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G Cooper

Publications and source records attributed to G Cooper.

At least 163 records · Page 9Linked to original sources
PubMed1987

Correlation of force-length area with oxygen consumption in ferret papillary muscle.

The ventricular systolic pressure-volume area correlates well with myocardial oxygen consumption. However, in isolated muscle preparations, there are experimental data based on both mechanical and energetic measurements that suggest that the pressure-volume area concept may not obtain. In the present study, force-length area, the analog of pressure-volume area for a linear muscle, was examined in the ferret papillary muscle preparation under a wide range of loading conditions. There were two major findings: first, force-length area is closely correlated with oxygen consumption (r = 0.94-0.98); this correlation is better than those for such other indexes as peak force and force-time integral. Furthermore, this relation of oxygen consumption with force-length area is independent of the mode of contraction (isometric or shortening), while the relations with the other indexes are not. Second, quick release imposed after end-systole during isometric contraction was found to curtail oxygen consumption. The first finding, the optimal correlation of force-length area with oxygen consumption, suggests both that the correlation of pressure-volume area with oxygen consumption on the ventricular level arises from a basic property of cardiac muscle and that force-length area may be the best mechanical index to use in calculating regional oxygen consumption for a ventricular segment. The second finding, however, suggests that the time-varying elastance model, on which the concepts of pressure-volume area and force-length area are based, may not provide a complete description of the mechanical basis of cardiac muscle energetics, especially during the isometric contraction.

Animals↗
PubMed1987

Dermoid cyst of the testis.

We present a case of testicular dermoid cyst in a 36 year old male. The relationship between this rare tumour and other differentiated teratomas is discussed.

Adult↗
PubMed1986

Early detection and treatment of spinal epidural metastases: the role of myelography.

Spinal epidural metastases were detected in 75 of 140 cancer patients with back pain who were evaluated prospectively by clinical criteria, spine roentgenography, and bone scan. Fifty-five of the 75 patients with epidural metastases had no evidence of myelopathy when diagnosed. Of the patients diagnosed and treated while still ambulatory, more than 90% remained so. Myelograms were performed in 127 patients to diagnose the 75 with epidural disease. To try to reduce the number of myelograms needed, we attempted to design radiotherapy ports based on clinical symptoms and the plain spine films alone. A port could not be designed for 64 of the 127 patients, either because of diffuse vertebral metastases or a normal plain roentgenogram. A port could be designed for 63 patients, and all epidural disease would have been encompassed in 50 of the 54 patients who had spinal epidural metastases (93%). Most patients with cancer and back pain require myelography for accurate treatment planning. There are, however, situations in which treatment can be determined based on symptoms and plain films alone, with a low risk of missing epidural cancer.

Back Pain↗
PubMed1986

Reversibility of the structural effects of pressure overload hypertrophy of cat right ventricular myocardium.

The purpose of the present quantitative structural study was to determine whether the histological alterations seen in pressure overloaded myocardium return to normal, as in vitro contractile function does, upon removal of the pressure overload stimulus. Three experimental groups of four cats each were studied: a group with pulmonary artery banding to create a pressure overload, a group that had been subjected to an equivalent duration of pressure overload and then had that pressure overload removed, and a group of sham-operated controls. Seven to 10 weeks after each operative procedure, the right ventricular pressure was elevated only in the pulmonary artery-banded group. The right ventricle/body weight ratio was significantly increased in the pressure overloaded group only. The body weight at sacrifice, the left ventricle/body weight ratio, and the right ventricular end-diastolic pressure did not differ significantly in the three groups. The striking histological changes in the right ventricular myocardium hypertrophing in response to a pressure overload were the decrease in the volume density of cardiocytes and the increase in connective tissue in papillary muscles. These were reversed when the pressure overload was removed. This study demonstrates that when a pressure overload is removed, myocardial structure returns to normal as the function returns to normal. Given the critical importance of the proportion of cardiocytes and connective tissue components to both systolic and diastolic cardiac function, these data support the hypothesis that the abnormal proportions of these structures provide a potential morphological basis for at least some of the functional abnormalities observed in pressure overload hypertrophy of the cat right ventricle.

Animals↗
PubMed1986

A monoclonal antibody reactive with an activated ras protein expressing valine at position 12.

