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Biomedical subjects

A Anderson

Publications and source records attributed to A Anderson.

At least 253 records · Page 14Linked to original sources
PubMed1986

cDNA clones for liver cytochrome P-450s from individual aroclor-treated rats: constitutive expression of a new P-450 gene related to phenobarbital-inducible forms.

Differential hybridization and screening with cloned inserts was used to identify two families of cytochrome P-450 cDNA clones in libraries prepared from total liver poly(A)+RNA of individual Aroclor-treated rats. One family has cDNA inserts for the major phenobarbital-inducible P-450s, P-450b and P-450e. Two types of P-450e inserts were identified. In addition, irregular inserts were characterized from two clones (PB23 and PB24) of this group. The other family has cDNA inserts for the major 3-methylcholanthrene-inducible species, P-450c and P-450d. No coding sequence restriction site variants were detected among 26 P-450d and P-450c inserts analyzed. The restriction map of the irregular 2.2-kb PB23 insert has a P-450b-like portion, followed by a 3' extension that hybridizes to RNAs of 2.7 and 4.8 kb, which are also detectable with a classical P-450b probe. The PB23 insert and the 2.7- and 4.8-kb RNAs presumably represent 3' extensions of P-450b/P-450e mRNAs, polyadenylated at downstream sites. The 858-bp sequence of the PB24 insert encodes the carboxy-terminal portion of a P-450b/P-450e-like protein. There is approximately 20% divergence at the polypeptide level between the PB24 and P-450b/P-450e sequences; nevertheless, they share many essential features. A PB24-specific probe hybridizes to a 1.9-kb RNA species which is present in the liver of untreated rats and which is not appreciably induced by phenobarbital or Aroclor. The PB24 cDNA most likely represents a constitutive cytochrome P-450, related to phenobarbital-inducible forms.

Amino Acid Sequence↗
PubMed1986

Expression of glial filament protein (GFP) in nerve sheaths and non-neural cells re-examined using monoclonal antibodies, with special emphasis on the co-expression of GFP and cytokeratins in epithelial cells of human salivary gland and pleomorphic adenomas.

We describe two novel monoclonal antibodies specific for glial filament protein (GFP), i.e., GF12.23 and GF12.24 (both IgG2a]. These cross-react over a broad range of species with epitopes located in the alpha-helical rod domain typical of all intermediate filament (IF) proteins. These monoclonal antibodies were used, in conjunction with other monoclonal GFP antibodies, rabbit antiserum to GFP, and various antibodies to other cytoskeletal proteins, to examine the occurrence of GFP in cells outside of the central nervous system of rodents, cows, and humans. We detected some scattered GFP-containing cells in the neural sheaths in some species but not in others, and we obtained different results when comparing the rabbit antisera with the monoclonal GFP antibodies. In the enteric glia of rats, we observed GFP-positive cells with all of the antibodies used, whereas in human intestine, the various monoclonal antibodies showed no reaction with any intestinal cells. Similarly, no GFP was detected in surface cells of the lens of cows and rats using any of the GFP antibodies, whereas some reaction was seen in murine lens tissue. We were also unable to detect GFP-positive cells in human, bovine, or rat liver with any of the monoclonal antibodies, which is in contrast to the reactivity of the rabbit GFP antisera with some stellate perisinusoidal cells of rat but not bovine or human liver. The possible reasons for the discrepancies between the different species and the different antibody preparations used are discussed. In addition, using double-label immunofluorescence microscopy, we showed that normal human parotid glands contain a certain type of epithelial cell that co-expresses cytokeratins and desmosomal proteins with GFP. The histological distribution of these GFP-positive cells suggests that they represent a subset of the myoepithelial cells present in this tissue. Cells co-expressing cytokeratins and GFP - in some cases, apparently together with vimentin as the third IF protein present - were also identified in tumors derived from this salivary-gland epithelium, i.e., pleomorphic adenomas, in which GFP-positive cells were relatively frequent in the myxoid and chondroid components, thus confirming the work of other investigators. Possible implications for the concept of histogenesis of these tumor cells are discussed, as are possible mechanisms resulting in the co-expression of IF proteins.

Adenoma↗
PubMed1986

Regional hyperthermia for extensive pelvic tumours using an annular phased array applicator: a feasibility study.

Twenty patients with extensive pelvic tumours have been treated with radiotherapy and regional hyperthermia using an annular phased array applicator (APA). The majority of patients had bulky disease with a mean tumour volume of 206 cm3. In 63 of 67 attempted treatments heating was achieved, temperatures in excess of 42 degrees C being reached in the pelvis in 78%. Heat doses, however, were low, only 41% of treatments exceeding 5 min equivalent at 43 degrees C. Treatment was usually limited by acute toxicity and, although this was marked, it was of short duration and no long-term sequelae have been noted. With gain in operator experience, later treatments have achieved improved thermal doses. Response was difficult to assess but we have documented responses in six of 12 assessable patients. Palliation has been achieved in all patients with symptoms. Preliminary attempts to shift the region of maximum heating by phase variations in the APA output are promising, and this technique should improve the quality of treatments and reduce toxicity. The APA is thus capable of inducing pelvic regional hyperthermia, and a randomised controlled study is now planned to assess the value of pelvic hyperthermia as a treatment modality.

