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Biomedical subjects

A Prior

Publications and source records attributed to A Prior.

At least 19 recordsLinked to original sources

Could insecticide-treated cattle reduce Afrotropical malaria transmission? Effects of deltamethrin-treated Zebu on Anopheles arabiensis behaviour and survival in Ethiopia.

Anopheles arabiensis Patton (Diptera: Culicidae) is the most widespread vector of malaria in the Afrotropical Region. Because An. arabiensis feeds readily on cattle as well as humans, the insecticide-treatment of cattle--as employed to control tsetse (Diptera: Glossinidae) and ticks (Acari: Ixodidae)--might simultaneously affect the malaria vectorial capacity of this mosquito. Therefore, we conducted field experiments in southern Ethiopia to establish whether Zebu cattle (Bos indicus L.) treated with a pour-on pyrethroid formulation of 1% deltamethrin, widely used to control ticks and tsetse, would be effective against An. arabiensis or cause the female mosquitoes to feed more frequently on humans, due to behavioural avoidance of insecticide-treated cattle. Contact bioassays (3 min exposure) showed that the insecticide remained effective for about 1 month (kill rate > 50%) against mosquitoes feeding on the flanks of treated cattle. A novel behavioural assay demonstrated that An. arabiensis readily fed on insecticide-treated cattle and were not deflected to human hosts in the presence of treated cattle. DNA-fingerprinting of bloodmeals revealed that An. arabiensis naturally feeds most frequently on older animals, consistent with the established practice of applying insecticide only to older cattle, while allowing younger untreated animals to gain immunity against infections transmitted by ticks. These encouraging results were tempered by finding that > 90% of An. arabiensis, An. pharoensis and An. tenebrosus females feed on the legs of cattle, farthest from the site of pour-on application along the animal's back and where the treatment may be least residual due to weathering. Observations of mosquitoes feeding naturally on insecticide-treated cattle showed that the majority of wild female anophelines alighted on the host animal for less than 1 min to feed, with significantly shorter mean duration of feeding bouts on insecticide-treated animals, and the effective life of the insecticide was only 1 week. Thus the monthly application of deltamethrin to cattle, typically used to control tsetse and ticks, is unlikely to be effective against An. arabiensis populations or their vectorial capacity. Even so, it seems likely that far greater impact on anopheline mosquitoes could be achieved by applying insecticide selectively to the legs of cattle.

Animals↗

The prevalence of Helicobacter pylori infection in malignant and premalignant conditions of the head and neck.

Helicobacter pylori is an accepted cause of chronic active gastritis and has a major causative role in peptic ulceration. It is a gastric carcinogen. Its role in non-ulcer dyspepsia (NUD) is less clear; yet 50 per cent of patients with NUD are infected with H pylori. H pylori has been investigated in several other organ systems, but has not been investigated extensively in squamous cell carcinoma of the upper aerodigestive tract, a region which could be directly exposed to the bacterium by gastro-oesophageal reflux (GOR). In this study 61 patients with severe laryngeal dysplasia or frank carcinoma of the head and neck are striated by age, investigated for the presence of antibodies to H pylori and compared to age and sex matched controls. In the age group of 46-61 years, the presence of H pylori antibodies was marginally greater in the experimental (63.0 per cent) than the control group (40.7 per cent) (Pearson Chi square p = 0.055, Fisher 2-sided exact test p = 0.066). When combining this age group with the younger age group and thereby creating two roughly equal groups (n = 31 and n = 30) there was also a statistical trend towards increased positivity in the experimental group. These findings are discussed in the light of other studies with gastro-oesophageal reflux disease (GORD).

Adult↗

The prevalence of Helicobacter pylori infection in benign laryngeal disorders.

