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Biomedical subjects

D R Murray

Publications and source records attributed to D R Murray.

At least 37 records · Page 2Linked to original sources

A ten-year follow-up on stage II malignant melanoma patients treated postsurgically with Newcastle disease virus oncolysate.

Newcastle disease virus oncolysate was examined as an adjunctive immunotherapeutic agent in the postsurgical management of 83 cases of Stage II malignant melanoma. At this time, all the patients have been under observation for at least 10 years, and over 60% are alive and free of recurrent disease. Older studies in the United States report postsurgical survival figures for Stage II cases of 5-15%. More contemporary studies indicate a 33% survival at 10 years. The unusual disease-free survival periods in the present study, including exceptional survivals in 21 patients with head and neck disease and six cases with cerebral metastases, suggest a unique role for the administration of Newcastle disease virus oncolysate in the management of Stage II malignant melanoma patients.

Adult↗

Sympathetic and immune interactions during dynamic exercise. Mediation via a beta 2-adrenergic-dependent mechanism.

BACKGROUND: The relation between the sympathetic nervous system and the immune system has not been fully defined. Recent investigations have suggested an adrenergically driven efflux of specific beta 2-receptor-rich lymphocyte subsets into the circulation with either exercise or infusion of exogenous catecholamines. METHODS AND RESULTS: To determine whether acute sympathetic stimulation mediates immunoregulatory cell traffic and function via a beta 2-receptor mechanism, we exercised 20 healthy volunteers before and after 1 week of treatment with either the nonselective beta-antagonist propranolol or the beta 1-selective antagonist metoprolol. Before treatment, exhaustive exercise according to the Bruce protocol led to a marked lymphocytosis. Tsuppressor/cytotoxic (Ts/c) and natural killer cells, subtypes with the largest density of beta-receptors, showed the most pronounced increases after exercise, with less impressive elevations in T(helper) and B cells. With respect to function, exhaustive exercise led to a decrease in concanavalin A-stimulated IL-2 receptor expression and [3H]thymidine incorporation while enhancing natural killer cell activity. One week of propranolol therapy blunted the exercise-induced increases in circulating Ts/c and natural killer subpopulations as well as the previously observed alterations in cellular immune function. Treatment with the beta 1-selective antagonist metoprolol, however, did not impair the influence of exercise on any of the above parameters. CONCLUSIONS: Acute sympathetic stimulation by exhaustive exercise leads to selective release of immunoregulatory cells into the circulation with subsequent alterations in cellular immune function, either secondary to subset changes or as a result of direct catecholamine effects on function. These changes are attenuated by propranolol but not metoprolol, suggesting a beta 2-mediated mechanism.

Adult↗

Randomized study of interleukin 2 (IL-2) alone vs IL-2 plus lymphokine-activated killer cells for treatment of melanoma and renal cell cancer.

The purpose of this study was to evaluate the efficacy and safety of a continuous-infusion interleukin 2 (IL-2) regimen for patients with metastatic melanoma and renal cell cancer. To investigate the contribution of adoptively transferred lymphokine-activated killer cells, patients were randomized to receive either IL-2 alone or IL-2 plus lymphokine-activated killer cells. Twenty-three patients with renal cell carcinoma and 20 with melanoma were entered into the protocol. There were no objective responses noted in the 38 assessable patients (20 with renal cell carcinoma, 18 with melanoma). Most patients demonstrated progressive disease following one 31-day cycle of weekly continuous-infusion IL-2. Grade I and II toxic reactions, including fever, rash, anorexia, and weight gain, were common and treated symptomatically. Significant in vivo stimulation of lymphokine-activated killer and natural killer cell activity was noted in most patients. This continuous-infusion IL-2 regimen with or without lymphokine-activated killer cells was ineffective in the treatment of melanoma and renal cell carcinoma.

Adult↗

Preoperative localization of focal liver lesions to specific liver segments: utility of CT during arterial portography.

The authors retrospectively studied 36 hepatic masses in 20 patients who underwent computed tomography during arterial portography (CTAP) and subsequent hepatic tumor resection. The authors used the right main and left main portal veins as landmarks for the transverse scissura, along with the hepatic veins, the gallbladder fossa, and the umbilical fissure to blindly predict the segmental location of each tumor confirmed at surgery. The right main and left main portal veins were found to be consistently near the middle sections through the liver. CTAP findings and surgical descriptions agreed on the primary segmental location of 33 of 36 focal lesions (92%) but disagreed on the extent of 11 of 36 lesions (31%). Further review of the CTAP scans of the 11 lesions revealed that the extent of the lesion was more correctly described at surgery in six masses and at CTAP in four masses; in one lesion, opposite margins of the same mass were correctly described at both surgery and CTAP. Since it may be difficult or impossible to localize deep hepatic lesions intraoperatively by means of palpation or inspection, CTAP is a helpful preoperative tool for determining the segmental location of lesions and for planning the surgical approach.

