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Biomedical subjects

E Murray

Publications and source records attributed to E Murray.

At least 109 records · Page 6Linked to original sources

Vasoconstrictors in spinal anesthesia with tetracaine--a comparison of epinephrine and phenylephrine.

A randomized double-blind study was conducted in 50 orthopedic patients to determine the effect of epinephrine and phenylephrine on the anesthetic properties of intrathecally administered tetracaine. Two doses of each vasoconstrictor agent were studied: 0.2 mg of epinephrine, 0.3 mg of epinephrine, 1 mg of phenylephrine, and 2 mg of phenylephrine. The results show that both vasoconstrictor agents in the doses used significantly prolong duration of sensory anesthesia and motor blockade produced by the subarachnoid administration of tetracaine. At equipotent doses no differences existed between the ability of epinephrine and phenylephrine to prolong the duration of spinal anesthesia produced by tetracaine.

Adult↗

Increased sulphation level and altered composition of glycosaminoglycans synthesized by cultured smooth muscle cells in the presence of beta-D-xylosides.

Cultured rat and bovine smooth muscle cells incorporated more 35SO4 into macromolecular glycosaminoglycans in the presence of beta-D-xylosides than in their absence. More than 90% of the xyloside-initiated glycosaminoglycans were secreted rapidly into the culture medium and were more highly sulphated than glycosaminoglycans polymerized on core protein. The increased extents of sulphation were associated with increased synthesis of dermatan sulphate and a decrease in that of nitrous acid-sensitive glycosaminoglycans.

Animals↗

Expression of Thy-1 antigen on human melanoma cells.

The expression of Thy-1 was examined on fresh frozen sections of melanoma and control skin lesions using a monoclonal antibody to Thy-1 and immunoperoxidase-labelled second antibodies. Thy-1 was detected on 12 of 19 primary melanomas but on only 1 of 23 melanoma metastases in lymph nodes, skin or brain. Expression of Thy-1 did not appear related to other known histological features of primary melanoma. Thy-1 was also expressed on 2 of 7 naevi but not on normal melanocytes or carcinoma of squamous cells, basal cells and sweat glands of the skin. Some lymphocytes below primary melanomas were Thy-1 positive. These results suggest that Thy-1 may be a marker of melanocytes at certain stages of differentiation analogous to its expression on cell lineages in the haemopoietic system. The relative paucity of Thy-1 on metastases may indicate that its expression on melanoma cells has prognostic significance for behaviour of the tumour in its host.

Adult↗

Nitrogen balance response in young men given one of two isolated soy proteins or milk proteins.

The protein nutritional value of two isolated soy proteins was compared with that of dried skim milk proteins in healthy young men. Eight subjects received one of the isolated soy proteins and six subjects received the dried skim milk as the test protein source. Each protein was tested at intakes of 0.35, 0.45, 0.55 and 0.65 g protein (N X 6.25) per kilogram per day during 10-day diet periods separated by break periods of 3 days and a 1-day protein-free period. Nitrogen balances were determined for the final 5 days of each experimental diet period. From regression analysis of nitrogen intake minus nitrogen output data, intakes of each protein source to meet mean nitrogen requirements were 124, 146 and 144 mg N/kg per day for the two isolated soy proteins and skim milk protein, respectively. It is concluded that well-processed isolated soy proteins are indistinguishable from milk as a protein source for maintenance of short-term N balance in adult human nutrition.

Adolescent↗

An evaluation of the nutritional value of a soy protein concentrate in young adult men using the short-term N-balance method.

Eight healthy young men participated in a metabolic balance study designed to assess the protein quality of soy protein concentrate (STAPRO-3200). Subjects received varying intakes of the test protein [0.35, 0.45, 0.55 and 0.65 g protein (N X 6.25) per kilogram body weight per day] during 10-day experimental periods. Each was preceded by a 1-day protein-free diet. A final diet period with a 0.65 g milk protein intake was included for comparative purposes. During this period and that with the 0.65 g test intake of soy concentrate the stable isotopes 70Zn and 58Fe were added to the diet for 2 days to obtain initial data on the absorption of zinc and iron when soy concentrate was the sole source of protein intake. Mean (+/- SEM) intake of soy concentrate determined to be sufficient for N balance (including allowance of 5 mg N/kg per day for integumental and miscellaneous losses) was 95 (+/- 7) mg N/kg per day. Absorption of the extrinsic doses of labeled iron and zinc did not differ between the soy protein- and milk-based diets. Comparison of these data was made with findings obtained previously with other protein sources evaluated in the same way. The conclusion is that the capacity of the soy concentration to support short-term nitrogen equilibrium in adult protein nutrition is the same as that for good quality animal protein sources. Thus, well-processed soy concentrates can make a nutritionally significant contribution to meeting adult human protein needs.