Adult↗
PubMed1986

C3 nephritic factor in an individual with recurrent viral infection and lipodystrophy.

A patient with nephritic factor in the serum following an attack of disseminated herpes is described. In the majority of cases, the factor is associated with mesangio-capillary glomerulonephritis, with or without partial lipodystrophy. It has, however, been described in cases of partial lipodystrophy alone, in one patient with recurrent pyogenic infections, and in one healthy individual. It has not previously been described in an individual with disseminated viral infection.

Adult↗
PubMed1985

Ureteral obstruction secondary to a patent umbilical artery in a 79-year-old man: a case report.

Aberrant blood vessels are a rare cause of ureteral obstruction, with 9 cases having been reported, mostly in children. A 79-year-old man presented with left flank pain. At operation a patent left umbilical artery was partially obstructing the distal left ureter. Partial ureterectomy and ureteroureterostomy provided relief of symptoms. Aberrant blood vessels should be considered in the differential diagnosis of extrinsic distal ureteral obstruction.

Aged↗
PubMed1984

Segmental homologies in the coding and 3' non-coding sequences of rat liver cytochrome P-450e and P-450b cDNAs and cytochrome P-450e-like genes.

The nucleotide sequence of a cloned cDNA insert carried by pHDQ14 was determined and found to code for the 107 C-terminal amino acids of rat liver cytochrome P-450e. Comparison of the pHQ14 cDNA sequence with those of cloned cDNAs for cytochrome P-450b and of 2 P-450e-like genes revealed segmental homologies that may have resulted from gene conversion. These results suggest that gene conversion may generate sequence variants of genes for rat liver cytochrome P-450s.

Amino Acid Sequence↗
PubMed1984

Some clinical implications of recombinant DNA technology with emphasis on prenatal diagnosis of hemoglobinopathies.

Recombinant DNA technology has made possible remarkable advances in understanding the molecular genetics of human and other eucaryotic cells. This technology also has clinical applications, some of which may soon involve clinical laboratories. Restriction endonucleases and cloned DNA probes permit the direct analysis of cellular DNA to detect sequence abnormalities associated with particular genetic disorders. Use of this approach in the antenatal diagnosis of hemoglobinopathies is now possible on a routine basis. The principles behind the methods are quite general and may be applied to other hereditary diseases once suitable DNA probes become available. The same approach may be used to detect carriers of recessive gene defects and so improve genetic counselling. Other clinically related applications of recombinant DNA technology include the production of antigens for vaccine preparation and of specific human proteins (e.g. interferon and human growth hormone) for therapeutic use, as well as the use of nucleic acid hybridization for identification of microbial pathogens. It seems likely that recombinant DNA technology will, in the future, play an increasingly important role in the diagnosis, prevention and treatment of human disease.

Alleles↗
PubMed1983

Rapid suppression of alpha 1-fetoprotein gene transcription by dexamethasone in developing rat liver.

The administration of glucocorticosteroid hormones to newborn rats interrupts selectively (and reversibly, if the hormone is withdrawn) the hepatic production of alpha 1-fetoprotein (AFP). This results from a decreased concentration of AFP mRNA in the liver [Bélanger, L., Frain, M., Baril, P., Gingras, M.C., Bartkowiak, J., & Sala-Trepat, J.M. (1981) Biochemistry 20, 6665]. We have delineated further the mechanism and time course of this hormonal action in 4-day-old rats treated with dexamethasone (DEX). DNA from a recombinant plasmid containing a 578-bp insert of rat AFP cDNA was used to develop a cell-free nuclear run-off system and directly assess AFP gene transcription activity. Five minutes after DEX injection, AFP gene transcription activity is unchanged, but after 30 min, it drops to 25% that of the control; this correlates with the time required for translocation of DEX receptors to the nucleus. Dose-response curves also show that the degree of AFP gene suppression is closely correlated with the amount of DEX receptor translocated to the nucleus. The nuclear concentration of AFP mRNA, monitored by dot-blot hybridization, decreases to undetectable levels within 48 h, whereas that of albumin mRNA increases slightly, which indicates the selectivity of DEX action. These results show that DEX suppresses AFP gene expression at the transcriptional level and suggest a direct negative action of DEX-receptor complexes on the AFP chromatin transcription unit.

Animals↗
PubMed1983

Curing and induction of the Fels 1 and Fels 2 prophages in the Ames mutagen tester strains of Salmonella typhimurium.

