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Biomedical subjects

L M Young

Publications and source records attributed to L M Young.

At least 19 recordsLinked to original sources

Cloning and characterization of human astrovirus immunoreactive epitopes.

We report the cloning of antigenic, protein-coding regions of human astrovirus serotype 1 that appear to be common to most, if not all, serotypes of human astrovirus. Screening of lambda gt11 libraries identified three different but overlapping clones (A43, A35, and A1) and one independent clone (A14) that reacted with serum from a rabbit repeatedly immunized with purified astrovirus particles but not with its preimmunization serum. These clones were shown to be astrovirus specific. Of note, a radiolabeled probe representing the immunoreactive clones A43-A35-A1 hybridized exclusively to the 7.2-kb astrovirus genomic RNA, while a clone A14-specific probe hybridized with both the genomic and the 2.8-kb astrovirus subgenomic RNAs. This suggests that the immunoreactive epitopes, selected by antiserum to purified astrovirus particles, are encoded by the subgenomic RNA as well as other regions of the genomic RNA.

Amino Acid Sequence

Hepatitis E virus (HEV): strain variation in the nonstructural gene region encoding consensus motifs for an RNA-dependent RNA polymerase and an ATP/GTP binding site.

Hepatitis is transmitted by a number of infectious agents. The epidemiological characterization of waterborne or enterically transmitted non-A, non-B hepatitis (ET-NANBH) is unique when compared with other known hepatitides. We have reported on the molecular cloning of a cDNA clone derived from the etiologic agent associated with ET-NANBH, the hepatitis E virus (HEV). The complete sequence of these first molecular clones, isolated from an HEV-infected human after passage in Macaca fascicularis (cynomolgus macaques), illustrates a distant relationship to other known positive-strand RNA viruses of plants and animals. The translated major open reading frame (ORF-1) from these clones indicates that this portion of the genome encodes a polyprotein with consensus sequences found in RNA-dependent RNA polymerase and ATP/GTP binding domains. The latter activity has been associated with putative helicases of positive-strand RNA viruses. These viral-encoded enzymatic activities identify this region and ORF-1 as containing at least two different nonstructural genes involved in HEV replication. Molecular clones obtained from two other geographically distinct HEV isolates demonstrated sequence heterogeneity in this nonstructural gene region. Further study will be required to elucidate the pathogenic significance (if any) of this observed divergence in the nonstructural region.

Adenosine Triphosphate

Symptom monitoring in schizophrenia: potential for enhancing self-care.

In this study a symptom self-regulation model was used as a framework to examine the characteristics and stability of indicators of illness identified by individuals with schizophrenia. Subjects were interviewed to determine if they could identify indicators of illness and describe characteristics of their primary indicator. Primary indicators of illness from 51 subjects were categorized as anxiety-based, depressive, or psychotic. Subjects who identified psychotic indicators were more confident that their indicator occurred when they were getting ill than subjects with anxiety-based or depressive indicators, and subjects who identified psychotic and depressive indicators reported that their indicators were more troublesome than those identifying anxiety-based indicators. Anxiety-based indicators were reported by subjects to occur more frequently than indicators from the other two categories. Findings from a follow-up interview of 28 subjects 1 year later showed that approximately half reported either the same primary indicator of illness or identified an indicator in the same category (anxiety-based, depressive, or psychotic) as they had 1 year previously. The implications of the findings for enhancing self-care through monitoring symptoms are discussed.

Adult

Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis.

Major epidemic outbreaks of viral hepatitis in underdeveloped countries result from a type of non-A, non-B hepatitis distinct from the parenterally transmitted form. The viral agent responsible for this form of epidemic, or enterically transmitted non-A, non-B hepatitis (ET-NANBH), has been serially transmitted in cynomolgus macaques (cynos) and has resulted in typical elevation in liver enzymes and the detection of characteristic virus-like particles (VLPs) in both feces and bile. Infectious bile was used for the construction of recombinant complementary DNA libraries. One clone, ET1.1, was exogenous to uninfected human and cyno genomic liver DNA, as well as to genomic DNA from infected cyno liver. ET1.1 did however, hybridize to an approximately 7.6-kilobase RNA species present only in infected cyno liver. The translated nucleic acid sequence of a portion of ET1.1 had a consensus amino acid motif consistent with an RNA-directed RNA polymerase; this enzyme is present in all positive strand RNA viruses. Furthermore, ET1.1 specifically identified similar sequences in complementary DNA prepared from infected human fecal samples collected from five geographically distinct ET-NANBH outbreaks. Therefore, ET1.1 represents a portion of the genome of the principal viral agent, to be named hepatitis E virus, which is responsible for epidemic outbreaks of ET-NANBH.

