Primary and secondary structure of bovine retinal S antigen (48-kDa protein).

The complete amino acid sequence of bovine S antigen (48-kDa protein) has been determined by cDNA and partial amino acid sequencing. A 1623-base-pair (bp) cDNA contains an open reading frame coding for a protein of 404 amino acids (45,275 Da). Tryptic peptides and cyanogen bromide peptides of native bovine S antigen were purified and partially sequenced. All of these peptides were accounted for in the long open reading frame. Searching of the National Biomedical Research Foundation data bank revealed no extensive sequence homology between S antigen and other proteins. However, there are local regions of sequence similarity with alpha transducin, including the sites subject to ADP-ribosylation by Bordetella pertussis and cholera toxins and the phosphoryl binding-sites. Secondary structure prediction and circular dichroic spectroscopy show that S antigen is composed predominantly of beta-sheet conformation. Acid-catalyzed methanolysis suggests the presence of low levels of carbohydrate in the molecule.     

An immunological determinant of RNase P protein is conserved between Escherichia coli and humans.

RNase P, an enzyme with RNA and protein subunits, cleaves tRNA precursor molecules to form the 5' termini of mature tRNAs in both prokaryotes and eukaryotes. Rabbit antibodies made against the protein subunit, C5 protein, of Escherichia coli RNase P bound RNase P protein from E. coli and Bacillus subtilis in immunoblots and solid-phase immunoassays. These rabbit anti-C5 antibodies also bound a protein (Mr approximately 40,000) in preparations of RNase P from human (HeLa) cells and depleted the enzymatic activity from preparations of RNase P from both human and E. coli cells. Finally, rabbit anti-C5 antibodies immunoprecipitated from crude extracts of human cells a ribonucleoprotein complex containing H1 RNA, the putative RNA component of human RNase P. These results show that an antigenic determinant is shared by C5 protein from E. coli RNase P and a protein component of RNase P from human cells.     

snRNPs and scRNPs as autoantigens: clues to the etiology of the connective tissue diseases

Clinical Rheumatology -     

Cognitive effects of short-term manipulation of serum sex steroids in healthy young men

We examined the effects of sex steroids on cognitive functioning by exogenously manipulating circulating T levels in a group of healthy young men. Thirty-two men were randomized to receive 8 wk of treatment including: 1) im T enanthate 100 mg/wk plus daily oral placebo (T); 2) im placebo/wk plus 125 microg daily oral levonorgestrel (LNG); 3) im T enanthate 100 mg/wk plus 125 microg daily oral LNG (T + LNG); 4) im placebo/wk plus daily oral placebo. Cognitive functions were assessed at baseline and twice during treatment. Serum T and E2 levels were significantly increased in the T and T + LNG groups compared with baseline (P < 0.01) and T levels were significantly decreased in the LNG group (P < 0.05). Verbal memory significantly decreased in the LNG group (P < 0.01) and was maintained by coadministration of T in the T + LNG group. Divided attention was unaffected in the LNG group but improved significantly in the T + LNG group. In summary, decreased serum T levels induced by LNG or direct effects of the progestin, LNG, adversely affects verbal memory in normal young men. These results suggest that short-term changes in sex steroid levels have effects on cognitive function in healthy young men.     

Instructional design affects the efficacy of simulation-based training in central venous catheterization

Background

Simulation-based learning is a common educational tool in health care training and frequently involves instructional designs based on Experiential Learning Theory (ELT). However, little research explores the effectiveness and efficiency of different instructional design methodologies appropriate for simulations. The aim of this study was to compare 2 instructional design models, ELT and Guided Experiential Learning (GEL), to determine which is more effective for training the central venous catheterization procedure.

Methods

Using a quasi-experimental randomized block design, nurse anesthetists completed training under 1 of the 2 instructional design models. Performance was assessed using a checklist of central venous catheterization performance, pass rates, and critical action errors.

Results

Participants in the GEL condition performed significantly better than those in the ELT condition on the overall checklist score after controlling for individual practice time (F[1, 29] = 4.021, P = .027, Cohen's d = .71), had higher pass rates (P = .006, Cohen's d = 1.15), and had lower rates of failure due to critical action errors (P = .038, Cohen's d = .81).

Conclusions

The GEL model of instructional design is significantly more effective than ELT for simulation-based learning of the central venous catheterization procedure, yielding large differences in effect size.     

Autoantibodies to small nuclear and cytoplasmic ribonucleoproteins in japanese patients with inflammatory muscle disease

Objective. To elucidate the profile and clinical significance of autoantibodies to small nuclear and small cytoplasmic ribonucleoproteins in Japanese patients with polymyositis and dermatomyositis (PM/DM). Methods. Radioimmunoprecipitation assays were performed with sera from 91 patients with various inflammatory muscle diseases and from 254 control patients with other rheumatic diseases. Patients with PM/DM were categorized according to autoantibody specificities, and clinical comparisons were made. Results. Antibodies to aminoacyl transfer RNA (tRNA) synthetases and the signal recognition particle (SRP) were found to be specific for PM/DM. PM/DM patients with antibodies to 3 aminoacyl-tRNA synthetases (histidyl, threonyl, and glycyl) appeared to form a distinct clinical subset, associated with chronic interstitial lung disease, polyarthritis, and myositis, while 3 patients with antibodies that bound the SRP had severe myositis that was resistant to corticosteroid therapy. In general, the frequency and clinical correlations of anti—aminoacyl-tRNA synthetase antibodies in Japanese patients were similar to those in North American populations. In contrast, among this Japanese cohort, the occurrence of anti-PM/ScI appeared to be reduced in frequency, whereas anti-Ku and anti—U2 RNP antibodies were accentuated in patients with overlap syndromes. Conclusion. We conclude that racial groups differ somewhat in their characteristic autoimmune responses to individual autoantigens. These differences could reflect variation in immunogenetic background or different etiologic mechanisms which might occur at different geographic locations.     