Absorption↗

The nutritional value of a soy protein concentrate (STAPRO-3200) for long-term protein nutritional maintenance in young men.

Six healthy young male M.I.T. students participated in a metabolic study to assess the capacity of a soy protein concentrate (STAPRO-3200) to serve as the sole source of dietary protein for long-term maintenance of protein nutritional status. Following an initial 9-day period, during which the subjects received an egg-protein, formula diet supplying 1.5 g protein per kilogram per day, the soy protein was given at a level of 0.8 g protein (N X 6.25) per kilogram per day for 82 days. Throughout, nitrogen balances were measured, and at intervals of 3 to 4 weeks, blood chemistries were determined, and evaluations of physical performance were undertaken. In addition measurements were made of zinc absorption and balance and of iron absorption, with the aid of 70Zn and 58Fe. Mean nitrogen balances were slightly positive for all subjects and the protein source was judged to support adequately maintenance of protein nutritional status, confirmed by the absence of changes in relevant blood parameters and maintenance of performance in the exercise tests. Mean zinc absorption was 23% of intake and did not change during the 82-day soy period and crude zinc balances remained slightly positive throughout. Iron intake was solely from the soy concentrate, and each meal was supplemented with ascorbic acid. Iron absorption was highly variable between and within subjects, as determined by the stable isotope balance procedure. Associated with the withdrawal of blood for purposes of monitoring the subjects, serum ferritin declined indicating a reduction in iron stores. These blood changes were used to approximate iron absorption and it was estimated to be 16%. It is concluded that well-processed soy concentrate can serve as the sole source of nitrogen and essential amino acids for long-term maintenance in adult humans.

Absorption↗

The synthesis of vitamin D metabolites by human melanoma cells.

Two melanin-producing human melanoma cell lines originally established from fresh surgical specimens were incubated with 25 hydroxyvitamin D3 (25 OHD3). Both cell lines produced material comigrating with 1,25 dihydroxy-vitamin D3 (1,25(OH)2D3) and 24,25 dihydroxyvitamin D3 (24,25(OH)2D3) in straight and reverse phase high performance liquid chromatography systems and displacing the relevant labeled ligands in competitive binding assays. The material designated 1,25(OH)2D3 was found almost entirely within the cells, whereas 24,25(OH)2D3 was evenly distributed between cells and medium. The synthesis of dihydroxylated materials was time dependent and was not observed if the cells were boiled before incubation with 25 OHD3. Preincubation with 1,25(OH)2D3 caused an increase in the synthesis of 24,25(OH)2D3 and a decrease in the synthesis of 1,25(OH)2D3. Michaelis-Menten constant (Km) values were 1.4 X 10(-9) mol/liter 25 OHD3 for the 1-alpha-hydroxylase enzyme and 72 X 10(-9) mol/liter for 24-hydroxylase. These studies constitute further evidence for the extrarenal synthesis of 1,25(OH)2D3. The suppressibility of 1 alpha-hydroxylase by preincubation with 1,25(OH)2D3 suggests a regulatory function for this system in the skin.

24,25-Dihydroxyvitamin D 3↗

High-affinity Ca2+-stimulated and Mg2+-dependent ATPase from rat osteosarcoma plasma membranes.

Transplantable rat osteosarcoma plasma membrane preparations contain high-affinity and low-affinity calcium-stimulated ATPases. The high-affinity enzyme displayed a K0.5 for calcium of 0.03 microM, a Vmax of 99.2 nmol/min/mg, and a requirement for magnesium ions. It was not inhibited by 20 microM trifluoperazine nor stimulated by the addition of 2 ng of calmodulin. Lack of stimulation with exogenous calmodulin may be related to the high endogenous calmodulin content of the membrane preparations. The low-affinity Ca2+- or Mg2+-ATPase displayed a K0.5 for calcium of approximately 2.40 mM (Vmax of 185 nmol/min/mg) and a K0.5 for magnesium of approximately 2.75 mM (Vmax of 250 nmol/min/mg).

Animals↗

Prognostic significance of leukocyte-dependent antibody activity in melanoma patients.

