Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice reconstituted with human peripheral blood lymphocytes

Vitamin A deficiency is associated with increased childhood morbidity and mortality from respiratory and diarrheal diseases. In order to evaluate the effect of vitamin A on human antibody responses, we developed a vitamin A-deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-deficient mice were produced by depriving them of vitamin A at day 7 of gestation. Mice were reconstituted with human peripheral blood lymphocytes (huPBL) from tetanus toxoid immune donors at 6 weeks of age and immunized with tetanus toxoid at 6 and 8 weeks of age. Secondary human antibody responses were determined 10 days later. The geometric mean human anti-tetanus toxoid immunoglobulin G concentrations were 3.75 micrograms/ml for the deficient mice and 148 micrograms/ml for controls (P = 0.0005). Vitamin A-deficient mice had only a 2.9-fold increase in human anti-tetanus toxoid antibody compared with a 74-fold increase in controls (P < 0.01). Supplementation with vitamin A prior to reconstitution restored human antibody responses to normal. These data suggest that vitamin A deficiency impairs human antibody responses. We speculate that impaired responses could increase susceptibility to certain infections. Furthermore, we propose that effects of other nutritional deficiencies on the human immune system could be evaluated in the SCID-huPBL model.     

Differential metabolism of exogenous platelet-activating factor by glandular epithelial and stromal cells of rabbit endometrium

Significant changes in platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) concentration have been observed in rabbit endometrium during the preimplantation period, but, under in vitro conditions, constitutive PAF biosynthesis by isolated endometrial tissues was not easily demonstrable. Relative changes in enzymes involved in the synthesis and metabolism of PAF in the tissues may account for this disparity. In addition, during this period of preimplantation, marked changes in PAF receptor concentration have been noted. The present study examines the factors that may modulate the metabolism of exogenous [3H]PAF in the endometrium of rabbits on day 6 of pregnancy. Since preferential [3H]PAF binding in situ by the glandular epithelial, but not by the stromal, cells was demonstrated, their cell-specific metabolism of exogenous [3H]PAF was also examined. After entry into the endometrial cell, [3H]PAF was rapidly metabolized by the sequential action of cytosolic Ca(2+)-independent acetylhydrolase to [3H]lyso-PAF and this was in turn acylated by membrane-associated transacylase to [3H]alkylacyl-glycerylphosphorylcholine. PAF resynthesis was not observed and, in stromal cells, there was a significant build-up of [3H]lyso-PAF, suggesting that lyso-PAF:acetyl-CoA acetyl-transferase may be a limiting factor. In the glandular epithelial cells, however, there was a significant accumulation of a neutral lipid without a significant build-up of [3H]lyso-PAF or [3H]PAF. The neutral lipid co-migrated with the product of phospholipase C-catalysed metabolism of PAF and authentic 1-O-hexadecyl-2-acetyl-glycerol. In addition, the elution times of phospholipase C digestion of C18 PAF and the neutral lipid produced by cellular metabolism of [3H]PAF, determined by gas chromatography/flame ionization detection, were similar. It seems that it is the synthesis of the neutral lipid from reacetylated [3H]lyso-PAF that prevented [3H]PAF accumulation under in vitro conditions. This is the first documentation of the synthesis of this lipid in the mammalian uterus. The lipid may serve as the precursor for de novo PAF synthesis in the glandular epithelial cells during endometrial proliferation.     

US national survey of physician practices for the secondary and tertiary prevention of ischemic stroke. Design, service availability, and common practices

