PubMed Health⌕ Search

Biomedical subjects

H Wells

Publications and source records attributed to H Wells.

At least 19 recordsLinked to original sources
PubMed2003

Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease.

Prion diseases are fatal, chronic neurodegenerative diseases of mammals, characterized by amyloid deposition, astrogliosis, microglial activation, tissue vacuolation and neuronal loss. In the ME7 model of prion disease in the C57BL/6 J mouse, we have shown previously that these animals display behavioural changes that indicate the onset of neuronal dysfunction. The current study examines the neuropathological correlates of these early behavioural changes. After injection of ME7-infected homogenate into the dorsal hippocampus, we found statistically significant impairment of burrowing, nesting and glucose consumption, and increased open field activity at 13 weeks. At this time, microglia activation and PrPSc deposition was visible selectively throughout the limbic system, including the hippocampus, entorhinal cortex, medial and lateral septum, mamillary bodies, dorsal thalamus and, to a lesser degree, in regions of the brainstem. No increase in apoptosis or neuronal cell loss was detectable at this time, while in animals at 19 weeks postinjection there was 40% neuronal loss from CA1. There was a statistically significant reduction in synaptophysin staining in the stratum radiatum of the CA1 at 13 weeks indicating loss of presynaptic terminals. Damage to the dorsal hippocampus is known to disrupt burrowing and nesting behaviour. We have demonstrated a neuropathological correlate of an early behavioural deficit in prion disease and suggest that this should allow insights into the first steps of the neuropathogenesis of prion diseases.

Animals↗
PubMed2000

Repeat HIV testing: high-risk behaviour or risk reduction strategy?

OBJECTIVE: To examine the characteristics of repeat and first-time HIV testers and consider their implications for HIV test counselling. METHODS: An anonymous questionnaire was completed by nearly 1500 people seeking an HIV test between September 1997 and July 1998 at a same-day HIV testing clinic in London, United Kingdom. Repeat testers were those people who had previously tested HIV negative and were returning for another test. Information was collected on self-reported unprotected penetrative sex (UPS) in the previous 3 months and reasons for seeking the present test. RESULTS: Overall, 50.6% (721/1446) of all clinic attenders were repeat testers: gay men 71.7% (337/470), heterosexual men 42.1% (208/494) and heterosexual women 38.6% (186/482). No significant differences were found between repeat and first time testers in the frequency of UPS (P > or = 0.06). However, gay men (but not heterosexual men and women) reporting three or more previous HIV tests were significantly more likely to report higher-risk UPS (i.e. with a partner whose HIV status was either positive or unknown) (42.2%) than those who had had one-two or no previous tests (25.3 and 25.4%, respectively; P = 0.002). Over half the heterosexual men and women, and one third of gay men said they were seeking the current HIV test in preparation for a new relationship; these proportions did not differ significantly between repeat and first-time testers (P > 0.1). CONCLUSION: In this London HIV testing clinic, no significant differences were found in the frequency of UPS between repeat and first-time testers with the exception of gay men with a history of three or more previous HIV tests, who reported elevated levels of high-risk sexual behaviour. For many people, repeat HIV testing has become part of a risk reduction strategy to establish seroconcordance with a regular partner. HIV test counselling provides the opportunity both to address high-risk behaviour and to reinforce personal risk-reduction strategies.

Female↗
PubMed1999

Do people attending a same day testing clinic discuss their need for a HIV test with their GP?

In the United Kingdom, people with HIV infection present with advanced disease and general practitioners (GPs) are currently an underused resource for HIV testing. We describe the reasons for using an open-access clinic rather than primary care for testing for HIV. People attending the clinic were asked to complete a questionnaire asking about GP registration, access, and whether HIV testing was discussed in primary care. Despite access to GPs, HIV testing in primary care was rarely discussed. If HIV testing is to move to a general practice setting, GPs could address the issues, such as the recording of sensitive information in notes, future life insurance, and confidentiality, which this report identifies as the main barriers for using primary care.

