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Biomedical subjects

S Land

Publications and source records attributed to S Land.

14 recordsLinked to original sources
PubMed1998

Latent structure of EEG sleep variables in depressed and control subjects: descriptions and clinical correlates.

In this study, we aimed to determine the latent structure of multiple EEG sleep variables in patients with major depressive disorder (MDD) and in healthy control subjects and to examine associations between sleep factors and clinical variables. Subjects included 109 women with MDD and 54 healthy control women. EEG sleep data were collected prior to any treatment. Principal components analysis (PCA) was conducted on a set of 24 sleep variables. Separate PCAs were run for patients with MDD, control subjects, and a matched group of patients and controls. Other analyses included correlations, t-tests and MANOVA. Each PCA identified four sleep factors that explained 70% of the total variance in individual sleep variables: slow wave sleep, REM sleep, sleep continuity and REM latency/delta sleep ratio (RL/DSR). Patients with MDD and healthy controls differed on the mean value of the sleep continuity factor, and a multivariate analysis of variance based on the PCA identified MDD-control differences in REM sleep and sleep continuity. In the MDD group, slow wave sleep correlated inversely with age and personality disorder symptoms; sleep continuity correlated with subjective sleep quality and anxiety; and RL/DSR correlated inversely with age. The mean value of the REM factor was higher among treatment non-responders than responders. EEG sleep variables have a similar latent structure in women with MDD and in healthy controls. These sleep factors are supported conceptually and empirically, and correlate with clinical measures in women with MDD. Multivariate statistical techniques decrease the risk of Type I and Type II errors when using a large number of collinear sleep measures, and can clarify conceptual issues related to sleep and depression.

Adult↗
PubMed1998

Stability of human immunodeficiency virus RNA in blood specimens as measured by a commercial PCR-based assay.

We investigated the effects of conditions often encountered during handling, transit, and storage of blood specimens on the quantity of detectable human immunodeficiency virus (HIV) RNA in plasma. HIV RNA copy numbers were measured with a commercially available assay (the Amplicor HIV-1 Monitor test kit). Variables examined were the time to processing of blood and plasma, the holding temperature of blood and plasma prior to processing, the effect of freezing and thawing of plasma, and the use of different anticoagulants. The relationship between the HIV RNA copy number and the HIV isolation rate by peripheral blood mononuclear cell (PBMC) coculture was also examined. We found that RNA copy numbers were maintained to within 0.5 log10 (approximately threefold) in blood and plasma samples held at room temperature or 4 degrees C for up to 3 days and remained stable despite (limited) freezing and thawing of the plasma. HIV RNA copy numbers were also maintained after long-term storage of plasma at -70 degrees C. The ability to isolate HIV from PBMCs was directly proportional to the HIV RNA copy number.

Adolescent↗
PubMed1996

An in vivo mutation from leucine to tryptophan at position 210 in human immunodeficiency virus type 1 reverse transcriptase contributes to high-level resistance to 3'-azido-3'-deoxythymidine.

Sequencing of the reverse transcriptase (RT) region of 26 human immunodeficiency virus type 1 (HIV-1) isolates from eight patients treated with 3'-azido-3'-deoxythymidine (AZT) revealed a mutation at codon 210 from TTG (leucine) to TGG (tryptophan) exclusively in association with resistance to AZT. The mutation Trp-210 was observed in 15 of the 20 isolates phenotypically resistant to AZT, being more commonly observed than resistance-associated mutations at codons 67, 70, and 219. Trp-210 was never observed before the emergence of resistance-associated mutations Leu-41 and Tyr-215, and in a sequential series of five isolates from one patient the order of emergence of mutations was found to be Tyr-215, Leu-41, and then Trp-210. Trp-210 was also found in association with the Leu-41, Asn-67, Arg-70, and Tyr-215 resistance genotype. To define the role of Trp-210 in AZT resistance, molecular HIV-1 clones were constructed with various combinations of RT mutations at codons 41, 67, 70, 210, and 215 and tested for susceptibility to AZT. In clones with polymerase genes derived either from HXB2-D or clinical isolates, Trp-210 alone did not increase AZT resistance, whereas in conjunction with Leu-41 and Tyr-215, Trp-210 contributed to high-level resistance (50% inhibitory concentration of >1 microM). In HXB2-D, Trp-210 with Tyr-215 generated a virus with resistance comparable to one with Leu-41, Tyr-215, and Trp-210. Inserting Trp-210 into the genetic context of mutations at codons 41, 67, 70, and 215 further enhanced resistance from a 50% inhibitory concentration of 1.44 microM to 8.41 microM. Molecular modeling of the tertiary structure of HIV-1 RT revealed that the distance between the side chains of Trp-210 (in helix alphaF) and Tyr-215 (in strand beta11a) approximated 4 A (1 A = 0.1 nm), sufficiently close to result in significant energetic interaction between these two aromatic side chains. In conclusion, Trp-210 contributes significantly to phenotypic AZT resistance of HIV-1 by augmenting resistance at least three- to sixfold in the context of two resistant genotypes, and its effect may require an interaction with an aromatic amino acid at position 215.

