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Biomedical subjects

C Parker

Publications and source records attributed to C Parker.

At least 163 records · Page 9Linked to original sources
PubMed1988

Isolation and characterization of epididymal epithelial cell plasma membranes.

Sperm maturation and storage occur in a unique milieu created in large part by the epididymal epithelium. To learn more about the interaction of the epididymal epithelial cell with both luminal and systemic environments, we now report on the preparation and characterization of epididymal epithelial cell plasma membranes. A preparation enriched for epididymal epithelial cell plasma membranes was isolated from collagenase-digested epididymal tubule fragments by hand-Dounce homogenization, differential centrifugation, and sucrose gradient centrifugation. The final membrane fraction was enriched 11-fold for the plasma membrane marker 5'-nucleotidase; 2.6-fold for the lysosomal marker acid phosphatase, and 3-fold for the Golgi marker thiamine pyrophosphatase. No enrichment was observed for mitochondrial or endoplasmic reticulum enzyme markers. Specific and saturable transferrin-binding activity was also detected in the final preparation. Electron microscopy revealed the presence of vesicles and sheets of membranes as well as an occasional Golgi apparatus. The plasma membrane fraction was used to generate monoclonal antibodies. Of 102 wells exhibiting growth, 12 were positive by immunofluorescent staining of frozen sections. Ten of these recognized determinants in epithelial cells, and 2 stained peritubular smooth muscle cells. Most of the epithelial cell-specific antibodies stained brush border alone or in combination with the basolateral plasma membrane. Three antibodies stained the Golgi apparatus. Most antibodies were specific for particular epididymal regions, 3 also recognized determinants in the kidney, and 1 stained residual bodies in the testis.

Animals↗
PubMed1988

Influence of an enriched dietary sodium chloride regime during gestation and suckling and post-natally on the ontogeny of hypertension in the rat.

Brattleboro rats without diabetes insipidus were subjected to sodium chloride enrichment (20-fold increase in dietary salt) at various stages of their development. Salt supplementation in the adult rat produced higher systolic blood pressure (SBP), particularly in males (142 +/- 3 versus 110 +/- 3 mmHg in control. The blood pressures of females on salt-supplemented diets during pregnancy decreased from 136 +/- 1 to 121 +/- 2 mmHg, although throughout this period the blood pressures for these rats were greater than for the control pregnant rats. Pregnant females on salt-supplemented diets also showed higher sodium concentrations in the amniotic fluid compared with controls (155 +/- 3.4 versus 134.1 +/- 6.0 mmol/l). Salt supplemented lactating mothers produced milk with similar sodium concentrations to those of the controls, but the urinary sodium concentrations of pups suckling on the former were greater than in the controls. It is concluded that the suckling pups were also salt-enriched. Rats were submitted to salt-enriched regimes in utero, during suckling, post-weaning and post-pubertally, or permutations thereof. Salt supplementation post-weaning led to consistent elevation in arterial blood pressure with males being more susceptible than females. The degree of elevation was increased if the salt-supplement was present during suckling (132 +/- 1 versus 112 +/- 1 mmHg) and was greatest when the salt-supplemented regime was administered both in utero and during the post-weaning period (154 +/- 2 versus 112 +/- 1 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

18-Hydroxydesoxycorticosterone↗
PubMed1988

Effect of hyaluronidase on mortality and morbidity in patients with early peaking of plasma creatine kinase MB and non-transmural ischaemia. Multicentre investigation for the limitation of infarct size (MILIS).

