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R Rosenbaum

Publications and source records attributed to R Rosenbaum.

15 recordsLinked to original sources
PubMed1990

Recombinant interleukin-1 beta interacts with high-affinity receptors to activate neutrophil leukotriene B4 synthesis.

The capacity of interleukin-1 (IL-1) to function as a neutrophil (PMN) activator has been the subject of controversy. While IL-1 purified from mononuclear cell supernatants induced PMN activation, these observations have not been confirmed with recombinant IL-1. To document a cellular basis for a putative PMN-IL-1 interaction, we investigated the presence of IL-1 receptors on the PMN. Using an [35S]methionine-labeled preparation, specific binding of IL-1 to PMNs was demonstrated. Through Scatchard analysis PMNs were calculated to have a mean of 469 +/- 337 receptors per PMN with an affinity (Kd) of 0.32 +/- 0.09 nM. As IL-1 frequently activates arachidonic acid metabolism in other cell types, we investigated eicosanoid production as a putative consequence of the IL-1-PMN interaction. HPLC analysis of extracted supernatants of IL-1-treated PMNs demonstrated the release of leukotriene B4 (LTB4), its oxidative products, and 5-hydroxyeicosatetraenoic acid (5-HETE). Production of LTB4 was quantified using a commercial RIA. LTB4 secretion increased from 17.2 +/- 1.1 to 96.7 +/- 16.4 ng, also with 10.0 ng of IL-1. In time-course studies, it was shown that maximal eicosanoid secretion required a 30-min incubation with IL-1. These observations confirm the proinflammatory activity of IL-1 on neutrophils and resolve the controversy concerning a direct effect of IL-1 on neutrophils. In conclusion, recombinant IL-1 beta interacts with neutrophils through the presence on the PMN of a high-affinity receptor and results in the secretion of arachidonate metabolites.

Humans↗
PubMed1989

Activation of neutrophils by recombinant interleukin 6.

The cytokine interleukin 6 (IL-6) has been shown to have multiple biological activities against many cellular targets. The present studies were designed to determine whether these activities extended to the neutrophil (PMN). Initially, we investigated the ability of IL-6 to modulate PMN-mediated antibody-dependent cellular cytotoxicity. The presence of IL-6 stimulated 51Cr release from labeled, opsonized targets by 67.1% (from 21.6 +/- 1.4% to 36.1 +/- 1.3% at 10 U of IL-6 (P less than 0.01)). IL-6 was not directly toxic to the target cells and stimulation of ADCC was shown to occur across a range of effector-to-target ratios. To investigate the basis of the capacity of IL-6 to stimulate PMN, we studied the effects of IL-6 on PMN chemotaxis, degranulation, and the respiratory burst. IL-6 was not chemotactic or chemokinetic for PMN. However, IL-6 stimulated lysozyme secretion from 14.1 +/- 2.5 to 23.7 +/- 3.6% at 100 U (P less than 0.01). IL-6 was a complete secretagogue, being able to induce the secretion of both the secretory granule marker lactoferrin (11.2 +/- 2.0 to 23.5 +/- 2.2%) and the primary granule marker beta-glucuronidase (5.0 +/- 1.0 to 18.2 +/- 4.0%). IL-6 was not able to directly stimulate the PMN respiratory burst. However, IL-6 did "prime" PMN, enhancing superoxide secretion by fMLP (10(-7) M)-treated PMN by 50.8% (5.9 +/- 1.0 to 8.9 +/- 1.5 nmol superoxide at 100 U of IL-6; P less than 0.01) and PMA (5.0 nM) by 54.3% (8.1 +/- 2.6 to 12.5 +/- 3.6 nmol; P less than 0.05). In conclusion, IL-6 is a PMN stimulant, enhancing the toxicity of PMN in an antibody-dependent cellular cytotoxicity assay. Enhanced cytotoxicity may have been mediated, at least in part, by the stimulation of secretion of toxic components from PMN targets and by the priming of stimulating respiratory burst activity.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1989

Interleukin-4 is a neutrophil activator.