Base Sequence↗
PubMed1993

Antigen processing gene polymorphisms in HLA-DR2 multiple sclerosis.

The association between multiple sclerosis (MS) and alleles of the HLA class II genes indicates that at least one MS susceptibility gene is linked to the HLA class II region. However, the actual locus responsible has not been precisely identified. The recent cloning of new genes involved in antigen processing that map within the HLA class II region led us to investigate--using the restriction fragment length polymorphism (RFLP) technique and sequence-specific oligonucleotide analysis--whether these genes might play a role in conferring susceptibility to MS. We studied large multifunctional protease (LMP) 2 and 7 and transporter associated with antigen processing (TAP) 1 and 2 gene polymorphisms in 60 HLA-DR2 MS patients and 60 HLA-DR2 healthy subjects and found no specific or preferential RFLP patterns or coding sequence variants in the patient group. Our data do not support a role for these genes in MS susceptibility.

Adult↗
PubMed1992

Incidence of zidovudine-resistant human immunodeficiency virus isolated from patients before, during, and after therapy.

The zidovudine sensitivity of 372 isolates of human immunodeficiency virus (HIV) obtained from 237 patients before, during, and after treatment with zidovudine was examined. Virus resistant to > 0.5 micrograms/mL (1.87 microM) zidovudine was isolated from most patients (93%) after 36 months of therapy. Zidovudine-sensitive virus was isolated from 5 of 15 patients who had ended antiretroviral therapy but had previously shed resistant virus. The emergence of sensitive virus after end of therapy appeared to be influenced by both the duration of treatment and the time off drug. Patients with resistant virus tended to have low CD4 cell counts and HIV antigenemia at the commencement of therapy, suggesting that these two factors are important in the development of drug resistance.

CD4 Antigens↗
PubMed1992

Interaction between vasopressin and endothelin in renal papillary tubules: uncoupling following cell isolation and culture.

1. In freshly prepared rat renal papillary tubules, endothelin-related peptides inhibited the vasopressin-stimulated accumulation of cAMP. No inhibition was observed when tubules were cultured overnight ex vivo. 2. Endothelin-1, endothelin-3 and sarafatoxin S6b had similar potencies as inhibitors of cAMP accumulation, indicating an endothelin (ETb) receptor. 3. These results demonstrate an interaction between ETb receptors and vasopressin receptors at the level of their signal transduction pathways, and show that this relationship is lost following cell culture.

Animals↗
PubMed1991

Endothelin receptors in rat renal papilla with a high affinity for endothelin-3.

A high density of binding sites for endothelin has been described in rat renal papilla but the nature and significance of papillary endothelin receptors have not yet been evaluated. In the current study, the effect of endothelin peptides on phosphatidylinositol turnover in papillary tubules has been investigated. Endothelin-1, endothelin-3 and the endothelin-related peptide sarafatoxin S6b all stimulated the accumulation of inositol phosphates in [3H]inositol-labelled papillary tubule preparations. However, at these papillary receptors endothelin-3 was more potent than endothelin-1. In other tissues, endothelin-1 is more potent than endothelin-3 at endothelin receptors coupled to phosphatidylinositol turnover. The EC50 value for endothelin-3 expressed as the negative logarithm was 9.3 +/- 0.13 compared with 8.42 +/- 0.11 for endothelin-1 (mean +/- S.E.M., n = 5 in each case, P less than 0.01). The affinity of sarafatoxin S6b was similar to that for endothelin-3 (9.2 +/- 0.15, n = 3). These findings raise the possibility of a direct tubular function of endothelin and suggest that endothelin-3 rather than endothelin-1 may be the natural agonist for these papillary receptors.

Animals↗
PubMed1991

Culturing rat neonatal myocytes causes changes in the phosphatidylinositol turnover pathway.

1. Cultured neonatal myocytes are commonly used as a model system for the study of cardiac phosphatidylinositol (PI) turnover. 2. In neonatal myocytes stimulation with noradrenaline causes the release of the Ca2(+)-releasing compound inositol-1,4,5-trisphosphate and the generation of the Ca2(+)-regulatory compound inositol-1,3,4,5-tetrakisphosphate. 3. Addition of noradrenaline to intact, neonatal rat hearts stimulates the release of inositol-1,4,5-trisphosphate, but not inositol-1,3,4,5-tetrakisphosphate. 4. These findings show that the isolation and culture of the neonatal myocyte causes changes in the PI turnover pathway so that it becomes similar to that described in other cell types and different from that in intact myocardial tissue. 5. The neonatal myocyte is not a useful model for the study of cardiac PI turnover.

Animals↗
PubMed1990

Decreased in vitro susceptibility to zidovudine of HIV isolates obtained from patients with AIDS.

