Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function

Coat colors in the chestnut horse, the yellow Labrador retriever, the red fox, and one type of yellow mouse are due to recessive alleles at the extension locus. Similarly, dominant alleles at this locus are often responsible for dark coat colors in mammals, such as the melanic form of the leopard, Panthera pardus. We show here that the murine extension locus encodes the melanocyte-stimulating hormone (MSH) receptor. In mice, the recessive yellow allele (e) results from a frameshift that produces a prematurely terminated, nonfunctioning receptor. The sombre (Eso and Eso-3J) and tobacco darkening (Etob) alleles, which both have dominant melanizing effects, results from point mutations that produce hyperactive MSH receptors. The Eso-3J receptor is constitutively activated, while the Etob receptor remains hormone responsive and produces a greater activation of its effector, adenylyl cyclase, than does the wild-type allele.     

Lessons learned from the DIASTAT vascular access graft

In male Syrian hamsters, short days induce regression of the reproductive system, but eventually spontaneous recrudescence occurs ensuing from refractoriness to the inhibitory photoperiod. Although the photoperiod of 12 L:12 D (12 h light:12 h dark) may act like a short day by inducing the testicular cycle outlined above, it may fail to evoke the increase of circulating concentrations of prolactin that accompanies testicular recrudescence. This photoperiod may fail to induce photorefractoriness, as indicated by the prolonged low concentrations of prolactin in the blood. Herein, hamsters were exposed to either 8 L:16 D or 12 L:12 D from weaning and by 28 weeks exposure to either photoperiod, the hamsters had large testes following recrudescence from a photoperiod induced-regression). Transfer to 8 L:16 D from 12 L:12 D at 28 weeks resulted in a second testicular regression and recrudescence. In a second experiment, the testes of hamsters moved to 8 L:16 D from 12 L:12 D after 29 weeks exposure to the latter photoperiod similarly regressed and then regrew. Serum concentrations of prolactin decreased in these males after transfer to the shorter daylength but also decreased in hamsters kept under 12 L:12 D both groups were usually below those of hamsters moved to 14 L:10 D. These results show that exposure for 28 or 29 weeks to 12 L:12 D was insufficient to induce photorefractoriness, despite the recrudescence of the testes following involution.     

Systemic lupus erythematosus in three ethnic groups: II. Features predictive of disease activity early in its course. LUMINA Study Group. Lupus in minority populations, nature versus nurture

OBJECTIVE: To determine the factors associated with disease activity in patients with recent-onset (< or =5 years) systemic lupus erythematosus (SLE) who were of Hispanic, African-American, or Caucasian ethnicity. METHODS: Incident and prevalent cases of SLE, as defined by the American College of Rheumatology criteria for SLE, among the 3 ethnic groups were identified in Alabama (The University of Alabama at Birmingham) and Texas (The University of Texas-Houston Health Science Center and The University of Texas Medical Branch at Galveston). Variables from the sociodemographic, clinical, immunologic, immunogenetic, behavioral, and psychological domains were obtained using validated instruments. Disease activity was ascertained with the Systemic Lupus Activity Measure (SLAM). Stepwise domain regressions with SLAM score as the dependent variable were performed. Final ethnic-specific and overall regression models were obtained by entering variables that were retained in the domain regressions. RESULTS: SLAM scores at study entry were higher in the African Americans (mean +/- SD 12.6 +/- 6.9) and Hispanics (11.0 +/- 6.2) than in the Caucasians (8.5 +/- 3.7) (P < or = 0.001). The final overall regression model (R2 = 28%) for higher SLAM score included the following variables: African-American ethnicity, lack of private health insurance, abrupt disease onset, presence of anti-Ro antibodies, absence of HLA-DRB1*0301, higher levels of helplessness, and abnormal illness-related behaviors. CONCLUSION: Socioeconomic, immunologic, immunogenetic, behavioral, and psychological variables were all predictive of disease activity early in the course of SLE, irrespective of ethnic group. However, there remain ethnic group differences in disease activity that were not explained by these factors.     

Paramagnetic 1H-NMR relaxation probes of stereoselectivity in metalloporphyrin catalyzed olefin epoxidation

Enantioselective catalytic epoxidation of olefins is an important problem from both practical and mechanistic points of view. The origins of chiral induction by asymmetric porphyrin and salen complexes were investigated by FT-NMR T1 relaxation techniques. A new chiral vaulted porphyrin (1) that carries (S)-binaphthyl-L-alanine straps across both faces of the porphyrin macrocycle was synthesized and characterized. (R)-styrene oxide was obtained in > 90% ee in the initial stages of styrene epoxidation with F5PhIO catalyzed by 1-Fe(III)Cl. The transition state for olefin epoxidation with high-valent metal-oxo species was modeled by coordinating epoxides to paramagnetic copper complexes of the corresponding ligands. The epoxide enantiomer that better fit the chiral cavity of the catalyst, as revealed by T1 relaxation measurements, was also the major product of catalytic olefin epoxidation. These results are consistent with the "lock-and-key" mechanism of asymmetric catalysis by metalloporphyrins. The copper complex of a chiral salen ligand showed no differentiation in terms of T1 relaxation rates between the enantiomers of cis-beta-methylstyrene oxide in contrast to the high enantioselectivity observed for catalytic epoxidation.     

