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Biomedical subjects

D Moser

Publications and source records attributed to D Moser.

49 records · Page 3Linked to original sources

The humoral response to heat shock protein 70 in human and murine Schistosomiasis mansoni.

We have expressed two cDNA sequences encoding 121 and 230 amino acids of the C-terminus of the Schistosoma mansoni Hsp 70 in Escherichia coli. The products were synthesized as polypeptides fused to the RNA polymerase of bacteriophage MS2, and their reactivities were tested in ELISAs, using sera from human and murine infections. Anti-Hsp70 antibodies were detected in a significant number of individuals suffering from chronic schistosomiasis mansoni, but not in patients with known recent infections. This, together with the finding that antibodies directed at S. mansoni-specific Hsp70 determinants during the course of infection of experimental mice were not detectable until 5-6 weeks post-infection, suggests that the protein may be a useful marker for distinguishing late and early infections. The diagnostic specificity of Hsp70 was evaluated with sera from humans infected with different schistosome species and other parasitic diseases. While some subjects infected with S. haematobium produced antibodies which recognized the S. mansoni Hsp70, no such antibodies were generated in S. japonicum infected individuals. However, cross-reactive antibodies were elicited in donors with other parasitic diseases such as filariasis and malaria. The absence of antibodies in early infection and the observed cross-reactivities led us to conclude that Hsp70 will be of limited value in the diagnosis of schistosomiasis.

Animals↗

Construction of Onchocerca volvulus cDNA libraries and partial characterization of the cDNA for a major antigen.

Adult Onchocerca volvulus were isolated from nodules removed from onchocerciasis patients at four locations--two in the West African Sudan-savanna region (near Bamako, Mali, and Touboro, Cameroon), one in a West African forest region (Kumba, Cameroon) and one near Guatemala City, Guatemala. Four different cDNA expression libraries were constructed in bacteriophage lambda gt11 using poly(A)+ RNA from the adult female worms. Individual cDNA clones of single copy genes were used to compare the genomes of parasites from the different locales and to show that the haploid genome of O. volvulus is 1.5 x 10(8) base pairs. About 1 in 700 recombinant clones in each of the four amplified cDNA libraries produces a fusion protein recognized by pooled human anti-O. volvulus antisera. Partial sequence determination of a 2.0 kb cDNA clone for an O. volvulus protein that induces an immunodominant response in rabbits revealed that this antigen has sequence similarities with Caenorhabditis elegans myosin and with schistosome paramyosin (which confers partial protection against schistosome infection). The four cDNA libraries have been deposited with American Type Culture Collection (ATCC), 12301 Parklawn Drive, Rockville, MD 20852, U.S.A., for general distribution under ATCC Number 37509.

Animals↗

Management of rhegmatogenous retinal detachment with macula detached. Steroids, choroidal detachment, and acuity.

One hundred thirty-four consecutive eyes with rhegmatogenous retinal detachment involving the macula were evaluated with reference to the effectiveness of systemic steroids in preventing choroidal detachment after scleral buckling surgery and in facilitating both anatomic and functional success. The occurrence of postoperative choroidal detachment was inversely related to the routine intravenous administration of steroids under antibiotic coverage beginning in the recovery room (P = 0.014). Eyes so treated were free of both clinically significant infection and extrusion. The infrequent but worrisome complication of angle closure sufficient to require choroidal tap did not occur among treated eyes. Routine steroid use may have been associated with increased preservation of acuity at the level of 20/200 or better (P = 0.043).

Choroid↗

Evaluation of vascular rings with digital subtraction angiography.

Seven patients with vascular rings were evaluated over a 2-year period with intravenous digital subtraction angiography (DSA), which was compared with screen-film aortography or cineangiography. The seven patients were also evaluated with barium esophagography. Six of the seven DSA images were totally diagnostic and one study was only partly diagnostic. Six of the seven vascular anomalies were confirmed surgically. DSA is suggested as an alternative to arteriography in evaluating patients with suspected vascular rings.

Aorta, Thoracic↗

Multiple forms of Drosophila hexokinase. Purification, biochemical and immunological characterization.

Major forms of hexokinases (Hex A and Hex C) in Drosophila melanogaster were purified to homogeneity by utilizing affinity chromatography and preparative isoelectric focusing column as the key steps. Three different affinity ligands immobilized on Sepharose (3-amino pyridine adenine dinucleotide, glucosamine, and 8-(6-aminohexyl)-amino-ATP) were employed during different stages of enzyme purification. Antisera against purified Hex A and Hex C were raised in rabbits. Hex A, the major form in adults, and Hex B, the predominant form in larvae, showed complete immunological identity by double immunodiffusion and enzyme immunoinactivation studies. No cross-reactivity was observed between the antiserum to Hex A and Hex C or between the antiserum to Hex C and Hex A. By gel filtration chromatography and sodium dodecyl sulfate-acrylamide gel electrophoresis, all of the Drosophila hexokinases were shown to be monomers of molecular weights ranging from 40,000 to 50,000. Multiple forms of Drosophila hexokinase were studied extensively with respect to their biochemical properties including Michaelis constants, substrate and coenzyme specificities, pH-dependent activity, and thermal stability. Consistent with previous genetic evidence, the results of our studies also suggest that Hex A and Hex B (with subforms B1 and B2) are products of a single structural gene but are modified post-translationally, whereas the allelic forms of Hex C (C1 and C2) are derived from a different structural gene from that of Hex A and Hex B.

