Biomedical subjects
D Murray
Publications and source records attributed to D Murray.
The extensor retinacular system at the metacarpophalangeal joint. Anatomical and histological study.
The anatomy of the sagittal bands was studied in 56 cadaver digits. The sagittal band is part of an extensor retinacular system which is integrated with the extrinsic and intrinsic musculotendinous structures. The extensor retinacular system is a single unit with radial and ulnar components and has transverse, sagittal and oblique fibres. The transverse-sagittal fibres, along with the palmar plate, form a closed cylindrical tube which surrounds the metacarpal head. The oblique fibres form the triangular lamina distal to the sagittal band. The radial component of the sagittal band is often thinner and longer than the ulnar component. The sagittal band envelops the extensor digitorum tendon and the superficial fibres are thinner than deep fibres, especially in the central digits. The central digits have palmar soft tissue confluence on each side consisting of the sagittal band, palmar plate, annular pulley and deep transverse metacarpal ligament. The sagittal band also appears to envelop the superficial interosseous tendons on both sides. Our findings explain the propensity for radial sagittal band injuries and suggest that the sagittal band is the primary stabilizer of the extensor digitorum at the metacarpophalangeal joint.
A GFP reporter system to assess gene transfer and expression in human hematopoietic progenitor cells.
Hematopoietic stem cells are widely recognized as attractive targets for gene therapy but current protocols to transduce these cells using recombinant retroviral vectors are inefficient. To evaluate optimization of retroviral transduction of hematopoietic stem cells and stability of gene expression in their progeny, the green fluorescent protein (GFP) was explored as a reporter. We first improved sensitivity of detection > 100-fold over that achieved previously by using a novel retroviral vector (termed MGIN) expressing a high level of an enhanced GFP gene. Primitive human hematopoietic cells bearing the CD34 surface antigen and lacking lineage differentiation markers (CD34+ Lin-) were transduced with the MGIN vector using a clinically applicable supernatant procedure. Under the conditions employed, > 75% of the target cells retained the CD34+ Lin- primitive phenotype after 4-5 days in culture, of those > or = 25% expressed a high level of GFP detectable by both flow cytometric analysis and fluorescence microscopy. When transduced cells were cultured in clonogenic progenitor assays, GFP fluorescence was readily detected in situ, indicating that GFP expression was stable and not detrimental to the differentiative potential of the transduced CD34+ Lin- cells. We conclude that GFP is effective as a vital marker to quantity retrovirus-mediated gene transfer into human hematopoietic and perhaps other types of stem/progenitor cells, and monitor gene expression during their subsequent cell lineage determinations.
Elevated levels of plasma triglycerides are associated with histologically defined premenopausal breast cancer risk.
Lipids and lipoproteins have been associated with breast cancer risk; however, published results have been inconsistent. To clarify these associations, we measured fasting lipids in women undergoing breast biopsies. A case-control study examined the association of fasting levels of lipids with histologically defined breast cancer risk. Four groups of premenopausal women were assembled on the basis of histological appearance of breast tissue: 1) no epithelial proliferation (n = 102), 2) proliferation without atypia (n = 53), 3) atypical hyperplasia or carcinoma in situ (n = 53), and 4) node-negative invasive cancer (n = 102). A postoperative fasting blood specimen was analyzed for cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Demographics, risk factors, diet, physical activity, fasting weight, and skin-fold thickness were measured. Triglyceride levels were significantly higher in women with node-negative invasive cancer (0.94 +/- 1.04 mg/ml) than in those with no epithelial proliferation (0.83 +/- 1.04 mg/ml, p = 0.03). This association persisted after adjustment for age, body size, lipids, reproductive and familial risk factors, and previous benign breast problems (p < 0.01), in keeping with an independent association of elevated triglycerides with breast cancer risk.
Increased survival of patients treated with a vaccinia melanoma oncolysate vaccine: second interim analysis of data from a phase III, multi-institutional trial.
