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Biomedical subjects

J R Carlson

Publications and source records attributed to J R Carlson.

At least 73 records · Page 4Linked to original sources
PubMed1993

Identification of goat and mouse urinary metabolites of the pneumotoxin, 3-methylindole.

1. Urine from goats dosed i.v. with 3-methylindole (3MI; 15 mg/kg) or [methyl-14C] 3MI (15 mg/kg, 0.5 microCi/kg) contained at least 11 metabolites of 3MI. 2. Goat metabolized 3MI to sulfate conjugates of 4- or 7-hydroxy-3-methyloxindole, 5- or 6-hydroxy-3-methyloxindole, and 3,5- or 6-dihydroxy-3-methyloxindole; glucuronic acid conjugates of indole-3-carboxylic acid and 4- or 7-hydroxy-3-methyloxindole; and unconjugated 3-hydroxy-3-methyloxindole. Diastereoisomeric glucuronic acid conjugates of 3-hydroxy-3-methyloxindole were also identified in goat urine. 3. Urine from mice dosed i.p. with 3MI (400 mg/kg) or [ring-UL-14C] 3MI (400 mg/kg, 125 microCi/kg) contained at least six metabolites of 3MI. 4. Mice metabolized 3MI to glucuronic acid conjugates of 3,5- or 6-dihydroxy-3-methyloxindole, 5- or 6-hydroxy-3-methyloxindole, and indole-3-carboxylic acid; and unconjugated indole-3-carboxylic acid. Unconjugated 3-hydroxy-3-methyloxindole was identified in mouse urine in a previous report. 5. Both goats and mice metabolized 3MI to a mercapturate, 3-[(N-acetyl-L-cystine-S-yl)methyl]indole, which has been previously identified and was confirmed in this study. 6. 3-Methyloxindole was not identified in the urine of either goats or mice. 7. The major pathways of 3MI biotransformation in goats and mice is the formation of mono- and dihydroxy-3-methyloxindoles and their subsequent conjugation with glucuronic acid or sulfate. 8. There are no apparent qualitative differences in the biotransformation of 3MI between goats and mice that can account for their different sensitivities to 3MI-induced lung injury.

Animals↗
PubMed1993

Osteotomy of the proximal tibia in the treatment of adolescent tibia vara.

Between 1983 and 1990, 9 patients with 13 involved lower extremities had proximal tibial osteotomies for the treatment of adolescent tibia vara. Average age at the time of onset was 11 years, 8 months. All patients were black and obese. The interval between awareness of the bowleg deformity and presentation averaged 1.7 years. The mean preoperative tibiofemoral angle was 13 degrees varus. Stabilization was achieved by external fixation (6 extremities), crossed pins (4 extremities), or staples (3 extremities). One patient with bilateral deformity experienced multiple postoperative complications including osteomyelitis and recurrent varus deformity at the osteotomy sites, both successfully treated. Another patient had recurrence of the varus deformity and a leg-length discrepancy secondary to early closure of the medial proximal tibial physis. At an average follow-up of 4 years, two patients complained of occasional pain; none complained of pain that restricted normal activities. The mean improvement in the tibiofemoral angle at follow-up was 20 degrees, with a mean tibiofemoral angle of 6 degrees valgus. Overall, there were 10 good, no fair, and 3 poor results.

Adolescent↗
PubMed1992

Prenatal diagnosis by enzymatic amplification and restriction endonuclease digestion for detection of haemoglobins A, S and C.

The detection of the single base pair mutations at codon 6 of the beta-globin gene is important for the prenatal diagnosis of sickle-cell anaemia and SC disease. A novel procedure has been designed to create a restriction site at both the beta A and beta C alleles to facilitate the discrimination of haemoglobins A, S and C. The general principle of this procedure is to enzymatically amplify genomic DNA using a modified primer containing an altered 3'-terminal nucleotide to create these restriction sites. After this modified primer has been efficiently incorporated into amplified DNA, the PCR products are digested with the restriction enzymes Ava I and Sty I. Ava I recognizes a site in amplified DNA containing a beta A allele, and Sty I recognizes a site in DNA containing a beta C allele. Since the beta A and beta C alleles can be distinguished directly by the presence of a restriction site, the beta S allele can be identified indirectly. All three beta-globin alleles are easily distinguished by size and pattern of electrophoresed fragments on agarose gels. This procedure is specific and sensitive, thus permitting rapid, economical diagnosis of sickle-cell anaemia and SC disease.

Anemia, Sickle Cell↗
PubMed1992

Decreases in unintegrated HIV DNA are associated with antiretroviral therapy in AIDS patients.

