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Biomedical subjects

C M Brown

Publications and source records attributed to C M Brown.

At least 91 records · Page 5Linked to original sources

The effects of health and treatment perceptions on the use of prescribed medication and home remedies among African American and white American hypertensives.

This study examines the relationships between health beliefs and the use of both prescribed medication and home remedies among a group of African American and White American hypertensives. Data were collected via telephone interviews with 300 individuals who had been medically diagnosed as having hypertension and had been prescribed at least one antihypertensive medication. Using the health belief model (HBM) as the theoretical framework, 4 primary hypotheses involving the perceptions of severity, susceptibility, benefits and costs of each treatment and compliance with prescribed mediation (Rx) and use of home remedies (HR) were tested. Multivariate logistic regression analyses indicated that age, costs of Rx and benefits of HR predicted compliance with Rx. The primary predictors of use of HR were ethnicity, poverty status, education, severity, benefits and costs of HR. The differences in predictor variables for each treatment behavior are discussed and speculations about the nature and importance of these differences are offered. Study findings support the suggestion that patient beliefs about their disease and their evaluations of treatment options should be considered when developing therapeutic plans and when monitoring patient outcomes.

Black or African American↗

Characterization of Escherichia coli isolated from foals.

Serotype, biotype, antibiogram, hemolysin production, fimbrial hemagglutinins, select toxin genes (STb, STaP, LT, slt1 and slt2) and the attaching effacing (eae) gene were determined for 99 foal strains of E. coli. E. coli from diarrheic and normal foals could not be distinguished by serotype, biotype, or antibiogram. Differences (P < or = 0.05) were observed in hemolysin production (11.5% vs 0%) and the expression of mannose-resistant hemagglutinins (23% vs 13%) among E. coli from diarrheic and healthy foals, respectively. Three of the E. coli strains from diarrheic foals were positive with probes for slt genes and one was positive for STb and LT genes. One strain from a healthy foal possessed the STb gene. As determined by the polymerase chain reaction, 8 strains possessed the eae gene. Seven of the 8 strains were from diarrheic foals and one eae-positive strain was from a healthy foal. The slt-positive strains did not possess eae genes and the eae-positive strains did not possess slt genes. These results indicate that enterotoxigenic strains of E. coli are not implicated in any substantial degree in sporadic foal diarrhea. However, the identification of slt-positive and eae-positive strains in foal feces indicate the presence of potentially virulent strains among foals.

Animals↗

Analysis of V kappa genes in rheumatoid arthritis (RA) synovial B lymphocytes provides evidence for both polyclonal activation and antigen-driven selection.

To define mechanisms of sustained activation of synovial B lymphocytes in RA, we studied hybridomas established from the local synovial B cell repertoire of two RA patients for V kappa gene expression and for antigen-binding specificity. The analyses revealed that members of the main V kappa families (I, II and III) were utilized at frequencies consistent with random V kappa gene family use. Furthermore, although the hybridomas expressed genes frequently seen in response to other self- and exogenous antigens, only one V kappa I- and two of three V kappa III-expressing hybridomas exhibited reactivity with self-antigens. Nucleotide sequence analysis revealed that all hybridomas, with the exception of rheumatoid factor (RF)-producing hybridomas, expressed V kappa genes highly related to known germ-line genes (99.3-100% homology) and that diversity was generated by deletions and random nucleotide insertions at the V kappa-J kappa junction. Examination of the few nucleotide changes seen with the V kappa genes revealed a predominance of silent to replacement changes. Moreover, most of these changes can be attributable either to allotypic variations or to limited random nucleotide replacements independent of antigen selection. In contrast, one IgG-RF (B4D8) exhibited predominantly replacement nucleotide changes in the complementarity-determining regions, suggestive of antigen-driven selection. The random expression of immunoglobulin variable region genes with no, or little, evidence of mutation in the synovial B lymphocyte repertoire, including natural polyreactive antibodies, alongside mutated IgG-RF, suggest that both polyclonal activation and antigen-driven responses occur in RA synovia.

Amino Acid Sequence↗

Lexical-semantic event-related potential effects in patients with left hemisphere lesions and aphasia, and patients with right hemisphere lesions without aphasia.

