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J L Murray

Publications and source records attributed to J L Murray.

At least 109 records · Page 6Linked to original sources
PubMed1988

Immunospecific saturable clearance mechanisms for indium-111-labeled anti-melanoma monoclonal antibody 96.5 in humans.

Liver uptake of 111In-labeled monoclonal antibodies (MoAb) remains a significant problem in radioimaging studies to date. To determine if the observed liver uptake of an 111In-labeled anti-melanoma antibody 96.5 (111In-96.5) was dependent on the presence of hepatic antigen or on recognition of circulating murine antibody, escalating doses of an unlabeled nonimmunoreactive MoAb (NIR-MoAb) were administered to 18 patients with metastatic malignant melanoma either 1 or 24 h prior to an infusion of 1 mg of 111In-96.5. The number of metastases imaged, pharmacokinetics, and the ratio of radioactivity (expressed as average counts/pixel) in liver (L), spleen (S), bone (B), and kidney (K) compared to blood pool (heart = H) were examined. Results were prospectively compared with data from six patients who received immunoreactive unlabeled 96.5 prior to 111In-96.5. Increasing dose or changes in the preinfusion time of NIR-MoAb had no significant effect on the biodistribution of 111In-96.5. In contrast, patients who received unlabeled, immunoreactive 96.5 prior to 111In-96.5 infusion demonstrated a significant drop [P less than 0.001] in the liver/heart ratio of radioactivity [2.81 +/- 0.35 (SEM)] compared to patients receiving the identical dose of NIR-MoAb [10.35 +/- 1.33]. Significant decreases in spleen/heart and bone/heart ratios were also observed. Pharmacokinetic studies showed that the volume of distribution (Vd) and the plasma t1/2 both decreased when 96.5 was administered compared to NIR-MoAb. In addition, a 4-fold increase in concentration X time was obtained after 96.5 antibody was administered compared to NIR-MoAb. More metastases were imaged in patients receiving preinfusions of 96.5 (23 of 28) than in patients receiving NIR-MoAb (10 of 18; P less than 0.05). Although tissue distribution of 111In-labeled antibody can be ascribed to nonspecific organ clearance of murine antibodies, a substantial component of tissue disposition of antibody 96.5 was shown to be a consequence of specific clearance of immunoreactive antibody which may cross-react with tissue antigens.

Antibodies, Monoclonal↗
PubMed1988

Interferon-induced changes in pharmacokinetics and tumor uptake of 111In-labeled antimelanoma antibody 96.5 in melanoma patients.

The type I interferons [both partially purified human leukocyte interferon (HuIFN-alpha) and recombinant alpha interferon] and the type II interferons have been shown to increase the expression of tumor-associated antigens in vitro. To determine whether HuIFN-alpha could increase tumor acquisition of the antimelanoma antibody 96.5 in vivo, five patients with metastatic malignant melanoma were treated with HuIFN-alpha at a dose of 3 X 10(6) units daily by im administration. Twenty-four hours after the first dose of HuIFN-alpha, 1 mg of antibody 96.5 labeled with 5 mCi of 111In was coadministered with 19 mg of unlabeled 96.5. Five patients matched for metastatic site and lesion size who had not received HuIFN-alpha were also given a dose of 5 mCi of radiolabeled 96.5 at the same total antibody dose (20 mg). In patients treated with HuIFN-alpha, there was a statistically significant increase in the plasma half-life of the 111In label (39.7 +/- 3.3 hr) compared to the untreated control group (29.8 +/- 3.2 hr). In addition, there was an increase in the apparent volume of distribution of the antibody in the HuIFN-alpha group (5.56 +/- 0.67 L) compared to controls (3.15 +/- 0.5 L) suggesting both an increased immediate extravascular distribution of radiolabeled antibody and a decrease in the subsequent rate of clearance of antibody from plasma. These two phenomena result in a 28% decrease in the area under the concentration curve in the HuIFN-alpha-treated group compared to controls. Computer analysis of whole-body scans from patients showed a threefold increase in radiolabeled antibody distributed to tumor relative to blood pool but no change in organ:blood ratios for liver, spleen, bone, or kidney compared to controls. This pilot study suggests that treatment of patients with HuIFN-alpha results in an improved distribution of radiolabeled antibody to tumor target without a concomitant increase of label in normal nontarget tissues. In addition, this change in whole-body distribution of antibody is manifested by changes in the pharmacokinetic parameters measured for monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1988