Activated ras transforming genes have been described in a variety of neoplasms and encode 21,000-Dalton (p21) proteins with amino acid substitutions at positions 12, 13, and 61. In this report we describe a monoclonal antibody designated DWP that reacts specifically with synthetic dodecapeptides containing valine at position 12, to a lesser extent with peptides containing cysteine at position 12 and not with peptides containing glycine, arginine, serine, aspartic acid, glutamic acid or alanine at the same position. Western blot and immunoperoxidase studies showed that DWP specifically reacts with activated rasH or rasK proteins in NIH cells transformed by DNA from the human carcinoma cells that encode valine at position 12. DWP did not react with normal p21s encoding glycine at position 12, nor with activated p21s encoding aspartic acid, glutamic acid, arginine, serine, or cysteine at position 12. A survey of human tumor cell lines demonstrated that DWP reacted with the human bladder carcinoma cell line T24 but not with human tumor cell lines previously shown to contain other activating mutations at positions 12 or 61. DWP and perhaps additional antibodies that specifically react with alterations at positions 12 or 61 of the ras protein may be valuable in determining the presence and frequency of activated ras proteins in human malignancy.

Amino Acid Sequence↗
PubMed1986

Duodenal ulcer healing after presentation with haemorrhage.

Forty patients who were managed conservatively after haemorrhage from an endoscopically verified duodenal ulcer were randomised at discharge from hospital to enter a blind study of ranitidine therapy (150 mg bd) versus a placebo tablet. The patients were re-endoscoped after four weeks, ulcer status defined and the trial code broken revealing that five of 20 placebo patients had healed their duodenal ulcer compared with 16 of 20 ranitidine patients (p = 0.001). Lifestyle parameters of both groups improved during the study period but no directly related benefit in duodenal ulcer healing could be shown. We conclude that effective anti-ulcer therapy, such as ranitidine, is required to heal a duodenal ulcer which presents with haemorrhage.

Clinical Trials as Topic↗
PubMed1986

Load regulation of the properties of adult feline cardiocytes. The role of substrate adhesion.

We have recently described rapid and reversible changes in cardiac structure, function, and composition in response to surgical load alteration in vivo. In the present study, we used a simple, well-defined in vitro experimental model system, consisting of terminally differentiated quiescent adult cat ventricular cardiocytes maintained in serum-free culture medium, to assess more definitively the role of loading conditions in regulating these same biological properties of heart muscle. Cardiocytes considered to be externally loaded were adherent throughout their length to a protein substrate, such that the tendency for the ends of the cells to retract was prevented. Cardiocytes considered to be unloaded were not adherent to a substrate and, thus, were free to assume a spherical shape. Cardiocyte structure and surface area were assessed, in initially identified cells, both by serial light microscopy and by terminal electron microscopy. Cardiocyte function was assessed in terms of the ability to exclude trypan blue, to remain quiescent with relaxed sarcomeres containing I-bands, and to shorten in response to electrical stimulation. Cardiocyte composition was first assessed by quantitative gel electrophoresis of proteins and then by microfluorimetric measurement of ribonucleic acid, protein, and deoxyribonucleic acid. In addition, cardiocyte incorporation of [3H]thymidine into deoxyribonucleic acid and [3H]uridine into ribonucleic acid were measured. Loading via substrate adhesion was found to be very effective in terms of each of these measurements in retaining the differentiated features of adult cardiocytes for up to 2 weeks in culture; unattached and thus unloaded cardiocytes quickly dedifferentiated. Conditions thought to stimulate cardiac growth, including catecholamine stimulation, were found to be ineffective. These experiments demonstrate that external load has a primary role in the maintenance of the basic differentiated properties of adult mammalian cardiocytes.

Animals↗
PubMed1986

Beta adrenergic receptor blockade of feline myocardium. Cardiac mechanics, energetics, and beta adrenoceptor regulation.

