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Biomedical subjects

J Connolly

Publications and source records attributed to J Connolly.

At least 91 records · Page 5Linked to original sources
PubMed1990

Tumor progression in four mammary epithelial cell lines derived from the same patient.

Two primary and two metastatic cell lines with distinct phenotypes and genotypes have been established from a patient diagnosed as having infiltrating and intraductal mammary carcinoma (21T series). All four lines can be cultured in the same medium, DFCI-1, which also supports long-term growth of normal epithelial cells. Therefore, we have been able to compare normal and tumor cells at the cellular and molecular levels. The mammary origin of the 21T series was confirmed by using antibodies against the human milk fat globule antigen-2 epitope. The two primary tumor lines (21NT and 21PT) are both immortal and aneuploid, although only 21NT is tumorigenic in the nude mouse assay. The two populations derived from the metastatic pleural effusion (21MT-1 and 21MT-2) each exhibit distinct characteristics in morphology and growth factor requirements. The erbB2 gene is amplified and overexpressed in all of these cell lines compared to normal epithelial cell controls. These four tumor cell lines from a single patient represent a mammary tumor progression series that has been established in long-term cell culture.

Adult↗
PubMed1990

Conservative surgery and radiotherapy for early breast cancer.

In 1984, as part of a prior American Cancer Society National Conference on Breast Cancer, the authors reported on the status of conservative surgery (CS) and radiotherapy (RT) as primary local treatment for women with early stage breast cancer. Since that time, additional data have become available regarding the use of this approach and its comparability to mastectomy. In general, these data support the use of CS and RT and, as a result, this approach is now more widely employed in the United States and abroad than it was in 1984. The current focus of inquiry has shifted from whether or not CS and RT is an acceptable option for patients with early stage breast cancer to the following questions. For which patients are CS and RT suitable? What are the best techniques of surgery and RT? Are there any patients who can be treated safely with CS without RT? How should RT and systemic therapy be integrated when both are to be used? In this report, recent results on the use of CS and RT from both retrospective and prospective trials are summarized, and these current areas of inquiry are addressed.

Breast Neoplasms↗
PubMed1989

A newly established metastatic breast tumor cell line with integrated amplified copies of ERBB2 and double minute chromosomes.

A continuous line of human mammary tumor cells, called 21MT, has been established in culture from a pleural effusion of a 36-year-old woman with metastatic breast cancer. The cells are epithelial as shown by morphology and expression of keratins and are mammary tumor cells as shown by expression of the HMFG-2 antigenic determinant. The cells grow well both in DFCI-1, a partially defined medium containing pituitary extract and 1% fetal bovine serum, and in alpha-minimum essential medium (alpha-MEM) supplemented with 10% serum, epidermal growth factor (EGF), insulin, and hydrocortisone. Karyotypic analysis of cells at early passage has shown the presence of rearranged (marker) chromosomes as well as aneuploidy with a net DNA content in the tetraploid range, confirmed by DNA cytofluorography, as well as double minute chromosomes in about 5% of the cells. Southern blots have revealed a 40-fold amplification of the ERBB2 gene and a 50-fold overexpression of its mRNA. The amplification of ERBB2 DNA was localized by in situ hybridization to one of the marker chromosomes but not to the double minutes. It is inferred, therefore, that at least two genes have been amplified in these cells.

Adult↗
PubMed1989

Hepatitis B screening in a northern Irish mental handicap institution: relevance to hepatitis B vaccination.

The current DHSS guidelines on immunisation against hepatitis B in mental handicap hospitals recommend vaccination for personnel at risk directly involved in patient care (who may have direct contact with patients or their body fluids) and for new admissions into institutions where the incidence is known to be high. We report a serological survey of hepatitis B markers in over 99% of the residents of a large mental handicap hospital. Of 720 patients tested only one carried hepatitis surface antigen. This patient was anti-HBe positive. Only 4.5% of the residents carried any hepatitis marker. These results do not suggest the need for a local vaccination programme for patients or staff.

Cross Infection↗
PubMed1989

Nocturnal home oxygen in the treatment of hypoxemic cystic fibrosis patients.

