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Biomedical subjects

M Burke

Publications and source records attributed to M Burke.

At least 343 records · Page 19Linked to original sources

Steroid therapy in inappropriate secretion of antidiuretic hormone due to malignant thymoma.

The authors present the case of a 48-year-old female known to have malignant thymoma with metastases for 6 years and treated continuously for 4 years by corticosteroids with marked regression of tumor. The patient ceased medication on her own accord, and was admitted with extensively enlarged tumor and metastases in association with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In view of the previous excellent response of the thymoma to corticosteroids, the same treatment was given again with disappearance of the tumor and the features of SIADH. The authors are unaware of previous use of corticosteroids in SIADH as a consequence of their effect on tumor regressions.

Female↗

The effect of undernutrition and disease site and stage on cell-mediated immunity in gastrointestinal cancer.

In order to assess whether impairment of cell-mediated immunity in cancer was due to the presence, site and stage of malignant disease or to associated undernourishment, 48 patients with gastrointestinal cancer were compared to 27 patients with benign gastrointestinal disease. Cell-mediated immunity (CMI) was assessed by delayed hypersensitivity (DHS) skin test response to recall antigens and lymphocyte mitogenic response to phytohaemagglutinin (PHA). Patients were grouped according to nutritional status assessed from a history of weight loss and changes in the ratio of total body potassium (TBK mmol) to total body water (TBW kg). The results showed that, whilst cancer patients as a whole had significantly worse DHS response, there were no significant differences between benign and malignant groups of equivalent nutritional status and in both types of disease response decreased significantly with worsening nutritional status (chi 2(2) = 6.83 cancer, 6.11 benign, p less than 0.05). PHA response was significantly worse in the worst nourished cancer patients than in those with normal nutritional status (p less than 0.05, Wilcoxon). Disease site and stage had no significant effect on either test. The results suggest that depression of CMI response in gastrointestinal cancer is due to undernutrition and is not a cancer specific effect.

Adult↗

The free heavy chain of vertebrate skeletal myosin subfragment 1 shows full enzymatic activity.

Vertebrate skeletal fast-twitch muscle myosin subfragment 1 is comprised of a heavy polypeptide chain of 95,000 daltons and one alkali light chain of either 21,000 daltons (A1) or 16,500 daltons (A2). In the present study, the heavy chain of subfragment 1 has been separated from the alkali light chain under nondenaturing conditions resembling those in vivo. The heavy chain exhibits the same ATPase activity as myosin subfragment 1, indicating that the heavy chain alone contains the catalytic site for ATP hydrolysis and that the alkali light chains are nonessential for activity. The free heavy chain associates readily at 4 degrees C or 37 degrees C with free A1 or A2 to form the subfragment 1 isozymes SF1(A1) or SF1(A2) respectively. Actin activates the MgATPase activity of the heavy chain in the same manner as occurs with the native isozyme, indicating that the heavy chain possesses the actin binding domain.

Adenosine Triphosphatases↗

Long-term hyperalimentation in children through saphenous central venous catheterization.

During a 3.5 year period, 151 Silastic central venous catheters were inserted into the inferior vena cava through the saphenous vein in 132 children younger than age 19 years at UCLA Hospital. The major indications for catheter insertion included inflammatory bowel disease, cancer or bone marrow transplantation, and short bowel syndrome. The 151 catheters were used for a total of 13,288 days of fluid administration (mean 88 days). Complications requiring removal of the catheter occurred in 31 patients, but there were no deaths attributable to complications from the catheters. The total incidence of complications was one per 225 days of catheter use, less than that occurring in catheters placed in the external jugular and cephalic veins in young children in our hospital. The ease of insertion, the low complication rate and the simplicity of patient management when catheters are placed into the vena cava through the saphenous vein appear to make this an optimal site for administering parenteral nutrition in infants and children.

Catheterization↗

Transposon-specified site-specific recombination.

Cointegrate DNA molecules containing two copies of a transposable element appear to be intermediates in the transposition process. These structures are resolved by site-specific recombination to yield the normal end products of transposition. The transposable element gamma delta (Tn1000) synthesizes a product interchangeable with the Tn1/3tnpR protein in promoting Tn1/3 site-specific recombination. These data support the hypothesis that cointegrates containing directly repeated copies of Tn1/3 are obligatory intermediates in interreplicon transposition of Tn1/3. In addition, we show here that the reaction is independent of the element-encoded tnpA gene product. Tn501, which specifies mercury resistance, also produces cointegrates as intermediates in interreplicon transposition. The appearance of Tn501-specified recombination activity that can act on these cointegrates requires growth of cells in the presence of Hg2+.

