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W J Anderson

Publications and source records attributed to W J Anderson.

At least 19 recordsLinked to original sources
PubMed2004

The needs of people with HIV in the UK: findings from a national survey.

The aim of this study was to describe the needs of people living with HIV in the UK. A questionnaire addressing 17 areas of need was completed by 1821 people living with HIV in the UK. The core need indicator was a personal assessment of happiness with current state. A quarter of all respondents were happy with their current state across all needs. For each need, the following proportions were unhappy with their current state: sex, 40%; anxiety/depression, 33%; sleep, 32%; self-confidence, 32%; money, 28%; household chores and self-care, 18%; housing, 18%; appetite, eating and drinking, 17%; friendships, 17%; discrimination, 16%; mobility, 15%; dealing with health professionals, 15%; relationships, 14%; drugs and alcohol, 9%; taking treatments regularly, 5%; HIV treatment knowledge, 4%; looking after children, 2%. Although some people with HIV are coping well with minimal unmet need, the overall picture of need is dominated by personal, social and economic issues.

Female↗
PubMed2002

Intracellular accumulation of beta-amyloid(1-42) in neurons is facilitated by the alpha 7 nicotinic acetylcholine receptor in Alzheimer's disease.

Amyloid beta(1-42), a major component of amyloid plaques, binds with exceptionally high affinity to the alpha 7 nicotinic acetylcholine receptor and accumulates intracellularly in neurons of Alzheimer's disease brains. In this study, we investigated the possibility that this binding plays a key role in facilitating intraneuronal accumulation of amyloid beta(1-42). Consecutive section immunohistochemistry and digital imaging were used to reveal the spatial relationship between amyloid beta(1-42) and the alpha 7 receptor in affected neurons of Alzheimer's disease brains. Results showed that neurons containing substantial intracellular accumulations of amyloid beta(1-42) invariably express relatively high levels of the alpha 7 receptor. Furthermore, this receptor is highly co-localized with amyloid beta(1-42) within neurons of Alzheimer's disease brains. To experimentally test the possibility that the binding interaction between exogenous amyloid beta(1-42) and the alpha 7 receptor facilitates internalization and intracellular accumulation of amyloid beta(1-42) in Alzheimer's disease brains, we studied the fate of exogenous amyloid beta(1-42) and its interaction with the alpha 7 receptor in vitro using cultured, transfected neuroblastoma cells that express elevated levels of this receptor. Transfected cells exhibited rapid binding, internalization and accumulation of exogenous amyloid beta(1-42), but not amyloid beta(1-40). Furthermore, the rate and extent of amyloid beta(1-42) internalization was related directly to the alpha 7 receptor protein level, since (1) the rate of amyloid beta(1-42) accumulation was much lower in untransfected cells that express much lower levels of this receptor and (2) internalization was effectively blocked by alpha-bungarotoxin, an alpha 7 receptor antagonist. As in neurons of Alzheimer's disease brains, the alpha 7 receptor in transfected cells was precisely co-localized with amyloid beta(1-42) in prominent intracellular aggregates. Internalization of amyloid beta(1-42) in transfected cells was blocked by phenylarsine oxide, an inhibitor of endocytosis. We suggest that the intraneuronal accumulation of amyloid beta(1-42) in Alzheimer's disease brains occurs predominantly in neurons that express the alpha 7 receptor. In addition, internalization of amyloid beta(1-42) may be facilitated by the high-affinity binding of amyloid beta(1-42) to the alpha 7 receptor on neuronal cell surfaces, followed by endocytosis of the resulting complex. This provides a plausible explanation for the selective vulnerability of neurons expressing the alpha 7 receptor in Alzheimer's disease brains and for the fact that amyloid beta(1-42) is the dominant amyloid beta peptide species in intracellular accumulations and amyloid plaques.

Aged↗
PubMed2001

Telomere associations in interphase nuclei: possible role in maintenance of interphase chromosome topology.

The relative sizes of individual telomeres in cultured human cells under conditions of cell cycling, replicative quiescence, cell transformation and immortalization were determined using quantitative fluorescence in situ hybridization (Q-FISH) with a telomere-specific peptide nucleic acid (PNA) probe. Results obtained from analysis of telomere length profiles (TLPs), which display the distribution of relative telomere lengths for individual cells, confirmed telomere length heterogeneity at the single cell level and proportional shortening of telomere length during replicative aging of virus-transformed cells. TLPs also revealed that some telomeric ends of chromosomes are so closely juxtaposed within interphase nuclei that their fluorescent signals appear as a single spot. These telomeric associations (TAs) were far more prevalent in interphase nuclei of noncycling normal and virus-transformed cells than in their cycling counterparts. The number of interphase TAs per nucleus observed in late-passage E6/E7-transformed cells did not increase during progression to crisis, suggesting that telomere shortening does not increase the frequency of interphase TAs. Furthermore, interphase TAs were rarely observed in rapidly cycling, telomerase-positive, immortalized cells that exhibit somewhat shortened, but stabilized, telomere length through the activity of telomerase. Our overall results suggest that the number of interphase TAs is dependent more on whether or not cells are cycling than on telomere length, with TAs being most prominent in the nuclei of replicatively quiescent cells in which nonrandom (even preferred) chromosome spatial arrangements have been observed. We propose that interphase TAs may play a role in the generation and/or maintenance of nuclear architecture and chromosome positional stability in interphase nuclei, especially in cells with a prolonged G(1)/G(0) phase and possibly in terminally differentiated cells.