Family Practice↗
PubMed1997

Spontaneous flower constancy and learning in honey bees as a function of colour

When presented with an artificial flower patch of blue and yellow pedicellate flowers, individual honey bees, Apis mellifera L., became constant to one of the two flower colours, rarely even sampling the alternative colour. Some bees visited only blue flowers while others visited only yellow flowers. This paper describes the onset of constancy for bees that had had no experience with the experimental apparatus. In 3020 visits, bees failed to land on or drink from the flower colour on which they first landed only 17 times. This behaviour was not modified by quality or quantity of reward, training to the experimental site, group effects or presence of odour during trials. However, when we trained bees to a target painted with two colours and then forced them to sample monomorphic flower patches in sequence, all bees visited the only colour present: yellow or blue. When we subsequently offered these same bees yellow and blue flowers simultaneously (rewarded choices), they became constant. Eleven of 23 bees showed constancy to the less rewarding flower morph without even sampling the alternative. Those bees failed to sample even though they had previously been forced to visit the alternative flower morph, which offered a reward with twice the calories/volume. Constancy is thus spontaneous in honey bees, but it can be hidden by some experimental protocols designed to study learning.1997The Association for the Study of Animal Behaviour

Journal Article↗
PubMed1988

Ceftazidime with or without vancomycin vs. cephalothin, carbenicillin and gentamicin as the initial therapy of the febrile neutropenic pediatric cancer patient.

In a 28-month randomized trial we compared ceftazidime (CAZ), an extended spectrum cephalosporin, with cephalothin, carbenicillin and gentamicin (KCG) as empiric therapy for febrile neutropenic pediatric cancer patients. Because of the occurrence of ceftazidime-resistant Gram-positive primary infections, vancomycin was added to CAZ after the first year of study. Of 206 evaluable episodes 76 (37%) were documented infections including 20 bacteremias; 130 (63%) episodes were caused by fever of unknown origin. The number of complete responses to initial therapy in patients with documented infections did not differ among regimens: 26 of 43 (61%) for KCG, 9 of 16 (56%) for ceftazidime and 8 of 16 (50%) for CAZ + vancomycin (not significant). In patients with fever of unknown origin, response without modification of the initial regimen was 52 of 62 (84%) in the KCG arm, 32 of 40 (80%) on CAZ and 23 of 29 (80%) in patients treated with CAZ + vancomycin (not significant). Modifications of the regimen were similar among all three groups and were due primarily to the use of empiric antifungal or antiviral therapy and to empiric treatment of interstitial pneumonia. Hypokalemia occurred in 25 of 105 patients treated with KCG and in 4 of 101 treated with CAZ or CAZ + vancomycin (P less than 0.001). No differences between the efficacy of KCG, CAZ and CAZ + vancomycin as initial empiric therapy were demonstrated.

Agranulocytosis↗
PubMed1982

Purification and partial characterization of a protein from cancer ascites fluid which stimulates the resorption of bone explants in vitro.

A protein capable of stimulating bone resorption in vitro has been purified approximately 1250-fold from cancer ascites fluid. Purification was accomplished employing successive fractionation with ammonium sulfate, ion exchange, and Cibacron blue affinity chromatography, isoelectric focusing, and selective adsorption on hydroxylapatite. The bone-resorptive protein obtained by this procedure appeared homogeneous in polyacrylamide gels at pH 9.5, migrating with the mobility of an alpha 2-globulin, and in sodium dodecyl sulfate polyacrylamide gels from which an apparent molecular weight of 43,000 was calculated. The amino acid composition of the bone-resorptive protein distinguished itself by the absence of methionine and by its relatively high content of glycine (17%) and proline (11%). Furthermore, the protein possesses a single NH2-terminal amino acid residue (glycine). The ascites protein was found to contain 19% carbohydrate by weight including a high content of sialic acid (15 residues/mol) as compared to the other sugars (27 residues/mol). As to its biological properties, the homogeneous ascites glycoprotein proved to be as potent as parathyroid hormone in its ability to stimulate bone resorption in vitro.

Adult↗
PubMed1982

Experimental osteogenesis with demineralized allogeneic bone matrix in extraskeletal sites.

