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Biomedical subjects

M Burke

Publications and source records attributed to M Burke.

At least 289 records · Page 16Linked to original sources

Subunit interactions of skeletal muscle myosin and myosin subfragment 1. Evidence for heavy chain-alkali light chain association-dissociation equilibrium.

Modification of the free alkali light chains of myosin by iodoacetylation results in a much lower extent of exchange into myosin subfragment 1 by the thermal hybridization procedure (Burke, M., and Sivaramakrishnan, M. (1981) Biochemistry 20, 5908-5913). As reported by others (Wagner, P. D., and Stone, D. B. (1983) J. Biol. Chem. 258, 8876-8882), free alkali light chains modified by iodoacetate at their single sulfhydryl residue exhibit minimal exchange into intact myosin. However, when unmodified alkali light chain is used to probe for exchange, close to the theoretical limit of exchange is observed for subfragment 1, and significant levels of exchange are found for myosin. It appears that modification of the free alkali light chain alters the structure of the protein, and this causes either a marked reduction in its affinity for the heavy chain or in its ability to enter the light chain binding site. This conclusion is supported by tryptic digestions done on the unmodified and modified free light chains where it is found that the latter is degraded at a much faster rate, indicating a more open structure for the modified protein. The observation that alkali light chain exchanges into myosin when unmodified alkali light chains are used indicates that the presence of the associated 5,5'-dithiobis-(2-nitrobenzoic acid) light chains does not preclude the reversible dissociation of this subunit from myosin under ionic and temperature conditions approaching the physiological state.

Animals↗

Studies of the agonist and antagonist activity of cicloprolol in man.

To assess the partial agonist activity of cicloprolol in man, four studies were carried out in normal male volunteers. I and II. Open dose escalating studies of the effects of oral doses of the drug on exercise tachycardia and sleeping heart rate. III and IV. Double-blind randomized studies of the effects of placebo, cicloprolol 25 mg, cicloprolol 50 mg, cicloprolol 100 mg, atenolol 50 mg, pindolol 10 mg, salbutamol 8 mg and prenalterol 50 mg on sleeping heart rate, resting supine heart rate, blood pressure, forearm blood flow, finger tremor and exercise tachycardia. All doses of cicloprolol above 2.5 mg reduced an exercise tachycardia but there was no increase in effect above a dose of 50 mg. Cicloprolol caused a dose dependent increase in sleeping heart rate up to 200 mg. Cicloprolol increased resting supine heart rate, systolic blood pressure, forearm blood flow and finger tremor. None of the drugs affected quality of sleep. Cicloprolol has significant partial agonist activity at the beta 1-adrenoceptor as indicated by increases in heart rate and systolic blood pressure. The increases in finger tremor and forearm blood flow suggest that cicloprolol has some partial agonist activity at the beta 2-adrenoceptor.

Adult↗

Clinicopathological features of nonsteroidal antiinflammatory drug-induced small intestinal strictures.

The clinicopathological features in 4 patients are described where nonsteroidal antiinflammatory drugs appear to have caused small intestinal strictures. Two patients had rheumatoid arthritis and 2 patients had osteoarthritis; all had received nonsteroidal antiinflammatory drugs for 1.5-30 yr. Three patients had an initial illness characterized by diarrhea, profound weight loss, and hypoalbuminemia. Intestinal radiology at this stage ranged from subtle changes to those of Crohn's disease. Three patients underwent surgery. At operation the bland external appearance contrasted with the striking mucosal appearances of multiple concentric, circumferential, diaphragmatic strictures that caused luminal stenosis to a pinhole. These septa were due to submucosal fibrosis and the histopathological picture appears to represent a new nosological entity.

Adult↗

Virilization due to a rare ovarian tumor in a postmenopausal woman.

A 60-year-old postmenopausal woman presented with evidence of hirsutism, alopecia and mild virilization. Clinical examination and biochemical abnormalities suggested that the source of androgen excess was ovarian, and an ovarian tumor was confirmed and removed at laparotomy followed by normal endocrine profile in the postoperative period.

Female↗

Paget's disease, melanocytic neoplasia and hidradenoma papilliferum of the vulva.

We present a case of invasive melanoma of the vulva with contiguous changes including melanocytic atypia showing, in part, the features of melanocytic dysplasia and, in part, an in situ malignant component and extramammary Paget's disease. A benign hidradenoma papilliferum was also present. We can find no other reported cases of this combination of lesions. The possible histogenesis is discussed and an origin from a common local stem cell is suggested.

Adenoma, Sweat Gland↗

Child temperament and parental perceptions of individual child adjustment: an intrafamilial analysis.

