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Biomedical subjects

M D Roth

Publications and source records attributed to M D Roth.

50 records · Page 3Linked to original sources
PubMed1982

Medical, legal and ethical issues in critical care.

This report is intended to familiarize the reader with the current legislation concerning state definitions of death, the pertinent judicial decisions concerning termination of life support and the current status of medical/ethical committees. However, it is of paramount importance to all health care personnel to become involved in the resolution of these problems. Current information regarding legal clarity to these issues leaves much to be desired. Unless we wish major decisions that will affect us all to be decided by others, it is strongly suggested that we become directly involved in this process and accept the challenge and the opportunity to influence major legal, ethical, and medical decisions.

Critical Care↗
PubMed1980

Induction of hyperglycemia with insulin antibodies to B-chain determinants.

Insulin antibodies measured by a radioimmune method (ABR) are significantly better inducers of hyperglycemia than are insulin antibodies measured by an immune hemolysis method (ABH) when injected intraperitoneally into mice. The ability to induce hyperglycemia by an insulin antiserum can be predicted by the titer of ABR measured. ABR interact in vitro with determinants severely perturbed on nickel-insulin, partially perturbed on proinsulin and desasparagine-desalanine insulin, and unaffected on zinc-insulin or zinc-free monocomponent insulin. ABH, on the other hand, interact in vitro with determinants severely perturbed on proinsulin and desasparagine-desalanine insulin but stabilized on nickel-insulin and zinc-insulin. Since the connecting peptide of proinsulin is probably in apposition to the A-chain residues on the solvent surface, the more effective reaction of proinsulin with ABR than with ABH is submitted as evidence that ABR are directed toward residues on the B-chain surface of insulin. Because ABR are more effective inducers of hyperglycemia than are ABH, it is proposed that the degree of hyperglycemia induced by antibodies in vivo is a result of interactions with determinants on the B-chain surface of insulin. These results support the possibility that insulin in vivo is more accessible for interaction with antibodies directed to the B-chain of insulin. It is also possible that ABR, which are directed to B-chain determinants, are of higher affinity than is the affinity between insulin and receptors or that the active site of insulin for maintaining euglycemia includes the B-chain surface residues.

Animals↗
PubMedDate not supplied

Regulation of natural killer function by nonlymphoid cells.

Natural killer (NK) cells and interleukin-2 activated NK cells, termed lymphokine-activated killer (LAK) cells, can lyse tumor cells without restriction by the MHC complex. The cytotoxic activity of these cells is subject to regulation by nonlymphoid cells in vitro. Interaction of NK cells with red blood cells (RBC) increases NK cytotoxicity. Interaction with polymorphonuclear neutrophils (PMN) suppresses LAK development and also inhibits NK- and LAK-mediated cytotoxicity at the effector cell phase. Exposure to tumor necrosis factor-alpha greatly enhances the inhibitory effect of PMN at the effector cell phase. Depending on their states of activation and differentiation, monocytes have the capacity to either enhance or suppress LAK induction. In contrast, macrophages derived from the lung are potent inhibitors of NK and LAK activity at both the induction and effector cell phases. Several cytokines are secreted by monocytes and macrophages and these include both suppressive and enhansive factors of cytotoxic function. Platelets are also capable of releasing suppressive factors. NK cells are believed to be involved in host surveillance of tumors, control of microbial infections and regulation of hematopoiesis. Regulation of NK cells by nonlymphoid cells and their products likely provides an in vivo mechanism for locally regulating NK function.

Blood Cells↗
PubMedDate not supplied

Interleukin-7 gene transfer in non-small-cell lung cancer decreases tumor proliferation, modifies cell surface molecule expression, and enhances antitumor reactivity.

Cytokine gene transfer to tumor cells can augment host antitumor responses and modify tumor phenotype. To evaluate the immunoregulatory and antitumor capacities of lung tumor-derived interleukin-7 (IL-7), we transduced non-small-cell lung cancer (NSCLC) cell lines with the IL-7/HyTK internal ribosomal entry site (IRES) retroviral vector and evaluated modifications in tumor phenotype and cocultured effector activities. In vitro proliferation of IL-7-transduced tumor cells was significantly less than control vector-transduced and parental tumor cells. The decreased proliferation rates of IL-7-transduced cells could be reproduced by adding high concentrations of recombinant IL-7 to the parental cells. Anti-IL-7 monoclonal antibody significantly increased the proliferation of the IL-7-transduced cells (P < .05). Parental NSCLC cells were found to express the IL-7 receptor, and IL-7 gene transduction did not alter expression of the IL-7 receptor. IL-7 transduction significantly altered tumor cell expression of intracellular adhesion molecule 1, major histocompatibility complex 1, lymphocyte function-related antigen 3, very late activation antigen beta 1, and p185neu. Peripheral blood lymphocytes cocultured with either IL-7-transduced tumor cells or tumor supernatants had enhanced cytolytic and proliferative capacities compared with coculture with control vector-transduced or parental cells. Our findings indicate that IL-7 gene transfer in NSCLC significantly augments cocultured effector activities in vitro, inhibits tumor cell proliferation, and modifies tumor cell surface phenotype. These findings suggest that IL-7 gene therapy may be effective in modifying host antitumor responses in NSCLC.

Antibodies, Monoclonal↗
PubMedDate not supplied

A comparison of gene transfer methods in human dendritic cells.

Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) for the initiation of antigen-specific T-cell activation. DCs may be highly enriched from peripheral blood-adherent leukocytes by short-term (7-day) culture in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor. Various methods of gene transfer were studied, including DNA/liposome complexes, electroporation, CaPO4 precipitation, and recombinant adenovirus (AdV) vectors. Low levels of expression were obtained with the physical methods tested. In contrast, AdV vectors expressing luciferase, beta-galactosidase, IL-2, and IL-7 all readily transduced human DCs. Increasing levels of gene expression were observed over a range of multiplicity of infection (MOI) of 10:1 to 10,000:1, with transduction efficiencies exceeding 95% at higher MOI. Although levels of maximal gene expression in DCs were significantly lower than those obtained using human tumor cell lines, IL-2 and IL-7 production of up to 5 x 10(2) ng/10(6) DC were achieved. These results suggest that AdV vectors are a promising vehicle for genetically engineering human DCs.

Dendritic Cells↗