Search PubMed⌕ Search

Biomedical subjects

C Oakley

Publications and source records attributed to C Oakley.

At least 37 records · Page 2Linked to original sources
PubMed1993

Increased expression of specific protein tyrosine phosphatases in human breast epithelial cells neoplastically transformed by the neu oncogene.

Protein tyrosine phosphorylation/dephosphorylation is a fundamental mechanism in the regulation of cell proliferation and neoplastic transformation; this metabolic process is modulated by the opposing activities of protein tyrosine kinases and protein tyrosine phosphatases (PTPases). While the role of protein tyrosine kinases has been examined extensively in human breast tumorigenesis, the role of PTPases in this process is virtually unknown. To address this issue, an activated neu oncogene was introduced into an immortalized nontumorigenic human breast epithelial cell line (184B5). This resulted in a substantial increase in P185neu expression, which led to the formation of progressively growing carcinomas after such cells were inoculated into athymic nude mice. Importantly, a striking increase in the expression of specific PTPases, LAR and PTP1B, was observed in 3 independently neu transformed cell lines and their derived tumors. This elevation was verified at both the mRNA and protein levels. TC-PTP PTPase expression was only slightly increased in these neu transformed cells, and no expression of CD45 PTPase was observed. The level of neu expression, as well as the differential expression between P185neu and LAR/PTP1B, directly correlated with tumorigenicity. Furthermore, rat mammary carcinomas with elevated neu expression (neu-induced) also had sharply elevated LAR-PTPase expression when compared to rat mammary carcinomas with little or no neu expression (7,12-dimethylbenzanthracene induced); the level of expression of LAR PTPase was directly correlated with the level of neu expression. Thus, our results provide the first evidence that, in human breast carcinoma cells and in rat mammary carcinomas that have an induced increase in neu expression, a consistent and substantial increase in the expression of specific PTPases occurs. The relationship between P185neu-protein tyrosine kinase expression and specific PTPase expression may play a critical role in human breast tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Identification of a mutation in the beta cardiac myosin heavy chain gene in a family with hypertrophic cardiomyopathy.

OBJECTIVE: To investigate the molecular genetic basis of the cause of disease in a family with hypertrophic cardiomyopathy. BACKGROUND: Mutation within the beta cardiac myosin heavy chain gene has been shown to be the pathogenetic mechanism underlying the disease in several families, though clear evidence of heterogeneity has been reported. PATIENTS: A family with a history of hypertrophic cardiomyopathy. RESULTS AND CONCLUSION: This paper reports a mutation at aminoacid position 908 within exon 23 of the beta cardiac myosin heavy chain gene, resulting in a conversion of a leucine to valine. This base substitution was identified in an individual with a confirmed family history but with equivocal symptoms of the disease. Inheritance of the mutation by his symptom free juvenile offspring demonstrates the application of the technique to presymptomatic diagnosis.

Adolescent↗
PubMed1993

The sequence of alignment of microtubules, focal contacts and actin filaments in fibroblasts spreading on smooth and grooved titanium substrata.

