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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 595 records · Page 33Linked to original sources

Origin of the fourth component of complement related Chido and Rodgers blood group antigens.

We have reviewed the relationship between C4 and its related blood group and discussed the mechanisms whereby a fragment of C4 could become attached to erythrocytes (E). We hypothesize that there is chronic fluid-phase activation of C4 by either C1 to form C4b or spontaneous cleavage of the thioester to form iC4. These activated molecules bind to E. Proteolytic degradation of the bound C4b or iC4 would leave a covalently attached fragment of C4 on E and thereby give rise to the Ch and Rg blood group antigens. This system is of further immunopathologic interest since this 'normal' activation or turnover of C4 is closely regulated. In patients deficient in regulatory proteins, this spontaneous or normal turnover of C4 and C3 may initiate a pathologic condition.

Animals↗

Effects of posture on stimulated ventilation in quadriplegia.

Quadriplegics are able to compensate for alterations of operational length of the diaphragm by reflexly increasing neural drive to the diaphragm. This increase in neural drive is adequate to maintain required tidal volume and minute ventilation during quiet breathing in these patients with limited inspiratory muscle function. It is not known, however, if this neural compensation is sufficient to preserve ventilation when the diaphragm is stressed by simultaneously changing its operational length and increasing ventilatory demands. This issue was explored in 7 quadriplegics whose vital capacity was reduced to 15 to 53% of predicted. The diaphragm was stressed by shortening its length from the supine to a 60 degree tilted position, and also by inducing hyperventilation by having the subjects rebreathe 7% CO2. Response to this stress was recorded by monitoring the ventilatory response to rebreathing CO2 (delta VE/delta PCO2), and also by measuring mouth pressure 0.1 s after occluding the airway at the start of inspiration during CO2 rebreathing (delta P0.1/delta PCO2). A change from the supine to the tilted position caused an increase in resting end-expiratory volume of 0.8 +/- 0.2 L (SD) and therefore shortened the diaphragm. Despite this shortening of diaphragm length and the stress of CO2 rebreathing, there was no significant change in delta VE/delta PCO2 and delta P0.1/delta PCO2 with changes in posture. The delta VE/delta PCO2 was 0.82 +/- 0.42 L/min/mm Hg supine versus 0.95 +/- 0.65 L/min/mm Hg when tilted. The delta P0.1/delta PCO2 was 0.18 +/- 0.08 cm H2O/mm Hg supine versus 0.20 +/- 0.10 cm H2O/mm Hg tilted.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide↗

Effect of chronic treatment with the calcium antagonist diltiazem in Duchenne muscular dystrophy.

We conducted a double-blind trial with the calcium antagonist, diltiazem (8 mg/kg/d), for 24 to 32 months in 22 boys with Duchenne muscular dystrophy, who were paired by functional activity and age. No adverse clinical or ECG effects of diltiazem were detected. In eight matched pairs, completing 28 months, manual muscle testing scores fell somewhat less in the diltiazem group (from 5.5 to 4.6) than in the placebo group (from 5.3 to 4.2), although the difference between groups was not significant (p = 0.06). The 95% confidence interval for the difference in slopes of regression lines obtained from trimonthly manual muscle tests on all subjects was markedly asymmetric in favor of the diltiazem group, but this difference was also not significant. There was less deterioration of functional activity of lower extremities in the diltiazem-treated group, when beginning and end values were analyzed (p = 0.03). However, the difference in slopes of regression lines obtained from trimonthly determinations was nonsignificant. Similarly, the beginning versus end comparisons of systolic and diastolic blood pressure showed a significantly (p less than 0.05) smaller elevation of blood pressure in the diltiazem-treated group, but no difference was observed when the slopes of all values were analyzed. All other clinical and laboratory variables were unaffected by diltiazem treatment. The findings in manual muscle tests and functional activity suggest a beneficial trend with chronic diltiazem treatment in DMD.

Adolescent↗

Activated N-ras controls the transformed phenotype of HT1080 human fibrosarcoma cells.

To investigate whether the activated N-ras oncogene of HT1080 human fibrosarcoma cells contributes to the expression of the transformed phenotype, we have isolated flat revertants. In two independent revertant lines, an increase in chromosomal ploidy occurred without a concomitant increase in the number of copies of the N-ras transforming allele. Immunoprecipitation confirms that the level of the mutant N-ras p21 gene product in the revertants is correspondingly lower than in HT1080. Analysis of sporadic tumors derived from the revertant cells reveals an increased dosage of the transforming allele. The revertants also retransform after transfection of cloned activated ras oncogenes. These results imply direct participation of an N-ras oncogene in maintaining the transformed phenotype of a human tumor cell line.

Alleles↗

Effects of the Mueller maneuver on global and regional left ventricular function in angina pectoris with or without previous myocardial infarction.