Myocardial oxygen consumption is regulated by interrelated mechanical and inotropic conditions; there is a parallel increase in the aerobic metabolism and inotropic state during beta-adrenergic stimulation under fixed mechanical conditions. In contrast, there is some evidence that beta-blockade may reduce oxygen consumption through effects independent of its influence on mechanical conditions and contractile state, and that prolonged beta-blockade may sensitize the myocardium to beta-adrenergic stimulation. To clarify these two points, the present study examined the relationship of myocardial energetics to mechanics and inotropism during acute beta-blockade and after the withdrawal of long-term beta-blockade, whereupon the basis for any effect observed was sought by characterizing the number, affinity, and affinity states of the beta-receptors as well as the coupling of activated beta-receptors to cyclic AMP generation. Studies of right ventricular papillary muscles from control and chronically beta-blocked cats demonstrated contractile and energetic properties as well as dose-response behavior and inotropic specificity suggestive of an increase in myocardial sensitivity to beta-adrenoceptor stimulation in the latter group. Assays of cardiac beta-adrenoceptors from further groups of control and pretreated cats, both in cardiac tissue and in isolated cardiac muscle cells, failed to define a difference between the two groups either in terms of receptor number and affinity or in terms of the proportion of receptors in the high-affinity state. However, coupling of the activated beta-adrenoceptors to cyclic AMP generation was enhanced in cardiac muscle cells from chronically beta-blocked cats. These data demonstrate that beta-adrenoceptor blockade (a) produces parallel effects on inotropic state and oxygen consumption without an independent effect on either and (b) increases myocardial sensitivity to beta-adrenergic stimulation after beta-blockade withdrawal, not by "up-regulation" of the cardiac beta-adrenoceptors, but instead by more effective coupling of these receptors when activated to cyclic AMP generation.

Adrenergic beta-Antagonists↗
PubMed1985

Amyotrophic lateral sclerosis. A study of its presentation and prognosis.

All identified Israeli patients with amyotrophic lateral sclerosis (ALS) with onset of the disease from 1959 through 1975 (n = 318) were evaluated clinically. Most of our patients (63%) presented with weakness; only 10% presented with atrophy and 3% with fasciculations. In 31% of the cases, the onset of the disease was focal and 22% of the patients presented with bulbar signs, but only 6 patients presented with emotional lability (pseudo-bulbar). Twelve per cent of the patients presented with muscle cramps, pain or paraesthesia. Atypical signs such as motor cranial nerve lesion, dementia, sphincter disturbance and deep sensation loss are discussed. A relatively high proportion of our patients suffered from malignant tumour, but with no association with any specific tumour. The median survival time was 3 years. Patients with onset of their disease with bulbar signs had a shorter life expectancy (2.2 years): Twenty nine per cent of our patients survived for more than 5 years and 16% for more than 10 years.

Adult↗
PubMed1985

Anti-sperm antibodies, detected by agglutination, immobilization, microcytotoxicity and immunobead-binding assays.

To determine the reliability of tests currently utilized in the detection of sperm-reactive antibodies, sera were provided as unknowns and studied without knowledge of the clinical histories. Four laboratories performed tray agglutination tests (TAT), three complement-dependent immobilization (SIT), and single laboratories sperm cytotoxicity (SCT), passive haemagglutination (PHA) and immunobead binding (IBB). Most investigators demonstrated an excellent correlation between duplicate sample results. Nearly all of the female sera were free of anti-sperm antibodies and positive results did not appear in greater frequency in women with unexplained infertility as compared with other categories. For the male sera, the highest incidence of anti-sperm antibodies in the infertile group (21% positive for sperm-reactive IgGs) was obtained by immunobead binding. The GAT and TAT results gave 7 and 12% positives, except for lower results in one laboratory. Sperm-reactive antibodies were detected most commonly in vasectomized men, with all assays except SCT and PHA. Of the newer techniques studied, IBB results correlated well with TAT, GAT and SIT, while SCT and PHA did not, suggesting that a different group of antibodies, perhaps directed against other sperm-associated antigens, was being detected by the latter procedures. In this light, emphasis was placed on the need to validate whether results of particular methodologies correlated with impaired sperm function and to develop methods that provided evidence for this premise, either on the basis of clinical criteria or altered gamete interaction in vitro.

Antibodies↗
PubMed1985

Conception rates in couples where autoimmunity to sperm is detected.

In men with autoimmunity to sperm, a varying proportion of spermatozoa in the ejaculate are found to have surface-bound immunoglobulins. We asked whether the extent of autoimmunity, as judged by this criterion, would have predictive value in determining the chance of conception. Infertile couples where husbands were found to have antisperm antibodies were treated for other factors leading to impaired reproduction, but no specific treatment was offered for reduction of these antibodies. The chance of pregnancy for those couples where autoimmunity to sperm was the sole definable factor leading to infertility was 15.3% when most spermatozoa were antibody-bound. A significantly greater number of wives whose husbands had less than 50% of their sperm bound by immunoglobulins conceived (66.7%; P less than 0.005).

Autoantibodies↗
PubMed1985

Biochemical and structural correlates in unloaded and reloaded cat myocardium.