Male albino rats were used to study the osteogenic potential of demineralized allogeneic bone matrix (DABM) grafts, in different stages of demineralization, placed in the anterior abdominal wall. The clinical evaluation, radiologic examination, calcium determination, and histologic (light and electron microscopic) studies showed that completely demineralized allogeneic bone matrix (CDABM) grafts were not rejected and that they stimulated new bone formation at the transplant sites. On the other hand, partially demineralized allogeneic bone matrix (PDABM) grafts were frequently rejected and showed minimal bone induction and gradual demineralization.

Abdominal Muscles↗
PubMed1980

Effects of a bone resorptive factor from human cancer ascites fluid on rat bone cell calcium and cyclic AMP.

The effects of a bone resorptive protein isolated from human cancer ascites fluid on bone cell calcium and cyclic AMP were studied with fetal rat cells. The osteoclast-activating factor increased bone cell calcium uptake at 37 degrees C and 4 degrees C with no direct effects on calcium efflux. Concentrations of the resorptive factor that increased in vitro bone resorption and cell calcium uptake had no effect on cyclic AMP. The effects of the protein on calcium uptake were not specific for bone cells, and large increases were also observed in isolated fetal rat skin cells. These studies suggest that increases in the permeability of the cell membrane to calcium are involved in the mechanism of action of the ascites fluid resorptive protein.

Animals↗
PubMed1979

Cyclic AMP formation and release by cultured bone cells stimulated with prostaglandin E2.

PGE2 produced a marked and dose-related increase in cAMP content of cultured bone cells and in the release of cAMP into the incubation medium. The amount of cAMP released from the cells by PGE2 was proportional to the cellular concentration, and was dependent upon the time of incubation with PGE2. The cAMP levels released into the media increased slowly at a linear rate during a 60 min treatment with PGE2. This release was blocked by theophylline, probenecid, ouabain and dinitrophenol, suggesting that the release of cAMP was not a simple diffusive process and required energy. SC-19220 reduced the formation of cAMP more than the release, suggesting that the formation and the release may arise from separate events. Inability of D600 to inhibit PGE2-induced release of cAMP indicates that the release does not require calcium.

Animals↗
PubMed1978

Suppression of calcific fibrous-fatty plaque formation in rabbits by agents not affecting elevated serum cholesterol levels. The effect of thiophene compounds.

We tested the suppressive effect of antihypercalcemic-hyperphosphatemic agents on atherogenesis. We studied five groups of rabbits for 8 weeks, one control group and four groups on a fibrogenic atherogenic diet. One group received the atherogenic diet alone, and the remaining three atherogenic groups were treated simultaneously with 2-thiophenecarboxylic acid (ThCA), 5-methyl-2-thiophenecarboxylic acid (5-CH3-ThCA), and 5-bromo-2-thiophenecarboxaldehyde (5-Br-ThCA). Rabbits receiving the atherogenic diet alone developed: (1) elevations of serum cholesterol, calcium, and phosphorus; (2) massive fibrous-fatty aortic plaques with excessive accumulation of aortic collagen, elastin, and lipids; (3) marked deposition of calcium and phosphorus in both aortic tissue and elastin; and (4) severe lipid infiltration of the liver. Treatment with all three drugs normalized the elevated serum calcium but not the cholesterol levels, and effectively inhibited all aspects of the atherosclerotic process as determined morphologically and biochemically. The order of effectiveness was: 5-CH3-ThCa greater than 5-Br-ThCA greater than ThCA. No bone resorption occurred in the treated groups. The normalizing effects of the thiophene compounds on serum phosphorus levels were not significant at the dosages used.

Animals↗
PubMed1978

Isolation of a bone-resorptive factor from human cancer ascites fluid.

A protein fraction that induces the resorption of bone explants in organ culture was isolated from the ascitic fluid of patients with advanced cancer metastatic to the peritoneal cavity. Partial purification was achieved by means of gel filtration, affinity chromatography, and ion-exchange chromatography. The isolated fraction, the components of which have an apparent molecular weight of 60,000, was found to be heterogeneous by disc gel electrophoresis and to be composed primarily of proteins with relatively acidic electrophoretic properties. The specific bone-resorptive activity of this protein fraction was greatly increased over that of the unfractionated starting material, and the activity could be completely destroyed upon incubation with pronase and on heating. As determined by immunoassay and extraction procedures with various solvents, the bone-resorptive action of the isolated fraction was not attributable to the presence of parathyroid hormone, prostaglandin E2 or vitamin D-like sterols. In parallel experiments the supernatants of phytohemagglutinin-stimulated normal human peripheral leukocytes were subjected to identical chromatographic techniques, and a proten fraction with a molecular weight of 60,000, which resembled the resorptive fraction isolated from cancer ascites fluid and which contained significant bone-resorptive activity, was also partially purified.

