EPISODE OF ACUTE HEMOLYSIS DUE TO UNDIAGNOSED GLUCOSE-6-PHOSPHATE DEHIDROGENASE DEFICIENCY IN AN ADOLESCENT WITH NEWLY DIAGNOSED TYPE 1 DIABETES MELLITUS: CASE REPORT AND REVIEW OF LITERATURE.

Glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency is common in the community. The most important clinical manifestation of G6PD deficiency is acute hemolytic anemia due to oxidative stressors. Diabetes Mellitus (DM) can precipitate hemolysis in patients with G6PD deficiency. Here, we described a 15-year-old male with newly diagnosed type 1 DM (T1DM) and unknown G6PD deficiency who suffered from hemolytic anemia during normalization of blood glucose. On admission, the patient did not have ketoacidosis. After the patient's blood sugars were regulated with insulin therapy, he presented five days later with hemolytic anemia. The cause of hemolytic anemia was G6PD deficiency. The patient had no previous episodes of hemolysis and had no relevant family history. Hypoglycemia did not occur during blood glucose regulation. The return of blood sugar to normal after a long period of hyperglycemia was thought to be the possible cause of hemolysis. In conclusion, G6PD deficiency should be considered when there is an episode of hemolysis in newly diagnosed children and adolescents with T1DM, especially in the absence of ketoacidosis and hypoglycemia.

Tracing the Sources of Atmospheric Phosphorus Deposition to a Tropical Rain Forest in Panama Using Stable Oxygen Isotopes.

Atmospheric dust deposition can be a significant source of phosphorus (P) in some tropical forests, so information on the origins and solubility of atmospheric P is needed to understand and predict patterns of forest productivity under future climate scenarios. We characterized atmospheric dust P across a seasonal cycle in a tropical lowland rain forest on Barro Colorado Nature Monument (BCNM), Republic of Panama. We traced P sources by combining remote sensing imagery with the first measurements of stable oxygen isotopes in soluble inorganic phosphate (δ(18)OP) in dust. In addition, we measured soluble inorganic and organic P concentrations in fine (<1 µm) and coarse (>1 µm) aerosol fractions and used this data to estimate the contribution of P inputs from dust deposition to the forest P budget. Aerosol dry mass was greater in the dry season (December to April, 5.6-15.7 µg m(-3)) than the wet season (May to November, 3.1-7.1 µg m(-3)). In contrast, soluble P concentrations in the aerosols were lower in the dry season (980-1880 µg P g(-1)) than the wet season (1170-3380 µg P g(-1)). The δ(18)OP of dry-season aerosols resembled that of nearby forest soils (∼19.5‰), suggesting a local origin. In the wet season, when the Trans-Atlantic Saharan dust belt moves north close to Panama, the δ(18)OP of aerosols was considerably lower (∼15.5‰), suggesting a significant contribution of long-distance dust P transport. Using satellite retrieved aerosol optical depth (AOD) and the P concentrations in aerosols we sampled in periods when Saharan dust was evident we estimate that the monthly P input from long distance dust transport during the period with highest Saharan dust deposition is 88 ± 31 g P ha(-1) month(-1), equivalent to between 10 and 29% of the P in monthly litter fall in nearby forests. These findings have important implications for our understanding of modern nutrient budgets and the productivity of tropical forests in the region under future climate scenarios.

Potential cognitive actions of (n-propargly-(3r)-aminoindan-5-yl)-ethyl, methyl carbamate (tv3326), a novel neuroprotective agent, as assessed in old rhesus monkeys in their performance of versions of a delayed matching task.

(N-propargyl-(3R)-aminoindan-5-yl)-ethyl, methyl carbamate (TV3326), a known neuroprotective agent exhibiting the properties of both an inhibitor of monoamine oxidase (brain selective) and an inhibitor of acetylcholinesterase was administered to seven old rhesus monkeys well trained to perform versions of a delayed matching-to-sample (DMTS) task. An increasing dose regimen of TV3326 was administered orally according to a schedule that allowed the animals to perform the standard DMTS task and a self-titrating version of the DMTS task each week during the study. A distractor version of the task was administered during two of the doses of TV3326. Under the conditions of this experiment TV3326 failed to significantly affect accuracy on the standard DMTS task; however, the drug was very effective in improving the ability of subjects to titrate to longer-duration delay intervals in the titrating version of the task. The maximal drug-induced extension of the self-titrated delay interval amounted to a 36.7% increase above baseline. This increase in maximum delay duration occurred without a significant change in overall task accuracy. TV3326 also significantly improved task accuracy during distractor (interference) sessions. The compound was effective enough to return group performance efficiency to standard DMTS vehicle levels of accuracy. These results were independent of whether trials were associated with a distractor or non-distractor delay interval, and they were independent of delay interval. The lack of delay selectivity in task improvement by TV3326 may not be consistent with a selective effect on attention. TV3326 was not associated with any obvious side effect or untoward reaction of the animals to the drug. Thus, TV3326 may be expected to offer a significant positive cognitive outcome in addition to its reported neuroprotective action.

