A single VH family and long CDR3s are the targets for hypermutation in bovine immunoglobulin heavy chains

Summary: Bovine immunoglobulins are made from genes belonging to a small family of closely related Vh, genes. In this respect cattle resemble all species of domesticated mammals, which also use one VH family The family, named BoVH1, is homologous to the mouse Q52 family, and there are no more than 20 genes of this family in the bovine genome. Another feature of bovine heavy chains is the use of long CDR3s, which have an average of 21 codons. It seems that there are several families of long, closely related D genes rich in glycine and tyrosine responsible for this length. Sequences described as targets for mutations in other species can be found in CDR1, CDR2, and the putative D genes. The mutation mechanism starts at some point between late fetal stage and birth and seems to be antigen Independent. Diversity seems to be generated by hypermutation, although other mechanistns cannot be discomited at this time. Contrary to humans and mice, which have several Vh gene families comprising more than 100 genes, cattle use only a few genes and long CDR3s followed by somatic mutation to generate the necessary diversity to recognize the universe of antigens they will encounter during their life.     

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Estimation of nitrogen balance based on a six-hour urine collection in infants

The accuracy of a 6-hr vs a 24-hr urine collection for the determination of urinary urea nitrogen was studied in 15 infants. Patient's age ranged from 2 weeks to 3 yr, encompassing a wide variety of diagnoses. All patients had normal renal function at the time of the study. Participants had indwelling foley catheters throughout the study. Urine specimens were collected over a continuous 24-hr period. Aliquots obtained from urine collected over 0 to 6 hr and the total urine collection were analyzed utilizing the urease enzymatic method in the Astra. Statistical analysis was performed comparing the actual 24-hr determination to the estimation based on the 6-hr collection, utilizing linear regression. The analysis of data produced a highly significant correlation (r = 0.904, p less than 0.0001). When a 24-hr urine collection is not possible, a 6-hr collection is a useful alternative for the calculation of nitrogen balance in infants.     

Application of ECCLS guidelines to the analysis of Toxoplasma IgG and Rubella IgG using laboratory kits based on the Meia method.

The Meia method is an enzymo-immunoassay involving fluorometric detection, which is used in the Abbott IMx automatic analyzer. The purpose of this report was to analyse the Meia Toxoplasma gondii IgG antibody and Rubella IgG antibody assays, following ECCLS guidelines for the analysis of laboratory kits. The results showed that between-run imprecision for Rubella IgG was close to 15%; for Toxoplasma IgG the percentage was 13%. The mean recovery for Rubella IgG was 104% and 94% for Toxoplasma IgG. The carry-over for Rubella IgG was 0.64% and 0.26% for Toxoplasma IgG which, in both cases, was less than the analytical variability. Both Meia and Elisa showed a linear relationship in the analytical range of the method. Comparing Meia with the Elisa method, constant and proportional differences were found for IgG Rubella and proportional differences for IgG Toxoplasma. The Meia method has many positive analytical features to recommend and it can easily be used in a multidisciplinary laboratory, needing only a small number of serum samples.     

Pathophysiology of HPA axis abnormalities in patients with major depression: an update

Four hypotheses have been proposed to explain why nonsuppression on the dexamethasone suppression test occurs in patients with major depression. These include 1) increased metabolism of dexamethasone, 2) decreased sensitivity of pituitary glucocorticoid receptors to dexamethasone, 3) hyperresponsivity of the adrenal gland to ACTH stimulation, and 4) increased central drive of the pituitary from hypothalamic/limbic structures that overrides the action of the dexamethasone. A critical review of the literature suggests that the last hypothesis is most closely supported by the data. Despite this conclusion, factors other than depression may be involved in hypothalamic-pituitary-adrenal axis dysfunction.     

Group protocol to mitigate disaster stress and enhance social support in adolescents exposed to Hurricane Hugo.

Literature reports that cognitive understanding and social support can mitigate stress in both adults and adolescents. As a subcomponent of the Carolina Adolescent Health Project (CAHP), this research evaluated the efficacy of a Cognitive Social Support (CSS) group protocol designed to mitigate the disaster stress of adolescents who had been exposed seriously to Hurricane Hugo. A purposive sample of 259 students participated in and evaluated the CSS. This article reports the specific structure, content, process, rationale, and cost of the CSS. Evaluations indicated that 82% of the students evaluated the small-group component of the CSS as "very good" or "excellent," while 70% rated the large-group component as "very good" or "excellent."     

Partial purification of parathyrin from the corpuscles of Stannius (PCS) of the eel (Anguilla anguilla, L.)

It has been previously shown that the eel corpuscles of Stannius (CS) synthesize and secrete a substance (PCS) which is functionally and immunologically related to the mammalian parathyrin family. Purification of PCS, including anion-exchange chromatography, ODS C-18 reverse-phase HPLC, and affinity chromatography, showed that a biologically active peak, eluted in 32% acetonitrile, contains a 32- to 34-kDa protein which is 600-fold more potent than the crude extract is a test involving the hypocalcemic response in the CS-deprived eel. Specific immunoprecipitation of protein encoded by mRNA extracted from eel CS indicates that a 45-kDa precursor is involved in PCS synthesis. The hypothetical significance of a "large" parathyrin-like molecule in fish is suggested in relation to what is known about mammalian parathyrin gene expression.