Lexical-semantic processing impairments in aphasic patients with left hemisphere lesions and non-aphasic patients with right hemisphere lesions were investigated by recording event-related brain potentials (ERPs) while subjects listened to auditorily presented word pairs. The word pairs consisted of unrelated words, or words that were related in meaning. The related words were either associatively related, e.g. "bread-butter', or were members of the same semantic category without being associatively related, e.g. "church-villa'. The latter relationships are assumed to be more distant than the former ones. The most relevant ERP component in this study is the N400. In elderly control subjects, the N400 amplitude to associatively and semantically related word targets is reduced relative to the N400 elicited by unrelated targets. Compared with this normal N400 effect, the different patient groups showed the following pattern of results: aphasic patients with only minor comprehension deficits (high comprehenders) showed N400 effects of a similar size as the control subjects. In aphasic patients with more severe comprehension deficits (low comprehenders) a clear reduction in the N400 effects was obtained, both for the associative and the semantic word pairs. The patients with right hemisphere lesions showed a normal N400 effect for the associatively related targets, but a trend towards a reduced N400 effect for the semantically related word pairs. A dissociation between the N400 results in the word pair paradigm and P300 results in a classical tone oddball task indicated that the N400 effects were not an aspecific consequence of brain lesion, but were related to the nature of the language comprehension impairment. The conclusions drawn from the ERP results are that comprehension deficits in the aphasic patients are due to an impairment in integrating individual word meanings into an overall meaning representation. Right hemisphere patients are more specifically impaired in the processing of semantically more distant relationships, suggesting the involvement of the right hemisphere in semantically coarse coding.

Adult↗

Local and distant sequences are required for efficient readthrough of the barley yellow dwarf virus PAV coat protein gene stop codon.

Many viruses use stop codon readthrough as a strategy to produce extended coat or replicase proteins. The stop codon of the barley yellow dwarf virus (PAV serotype) coat protein gene is read through at a low rate. This produces an extended polypeptide which becomes part of the virion. We have analyzed the cis-acting sequences in the barley yellow dwarf virus PAV genome required for this programmed readthrough in vitro in wheat germ extracts and reticulocyte lysates and in vivo in oat protoplasts. Two regions 3' to the stop codon were required. Deletion of sections containing the first 5 of the 16 CCN NNN repeats located 3' of the stop codon greatly reduced readthrough in vitro and in vivo. Surprisingly, readthrough also required a second, more distal element that is located 697 to 758 bases 3' of the stop codon within the readthrough open reading frame. This element also functioned in vivo in oat protoplasts when placed more than 2 kb from the coat protein gene stop in the untranslated region following a GUS reporter gene. This is the first report of a long-range readthrough signal in viruses.

Avena↗

Ethnic differences in temporal orientation and its implications for hypertension management.

Research indicates that health beliefs and perceptions are shaped and organized by life experiences. Time perception, also structured by life experiences, can systematically alter individuals' perceptions of disease and evaluations of treatment options. Using the Health Belief Model (HBM), this study examines the effects of ethnicity and hypertension temporal orientation on the health perceptions of 300 African Americans and White Americans with hypertension. Results revealed that African Americans were more present-oriented than White Americans regarding their daily experiences with managing hypertension. Compared to more future-oriented respondents, present-oriented people perceived themselves to be less susceptible to the consequences of hypertension, believed more in the benefits of home remedies and negative aspects of prescribed medication, and believed less in the benefits of prescribed medication and negative aspects of home remedies. We concluded that ethnicity influences hypertension temporal orientation and that hypertension temporal orientation affects perceptions about hypertension and its management. Implications for health and medical care are addressed.

Black or African American↗

The relationship between the adrenoceptor and nonadrenoceptor-mediated effects of imidazoline- and imidazole-containing compounds.