Induction of adenosine deaminase and 5' nucleotidase activity in cultured human blood monocytes and monocytic leukemia (THP-1) cells by differentiating agents.

The in vitro effect of short-term culture as well as the effect of retinol (ROH), retinoic acid (RA), muramyl dipeptide [( Abu']MDP), lipopolysaccharide (LPS), and gamma interferon (IFN-gamma) on the induction of the purine metabolic enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'nucleotidase (5NT) in human peripheral blood monocytes (HPBM) was examined. HPBM isolated by centrifugal elutriation were cultured for up to 96 h. Following an initial time lag of 24 h, mean ADA activity from seven separate experiments as measured in nmoles/10(6) cells/h increased from a baseline of 31.3 +/- 9.3 to 57.8 +/- 16.4 (P less than 0.005) at 72 h and to 72 +/- 21.5 (P less than .025) by 96 h. 5NT activity increased from a baseline of 2.2 +/- 0.9 to a maximum of 44 +/- 10.1 by 72 h and then declined to 29 +/- 18 (P less than 0.005) by 96 h, while no significant change in PNP activity was observed. HPBM incubated for 3 d with optimal concentrations of LPS, RA, and IFN-gamma had increases in ADA and 5NT activity ranging from three- to 10-fold compared to HPBM cultured in media alone, whereas no effect was observed with ROH and [Abu']MDP. RA, but not ROH, significantly enhanced ADA activity in a monocytic leukemia cell (THP-1) line. Addition of RA or the tumor promoter, phorbol 12-myristic 13-acetate (PMA), to HPBM or THP-1 cells resulted in significant increases in 5NT activity with opposite effects on ADA activity. These findings suggest that the biological mechanisms associated with differentiation in normal and malignant monocytes seem to be related and that the sequence and degree to which the various differentiation agents induce the enzyme elevations are also related to the mechanisms of activation/differentiation.

5'-Nucleotidase↗
PubMed1988

Radioimmunodetection of cancer with monoclonal antibodies: current status, problems, and future directions.

Early studies of immunoscintography with affinity-purified 131I-labeled polyclonal antibodies reactive against oncofetal antigens such as carcinoembryonic antigen (CEA) were moderately successful in detecting metastatic colorectal carcinoma. However, because of low tumor to background ratios of isotope, background subtraction techniques using 99Tc-labeled albumin were required to visualize small lesions. Antisera were often of low titer and lacked specificity. These problems could be overcome for the most part following the development of highly specific monoclonal antibodies (MoAb) against a variety of tumor-associated antigens. A number of clinical trials using 131I- or 111In-labeled MoAb to image tumors have demonstrated successful localization without the use of subtraction techniques. Variables limiting the usefulness of murine MoAb for diagnosis have included increased localization in liver and spleen, tumor vascularity and heterogeneity of antigen expression, and development of human antimurine globulins. Methods to overcome some of these problems are discussed. Radiolabeled MoAb appear useful as an adjunct to conventional diagnostic techniques both as a means to predict which antibodies might be useful for treatment and, in select patients, as a basis for treatment decisions.

Animals↗
PubMed1988

Effect of unlabelled monoclonal antibody (MoAb) on biodistribution of 111indium labelled (MoAb).

