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Biomedical subjects

K Cowan

Publications and source records attributed to K Cowan.

At least 37 records · Page 2Linked to original sources
PubMed1994

Acute arterial thrombosis in a patient with breast cancer after chemotherapy with 5-fluorouracil, doxorubicin, leucovorin, cyclophosphamide, and interleukin-3.

BACKGROUND: Interleukin-3 (IL-3) is an experimental agent used to ameliorate neutropenia in patients receiving chemotherapy. Arterial thrombotic episodes after use of IL-3 have not been reported previously. METHODS: The case of a patient with Stage III adenocarcinoma of the breast who developed hypotension and acute cerebellar artery and superior mesenteric artery thrombosis after receiving chemotherapy and treatment with IL-3 is reported. RESULTS: To the authors' knowledge, this is the first patient with arterial thrombosis reported after treatment with IL-3. CONCLUSIONS: Interleukin-3 may be associated with increased propensity for thrombosis.

Acute Disease↗
PubMed1994

Topoisomerase II levels and drug sensitivity in adult acute myelogenous leukemia.

The topoisomerase (topo) II-directed agents etoposide, daunorubicin (DNR), and amsacrine (m-AMSA) are widely used in the treatment of acute myelogenous leukemia (AML). In the present study, multiple aspects of topo II-mediated drug action were examined in marrows from adult AML patients. Colony-forming assays revealed that the dose of etoposide, DNR, or m-AMSA required to diminish leukemic colony formation by 90% (LD90) varied over a greater than 20-fold range between different pretreatment marrows. Measurement of nuclear DNR accumulation in the absence and presence of quinidine revealed evidence of P-glycoprotein (Pgp) function in 8 of 82 samples at diagnosis and 5 of 36 samples at first relapse, but the largest quinidine-induced increment in DNR accumulation (< 2-fold) was too small to explain the variations in drug sensitivity. Restriction enzyme-based assays and sequencing of partial topo II alpha and topo II beta cDNAs from the most highly resistant specimens failed to demonstrate topo II gene mutations that could account for resistance. Western blotting of marrow samples containing greater than 80% blasts revealed that the content of the two topo II isoenzymes varied over a greater than 20-fold range, but did not correlate with drug sensitivity in vitro or in vivo. In addition, levels of topo II alpha and topo II beta in 46 of 47 clinical samples were lower than in human AML cell lines. Immunoperoxidase staining showed that these low topo II levels were accompanied by marked cell-to-cell heterogeneity, with topo II alpha being abundant in some blasts and diminished or absent from others. There was a trend toward increasing percentages of topo II alpha-positive cells in pretreatment marrows that contained more S-phase cells. Consistent with this observation, treatment of patients with granulocyte-macrophage colony-stimulating factor for 3 days before chemotherapy resulted in increases in topo II alpha-positive cells concomitant with increases in the number of cells traversing the cell cycle. These observations have implications for the regulation of topo II in AML, for the use of topo II-directed chemotherapy, and for future attempts to relate drug sensitivity to topo II levels in clinical material.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Drug resistance and cancer.

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ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Acute effects of marijuana smoking on aggressive, escape and point-maintained responding of male drug users.

Aggressive, escape and point-maintained operant responding of male marijuana smokers were measured during six 25-min sessions conducted over an 8-h experimental day. Aggressive responding ostensibly subtracted points exchangeable for money from another subject. Escape responding protected the subject's counter from point subtractions initiated by the other subject for some period of time. Aggressive and escape responding were engendered by subtracting points from the subjects and maintained by initiation of intervals free of point subtractions. Point subtractions presented to the subjects were attributed to other persons. Subjects earned points exchangeable for money on a third response option. Subjects participated in one session prior to smoking and five sessions after smoking. Subjects smoked placebo or three different potencies of active marijuana cigarettes. Marijuana smoking effects on escape responding were not significant and depended upon the frequency of provocation. Point-maintained responding was decreased after marijuana smoking. Aggressive responding was increased for the first hour after smoking and returned to placebo levels later in the day. These effects of marijuana smoking on aggressive responding are discussed in terms of subject characteristics, particularly drug use history.

Adult↗
PubMed1993

Factor stationarity and invariance of the POMS in cocaine patients.

