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Biomedical subjects

R C Kahn

Publications and source records attributed to R C Kahn.

At least 19 recordsLinked to original sources
PubMed1996

Molecular cloning of the human rad gene: gene structure and complete nucleotide sequence.

We have isolated and sequenced human genomic DNA clones encoding the Ras-related GTP-binding protein, Rad. The gene spans 3.75 kb and consists of five exons and four introns. Translation initiates from the first of two in-frame methionine residues in the second exon. Several potential transcription cis-elements were revealed throughout the 1.7 kb 5'-flanking region, including 'E box' and CArG binding sites for regulators of transcription in muscle.

Amino Acid Sequence↗
PubMed1996

Signal transduction pathways for interleukin 4 and insulin in human hepatoma cells.

IRS-1 has been found to relay the signals from the receptors for insulin, insulin-like growth factor-1, growth hormone, and many cytokines for the downstream effects in the various cell types tested. For interleukin 4 signaling, most studies were performed on hematopoietic cells and cell lines transfected with rat liver IRS-1 cDNA. In a liver cell lineage, IRS-1 expression has been found to be increased in hepatoma cells and hepatocytes in regenerating liver. To elucidate the possible function and the signal transduction pathway for interleukin 4, in comparison with insulin, in liver cells, we used the Hep 3B hepatoma cell line as a model system. Following insulin and interleukin 4 stimulation, rapid tyrosyl phosphorylation of IRS-1 occurred. Interleukin 4, but not insulin, stimulated the tyrosine phosphorylation of JAK1 and, to a lesser extent, JAK2. In contrast to the other cell types, the association of IRS-1 and Grb2 through the SH2 of Grb2 was demonstrated after IL-4 and insulin stimulation of the Hep3B hepatoma cells. Both insulin and interleukin 4 stimulated tyrosine phosphorylation and the enzyme activity of Erk1 kinase. Our results indicate that interleukin 4 and insulin might modulate hepatic cell growth and differentiation through many different or common pathways for the activation of JAK kinases and the usage of IRS-1 as a docking protein. The binding of IRS-1 with Grb2 after IL-4 as well as insulin stimulation may lead to MAP kinase activation, probably through the Grb2/sos/p21ras pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1988

Shock as a complication of cancer.

Shock is a syndrome in which multiple etiologies converge on a pathway of response which, although preservative and compensatory early on, rapidly becomes irreversible and fatal. The mechanisms of this response are under intense investigation, though little therapeutic improvement has accompanied our understanding. The patient with malignancy is at risk for developing shock both as a result of his disease and therapy for his disease, yet he is by no means alone in his vulnerability. Technologic advances may still bring more effective support to the shock patient, while immunologic advances may ultimately provide support to the shock patient, while immunologic advances may ultimately provide answers and cure.

Critical Care↗
PubMed1987

Direct visualization of the phosphorylated epidermal growth factor receptor during its internalization in A-431 cells.

Epidermal growth factor (EGF) rapidly stimulates receptor autophosphorylation in A-431 cells. After 1 min the phosphorylated receptor can be identified at the plasma membrane using an anti-phosphotyrosine antibody. With further incubation at 37 degrees C, approximately 50% of the phosphorylated EGF receptor was internalized (t1/2 = 5 min) and associated with the tubulovesicular system and later with multivesicular bodies, but not the nucleus. During this period, there was no change in the extent or sites of phosphorylation. At all times the phosphotyrosine remained on the cytoplasmic side of the membrane, opposite to the EGF ligand identified by anti-EGF antibody. These data indicate that (a) the tyrosine-phosphorylated EGF receptor is internalized in its activated form providing a mechanism for translocation of the receptor kinase to substrates in the cell interior; (b) the internalized receptor remains intact for at least 60 min, does not associate with the nucleus, and does not generate any tyrosine-phosphorylated fragments; and (c) tyrosine phosphorylation alone is not the signal for receptor internalization.

Amino Acids↗
PubMed1986

Hemodynamic oxygen transport and 2,3-diphosphoglycerate changes after transfusion of patients in acute respiratory failure.

The goals of management of patients with respiratory failure include improving arterial oxygenation with PEEP and red cell transfusion to maintain oxygen carrying capacity, both of which contribute to improving tissue oxygen delivery. However, standard CPD-stored blood is rapidly depleted of 2,3 diphosphoglycerate (2,3 DPG) and ATP, with resultant inadequacy of the red cell oxygen transport function. In 15 patients requiring mechanical ventilation with PEEP whose initial Hct less than or equal to 35%, we studied the effect of transfusion of 7 ml/kg of CPD-stored packed red blood cells on hemodynamic and oxygen delivery variables, pulmonary venous admixture (QA/QT), and erythrocytic P50, 2,3 DPG and ATP concentrations. Hemodynamics were not significantly altered by transfusion. 2,3 DPG decreased significantly from 14.5 +/- 1.1 to 13.1 +/- 1.5 mcmol/g Hb (mean +/- SD, p less than 0.05). There was no significant change in P50 or ATP. QA/QT rose significantly, from 20.1 +/- 7.8 to 28.9 +/- 12.3% (mean +/- SD, p less than 0.02). In our patients, an increase in arterial oxygen content obtained by transfusion was not followed by any associated decrease in cardiac work, as implied by solution of equations for oxygen delivery and oxygen consumption. The rise in QA/QT is undesirable in patients requiring PEEP, since it complicates management of their mechanical ventilatory support.

