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Biomedical subjects

L Brown

Publications and source records attributed to L Brown.

At least 19 recordsLinked to original sources
PubMed1992

The Crithidia fasciculata CRK gene encodes a novel cdc2-related protein containing large inserts between highly conserved domains.

A gene (CRK) encoding a cdc2-related protein has been identified in the trypanosomatid Crithidia fasciculata. CRK has a high degree of sequence identity with the human cdc2 gene and contains the sixteen amino acid PSTAIR motif, characteristic of p34cdc2 protein-serine/threonine kinases, with four amino acid substitutions in the motif. In addition, two inserts of more than sixty amino acids have been found between conserved domains of this putative protein-serine/threonine kinase. CRK is a single copy gene and is expressed on a 3.8 kb mRNA. Anti-CRK antibodies detect a 53kDa protein in extracts of C.fasciculata in agreement with the size predicted from the nucleotide sequence of the cloned gene. These antibodies also recognize proteins of 48 and 60 kDa in extracts of the trypanosomatid Leishmania tarentolae. Antibodies against the human PSTAIR peptide detect the p34cdc2 protein in human nuclear extracts but fail to detect a 34 kDa protein in C.fasciculata extracts. These results suggest that novel higher molecular weight forms of the cdc2 protein family may be involved in cell cycle control in trypanosomes.

Amino Acid Sequence↗
PubMed1992

HEN1 and HEN2: a subgroup of basic helix-loop-helix genes that are coexpressed in a human neuroblastoma.

An important family of regulatory molecules is made up of proteins that possess the DNA-binding and dimerization motif known as the basic helix-loop-helix (bHLH) domain. The bHLH family includes subgroups of closely related proteins that share common functional properties and overlapping patterns of expression (e.g., the MyoD1 and achaete-scute subgroups). In this report we describe HEN1 and HEN2, mammalian genes that encode a distinct subgroup of bHLH proteins. The HEN1 gene was identified on the basis of cross-hybridization with TAL1, a known bHLH gene implicated in T-cell acute lymphoblastic leukemia. In situ fluorescence hybridization was used to localize the human HEN1 gene to chromosome band 1q22. HEN1 and HEN2 are coexpressed in the IMR-32 human neuroblastoma cell line, and they encode highly related proteins of 133 and 135 residues, respectively, that share 98% amino acid identity in their hHLH domains. These data imply that the bHLH protein subgroup encoded by HEN1 and HEN2 may serve important regulatory functions in the developing nervous system.

Amino Acid Sequence↗
PubMed1992

A controlled trial of a formalin-inactivated hepatitis A vaccine in healthy children.

BACKGROUND: Although inactivated hepatitis A vaccine is known to be well tolerated and immunogenic in healthy children and adults, its efficacy has yet to be established. METHODS: To evaluate the efficacy of the hepatitis A vaccine in protecting against clinically apparent disease, we conducted a double-blind, placebo-controlled trial in an Hasidic Jewish community in upstate New York that has had recurrent outbreaks of hepatitis A. At the beginning of a summer outbreak, 1037 healthy seronegative children 2 to 16 years of age were randomly assigned to receive one intramuscular injection of a highly purified, formalin-inactivated hepatitis A vaccine or placebo. A case was defined by the presence of typical signs and symptoms, a diagnostic increase in IgM antibody to hepatitis A, and a serum concentration of alanine aminotransferase at least twice the upper limit of normal. Cases occurring greater than or equal to 50 days after the injection were included in the evaluation of efficacy. The children were followed for a mean of 103 days. RESULTS: A total of 519 children received vaccine, and 518 received placebo. The vaccine was well tolerated, with no serious adverse reactions. From day 50 after the injection, 25 cases of clinically apparent hepatitis A occurred in the placebo group and none in the vaccine group (P less than 0.001), confirming that the vaccine had 100 percent protective efficacy. Before day 21, seven cases occurred in the vaccine group and three cases in the placebo group. After that time, there were no cases among vaccine recipients and 34 cases among placebo recipients. CONCLUSIONS: The inactivated purified hepatitis A vaccine that we tested is well tolerated, and a single dose is highly protective against clinically apparent hepatitis A.

