Search PubMed⌕ Search

Biomedical subjects

S Cole

Publications and source records attributed to S Cole.

At least 73 records · Page 4Linked to original sources
PubMed1998

Visual search for features and conjunctions in development.

Visual search performance was examined in three groups of children 7 to 12 years of age and in young adults. Colour and orientation feature searches and a conjunction search were conducted. Reaction time (RT) showed expected improvements in processing speed with age. Comparisons of RT's on target-present and target-absent trials were consistent with parallel search on the two feature conditions and with serial search in the conjunction condition. The RT results indicated searches for feature and conjunctions were treated similarly for children and adults. However, the youngest children missed more targets at the largest array sizes, most strikingly in conjunction search. Based on an analysis of speed/accuracy trade-offs, we suggest that low target-distractor discriminability leads to an undersampling of array elements, and is responsible for the high number of misses in the youngest children.

Adult↗
PubMed1998

Is a rising caesarean section rate inevitable?

OBJECTIVE: To determine the indications for singleton caesarean sections in Scotland in 1994. DESIGN: Prospective survey of singleton caesarean sections using information provided by clinicians entering data onto a computer in labour wards. SETTING: Twenty-three consultant-led obstetric units in Scotland. POPULATION: Women undergoing caesarean section in participating Scottish maternity units during 1994. RESULTS: Using routinely collected data it was found that the caesarean section rate varied by maternal age, parity, gestation, history of previous section and hospital of delivery, but there was no difference by area of deprivation. 87.4% (8369/9573) of Scottish caesarean sections were included in the survey of which 8098 were in women with singleton pregnancies. Most singleton caesarean sections were undertaken in primiparae (50.5%), 31.2% were in women with a history of previous section and 18.3% were in multiparous women who had not had a previous section; 38.9% of the operations were elective, 13.9% were emergencies before labour and 47.2% were emergencies during labour. Four main indications--elective section for breech presentation (10.7% of all sections); emergency caesarean section before labour because of fetal problems (2.8%); emergency caesarean section during labour for fetal distress and/or failure to progress (30.3%); repeat section for reasons other than above (16.2%) accounted for 60% of all caesarean sections in women with no other recorded complications. 7.7% of all singleton caesarean sections (19.8% of elective operations) were associated with maternal request for the operation. DISCUSSION: The survey has identified why caesarean sections are performed by Scottish obstetricians and highlighted some areas where there would be scope to increase the vaginal delivery rate. Before this can be attempted, agreement must be reached by clinicians about effective management of particular problems. Women also need to have ready access to evidenced-based information about caesarean section.

Algorithms↗
PubMed1998

The impact of molecular diagnosis on familial colorectal cancer.

We have shown the impact of molecular diagnostics related to mutation detection in an extensive family with a strong history of colorectal cancer. The nature and presentation of the cancers suggested that hereditary nonpolyposis colorectal cancer was the most likely cause. The strategies employed have enabled the detection and characterisation of the causative mutation in the proband and predictive testing in the remaining relatives where requested. Using the chemical cleavage of mismatches technique and direct sequencing, the MSH2 and MLH1 genes of the proband were investigated. A single base substitution, C-->T at nucleotide 350, codon 117, of the MLH1 gene was identified. Across the family pedigree at specific points, 22 other relatives have been tested for the mutation by direct DNA sequencing from genomic DNA. Of the total of 23 patients tested to date, 11 have the mutation. In conjunction with appropriate genetic counselling, this service has clarified the genetic status of many individuals within this family. Predictive information provided prior to the development of symptoms enables individuals to make informed choices regarding disease management and the future, removing the anxiety associated with the unknown.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Increasing consumer satisfaction. One social service and public health initiative shows how social marketing can increase consumer satisfaction.

The key to a successful social marketing approach to health care is continually listening to consumers' feedback and being willing to change the health product or service according to their needs and preferences. This approach can increase the likelihood of consumers being satisfied with, and continuing to utilize or provide the particular health service.