We have evaluated immunoscintigraphy in cancer patients using four 111In-labelled murine monoclonal antibodies (MoAb): 96.5 (anti-P97 of melanoma), ZME-018 (anti-high molecular weight antibody of melanoma), ZCE-025 (anti-CEA for colon cancer) and PAY-276 (anti-prostatic acid phosphatase for prostatic cancer). The effect of increasing the doses of unlabelled MoAb (co-infused with 1 mg labelled MoAb) on the relative body distribution of each labelled MoAb was assessed. Localization in the liver decreased significantly in all cases, with increasing MoAb dose, except for ZME-018. Localization in other organs increased significantly as the liver activity decreased. The spleen activity, however, fell in the case of MoAb ZME-018. Blood-pool activity increased with MoAb dose in all four MoAbs. These findings correlated with the rise in the detection rate of metastases, the plasma half-life, and other pharmacokinetic parameters. However, the dose level at which this correlation occurred varied with each antibody. These data demonstrate that co-infusion of unlabelled MoAb with 111In-labelled MoAb could alter the organ distribution, pharmacokinetics and tumour uptake in a favourable manner, though the degree to which this occurs depends on the antibody in question.

Antibodies, Monoclonal↗
PubMed1988

Improved tumor localization with increasing dose of indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody ZCE-025 in metastatic colorectal cancer.

Monoclonal antibodies (MoAbs) against carcinoembryonic antigen (CEA) react with human colorectal cancer cells, and when labeled with a gamma-emitting radioisotope, may help to localize known and occult metastatic disease. We tested ZCE-025 (Hybritech, Inc, San Diego), a high-affinity immune gamma globulin1 (IgG1) MoAb anti-CEA that does not react with normal granulocyte glycoproteins in a phase I/II trial to determine the reagent's toxicity and its maximum efficacy in detecting metastatic colorectal cancer. Increasing doses of unlabeled ZCE-025 were mixed with 1 mg of Indium-111 (111In)-radiolabeled MoAb and administered intravenously (IV) to 34 patients who had metastatic colorectal cancer. Planar nuclear or single photon emission computed tomographic (SPECT) scans were performed 48 to 72 and 120 to 144 hours later. Total dose of MoAb and scanning sensitivity (number of imaged lesions/number of known lesions) were correlated up to 80 mg. At doses of 2.5 to 20 mg, a mean of 22% of the lesions were imaged; at 40 mg, 77% were imaged (P less than .01). Liver metastases were detected as areas of increased activity ("hot") at the 40 mg dose but showed decreased MoAb uptake at lower doses. At the 40 mg dose normal liver parenchymal uptake of the labeled MoAb was lower with respect to blood pool compared with the other doses. At 80 mg, however, sensitivity of detection declined to 21%. One milligram of 111In-labeled ZCE-025 antibody coinfused with 39 mg of unlabeled antibody appeared optimal for detecting metastatic colorectal cancer, particularly in the liver. Although the exact mechanism(s) for this dose effect is currently unknown, a partial "blocking" effect of unlabeled antibody with a change in MoAb biodistribution may be occurring.

Adult↗
PubMed1988

Differential in vitro effects of recombinant alpha-interferon and recombinant gamma-interferon alone or in combination on the expression of melanoma-associated surface antigens.

The effect of individual in vitro concentrations of recombinant alpha-interferon species A (rIFN-alpha-A), recombinant gamma-interferon (rIFN gamma), and combinations of both interferons on the expression of melanoma-associated surface antigens p97 and the high molecular weight proteoglycan (HWM-MAA-240K) as detected by monoclonal antibodies (MoAb) 96.5 and ZME 018 respectively, was examined. rIFN-alpha-A at optimal concentrations of 50 and 500 U/ml caused significant (p less than 0.05 and p less than 0.01, respectively) increases in expression of p97 on the melanoma cell line Hs 294t following a 48-h incubation. No change in 96.5 binding was noted with rIFN-alpha-A concentrations up to 1000 U/ml after a 24-h incubation. Likewise, rIFN gamma at an optimal concentration of 500 U/ml enhanced p97 expression slightly at 24 h (p = 0.053) and more significantly by 48 h at concentrations of 50, 500, and 1,000 U/ml (p less than 0.01, p less than 0.05, and p less than 0.025, respectively). In contrast, neither rIFN gamma nor rIFN-alpha-A had an effect on modulation of the HMW-MAA as detected by ZME 018, irrespective of dose or incubation time. Optimal and suboptimal concentrations of rIFN-alpha-A plus rIFN gamma in combination did not significantly enhance expression of either antigen to a greater extent than that observed with optimal concentrations of each IFN alone, despite the fact that the combination had a synergistic anti-proliferative effect. These data demonstrate that the effects of each interferon (IFN) on the expression of melanoma-associated antigens (MAA) are heterogeneous and depend on IFN type and concentration, exposure time, and characteristics of the antigen studied. Moreover, the data regarding combinations of rIFN-alpha-A and rIFN gamma suggest that mechanisms responsible for IFN effects on MAA modulation are independent from its effects on proliferation. These findings may have clinical relevance with respect to trials using combinations of alpha- and/or gamma-IFN plus MoAb in vivo.