Amino Acid Sequence

Urinary excretion of pentoxifylline and its metabolites by standardbred mares.

The urinary excretion of a sustained-release formulation of pentoxifylline was studied in the horse after the oral administration of 4.0 grams of Trental tablets. Urine samples were collected for 24 hours after dosing and analyzed for pentoxifylline and its metabolites using high-performance liquid chromatography coupled with an ultraviolet detector. Six metabolites of pentoxifylline were identified in horse urine in addition to less than 0.2% of unchanged drug. Concomitant use of gas chromatography/mass spectrometry allowed for the elucidation of the chemical structures of the metabolites. Metabolism of pentoxifylline yields one demethylated derivative, four hydroxylated metabolites and a conjugate of one of the hydroxymetabolites as urine products. The demethylated derivative, 3-methyl-1-(5-oxohexyl)-xanthine, was found to be the predominant metabolite in the urine.

Animals

Presence of salicylic acid in standardbred horse urine and plasma after various feed and drug administrations.

Plasma and urinary levels of salicylic acid were examined in Standardbred mares after administration of various feeds, containing different compositions of hay. In addition, horses were administered acetylsalicylic acid orally and methyl salicylate topically. Elevated salicylic acid levels were observed in horse urine and plasma in animals fed lucerne hay. The plasma and urinary elimination of salicylic acid exhibited a diurnal pattern which was related to the type of feed and the feeding schedule. Within 24 h after oral administration of acetylsalicylic acid, plasma and urine salicylic acid levels were consistent with residual levels observed after feeding lucerne hay. Elimination of salicylic acid was rapid and complete, with a half-life between 5 and 7 h. Topical administration of methyl salicylate (8.4 g) produced elevated urinary salicylic acid levels for 6 h. A smaller dose of methyl salicylate (3.4 g) did not elevate plasma or urine salicylic acid levels above those observed following administration of lucerne hay.

Administration, Oral

Fetal biophysical profile and perinatal death.

Antepartum assessment of 5034 high-risk pregnancies to predict perinatal death included five biophysical variables (nonstress test, fetal breathing movements, fetal movements, fetal tone, and amniotic fluid volume) which combined to form a biophysical profile score. We assessed 4148 fetuses within seven days of delivery. The ability of each variable to predict perinatal death was expressed as the likelihood ratio, which incorporates sensitivity and specificity into one number. The predictive ability was most accurate with fetal movement (likelihood ratio 48.1) and the combined biophysical profile score (likelihood ratio 51.0). The biophysical profile score was more likely to predict perinatal death due to asphyxia (seven of eight) than lethal anomaly (six of 19). The overall perinatal mortality was 7.6 per 1000 total births. The perinatal mortality rate was 1.0 for a normal biophysical profile score, 31.3 for an equivocal score, and 200.0 for an abnormal score. The false-negative rate for the biophysical profile score was 0.7 per 1000.

Amniotic Fluid

Antepartum fetal assessment using a fetal biophysical profile score.

The application of the fetal biophysical profile score in the management of 2,400 high-risk pregnancies was assessed. The negative predictive value for normal perinatal outcome was not improved compared to single variable tests. The positive predictive value for abnormal perinatal outcome was improved. The overall perinatal mortality in 2,485 fetuses was 9.2 per 1,000. In the 1,980 fetuses with a normal biophysical profile score within 7 days of delivery, excluding lethal anomalies, the perinatal mortality was 1 per 1,000. Fetal movement counting is supported as the most valid and appropriate test for universal fetal screening.

Amniotic Fluid

Riboflavin use as a drug marker in Veterans Administration cooperative studies.

