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Biomedical subjects

J Rogers

Publications and source records attributed to J Rogers.

At least 253 records · Page 14Linked to original sources

Small bowel motility following major intra-abdominal surgery: the effects of opiates and rectal cisapride.

BACKGROUND/AIMS: Human small bowel motility is altered after laparotomy. Opiate analgesia is a possible cause of these alterations, and cisapride is a potential therapy. METHODS: Continuous proximal small bowel manometry was performed for up to 92 hours in 23 patients after major intra-abdominal surgery. They were treated with rectal cisapride (30 mg three times daily) or placebo until the clinical resolution of ileus. Small bowel manometry was performed for 30 hours in 5 volunteers receiving 1 mg/kg meperidine over 3 hours. RESULTS: Phase III activity was present within 3 hours of the end of surgery in all patients. Initially, the migrating motor complex (MMC) period was markedly reduced (mean, 22 minutes) but gradually increased. Phase II activity was absent until a median of 40 hours had elapsed. Phase III contractile amplitude was markedly attenuated in the jejunum, in contrast to that in the duodenum, presumably as a result of dilatation and/or altered tone, increasing to normal by 72 hours. In the volunteer group, although the MMC period was reduced by meperidine, it remained significantly greater than that of the placebo patient group for approximately 48 hours and phase II was reduced but not eliminated. Cisapride induced some changes in motor activity but did not accelerate the recovery of normal motility. Clinical outcome, assessed by the return of bowel sounds and passage of flatus, was accelerated by cisapride, but the trend was not significant (P = 0.11). CONCLUSIONS: This is the first published study using prolonged manometry to show the gradual evolution of small bowel motor activity after major intra-abdominal surgery. The findings suggest that surgery decreases the MMC period to the equivalent of the absolute refractory period, thereby eliminating phase II, which returns as the MMC period lengthens. Cisapride, at the dosage given, confers only modest benefit.

Abdomen↗

Comparative study of the effects of mu, delta and kappa opioid agonists on 3H-dopamine uptake in rat striatum and nucleus accumbens.

The effect of the mu opioid agonist DAGO, delta opioid agonist DPDPE and kappa opioid agonist U50,488H on 3H-dopamine (3H-DA) uptake was studied in synaptosomes prepared from rat striatum and nucleus accumbens. Over the range of concentrations tested (1 nM-10 microM) DAGO and DPDPE were devoid of effects on 3H-DA uptake in the striatum and the nucleus acumbens. In contrast, U50,488H significantly decreased 3H-DA uptake in both structures. The inhibition of uptake induced by the kappa agonist was not reversed in the presence of the opiate antagonists naloxone (10 microM) or nor-binaltorphimine (0.1 microM). Dynorphin A (1-13) also induced a significant reduction in 3H-DA uptake in both structures at the concentrations of 10 and 30 microM. This inhibitory effect was not reversed by naloxone (10 microM). These data suggest that kappa opioid agonists modulate dopamine uptake in the striatum and the nucleus accumbens and their effects may not be due to an activation of opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Use of AMI-227 as an oral MR contrast agent.

We report the use of an ultrasmall superparamagnetic iron oxide colloid AMI-227 as an oral contrast agent. Due to the small size, AMI-227 has a larger effect on T1 than larger superparamagnetic iron oxides colloids like ferumoxsil. At 2 T, AMI-227 had an R2/R1 of 11.4 compared with an R2/R1 for the superparamagnetic iron oxide ferumoxsil of 179. The R1s of the two agents were 7.1 and 1.6 mM-1 s-1, for AMI-227 and ferumoxsil, respectively. Due to its smaller R2/R1, orally administered AMI-227 can produce brightening or darkening of the lumen of the GI tract, depending on instrument parameters. At 1 mM Fe, image brightening (2 T, TR = 300, TE = 25) or image darkening of the GI tract (2 T, TR = 1500, TE = 80) was obtained. The ability of AMI-227 to produce either image brightening or darkening suggests it may be useful as an MR contrast agent for the GI tract.

Abdomen↗

Biodistribution of an ultrasmall superparamagnetic iron oxide colloid, BMS 180549, by different routes of administration.

The ultrasmall superparamagnetic iron oxide colloid BMS 180549 can be found lymph nodes by either subcutaneous (SC) or intravenous (IV) injection. With an SC injection in the front extremities, the axillary and brachial nodes attain the highest accumulations of the agent. With an SC injection in the rear extremities, the popliteal, iliac, and axillary nodes attain highest accumulations of the agent. With IV injection of the agent, the iliac, mediastinal and mesenteric nodes attain highest accumulations of the agent. Though the spleen is not involved with the drainage of the interstitial space near the site of SC injections, the mobility of BMS 180549 from such injection sites increases splenic relaxation rates. Based on a knowledge of the lymphatic system, a route of administration of BMS 180549 can be chosen to maximize the delivery of the agent to specific lymph nodes.

