Search PubMed⌕ Search

Biomedical subjects

J J Anderson

Publications and source records attributed to J J Anderson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Topoisomerase II alpha and II beta expression in childhood acute lymphoblastic leukaemia: relation to prognostic factors and clinical outcome.

BACKGROUND/AIMS: Many regimens used in the treatment of childhood acute lymphoblastic leukaemia (ALL) include Daunorubicin or Etoposide, which act as topoisomerase poisons. It has been suggested that there may be a relation between topoisomerase expression and response to topoisomerase poisons, based mainly on results from in vitro studies. Therefore, the aim of this study was to investigate this relation in a clinical setting and determine whether topoisomerase II alpha and II beta might be of predictive value in ALL. METHODS: Cellular expression of topoisomerases II alpha and II beta was assessed in 177 cases of ALL by immunohistochemistry using monoclonal antibodies to the two enzymes. The percentages of cell nuclei showing positive staining for topoisomerase II alpha and II beta expression were assessed. RESULTS: Taking the series as a whole, a clear separation of survival curves was seen with the established prognostic markers white blood cell (WBC) count, CD10 status, and sex. However, topoisomerase II alpha and II beta expression showed no relation to survival. No association was found between the topoisomerases and the prognostic markers CD10 and WBC count; however, topoisomerase II alpha expression was found to be related to sex, with expression being lower in girls (p = 0.002). CONCLUSIONS: These results suggest that the response to topoisomerase poisons cannot be predicted by the assessment of topoisomerase II alpha and II beta expression as defined by immunohistochemistry.

Adolescent↗
PubMed2000

Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration.

OBJECTIVE: To use individual patient data from rheumatoid arthritis (RA) clinical trials to identify factors that affect the response to treatment as defined by the American College of Rheumatology (ACR) criteria for improvement (the "ACR response"). METHODS: Primary trial data from 14 diverse, randomized, controlled trials of second-line drugs or devices in RA were analyzed. The trials included 11 methotrexate (MTX) trials (5 placebo controlled and 6 comparative, of which 2 were unpublished), 1 combination trial of cyclosporine plus MTX, 1 induction trial of a combination treatment in early RA (the COBRA trial), and 1 placebo-controlled trial of a new device (Prosorba). Both patient factors and disease activity measures (primarily, items from the ACR core criteria set) were available. RESULTS: A total of 1,435 patients (549 in placebo-controlled trials, 886 in comparative trials) were studied. In both active treatment and placebo groups, disease duration had a strong effect on the likelihood of patient response (e.g., with any active treatment, the response rate was 53% for patients with < or =1 year of disease, 43% for 1-2 years' disease duration, 44% for 2-5 years, 38% for 5-10 years, and 35% for > 10 years; P = 0.001). Decreasing response with greater disease duration was seen during treatment with most of the individual active drugs, as well as with placebo. Other factors decreasing the rate of response to treatment included any prior use of a disease-modifying antirheumatic drug (DMARD), higher disease functional class (according to the Steinbrocker criteria), low disease activity (according to patient's global assessment), and female sex. Each ACR core set variable exhibited a diminished response to treatment in patients with long-standing disease. The difference between active treatment and placebo response rates was not affected by disease duration nor by other factors associated with the ACR response. CONCLUSION: RA patients with longer disease duration do not respond as well to treatment compared with patients with early disease, and female sex, prior DMARD use, disease functional class, and disease activity also have effects on the likelihood of patient response to treatment. This has implications for trial interpretation and for the clinical expectations of RA patients.

Antirheumatic Agents↗
PubMed2000

An LC/MS/MS method for improved quantitation of the bound residues in the tissues of animals orally dosed with [(14)C]Benomyl.