The effect of nocturnal oxygen therapy on mortality and morbidity rates and on progression of disease was tested in a double-blind, randomized trial of 28 subjects with advanced cystic fibrosis. Patients were selected on the basis that their awake arterial oxygen tension was less than 65 mm Hg when they were clinically stable. Oxygen was prescribed in 1 L/min increments to obtain an awake arterial oxygen tension of greater than or equal to 70 mm Hg. Subjects received humidified oxygen or room air from modified concentrators. They were enrolled over a 3-year period and followed for an average (+/- SD) of 26 +/- 9 months. The average number of hours per night of concentrator use was 5.3 +/- 3.2 hours in the air group and 7.0 +/- 1.9 hours in the oxygen group. Over the follow-up period there were four deaths in each group, and oxygen therapy had no significant effect on the frequency of hospitalizations. Progression of disease was ascertained from nutritional status, pulmonary function, blood gas values, exercise ability, and right ventricular ejection fraction response to exercise (as measured by equilibrium-gated radionuclide angiocardiography), and psychologic status was measured by standardized tests of mood, self-esteem, and cognitive function; group comparisons for the first year revealed no significant differences; however, school or work attendance was maintained in the oxygen group but deteriorated in the air group. Clinical signs of cor pulmonale were documented during follow-up in 10 patients in toto, and all lived at least 9 months from the onset of these signs. The lack of association between the onset of these signs and imminent death, or the usefulness of measurements of the maximal oxygen uptake during progressive exercise and the right ventricular ejection fraction response to exercise as prognostic indicators, suggest that death may not be the result of cor pulmonale. We conclude that nocturnal oxygen treatment in patients with cystic fibrosis did not appear to affect mortality rates, the frequency of hospitalizations, or the progression of disease; oxygen use should be instituted only after the development of symptoms related to hypoxemia.

Adult↗
PubMed1989

M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) chemotherapy for transitional cell carcinoma: the Princess Margaret Hospital experience.

We treated 41 patients with transitional cell carcinoma with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy. Median patient age was 56 years. Of the patients 33 had either distant metastases or locoregional disease that could not be cured by an operation or radiation. Of these patients 30 had measurable disease and 12 responded (4 complete and 8 partial responses, response rate 40 per cent, 95 per cent confidence limits 23 to 59 per cent). Only 2 of these patients remain with an unmaintained complete response at 34 and 52 months. Of 5 patients 3 responded who were treated with neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for locally advanced bladder cancer before radiation or cystectomy, and only 1 of these patients is free of disease. The remaining 3 patients were treated postoperatively because they were at high risk for recurrence and all are well. Toxicity of the regimen was severe: 41 per cent of the patients experienced neutropenic sepsis and 54 per cent required hospitalization for management of toxic complications. Three patients experienced pulmonary embolism and 1 had deep vein thrombosis. There was 1 drug-related death of sepsis. Although a patient occasionally may have long-term benefit from this chemotherapy our results suggest caution in the widespread application of this protocol.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Genes encoding neuronal nicotinic acetylcholine receptors.

Four genes (alpha 2, alpha 3, alpha 4, and beta 2), which encode proteins homologous to the Torpedo electric organ and vertebrate muscle nicotinic acetylcholine receptors, have been identified by cloning rat brain cDNAs. Injection of transcripts derived from these cDNAs into Xenopus laevis oocytes results in the formation of three nicotinic acetylcholine receptors. Two of these receptors, alpha 3/beta 2 and alpha 4/beta 2, have the characteristics of ganglionic nicotinic receptors. The third (alpha 2/beta 2) exhibits a previously undescribed pharmacology and thus represents a novel subtype that may be expressed in the brain. The wide distribution of alpha 2, alpha 3, alpha 4, and beta 2 transcripts in the brain indicates that neuronal nicotinic acetylcholine receptors are a major neurotransmitter receptor system.

Animals↗
PubMed1989

Alteration of neuritic cytoarchitecture in Alzheimer disease.

Individuals afflicted with Alzheimer disease (AD) demonstrate two prominent brain structural alterations: senile plaques and neurofibrillary tangles (NFT) (Selkoe, 1986). Not appreciated until recently is a third quantitatively significant structure, the dystrophic neurite. Many of these altered neurites are focally associated with amyloid deposits, and together they comprise the senile plaque. However, the great majority of the abnormal neurites in AD are independent of senile plaques (Braak, et al., 1986). Recent advances have yielded considerable information on the chemical nature of the extracellular amyloid (Kang, et al., 1987; Tanzi, et al., 1988) which comprises the central portion of the senile plaque, but there is much yet to be unraveled concerning both the nature of NFT and the relationship between senile plaques and NFT (Selkoe, 1987). While the NFT is principally comprised of 20 nm helically wound filaments, descriptively termed paired helical filaments (PHF) (Kidd, 1963; Wisniewski, et al., 1976) occasionally 12-15 nm straight filaments are also present (Perry, et al., 1987c). We have found that the predominant filaments in dystrophic neurites of AD are straight filaments which are morphologically indistinguishable from those found within NFT. The abnormal neuritic filaments and PHF share microtubule associated protein, tau, and ubiquitin immunoreactivity. The prevalence of altered neurites suggests that reorganization of neuritic cytoarchitecture in AD, as demonstrated by the formation of abnormal polymers structurally, and by inference functionally distinct from the normal cytoskeleton, may constitute a more important part of the cytopathological change of AD than previously appreciated.

Alzheimer Disease↗
PubMed1989

The interpretation of office radiographs by family physicians.