OBJECTIVE: The efficacy of vaccinia melanoma oncolysate (VMO) vaccine to increase overall survival and disease-free survival of patients with surgically resected International Union Against Cancer (UICC) stage II melanoma was studied in a phase III, randomized, multi-institutional trial. SUMMARY BACKGROUND DATA: Phase I and II trials with VMO showed minimal toxicity and clinical efficacy in patients with melanoma. In a recently completed phase III VMO trial, the first interim analysis performed in April 1994 showed an increasing trend in the survival of patients treated with VMO. The second interim analysis was performed in April 1995. METHODS: Patients with surgically resected stage II (UICC) melanoma were treated with VMO (N = 104) or placebo vaccinia vaccine virus (V) (N = 113) once a week for 13 weeks and then once every 2 weeks for a total of 12 months. Patients' clinical data were collected as of May 1995 and analyzed for survival. RESULTS: In this second interim analysis, the mean follow-up time is 42.28 months. No survival difference was observed between VMO and V treatments. However, in a retrospective subset analysis, a subset of males between the ages of 44 and 57 years and having one to five positive nodes (at 2-, 3-, and 5-year intervals, 13.6%, 15.9%, and 20.3% difference insurvival in favor of VMO [N = 20] when compared to V [N = 18] [p = 0.037]) and another subset of patients with clinical stage I (at 3- and 5-year intervals, 30% and 7% difference in survival in favor of VMO [N = 20] when compared to V [N = 23], [p = 0.05]) showed significant survival advantage with VMO. CONCLUSIONS: Although VMO vaccine therapy in surgical adjuvant setting did not produce a significant survival benefit to all patients with melanoma, patients from the above two subsets had significant survival benefit.
Acetabular notch.
Ultrasound images of dysplastic and/or unstable hips often display an indentation or notch at the superolateral part of the acetabulum where the iliac wing joins the acetabular roof. We reviewed the ultrasound and subsequent radiographic examinations of 295 babies examined in our hip screening clinic. Of the hips with a notch demonstrable at the first ultrasound, 97% had a persistent notch at the second ultrasound and in 79% the notch was apparent on the 3-month radiograph. When the notch persists, we believe that it represents damage to the lateral acetabular ring epiphysis and delayed maturation of the lateral acetabulum.
Environmental predictors of drinking and drinking-related problems in young adults.
We examined relationships among drinking norms, peer alcohol use, alcohol availability, drinking location, alcohol consumption, and drinking-related problems among young adult drinkers. The specific objectives of our study were to assess the relative contribution of normative and physical environmental factors to drinking and drinking consequences. Subjects were 3,095 young adults, aged eighteen to twenty years old who participated in the Communities Mobilizing for Change on Alcohol Project baseline survey. Alcohol consumption (i.e., number of drinks on the last occasion) and drinking consequences served as dependent variables. Multiple linear regression was used to identify predictors of alcohol consumption, and logistic regression was employed to identify predictors of drinking consequences. Drinking norms and peer alcohol use were positively related to alcohol consumption and to drinking consequences. Drinking in a public setting was positively related to alcohol consumption, but not to drinking-related problems. Findings suggest that policies and programs that alter the normative and physical environment surrounding drinking may reduce alcohol consumption and subsequent problems in young adults.
Constancy of the relative biological effectiveness of 42 MeV (p-->Be+) neutrons among cell lines with different DNA repair proficiencies.
An important approach to understanding the role of the various DNA repair pathways in the cellular response to DNA-damaging agents is through the study of repair-deficient mutant cell lines. In the present study we used this strategy to assess the relative importance of four of these pathways for the repair of DNA damage induced by low-linear energy transfer (LET) gamma rays and intermediate-LET 42 MeV (p-->Be+) fast neutrons. The panel of hamster cell mutants that we characterized for their relative sensitivity to fast neutrons and gamma rays includes cell lines with defects in the nucleotide excision repair pathway; these can be further subdivided into mutants which are defective in nucleotide excision repair alone [UV5 (ERCC2-), UV24 (ERCC3-), UV135 (ERCC5-) and UV61 (ERCC6-)] compared to those which have an associated defect in the distinct but overlapping pathway for the repair of DNA crosslinks [UV20 (ERCC1-) and UV41 (ERCC4-)]. We also examined mutants with defects in the base excision repair pathway [EM9 (XRCC1-)] and the DNA-dependent protein kinase (DNA-PK)-mediated DNA double-strand break (DSB) repair pathway [xrs5 (XRCC5-)]. None of the mutants defective in nucleotide excision repair was differentially sensitized to fast neutrons or gamma rays; in fact, the slight radiosensitivity of these mutants under aerated conditions may be secondary to their defect in nucleotide excision repair. In contrast, deficiency in the base excision repair pathway resulted in a significant primary sensitization to both types of radiation (1.95-fold to gamma rays and 1.79-fold to neutrons). Deficiency in the DSB repair pathway mediated by DNA-PK resulted in a marked, but again similar, primary sensitization to gamma rays (4.2-fold) and neutrons (5.1-fold). Thus none of the repair pathways examined here exhibited a preferential role for the repair of damage induced by low-LET compared to intermediate-LET radiations; this resulted in an essentially constant relative biological effectiveness (RBE) of approximately 2 among the cell lines studied, independent of their DNA repair proficiency. However, consideration of these data along with data published previously for high-LET alpha particles suggests that, whereas the DNA-PK pathway is important for the repair of DSBs induced by low- and intermediate-LET radiations, it becomes less important as the LET increases beyond 100 keV/microm; thus this pathway may not be involved in repairing the more complex lesions induced by densely ionizing high-LET particles.
