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Biomedical subjects

C Collins

Publications and source records attributed to C Collins.

At least 55 records · Page 3Linked to original sources
PubMed1995

Mutagenesis analysis of the membrane-proximal ligand binding site of the TGF-beta receptor type III extracellular domain.

There are two TGF-beta binding subdomains in the extracellular domain of receptor type III (proximal and distal in relation to the transmembrane domain). Here we present an extension of our analysis of the proximal binding site of receptor type III. Due to the original deletion mutagenesis strategy, our proximal binding site contained 19 amino acids from the N-terminal part of the receptor. By deleting these, we demonstrated that they did not contribute to the binding ability of the proximal binding site. We also produced a soluble, secreted form of the proximal binding site and demonstrated that it was able to bind TGF-beta. Finally, we analyzed the role of the three asparagine residues (580, 591, 595) that are located in the region of the receptor that is necessary for expression of a functional proximal binding site, and found that mutation of these residues individually to alanine did not affect ligand binding.

Animals↗
PubMed1995

Interchromosomal recombination is suppressed in mammalian somatic cells.

Homologous recombination occurs intrachromosomally as well as interchromosomally, both in mitotic (somatic) cells as well as meiotically in the germline. These different processes can serve very different purposes in maintaining the integrity of the organism and in enhancing diversity in the species. As shown here, comparison of the frequencies of intra- and interchromosomal recombination in meiotic and mitotic cells of both mouse and yeast argues that interchromosomal recombination is particularly low in mitotic cells of metazoan organisms. This result in turn suggests that the recombination machinery of metazoa might be organized to avoid the deleterious effects of homozygotization in somatic cells while still deriving the benefits of species diversification and of DNA repair.

Animals↗
PubMed1995

Interaction of the microtubule cytoskeleton with endocytic vesicles and cytoplasmic dynein in cultured rat hepatocytes.

In a recent study (Goltz, J.S., Wolkoff, A.W., Novikoff, P.M., Stockert, R.J., and Satir, P. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 7026-7030), we found that ligand- and receptor-containing endocytic vesicles bind to endogenous microtubules in vitro after 60 min of receptor-mediated endocytosis of asialo-orosomucoid. In the presence of ATP, ligand-containing endocytic vesicles are released from microtubules, while those containing receptor are not. We hypothesized that cytoplasmic dynein may associate with ligand-containing, but not receptor-containing, domains of endocytic vesicles and might be involved in the movement of ligand-containing vesicles along microtubules during sorting of ligand from receptor. Direct evidence in support of this hypothesis has been obtained in the present study. Binding of ligand-containing vesicles to microtubules correlates highly (p < 0.001) with binding of dynein, but not kinesin, under a variety of conditions. Binding of receptor-containing vesicles to microtubules is independent of both cytoplasmic dynein and kinesin binding. Tight association of cytoplasmic dynein with a population of ligand-containing vesicles is seen directly by immunoprecipitation. These results support the view that in receptor-mediated endocytosis, ligand-containing vesicles become bound to microtubules by cytoplasmic dynein. While receptor domains of endosomes remain attached to microtubules in an ATP-independent manner, ligand-containing domains might be moved away toward pericentrosomal lysosomes by this motor molecule.

Adenosine Triphosphate↗
PubMed1995

Rapid physical mapping of the human trk protooncogene (NTRK1) to human chromosome 1q21-q22 by P1 clone selection, fluorescence in situ hybridization (FISH), and computer-assisted microscopy.

Physical mapping of small genomic DNA fragments or expressed sequences by in situ hybridization is typically limited by the size of the target DNA sequence. Isolation of large insert DNA clones from libraries containing the target DNA sequence facilitates physical mapping by fluorescence in situ hybridization and allows rapid assignment of genes to cytogenetic bands. Here, we demonstrate the scheme by mapping the human protooncogene trk (NTRK1), a tyrosine kinase receptor type I gene that has earlier been assigned to two different cytogenetic loci. Large DNA insert library screening was carried out by in vitro DNA amplification using oligonucleotide primers flanking exon 4 of trk. The scheme presented here can easily be generalized to map physically very small nonrepetitive genomic DNA fragments or incomplete cDNAs.

Bacteriophage P1↗
PubMed1995

A physical map of chromosome 20 established using fluorescence in situ hybridization and digital image analysis.