A multicentred, randomised, blind study was started in 1978 to compare propranolol or hyaluronidase with placebo in patients with acute myocardial infarction admitted within 18 hours of onset of symptoms. Patients were randomised to group A and received hyaluronidase, propranolol, or placebo, or, if propranolol was contraindicated, to group B and received hyaluronidase or placebo. Hyaluronidase (500 U/kg given every six hours for 48 hours) had no effect on mortality or infarct size in the overall population. Because spontaneous reperfusion was more common in patients with early peaking of plasma creatine kinase MB or non-transmural electrocardiographic changes or both, the results were reanalysed for two subgroups: those in whom plasma creatine kinase peaked less than 15 hours after the onset of symptoms (early peak, n = 184) and those with a peak greater than 15 h after the onset of symptoms (late peak, n = 546). The distribution of time to peak activity of creatine kinase MB was similar in the hyaluronidase and placebo groups. In the early peak patients who were given hyaluronidase (groups A and B) total mortality and cardiac-specific four year mortality were significantly lower. This was most pronounced in group B in which the total mortality was 45% and cardiovascular mortality was 47% less than in the placebo group. Similarly, mortality from cardiovascular disease in patients (groups A and B) with nontransmural ischaemia (ST-T changes) given hyaluronidase was significantly lower, with group B showing a 50% reduction. In the subsets of patients with late peaking of creatine kinase MB or those presenting with transmural electrocardiographic changes there was no difference in total mortality or deaths from cardiac disease between those given hyaluronidase and those given placebo. Hyaluronidase was associated with improved survival in patients with early peaking of plasma creatine kinase MB, suggesting the possibility of salvage of myocardium in patients who have early spontaneous reperfusion and possibly after therapeutic reperfusion.

Clinical Trials as Topic↗
PubMed1988

Neutrophil-mediated killing, opsonization, and serum-mediated killing of Escherichia coli K1 by neonatal rats.

Neonates are particularly susceptible to infection with Escherichia coli K1. To investigate the mechanisms which lead to this susceptibility, we examined: (a) the bactericidal activity of neutrophils; (b) opsonization, and (c) the bactericidal activity of serum in developing rats. Neutrophils from adult rats killed E. coli K1 more efficiently than did neutrophils from young animals. Opsonization of E. coli by serum of prematurely delivered rats was poor. Serum from prematurely delivered and term rats promoted growth of E. coli K1, while serum from adult rats killed greater than 95% of the organisms within 90 min. However, the mixture of heat-inactivated serum from adult rats plus serum from prematurely delivered rats killed E. coli K1.

Animals↗
PubMed1987

Measurement of heparin in plasma: influence of inter-subject and circadian variability in heparin sensitivity according to method.

Heparin was measured, with respect to standard curves prepared with normal pooled plasma, by five methods (APTT, thrombin time, one and two stage coagulation, anti-factor Xa and chromogenic anti-factor Xa) after addition at three concentrations to plasmaprepared from normal young volunteers, hospitalized patients with malignancy and geriatric patients. By the APTT and TT, differences in sensitivity were observed at 0.4iu heparin/ml corresponding to an apparent difference in heparin level of 10 and 14 fold between high and low responding individuals. Such large differences were not apparent by anti-factor Xa assay. A circadian difference in sensitivity was also observed in the patient group such that in samples taken at night, heparin levels were 30-50% higher on average when measured in the APTT and TT. Again, such large differences were not apparent by anti-factor Xa methods. In light of recent findings about the usefulness of anti-factor Xa methods for efficient monitoring of heparin, it is suggested that this conclusion may arise from the tendency for anti-factor Xa methods to determine actual concentrations of heparin.

Adult↗
PubMed1987

High-risk subgroups of patients with non-Q wave myocardial infarction based on direction and severity of ST segment deviation.

To determine the significance of the direction of ST segment deviation on admission of patients who evolved non-Q wave myocardial infarction (MI), 97 patients with initial ST segment depression were compared to 207 patients with initial ST segment elevation. Patients with ST segment depression developed smaller infarcts than those with ST segment elevation (creatine kinase MB isoenzyme 8.2 vs 13.3 gmEq/m2, p less than 0.002), but had a lower left ventricular ejection fraction on admission (44% vs 51%, p less than 0.001), more in-hospital complications, and a higher cumulative 1-year mortality (29% vs 11%, p less than 0.001) that could be accounted for by an excess of adverse baseline characteristics. Although a severity index (combining magnitude and extent of the initial ST segment deviation) was not useful for discriminating prognosis of patients with non-Q wave MI who presented with ST segment depression, it was useful in identifying a subgroup of patients with ST segment elevation with an adverse prognosis. The poor outcome of patients with non-Q wave MI presenting with either ST segment depression or severe ST segment elevation on admission suggests that patients in these subgroups should receive close surveillance and should possibly be considered for aggressive therapy.