This article brings together work on imidazoline or imidazole-containing compounds concerned with the pharmacology of alpha-adrenoceptors, principally on smooth muscle, to illustrate how imidazolines have contributed to the subclassification of alpha-adrenoceptors and how, against this background, attempts have been made to use this knowledge to uncover "nonadrenoceptor"-mediated biological effects of previously uncharacterized compounds, notably imidazole-containing dipeptides and "clonidine displacing substance" (CDS). Recent data are included on (1) the pharmacology of UK-14304, (2) nonadrenoceptor actions of phentolamine, (3) the pharmacology of tissue extracts containing imidazole-containing dipeptides and CDS activity, and (4) ligand binding data at I1 and I2 sites.

Animals↗

Translational termination efficiency in mammals is influenced by the base following the stop codon.

The base following stop codons in mammalian genes is strongly biased, suggesting that it might be important for the termination event. This proposal has been tested experimentally both in vivo by using the human type I iodothyronine deiodinase mRNA and the recoding event at the internal UGA codon and in vitro by measuring the ability of each of the 12 possible 4-base stop signals to direct the eukaryotic polypeptide release factor to release a model peptide, formylmethionine, from the ribosome. The internal UGA in the deiodinase mRNA is used as a codon for incorporation of selenocysteine into the protein. Changing the base following this UGA codon affected the ratio of termination to selenocysteine incorporation in vivo at this codon: 1:3 (C or U) and 3:1 (A or G). These UGAN sequences have the same order of efficiency of termination as was found with the in vitro termination assay (4th base: A approximately G >> C approximately U). The efficiency of in vitro termination varied in the same manner over a 70-fold range for the UAAN series and over an 8-fold range for the UGAN and UAGN series. There is a correlation between the strength of the signals and how frequently they occur at natural termination sites. Together these data suggest that the base following the stop codon influences translational termination efficiency as part of a larger termination signal in the expression of mammalian genes.

Animals↗

The identity of the base following the stop codon determines the efficiency of in vivo translational termination in Escherichia coli.

A statistical analysis of > 2000 Escherichia coli genes suggested that the base following the translational stop codon might be an important feature of the signal for termination. The strengths of each of 12 possible 'four base stop signals' (UAAN, UGAN and UAGN) were tested in an in vivo termination assay that measured termination efficiency by its direct competition with frameshifting. Termination efficiencies varied significantly depending on both the stop codon and the fourth base, ranging from 80 (UAAU) to 7% (UGAC). For both the UAAN and UGAN series, the fourth base hierarchy was U > G > A approximately C. UAG stop codons, which are used rarely in E. coli, showed efficiencies comparable with UAAN and UGAN, but differed in that the hierarchy of the fourth base was G > U approximately A > C. The rate of release factor selection varied 30-fold at UGAN stop signals, and 10-fold for both the UAAN and UAGN series; it correlated well with the frequency with which the different UAAN and UGAN signals are found at natural termination sites. The results suggest that the identity of the base following the stop codon determines the efficiency of translational termination in E. coli. They also provide a rationale for the use of the strong UAAU signal in highly expressed genes and for the occurrence of the weaker UGAC signal at several recording sites.

Base Composition↗

Evidence for the presence of a non-catecholamine, clonidine-displacing substance in crude, methanolic extracts of bovine brain and lung.

In the present study we have prepared crude, methanolic extracts of bovine lung and bovine brain and, using radioligand binding assays in conjunction with a number of simple chromatographic techniques, provided evidence for the presence of a non-catecholamine 'clonidine-displacing substance' (CDS). The level of CDS in lung extracts (9 units/g wet weight n = 11) is approximately 3 times that in the brain extracts. Furthermore, the effect of the crude, methanolic extracts are selective for non-adrenoceptor, imidazoline (labelled by [3H]-idazoxan) and alpha 2-adrenoceptor binding sites (labelled by [3H]-clonidine); both extracts are 5-10-fold more potent displacers of ligand binding to alpha 2-adrenoceptors compared with binding to opiate receptors (labelled by [3H]-etorphine) and practically inactive against alpha 1-adrenoceptor and muscarinic binding sites (labelled by [3H]-prazosin and [3H]-quinuclidinyl benzilate, respectively). With the exception of the non-adrenoceptor, imidazoline binding assay, which used rat kidney membranes labelled by [3H]-idazoxan in the presence of the alpha 2-adrenoceptor antagonist RS-15385-197, all radioreceptor assays involved bovine cerebral cortex membranes. Although the extracts contain catecholamines (brain only), histamine (lung only) and monovalent cations (both), which have the potential to interfere with the radioligand binding assays, their concentrations were too low to account for the effects observed. Preliminary attempts at purification of the extracts revealed that CDS activities from the two tissues are similar, i.e., practically insoluble in organic solvents at room temperature, not affected by either Sep-Pak C18 column or anion exchange resins but retained (along with the monovalent cations) by cation exchange resin. However, following chromatographic separation on a Biogel P2 column, the CDS-containing eluates are cation-free and exhibit qualitatively similar elution profiles. Future experiments will involve further purification of 'clonidine-displacing substance' to characterize its interaction with alpha 2-adrenoceptor binding sites in greater detail and establish whether it has biological activity consistent with the properties implied by its effects in radioligand binding assays.