Animals↗

Blastomycosis of the esophagus.

A patient had clinical, endoscopic, and roentgenographic signs of esophageal carcinoma, but biopsies and brushings were negative. At operation he was found to have blastomycosis localized to the esophagogastric region and adjacent lymph nodes. There was no evidence of pulmonary disease. He was treated successfully by partial esophagectomy and amphotericin. The literature on esophageal blastomycosis is reviewed.

Adult↗

Purification and characterization of mouse glucose 6-phosphate dehydrogenase.

Glucose-6-phosphate dehydrogenase was purified to homogeneity from testes and kidneys of the inbred strain of mice (DBA/2J) by a simple two-step affinity column procedure. This involved the sequential application of 8-(6-aminohexyl)-amino-AMP- and -2', 5'-ADP-Sepharose columns and biospecific elution with NADP+ in both steps. The molecular and biochemical properties of the purified enzyme were studied in detail. These include the molecular weight determination, amino acid composition, steady-state kinetics, inactivation by high temperature, urea and iodoacetate, and immunology. The purified enzyme from mouse kidneys or testes was shown to be a tetramer with a molecular weight of 220,000. The enzyme is highly specific for glucose-6-phosphate, exhibits almost no activity with NAD+ as a coenzyme and is little inhibited by AMP or ATP. Michaelis constants for glucose-6-phosphate and NADP+ were determined to be 50 microM and 10 microM respectively. NADPH is a competitive inhibitor of NADP+ and has a Ki of 18 microM. Rabbit antisera against glucose-6-phosphate dehydrogenase were raised. The antisera also cross-react with the same enzyme from human and guinea pig.

Amino Acids↗

Cytoplasmic malic enzyme from mouse kidneys.

NADP+-dependent cytoplasmic malic enzyme was purified to homogeneity from mouse kidneys by a two-step procedure involving 8-(6-aminohexyl)-amino-2', 5'-ADP-Sepharose affinity chromatography and DEAE-Sephadex ion exchange chromatography. The biochemical properties of the purified enzyme from DBA/2J mice were characterized. These include the determination of molecular weight and amino acid compositions, steady-state kinetics, thermal stability and inactivations by iodoacetate and urea. The native enzyme is a tetramer with a molecular weight of 270,000.Km's for NADP+, L-malate, NADPH and pyruvate were determined to be 3.3 micrometer, 50 micrometer, 10.5 micrometer respectively. Similar to the pigeon liver enzyme, the mouse enzyme exhibits an ordered kinetic mechanism proceeding with the binding of coenzyme first. The enzyme is only weakly inhibited by ATP and other cellular metabolites. A remarkable similarity in amino acid compositions was found between the mouse and rat liver malic enzymes.

Amino Acids↗

Performance on the Hooper Visual Organizational Test in patients diagnosed with subcortical vascular dementia: relation to naming performance.

OBJECTIVE: To examine the performance of individuals with vascular dementia (VaD) on the Hooper Visual Organization Test (HVOT) and to determine the influence of naming on HVOT performance in this population. BACKGROUND: The HVOT is commonly administered to assess visuospatial perception among neurologic patients, but the test requires verbal identification of stimuli as well as spatial ability. Previous studies have examined the influence of naming on the HVOT, but the issue has not been systematically addressed in individuals with subcortical VaD. METHOD: Individuals with a diagnosis of VaD were administered the HVOT, three additional measures of visuospatial function (Block Design and Picture Completion subtests of the Wechsler Adult Intelligence Scale-Revised, Rey-Osterrieth Complex Figure Test copy trial), and the Boston Naming Test (BNT). RESULTS: On average, the VaD patients performed poorly compared with normative data on each of the cognitive measures, with the most pronounced deficit evident on the BNT. Regression analyses revealed that more than 60% of the variance in performance on the HVOT was accounted for by performance on the Block Design subtest of the Wechsler Adult Intelligence Scale-Revised; performance on the BNT did not contribute significantly. CONCLUSIONS: The results suggest that VaD patients perform below expectations on the HVOT and that the measure is robust to naming deficits in this population.

Brain↗

Cognitive and neurologic predictors of functional impairment in vascular dementia.

OBJECTIVE: The purpose of this study is to investigate associations between executive dysfunction, neuroimaging findings, and functional impairment in patients with vascular dementia (VaD). METHODS: Twenty-nine VaD patients completed the Dementia Rating Scale and underwent MRI scanning to generate quantitative ratings of subcortical hyperintensities (SH) and cortical volume. Patients' caregivers completed items from the Lawton and Brody Activities of Daily Living Questionnaire, designed to measure instrumental activities of daily living (IADLs). The authors hypothesized that performance on the Initiation/Perseveration (IP) subscale, a measure of executive abilities, and SH would significantly predict levels of IADLs. RESULTS: A hierarchical multiple-regression analysis revealed that IP and SH accounted for 42% of the variance in IADLs; IP alone accounted for 28%, and SH accounted for 14% beyond the contribution made by IP. CONCLUSION: Findings indicate that specific cognitive and neuropathological factors are associated with functional impairment in VaD.

Activities of Daily Living↗