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Biomedical subjects

M A Thompson

Publications and source records attributed to M A Thompson.

At least 91 records · Page 5Linked to original sources
PubMed1991

The amino-terminal region of a proteochondroitin core protein, secreted by aortic smooth muscle cells, shares sequence homology with the pre-propeptide region of the biglycan core protein from human bone.

Smooth muscle cells, isolated from rat and bovine aortae and grown in vitro, synthesize chondroitin sulfate proteoglycans which are secreted into the growth media. Analysis of metabolically [35S]-labeled macromolecules, employing ion-exchange chromatography, revealed a single peak of radioactivity, upon elution with a linear salt gradient. Treatment of the material with enzymes that specifically degrade chondroitin sulfate demonstrated that chondroitin-4-sulfate was the predominant species isolated from rat smooth muscle cells and that chondroitin-4-sulfate and dermatan sulfate were the predominant species isolated from bovine aortic smooth muscle cells. Treatment of the native proteoglycans with chondroitinase ABC and subsequent SDS-PAGE analysis of the digestion products resulted in the appearance of a band with an apparent molecular weight of 45,000. Electrotransfer of the core protein to Immobilon-P membrane and gas phase sequencing of the amino-terminal region revealed striking homology between the core proteins of the rat and bovine proteochondroitin with the pre-propeptide region of human bone biglycan.

Aggrecans↗
PubMed1991

Structural and functional integrity of ovarian tumor tissue obtained by ultrasonic aspiration.

For patients with ovarian epithelial cancer, survival increases when residual disease approaches zero after surgical removal of the tumor. A previous study using the Cavitron Ultrasonic Surgical Aspirator (CUSA) (Cavitron Lasersonic Corp., Stamford, CT) showed the successful removal of ovarian tumors from areas often considered unresectable: the diaphragm, spleen, stomach, and small bowel. However, the CUSA has not yet been approved by the Food and Drug Administration for gynecologic surgery except on an experimental basis. This study was designed to test whether ultrasonic irradiation produced by the CUSA caused alterations in cell structure or physiology of gynecologic tissue in adjacent areas. Paired tumor samples, unirradiated and irradiated, were obtained from ten patients, and portions were sent for pathologic structural evaluation and physiologic tissue culture evaluation. Histologic sections, stained with hematoxylin and eosin, showed that CUSA irradiation produced only minor tissue distortion as observed under the light microscope. A correct diagnosis would have been made in all cases had only tissue fragments obtained from the CUSA specimen trap been stained. For nine of ten patients, initial tumor cell viability was similar in the two specimen types. Flow cytometric DNA analysis confirmed that surgical methods produced matched samples. Cells that survived high-frequency ultrasound appeared functionally intact. For five of eight patients, the cells from the CUSA specimen traps survived and/or divided to a greater extent than those from the knife-dissected tumors. Cells from both surgical routes attained a similar number of passages in culture. It seems reasonable to extrapolate these in vitro observations with pelvic tumor tissues to normal surrounding tissue left in situ. Thus pelvic tissue is believed to be uninjured by CUSA ultrasonic irradiation.

Biopsy, Needle↗
PubMed1991

Neurologic complications of nonneuronopathic Gaucher's disease.

We describe eight patients with type 1 Gaucher's disease who developed neurologic complications that were secondary to systemic features of the illness. Four patients experienced neurologic difficulties because of coagulopathy, and the other four patients had involvement of the nervous system secondary to skeletal disease. Early recognition of these complications in patients with type 1 Gaucher's disease may lead to improved neurologic outcome.

Aged↗
PubMed1991

Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum-free medium.

Some patients with recurrent ovarian epithelial cancer respond favorably to treatment with GnRH agonists. This effect was proposed to be mediated by suppression of pituitary gonadotropin release. The present in vitro study investigated effects of human gonadotropin (Pergonal LH/FSH, 1:1) and Lupron, a GnRH agonist, on proliferation of an ovarian cancer cell line, 2774, which is estrogen receptor negative and grows well in serum-free, defined medium. Pergonal, 10 IU/mL or 30 IU/mL, did not enhance cell proliferation, which argues against stabilization of ovarian tumors in vivo due to decreased serum gonadotropin. Lupron, 1.4 micrograms/mL and 140 micrograms/mL, retarded cell division by day 6-8 of culture, in a dose-dependent manner. Flow cytometric cell cycle phase DNA analysis demonstrated Lupron caused a reversible 5-6% increase in the portion of cells in rest phase, G0/G1, compared to controls during log growth, and a corresponding decrease in the portion of cells in DNA synthesis, S phase. However, long-term culture, 3 weeks, with Lupron failed to arrest cells in G0/G1, and experimental cultures plateaued at cell number similar to control cultures. We conclude Lupron's effect on ovarian cancer cell proliferation is independent of gonadotropin and steroid, involves a cell cycle regulatory event, and duration of benefit observed in vivo for some patients may be related to total tumor volume at the time of treatment.

Antineoplastic Agents↗
PubMed1990

Autocrine regulation of human tumor cell proliferation by insulin-like growth factor II: an in-vitro model.