Helicobacter pylori (HP) is an accepted cause of chronic active gastritis and has a major causative role in peptic ulcers. It is a gastric carcinogen. Its role in nonulcer dyspepsia (NUD) is less clear, yet 50% of patients with NUD are infected with HP, and some recent literature demonstrates long-term improvement of symptoms following eradication. HP has been investigated in several other organ systems, but has not been investigated to any major degree in laryngeal disorders, a region that could be directly exposed to the bacterium from pharyngolaryngeal reflux. This study represents one arm of a larger study designed to investigate such a relationship. Of 101 patients with nonmalignant voice disorders presenting to our voice clinics, 54.5% tested positive for the H. pylori organism. Of the controls, 47.1% tested positive. When striated into age groups of < 45 years, 46-61 years, and > 62 years, and then age-matched with the controls, the likelihood of infection with the H. pylori organism was greater in both the experimental middle group, and in the middle group when combined with the elder group, than in the matched controls, and this difference demonstrated a trend approaching statistical significance. This finding is discussed in the light of other studies on HP and on gastroesophageal reflex (GER).

Adult↗

Host selection by Anopheles arabiensis and An. quadriannulatus feeding on cattle in Zimbabwe.

In the Zambezi valley, mosquito females of the Anopheles gambiae Giles complex (Diptera: Culicidae) were collected from a hut containing pairs of cattle distinguishable by known DNA markers. DNA was extracted from the blood-fed mosquito abdomens and primer sets for ungulate and mosquito DNA loci were used to identify the mosquito sibling species and individual host source(s) of their bloodmeals. The 67 mosquitoes comprised a mixture of An. arabiensis Patton (31%) and An. quadriannulatus Theobald (69%). DNA from one or both of the cattle present in the hut was detected in 91% of samples. When the hut contained an adult and a calf, the percentage of bloodmeals from the adult, the calf and adult + calf were 58%, 27% and 15%, respectively; the trend towards meals from the adult host was consistent but not always significant. When the pair of cattle comprised two adults of roughly equal size and age, then mosquitoes generally showed no significant bias towards feeding from one individual. There was no significant difference in the pattern of host selection made by An. arabiensis and An. quadriannulatus but the former had a significantly higher percentage (20%) of mixed meals than An. quadriannulatus (9%). These two members of the An. gambiae complex appear to be less selective in their choice of cattle hosts compared to day-active Diptera such as tsetse and Stomoxys, possibly because the hosts are generally asleep when Anopheles are active and there is therefore less selective pressure to adapt to host defensive behaviour. The slight bias of Anopheles towards older and/or larger cattle may be related to the host's larger surface area.

Age Factors↗

A surface-associated retinol- and fatty acid-binding protein (Gp-FAR-1) from the potato cyst nematode Globodera pallida: lipid binding activities, structural analysis and expression pattern.

Parasitic nematodes produce at least two structurally novel classes of small helix-rich retinol- and fatty-acid-binding proteins that have no counterparts in their plant or animal hosts and thus represent potential targets for new nematicides. Here we describe a protein (Gp-FAR-1) from the plant-parasitic nematode Globodera pallida, which is a member of the nematode-specific fatty-acid- and retinol-binding (FAR) family of proteins but localizes to the surface of this species, placing it in a strategic position for interaction with the host. Recombinant Gp-FAR-1 was found to bind retinol, cis-parinaric acid and the fluorophore-tagged lipids 11-(dansylamino)undecanoic acid and dansyl-D,L-alpha-amino-octanoic acid. The fluorescence emission characteristics of the dansylated analogues indicated that the entire ligand enters the binding cavity. Fluorescence competition experiments showed that Gp-FAR-1 binds fatty acids in the range C(11) to C(24), with optimal binding at C(15). Intrinsic fluorescence analysis of a mutant protein into which a tryptophan residue had been inserted supported computer-based predictions of the position of this residue at the protein's interior and possibly also at the binding site. Of direct relevance to plant defence systems was the observation that Gp-FAR-1 binds two lipids (linolenic and linoleic acids) that are precursors of plant defence compounds and the jasmonic acid signalling pathway. Moreover, Gp-FAR-1 was found to inhibit the lipoxygenase-mediated modification of these substrates in vitro. Thus not only does Gp-FAR-1 function as a broad-spectrum retinol- and fatty-acid-binding protein, the results are consistent with the idea that Gp-FAR-1 is involved in the evasion of primary host plant defence systems.

