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Biomedical subjects

H Barnes

Publications and source records attributed to H Barnes.

At least 19 recordsLinked to original sources
PubMed2001

Tyrosine-phosphorylated low density lipoprotein receptor-related protein 1 (Lrp1) associates with the adaptor protein SHC in SRC-transformed cells.

v-Src transforms fibroblasts in vitro and causes tumor formation in the animal by tyrosine phosphorylation of critical cellular substrates. Exactly how v-Src interacts with these substrates remains unknown. One of its substrates, the adaptor protein Shc, is thought to play a crucial role during cellular transformation by v-Src by linking v-Src to Ras. We used Shc proteins with mutations in either the phosphotyrosine binding (PTB) or Src homology 2 domain to determine that phosphorylation of Shc in v-Src-expressing cells depends on the presence of a functional PTB domain. We purified a 100-kDa Shc PTB-binding protein from Src-transformed cells that was identified as the beta chain of the low density lipoprotein receptor-related protein LRP1. LRP1 acts as an import receptor for a variety of proteins and is involved in clearance of the beta-amyloid precursor protein. This study shows that LRP1 is tyrosine-phosphorylated in v-Src-transformed cells and that tyrosine-phosphorylated LRP1 binds in vivo and in vitro to Shc. The association between Shc and LRP1 may provide a mechanism for recruitment of Shc to the plasma membrane where it is phosphorylated by v-Src. It is at the membrane that Shc is thought to be involved in Ras activation. These observations further suggest that LRP1 could function as a signaling receptor and may provide new avenues to investigate its possible role during embryonal development and the onset of Alzheimer's disease.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Tuberculosis and poverty in the ethnic minority population of West Yorkshire: an ecological study.

The rising incidence of TB in the UK in the last decade has been attributed mainly to the persistently high TB rates amongst ethnic minority groups. The epidemiology of TB in these groups is presently poorly understood. The aim of this ecological study was to investigate the relationship between TB and poverty in the South Asian ethnic groups. TB notification rates in South Asians residing in Kirklees (West Yorkshire) were correlated with eight indices of deprivation. Spearman's correlation coefficient analysis suggested a strong relationship between notification rates and material deprivation (r = 0.58 [p value = 0.009 for a two-tailed test]). A similar association was also observed for unemployment (r = 0.51 [p value = 0.02 for a two-tailed test]), but not for overcrowding. This study suggests a link between TB and deprivation in ethnic minority groups in the UK.

England↗
PubMed1999

Reduction in phosphorylated heavy neurofilament in the cerebellum in HIV disease.

In the absence of significant neuronal infection HIV induces neuronal damage and death. The pathogenesis of this process is not clear and can only be assessed in the HIV infected brain by examining surviving neuronal populations. Cerebellar Purkinje cells are a model population. We have already demonstrated glutamate receptor alterations in these neurons in AIDS, and in the current study we have investigated the phosphorylation status of heavy neurofilament (NF-H), which is under the control of various intracellular kinases. While the number of Purkinje cells expressing non-phosphorylated NF-H was unchanged, the number of Purkinje cells expressing phosphorylated NF-H was decreased by 36% in the HIV group. This may be a marker of neuronal damage, and possibly indicate alteration in the activity of various intracellular signalling kinase pathways in the HIV infected brain.

AIDS Arteritis, Central Nervous System↗
PubMed1997

Circular forms of unintegrated human immunodeficiency virus type 1 DNA and high levels of viral protein expression: association with dementia and multinucleated giant cells in the brains of patients with AIDS.

Thirty-one histologically abnormal brains from patients with AIDS were studied in order to establish the relationship between multinucleated giant cells, viral protein expression, the various forms of human immunodeficiency virus type 1 (HIV-1) DNA, and clinical evidence of dementia. Unintegrated HIV-1 DNA of 2 to 8 kb was found in 22 of the 31 brains. Multinucleated giant cells without any other pathology were found in 14 cases; unintegrated 1-long terminal repeat (1-LTR) circular forms of HIV-1 DNA and strongly positive immunohistochemistry for gp41 and p24 were found in most of these brains. Most of these patients had a clinical diagnosis of HIV-1-associated dementia and cerebral atrophy. In all the other brains studied, 1-LTR circles were absent and immunohistochemistry for gp41 and p24 was usually negative. Very few of these patients had a clinical diagnosis of dementia. Sequence comparison of the LTR region from integrated HIV-1 DNA with that from unintegrated 1-LTR circular forms of HIV-1 DNA in 12 cases showed no significant differences. A further comparison of these brain-derived LTR sequences with LTR sequences derived directly from lymphoid tissue also showed strong sequence conservation. The V3 loop of the virus from the brain was sequenced in 6 cases and had a non-syncytium inducing-macrophage-tropic genotype. Our results show that (i) although unintegrated HIV-1 DNA was present in most brains from patients with AIDS, molecular evidence of high levels of viral replication was associated with the presence of multinucleated giant cells and dementia, and that (ii) the HIV-1 LTR is not a determinant of neurotropism. These observations suggest that replication of HIV-1 and not just the presence of HIV-1 DNA within giant cells makes the important contribution to central nervous system damage.