Livers of goats orally dosed with [phenyl(U)-(14)C]benomyl contained radioactive residues which were not extractable using conventional, solvent-based extraction methods. We report a new residue method capable of enhanced extraction of benomyl-derived residues with selective and sensitive quantitation capability for methyl 4-hydroxybenzimidazol-2-ylcarbamate (4-HBC), methyl 5-hydroxybenzimidazol-2-ylcarbamate (5-HBC), and methyl benzimidazol-2-ylcarbamate (MBC). This method involves rigorous Raney-nickel reduction of hypothesized thioether bonds between benomyl residues and polar cellular components. Following acidic dehydration (desulfurization), the polar benomyl-derived residues are extracted into ethyl acetate and analyzed by LC/MS/MS. We have shown this method to be superior to alternative extraction approaches. When applied to goat liver tissue containing [phenyl(U)-(14)C]benomyl-bound residues, the extraction efficiency of total radioactive residues was approximately 30%, and the major benomyl-derived residue was 5-HBC (91-95% of extractable residue) with minor levels of carbendazim (MBC) (5-9%). HPLC/LSC data were consistent with the LC/MS/MS data. The overall method satisfies U.S. regulatory requirements in extraction efficiency, selectivity in detection, and limits of quantitation for benomyl-bound residues.

Administration, Oral↗
PubMed2000

Monoclonal antibodies recognizing CD5, CD10 and CD23 in formalin-fixed, paraffin-embedded tissue: production and assessment of their value in the diagnosis of small B-cell lymphoma.

AIMS: Assessment of the expression of antigens CD5, CD10 and CD23 can be of value in the differential diagnosis of small B-cell lymphoma. Correct subclassification is important since optimal treatment regimes differ between the subtypes. The aim of this study was to generate monoclonal antibodies recognizing these antigens in paraffin-embedded tissue and to assess their efficacy using a panel of cases of small B-cell lymphoma of various subtypes. METHODS AND RESULTS: For each antibody synthetic recombinant protein and conventional murine hybridoma technology was employed. Monoclonal antibodies effective in formalin-fixed, paraffin-embedded tissue were successfully generated, designated NCL-CD5-4C7, NCL-CD10-270 and NCL-CD23-1B12, respectively. A series of 58 cases of small B-cell lymphoma including examples of each subtype (lymphocytic, follicle centre cell, mantle cell, marginal zone and lymphoplasmacytoid) was assembled and immunostaining for the respective antigens carried out using the monoclonal antibodies produced. Our results indicate that the antibodies are specific for their respective antigens and give the predicted phenotypic profile in the small B-cell lymphoma subtypes. CONCLUSIONS: These novel monoclonal antibodies may be of value in routine diagnostic practice.

Animals↗
PubMed2000

Expression of topoisomerase IIIalpha in normal and neoplastic tissues determined by immunohistochemistry using a novel monoclonal antibody.

Topoisomerases are nuclear enzymes that modulate the topological structure of DNA in order to facilitate cellular events such as replication and transcription. These enzymes are also the cellular targets of certain classes of chemotherapeutic agents termed topoisomerase poisons. A new human topoisomerase isoform, IIIa, was discovered in 1996, which is thought to have roles in genome stability and possibly chromosome separation during mitosis. It is possible that novel or existing anti-topoisomerase agents target topoisomerase IIIa, suggesting that this enzyme may have potential as a prognostic marker and chemotherapeutic target. In order to study expression patterns of topoisomerase IIIa we have produced a novel monoclonal antibody to human topoisomerase IIIa (TOPO3a-1A4), and used it to assess topoisomerase IIIa expression in a wide range of normal and neoplastic tissues. We have found that topoisomerase IIIa is expressed in a wide range of tissue types, with especially high concentrations in endothelial cells and stromal fibroblasts. No general relationship was observed between expression of topoisomerase IIIa and proliferation. Expression in neoplastic tissues often paralleled their normal counterparts, although certain tumours showed either increased (e.g. colonic adenoma) or reduced (e.g. gastric carcinoma, small cell carcinoma of bronchus) expression. If topoisomerase IIIa is found to be a target for chemotherapeutic agents, clinical response in different tumour types may be related to topoisomerase IIIa expression, which may be assessed using TOPO3a-1A4.

Animals↗
PubMed2000

Are we improving the quality of nursing home care: the case of pressure ulcers.

