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Biomedical subjects

L Brown

Publications and source records attributed to L Brown.

At least 181 records · Page 10Linked to original sources
PubMed1994

Angiotensin receptors in cardiovascular diseases.

1. Angiotensin II (AII) plays a major role in cardiovascular function via direct actions on the vasculature, kidney, adrenal, heart, brain and sympathetic nerves. The cellular effects of AII are extensive and encompass hypertrophy, hyperplasia and the deposition of extracellular matrix. 2. The actions of AII are mediated by the AT1 and AT2 membrane receptor subtypes, and additional forms of each subtype. Evidence is emerging that selective changes in AII receptor subtypes occur in cardiovascular diseases. 3. Thyroid dysfunction increased cardiac, liver and kidney AII receptor density but decreased adrenal gland receptor density. In the heart, there was a selective increase in AT2 receptor density. 4. Diabetes increased cardiac, liver and adrenal gland AII receptor densities but decreased kidney receptor density. 5. Hypertension increased AII receptor density in the heart and kidney. A corresponding increase in receptor mRNA was prevented by selective AT1 receptor antagonists. 6. The human heart contained AII receptors in all chambers; right atrial receptor density was increased in coronary artery bypass graft patients. 7. The presence of AII receptor changes in these models of cardiac hypertrophy and hypertension raises the possibility of using orally active, subtype-selective agonists and antagonists to treat particular forms of cardiovascular diseases.

Acromegaly↗
PubMed1994

Ion channel modulators as potential positive inotropic compound for treatment of heart failure.

1. Current positive inotropy therapy of heart failure is associated with major problems: digoxin and the phosphodiesterase inhibitors can cause life-threatening toxicity while beta-adrenoceptor agonists become less effective inotropic compounds as heart failure progresses. A new approach to positive inotropy is ion channel modulation. 2. An increased influx of Na+ during the cardiac action potential, as measured with DPI 201-106 and BDF 9148 which increase the probability of the open state of the Na+ channel, will increase force of contraction. 3. Activation of L-type Ca2+ channels with Bay K 8644 will increase influx of Ca2+ and increase the force of contraction. However the Ca2+ channel activators developed to date have little potential for the treatment of heart failure as they are vasoconstrictors. 4. Blocking cardiac K+ channels is a possible mechanism of positive inotropy. Terikalant inhibits the inward rectifying K+ channel, tedisamil inhibits the transient outward K+ channel and dofetilide is one of the newly developed inhibitors of the slow delayed outward rectifying K+ channel. All these drugs prolong the cardiac action potential to increase Ca2+ entry and force of contraction. 5. Thus drugs which increase Na+ influx or block K+ channels represent exciting possibilities for positive inotropy and the potential of these compounds for the treatment of heart failure needs to be fully evaluated.

Animals↗
PubMed1994

Disease-induced changes in alpha-adrenoceptor-mediated cardiac and vascular responses in rats.

1. The physiological relevance of cardiac and vascular alpha-adrenoceptors may increase in disease states in which beta-adrenoceptors are altered. To test this, positive inotropic and vasoconstrictor responses to phenylephrine were measured in isolated tissues from rats with experimentally-induced hyperthyroidism, hypothyroidism and diabetes as well as in genetically spontaneous hypertensive rats (SHR). 2. In left atria, positive inotropic responses to phenylephrine were increased in hypothyroid and diabetic rats and abolished in hyperthyroid and SHR. 3. In contrast, phenylephrine produced increased positive inotropy in left ventricular papillary muscles from hyperthyroid rats, increased potency in diabetic rats and negative inotropic responses in hypothyroid rats. 4. The potency of phenylephrine as a vasoconstrictor in thoracic aortic rings was increased in hyperthyroid and SHR and decreased in hypothyroid rats. 5. Thus, disease states which alter beta-adrenoceptor responsiveness can independently regulate atrial, ventricular and vascular responses to the alpha 1-adrenoceptor agonist, phenylephrine. Therefore, these disease states may alter the physiological control of the cardiovascular system by noradrenaline and adrenaline as well as the responsiveness in disease states to therapeutic agents acting via alpha-adrenoceptors.

