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Biomedical subjects

J O'Connell

Publications and source records attributed to J O'Connell.

At least 19 recordsLinked to original sources
PubMed1992

The matrix metalloproteinases and their natural inhibitors: prospects for treating degenerative tissue diseases.

Uncontrolled matrix metalloproteinase activity is thought to be a cause of the tissue damage observed in many disease processes. None of the drugs currently in use can prevent tissue destruction, and strategies for the development of synthetic inhibitors have been hampered by a poor understanding of the biochemistry of matrix metalloproteinases. Recent cDNA cloning efforts and characterization of recombinant human matrix metalloproteinases have permitted structure-function analysis of the enzymes and their inhibitors. Progress in this area should help indicate a route to rational strategies for designing lead therapeutic compounds.

Amino Acid Sequence↗
PubMed1990

Survival associated with renovascular disease in Glasgow and Newcastle: a collaborative study.

Data from 121 consecutive patients with hypertension and renovascular disease, first diagnosed between 1975 and 1982 in Glasgow and Newcastle, were analysed retrospectively to determine the factors which influenced their outcome. Thirty-six patients died between the data of arteriography and 1st January 1987, giving five and ten year survival rates of 83% and 67%. Survival was greatly reduced in comparison with that of age-sex-matched controls in the general population of the West of Scotland, and was also less than that of essential hypertensives matched for age, sex, initial diastolic blood pressure and smoking habit who had attended the Glasgow Blood Pressure Clinic during the same period. Multivariate analysis showed that age, cigarette smoking and presence of atheromatous disease were significantly and independently related to outcome among the patients with renovascular disease, whereas male sex, centre of origin, severity of hypertension when first seen, initial renal function and presence of bilateral disease were not. Despite a trend towards benefit from surgical intervention (ten year survival in medical group 62%, in surgical group 71%; p = 0.19) our data do not prove that intervention is better than medical treatment, largely because the decision on intervention was not randomised. A prospective trial would be required to answer this important question.

Adult↗
PubMed1988

Malignant progression of papilloma-derived keratinocytes: differential effects of the ras, neu, and p53 oncogenes.

The p117 keratinocyte cell line was derived in culture from chemically induced mouse papillomas. The benignly transformed nature of these cells was demonstrated by their ability to re-form benign papillomas when grafted back onto the animal. Retroviral vectors were used to introduce into the p117 cells three distinct oncogenes: v-Ha-ras, p53, and neu. All three oncogenes were able to induce tumorigenic conversion of the p117 keratinocytes when assayed by subcutaneous injection into nude mice. However, grafting the oncogene-transformed cells onto the back of the mouse revealed important differences in the ability of the three oncogenes to induce a fully malignant phenotype. While the ras-transformed papilloma cells formed aggressive carcinomas, p53 and neu transformation yielded an intermediate phenotype, with formation of large exophytic tumors, not yet invasive but with highly dysplastic features remarkably similar to those of in situ carcinomas. These findings establish a homologous, genetically modifiable cell system in which various stages of malignant transformation can be directly compared.

Animals↗
PubMed1988

Venovenous extracorporeal membrane oxygenation for noncardiogenic pulmonary edema after coronary bypass surgery.

A 71-year-old woman with noncardiogenic acute pulmonary edema early after having a coronary operation was treated with venovenous extracorporeal membrane oxygenation for uncontrollable hypoxia. Adequate oxygenation was achieved, the rapid deterioration of her condition was reversed, and ventilatory settings could be moderated. Two and a half days later, the patient was weaned from the system. At the time of this writing, the patient was in her sixth postoperative month and doing well. Details of this fairly simple but powerful technique are described.

Aged↗
PubMed1987

Tort versus no-fault: compensation and injury prevention.

The tort system, as a means of compensating the victims of injury, no longer fulfills the purpose for which it was intended. The attempt to achieve a fair and rational method of compensation, especially in the areas of medical malpractice and products liability, has been displaced by a form of litigation lottery which permits attorney's fees to divert great amounts of money from victims in needs. A reform of this system is much in need and long overdue. Following a discussion of these and other problems with the tort system, this paper will present a method for ensuring the prompt settlement of most personal injury claims through payment of the victim's net economic losses. The parallels to no-fault auto insurance and workers' compensation are examined and attention is given to the likely impact of this proposal on the conduct of potential injurers and victims.

Consumer Product Safety↗
PubMed1987

Health significance of chlorination byproducts in drinking water: the Houston experience.