The Profile of Mood States (POMS) factor scores are commonly used to evaluate the clinical pharmacologic effects of a drug. Two assumptions made when using the POMS in this manner are that its factor structure remains constant across time (factor stationarity) and that the factor structure is identical across experimental groups (factor invariance). If these assumptions are not met, then interpreting change in POMS factor scores becomes problematic. Structural equation modeling programs (e.g., LISREL) may be used to explicity test assumptions of factor stationarity and invariance. As part of a National Institute on Drug Abuse grant-funded, double-blind, placebo-controlled trial to assess effectiveness of treating cocaine-abusing patients with fluoxetine, POMS data were collected at baseline and at 6 weeks (n = 90). Applying a longitudinal factor analysis strategy, factor stationarity and invariance of two POMS factors were assessed in this patient sample.

Adult↗
PubMed1992

Regulated expression of syndecan in vascular smooth muscle cells and cloning of rat syndecan core protein cDNA.

cDNA encoding the core protein of rat syndecan was cloned from a neonatal rat aortic cDNA library by polymerase chain reaction amplification. Expression of syndecan mRNA in rat aortic vascular smooth muscle (VSM) cells was demonstrated by reverse transcriptase-linked polymerase chain reaction amplification of syndecan sequences using total RNA from rat aortic VSM cells as templates. Polyclonal antibodies against rat syndecan core protein were produced by immunizing rabbits with a recombinant fusion protein containing a fragment of the extracellular domain. The anti-syndecan antibodies immunoprecipitated a large 35SO4-labeled molecule synthesized by cultured rat aortic VSM cells. The immunoprecipitated molecule was identified as a hybrid proteoglycan, based on results of alkaline, nitrous acid, and chondroitinase ABC digestions. On immunoblots the antibodies recognized a proteoglycan of greater than 200 kDa, with a core protein size after deglycosylation of approximately 50 kDa. The anti-syndecan antibodies stained cultured rat aortic VSM cells as well as tissue sections of neonatal and adult rat aortas in the medial, smooth muscle layer. On Northern blots of RNA isolated from cultured VSM cells, a syndecan cDNA probe hybridized to a major RNA species of 2.6 kilobases. Quantitative Northern blot analysis of total RNA isolated from VSM cells harvested at different cell densities revealed a decrease in syndecan mRNA levels with increased cell density. These results demonstrate the regulated synthesis of syndecan by rat VSM cells.

Amino Acid Sequence↗
PubMed1992

Results of the National Cancer Institute early breast cancer trial.

In 1979, a prospective, randomized trial was begun at the National Cancer Institute comparing lumpectomy, axillary dissection, and radiation therapy (XRT) to modified radical mastectomy for the treatment of invasive breast cancer, clinical stage T1-2, N0-1, M0. Treatment in the radiation arm consisted of full axillary dissection and gross removal of the tumor, followed by 4500 to 5000 cGy to the whole breast and a boost to the tumor bed of 1500 to 2000 cGy. Patients with positive axillary dissections received radiation to the supraclavicular nodes, in addition to cyclophosphamide and doxorubicin. Two hundred thirty-seven patients entered in the trial between 1979 and 1987 are available for analysis, 116 in the mastectomy arm and 121 in the radiation arm. With a median follow-up of 67.7 months, there are no significant differences in 5-year overall survival (85% vs 89%, mastectomy vs radiation) or 5-year disease-free survival (82% vs 72%, mastectomy vs radiation). Patients in the radiation arm had an actuarial in-breast recurrence rate of 12% at 5 years and 20% at 8 years. There were no major differences between complication rates in the treatment arms. The results of the study indicate that patients with invasive breast cancer, stage I and II, can be treated with lumpectomy, axillary dissection, and radiation therapy with results comparable to those with modified radical mastectomy.

Actuarial Analysis↗
PubMed1991

Expression of antisense transcripts encoding an extracellular matrix protein by stably transfected vascular smooth muscle cells.

The ability to selectively inhibit the expression of various extracellular matrix proteins would provide an approach towards elucidating not only the function of these molecules but allow some insight to be gained into the mechanisms by which these molecules influence various aspects of vascular smooth muscle cell behavior such as growth, migration, morphology, and extracellular matrix assembly. The present study explores the feasibility of employing an antisense RNA approach to study vascular smooth muscle extracellular matrix proteoglycan function. Vascular smooth muscle cells were transfected with a test plasmid designed to express an antisense transcript encoding an extracellular matrix protein. The test plasmid was constructed by inserting the cDNA encoding the majority of the rat chondrosarcoma extracellular matrix link protein in an antisense orientation relative to the rat metallothionein-I promoter. Several stably transfected cell lines were isolated and characterized with respects to link antisense transcript expression, morphology, growth, and smooth muscle cytoskeletal protein expression. Results from these studies have shown that vascular smooth muscle cells could be stably transfected and link antisense transcript could be expressed at high levels by these cells. In addition, the rat metallothionein-I promoter was found to be a strong inducible promoter in vascular smooth muscle cells. Cell biology characterization of the various transfected vascular smooth muscle cell lines generated in this study has shown that one type of transfected vascular smooth muscle cell line expressed cellular characteristics indicative of early passaged vascular smooth muscle cells while a second type of transfected cell line was morphologically similar to vascular smooth muscle cells recovered from neonatal rat aortas and mechanically injured arteries obtained from adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Vascular smooth muscle biglycan represents a highly conserved proteoglycan within the arterial wall.