Animals↗
PubMed1994

A sociodemographic comparison of families of very low-birthweight infants: 1982-1991.

Social and demographic characteristics were investigated in families who had very low birthweight infants between 1982 and 1984 (historical cohort). Since those data were collected, the number of women using drugs during pregnancy has increased significantly. Therefore, between 1989 and 1991 (current cohort) we continued to document sociodemographic characteristics of families of very low-birthweight infants (144 mothers, 156 infants). Data were collected from review of hospital charts and outpatient health records, and monthly interviews. The two cohorts were similar demographically. Changes in family composition occurred more frequently in the current cohort. There was a startling increase in illicit drug use between the two groups of women 3% in the historic cohort and 20% in the current cohort. In the historical cohort all infants went home to their mothers; however, in the current cohort 7.8% of infants were placed with other family caretakers. Infant health outcomes for the first six months after hospital discharge were similar in both groups. From 1982 to 1991 the increases in substance abuse, nonmaternal caretakers, family moves, and changes in family composition have implications for health care providers involved in infant follow-up care.

Adolescent↗
PubMed1994

Percutaneous removal of infected permanent pacemaker leads using a simple coaxial dilating system.

A simple traction-countertraction technique using common and readily available materials was successfully used to remove infected pacemaker leads from two patients. The specific methodology is presented. Although somewhat technically demanding, this approach appears safe and cost-effective. This method provides another way to remove pacemaker leads without resorting to thoracotomy.

Humans↗
PubMed1994

Antimalarial activity of WR 243251, a Dihydroacridinedione.

WR 243251 is a dihydroacridinedione that was evaluated for antimalarial blood schizonticidal activity in vitro and in vivo. The in vitro doses calculated to kill 50% of organisms were 11 nM for a chloroquine-susceptible, mefloquine-resistant standard strain and 25 nM for a chloroquine- and pyrimethamine-resistant standard strain. The total dose needed to cure 100% of mice infected with a drug-susceptible strain of Plasmodium berghei was 12 to 20 mg/kg of body weight for both oral and subcutaneous administration. The regimen needed to cure 100% of Aotus monkeys infected with Plasmodium falciparum was 8 mg/kg/day for 3 days (chloroquine-susceptible strain) and 16 mg/kg/day for 3 days (chloroquine-resistant strain). The 100% curative doses for Aotus monkeys did not increase for parasites previously exposed to subcurative doses. The absolute value of the curative doses of WR 243251 was comparable to or lower than the values for clinical antimalarial agents. The high absolute activity, comparability of activities against susceptible and resistant parasites, and inability to induce resistance by exposure to subcurative doses suggest that WR 243251 has strong potential as a blood schizonticidal agent.

Acridines↗
PubMed1994

Novel features of the respiratory tract T-cell response to influenza virus infection: lung T cells increase expression of gamma interferon mRNA in vivo and maintain high levels of mRNA expression for interleukin-5 (IL-5) and IL-10.

Analysis of the respiratory tract before and after primary influenza virus infection revealed a virus-induced preferential accumulation of a CD8+ T-cell population that coexpresses mRNA for interleukin-5 (IL-5) and IL-10 with virus dose-dependent high levels of gamma interferon. However, cytokine production in lung tissues was not restricted to the T-cell population, since CD3- cells were found to express mRNA for various cytokines, including IL-4 and particularly IL-6 and granulocyte-macrophage colony-stimulating factor. These data provide in vivo evidence for a local respiratory tract immune response to influenza virus infection dominated by cytokine-producing CD8+ T cells.

Animals↗
PubMed1994

HEN1 encodes a 20-kilodalton phosphoprotein that binds an extended E-box motif as a homodimer.

