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Biomedical subjects

P Hudson

Publications and source records attributed to P Hudson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures.

Activation of brain glial cells with the bacterial endotoxin lipopolysaccharide (LPS), the HIV-1 coat protein gp120, or beta-amyloid-derived peptides, stimulates the expression of several cytokines, including tumor necrosis factor-alpha (TNFalpha), interleukin-1 (IL-1) and IL-6. and nitric oxide (NO) which have been proposed as causes of neurodegeneration in the brain. In the present study, the neurotoxic effects of several cytokines, alone or in various combinations, and the correlations of the release of lactate dehydrogenase, the loss of neurons, and the secretion of NO in brain neuronal cell injury were investigated in murine primary mixed neuronal/glial cell cultures. A specific combination of cytokines, i.e., IL-1 (1 ng/ml)+ TNFalpha (10 ng/ml)/interferon-gamma (IFNgamma) (200 u/ml), induced a dramatic neuronal cell injury in the neuron/glia cultures, and its cytotoxic profile was very similar to that seen with the LPS/IFNgamma-induced neuron injury. This indicates that among the many toxic immune mediators secreted in response to LPS, IL-1 and TNFalpha can mimic LPS as the triggering signals and primary mediators for glia-mediated neuron injury in the presence of IFNgamma. This study provides new insights about the cytotoxic mechanism(s) for cytokine-mediated neuron injury.

Animals↗
PubMed1998

Total serum homocysteine in senile dementia of Alzheimer type.

OBJECTIVE: The main hypothesis was that subtle vitamin B12 deficiencies occur more commonly in senile dementia of Alzheimer type (SDAT) that in healthy elderly individuals, and may be revealed by elevated total serum homocysteine (tHcy). A subsidiary hypothesis was that such deficiencies would be nutritionally independent as determined by retinol binding protein (RBP). DESIGN: A prospective case-controlled survey. SETTING: A Welsh urban psychogeriatric assessment centre and local general practice. PATIENTS: Thirty patients, aged 65 or over, seen consecutively in 1994 with features compatible with DSM-III-R criteria for primary degenerative dementia of Alzheimer type and 30 cognitively intact age-matched control subjects. MEASURES: Diagnosis was assessed using the CAMDEX. Cognitive scores were evaluated with the CAMCOG scale for patients and MMSE scores for control subjects. THcy was measured using high performance liquid chromatography (HPLC), and RBP assayed by a radial immunodiffusion method. RESULTS: Patients had a highly significant elevation of tHcy compared with control (p < 0.0001). Multiple regression highlighted the interrelated effects of tHcy and total serum cobalamin on cognitive scores. RBP did not differ between groups. Macrocytosis was absent, and neutrophil hypersegmentation uncommon, in hyperhomocysteinaemic patients. CONCLUSIONS: SDAT patients have significantly elevated tHcy. This is independent of RBP determined nutritional status. 'Classical' haematological changes of cobalamin or folate deficiency are poor predictors of tHcy in these patients. Aberrant cobalamin tissue delivery appears to contribute to SDAT cognitive decline. Relative contributions of other tHcy determinants require further investigation.

Aged↗
PubMed1998

Treatment with finasteride preserves usefulness of prostate-specific antigen in the detection of prostate cancer: results of a randomized, double-blind, placebo-controlled clinical trial. PLESS Study Group. Proscar Long-term Efficacy and Safety Study.

