the duration of NMBA treatment is of critical importance in the tumorigenic potential of the carcinogen.     

Further Archeological and Ethnological Findings on the Obscure, Late 20th Century, Quasi-Religious Earth Group Known as "the Therapists" (A Fantasy About the Future of Psychotherapy).

This article reviews the history of the field of therapy from the perspective of an extraterrestrial archeological survey team. By the time of their visit in the distant future, a collision between a comet and the planet Earth has wiped out civilization as a whole. The group discovers, however, that the field of mental health died out long before this cataclysm. A scheme for classifying the various schools of therapy is developed on the basis of the aliens' understanding of Earth religions and philosophical traditions. The emergence and eventual disappearance of the field is then explored and explained according to principles of evolutionary biology (including overpopulation, ecological competition, assimilation, and genetic drift). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preoperative cardiac evaluation is unnecessary in most patients undergoing vascular operations

OBJECTIVES AND METHODS: Our goal was to describe nutritional homeostasis in healthy exclusively breastfed infants (n = 175) during their first 5 d, by cross-sectional measurements of body weight, blood glucose, plasma insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding-protein-1 (IGFBP-1), free fatty acids (FFA), glycerol, ketone (3-OH-butyric acid) and lactate. We also investigated whether nutrition affected feeding behaviour by timing the interval between feedings. RESULTS: A progressive loss of body weight, as percentage of birthweight, occurred up to 2 d of age, with a maximal decrease of 5.8 +/- 2.1% (mean +/- SD); this was accompanied by inhibition of anabolic hormone and metabolic pathways and an increased mobilization of stored fat and ketogenesis. The interval between feedings decreased between d 1 and 2. Weight gain occurred at 3 d and the following re-feeding phase returned fuel stores to their previous levels and established an anabolic hormonal and metabolic situation. Infants with weight loss exceeding 10% had a further accentuation in their peripheral picture of starvation and a further 7% shortening of the interval between feedings. CONCLUSIONS: breastfeeding on demand is accompanied by a balanced nutritional situation and an increased drive to eat when weight reduction is <6%. However, a weight loss of > or = 10%, probably elicits hunger sensations in response to decreased fuel availability.     

Prevalence of harassment and discrimination among 1996 medical school graduates: a survey of eight US schools

CONTEXT: Harassing and discriminating behaviors on the part of instructors or supervisors are known to affect the quality of work performed by medical students, influence their career decisions, and have other undetermined long-term consequences. OBJECTIVE: To assess the prevalence and forms of harassment and discrimination experienced by 1996 medical school graduates. DESIGN: A self-administered survey of harassment and discrimination mailed to graduating medical students. SETTING AND PARTICIPANTS: A total of 1001 graduating medical students at 8 US medical schools (4 public and 4 private), chosen from each of the 4 regions designated by the Association of American Medical Colleges for geographic categorization. OUTCOME MEASURE: The number of reported experiences of various forms of harassment and discrimination while attending medical school. RESULTS: Of 1001 surveys, 548 (55%) were returned. Overall, 46% of the students reported experiencing some form of harassment and 41% some form of discrimination from instructors or supervisors while attending medical school. Nonsexual verbal harassment was reported by 41%; sexual verbal harassment was reported by 10%. Discrimination based on gender was reported by 29% of students; discrimination based on race was reported by 12%. CONCLUSIONS: Harassment and discrimination of medical students by instructors and supervisors continue to occur frequently, and new approaches are needed to address these problems.     

Angioplasty of the occluded internal carotid artery

PURPOSE: To review patients who have presented with acute strokes from a middle cerebral artery occlusion in whom in addition to the middle cerebral artery thromboembolus, an internal carotid artery occlusion has been present, and in whom angioplasty of these totally occluded internal carotid arteries has bee n successful. METHODS: We reviewed retrospectively our experience in treating a cute stroke patients with intracranial, intraarterial urokinase. Six of 27 patients had internal carotid artery occlusions in addition to middle cerebral artery occlusions. Two patients presented with spontaneous carotid dissections for wh ich no further intervention from the ipsilateral internal carotid artery was attempted. In the remaining four internal carotid artery occlusions secondary to atherosclerotic disease, standard guide wires and catheters were negotiated across the level of the internal carotid artery occlusion, which expedited intracranial catheterization for thrombolysis. Subsequently, angioplasty of the internal carotid artery was performed. RESULTS: All four occluded internal carotid arteries could be traversed. No new neurologic deficits occurred. No vascular injuries occurred. No deaths occurred. Four- to 6-month follow-up showed all four internal carotid arteries remained patent. CONCLUSION: In acute occlusions of the internal carotid artery from atherosclerosis, the occluded vessel can sometimes be recanalized with low morbidity. In addition, endovascular access to the intracranial circulation can be expedited by using the recanalized internal carotid artery.     