In patients with coronary artery disease, left ventricular (LV) regional wall akinesia can develop during the Mueller maneuver. The present study determines if the presence of myocardial ischemic disease with no infarction is a sufficient condition for this to occur, or if the presence of prior acute myocardial infarction (MI) is necessary. In men, first-pass radionuclide ventriculography was performed in the 30 degree left anterior oblique supine position to measure LV ejection fraction, end-diastolic and end-systolic volumes and heart rate, and to obtain an image of the LV cavitary perimeter. This procedure was performed in 4 subject groups: 13 normal volunteers, 25 patients with coronary artery disease but no prior MI, 13 patients with coronary artery disease and prior nontransmural MI, and 36 patients with coronary artery disease and prior transmural MI. All patients had angina and underwent routine contrast coronary angiography; 60 also underwent contrast coronary angiography; 60 also underwent contrast LV angiography. Ejection fraction decreased during the Mueller maneuver in each of all the coronary artery disease groups (p less than 0.01), but not in the normal subjects. Heart rate increased in groups 1, 2 and 4 (p less than 0.01), and end-diastolic volume decreased in all 4 groups (p less than 0.01), whereas end-systolic volume did not change. Only in group 4 did regional wall akinesia develop (17 patients) during the Mueller maneuver. Among patients who had akinesia during the Mueller maneuver and also underwent routine contrast ventriculography, half of the akinetic segments were not seen on routine contrast study, but were seen only on radionuclide ventriculography during the Mueller maneuver.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Infertile or childless by choice? A multipractice survey of women aged 35 and 50.

Eleven general practitioners examined the medical records of all women on their lists born in 1950 (617 patients) and 1935 (533 patients) to determine the prevalence of childlessness and specialist consultations about infertility. Eighty eight (14.3%) of the women born in 1950 and 41 (7.7%) of those born in 1935 were childless. Sixty eight women born in 1950 (11.0%) and 17 born in 1935 (3.2%) were considered childless by choice. Involuntary childlessness was found in 20 (3.3%) of the women born in 1950 and 24 (4.5%) born in 1935. Forty two (6.8%) of the women born in 1950 had consulted a specialist about infertility as compared with 19 (3.6%) born in 1935. This study found a significant increase in voluntary childlessness among the younger women; there was no evidence of a change in the prevalence of involuntary childlessness despite the increasing demand for specialist referral, which appeared to be made by women who were parous or destined to become so.

Adult↗

Pathologic changes following acute methyl isocyanate inhalation and recovery in B6C3F1 mice.

Male and female mice were exposed by inhalation to 0, 3, 10, and 30 ppm methyl isocyanate for 2 hr followed by a 91-day recovery period. Sixteen of 80 (20%) male mice in the 30-ppm group died following exposure with seven deaths occurring in the first 24 hr. Two female mice died, one each in the 30- and 10-ppm concentration groups. Five mice/sex/group were examined at 2 hr and at 1, 3, 7, 14, 28, 49, and 91 days following exposure. Treatment-related changes were restricted to the respiratory system. At 30 ppm there was extensive necrosis and erosion of the respiratory and olfactory epithelia in the nasal cavity. Severe necrosis and epithelial erosion were also found in the trachea and main bronchi. Epithelialization occurred rapidly and most of the denuded turbinates were covered by flattened epithelium by Day 3. On the turbinates, recovery was essentially complete with the exception of small areas in the olfactory epithelia where lesions were present in the male mice through Day 91. In the trachea and major bronchi, fibrin and cellular debris were present in the airways, which in some cases had organized and formed intraluminal fibrotic projections. These projections became covered by respiratory epithelium. The intraluminal projections and bronchial fibrosis persisted to Day 91. In the males, where the fibrosis was more severe, chronic alveolitis and atelectasis were found. In mice exposed to 3 or 10 ppm, there appeared to be complete recovery. These inhalation studies indicate that methyl isocyanate exposure of mice at or near lethal concentrations causes reversible lesions in the nose and persistent intraluminal and mural fibrosis of the major bronchi.

Administration, Inhalation↗

Parameters of sexual contact of boys with women.

The incidence of sexual contact with boys by women was found more prevalent than had been contended in the clinical literature. Male penitentiary inmates reported higher heterosexual contact as children than did college men. The effects upon the boy and his later adult sex life were generally reported as not traumatic, although coercion by the woman tended to be associated with a bad feeling about the experience at the time and a negative effect upon adult sex life. The majority of women were friends, neighbors, baby sitters, and strangers to the boy. Intercourse and genital touching were the predominant forms of sexual activity. Prison women who reported having such contact were significantly higher than the prison women who did not report contact on the Mini-Mult Schizophrenia and Hypomania scales and significantly lower on the Lie scale. Educational levels of the men and their parents were inversely associated with history of sexual contact.

Adolescent↗

Mueller maneuver and LV function in coronary artery disease.

