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Biomedical subjects

F Hughes

Publications and source records attributed to F Hughes.

At least 19 recordsLinked to original sources
PubMed1999

Retroviral transduction of human periodontal cells with a temperature-sensitive SV40 large T antigen.

The periodontal ligament (PDL) is considered to contain subpopulations of cells responsible for the development, repair and regeneration of the periodontium. Cell cultures have been used as model systems in order to understand the complex cellular and biochemical events underlying these processes. In order to obtain long-term cultures of these cells that can be cloned and characterized, primary cultures of PDL and gingival cells were infected with an amphotropic retroviral construct encoding a temperature-sensitive SV40 large T antigen (tsT). After selection for drug resistance, the cells expressed the T antigen and proliferated at 34 degrees C for more than 40 passages. However, when the T antigen was inactivated by incubation at 39 degrees C, the cultures became growth-arrested and the granularity of the cells increased, possibly as a result of differentiation. Reverse transcribed-polymerase chain reaction and flow cytometry showed that the tsT-transduced cells expressed a number of soft and hard connective-tissue antigens, including osteocalcin, osteonectin, osteopontin, collagen type I and alkaline phosphatase. Moreover, incubation of the transduced PDL cells at 39 degrees C was found to upregulate the expression of osteocalcin, osteopontin and collagen type I, but downregulate osteonectin. At this temperature, the presence of the dexamethasone downregulated type I collagen, while vitamin D3 had no effect on the expression of any of the antigens examined. Under all culture conditions, antigen expression was far higher in the transduced PDL cells than the gingival cells. The findings thus show that growth of the tsT-transduced PDL and gingival cells is temperature-dependent and that the presence of the T antigen increases their lifespan but does not ablate the expression of certain of their characteristic phenotypic and functional features.

Alkaline Phosphatase↗
PubMed1997

The relationship between life-events and periodontitis. A case-control study.

This case-control study (n = 100 dental patients, matched for age and sex) investigated the role of life-events in periodontitis. Data collected included life events, tobacco use, oral health behaviours and socio-demographics. The results of conditional simple logistic regression analysis showed that periodontitis was associated with the negative impact of life-events (p < 0.01), the number of negative life-events (p < 0.05), high levels of dental plaque (p < 0.01), tobacco smoking (p < 0.01) and being unemployed (p < 0.05). These associations remained statistically significant after adjusting for oral health behaviour and socio-demographic variables, but not tobacco smoking (p > 0.05). Marital status became statistically significant after adjusting for the other variables (p < 0.05). A model is suggested to explain the pathways through which life events may affect periodontal health. It was concluded that psychosocial factors and oral health risk behaviours cluster together as important determinants of periodontitis.

Adolescent↗
PubMed1994

Mental attitude.

Explore the source record for details and available documents.

Community Mental Health Services↗
PubMed1993

A comparative study of cefepime and ceftazidime in the treatment of community-acquired lower respiratory tract infections.

Antibiotic treatment for community-acquired pneumonia must target Gram-positive pathogens, especially frequently isolated organisms such as Streptococcus pneumoniae. The severity of community-acquired pneumonia is often related to underlying factors. Occasionally it may be complicated by staphylococcal or Gram-negative bacillary infection. We have compared the safety and efficacy of cefepime 1 g bd with ceftazidime 1 g tds as empirical treatment in adults with community-acquired lower respiratory tract infections (LRTIs). One hundred and thirty-one patients with moderate to severe LRTIs were randomized to two treatment groups: 87 received cefepime and 44 received ceftazidime. The treatment groups were comparable with regard to sex, age and treatment duration. Of the 116 pathogens isolated, 57 were Gram-positive (46 strains of S. pneumoniae) and 59 were Gram-negative (33 strains of Haemophilus influenzae). Of the 111 patients evaluated, clinical cure rates were 87% (65/75) in the cefepime group and 86% (31/36) in the ceftazidime group. Pathogen eradication rates were 95% (74/78 and 36/37, respectively) in both groups. Both drugs were well tolerated and the incidence of adverse events in each group was comparable. Cefepime 2 g per day (1 g bd) was as safe and effective as ceftazidime 3 g per day (1 g tds) in the treatment of community-acquired LRTIs.