We investigated the ability of the lymphokine, interleukin-4 (IL-4), to function as a neutrophil (PMN) activator. IL-4 enhanced PMN-mediated killing of opsonized bacteria (by up to 91.6% at 3 units of IL-4; p less than 0.05). IL-4 was a weak secondary granule secretagogue and did not by itself generate a respiratory burst. However, IL-4 did increase in a dose-dependent fashion the respiratory burst mediated by the peptide formyl-methionyl-leucyl-phenylalanine (10(-7) mol/L). Maximal potentiation of PMN activity occurred at 100 units of IL-4 (6.3 nmol superoxide produced without IL-4 to 9.8 nmol at 100 units; p less than 0.01). Enhancement of the respiratory burst was not a generalized phenomenon, since IL-4 did not potentiate the respiratory burst mediated by either phorbol myristate acetate, calcium ionophore A23187, or zymosan-treated serum. Similarly, IL-4 potentiated the formyl-methionyl-leucyl-phenylalanine-stimulated secretion of both lysozyme (40.2%) and beta-glucuronidase (108.2%). Finally, IL-4 was demonstrated to enhance the ability of PMN to phagocytose sheep erythrocytes opsonized with rabbit IgG (by up to 94.2% at 30 units of IL-4). This increased phagocytosis correlated with the recruitment of a population of PMNs that did not phagocytose targets in the absence of IL-4. In conclusion, IL-4 enhanced neutrophil-mediated bactericidal activity. This increase may have occurred secondary to the stimulation of phagocytosis by IL-4 or by potentiation of degranulation and the respiratory burst.

Blood Bactericidal Activity↗
PubMed1989

Comparison of the antihypertensive effects of betaxolol and chlorthalidone as monotherapy and in combination.

In this multicenter, double-blind, parallel study, the antihypertensive effects of betaxolol (20 mg once daily) and/or chlorthalidone (25 mg once daily) were analyzed in 186 patients with essential hypertension. Following a 2- to 4-week placebo baseline period, patients were randomized to one of two treatment groups (betaxolol or chlorthalidone) and studied for 6 weeks while receiving single therapy and an additional 6 weeks with a combination of the two agents. Significant decreases from baseline supine diastolic blood pressure (SDBP) were observed in both groups at the end of the single-therapy phase (11 mm Hg in SDBP for betaxolol and 12 mm Hg in SDBP for chlorthalidone); a further significant decrease (7 mm Hg for betaxolol and 8 mm Hg for chlorthalidone in SDBP) was observed from the end of the single-therapy phase to the end of the combination-therapy phase. Changes in supine systolic blood pressure (SSBP) from baseline to the end of the single-therapy phase were 10 mm Hg for the betaxolol and 16 mm Hg for the chlorthalidone group. In all cases, within-group changes were statistically significant. From the end of single therapy to end of combination therapy there was an additional 14-mm Hg and 13-mm Hg reduction in SSBP in the betaxolol and chlorthalidone groups, respectively. Overall, 89% of the randomized patients completed the single-treatment phase (phase I), and 89% of those patients completed the combined therapy phase (phase II). There was no significant difference between treatment groups in the clinical response rate (SDBP at or below 90 mm Hg or a decrease from baseline of at least 10 mm Hg). A substantial percentage of patients completing phase I responded to either single agent (58% for betaxolol and 65% for chlorthalidone). Among patients completing phase II therapy, the combination of the two agents produced a greater response rate (83% for the betaxolol-first group and 85% for the chlorthalidone-first group). In conclusion, both agents were effective and well tolerated. The most frequent adverse events in the single-therapy phase were headache, arthralgia, and dizziness, while bradycardia, rhinitis, arthralgia, and dizziness were most frequent in the combination-therapy phase. The combination of betaxolol (20 mg) and chlorthalidone (25 mg) once daily produced an additive antihypertensive effect regardless of which drug was administered first.

Betaxolol↗
PubMed1988

Enhancement of the function of neutrophil type-1 and type-3 complement receptors by human leukocyte inhibitory factor (LIF).