This study tested isolates of human immunodeficiency virus, obtained before and after zidovudine therapy from 10 patients, for susceptibility to the drug in vitro. The isolates collected after therapy were less susceptible to zidovudine as assessed by replication in MT-2 cells and production of reverse transcriptase activity by infected mononuclear leucocytes in the presence of the drug. Furthermore, pretherapy isolates were sensitive to a range of zidovudine concentrations when 100% inhibition was used as the end point. The loss of zidovudine susceptibility did not correlate with any clinical or virologic consequences in this small group of patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Comparison of core antigen (p24) assay and reverse transcriptase activity for detection of human immunodeficiency virus type 1 replication.

This report compares two assay systems for monitoring human immunodeficiency virus (HIV) replication in peripheral blood leukocyte cultures. A commercial enzyme-linked immunoassay detected core antigen (p24) in 80% of cell cultures from HIV-seropositive individuals, whereas 67% of the cell cultures produced detectable levels of reverse transcriptase activity. There were clearly three patterns of reverse transcriptase activity produced, two of which may evade detection without regular sampling and maintaining cell cultures for more than 4 weeks. Once established, core antigen levels remained high so that cell cultures could be confidently monitored by an intermittent screening regimen.

Cells, Cultured↗
PubMed1989

Purification and biochemical characterization of hepatic arylamine N-acetyltransferase from rapid and slow acetylator mice: identity with arylhydroxamic acid N,O-acyltransferase and N-hydroxyarylamine O-acetyltransferase.

An inbred mouse model for the human N-acetylation polymorphism has been used to investigate the biochemical basis for the arylamine N-acetylation polymorphism and the relationship between the cytosolic enzymes arylamine N-acetyltransferase (NAT), arylhydroxamic acid N,O-acyltransferase, and N-hydroxyarylamine O-acetyltransferase. Biochemical studies of partially purified NAT from rapid and slow acetylator mice revealed identical molecular weights of 31,500, activation energies of 21,000 cal/mol, equivalent affinities for acetyl coenzyme A, broad pH optima, the presence of an active site sulfhydryl group, and similar behavior during purification with anion exchange, gel filtration, and hydrophobic interaction chromatography. The enzymes differed in inhibition by hydrogen peroxide and dithiobis(2-nitrobenzoic acid). These observations taken in conjunction with previous investigations indicate that the rapid and slow mouse NAT enzymes are isozymes with minimal structural differences. NATs from rapid and slow acetylator mice were purified more than 10,000-fold by the following sequence of methods: homogenization and fractional centrifugation, protamine sulfate precipitation, and chromatography on DEAE-Trisacryl M, Sephadex G-100, Amethopterin-AH-Sepharose 4B, butyl agarose, and Sephacryl S-200, with a 15-25% recovery. NAT from B6 mice was purified to greater than 95% purity, as judged by silver staining of sodium dodecyl sulfate-polyacrylamide gels. Although only NAT appeared to be subject to a genetic polymorphism as evidenced by N-acetylation activities in liver cytosol, the purified NAT protein possessed arylhydroxamic acid N,O-acyltransferase, N-hydroxyarylamine O-acetyltransferase, and NAT activities. Thus, the cytosolic N-acetyltransferase of mouse liver may catalyze N-, O-, and N,O-acetyltransfer reactions through a common acetylated intermediate of a single protein.

Acetylation↗
PubMed1986

Trauma center and the OR. A cooperative approach to caring for the massively injured.

Communication must be established between the operating room and trauma center. At SNJRTC, perioperative nurses rotate through the trauma center and are part of nursing grand rounds on trauma patients. This system has improved interdepartmental relations, educational development, and most importantly, established a system in which patients have the best chance of survival as a result of the cooperative approach to the care of the massively injured.

Communication↗
PubMed1985

The aging thyroid. Relationship between elevated serum thyrotropin level and thyroid antibodies in elderly patients.

The relationship of thyroid antibodies and the serum level of thyrotropin in older adults (over age 60) was studied to determine whether thyroid antibodies were a good clue to thyroid failure in elderly persons. Of those with thyroid failure, evidenced by clearly elevated serum thyrotropin values (more than 10 microU/ml), 67 percent had positive antimicrosomal antibody levels, a prevalence much greater (p less than 0.001) than that among those of comparable age with normal thyroid function (18 percent). Nevertheless, one third (33 percent) had thyroid failure without positive antimicrosomal antibody levels; this was true whether or not a low serum thyroxine value was present. Furthermore, of those with positive antimicrosomal antibody levels, most (68 percent) did not have thyroid failure. Thus, although positive antimicrosomal antibody levels occurred more often in elderly patients with thyroid failure than in those with normal thyroid function, a sizable fraction of those with thyroid failure did not have positive antimicrosomal antibody levels. Hence, measurement of thyroid antimicrosomal antibodies is not a good test of early thyroid failure in older patients; direct demonstration of a clearly elevated serum thyrotropin value is a better approach.

Adult↗