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Biomedical subjects

A Grewal

Publications and source records attributed to A Grewal.

11 recordsLinked to original sources
PubMed1998

Examination of micro-tip reversed-phase liquid chromatographic extraction of peptide pools for mass spectrometric analysis.

Mass spectrometry occupies a central position in most current protein identification schemes. So-called 'mass fingerprinting' techniques rely on composite mass patterns of proteolytic fragments, or dissociation products thereof, to query databases. Keys to successful analysis of ever smaller amounts are sensitivity and complete spectral information, both of which depend for a large part on proper sample preparation. Clean-up and concentration of peptide mixtures over eppendorf gel loading tips filled with chromatographic media (i.e. 'micro-tips') are believed to be quite useful in this regard. We have studied quantitative and qualitative aspects of polypeptide extraction using these small manual devices. Optimization of sample volume and additives, micro-tip bed volume, and eluent composition and volume, all contribute to effective recovery (approximately 65-70%, on average). Improper digest conditions can, in fact, lead to far bigger losses, suggesting the need for at least trace amounts of Zwittergent 3-16. Of particular interest is our finding that partial fractionation, obtained by two-step micro-tip elution, generally results in more and better signals during subsequent mass analysis. Thus, by using optimized micro-tips, in combination with adequate sample handling and instrumentation, direct mass spectrometric identification can be routinely and successfully done in any resource facility type setting.

Amino Acid Sequence↗
PubMed1996

Effects of rapid tryptophan depletion in patients with seasonal affective disorder in remission after light therapy.

BACKGROUND: Previous studies show that rapid tryptophan depletion reverses the effects of therapy with serotonergic, but not noradrenergic, antidepressant drugs in patients with remitted nonseasonal depression. The objective of this study was to investigate the effects of rapid tryptophan depletion in patients with seasonal affective disorder (SAD) that was in clinical remission after light therapy. METHODS: Patients who met DSM-III-R criteria for recurrent major depressive episodes, seasonal (winter) pattern (equivalent to SAD), were treated with a standard course of light therapy. Ten patients with SAD in clinical remission after light therapy underwent rapid tryptophan depletion in a placebo-controlled, double-blind crossover study. Behavioral ratings and plasma tryptophan levels were obtained before and after rapid tryptophan depletion. RESULTS: Plasma total and free tryptophan levels were significantly reduced to 20% of normal levels by the rapid tryptophan depletion. The depletion session resulted in significant increases in depression scores compared with the sham control session. Six of 10 patients had a clinically significant relapse of their depression following the tryptophan depletion session. CONCLUSIONS: Rapid tryptophan depletion appears to reverse the antidepressant effect of bright light therapy in patients with SAD. This suggests that the therapeutic effects of bright light in SAD may involve a serotonergic mechanism.

Adult↗
PubMed1996

Seasonality of symptoms in anorexia and bulimia nervosa.

OBJECTIVE: Recent research has suggested that a large proportion of patients with bulimia nervosa have seasonal (winter) worsening of mood symptoms similar to seasonal affective disorder (SAD). The objectives of this study were to determine the specificity of this finding in anorexia and bulimia nervosa, and to further delineate the seasonal mood and eating patterns in bulimia nervosa. METHOD: A modified Seasonal Pattern Assessment Questionnaire (SPAQ) was administered to consecutive female patients assessed at an Eating Disorders Clinic with DSM-III-R diagnoses of bulimia nervosa (BN, N = 60) and anorexia nervosa (AN, N = 31), and to female nonclinical comparison subjects (NC, N = 50). RESULTS: The BN group had higher global seasonality scores and more presumptive diagnoses of SAD than the other two groups; the AN patients, whether they had the restricting or binge eating/purging subtype, did not differ from the NC subjects. Thirty-two percent of the identified seasonal BN patients did not have parallel worsening of mood and eating symptoms in the same season. DISCUSSION: These results suggest that seasonality of symptoms is specific to BN and that there may be separate mechanisms for the seasonality of mood and eating symptoms in some BN patients.

Adult↗
PubMed1995

Genetic ablation of IGFBP-2 suggests functional redundancy in the IGFBP family.

Gene targeting allows mutations to be introduced selectively into any mouse locus of interest. This approach has already been used to demonstrate that insulin-like growth factor (IGF) peptides and receptors are required in vivo for normal prenatal growth. One of the IGFBP genes, IGFBP-2, has also been disrupted using gene targeting, and homozgyous null BP-2 mice are characterized by a decreased spleen size most apparent during early postnatal stages and increased adult circulating levels of several other IGFBPs. These alterations are considered less dramatic than the phenotypes initially predicted based on the fetal IGFBP-2 expression pattern, although several physiological paradigms can be envisioned that will provide additional tests for specific aspects of IGFBP function. Since all six IGFBP genes are expressed during prenatal rodent development, as well as in adult tissues, the IGFBP-2 null phenotype must also be compared with genetic ablations involving members of other gene families and in the context of the other IGFBP expression patterns in rodent embryonic, extraembryonic, and uterine tissues.