Animals↗

Neural influences on human esophageal and salivary alkali secretion.

Esophageal secretion HCO3- ions occurs in opossum and man and may contribute to mucosal defense. Using a perfusion technique, neuroregulatory influences on esophageal and salivary HCO3- secretion were investigated in 24 healthy human subjects. The sight and smell of food increased median salivary HCO3- output from 424 to 573 mumol/15 min (P = 0.014), without significantly altering esophageal HCO3- secretion (74-105 mumol/15 min, P = 0.24). Atropine reduced both salivary (610 to 68, 17, 10, and 3 mumol/15 min in successive periods; P < 0.028) and esophageal HCO3- output (108 to 78, 35, 18, and 7 mumol/10 cm/15 min; P < 0.028, respectively. Following atropinization, cholinergic stimulation failed to increase salivary secretion but did "unmask" a small rise in esophageal alkali output (7 to 27 mumol/10 cm/15 min, P = 0.036), implicating a noncholinergic mechanism. Cold-induced pain activated sympathetic reflexes and reduced esophageal HCO3- output (91 to 64 mumol/10 cm/15 min, P = 0.041) without influencing salivary secretion. These observations support a role for the autonomic nervous system in modulating human esophageal and salivary HCO3- secretion.

Adolescent↗

Ineffectiveness of hypothalamic serotonin to block neuropeptide Y-induced feeding.

A variety of recent research has suggested that the feeding associated with enhanced neuropeptide Y (NPY) activity within the hypothalamus may operate in part by interacting antagonistically with other neural processes responsive to serotonin (5-hydroxytryptamine or 5-HT). To test this possibility further, experiments were performed to determine if the magnitude of feeding produced by injecting NPY into the paraventricular nucleus (PVN) or the perifornical hypothalamus (PFH) was diminished by coinjections of 5-HT into these two sites or peripheral injections of the 5-HT agonist, d-fenfluramine. Adult male Sprague-Dawley rats were implanted unilaterally with stainless steel cannulae aimed to terminate either in the PVN or the PFH. In both studies, NPY (235 pmol) produced significant feeding in both sites either 1 or 2 h after injection when compared to saline. This enhanced feeding response was significantly greater in the PFH 2 h after injection (40% in the central study; 70% in the peripheral study). Coinjection of 5-HT (6.3, 12.5, or 25.0 nmol) into either site had no effect on the induction of this NPY-induced feeding response. However, peripherally injected d-fenfluramine (0.32, 0.63, or 1.25 mg/kg) produced strong dose-dependent attenuation both 1- and 2-h food intake elicited by 235 pmol NPY in either site, with the PFH being proportionately more sensitive to this effect. Viewed together, these results suggest that the feeding-suppressant effects of systemic fenfluramine on hypothalamic NPY-induced feeding may operate largely via peripheral mechanisms and/or central ones that have little to do with its 5-HT agonistic effects within the PVN or PFH.

Animals↗

Review article: factors protecting the oesophagus against acid-mediated injury.

