The BCL11 gene family: involvement of BCL11A in lymphoid malignancies.

Many malignancies of mature B cells are characterized by chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus on chromosome 14q32.3 and result in deregulated expression of the translocated oncogene. t(2;14)(p13;q32.3) is a rare event in B-cell malignancies. In contrast, gains and amplifications of the same region of chromosome 2p13 have been reported in 20% of extranodal B-cell non-Hodgkin lymphomas (B-NHL), in follicular and mediastinal B-NHL, and in Hodgkin disease (HD). It has been suggested that REL, an NF-kappaB gene family member, mapping within the amplified region, is the pathologic target. However, by molecular cloning of t(2;14)(p13;q32.3) from 3 cases of aggressive B-cell chronic lymphocytic leukemia (CLL)/immunocytoma, this study has shown clustered breakpoints on chromosome 2p13 immediately upstream of a CpG island located about 300 kb telomeric of REL. This CpG island was associated with a Krüppel zinc finger gene (BCL11A), which is normally expressed at high levels only in fetal brain and in germinal center B-cells. There were 3 major RNA isoforms of BCL11A, differing in the number of carboxy-terminal zinc fingers. All 3 RNA isoforms were deregulated as a consequence of t(2;14)(p13;q32.3). BCL11A was highly conserved, being 95% identical to mouse, chicken, and Xenopus homologues. BCL11A was also highly homologous to another gene (BCL11B) on chromosome 14q32.1. BCL11A coamplified with REL in B-NHL cases and HD lymphoma cell lines with gains and amplifications of 2p13, suggesting that BCL11A may be involved in lymphoid malignancies through either chromosomal translocation or amplification.

Lack of evidence that feedback from lifestyle alters the amplitude of the circadian pacemaker in humans.

Two groups of healthy subjects were studied indoors, first while living normally for 8 days (control section) and then for 18 x 27 h "days" (experimental section). This schedule forces the endogenous (body clock-driven) and exogenous (lifestyle-driven) components of circadian rhythms to run independently. Rectal temperature and wrist movement were measured throughout and used as markers of the amplitude of the circadian rhythm, with the rectal temperature also "purified" by means of the activity record to give information about the endogenous oscillator. Results showed that, during the experimental days, there were changes in the amplitude of the overt temperature rhythm and in the relative amounts of out-of-bed and in-bed activity, both of which indicated an interaction between endogenous and exogenous components of the rhythm. However, the amplitude and the amount of overlap were not significantly different on the control days (when endogenous and exogenous components remained synchronized) and those experimental days when endogenous and exogenous components were only transiently synchronized; also, the amplitudes of purified temperature rhythms did not change significantly during the experimental days in spite of changes in the relationship between the endogenous and exogenous components. Neither result offers support for the view that the exogenous rhythm alters the amplitude of oscillation of the endogenous circadian oscillator in humans.

The laryngeal mask airway for awake diagnostic bronchoscopy. A retrospective study of 200 consecutive patients.

The laryngeal mask airway (LMA) provides a view of the larynx and moving vocal cords without loss of airway control and can be used in flexible fibreoptic bronchoscopy for both anaesthetized and awake patients. In this retrospective review of 200 consecutive patients over a 30 month period, bronchoscopy was successful via the LMA in all but one patient using a technique of topical anaesthesia and sedation. The LMA directs the fibrescope to the glottis, allows respiratory function to be monitored and oxygen to be given. Complication rates were similar to those reported for transnasal awake bronchoscopy. Insertion of the LMA in the awake fasted patient is safe and easily achieved.

Crystal structure of a purple acid phosphatase containing a dinuclear Fe(III)-Zn(II) active site.

Kidney bean purple acid phosphatase (KBPAP) is an Fe(III)-Zn(II) metalloenzyme resembling the mammalian Fe(III)-Fe(II) purple acid phosphatases. The structure of the homodimeric 111-kilodalton KBPAP was determined at a resolution of 2.9 angstroms. The enzyme contains two domains in each subunit. The active site is located in the carboxyl-terminal domain at the carboxy end of two sandwiched beta alpha beta alpha beta motifs. The two metal ions are 3.1 angstroms apart and bridged monodentately by Asp164. The iron is further coordinated by Tyr167, His325, and Asp135, and the zinc by His286, His323, and Asn201. The active-site structure is consistent with previous proposals regarding the mechanism of phosphate ester hydrolysis involving nucleophilic attack on the phosphate group by an Fe(III)-coordinated hydroxide ion.

Amebic colitis mistaken for inflammatory bowel disease.

In ten patients, amebic colitis was mistakenly diagnosed as ulcerative colitis or Crohn disease of the colon because of the similarity of history, physical examination, and routine laboratory studies as well as findings on proctoscopic and barium enema examination. Multiple stool examinations failed to demonstrate ova or trophozoites of Entamoeba histolytica. Routine examinations of stools for ova and parasites are inadequate and even a meticulous search for amebas in fresh stool, in scrapings from bowel ulcer, or in biopsy material may give negative results. The indirect hemagglutination test was shown to be a reliable diagnostic test in the evaluation of these cases. Because corticosteroid treatment of patients with amebic colitis may lead to undesirable complications the indirect hemagglutination test results should be obtained in patients in whom such diagnostic confusion is likely.