Cell Cycle↗
PubMed2000

Radical radiotherapy for inoperable non-small cell lung cancer: what factors predict prognosis?

We set out to determine the factors that predict the outcome of conventional radical radiotherapy for inoperable non-small cell lung cancer. A retrospective casenote review was carried out of all 69 patients treated between 1986 and 1992 at the Northern Ireland Centre for Clinical Oncology, Belfast, with radical radiotherapy for inoperable non-small cell lung cancer. The tumour dose ranged from 45 Gy to 67.5 Gy, delivered in 15-30 fractions, 5 days per week over 3-6 weeks. All patients were followed up for 5 years. The disease was TNM Stage T1-T4N0-N2M0. The majority of tumours (51) were squamous. Overall survival was 63.8% (44-patients; 95% confidence interval (CT) 51.3-75.2) at one year; median survival was 16 months and 5-year survival was 13% (nine patients; 95% CI 6.1-23.3). Five-year survival for the 36 patients with stage T1 or T2 disease was 5.6% (2 patients). Five-year survival for the 33 patients with stage T3 or T4 disease, all with tumours at or near the carina, was 21.2% (seven patients). A WHO performance status of 0 or 1 (P = 0.03, Cox proportional hazards model) was associated with a better chance of survival.

Adult↗
PubMed2000

Childhood exposure to infection and risk of adult onset wheeze and atopy.

BACKGROUND: The prevalence of asthma and allergic diseases in children and young adults is inversely associated with family size. It has been suggested that more frequent exposure to infections in a large family group, particularly those spread by the faecal-oral route, may protect against atopic diseases, although not all published data support this hypothesis. Whether similar considerations apply to adult onset wheeze is unknown. The relationship between adult onset wheezing and atopy measured in adulthood and childhood exposure to a range of infections was investigated. METHODS: A nested case control study of participants in a 30 year follow up survey was conducted. Questionnaire data on childhood infections had been obtained in a 1964 survey. In 1995 a further questionnaire on respiratory symptoms and other risk factors for wheezing illness was administered, total IgE, skin and RAST tests were performed, and serum was stored. In 1999 serological tests for hepatitis A, Helicobacter pylori, and Toxoplasma gondii were performed on the stored samples. Information from the 1964 questionnaires was available for 97 cases and 208 controls and serological tests were obtained for 85 cases and 190 controls. The potential risk factors were examined for all cases, those who reported doctor diagnosed asthma, those who described persistent cough and phlegm with wheeze, and subjects stratified by atopic status. RESULTS: The sibship structure was similar in cases and controls. In univariate analysis of all cases, childhood infections reported by parents as acquired either before or after the age of three years did not influence case:control or atopic status. Seropositivity was also similar for all cases and controls, but cases in the subgroup with chronic cough and phlegm were more likely to be seropositive for hepatitis A and H pylori. Seropositivity was unrelated to atopic status. In multivariate analyses both the effect of having two or more younger siblings (OR 0.1, 95% CI 0.03 to 0.8) and of acquiring measles up to the age of three (OR 0.2, CI 0.03 to 0.8) were significantly related to a lower risk of doctor diagnosed asthma. CONCLUSIONS: In these well characterised subjects, exposure to infections as measured by parental reports obtained at age 10-14 years and by serological tests obtained in adulthood did not influence the development of wheezing symptoms or atopic status in adulthood. However, early exposure to measles and family size may be associated with a lower risk of adult onset doctor diagnosed asthma.

Adolescent↗
PubMed2000

Dendritic alterations of cerebellar Purkinje neurons in postnatally lead-exposed kittens.