Antigens, Neoplasm↗
PubMed1988

Echocardiographic evaluation of potential cardiac transplant donors.

Since the initiation of the UTAH Cardiac Transplant Program, echocardiography has been used to evaluate 74 potential donors including 65 of 71 hearts ultimately used for transplantation. Of these 65 donors, 46 had normal studies, nine had pericardial effusions, five had mild septal hypokinesia with otherwise normal function, four had equivocal mitral valve prolapse, and only one heart could not be visualized. All transplants were successful and all donor hearts exhibited satisfactory hemodynamic function immediately after transplantation, including the hearts that were mildly abnormal before transplantation. These hearts included 21 (29%) that could have been excluded by conventional screening criteria. Nine potential donor hearts with grossly abnormal echocardiograms were not used for transplantation, including eight hearts with severe hypokinesia and one heart with significant mitral and tricuspid regurgitation. Inspection or histologic analysis confirmed the presence of severe dysfunction or morphologic damage in those hearts subjected to these additional measures. We conclude that echocardiographic screening is a useful method of evaluating potential cardiac transplant donors. It can identify potential donors that would otherwise have been excluded and it can identify potential donors with severe cardiac dysfunction without the need for direct surgical inspection.

Adult↗
PubMed1987

Comparative clinical pharmacology of [111In]-labeled murine monoclonal antibodies.

Patients with metastatic melanoma received either the murine antimelanoma antibody ZME-018 (20 patients) or antibody 96.5 (26 patients) at doses ranging from 1 to 20 mg and coupled to 2.5 or 5 mCi of [111In]. The pharmacokinetics and tissue disposition of these antibodies were measured at various times after infusion of the radiolabel. The clearance of the [111In]label from plasma closely fit (r2 greater than 0.90) an open, one-compartment mathematical model after administration of antibody 96.5. Clearance of [111In] from plasma after administration of ZME-018 fit a one-compartment model in some patients and a two-compartment model in others. The terminal phase half-lives of 96.5 and ZME-018 antibodies at the 20-mg dose were almost identical (27 +/- 2 h and 29 +/- 5 h, respectively). The half-lives calculated for 96.5 were not dependent upon the total antibody dose; however, with increasing doses of ZME-018 there was a dose-dependent increase in t 1/2 (from 17.8 +/- 2 h at the 2.5-mg dose to 29 +/- 5 h at the 20-mg dose). For 96.5 antibody, the apparent volume of distribution (Vd) approximated the total blood volume (7.8 +/- 0.71) at the 1-mg dose and decreased significantly at the 20-mg dose, suggesting saturation of extravascular antigen sites. In contrast, the Vd calculated for ZME-018 did not appear to be dependent upon the administered dose. Improved imaging occurred with increasing doses of unlabeled 96.5 above 2 mg, a finding not observed with ZME-018. The cumulative urine excretion of [111In] after administration of 96.5 or ZME-018 was 10%-14% of the total dose. These studies show that murine monoclonal antibodies of the same subtype but recognizing different surface antigens can exhibit markedly different in vivo pharmacokinetic behavior, which may partially explain differences in imaging noted with increasing doses of monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1987

Decreased 5'-nucleotidase activity in suppressor (OKT8) T lymphocytes from homosexuals with AIDS-related complex: nonassociation with enhanced deoxynucleoside toxicity.