Better markers are needed to monitor the efficacy of antiretroviral drugs in persons infected with human immunodeficiency virus (HIV). We investigated the effects of zidovudine (ZDV) and dideoxycytidine (ddC) on the presence of unintegrated HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) from AIDS patients. DNA was extracted from PBMCs and separated into low molecular weight (unintegrated) and high molecular weight (integrated) chromosomal fractions. These DNA fractions were then amplified by a quantitative polymerase chain reaction (PCR) and the amount and percentage of unintegrated HIV DNA were determined. Very high levels of unintegrated HIV DNA were found in AIDS patients not receiving treatment with ZDV or ddC (median = 95% unintegrated HIV DNA). In contrast, most patients who had received 4 or more weeks of antiretroviral therapy had lower levels of unintegrated HIV DNA (median = 30% unintegrated HIV DNA for patients receiving ZDV). Paired samples taken from five patients before and after therapy showed a striking reduction in the percentage of unintegrated HIV DNA. The decrease in the proportion of unintegrated HIV DNA in AIDS patients was due to both a reduction in the copy number of unintegrated HIV DNA and an increase in the copy number of integrated HIV DNA. Thus, measurements of unintegrated and integrated HIV DNA may be useful in providing objective assessments of the effectiveness of antiretroviral therapies.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Effect of monensin and supplemental hay on ruminal 3-methylindole formation in adult cows after abrupt change to lush pasture.

The effect of feeding monensin, with or without dry hay plus wilted forage, on ruminal formation of 3-methylindole (3MI) was investigated in pastured cattle. Eighty-two cows were allotted to 3 groups. Cows of group-1 served as controls and were given a daily energy supplement (1 kg/head) without monensin for 1 day before and for 7 days after being allowed access to lush pasture. Cows of groups 2 and 3 were given the same daily energy supplement, which also contained monensin (200 mg/kg of supplement). Cows of group 3 also were fed dry hay for 5 days before the start of the study and continued to be given supplemental hay for 4 days after being allowed access to lush pasture containing a layer of wilted forage. Ruminal 3MI and indole concentrations increased on day 1 after all groups were allowed access to lush pasture. By day 7, 3MI concentration in all cows had decreased to pregrazing concentration. Indole concentration did not reach pregrazing concentration until day 10 for cows of groups 1 and 2. Group-3 cows had pregrazing indole concentration on day 7. Ruminal indole concentration did not differ (P greater than 0.05) between groups 1 and 2. Ruminal indole concentration was lower (P less than 0.01) in group-3 cows on all sample collection days, except day 10, compared with that in the other groups. Monensin reduced (P less than 0.01) 3MI formation on days 1 and 7 in group-2 cows, compared with group-1 cows. Group-3 cows had lower 3MI concentration than did group-1 cows (P less than 0.01) on days -1, 1, 4, and 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Isolation of a mercapturate adduct produced subsequent to glutathione conjugation of bioactivated 3-methylindole.

Bioactivation of the pneumotoxin 3-methylindole (3MI) to a methylene imine intermediate has been demonstrated previously by trapping the electrophile with glutathione in goat lung microsomal incubations. To determine whether the same bioactivation process occurs in whole animals, 3MI was administered to goats, mice, and rats, and the urinary metabolites from these three species were analyzed by HPLC for the presence of the mercapturate that would be expected as the processed and excreted form of the 3MI-glutathione adduct. The mercapturate, 3-[(N-acetylcysteine-S-yl)-methyl]indole (3MI-NAC), was identified in the urine from all three species and was isolated from rat urine for structural identification by uv, NMR, and mass spectrometry. Synthetic 3MI-NAC had uv, NMR, and chromatographic characteristics identical to the isolated metabolite. The presence of this mercapturate in the urine of treated animals unequivocally demonstrates that 3MI is bioactivated to the methylene imine in vivo and that the glutathione adduct is also formed, presumably to detoxify the methylene imine.

Acetylcysteine↗
PubMed1991

A simple, rapid immunoassay for the detection of simian immunodeficiency virus antibodies.

Detection of simian immunodeficiency virus (SIV) antibodies has proved useful in a wide variety of research studies. Conventional immunoassays, however, are difficult to perform outside the well-equipped laboratory or under field conditions. We have developed an inexpensive, simple, rapid immunoassay for the detection of SIV antibodies that utilizes inactivated SIV antigen and Fast-Chek (F-C) (E.Y. Laboratories, San Mateo, Ca)., which is a membrane/filter paper device that uses protein A gold to detect antibody and/or antigen. This low-cost 10-min assay requires minimal technical skill and no refrigeration, electrical power, or sophisticated laboratory equipment. In a study of 155 banked sera, from a number of monkey species in a variety of geographic locations, F-C and Western immunoblot result concordance was 96%. Relative sensitivity and specificity were 98% and 95%, respectively.

Animals↗
PubMed1991

SIV vaccine protection of rhesus monkeys.