Amino Acid Sequence↗

New thioredoxins and glutaredoxins as electron donors of 3'-phosphoadenylylsulfate reductase.

Reduction of inorganic sulfate to sulfite in prototrophic bacteria occurs with 3'-phosphoadenylylsulfate (PAPS) as substrate for PAPS reductase and is the first step leading to reduced sulfur for cellular biosynthetic reactions. The relative efficiency as reductants of homogeneous highly active PAPS reductase of the newly identified second thioredoxin (Trx2) and glutaredoxins (Grx1, Grx2, Grx3, and a mutant Grx1C14S) was compared with the well known thioredoxin (Trx1) from Escherichia coli. Trx1, Trx2, and Grx1 supported virtually identical rates of sulfite formation with a Vmax ranging from 6.6 units mg-1 (Trx1) to 5.1 units mg-1 (Grx1), whereas Grx1C14S was only marginally active, and Grx2 and Grx3 had no activity. The structural difference between active reductants had no effect upon Km PAPS (22.5 microM). Grx1 effectively replaced Trx1 with essentially identical Km-values: Km trx1 (13.7 microM), Km grx1 (14.9 microM), whereas the Km trx2 was considerably higher (34.2 microM). The results agree with previous in vivo data suggesting that Trx1 or Grx1 is essential for sulfate reduction but not for ribonucleotide reduction in E. coli.

Electron Transport↗

Structural and kinetic properties of adenylyl sulfate reductase from Catharanthus roseus cell cultures.

A cDNA encoding a plant-type APS reductase was isolated from an axenic cell suspension culture of Catharanthus roseus (Genbank/EMBL-databank accession number U63784). The open reading frame of 1392 bp (termed par) encoded for a protein (Mr=51394) consisting of a N-terminal transit peptide, a PAPS reductase-like core and a C-terminal extension with homology to the thioredoxin-like domain of protein disulfide isomerase. The APS reductase precursor was imported into pea chloroplasts in vitro and processed to give a mature protein of approximately 45 kDa. The homologous protein from pea chloroplast stroma was detected using anti:par polyclonal antibodies. To investigate the catalytical function of the different domains deleted par proteins were purified. ParDelta1 lacking the transit sequence liberated sulfite from APS (Km 2.5+/-0.23 microM) in vitro with glutathione (Km 3+/-0.64 mM) as reductant (Vmax 2.6+/-0.14 U mg-1, molecular activity 126 min-1). ParDelta2 lacking the transit sequence and C-terminal domain had to be reconstituted with exogenous thioredoxin as reductant (Km 15. 3+/-1.27 microM, Vmax 0.6+/-0.014 U mg-1). Glutaredoxin, GSH or DTT were ineffective substitutes. ParDelta1 (35.4%) and parDelta2 (21. 8%) both exhibited insulin reductase activity comparable to thioredoxin (100%). Protein disulfide isomerase activity was observed for parDelta1.

Amino Acid Sequence↗

Chlamydia trachomatis infection: is it relevant in irritable bowel syndrome?

BACKGROUND: Irritable bowel syndrome can present with gynaecological symptoms similar to those of chronic pelvic inflammatory disease, which is commonly caused by Chlamydia trachomatis. Infection with this organism might therefore lead to diagnostic and management difficulties in patients, not only as a result of symptom overlap between the two disorders but also because chlamydial infection might exacerbate the symptoms of irritable bowel syndrome. This study was designed to investigate any possible link between chlamydial infection and irritable bowel syndrome. PATIENTS/METHODS: The prevalence of antibodies to C. trachomatis and abdominal symptomatology was assessed in a group of 100 female patients with irritable bowel syndrome and 100 matched female controls. RESULTS: 25% of patients and 17% of controls were found to have evidence of previous chlamydial infection. This difference was not statistically significant. Within the patient group, no association was found between chlamydial infection and any particular pattern of symptomatology. CONCLUSIONS: The results of this study indicate that occult chlamydial infection is not a major problem in irritable bowel syndrome and that routine investigation for this organism is unnecessary. They also provide some reassurance that pelvic inflammatory disease and all its potentially serious consequences is not being significantly overlooked in gastroenterological practice.