Contact guidance refers to the reactions of cells with the topography of their substratum. Current hypotheses on the mechanism of contact guidance focus on the dynamic behaviour of the cytoskeletal components, but most observations have been made on cells that have already become oriented with topographic features of the substratum. The purpose of this study was to examine the sequence in which microtubules, focal contacts and microfilament bundles become aligned to the substratum topography as fibroblasts spread on grooved substrata. Human gingival fibroblasts were trypsinized and seeded onto grooved titanium surfaces produced by micromachining, as well as onto control smooth surfaces. After observation and photography of the spreading cells at times up to 6 hours, the cells were fixed and exposed to one or more of the following antibodies or fluorescent stains: phallacidin to stain actin filaments, monoclonal anti-tubulin, monoclonal anti-vinculin, anti-mouse IgG labelled with Texas-Red or FITC, and/or an aldehyde-reactive stain to identify the cell outline. The cells were photographed and cell area, shape and orientation were calculated. Cells were also examined with confocal microscopy to obtain optical sections so that cell height as well as the precise locations of the cytoskeletal components with respect to the vertical dimension of the grooved substrata could be determined. Microtubules were the first element to become oriented parallel to the direction of the grooves and were first aligned at the bottom of the grooves. This alignment of microtubules was evident as early as 20 minutes after plating and preceded the orientation of the cell as a whole. Aligned actin microfilament bundles were not observed until 40-60 minutes and were observed first at the wall-ridge edges. At early times, focal contacts were distributed radially, but only after 3 hours did the majority of cells demonstrate aligned focal contacts. If the first cytoskeletal component to become aligned is the prime determinant of cell orientation, then these data suggest that microtubules in human gingival fibroblasts may determine cell orientation on grooved titanium surfaces. By analogy with microtubule behaviour in other systems, we suggest that microtubule orientation on grooved substrata may occur as a result of the substratum establishing shear-free planes.

Actin Cytoskeleton↗
PubMed1992

Effect of free gingival grafts on naturally-occurring recession in miniature swine.

Miniature swine exhibit naturally-occurring, progressive recession on facial surfaces of the permanent mandibular incisors. The purpose of this study was to determine whether placing a free gingival graft to augment the width of keratinized gingiva of mandibular incisors in miniature swine would prevent or retard recession at the grafted site compared to an untreated contralateral control site. In 8 litter-mate miniature swine, free gingival grafts were placed on the facial surface of the permanent central and lateral incisors on one side of the mandible. The contralateral mandibular incisors did not receive any treatment and served as controls. Clinical measurements, including eruption, recession, pocket depth, attachment level, and keratinized gingival width were obtained preoperatively, 2 to 3 weeks after surgery to assess the success of gingival augmentation, and 3, 6, and 9 months postoperatively. Eight grafted sites were successful and showed significant augmentation of the keratinized gingival width, with a mean increase of 5.8 +/- 0.7 mm, while 6 grafts failed and showed a slight decrease in the mean width of -0.4 +/- 0.5 from the preoperative to postoperative examination. All sites showed significant recession during the experimental period. Successful sites showed no statistically significant or clinically major difference in the rate or amount of recession than contralateral control sites. By 9 months, the average increase in recession from the baseline examination was 2.8 +/- 1.5 mm for successfully grafted sites and 2.6 +/- 1.3 mm for contralateral controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

G-induced loss of consciousness accidents: USAF experience 1982-1990.

Discussion of acceleration protection measures should be based on analysis of relevant accident data, including determination of high risk aircraft, G profiles, and pilot descriptions. There were 18 accidents (14 fatalities) attributed to G-induced loss of consciousness (G-LOC) in the United States Air Force (USAF) from 1982 through 1990. All 18 accidents occurred during single crewmember sorties, for an average rate of 2.1 per million single-seat flying hours (pmfh). The average G-LOC accident rate for 1982-4 was 4.0 pmfh, decreasing significantly to 1.3 pmfh for 1985-90. This decrease is associated with the USAF initiation of an anti-G-LOC training program. We reviewed accident records for G-LOC cofactor data and compared them to normal data for USAF pilots for age, height, weight, systolic and diastolic blood pressures, heart rate, total flying time, and aircraft-specific flying hours. Only for systolic blood pressure (higher) and aircraft-specific flying hours (shorter) were the mishap pilots significantly different from other USAF pilots. We found no evidence to support weight training vs. aerobic training, missed meals, or heat in causing G-LOC accidents. Thus the mishap pilots appeared to be a representative cross section of USAF pilots with respect to personal variables. More significant factors appeared to be G duration, G magnitude, use of G trousers, and experience in assigned aircraft.

Accidents, Aviation↗
PubMed1991

Difference in mortality between patients treated with captopril or enalapril in the Xamoterol in Severe Heart Failure Study.