Sera from patients with melanoma and control subjects were examined for leukocyte-dependent antibody (LDA) activity against cultured melanoma and control nonmelanoma target cells in 51Cr release cytotoxicity assays. In over a third of 344 melanoma patients, LDA activity against melanoma cells was related to tumor growth, shown by disappearance of the LDA after surgical removal of melanoma. Tumor-related LDA activity was not detected in 143 controls with various nonmelanoma malignant conditions and benign skin lesions. Approximately 5% of the patients had high-titer melanoma LDA that was unchanged by surgical removal of the tumor, and 15% had melanoma LDA revealed in their sera only after the sera had been treated to dissociate immune complexes. In patients with stage I melanoma, the disease-free interval was significantly longer in those with tumor-related LDA compared to those with no LDA. Analysis of the data in relation to known prognostic variables suggested that the main influence of LDA on prolongation of the disease-free interval was in males. An association between tumor-related LDA and a longer disease-free interval was also apparent in patients with stage II melanoma at first presentation but not in those with recurrence after prior treatment of primary melanoma. The results suggest that LDA activity against melanoma cells in the sera of patients after surgical removal of stage I or stage II melanoma is a favorable prognostic factor. Further studies are needed to determine whether induction of melanoma LDA by immunotherapy may improve the outcome in patients without naturally occurring LDA.

Antibodies, Neoplasm↗

Evaluation of assays to detect immune complexes as an immunodiagnostic aid in patients with melanoma.

Sera from 211 melanoma patients were tested before and after surgery for the presence of immune complexes (i.c.) by the 125I-C1q radioimmunoassay (C1q RIA) and a nephelometric monoclonal rheumatoid factor assay (mRhF). The patients were grouped according to stage of disease and therapy. Before surgery stage III patients had a higher incidence of i.c. (26.9%) than stage II (17.5%) and stage I (6.1%) patients. The incidence of i.c. in the latter patients did not differ from that of normal controls. Stage I patients treated with BCG therapy had a higher incidence of i.c. before and after surgery to remove melanoma compared with untreated patients. The incidence of i.c. in stage I and II patients was higher in sera taken after surgical removal of tumour compared to that in sera taken before surgery. Sequential studies revealed that i.c. often appeared then disappeared prior to clinical detection of recurrences. These results suggested that antigen excess was a frequent cause for failure to detect i.c. A prospective evaluation of the usefulness of assays for i.c. to monitor disease activity in melanoma patients was conducted. In some individual patients detection of i.c. was a prelude to recurrence from melanoma but the high false negative rate and the presence of elevated i.c. levels unrelated to recurrent tumour suggested that these assays wound be of limited diagnostic value in the management of melanoma.

Adult↗

Induction of cytotoxic activity in human lymphocytes against autologous and allogeneic melanoma cells in vitro by culture with interleukin 2.

The influence of interleukin 2(IL2) on the cytotoxic activity of lymphocytes from patients with melanoma against autologous and a variety of allogeneic melanoma cells was studied. IL2 was produced from blood lymphocytes cultured for 24 h with phytohaemagglutinin (PHA) and purified by membrane chromatography to exclude PHA. Lymphocytes from 13 patients with melanoma at various clinical stages were cultured fro 6 days with IL2 (2 U/ml) and then tested for cytotoxic activity against autologous melanoma cells, three allogeneic melanoma and three non-melanoma cells. Autologous cytotoxicity was generated by culture with IL2 alone and was not increased by culture with both IL2 and autologous tumour cells. Marked increases in cytotoxic activity were also generated against the allogeneic target cells and were maximal against the NK-insensitive Chang target cells. Similar degrees of cytotoxicity were induced by IL2 stimulation of lymphocytes from melanoma patients, patients with nonmelanoma carcinoma and normal subjects against the allogeneic target cells. Cold target inhibition studies were carried out against IL2 induced autologous cytotoxicity in five patients. In four of five studies the autologous target cells inhibited more than the allogeneic target cells. There was no significant difference between the inhibition produced by allogeneic melanoma cells and that produced by non-melanoma cells. Similarly, in studies against allogeneic target cells, there was no significant difference in the inhibition produced by allogeneic melanoma compared to non-melanoma target cells. This applied irrespective of whether effector cells were from melanoma or non-melanoma subjects. These results suggest that lymphocytes from patients with melanoma are primed against autologous antigens in vivo and that provision of a second signal, IL2, in vitro can induce cytotoxicity against the autologous tumour. The cytotoxicity generated against the allogeneic target cells did not appear to have specificity to melanoma. Several results, such as the pattern of cytotoxicity against the target cells and change in cell surface markers on the lymphocytes during culture, suggested that cytotoxicity was mediated by activated T cells rather than by nature killer cells. These findings appear to have important implications both in the understanding of tumor host relationships and for the use of IL2 in therapy.