Adult↗

A segmental approach to computerized tomographic portography for hepatic resection.

Surgical treatment has proved to be of benefit to patients with primary and metastatic tumors of the liver. However, the ability to localize tumors preoperatively to particular segments within the liver has not been emphasized. The large size of this organ and its complex vascular structure have not allowed the surgeon either to determine accurately the hepatic segment occupied by the tumor or to identify major vascular structures adjacent to the tumor. We have expanded the use of a new roentgenologic technique to determine preoperatively with more clear definition the segmental anatomy of the liver. Computerized tomographic portography (CT-P) images hepatic veins and the segmental branches of portal vein and identifies the anatomic location of tumor nodules. To read the roentgenograms, one first identifies the middle CT-P slice that will cut the transverse scissura. Slices cephalad to the transverse scissura are through segments 7, 8, 4a and 2 in a clockwise order; slices caudad to the transverse scissura are through 6, 5, 4b and 3. Selected CT-P cuts from a series of patients show the typical CT-P configuration of the hepatic vasculature anatomy and the structures that can be identified roentgenologically. The CT-P provides valuable information not previously available preoperatively to the surgeon operating upon the liver.

Contrast Media↗

Mycotic abdominal aortic aneurysm induced by immunotherapy with bacille Calmette-Guérin vaccine for malignancy.

Successful surgical treatment of a mycotic abdominal aortic aneurysm infected with Mycobacterium bovis is described. The infecting organism can be traced to an intraneoplastic injection of bacille Calmette-Guérin (BCG) vaccine into a cutaneous malignant melanoma nodule 14 months before aneurysm detection (17 months before operation). Treatment consisted of aneurysm excision, in situ prosthetic graft placement, and antituberculous medications. This patient represents the first reported case of BCG-induced mycotic aortic aneurysm.

Aneurysm, Infected↗

Arginine deiminase system and bacterial adaptation to acid environments.

The arginine deiminase system in a variety of streptococci and in Pseudomonas aeruginosa was found to be unusually acid tolerant in that arginolysis occurred at pH values well below the minima for growth and glycolysis. The acid tolerance of the system allowed bacteria to survive potentially lethal acidification through production of ammonia to raise the environmental pH value.

Adaptation, Physiological↗

Malignant melanoma. Inflammatory mononuclear cell infiltrates in cerebral metastases during concurrent therapy with viral oncolysate.

Five patients with advanced malignant melanoma, treated with viral oncolysate, had solitary central nervous system metastases that were removed surgically. Histologic examination revealed striking and significant mononuclear inflammatory cell infiltrates, consisting of a mean of 60% plasma cells and a lesser proportion of lymphocytes at the edges of the lesions, within their supporting fibrovascular trabeculae, and among the tumor cells. Comparable inflammatory changes were not found in solitary metastatic malignant melanomas removed surgically from the brains of 19 patients not treated with viral oncolysate. Similarly, multiple metastatic malignant melanomas obtained postmortem from the brains of 12 patients not treated with viral oncolysate showed minimal inflammatory responses. Ultrastructural examination of material from a single treated patient revealed morphologic abnormalities of the blood-brain barrier, changes that were perhaps conducive to infiltration of the neoplasm by inflammatory cells. The authors suggest that administration of viral oncolysate enhances the inflammatory cell response to metastatic malignant melanoma in the brain.

Adult↗

Immunoglobulins associated with elevated riboflavin binding by plasma from cancer patients.

Plasma from 182 patients with different malignant diseases was tested for riboflavin binding by immunoglobulins, which have been recently identified as major carriers of this micronutrient. A wide range of binding (5.9 to 130 pmole/ml plasma) was observed, and significant elevations were found for patients having breast cancer (21.2 +/- 1.9, P less than 0.05) and melanoma (25.7 +/- 1.9, P less than 0.001) compared to controls (15.5 +/- 1.9). The proteins responsible for a majority of the higher binding were identified as immunoglobulins, based on their elution from gel filtration columns and the removal of 57-88% of the non-albumin binding by treating of plasma with Protein A-agarose. The binding was only weakly related to the total concentration of immunoglobulins (r = 0.11 by linear regression analysis), however, and is apparently due to a subclass that is elevated in some types of cancer. Elevated levels of these immunoglobulins may contribute to the lower urinary levels and clearance of riboflavin in cancer.