The double-blind, placebo-controlled, multinational trial Xamoterol in Severe Heart Failure randomized 290 patients treated with captopril and 217 treated with enalapril to xamoterol or placebo. At the end of the 100-day follow-up period, the cumulative probability of survival in patients with coronary artery disease or with dilated cardiomyopathy decreased in the captopril group (90.3%) when compared with the enalapril group (97.2%). The excess mortality in the captopril group could not be related to the indexes of the severity of heart failure, such as baseline exercise duration, functional class, cardiothoracic ratio, ejection fraction or dose of diuretic drugs. Furthermore, the excess in mortality was seen in all subsets of patients examined as well as across countries. Examination of the dosing regimen used, however, suggests that insufficient daily dosage of captopril or the inadequate schedule of administration, or both, might be responsible for different degrees of angiotensin-converting enzyme inhibition between the enalapril and captopril groups and hence for the difference in mortality. It is important in future clinical trials to determine to what extent complete circadian angiotensin-converting enzyme inhibition is necessary to provide the full benefit of this therapy in heart failure.

Adrenergic beta-Agonists↗
PubMed1991

Genesis of arrhythmias in the failing heart and therapeutic implications.

Between 50 and 70% of patients with heart failure die suddenly and unexpectedly before they have deteriorated to New York Heart Association class IV symptoms. It has long been known that ventricular ectopy predicts sudden cardiac death in coronary heart disease, and this has also been shown in dilated cardiomyopathy. It is less certain whether antiarrhythmic drugs reduce this risk and improve prognosis. Supraventricular arrhythmias frequently develop in heart failure of all causes. They nearly always cause symptoms, and the establishment of atrial fibrillation may mark a permanent deterioration. Except for sustained ventricular tachycardia, ventricular arrhythmias are often occult. Hypokalemia and digitalis toxicity may have been precipitated by diuretics or interaction with antiarrhythmic drugs. In coronary heart failure, arrhythmias may be related to scar tissue or ischemia, which may also be responsible in dilated cardiomyopathy. Use of inotropes and inodilators may precipitate arrhythmias, whereas drugs that conserve energy or potassium, such as beta blockers and angiotensin-converting enzyme inhibitors, may prevent them. Since suppression of ventricular arrhythmias has not been shown to prevent sudden death or prolong life in patients with heart failure, it may be that such arrhythmias do not directly presage ventricular fibrillation except in so far as they are markers of a poor prognosis with a risk of sudden death. If so, such arrhythmias are most likely to be suppressed by agents that result in improvement of left ventricular function and, through that, prolongation of life.

Arrhythmias, Cardiac↗
PubMed1990

The effects of acoustic orientation cues on instrument flight performance in a flight simulator.

An initial version of an acoustic orientation instrument (AOI), in which airspeed was displayed as sound frequency, vertical velocity as amplitude modulation rate, and bank angle as right-left lateralization, was evaluated in a T-40 (Link GAT-3) motion-based simulator. In this study, 15 pilots and 3 non-pilots were taught to use the AOI and flew simulated flight profiles under conditions of neither visual nor auditory instrumentation (NO INPUT), AOI signals only (AOI), T-40 simulator instrumentation only (VISUAL), and T-40 simulator instrumentation with AOI signals (BOTH). Bank control under AOI conditions was significantly better than under the NO INPUT condition for all flying tasks. Bank control under VISUAL conditions was significantly better than under the AOI condition only during turning and when performing certain complex secondary tasks. The pilots' ability to use the AOI to control vertical velocity and airspeed was less apparent. However, during straight-and-level flight, turns, and descents the AOI provided the pilots with sufficient information to maintain controlled flight. Factors of potential importance in using sound to convey aircraft attitude and motion information are discussed.

Acoustic Stimulation↗
PubMed1988

Importance of right ventricular function in congestive heart failure.