Consumer Behavior↗
PubMed1998

Diversity in nursing: a challenge for the profession.

Affirmative action policies and programs have been in place since the 1960's to afford academic and job opportunities for women and minorities. The past few years have brought about debate and controversy over the benefits of affirmative action. In spite of affirmative action, minorities continue to be underrepresented in nursing. With the increase of minorities in the general population, nursing will be ill prepared to meet the challenge of providing care to a diverse society. One of the major reasons cited for an underrepresented minority population in nursing is the lack of recruitment and retention strategies. The answers are not in affirmative action alone, but from within nursing itself.

Career Choice↗
PubMed1997

Enhancement of bioreductive drug toxicity in murine tumours by inhibition of the activity of nitric oxide synthase.

Nitro-L-arginine inhibits the production of nitric oxide and can thereby cause vasoconstriction in vivo. One consequence of this is that nitro-L-arginine can increase hypoxia in a range of transplantable and spontaneous murine solid tumours. Bioreductive drugs such as RB6145 are more active under hypoxic conditions, and the combination of RB6145 with nitro-L-arginine in vivo shows greater anti-tumour activity than either agent individually. In mice given nitro-L-arginine at 10 mg kg(-1) i.p. up to 1 h before or after 300 mg kg(-1) i.p. RB6145, survival of KHT tumour cells was reduced by 3-4 logs when assessed by clonogenic assay 24 h after treatment. RB6145 or nitro-L-arginine alone caused no more than 20% cell kill. Similar effects were found in SCCVII tumours. The tumour response to the drug combination was tumour size dependent, with increased tumour cell sensitivity occurring when the tumour volume at the time of treatment was increased. Further, the response of KHT tumours to the combination of RB6145 and nitro-L-arginine was also dependent on the time interval between treatment and on when tumours were excised for determination of survival in vitro. The relative surviving fraction was about 0.3 for intervals less than 4 h but was reduced to 0.01 at 12 h and 0.001 at 24 h. These results were supported by histological examination of tumours, when necrosis at 2 h after treatment was less than 5% but increased to greater than 90% at 24 h. RB6145-induced normal tissue damage, as measured by CFU-A survival, was not altered by combining with nitro-L-arginine. Hence, this drug combination may provide therapeutic benefit. It is likely that the substantial anti-tumour effects are due to enhancement of bioreductive toxicity through increased tumour hypoxia, although additional mechanism(s) may also contribute to the overall response.

Animals↗
PubMed1996

Making the diagnosis of depression in the primary care setting.

Making the diagnosis of depression in the primary care setting represents a challenge and an opportunity. With the numerous cultural, administrative, social, and financial obstacles to the assessment and management of mental disorders in primary care, it is a small wonder that so much treatment of depression actually does occur. However, much depression is missed, and even when the diagnosis is not missed, many depressed patients do not receive adequate treatment. This article reviews the different depressive conditions of importance that present in primary care, discusses complexities of differential diagnosis, and underscores the importance of the medical interview itself for eliciting relevant data, developing rapport, and educating the patient about the key issues of importance relevant to the management of depression.

Depression↗
PubMed1996

The adhesion molecule E-cadherin and a surface antigen recognized by the antibody 9C4 are selectively expressed on erythroid cells of defined maturational stages.