DNA Transposable Elements↗

Studies on the alkali light chains of vertebrate skeletal muscle myosin. Effect of tyrosyl modification on the ability to reassociate to heavy chains.

The structures of the alkali light chain subunits A1 and A2 have been studied by examining the effect of the conformationally sensitive reagent tetranitromethane, which reacts specifically with tyrosyl residues. Whereas reaction in the presence of 6 M guanidine hydrochloride results in modification of the three tyrosyl residues of both these light chains, only two tyrosyl residues are exposed to the reagent in the native conformations of these proteins. By gel chromatography of the CNBr-cleaved chains it was demonstrated that the two reactive tyrosyls are those located in the CB-1 and CB-3 segments and that these tyrosyl residues are modified simultaneously and not sequentially. The unreactive tyrosyl residue is in the CB-6 segment and is separated by two residues from the single cysteinyl residue of these chains. It is found that the modified light chains cannot be made to reassociate with the heavy chains by the NH4Cl hybridization procedure of Wagner and Weeds [J. Mol. Biol. 109, 455-470 (1977)] or by the thermal hybridization procedure [Burke and Sivaramakrishnan (1981) Biochemistry 20, 5908-5913]. Furthermore, reduction of the nitrotyrosyl groups to aminotyrosyl residues by sodium dithionite does not restore this effect. The data suggest that regions of the light chains at CB-1 and CB-3 are involved in the association to the heavy chains.

Adenosine Triphosphatases↗

Concealed bigeminy in acute myocardial infarction.

Concealed bigeminy represents a rhythm disorder in which bigeminy is ever-present, but the ventricular premature beats are not always detectable and there is an odd number of interectopic sinus beats. Retrospective examination of the ECG tracings of patients with acute myocardial infarction and ventricular premature beats demonstrated a statistically significant predominance of odd numbers of interectopic sinus beats. There were 20 cases of concealed bigeminy and in 10 of these the probability that this was a chance finding was less than 0.01. In 1 case with 79 consecutive odd series of interectopic beats the chance of such an occurrence was 2(-79). These results indicate that a predictable pattern may exist in the arrhythmias associated with some cases of acute myocardial infarction.

Cardiac Complexes, Premature↗

Occlusion of the vena cava in infants receiving central venous hyperalimentation.

During a five year period at UCLA Hospital, 118 Silastic, Broviac, central venous hyperalimentation catheters were inserted into 94 infants who were less than one year of age. The indications for total parenteral nutrition were malabsorption syndrome in 26, short bowel syndrome in 24, diarrhea in 15, nutritional support following operation in 11 and miscellaneous in 18. One hundren and two catheters were placed into the vena cava by way of the saphenous vein at the groin, and 16 were inserted through the external or internal jugular veins. The duration of catheter use varied from six to 925 days, a mean of 104 days. In six infants, obstruction of the vena cava developed, five in the inferior vena cava and one in the superior vena cava. Swelling of the extremity was minimal, and the thrombosis was insidious in each patient. None of the patients had pulmonary emboli. Although two of the six patients eventually died, in neither was thrombosis of the cava believed to be related. Thrombosis of the vena cava is a frequent sequela of long term central venous hyperalimentation in infants, but it is rarely fatal and produces remarkably few serious complications.

Catheters, Indwelling↗

How adequate are warnings and first and instructions on consumer product labels?: an investigation.

A random survey of 1,019 household product labels was conducted by the NYPCC in retail markets in the New York metropolitan area. The purpose of this survey was to determine whether household product labels adequately define what a consumer should do in the event of a poisoning. The quality of poison warnings, first aid instructions, and the extent of ingredients listed were evaluated. In a qualitative and quantitative analysis of 1,019 household product labels it was found that 85% of the product labels had inadequate first aid information. Of these, 53% demonstrated insufficient labeling, 6% had incorrect, potentially harmful instructions, and in 26% of the cases instructions were absent entirely. In addition, 31% of these 1,019 products had no ingredients' list.U

Consumer Product Safety↗

Subunit interactions of skeletal muscle myosin and myosin subfragment 1. Formation and properties of thermal hybrids.