The physical locations of 46 cosmid clones and 21 P1 clones were determined along the chromosome 20 axis relative to the p terminus (FLpter) using fluorescence in situ hybridization (FISH) and digital image microscopy. The cosmid clones were selected from the chromosomally enriched library LA20NC01. Nine P1 clones were selected from a pooled DuPont genomic library using PCR with primer pairs selected to amplify genetically mapped sequence-tagged sites. This information was used to relate the physical map to the genetic map. Twelve P1 clones were selected from the same library using PCR primer pairs that amplified known genes. Two of these, E2F and BCLX, had not been mapped previously.

Base Sequence↗
PubMed1995

Cardiovascular risk factor changes in the Kilkenny Health Project. A community health promotion programme.

The Kilkenny Health Project was a community research and demonstration programme which aimed to reduce risk of cardiovascular disease in a county in the south-east of Ireland with a total population of approximately 70,000. The health promotion programme was carried out in Kilkenny from 1985 to 1992. Outcome evaluation was by means of population surveys of independent samples of men and women aged 35 to 64 years in Kilkenny (n approximately 800) and in the reference county (n approximately 600) in 1985/1986 and in 1990/1991. Survey methods for health behaviour questionnaires and risk factor measurements were similar to those of the WHO MONICA Project. Mean systolic blood pressure (SBP) declined significantly (P < 0.01) in men and women in both counties, from 144.0 by 5.4 mmHg and from 143.2 by 5.4 mmHg in men and from 139.5 by 7.7 mmHg and from 136.5 by 6.6 mmHg in women in the intervention and reference counties. The prevalence of hypertension declined from 23.1% by 2.8% and from 26.1% by 6.0% in men in the two counties. Prevalence declined from 24.1% by 6.2% (P < 0.05) in women in the intervention county but was unchanged, increasing by 0.5% from 17.5%, in women in the reference county. Mean serum total cholesterol declined from 6.04 mmol.l-1 by 0.09 mmol.l-1 and from 6.00 by 0.44 mmol.l-1 (P < 0.01) in men and from 6.01 by 0.36 (P < 0.01) and from 5.90 by 0.31 (P < 0.01) in women in the intervention and reference counties, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A comparison of the efficacy and tolerability of moclobemide given as a single daily dose or in three divided doses per day for the treatment of patients with a major depressive episode (DSM-III-R)

This was a prospective, double-blind, randomized, multicenter trial comparing moclobemide once daily (OD) with three times daily (TDS) dosing. The duration of the study was 6 weeks with the initial dose of moclobemide being 450 mg/day (either 450 mg in the morning or 150 mg three times daily). Placebo tablets were used to ensure that the study was double blind. After 2 weeks, the dose could be increased to 600 mg/day if tolerability was acceptable and efficacy was judged insufficient by the investigator. Patients were assessed at baseline and at days 3, 7, 14, 21, 28, and 42. Efficacy was primarily judged on the Hamilton Rating Scale for Depression (HAM-D) (17item). Patients had to score at least 17 to enter the study. Safety and tolerability were judged on reported adverse events, safety parameters, premature withdrawals, and a physicians' global tolerability rating. There were also three secondary efficacy parameters--the Hamilton Rating Scale for Anxiety, Visual Analogue Scales for pain and irritability, and physicians' Clinical Global Impression (CGI). A total of 130 evaluable patients were required to detect a difference of more than 20% (alpha = 0.05 and beta = 0.8) between groups. A total of 189 patients entered the study, and the standard analysis comprised 145 patients. The efficacies between the two dosing regimens as determined by the HAM-D score and from the CGI were found not to differ significantly. For the standard analysis population, there was a reduction in mean HAM-D of 73.8 and 72.9% for the OD and TDS groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Safety, efficacy, and lipid profile of doxazosin at a VA medical center.

The Veterans Administration Lakeside Medical Center (VALMC) is a 500-bed hospital located in downtown Chicago providing a broad scope of inpatient and outpatient medical services for more than 12,000 veterans. The VALMC Pharmacy and Therapeutics Committee requested a study to evaluate doxazosin mesylate (Cardura) to determine if this agent would be an acceptable alternative to other formulary agents. It appears that doxazosin provides several therapeutic advantages, including once-daily dosing, when compared with other more costly antihypertensive agents.

Chicago↗
PubMed1995

Beyond patient dependency: family characteristics and access of elderly patients to home care services following hospital discharge.

Access to Skilled Nursing and Home Health Aid services among elderly patients (N = 580) and their family caregivers post hospital discharge was examined using logistic regression. A majority of the sample (65%) were referred for Skilled Nursing services while only 28% were referred for Home Health Aid services. Caregiving situations in which the spouse was the primary caregiver were less than half as likely to be referred for either service when compared to non-spouses. As expected, ADL limitations were a significant predictor of referral for both services. Women patients with the same ADL limitation as men were only about a fourth as likely to be referred for Home Health Aid services as men. Findings are discussed in terms of access to care and the need for policy to consider more than patient limitations in the referral criteria.