The importance of the ERCC1/ERCC4[XPF] complex for hypoxic-cell radioresistance does not appear to derive from its participation in the nucleotide excision repair pathway.
The repair-deficient mutant rodent cell lines UV20 and UV41, which are defective in the ERCC1/ERCC4[XPF]-mediated 5'-endonuclease activity, are unusually sensitive to gamma-irradiation under hypoxic (but not oxic) conditions. Because this 5'-endonuclease appears to be involved in two distinct (but overlapping) DNA-repair pathways-the nucleotide excision repair pathway and the recombination-dependent pathway for the removal of DNA interstrand cross-links-it is unclear which of these defective activities is responsible for the hypoxic radiosensitivity of UV20 and UV41 cells. Accordingly, we have extended these measurements to the UV5 and UV24 lines which carry mutations in the ERCC2[XPD] and ERCC3[XPB] genes, respectively; both of these genes encode DNA helicases. These two mutants display a sensitivity to ultraviolet light that is similar to that of UV20 and UV41 cells, reflecting their defect in the incision step of the nucleotide excision repair pathway. However, neither UV5 nor UV24 cells are especially cross-sensitive to agents that produce DNA interstrand cross-links, suggesting that the ERCC2 and ERCC3 activities are not crucial for the repair of these lesions. We show that neither UV5 nor UV24 cells exhibit the unusual hypoxic radiosensitivity that characterizes UV20 and UV41 cells. Based on these data and on a comparison of the patterns of cross-sensitivity of these various mutants to other DNA-damaging agents, we conclude that the increased hypoxic radiosensitivity observed in the UV20 and UV41 mutants is due to a defect in the ERCC1/ERCC4-dependent pathway for the repair of DNA cross-links and not in the nucleotide excision repair pathway. The evidence suggests that this sensitivity may be mediated by some type of radiation-induced cross-links, possibly DNA-protein cross-links.
Validation of the Edinburgh Postnatal Depression Scale (EPDS) in non-postnatal women.
This paper reports the validation of the EPDS against a Research Diagnostic Criteria diagnosis of Major and Minor depression. The EPDS was administered to non-postnatal women with older children (mean age of youngest child 3 years 9 months) and to postnatal women (baby aged 6 months). All who scored 9 or above and one third of low scorers were interviewed, using Goldberg's Clinical Interview Schedule. The study confirmed good user acceptability of the EPDS when administered as a postal questionnaire (92% response rate). The EPDS was found to have satisfactory sensitivity (79%) and specificity (85%). Our findings suggest that the EPDS take a place alongside other screening scales for depression in Community samples. It is proposed that when used in these settings it is referred to as the Edinburgh Depression Scale.
Urological emergencies in general practice. Simple test diagnoses or excludes epididymo-orchitis.
Explore the source record for details and available documents.
Electronic records solved this practice's problems.
Explore the source record for details and available documents.
Drowning in paper? You can toss more than you think.
Explore the source record for details and available documents.
Isolation and preliminary characterization of a Chinese hamster ovary cell line with high-degree resistance to hydrogen peroxide.
