Mtr1, a novel biallelically expressed gene in the center of the mouse distal chromosome 7 imprinting cluster, is a member of the Trp gene family.

We recently described a novel putative Ca(2+) channel gene, MTR1, which shows a high level of homology to the human TRPC7 gene and the melastatin 1 (MLSN1) gene, another Trp (transient receptor potential protein)-related gene whose transcript was found to be downregulated in metastatic melanomas. It maps to human chromosome band 11p15.5, which is associated with the Beckwith-Wiedemann syndrome and predisposition to a variety of neoplasias. Here we report the isolation and characterization of the murine orthologue Mtr1. The chromosomal localization on distal chromosome 7 places it in a cluster of imprinted genes, flanked by the previously described Tapa1 and Kcnq1 genes. The Mtr1 gene encodes a 4.4-kb transcript, present in a variety of fetal and adult tissues. The putative open reading frame consists of 24 exons, encoding 1158 amino acids. Transmembrane prediction algorithms indicate the presence of six membrane-spanning domains in the proposed protein. Imprinting analysis, using RT-PCR on RNA from reciprocal mouse crosses harboring a sequence polymorphism, revealed biallelic expression of Mtr1 transcripts at all stages and tissues examined.

Direct cellular interaction with activated CD4(+) T cells overcomes hyporesponsiveness of B-cell chronic lymphocytic leukemia in vitro.

The proliferative response of clonal B cells from patients with chronic lymphocytic leukemia (B-CLL) is drastically reduced compared to normal B lymphocytes stimulated via the B cell antigen receptor complex or by CD40 ligation. In the present study we demonstrate that hyporesponsiveness of CLL-B cells can be overcome by stimulatory pathways mediated by activated CD4(+) T cells. In contrast to CD40 ligation, costimulation with activated T cells promotes a proliferative response in CLL-B cells identical to that in normal B cells. Furthermore, coculture with activated T cells improved survival of CLL-B cells in vitro. Differentiation of CLL-B cells into IgM producing cells was promoted, as well. However, the capacity for IgM secretion remained impaired compared to that of normal B cells. For T-cell-mediated B cell activation direct cellular contact with activated T helper cells is absolutely required. Prevention of CD40/CD40L interaction by CD40 antibody caused only partial inhibition of B cell activation, suggesting that additional signals are involved in T-B cell interaction. Whereas interruption of the ligand pairs CD11a/CD54, CD5/CD72, CD27/CD70 had no influence, the addition of CD58 antibody completely inhibited B cell activation by activated T cells. In costimulation with cellular signals the presence of B-cell-tropic cytokines, such as IL-2 and IL-4, was required to optimize B-CLL proliferation, as demonstrated by the use of neutralizing antibodies. We conclude from these results that proliferative hyporesponsiveness by CLL-B cells can be circumvented by antigen-nonspecific signals in addition to CD40 which are mediated by direct contact with activated T helper cells.

Paresis of a vertical rectus muscle after cataract extraction.

Nine patients had a permanent paresis of a vertical rectus muscle after cataract extraction. We sought to determine the common factors associated with and their contribution to vertical muscle paresis after cataract extraction. The study design included a survey that was conducted among the referring cataract surgeons and anesthesiologists with particular attention to surgical technique and anesthetic administered, as well as a medical history and examination and appropriate laboratory tests. Patients had a complete ophthalmic examination including prism cover testing in all nine diagnostic positions, forced-duction testing, and saccadic velocity and generated muscle force estimation. The results of the study demonstrate no correlation between the pareses and the use of a bridle suture, antibiotic or corticosteroid injection, systemic disease, or surgical technique. Peribulbar anesthesia was the most consistent feature in seven of the nine cases. In the other two, an atypical retrobulbar injection had been given. On the basis of the location of the injections, the needle type, and the concentration and quantity of the anesthetic injected, we conclude that permanent pareses of a vertical rectus muscle may be caused by a myotoxic effect of the local anesthetic.

Comparison of surgical methods in the treatment of dissociated vertical deviation.

The effectiveness of 3- to 5-mm recession of the superior rectus muscle with and without posterior fixation sutures was compared with 7- to 9-mm superior rectus muscle recessions in 228 patients with dissociated vertical deviation. We examined the patients at intervals ranging from six months to three years, and the results were classified as corrected, improved, or failed. Superior rectus muscle recessions of 3 to 5 mm were the least successful treatment. When 3- to 5-mm recession was combined with posterior fixation, the short-term results were more encouraging but the failure rate after three years was nearly the same in both groups (59% and 55%, respectively). The best results (P = .021) were achieved with 7- to 9-mm recessions. After three years the dissociated vertical deviation of most patients treated with this technique remained corrected or improved.