Adolescent↗
PubMed1992

Serum triglyceride and insulin levels are associated with erythrocyte sodium-lithium counter-transport activity in normoglycaemic individuals.

The relationship between erythrocyte sodium-lithium counter-transport activity, serum insulin, lipids and demographic factors was examined in 93 normoglycaemic predominantly normotensive individuals with mild fasting hypercholesterolaemia (greater than 5.2 mmol/l). The major significant univariate correlates of sodium-lithium counter-transport activity were fasting serum triglycerides, HDL cholesterol, the ratio of fasting glucose: insulin, apo A1, alcohol consumption and apo B. Stepwise multiple regression analysis revealed 24% of the variability in sodium-lithium counter-transport activity could be accounted for by independent contributions of fasting serum triglycerides, alcohol consumption, the fasting glucose/insulin ratio and apo A1 and ANOVA confirmed a significant relationship with fasting insulin measures that was independent of serum triglycerides (P less than 0.05). The relationship between erythrocyte sodium-lithium counter-transport activity and concentrations of serum triglycerides, HDL components, insulin and additionally alcohol consumption, could reflect the influence of those variables on erythrocyte structure and function.

Alcohol Drinking↗
PubMed1992

The translocation (1;14)(p34;q11) in human T-cell leukemia: chromosome breakage 25 kilobase pairs downstream of the TAL1 protooncogene.

Nearly 30 percent of patients with T-cell acute lymphoblastic leukemia (T-ALL) exhibit a tumor-specific rearrangement of the TAL1 gene (also called TCL5 or SCL). These rearrangements are generated by either local DNA deletion or a (1;14)(p34;q11) chromosome translocation, and they typically result in structural alterations of the TAL1 transcription unit. In this report we present a molecular characterization of the t(1;14)(p34;q11) from a T-ALL patient. As a consequence of the translocation, TAL1 is transposed from its normal position on chromosome 1 into the T-cell receptor alpha/delta chain locus on chromosome 14. Unlike previous cases, the chromosome 1 breakpoint in this patient did not disrupt the continuity of the TAL1 transcription unit, but instead occurred approximately 25 kilobase pairs (kb) downstream of TAL1. This observation suggests that malignant alteration of TAL1 can be mediated by long-range cis-activating mechanisms that are triggered by DNA rearrangement at a distant site. Genes Chrom Cancer 4:211-216 (1992).

Base Sequence↗
PubMed1992

Glucose administration combined with photodynamic therapy of cancer improves therapeutic efficacy.

Both the scope and the levels of activity in basic research and in the clinical applications of PDT, have grown enormously during the past few years. Several studies have examined the synergism of hyperthermia and chemotherapeutic agents in combination with PDT to enhance tumor eradication. The present study investigates the synergism of glucose administration combined with phototherapy. The results of this study suggest that glucose administration is simple and well tolerated, and combined with PDT produces a larger percentage of animals cured than using PDT alone. Furthermore, the results indicate that this approach requires lower amounts of light and might enable dosage reduction of photosensitizer for optimal response, with minimal side effects, to the treatment of cancer.

Adenocarcinoma↗
PubMed1992

A human aldehyde dehydrogenase (aldose reductase) pseudogene: nucleotide sequence analysis and assignment to chromosome 3.

Four cosmid clones containing putative pseudogenes for human aldehyde dehydrogenase (Aldose reductase) were isolated from libraries made to two individuals. These clones show different patterns on digestion with restriction endonucleases and probably represent distinct and separate loci. The DNA sequence of one of the putative pseudogenes (cosmid AR.F) was determined, and comparisons demonstrate 89.7% homology with the cDNA sequence of the functional aldose reductase gene. This pseudogene sequence contains no intronic sequences, whereas the functional aldose reductase has nine introns. In addition, the homology disappears in region 5' to the transcription start site for the cDNA, implying that regulatory elements such as the promoter are missing from this pseudogene. The pseudogene defined by cosmid AR.F has been mapped to chromosome 3 by polymerase chain reaction using amplimers specific for this pseudogene to amplify DNA from somatic cell hybrids.