The antigen expression of immature erythroid bone marrow cells was studied using two recently generated monoclonal antibodies (mAb), mAb 67A4 and 9C4, with specificities for the epithelial cell adhesion molecule E-cadherin (E-cad; mAb 67A4), and a novel 110 kDa differentiation antigen (mAb 9C4) with unknown molecular structure. Pappenheim staining of FACS-purified cells labeled with mAb 9C4 and anti-glycophorin A (GA) revealed that the majority of the 9C4+GA- and 9C4+GA+ cells consisted of erythroblasts. In contrast, the E-cad-positive population comprised normoblasts and erythroblasts. While the E-cad+GA- fraction contained mainly erythroblasts and basophilic normoblasts, the E-Cad+GA+ population was enriched in orthochromatic and polychromatophilic normoblasts. By colony assays of affinity column-purified cells it could be shown that erythroid colony forming units (CFU-E) were enriched and erythroid burst forming units (BFU-E) were depleted in the 9C4- and E-cad-positive fractions. Flow cytometric analysis of bone marrow cells double-labeled with mAb 67A4 and anti-CD71, anti-CD117, anti-CD34, or anti-GA revealed that about 90% of the E-cad-positive cells coexpressed CD71, about 70% were positive for CD117, about 50% for GA, and only about 5% coexpressed CD34. The expression pattern of 9C4 antigen was similar to that of E-Cad with the exception that only a minority of the 9C4-positive cells coexpressed GA. Lymphoid and myeloid markers were negative on both the E-Cad- and 9C4-positive populations. In these studies we describe the identification of a new mAb-defined antigen which is specifically expressed on erythroblasts and CFU-E(9C4) and demonstrate that E-Cad is not only expressed on epithelial cells but also on erythropoietic cells of defined maturational stages.

Antibodies, Monoclonal↗
PubMed1995

Post-translational processing of membrane-associated neu differentiation factor proisoforms expressed in mammalian cells.

Expression vectors constructed from human and rat pro-neu differentiation factor (NDF) cDNAs were transfected in Chinese hamster ovary cells for expression of recombinant NDF molecules. Soluble NDF forms were released into culture medium after post-translational processing of the membrane-bound pro-NDF forms. Different human and rat NDF isoforms, after being purified from the culture medium, were subjected to structural and biochemical characterizations. The isolated human and rat NDF isoforms have been proteolytically processed at a specific site at the N terminus, which is different from that observed for the processing of rat or human NDF molecule prepared from natural origins. The processing of each recombinant NDF isoform at its C terminus was heterogeneous but consistently occurred at nearby peptide bonds. Specific N- and C-terminal processing by Chinese hamster ovary cells has resulted in the production of two types (alpha and beta) of recombinant NDFs containing 222-225 amino acid residues. Both human and rat NDF molecules are heavily glycosylated at two of the three potential Asn-linked glycosylation sites and contain O-linked sugars at 11 of the Thr/Ser sites. Glycosylation occurs at a short, Ser/Thr-rich spacer region that connects the N-terminal immunoglobulin homology unit to the epidermal growth factor domain. Cellular phosphorylation assay indicated that these secreted forms contain similar biological activity in receptor tyrosine autophosphorylation of mammary tumor cells.

Amino Acid Sequence↗
PubMed1995

Fused pyrazine mono-N-oxides as bioreductive drugs. III. Characterization of RB 90740 in vitro and in vivo.

RB 90740 is the lead compound in a series of aromatic mono-N-oxide bioreductive drugs. The compound shows considerably greater toxicity towards hypoxic verses aerobic mammalian cells in vitro. The differential in concentration required to give the same level of cell killing under these conditions ranges from 3.5 in a human bronchio-alveolar tumor cell line up to 120 in a rodent cell line defective in the repair of DNA strand breaks. The ability of RB 90740 to cause DNA strand breaks under hypoxic conditions was confirmed by alkaline sucrose gradient and pulsed field gel electrophoresis techniques. Despite these properties demonstrated in vitro, RB 90740 was shown not to be cytotoxic to hypoxic cells in experimental murine tumors in vivo. This may be due, in part, to the level of hypoxia (< 0.02% O2) necessary to produce toxicity in vitro.

Animals↗
PubMed1995

Cloning, sequencing, and expression of the apa gene coding for the Mycobacterium tuberculosis 45/47-kilodalton secreted antigen complex.