HEN1 and HEN2 encode neuron-specific polypeptides that contain the basic helix-loop-helix (bHLH) motif, a protein dimerization and DNA-binding domain common to several known transcription factors. We now describe characteristics of the HEN1 gene product that are consistent with its postulated role as a transcription factor that functions during development of the mammalian nervous system. Thus, transcription of the HEN1 gene is activated upon the induction of neural differentiation in PC12 cells by nerve growth factor. HEN1 encodes a 20-kDa polypeptide (pp20HEN1) that is phosphorylated exclusively at serine residues and forms dimeric bHLH complexes either by self-association or by heterologous interaction with the E2A gene products (E12 or E47). The resultant HEN1/HEN1 homodimers and HEN1/E2A heterodimers bind DNA in a sequence-specific manner. Moreover, a binding site selection procedure revealed that HEN1-HEN1 homodimers preferentially recognize E-box motifs represented by an 18-bp consensus sequence (GGGNCG CAGCTGCGNCCC). The E-box half-site recognized by HEN1 polypeptides (GGGNCGCAG) is distinct from those of other known bHLH proteins, suggesting that HEN1 binds, an regulates the transcription of, a unique subset of target genes during neural development.

Amino Acid Sequence↗
PubMed1994

Bradykinin and FMLP stimulate prostanoid production by adult rabbit colonocytes in culture.

Normal colonocytes in culture produce prostaglandins both constitutively and in response to inflammatory stimuli. These highly purified proliferative cell populations were isolated from normal adult rabbit proximal and distal colon. Basal prostaglandin production ranged from 3.4 to 11.7 ng.15 min-1 x 10(6) cells-1. Cultures were incubated at 37 degrees C in the presence or absence of bradykinin or N-formyl-methionine-leucine-phenylalanine (FMLP) over concentrations from 10(-9) to 10(-5) M. In both distal and proximal colonocytes bradykinin stimulated a dose-dependent increase in prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha, the stable metabolite of prostacyclin; production peaked at 10(-6) M. Proximal colonocytes responded to FMLP with a bell-shaped curve, with maximal stimulation of both PGE2 and 6-keto-PGF1 alpha occurring at 10(-8) M. Distal colonocytes responded variably to FMLP. Arachidonic acid also stimulated prostanoid production in a concentration-dependent manner, with maximal stimulation occurring at 100 microM. The full synthetic profile of prostanoid production was determined by labeling with [14C]arachidonic acid and by analyzing metabolites using radiochromatography on reverse-phase high-pressure liquid chromatography. Only PGE2 and 6-keto-PGF1 alpha were detected. A similar profile of labeled metabolites occurred when colonocytes were prelabeled with [14C]arachidonic acid and stimulated with bradykinin or FMLP. The degradative capacity of the colonocytes appeared very low. Colonocyte production of protective prostaglandins in response to luminal or other inflammatory stimuli may serve as a mucosal defense mechanism. Prostanoids so produced may also modulate the functions of colonocytes, surrounding cells, or both.

Animals↗
PubMed1994

Diagnosing and managing unstable angina. Agency for Health Care Policy and Research.

This Quick Reference Guide for Clinicians contains recommendations on the care of patients with unstable angina based on a combination of evidence obtained through extensive literature reviews and consensus among members of an expert panel. Principal conclusions include the following. (1) Many patients suspected of having unstable angina can be discharged home after adequate initial evaluation. (2) Further outpatient evaluation may be scheduled for up to 72 hours after initial presentation for patients with clinical symptoms of unstable angina judged at initial evaluation to be at low risk for complications. (3) Patients with acute ischemic heart disease judged to be at intermediate or high risk of complications should be hospitalized for careful monitoring of their clinical course. (4) Intravenous thrombolytic therapy should not be administered to patients without evidence of ST segment elevation and acute myocardial infarction. (5) Assessment of prognosis by noninvasive testing often aids selection of appropriate therapy. (6) Coronary angiography is appropriate for patients judged to be at high risk for cardiac complications or death based on their clinical course or results of noninvasive testing. (7) Coronary artery bypass surgery should be recommended for almost all patients with left main disease and many patients with three-vessel disease, especially those with left ventricular dysfunction. (8) The discharge care plan should include continued monitoring of symptoms; appropriate drug therapy, including aspirin; risk-factor modification; and counseling.