Adult↗
PubMed1976

Effects of prostaglandins and other drugs on the cyclic AMP content of cultured bone cells.

Prostaglandins of the E-series (PGE1 and PGE2) may be involved in disease-related, localized loss of bone. E-prostaglandins increase the cyclic AMP content of many cells; and, to determine if their effects on bone are mediated by cyclic AMP, we examined the effects of E-prostaglandins and of other agents on the cyclic AMP content of cultured bone cells. PGE2 produced a rapid, marked and dose-related increase in the cyclic AMP content of confluent monolayers of bone cells isolated from newborn rat calvaria. At 2.8 X 10(-6) M, PGE1 and PGE2 had approximately the same effect, while the effect of PGF2alpha was much less pronounced. In the presence of theophylline, PGE2 had a more marked effect than parathyroid hormone (PTH) and the combination of PGE2 and PTH had a synergistic effect. The divalent, cationic, ionophore, A23187, produced an increase in cellular cyclic AMP and had an additive effect in combination with PGE2. Synthetic salmon calcitonin (CT), which inhibits the bone resorptive effect of PGE2, increased cellular cyclic AMP and had an additive effect in combination with PGE2. A prostaglandin antagonist, SC-19220, partially inhibited the resorptive effect of PGE2 and reduced its effect on cellular cyclic AMP. The calcium antagonist, D600, inhibited the bone resorptive effects of PGE2 but had no effect on increased cellular cyclic AMP produced by PGE2. The marked effect of PGE2 on bone cell cyclic AMP suggests that this action is involved in the mechanism of PGE2-related bone loss. The fact that agents with different effects on PGE2-induced increases in cellular cyclic AMP can inhibit its resorptive actions, suggests that PGE2-induced changes in cyclic AMP may be related less to its resorptive actions than to its inhibitory effect on bone formation.

Animals↗
PubMed1976

Relative accretion of 99mTc-polyphosphate by forming and resorbing bone systems in rats: its significance in the pathologic basis of bone scanning.

The relative roles of osteogenesis andd osteolysis in the production of positive radionuclide images of skeletal lesions were investigated. The uptake of 99mTc-polyphosphate (Tc-PP) by each process was measured in an animal model that permitted bone formation and resorption to be studied independently. Ten rats received intramuscular implants of bone-forming demineralized matrix (DM) and resorbing devitalized bone (DV). Radiographs and Tc-PP scintiscans were made each week thereafter. At 6-10 weeks, the implants and normal bone samples were removed, counted for 99mTc, and examined histologically. The uptake of Tc-PP BY DM implants was first detected on images made 3 weeks after implanatation, and by DV implants, 1-2 weeks later. Serial radiography showed progressive calcification of DM an resorption of DV implants. Microscopic examinations of undecalcified sections, stained with a modified Goldner preparation, revealed vital-bone formation in the DM implants and osteoclastic resorption in the DV. Activity counts per gram of DM and DV implants were, respectively, 200% and 90% that of normal bone. Since only the bone-forming system (DM) accumulated Tc-PP at greater than normal concentrations, this study indicates that positive bone images of osteolytic lesions solely reflect compensatory osteogenic responses.

Animals↗
PubMed1975

Osteogenesis within polyethylene implants at fracture gaps.

Sterile 7 mm. polyethylene implants were implanted in standard 6 mm. bilateral midfibular fracture gaps in thirty rats (sixty defects), and six rats were used as controls with identical bilateral midfibular fracture gaps. Clinical, radiologic, and histologic studies at a 12-week interval revealed osteogenesis at internal and external surfaces of implants resulting in bony union; however, gaps without implants resulted in fibrous union and nonunion.

Animals↗