Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Hemorrhagic and nonhemorrhagic brain lesions: evaluation with 0.35-T fast MR imaging

Two fast magnetic resonance (MR) imaging techniques, advanced Fourier and partial-flip imaging, were used at 0.35 T to examine 21 patients with suspected intracranial lesions; the results were quantitatively compared with a conventional spin-echo study. Both of the fast MR techniques yielded a fourfold reduction in imaging time per section. The advanced Fourier sequence showed contrast that was identical to the conventional spin-echo study with signal-to-noise ratios of 58% and 57% for the first and second echoes, respectively. The partial-flip sequence showed a contrast of 109% and 57% for lesions versus substantia alba, and 107% and 78% for substantia grisea versus substantia alba relative to the first and second echoes of the conventional spin-echo study. The partial-flip sequence was particularly sensitive to magnetic susceptibility; this produced artifacts that may undermine the usefulness of partial flip for routine screening in certain parts of the brain. However, this susceptibility significantly improved the detection of intracranial hemorrhage when compared with the spin-echo sequence, particularly when combined with phase mapping of the partial-flip study.     

Duodenoesophageal reflux and the development of esophageal adenocarcinoma in rats.

BACKGROUND. The carcinogenic effect of duodenoesophageal reflux, gastroesophageal reflux, and nitrosamines was studied in the rat esophagus. METHODS. Twenty male Sprague-Dawley rats underwent esophagogastroplasty to produce gastroesophageal reflux and 60 underwent duodenoesophageal anastomosis to produce duodenoesophageal reflux. Forty-three animals underwent no operation and acted as controls. Carcinogens known to produce squamous tumors in the rat esophagus (2,6-dimethylnitrosomorpholine [DMNM] or methyl-n-amylnitrosamine [MNAN]) were tested in each group. RESULTS. The rate of squamous carcinoma was 25% for rats with DMNM alone, 30% for rats with MNAN alone, and 20% for rats with induced gastroesophageal reflux plus DMNM. The rate of malignant change rose to 80% in rats with induced duodenoesophageal reflux and DMNM and 67% with duodenoesophageal reflux and MNAN. With duodenoesophageal reflux, 50% of tumors were adenocarcinoma, in contrast to 100% squamous differentiation of tumors in rats given the carcinogens with esophagogastroplasty or no operation. CONCLUSION. The presence of duodenoesophageal reflux increased the frequency and changed the histologic type of esophageal cancer in nitrosamine-treated rats. This indicates that duodenoesophageal reflux plays a role in the development of esophageal adenocarcinoma.     

Circadian esophageal motor function in patients with gastroesophageal reflux disease

Effective esophageal peristalsis is a major determinant of esophageal clearance function and may contribute to the development of complications in gastroesophageal reflux disease. Using 24-hour ambulatory esophageal manometry, we compared the circadian esophageal motor activity of normal volunteers to that of patients with increased esophageal exposure to gastric juice and various grades of mucosal injury (no mucosal injury, esophagitis, stricture, or Barrett's esophagus). The prevalence of a mechanically defective lower esophageal sphincter, esophageal acid exposure time, and the frequency of nonperistaltic esophageal contractions during the supine, upright, and meal periods increased with increasing severity of mucosal injury. The median amplitude of esophageal contractions was compromised only in patients with a mechanically defective sphincter. This was particularly so in patients with stricture or Barrett's esophagus and was associated with an increased frequency of ineffective contractions (less than 30 mm Hg). These data show that esophageal motor function deteriorates with increasing severity of mucosal injury. This appears to be caused by persistent reflux of gastric juice across a mechanically defective lower esophageal sphincter. The need for surgical correction of a mechanically defective sphincter before the loss of esophageal body function is implicated.     

Flat adenomas in a colon cancer-prone kindred

We describe new pathologic findings in a hereditary nonpolyposis colorectal cancer family. Affected family members developed multiple small adenomas with right-sided predominance; many adenomas had an unusual appearance featuring slightly elevated lesions with adenomatous changes confined to the upper regions of the colonic crypts. We have adopted the previously established term "flat adenoma" for these lesions. This phenotype may be a morphologic marker for at least one subset of hereditary nonpolyposis colorectal cancer.     

Genetic linkage of the tricho-dento-osseous syndrome to chromosome 17q21

Tricho-dento-osseous syndrome (TDO), MIM# 190320, is transmitted as a highly penetrant autosomal dominant trait that is characterized by variable clinical expression. The principal clinical features include kinky/curly hair in infancy, enamel hypoplasia, taurodontism, as well as increased thickness and density of cranial bones. Possible genetic linkage has been reported for TDO with the ABO blood group locus, but the gene defect remains unknown. We have identified four multiplex families (n = 63, 39 affected, 24 unaffected) from North Carolina segregating TDO. We previously have excluded a major locus for TDO in the ABO region for these families. Utilizing a genome-wide search strategy, we obtained conclusive evidence for linkage of the TDO syndrome locus to markers on chromosome 17q21 (D17S791, Z max = 10.54, Theta = 0.00) with no indication of genetic heterogeneity. Multipoint analysis suggests the TDO locus is located in a 7 cM chromosomal segment flanked by D17S932 and D17S941. This finding represents the first step towards isolation and cloning of the TDO gene. Identification of this gene has important implications for understanding normal and abnormal craniofacial development of hair, teeth and bone.      

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

Novel germline p16(INK4) allele (Asp145Cys) in a family with multiple pancreatic carcinomas. Mutations in brief no. 148. Online

As part of a search for causative genes of familial pancreatic carcinoma, the p16 genes were sequenced in members of 21 families with a phenotype of familial pancreatic carcinoma (2 or more first degree relatives affected). One family was found in which members carried a novel p16 allele with a G to T transversion at position 451, creating a missense amino acid change at codon 145 (Asp to Cys) and possibly disrupting the donor splice site of the exon 2/3 boundary. This coding change is not a known polymorphism, and occurs at a codon position in which another missese/splicing change has been shown to be linked to familial melanoma/pancreas cancer.