BACKGROUND AND PURPOSE: Stroke is largely a preventable disease. However, there are little data available concerning the use of stroke prevention diagnostic and treatment modalities by practicing physicians. These data are critical for the rational allocation of resources and targeting of educational efforts. The purposes of this national survey were to gather information about physicians' stroke prevention practice patterns and their attitudes and beliefs regarding secondary and tertiary stroke prevention strategies. METHODS: We conducted a national survey of stroke prevention practices among a stratified random sample of 2000 physicians drawn from the American Medical Association's Physician Masterfile. The survey focused on the availability of services and the use of diagnostic and preventive strategies for patients at elevated risk of stroke. RESULTS: Sixty-seven percent (n = 1006) of eligible physicians completed the survey. Diagnostic studies considered readily available by at least 90% of physicians included carotid ultrasonography, transthoracic echocardiography, Holter monitoring, and brain CT and MRI scans. MR angiography was perceived as being readily available by 68% and transesophageal echocardiography by 74% of respondents. Twelve percent of physicians reported cerebral arteriography and 10% reported carotid endarterectomy as not being readily available. Multiple logistic regression analyses showed that the availability of services varied with physician specialty (noninternist primary care, internal medicine, neurology, surgery), practice setting (nonmetropolitan versus small metropolitan or large metropolitan areas), and for carotid endarterectomy, region of the country (South, Central, Northeast, and West). The odds of carotid endarterectomy being reported as readily available were approximately 2.5 to 3.5 times greater for physicians practicing in the central, northeastern, and western regions compared with those practicing in the South, independent of practice setting and specialty. With regard to stroke prevention practices, 61% of physicians reported prescribing 325 mg of aspirin for stroke prevention, while 33% recommend less than 325 mg and 4% use doses of 650 mg or more. Seventy-one percent of physicians using warfarin reported monitoring anticoagulation with international normalized ratios, and 78% reported monitoring anticoagulated patients at least once a month. Fewer than 20% of physicians reported knowing the perioperative carotid endarterectomy complication rates at the hospital where they perform the operation themselves or refer patients to have the procedure done. CONCLUSIONS: Although all routine and most specialized services for secondary and tertiary stroke prevention are readily available to most physicians, variation in availability exists. The use of international normalized ratios for monitoring warfarin therapy has not yet become universal. Physician knowledge of carotid endarterectomy complication rates is generally lacking. Depending on their causes, these problems may be addressed through targeted physician education efforts and systematic changes in the way in which services are provided.     

How potassium affects the activity of the molecular chaperone Hsc70. I. Potassium is required for optimal ATPase activity

Several functions of the 70-kilodalton heat shock cognate protein (Hsc70), such as peptide binding/release and clathrin uncoating, have been shown to require potassium ions. We have examined the effect of monovalent ions on the ATPase activity of Hsc70. The steady-state ATPase activities of Hsc70 and its amino-terminal 44-kDa ATPase fragment are minimal in the absence of K+ and reach a maximum at approximately 0.1 M [K+]. Activation of the ATPase turnover correlates with the ionic radii of monovalent ions; those that are at least 0.3 A smaller (Na+ and Li+) or larger (Cs+) than K+ show negligible activation, whereas ions with radii differing only approximately 0.1 A from that of K+ (NH4+ and Rb+) activate to approximately half the turnover rate observed with K+. Single turnover experiments with Hsc70 demonstrate that ATP hydrolysis is 5-fold slower with Na+ than with K+. The equilibrium binding of ADP or ATP to Hsc70 is unperturbed when K+ is replaced with Na+. These results are consistent with a role for monovalent ions as specific cofactors in the enzymatic hydrolysis of ATP.     

Alcohol and stress response dampening: pharmacological effects, expectancy, and tension reduction

Alcohol consumption and alcohol expectation were separately evaluated in terms of effects on psychophysiological levels prior to stress and reduction of the magnitude of response to stress. 96 male, experienced drinkers were assigned to 8 conditions in a between-Ss design in which beverage consumed (alcohol or tonic), beverage expected (alcohol or tonic), and stressor (self-disclosing speech or threat of shock) were manipulated. Dosage for Ss receiving alcohol was 1 g ethanol/kg. Results indicate strong effects of alcohol consumption on prestress levels, consisting of accelerated heart rate (HR), lower HR variability, higher skin conductance, longer pulse transmission time (PTT), higher "cheerfulness" and lower "anxiety" ratings. Alcohol consumption significantly reduced the magnitude of the HR, PTT, and anxiety responses of Ss to the stressors. No effects attributable to alcohol expectation were found. Results are integrated with the existing literature concerned with pharmacological and cognitive effects of alcohol as they pertain to stress, psychophysiological responses to stress, and tension reduction. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Some failures of intermanual and cross-lateral transfer in chronic schizophrenia.