Ambulatory Care↗
PubMed1994

Beta-adrenoceptor antagonism and the hyperthyroid rat heart.

beta-Adrenoceptor antagonists such as propranolol and atenolol ameliorate the symptoms of human hyperthyroidism. We wished to define whether the cardiac changes of hyperthyroidism are attenuated by treatment with the beta-adrenoceptor antagonist atenolol. Rats were treated with triiodothyronine (T3) [1 mg/kg/day subcutaneously (s.c.) for 14 days] together with oral atenolol (100 mg/day on days 8-14); physiological parameters, inotropic and chronotropic responses in isolated cardiac tissues to compounds that increase intracellular cyclic AMP, and ventricular beta 1- and beta 2-adrenoceptors were measured. Administration of T3 produced marked hyperthyroidism, leading to increased metabolism, cardiac hypertrophy, tachycardia, hypertension, marked decrease in or loss of positive inotropic responses to calcium chloride, norepinephrine (NE), forskolin, and theophylline and increased ventricular beta 1- and beta 2-adrenoceptor density. Atenolol treatment of hyperthyroid rats attenuated the increases in heart rate (HR), rectal temperature, and O2 consumption but did not alter cardiac hypertrophy, hypertension, decreased positive inotropic responses or increased beta-adrenoceptor density. We conclude that beta-adrenoceptor antagonists produce only limited changes in hyperthyroidism-induced cardiovascular responses; furthermore, beta-adrenoceptor antagonists are unlikely to attenuate the cardiovascular risk factors of hyperthyroidism.

Adrenergic beta-Antagonists↗
PubMed1993

Adrenoceptor-mediated cardiac and vascular responses in genetically growth hormone-deficient rats.

This study has measured cardiovascular parameters, pharmacological responses to alpha- and beta-adrenoceptor agonists, and cardiac beta-adrenoceptor characteristics in growth hormone (GH)-deficient (dwarf) Lewis rats, normal Lewis rats and dwarf rats treated with GH (2 mg/kg/day for 28 days). Dwarf rats showed a decrease mean blood pressure and heart rate but an increased ventricular weight relative to body weight when compared with age-matched normal Lewis rats. Positive chronotropic responses in vivo to the non-selective beta-adrenoceptor agonist, isoprenaline, were unchanged in dwarf rats. The selective beta 1-adrenoceptor agonist, noradrenaline, was less potent in isolated right atria from dwarf rats although maximal responses were unchanged. Basal force of contraction was greater in isolated cardiac muscles from dwarf rats than from normal rats. Maximal positive inotropic responses to both calcium chloride and noradrenaline were reduced in left atria but increased in left ventricular papillary muscles from dwarf rats. Responses to the alpha 1-adrenoceptor agonist, phenylephrine, were markedly increased in isolated cardiac tissues from dwarf rats. Maximal contractile responses of isolated thoracic aortic rings from dwarf rats to KCl (100 mM) and the alpha-adrenoceptor agonist, noradrenaline, were markedly reduced compared to responses in normal rats. Left ventricular beta-adrenoceptor density measured by 125I-cyanopindolol binding was significantly increased in dwarf rats. Administration of GH (2 mg/kg/day for 28 days) reversed the altered responses in dwarf rats. We conclude that GH: (a) is required for the development of normal contractile capability of cardiac and vascular tissues; (b) regulates both beta-adrenoceptors and alpha- and beta-adrenoceptor-mediated responses; (c) differentially regulates atrial and ventricular responsiveness.