Animals↗

Neuroimmune mechanisms in Alzheimer disease pathogenesis.

Lesions in Alzheimer disease are characterized by the assembly of a variety of cells and proteins associated with the immune system. Activated microglia express high levels of major histocompatibility complex glycoproteins and receptors for complement. Small numbers of T lymphocytes infiltrate tissue. Proteins of the classical complement pathway are closely connected with beta-amyloid deposits. beta-Amyloid protein binds C1q in vitro and activates the pathway. The membrane attack complex of complement, as well as proteins that defend against that complex, colocalize with dystrophic neurites. These data imply that an autodestructive process is occurring in Alzheimer disease, that overactive microglia might be responsible, and that antiinflammatory drugs might be an effective form of therapy.

Aged↗

Use of daily Acute Physiology and Chronic Health Evaluation (APACHE) II scores to predict individual patient survival rate.

OBJECTIVE: To evaluate the use of daily Acute Physiology and Chronic Health Evaluation (APACHE) II scoring in the prediction of individual mortality rates for intensive care unit (ICU) patients. DESIGN: A prospective study of consecutive patients admitted to four university-affiliated ICUs. SETTING: Medical-surgical ICUs of four tertiary care academic hospitals. PATIENTS: Daily data from 3,350 consecutive ICU admissions, excluding postoperative cardiac patients, were collected from January to December 1991. MEASUREMENTS AND MAIN RESULTS: Daily APACHE II scores were calculated for all patients and correlated with both ICU and hospital mortality. The ability of an absolute level or a predetermined algorithm, based on these scores, to predict mortality was examined. Day 1 APACHE II scores ranged from 0 to 55 (mean 18). We were unable to replicate the suggestion by Chang et al. that 100% hospital mortality was predicted by the following APACHE II scores: a) > 35 at admission; b) 30 to 35 at admission, with a decrease of < or = 3 from day 1 to day 2; or c) > 27 on any day, with an increase of > 2 from the previous day. We were unable to adjust these criteria to avoid a false prediction of death with any remaining useful sensitivity. Mortality rates of 158 (69%) deaths per 229 patients, 68 (62%) deaths per 110 patients, and 110 (48%) deaths per 230 patients were obtained, respectively, for these criteria. CONCLUSIONS: Admission or daily APACHE II scores do not predict individual patient mortality. The adjustments needed in the algorithm that was used to avoid a false prediction of death render sensitivity so low that it would be impractical to limit therapy on this basis alone.

Adolescent↗

Influence of temperature and plumbing material selection on biofilm formation and growth of Legionella pneumophila in a model potable water system containing complex microbial flora.

Survival and growth of Legionella pneumophila in both biofilm and planktonic phases were determined with a two-stage model system. The model used filter-sterilized tap water as the sole source of nutrient to culture a naturally occurring mixed population of microorganisms including virulent L. pneumophila. At 20 degrees C, L. pneumophila accounted for a low proportion of biofilm flora on polybutylene and chlorinated polyvinyl chloride, but was absent from copper surfaces. The pathogen was most abundant on biofilms on plastics at 40 degrees C, where it accounted for up to 50% of the total biofilm flora. Copper surfaces were inhibitory to total biofouling and included only low numbers of L. pneumophila organisms. The pathogen was able to survive in biofilms on the surface of the plastic materials at 50 degrees C, but was absent from the copper surfaces at the same temperature. L. pneumophila could not be detected in the model system at 60 degrees C. In the presence of copper surfaces, biofilms forming on adjacent control glass surfaces were found to incorporate copper ions which subsequently inhibited colonization of their surfaces. This work suggests that the use of copper tubing in water systems may help to limit the colonization of water systems by L. pneumophila.

Bacterial Adhesion↗

Influence of Plumbing Materials on Biofilm Formation and Growth of Legionella pneumophila in Potable Water Systems.

A two-stage chemostat model of a plumbing system was developed, with tap water as the sole nutrient source. The model system was populated with a naturally occurring inoculum derived from an outbreak of Legionnaires' disease and containing Legionella pneumophila along with associated bacteria and protozoa. The model system was used to develop biofilms on the surfaces of a range of eight plumbing materials under controlled, reproducible conditions. The materials varied in their abilities to support biofilm development and the growth of L. pneumophila. Elastomeric surfaces had the most abundant biofilms supporting the highest numbers of L. pneumophila CFU; this was attributed to the leaching of nutrients for bacterial growth from the materials. No direct relationship existed between total biofouling and the numbers of L. pneumophila CFU.

Journal Article↗

Infection of a yellow baboon with simian immunodeficiency virus from African green monkeys: evidence for cross-species transmission in the wild.