The lymphokine leukocyte inhibitory factor (LIF) has previously been documented to enhance several neutrophil (PMN) functions, including stimulated chemotaxis and superoxide generation, phagocytosis and adherence of opsonized targets, and antibody-dependent cellular cytotoxicity. The present studies were designed to investigate the effects of LIF on PMN function mediated by the complement components C3b and C3bi. LIF induced a dose-dependent increase in superoxide production generated by opsonized zymosan (up to 97.1 +/- 31.4% at 16 U LIF/ml; P less than 0.01). While neither control nor LIF-treated PMN were capable of inducing phagocytosis of either C3b- or C3bi-opsonized sheep erythrocytes (E) directly, exposure to LIF caused a significant (P less than 0.05) increase in their adherence to E (137.4 and 59.4%, respectively). Specificity for complement receptor function was confirmed by the ability of anti-CR1 antibody to block adherence of LIF-treated PMN to EAC3b (77.0% inhibition) and anti-CR3 antibody to block adherence to EAC3bi (70.2% inhibition). Increased C3b and C3bi function may have been due, at least in part, to increased expression of their respective surface membrane receptors. Thus, using indirect immunofluorescence, LIF induced a 38.2% increase in fluorescence of the anti-CR1 antibody and a 96.1% increase in anti-CR3 binding. These studies describe an additional mechanism through which LIF may have an important pro-inflammatory role in vivo.

Antibodies, Monoclonal↗
PubMed1978

Hyperkalemia after renal transplantation. Occurrence in a patient with insulin-dependent diabetes.

An insulin-dependent diabetic patient received a renal transplant from a living related donor without evidence of rejection. In the posttransplant period, his serum potassium concentration (3.7 to 6.7 mEq/liter) fluctuated widely with the serum glucose concentration (165 to 470 mg/dl) during the day. Serum glucose and potassium concentrations were directly correlated (r = .734, P less than .001). Other factors controlling the serum potassium concentration were examined. Plasma and urinary aldosterone levels were normal, plasma renin activity and aldosterone levels rose during upright activity, and urinary potassium excretion increased with the administration of exogenous mineralocorticoid. Thus, mineralocorticoid secretion and responsiveness were intact. These observations indicate that hyperkalemia in a diabetic patient can occur in the absence of a defect in potassium excretion and are consistent with the interpretation that insulinopenia, as evidenced by hyperglycemia, can result in hyperkalemia due to diminshed translocation of both potassium and glucose from the extracellular to the intracellular compartment.

Adult↗
PubMed1978

Hypomagnesemia and impaired parathyroid hormone secretion in chronic renal disease.

Severe hypocalcemia secondary to magnesium depletion has been described in numerous patients with gastrointestinal disorders. The development of profound hypomagnesemia in chronic renal disease is a rare finding. We studied three patients with advanced renal failure and magnesium depletion. Severe hypocalcemia also was present in these patients. Despite hyperplasia of the parathyroid glands, the levels of immunoreactive parathyroid hormone (PTH) in blood were inappropriately low for the degree of renal insufficiency. After the administration of magnesium there was a significant increase in the levels of circulating i-PTH in serum with a concomitant improvement in the hypocalcemia.

Adult↗
PubMed1977

Hyperphosphatemia.

Serum phosphorus concentrations are maintained within narrow limits in humans. In the extracellular fluid most of the phosphorus is present in the inorganic form and at the level of the glomerulus greater than 90% of PO4 is ultrafilterable. The kidney plays a key role in PO4 homeostasis. Micropuncture experiments have demonstrated that 60 to 70% of the filtered PO4 is reabsorbed in the proximal tubule; however, there is evidence that a significant amount of PO4 is reabsorbed in the distal tubule. Phosphate secretion probably plays a minor role in the overall renal regulation of phosphate. In normal individuals the amount of PO4 ingested plays a key role in the amount that ultimately will be excreted in the urine. The reabsorption of PO4 along the nephron is regulated by a series of factors of which parathyroid hormone is the most important one. Hyperphosphatemia is seen frequently in clinical medicine and by far, the most common cause is a decrease in urinary PO4 excretion secondary to renal failure. From the practical point of view, the most effective way to treat hyperphosphatemia is to decrease PO4 absorption in the GI tract by the use of PO4 binders.

Acromegaly↗