Most Veterans Administration (VA) cooperative studies have used only the pill count method to measure and describe patient adherence to a drug regimen. The use of a drug marker is considered when adherence is expected to be a problem in a study, especially if the therapeutic drug or metabolite cannot be measured in the blood or urine of all patients or if reliability of pill counts is open to serious question. In a VA-NHLBI hypertension study using riboflavin as a marker for assessing patient adherence, group data suggest that similar adherence scores can be expected when comparing pill counts and urine tests. However, when an individual patient's adherence was examined by each method at a particular visit, discrepancies were noted. In a VA cooperative study on disulfiram for the treatment of alcoholism, riboflavin used as a marker provided additional information that was needed to assess the adherence of the study population. By employing this second measure of adherence in this study, we were able to obtain at least one measure of adherence at 84% of all clinic visits. If the pill count method had been the sole adherence measure, only 60% of visits would have produced an adherence score. At 65% of clinic visits, the pill count and urine test were in agreement. Results of urine tests taken in the interval between visits were similar to those taken at the clinic visit. Patient cooperation in providing urine specimens or in returning pills to the clinic was slightly associated with positive adherence scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism

National survey of pharmacy-coordinated investigational drug services.

A national survey of 703 pharmacy departments was conducted to obtain information on the status and scope of investigational drug services (IDS). Questionnaires were mailed to the directors of pharmacy departments of general medical and surgical hospitals with 300 or more beds and a university affiliation. The survey consisted of 27 questions that were primarily based on the ASHP guidelines for the use of investigational drugs in institutions. A total of 403 questionnaires were returned, 386 of which could be evaluated, 386 of which could be evaluated. Only 33% of the pharmacy departments adopted a minimal subset (7 of 11) of the recommended procedures based on the ASHP guidelines. All pharmacy departments with more than 40 protocols reported having a research pharmacist or a need for one. Of all of the protocols, 43% were sponsored by the National Institutes of Health, 34% by pharmaceutical companies, 16% by investigators and physicians, and 7% by various other sponsors. Drug information, monetary reimbursement for services,a dn coordination and communication were the most frequently cited areas in need of improvement by the drug sponsors. The most common types of protocols involved cancer research (56%) and infectious disease and cardiovascular studies (12% and 13%, respectively). Directors of pharmacy departments should review their investigational drug policies and procedures for compliance with ASHP guidelines as the first step in developing the IDS concept.

Drug Information Services

"Bare lymphocytes" without immunodeficiency.

"Bare lymphocytes," which cannot be typed for the HLA-A,B, and C antigens were observed in two siblings, nine and six years of age. The elder child presented with aplastic anemia and was being considered for bone marrow transplantation. The younger child was healthy. The inability to phenotype both children for these three gene products persisted throughout the 21-month period of observation. The DR antigens were demonstrable which rendered it possible to deduce their A, B, and C genotype from the typing of the other four family members. Although alloantisera failed to detect the antigens on peripheral blood lymphocytes, monoclonal antibodies demonstrated reduced amounts of the HLA-A,B, and C antigens on the cells. The reduced level was confirmed following EBV transformation of the cells. After prolonged culture, HLA antigens immunoprecipitated from the cell extracts were normal in amount, molecular weight, and polypeptide composition. Southern blot analysis did not reveal gross genomic rearrangements. A regulatory defect leading to the expression of these Class I antigens is postulated.

Anemia, Aplastic

A field expander for patients with retinitis pigmentosa: a clinical study.

An inexpensive, commercially available optical device was tested on 10 patients with retinitis pigmentosa to determine its value as a field expander for scanning and as an aid to mobility. Visual acuity and visual fields were measured with and without the expander, and the patients' subjective responses were monitored by a questionnaire that was administered at regular intervals during a 2- to 4-week period between test sessions. Six of the 10 subjects considered the device helpful in at least 1 important visual task and planned to continue using it.

Adult

Identification of metabolites of methylprednisolone in equine urine.

Methylprednisolone and three metabolites, 17,21-dihydroxy-6 alpha-methyl-1,4-pregnadiene-3,11,20-trione, 6 alpha-methyl-17,20 beta,21-trihydroxy-1,4-pregnadiene-3,11-dione, and 6 alpha-methyl-11 beta,17,20 beta,21-tetrahydroxy-1,4-pregnadien-3-one were detected in equine urine after intraarticular administration of methylprednisolone acetate. All four compounds were excreted both in the unconjugated form and as glucuronic acid conjugates. They were identified by comparing data obtained from analyses by high performance liquid chromatography, thin-layer chromatography, ultraviolet spectroscopy and gas chromatography/mass spectrometry to those of the synthesized standards. The presence of trace amounts of a fourth metabolite, 6 alpha-methyl-11 beta,17,20 alpha,21-tetrahydroxy-1,4-pregnadien-3-one, was indicated by high performance liquid chromatography but confirmation has not been attained by the other methods.

Animals