Effective protection against a virulent challenge with Mycobacterium tuberculosis is induced mainly by previous immunization with living attenuated mycobacteria, and it has been hypothesized that secreted proteins serve as major targets in the specific immune response. To identify and purify molecules present in culture medium filtrate which are dominant antigens during effective vaccination, a two-step selection procedure was used to select antigens able to interact with T lymphocytes and/or antibodies induced by immunization with living bacteria and to counterselect antigens interacting with the immune effectors induced by immunization with dead bacteria. A Mycobacterium bovis BCG 45/47-kDa antigen complex, present in BCG culture filtrate, has been previously identified and isolated (F. Romain, A. Laqueyrerie, P. Militzer, P. Pescher, P. Chavarot, M. Lagranderie, G. Auregan, M. Gheorghiu, and G. Marchal, Infect. Immun. 61:742-750, 1993). Since the cognate antibodies recognize the very same antigens present in M. tuberculosis culture medium filtrates, a project was undertaken to clone, express, and sequence the corresponding gene of M. tuberculosis. An M. tuberculosis shuttle cosmid library was transferred in Mycobacterium smegmatis and screened with a competitive enzyme-linked immunosorbent assay to detect the clones expressing the proteins. A clone containing a 40-kb DNA insert was selected, and by means of subcloning in Escherichia coli, a 2-kb fragment that coded for the molecules was identified. An open reading frame in the 2,061-nucleotide sequence codes for a secreted protein with a consensus signal peptide of 39 amino acids and a predicted molecular mass of 28,779 Da. The gene was referred to as apa because of the high percentages of proline (21.7%) and alanine (19%) in the purified protein. Southern hybridization analysis of digested total genomic DNA from M. tuberculosis (reference strains H37Rv and H37Ra) indicated that the apa gene was present as a single copy on the genome. The N-terminal identity or homology of the M. tuberculosis and M. bovis BCG purified molecules and their similar global and deduced amino acid compositions demonstrated the perfect correspondence between the molecular and chemical analyses. The presence of a high percentage of proline (21.7%) was confirmed and explained the apparent higher molecular mass (45/47 kDa) determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis resulting from the increased rigidity of molecules due to proline residues.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1995

Rapid Mycobacterium species assignment and unambiguous identification of mutations associated with antimicrobial resistance in Mycobacterium tuberculosis by automated DNA sequencing.

OBJECTIVE: To develop and demonstrate the utility of automated DNA sequencing strategies for rapid and unambiguous identification of Mycobacterium species and mutations associated with antimicrobial resistance in Mycobacterium tuberculosis. DESIGN AND SPECIMENS: A 360-base pair segment of the gene (hsp65) encoding a 65-kd heat shock protein was characterized from 91 isolates assigned to 24 Mycobacterium species by traditional biochemical techniques. Areas of seven genes recently shown to contain mutations associated with antimicrobial resistance in M tuberculosis strains were also sequenced in a sample of 128 resistant organisms. Early positive BACTEC 460 cultures and acid-fast, bacterium-positive sputum specimens from patients with tuberculosis were also studied. RESULTS: Automated DNA sequencing identified species-specific polymorphism in the target segment of hsp65, successfully identified organisms to the species level in smear-positive sputum samples, and unambiguously characterized seven genes associated with antimicrobial resistance in M tuberculosis. CONCLUSIONS: Rapid identification of M tuberculosis and other Mycobacterium species is possible by automated DNA sequencing of a portion of hsp65. The technique is also feasible for analysis of some smear-positive sputum specimens. Unambiguous characterization of target segments of genes harboring mutations associated with antimicrobial resistance in M tuberculosis is possible from primary patient specimens. Taken together, the data demonstrate the feasibility of mycobacterial species identification and potential to identify mutations associated with antimicrobial resistance in less than 48 hours.

Alleles↗
PubMed1994

Cellular and karyotypic characterization of two doxorubicin resistant cell lines isolated from the same parental human leukemia cell line.