Many African primates are known to be naturally infected with simian immunodeficiency viruses (SIVs), but only a fraction of these viruses has been molecularly characterized. One primate species for which only serological evidence of SIV infection has been reported is the yellow baboon (Papio hamadryas cynocephalus). Two wild-living baboons with strong SIVAGM seroreactivity were previously identified in a Tanzanian national park where baboons and African green monkeys shared the same habitat (T. Kodama, D. P. Silva, M. D. Daniel, J. E. Phillips-Conroy, C. J. Jolly, J. Rogers, and R. C. Desrosiers, AIDS Res. Hum. Retroviruses 5:337-343, 1989). To determine the genetic identity of the viruses infecting these animals, we used PCR to examine SIV sequences directly in uncultured leukocyte DNA. Targeting two different, nonoverlapping genomic regions, we amplified and sequenced a 673-bp gag gene fragment and a 908-bp env gene fragment from one of the two baboons. Phylo-genetic analyses revealed that this baboon was infected with an SIVAGM strain of the vervet subtype. These results provide the first direct evidence for simian-to-simian cross-species transmission of SIV in the wild.

Amino Acid Sequence↗

Is tibiofemoral osteoarthritis in the knee joint a new disease?

OBJECTIVES: To compare the prevalence of osteoarthritis (OA) of the hip, tibiofemoral and patellofemoral joints in a skeletal population. METHODS: A total of 785 adult English skeletons (695 Saxon or Mediaeval origin) were examined for OA using established criteria. RESULTS: Twenty nine skeletons had hip OA, compared with 14 with patellofemoral joint OA, and only four tibiofemoral joint OA. CONCLUSION: Tibiofemoral OA was far less prevalent in ancient skeletons than hip or patellofemoral disease. Tibiofemoral OA may be a 'new' disease.

England↗

Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis.

The short chain fatty acids, acetate, propionate, and butyrate are produced by colonic bacterial fermentation of non-starch polysaccharides. Butyrate is the major fuel source for the colonic epithelium and there is evidence to suggest that its oxidation is impaired in ulcerative colitis. Triplicate biopsy specimens were taken at colonoscopy from five regions of the large bowel in 15 sufferers of ulcerative colitis. These patients all had mild or quiescent colitis as assessed by clinical condition, mucosal endoscopic and histological appearance. The rate of oxidation of glucose, glutamine, and butyrate through to carbon dioxide was compared with that in biopsy specimens from 28 patients who had no mucosal abnormality. Butyrate (272 (199-368)) was the preferred fuel source for the colitic mucosa followed by glutamine (33 (24-62)) then glucose (7.2 (5.3-15)) pmol/micrograms/hour; medians and 95% confidence intervals, p < 0.01. There was no regional difference in the rate of utilisation of these metabolites. In the group with colitis the rate of butyrate oxidation to carbon dioxide was significantly impaired compared with that in normal mucosa decreasing from 472 (351-637) pmol/micrograms/hour to 272 (199-368) pmol/micrograms/hour; median and 95% confidence intervals, p = 0.016. The rate of glucose and glutamine utilisation were not significantly different between normal and colitic mucosa. These data confirm that in quiescent ulcerative colitis there is an impairment of butyrate oxidation.

Adult↗

Pelvic floor function in multiple sclerosis.

The aim of this study was to define pelvic floor function in patients with multiple sclerosis and bowel dysfunction, either incontinence (MSI) or defecation difficulties without incontinence (MSC). Normal controls and patients with idiopathic neurogenic faecal incontinence without multiple sclerosis (FI, disease controls) were also studied. Thirty eight multiple sclerosis patients (20 incontinent, 18 incontinent) 73 normal controls, and 91 FI patients were studied. The FI group showed the characteristic combined sensorimotor deficit previously described in these patients of low resting and voluntary contraction and pressures, increased sensory threshold to mucosal stimulation, and increased pudendal nerve terminal motor latencies and fibre densities. MSI patients had significantly lower anal resting pressures (80 (30-140) cm H2O, median (range) v 98 (30-200), normal controls, p = 0.002) and both MSC and MSI patients had significantly lower anal maximum voluntary contraction pressures (65 (0-260) cm H2O, MSC and 25 (0-100), MSI v 120 (30-300), normal controls, p = < 0.0004) and higher external anal sphincter fibre densities (1.7 (1.1-2.6), MSC and 1.7 (1.1-2.4), MSI v 1.5 (1.1-1.75), normal controls, p < 0.006) compared with normal controls but pudendal nerve terminal motor latencies were similar and no sensory deficit was found. This contrasted with the idiopathic faecal incontinent patients who, in addition to significantly higher fibre densities (1.8 (1.1-3), p = 0.001) had increased pudendal latencies (2.5 (1.1-5.5) mS v 2.08 (1.4-2.6), p = 0.001) compared with normal controls. The idiopathic faecal incontinent group had significantly lower resting anal pressures (50 (10-160) cm H2O, p=0.02) than the MSI group. Comparison with the incontinent and continent multiple sclerosis groups showed that incontinence was associated with lower voluntary anal contraction pressures (25 (0-100) v 65 (0-260), p=0.03) but that there were no other differences between these two groups. Pelvic floor function is considerably disturbed in multiple sclerosis, showing muscular weakness with preservation of peripheral motor nerve conduction, providing indirect evidence that this is mainly a result of lesions within the central nervous system.