Adult↗

Assessment by nasal biopsy of long-term use of mometasone furoate aqueous nasal spray (Nasonex) in the treatment of perennial rhinitis.

Allergic rhinitis is associated with specific histopathologic changes in the nasal mucosa including squamous metaplasia and local eosinophilia. Previous studies have shown that mometasone furoate aqueous nasal spray is effective and well tolerated in reducing perennial rhinitis and seasonal allergic rhinitis symptoms. We undertook a multicenter, open-label study to evaluate, by nasal biopsy, the tissue changes associated with mometasone furoate use (200 microg/day) during a 12-month treatment period in patients with perennial rhinitis. Of the 69 patients enrolled in the study, 52 completed all 12 months of treatment. Nasal biopsy specimens obtained from patients at baseline and after treatment were evaluated in a blinded fashion by computerized image analysis, qualitative histologic examination, and immunocytochemistry. Morphologic examination of nasal biopsy specimens showed a decrease in focal metaplasia, no change in epithelial thickness, and no sign of atrophy after treatment with mometasone furoate. Immunocytochemical analyses of nasal biopsy specimens obtained before and after treatment revealed a significant decrease in major basic protein-positive eosinophils and tryptase-positive mast cells in the epithelium and lamina propria after treatment. Mometasone furoate appeared to attenuate the inflammatory process by reducing the extent of inflammatory cell infiltration, particularly of eosinophils. This study demonstrated that long-term administration of mometasone furoate is not associated with adverse tissue changes in the nasal mucosa of patients with perennial rhinitis.

Administration, Intranasal↗

Habitual intake of fruits and vegetables amongst patients at increased risk of colorectal neoplasia.

We assessed consumption of fruit and vegetables amongst patients with ulcerative colitis, colorectal polyps or previous carcinoma. The dietary intakes for 119 patients attending a gastroenterology clinic for colonoscopy were assessed using a questionnaire. A single age- and sex-matched control subject was recruited for each patient. The patients consumed 12.8% less energy than the controls (P < 0.02) and 28.9% less fruit and vegetables (P < 0.0001). Patients with neoplastic disease consumed 21% less fruit and vegetables than the controls (n = 60; P < 0.01). This group of patients at increased risk of colorectal cancer selected diets containing significantly less fruit and vegetables than symptomless controls.

Case-Control Studies↗

Preparative desalting of bovine serum albumin by continuous annular chromatography.

Bovine serum albumin (BSA) was continuously desalted from alkaline salts (a mixture of sodium phosphate, sodium chloride and potassium chloride) using a size-exclusion gel as the stationary phase. An annular chromatograph was used to achieve a continuous mode of operation and therefore a reasonable throughput. Distribution and mass transfer coefficients of the substances as well as bed properties were obtained by batch chromatography. These separations were simulated mathematically applying an approximate linear chromatographic theory. It was shown experimentally and theoretically that the BSA and the salt solution could be recovered continuously in a purity higher than 98%. The influence of rotation rate on the resolution of the individual peaks was investigated.

Chromatography↗

Reaction mechanism of thioredoxin: 3'-phospho-adenylylsulfate reductase investigated by site-directed mutagenesis.