Aldehyde Reductase↗
PubMed1992

Spare receptors for beta-adrenoceptor-mediated positive inotropic effects of catecholamines in the human heart.

We studied whether the human heart has spare receptors for beta-adrenoceptor-mediated positive inotropic effects. Thus, we assessed in right atria and left papillary muscles of patients with different degrees of heart failure under identical experimental conditions affinity (pKI values from (-)-[125I]iodocyanopindolol binding) and potency (pD2 values from contractile responses) for isoprenaline, adrenaline, and noradrenaline in comparison with rat heart. Plots of beta-adrenoceptor occupancy versus responses constructed from these data revealed that rat left atria and papillary muscles had a large receptor reserve for all three beta-adrenoceptor agonists: 50% of maximal response was produced with only 1-3% of beta-adrenoceptor occupancy. In human heart, however, receptor reserve was considerably lower: 50% of maximal response required 8-10% (in right atria) and 20-25% (in left papillary muscles) occupation of beta-adrenoceptors. Receptor reserve declined further with an increasing degree of heart failure (and decreasing beta-adrenoceptor number): in end-stage heart failure (New York Heart Association class IV) both in right atria and left papillary muscles a 1:1 ratio between beta-adrenoceptor occupancy and responses was observed. These data show that the human heart has only a small receptor reserve for beta-adrenoceptor agonists. This may explain why a decrease in beta-adrenoceptor number leads to a decrease in beta-adrenoceptor function early in the development of heart failure.

Adenylyl Cyclases↗
PubMed1992

Cardiac responses after norepinephrine-induced ventricular hypertrophy in rats.

The increase in norepinephrine (NE) blood levels in human heart failure correlates with prognosis. In this study, we determined whether continuous NE infusion alters the positive inotropic and chronotropic responses of isolated rat cardiac muscles. Osmotic minipumps were implanted subcutaneously (s.c.) in 43 adult male rats to deliver NE (160 micrograms/kg/h for 14 days); 42 rats were sham-operated. Isolated left and right atria and left and right ventricular (LV, RV) papillary muscles were prepared to measure positive inotropic or chronotropic responses to NE, phenylephrine, forskolin, dibutyryl cyclicAMP (dbcyclicAMP), and calcium chloride. NE infusion caused (a) a 22% increase in LV wet weight without altering atrial or RV wet weights; (b) an 18% decrease in maximal inotropic response to calcium chloride in LV papillary muscles only; (c) a significantly decreased peak response to NE [72 +/- 5 vs. 93 +/- 5% (sham rats) of calcium chloride] but not to forskolin or dbcyclicAMP in RV papillary muscles; (d) an increased incidence of ectopy at low concentrations of NE, forskolin, and dbcyclicAMP in LV papillary muscles; (e) no alteration in papillary muscle responses to phenylephrine but significantly increased left atrial inotropic responses [51 +/- 5 vs. 33 +/- 2% (sham rats) of calcium chloride] and right atrial chronotropic responses [30 +/- 2 vs. 18 +/- 4 (sham rats) beats/min]; and (f) a selective decrease in beta 1-adrenoceptor density in both ventricles. Thus, NE infusion causes selective LV hypertrophy; responses of compounds that increase intracellular cyclicAMP are affected to a greater extent in papillary muscles from the hypertrophied ventricle than in tissues from the other chambers of the heart.

Animals↗
PubMed1992

Cardiac beta-adrenoceptor changes in experimental hyperthyroidism in dogs.

