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Biomedical subjects

R Rosenbaum

Publications and source records attributed to R Rosenbaum.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1987

Corticosteroid-responsive pure red cell aplasia in chronic lymphatic leukemia.

Acquired pure red cell aplasia characterized by selective failure of erythropoiesis was seen in a 37-yr-old female patient with a diagnosis of chronic lymphatic leukemia (CLL). Though different immunosuppressive therapies have been tried in the past with variable response, there has been no case report of such favorable response to corticosteroids alone. We report this rare and unusual case of PRCA associated with CLL who responded to steroid therapy.

Adult↗
PubMed1987

Role of calcium in the activation of neutrophils by leukocyte inhibitory factor (LIF).

We investigated the role of calcium in the activation of neutrophils (PMN) by the human lymphokine leukocyte inhibitory factor (LIF). Using the fluorescent probe fura 2, we demonstrated that LIF (1/2-2 units) induced a small but significant dose-dependent increase in intracellular calcium in the presence of both calcium-containing (71 nM to 158 nM) and calcium-free (53 nM to 144 nM) buffer solutions. Thus, LIF is able to release calcium from both membrane channels and from intracellular stores. However, increases in intracellular calcium were not due to a release of Ca+2 from membrane stores, as shown by the inability of LIF to diminish fluorescence of the membrane-bound calcium probe chlortetracycline. In contrast to formyl-methionyl-leucyl-phenylalanine (fMLP), maximal calcium fluxes caused by LIF were of a much lower magnitude and not observed until 10-15 min after its application. The importance of calcium to the metabolic effects of LIF was demonstrated by the abilities of the calmodulin inhibitor trifluoroperazine (51.5% inhibition) and the extracellular calcium chelator EGTA (50.5% inhibition) to suppress LIF-mediated degranulation. The intracellular calcium chelator fura 2 also significantly inhibited LIF-mediated degranulation (61.8% inhibition). However, inhibition of the release of calcium from intracellular stores by TMB-8, had no effect on LIF-mediated degranulation. These data suggest that the ability of LIF to activate PMN is dependent on the availability of intracellular calcium and that this calcium is primarily derived from the slow influx of calcium from the extracellular pool.

Calcium↗
PubMed1986

Diagnosis of spontaneous perforation of the biliary tract in the newborn.

This report is of a 2-month-old child with spontaneous perforation of the common bile duct diagnosed by 99m-Tc disofenin nuclear hepatobiliary imaging. Of the agents available, the radiopharmaceutical properties of this compound allow the most accurate, safe, high-resolution imaging of the hepatobiliary tree in the diagnostic evaluation of jaundiced infants.

Bile Ducts↗
PubMed1986

Clinical trial of Wistar Institute 17-1A monoclonal antibody in patients with advanced gastrointestinal adenocarcinoma: a preliminary report.

Immunotherapy using monoclonal antibody 17-1A has been performed on 22 patients with metastatic gastrointestinal cancer. Criteria for treatment included objective evidence of advanced colon, gastric, or pancreatic cancer (positive CAT scan or x-rays, elevated tumor markers, and/or abnormal liver function tests). The tumor tissue was antigenically positive in all cases. Performance status ranged from 50 to 100%. No adverse reactions were noted. Of the 22 cases treated, 4 (18%) have died, none have rapidly progressive disease, 4 (18%) have slowly progressive disease, 10 (45%) are considered stable with disease, and none are considered partial or complete responses. It is too early to classify the response in 4 cases. In 6 of 8 patients where anti-idiotypic data was available, death or progressive disease was correlated to negative anti-idiotypic response, and clinical stability to a positive anti-idiotypic response. In the patients considered to be stable, the percent change from pre-treatment serum 19-9 concentrations to current values ranged from -10% to +353%. In the patients who have died or have been classified as slowly progressive the serum 19-9 changes ranged from +13% to +707%.

Adenocarcinoma↗
PubMed1984

Brief psychotherapy of bereavement reactions. The relationship of process to outcome.