We have shown that a pleomorphic cell line of abnormal human karyotype derived from a stomach carcinoma (LIM-1839) proliferates in serum-free medium, expresses insulin-like growth factor II (IGF-II) mRNA, and secretes IGF-II (up to 56 ng/ml in serum-free conditioned medium, as measured in a rat liver RRA. No detectable levels of IGF-I can be measured in serum-free conditioned medium by RIA. These cells also secrete IGF-binding proteins, detected by a charcoal adsorption assay. The release of IGF-II and IGF binding proteins into serum-free conditioned medium (1.7 pmol/10(6) cells.24 h and 0.8 pmol binding sites/10(6) cells.24 h for 3 days, respectively) is inhibited 80% by cycloheximide (10 micrograms/ml). The LIM-1839 cells have type I and type II IGF receptors, determined by affinity cross-linking and competition binding studies. These cells proliferated 1.6-fold over 4 days in serum-free medium, with fresh medium changes on days 0 and 2: their growth was inhibited 56% by 40 micrograms/ml Sm 1.2, a monoclonal antibody which recognizes IGF-I and IGF-II. The addition of 20 and 50 ng/ml multiplication stimulating activity (rat IGF-II) caused 1.8- and 1.7-fold increases in cell growth between days 0 and 4 compared to controls, while [Thr59]IGF-I, at 20 and 50 ng/ml, caused 1.6- and 2.0-fold increases. Insulin, at 2 and 10 micrograms/ml, had no significant effect. The stimulatory effects of endogenous and exogenous IGFs on LIM-1839 cell proliferation were inhibited by a monoclonal antibody to the type I IGF receptor, alpha IR-3. These results suggest that the LIM-1839 cells are biologically responsive to endogenously produced IGF-II, and may thereby provide an in vitro model for autocrine regulation of human tumor growth by IGF-II.

Antibodies, Monoclonal↗
PubMed1989

Structure of the gene encoding peripherin, an NGF-regulated neuronal-specific type III intermediate filament protein.

We have cloned the rat gene encoding peripherin, a neuronal-specific intermediate filament protein that is NGF-regulated. Determination of the complete sequence, including 821 nucleotides of the 5'-flanking region, allows us to make conclusions about the evolutionary origin of the peripherin gene, its homology with other intermediate filament proteins, and possible mechanisms of regulation of peripherin expression in neurons. The positions of the eight peripherin gene introns correspond to the intron patterns of desmin, vimentin, and GFAP, with one example of intron sliding. Together with protein sequence homologies, this conclusively demonstrates that peripherin is a type III intermediate filament protein. The peripherin promoter contains sequences homologous to regions of other NGF-regulated promoters, which may function in peripherin induction by NGF.

Amino Acid Sequence↗
PubMed1988

Aromatization of testosterone by epithelial tumor cells cultured from patients with ovarian carcinoma.

Ovarian epithelial carcinoma originates from the surface mesothelium. It is controversial whether these tumors possess steroidogenic enzymes, similar to malignancies of other ovarian cell types. This study reports aromatase enzymatic activity for three epithelial cell lines, OV1225, OV166, and 2774, established from patients with ovarian adenocarcinoma. Aneuploidy of the cells was demonstrated by flow cytometric DNA analyses which showed OV1225 tetraploid, OV166 near diploid, and 2774 triploid. Estrogen synthesis was confirmed by measurement of estradiol (6 to 11 pg/10(7) cells/24 h) by radioimmunoassay in extracts of conditioned medium. To directly assay aromatase enzymatic activity, intact cells were incubated with tritiated testosterone. Medium was extracted with organic solvent after addition of trace 14C-labeled 17 beta-estradiol and 14C-labeled estrone. Androgen was separated from estrogen by celite column chromatography. Estrogen was further purified by silica gel thin-layer chromatography and derivatization of separate products to acetates. Purity of compounds was confirmed by consistency of the 3H:14C ratio of acetylated product versus that of product recrystallized with authentic standard. Conversion of testosterone to estradiol proceeded with apparent Michaelis-Menten kinetics. The apparent Km was 4 microM, 15 microM, and 59 microM, and the Vmax was 20 pmol/h/mg of cell protein, 52 pmol/h/mg of cell protein, and 152 pmol/h/mg of cell protein for 2774, OV166, and OV1225, respectively. We conclude that at least a portion of ovarian adenocarcinoma possesses sufficient aromatase activity to convert ovarian stromal androgen to estrogen.

Aromatase↗
PubMed1988

Regulation of the metastatic phenotype by the E1A gene of adenovirus-2.

We have previously demonstrated that rat embryo cells transformed by the ras oncogene alone are both tumorigenic and highly metastatic when injected into nude mice. In contrast, rat embryo cells transformed with the ras oncogene and the adenovirus 2 (Ad2) Ela gene are tumorigenic but either fail to metastasize, or exhibit a very low metastatic potential. Here we demonstrate that transfection of the Ad2 Ela gene into several of the ras transformed rat embryo cell lines results in a dramatic reduction in metastatic potential relative to the parental cell line. Transfection of cDNAs for the 12S and 13S Ela transcripts showed that both gene products are capable of reducing the metastatic potential of the ras transformed cell lines, however the 12S cDNA was more effective. This effect is specific to the Ad2 Ela gene as ras transformed cell lines expressing the Ad12 Ela gene or the human N-myc gene maintained their high metastatic potential. We hypothesize that the Ad2 Ela gene may regulate the expression of one or more cellular genes that contribute to the metastatic phenotype.