1. Triiodothyronine (T3; 1.0 mg/kg per day subcutaneously) was administered to 10 dogs for 14 days; 10 saline-treated dogs served as controls. T3-treated dogs showed the expected physiological responses of hyperthyroidism; further, chronotropic responses to isoprenaline in vivo were significantly increased in T3-treated dogs. 2. Beta-adrenoceptor subtype density was measured in membrane preparations by displacement of 125I-iodocyanopindolol binding by the selective beta 2-adrenoceptor antagonist, ICI 118, 551. T3 treatment led to a 93% increase in right atrial beta 1-adrenoceptor density and a 141% increase in left ventricular beta 1-adrenoceptor density; beta 2-adrenoceptor densities in right atrial, left ventricular and lung membranes were unchanged. 3. T3-treatment did not change basal or maximally stimulated adenylate cyclase activities in left ventricular membranes. 4. Thus, the cardiovascular changes in experimental hyperthyroidism in dogs were accompanied by an increased chronotropic response in vivo to isoprenaline and an increased beta 1-adrenoceptor density in atrial and ventricular membranes. However, there was no corresponding change in basal or maximal responsiveness of adenylate cyclase in ventricular membranes.

Adenylyl Cyclases↗
PubMed1992

Relation between insulinemia, body mass index, and lipoprotein composition in healthy, nondiabetic men and women.

Altered lipoprotein composition may be a better predictor of cardiovascular disease than modestly increased serum lipid concentrations, although possible interactions between lipoprotein composition, obesity, and insulinemia have not been fully elucidated. Therefore, we investigated the association between different measures of insulinemia and lipoproteins in 297 healthy Caucasian men (body mass index [BMI] less than 27 in 233, greater than 27 [obese] in 64) and 295 healthy Caucasian women (BMI less than 25 in 198, greater than 25 [obese] in 97). Associations observed in both obese and nonobese men and women were between increasing tertiles of most insulin measures and serum triglyceride concentrations (p = 0.079-0.004) and the ratio of low density lipoprotein to high density lipoprotein cholesterol (p = 0.094-0.008). Graded reductions in the high density lipoprotein cholesterol to apolipoprotein A-I ratio were also recorded in obese women, with increasing tertiles of fasting (p = 0.014-0.007) and postglucose load (p = 0.001) serum insulin levels, after correcting for BMI and triglyceride concentrations. Less marked graded increases in the triglyceride to apolipoprotein B ratios were recorded in obese women with increasing tertiles of fasting (p = 0.001-0.006) and postglucose challenge (p = 0.081) insulinemic measures. In men with normal or slightly elevated cholesterol levels (fasting serum cholesterol less than 6.5 mmol/l), hyperapobetalipoproteinemia was recorded with increasing tertiles of insulinemia (p = 0.006, correcting for BMI and triglyceride concentrations), as well as in subjects with hypertriglyceridemia (fasting serum triglycerides greater than 1.70 mmol/l) (p = 0.004, correcting for BMI and age). Hyperinsulinemia and insulin resistance are associated with altered lipoprotein composition in obese women, presumably reflecting a complex interplay between sex hormones, body mass, and insulin action. Insulin resistance appears to be more associated with apolipoprotein B concentrations in men. The hyperinsulinemic nondiabetic subject may be at increased risk of cardiovascular disease because of altered concentrations of apolipoprotein concentrations and lipoprotein composition.

Adult↗
PubMed1992

Support for AuD.

Explore the source record for details and available documents.

Audiology↗
PubMed1991

TAL2, a helix-loop-helix gene activated by the (7;9)(q34;q32) translocation in human T-cell leukemia.

Tumor-specific alteration of the TAL1 gene occurs in almost 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL). We now report the identification of TAL2, a distinct gene that was isolated on the basis of its sequence homology with TAL1. The TAL2 gene is located 33 kilobase pairs from the chromosome 9 breakpoint of t(7;9)(q34;q32), a recurring translocation specifically associated with T-ALL. As a consequence of t(7;9)(q34;q32), TAL2 is juxtaposed with sequences from the T-cell receptor beta-chain gene on chromosome 7. TAL2 sequences are actively transcribed in SUP-T3, a T-ALL cell line that harbors the t(7;9)(q34;q32). The TAL2 gene product includes a helix-loop-helix protein dimerization and DNA binding domain that is especially homologous to those encoded by the TAL1 and LYL1 protooncogenes. Hence, TAL2, TAL1, and LYL1 constitute a discrete subgroup of helix-loop-helix proteins, each of which can potentially contribute to the development of T-ALL.