Rhesus macaques (M. mulatta), immunized with an inactivated whole SIVmac vaccine and muramyl dipeptide or Freund's incomplete adjuvant, were protected against IV challenge infection with 10 animal infectious doses of the homologous virus. The protection in these animals appeared to be complete, with no breakthrough of latent virus infection over a 10-month period. Vaccine protection in this model was correlated generally with a high level of SIVmac envelope antibody by ELISA and immunoblot, high titers of syncytial inhibiting antibody, and, more specifically, with the presence of antibodies binding to a putative V3 loop synthetic peptide of the SIVmac outer envelope. This model can now be used for further identification of the protective epitopes and protective host immune responses as well as for development of novel and better AIDS vaccines.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

HIV-1 proviral copy number in blood mononuclear cells from AIDS patients on zidovudine therapy.

The effect of treatment with 400-1,200 mg/day of zidovudine (ZDV) on HIV DNA concentrations in patient peripheral blood mononuclear cells (PBMCs) was studied in six patients during a 5- to 14-month period of therapy. HIV DNA was measured in PBMCs at intervals using a recently developed quantitative polymerase chain reaction assay. The amount of HIV DNA ranged from 2,000 to 40,000 copies of provirus per microgram of cellular DNA. The HIV provirus copy number showed little change with time in five patients, and increased and then remained constant in one patient. Thus, prolonged treatment with ZDV does not decrease the levels of HIV DNA in PBMCs.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Prevalence of antibodies interactive with HTLV-I antigens in selected Solomon Islands populations.

Serum samples obtained in 1986 from healthy individuals in three distinct Solomon Islands populations were screened for antibodies to human lymphotropic virus type I (HTLV-I). One of the populations tested lives on the remote Polynesian outlier atoll, Ontong Java. The other two groups, the Baegu and the Lau, are Melanesians living on Malaita, the most populous of the larger Solomon Islands. Eighty-eight of a total of 601 (14.6%) sera tested were repeatably reactive in an enzyme-linked immunosorbent assay (ELISA) that uses as antigen a lysate of HTLV-I viral particles. The prevalence of antibodies interactive with HTLV-I viral particles. The prevalence of antibodies interactive with HTLV-I antigens varied among the three groups, ranging from 8.5% (16/188) in the Baegu, through 13% (7/54) in the Lau, to 18.1% (65/359) among the Ontong Java population. The specificity of the screening ELISA was confirmed by protein immunoblot. No serum samples were obtained from children under 9 years of age. Although 121 of the 601 sera came from children between the ages of 9 and 19, none of these were reactive in the HTLV-I ELISA. Starting in the third decade, the prevalence of HTLV-I seropositivity increased with age, from 8.8% (10/113) between the ages of 20 and 29 to a peak of 25.9% (15/58) and 25% (15/60) in the sixth and seventh decade, respectively. This age-specific prevalence pattern is strikingly similar to that which is seen in populations where HTLV-I infection is endemic.

Adolescent↗
PubMed1990

Vaccine protection of rhesus macaques against simian immunodeficiency virus infection.

Rhesus macaques (Macaca mulatta) immunized with an inactivated whole SIVmac vaccine and muramyl dipeptide (MDP), incomplete Freund's adjuvant (IFA), or aqueous suspension were challenged intravenously with 0.1 TCID50 of cell-free SIVmac. Whereas virus was readily recovered from the peripheral blood lymphocytes of 10 of 10 nonvaccinated controls following this challenge dose, virus was not recovered from the three animals that received the vaccine with MDP nor from one of two animals that received the vaccine with IFA and one of three animals that received the aqueous vaccine. The animals that were protected against challenge were those that had detectable SIV antibody response to the envelop, both the outer glycoprotein (gp120) and the truncated transmembrane glycoprotein (gp31). Protected monkeys tended to have higher titers of syncytial inhibition antibody prior to challenge. An anamnestic response after challenge was observed only in the vaccinated monkeys that became infected. Vaccinated animals that became challenge-infected tended to live longer than infected controls. These results confirm those at two other primate centers and indicate that killed whole SIV vaccines can protect against low challenge doses of SIV and prevent early death in those monkeys that do become infected. The mechanism of this protection remains undetermined. This finding adds optimism to the possibility of an eventual AIDS vaccine.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Assay for the enzymatic conversion of indoleacetic acid to 3-methylindole in a ruminal Lactobacillus species.