In 1954, following the construction of Lake Houston, a change from lightly chlorinated ground sources to a heavily chlorinated surface source of drinking water took place for a sizable part of the population in the city of Houston, Texas. This has provided the opportunity to compare the incidence of urinary tract cancer mortality in populations exposed to heavily chlorinated and lightly chlorinated drinking water. The spatial, diurnal, and seasonal concentrations of chlorination byproducts (trihalomethanes) in Houston water were assessed. The range of concentrations varied from below the limits of detection in treated ground water, to more than 200 mg/l (twice the level allowed by US drinking water standards) in treated lake water. The mortality experience by gender, by race, and by age cohorts for the period 1940 to 1970 from urinary tract cancers and three comparison causes was determined for 56 of Houston's census tracts classified by the duration of exposure to the surface water. By the 1970's 20 years following the switch to surface water, an increase was detected in urinary cancer mortality rates for white females without a corresponding increase observed for white males. No clear-cut trends were found for the non-white population. On balance, a detrimental urinary cancer effect associated with a switch to chlorinated surface water has not been demonstrated yet.

Adolescent↗
PubMed1986

Nocardia epididymo-orchitis in an immunosuppressed patient.

The immunocompromised patient after organ transplantation is susceptible to unusual and life-threatening infections. We report a case of epididymitis that evolved into testicular nocardiosis after cardiac transplantation. An awareness of the potential for these infections and early diagnosis may prevent extensive morbidity in the post-transplantation patient.

Adult↗
PubMed1986

Aneuploidy, an early event in mouse skin tumor development.

It has been suggested that chromosomal alterations can play a role in mouse skin carcinogenesis. These changes have been proposed as a possible mechanism of action of tumor promoters and they have also been related to the conversion of benign papillomas to carcinomas. However, direct evidence showing the chromosomal constitution of these tumors has not been previously described. Here we show the presence of aneuploid cells in very early papillomas and the eventual displacement of the diploid stem line by aneuploid clones at later stages. Squamous cell carcinomas (SCC) induced by the same protocol were highly aneuploid. These results suggest that genomic imbalance produced by aneuploidy may be related to the malignant conversion of the benign papillomas.

Aneuploidy↗
PubMed1986

Critical genetic determinants and molecular events in multistage skin carcinogenesis.

Carcinogenesis can be operationally and mechanistically divided into at least three major stages--initiation, promotion, and progression. Variations among stocks and strains of mice to susceptibility to multistage skin and liver carcinogenesis appear to be more related to alterations in tumor promotion than tumor initiation; however, the critical events have not been determined. In the mouse skin model the first stage is thought to involve the interaction of a tumor initiator with the genetic material of stem cells leading to an alteration in some aspect of growth control, differentiation, or both. The major effect of tumor promoters, regardless of the type, is the specific expansion of the initiated stem cells in the skin. This appears to occur by both direct and indirect mechanisms that involve the loss of glucocorticoid receptors, differentiation alterations, a direct growth stimulation of the initiated cells, or selective cytotoxicity. The progression stage is characterized by a high level of genetic instability that produces a number of chromosomal alterations. These changes may be responsible for the loss of the high-molecular-weight keratin proteins and filaggrin, increase in gamma-glutamyl-transpeptidase activity, and changes in oncogene expression in squamous cell carcinomas. We have found that a high percentage of squamous cell carcinomas have a trisomy in chromosome 2 that carries both src and abl genes and an increased expression of src and abl. We have also found increased Ha-ras on RNA expression in both papillomas and squamous cell carcinomas. We suggest that the genetic instability of the initiated cells is responsible for most observed changes during skin carcinogenesis.

Animals↗
PubMed1986

Cytogenetic evidence for gene amplification in mouse skin carcinogenesis.

Using our recently developed methodology for cytogenetic evaluation of solid tumors, we analyzed the occurrence of double minutes (DM) in chemically induced mouse skin carcinomas and papillomas. These studies revealed that DM were observed in 10% of the squamous cell carcinomas and in none of the papillomas screened. In addition, we analyzed four cell lines derived from mouse skin papillomas and one spontaneously transformed mouse epidermal cell line. The presence of DM was a consistent feature in all the studied cell lines. In the papilloma cell lines, the degree that DM occurred correlated with the cell line's capacity to form malignant tumors in immunosuppressed mice. DM were also observed in direct chromosomal preparations from tumors induced by one of the papilloma cell lines. Homogeneously staining regions were also present in metaphases from the spontaneously transformed cell line. We have shown here, for the first time, DM and homogeneously staining regions in mouse skin tumors and transformed cells derived from mouse skin. Since DM and homogeneously staining regions are the cytogenetic equivalents of gene amplification, which is a mechanism of increased expression of normal or altered gene products, these findings may play a relevant role in mouse epidermal carcinogenesis.

Animals↗