NMDA antagonist modulation of morphine antinociception in female vs. male rats

NMDA antagonists may be useful for their potential to increase or prolong opioid analgesia while attenuating the development of opioid tolerance and dependence. The purpose of this study was to determine whether there are sex differences in NMDA antagonist modulation of morphine antinociception. Adult female and male Sprague–Dawley rats were injected s.c. with saline or one dose of MK-801 (0.005, 0.01, 0.02, or 0.04 mg/kg), dextromethorphan (5, 10, or 20 mg/kg), or LY235959 (0.5, 1.0, or 2.0 mg/kg) in combination with saline or one dose of morphine (1.8, 3.2, or 5.6 mg/kg), and tested on the 50 °C hotplate and tail withdrawal assays 15–120 min post-injection. At the doses examined, only LY235959 produced any antinociception when administered alone. MK-801 attenuated morphine antinociception on both assays, but only at sporadic (inconsistent) dose-combinations. Dextromethorphan increased morphine antinociception on the hotplate but not tail withdrawal assay, at all three morphine doses in males, but only the higher morphine doses in females. In contrast, LY235959 modulated morphine antinociception on both assays; the lowest dose attenuated, and higher doses enhanced morphine antinociception, but the particular morphine doses and assay in which these effects occurred depended on the sex of the subject. Thus, all three NMDA antagonists modulated morphine antinociception in female and male rats, but the direction of this modulation depended on the particular antagonist examined, the nociceptive test, the dose of antagonist and of morphine, and time post-injection.     

Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose

BACKGROUND: Increasing plasma glucose levels improves memory in patients with Alzheimer disease (AD). Increasing plasma glucose levels also increases endogenous insulin levels, raising the question of whether memory improvement is due to changes in insulin, independent of hyperglycemia. We address this question by examining memory and counterregulatory hormone response during hyperglycemia when endogenous insulin was suppressed by concomitant infusion of the somatostatin analogue octreotide (Sandostatin). METHODS: Twenty-three patients with AD and 14 similarly aged healthy adults participated in 4 metabolic conditions on separate days: (1) hyperinsulinemia (538 pmol/L) with fasting glucose (5.6 mmol/L [100 mg/dL]), achieved by insulin and variable dextrose infusion; (2) hyperglycemia (12.5 mmol/L [225 mg/dL]) with fasting insulin (57 pmol/L), achieved by dextrose and somatostatin (octreotide) infusion (150 mg/h); (3) placebo with isotonic sodium chloride solution (saline) infusion (fasting insulin and glucose); and (4) an active control condition in which somatostatin alone was infused (150 mg/h). Declarative memory (story recall) and selective attention (Stroop interference test) were measured during steady metabolic states. RESULTS: Patients with AD showed improved memory during hyperinsulinemia relative to placebo (P = .05) and relative to hyperglycemia (P<.005). Memory did not improve during hyperglycemia when insulin was suppressed. Somatostatin analogue infusion alone also improved memory for patients with AD (P<.05). Hyperinsulinemia increased cortisol levels in subjects with AD, whereas somatostatin alone lowered cortisol concentrations. CONCLUSIONS: These results confirm that elevated insulin without hyperglycemia enhances memory in adults with AD, and indicate that insulin is essential for hyperglycemic memory facilitation. These results also suggest a potential therapeutic role for somatostatin in AD.     

Navy Asbestos Medical Surveillance Program (1991-1999): linear regression analysis for the effect of asbestos exposure on pulmonary function testing

The effect of asbestos exposure on pulmonary function was studied using data from the Navy Asbestos Medical Surveillance Program. Records were selected for Caucasian men from 1991 to 1999 (N = 89,318) and were analyzed using a cross-sectional, linear regression model. Dependent variables were forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), with independent continuous variables of age, height, weight, smoking, and asbestos history. Overall, the continuous variable for asbestos exposure demonstrated significant protection of +1.1 cm3/year (t = 3.278, p = 0.001) for FEV1 and +1.6 cm3/year (t = 4.225, p = 0.000) for FVC. There was significant interaction between asbestos exposure and smoking history (FEV1, -0.09 cm3/year2, t = -6.467, p = 0.000; FVC, -0.097 cm3/year2, t = -5.663, p = 0.000). This study suggests that workers within the program demonstrated minimal additional pulmonary function changes during the period, particularly if they do not smoke tobacco. The study also supports continuing smoking cessation efforts for all asbestos-exposed workers.