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R P Sen

Publications and source records attributed to R P Sen.

13 recordsLinked to original sources

Nitrobenzylthioinosine binding cooperativity in chromaffin tissue membranes.

The nucleoside transporter present in chromaffin tissue membranes has been studied by [3H]nitrobenzylthioinosine (NBTI) binding. This ligand presents a high affinity, with a Kd value of 2.1 +/- 0.2 nM and a Bmax of 1.7 +/- 0.2 pmol/mg protein. From the Scatchard and the semilogarithmic graphical representations a positive cooperativity was deduced, with a Hill coefficient of 1.7 +/- 0.4. In displacement studies of NBTI by the non labelled compound, the Hill coefficient was also higher than 1 (1.44 +/- 0.11) in the presence of ATP. This nucleotide seems necessary to maintain the number of high affinity binding sites.

Adenosine Triphosphate

Effects of phorbol esters and secretagogues on nitrobenzylthioinosine binding to nucleoside transporters and nucleoside uptake in cultured chromaffin cells.

Secretagogues inhibited adenosine uptake in chromaffin cells without causing apparent changes in the uptake affinity. The inhibition caused by carbachol, nicotine and acetylcholine reached 50%. This inhibition was reproduced by the action of protein kinase C activators such as phorbol 12-myristate 13-acetate (PMA; 100 nM), phorbol 12,13-dibutyrate (PDBu; 100 nM), dicaproin (10 micrograms/ml) and tricaprylin (10 micrograms/ml), with inhibitions of Vmax. of 18, 20, 37 and 47% respectively. No changes in the affinity of uptake were observed with these effectors. Down-regulation of protein kinase C by phorbol esters decreased the inhibitory effects of carbachol on adenosine uptake. Binding studies with nitrobenzylthioinosine (NBTI) showed a similar decrease in the number of transporters when chromaffin cells were treated with the same effectors used for the uptake studies. The high-affinity dissociation constants showed minor changes with respect to the control. The ratio between maximal uptake capacity and the transporter number per cell was not significantly modified by the action of secretagogues or direct effectors of protein kinase C. The number of high-affinity binding sites for NBTI was decreased in cellular homogenates by the direct action of protein kinase C activators, with staurosporine able to reverse this action. Protein kinase C from bovine brain in the presence of ATP and effectors, decreased the number of high-affinity NBTI-binding sites in purified chromaffin cell plasma membranes. These data suggest the possibility of a molecular modification at the transporter level.

Adenosine

Pulmonary complications of combination therapy with cyclophosphamide and prednisone.

Oral cyclophosphamide and prednisone are standard treatment for some neoplasms and necrotizing systemic vasculitis and are advocated with increasing frequency for idiopathic interstitial lung disease. During a 15-month period, we observed four cases of acute respiratory failure from Pneumocystis carinii pneumonia (PCP) in patients treated with oral cyclophosphamide and prednisone. One patient each had polyarteritis nodosa, Wegener's granulomatosis, bronchiolitis obliterans with organizing pneumonia, and chronic lymphocytic leukemia with red blood cell aplasia. Hypoalbuminemia (serum albumin level less than 3.0 g/dl) and daily therapy were associated with increased risk for development of PCP (p less than 0.05). None of the patients had leukopenia (less than 3,500/cu mm) or neutropenia (less than 1,000/cumm) at diagnosis. All were negative for the human immunodeficiency virus. Patients receiving oral cyclophosphamide and prednisone may be at higher or increasing risk for PCP. A high index of suspicion and aggressive evaluation for opportunistic infection are needed in these patients; consideration for trimethoprim-sulfamethoxazole prophylaxis and development of more quantitative measures of immunosuppression are needed.

Aged

Fiberoptic bronchoscopy for refractory cough.