The suggestion that split-brain symptoms are present in schizophrenia was investigated by using tests of intermanual and cross-lateral transfer. Ss were 24 chronic schizophrenics (mean age 52.1 yrs), 6 matched depressive and anxious patients, and 6 normal controls. All Ss were right-handed. Disconnections were seen on a variety of manual and cross-lateral transfer tasks involving position location on the hands, the arms, and the body as well as on tasks of manual tapping transfer. These are interpreted as communication failures of the brain related to callosal disturbance. (7 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Palladium-palladium oxide miniature pH electrode

A wire-form miniature palladium-palladium oxide electrode has been fabricated for pH measurement. The electrode exhibits a super-Nernstian behavior and gives a mean pH response of 71.4 millivolts per [pH] (standard deviation, 5.2 millivolts). Uncorrected zero current potential values can be used to determine the pH value of the medium to within 0.012 pH. The electrode should find applications in biological, medical, and clinical studies.     

Textural and microstructural gradient effects on the mechanical behavior of a tantalum plate

The effects of gradients in the texture and microstructure of a tantalum plate on mechanical behavior are examined. In particular, the effects of variations in grain size and texture from the surface of the plate to the centerline on the yield behavior and final shape of compression samples are investigated. Individual lattice orientations were measured on samples both before and after deformation using automatic analysis of electron backscatter diffraction patterns. These data were used as input to a polycrystal plasticity model based on the Taylor assumption of uniform strain. Results are compared from experimental and simulated compression tests. The effects of the texture and grain size gradients on these results are discussed. The influence of the texture gradient was found to be the dominating factor controlling the nonuniform plastic response of the material. This work also demonstrates the capability of currently available tools for characterizing inhomogeneous microstructures and modeling the effects of variations in texture and microstructure on mechanical behavior.     

Carcinoid tumours of the thymus

Analysis by isoelectric focusing of serum alpha 1-antitrypsin phenotype of 167 consecutive cases from an occupational health outpatient clinic, from university hospital departments and from private practitioners showed an excessive presence of rare gene alleles S, Z, I and anodal variants compared to their frequencies in blood donors from Lausanne or in the general Swiss population. It seems that analysis has been well grounded in most cases and helps to establish diagnosis in many respiratory diseases, in unexplained liver cirrhosis and even in aortic rupture.     

Effects of 3,3'-iminodipropionitrile on acquisition and performance of spatial tasks in rats

3,3'-Iminodipropionitrile (IDPN) has been reported to disrupt learning and memory in rats (24). The present work addressed the effects of IDPN on tasks requiring the use of spatial information. Separate groups of male rats were dosed with IDPN (IP, in 1 ml/kg saline) for 3 consecutive days and tested in the following procedures: (a) step-through passive avoidance conditioning (0, 100, 150, and 200 mg/kg/day); (b) Morris water maze (MWM) acquisition and retention (0, 125, 150, 175, and 200 mg/kg/day); (c) radial arm maze (RAM) acquisition (0, 100, 200, and 400 mg/kg/day); (d) RAM steady-state performance (0, 200, and 400 mg/kg/day); (e) repeated acquisition in the RAM (0, and 200 mg/kg/day). The vestibular toxicity of IDPN resulted in alterations in spontaneous behavior or swimming deficits in 5 of 8 rats treated with 175 mg/kg/day and in all the animals dosed with 200 or 400 mg/kg/day. IDPN increased step-through PA latencies at 200 mg/kg/day but not at lower doses. In the MWM, no performance deficits were observed at the dose levels preserving the swimming ability of the animals. In both the acquisition and the steady-state RAM tasks, IDPN (400 mg/kg/day) induced an increase in both choice errors and perseverative errors. In the RAM repeated acquisition paradigm, IDPN (200 mg/kg/day) induced performance deficits that included a decreased rate of within-session reduction in errors. The present data show that IDPN disrupts performance of tasks requiring spatial learning and memory and indicate that these deficits can be in part caused by an acquisition deficit.