Search PubMed⌕ Search

Biomedical subjects

J Rogers

Publications and source records attributed to J Rogers.

At least 289 records · Page 16Linked to original sources
PubMed1992

Paleohistology of Paget's disease in two medieval skeletons.

Paget's disease has been ascribed several times to specimens of archeological bone but, in the absence of microscopic examination, the evidence remains insubstantial. Suspected metabolic bone disease is described here in the archeological remains of a skeleton from a 16th century burial ground at Wells Cathedral, England and from a single medieval sacrum recovered from a large deposit of disarticulated bones from a churchyard at Barton-on-Humber, England. Radiographs showed apparent structural abnormality in one femoral shaft and calcaneus and in the isolated sacrum. Histomorphometry on undecalcified bone cores confirmed the regions of abnormality and showed not only increased trabecular width but also areas of "mosaic" woven bone together with extensive resorption cavities; these features contrasted with the normal structure and organized lamellar bone from sites elsewhere. Despite post-interment changes in surrounding tissues, the morphological stability of some of the osteocytes was remarkable. Preservation of the histology was sufficient to permit the assignment of a metabolic bone disorder and the nature of the sclerosis was consistent with Paget's disease.

England↗
PubMed1992

Marathon running: physiological and chemical changes accompanying late-race functional deterioration.

Twenty-one experienced runners were studied before, during and immediately after a marathon race to ascertain whether either depletion of energy substrate or rise in body temperature, or both, contribute to late-race slowing of running pace. Seven runners drank a glucose/electrolyte (GE) solution ad libitum (Na+ 21 mmol l-1, K+ 2.5 mmol l-1, Cl- 17 mmol l-1, PO4(2-) 6 mmol l-1, glucose 28 mmol l-1) throughout the race; 6 drank water and 8 drank the GE solution diluted 1:1 with water. Although average running speeds for the three groups were not significantly different during the first two-thirds (29 km) of the race, rectal temperature was significantly higher (P < 0.05) and reduction of plasma volume was greater (P < 0.05) in runners who replaced sweat losses with water. During the last one-third of the race, the average running pace of the water-replacement group slowed by 37.2%; the pace slowed by 27.9% in the 8 runners who replaced their sweat loss with GE diluted 1:1 with water (1/2 GE) and 18.2% in runners who replaced fluid loss with full-strength solution (GE). Eleven runners (5 in the water group, 4 in the 1/2 GE group and 2 in the GE group) lapsed into a walk/run/walk pace during the last 6 miles of the race. Ten of these had a rectal temperature of 39 degrees C or greater after 29 km of running, and plasma volume in these runners was reduced by more than 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Testing for and the role of anal and rectal sensation.

The rectum is insensitive to stimuli capable of causing pain and other sensations when applied to a somatic cutaneous surface. It is, however, sensitive to distension by an experimental balloon introduced through the anus, though it is not known whether it is the stretching or reflex contraction of the gut wall, or the distortion of the mesentery and adjacent structures which induces the sensation. No specific sensory receptors are seen on careful histological examination of the rectum in humans. However, myelinated and non-myelinated nerve fibres are seen adjacent to the rectal mucosa, but no intraepithelial fibres arise from these. The sensation of rectal distension travels with the parasympathetic system to S2, S3 and S4. The two main methods for quantifying rectal sensation are rectal balloon distension and mucosal electrosensitivity. The balloon is progressively distended until particular sensations are perceived by the patient. The volumes at which these sensations are perceived are recorded. Three sensory thresholds are usually defined: constant sensation of fullness, urge to defecate, and maximum tolerated volume. The modalities of anal sensation can be precisely defined. Touch, pain and temperature sensation exist in normal subjects. There is profuse innervation of the anal canal with a variety of specialized sensory nerve endings: Meissner's corpuscles which record touch sensation, Krause end-bulbs which respond to thermal stimuli, Golgi-Mazzoni bodies and pacinian corpuscles which respond to changes in tension and pressure, and genital corpuscles which respond to friction. In addition, there are large diameter free nerve endings within the epithelium. The nerve pathway for anal canal sensation is via the inferior haemorrhoidal branches of the pudendal nerve to the sacral roots of S2, S3 and S4. Anal sensation may be quantitatively measured in response to electrical stimulation. The technique involves the use of a specialized constant current generator and bipolar electrode probe inserted in the anal canal. The equipment is generally available and the technique has been shown to be an accurate and repeatable quantitative test of anal sensation.