Amino Acid Sequence↗
PubMed1991

Structure of the human aldose reductase gene.

The structure and sequence of the human gene for aldose reductase (AR) was determined by analysis of cDNA and genomic clones. The AR gene was independently isolated from two different cosmid libraries and the clones were characterized by restriction mapping, Southern blotting, and DNA sequencing. The gene extends over approximately 18 kilobases and consists of 10 exons giving rise to a 1,384 nucleotide mRNA (excluding the poly(A) tail). The human aldose reductase gene codes for a 316-amino acid protein with a molecular mass of 35,858 daltons. The size range for the exons is 82-168 base pairs (bp), whereas that for the introns is 325 to about 7,160 bp. A major site of transcription initiation in liver was mapped to an A residue 31 nucleotides upstream from the A of the ATG initiation codon. The promotor region of the gene contains a TATA (TATTTA) box and a CCAAT box which are located 37 and 104 nucleotides upstream, respectively, from the transcription initiation site. We have found four Alu elements in the AR gene; two are found in intron 1 and one each in intron 4 and intron 9.

Aldehyde Reductase↗
PubMed1991

Melanoma incidence in Tauranga 1980-9.

This study was a retrospective case series of melanoma taken from pathology records. The denominator population was the nonMaori population of the old Tauranga Hospital Board area. The age standardised incidence over the period 1980-9 was 33.0 per 100,000, males 31.4, females 36.8. Age specific rates showed a double peak in middle aged and elderly age groups due to female rates peaking at 40 to 59 and male rates peaking at 65+. Younger people presented with thinner lesions than old people, women had thinner lesions than men and thin lesions became increasingly common during the decade, being approximately 50% of lesions in 1988-9. The incidence increased by 2.25 times in ten years and Tauranga incidence is between that of Queensland and other Australian states.

Adolescent↗
PubMed1991

Amiloride analogues induce responses in isolated rat cardiovascular tissues by inhibition of Na+/Ca2+ exchange.

The role of inhibition of Na+/Ca2+ exchange in the positive inotropic, negative chronotropic and vasorelaxant responses to amiloride and some of its analogues was investigated in isolated cardiovascular tissues from female Wistar rats. The compounds tested were amiloride, 5-(N-ethyl-N-isopropyl)amiloride (EIPA, a potent inhibitor of Na+/H+ exchange), phenamil and 2',4'-dimethylbenzamil (DMB), both potent Na+ channel inhibitors with activity against Na+/Ca2+ exchange, and 5-(N-4-chlorobenzyl)-2',4'-dimethylbenzamil (CBDMB), a potent inhibitor of Na+/Ca2+ exchange with reduced activity against Na+ channels compared with its parent compound DMB. Phenamil, DMB and CBDMB increased the force of contraction of right ventricular papillary muscles with similar potencies (-log EC50 values: 4.77 +/- 0.06, 5.09 +/- 0.09, 4.97 +/- 0.17 respectively), while amiloride and EIPA gave small negative inotropic responses. All compounds gave negative chronotropic responses at similar concentrations to those which exerted inotropic effects. Inhibition of KCl contraction of endothelium-free aortic rings was observed with all compounds tested. Phenamil, DMB and CBDMB but not amiloride or EIPA showed a shift to the left of the concentration-response curves in the presence of intact endothelium. These results provide further evidence for positive inotropic and endothelium-dependent vasorelaxant effects of amiloride analogues mediated by inhibition of Na+/Ca2+ exchange.

Amiloride↗
PubMed1991

Compliance with hormonal replacement therapy.

One hundred post-menopausal women given HRT were reviewed 12 months after their first visit to determine their compliance with treatment. Sixty-one percent continued to take the therapy while 27% ceased. Most often the reason for ceasing HRT was return of bleeding but a number of women expressed fear of developing cancer or other long term complications.

Attitude to Health↗