Molecular characterization of Waldenstrom's macroglobulinemia reveals frequent occurrence of two B-cell clones having distinct IgH VDJ sequences.

PURPOSE: Malignant B lineage cells in Waldenstrom's macroglobulinemia (WM) express a unique clonotypic IgM VDJ. The occurrence of biclonal B cells and their clonal relationships were characterized. EXPERIMENTAL DESIGN: Bone marrow and blood from 20 WM patients were analyzed for clonotypic VDJ sequences, clonal B-cell frequencies, and the complementary determining region 3 profile. RESULTS: Two different clonotypic VDJ sequences were identified in 4 of 20 WM. In two cases, partner clones had different VDJ rearrangements, with one clonotypic signature in bone marrow and a second in blood. For both cases, the bone marrow clone was hypermutated, whereas the blood clone was germ line or minimally mutated. In two other cases, partner clones shared a common VDJ rearrangement but had different patterns of somatic mutations. They lacked intraclonal diversity and were more abundant in bone marrow than in blood. VDJ mutation profiles suggested they arose from a common IgM progenitor. Single-cell analysis in one case indicated the partner clones were reciprocally expressed, following rules of allelic exclusion. CONCLUSIONS: The existence of two B-cell clones having distinct VDJ sequences is common in WM, suggesting that frequent transformation events may occur. In two cases, the partner clones had distinct tissue distributions in either blood or bone marrow, were of different immunoglobulin isotypes, and in one case exhibited differential response to therapy. The contributions of each clone are unknown. Their presence suggests that WM may involve a background of molecular and cellular events leading to emergence of one or more malignant clones.     

Dichapetalin-type triterpenoids and lignans from the aerial parts of Phyllanthus acutissima

Chemical investigation of the aerial parts of Phyllanthus acutissima resulted in the isolation of five new dichapetalin-type triterpenoids, acutissimatriterpenes A-E ( 1- 5), and two new lignans, acutissimalignans A ( 6) and B ( 7), along with two known lignans and three known ellagic acid derivatives. The structures of 1- 7 were determined mainly on the basis of spectroscopic methods. The compounds obtained were evaluated for cytotoxic and anti-HIV-1 activities.     

Small Intestinal Manometric Studies in Patients with Familial Visceral Myopathies

We studied jejunal manometry on 10 patients with type 1 familial visceral myopathy (FVM), and one patient each with types II and III. Two patients of type I and both patients of types II and III had intestinal pseudo-obstruction syndrome. The record was obtained in each patient for 4 to 5 hours during fasting, and 1 hour after feeding. In type I FVM, migrating motor complexes were present in six and absent in four patients. In these four patients (two with intestinal pseudo-obstruction syndrome) with absent migrating motor complexes, there was infrequent low-amplitude contractions during fasting, and after feeding. In six patients with migrating motor complexes, the motility indices of phases 2, 3, and fed period were 59%, 49%, and 24% of those of control subjects, respectively, and the frequency of contractions of phases 2, 3 and the fed period were 70%, 79%, and 32% of those of control subjects, respectively. In both patients with types II and III FVM, only infrequent low-amplitude contractions were recorded during fasting and after feeding. We concluded that intestinal contractions in patients with familial visceral myopathies were weak, and the weakness was more severe in patients with intestinal pseudo-obstruction syndrome.     

Iso-electricfocusing of Bithynia snail antigens for IgG- and IgG(1-4)-ELISA detection of human opisthorchiasis

Diagnosis of opisthorchiasis is confirmed by the presence of characteristic eggs and worms. However, misdiagnosis may occur in light infections, and also due to the morphological similarity of opisthorchid eggs to other species. A finding of specific immune mediators can help confirm infection. This study used indirect ELISA to detect total IgG and IgG(1-4) with selected antigens of Bithynia siamensis goniomphalos extract, which were derived by liquid-phase iso-electricfocusing (IFE). Antigens (Iso-AgF) from 20 IEF fractionated fractions were selected based on a high ELISA-OD ratio between pooled-positive and pooled-negative sera. Iso-AgF 7, 7, 6, 2, and 10 resulted in high OD-ratio to total IgG, IgG1, 2, 3, and 4, respectively. A full-scale ELISA was conducted with sera from 50 opisthorchiasis cases, 196 from other parasitic-disease cases, and 35 healthy controls. Iso-AgF7 to IgG1 showed the best result, with sensitivity, specificity, positive and negative predictive value of 100, 96, 86, and 100%, respectively, at a cut-off 0.221. Low cross-reactivity to IgG1 was found in one case each of gnathostomiasis, trichinellosis, toxocariasis, angiostrongyliasis, bancroftian filariasis, enterobiasis, neurocysticercosis, and taeniasis. Thus, Iso-AgF7 to IgG1 was a good candidate antigen to be developed for detection of antibodies against Opisthorchis viverrini.     

Traumatic central cord syndrome: neurologic recovery after surgical management

The purpose of this study was to evaluate neurologic recovery following an acute, traumatic central cord syndrome (TCCS) injury. We retrospectively reviewed 69 patients who were treated surgically following an acute TCCS injury. The American Spinal Injury Association (ASIA) motor scores (AMS) were obtained from the time of presentation, from the time of hospital discharge, and from the most recent follow-up visit. The mean AMS was 63.2±25.8 at presentation and 89.9±14.6 at final follow-up (P<.001). Overall, 74% of the patients improved at least one ASIA impairment scale grade. Surgery was performed at a mean of 2.9 days (range, 0.25-24 days) following the injury using a posterior approach in 33 patients (48%), anterior approach in 22 patients (32%), and combined anterior-posterior approach in 14 patients (20%). Neither surgical timing nor approach appears to affect motor recovery. Adverse events were encountered in 24.6% of the patients. There were no deaths. A history of a loss of consciousness, decreased rectal tone at presentation, the presence of a fracture, the timing of surgery, and surgical approach did not have a significant impact on motor recovery.