Adult↗

Design and specificity of hammerhead ribozymes against calretinin mRNA.

We obtained a partial sequence of mouse calretinin mRNA from cDNA clones, and designed hammerhead ribozymes to cleave positions within it. With a view to optimising hammerhead ribozymes for eliminating the mRNA in vivo, we varied the length and sequence of the three duplex 'arms' and measured the cleavage of long RNA substrates in vitro at 37 degrees C (as well as 50 degrees C). Precise cleavage occurred, but it could only go to completion with a large excess of ribozyme. The evidence suggests that the rate-limiting step with a large target is not the cleavage, but the formation of the active ribozyme: substrate complex. The efficiency varied unpredictably according to the target site, the length of the substrate RNA, and the length of the ribozyme; secondary structure in vitro may be responsible. We particularly investigated the degree of sequence-specificity. Some mismatches could be tolerated, but shortening of the total basepairing with the substrate to less than 14 bp drastically reduced activity, implying that interaction with weakly-matched RNAs is unlikely to be a serious problem in vivo. These results suggest that specific and complete cleavage of a mRNA in vivo should be possible, given high-level expression of a ribozyme against a favourable target site.

Animals↗

The chemical step is not rate-limiting during the hydrolysis by phospholipase A2 of mixed micelles of phospholipid and detergent.

The effect of detergents on the overall catalytic turnover by secreted phospholipase A2 (PLA2) on codispersions of the substrate phospholipid is characterized. The overall rate of interfacial catalytic turnover depends on the effective substrate "concentration" (mole fraction) that the bound enzyme "sees" at the interface. Therefore, besides the intrinsic catalytic turnover rate determined by the Michaelis-Menten cycle in the interface [Berg et al. (1991) Biochemistry 30, 7283], two other interfacial processes significantly alter the overall effective rate of hydrolysis: first, the fraction of the total enzyme at the interface; second, the rate of replenishment of the substrate. At low mole fractions (< 0.3), bile salts promote the binding of pig pancreatic PLA2 to zwitterionic vesicles, and the rate of hydrolysis increases with the fraction of the enzyme in the interface. At higher (> 0.3) mole fractions of the detergent, the bilayer is disrupted, and the rate of hydrolysis decreases by more than a factor of 10. The detergent-dependent decrease in the rate of hydrolysis of the sn-2-oxyphospholipids is much larger than that of sn-2-thiophospholipid, and therefore the element effect (O/S ratio) decreases from about 10 in bilayers to less than 2 in mixed micelles. This loss of the element effect in mixed micelles shows that the chemical step is no longer rate-limiting during the hydrolysis of mixed micelles formed by the disruption of vesicles by the detergent. Such effects were observed with phospholipase A2 from several sources acting on substrates dispersed in a variety of detergents including bile salts, 2-deoxylysophosphatidylcholine, and Triton X-100.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Epidermal growth factor receptor expression in demented elderly: localization to vascular endothelial cells of brain, pituitary and skin.

We have previously demonstrated that expression of epidermal growth factor receptor (EGFR) was upregulated on vascular endothelial cells from brains of patients with dementia but not in brains from non-demented patients. The present study used a monoclonal antibody against EGFR to examine its expression in pituitary gland, scalp, abdominal skin and brain of 29 patients with and without various dementias and neurological deficits, as well as normal aged controls. Of 20 clinically demented patients examined postmortem, 15 exhibited EGFR immunoreactivity (IR) on brain and peripheral vascular endothelial cells. Examination of nine non-demented patients revealed only 1 patient with EGFR-IR. EGFR-IR was expressed on all blood vessels, regardless of size or location within the tissue examined. Ultrastructural analysis of EGFR revealed that in pituitary, like brain, the receptor was restricted to the lumenal cell surface of vascular endothelial cells. In all cases of EGFR-IR there was an absolute correlation between central nervous system and peripheral expression; if there was EGFR-IR in brain vessels it was present in skin. If there was no staining in brain there was no peripheral skin vessel staining; and vice versa. Increased EGFR expression may indicate proliferative or regenerative changes in the vasculature of affected patients and may provide a biological marker supporting the diagnosis of dementia by analysis of skin biopsy.

Aged↗