Adenovirus Early Proteins↗
PubMed1988

Bronchospasmolytic effects of RU 42173.

The bronchodilator properties of RU 42173, a new beta-adrenergic stimulant with an original structure, as a cyclic analogue of an arylethanolamine, have been evaluated on different in vitro and in vivo models and compared with those of salbutamol and isoprenaline. RU 42173 equipotently inhibited histamine-, acetylcholine-, and KCl-induced contractions in isolated guinea pig trachea or small bronchus and in isolated human bronchus. When administered to guinea pigs by the IV or aerosol route, RU 42173 dose-dependently inhibited bronchospasm induced by histamine, acetylcholine, and methacholine. It also inhibited PAF-induced bronchoconstriction and PAF-induced hyperreactivity to histamine. Moreover, RU 42173 had a rapid onset and prolonged duration of action. The potency of RU 42173 was similar to that of salbutamol.

Acetylcholine↗
PubMed1988

The E1a gene of adenovirus type 2 reduces the metastatic potential of ras-transformed rat embryo cells.

We have previously demonstrated that second-passage rat embryo cells transformed by the ras oncogene alone are both tumorigenic and highly metastatic when injected into nude mice. In contrast, rat embryo cells cotransformed with the ras oncogene and the adenovirus type 2 (Ad2) E1a gene are tumorigenic but either fail to metastasize or exhibit a very low metastatic potential. In this report, we demonstrate that transfection of the Ad2 E1a gene into four independent ras-transformed rat embryo cell lines results in a dramatic reduction in metastatic potential relative to that of the parental cell line. Transfection of cDNAs for the 12S and 13S E1a transcripts showed that the 12S cDNA was highly effective in reducing the metastatic potential of ras-transformed cell lines, while the 13S cDNA showed an effect in only one of the two cell lines tested. This effect is specific to the Ad2 E1a gene, since ras-transformed cell lines expressing the Ad12 E1a gene maintained their high metastatic potential. We hypothesize that the Ad2 E1a gene may regulate the expression of one or more cellular genes that contribute to the metastatic phenotype.

Adenovirus Early Proteins↗
PubMed1988

Cytoreduction of ovarian cancer with the Cavitron ultrasonic surgical aspirator.

The Cavitron ultrasonic surgical aspirator was used for cytoreduction in ten patients with intra-abdominal malignancy (nine ovarian and one fallopian tube). The mean age was 65 years, and eight patients had stage IIIC disease. Standard surgical techniques were used to resect the adnexa, uterus, and omentum. The Cavitron was used to remove disease from the diaphragm, spleen, stomach, and small bowel without resection or injury. These nongenital viscera would have required resection using surgical techniques for cytoreduction. The mean Cavitron surgical time was 49 minutes. Cytoreduction by the Cavitron facilitates tumor removal and reduces the requirement for nongenital visceral resection.

Aged↗
PubMed1987

Sulphur dioxide in Greater London, 1931-1985.

Annual mean sulphur dioxide concentrations measured at County Hall in central London between 1931 and 1985 showed no clear trend until 1963/64, when a steady decline set in. Results for a number of sites across London for the period 1964/65 to 1984/85 have been divided into three geographic zones: the City of London, a central zone and an outer zone. A steady downward trend is evident in each zone, but is most pronounced in the City of London, especially after 1970. This could reflect the successful introduction of a 1% limit on the sulphur content of oil used within the City, but not elsewhere in London. Annual mean sulphur dioxide concentrations are now around 40 microg m(-3) in all three zones. Highest daily sulphur dioxide levels in both summer and winter have also declined steadily during the period 1964/65 to 1984/85, while at the same time the seasonal pattern of higher winter peaks in daily maxima, which was strong at the beginning of the period, has been virtually eliminated.

Journal Article↗
PubMed1987

Complete nucleotide sequence of the chicken alpha A-crystallin gene and its 5' flanking region.

The chicken alpha A-crystallin gene and 2.6 kb of its 5' flanking sequence have been isolated and characterized by electron microscopy and sequencing. The structural gene is 4.5 kb long and contains two introns, each approx. 1 kb in length. The first intron divides codons 63 and 64, and the second intron divides codons 104 and 105, as in rodents. There is little indication that the insert exon of rodents (an alternatively spliced sequence) is present in complete form in the chicken alpha A-crystallin gene; small stretches of similarity to this sequence were found throughout the gene. The 5' flanking sequence of the chicken alpha A-crystallin gene shows considerable sequence similarity with other mammalian alpha B-crystallin genes. In addition, one consensus sequence (GCAGCATGCCCTCCTAG) present in the 5' flanking region of the chicken alpha A-crystallin gene was found in the 5' flanking region of most reported crystallin genes.

Amino Acid Sequence↗