The purine metabolic enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'nucleotidase (5NT) have been shown to be important for normal lymphocyte maturation. Abnormalities of these enzymes have been associated with hereditary as well as acquired immunodeficiency states. Enzyme activity was measured in helper (OKT4) and suppressor (OKT8) lymphocyte subsets from 10 homosexuals with AIDS-related complex (ARC) and in 10 healthy controls. There were no significant differences in either mean ADA activity or mean PNP activity between ARC OKT4 cells and control OKT4 cells and between ARC OKT8 cells and control OKT8 cells. By contrast, mean 5NT activity was slightly decreased in OKT4 cells from ARC patients compared with that of controls and more significantly diminished in ARC OKT8 cells compared with that of controls. Both deoxyadenosine and deoxyguanosine, when incubated separately with OKT4 and OKT8 cells in the presence of EHNA, an ADA inhibitor, did not significantly inhibit lymphocyte blastogenesis to a greater extent in ARC patients than in controls. Hence, the decreases in 5NT activity most likely reflect lymphocyte immaturity and are not associated with biochemical abnormalities leading to increased deoxynucleoside toxicity.

5'-Nucleotidase↗
PubMed1987

Radioimmunological imaging of metastatic prostatic cancer with 111indium-labeled monoclonal antibody PAY 276.

A total of 25 patients with histologically proved adenocarcinoma of the prostate, whose disease was staged clinically as D2 by appropriate radiographic and nuclear medicine studies, received increasing doses of PAY 276, an antiprostatic acid phosphatase monoclonal antibody for radioimmunological imaging. The patients were divided into 5 groups of 5. Groups 1 through 5 received an infusion of 5, 10, 20, 40 or 80 mg. monoclonal antibody, respectively, 1 mg. of which was labeled to 5 mCi. of 111indium, while stable monoclonal antibody was added to achieve the desired antibody concentration. No patient had an allergic reaction, and no significant change in serial hemoglobin levels, platelet count, chemistry profile or results of urinalyses was noted. The monoclonal antibody scan visualized at least 1 lesion in 19 of 25 patients (76 per cent): 4 in groups 1 and 2, and all 15 in groups 3 to 5. With results of conventional radiography and bone scintigraphy considered definitive for metastases, monoclonal antibody scans detected 7 of 32 metastases (21.8 per cent) in group 3 (20 mg.), 31 of 58 (53.4 per cent) in group 4 (40 mg.) and 101 of 134 (75.4 per cent) in group 5 (80 mg). In group 5 the incidence of false positive and false negative scans was 2.3 per cent (3 of 132) and 24.6 per cent (33 of 134), respectively. The detection of metastatic lesions increased as the concentration of unlabeled monoclonal antibody increased. Radioimmunological imaging of prostatic cancer with antiprostatic acid phosphatase monoclonal antibody seems to be feasible.

Acid Phosphatase↗
PubMed1987

A pilot clinical trial of the toxicity and immunorestorative effects of T cell reconstituting factor (SR 270258) in immunosuppressed cancer patients.

