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J O Benditt

Publications and source records attributed to J O Benditt.

27 records · Page 2Linked to original sources

Restrictive pulmonary disease due to interlobular septal fibrosis associated with disseminated infection by Strongyloides stercoralis.

Strongyloidiasis is caused by the nematode Strongyloides stercoralis. The parasite has a unique life cycle that enables it to cause a hyperinfection syndrome in which pulmonary involvement is characteristic. We describe the case of a 68-yr-old Hispanic male from Puerto Rico with disseminated strongyloidiasis who developed intense granulomatous reaction in the lung associated with interlobular septal fibrosis. Granulomatous lung disease leading to fibrosis within the lung has been well demonstrated in schistosomiasis, another parasitic disease. This case represents the first report, as far as we are aware, of fibrosis within the lung and restrictive pulmonary disease in association with Strongyloides stercoralis.

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GTP-binding proteins in rat liver nuclear envelopes.

Nuclear transport as well as reassembly of the nuclear envelope (NE) after completion of mitosis are processes that have been shown to require GTP and ATP. To study the presence and localization of GTP-binding proteins in the NE, we have combined complementary techniques of [alpha-32P]GTP binding to Western-blotted proteins and UV crosslinking of [alpha-32P]GTP with well-established procedures for NE subfractionation. GTP binding to blotted NE proteins revealed five low molecular mass GTP-binding proteins of 26, 25, 24.5, 24, and 23 kDa, and [alpha-32P]GTP photoaffinity labeling revealed major proteins with apparent molecular masses of 140, 53, 47, 33, and 31 kDa. All GTP-binding proteins appear to localize preferentially to the inner nuclear membrane, possibly to the interface between inner nuclear membrane and lamina. Despite the evolutionary conservation between the NE and the rough endoplasmic reticulum, the GTP-binding proteins identified differed between these two compartments. Most notably, the 68- and 30-kDa GTP-binding subunits of the signal recognition particle receptor, which photolabeled with [alpha-32P]GTP in the rough endoplasmic reticulum fraction, were totally excluded from the NE fraction. Conversely, a major 53-kDa photolabeled protein in the NE was absent from rough endoplasmic reticulum. Whereas Western-blotted NE proteins bound GTP specifically, all [alpha-32P]GTP photolabeled proteins could be blocked by competition with ATP, although with a competition profile that differed from that obtained with GTP. In comparative crosslinking studies with [alpha-32P]ATP, we have identified three specific ATP-binding proteins with molecular masses of 160, 78, and 74 kDa. The localization of GTP- and ATP-binding proteins within the NE appears appropriate for their involvement in nuclear transport and in the GTP-dependent fusion of nuclear membrane vesicles required for reassembly of the nucleus after mitosis.

Adenosine Triphosphate↗

Intrathoracic lymphadenopathy. A rare manifestation of rheumatoid pulmonary disease.

This is the first antemortem report of a patient with long-standing RA and interstitial lung disease who developed reactive mediastinal adenopathy coincident with increases in the activity of his interstitial process. Mediastinal adenopathy was discovered by means of CT of the chest as part of an evaluation of interstitial lung disease. The increasing use of better imaging techniques for this purpose will undoubtedly reveal more patients with this finding. Mediastinal lymphadenopathy complicating rheumatoid lung is clinically relevant; speculation is provided regarding the mechanism of the lymph node enlargement in this setting.

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Interaction of a nuclear location signal with isolated nuclear envelopes and identification of signal-binding proteins by photoaffinity labeling.

The nuclear envelope (NE) separates the two major compartments of eukaryotic cells, the nucleus and the cytoplasm. Recent studies suggest that the uptake of nuclear proteins into the nucleus is initiated by binding of nuclear location signals (NLSs) contained within these proteins to receptors in the NE, followed by translocation through the nuclear pore complex. To examine the binding step without interference from intranuclear events, we have used a system consisting of (i) purified rat liver NEs fixed onto glass slides and (ii) the prototype simian virus 40 large T antigen (SV40 T) NLS conjugated to nonnuclear carrier proteins, and we have visualized the receptor-ligand interaction by indirect immunofluorescence. In this system, incubation of isolated NEs with the wild-type SV40 T NLS conjugate with carrier proteins resulted in binding that was signal sequence-dependent, could be competitively blocked with excess conjugated and unconjugated wild-type peptide, did not require ATP, and was not affected by the transport-inhibiting lectin wheat germ agglutinin. In contrast, only minimal binding was observed with a mutant SV40 T NLS conjugate. These results are consistent with those obtained in other, more complex in vitro systems and suggest that binding of the SV40 T NLS is receptor-mediated. Binding is largely abolished by extraction of the NE with the nonionic detergent Triton X-100, suggesting that the receptor is soluble in detergent. We find in the Triton X-100 supernatant four major NLS-binding proteins with apparent molecular masses of 76, 67, 59, and 58 kDa by photoaffinity labeling with a highly specific crosslinker, azido-NLS. The reduced complexity of the system described here should be useful for the functional study of other potential NLSs for the identification and isolation of their binding sites and for the screening of antibodies raised against these binding sites.

Affinity Labels↗

Arm training reduces the VO2 and VE cost of unsupported arm exercise and elevation in chronic obstructive pulmonary disease.

BACKGROUND: Patients with severe chronic obstructive pulmonary disease (COPD) may develop dyspnea with minimal arm activity, thoracoabdominal dyssynchrony with unsupported arm exercise (UAEX) and increased oxygen uptake (VO2), and minute ventilation (VE) with simple unsupported arm elevation (UAE) and UAEX. We investigated whether unsupported arm training, as the only form of exercise, could decrease the VO2 and VE cost (percentage increase from resting baseline) associated with unsupported arm elevation and exercise, respectively. METHODS: Twenty-six patients with severe COPD were randomized to 21-24 sessions of unsupported arm (ARMT) or low-intensity resistive breathing (RBT) training as the only form of exercise. Patients were studied before and after training using a metabolic cart and esophageal and gastric pressures to evaluate metabolic and respiratory muscle function. RESULTS: After ARMT, the VO2 (58% vs 38% increase, P < 0.05) and VE (41% v. 21% increase, P < 0.05) cost for UAEX at exercise isotime decreased and endurance time increased. Similarly the VO2 (25% vs 18% increase, P < 0.05) cost decreased and VE no longer increased in response to 2 minutes of UAE after ARMT. The RBT group showed no such change. No improvement in ventilatory load or respiratory muscle function could be identified to explain the physiologic changes observed. After ARMT, mean inspiratory flow (VT/TL), a measure of central respiratory drive, was reduced during UAEX and the expected increase during UAE did not occur. CONCLUSION: We conclude that arm training reduces the VO2 and VE cost of UAE and UAEX, possibly through improved synchronization and coordination of accessory muscle action during unsupported arm activity.

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