Separate mechanisms underlying the multidrug resistant (MDR) phenotype were identified in 2 independent approaches to select tumour cells resistant to low concentrations of doxorubicin (Dox) from the sensitive T cell leukemia cell line CCRF-CEM. The CEM/A7 cell line was selected at an initial concentration of 0.005 microgram/ml of Dox and maintained at 0.07 microgram/ml. In contrast, the CEM/A5 line was selected using an initial concentration of 0.01 microgram/ml and maintained in Dox at a concentration of 0.05 microgram/ml. P-glycoprotein expression was demonstrated in the CEM/A7 line but not the CEM/A5 line. Amplification of the mdrI gene was not observed in the CEM/A7 cell line. Both cell lines showed cross-resistance to a number of structurally unrelated cytotoxic drugs including anthracyclines and etoposide (VP-16), although only the CEM/A7 line was cross resistant to Vinca alkaloids. Immunoblots of total cell lysates of the CEM/A5 line have revealed almost undetectable levels of topoisomerase II alpha and beta in this line. Cytogenetic analyses of both lines revealed numerous karyotypic abnormalities which were present in the parental cell line as well as both resistant cell lines. The CEM/A7 line also demonstrated a duplication of part of the long arm of chromosome 7 which included the region containing the mdrI gene, a finding not seen in the parental or CEM/A5 line. CEM/A5, however, demonstrated an abnormality of chromosome 7, outside the region of the mdrI gene, and it also contained a deletion of the short arm of chromosome 2. Abnormalities in this latter region of genome have been associated with non-P-glycoprotein-mediated MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Pharmacokinetics, metabolism and distribution of 1,2-dihydro-8-(4-methylpiperazinyl)-4-phenylimidazo [1,2-A] pyrido [3,2-E] pyrazine-5-oxide in C3H mice.

PURPOSE: 1,2-Dihydro-8-(4-methylpiperazinyl)-4-phenylimidazo [1,2-a] pyrido [3,2-e] pyrazine-5-oxide (RB90740) is a bioreductive drug with an oxic to hypoxic toxicity ratio of 16 in cultured V79 cells in vitro. The aim of this study was to examine the pharmacokinetics, metabolism and distribution of the drug in tumor bearing C3H mice. METHODS AND MATERIALS: A high pressure liquid chromatography assay for the quantitative determination of concentrations of the drug and its metabolites has been developed and used to examine their distribution in blood, RIF-1 and KHT tumors, brain, muscle, and liver tissue. Urine and feces collected for 24 h after drug administration have been examined for the drug and its metabolism products. RESULTS: Three metabolites, two of which have been identified, have been observed in mouse tissue. 1,2-Dihydro-8-(4-methylpiperazinyl)-4-phenylimidazo [1,2-a]pyrido[3,2-e]pyrazine (RB92815) is the two-electron reduced species, which is observed in liver, urine and occassionally in tumor samples. 1,2-dihydro-8-(4-piperazinyl)-4-phenylimidazo [1,2-a]pyrido[3,2-e]pyrazine-5-oxide (RB1739), the N-demethylated compound, is observed in urine and liver. Elimination of the drug after an intraperitoneal dose of 50 mg/kg is biphasic with t(1)2 alpha = 3 min and t(1)2 beta = 219 min. The area under the curve for blood concentration vs. time is 1.4 mg ml min-1. The drug is preferentially taken up into tumor tissue as is apparent from the area under the curve values for RIF-1 (28.3 mg ml min-1) and KHT (18.4 mg ml min-1) tumors. CONCLUSION: From these values of the area under the curve it is suggested that the drug is present in tumor tissue at concentrations sufficient to eliminate the hypoxic fraction provided reduction to a toxic species occurs. Bioreduction by the addition of two electrons to form RB92815 occurs in some tumors, but it is not known if this is due to an obligate two-electron detoxifying step or if reduction occurs by single electron additions via a toxic free radical species.

Animals↗