Electrocardiography↗
PubMed1987

Linkage studies with chromosome 17 DNA markers in 45 neurofibromatosis 1 families.

A locus for von Recklinghausen neurofibromatosis (NF1) has recently been mapped near the chromosome 17 centromere. We have extended these linkage studies by genotyping 45 NF1 families with three DNA probes known to be linked to the chromosome 17 centromeric region. Of 34 families informative for NF1 and at least one of the three probes, 28 families show no recombinants with the disease gene. These data provide additional support for genetic homogeneity of NF1 and for a primary NF1 locus linked to the chromosome 17 centromere. Among the informative families were 7 families with apparent new NF1 mutations. Our data suggest that these mutations are probably at the chromosome 17 NF1 locus.

Chromosomes, Human, Pair 17↗
PubMed1987

Prognostic implications of an early peak in plasma MB creatine kinase in patients with acute myocardial infarction.

To determine the prognostic implications of an early peak in plasma MB creatine kinase (MB CK) in patients with acute myocardial infarction who were not treated with an acute intervention, 342 patients with myocardial infarction confirmed by MB CK were retrospectively studied. The patients were classified into those with an early peak MB CK (less than or equal to 15 hours after the onset of symptoms, n = 84) and those with a late peak MB CK (greater than 15 hours after the onset of symptoms, n = 258). Patients with an early peak MB CK were slightly older, were more frequently female and had a higher incidence of prior myocardial infarction, congestive heart failure and arrhythmias compared with patients with a late peak MB CK. Patients with an early peak MB CK more frequently presented with ST segment depression (23 versus 11%, p less than 0.01), with anterior location of ischemia or infarction (71 versus 52%, p less than 0.01) and with a lower mean left ventricular ejection fraction (41.4 versus 47.4%, p less than 0.01). Despite more extensive left ventricular dysfunction at initial presentation, patients with an early peak MB CK had a smaller mean MB CK infarct size index (12.6 versus 18.9 g-Eq/m2, p less than 0.01), with no difference in the incidence of in-hospital complications, including death. The early left ventricular dysfunction improved in the patients with an early peak MB CK, evidenced by a 4.5% increase in ejection fraction from admission to 10 days after infarction, whereas the ejection fraction did not improve in patients with a late peak MB CK. However, the patients with an early peaking MB CK had myocardium in jeopardy as reflected by a higher incidence of ST segment depression and a decrement in the global left ventricular ejection fraction with exercise. The 4 year life table estimate for the rate of recurrent myocardial infarction after hospital discharge was higher in patients with an early peak MB CK (33 versus 22%, p less than 0.05), with an even more striking difference in the 4 year estimate for the rate of fatal recurrent infarction (20 versus 8%, p less than 0.001). The 4 year mortality estimate was markedly higher in hospital survivors with an early peak MB CK than in those with a late peak (47 versus 19%, p less than 0.0001) and, even after adjustment for differences in baseline characteristics, the residual excess mortality in those with an early peak was still significant (p less than 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1987

Phosphorylation characteristics of brain clathrin-coated vesicle endogenous proteins.