Anal Canal↗
PubMed1992

DNA sequence polymorphism within hominoid species exceeds the number of phylogenetically informative characters for a HOX2 locus.

Within- and between-species variability was examined in a noncoding 238-bp segment of the HOX2 cluster. DNA of 4-26 individuals of four species (Pongo pygmaeus, Pan troglodytes, Gorilla gorilla, and Homo sapiens) was PCR amplified and electrophoresed in a denaturing gradient gel to screen for variability. Coupled amplification and sequencing was used to determine the complete sequence for each of the different alleles identified, one each in humans and orangutans, two in chimpanzees, and four in gorillas. Maximum-parsimony methods were used to construct a gene tree for these sequences. Alleles in all four species cluster into groups consisting of only one species (i.e., alleles within a species are monophyletic). The number of base-pair differences observed among alleles within P. troglodytes and within G. gorilla is larger than the number of base-pair substitutions that phylogenetically link Pan with Homo. Given these and other published data, it is premature to accept any particular phylogenetic tree that relates these three genera through two separate speciation events.

Animals↗
PubMed1992

Oral or intravenous erythromycin has no effect on human distal colonic motility.

Erythromycin is a prokinetic agent for the lower oesophageal sphincter, the stomach, the gallbladder and the small bowel, acting directly on motilin receptors. Its effect on pressure activity of the human colon has not been investigated. Eight healthy volunteers were studied on 2 occasions and given intravenous or oral erythromycin, or placebo in a single-blind, randomized crossover study. Sigmoid pressure activity was measured using a 4-lumen water perfused system placed sigmoidoscopically at 50, 45, 30 and 15 cm from the anal verge. The pressures were analysed for activity index (mmHg.min) for the 35 cm colonic study segment using dedicated software. No significant difference was found in the activity index following oral erythromycin (500 mg) or placebo, or following intravenous erythromycin 1.8 mg/kg or placebo. A further 8 subjects were studied in a single-blind crossover study to determine the effect of oral erythromycin (500 mg) b.d. on colonic transit, measured with radio-opaque markers and a single abdominal X-ray. Mean or segmental colonic transit times were not statistically significantly different (Student's paired t-test) in the subjects on placebo or erythromycin. This lack of effect of erythromycin on the distal large intestine may indicate the absence of receptors for motilin in that part of the gut.

Administration, Oral↗
PubMed1992

Phase II clinical trial of recombinant alpha-2 interferon for biopsy-proven metastatic or recurrent renal carcinoma.

Twenty patients with histologically confirmed metastatic or recurrent renal carcinoma were treated in a phase II study with alpha-interferon (2-5 x 10(6) U/m2 subcutaneously, 3 times a week). Nineteen patients had multiple sites of disease and 18 had previously undergone nephrectomy; 9 had an ECOG performance status of 0.1, and 11 had a performance status of 2-3. There was one partial response, yielding an overall response rate of 5%. Treatment was well tolerated, although 7 patients developed influenza-like symptoms, and in 2 cases this was sufficiently severe for the patients to request cessation of treatment. As a single agent at this dose schedule, alpha-interferon has minimal activity in the treatment of renal carcinoma and cannot be recommended as standard therapy. The difference in outcome between this and some published series may reflect the stringent requirement for histological proof of the presence of metastases.

Adult↗
PubMed1992

Immunogold and fluorescein immunolabelling of Legionella pneumophila within an aquatic biofilm visualized by using episcopic differential interference contrast microscopy.