Clinical outcomes of renal cholesterol crystal embolization.

Cholesterol crystal embolization is an increasingly recognized disease, presenting with a wide clinical spectrum, usually occurring in elderly men who undergo an angiographic procedure or vascular surgery. We report three patients who developed systemic cholesterol embolic disease and varying degrees of renal failure after angiographic interventions of the coronaries.

Absence of negative growth regulation in three new murine radiation-induced myeloid leukemia cell lines with deletion of chromosome 2.

Murine radiation-induced acute myeloid leukemia (RI-AML) may be considered as the experimental counterpart of human secondary leukemia. Three new myelomonocytic cell lines derived from RI-AML and carrying a partially deleted chromosome 2 are described. The RI-AML cells responded with increased proliferation after being incubated with the hemopoietic growth factors rG-CSF, rGM-CSF and IL-3. Increased proliferation of the same extent without any effect in differentiation, was also demonstrated in the RI-AML cells after incubation with IL-6 and with mouse lung conditioned medium (CM) and Krebs ascites tumor cells CM which induce differentiation in normal and most leukemic myeloid cells. Down-regulation of the c-myc gene and induction of (2'-5') oligo-adenylate synthetase (reflecting autocrine interferon secretion), two essential mechanisms operating during arrest of growth and concomitant differentiation, were demonstrated to be absent in RI-AML cells. In contrast, the M1 cells responded to the above differentiating factors with growth arrest and differentiation and with appropriate c-myc down-regulation and synthetase induction. The genetic basis for the distinct RI-AML cells' behavior may be connected with the loss or structural and/or functional abnormalities of DNA sequences located in the deleted part of chromosome 2 or in the respective allele. The presently described new RI-AML cell lines may be used for studies concerning myeloid leukemogenesis in general and secondary leukemia in particular.

Metabolic, hematological, and cardiac effects of long-term isradipine treatment in mild-to-moderate essential hypertension.

Twenty-four patients with mild-to-moderate hypertension (19 women, 5 men; mean age of 49 +/- 9.1 years) completed a 2-week washout phase followed by 1 week of single-blind placebo. Patients were then given isradipine at 2.5 mg twice daily, which was increased to up to 7.5 mg twice daily according to the blood pressure response, over a 12-month period. Thirteen patients completed the trial. The supine and sitting blood pressure decreased to normal levels within 6 weeks of starting active treatment. Heart rate remained unchanged. Plasma cholesterol and triglycerides did not change significantly. Plasma high-density lipoprotein (HDL) cholesterol increased significantly (p less than 0.05) and a decrease (NS) was observed in low-density lipoprotein (LDL) cholesterol and in the LDL/HDL cholesterol ratio. Very-low-density lipoprotein (VLDL) cholesterol did not change, nor did other biochemical laboratory tests, or electrocardiographic and echocardiographic parameters. The most notable side effects were headache (n = 1), flushing (n = 1), palpitations (n = 3), and pretibial edema (n = 1). In conclusion, our results indicate that isradipine is safe and effective in the long-term treatment of mild-to-moderate hypertension. It also appears to have beneficial effects on lipid metabolism.

Expression of calmodulin mRNA in rat olfactory neuroepithelium.

A calmodulin (CaM) cDNA was isolated by differential hybridization screening of a lambda gt10 library prepared from rat olfactory mucosa. This cDNA fragment, containing most of the open reading frame of the rat CaMI gene, was subcloned and used to characterize steady-state expression of CaM mRNA in rat olfactory neuroepithelium and bulb. Within the bulb mitral cells are the primary neuronal population expressing CaM mRNA. The major CaM mRNA expressed in the olfactory mucosa is 1.7 kb with smaller contributions from mRNAs of 4.0 and 1.4 kb. CaM mRNA was primarily associated with the olfactory neurons and, despite the cellular complexity of the tissue and the known involvement of CaM in diverse cellular processes, was only minimally evident in sustentacular cells, gland cells or respiratory epithelium. Following bulbectomy CaM mRNA declines in the olfactory neuroepithelium as does olfactory marker protein (OMP) mRNA. In contrast to the latter, CaM mRNA makes a partial recovery by one month after surgery. These results, coupled with those from in situ hybridization, indicate that CaM mRNA is expressed in both mature and immature olfactory neurons. The program regulating CaM gene expression in olfactory neurons is distinct from those controlling expression of B50/GAP43 in immature, or OMP in mature, neurons respectively.