An assay to measure the rate of enzymatic formation of 3-methylindole (3MI) from indoleacetic acid (IAA) in Lactobacillus sp. strain 11201 was developed. The reaction mixture contained 50 micrograms of microbial protein per ml (range, 25 to 100 mg/ml), essential low-molecular-weight reaction ingredients, and radiolabeled IAA as substrate (range, 0 to 2 mM IAA). The reaction was anaerobic for 25 min at 39 degrees C. The apparent Michaelis-Menten constants were: Km, 0.14 mM IAA; and Vmax, 64 nmol 3MI.mg-1.min-1. The inhibitors avidin, aminopterin, and EDTA had no effect on the 3MI-forming enzyme. Dithionite stimulated the 3MI-forming enzyme. The product of the reaction, 3MI, acted as a noncompetitive inhibitor of the enzyme. Enzyme activity was associated with the cell wall fraction after sonication; treatment with the French press; or treatment with detergents, proteolytic enzymes, and EDTA.

Animals↗
PubMed1990

Effect of Indoleacetic Acid and Related Indoles on Lactobacillus sp. Strain 11201 Growth, Indoleacetic Acid Catabolism, and 3-Methylindole Formation.

A study was conducted to determine the activity of the 3-methylindole (3MI)-forming enzyme in Lactobacillus sp. strain 11201. Cells were incubated anaerobically with 17 different indolic and aromatic compounds. Indoleacetic acid (IAA), 5-hydroxyindoleacetic acid, 5-methoxy-3-indoleacetic acid, indole-3-pyruvate, or indole-3-propionic acid induced 3MI-forming activity. The highest total enzyme activity induced by IAA was observed in cells incubated with an initial concentration of 1.14 mM IAA. Peak activity of the 3MI-forming enzyme occurred 4 h after bacteria were incubated with either 0.114 or 1.14 mM IAA. Enzyme activity peaked earlier (2 h) and disappeared more rapidly at 5.7 mM IAA than at other concentrations of IAA. The effects of IAA and 3MI on the growth of Lactobacillus sp. strain 11201 and formation of 3MI from IAA also were determined. Bacterial growth and 3MI formation from IAA were reduced in medium containing exogenous 3MI. The growth depression observed in medium containing 5.7 mM IAA appears to be due to the toxicity of 3MI rather than IAA. The formation of 3MI in this ruminal Lactobacillus sp. is mediated by an inducible enzyme, and as 3MI accumulates, bacterial growth and rates of 3MI formation from IAA are reduced.

Journal Article↗
PubMed1990

Quantitation of human immunodeficiency virus DNA by using the polymerase chain reaction.

The polymerase chain reaction was used to measure the DNA copy number of human immunodeficiency virus (HIV). Differences in polymerase chain reaction amplification efficiency were controlled by amplifying known amounts of HIV DNA in parallel with samples. This technique is a sensitive, accurate, and reproducible method for the quantitation of HIV DNA.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Isolation and characterization of an olfactory mutant in Drosophila with a chemically specific defect.

A Drosophila mutant was isolated and shown to exhibit defective response to the chemical odorant benzaldehyde in two distinctly different behavioral assays. The defect exhibited chemical specificity: response to three other chemicals was normal. The mutant also showed abnormalities in pigmentation and fertility. Genetic mapping and complementation analysis provide evidence that the olfactory, pigmentation, and fertility defects arise as a result of a lesion at the pentagon locus. The specificity of the olfactory defect suggests the possibility that the mutation may define a molecule required in reception, transduction, or processing of a specific subset of chemical information in the olfactory system.

Alleles↗
PubMed1989

Antigen detection for human immunodeficiency virus.

The recent development of enzyme immunoassay procedures for the direct determination of human immunodeficiency virus (HIV) antigens has been of significant benefit in both clinical and research applications. The historical development of HIV antigen assays as well as their current and future applications for use in the clinical microbiology laboratory are reviewed. A detailed description of selected commercially available assays is presented, and a comparison is made of various parameters, including sensitivity, specificity, and cost. The use of the HIV antigen assay as an alternative to the reverse transcriptase assay in virus culture applications is also discussed. In addition, the diagnostic and prognostic utility of the HIV antigen assay is considered for various patient groups, including neonatal, high-risk asymptomatic, seronegative, and seropositive patient populations. The use of the HIV antigen assay as an adjunct to anti-HIV antibody testing, as well as its utility in assessing the therapeutic efficacy of antiviral drug therapy, is discussed. The biology of HIV antigen expression and modulation of anti-HIV antibody titers during infection are also discussed in terms of two possible models.

AIDS Serodiagnosis↗
PubMed1989

Postexposure immunotherapy of simian immunodeficiency virus (SIV) infected rhesus with an SIV immunogen.

An inactivated whole simian immunodeficiency virus (SIV) immunogen given to healthy, seropositive rhesus macaques 4 months after infection had no effect on the humoral immune response to SIV, the presence of antigenemia, cell-associated viremia, or disease course. Further immunotherapeutic trials in this highly susceptible animal model should be carried out sooner after exposure, before significant loss of CD4 cells has occurred. The SIV infected macaque model will continue to serve an essential role in development and testing of anti-AIDS drugs and immunogens.

Animals↗