Infections due to Lancefield group F and related Streptococci (S. milleri, S. anginosus)

We can no longer accept classification of streptococci solely on the basis of hemolytic reactions or Lancefield agglutinations. While the "viridans" streptococci cannot be serologically differentiated, physiological separation of the species offers a satisfactory method of classifying human isolates. We review the microbiology of Lancefield group F and related streptococci (S. milleri, S. anginosus), emphasizing microbial ecology and current taxonomic considerations. A series of 28 patients infected with these organisms is presented. There was a striking male predominance in the series (6:1) as well as an obvious association with underlying diseases and/or antecedent trauma. The most remarkable feature of these pathogens is their predilection for abscess formation, confirming their overdue recognition as the most common "viridans" streptococcus recovered from abscesses within internal organs. We observed purulent disease of the nervous and skeletal systems, oral cavity, lung and pleural space, abdomen and subcutaneous tissues. Microbial synergy (i.e. polymicrobic infection) was not a requisite for abscess formation. Four of the five deaths in this series occurred in patients 60 years of age of older. Some degree of variability in antimicrobial susceptibility was noted, so speciation alone may not always provide sufficient information on which to base a therapeutic decision.     

Yb:YAG absorption at ambient and cryogenic temperatures

We have performed absorption measurements and generated absorption cross sections as a function of wavelength for the laser material YAG doped with ytterbium at 300, 175, and 75 K. This data was generated to enable a direct comparison of the absorption intensity and linewidths at room and cryogenic temperatures, and in particular near the temperature of liquid nitrogen at 77 K. The data have been used to compute universal absorption contour plots that display absorption as a function of the incident light center wavelength and optical thickness (doping density times penetration depth) for a number of bandwidths, and assuming that the spectrum of the incident light can be described as a Gaussian. Curves are presented for both 300 and 75 K, and may be used to optimize the absorption and laser efficiency.     

Attenuation of cocaine-induced locomotor activity by butyrylcholinesterase.

A primary enzyme for the metabolism of cocaine is butyrylcholinesterase (BChE). To determine whether the systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect, rats were tested in a locomotor activity chamber after receiving 17 mg of cocaine per kg intraperitoneally. In rats pretreated intravenously with 5,000 IU of horse serum-derived BChE, the locomotor activity effect was significantly attenuated. BChE pretreatment increased plasma BChE levels approximately 400-fold. When added to rat plasma, this amount of BChE reduced the cocaine half-life from over 5 hr to less than 5 min. BChE altered the cocaine metabolic pattern such that the relatively nontoxic metabolite ecgonine methyl ester was produced, rather than benzoylecgonine. These results suggest that systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect of cocaine and thus should be investigated as a potential treatment for cocaine abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The physiological diagnosis of neurocirculatory dystonia

The authors of the present article were the first to work out theoretical foundations and methods of physiological diagnosis of neurocirculatory dystonia. Criteria of tension of myocardial functional structures and central regulatory mechanisms have been identified both in healthy subjects and cardiological patients. It has been ascertained that degree and systematic character of tension cause the physiological risk factors for cardio-pathology to develop, 6 types were identified of loading adaptation of the heart caused by extent of its tension, in individuals with neurocirculatory dystonia. Each of the types disclosed is characterized by a dynamics of the functional volumes proportions as well as by peculiarities of the adaptation mechanisms. Physiological diagnosis of functioning of the heart is one of major methods of the primary prophylaxis of neurocirculatory dystonias as well as prevention of aggravation of their course.     

Design of constructions for the expression of proteolytic antibody light chain

A new system for the expression of a catalytic light chain antibody to the vasoactive intestinal peptide is described. The system made possible the isolation the large amounts of a homogeneous protein without any additional peptide domains. The preparation obtained can be used in further experiments on light chain crystallization and in X-ray-structural analysis of its catalytic center.     

Necrotizing fasciitis

Necrotizing fasciitis is a rare soft tissue infection with a high rate of mortality. Decreased capacity of the immune response is the overall disposing factor. Necrotizing fasciitis can develop very rapidly, and a rapid diagnosis and aggressive surgery provides the best prognosis.