The association between child temperament and mothers' and fathers' perceptions of child adjustment was investigated in a study of 70 married couples, each of whom had two children of the same gender--36 brother pairs and 34 sets of sisters. The parents' perceptions of their children's levels of activity, persistence, and emotional intensity were found to be related to their perceptions of child adjustment. Implications of the findings are discussed and directions for further research indicated.

Adaptation, Psychological↗

Diaphragm disease: pathology of disease of the small intestine induced by non-steroidal anti-inflammatory drugs.

Operative small bowel resection specimens received over a period of 16 years were reviewed to assess whether any intestinal disease could be directly attributed to the use of non-steroidal anti-inflammatory drugs (NSAID). Seven cases of intestinal disease associated with the use of NSAID were identified, all of which occurred in the final six years of the survey, which may reflect the increasing use of these compounds. A spectrum of patterns was found from multiple pathognomonic ileal mucosal diaphragms to broad strictures similar to those seen as a complication of enteric potassium. It seems likely that the formation of diaphragm lesions requires an additional factor, but what is not known as yet is whether the effects of NSAID are local or systemic.

Adult↗

Obstructive pneumonitis: a pathologic and pathogenetic reappraisal.

It is widely accepted that pneumonitis distal to an obstructing airway tumor is the result of infection. The authors performed a prospective study to reevaluate this concept and to clarify the nature of the pathologic findings underlying the observed radiographic changes. Specimens were examined for 50 consecutive patients undergoing resection of pulmonary carcinoma. Histologic changes interpreted as noninfectious were found in 42 cases. Findings suggestive of recent or remote infection were also present in nine of these 42 specimens and were localized predominantly in relation to small- to medium-sized airways (acute bronchitis or bronchiolitis); these changes were always present in a background of noninfectious pneumonitis. The authors conclude that the radiographic changes seen in airway obstruction in surgically excised lungs are usually due to consolidation of lung parenchyma by a noninfectious process. When infection does occur, it involves primarily the airways and is not likely to be radiographically detectable.

Adenocarcinoma↗

An unusual presentation of gluteal hematoma during anticoagulation therapy for deep venous thrombosis in spinal cord injury.

Soft tissue bleeding can be manifested clinically by swelling, skin discoloration, pain and tenderness. Early recognition can be difficult in the spinal cord-injured population in whom sensation is impaired. We are presenting a case of occult bleeding into the gluteal region during anticoagulation therapy in a paraplegic patient that presented as migrating pain and tenderness in the hip and pelvic area.

Adolescent↗

Serum myoglobin levels in patients with ischemic myocardial insult.

Serum myoglobin levels were studied in 178 consecutive patients admitted for chest pain due to ischemic cardiac injury. Serum myoglobin level was compared with the clinical condition, electrocardiographic changes, and serum creatine kinase levels. Elevated serum myoglobin concentration was present in all patients with acute myocardial infarction, as defined by World Health Organization, Geneva, criteria, and, in addition, in about 50% of patients with so-called acute coronary insufficiency. On this basis we could define two different groups of patients with acute coronary insufficiency: cases exhibiting elevated serum myoglobin levels (group 1) and those with normal levels (group 2). In group 1 although creatine kinase levels were in the normal range, they were significantly higher than in group 2. Four patients from group 1 developed heart failure and another a typical acute myocardial infarction during hospitalization, whereas no patients of group 2 had such complications. In patients with acute myocardial infarction, the elevation of serum myoglobin preceded that of creatine kinase in most cases. Myoglobin release appears to be related to infarct size, the highest levels were found in extensive myocardial infarction and less marked elevations in cases of subendocardial infarction and in half of the cases with acute coronary insufficiency. It is proposed that serum myoglobin is a reliable measure of myocardial necrosis and serves to detect a hitherto undefined population of small-size acute myocardial infarction, with its attendant clinical and prognostic implications.

Coronary Disease↗

Proximity and ligand-induced movement of interdomain residues in myosin subfragment 1 containing trapped MgADP and MgPPi probed by multifunctional cross-linking.