Human monocytes and lymphocytes produce different mixtures of alpha-interferon subtypes.

alpha-Interferon (IFN-alpha) was produced by either peripheral blood lymphocytes or by monocytes and purified by an anti-IFN-alpha affinity column. When these preparations were analyzed by reversed-phase HPLC, a difference in the distribution of IFN-alpha subtypes from the two cell types was found. While the two major subtypes of IFN from induced lymphocytes had apparent molecular weights of 20K and 21K, monocytes produce an additional subtype of molecular weight 26K in large quantities (50%). This subtype had greater activity on human cells than on bovine cells in comparison to other IFN-alpha subtypes.

Priming of leukocytes selectively increases the level of some interferon-alpha subtypes and not others.

The effect of pretreatment with interferon (IFN) ('priming') on the production of individual IFN subtypes was studied in subpopulations of human peripheral blood mononuclear cells and in the myeloid cell line KG-1. It was found that priming had a selective enhancing effect on the production of certain IFN-alpha subtypes (IFN-alpha 20K and IFN-alpha 21K) and not on others. KG-1 cells produce both IFN-alpha and -beta; however, only the production of IFN-alpha was enhanced by priming with either IFN-alpha, beta or gamma.

1-Ene-steroid reductase of Mycobacterium sp. NRRL B-3805.

The microbial enzymatic reduction of 1,4-androstadiene-3,17-dione (ADD) to 4-androstene-3,17-dione (AD), testosterone and 1-dehydrotestosterone (DHT) is described. Two reducing activities observed in washed cell suspensions and cell free extracts of Mycobacterium sp. NRRL B-3805 were found to account for these bioconversions. One was a 1-ene-steroid reductase and the other a 17-keto steroid reductase. The first reducing activity was found to appear in the soluble cell fraction whereas the latter could be precipitated by centrifugation. Maximum 1-ene-steroid reductase specific activity was achieved during the exponential growth phase of the organism and significantly increased upon induction with ADD. The 1-ene-steroid reductase was partially purified (30-fold) by ammonium sulfate fractionation, gel-filtration and ion-exchange chromatography, and was eluted from a Sephacryl S-300 column with an Mr = 115,000. The 1-ene-steroid reductase activity was NADPH-dependent and had specificity towards steroid compounds containing C-1,2 double bond with an apparent Km for ADD of 2.2 X 10(-5) M. The reverse reaction catalyzing C-1,2 dehydrogenation could not be detected in our preparations. The results suggest that in Mycobacterium sp NRRL B-3805 and B-3683 the steroid C-1,2 dehydrogenation and 1-ene reduction are two separable activities.

High and low potency interferon-alpha subtypes induce (2'-5') oligoadenylate synthetase with similar efficiency.

Three major subtypes of human interferon-alpha (IFN-alpha), isolated from virus-induced leukocytes, were compared for their antiviral and anticellular activities on one hand, and for their ability to induce (2'-5') oligoadenylate synthetase on the other hand. One subtype, IFN-alpha 1, was found to have low specific antiviral (6.10(6)-5.10(7) units/mg) and anticellular activities when measured on a variety of human cells. A second subtype, exhibiting an unusually high molecular weight (26,000) by SDS-polyacrylamide gel electrophoresis (IFN-alpha 26K), was found to have the highest known specific antiviral (8.10(8)-2.10(9) units/mg) and anticellular activities. Thus, these two subtypes of IFN-alpha differ by a factor of 330 and represent the two extremes in the antiviral scale on human cells. A third subtype, IFN-alpha 2, was tested as well and was found to have intermediate antiviral and anticellular activities. The ability of these three subtypes to induce (2'-5') oligoadenylate synthetase in human cells was then measured. It was found that on a weight basis, the three subtypes were equally effective in inducing the enzyme. Since the level of (2'-5') adenylate oligomers is affected also by the interferon-induced (2'-5') phosphodiesterase, the ability of these subtypes to induce this enzyme was compared as well and was found to be very similar. We therefore conclude that the differences in potency between these IFN-alpha subtypes are not related to their ability to induce (2'-5') oligoadenylate synthetase.