The formation of hybrid myosin and subfragment 1 species by incubation of these proteins with free alkali light chains at physiological ionic and temperature conditions is described. Exchange of bound alkali light chain on myosin by free alkali light chains under these conditions is readily demonstrated from the subunit composition of the isolated myosin. Therefore, the light chain exchange previously described for the one-headed subfragment 1 [Sivaramakrishnan, M., & Burke, M (1981) J. Biol. Chem. 256, 2607--2610] also occurs in the two-headed myosin molecule. It is found than the isozyme to hybrid transformation is dependent on both the temperature and the ionic strength of the incubation mixture but is relatively independent of pH in the range 6.5--8.0. A comparison of the SF1(A1) leads to SF1(A2)h system with the SF1(A2) leads to SF1(A1)h system indicates that more hybrid is formed in the latter case. With the assumption that hybrid formation reflects the degree of reversible dissociation exhibited by the isozyme, under the particular experimental condition employed, the data signify that the subunit interactions in the two isozymes are not identical and that the heavy chain--A1 interactions are significantly more stable that the heavy chain--A2 ones. An examination of the ATPase properties of the thermal hybrids in the presence and absence of actin indicates close similarities to their corresponding "native" isozymic counterparts.

Adenosine Triphosphatases↗

Subunit interactions in myosin subfragment 1. Subunit scrambling is independent of catalytic center involvement.

Evidence is presented that, under conditions of 4.7 M NH4Cl and 10 mM Mg-ATP where no subunit dissociation can be detected by transport methods, a dynamic equilibrium exists in subfragment 1 between the associated and dissociated subunits. This is readily discerned by the formation of hybrid subfragment 1 species when a subfragment 1 isozyme is incubated with excess free light chains of the alternate isozyme. A similar process occurs with p-N,N'-phenylenedimaleimide (pPDM)-modified subfragment 1 containing [14C]Mg-ADP, but in this case, although extensive amounts of hybrid are formed, no loss of the trapped nucleotide is observed. Subunit scrambling without loss of the trapped nucleotide is apparent from incubating pPDM-SF1(A2)-[14C]Mg-ADP with unmodified SF1(A1) under similar conditions since the mixture subsequently contains SF1(A1), SF1(A2)h, pPDM-SF1(A1)h-[14C]Mg-ADP and pPDM-SF1(A2)-[14C]Mg-ADP. These data show that the nucleotide trapped in the presumptive active site does not escape during the dissociation-reassociation cycle, and suggest that the ATPase site resides solely on the heavy chain.

Adenosine Diphosphate↗

Studies on the subunit interactions of skeletal muscle myosin subfragment 1. Evidence for subunit exchange between isozymes under physiological ionic strength and temperature.

Evidence is presented that under physiological conditions of ionic strength and temperature, where myosin Subfragment 1 is hydrolyzing MgATP, the interaction between its subunits is extremely labile. Incubation of [3H]N-ethylmaleimide-SF1(A1) with N-ethylmaleimide-SF1(A2) in the presence of 10 mM MgATP at 37 degrees C resulted in the exchange of subunits between these isozymes. This is readily discernible from the subunit composition and distribution of the 3H label after separation of the isozymes by ion exchange chromatography. Moreover, incubation of unmodified SF1(A1) or SF1(A2) with the free Alkali light chains A2 and A1, respectively, under the same conditions led to the formation of significant amounts of the hybrid species. These findings suggest that in vivo the Alkali light chain-heavy chain interaction of Subfragment 1 is in a state of dynamic equilibrium between associated and dissociated states.

Adenosine Triphosphatases↗

Studies on the interaction of myosin subfragment 1 and immobilized nucleotide. Evidence for different binding domains operating under different solvent conditions.

The binding interaction between myosin subfragment 1 isozymes with immobilized nucleotide, where they show differential behavior, has been examined. By employing subfragment 1 hybrids formed by crosses between heavy and alkali light chains, it is possible to demonstrate that the differential behavior is modulated by the alkali light chain component of the protein and not by differences in the heavy chain subunits in these isozymes resulting from the proteolytic treatment used in their formation. The fact that the free alkali light chains show weak differential binding under these conditions suggests that the binding in the case of the subfragment 1 isozymes may occur at a site distinct from the ATPase site. This was substantiated by examining the behavior of subfragment 1 containing [14C] MgADP noncovalently trapped in the ATPase site by the bifunctional reagent N, N-p-phenylenedimaleimide, on agarose-ATP. The data suggest that different ATP binding domains may be operating in myosin depending on the ionic conditions being employed.

Adenosine Triphosphatases↗