Adult↗
PubMed1991

Osteogenic progenitor cells in rat bone marrow stromal populations exhibit self-renewal in culture.

Marrow stromal cells are a heterogeneous population, comprising a variety of lineages including osteogenic cells. In the presence of ascorbic acid, sodium beta-glycerophosphate, and dexamethasone, rat bone marrow stromal cells form discrete nodules of mineralized, bonelike tissue. We used nodule formation by rat bone marrow stromal cells to assay for the self-renewal capacity of osteogenic progenitor cell populations. Cultures were subcultured every 5 days up to six times. Osteogenesis was assayed from second to sixth subcultures by counting the number and measuring the areas of mineralized nodules formed in cultures grown with 10(-8) mol/L dexamethasone. Nodule number and area decreased progressively between second and sixth subcultures. Alkaline phosphatase activity associated with individual cells and measured videodensitometrically decreased exponentially between the second and sixth subculture. The number of cells with alkaline phosphatase activity also decreased with progressive subculturing. The proportions of 3H-thymidine-labeled cells after continuous labeling from the beginning of the culture period showed 90% labeling for cells with alkaline phosphatase activity and fibroblastlike cells. Cultures labeled for only the first 3 days exhibited higher labeling of alkaline phosphatase-positive cells than fibroblastlike cells (P less than .05). Cultures that were flash-labeled at the end of the culture period demonstrated low labeling indices for cells with alkaline phosphatase activity and up to 10-fold higher labeling indices for fibroblastlike cells. Separate cultures treated with a cytocidal dose of high specific activity 3H-thymidine did not form nodules. These results indicate that osteogenic progenitor cells or another cell type required for nodules to develop must divide early in culture if nodule formation is to occur, and that osteoprogenitor cells express a limited capacity for self-renewal.

Alkaline Phosphatase↗
PubMed1986

Primary lymphoma of the thyroid: clinical features, prognostic factors, and results of treatment.

This study analyzes the results of 46 cases of biopsy-proven primary lymphoma of the thyroid, localized at diagnosis and treated at the Royal Marsden Hospital between 1948-1980. In all cases, disease was limited to the thyroid and cervical lymph nodes. There were 43 females and 3 males, with a mean age of 64.4 years (median 66 years; range 17-86). A short history (less than 3 months) of a neck mass and local compressive symptoms was the typical presentation. The majority of patients (91%) had adverse histologies, with diffuse histiocytic lymphomas being most common (78%). The overall crude 5-year survival rate was 40%, with 30% of patients surviving beyond 10 years. Disease-free and overall survival were virtually identical, indicating the ineffectiveness of salvage therapy. The important prognostic factors were: size of tumor, fixation, extra-capsular extension, and retrosternal involvement. Survival was not correlated with age, sex, histology, thyroid status, or stage of disease, as defined by the Ann Arbor classification. Patients who had total macroscopic removal of tumor had the highest rate of local control and long survival (p less than 0.005). No significant difference was seen between lobectomy, subtotal or total thyroidectomy, but 7 of 9 long-term survivors (58-129 months) have had total thyroidectomy. A radiotherapy dose to the tumor, of at least 40 Gy, was required to produce consistent local control in patients with unresected disease. The majority of patients who died had generalized disease. Only 52% of these patients were free of local recurrence. In view of the frequency of occult disseminated disease, adjuvant chemotherapy is one recommendation for patients with poor prognostic factors. For optimal local control, complete surgical eradication is recommended followed by high-dose local radiotherapy. The use of aggressive cytoreductive chemotherapy prior to radiotherapy is a possible alternative option which needs to be explored.

