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Biomedical subjects

A Thornton

Publications and source records attributed to A Thornton.

At least 55 records · Page 3Linked to original sources

Motor and cognitive function in Lewy body dementia: comparison with Alzheimer's and Parkinson's diseases.

OBJECTIVE: Motor and cognitive function were compared in patients with Lewy body dementia, Parkinson's disease, or Alzheimer's disease, to identify features that may be clinically useful in differentiating Lewy body dementia from Alzheimer's disease and Parkinson's disease. METHODS: A range of neuropsychological function and extrapyrimidal signs (EPS) was assessed in 16 patients with Lewy body dementia, 15 with Parkinson's disease, 25 with Alzheimer's disease, and 22 control subjects. RESULTS: The severity of total motor disability scores increased in the following order: controls approximately = Alzheimer's disease << Parkinson's disease < Lewy body dementia. Compared with patients with Parkinson's disease, patients with Lewy body dementia had greater scores for rigidity and deficits in the finger tapping test, but rest tremor and left/right asymmetry in EPS were more evident in Parkinson's disease. Patients with Lewy body dementia were also less likely to present with left/right asymmetry in EPS at the onset of their parkinsonism. "Sensitivity" to neuroleptic drugs was noted in 33% of patients with Lewy body dementia. Alzheimer's disease and Lewy body dementia groups had greater severity of dementia compared with the Parkinson's disease group and controls. Neuropsychological evaluation disclosed severe but similar degrees of impaired performances in tests of attention (digit span), frontal lobe function (verbal fluency, category, and Nelson card sort test) and motor sequencing in both Lewy body dementia and Alzheimer's disease groups, than Parkinson's disease and controls. In the clock face test, improved performance was noted in the "copy" compared to "draw" part of the test in controls, patients with Alzheimer's disease, and those with Parkinson's disease, but not in the patients with Lewy body dementia, who achieved equally poor scores in both parts of the test. CONCLUSIONS: EPS in Lewy body dementia resemble those seen in idiopathic Parkinson's disease, although less rest tremor and left/right asymmetry but more severe rigidity favours a diagnosis of Lewy body dementia. The unique profile of patients with Lewy body dementia seen in the clock face test suggests that this simple and easy to administer test may be useful in the clinical setting to differentiate Lewy body dementia and Alzheimer's disease.

Aged↗

Expression of IFN regulatory factor family proteins in lymphocytes. Induction of Stat-1 and IFN consensus sequence binding protein expression by T cell activation.

Interferon consensus sequence binding protein (ICSBP) is a transcription factor of the IFN regulatory factor (IRF) family. Evidence indicates that this family has a function in the immune system. Unlike other members of the family, ICSBP is expressed exclusively in the immune system. In this work, immunoblot analysis was performed to study expression of ICSBP and other members of the family in various murine lymphocytes. The results show that all IRF family members are expressed constitutively in B cells throughout development, and in resting and activated cells. In contrast, ICSBP expression was undetectable in thymocytes and resting T cells, while all other IRF proteins tested (IRF-1, IRF-2, and ISGF3-gamma) were detected in these cells. Induction of ICSBP (and weakly IRF-1, but not other members) was observed upon activation of T cells following anti-CD3 Ab binding or Con A stimulation. Once T cells were activated, ICSBP was expressed stably in both Th1 and Th2 cells. We show that Stat-1, which binds to the IFN-gamma-responsive element of the ICSBP promoter, was induced following anti-CD3 Ab and Con A stimulation. Stat-1 induction was found in T cells of IFN-gamma+/+, but not of IFN-gamma-/- mice, indicating that T cell activation stimulates the Stat pathway of transcription that is mediated through IFN-gamma. IFN-gamma-activated Stat-1 partly accounted for ICSBP induction in activated T cells, as levels of induction were lower in IFN-gamma-/- than in IFN+/+ T cells. Taken together, these results show that activation of ICSBP is coupled with T cell activation that is partly due to IFN-gamma-induced Stat-1.

Amino Acid Sequence↗

Infiltration by immunocompetent cells in early stage invasive carcinoma of the uterine cervix: a prognostic study.