Activities of Daily Living↗
PubMed1995

Clinical nurse practitioner in a surgical team.

The role of a nurse taking on many of the duties of PRHO in a surgical team is described with the responsibilities, relationships and limitations. A nurse can carry out almost all of the elective activity of a PRHO and significantly relieve the pressure of work on others. She cannot completely substitute for PRHOs out of hours. As more consultants are appointed without additional medical members of the team, it is suggested that two consultant teams might be best served by one PRHO working with one Clinical Nurse Practitioner.

Education, Nursing, Continuing↗
PubMed1995

Amplification of chromosomal region 20q13 in invasive breast cancer: prognostic implications.

Amplification of the chromosome 20q13 region was recently discovered in breast cancer by comparative genomic hybridization and subsequently further defined by fluorescence in situ hybridization with specific probes. The target gene of the amplification remains unknown. Here, fluorescence in situ hybridization with a cosmid probe for the minimal region of amplification (RMC20C001) was used to study 20q13 amplification in 132 primary breast carcinomas and 11 metastases. The size of the amplicon was studied with four flanking probes. Thirty-eight (29%) primary tumors and 3 (27%) metastases showed increased copy number of the RMC20C001 probe (>1.5-fold relative to the p-arm control). Nine (6.8%) of the primary tumors were highly (>3-fold) amplified. Although the size and location of the amplified region varied from one tumor to another, only the RMC20C001 probe was consistently amplified. 20q13 amplification was significantly associated with a high histological grade (P = 0.01), DNA aneuploidy (P = 0.01), and high S-phase fraction (P = 0.0085). High-level amplification was also associated with short disease-free survival of patients with node-negative breast cancer (P = 0.002). We conclude that high-level 20q13 amplification may be an indicator of poor clinical outcome in node-negative breast cancer and that this chromosomal region is likely to contain a gene with an important role in breast cancer progression. A large definitive study is warranted to assess the independent prognostic value of 20q13 amplification.

Adult↗
PubMed1994

Increased copy number at 20q13 in breast cancer: defining the critical region and exclusion of candidate genes.

Studies by comparative genomic hybridization have indicated that a major new locus for DNA amplification in breast cancer is 20q13 and suggested that this genetic event is associated with aggressive clinical behavior. We used interphase fluorescence in situ hybridization with anonymous cosmid probes and gene-specific P1 clones to determine the minimal common region of increased copy number and to study involvement of known genes at 20q13. Based on high-level copy number increases (3 to 10-fold) found with one or more probes in 5 of 14 (35%) breast cancer cell lines and in 3 of 36 (8%) primary tumors, the critical region was narrowed to approximately 1.5 megabases at 20q13.2 defined by fractional length pter values 0.81-0.84. Previously known genes were excluded as candidates, implying that this chromosomal region harbors a novel oncogene that contributes to the malignant progression of breast cancer.

Breast Neoplasms↗
PubMed1994

Infectious disease surveillance during emergency relief to Bhutanese refugees in Nepal.

OBJECTIVE: To implement simplified infectious disease surveillance and epidemic disease control during the relocation of Bhutanese refugees to Nepal. DESIGN: Longitudinal observation study of mortality and morbidity. SETTING: Refugee health units in six refugee camps housing 73,500 Bhutanese refugees in the eastern tropical lowland between Nepal and India. INTERVENTIONS: Infectious disease surveillance and community-based programs to promote vitamin A supplementation, measles vaccination, oral rehydration therapy, and early use of antibiotics to treat acute respiratory infection. MAIN OUTCOME MEASURES: Crude mortality rate, mortality rate for children younger than 5 years, and cause-specific mortality. RESULTS: Crude mortality rates up to 1.15 deaths per 10,000 persons per day were reported during the first 6 months of surveillance. The leading causes of death were measles, diarrhea, and acute respiratory infections. Surveillance data were used to institute changes in public health management including measles vaccination, vitamin A supplementation, and control programs for diarrhea and acute respiratory infections and to ensure rapid responses to cholera, Shigella dysentery, and meningoencephalitis. Within 4 months of establishing disease control interventions, crude mortality rates were reduced by 75% and were below emergency levels. CONCLUSIONS: Simple, sustainable disease surveillance in refugee populations is essential during emergency relief efforts. Data can be used to direct community-based public health interventions to control common infectious diseases and reduce high mortality rates among refugees while placing a minimal burden on health workers.

Adolescent↗