Biofilms containing diverse microflora were developed in tap water on glass and polybutylene surfaces. Legionella pneumophila within the biofilms was labelled with monoclonal antibodies and visualized with immunogold or fluorescein isothiocyanate conjugates. Development of a differential interference contrast technique in an episcopic mode enabled simultaneous visualization of the total biofilm flora and gold-labelled legionellae. The legionellae occurred in microcolonies within the biofilm in the absence of amoebae, suggesting that the bacterial consortium was supplying sufficient nutrients to enable legionellae to grow extracellularly within the biofilm.

Antibodies, Monoclonal↗
PubMed1992

Radiographic assessment of the knee joint in osteoarthritis.

The development of radiographic systems for the grading of osteoarthritis requires knowledge of the reproducibility of their individual component features. This paper reports the reproducibility, both within and between observers, for five commonly used radiographic features of osteoarthritis in the tibiofemoral and patellofemoral compartments of the knee joint. The results suggest that assessments of joint space narrowing, osteophyte, and bony contour in the tibiofemoral compartments are more reproducible than those of sclerosis and cyst. Patellofemoral assessments, with the exception of osteophyte, are considerably less reproducible between observers than tibiofemoral assessments.

Aged↗
PubMed1992

Anti-inflammatory agents as a therapeutic approach to Alzheimer's disease.

Postmortem analyses of Alzheimer's disease (AD) brain tissue reveal reactive microglia expressing high levels of major histocompatibility complex (MHC) glycoproteins, immunoglobulin receptors, and complement receptors; small but significant numbers of T-lymphocytes infiltrating tissue; enhanced cytokine and cytokine receptor expression; and profuse immunoreactivity for complement proteins of the classic pathway colocalized with senile plaques, dystrophic neurites, and some neurofibrillary tangles. Protectin, clusterin, and vitronectin, three proteins designed to defend host cells against "bystander lysis" caused by the membrane attack complex of complement, are all expressed at high levels in AD tissue but not in normal tissue. Taken together, these findings indicate that immune-mediated autodestructive processes may occur in AD. In view of the urgency to find treatments for AD and disappointing results with the many classes of pharmacologic agents that have so far been given clinical trials, exploration of the effectiveness of anti-inflammatory agents may now be warranted.

Alzheimer Disease↗
PubMed1992

Large-scale finite element analysis of the beating heart.

The regional mechanics of the beating heart are directly related to factors such as ventricular pumping performance, coronary blood flow, myocardial energetics and oxygen consumption, vulnerability to ischemia and injury, hypertrophy and remodeling, and arrhythmogenesis. Important characteristics include: the complex three-dimensional geometry and fibrous architecture; the nonlinear, nonhomogeneous, anisotropic material properties of the myocardium; the hierarchical collagen connective tissue matrix; the time- and history-dependent active tension development of the cardiac muscle cells; and the three-dimensional anisotropic patterns of cardiac impulse propagation. To model these features realistically requires large-scale computational analysis with sophisticated numerical methods. As described in the chapter by Dr. Hunter and colleagues, an accurate three-dimensional finite element model has been developed to describe the geometry, fiber architecture, and extracellular matrix structure of the heart. The model is based on extensive anatomical measurements in the left and right ventricles (LV and RV) of the canine heart. In this chapter, we illustrate some new approaches to the special problems of large-scale finite element modeling in biomechanics using examples from the analysis of stress and electrical activation in the heart. Prospects for further progress--particularly in coupled problems such as cardiac electromechanics--are examined in light of new developments in high-performance computing.

Animals↗
PubMed1991

Active-site-directed specific competitive inhibitors of phospholipase A2: novel transition-state analogues.