Properties of purified recombinant adenosine 3'-phosphate 5'-phosphosulfate (PAdoPS) reductase from Escherichia coli were investigated. The Michaelis constants for reduced thioredoxin and PAdoPS are 23 microM and 10 microM, respectively; the enzyme has a Vmax of 94-99 mumol min-1 mg-1 and a molecular activity/catalytically active dimer of 95 s-1. Adenosine 3',5'-bisphosphate (PAdoP) inhibits competitively (Ki 4 microM) with respect to PAdoPS; adenosine 2',5'-bisphosphate and sulfite are not inhibitory. Alkylation by SH-group inhibitors irreversibly inactivates the enzyme. The structural gene (cysH) encodes for a small polypeptide with a single Cys residue located in a conserved cluster (KXECGI/LH) of amino acids. Involvement of the only Cys and of Tyr209 in the reduction of PAdoPS to sulfite was investigated by site-specific mutagenesis: cysH was mutated by single-strand-overlay extension PCR; the mutated genes were cloned in pBTac1 and expressed in E. coli RL 22 (delta cysHIJ). Homogenous Cys239Ser and Tyr209Phe mutant PAdoPS reductases were investigated for altered catalytic properties. Mutation of the single Cys reduced Vmax by a factor of 4.5 x 10(3) (Vmax = 0.02-0.013 mumol min-1 mg-1) with marginal effects on Km for PAdoPS (19 microM) and reduced thioredoxin (14 microM). Mutation of Tyr209 drastically affected saturation with thioredoxin (Km 1.5 microM) and decreased Vmax (0.22-0.25 mumol min-1 mg-1) in addition to a small increase in Km for PAdoPS (31 microM). Chromophores as prosthetic groups were absent from recombinant PAdoPS reductase. Difference absorption spectra between reduced and oxidized forms of wild-type and mutated proteins indicated that, in addition to Cys239 and Tyr209, an unidentified Trp (delta lambda max 292 nm) appears to be involved in the reduction. The data suggest a special ping-pong mechanism with PAdoPS reacting with the reduced enzyme isomer in a Theorell-Chance type mechanism.

Amino Acid Sequence↗

The microbiology and antibiotic treatment of peritonsillar abscesses.

Pus from 53 peritonsillar abscesses was cultured and associations between the microbiological results and clinical data were investigated with the aim of developing a clinical protocol for treatment. A positive culture grew in 85% of quinsies and of these 16% produced aerobes and 84% anaerobes. Penicillin-resistant organisms were grown from 32% of patients and all but one of these organisms (Haemophilus influenzae) was sensitive to metronidazole. There was no association between clinical presentation and cultured organism which could guide treatment, hence we recommend penicillin and metronidazole as the antibiotic regimen of choice in the treatment of peritonsillar abscesses because of its effectiveness in 98% of patients.

Adolescent↗

Lymphocyte infiltration and thickness of the nasal mucous membrane in perennial and seasonal allergic rhinitis.

We have used immunocytochemical techniques to study infiltration by lymphocytes in biopsy specimens of the nasal mucosal membrane in 24 atopic patients and 10 normal volunteers. Twelve patients had perennial rhinitis and 12 had seasonal allergic rhinitis (SR) to grass pollen. Biopsy specimens were taken both in and out of the pollen season in patients with SR. Biopsy specimens were strained with the indirect immunoperoxidase technique and monoclonal antibodies to CD3, CD4, CD8, CD22, and CD25. T helper cells (CD4+) and CD24+ cells were significantly more numerous in patients exposed to allergen (those with perennial rhinitis and SR in season) compared with normal volunteers, whereas values for SR out of season were intermediate. The thickness of the nasal epithelium was significantly (p < 0.05) greater in biopsy specimens from patients with perennial rhinitis (mean, 51.43 microns) than in those from patients with SR in season (median, 32.44 microns). These results suggest that in allergic rhinitis, natural exposure to allergen is accompanied by increased infiltration of the nasal mucous membrane by T-helper and CD25+ cells.

Adolescent↗

Validation of a simple technique for the detection of abnormal mucosal cell replication in humans.