BACKGROUND: There are widespread concerns regarding the quality of nursing home care and whether care is improving. We evaluated a large provider of nursing home care to determine whether risk-adjusted rates of pressure ulcer development have changed. METHODS: We used the Minimum Data Set to study National HealthCare Corporation nursing homes from 1991 through 1995. Rates of pressure ulcer development were calculated for successive 6-month periods by determining the proportion of residents initially ulcer-free having a stage 2 or larger pressure ulcer on subsequent assessments. Rates were risk-adjusted for patient characteristics. The proportion of new ulcers that were deep (stages 3 or 4) were also calculated. RESULTS: We examined risk-adjusted rates of pressure ulcer development based on 144,379 observations of 30,510 residents at 107 nursing homes. The number of observations per 6-month period ranged from 11,041 to 15,805. Between 1991 and 1995, there was a significant (P<.05) rate decline of more than 25%. Additionally, the proportion of new ulcers that were stages 3 or 4 declined from 30 to 22% (P<.01). CONCLUSIONS: Nursing homes showed significant improvement in the quality of pressure ulcer preventive care from 1991 to 1995.

Age Distribution↗
PubMed2000

Transmyocardial laser revascularization.

Transmyocardial laser revascularization is an alternative treatment option for patients with refractory angina who are not suitable candidates for more conventional coronary intervention or surgery. The laser creates channels that provide blood flow from the left ventricular chamber to areas of ischemic myocardium. Results have been impressive with patients reporting a reduction in angina of two classes according to the Canadian Heart Association Angina Classification. Care of the patient post transmyocardial laser revascularization procedure is comparable to that of other cardiac surgery patients. Innovations in this relatively new procedure include less invasive approaches and using it as an adjunctive or delivery modality for gene therapy.

Angina Pectoris↗
PubMed1999

NCL-CD10-270: a new monoclonal antibody recognizing CD10 in paraffin-embedded tissue.

CD10 (CALLA) antigen is expressed in a wide variety of epithelial and nonepithelial tissues, but its most significant application is in the diagnosis and classification of certain types of malignant lymphoma and leukemia. CD10 is expressed in a high percentage of cases of acute lymphoblastic leukemia (ALL), follicular lymphoma, Burkitt's lymphoma, and some hematopoietic tumors. Although the antigen is not lineage specific, CD10 expression is widely used to define subgroups within B-ALL and is a useful tool for detecting the presence of leukemic blasts in the bloodstream. Currently available monoclonal antibodies to CD10 have been found to be effective only in fresh-frozen tissue and for techniques such as flow cytometry. We have used a recombinant protein corresponding to the whole of CD10 to generate a monoclonal antibody that is effective in paraffin-embedded tissue sections. We have used this antibody to assay for the presence of CD10 on a range of normal and pathological tissues. Strong staining was seen in lymphoid germinal centers, renal tubules, glomeruli, syncytiotrophoblast, hepatic parenchymal canaliculi, B-lineage ALL, follicle center cell lymphoma, and a proportion of cases of large-B-cell lymphoma. We believe that this antibody will be of value in the characterization of malignant lymphoma, in particular the differential diagnosis of small-B-cell lymphoma and subtyping of lymphoblastic leukemia, as well as the investigation of the significance of expression of CD10 in other normal and pathological tissues.

Animals↗
PubMed1999

Reduced cerebrospinal fluid levels of alpha-secretase-cleaved amyloid precursor protein in aged rats: correlation with spatial memory deficits.