Cardiocytes of unloaded myocardium rapidly lose structural and functional integrity through a combined loss of myofibrils and contractile activity; both changes are reversible with load restoration. The present study correlates the biochemical composition of unloaded and reloaded myocardium with these alterations in structure and function. Cardiac muscle was unloaded by transecting the chordae tendineae of a cat right ventricular papillary muscle and was reloaded by suturing these same chordae tendineae to the ventricular wall at the base of the valve; an adjacent intact muscle served as the control. Muscles unloaded for 1 to 14 days were assayed for DNA, protein, total creatine and hydroxyproline content. The ratios of wet weight/DNA and creatine/DNA decreased by 30 and 22% respectively, in parallel with a 38% reduction in cardiocyte cross-sectional area. Protein/unit wet weight was decreased by 50% after 14 days of unloading, so that both protein/DNA and protein/creatine were markedly reduced. Reloading of the muscle restored cardiocyte size, protein per unit wet weight and protein/DNA to normal. Parallel reductions in both contractile filaments and contractile proteins after unloading and parallel increases in each following load restoration were demonstrated by morphometric analysis of electron micrographs and analysis of actin and myosin by gel electrophoresis. In summary, the myocardium undergoes marked, parallel changes in structure, function and biochemical composition in response to the removal and restoration of load.

Actins↗
PubMed1985

Structural analysis of pressure versus volume overload hypertrophy of cat right ventricle.

Pressure overload of cat right ventricle causes progressive abnormalities of in vitro contractile function at a time when in vivo contractile function is normal. In marked contrast, the same degree and duration of volume overload of cat right ventricle results in neither in vitro nor in vivo contractile dysfunction. The purpose of the present quantitative structural study was to determine whether there were any histological alterations in pressure-overloaded myocardium that might be causally related to the contractile dysfunction found only in this model. Four experimental groups of eight cats each were studied: a group with pulmonary arterial banding to create a pressure overload, sham-operated controls for this group, a group with atrial septal defects to create a volume overload, and sham-operated controls for this group. Seven to ten weeks after each operative procedure, right ventricular pressure was elevated only in the pressure-overloaded group, pulmonary-to-systemic blood flow ratio was increased only in the volume-overloaded group, and right ventricle-to-body weight ratio was significantly and comparably increased in both the pressure- and the volume-overloaded groups. There was a single striking histological distinction between myocardium hypertrophying in response to pressure as opposed to volume overload: the volume density of cardiocytes in papillary muscles from pressure-overloaded right ventricles was decreased significantly with a proportional increase in connective tissue. Given the critical importance of these two myocardial components to both systolic and diastolic cardiac function, these data provide a potential structural basis for at least some of the functional abnormalities observed in pressure but not in volume overload hypertrophy of the cat right ventricle.

Animals↗
PubMed1985

Hemodynamic versus adrenergic control of cat right ventricular hypertrophy.

The purpose of this study was to determine whether cardiac hypertrophy in response to hemodynamic overloading is a primary result of the increased load or is instead a secondary result of such other factors as concurrent sympathetic activation. To make this distinction, four experiments were done; the major experimental result, cardiac hypertrophy, was assessed in terms of ventricular mass and cardiocyte cross-sectional area. In the first experiment, the cat right ventricle was loaded differentially by pressure overloading the ventricle, while unloading a constituent papillary muscle; this model was used to ask whether any endogenous or exogenous substance caused uniform hypertrophy, or whether locally appropriate load responses caused ventricular hypertrophy with papillary muscle atrophy. The latter result obtained, both when each aspect of differential loading was simultaneous and when a previously hypertrophied papillary muscle was unloaded in a pressure overloaded right ventricle. In the second experiment, epicardial denervation and then pressure overloading was used to assess the role of local neurogenic catecholamines in the genesis of hypertrophy. The degree of hypertrophy caused by these procedures was the same as that caused by pressure overloading alone. In the third and fourth experiments, beta-adrenoceptor or alpha-adrenoceptor blockade was produced before and maintained during pressure overloading. The hypertrophic response did not differ in either case from that caused by pressure overloading without adrenoceptor blockade. These experiments demonstrate the following: first, cardiac hypertrophy is a local response to increased load, so that any factor serving as a mediator of this response must be either locally generated or selectively active only in those cardiocytes in which stress and/or strain are increased; second, catecholamines are not that mediator, in that adrenergic activation is neither necessary for nor importantly modifies the cardiac hypertrophic response to an increased hemodynamic load.

Animals↗