Dynamic changes of serum gamma-glutamyl transferase in chronic alcoholism.

Elevated serum gamma-glutamyl transferase (GGT) levels were found in 29% of 155 chronic alcoholics undergoing detoxification treatment. Alkaline phosphatase (AP) was increased in 16%, alanine aminotransferase--SGPT (ALT) in 12% of the patients, while 23% had elevations of either AP or ALT or both. Of the foregoing parameters, GGT was the best single indicator of liver involvement. In course of the follow-ups GGT/ALT correlation improved, but GGT/AP correlation deteriorated. In 9 patients, abstinence during follow-up was associated with progressive decrease in previously elevated serum GGT. Because of its unique sensitivity, GGT may be useful as a screening and/or monitoring aid in alcoholism.     

Synaptic mutation-driven male sterility in Panax sikkimensis Ban. (Araliaceae) from Eastern Himalaya, India

In higher plants, synaptic mutation-associated gametic abnormalities are reported mostly in crop plants, but studies have rarely focused on the natural plant populations. This is particularly so in threatened herbaceous perennials, some of which are known to suffer from loss of sexual reproduction driven by the genetic mutations. Cytological investigations of Panax species, viz. P. sikkimensis, P. sokpayensis and P. bipinnatifidus, revealed that all the species were diploid with 2n = 24 chromosomes. Natural occurrence of synaptic mutation was recorded in Panax sikkimensis in the Kalep population of North Sikkim, India. We recorded that 86.03% of pollen mother cells (PMCs) lacked bivalent formation and had 24 distinct univalents at prophase I in the mutant plants of P. sikkimensis. We found a significantly lower mean number of chiasmata per cell (0.31 ± 0.91; t test = 38.24, P < 0.001) in the mutant plants as compared to the normal plants (21.04 ± 4.56). The chromosomal associations in the PMCs of the synaptic mutants ranged from 25% bivalents and 75% univalents to 100% univalents at diplotene/diakinesis. The unequal distribution of chromosomes at anaphase I and II resulted in the formation of microspores and microcytes of differing sizes. The pollen stainability test in the mutant population of P. sikkimensis revealed very low (0.12%) pollen fertility reflecting the consequences of synaptic mutation. Synaptic mutation in the herbaceous perennial P. sikkimensis was considered to be responsible for the male sterility in the species.     

Aluminium bone disease in patients receiving plasma exchange with contaminated albumin.

Aluminium balance studies were carried out on eight patients with various immunological disorders who were receiving plasma exchange with albumin solutions known to be contaminated with aluminium. Four patients with impaired renal function (creatinine clearance less than 50 ml/min) retained between 60% and 74% of the aluminium infused during a single plasma exchange. Transiliac bone biopsy specimens from three patients in this group had a high content of aluminium and showed histological evidence of current or previous bone disease related to aluminium. Two of these patients suffered intermittent bone pain. The main route of excretion of injected aluminium was in urine, only a small proportion of the total input being removed in the "plasma bag" during plasma exchange. The extent of aluminium retention and bone deposition was not reflected by the plasma aluminium concentration before or after plasma exchange. Treatment of five patients with intravenous desferrioxamine increased the plasma aluminium concentration and urinary output of aluminium in those with evidence of aluminium retention. These studies show that patients with poor renal function receiving treatment with albumin contaminated with aluminium retain the metal and deposit it in bone, where it may eventually cause aluminium bone disease. Plasma exchange should be used with caution in patients with renal impairment.     

Mobility of the spin-labeled side chains of some novel antifolate inhibitors in their complexes with dihydrofolate reductase

Four spin-labeled inhibitors of dihydrofolate reductase (DHFR) have been synthesized, each of which has the 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) reporting group at a different distance from the 2,4-diaminopyrimidine moiety by which the inhibitors are anchored and oriented in the active site. Inhibitors in which the TEMPO group is attached by a short side chain are weakly bound to DHFR from bacteria (Streptococcus faecium and Lactobacillus casei), to the bovine enzyme and to recombinant human DHFR. However, binding is sufficiently tight, especially in the ternary complexes with NADPH, for recording of the EPR spectra of the bound ligands. The spectra indicate that when these inhibitors are bound to the enzyme the TEMPO group is highly immobilized with correlation time, tau c, 4-20ns. Inhibitors that have the reporter group attached to the glutamate moiety of methotrexate bind to all four DHFRs more tightly than the inhibitors with shorter side chains by factors of up to 10(6). However, in most complexes formed by the inhibitors with longer side chains immobilization of the TEMPO group is slight (tau c 0.2-4 ns). These results are in general agreement with predictions from X-ray crystallographic results including thermal factors but there are some unanticipated differences between some results for bacterial and eukaryotic enzymes. Three of the splin-labeled inhibitors would provide good probes for distance measurements in and around the active site of mammalian DHFR.     