Clathrin-coated vesicles purified from bovine brain express protein kinase activity on two principal endogenous vesicle-associated substrates: a 50,000-Mr polypeptide (pp50) and clathrin-associated protein2 (CAP2; the faster-migrating clathrin light chain). Various exogenous substrates, e.g., casein, phosvitin, histone II, and histone III, also are phosphorylated. The pp50 protein kinase activity of clathrin-coated vesicles is not modulated by Ca2+, calmodulin, phosphatidylserine, or cyclic AMP. On the other hand, phosphorylation of the other endogenous substrates requires certain activators, including histone, polylysine, polyarginine, or polyethylenimine. Phosphate incorporation into pp50 was sensitive to divalent cations that inhibit sulfhydryl-dependent enzymes in the following order of potency: Zn2+ greater than Hg2+ greater than Cd2+, Cu2+, and Pb2+. Phosphate incorporation into CAP2 with polylysine present was insensitive to divalent cations. The alkylating agents dithiodinitrobenzene, phenacyl bromide, and N-ethylmaleimide inhibited phosphate incorporation into pp50 up to 90% without affecting incorporation into the other substrates. Vanadium pentoxide inhibited phosphorylation of CAP2 but had a minimal effect on pp50. CAP2 kinase activity was separated from the coated vesicle membrane and from dis-assembled clathrin triskelions, coeluting with the assembly polypeptide complex on a Sepharose 4B column. It retained phosphorylation properties similar to those of intact vesicles. These data imply that clathrin-coated vesicle kinases are elements of the coat proteins and may be involved in the assembly/disassembly of clathrin triskelions or interactions of coated vesicles with other cellular components.

Animals↗
PubMed1986

Implications for acute intervention related to time of hospital arrival in acute myocardial infarction.

The time from onset of symptoms to arrival in the hospital emergency room (ER) was studied in 778 patients randomized into a study of acute myocardial infarction (AMI) size limitation. Patients at relatively high risk of death after AMI (including those with preexisting diabetes mellitus, systemic hypertension or congestive heart failure), women and older patients arrived significantly later in the ER than did patients without these characteristics. A significantly higher mortality rate was observed in patients who arrived late, i.e., those who arrived more than 2 hours after the onset of chest pain, even though patients with hemodynamic compromise (bradycardia, hypotension) tended to arrive earlier. The difference in long-term mortality between those who arrived early (within 2 hours of onset of chest pain) and those who arrived late was accounted for by the baseline differences between these 2 groups. These baseline differences may influence the effects of early interventions in AMI. In addition, these findings have implications for education of high-risk patients who could benefit the most from aggressive early intervention.

Age Factors↗
PubMed1986

Prognostic significance of the treadmill exercise test performance 6 months after myocardial infarction.

A submaximal treadmill exercise test performed before hospital discharge after an uncomplicated myocardial infarction is often utilized to estimate prognosis and guide management, but there is little experience with a maximal exercise test performed 6 months after infarction to identify prognosis later in the convalescent period. The performance characteristics during an exercise test 6 months after myocardial infarction were related to the development of death, recurrent nonfatal myocardial infarction and coronary artery bypass surgery in the subsequent 12 months (that is, 6 to 18 months after infarction) in 473 patients. Mortality was significantly greater in patients who exhibited any of the following: inability to perform the exercise test because of cardiac limitations, the development of ST segment elevation of 1 mm or greater during the exercise test, an inadequate blood pressure response during exercise, the development of any ventricular premature depolarizations during exercise or the recovery period and inability to exercise beyond stage I of the modified Bruce protocol. By utilizing a combination of four high risk prognostic features from the exercise test, it was possible to stratify patients in terms of risk of mortality, from 1% if none of these features were present to 17% if three or four were present. Recurrent nonfatal myocardial infarction was predicted by an inability to perform the exercise test because of cardiac limitations, but not by any characteristics of exercise test performance. Coronary artery bypass surgery was associated with the development of ST segment depression of 1 mm or greater during the exercise test. Although clinical evidence of angina and heart failure 6 months after infarction was predictive of subsequent mortality among all survivors, among the low risk group without severely limiting cardiac disease, the exercise test provided unique prognostic information not available from clinical assessment alone. Therefore, a maximal exercise test performed 6 months after myocardial infarction is a valuable, noninvasive tool to evaluate prognosis. It provides information that is independent of and additive to clinical evaluation performed at the same time.

Adrenergic beta-Antagonists↗
PubMed1986

Multiple-section radionuclide tomography of the kidney: a clinical evaluation.