Failure of the right ventricle may be due to a congenital anomaly, intrinsic disease, pulmonary stenosis or pulmonary hypertension. Left ventricular failure may also lead to right ventricular failure if the heart fails totally or secondary to pulmonary hypertension, or if filling of the right ventricle is decreased due to left ventricular dilation or hypertrophy. Treatment of right ventricular failure has yielded disappointing results, except when caused by left ventricular failure that responds to therapy. Digitalis and diuretics may have more adverse than beneficial effects. In patients with both left and right ventricular failure, survival is usually less than 2 years.

Cardiomyopathy, Dilated↗
PubMed1987

Ten year clinical evaluation of Starr-Edwards 2400 and 1260 aortic valve prostheses.

The long term performance characteristics of the 2400 and 1260 series of Starr-Edwards aortic prostheses were investigated by a follow up study of clinical outcome of 327 patients discharged from hospital with isolated aortic valve replacement. Follow up lasted for up to 10 years and was based on 1616 patient-years. The 2400 series cloth covered tracked valve was implanted in 182 patients from 1974 to 1980 and the 1260 series bare strut silastic ball valve was inserted in 145 patients from 1979 to 1983. Total 10 year mortality and valve related morbidity were low and no cases of mechanical valve failure were recorded. There were no significant actuarial differences in mortality or valve related morbidity between the 2400 and 1260 valves. Starr-Edwards models 2400 and 1260 aortic valve prostheses showed excellent durability without any mechanical failures over a 10 year period. The long term outcome of isolated aortic valve replacement with these models is associated with a low frequency of valve related complications.

Adolescent↗
PubMed1985

Rheumatoid arthritis and pulmonary hypertension. A report of three cases.

Three women with well established rheumatoid arthritis (RA) who developed pulmonary hypertension during the course of their disease are reported. In one patient there was mild pulmonary fibrosis but this appeared unrelated to the severity of the pulmonary hypertension. Another patient had increased platelet stickiness which may have contributed to this complication, whereas in the third patient, no contributing factors were apparent. The pulmonary complications of RA and their relationship to the development of pulmonary hypertension are discussed.

Adult↗
PubMed1984

Constrictive pericarditis as a complication of coronary artery bypass surgery.

Although it is now recognised as a rare complication of cardiac surgery, constrictive pericarditis was diagnosed in three patients after coronary artery bypass surgery. The time interval between cardiac surgery and the development of constrictive features varied from two to six weeks. All three patients presented with severe congestive heart failure. Haemodynamic findings were characteristic of constrictive pericarditis. Pericardial thickening detected by computed tomography in one patient was useful in establishing a definite diagnosis. One of the patients had a serous constrictive effusive pericarditis, and surgical pericardial drainage was needed. The other patient underwent pericardiectomy with preservation of the grafts. The diagnosis of constrictive pericarditis should be considered in patients presenting with unexplained right sided heart failure after cardiac surgery.

Aged↗
PubMed1983

Surgical treatment of infective endocarditis with special reference to prosthetic valve endocarditis.

Patients with native valve endocarditis treated surgically between 1968 and 1978 (n = 15) and all patients presenting with prosthetic valve endocarditis during this period (n = 21) were followed up for at least four years. Five of the patients with native valve endocarditis required urgent early surgical intervention, of whom two died. The remaining 10 underwent valve replacement after a course of antibiotic treatment: all survived, though one required further valve replacement. The 21 patients with prosthetic valve endocarditis suffered 25 attacks. Nine were cured by medical treatment alone; two died before surgical intervention was possible; 11 required valve replacement, of whom three died; and two required valve replacement after a course of antibiotic treatment. The incidence of early prosthetic valve endocarditis--that occurring within two months of operation--was 0.67%, but that of late prosthetic valve endocarditis could not be determined. Medical treatment when started early should cure endocarditis in most patients, but vigilance should be maintained for the appearance of indications for surgery. When such indications exist surgery should not be delayed.

Adult↗