The in vivo immunorestorative effects of a highly purified protein fraction from human serum--designated SR 270258, prealbumin, or T cell reconstituting factor--was examined in cancer patients following radiation therapy. Sixteen patients with either Stage III head and neck cancer, nonoat cell lung cancer, or esophageal cancer were randomized to either receive (11 patients) or not receive (five patients) subcutaneous injections or SR 270258 at a dose of 2 mg/m2 three times per week for a total duration of 1 month. Treated patients were observed frequently for signs of toxicity. Blood was drawn initially and at weekly intervals for measurement of immunologic tests, which included percentage and absolute number of T cells, B cells, and other lymphocyte subpopulations; lymphocyte blastogenic responses to the mitogens phytohemagglutinin, concanavalin A, and pokeweed; and one-way mixed lymphocyte responses. Delayed type hypersensitivity responses to seven recall antigens were also tested. Mean lymphocyte blastogenic responses were significantly suppressed in patients relative to normal (p less than 0.05). There were no consistent changes in lymphocyte blastogenic responses, the percentage of lymphocyte subpopulations, or skin test responses in patients receiving SR 270258 versus untreated patients. However, the absolute number of OKT11 positive (E rosette receptor positive) T lymphocytes increased a mean of 52% (406 +/- 356 to 617 +/- 344/mm3; p = 0.03) in treated patients whereas no change was observed in untreated patients (366 +/- 226 to 446 +/- 327). Significant increases in the absolute number of OKT4 positive helper cells (158 +/- 109 to 221 +/- 112; p less than 0.05), OKT8 positive suppressor cells (179 +/- 186 to 279 +/- 184; p less than 0.05), and surface immunoglobulin-bearing B cells (49 +/- 47 to 155 +/- 268; p less than 0.05) also occurred. Prealbumin can induce a significant lymphocytosis in heavily irradiated, lymphopenic cancer patients. Lymphocyte blastogenesis and skin tests, however, were not improved at this dose and schedule.

Antigens, Surface↗
PubMed1987

Clinical parameters related to optimal tumor localization of indium-111-labeled mouse antimelanoma monoclonal antibody ZME-018.

Radioimmunolocalization of an 111In-labeled mouse antimelanoma monoclonal antibody (MoAb), ZME-018, was examined in 21 patients with metastatic malignant melanoma. Each patient received a single. i.v. infusion of MoAb at concentrations ranging from 1 mg to 20 mg, coupled to 5 mCi 111In by the chelating agent DPTA. No toxicity was observed in any patient. Total-body and regions of interest scans performed at 4, 24, and 72 hr following MoAb administration revealed uptake in 63 out of 105 previously diagnosed metastases for an overall sensitivity of 60%. Uptake was consistently observed in liver/spleen, and less frequently in bowel, testes, axillae and bone. Sensitivity of detection increased significantly at doses of MoAb above 2.5 mg, with 74% of lesions imaging at 20 mg/5 mCi compared with 29% at 2.5 mg/5 mCi (p less than 0.005). A significant correlation was observed between tumor uptake of 111In-MoAb conjugate and increasing tumor size. Soft-tissue lesions such as skin and lymph node metastases were imaged to a greater extent (76%) than visceral metastases (19%). In five of six patients, biopsies obtained from 3 days to 14 days after MoAb administration showed antibody present on tumor cells as demonstrated by flow cytometry and/or radioimmunoassay. Human anti-murine immunoglobulin responses were observed in seven of 17 patients studied. Mean plasma clearance of ZME-018 was prolonged with a T1/2 of 24.7 hr and increased slightly with increasing MoAb dose. Urinary excretion of 111In averaged 12.4% of the injected dose over 48 hours. Radioimmunolocalization of melanoma with 111In-labeled ZME-018 appears feasible. The sensitivity of the technique was related to dose, tumor size, and disease site.

Antibodies, Monoclonal↗
PubMed1987

Radioimmunoimaging in malignant melanoma patients with the use of indium-111-labeled antimelanoma monoclonal antibody (ZME-018) to high-molecular-weight antigen.