Breast Neoplasms↗

Plasma L-dopa in the diagnosis of malignant melanoma.

We determined the concentration of L-dopa in the plasma of 98 patients with biopsy-proven melanoma, a dermatological neoplasm that is characterized biochemically by abnormal tyrosine metabolism. For 21 patients previously diagnosed as having melanoma but who were clinically free of disease (stage I), the mean concentration of L-dopa in plasma, 1.01 (SD 0.12) micrograms/L, was not significantly different from that of 32 normal controls, 1.23 (SD 0.16) micrograms/L. However, L-dopa was increased significantly (p less than 0.001) in the plasma of all of 65 patients with active disease (stage II), 2.08 (SD 0.46) micrograms/L, and was highest in 12 patients with stage III malignant melanoma, 8.40 (SD 3.50) micrograms/L. The development of metastases in four patients with stage II melanoma was accompanied by an increase in the concentration of plasma L-dopa. These studies suggest that measurement of plasma L-dopa may be useful in the diagnosis of melanoma.

Adult↗

Economy of water, carbon, and nitrogen in the developing cowpea fruit.

The nutritional economy of the fruit of cowpea (Vigna unguiculata (L.) Walp cv Vita 3) was assessed quantitatively from intake and utilization of carbon, nitrogen, and water. Fruits failed to make net gains of CO(2) from the atmosphere during daytime, although pod photosynthesis did play a role in the fruit's carbon economy by refixing a proportion of the fruit's respired CO(2). Of every 100 units by weight of carbon entering the fruit, 70.4 were finally incorporated into seeds, 10.3 remained as nonmobilizable material in pod walls, and the remaining 19.3 were lost in fruit respiration. Phloem supplied 97% of the fruit's carbon and 72% of its nitrogen. The xylem contribution of nitrogen occurred mainly in early growth. Ninety-six% of the fruit's nitrogen was incorporated into seeds, approximately 10% of this mobilized from the senescing pod. The mean transpiration ratio of the fruit was very low-8 milliliters water transpired per gram dry matter accumulated. Models of carbon, nitrogen, and water flow were constructed for the two consecutive 11 day periods of fruit development, and indicated a considerably greater entry of water through xylem and phloem than could be accounted for in changes in fruit tissue water and transpiration loss. This discrepancy was greater in the second half of fruit growth and was interpreted as evidence that a significant fraction of the water entering the fruit through phloem cycled back to the parent plant via the xylem.

Journal Article↗

Nitrogen nutrition and metabolic interconversions of nitrogenous solutes in developing cowpea fruits.

Budgets for import and utilization of ureide, amides, and a range of amino acids were constructed for the developing first-formed fruit of symbiotically dependent cowpea (Vigna unguiculata [L.] Walp. cv Vita 3). Data on fruit total N economy, and analyses of the xylem and phloem streams serving the fruit, were used to predict the input of various solutes while the compositions of the soluble and protein pools of pod, seed coat, and embryo were used to estimate the net consumption of compounds. Ureides and amides provided virtually all of the fruit's N requirements for net synthesis of amino compounds supplied inadequately from the parent plant. Xylem was the principal source of ureide to the pod, while phloem was the major source of amides to pod and seed. All fruit parts showed in vitro activity of urease (EC 3.5.1.5), allantoinase (EC 3.5.2.5), asparaginase (EC 3.5.11), ammonia-assimilating enzymes and aspartate and alanine aminotransferases (EC 2.61.1 and EC 2.6.1.1.2). Asparagine:pyruvate aminotransferase (EC 2.6.1.14) was recovered only from the pod. The pod was initially the major site for processing and incorporating N; later seed coats and finally embryos became predominant. Ureides were broken down mainly in the pod and seed coat. Amide metabolism occurred in all fruit organs, but principally in the embryo during much of seed growth. Seed coats released N to embryos mainly as histidine, arginine, glutamine, and asparagine, hardly at all as ureide. Amino compounds delivered in noticeably deficient amounts to the fruit were arginine, histidine, glycine, glutamate, and aspartate, while seeds received insufficient arginine, histidine, serine, glycine, and alanine. Quantitatively based schemes are proposed depicting the principal metabolic transformation accompanying N-flow between seed compartments during development.

Journal Article↗

A phase II study on the postsurgical management of Stage II malignant melanoma with a Newcastle disease virus oncolysate.