More than 100 amphiphilic phosphoesters, possible tetrahedral transition-state analogues capable of coordinating to the calcium ion at the active site of phospholipase A2, were designed, synthesized, and tested as inhibitors for the hydrolysis of 1,2-dimyristoyl-sn-glycero-3-phosphomethanol vesicles in the scooting mode. This assay system permits the study of structurally diverse inhibitors with phospholipase A2S from different sources, and it is not perturbed by factors that change the quality of the interface. As a prototype, 1-hexadecyl-3-trifluoroethylglycero-2-phosphomethanol (MJ33) was investigated in detail. Only the (S)-(+) analogue of MJ33 is inhibitory, and it is as effective as the sn-2 phosphonate or the sn-2 amide analogues of sn-3 phospholipids. The inhibitory potencies of the various phosphoesters depended strongly on the stereochemical and structural features, and the mole fractions of inhibitors required for 50% inhibition, X1(50), ranged from more than 1 to less than 0.001 mole fraction. The affinity of certain inhibitors for enzymes from different sources differed by more than 200-fold. The inhibitors protected the catalytic site residue His-48 from alkylation in the presence of calcium but not barium as expected if the formation of the EI complex is supported only by calcium. The equilibrium dissociation constant for the inhibitor bound to the enzyme at the interface was correlated with the XI(50) values, which were different if the inhibition was monitored in the pseudo-zero-order or the first-order region of the progress curve. These results show that the inhibitors described here interfered only with the catalytic turnover by phospholipase A2's bound to the interface, their binding to the enzyme occurred through calcium, and the inhibitors did not have any effect on the dissociation of the enzyme bound to the interface.

Animals↗
PubMed1991

Interfacial catalysis by phospholipase A2: determination of the interfacial kinetic rate constants.

Hydrolysis of vesicles of 1,2-dimyristoyl-sn-glycero-3-phosphomethanol (DMPM) by pig pancreatic phospholipase A2 (PLA2) occurs in a highly processive "scooting" mode, and the rate is comparable to or exceeds the rates observed with detergent-dispersed mixed micelles under optimal conditions. A complete kinetic description of the steady-state time course of the hydrolysis is developed. The analysis covers the whole Michaelis-Menten space: it emphasizes the key features of interfacial catalysis by a detailed theoretical analysis, describes the experimental protocols to determine the values of the kinetic and equilibrium constants for interfacial catalysis, and provides an interpretation of the effect of calcium, substrate, products, apparent activators, and competitive inhibitors on the reaction progress curve by a single set of rate and equilibrium parameters. In this paper, the integrated reaction progress curve was rigorously interpreted in terms of a minimal model involving the Michaelis-Menten reaction sequence in the interface: E* + S in equilibrium E*S----E*P in equilibrium E* + P, and most of the individual rate and equilibrium constants for the catalytic cycle were determined. This rigorous description of interfacial catalysis was made experimentally possible by examining the action of PLA2 in the scooting mode under conditions of at most one enzyme per vesicle, where it hydrolyzed all of the substrate in the outer monolayer of vesicles without leaving the surface. Other experimentally verified constraints for this analysis include the following: all enzyme was bound to vesicles; the integrity of vesicles was maintained during the course of hydrolysis; and the substrate, enzyme, and products did not exchange between vesicles nor did they exchange across the bilayer. The mechanistic significance of the rate constants is discussed in the accompanying papers.

Animals↗
PubMed1991

Interfacial catalysis by phospholipase A2: dissociation constants for calcium, substrate, products, and competitive inhibitors.

Interpretation of the kinetics of interfacial catalysis in the scooting mode as developed in the first paper of this series [Berg et al. (1991) Biochemistry 30 (first paper of six in this issue)], was based on the binding equilibrium for a ligand to the catalytic site of phospholipase A2. In this paper, we describe direct methods to determine the value of the Michaelis-Menten constant (KMS) for the substrate, as well as the equilibrium dissociation constants for ligands (KL) such as inhibitors (KI), products (KP), calcium (KCa), and substrate analogues (KS) bound to the catalytic site of phospholipase A2 at the interface. The KL values were obtained by monitoring the susceptibility to alkylation of His-48 at the catalytic site of pig pancreatic PLA2 bound to micellar dispersions of the neutral diluent 2-hexadecyl-sn-glycero-3-phosphocholine. The binding of the enzyme to dispersions of this amphiphile alone had little effect on the inactivation rate. The half-time for inactivation of the enzyme bound to micelles of the neutral diluent depended not only on the nature of the alkylating agent but also on the structure and the mole fraction of other ligands at the interface. The KL values for ligands obtained from the protection studies were in excellent accord with those obtained by monitoring the activation or inhibition of hydrolysis of vesicles of 1,2-dimyristoyl-sn-glycerophosphomethanol. Since only calcium, competitive inhibitors, and substrate analogues protected phospholipase A2 from alkylation, this protocol offered an unequivocal method to discern active-site-directed inhibitors from nonspecific inhibitors of PLA2, such as local anesthetics, phenothiazines, mepacrine, peptides related to lipocortin, 7,7-dimethyleicosadienoic acid, quinacrine, and aristolochic acid, all of which did not have any effect on the kinetics of alkylation nor did they inhibit the catalysis in the scooting mode.