Reflux of gastric acid and pepsins into the lower oesophagus causes symptoms such as heartburn and nausea, and tissue injury leading to erosive oesophagitis and stricture formation. This article reviews the mechanisms involved in protecting the oesophagus against acid-mediated injury, including the role of the lower oesophageal sphincter, secondary oesophageal peristalsis and swallowed saliva. The oesophageal mucosa has inherent abilities to resist acid damage, and recent data from three laboratories suggest a secretory function with local production of bicarbonate and mucus responsive to local acidification. The evidence for these putative oesophageal defence mechanisms is discussed.

Animals↗

The N400 as a function of the level of processing.

In a semantic priming paradigm, the effects of different levels of processing on the N400 were assessed by changing the task demands. In the lexical decision task, subjects had to discriminate between words and nonwords, and in the physical task, subjects had to discriminate between uppercase and lowercase letters. The proportion of related versus unrelated word pairs differed between conditions. A lexicality test on reaction times demonstrated that the physical task was performed nonlexically. Moreover, a semantic priming reaction time effect was obtained only in the lexical decision task. The level of processing clearly affected the event-related potentials. An N400 priming effect was only observed in the lexical decision task. In contrast, in the physical task a P300 effect was observed for either related or unrelated targets, depending on their frequency of occurrence. Taken together, the results indicate that an N400 priming effect is only evoked when the task performance induces the semantic aspects of words to become part of an episodic trace of the stimulus event.

Adult↗

[3H]-lifarizine, a high affinity probe for inactivated sodium channels.

1. [3H]-lifarizine bound saturably and reversibly to an apparently homogeneous class of high affinity sites in rat cerebrocortical membranes (Kd = 10.7 +/- 2.9 nM; Bmax = 5.10 +/- 1.43 pmol mg-1 protein). 2. The binding of [3H]-lifarizine was unaffected by sodium channel toxins binding to site 1 (tetrodotoxin), site 3 (alpha-scorpion venom) or site 5 (brevetoxin), Furthermore, lifarizine at concentrations up to 10 microM had no effect on [3H]-saxitoxin (STX) binding to toxin site 1. Lifarizine displaced [3H]-batrachotoxinin-A 20-alpha-benzoate (BTX) binding with moderate affinity (pIC50 7.31 +/- 0.24) indicating an interaction with toxin site 2. However, lifarizine accelerated the dissociation of [3H]-BTX and decreased both the affinity and density of sites labelled by [3H]-BTX, suggesting an allosteric interaction with toxin site 2. 3. The binding of [3H]-lifarizine was voltage-sensitive, binding to membranes with higher affinity than to synaptosomes (pIC50 for cold lifarizine = 7.99 +/- 0.09 in membranes and 6.68 +/- 0.14 in synaptosomes). Depolarization of synaptosomes with 130 mM KCl increased the affinity of lifarizine almost 10 fold (pIC50 = 7.86 +/- 0.25). This suggests that lifarizine binds selectively to inactivated sodium channels which predominate both in the membrane preparation and in the depolarized synaptosomal preparation. 4. There was negligible [3H]-lifarizine and [3H]-BTX binding to solubilized sodium channels, although [3H]-STX binding was retained under these conditions. 5. The potencies of a series of compounds in displacing [3H]-lifarizine from rat cerebrocortical membranes correlated well with their affinities for inactivated sodium channels estimated from whole-cell voltage clamp studies in the mouse neuroblastoma cell line, NIE-115 (r=0.96).6. These results show that [3H]-lifarizine is a high affinity ligand for neuronal sodium channels which potently and selectively labels a site, allosterically linked to toxin binding site 2, associated within activated sodium channels.

Animals↗

Neuroprotective properties of lifarizine compared with those of other agents in a mouse model of focal cerebral ischaemia.