We studied the relationship of dispositional and process variables with outcome in 52 bereaved patients given time-limited dynamic psychotherapy. Outcomes were generally favorable in symptom relief and improvement in relationship and occupational functioning. Patients' symptoms improved more than did their social and work functioning. Pretreatment levels of impairment or distress were significantly related to outcome, but most demographic and dispositional variables did not predict outcome. Process variables examined in relation to outcome--therapeutic alliance and actions by the therapist--were not significantly related to either type of outcome. When we considered the same process variables in interaction with two dispositional variables, motivation for dynamic therapy and developmental level of the self-concept, we found significant predictions of outcome. The major findings suggest that more exploratory actions were more suitable for highly motivated and/or better-organized patients and less suitable for patients with lower levels of motivation or organization of self-concept. More supportive actions were more suitable for patients at lower dispositional levels and less therapeutic for patients at higher levels.

Adjustment Disorders↗
PubMed1984

The association of transient acantholytic dermatosis with other skin diseases.

A retrospective study of 375 patients with transient acantholytic dermatosis (TAD) showed significant statistical associations between TAD and asteatotic eczema, allergic contact dermatitis, atopic dermatitis, and irritation from adhesive tape, and these associations were believed to be clinically significant. A similar statistical correlation between TAD and the presence of skin cancer was not deemed significant on clinical grounds. There was a clinical suggestion of an etiologic relationship between TAD and bullous pemphigoid, but this was not demonstrated statistically. Most of these associations seem explicable in terms of the Koebner phenomenon, and it is suggested that prevention and treatment of eczematous inflammation and irritation of the skin may be helpful in the management of TAD.

Acantholysis↗
PubMed1984

Chlorthalidone-triamterene: a potassium-sparing diuretic combination for the treatment of oedema.

The efficacy of a once-daily combination of chlorthalidone 50 mg plus triamterene 50 mg or chlorthalidone 100 mg plus triamterene 100 mg was compared to that of chlorthalidone 50 mg or 100 mg. This double-blind study was carried out in eighty-eight patients over a treatment period of 12 weeks. All patients entered the active medication period of 12 weeks after a placebo run-in period of 3 to 7 days, during which pretibial or malleolar pitting oedema averaging 2 to 4 mm developed. All patients started at the lower doses, i.e. forty-one started on chlorthalidone 50 mg plus triamterene 50 mg and forty-seven started on chlorthalidone 50 mg. The protocol provided for doubling the dose (but not for reducing it thereafter) at any time during the 12-week period when control of oedema was deemed inadequate. Eight of the combination therapy patients and sixteen of those on chlorthalidone required the higher doses. By Week 12, 96% of the chlorthalidone plus triamterene patients and 100% of the chlorthalidone patients had shown a reduction of at least 2 mm in depth of pits, and 92% and 72%, respectively, had complete disappearance of oedema. The decreases in pitting oedema were paralleled by mean weight losses of 2.4 kg and 3.1 kg, respectively, for the combination treatment group and the chlorthalidone group. Average serum potassium levels throughout the 12-week treatment period were 3.70 mEq/L for the patients taking the combination compared to 3.41 mEq/L of those taking chlorthalidone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Concomitant renal and hepatic failure treated by polyacrylonitrile membrane hemodialysis.

A patient with fulminant hepatic encephalopathy and acute renal failure progressively deteriorated following daily hemodialysis with a hollow fiber artificial kidney improved dramatically after an initial dialysis with a polyacrylonitrile membrane system. Following repetitive dialysis with this system the patients continued to improve and is well many months following discharge. His course during hemodialysis with membrane systems having different clearances for substances of various molecular weights suggests the hypothesis that a substance(s) with a molecular weight between 1,500 and 15,000 daltons is involved in the pathogenesis of hepatic encephalopathy and offers and additional therapeutic modality for his devastating disease.

Acrylic Resins↗
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↗