Many investigations have sought to determine the effect of lead exposure on the development of the cerebellum. This study addresses the effects of postnatal lead exposure in kittens on dendritic development of Purkinje cells. Golgi-Cox filled cells were used to measure dendritic branching patterns, spine density, height, width and distance from the cerebellar surface. The results revealed a significant increase in spine density and altered patterns of dendritic branching. Complex dendritic branching was evident with a progressive shift in peak branching peripherally. Lead-exposed Purkinje cells showed early sprouting with subsequent pruning. At 5 weeks of age dendritic branches on experimental cells were increased along the entire dendritic extent. Control Purkinje cells showed initial sprouting with subsequent pruning. Normal developmental growth spurts and lead-induced effects were evident on dendritic height, width and distance from the surface. Cerebella stained with hematoxylin and eosin and cresyl violet acetate showed no evidence of vascular damage or other pathologies. These findings corroborate the evidence of hyperspiny dendritic formation representing an important mechanism of neuronal plasticity. In regard to morphological effects of lead on rodents, the hyperspiny Purkinje cell dendrites and patterns of dendritic growth in lead-treated kittens offer an alternative interpretation of neurobehavioral findings of lead-burdened children. The results are discussed with reference to other aspects of lead exposure and neural development.

Animals↗
PubMed1995

Clinical toxicity of peripheral nerve to intraoperative radiotherapy in a canine model.

PURPOSE: The clinical late effects of intraoperative radiotherapy (IORT) on peripheral nerve were investigated in a foxhound model. METHODS AND MATERIALS: Between 1982 and 1987, 40 animals underwent laparotomy with intraoperative radiotherapy of doses from 0-75 Gy administered to the right lumbosacral plexus. Subsequently, all animals were monitored closely and sacrificed to assess clinical effects to peripheral nerve. This analysis reports final clinical results of all animals, with follow-up to 5 years. RESULTS: All animals treated with > or = 25 Gy developed ipsilateral neuropathy. An inverse relationship was noted between intraoperative radiotherapy dose and time to neuropathy, with an effective dose for 50% paralysis (ED50) of 17.2 Gy. One of the animals treated with 15 Gy IORT developed paralysis, after a much longer latency than the other animals. CONCLUSIONS: Doses of 15 Gy delivered intraoperatively may be accompanied by peripheral neuropathy with long-term follow-up. This threshold is less than that reported with shorter follow-up. The value of ED50 determined here is in keeping with data from other animal trials, and from clinical trials in humans.

Animals↗
PubMed1995

Dendritic alterations of cortical pyramidal neurons in postnatally lead-exposed kittens: a Golgi-Cox study.

Cortical pyramidal cell development was studied in postnatally lead-exposed kittens by light microscopic and Golgi staining methods. The most evident finding was an elevation of spine density on the distal apical dendritic branches of lead-treated kittens. Also, the branching pattern of the apical dendrites in lead-treated animals was different from control, but there was no overall change in total branch number of the dendritic arbor. Pyramidal cell height and cortical thickness were unaffected. No evidence of vascular damage or other pathologies were found in hematoxylin and eosin-stained sections. The results are discussed with reference to dendritic spine development and function and to other reports of hyperspiny dendrites. Evidence of hyperspiny dendrites in the present study indicates this represents a useful protocol for investigating dendritic spine development and differentiation.

Aging↗
PubMed1994

Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model.

PURPOSE: The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. METHODS AND MATERIALS: Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. RESULTS AND CONCLUSION: Dogs receiving IORT to the retroperitoneum through a 4 x 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses > or = 30 Gy. Radiation changes were present in the aorta and vena cava at doses > or = 40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed a few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT.

Anastomosis, Surgical↗
PubMed1994

Noradrenergic innervation of ectopic granule cells following low-level X-irradiation.

The distribution pattern of the noradrenergic system within the cerebellar cortex following low-level X-irradiation was studied using immunocytochemistry. Following one X-irradiation exposure on postnatal day 1, the laminar distribution of tyrosine hydroxylase-like immunoreactive (THIR) fibers was similar to controls at postnatal day 30, but the orientation of the fibers in the molecular layer (ML) was slightly changed. Successive daily doses, however, produced alterations in both the pattern and concentration of THIR fibers within the ML of the cerebellar cortex. In addition, THIR fibers were found among ectopic cell clusters within the ML. This relationship suggests a potential role for the noradrenergic system in the development and/or maintenance of the ectopic cell clusters.

Aging↗
PubMed1994

Noradrenergic innervation of the external granular layer of the rat following low-level X-irradiation.

The distribution of the noradrenergic system within the rat cerebellar cortex following low-level X-irradiation was studied using tyrosine hydroxylase immunocytochemistry. X-Irradiation treatments consisted of 1, 3, or 5 successive daily dose beginning on postnatal day 1. When studied 24 h after the last exposure, a dense plexus of tyrosine hydroxylase-like immunoreactive (THIR) fibers, not found in age-matched controls, was observed in the reduced external granular layer (EGL) in each treatment group. At 10 days of age, the THIR fibers were found in association with the reconstituted cells of the premigratory zone of the EGL. The rapid and abnormal innervation of the EGL by the THIR fibers suggests that the noradrenergic system could play a role in the regeneration of this layer.

Animals↗