AIDS Dementia Complex↗
PubMed1996

Beyond CAGE. A brief clinical approach after detection of substance abuse.

Generalist physicians should incorporate alcohol and drug abuse detection and brief intervention in the care of their patients. A suggestion of alcohol or drug abuse or a positive response to the CAGE questions deserves further assessment such as clarification about adverse consequences, inquiry about loss of control, determination of the patient's perception of the substance use, and an assessment of the patient's readiness to change behavior. Brief intervention with the patient in the clinical setting about alcohol or drug use can be effective. Motivational interviewing, a directive, patient-centered counseling style for enhancing motivation for change, can make brief interventions more effective by incorporating the patient's readiness to address alcohol or drug use. A useful clinical approach is presented that is tailored to the patient's stage of readiness to change alcohol or drug abuse behavior.

Attitude to Health↗
PubMed1995

Assessment of neuronal density in the putamen in human immunodeficiency virus (HIV) infection. Application of stereology and spatial analysis of quadrats.

Human immunodeficiency virus causes neuronal loss in various brain regions, but it has not been reported in the putamen. However, decrease in the volume of the putamen has been observed by magnetic resonance imaging. In order to clarify this issue two complementary methods; the stereological probe, the disector, and spatial analysis of quadrats, were applied in nondemented individuals who had died of acquired immune deficiency syndrome. A 21% decrease in neuronal density was observed in the human immunodeficiency virus group, especially those cases with human immunodeficiency virus encephalitis; however the statistical significance of this finding was borderline.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Right ventricular infarction: a clinical case study.

In this article we review the specific case of Mrs. F., a 63-year-old white woman who recently had classical right ventricular infarction associated with left ventricular inferior wall myocardial infarction. The presentation covers her medical history, clinical course pathophysiology of the right ventricular infarction, and goals of the medical modalities used in treatment. Nursing problems are identified specifically related to right ventricular infarcts, and treatment considerations are discussed. A brief conclusion recaps Mrs. F.'s discharge course and reviews some specific problems associated with right ventricular infarcts, of which critical care nurses need to be aware.

Cardiac Catheterization↗
PubMed1988

Psychiatric UR worksheet.

This worksheet was developed in response to an ever increasing number and intensity of admission and concurrent telephone reviews conducted by third and fourth-party payors. This worksheet was developed as an aid in information gathering for subsequent telephone and other reviews. The left-margin headings evolved from queries for information from the most demanding psychiatric nurse reviewers. When I have fully addressed all the information in my review, it is usually no problem in obtaining certification for admission or continued stay for the patient.

Alcoholism↗
PubMed1987

Intraspecies individuality for the metabolism of steroids.

A variety of regulatory factors contribute to differences in the rates of 6 beta-hydroxylation, 16 alpha-hydroxylation and 21-hydroxylation of progesterone as catalysed by liver microsomes prepared from individual rabbits. It is likely that the 6 beta-hydroxylation of progesterone is catalysed primarily by cytochrome P-450 3c, an enzyme that exhibits allosteric activation by alpha-napthoflavone, and by a form of P-450 3b, 6 beta+, that is expressed in some rabbits in an autosomal dominant manner. The mechanism of activation for P-450 3c appears to reflect an effector mediated increase of the affinity of the enzyme for substrate as judged by substrate binding studies. A second form of P-450 3b, 6 beta-, catalyses a major portion of hepatic progesterone 16 alpha-hydroxylation and exhibits activation by a variety of C21 steroids of which 5 beta-pregnane-3 beta,20 alpha-diol is the most efficacious. P-450 1, which catalyses the 21-hydroxylation of progesterone, is expressed at 10-fold higher levels in the 21H phenotype than the 21L phenotype, and the former is inherited as an autosomal dominant characteristic. A cDNA encoding a P-450 1-related gene product exhibits a predicted amino acid sequence that is 95% homologous to that of P-450 1. The P-450 1-related gene product is expressed in liver to a similar degree in both 21H and 21L rabbits.

Allosteric Regulation↗
PubMed1987

Studies on the metabolic fate of valproic acid in the rat using stable isotope techniques.

