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Biomedical subjects

B Friedman

Publications and source records attributed to B Friedman.

At least 91 records · Page 5Linked to original sources

Monoclonal antibody rat 401 recognizes Schwann cells in mature and developing peripheral nerve.

Monoclonal antibody Rat 401 recognizes subsets of cells in the developing central and peripheral nervous systems. Previous studies have shown that in the central nervous system (CNS) Rat 401 immunoreactivity diminishes sharply with cellular differentiation. Here we have examined the time course, cellular localization, and biochemical nature of the Rat 401 antigen in the rat peripheral nerve. In contrast to the CNS, in the periphery Rat 401 immunoreactivity is maintained into adulthood. Rat 401 staining is restricted to Schwann cells in mature peripheral nerve. Myelin-related Schwann cells are intensely immunoreactive, whereas nonmyelin-related Schwann cells are weakly immunoreactive. Unlike many Schwann cell markers, Rat 401 staining is maintained in cultured Schwann cells that lack axon contact. Biochemical analyses show that the antigen recognized by Rat 401 in the peripheral nerve is identical to that in embryonic CNS. The results demonstrate that the capacity for maintained Rat 401 immunoreactivity is restricted to Schwann cells as these cells are stained in adult animals as well as in embryos. In contrast, the same antigens are lost from the CNS at an early stage of development.

Animals↗

Regulation of the epidermal growth factor receptor by growth-modulating agents: effects of staurosporine, a protein kinase inhibitor.

Staurosporine is a potent microbial inhibitor of a number of protein kinases, including protein kinase C, cyclic AMP-dependent kinase, and the tyrosine kinase pp60src. We have used staurosporine to investigate the role of phosphorylation in the regulation of the epidermal growth factor (EGF) receptor in both human epidermal carcinoma A431 cells and mouse Swiss 3T3 fibroblasts. We report here that staurosporine treatment causes enhancement in high affinity EGF binding and a decrease in the phosphorylation state of the unstimulated receptor at a number of residues, including threonine 669. Staurosporine also antagonizes the inhibition of high affinity EGF binding and the increase in phosphorylation state of the unstimulated EGF receptor by phorbol esters and the calcium ionophore A23187. Staurosporine is an effective inhibitor of the EGF-stimulated receptor tyrosine kinase in vitro and thus does not enhance EGF stimulation of EGF receptor autophosphorylation in vivo. These results suggest that phosphorylation plays a major role in the regulation of the high affinity binding state of the EGF receptor in both unstimulated and mitogenically activated cells.

Alkaloids↗

Acute theophylline toxicity and the use of esmolol to reverse cardiovascular instability.

Theophylline overdoses are frequent conditions that may require emergency treatment. Clinical features common to severe theophylline toxicity include nausea and vomiting, tachydysrhythmias, metabolic disturbances, seizures, and cardiovascular collapse. Several reports have described these manifestations and their treatments. We report the case of a patient suffering from an acute, intentional theophylline overdose who exhibited the classic features of a toxic ingestion and describe the first reported use of IV esmolol in the treatment of accompanying cardiovascular manifestations.

Adrenergic beta-Antagonists↗

Septic arthritis of the sternoclavicular joint in healthy adults.

Septic arthritis of the sternoclavicular joint (SCJ) is a rare disorder, and is usually associated with predisposing factors such as contiguous foci of infection, heroin addiction, rheumatoid arthritis and diabetes mellitus. Three cases in previously healthy adults are reported here. The aetiology, clinical manifestations and treatment are briefly reviewed. The considerable difficulty in diagnosing this disorder in adults is emphasized. In summary, diagnosis of septic arthritis of the SCJ in adults requires a high index of suspicion, and must be considered not only in patients with predisposing factors, but also in previously healthy adults.

Adult↗

Care for the underinsured: who should pay?

Inner-city medically underinsured adults describe their preferences for health care and willingness to pay for health care services. The responses of 146 patients attest to the burden of administrative and economic responsibility placed on the public health care sector for indigent patient care. The results of this survey address the information required by the nurse managers who must balance patient needs against administrative pressures to generate revenue from patient fees.

Attitude to Health↗

Splenectomy in the management of systemic mast cell disease.