Adolescent↗
PubMed1983

An assessment of the value of epithelial membrane antigen and other epithelial markers in solving diagnostic problems in tumour histopathology.

Using standard immunohistological techniques on formalin-fixed paraffin-embedded sections, we have evaluated the role of epithelial membrane antigen in the histopathological diagnosis of tumours. Of the 70 samples examined, 22 were taken for staging purposes from patients known to have carcinoma and, in half these cases, malignant cells were seen which could not be identified with confidence by conventional means. Forty-eight tumours were stained in order to determine their histogenesis. Twenty-two of these were positive and 20 subsequently proved to be epithelial on follow-up studies, including six in which a diagnosis of non-epithelial malignancy had been made on conventional preparations. The distinction of anaplastic carcinoma from malignant lymphoma and of spindle-cell carcinoma from sarcoma were the most useful applications. One of the positive tumours was of germ cell origin and in one the histogenesis is still not clear. Comparison with carcinoembryonic antigen and pre-keratin showed that epithelial membrane antigen was the most sensitive marker of epithelial differentiation in formalin-fixed tissue. A combination of all three reagents, though, increases diagnostic accuracy and allows tentative suggestions to be made about the possible site of origin of a metastatic carcinoma.

Antigens, Surface↗
PubMed1977

Primary carcinoma of the trachea.

Two cases of primary carcinoma of the trachea are described. Both patients were female and had smoked cigarettes for many years. One of the tumours was a squamous cell carcinoma and the other an oat cell carcinoma, the commonest and the rarest forms of tracheal cancer respectively. The diagnosis in the case of oat cell carcinoma was confirmed by electron-microscopic demonstration of neurosecretory granules, a unique observation at this site. Oat cell carcinoma of the trachea does not appear to have been recorded previously in a female.

Carcinoma, Small Cell↗
PubMed1976

Spin-labeled stearates as probes for microenvironment of murine thymocyte adenylate cyclase-cyclic adenosine 3':5'-monophosphate system.

The interaction of various spin-labeled compounds with the murine thymocyte adenylate cyclase-cyclic AMP system was investigated. Electron paramagnetic resonance spectra from spin-labeled compounds were used to calculate the order parameter, S, and indicated that the thymocyte plasma membrane is a relatively rigid structure. Increasing concentrations of spin-labeled stearates, but not their corresponding methyl esters, resulted in increased membrane fluidity, partial lysis, and concomitant complete inhibition of cholera toxin-mediated increases in cyclic AMP content. Upon subsequent isolation of plasma membranes from these cells, cholera toxin-stimulated adenylate cyclase activity was also completely inhibited. Direct addition of spin-labeled stearates, but not spin-labeled methyl stearates, to thymocyte homogenates caused a dramatic reduction of basal, cholera toxin-, isoproterenol-, NaF-, and prostaglandin E1-stimulated adenylate cyclase activity. Inhibition was complete within the first minute of addition to homogenates and required approximately 0.2 mM spin-labeled stearate I(12,3) for half-maximal inhibition. This inhibition occurred in the presence or absence of an ATP-regenerating system and was not readily reversible. Furthermore, since the membrane cyclic phosphodiesterase activity was not altered by spin-labeled stearates, their inhibition was attributed to a direct action of stearate spin labels on adenylate cyclase. Neither stearate, methyl stearate, spin-labeled methyl stearates nor 2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempo) altered cell viability or enzyme activities at the concentrations studied. Spin-labeled stearates seemed to intercalate into different areas of the plasma membrane than their corresponding methyl esters. Furthermore, the action of spin-labeled stearates appeared to be on the exterior of the plasma membrane rather than the interior. These results illustrate the presence of multilipid domains and the importance of selected lipids and lipid-protein interactions in the adenylate cyclase-cyclic AMP system. Thymocyte adenylate cyclase is described in terms of a current model for membrane proteins.

Adenylyl Cyclases↗