In various tumor types dentritic cell, infiltration and the presence of tumor-infiltrating lymphocytes have been associated with an improved clinical outcome. In the uterine cervix these immunocompetent cells have been associated with improved prognosis in high stage disease. The current study examines the significance of stromal and tumor T-lymphocyte infiltration together with S-100 positive dendritic cell infiltration in a series of 73 women with low stage (FIGO 1b) invasive squamous and adenosquamous cervical carcinoma. Thirty four percent of cases contained S-100 positive dendritic cells. These were under-represented in cases showing pelvic recurrence or distant disease (1 of 11 compared to 24 of 62 free of recurrence, P = 0.05) and over-represented in cases showing lymphatic/capillary space involvement (12 of 23 compared to 13 of 46 without vascular space invasion, P = 0.05). The women were followed up for an average of 5.2 years and the five-year survival for women whose tumors contained S-100 positive dendritic cells was 92% compared to 73% for negative cases (P = 0.04). There was a significant association between a low density of tumor infiltrating T-cells and risk of pelvic lymph node spread and subsequent local or distant disease control failure (P = 0.008). A five year survival advantage was seen with five or more CD 3 positive tumor infiltrating T-lymphocytes per high power field (90%) compared to a lower count (68%) (P = 0.04). A similar advantage could not be demonstrated for a high stromal infiltrate of T-cells. As yet neither the specific mechanisms that induce these cells to infiltrate some cervical carcinomas nor the nature of the immunological injury that the cells co-ordinate in tumor tissue are well understood.

Adult↗

Immunopathology of fatal soybean dust-induced asthma.

A hypothesis was postulated that the characteristic clinical course of fatal soybean asthma may be reflected by specific immunopathological findings. Seven cases of fatal soybean dust-induced asthma from Barcelona, Spain were compared with 25 fatal asthma cases from New Zealand. Sections of lung tissue were stained by monoclonal antibodies using standard streptavidin-biotin peroxidase technique. The following cell types were identified: mast cells, "activated" eosinophils, neutrophils, monocytes/macrophages, CD3+ T-cells and CD8+ T-cells. The positively staining cells were counted in the epithelium and the submucosa and their numbers expressed per mm and mm2, respectively. The airways were divided into larger (internal perimeter (Pi) > 2 mm) and smaller (Pi < 2 mm). Firstly, all airways were studied together; and subsequently, larger and smaller airways were studied separately. Differences in the numbers of mast cells, eosinophils, neutrophils and monocytes/macrophages between the two groups were not significant. The numbers of CD3+ and CD8+ T-cells were significantly reduced in fatal soybean asthma when all airways were taken together. In larger airways, the difference was not significant in the epithelium, but was significant in the submucosa for CD3+ cells. CD8+ cells were significantly reduced in fatal soybean asthma both in the epithelium and the submucosa. The cell counts in smaller airways were not significantly different either in the epithelium or in the submucosa for CD3+ cells. The numbers of CD8+ cells were not different in the epithelium, but were significantly reduced in the submucosa of fatal soybean asthma cases. We conclude that the numbers of CD3+ and CD8+ T-cells are substantially reduced in fatal soybean asthma. These data together with the clinical features of the fatal attack suggest a different mechanism(s) from that described for most asthma deaths, probably involving anaphylaxis.

Adult↗

The influence of parents' martial dissolutions on children's attitudes toward family formation.

We investigate the influence of parents' martial dissolutions on their children's attitudes toward several dimensions of family formation. Hypotheses focus on the role of patients' attitudes as a mechanism linking parents' behavior to their children's attitudes. We test these hypotheses using intergenerational panel data that include measures of children's attitudes taken directly from children. Results demonstrate strong effects of parental divorce, remarriage, and widowhood on children's attitudes toward premarital sex, cohabitation, marriage, childbearing, and divorce. The results also show that parents' own attitudes link their behavior to their children's attitudes, although substantial effects of parental behavior remain after controlling for parents' attitudes.

Adolescent↗

Proliferation of renal cell carcinoma assessed by fixation-resistant polyclonal Ki-67 antibody labeling. Correlation with clinical outcome.

BACKGROUND: Although tumor staging is an important prognostic parameter for renal cell carcinoma (RCC), postnephrectomy survival interval is often difficult to predict for individual patients. This is the result of varied growth characteristics, which in tumors of similar stage govern both time to recurrence and rate of tumor dissemination. Polyclonal Ki-67 antibody labels a proliferation-specific antigen expressed in actively proliferating cells and is applicable to formalin fixed paraffin embedded archival tissue. This study was designed to test the prognostic utility of Ki-67 antigen labeling in a series of RCC and to compare the data with those derived from other markers of cell proliferation. METHODS: Polyclonal Ki-67 antibody staining of 206 cases of RCC was undertaken using the streptavidin-biotin method. Cases were grouped according to Ki-67 indices and Kaplan-Meier survival curves were constructed. Groups were compared in terms of survival for all cases and for each of Robson's stages using the log rank test. Further sections were stained for proliferating cell nuclear antigen (PCNA) and silver-staining nucleolar organizer regions (AgNORs). The prognostic significance of Ki-67 antigen, PCNA and AgNOR staining, histologic grade, and tumor stage were compared using Cox's proportional hazard model. RESULTS: Ki-67 immunostaining was achieved for 173 cases with indices ranging from 0.1% to 30.4%. Division of tumors with indices 6% or less and greater than 6% showed a significant difference in survival between groups for all cases and for each Robson stage. Ki-67 and PCNA indices, AgNOR scores, and tumor dissemination (Robson Stage 3 and 4) retained a significant association with survival on multivariate analysis. CONCLUSIONS: Polyclonal Ki-67 antibody immunostaining provides significant survival information that complements that derived by other markers of cell proliferation and tumor staging.

