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T J O'Brien

Publications and source records attributed to T J O'Brien.

At least 109 records · Page 6Linked to original sources

Cloning of a mu-class glutathione S-transferase complementary DNA and characterization of its glucocorticoid inducibility in a smooth muscle tumor cell line.

A cDNA (designated hGSTYBX) encompassing the complete coding sequence of a hamster mu-class glutathione S-transferase (GST) subunit was cloned from a lambda ZAP library constructed with mRNA isolated from triamcinolone acetonide-treated smooth muscle tumor cells (DDT1 MF-2). Analysis of its nucleotide and deduced amino acid sequences demonstrated highest homology to the rat mu-class GST YB2 subunit. In proliferating subconfluent cells, in which constitutive expression of hGSTYBX mRNA was undetectable, glucocorticoid treatment induced hGSTYBX expression after a time lag of 3 h, and maximal induction occurred at 10 h. Nuclear run-on analysis showed that glucocorticoid induction resulted at least in part from an increased rate of transcription. Simultaneous treatment with glucocorticoid and cycloheximide prevented glucocorticoid induction, but had little effect on basal expression in confluent cells. In contrast, cycloheximide treatment 3 h after glucocorticoid treatment resulted in nearly full induction. These results taken together suggest that hGSTYBX induction may be a secondary glucocorticoid response.

Amino Acid Sequence↗

Distribution of CA 125 in embryonic tissues and adult derivatives of the fetal periderm.

New murine monoclonal antibodies to a partially purified CA 125 antigen were developed and identified as M 2 and M 11. With immunohistochemical techniques, these new antibodies and OC 125 antibody were used to search for CA 125 in embryonic tissues and adult apocrine sweat glands and mammary glands. The embryonic skin, the periderm, expressed CA 125 antigen and its adult derivatives, the mammary glands and apocrine sweat glands, expressed CA 125 while in the active state of secretion. In a 6-week-old formalin-fixed and paraffin-embedded ectopic embryo specimen, antibodies M 2 and M 11 recognized CA 125 in the periderm, the notochord, the myocardium, the pericardium, the gastroenteric tract, enteric duct remnants in the umbilical cord (vitelline and allantoic ducts), the mesonephric duct, and the amnion. OC 125 staining of these formalin-fixed specimens was either very faint or absent. In a formalin-fixed and paraffin-embedded specimen of apocrine sweat glands from the axilla, antibodies M 2 and M 11 detected CA 125 antigen intracellularly in the secretory cells. Again no staining was observed with OC 125 antibody. In a frozen and acetone-fixed specimen of lactating mammary glands, antibodies M 2 and OC 125 detected CA 125 antigen intraductally. Colostrum and milk collected from 25 mothers at various stages post partum had mean CA 125 levels of 34,213 U/ml in colostrum, 1469 U/ml at 3 to 7 days, and 105 U/ml at 5 to 26 weeks.

Amnion↗

Expression of the ras oncogene in gynecologic tumors.

Control of oncogene expression has been shown to be a coordinated regulatory mechanism in normal growth and development. Overt expression of these genes also has been noted in transformed or neoplastic cell types. The ras family of oncogenes has been shown to be particularly evident among genes expressed in malignant tissues. We provide evidence, using ribonucleic acid dot analysis and Western blot analysis of gynecologic tumor extracts, that ras expression may be a common occurrence in these malignancies. Furthermore, the ras-related peptides can be detected in sera of some patients with tumors.

Electrophoresis, Polyacrylamide Gel↗

The effect of psoralen photochemotherapy (PUVA) on symptomatic dermographism.

A controlled trial of 4-weeks oral photochemotherapy (PUVA) on 14 patients with severe symptomatic dermatographism produced a clinically useful reduction in itching in five patients. In four of these patients itching had relapsed to pre-treatment levels within 3 months of finishing the PUVA course. A comparison of the weal and flare responses on exposed and covered (control) skin using a calibrated dermographometer showed no significant change in skin reactivity, even in the patients who experienced symptomatic relief. While PUVA may temporarily reduce itching in some patients with symptomatic dermographism, its use cannot generally be justified for treating this type of physical urticaria.

Adult↗

ras oncogene is expressed in adenocarcinoma of the endometrium.