Abnormal intestinal crypt cell proliferation is considered to be an important early risk marker for colorectal cancer but measurement of the rate and spatial distribution of cell division by histochemical localization of DNA synthesis is labour-intensive and expensive. We developed and evaluated a simpler technique for measurement of these parameters using direct visual analysis of mitotic figures in microdissected crypts. The direct crypt analysis technique was applied to colorectal biopsies from patients with ulcerative colitis or no mucosal abnormality. A characteristic shift of cell division toward the intestinal lumen was detected in patients with ulcerative colitis. The direct method was validated using rats fed diets containing cellulose, or guar gum to stimulate mucosal cell proliferation. The crypt cell proliferation rate (CCPR) was measured by the metaphase-arrest technique and the results were compared with direct crypt analysis. There was a fivefold range of CCPR values at three sampling sites across the dietary groups. An excellent linear correlation between the results by the two techniques was obtained (r = 0.98; P < 0.001). In a second experiment the spatial distribution of dividing cells between five zones in colonic crypts, determined by the new method or by staining with BrdU, was compared. Good agreement was again achieved. Visual analysis of intact crypts is a valid technique for the measurement of crypt cell cytokinetics and it is particularly suited for use in a clinical environment.

Animals↗

Reduction of rectal sensitivity and post-prandial motility by granisetron, a 5 HT3-receptor antagonist, in patients with irritable bowel syndrome.

The effect of granisetron, a specific 5-hydroxytryptamine 3-receptor antagonist, on the anorectal responses to rectal distension and a 1000-calorie meal was assessed in 12 patients with irritable bowel syndrome. Each patient was studied on three occasions, receiving intravenously either 40 mcg/kg granisetron, 160 mcg/kg granisetron or normal saline. Granisetron caused a dose-dependent reduction in rectal sensitivity, manifested by an increase in the threshold volumes at which the sensations of gas, desire to defecate, urgency and discomfort were perceived. This reached significance for all sensations at the higher dose level (P < 0.01). No significant changes in anal pressures, rectal compliance or distension-induced motor activity occurred following drug administration. A dose-dependent reduction in post-prandial motility was observed following intravenous granisetron and this was highly significant at 160 mcg/kg (P = 0.005). These results suggest that the 5 hydroxytryptamine receptor antagonists may have a therapeutic role in patients with irritable bowel syndrome.

Adult↗

Effect of hysterectomy on anorectal and urethrovesical physiology.

To investigate whether vaginal or total abdominal hysterectomy is associated with changes in anorectal and urethrovesical physiology, 26 women were studied before operation and six weeks and six months afterwards. The results showed a postoperative increase in both rectal and vesical sensitivity (p less than 0.01). Similar results were observed irrespective of the type of hysterectomy. No significant changes in rectal or bladder compliance were noted, and anal pressure and urethral pressure and length were unchanged after surgery. Whole gut transit was not affected by hysterectomy. Urinary symptoms occurred de novo in 6/26 women and gastrointestinal symptoms in 2/26 women. These results show that significant changes in rectal and vesical sensitivity occur after hysterectomy for benign disease. These persist for at least six months postoperatively but are not always associated with development of urinary or gastrointestinal symptoms.

Adult↗

Relation between hysterectomy and the irritable bowel: a prospective study.

Some women with irritable bowel syndrome date the onset of symptoms to previous hysterectomy. To assess prospectively the incidence of gastrointestinal symptomatology arising de novo after hysterectomy, and to study the effect of surgery on pre-existing symptoms, 205 women completed a symptom questionnaire before and six weeks and six months after surgery. Beforehand, symptoms suggestive of irritable bowel syndrome occurred in 22% of patients. At six months after operation, 60% of these had improved or were symptom free while 20% had increased symptomatology. New gastrointestinal symptoms were present more than once per week in 10% of previously asymptomatic women. Constipation predominant irritable bowel syndrome was the commonest symptom complex seen de novo, occurring more than once per week in 5% of the group. No relation was found between new symptomatology and the type of hysterectomy, oophorectomy, or the administration of perioperative antibiotics. This study suggests that many women with pre-existing gastrointestinal symptomatology improve after hysterectomy. However, symptoms suggestive of irritable bowel syndrome do arise de novo in 10%. As hysterectomy is common, gastroenterologists can expect to see women presenting with post-hysterectomy problems.

Adult↗