OBJECTIVES: To evaluate prostate cancer detection and prostate-specific antigen (PSA) among men with benign prostatic hyperplasia treated with finasteride. METHODS: Three thousand forty men 45 to 78 years of age with PSA less than 10 ng/mL and no history of prostate cancer were randomized in a double-blind, placebo-controlled trial to finasteride (n = 1524) or placebo (n = 1516) for up to 4 years. A prerandomization biopsy negative for prostate cancer was obtained in 98% of patients with a screening PSA of 4.0 ng/mL or more, and an end-of-study biopsy was requested of all such patients without a recent second negative biopsy or a prostate cancer diagnosis. RESULTS: Overall, 644 patients (21%) underwent biopsy and 201 (6.6%) underwent transurethral resection of the prostate. Prostate cancer was diagnosed in 4.7% of men on finasteride and 5.1% on placebo (P = 0.7). Elevated PSA prompted diagnosis in 35% of cases on finasteride and 34% on placebo. The area under the receiver operating characteristic curve for last PSA was 0.84 on finasteride and 0.79 on placebo (P = 0.07). Use of an upper limit of normal for last PSA of 2.0 ng/mL for finasteride and 4.0 ng/mL for placebo yielded similar sensitivity (66% versus 70%, P = 0.6), higher specificity (82% versus 74%, P < 0.0001), and a higher likelihood ratio (3.6 versus 2.7, P < 0.05) for finasteride than for placebo. CONCLUSIONS: In men treated with finasteride, multiplying PSA by 2 and using normal ranges for untreated men preserves the usefulness of PSA for prostate cancer detection.

Aged↗
PubMed1998

Expansion rates of small abdominal aortic aneurysms.

BACKGROUND: The present study was carried out in order to examine those factors that influence the rate of expansion of small abdominal aortic aneurysms. METHODS: A retrospective study was undertaken of 112 patients who attended the St George Vascular Laboratory between 1987 and 1997. These patients had abdominal aortic aneurysms that were considered to be too small to warrant surgical repair at the time of presentation. Sequential ultrasound examinations were used to measure maximal anteroposterior aneurysm diameter. From these data, annual growth rates were calculated. Growth rate per annum was then compared with gender, age, initial aortic aneurysm diameter, presence of hypertensive disease, cardiac disease, family history of aneurysmal disease, diabetes mellitus, smoking, beta-adrenergic blockade and lipid lowering drugs. RESULTS: Univariate analysis showed that three factors were significantly related to growth rate: the initial size of the aortic aneurysm, the presence of cardiac disease and the presence of beta-adrenergic blockade. CONCLUSIONS: The presence of beta-adrenergic blockade appeared to have an independent effect on aneurysm growth rate, and suggests a possible role for beta-adrenergic blockade as a therapeutic strategy in controlling expansion rates of small abdominal aortic aneurysms. A controlled double-blind clinical trial is required to demonstrate this conclusively.

Adrenergic beta-Antagonists↗
PubMed1997

Characterization of the long-lasting activator protein-1 complex induced by kainic acid treatment.

Kainic acid is known to induce seizures, neuronal damage and cell loss in the rat hippocampus. Our laboratory has shown that a single kainic acid injection elicits acute increases of activator protein-1 DNA-binding activity and this activity stays at an elevated level for 2 weeks after kainic acid injection. However, some pathological changes such as mossy fiber sprouting do not occur until 2-3 weeks after the kainic acid injection and the specific transcription factors regulating the long-term events after kainic acid treatment are not clear. To determine the involvement of activator protein-1 transcription factors in the long-term events after kainic acid treatment, gel mobility-shift and Western blot analyses were used. The results showed that two activator protein-1 complexes with different mobilities occur during the acute stage. However, only the faster-migrating complex as well as the 35-37-kDa fos-related antigen and Jun-D proteins were seen during the late stage. These results suggest that different activator protein-1 complexes exist at different stages after convulsions and that they regulate ensembles of different genes.

Animals↗
PubMed1997

A single dose of kainic acid elevates the levels of enkephalins and activator protein-1 transcription factors in the hippocampus for up to 1 year.