Two overlapping cDNA clones containing sequences homologous to human bone biglycan were isolated from a rat vascular smooth muscle (VSM) cell cDNA library. Nucleotide sequence analysis demonstrated that these clones encoded the rat VSM biglycan complete core protein sequence. A high degree of genetic conservation was observed for biglycan since nucleotide sequence homology comparisons revealed an 88% homology occurring between rat and human biglycan cDNA coding regions. The deduced core protein for the secreted form of VSM biglycan was found to be composed of ten leucine-rich repeating units whose consensus sequence was similar to that present in human bone and bovine cartilage biglycans. Protein homology comparisons revealed that the mature rat VSM biglycan core protein was 97% homologous to both human bone and bovine cartilage biglycan core proteins. Most of the amino acid substitutions in the secreted form of rat VSM biglycan are of the conservative type thereby maintaining the hydrophobic property of this proteoglycan within the arterial wall. The highest frequency of amino acid substitutions occurring between rat, bovine and human biglycan core proteins was found to reside within a small hypervariable region located near the N-terminus of these proteoglycans. Rat VSM biglycan was found to contain dinucleotide repeat elements located in the 3' untranslated region of its mRNA which may influence the expression of this transcript. Biglycan mRNA levels were not found to vary significantly as a function of VSM cell density. However, biglycan transcript levels did vary significantly as a function of VSM cell growth state. Similar studies revealed that collagen, fibronectin, and laminin were able to influence biglycan mRNA levels in quiescent VSM cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Characterization of extracellular matrix proteoglycan transcripts expressed by vascular smooth muscle cells.

Northern blot analysis using intraspecies and cross-species cDNA probes encoding a variety of proteoglycan (PG) core proteins was employed to examine in vitro and in vivo vascular smooth muscle cell (VSMC) extracellular matrix (ECM) PG gene expression. Similar studies were performed using a cDNA probe encoding the rat chondrosarcoma link protein. VSMCs maintained in vitro as well as in vivo expressed a 1.8 kb transcript homologous to a cDNA encoding the bovine bone small PGII. Densitometric analysis revealed an 11-fold increase in the in vivo level of this transcript when compared to an equivalent amount of RNA extracted from rat VSMCs maintained in vitro. Rat aorta medial tissue contained approximately a 10-fold higher level of the bovine bone PGII homologous transcript when compared to rat chondrosarcoma tissue. A 2.9 kb transcript homologous to a cDNA encoding the human bone small PGI (biglycan) was detected in poly(A)+ RNA isolated from rat VSMCs maintained in vitro as well as within rat thoracic aorta medial tissue. Densitometric analysis revealed a 0.55-fold increase in the in vitro level of the PGI transcript when compared to in vivo levels. Rat chondrosarcoma expressed approximately a 3-fold higher level of a human bone PGI homologous transcript when compared to rat aorta medial tissue. A 7.3 kb and an 8.4 kb transcript homologous to a cDNA encoding the rat chondrosarcoma large hyaluronic acid (HA) binding chondroitin-sulfate (CS) PG core protein was detected in poly(A)+ RNA extracted from rat VSMCs maintained in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Short stature in anorexia nervosa patients.

In the treatment of many anorexia nervosa (AN) patients, we observed clinically that these girls were short in stature. In order to test this hypothesis, we reviewed the height records of all patients seen with a previous diagnosis of AN in an eight-year period. Of 104 patients, 85 were suitable for study and were compared to a control group of 85 age-matched subjects. Seventy-six percent of the AN patients (mean age 15.8 years) were below the 50th height percentile for age; 14.1% were below the 5th percentile; and 25.8% were between the 25th and 49th percentile. Parental height was available for 35 subjects. The AN patients were significantly shorter than their parents, and comparison suggests an impairment of growth rather than a familial etiology. As 80% of subjects developed AN after menarche, malnutrition does not appear to be responsible for the observed height deficits.

Adolescent↗