A Newcastle disease virus lysate of malignant melanoma cells was examined for its possible value in delaying the progression of malignant melanoma with palpable regional node disease (Stage II) to disseminated melanoma (Stage III). This Phase II study was carried out in a group of 32 patients following therapeutic lymphadenectomy. The patients were not prospectively randomized. In each patient, the viral oncolysate was administered subcutaneously at regular intervals over 3 years. The cumulated progressions to disseminated disease at 1, 2 and 3 years were 6%, 8% and 12% of the study group, respectively. These experienced losses were considerably lower than in the control group and in similar control groups described by other investigators. The results suggest that an oncolysate prepared with Newcastle disease virus is a helpful adjunct to surgery in the management of Stage II malignant melanoma.

Adolescent↗

Melanoma detection by enzyme-radioimmunoassay of L-dopa, dopamine, and 3-O-methyldopamine in urine.

This enzyme-radioimmunoassay for the measurement of L-dopa, dopamine, and 3-O-methyldopamine is based on the incubation of urine in the presence of catechol-O-methyltransferase, aromatic-L-amino-acid decarboxylase, and S-adenosylmethionine. The O-methylated dopamine metabolite formed, 3-O-methyldopamine, was characterized by radioimmunoassay. To evaluate the role of L-dopa metabolism in melanoma, we used the enzyme-radioimmunoassay to assess concentrations of L-dopa, dopamine, and 3-O-methyldopamine in urine from 10 healthy subjects, 10 hospitalized patients without melanoma and 28 patients with different degrees of melanoma. The effect of surgery for melanoma on urinary output of these catechols of melanoma patients was also evaluated. No significant difference in urinary L-dopa, dopamine, and 3-O-methyldopamine excretion rates was seen between normal subjects (L-dopa 1.3 +/- 0.3, dopamine 147 +/- 38, and 3-O-methyldopamine 31.4 +/- 13.6 microgram/24 h), hospitalized patients without melanoma, and amelanotic melanoma patients. However, the excretion rates for these metabolites in melanotic melanoma (L-dopa 5.6 +/- 1.2, dopamine 555 +/- 121, and 3-O-methyldopamine 178 +/- 40.3 microgram/24 h) were significantly (p < 0.005) higher than in control or amelanotic melanoma subjects. After surgery, there was a substantial decrease in urinary output of L-dopa and its metabolites by these patients.

Adolescent↗

Changes in Activities of Enzymes of Nitrogen Metabolism in Seedcoats and Cotyledons during Embryo Development in Pea Seeds.

In the seedcoats of developing pea seeds, the maximal activities of asparaginase (EC 3.5.1.1) and aspartate: alpha-ketoglutarate aminotransferase (EC 2.6.1.1) are attained early in development, before the embryo has expanded to fill the embryo sac. These two enzyme activities could account for the early absence of asparagine and aspartate from the fluid secreted by the seedcoats into the embryo sac.CHANGES IN THE ACTIVITIES OF ALANINE: alpha-ketoglutarate aminotransferase (EC 2.6.1.2), glutamate dehydrogenase (EC 1.4.1.3), glutamine synthetase (EC 6.3.1.2), and glutamate synthase (EC 1.4.1.13) have also been measured, in cotyledons as well as seedcoats. On a fresh weight basis, the highest activities of asparaginase and both aminotransferases developed in the seedcoats, whereas the highest activities of the remaining enzymes developed in the cotyledons.The data indicate that the amide groups of imported asparagine and glutamine are metabolized differently, largely by asparaginase and glutamate synthase, respectively. The NH(4) (+) released by the action of asparaginase is evidently reassimilated in cotyledon cells by the joint action of glutamate dehydrogenase, glutamine synthetase, and glutamate synthase. The data emphasize the central importance of alpha-ketoglutarate-glutamate cycling in the redistribution of amino groups associated with the net synthesis of amino acids and reserve proteins.

Journal Article↗

Nutritive Role of the Seedcoats during Embryo Development in Pisum sativum L.

Structural and metabolic features of the seedcoats of the developing pea seed indicate that events in the cells of the seedcoats are of major importance in controlling the development of the embryo. Information has been obtained on the distribution of N and P constituents of the seedcoats, embryo sac liquid, and the cotyledons of the embryo, in relation to the changes in the activities of several enzymes: aminopeptidases, beta-glucosidase, and acid phosphatase. The liquid contents of the embryo sac are considered to arise as a secretion from the tegmen. High concentrations of amino acids (about 0.3 molar), NH(4) (+) (about 0.1 molar), and orthophosphate (Pi) (up to 4 millimolar) were measured in this fluid. Since Pi was the only form of P present, the data confirm the possible function of some of the seedcoat acid phosphatase activity in the provision of Pi to the embryo.

Journal Article↗