The amyloid precursor protein undergoes proteolysis at several sites to yield a number of functionally relevant peptides, including beta-amyloid and the soluble amyloid precursor protein derivatives alpha-soluble amyloid precursor protein and beta-soluble amyloid precursor protein. beta-Amyloid is the primary constituent of senile plaques associated with Alzheimer's disease, while a-soluble amyloid precursor protein promotes synaptogenesis and plays a role in neuroprotective processes. We tested for age-related alterations in these amyloid precursor protein proteolytically derived peptides by measuring the levels of alpha-soluble amyloid precursor protein, total soluble amyloid precursor proteins (alpha- and beta-soluble amyloid precursor protein combined) and beta-amyloid in cerebrospinal fluid from three-, 13- and 23-month-old Fischer-344 rats. Western blot analysis using selective antibodies revealed 50% less total soluble amyloid precursor protein and a-soluble amyloid precursor protein in cisternal cerebrospinal fluid from 23-month-old rats compared with three- and 13-month-old animals. Mass spectrometric analysis indicated, however, that beta-amyloid in cerebrospinal fluid was not different between the three age groups. In a second group of young (five to six months of age) and aged (24-25 months of age) rats, spatial working and reference memory were assessed in a water maze followed by collection of cerebrospinal fluid. As a group, the aged rats consistently performed below the young rats in both working and reference memory tests. The aged rats also had 49% less cerebrospinal fluid alpha-soluble amyloid precursor protein than did their younger counterparts. There was a positive correlation (r= 0.52-0.57, P < 0.001) between performance in spatial memory tasks and cerebrospinal fluid alpha-soluble amyloid precursor protein in these young and aged rats. These results suggest that there is a positive association between cerebrospinal fluid levels of alpha-soluble amyloid precursor protein and cognitive performance in rats, and that alpha-soluble amyloid precursor protein may be involved in the spatial learning and memory changes that accompany ageing.

Aging↗
PubMed1999

Health potential of soy isoflavones for menopausal women.

OBJECTIVE: To review the current literature on the effects of soy isoflavones, one class of phyto-oestrogens, on cardiovascular diseases, osteoporosis, cancer and climacteric symptoms. DESIGN: Many study designs were employed in the reports reviewed here, including prospective human trials, observational human studies, animal experiments and in vitro cell studies that explored the protective or preventive effects of soy isoflavones (genistein, daidzein and glycitein alone or mixed). SETTING: Diverse settings were employed, depending on study design. SUBJECTS: Human subjects, mostly menopausal or postmenopausal, were included, as were animal models and specific cell types. RESULTS: The findings were: (i) isoflavones plus soy protein together were needed to obtain the highly significant beneficial results on blood lipids and arterial dimensions; (ii) isoflavone treatments alone at high doses (relative to above) consistently improved bone parameters in rodent ovariectomized models, but not in humans or primates; (iii) isoflavones were not consistent in exerting positive effects regarding the prevention or treatment of cancers of the mammary glands, uterus and colon; and (iv) the effects of isoflavones on climacteric symptoms were not clear-cut. CONCLUSIONS: The promise of soy isoflavones reducing chronic disease risk seems to be non-uniform, with the most conclusive benefits occurring in the prevention of cardiovascular diseases, but other organ systems, such as skeletal and reproductive tissues, may also benefit from the consumption of soy and soy-derived products.

Animals↗
PubMed1999

Metabolism of [(14)C]flusilazole in the goat.

[Phenyl(U)-(14)C] and [triazole(3)-(14)C]flusilazole ([(bis 4-fluorophenyl)]methyl(1H-1,2,4-triazole-1-ylmethyl)silane; I) were extensively metabolized when fed to lactating goats (Capra hircus). The primary metabolites identified in goat tissues and milk were bis(4-fluorophenyl)(methyl)silanol (II) and 1H-1,2,4-triazole (III). Concentrations of total radiolabeled residues in the milk ranged from 0.09 to 0.74 microg/mL. Concentrations of radiolabeled residues found in tissues when the [(14)C] label was in the phenyl or triazole position, respectively, were 13.5 and 3.54 microg/g (liver), 8.74 and 0.75 microg/g (kidney), 0.41 and 0.52 microg/g (leg muscle), and 4.07 and 0.94 microg/g (back fat). Urine contained an additional major metabolite identified as [bis(4-fluorophenyl)](methyl)silylmethanol (IV) and its glucuronic acid conjugate (V). With either labeled form of flusilazole, the majority of the recovered radiolabel was excreted in urine or feces.

Animals↗