Animals↗
PubMed1993

Maori attitudes to diabetes and diabetes health care delivery in north Canterbury.

AIMS: The study aims were as follows: (1) To obtain information regarding Maori attitudes to diabetes and to the services provided by a specialist diabetes clinic in Christchurch; (2) to initiate discussion about local diabetes health care delivery for Maori. METHODS: A questionnaire was designed following advice from professional Maori health researchers, with the aim of assessing Maori attitudes to diabetes and specialist diabetes services, available in Christchurch. RESULTS: The questionnaire was delivered to 51 (77%) of the 66 Maori with noninsulin dependent diabetes (NIDDM), attending a specialist diabetes clinic in Christchurch. Although 47 of the 51 subjects were able to name one or more diabetes complications, only five subjects named heart disease as a complication, despite the fact that heart disease is a major cause of mortality in NIDDM: Subjects were selected on the basis of being hospital specialist clinic attenders and the majority were satisfied with currently available services, yet 10 of the 51 subjects indicated that they would prefer marae-based to hospital-based diabetes health care, if they had a choice. CONCLUSIONS: The process of questionnaire interview and dissemination of results proved to be a cost-effective means of initiating local discussion about future directions for Maori diabetes health care delivery.

Adult↗
PubMed1993

Ab-interno erbium (Er):YAG laser sclerostomy with iridotomy in Dutch cross rabbits.

An ab-interno technique using a pigmented rabbit model has been developed that uses a pulsed erbium:YAG laser to create an iridotomy with a sclerostomy through the same corneal incision. Laser energy was delivered with an articulated arm terminating in side-firing (850 or 650 microns OD) or end-firing (850 or 400 microns OD) fiber optic endoprobes, which allowed iridotomies and sclerostomies, respectively, to be created. Initially, sclerostomies (8-10, 8 mJ/300 microseconds pulses) and basal iridotomies (1-3, 4 mJ/200 microseconds pulses) were created with the larger probes. Problems encountered with this technique included corneal decompensation and rapid formation of peripheral anterior synechiae with occlusion of sclerostomies. The smaller endoprobes were then used to create mid-peripheral iridotomies and sclerostomies utilizing the same energy parameters. Sclerostomies created in this manner remained patent in the first postoperative week until the animals were sacrificed to obtain material for histologic study.

Animals↗
PubMed1993

Genomic organization of the structural proteins of borna disease virus revealed by a cDNA clone encoding the 38-kDa protein.

Borna disease is a rare neurological disease of sheep and horses. The etiological agent, borna disease virus (BDV), has been shown to be an RNA virus but has not been characterized sufficiently to assign it to a virus family. Previous studies have shown that three BDV-specific proteins of 14, 24 and 38 to 39 kDa are found in infected animals and cell culture (Ludwig et al., 1988, Prog. Med. Virol. 35, 107-151). cDNA clones have been isolated that encode the 14- and 24-kDa proteins; using the nucleotide sequences from these clones additional cDNAs were isolated that contained a large open reading frame (ORF) corresponding to the 38-kDa protein. Monoclonal antibodies against the BDV 38- to 39-kDa protein recognized the protein product of the large ORF. The relative gene order of the three BDV proteins (5' 38, 14, and 24 kDa 3') can be deduced from cDNAs which include portions of both the 24- and 38-kDa ORFs. The abundance of these proteins in BDV-infected animals and cultured cells suggests that these proteins are structural components of the virus. Previously all BDV-specific mRNAs (10.5, 3.6, 2.1, and 0.85 kb) were thought to be organized as overlapping 3' coterminal RNAs. Oligonucleotide probes made to the nucleotide sequence of the cDNA that encodes the 38-kDa protein identified an additional BDV-specific mRNA of 1.4 kb. This 1.4-kb mRNA species partially overlaps with the 2.1-kb RNA but is not 3' coterminal.

Amino Acid Sequence↗