Decreasing pleural pressure impedes the ejection of blood from the left ventricle (LV), may lead to decreased LV compliance because of interdependence effects and leads to increased transmural LV systolic and diastolic pressure. Previous work from this laboratory has shown that patients with coronary artery disease (CAD) often develop akinetic segments of the LV wall during the Mueller maneuver. In the presence of increased LV transmural pressure regional akinesis could be caused either by the development of regional ischemia or by mechanical inhibition of motion of an area of nonfunctional myocardium as would be caused by previous myocardial infarction (MI). The present study was designed to distinguish between these two mechanisms by determining if the presence of CAD alone is sufficient to lead to regional akinesis or if prior MI is necessary. We used first pass radionuclide ventriculography (RVG) in the 30 degrees LAD supine position to measure LV ejection fraction (EF), end-diastolic (EDV) and end-systolic (ESV) volumes, heart rate and to assess regional wall motion during the Mueller maneuver. This was done in four groups of subjects: 13 normal subjects, 25 patients with CAD but no prior MI, 13 patients with prior nontransmural MI and 36 patients with prior transmural MI. All subjects had angina pectoris and underwent contrast coronary arteriography. Most also underwent routine contrast left ventriculography as well. There were no significant differences among the three patient groups as regards medications, extent and severity of CAD, and response to routine exercise tolerance testing. EF decreased significantly in the three patient groups (4%-9%, p less than 0.01) but not in the normals during the Mueller maneuver. Heart rate increased (5-10 bpm, p less than 0.05) in the normals and in patient groups 2 and 4. EDV decrease in all four subject groups (8%-10%, p less than 0.01), while ESV remained unchanged. Akinesis of the LV wall developed during the Mueller maneuver only in one group-2 patient, but did so in 17/36 patients with prior transmural MI (group 4, p less than 0.001). One-half of the akinetic LV wall segments seen during the Mueller maneuver on RVG were not seen on routine contrast ventriculography. We tested the effects of posture (supine versus upright) on the response to the Mueller maneuver in six normal subjects and found no changes in the response of EDV and ESV to the Mueller maneuver.(ABSTRACT TRUNCATED AT 400 WORDS)

Coronary Disease↗

Behaviourally conditioned modification of T cell subset ratios in rats.

Levamisole injection resulted in an elevation in the T helper:T suppressor (H:S) subset ratio in rats at 24 h after injection due to a selective depression in the cytotoxic/suppressor subset. This response was shown to be conditionable and could be reenlisted 14 days later by re-exposure to the conditioned stimulus. Rats were conditioned using a taste aversion paradigm by pairing levamisole injection with the novel taste of saccharin. Fourteen days later, after a second exposure to saccharin without levamisole injection, H:S ratios were elevated in the blood of these rats compared to control rats injected with levamisole but fed normal water or rats fed saccharin without levamisole injection.

Adjuvants, Immunologic↗

Four outbreaks of nosocomial systemic candidiasis.

Candida albicans has recently been described as a cause of nosocomial infection. This paper reports four further outbreaks occurring over a 12-month period in England. There were 13 systemic cases and 6 deaths. The outbreaks were defined by morphotyping and the new technique of immunoblot fingerprinting. Control of the outbreaks was produced by the implementation of strict cross-infection control policies without recourse to systemic chemoprophylaxis.

Adolescent↗

Genomic organization of human centromeric alpha satellite DNA: characterization of a chromosome 17 alpha satellite sequence.

We characterized a recombinant clone E7 containing a 1.6-kb Eco RI insert of human alpha satellite DNA (alpha DNA) which hybridized in situ predominantly to the centromere of chromosome 17. Three thousand copies of this sequence were detected on chromosome 17, although a lesser number of copies were also found on the centromeres of chromosomes 11, X, and the other human chromosomes, except Y. In the human genome, sequences homologous to E7 were organized principally as five major polymorphic (Pst I) forms of tandem alpha DNA repeats with molecular weights between 2.0 and 2.7 kb. We We studied the higher-order organization of these major forms using a series of 12 cosmid clones. Close linkage of the different polymorphic forms was demonstrated, with no two cosmids showing an identical linkage pattern. Six of the cosmid clones carried a considerable amount (20-25%) of nonhomologous (non-alpha) DNA, indicating that the repeat arrays are relatively frequently interrupted by other genomic DNA. In none of the cosmid inserts were the repeat arrays bound on both sides by non-alpha DNA, suggesting that short arrays are not common. However, some of the intervening non-alpha DNA sequences were relatively short, and vary in size from 6 to 24 kb. Our results suggest an irregular and complex pattern of organization of alpha DNA in the human genome.

Chromosome Mapping↗

Specular microscopy in aniridia.

Aniridia and the iridocorneal endothelial (ICE) syndromes both are conditions which include abnormalities of the cornea, iris, and progressive iridocorneal adhesions which may result in glaucoma. In order to investigate the similarities between aniridia and the ICE syndromes, we performed specular microscopy of the corneal endothelium in nine patients with aniridia. Morphology and density of the corneal endothelium appeared normal for age. We found no evidence of the beaten metal appearance classically seen on specular microscopy in patients with ICE symptoms. This study did not support either an anatomic or pathogenic relationship between aniridia and the ICE syndromes.

Adolescent↗