This study prospectively compared the interpretations of family practice residents and faculty with those of radiologists on 532 office radiographs using a uniform protocol. A total of 136 family practice residents (44 first-year, 40 second-year, 52 third-year) and 42 full-time and part-time faculty participated in the study along with 30 radiologists. The mix of radiographs evaluated was as follows: 44 percent chest, 20 percent lower extremity, 6 percent head, 4 percent lumbosacral spine, 3 percent cervical-thoracic spine, and 3 percent abdomen-pelvis. Interpretation concordance rates between family physicians and radiologists, by level of training, were as follows: first-year residents 83.0 percent, second-year residents 84.4 percent, third-year residents 86.0 percent, and faculty 88.6 percent. Concordance after the resident and faculty preceptor discussed the film and provided a collaborative interpretation was 92.1 percent. This finding compares with previously reported error rates of 10 to 40 percent between experienced radiologists. Only 10.3 percent of the discordant readings (0.8 percent of all radiographs) contained significant discordancies that may have affected patient management or outcome. Had the family physicians been given the option to refer an x-ray film to the radiologist, all x-ray films containing significant discordancies would have been referred.

Adult↗
PubMed1989

Development of an osteogenic bone-marrow preparation.

The osteogenic effect of bone marrow was tested in rabbits, using chambers that had been implanted in the peritoneal cavity (ectopic site) and in a delayed-union model (orthotopic site). Osteogenesis was accelerated in both sites after concentration of marrow elements by centrifugation, but not after unit gravity sedimentation. Chambers that were implanted with marrow that had been processed by simple and isopyknic centrifugation demonstrated a more pronounced increase in deposition of calcium compared with whole-marrow implants of equal volume (101 compared with 193 per cent). Orthotopic grafting of a rabbit delayed-union model with whole marrow and marrow that had been processed with simple centrifugation significantly increased osteogenesis, as measured biomechanically and biochemically. Significantly improved healing was evident radiographically at five weeks after grafting with bone marrow that had been concentrated by simple centrifugation.

Animals↗
PubMed1988

Functional expression of a new pharmacological subtype of brain nicotinic acetylcholine receptor.

A new type of agonist-binding subunit of rat neuronal nicotinic acetylcholine receptors (nAChRs) was identified. Rat genomic DNA and complementary DNA encoding this subunit (alpha 2) were cloned and analyzed. Complementary DNA expression studies in Xenopus oocytes revealed that the injection of messenger RNAs (mRNAs) for alpha 2 and beta 2 (a neuronal nAChR subunit) led to the generation of a functional nAChR. In contrast to the other known neuronal nAChRs, the receptor produced by the injection of alpha 2 and beta 2 mRNAs was resistant to the alpha-neurotoxin Bgt3.1. In situ hybridization histochemistry showed that alpha 2 mRNA was expressed in a small number of regions, in contrast to the wide distribution of the other known agonist-binding subunits (alpha 3 and alpha 4) mRNAs. These results demonstrate that the alpha 2 subunit differs from other known agonist-binding alpha-subunits of nAChRs in its distribution in the brain and in its pharmacology.

Amino Acid Sequence↗
PubMed1988

Primary structure and expression of beta 2: a novel subunit of neuronal nicotinic acetylcholine receptors.

A new subunit, beta 2, of the neuronal nicotinic receptor family has been identified. This subunit has the structural features of a non-agonist-binding subunit. We provide evidence that beta 2 can substitute for the muscle beta 1 subunit to form a functional nicotinic receptor in Xenopus oocytes. Expression studies performed in oocytes have demonstrated that three different neuronal nicotinic acetylcholine receptors can be formed by the pairwise injection of beta 2 mRNA and each of the neuronal alpha subunit mRNAs. The beta 2 gene is expressed in PC12 cells and in areas of the central nervous system where the alpha 2, alpha 3, and alpha 4 genes are expressed. These results lead us to propose that the nervous system expresses diverse forms of neuronal nicotinic acetylcholine receptors by combining beta 2 subunits with different agonist-binding alpha subunits.

Acetylcholine↗
PubMed1987

Adolescent self-reports of social activity: assessment of stability and relations to social adjustment.

Adolescents' self-reports of peer social activity were examined with regard to short-term stability and in relation to social adjustment. Two separate periods of data collection are reported; year 1 with 74 grade nine students and year 2 with 76 grade nine students. On both occasions, four administrations of a self-report questionnaire were undertaken. As well, in year 2, social adjustment ratings, indices of perceived competence and self-efficacy, and IQ were collected. The analyses of the measure's consistency indicated acceptable stability of the self reports across two weeks and high internal consistency. These findings indicate the potential utility of this methodology for studying peer activity. Zero-order and multiple correlation analyses between social activity, self-evaluations and social adjustment were computed. The analyses suggest that peer social activity is correlated with social self-esteem, enhanced social self-efficacy and teacher's ratings of social engagement. Social isolation appeared to be an independent dimension and was related to lowered self-esteem and teacher ratings of social withdrawal. Overall, the results of the study add to our understanding of the components of social adjustment in adolescence.

Adolescent↗