Biomarkers, Tumor↗

Proliferation kinetics of streptozotocin-induced renal tumours in mice.

Renal tumours were induced in female mice 132 days after intravenous administration of streptozotocin. The tumours exhibited papillary and/or solid architecture with papillary tumours showing no histological evidence of malignancy. Malignant behaviour, manifest as infiltration of adjacent renal tissue and lymphatic infiltration, was noted for tumours with solid architecture. Intermediate architectural forms exhibiting dual papillary and solid architecture were identified. Proliferation kinetics were evaluated by enumeration of silver-staining nucleolar organizer regions and proliferating cell nuclear antigen expression. The results showed a stepwise progress in cell proliferation between histologically normal renal tubule epithelium [untreated animals, mean AgNOR score (MAS) 2.32, mean PCNA index (MPI) 0.53%; treated animals, MAS, 2.44; MPI 0.99%], dysplastic tubule epithelium (MAS, 4.15; MPI 1.65%), papillary tumours (MAS, 5.90; MPI 3.89%) and solid tumours (MAS, 6.94; MPI, 6.80%). Solid tumours as a group were significantly larger than papillary tumours and were associated with a significantly longer mean post-injection survival interval. The findings suggest that at least some solid tumours evolve from tumours exhibiting papillary architecture.

Adenoma↗

Ultrasonographic appearance of external callus in long-bone fractures.

High-resolution real-time ultrasound (US) scanning was used to monitor serially 24 patients with an acute long-bone fracture and three patients with humeral non-union, looking at the fracture site over a period of 12 months following the fracture. In both these groups, we found that US gave important information about the soft tissues surrounding the fracture site, and indicated callus formation at an early stage. US was more sensitive than conventional radiography at showing the early phases of organization of the callus, and its progression to bridging new bone formation. US also clearly showed a disorganized echopattern at the fracture site of the patients with non-union.

Adolescent↗

Comparison of silver-staining nucleolar organizer region (AgNOR) counts and proliferating cell nuclear antigen (PCNA) expression in reactive mesothelial hyperplasia and malignant mesothelioma.

Previous workers have used counts of colloidal silver-stained nucleolar organizer regions (AgNORs) to help distinguish reactive from malignant mesothelial processes. We sought to compare the demanding technique of AgNOR counting with the identification of proliferating cell nuclear antigen (PCNA) in 10 pleural malignant mesotheliomas and 11 reactive mesothelial proliferations. The mean AgNOR count was significantly higher in malignant compared to reactive lesions (5.10 [95% confidence interval, CI 4.35-5.84] vs 3.68 [95% CI 3.17-4.19], p = 0.004), as was the PCNA index (26.9 [95% CI 17.37-36.49] vs 9.67 [95% CI 4.94-14.39], p = 0.004). Less overlap was seen with PCNA indices and no reactive mesothelial proliferations had a PCNA index greater than 20%, suggesting that scores over this level may be a specific indicator of malignancy in this setting. There was only a weak correlation between the 2 proliferation indices suggesting that PCNA and AgNORs are present at somewhat different times of the cell cycle and/or persist in the post-S phase cell for variable lengths of time.

Adult↗

Radiation dose reduction in paediatric fluoroscopy using added filtration.

Studies on a water phantom indicate that the insertion of extra tube filtration combined with the removal of the antiscatter grid can reduce the total energy imparted from paediatric fluoroscopy by a factor of more than four when automatic exposure control is used. The omission of the grid is responsible for up to 40% of the reduction while the addition of 0.7 mm steel filtration is found to account for a further reduction in energy imparted of between 57% and 70%, for depths of water simulating small patients of 6-16 cm thickness. For all contrast paediatric examinations the reduction in image quality was considered to be small and the diagnostic information unimpaired with the filter in place.

Child↗

Transcriptional induction of genes by IFN-beta in mouse cells is regulated by a transcription factor similar to human ISGF-3.