The conformations of myosin subfragment 1 containing trapped MgADP or MgPPi have been studied by investigating the spatial disposition of the remainder of the subfragment 1 structure to the covalently bridged ATPase-related thiols SH1 and SH2. This has been done by synthesizing a trifunctional photoactivatable reagent 4,4'-bis(N-maleimido)benzophenone and reacting it with subfragment 1 in the presence of these ligands. Modification of subfragment 1 by this reagent mimics closely the changes in the ATPase properties as noted previously for modification with p-phenylenedimaleimide. In addition, noncovalent trapping of nucleotide also results, presumably by the bridging of the SH1 and SH2 thiols. On photolysis, cross-linking from the reagent bridging the thiols to other regions in subfragment 1 can be observed, but the extent and course of the photoinduced cross-linking depend on the nature of the trapped ligand. For subfragment 1 with trapped MgADP, a high efficiency cross-linking occurs between the 21-kDa segment and the 50-kDa segment. With MgPPi as the trapped ligand, low efficiency cross-linking occurs between the bridged thiols and either the 27-kDa N-terminal or the 50-kDa segments of the heavy chain. These results indicate that without the adenosine moiety, the binding of MgPPi to subfragment 1 leaves the protein in a flexible state so that residues in both the 27-kDa and the 50-kDa segment can move within the cross-linking span of the activated benzophenone triplet. The trapping of MgADP apparently results in a more rigid state for the subfragment 1 in which residues in the 50-kDa segment are spatially close to the bridged thiols, thus enabling photocross-linking to proceed with higher efficiency.

Adenosine Diphosphate↗

Substructure of skeletal myosin subfragment 1 revealed by thermal denaturation.

The stability of myosin subfragment 1 (S1) to thermal denaturation has been followed by limited tryptic proteolysis. Digestions done during the thermal denaturation show that at temperatures at and above 37 degrees C there is a marked increase in the susceptibility of S1 to tryptic degradation, as evidenced by the loss of all bands corresponding to the normally trypsin-resistant fragments of 50, 27, and 21 kDa of the heavy chain and to the light chain. The enhanced digestion of S1 appears to be due to a general unfolding of all segments of S1, although the 50-kDa segment appears to unfold at a lower temperature than the remainder of the S1 structure. Digestions done after 30-min exposure to higher temperatures or after subsequent cooling to 25 degrees C show marked differences in the susceptibility of the S1 to trypsin. This suggests that, on cooling, a substantial portion of the S1, but not the 50-kDa segment, is capable of refolding to a state corresponding closely to that in the native S1. These data indicate that in terms of thermal denaturation the S1 behaves as though it is comprised of two domains--an unstable 50-kDa domain and a more stable domain comprised of the 27- and 21-kDa segments of the heavy chain interacting with the light chain, as proposed recently by Setton and Muhlrad [Setton, A., & Muhlrad, A. (1984) Arch. Biochem. Biophys. 235, 411-417]. The rates of thermal inactivation of the ATPase of S1 are found to correspond closely to the decay rates for the 50-kDa fragment, suggesting that this segment in S1 is closely associated with the ATPase function of the protein.

Adenosine Triphosphatases↗

Carcinoid tumours of the rectum and anus.

Carcinoid tumours of the anorectum comprise only 0.1 per cent of all rectal tumours. Their behaviour and treatment are still debatable. We identified 35 cases from the records of St Mark's Hospital; 31 were benign and 4 were malignant. Benign tumours were of three distinct histopathological patterns. All benign tumours were cured by local treatment. Malignant tumours can be identified clinically; the only consistent microscopic feature was invasion of the muscularis propria. All patients with malignant tumours died, despite radical surgical treatment; lymph node metastases were invariably present in the operation specimens. Because radical treatment for malignant carcinoid tumours of the anorectum is largely unsuccessful, a flexible surgical approach is advocated.

Adult↗

Serum myoglobin in detection of myocardial necrosis in patients with "coronary insufficiency".

Myoglobin, an oxygen-binding protein, is synthesized exclusively in striated and cardiac muscle, and is normally found in blood. Serum myoglobin determination has been used in the diagnosis of acute myocardial infarction. Experimental work has shown that myoglobin is released only after muscular necrosis. This prospective study included 101 patients: 62 with acute coronary insufficiency, 16 with acute myocardial infarction, and 23 controls. In all the patients with infarction the serum myoglobin levels were elevated. None of the controls showed serum myoglobin above normal. In patients with coronary insufficiency the peak serum myoglobin ranged from normal to 280 ng/ml. Half of all the patients with coronary insufficiency had a significant elevation of serum myoglobin (p less than 0.001). The obvious explanation of this finding is that myocardial necrosis to some extent develops in cases of so-called coronary insufficiency. Furthermore, this study confirms previous findings that serum myoglobin assessment constitutes a very early marker of myocardial damage.

Acute Disease↗

Obstructive jaundice by a dissecting aneurysm of celiac axis and hepatic artery.

We report a case of dissecting aneurysm of the celiac axis and hepatic artery resulting in obstructive jaundice. The aneurysm was demonstrated both by ultrasound and by angiography, but the associated aortic dissection was apparent only on CT scan. The patient was treated with percutaneous transhepatic biliary drainage, surgical exclusion of the aneurysm by ligation, and progressive dearterialization of the hepatic artery.

Aortic Dissection↗