We have isolated and conducted preliminary characterization of a cell line derived from the Chinese hamster ovary cell line AA8, which we have designated AG8 and which is highly resistant to the cytotoxic effects of H2O2 (approximately 17-fold when the H2O2 treatment was at 37 degrees; approximately 11-fold when the H2O2 treatment was at 4 degrees). AG8 cells were moderately (but significantly; P < 0.05) cross-resistant to CdCl2 (approximately 4-fold), NaAsO2 (approximately 2.3-fold), t-butyl hydroperoxide (approximately 2.9-fold), cumene hydroperoxide (approximately 3-fold), menadione (approximately 1.7-fold) and HgCl2 (approximately 1.5-fold), but were not significantly cross-resistant to hyperthermia (43 degrees), 254 nm UV light, 137Cs gamma-rays, and 42-MeV (p-->Be+) fast neutrons. As regards their biochemical status, AG8 and AA8 cells contain similar non-protein sulfhydryl levels per milligram of protein. Catalase activity (assessed by both spectrophotometry and polarography) was significantly higher in AG8 than in AA8 cells irrespective of whether enzyme activity was expressed per 10(6) cells (approximately 3.6-fold increase) or per milligram of protein (approximately 1.6-fold increase). AG8 cells also exhibited significantly greater glutathione reductase activity than wild-type cells when the data were expressed per 10(6) cells (approximately 2.9-fold) or per milligram of protein (approximately 1.3-fold). Glutathione peroxidase activity was immeasurably low in both cell lines. The susceptibility of the two cell lines to H2O2-mediated generation of DNA single-strand breaks (as measured by alkaline elution) indicated a slightly (approximately 1.5-fold) decreased yield in the resistant AG8 cell line. The two cell lines repaired these breaks with similar kinetics. In contrast, no measurable induction of DNA double-strand breaks (as measured by pulsed-field gel electrophoresis) was apparent in either cell line after survival-curve range concentrations of H2O2. On the basis of these data, it appears that the AG8 phenotype involves two previously identified resistance mechanisms, namely an adaptive component that may or may not involve increased antioxidant capacity, and a second component that does involve increased antioxidant (primarily catalase) capacity.
Oestrogen and postnatal depression.
Explore the source record for details and available documents.
Medicare changes you need to know about.
Explore the source record for details and available documents.
Nucleotide excision repair genes as determinants of cellular sensitivity to cyclophosphamide analogs.
UNLABELLED: The objective of this study was to determine the relative importance of the first six complementation groups of the nucleotide excision repair cross-complementing genes (ERCC1-ERCC6) and the first complementation group of the X-ray repair cross-complementing genes (XRCC1), in the repair of DNA damage induced by the in vitro active cyclophosphamide (CP) derivatives 4-hydroperoxycyclophosphamide (4HC) and phosphorodiamidic mustard (PM). We compared the sensitivity of the wild-type CHO cell line, AA8, with that of the CHO mutant cell lines UV4 and UV20 (ERCC1-), UV5 (ERCC2-), UV24 (ERCC3-), UV41 (ERCC4-), UV135 (ERCC5-), UV61 (ERCC6-), and EM9 (XRCC1-). Cell survival was determined using both growth inhibition and conventional clonogenic assays. The yield of DNA crosslinks in selected cell lines was determined using an ethidium bromide fluorescence assay. RESULTS: The rank ordering of sensitivity to both 4HC and PM, based on the combined survival data, was UV41/UV4/UV20 > > UV61/UV24/UV135/EM9 > or = UV5 approximately AA8. Thus mutations in the ERCC1 and ERCC4 genes impart a hypersensitivity to CP analogs. To confirm the importance of the ERCC1 gene for cellular resistance to 4HC and PM, UV20 cells were transfected with the human ERCC1 gene and subsequently exposed to 4HC and PM. The transfected cells displayed essentially wild-type resistance to both drugs. Furthermore, two interspecific hybrids derived from UV41, both of which retained the region of human chromosome 16 that harbors the ERCC4 gene, displayed essentially wild-type resistance to 4HC and PM, confirming the importance of ERCC4 for the repair of 4HC-induced DNA damage. When crosslinks were assayed after a 60-min treatment with 4HC or a 15-min treatment with PM, their yield paralleled the sensitivity of the cell lines to both drugs: UV41 cells showed markedly elevated levels of crosslinks, whereas AA8 and UV5 cells showed similar (low) levels of crosslinks. CONCLUSIONS: Our findings confirm the general pattern indicating that the ERCC1 and ERCC4 gene products are crucial for the repair of 4HC-induced DNA damage, while the other nucleotide excision repair genes examined are relatively unimportant. These data suggest that the hypersensitivity of ERCC1- and ERCC4- mutants to DNA crosslinking agents may reflect a defect in recombinational repair rather than nucleotide excision repair.