Search PubMed⌕ Search

Biomedical subjects

C Collins

Publications and source records attributed to C Collins.

At least 73 records · Page 4Linked to original sources
PubMed1996

RAG1, RAG2 and pre-T cell receptor alpha chain expression by adult human hepatic T cells: evidence for extrathymic T cell maturation.

Flow cytometric analysis of cell suspensions obtained from normal adult liver tissue at the time of transplantation revealed significant populations of T lymphocytes. These were examined for molecular evidence of local T cell maturation using reverse transcription-polymerase chain reaction to detect expression of recombination activation gene 1 (RAG1), RAG2 and pre-T cell receptor alpha chain (pTalpha), which occurs only in early thymocyte development. Four specimens of whole liver were positive for RAG1 and RAG2 expression, whereas peripheral blood mononuclear cells from the same individuals were negative. To localize RAG expression, immature (CD2+CD7+) and mature (CD45R0+) T cell subpopulations were isolated by magnetic separation from hepatic and peripheral blood mononuclear cell preparations. We detected the expression of RAG1, RAG2 and pre-TCRalpha in five specimens of hepatic CD2+CD7+ but not in CD45RO+ hepatic lymphocytes. Four out of six specimens of CD2+CD7+ cells from the peripheral blood were negative for RAG1 and RAG2 while all six specimens were positive for pTalpha expression. These results suggest that pre-T cells are trafficking from the bone marrow or the thymus to other tissues to continue differentiation and selection in the context of an appropriate cellular and molecular environment. The presence of immature populations of T cells in the adult liver and high levels of RAG expression suggests that the adult liver provides such an environment for extrathymic T cell maturation. These findings may have important implications for tolerance induction after liver transplantation and offer help in understanding the etiology of autoimmune liver disease.

Adult↗
PubMed1996

Amplifications of oncogene erbB-2 and chromosome 20q in breast cancer determined by differentially competitive polymerase chain reaction.

A new method of measuring gene copy number in small samples of DNA was used to measure amplification of the erbB-2 gene and of chromosome 20q in breast cancer. This method, termed 'differentially competitive polymerase chain reaction' (DC-PCR) combines the advantages of two other techniques for measuring amplification by PCR, namely differential PCR and competitive PCR. The DC-PCR methodology was evaluated for sensitivity and specificity by comparing amplification of erbB-2 measured by DC-PCR with that obtained by fluorescence in situ hybridization (FISH) for 42 cases or Southern blotting and/or slot blot analysis for 34 cases. There was over 90 percent concordance with both FISH and Southern blotting and/or slot blot analysis. DC-PCR was used to further characterize the newly described amplicon at chromosome 20q. By analyzing DNA from 10 breast cancer cell lines at 7 different loci, we identified a potential common region of amplification of approximately 5 centimorgans at chromosome 20q13 bordered by loci D20S52 and RMC20C100-S1. One hundred and seventeen cases of primary breast cancer were evaluated for amplification at these two loci. Amplification at one or more loci, defined as > 1.5 fold higher copy number than that of normal DNA, was found in 25 cases (21%). Sixteen cases were amplified at only one of the two probes (12 cases for RMC20C001-S1 and 4 cases for D20S52), suggesting that the target gene lies between the two markers or that there are two independent target genes within a small chromosome region.

Blotting, Southern↗
PubMed1996

Phase II study of high-dose cisplatin, etoposide, and cyclophosphamide for refractory ovarian cancer.

OBJECTIVES: A phase II trial of high-dose cyclophosphamide, etoposide, and cisplatin was done. STUDY DESIGN: Forty-eight patients with progressive or persistent disease and previous cisplatin-based chemotherapy and no paclitaxel therapy were entered for treatment on the basis of two cycles of cyclophosphamide (4500 mg/m2), etoposide (750 mg/m2), and cisplatin (120 mg/m2). RESULT: Seventy-four cycles were delivered. Six patients died during treatment (12.5%). Of 28 with measurable disease, there was a 25% response rate and 32% had stable disease. Median time to recurrence and survival were significantly different for minimal versus bulky disease (p = 0.0089, p = 0.0008, log rank) and for platinum-sensitive versus platinum-resistant disease (p = 0.18, p = 0.0012, log-rank). The number of prior regimens was not correlated with time to progression or survival. CONCLUSION: This study shows little advantage for high-dose protocols except for patients with a response to platinating agents and minimal residual disease.

Adult↗
PubMed1996

Genotype of the cystic fibrosis population of the Hunter Region of New South Wales.

OBJECTIVE: To determine the genotype of patients attending the cystic fibrosis clinic at John Hunter Hospital, Newcastle, Australia. METHODOLOGY: Seventy-five of the 76 patients attending the clinic over a 6 month period had blood collected for genetic analysis of 17 of the cystic fibrosis (CF) gene mutations. RESULTS: Sixty-one per cent of the patients were homozygous for the delta F508 mutation and all except one child had at least one delta F508 mutation. DISCUSSION: Nearly 80% of the CF genes were the delta F508 mutation. This prevalence suggests that the obligatory false negative rate of a newborn screening programme for CF based on a combination of immunoreactive trypsin and the delta F508 gene may be as low as 4-5%.

Adolescent↗
PubMed1996

Clonal analysis of human recurrent superficial bladder cancer by immunohistochemistry of P53 and retinoblastoma proteins.

PURPOSE: To investigate the clonal origin of malignant cells in recurrent superficial bladder cancer. MATERIALS AND METHODS: We compared the protein expression of p53 and retinoblastoma (Rb) by immunohistochemistry using antibody P1801 and PMG3-245, respectively, in 13 patients at the time of primary superficial bladder cancer resection (6 Ta and 7 T1) and their 15 corresponding recurrences of disease. Mutations in p53 and Rb were inferred on the basis of immunoperoxidase staining. RESULTS: At the time of initial tumor resection, a p53 mutation was observed in 5 patients (39%) and an Rb mutation was observed in 3 (23%). The p53/Rb mutation status of recurrent bladder cancers completely matched their corresponding primary bladder cancer. CONCLUSIONS: The chance that recurrent bladder cancer originated from independent clones in this study was extremely small (p < 10(-6)). This result strongly supports the monoclonal origin of recurrent superficial bladder cancer.

Carcinoma, Transitional Cell↗
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↗