Fiberoptic bronchoscopy (FB) has a low yield in the diagnosis of chronic cough (greater than 3 weeks) in unselected patients. We assessed the yield of FB for cough during a four-year period in patients with nonlocalizing chest roentgenograms who were refractory to diagnostic efforts and empiric bronchodilator or antitussive therapy. Seven (28 percent) of 25 patients undergoing FB for cough (of greater than 1,500 bronchoscopies) had diagnostic findings (broncholithiasis, two; tracheobronchopathia osteochondroplastica, two; and tuberculous bronchostenosis, laryngeal dyskinesia, and arytenoid polyp, one each). No tracheobronchial neoplasms were detected. Age greater than 50 years and female sex independently predicted positive results (p = 0.02 Fisher's exact test), while duration of cough (two to 240 months), airflow, and smoking status did not. When patients with prior pulmonary or extrathoracic neoplasms were excluded, seven (35 percent) of 20 studies were diagnostic. Diagnoses potentially could have been made by thoracic computed tomographic scanning in four patients and indirect laryngoscopy in two. Fiberoptic bronchoscopy has a respectable yield for diagnosis of refractory chronic cough and is a reasonable procedure in carefully selected patients.

Bronchial Diseases

Effect of 5'-(N-ethylcarboxamido)adenosine on adenosine transport in cultured chromaffin cells.

Extracellular adenosine is transported into chromaffin cells by a high-affinity transport system. The action of adenosine receptor ligands was studied in this cellular model. 5'-(N-Ethylcarboxamido)adenosine (NECA), an agonist of A2 receptors, activated adenosine transport. Km values for adenosine were 4.6 +/- 1.0 (n = 5) and 10.2 +/- 3.0 microM (n = 5) for controls and 100 nM NECA, respectively. The Vmax values were 66.7 +/- 23.5 and 170.2 +/- 30 pmol/10(6) cells/min for controls and 100 nM NECA, respectively. The A1 agonist N6-cyclohexyladenosine, the A1 antagonist 8-cyclopentyl-1, 3-dipropylxanthine, and the A1-A2 antagonist 1,3-dipropyl-8-(4-[(2-aminoethyl)amino]-carbonylmethyloxyphenyl)- xanthine did not significantly modify the adenosine transport in this system. Binding studies done with [3H]dipyridamole, a nucleoside transporter ligand, did not show changes in either the number or affinity of transporter sites after NECA treatment. This ligand can enter cells and quantifies the total number of transporters. The binding studies with [3H]-nitrobenzylthioinosine, which quantifies the plasma membrane transporters, showed a Bmax of 19,200 +/- 800 and 23,200 +/- 700 transporters/cell for controls and 100 nM NECA, respectively. No changes in the KD were obtained. The effects of NECA were not mediated through adenylate cyclase activation, because its action was not imitated by forskolin.

Adenosine

Hemoptysis: a manifestation of pulmonary disease confidently managed by military physicians.

Military physicians can confidently manage hemoptysis with a systematic approach and optimal timing of consultation. Begin with a thorough history, physical examination, and chest x-ray. In our series of 177 cases, a cause for hemoptysis was found in 78% of those with abnormal chest x-rays but in only 21% of those with normal chest x-rays. All 36 cases of bronchogenic carcinoma were associated with an abnormal chest x-ray. A normal chest x-ray was associated with no cause found for the hemoptysis (44 cases) or bronchitis (25 cases), with no carcinomas developing upon a 2-year follow-up. Hospitalization is indicated with excessive bleeding or to allay patient or physician) anxiety. Diagnostic bronchoscopy is usually indicated, especially to localize the bleeding in massive hemoptysis (greater than 600 cc per 24 hours) when surgery may be indicated. Prompt referral should be the rule with bleeding from a mycetoma, diffuse bronchiectasis, or with recurrent significant hemorrhage (greater than 200 cc). In an active-duty population, these instances are fortunately rare, and conservative management and elective referral are the norm.

Adult

MR and CT findings in pulmonary artery sarcoma.

Pulmonary artery sarcomas are a rare and frequently forgotten cause of pulmonary artery occlusion. We present a case report that details magnetic resonance and new CT findings, which may help establish early diagnosis of this infrequently encountered tumor.

Aged