How do I diagnose and treat wound infection?

ACRP30--adipocyte complement-related protein of 30 kDa or AdipoQ--is an abundant serum protein, secreted exclusively from fat cells, which is implicated in energy homeostasis and obesity [1,2]. ACRP30 is a close homologue of the complement protein C1q, which is involved in the recognition of microbial surfaces [3-5] and antibody-antigen complexes [6,7] in the classical pathway of complement. We have determined the crystal structure of a homotrimeric fragment from ACRP30 at 2.1 A resolution. The structure reveals an unexpected homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and C1q families. We suggest that TNFs--which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis--arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between C1q-like proteins and TNFs illuminates the shared functions of these two important groups of proteins.     

An important role for the chemokine macrophage inflammatory protein-1 alpha in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated, inflammatory demyelinating disease of the central nervous system (CNS) that serves as a model for the human demyelinating disease, multiple sclerosis. A critical event in the pathogenesis of EAE is the entry of both Ag-specific T lymphocytes and Ag-nonspecific mononuclear cells into the CNS. In the present report we investigated the role of two C-C chemokines (macrophage inflammatory protein-1 alpha (MIP-1 alpha) and monocyte chemotactic protein-1) and a C-x-C chemokine (MIP-2) in the pathogenesis of EAE. Production in the CNS of MIP-1 alpha, but not that of MIP-2, a rodent homologue of IL-8, or monocyte chemotactic protein-1, correlated with development of severe clinical disease. Administration of anti-MIP-1 alpha, but not that of anti-monocyte chemotactic protein-1, prevented the development of both acute and relapsing paralytic disease as well as infiltration of mononuclear cells into the CNS initiated by the transfer of neuroantigen peptide-activated T cells. Ab therapy could also be used to ameliorate the severity of ongoing clinical disease. Anti-MIP-1 alpha did not affect the activation of encepahlitogenic T cells as measured by cytokine secretion, surface marker expression, and ability to adoptively transfer EAE. These results demonstrate that MIP-1 alpha plays an important role in directing the chemoattraction of mononuclear inflammatory cells in the T cell-mediated autoimmune disease, EAE.     

Localization of the binding site for transforming growth factor-beta in human alpha2-macroglobulin to a 20-kDa peptide that also contains the bait region

alpha2-Macroglobulin (alpha2M) functions as a major carrier of transforming growth factor-beta (TGF-beta) in vivo. The goal of this investigation was to characterize the TGF-beta-binding site in alpha2M. Human alpha2M, which was reduced and denatured to generate 180-kDa subunits, bound TGF-beta1, TGF-beta2, and NGF-beta in ligand blotting experiments. Cytokine binding was not detected with bovine serum albumin that had been reduced and alkylated, and only minimal binding was detected with purified murinoglobulin. To localize the TGF-beta-binding site in alpha2M, five cDNA fragments, collectively encoding amino acids 122-1302, were expressed as glutathione S-transferase (GST) fusion proteins. In ligand blotting experiments, TGF-beta2 bound only to the fusion protein (FP3) that includes amino acids 614-797. FP3 bound 125I-TGF-beta1 and 125I-TGF-beta2 in solution, preventing the binding of these growth factors to immobilized alpha2M-methylamine (alpha2M-MA). The IC50 values were 33 +/- 5 and 26 +/- 6 nM for TGF-beta1 and TGF-beta2, respectively; these values were comparable with or lower than those determined with native alpha2M or alpha2M-MA. A GST fusion protein that includes amino acids 798-1082 of alpha2M (FP4) and purified GST did not inhibit the binding of TGF-beta to immobilized alpha2M-MA. FP3 (0.2 microM) neutralized the activity of TGF-beta1 and TGF-beta2 in fetal bovine heart endothelial (FBHE) cell proliferation assays; FP4 was inactive in this assay. FP3 also increased NO synthesis by RAW 264.7 cells, mimicking an alpha2M activity that has been attributed to the neutralization of endogenously synthesized TGF-beta. Thus, we have isolated a peptide corresponding to 13% of the alpha2M sequence that binds TGF-beta and neutralizes the activity of TGF-beta in two separate biological assays.