Previous studies of IFN-stimulated transcription factors in murine cells have identified a variety of trans-acting factors that bind to the IFN-stimulated response element (ISRE) whose role in gene expression remain unclear. The present investigation was undertaken to delineate the signal transduction pathway as well as to identify the transcription factors regulated by murine IFN-beta in L929 cells. Tyrosine kinase inhibitor, Genistein, abrogated gene induction and activation of transcription factors by IFN-beta. As early as 5 min after IFN-beta treatment, a transcription factor was activated in the cytoplasm which subsequently migrated into the nucleus. Anti-phosphotyrosine antibodies detected a specific transcription factor induced by mIFN-beta. Antibodies raised against human ISGF-3 subunit proteins p48, p84, p91 and p113 recognized this factor in the cytoplasm as well as in the nucleus of IFN-beta-treated L929 cells. An antibody raised against an oligopeptide of human p113 (residues 435-450) recognized the ISGF-3 complexes both in human and murine cells. However, a different antibody against the C-terminus of human p113 (residues 671-806) did not recognize the ISGF-3 like complex in mouse cells, indicating differences in the primary sequence of these proteins.

Animals↗

Differences between smokers, ex-smokers, passive smokers and non-smokers.

The extent to which current, ex- and passive smoking are associated with other risk factors, and the potential for confounding arising from these associations, was studied using a representative sample of 9003 British adults. The distribution of 33 lifestyle factors generally considered associated with adverse health were compared in current smokers, ex-smokers, never smokers living with a smoker ("passive smokers") and other never smokers. Of the 33 risk factors 27 showed a significantly higher prevalence in heavy smokers than in never smokers and only two showed a lower prevalence. For many risk factors, prevalence increased with amount smoked, decreased with time of smoking cessation and was increased in passive smokers. The possible magnitude of bias from confounding by the risk factors is estimated. It is concluded that confounding by multiple risk factors may be an important issue in smoking studies where weak associations are observed. This applies particularly to studies investigating the possible association of passive smoking with various health effects.

Adult↗

Acute dystonic reactions complicated by psychotic phenomena.

Four schizophrenic patients are reported in whom the acute development of dystonic muscle spasms, usually involving gaze deviation, was accompanied by the exacerbation or appearance of psychotic symptoms. In all cases the relationship between the neurological and psychiatric phenomena was close, and sometimes the presentation was bizarre or dramatic. The similarity of these states to the complex neuropsychiatric disturbances seen in post-encephalitic Parkinsonism is emphasised.

Adult↗

Family influences on family size preferences.

Several studies have demonstrated important effects of parents' childbearing behavior on their children's childbearing preferences and behavior. The study described here advances our understanding of these family influences by expanding the theoretical model to include parental preferences, siblings' behavior, and changes in children's preferences through early adulthood. Using intergenerational panel data from mothers and their children, we test the effects of both mothers' preferences for their own fertility and mothers' preferences for their children's fertility. Although both types of maternal preferences influence children's childbearing preferences, mothers' preferences for their children's behavior have the stronger and more proximate effects. Mothers' preferences continue to influence their children's preferences through early adulthood; siblings' fertility is an additional determinant of children's family size preferences.

Adolescent↗

Low-frequency sensorineural loss: clinical evaluation and implications for hearing aid fitting.

Spread of excitation in the cochlea places fundamental limits on the interpretation of audiometric pure-tone hearing loss as a simple map of dysfunction along the cochlear partition, and histologic evidence from human temporal bones will be presented to demonstrate the insensitivity of the audiogram to variations in pathology in the case of low-frequency hearing loss. This article will describe a clinical procedure using simultaneous pure-tone masking to improve upon the localization of cochlear disease, particularly for low-frequency hearing losses, and a model for using the Articulation Index (AI) to develop prognoses for hearing aid performance in these cases, which can then be tested. Fourteen patients with low-frequency hearing loss were divided into two groups based upon threshold shifts caused by a pure-tone masker: those that showed normal low-frequency threshold shifts and those that showed marked shifts at frequencies below the masker, indicating greater loss of function than shown by the unmasked audiogram. Hypothetical audiograms were then generated to model a complete loss of apical function for all patients. Measured speech recognition scores were then compared to AI predictions for the actual and hypothetical audiograms. Best agreement for the patients showing normal masking shifts was between the measured scores and the AI for the actual audiogram, whereas the best agreement for the patients showing marked shifts was with the AI for the hypothetical audiogram. The implications for hearing aid recommendation and fitting in these cases are discussed.

Acoustic Stimulation↗