Neuronal plasticity plays a very important role in brain adaptations to environmental stimuli, disease, and aging processes. The kainic acid model of temporal lobe epilepsy was used to study the long-term anatomical and biochemical changes in the hippocampus after seizures. Using Northern blot analysis, immunocytochemistry, and Western blot analysis, we have found a long-term elevation of the proconvulsive opioid peptide, enkephalin, in the rat hippocampus. We have also demonstrated that an activator protein-1 transcription factor, the 35-kDa fos-related antigen, can be induced and elevated for at least 1 year after kainate treatment. This study demonstrated that a single systemic injection of kainate produces almost permanent increases in the enkephalin and an activator protein-1 transcription factor, the 35-kDa fos-related antigen, in the rat hippocampus, and it is likely that these two events are closely associated with the molecular mechanisms of induction of long-lasting enhanced seizure susceptibility in the kainate-induced seizure model. The long-term expression of the proenkephalin mRNA and its peptides in the kainate-treated rat hippocampus also suggests an important role in the recurrent seizures of temporal lobe epilepsy.

Animals↗
PubMed1997

A novel human prostate-specific, androgen-regulated homeobox gene (NKX3.1) that maps to 8p21, a region frequently deleted in prostate cancer.

We have isolated a prostate-specific gene (NKX3.1) in humans that is homologous to the Drosophila NK homeobox gene family. Northern blot analyses indicate that this gene is expressed at high levels in adult prostate and at a much lower level in testis, but is expressed little or not at all in several other tissues. In an androgen-dependent prostate carcinoma line, LNCaP, NKX3.1 mRNA is expressed at a basal level that was increased markedly upon androgen stimulation; the NKX3.1 mRNA was undetectable in several other human tumor cell lines including two androgen-independent prostate carcinoma lines. The NKX3.1 gene maps to chromosome band 8p21, a region frequently reported to undergo a loss of heterozygosity associated with tissue dedifferentiation and loss of androgen responsiveness during the progression of prostate cancer. Based on these data we propose that NKX3.1 is a candidate gene for playing a role in the opposing processes of androgen-driven differentiation of prostatic tissue and loss of that differentiation during the progression of prostate cancer.

Adult↗
PubMed1997

Long-term expression of Fos-related antigen and transient expression of delta FosB associated with seizures in the rat hippocampus and striatum.

Systemic administration of kainic acid (KA), an analogue of glutamic acid, causes limbic seizures and pathophysiological changes in adult rats that are very similar to human temporal lobe epilepsy. One of the earliest changes in gene expression after treatment with KA is the induction of immediate-early genes. The fos and jun families are frequently studied immediate-early genes that are induced by KA. Several groups, including ours, have recently reported that a 35-kDa Fos-related antigen (FRA) is induced for a protracted time by various stimuli. It has been suggested that this FRA is delta FosB, which has a molecular mass of approximately 35 kDa. The present study characterizes the long-term expression of FRA and delta FosB after systemic treatment with KA. Immunocytochemistry and western blot analysis using an antibody that cross-reacts with all known FRAs showed that a 35-kDa FRA was induced at high levels in both the hippocampus and striatum for up to 1 month by KA. A semiquantitative PCR analysis showed that delta FosB was induced by KA, but its expression lasted for only 6 h. This result was also verified by northern blot analysis. These results suggested that the 35-kDa FRA with long-term elevated levels seen with western blot analysis and immunocytochemistry is a new species of the FRA and not delta FosB. The long-term expression of FRA in both the hippocampus and striatum may be associated with the pathophysiological changes after KA administration.

Animals↗
PubMed1997

Evaluating large scale health information systems: from practice towards theory.

With the introduction of large scale health information systems which are incrementally developed from legacy systems, evaluators are faced with difficult methodological and practical problems. Some of the problems involved in multidisciplinary multi-method evaluations care discussed. It is argued that the development of a framework for evaluation is necessary in order to successfully plan an evaluation, understand the implications of the results and make future predictions based upon them. Some suggestions for arriving at such a framework are put forward.

Evaluation Studies as Topic↗
PubMed1997

The epidemiology of louping-ill, a tick borne infection of red grouse (Lagopus lagopus scoticus).

