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Biomedical subjects

M R Mardiney

Publications and source records attributed to M R Mardiney.

At least 19 recordsLinked to original sources

Carcinoma of the lung and cigarette smoking. Effect on serum ribonuclease activity.

Serum ribonuclease levels were determined in 54 patients with lung carcinoma, 74 long-term cigarette smokers, and 172 nonsmokers. The mean serum ribonuclease level was significantly higher in patients with lung carcinoma and long-term smokers compared with healthy nonsmokers (P less than .001). The serum ribonuclease activity level was not related to chronological age, sex, or race of the smoker or nonsmoker population. Forty (75%) of 53 patients with lung cancer and 49 (66%) of 74 smokers had elevated serum ribonuclease levels compared with 13 (7%) of 179 nonsmoker healthy controls (P less than .001). The highest incidence of elevation was noted in patients with epidermoid carcinoma (95%).

Adenocarcinoma

Light transmission analysis of lymphocyte activation by mitogens: a new technique.

In vitro lymphocyte transformation was evaluated by laser light transmission cytometry. Criteria are given for optimal application of this system to assessment of total cells and proportion of lymphoblasts in cultures. The light transmission studies revealed that cell numbers in mitogen stimulated cultures increase steadily, reaching a plateau. The percentage of lymphoblasts reached a peak after 4 days culture. The kinetics of [3H]-thymidine incorporation are similar. The increase in total cell number concomitant with decrease in [3H]thymidine incorporation at the fifth and sixth days indicates discordance between the cell proliferation and utilization of exogenous thymidine. The kinetics of total cell numbers and percentage of lymphoblasts suggest that in vitro reversion of lymphoblasts to small lymphocytes occurred. In addition to examining directly the cellular events during blastogenesis with ease, the current method appeared to be more reproducible than the [3H]thymidine incorporation assay.

Absorption

Alteration of human serum ribonuclease activity in malignancy.

A review of the literature and current biochemical studies is presented which provides significant evidence of alteration in the level of the enzyme ribonuclease activity in cancer. Current studies reveal that 80% of all cancer patients have alteration in ribonuclease activity and that individuals known to be at high risk for the development of cancer also demonstrate significant alteration of ribonuclease activity. It is noted that while elevation of serum ribonuclease exists within the cancer state and appears to be independent of clinical status (relapse, remission, or cured), diminished activity is found within the tumor itself. Animal models are reviewed which demonstrate that ribonuclease activity becomes elevated in the murine species subsequent to the transplantation of tumor and following the infection of the host with oncogenic virus. The occurrence of elevated ribonuclease activity in high tumor incidence strain mice long before the development of overt tumor is alos discussed. To date it is not possible to assign a specific function to the changes in the level of ribonuclease in connection with the cancer state. However, evidence indicating that tumor chemotherapy is generally associated with early elevation of ribonuclease activity within the tumor cell suggests that increased ribonuclease activity may play a role in the process by which the host restricts neoplastic transformation. The potential of this enzyme as a biochemical marker in cancer is discussed.

Adult

Complexing Rauscher leukemia virus reverse transcriptase with human plasma ribonuclease from Hodgkin's disease patients.

Human ribonucleases were purified from the sera of Hodgkin's disease patients by sequential column chromatography. The purified enzyme interacted with reverse transcriptase of Rauscher leukemia virus and formed an additive complex of Mr = 130,000. RNase and oligo(dG)-directed reverse transcriptase activities were diminished in the complex. The complex could be dissociated with the subsequent restoration of both activities in the presence of spermidine. The molecular weight of the complex suggest that the 2 RNase molecules bind to a single reverse transcriptase molecule.

Hodgkin Disease

Herpes zoster and impaired cell-associated immunity to the varicella-zoster virus in patients with Hodgkin's disease.

Thirty-two patients with Hodgkin's disease and 12 normal donors were studied for their in vitro lymphocyte responsiveness to a membrane-associated varicella-zoster (VZ) antigen. When compared to the normal donors, patients with Hodgkin's disease in whom radiotherapy was recently completed and those with active, recurrent disease had markedly impaired cell-associated immunity to VZ antigen. In addition, there was a suggestion that patients in long-term remission who had received primary combined modality therapy (radiotherapy plus chemotherapy) had an impaired response when compared to normal persons or to patients who had received single modality therapy. Newly diagnosed, untreated patients with Hodgkin's disease did not differ significantly from normal persons as a group but two of six were unresponsive to the VZ antigen whereas all normal subjects were responsive. Most patients in remission for at least one year following therapy had normal in vitro responsiveness. In two patients herpes zoster developed after the demonstration of absent in vitro lymphocyte reactivity to the VZ antigen.

Adult

Application of laser cytometry to the analysis of immunologically induced in vitro lymphocyte responsiveness.

This study defines an assay (laser analysis) that is a significant advance in our ability to quantitate and analyze immunologically induced in vitro lymphocyte responsiveness. Laser analysis is demonstrated to parallel radionucleotide incorporation (3H-thymidine) in terms of kinetic pattern, dose response characteristics, and statistical accuracy while exeeding radionucleotide incorporation in sensitivity. Direct quantitation of lymphocyte responsiveness, in terms of cellular proliferation, disclosed that substantial numbers of small lymphocytes were produced during in vitro stimulation with mitogen (concanavalin A) or antigen (streptokinase-streptodornase) in addition to the expected increase in lymphoblasts. The magnitude of this "total cellular response" (lymphocytes plus lymphoblasts) was found to be similar for antigen and mitogen stimulation, a finding not suggested by routine radionucleotide incorporation or morphological assays.