A method is described for curing the Ames Salmonella mutagen tester strains of their Fels 1 and Fels 2 prophages with the aid of the antitumor drug daunorubicin. Non-lysogenic derivatives corresponding to TA100 and TA1535 were isolated and designated TAQ100 and TAQ1535 respectively. In addition, the Fels 1 monolysogens TAQ100F1 and TAQ1535F1, as well as the Fels 2 monolysogens TAQ100F2 and TAQ1535F2, were obtained. Finally, strains corresponding to TA98 and TA1538 cured of Fels 2, but retaining a cryptic Fels 1 (F1d) prophage were isolated and designated TAQ98F1d and TAQ1538F1d respectively. The various cured derivatives were identified by colony hybridization with 32P-labeled probes of Fels 1 and Fels 2 DNA. Southern blot hybridizations confirmed that phage-specific Fels DNA sequences were missing from the cured strains. The Fels 2-cured strains were resistant to Fels 2, but Fels 1 grew, albeit poorly, on the Fels 1-cured strains. Strains TAQ100F1, TAQ1535F1, TAQ100F2 and TAQ1535F2 were used in prophage induction assays, in the presence of rat-liver extract where necessary. Daunorubicin, bleomycin, mitomycin C, aflatoxin B1, 2-amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) were found to induce Fels 1 and/or Fels 2 in at least one of these strains. The induction of the Fels prophages in the TAQ monolysogens may provide a useful complement to the Ames test for the detection of DNA-damaging agents and potential carcinogens.

DNA, Bacterial↗
PubMed1983

Oncodevelopmental and hormonal regulation of alpha 1-fetoprotein gene expression.

The main features of the oncodevelopmental biology of alpha 1-fetoprotein (AFP) are reviewed. Progress made in the molecular biology of AFP gene regulation is discussed and we present our recent data on the mechanisms of AFP suppression by glucocorticoid hormones. The relationship between AFP gene transcription and cell replication is examined, and it is suggested that the degree of methylation of the AFP gene (or of co-methylated regulatory DNA sequences) conditions its response to hormones.

Albumins↗
PubMed1983

Mutagenic response of Ames strains cured of their inducible Fels 1 and Fels 2 prophages.

Ames strain TA100 was cured of its Fels 1 and Fels 2 prophages to yield the corresponding nonlysogenic derivative designated TAQ100. The two monolysogenic strains corresponding to TA100 lysogenic for Fels 1 (TAQ100F1) and for Fels 2 (TAQ100F2) were also isolated. In addition, the equivalent strains lacking pKM101 and designated TAQ1535, TAQ1535F1, and TAQ1535F2 were obtained. Ames strains TA98 and TA1538 are lysogenic for Fels 2 and were observed by colony hybridization to contain cryptic Fels 1 DNA sequences. Strains corresponding to TA98 and TA1538 cured of Fels 2 were isolated and designated TAQ98F1d and TAQ1538F1d, respectively. Fels 1 grew poorly on Fels 1-cured strains, and Fels 2 grew not at all on Fels 2-cured strains. The cured strains had therefore to be identified as such by their failure to react in colony hybridization with 32P-labeled probes of Fels 1 and/or Fels 2 DNA. The specificity of the labeled probes was confirmed with the aid of the nonlysogenic Salmonella typhimurium strain Q1 and its two monolysogenic derivatives Q1 (Fels 1) and Q1 (Fels 2). The cured strains were found to respond in the same manner as did the standard Ames strains to a variety of well-known mutagens, including aflatoxin B1, 7, 12-dimethylbenz(a)anthracene, daunorubicin, 2-amino-dipyrido[1,2-a:3',2'-d]imidazole, and beta-naphthylamine. Also, mitomycin C, bleomycin, and diethylstilbestrol were nonmutagenic to TAQ100 and TAQ98F1d as they are to TA100 and TA98. Since the Fels prophages are inducible by aflatoxin B1, by daunorubicin, and by other agents, it seems that mutagenesis and Fels prophage induction occur in separate subpopulations of cells; this situation had previously been reported to occur for mutagenesis and prophage lambda induction in Escherichia coli. In any case, the Fels prophages appear to have no major influence on the mutagenic response of the Ames strains.

Antineoplastic Agents↗
PubMed1982

Radioimmunoassay of thyroxine and 3,3',5'-triiodothyronine (reverse T3) in human amniotic fluid.

Measurement of amniotic fluid iodothyronine concentrations may enable antenatal detection of fetal thyroid abnormalities; however, the delineation of normal ranges is complicated by methodological problems associated with strong and highly variable protein-binding, and specificity of antisera. Improved radioimmunoassays of thyroxine (T4) and 3,3',5-triiodothyronine (reverse T3, rT3) have been developed to overcome these problems. In normal pregnancy, mean rT3 concentrations at less than 17 weeks, 17-22 weeks and 35-42 weeks gestation were 3.6 nmol/l (n = 21), 6.1 nmol/1 (n = 14) and 0.66 nmol/1 (n = 39) respectively; corresponding mean T4 concentrations were 2.4 nmol/1, 6.5 nmol/1 and 3.6 nmol/1. rT3 concentrations showed a strong positive correlation with T4 concentration in each age range; however, the molar ratio of rT3:T4 decreased progressively with gestational age, from 1.69 at less than 17 weeks to 0.19 at 35-42 weeks. In both mid- and late gestation, rT3 and T4 concentrations were strongly correlated with total amniotic fluid protein concentrations.

Amniotic Fluid↗