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Biomedical subjects

M L Frazier

Publications and source records attributed to M L Frazier.

60 records · Page 4Linked to original sources
PubMed1982

Bleomycin clinical pharmacology by radioimmunoassay.

Bleomycin pharmacokinetics were studied by radioimmunoassay in 11 patients who received 7-30 U intravenously (IV) and eight patients who received 4-30 U subcutaneously (SC). For patients who received IV bleomycin plasma disappearance was biphasic, with a mean initial half-life of 0.26 h and a terminal half-life of 2.3 h. Mean plasma drug clearance was 67.8 ml/min/m2 and the volume of distribution was 13.2 l/m2. Urinary excretion accounted for 63.9% of the drug in 24 h. After SC administration peak plasma levels occurred in 1.1 h, with a mean elimination half-life of 4.3 h. Mean plasma drug clearance was 60.5 ml/min/m2 and the volume of distribution was 19.2 l/m2. Bleomycin plasma clearance correlated well with serum creatinine (r2 = 0.72). Bleomycin has a rapid plasma elimination and urinary excretion. Bleomycin bioavailability after SC administration appears comparable to that seen after IV administration as determined by the areas under the plasma disappearance curves. Prolonged plasma levels are seen after SC injection, suggesting this route of administration can produce plasma concentrations comparable to those attained with continuous IV infusions.

Adolescent↗
PubMed1981

Insulin gene expression during development of the fetal bovine pancreas.

Poly(A+) RNA was isolated from the bovine pancreas at three stages of fetal development. Approximately 1% of the total RNA from first, second, and third trimester fetuses was polyadenylated, and the mean chain length of each RNA population was 1350 nucleotides. In cell-free protein synthesis experiments the concentration of insulin-immunoreactive translation products was 10.2%, 11.3%, and 9.7% for first, second, and third trimesters, respectively. Insulin mRNA sequences were estimated by transcription of insulin mRNA to [3H]cDNA and hybridization of cDNA with plasmid pI19 DNA containing rat proinsulin I sequences. Hybridization experiments gave insulin mRNA concentrations of 7.6%, 12.9%, and 3.9% for first, second, and third trimesters, respectively. These results show that insulin mRNA levels vary during development and become proportionally lower in third trimester, when the exocrine tissue is rapidly increasing in mass.

Animals↗
PubMed1977

Genetic loci of hemolysin production in Streptococcus faecalis subsp. zymogenes.

Two plasmids corresponding to molecular weights of 38.5 X 10(6) and 3.6 X 10(6) have been identified in Streptococcus faecalis subsp. zymogenes strain X-14. The larger plasmid is required for hemolysin-bacteriolysin production. Strain L2, a nonlytic nitrosoquanidine mutant of strain X-14, still harbors the hemolytic plasmid and produces the lysin component, but not the activator component, of the lytic system. Conjugal transfer of this plasmid from strain L2 to plasmid-free strains and strains cured of the 38.5-megadalton plasmid gives rise to hemolytic recipients. This implicates a gene in hemolysin production at a site other than the 38.5-megadalton plasmid.

Bacteriological Techniques↗
PubMedDate not supplied

Loci for efficient detection of microsatellite instability in hereditary non-polyposis colorectal cancer.

Most hereditary non-polyposis colorectal cancer (HNPCC) is due to germline mutations in DNA mismatch repair genes. Tumors arising as a result of these mutations display instability in microsatellites, which are short tandem repeats of DNA that are distributed throughout the genome. Although a subset of sporadic colorectal carcinomas also have microsatellite instability (MSI), the phenotype is a useful screening test in identifying patients with HNPCC caused by mutations in mismatch repair (MMR) genes. Studies have shown that some microsatellite markers are more efficient than others in identifying tumors with MSI. Furthermore, the frequency of instability can be assessed by categorizing patients into high (MSI-H, >/= 30-40% positive markers), low (MSI-L), and microsatellite stable (MSS) groups. Using a panel of 28 microsatellite markers, tumor and normal DNA from 10 HNPCC patients was used to identify the five most efficient markers for detecting MSI (BAT26, D2S123, FGA, D18S35, and TP53-DI). Each of the five markers detected MSI in 80-100% of the cases examined. We then expanded the sample size to 17 tumors from HNPCC patients. Each case had evidence for a mutation in either hMSH2 or hMLH1. We compared the efficiency of our panel of five best markers with another panel of five markers (BAT25, BAT26, D2S123, D17S250, and D5S346) identified as being efficient markers for detection of MSI at a recent NCI workshop. Our five selected markers were more efficient (85% vs. 79%) in detecting MSI. However, using either panel, 100% of the cases fell into the MSI-H category and the probability of misclassifying an MSI-H case as MSI-L is very low (0.002-0.008). We also examined four cases meeting the Amsterdam criteria for HNPCC, but with no evidence for mutation in either the hMSH2 or hMLH1 gene. With our panel, three were classified as MSI-H, while only two were classified as such with the NCI reference panel. The probability of misclassifying an MSI-L case as an MSI-H, using a panel of five markers is high (0.263).

Basic Helix-Loop-Helix Proteins↗
PubMedDate not supplied

Detection of mutated c-Ki-ras in the bile of patients with pancreatic cancer.

BACKGROUND: Because treatment of advanced pancreatic cancer is often unsuccessful, early detection is important. Codon 12 c-Ki-ras mutations have been found in 80-90% of pancreatic cancer cases and are a potential early marker for pancreatic cancer, but obtaining tissue or fluid for analysis can be difficult. We therefore evaluated whether mutant c-Ki-ras could be detected in bile samples obtained from pancreatic cancer patients. METHODS: DNA was isolated from bile specimens obtained from 20 patients with pancreatic cancer. The mutant-enriched PCR technique (ME-PCR) was used to amplify and detect point mutations at codon 12 of the c-Ki-ras oncogene. RESULTS: In 17 cases sufficient DNA for amplification was obtained; 14 had mutant c-Ki-ras alleles. Cytological evaluation of the bile was performed in 11 of these cases, but was positive in only two cases; both were positive for codon 12 c-Ki-ras mutations. Of the 9 cytologically negative biliary specimens, ME-PCR was positive in six. CONCLUSIONS: Codon 12 c-Ki-ras mutations can be successfully identified in PCR-amplified DNA from bile samples obtained from patients with advanced pancreatic cancer. This technique may supplement cytologic techniques for diagnosing pancreatic cancer and may be capable of identifying individuals at risk for this disease.

Bile↗