The epidemiology of louping-ill in red grouse was studied in northern Britain concentrating on the possible role of other species and mechanisms of disease persistence. This tick borne viral disease caused heavy mortality in red grouse, particularly chicks. Louping-ill induced mortality reduced the strength of the density dependence that generates the tendency of grouse populations to cycle and in some populations may cause population sinks. Four routes of transmission were examined and non-viraemic transmission of virus between ticks cofeeding on hares was considered significant. Field data supported the hypothesis that disease dynamics is influenced greatly by mountain hares, both as passive amplifiers and as hosts for the tick vector. Genetic variation in louping-ill within Britain was small.

Animals↗
PubMed1997

A survey to identify the important macroparasites of rock partridge (Alectoris graeca saxatilis) in Trentino, Italy.

A preliminary survey of the intestinal helminth community of rock partridge (Alectoris graeca saxatilis) was undertaken in the Italian province of Trentino where the host population exhibits cyclic fluctuations in abundance. Six helminth species were recorded from 38 rock partridge intestines collected during the hunting season between October and November 1994. Nematoda were the most prevalent (53%) with lower prevalence of Trematoda (11%) and Cestoda (8%). Ascaridia compar (Schrank, 1790) and Heterakis tenuicauda Linstow, 1883, were identified as the component species (each with prevalence > 10%) in the helminth intestinal community of rock partridge in Trentino. Both of these species exhibit an aggregated distribution.

Animals↗
PubMed1996

Evaluation of 15 commercial enzyme immunoassays for the detection of rubella-specific IgM.

BACKGROUND: Detection of rubella-specific IgM is a critical investigation in the diagnosis of recent or congenital rubella for which many commercial enzyme immunoassays (EIAs) are now available. OBJECTIVES: To evaluate 15 commercially-available EIA kits for the detection of rubella-specific IgM. STUDY DESIGN: A panel of 229 sera was established comprising 72 sera from cases of primary rubella, re-infection, congenital rubella and primary immunization in which rubella-specific IgM had been detected by M-antibody capture radioimmunoassay (MACRIA); 80 sera, negative by MACRIA and no evidence of recent illness; 77 sera from recent illness with a number of other microbial agents, sera containing rheumatoid factor, and sera previously shown to give non-specific reactivity by MACRIA. These sera were tested in 15 commercial EIA kits for rubella-specific IgM according to the manufacturers' instructions. Sensitivity and specificity for each assay was established. RESULTS: Specificities ranged from 82-98%, improving to 88-100% if the previously established non-specific reactive sera were excluded. Sensitivities ranged from 63-92%. Although only two sera from congenital rubella were tested, for one serum only four assays detected specific IgM. CONCLUSION: Some commercial EIAs for rubella-specific IgM now give an acceptable balance of sensitivity and specificity, but all assays may give reactivity with occasional sera where there is no supporting evidence for recent primary rubella or rubella reinfection.

Journal Article↗
PubMed1995

Selective killing of cholinergic neurons by microglial activation in basal forebrain mixed neuronal/glial cultures.

Microglia activation by lipopolysaccharides (LPS) significantly decreased choline acetyltransferase-immunopositive (ChAT+) neuron number and ChAT activity in rat primary basal forebrain mixed neuronal/glial cultures. The number of non-cholinergic (ChAT(-)) neurons was unaffected. LPS induced nitric oxide synthase (NOS) in microglia, increased the media level of the NO metabolite nitrite, and the NOS inhibitor Ng-nitro-L-arginine methylester (NAME) protected the ChAT+ neurons from LPS. The combination of beta-amyloid peptide (1-42) and interferon-gamma (INF-gamma) also increased the media nitrite level and decreased ChAT+ neuron number. Cholinergic neurons are lost early in the course of Alzheimer's disease, and the enhanced sensitivity of these neurons to microglial activation in mixed neuronal/glial culture may be useful for modeling Alzheimer's disease and developing therapeutic strategies to combat this disease.

Amyloid beta-Peptides↗