The clinical utility of radionuclide emission tomography of the kidney in comparison with conventional gamma-camera imaging has been assessed from scans of 60 patients suspected of having space-occupying lesions of the kidney. Nineteen patients had renal tumour, 17 had cysts and seven had renal pseudotumours; the remainder had no lesion. Objective trials using four observers showed only a slight, statistically insignificant advantage from the addition of tomographic sections to conventional images. However, in several individual cases tomography had aided diagnosis, particularly in obese patients, when an alternative non-invasive investigation (ultrasonography) was inconclusive. In seven patients a positive diagnosis of renal pseudotumour was made possible by tomography; definite identification of ectopic functioning cortical tissue at the location of a mass suspected after urography was considered to be a distinct diagnostic advantage gained from emission tomography of the kidney.

Adenocarcinoma↗
PubMed1985

Circadian variation in the frequency of onset of acute myocardial infarction.

To determine whether the onset of myocardial infarction occurs randomly throughout the day, we analyzed the time of onset of pain in 2999 patients admitted with myocardial infarction. A marked circadian rhythm in the frequency of onset was detected, with a peak from 6 a.m. to noon (P less than 0.01). In 703 of the patients, the time of the first elevation in the plasma creatine kinase MB (CK-MB) level could be used to time the onset of myocardial infarction objectively. CK-MB-estimated timing confirmed the existence of a circadian rhythm, with a three-fold increase in the frequency of onset of myocardial infarction at peak (9 a.m.) as compared with trough (11 p.m.) periods. The circadian rhythm was not detected in patients receiving beta-adrenergic blocking agents before myocardial infarction but was present in those not receiving such therapy. If coronary arteries become vulnerable to occlusion when the intima covering an atherosclerotic plaque is disrupted, the circadian timing of myocardial infarction may result from a variation in the tendency to thrombosis. If the rhythmic processes that drive the circadian rhythm of myocardial-infarction onset can be identified, their modification may delay or prevent the occurrence of infarction.

Adrenergic beta-Antagonists↗
PubMed1985

Electrocardiographic, enzymatic and scintigraphic criteria of acute myocardial infarction as determined from study of 726 patients (A MILIS Study).

Methods for detecting acute myocardial infarction (AMI) were compared in a prospective study of 726 patients with pain presumed to be caused by ischemia that lasted 30 minutes or longer and was associated with electrocardiographic changes (ST-segment deviation greater than or equal to 0.1 mV and/or new Q waves or left bundle branch block). Using MB-CK values of more than 12 IU/liter as the standard criterion for detection of AMI, 639 patients (88%) were judged to have AMI. Total plasma CK values, technetium-99m stannous pyrophosphate images 48 to 72 hours after admission, and serial 12-lead electrocardiograms over 10 days were analyzed by investigators blinded to other clinical and laboratory data. For detection of AMI, total CK, electrocardiograms (ECGs) and pyrophosphate imaging were all highly accurate and sensitive (total CK accuracy 97%, ECG 92%, pyrophosphate 88%; total CK sensitivity 98%, ECG 96% and pyrophosphate 91%). However, both pyrophosphate and ECG were less specific than total CK (p less than 0.01) (total CK specificity 89%, pyrophosphate 64% and ECG 59%). The sensitivity (p less than 0.05) and accuracy (p less than 0.01) of total CK and pyrophosphate for those patients with Q-wave development were slightly greater than for those in whom Q waves did not evolve. The ECG was less accurate (p less than 0.02) and pyrophosphate was less specific (p less than 0.04) in patients with prior MI compared with those with initial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatine Kinase↗
PubMed1985

Neutron brachytherapy is better than conventional radiotherapy in advanced cervical cancer.

Californium-252 (252Cf), a fast-neutron emitting radioisotope, was used for neutron brachytherapy (NT) of 82 patients with advanced (stage III and IV) cervical cancer. The results were compared with caesium-137 brachytherapy; both isotopes were given in combination with high-dose fractionated pelvic radiotherapy. In patients with stage IIIB disease (ie, tumour to the pelvic side-wall), 252Cf intracavitary therapy resulted in 54% 5-year survival compared with 12% in the caesium group. To be effective, Cf-NT must be given before external beam (photon) therapy.

Actuarial Analysis↗