Molecular Interactions of Etazolate with Benzodiazepine and Picrotoxinin Binding Sites

Pyrazolopyridines, such as etazolate (SQ 20009), enhance [3H]diazepam binding to a Lubrol-solubilized fraction that has specific binding sites for 3H benzodiazepines, [alpha-3H]dihydropicrotoxinin (DHP) and [3H]muscimol. Etazolate enhancement of [3H]diazepam binding was inhibited by picrotoxinin. Furthermore, etazolate inhibited the [3H]DHP binding in a Lubrol-solubilized fraction with an IC50 value of 6-8 microM. These results provide evidence that etazolate, like pentobarbital, modulates benzodiazepine binding via the DHP-sensitive site of the benzodiazepine-GABA receptor-ionophore complex.     

Somatoform disorders among patients attending walk-in clinics in Trinidad: prevalence and association with depression and anxiety

Objectives Somatoform disorders are common in international primary care settings, but have been little studied in the developing world. The objective of this study was to determine the prevalence of severe undifferentiated somatoform disorder, and its relationship to depression and anxiety, among patients attending walk-in clinics in Trinidad.Methods The study participants, who were all aged 18 years or older and attending walk-in clinics at 16 randomly selected health centres, were surveyed between May and August 2007 using the PRIME-MD questionnaire.Results There were 594 participants (the response rate was 92%), of whom 72.7% were female. Their ages ranged from 18 to 93 years, and 54.5% were over 50 years of age. In total, 37.2% were married and 25.9% were single. Indo-Trinidadians represented 43.1% and Afro-Trinidadians represented 36% of the study sample; 56.5% of the participants reported that their income was less than US$ 400 per month, and 65.7% were unemployed. At walk-in clinics in Trinidad, the estimated prevalence of severe undifferentiated somatoform disorder was 10.3% (95% CI: 7.86–12.74), that of hypochondriasis was 28.5% (95% CI: 24.9–32.1), and that of body dysmorphic disorder was 15.8% (95% CI: 11.9–18.7). Severe undifferentiated somatoform disorder was statistically significantly associated with gender and ethnicity but not with age, level of education, employment status or income. Chi-square testing found significant associations between the presence of severe undifferentiated somatoform disorder and both depression and anxiety (P < 0.05), between hypochondriasis and both anxiety and depression (P < 0.05), and between body dysmorphic disorder and depression (P < 0.05) but not anxiety. Regression analysis suggested that the demographic features that predicted severe undifferentiated somatoform disorder were being female or Indo-Trinidadian.Conclusions Walk-in clinics in Trinidad that serve older patients on a lower income have a high proportion of patients with somatoform disorders as measured by the PRIME-MD scale. These patients exhibit many features of anxiety and depression. These findings have implications for medical training and service delivery.     

Calcium Calmodulin Dependent Phosphorylation of Proteins: Fetal Cortical Neurons and Adult Cortex

In the present investigation, changes in the calcium calmodulin-dependent phosphorylation of proteins have been examined in murine fetal cortical neurons and adult cortex. An approximately 80-kD protein in the fetal neurons was not phosphorylated/dephosphorylated in a calmodulin-dependent manner. However, this protein was phosphorylated by PMA both in the presence and absence of calcium. These data suggest that calmodulin inhibits the phosphorylation of a approximately 80-kD protein by inhibiting PKC in murine fetal cortical neurons but not in the adult cortex. More importantly, we demonstrate that the calmodulin-mediated inhibition of phosphorylation was restored by preincubating the cortical neurons with KN-62, a CaM kinase inhibitor.     

Evolution of spore release mechanisms in the saprolegniaceae (Oomycetes): evidence from a phylogenetic analysis of internal transcribed spacer sequences

Classical studies on spore release within the Saprolegniaceae (Oomycetes) led to the proposition that different mechanisms of sporangial emptying represent steps in an evolutionary transition series. We have reevaluated this idea in a phylogenetic framework using internal transcribed spacer sequences of four genera. These data were compared with the response to osmotic stress exhibited by each taxon. Saprolegnia emerges as the most basal genus, sister to Achlya, Thraustotheca, and Dictyuchus. Achlya and Thraustotheca are most closely related, while Dictyuchus appears to have evolved along a separate evolutionary lineage. The resulting phylogenetic framework is consistent with the idea that the mechanism of sporangial emptying exhibited by Saprolegnia represents the plesiomorphic condition from which the other mechanisms were derived independently. These alternative mechanisms of spore release may have resulted from a small number of mutations that inhibited axonemal development and altered the temporal and spatial expression of lytic enzymes that degrade the sporangial wall. Copyright 1998 Academic Press.