The records of 26 patients with systemic mast cell disease (SMCD) treated during the past decade at the National Institutes of Health were reviewed to determine the role of splenectomy in the management of SMCD. Seventeen (65%) patients had indolent SMCD, manifested primarily by urticaria pigmentosa and mast cell infiltration of the skin, bone marrow, or gastrointestinal tract. None of these patients underwent splenectomy. These patients required only symptomatic therapy. Nine (35%) patients, including those with associated hematologic disorders and those with a lymphoma-like illness termed lymphadenopathic mastocytosis with eosinophilia, had aggressive SMCD. Five of nine patients with aggressive SMCD underwent splenectomy. Of the five patients with splenectomy, three were alive at the time of this report, whereas none of the four who did not have a splenectomy was still alive. Length of survival without splenectomy was 26 months. With splenectomy, length of survival at the time of this report was 34 months. Patients without splenectomy died of bleeding caused by severe thrombocytopenia. Patients with splenectomy appeared better able to tolerate chemotherapy. We thus conclude that while splenectomy is of no value in the management of indolent mastocytosis, it should be considered in patients with aggressive SMCD.

Adult↗

Basic fibroblast-like growth factor is present in the conditioned medium of simian sarcoma virus transformed NRK cells.

The conditioned medium of Simian sarcoma virus (SSV)-transformed NRK cells contains at least two activities that down regulate the epidermal growth factor receptor. To identify these activities, we analyzed the medium for the presence of factors both related to and distinct from the v-sis oncogene product. Fractionation of the conditioned medium from SSV-transformed NRK cells by chromatography on heparin-Sepharose yielded two active fractions capable of inhibiting EGF binding. The first component, which eluted at 0.8 M NaCl, is able to induce autophosphorylation of the platelet-derived growth factor (PDGF) receptor, is a mitogen for Swiss 3T3 cells and corresponds to the PDGF B chain product of the v-sis oncogene. The second component requires 2 M NaCl for elution, is mitogenic for Swiss 3T3 cells and inhibits high affinity EGF binding through a protein kinase C-independent pathway, all properties of basic FGF. These results suggest that the conditioned medium of v-sis-transformed cells contains at least two factors that can act in an autocrine capacity, one derived from v-sis and one corresponding to basic FGF.

Animals↗

Basic and acidic fibroblast growth factors modulate the epidermal growth factor receptor by a protein kinase C-independent pathway.

Human acidic and basic fibroblast growth factors (aFGF and bFGF) inhibit epidermal growth factor (EGF) receptor binding in mouse Swiss 3T3 cells. Scatchard analysis indicates that aFGF and bFGF cause a decrease in the high affinity EGF receptor population, similar to that observed for activators of protein kinase C such as phorbol esters, platelet-derived growth factor (PDGF) and bombesin. However, unlike phorbol esters, aFGF and bFGF inhibit EGF binding in protein kinase C-deficient cells. The time course and dose response of inhibition of EGF binding by both aFGF and bFGF are very similar, with an ID50 of approximately 0.10 ng/ml. In contrast to bombesin but like PDGF, neither aFGF nor bFGF act on the EGF receptor through a pertussis toxin-sensitive G protein. These results indicate that both acidic and basic FGF depress high affinity EGF binding in Swiss 3T3 cells with similar potency through a protein kinase C/Gi-independent pathway.

Animals↗

Immuno-ultrastructural localization of sodium channels at nodes of Ranvier and perinodal astrocytes in rat optic nerve.

Immuno-electron microscopic localization of sodium channels at nodes of Ranvier within adult optic nerve was demonstrated with polyclonal antibody 7493. The 7493 antisera, which is directed against purified sodium channels from rat brain, recognizes a 260 kDa protein in immunoblots of the crude glycoprotein fraction from adult rat optic nerve. Intense immunoreactivity with 7493 antisera was observed at nodes of Ranvier. Axon membrane at the node was densely stained, whereas paranodal and internodal axon membrane did not exhibit immunoreactivity. The axoplasm beneath the nodal membrane displayed variable immunostaining. Neither terminal paranodal oligodendroglial loops nor oligodendrocyte plasmalemma were immunoreactive with 7493 antisera. However, perinodal astrocyte processes exhibited intense immunoreactivity with the anti-sodium channel antisera. Optic nerves incubated with pre-immune sera, or with 7493 antisera that had been pre-adsorbed with purified sodium channel protein, displayed no immunoreactivity. These results demonstrate localization of sodium channels at high density at mammalian nodes of Ranvier and in some perinodal astrocyte processes. The latter observation offers support for an active role for perinodal astrocyte processes in the aggregation of sodium channels within the axon membrane at the node of Ranvier.