1. The metabolic fate of two specifically deuterated analogues of valproic acid (VPA), [2-2H1]VPA and [3,3-2H2]VPA, was studied in the rat following i.p. injection. 2. A total of 11 urinary metabolites of each labelled substrate were detected by g.l.c.-mass spectrometry. Those metabolites which resulted from oxidation of the drug at C-4 and/or C-5 retained the deuterium label(s), whereas products of oxidation at C-2 and/or C-3 exhibited varying degrees of deuterium loss. 3. The deuterium content of 3-hydroxy-VPA indicated that this metabolite has a dual origin, and arises in part by beta-oxidation of VPA and in part by direct hydroxylation at C-3. An apparent intramolecular isotope effect (kH/kD) of ca. 8 was associated with the latter process. 3-Oxo-VPA appeared to be formed mainly by oxidation of delta 2-VPA, rather than by oxidation of 3-hydroxy-VPA. 4. Evidence was obtained that delta 3-VPA is formed reversibly from delta 2-VPA, and that further desaturation of delta 3-VPA gives rise to a metabolite believed to have a 2,3'-diene structure. 5. The stable isotope method employed in this investigation represents a powerful technique for studies on the origin of drug metabolites and for the elucidation of complex metabolic inter-relationships in vivo.

Animals↗
PubMed1986

Rabbit endocervical epithelium: morphometric analysis of secretory cell populations.

In this report we quantitated ultrastructural changes in two cytologically distinct secretory cell populations from the rabbit endocervix. Type I and type II cells from estrous animals differ only in the presence of one or more empty cytoplasmic vacuoles in type II cells. Comparing type II cells from 5-day pseudopregnant (PSP) rabbits with type II cells from estrous controls, there is no increase (P greater than .05) in the average vacuole volume. When type I and type II cells from PSP animals are compared to cells from estrous controls, there is a decrease (P less than .01) in the average cell volume, a decrease (P less than .01) in the average nuclear volume, and a decrease (P less than .01) in the average granule volume. This reduction in the granule content of secretory endocervical cells was correlated with a dramatic decrease in protein glycosylation into the microsomal fraction. Serum estradiol concentrations for estrous (13.7 +/- 1.0 pg/ml) and PSP (18.1 +/- 1.5 pg/ml) animals were comparable. However, the 36-fold increase in serum progesterone concentrations for PSP (12.04 +/- 1.7 ng/ml) animals compared to estrous (0.33 +/- 0.1 ng/ml) animals may be responsible for the decrease in protein glycosylation.

Animals↗
PubMed1985

Multiple gene-like sequences related to the rabbit hepatic progesterone 21-hydroxylase cytochrome P-450 1.

Rabbits exhibit phenotypic differences, 21H and 21L, in the rate of hepatic progesterone 21-hydroxylation that reflect 10-fold higher microsomal concentrations of cytochrome P-450 1 in 21H rabbits. A cDNA library in pBR322 was prepared from liver mRNA isolated from a 21H rabbit. A clone, p1-8, producing a hybrid protein resulting from the insertion of the cDNA into the beta-lactamase gene of the plasmid expressed 5 distinct epitopes that were recognized by a panel of monoclonal antibodies developed toward P-450 1. RNAs selected from total hepatic mRNA by filter hybridization with p1-8 yield at least two electrophoretically distinct proteins when translated in vitro and immunoprecipitated with the 3C3 monoclonal antibody. Only one of the two proteins is recognized by the 1F11 monoclonal antibody, which is highly specific for P-450 1, and the immunoprecipitated protein exhibits the electrophoretic mobility of P-450 1. The other protein remains unidentified. Northern blot analysis indicates that the 3' noncoding portion of p1-8 hybridizes to higher steady state concentrations of polyadenylated RNA in the 21H as compared to 21L rabbits. This correspondence in expression with that of P-450 1 in the 21H and 21L phenotypes further suggests that p1-8 encodes P-450 1 or a closely related protein. The cDNA is 1871 base pairs in length and encodes a protein of 487 amino acids. Southern blot analysis indicates that several independent, gene-like sequences hybridize with the 3' noncoding region of p1-8 under conditions of high stringency. These results indicate that P-450 1 is a member of an extensive multigene family.

Amino Acid Sequence↗
PubMed1975

An improved method of assessing topical corticosteroid activity.

Topical application of ointment bases causes varying degrees of epidermal thickening in guinea-pigs. This is reproducible and can be accurately measured. Suppression of these changes was produced by addition of beta-methasone 17-valerate, fluocinolone acetonide, fluocinonide and hydrocortisone acetate. The inhibitory effect of these steroids was related to the type of corticosteriod, its concentration and the ointment base. The effect was still evident at extremely high dilutions of the steroids and could be measured at concentrations as low as 5 X 10(-5) % of fluocinonide in FAPG. This technique has the merits of being reproducible, sensitive and accurate. It should find a place among existing methods in assaying the efficacy of topical corticosteroids and in aiding in the selection of bases most suitable for formulation of these preparations.

Administration, Topical↗