Radioimmunolocalization of an 111In-labeled, mouse antimelanoma monoclonal antibody (MAb), ZME-018, was examined in 30 patients with metastatic malignant melanoma. Each patient received a single iv infusion of MAb at concentrations ranging from 0.6 to 40 mg, coupled to 5 mCi 111In by the chelating agent pentetic acid. No toxicity was observed in any patient. Total-body and region of interest scans performed at 4, 24, and 72 hours following MAb administration revealed uptake in 110 of 171 previously diagnosed metastases for a sensitivity of 64%. Nonspecific uptake of radioactivity was consistently observed in the liver and spleen, and less frequently in the bowel, testes, axillae, and bone. Sensitivity of detection increased significantly at doses of MAb above 2.5 mg, with 74% of the lesions imaging at 20 mg/5 mCi compared with 29% at 2.5 mg/5 mCi (P less than .005). Sensitivity actually decreased slightly at the 40-mg dose. There was a significant correlation between tumor uptake of MAb-111In-conjugate and increasing tumor size. Soft tissue lesions, such as skin and lymph node metastases, were imaged to a greater extent (77%) than were visceral metastases (40%). Mean plasma clearance of ZME-018 was prolonged with a half-life of 33.6 hours in patients receiving 40 mg, compared with 17.8 hours in patients given 2.5 mg (P less than .01). Urinary excretion of the isotope averaged 11.4% of the injected dose over 48 hours. Hence radioimmunolocalization of melanoma with 111In-ZME-018 appeared feasible. The sensitivity of the technique varies with MAb dose, specific activity of 111In-MAb conjugate, tumor size, and disease site.

Antibodies, Monoclonal↗
PubMed1986

Decreased adenosine deaminase (ADA) and 5'nucleotidase (5NT) activity in peripheral blood T cells in Hodgkin disease.

The purine metabolic enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'nucleotidase (5NT) play an important role in normal lymphocyte differentiation. Abnormal levels of one or all of these enzymes have been associated with immunodeficiency diseases and lymphoproliferative disorders. ADA, PNP, and 5NT activity was measured in peripheral blood T cells from 24 patients with Hodgkin disease (HD) (12 in complete remission and 12 with active disease) to determine whether an association existed between enzyme abnormalities and the decreased cellular immune function previously described in this disorder. HD patients had a significantly decreased absolute lymphocyte count (1,618 +/- 1107/mm3; mean +/- SD) compared to controls (2,320 +/- 980; p less than .001). ADA, PNP, and NT activity was assessed in lymphocyte extracts by measuring the conversion of radiolabeled substrates to products over time. ADA activity expressed as mean +/- SEM nanomoles/10(6) lymphocytes/hr was significantly decreased in T cells from HD patients (84.6 +/- 7.5) compared to controls (128 +/- 12.3; p less than 0.025). Likewise, 5NT was significantly decreased in HD patients (12.7 +/- 1.3) compared to controls (24.0 +/- 3.6; p less than .005). There was not a significant difference in PNP activity between both groups. Low 5NT activity was present irrespective of whether patients had active disease (12.1 +/- 1.5) or were in unmaintained complete remission (14.5 +/- 2.4). These findings suggest that biochemical abnormalities may be responsible for or related to the persistent abnormalities in T-cell function noted throughout the clinical course of HD.

5'-Nucleotidase↗
PubMed1986

In vitro inhibition of interleukin-2 production by peripheral blood lymphocytes from stage III melanoma patients by prostaglandin E2: enhancement of lymphocyte proliferation by exogenous interleukin-2 plus indomethacin.

Interleukin-2 (IL-2) production following concanavalin A stimulation and the response of peripheral blood mononuclear cells (PBMC) to both IL-2 alone and IL-2 plus indomethacin, a prostaglandin synthetase inhibitor, were examined in 16 melanoma patients and 12 healthy controls. Mean IL-2 production by PBMC in 11 melanoma patients with metastatic disease (Stage III) was significantly decreased compared with controls and was moderately decreased compared with five patients with resected nodal disease (Stage II). Indomethacin restored IL-2 production in Stage III PBMC to levels equivalent to that produced by control PBMC. The PBMC of stage III patients also produced 40 times more prostaglandin E2 than PBMC from controls or Stage II patients. Indomethacin plus IL-2, but not IL-2 alone, was capable of restoring the low blastogenic response of PBMC of Stage III patients to normal levels. Hence, these data emphasize the importance for using IL-2 along with indomethacin for in vivo immunorestoration in disseminated melanoma.

Concanavalin A↗