Animals↗
PubMed1993

Tissue-specific expression of the insulin-like growth factor binding protein (IGFBP) mRNAs in mouse and rat development.

The insulin-like growth factor binding proteins (IGFBPs) are polypeptides which are thought to modulate the bioactivity of IGF-I and IGF-II, and may also have activities independent of the IGFs. The expression patterns of IGFBPs-1, -3, -4, and -6 in midgestational rodents were analyzed using in situ hybridization to begin to characterize the role of these IGFBPs during development. All IGFBPs are expressed at least as early as rat embryonic day 14 (e14), and each has a unique pattern of expression. IGFBP-1 mRNA is expressed by the liver throughout mid and late gestation. IGFBP-3 mRNA is expressed at high levels in the urogenital tract, several muscle groups, and the nasal epithelia. IGFBP-3 transcripts are also expressed at lower levels by many non-neural tissue types, including the liver, stomach, and heart. IGFBP-4 is abundantly expressed by many tissues in the developing embryo, with the notable exceptions of the spinal cord, specific cartilage groups, and the thymic cortex. IGFBP-6 is expressed in the liver by e14, and also by a previously unrecognized cell population surrounding developing cartilage. Taken together these observations suggest distinct roles in development for each of the IGFBPs.

Animals↗
PubMed1990

Beta-alanine induced ion channels in the membrane of cultured spinal cord neurons.

beta-Alanine (beta-ALa) is a structural analog of the putative inhibitory transmitters gamma-aminobutyric acid (GABA) and glycine. beta-ALa itself depresses firing in cultured mouse spinal cord (SC) neurons, by selectively increasing membrane conductance to chloride ions. Patch clamp recordings now reveal that beta-ALa-sensitive chloride channels in SC cells can open to at least 5 conductance states, 4 of which are very similar to states seen when GABA or glycine is applied to these cells. However, a large, 80 pS conductance state is activated at detectable frequency only in the presence of beta-ALa itself.

Alanine↗
PubMed1989

Membrane channels activated by taurine in cultured mouse spinal cord neurons.

Patch-clamp methods were used to compare biophysical properties of anion channels activated by taurine and gamma-aminobutyric acid in the membrane of cultured mouse spinal neurons. Outside-out patches were voltage clamped at -80 mV at a temperature of 21-23 degrees C. Bath application of GABA (1.5-2 microM) or taurine (5-40 microM) induced chloride-dependent single-channel currents in 14/20 patches tested. Amplitude distributions of these currents showed peaks corresponding to conductance levels of 8, 16, 27 and 46 pS. Only a few percent of GABA-induced events reached the 46 pS level, while 30% of taurine-induced currents were of this size. The average lifetime of taurine-activated channels in the open state was 1.0 +/- 0.07 ms, significantly shorter than the corresponding value for GABA (1.6 +/- 0.08 ms). Taurine-induced currents were abolished by 10 microM strychnine, but persisted in the presence of 50 microM bicuculline.

Animals↗
PubMed1986

An association between encephalomyocarditis virus infection and reproductive failure in pigs.

An outbreak of reproductive failure, characterised by mummified foetuses and stillbirths, was investigated in an intensive piggery. Six foetuses that died towards the end of gestation had multifocal myocardial necrosis and encephalomyocarditis virus was recovered from 4 of these foetuses but not from 6 mummified foetuses. There was also a significant increase in failure of conception or early embryonic deaths in sows mated at the same time as sows which produced affected litters.

Animals↗
PubMedDate not supplied

Expression of IGF system genes during T-antigen driven pituitary tumorigenesis.

Expression of IGF-I, IGF-II, the Type-I IGF receptor and six IGF binding proteins were examined in three different T-ag-driven mouse tumors. Unlike the widespread expression of IGF-II in pancreatic beta-cell tumors, IGF-II was not widely expressed in the two different pituitary tumors examined indicating that a mechanism independent of focal IGF-II expression can also drive T-antigen tumorigenesis. In addition, multiple IGF binding proteins were expressed in all three tumor types. This expression, however, was generally heterogeneous with no specific changes to indicate a required role for any IGF binding protein in T-antigen tumorigenesis.

Animals↗