A safe high-yield technique for cutting needle biopsy of the lung in patients with diffuse lung disease

The approach to the diagnosis and management of patients with diffuse infiltrative lung disease (DILD) is controversial. The results of transbronchial biopsy are often unsatisfactory. The role of open lung biopsy is highly variable. Percutaneous cutting needle biopsy (CNB) is not recommended because of its reported high morbidity/mortality relative to its low diagnostic yield. We report a technique for CNB with a high diagnostic yield and a low morbidity and no mortality in 228 patients with DILD over the past 23 years. METHODS: The salient features of the technique for CNB are as follows: the anesthetic needle does not enter the pleural space; a Franklin Silverman needle is inserted into the intercostal space posteriorly at outer one-third of chest wall; the biopsy is performed with the breath held at normal end expiration; the plane of pleural space is broken with sudden insertion of needle 8 to 15 cm into lung; and the pathway of the needle is maintained parallel to the lateral chest wall. RESULTS: A diagnosis was established in 129 of 145 biopsies (89%) performed by a trained operator (A.H.N.). There were 36 pneumothoraces (25%), four minimal hemoptyses (3%), and two chest tube placements (1%). There were no deaths (0%). CONCLUSION: With meticulous attention to technique and careful selection of patients, the procedure offers a relatively safe alternative to open lung or thoracoscopic lung biopsy in patients with DILD.     

Anti-plasmodial and anti-trypanosomal activity of synthetic naphtho[2,3-b]thiopen-4,9-quinones

Naphtho[2,3-b]thiophen-4,9-quinone and five derivatives were prepared using the Friedel-Crafts reaction and tandem-lithiation of aromatic diethylamides. These quinones were evaluated for their trypanocidal and anti-plasmodial activities by their effects on: (1) growth of epimastigote forms of Trypanosoma cruzi in vitro, (2) lysis of trypomastigote forms of T. cruzi in murine blood, (3) growth of Plasmodium falciparum in vitro, and (4) inhibition of the recombinant enzyme trypanothione reducatase. The parent compound, naphtho[2,3-b]thiophen-4,9-quinone (3a), was among the most active quinone tested in vitro against P. falciparum at 0.2 microM. However, it was inactive against P. berghei-infected mice treated with 2.3 mmol/kg daily for 5 days. Most of the quinones prepared were active against T. cruzi epimastigotes in culture but exhibited weak activity at 4 degrees C against trypomastigotes in murine blood as well against the enzyme trypanothione reducatase. Further structural modifications will be necessary to improve the in vivo activity of the naphthothiophenquinones.     

Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin

Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine repeat in the HD protein huntingtin. Huntingtin's localization within the cell includes an association with cytoskeletal elements and vesicles. We previously identified a protein (HAP1) which binds to huntingtin in a glutamine repeat length-dependent manner. We now report that HAP1 interacts with cytoskeletal proteins, namely the p150 Glued subunit of dynactin and the pericentriolar protein PCM-1. Structural predictions indicate that both HAP1 and the interacting proteins have a high probability of forming coiled coils. We examined the interaction of HAP1 with p150 Glued . Binding of HAP1 to p150 Glued (amino acids 879-1150) was confirmed in vitro by binding of p150 Glued to a HAP1-GST fusion protein immobilized on glutathione-Sepharose beads. Also, HAP1 co-immunoprecipitated with p150 Glued from brain extracts, indicating that the interaction occurs in vivo . Like HAP1, p150 Glued is highly expressed in neurons in brain and both proteins are enriched in a nerve terminal vesicle-rich fraction. Double label immunofluorescence experiments in NGF-treated PC12 cells using confocal microscopy revealed that HAP1 and p150 Glued partially co-localize. These results suggest that HAP1 might function as an adaptor protein using coiled coils to mediate interactions among cytoskeletal, vesicular and motor proteins. Thus, HAP1 and huntingtin may play a role in vesicle trafficking within the cell and disruption of this function could contribute to the neuronal dysfunction and death seen in HD.