1. Changes in the peripheral type benzodiazepine binding site density following middle cerebral artery occlusion in the mouse, have been used as a marker of neuronal damage. These sites can be identified using the selective ligand [3H]-PK 11195 located on non neuronal cells, macrophages and astroglia, within the CNS. Glial cell proliferation and macrophage invasion is an unvoidable sequelae to cerebral ischaemic injury, secondary to neuronal loss. Following occlusion of the left middle cerebral artery (left MCA) a reproducible lesion was found in the parietal cortex within 7 days which gave rise to a significant increase in [3H]-PK 11195 binding. 2. Treatment of animals with the sodium channel blocker, lifarizine, significantly reduced the ischaemia-induced increase in [3H]-PK 11195 binding when given either 30 min pre-ischaemia and three times daily for 7 days at 0.5 mg kg-1, i.p. (P < 0.01) or delayed until 15 min post-ischaemia and three times daily for 7 days at 0.5 mg kg-1, i.p. (P < 0.001). Lifarizine was an effective neuroprotective agent in this model of focal ischaemia in the mouse. 3. Lifarizine also showed a dose-related protection against the ischaemia-induced increase in [3H]-PK 11195 binding with significant protection at doses of 0.1 mg kg-1, i.p. (P < 0.05), 0.25 mg kg-1, i.p. (P < 0.01) or 0.5 mg kg-1, i.p. (P < 0.01) 15 min post-ischaemia and b.i.d. for 7 days. No significant change is seen in the Kd for [3H]-PK 11195. The first dose could be delayed for up to 4 h after cerebralartery cauterization and protection was maintained.4. Phenytoin (28 mg kg-1, i.v. 15 min and 24 h post-ischaemia) was also neuroprotective in this model(P<0.01). This agent is thought to interact with voltage-dependent sodium channels to effect its anticonvulsantactions and this mechanism may also underlie its neuroprotective actions in focal cerebralischaemia.5. Agents with other mechanisms of action were also shown to have significant neuroprotection in this model. The non-competitive NMDA antagonist, MK 801, showed significant neuroprotection in the model when given at 0.5 mg kg-1, i.p. 30 min pre-ischaemia with t.i.d. dosing for 7 days (P< 0.001). The dihydropyridine calcium antagonist, nimodipine was not protective when given using the same dosing protocol as MK 801, 0.5 mg kg-1 30 min pre-occlusion and three times daily for 7 days but showed significant protection when given at 0.05 mg kg-1 15 min post-ischaemia and three times daily for 7days. The lipid peroxidation inhibitor, tirilazad (single dose 1 mg kg-1, i.v.) showed significant neuroprotection when given 5 min post-ischaemia but not when the first dose was delayed for 4 h.

Animals↗

[3H]-RS-45041-190: a selective high-affinity radioligand for I2 imidazoline receptors.

1. RS-45041-190 (4-chloro-2-(imidazolin-2-yl)isoindoline) is an I2 imidazoline receptor ligand with the highest affinity and selectivity so far described; [3H]-RS-45041-190 has a tritium atom attached to the 7-position on the isoindoline ring. 2. [3H]-RS-45041-190 binding to rat kidney membranes was saturable (Bmax = 223.1 +/- 18.4 fmol mg-1 protein) and of high affinity (Kd = 2.71 +/- 0.59 nM). Kinetic studies revealed that the binding was rapid and reversible, with [3H]-RS-45041-190 interacting with two sites or two affinity states. 3. Competition studies showed that 60-70% of [3H]-RS-45041-190 binding (1 nM) was specifically to imidazoline binding sites of the I2 subtype, characterized by high affinity for idazoxan (pIC50 7.85 +/- 0.03) and cirazoline (pIC50 8.16 +/- 0.05). The remaining 30-40% was displaced specifically by the monoamine oxidase A inhibitors, clorgyline and pargyline. 4. alpha 1- and alpha 2-adrenoceptor, I1 imidazoline, histamine, 5-hydroxytryptamine or dopamine receptor ligands had low affinity suggesting that [3H]-RS-45041-190 did not label receptors of these classes. 5. In autoradiography studies, [3H]-RS-45041-190 labelled discrete regions of rat brain corresponding to the distribution of I2 subtypes, notably the subfornical organ, arcuate nucleus, interpeduncular nucleus, medial habenular nucleus and lateral mammillary nucleus, and additional sites in the locus coeruleus, dorsal raphe and dorsomedial hypothalamic nucleus. 6. [3H]-RS-45041-190 therefore labels I2 receptors with high affinity, and an additional site which has high affinity for some monoamine oxidase inhibitors.

Adrenergic alpha-Antagonists↗