2,3-Diphosphoglycerate↗
PubMed1981

Clinical experience with high frequency jet ventilation.

High frequency jet ventilation (HFJV) has been used in recent years in some forms of respiratory failure, where the presence of barotrauma limited the application of high peak inspiratory pressure. In the present report, the authors describe the clinical experience with 17 patients, who could not be supported with conventional mechanical support and were placed on HFJV. Rates of 100 breath/min, inspiratory/expiratory ratio of 1:2 and cannula size of 1.06--1.62 mm (18--14) gauge were used. Driving pressure required to maintain a PaCO2 of 40--45 torr was 14--45 psig; however, except in 2 patients who developed hemorrhagic tracheitis with subtotal obstruction of both mainstem bronchi, a driving pressure higher than 27 psig was never required, even when PEEP up to 32 cm H2O was used. Of 17 patients treated, 8 survived. In all cases, alveolar ventilation could be maintained within the desired range with high frequency ventilation, even in those patients who eventually died; mechanical support never provided better oxygenation or alveolar ventilation than high frequency ventilation. Hemodynamic function was essentially unchanged with high frequency ventilation; indeed, in three cases, inotropic support with dopamine could be discontinued after initiation of high frequency ventilation.

Carbon Dioxide↗
PubMed1981

Technical aspects and clinical implications of high frequency jet ventilation with a solenoid valve.

High frequency jet ventilation (HFJV) is an incompletely studied technique of mechanical respiratory support. The authors have built a ventilator based on a solenoid valve, that allows independent selection of respiratory rate and inspiratory/expiratory ratio. The ventilator can be synchronized to the heart rate. Humidification is provided by warm saline dripped in front of the injector nozzle, so that the jet stream itself acts as a nebulizer. Tube diameter, length, and deformability are fundamental determinants of inspiratory flow rate and wave form. Cannula kinking and inadequate humidification were the most significant sources of complications.

Respiration, Artificial↗
PubMed1981

Dopamine administration in oliguria and oliguric renal failure.

Oliguric renal failure significanlty worsens the prognosis of many critical illnesses, particularly in patients with respiratory failure. In 52 patients, a continuous infusion of dopamine, 1.5-2.5 micrograms/kg . min, was administered when creatine clearance (Ccr) fell below 40 ml/min and urinary output was less than 1 ml/kg . h despite normal intravascular volume. In 18 patients, a continuous infusion of furosemide (3-5 mg/kg . day) was also administered. Daily, two 3-h collections of urine and blood specimens were obtained to determine Ccr, osmolar clearance (Cosm), free water clearance (CH2O) and excreted fraction of filtered sodium (FENa); one collection was made during dopamine infusion and one while the infusion was suspended. Cardiac output and pulmonary venous admixture were also measured. The authors obtained 199 urine collections in 52 patients; considering the aggregate patient pouplation, urinary output increased by 42.3% (30.2 +/- 3.45 (SEM) ml/h), on dopamine infusion. Cosm, FENa, and Ccr were also higher on dopamine. CH2O and hemodynamic variables were not altered by dopamine infusion. When patients were startified on the basis of mechanical ventilatory support, Ccr and furosemide administration, dopamine infusion essentially caused the same changes in the variables studied as described for the aggregate patient population. Diuresis and sodium excretion increased significantly on dopamine even in those patients receiving furosemide infusion. The authors conclude that fluid and osmolar load can be eliminated more effectively in critically ill patients with continuous infusion of 1.5-2.5 micrograms/kg . min of dopamine.

Anuria↗
PubMed1980

Calcium chloride administration in normocalcemic critically ill patients.

Ten normocalcemic critically ill patients who had experienced a decrease in cardiac index greater than or equal to 0.5 liter/min/m2 after incremental changes of PEEP received 7 mg/kg of CaCl2 as a slow iv bolus, followed by an infusion of 20 mg/kg CaCl2 over 60 min. Hemodynamic pressures and flow, oxygen uptake and transport, and blood chemistry variables were determined over a 120-min period. The results indicated that: (1) hemodynamic variables were not affected except for left ventricular stroke work index and mean blood pressure, which increased slightly; (2) both serum calcium and ionized calcium concentrations increased significantly, sometimes to dangerous levels; (3) colloid osmotic pressure and hemoglobin levels decreased slightly but consistently. In conclusion, CaCl2 administration failed to improve hemodynamic function depressed by PEEP. If CaCl2 can play a relevant role in the management of cardiovascular depression, further identification of appropriate doses and patients is necessary.

Aged↗