Activation of c-ras oncogenes has been implicated in human carcinomas of the colorectum, prostate, bladder and breast. The major peptide product of c-ras is a 21 kilodalton peptide (p21), but other larger "ras-related" peptides have been described in urine obtained from patients with several types of cancers. In the present investigation immunohistochemical methods were used to assess c-ras expression in tissues obtained from patients with endometrial adenocarcinoma. Formalin-fixed, paraffin-embedded tissues were processed in routine fashion, then incubated with a monoclonal antibody raised against a v-H-ras synthetic peptide. ras Peptides were not detected in proliferative or secretory endometrium or in benign adenomatous hyperplasia. One of four specimens of atypical adenomatous hyperplasia and two of 11 specimens of grade 1 (international Federation of Gynecology and Obstetrics) adenocarcinoma stained positive for ras peptides. A total of 95% of the grade 2 and 3 adenocarcinoma studied contained detectable ras peptides within neoplastic cells. In contrast to previous immunohistochemical studies that identified ras peptides only in neoplastic cells of bladder, prostate, colon, and breast cancers, we routinely found ras peptides within stromal cells of high-grade endometrial carcinomas. When stained with hematoxylin and eosin, these cells have the appearance of foamy macrophages.

Adenocarcinoma↗

CA 125 in tissues and amniotic fluid during pregnancy.

CA 125 was assayed in amniotic fluid and tissue extracts by immunoradiometric assay, and immunohistochemical studies were performed on paraffin-embedded sections of endometrium, decidua, and fetal membranes with the monoclonal antibody OC 125 used as primary antibody. The concentration of CA 125 in amniotic fluid changes during pregnancy so that levels of 800 to 1000 U/ml are found before 12 weeks. Thereafter, levels of 4000 to 10,000 U/ml are detected routinely. As term approaches, amniotic fluid CA 125 concentrations fall to a range of 1000 to 2000 U/ml. Levels of CA 125 in tissue extracts of secretory endometrium and decidua were 65,000 and 29,500 U/gm of tissue, respectively. CA 125 was readily detected on the apical surfaces of glandular epithelium and in the secretions of endometrial glands obtained throughout the menstrual cycle. It was also detected in the lumina of decidualized glands throughout pregnancy. No antigen was detectable within glandular epithelial cells. We have previously reported high concentrations of CA 125 in chorionic tissue extracts (42,000 U/gm) and low concentrations in amniotic tissue extracts (275 U/gm). In contrast to those findings, immunohistochemical techniques detected CA 125 within the intercellular canaliculi that surround amniotic epithelial cells but not in chorion. We conclude that the likely source of amniotic fluid CA 125 is the decidua and that it gains access to the amniotic fluid via the intercellular canalicular system that traverses the amniotic epithelium.

Amniotic Fluid↗

Iodic eruptions.

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Adrenal Cortex Hormones↗

CA 125 antigen in human amniotic fluid and fetal membranes.

The cancer antigen CA 125 is manifest by serous cystadenocarcinoma of the ovary and to a lesser extent by other gynecologic and nongynecologic tumors. Its presence was screened for in normal human fetal tissues and fluids. Appreciable quantities of CA 125 were discovered in amniotic fluid by both a dot blot assay and the commercially available immunoradiometric assay kit. The most likely source of this antigen was found not to be the developing fetus, since antigen was absent from cord blood and fetal urine, but rather the chorionic membrane, which contained significant quantities of the antigen. CA 125 was found in extracts of maternal decidua, but none was found in extracts of placenta or amnion. The CA 125 antigen was determined by gel filtration experiments to be in excess of 700,000 daltons and probably in the range of 2 to 3 X 10(6) daltons. Size heterogeneity based on gel filtration and anion heterogeneity based on anion exchange chromatography have both been demonstrated for the CA 125 molecule. The amniotic fluid antigen is composed of two subunits of approximately 240,000 and 180,000 daltons as detected by iodine 125-labeled OC 125 monoclonal antibody. The antigen may contain additional subunits not detected by the monoclonal antibody. Size and change heterogeneity as well as the poor definition of the subunit bands on polyacrylamide gels also suggest this molecule contains an appreciable carbohydrate component.

Amnion↗

Anti-androgen treatment in women with acne: a controlled trial.

Ninety female patients with acne were allocated randomly to one of three groups and treated either with Diane, a high dose cyproterone acetate (CPA) regime with ethinyloestradiol, or Minovlar. The same dose of oestrogen was common to all three treatment groups. Patients were assessed every 2 months for 6 months, by grading for severity of the acne, lesion counts and photography, and subjectively using a visual analogue scale. In addition, bacteriological sampling and sebum excretion rate (SER) measurements were performed. The results showed a clinical improvement in all three treatment groups, but a more rapid and complete response was seen in those groups who received CPA. There was also a consistent trend suggesting a more favourable response in those in the high dose CPA group. Although there was a marked reduction in SER in the groups treated with CPA, there was no correlation between reduction in SER and clinical improvement in individuals, nor could a reduction in the surface bacterial population be shown to be a primary event in the success of anti-androgen therapy. We have shown that the addition of CPA to oestrogen adds significantly to the therapeutic effect in acne and that anti-androgen and oestrogen combinations are more effective than standard oestrogen and progestagen contraceptive pills.

Acne Vulgaris↗