Concanavalin A

The effects of adrenergic agonists and blockers on antigen-induced DNA synthesis in vitro.

The effects of both alpha and beta adrenergic agonists and blockers on antigen-stimulated DNA synthesis in human lymphocyte cultures were studied. Results show that antigen-induced responses were enhanced by the presence of the beta blockers, propranolol and dichloroisoproterenol, and that this effect appeared to be specific blocking of the lymphocyte beta receptor since D (+) propranolol, a compound devoid of such acitvity, has no effect. Similarly, and alpha adrenergic agonist such as norepinephrine enhanced lymphocyte responsiveness.

Adrenergic Agonists

Latent homology of murine lymphoid antigens revealed through the complement mediated absorption of xenogeneic antiserum.

Xenoantiserum against C57BL/6 mouse spleen cells was produced by immunization of rabbits. Such antiserum displayed cytotoxic activity for several strains of mice. Standard "in vitro" absorption removed species specific antibody revealing antibody directed against the C57BL/6 strain. When the xenoantiserum was absorbed with DBA/2 spleen cells in the presence of complement, the binding of anti-C57BL/6 was increased. Such data suggest that xenoantibodies directed against spleen cells possess a broader capacity to react with cross-strain lymphoid antigens than previously described.

Animals

Antibody response in patients with acute nonlymphocytic leukemia.

Lymphocytotoxic (LCT) and anti-red blood cell (ABO) antibodies were measured serially in adult patients with acute nonlymphocytic leukemia (ANLL) receiving induction chemotherapy. The antigenic stimulus was provided by multiple platelet transfusions, many of which were ABO incompatible. Comparison of pretherapy titers 4-6 weeks into therapy shows that 50% (19/38) of patients became LCT positive (cytotoxicity against greater than 10% of panel of cells) and 54% (19/35) had increases in ABO titers (greater than 2 tube dilution). A total of 66% of patients had significant rises in at least one antibody. ABO and LCT titers tended to vary in parallel although exceptions were noted. The development of anti) remission rate or duration, 3) type of therapy, 4) number of platelet transfusions, 5) time relationship between the antigenic stimulus and the initiation of cytotoxic therapy, and 6) skin test reactivity. Antibody responders tended to have higher pretreatment lymphocyte counts. The ability to develop a secondary antibody response does not appear to be a major prognostic factor in ANLL.

ABO Blood-Group System

Differences in potentiation of melanoma growth by absorbable and nonabsorbable suture.

This study demonstrates that various suture materials have different influences on tumor take and growth. When used in an area containing 10(5) or greater tumor cells, all suture types studied potentiated tumor growth. At subclinical tumor cell doses- that is, 1,000 or fewer cells that do not normally grow to a clinically detectable tumor- silk and steel increased tumor occurrence. In comparison, monofilament nylon, polyglycolic acid, and chromic suture did not potentiate tumor growth. This phenomenon of increased tumor growth associated with certain suture types appears to be related to the physical characteristics of the suture involved, although the interaction of the chemical breakdown products of the suture material with the local tumor cells is under investigation. The type of suture material used may play a significant role in the subsequent development of local recurrence of cancer.

Animals

The demonstration of cell-associated immunity to viruses. In vitro lymphocyte responsiveness to Varicella-zoster antigen.

The demonstration of in vitro lymphocyte responsiveness to common pediatric viruses has previously been fraught with many technical and conceptual problems. Based upon our prior experience in demonstrating cell-associated immunity to mumps, rubella and measles viruses we illustrate our methodology and conceptual framework by documenting in vitro lymphocyte responsiveness to the Varicella-zoster virus, another ubiquitous virus of childhood. We discuss our approach to the problems of reactivity, specificity and reliability in the use of membrane-associated viral antigens.

Antigens, Viral

A proper sequence for the treatment of B16 melanoma: chemotherapy, surgery, and immunotherapy.

The therapeutic effectiveness of surgery, chemotherapy, and immunotherapy alone and in combination were studied in the B16 melanoma model. The sequence of chemotherapy and immunotherapy as adjuvants to surgery proved important: Chemotherapy was significantly better when given before surgery; immunotherapy was more effective when delivered after surgery. The most effective therapeutic regimen was a combination of all three modalities: a single course of chemotherapy preceding surgery followed by immunotherapy.

Animals

The synergistic effect of synthetic polynucleotides and mercaptoethanol in amplifying the murine mixed lymphocyte reaction.

Tritiated thymidine incorporation of one-way murine mixed lymphocyte reactions was compared in the presence of mercaptoethanol and/or poly AU. Each of these agents amplified specific responsiveness in this system without altering reaction kinetics and the combined use of these agents enhanced specific thymidine incorporation beyond that achieved by either alone. These agents may be useful in those situations where increased sensitivity of murine mixed lymphocyte reactions is required.

Animals

The age-dependent efficacy of polyadenylic-polyuridylic acid therapy upon the development of spontaneous leukemia in AKR mice.

The synthetic double-stranded polynucleotide, polyadenylic-polyuridylic acid, has been shown to increase the long-term survival of AKR mice. In order to determine whether this effect was age dependent, polyadenylic-polyuridylic acid was administered to AKR mice starting at 2, 4, 6, or 8 months of age. The best therapeutic effect was achieved when polyadenylic-polyuridylic acid treatments were begun at 2 months of age, and there was no beneficial effect when begun at 8 months of age.

Age Factors