Antigens, Neoplasm↗

Phase I clinical trial f mitoxantrone: a new anthracenedione anticancer drug.

Mitoxantrone, 1,4-dihydroxy-5,8-bis(((2-[(2-hydroxyethyl)amino]ethyl) amino))-9,10-anthracenedione dihydrochloride, a new antitumor agent was evaluated in nine cancer patients as part of a phase I trial. In general, the drug was well tolerated. Leukopenia was the dose-limiting toxic effect. Mild to moderate leukopenia (but not neutropenia or thrombocytopenia) occurred in four of six patients given 4 mg/m2/week after a mean of 2.75 doses (range, 2-4 doses) and in all three patients given 5 mg/m2/week after three doses. Only one patient had mild nausea and vomiting. No patient experienced alopecia or mucositis, and none showed evidence of any cardiac, renal, hepatic, or pulmonary abnormality. Mitoxantrone treatment induced two partial remissions (patients with metastatic squamous cell carcinomas of the hypopharynx and rectum) and one mixed response (patient with gastric carcinoma). For phase II studies the starting dose, when used on a weekly schedule, should be 5 mg/m2 in patients who are known to have adequate bone marrow reserve.

Aged↗

Phase I clinical investigation of 1,4-dihydroxy-5,8-bis (( (2-[(2-hydroxyethyl)amino]ethyl) amino))-9,10-anthracenedione dihydrochloride (NSC 301739), a new anthracenedione.

1,4-Dihydroxy-5,8-bis(( (2-[(2-hydroxyethyl)amino]ethyl)-amino))-9,10-anthracenedione dihydrochloride is a new anthracenedione derivative that was evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. injection, repeated at 4-week intervals. Twenty-five patients received a total of 41 courses of the drug in a dose range of 1.2 to 14 mg/sq m. Leukopenia and thrombocytopenia were dose limiting but were of short duration and rapidly reversible. Mild degrees of phlebitis were observed in 10% of courses, and a green discoloration of the urine was noted with doses of greater than or equal to 10 mg/sq m. One patient with adenocarcinoma of the lung experienced a partial response of his tumor secondary to the drug. Phase II studies of 1,4-dihydroxy-5,8-bis(( (2-[(2-hydroxyethyl)amino]ethyl)amino))-9,10-anthracenedione dihydrochloride are planned at a starting dose of 12 mg/sq m as a single dose repeated at 21- to 28-day intervals.

Adult↗

Detection of a low-molecular-weight antigen on melanoma cells by a human antiserum in leukocyte-dependent antibody assays.

Biochemical characterization of serologically detected human melanoma antigens was undertaken for the development of immunodiagnostic assays in melanoma. An antiserum from a human melanoma patient, which detected melanoma antigens expressed on a large proportion of different melanoma cells, was used in leucocyte-dependent cytotoxic antibody (LDA) 51Cr-release assays to monitor the purification of melanoma antigens in urea/acetate extracts of lactoperoxidase 125I-labelled melanoma cell membranes. The separation procedures included affinity chromatography on Concanavalin A, gel filtration on porous polyacrylamide beads and preparative isoelectric focusing. The fractions were also monitored by polyacrylamide electrophoresis in sodium dodecyl sulphate and by measurement of beta 2 microglobulin and carcinoembryonic antigen content. The antigens detected by this antiserum appeared to be acidic (pI 3.5) low-mol.-wt glycoproteins of approximately 15,000 daltons which were resistant to heating at 56 degrees C and digestion with neuraminidase, but susceptible to repeated freeze-thawing and trypsin digestion. They did not appear to be related to HLA antigens, beta 2 microglobulin or known foetal antigens. The nature of the antigens detected in these studies is as yet unknown, but they appear similar to those described in the sera and urine of melanoma patients in previous reports. Thes combined results and the frequent expression of these antigens on melanoma cells from different patients suggest that assays to detect this antigen may provide a valuable immunodiagnostic aid in the management of melanoma.

Aged↗