Animals↗
PubMed1991

Interfacial catalysis by phospholipase A2: activation by substrate replenishment.

Polymyxin B (Px), a cyclic cationic peptide, was shown to act as a potent activator of interfacial catalysis by phospholipase A2 (PLA2) acting on dimyristoylphosphatidylmethanol vesicles in the scooting mode. A 7-fold increase in the initial enzymatic velocity was seen with the pig pancreatic PLA2 in the presence of 1 microM Px. Initial experiments including the dependency of the degree of activation by Px on the source of the PLA2 suggested that Px bound to a cationic binding site on the enzyme. However, numerous additional observations led to the conclusion that activation by Px was due to its effects on the substrate interface. For example, the activation by Px was only seen when the PLA2 acted on small vesicles rather than larger ones, and all of the available substrate was eventually hydrolyzed in the presence of a small mole fraction of Px. Px did not promote the intervesicle exchange of PLA2, and it did not alter the binding of the evidence led to the conclusion that Px activated interfacial catalysis by promoting the replenishment of substrate in the enzyme-containing vesicles. When PLA2 was acting on small vesicles in the scooting mode, the observed initial velocity was lower than that measured with large vesicles because the surface concentration of substrate decreased relatively rapidly in the small vesicles. Px promoted the transfer of phospholipids between the vesicles and functioned as an activator by keeping the mole fraction of substrate in the enzyme-containing vesicles close to 1. This effect of Px was consistent with the ability of polycationic peptides to induce the intervesicle mixing of anionic phospholipids in vesicles [Bondeson, J., & Sundler, R. (1990) Biochim. Biophys. Act 1026, 186-194]. Activation by substrate replenishment was quantitatively predicted by the theory of interfacial catalysis on vesicles in the scooting mode. The role of substrate replenishment in the kinetics of interfacial catalysis in phospholipid micelles was discussed. Finally, the protocols developed in this paper were outlined in view of their utility in the analysis of activators of interfacial catalysis.

Amino Acid Sequence↗
PubMed1991

The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis.

BACKGROUND: In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease. METHODS: We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San José, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days. RESULTS: The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5). CONCLUSIONS: The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis.

Adolescent↗
PubMed1991

Benign prostatic hyperplasia--video image analysis and its relationship to androgen and epidermal growth factor receptor expression.

Androgens are essential for the development and maintenance of the prostate. However, prostatic growth may be mediated by epidermal growth factor (EGF) and the expression of the EGF receptor (EGFR) may be influenced by the androgenic milieu. We have characterized the expression of cytosolic androgen receptor (ARc), nuclear salt extractable androgen receptor (ARn) and EGFR in 89 consecutive cases of benign prostatic hyperplasia, 84 of which were treated by transurethral prostatic resections. Image analysis morphometry was performed on the histological sections to determine the epithelial content of the gland. Our results indicate that there is a vast heterogeneity of receptor expression in benign prostatic hyperplasia. Expression of ARc ranged from zero to 1312 fmol/gm. tissue (mean +/- SD 265 +/- 290), ARn ranged from zero to 531 fmol/gm. tissue (mean +/- SD 145 +/- 98) and EGFR ranged from zero to 316 fmol/gm. tissue (mean +/- SD 121 +/- 76). A statistically significant association was found between expression of ARn and EGFR, and these were both significantly correlated with the epithelial content of the gland.

Cell Nucleus↗