Animals↗

Regulation of human basophil mediator release by cytokines. I. Interaction with antiinflammatory steroids.

We have analyzed the effects of overnight culture of human basophils with a variety of cytokines in the presence or absence of the glucocorticoid dexamethasone. The 24-h culture of basophils with a range of concentrations of several cytokines (granulocyte-macrophage-CSF, TNF-alpha, IL-1, IL-2, and IL-4) had no effect either on anti-IgE-induced histamine release or the inhibitory effects of dexamethasone on histamine release. IFN-gamma enhanced postculture releasability of human basophils. The concentration range for this effect was from 50 to 50,000 U/ml and maximal enhancement of anti-IgE-induced basophil histamine release was approximately 200% of control. IFN-gamma did not increase the number of occupied or unoccupied Fc epsilon RI on human basophils, suggesting that the enhancement of histamine release is a result of an intrinsic increase in the releasability mechanism. rIL-3 also augmented basophil releasability (approximately 250% of control) by a mechanism independent of alterations in basophil cell surface IgE density. The increase in post culture releasability occurred in both partially purified basophils (12 to 90% purity) and mixed leukocytes (approximately 1% basophils) although it was more marked in the former. Enhanced postculture releasability after exposure to IL-3 occurred for both IgE-dependent (anti-IgE) and peptide-mediated (fmet-leu-phe) responses and included elevations in the release of both histamine and sulfidopeptide leukotriene, suggesting a global increase in releasability. Basophils cultured in the presence of IL-3 were insensitive to the inhibitory effects of dexamethasone; at 1,000 U/ml IL-3, dexamethasone inhibition of basophil mediator release was completely blocked. None of the other cytokines tested, with the exception of crude or partially purified IL-2 preparations, had this effect. IL-3 contamination may explain the ability of these partially purified "IL-2" preparations to block the inhibitory effects of dexamethasone, because this effect was abolished by a specific anti-IL-3 antibody. These results suggest that IFN-gamma and IL-3 may modulate the response of human basophils in allergic reactions. Furthermore, increased local production of IL-3 may "prime" basophils for increased releasability and override inhibitory effects of elevated systemic glucocorticoids on human basophils. Finally, we conclude that the effects of glucocorticoids on human basophils may be in part mediated indirectly by effects on cells which produce cytokines, such as IFN-gamma and IL-3, that can modulate basophil function.

Anti-Inflammatory Agents↗

Sodium channels in astrocytes of rat optic nerve in situ: immuno-electron microscopic studies.

Immuno-electron microscopic localization of sodium channels within astrocyte somata and processes of adult rat optic nerve was demonstrated with polyclonal antibody 7493. In immunoblots of crude glycoproteins from adult rat optic nerve, antisera 7493, which is directed against purified rat brain sodium channels, recognizes a 260 kDa protein. Antisera 7493 intensely immunostains axon membrane at nodes of Ranvier. Associated perinodal astrocyte processes are also stained with antisera 7493. In addition, astrocyte cell bodies and major processes exhibit immunoreactivity with antibody 7493. Immunostaining with antisera 7493 is heterogeneously distributed within astrocyte cytoplasm and also appears to be associated with some regions of astrocyte plasmalemma. Glial filaments are not immunostained with 7493 antisera. Astrocyte processes forming the glial limitans and surrounding blood vessels display reduced immunoreactivity to 7493 compared to longitudinally oriented or perinodal astrocyte processes. However, some focal regions of the glial limitans exhibit robust 7493 immunostaining. Oligodendrocytes do not display 7493 antisera immunoreactivity. Optic nerve sections incubated with preimmune sera or with 7493 antisera that had been previously adsorbed with purified sodium channel protein, exhibited no immunoreactivity. These results demonstrate localization of sodium channels within astrocytes in situ of rat optic nerve and extend previous electrophysiological and pharmacological findings of sodium channels in cultured astrocytes. Possible functional roles of sodium channels within astrocytes are discussed.

Animals↗