Immunoglobulin heavy chain Diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement.
DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences.
Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen.
The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.     

Taylor-type focal cortical dysplasia: is the epilepsy always resistant to medical treatment?

Patients with Taylor-type focal cortical dysplasia (TTFCD) generally present with medically intractable epilepsy and impaired neurological and/or intellectual functioning. Surgery usually proves to be the only treatment approach leading to control of seizures. We describe a 17-year-old girl with TTFCD who exhibited a very long period of seizure remission. Combined clinical and neuroimaging findings were compatible with a diagnosis of a balloon cell-subtype TTFCD. As for the clinical course, partial motor seizures began at one year of age and ceased at five: our patient has had no seizure recurrence over a 12-year-follow-up. Moreover, throughout the 15-year follow-up, neurological examinations and cognitive abilities always remained within normal limits. Neuropsychological assessment clearly showed no impairments in executive functions: planning abilities, working memory, attention and impulse control, or constructive aspects of motor coordination. The predominant deficits pertained to verbal abilities in the context of borderline intellectual performances. To our knowledge, this case report documents the longest duration of seizure remission in a patient with TTFCD, thus emphasizing the possible benign course of such dysplastic lesions which usually have a poor prognosis, leading to early surgical treatment.     

Mapping of α- and β-globin genes on Antarctic fish chromosomes by fluorescence in-situ hybridization

The pathways and mechanisms of genomic change that have led to the peculiar haemoglobinless phenotype of the white-blooded Antarctic icefishes (16 species in the family Channichthyidae) constitute an important model for understanding the rapid diversification of the Antarctic notothenioid fish flock. To provide complementary structural information on genomic change at globin-gene loci in Antarctic fish species, cytogenetic studies and in-situ chromosomal mapping have been undertaken. Using a DNA probe containing one α- and one β-globin gene from the embryonic/juvenile globin gene cluster of the red-blooded species Notothenia coriiceps, we mapped the cluster on the chromosomes of Antarctic teleosts by fluorescence in-situ hybridization. As anticipated on the basis of its molecular organization, the cluster was located on a single chromosome pair in all of the red-blooded fish species probed (N. coriiceps, N. angustata, Trematomus hansoni, T. pennellii). In contrast, the α/β-globin probe did not recognize complementary sequences on the chromosomes of the white-blooded species Chionodraco hamatus and Channichthys rhinoceratus. These results represent the first example of chromosomal mapping of embryonic/juvenile globin genes in teleostean fishes. Beyond its relevance to the evolutionary history of Antarctic notothenioids, this work contributes to our understanding of the evolution of the chromosomal loci of globin genes in fishes and other vertebrates. This revised version was published online in July 2006 with corrections to the Cover Date.     

Comparatice effects of loratadine and selected antihistamines on sleep-waking patterns in the cat

The central effects of the new antihistamine loratadine and three reference antihistamine agents were studied in the cat. As a sensitive measure of drug action on the central nervous system (CNS) we evaluated changes in sleep-waking patterns. For comparison, diphenhydramine was studied as an example of an antihistamine having potent central effects; astemizole and terfennadine were used as examples of new agents claimed to be free of CNS effects. Diphenhydramine, given at 3 mg/kg p.o., increased spindle sleep, i.e., the electrophysiological correlate of drowsiness, and suppressed rapid eye movement (REM) sleep. In addition, cats displayed unusual sleep postures during the various sleep stages. Loratadine had little or no effect on the various features of sleep-waking patterns over a broad dose range (3 and 30 mg/kg p.o.). Astemizole, at 30 mg/kg p.p., significantly increased wakefulness and reduced both slow-wave sleep and REM. No significant changes of the sleep patterns occurred after the low dose of 3 mg/kg. Terfenadine reduced REM duration at 30 mg/kg p.o. but had no effects on sleep patterns at 3 mg/kg. The cat appeared to be a sensitive animal model to the central action of antihistamines since the reference drug diphenhydramine affected sleep-waking patterns at a dose that closely approximates the dose requirements for adverse CNS effects in man. Under the same conditions, loratadine was free of central actions at a dose range far above that effective either therapeutically or in standard tests in other animal species. Astemizole and terfenadine seemed to be devoid of CNS effects at doses similar to those effective as antihistamines in man, but they produced some central actions at higher doses. Comparing the clinically effective doses of the antihistamines examined, loratadine appears to be the least liable to produce adverse effects on the CNS function.     

Drug-induced lupus erythematosus

Drug-induced lupus is a syndrome which share symptoms and laboratory characteristics with idiopathic systemic lupus erythematosus (SLE). The terms drug-induced lupus (DIL) and drug-induced lupus erythematosus (DILE) are preferred, but other ones are also used-drug-related lupus, lupus-like syndrome and lupus erythematosus medicamentosus. The first case of DILE was reported in 1945 and associated with sulfadiazine. In 1953, it was reported that DILE was related to the use of hydralazine. More than 80 drugs have been associated with DILE. The average age of patients with DILE is nearly twice that of patients with idiopathic SLE. Approximately half the patients with drug-induced SLE are women, compared with 90% of patients with idiopathic SLE. Similarly to idiopathic lupus, DILE can be divided into systemic, sub-acute cutaneous and chronic cutaneous lupus. The syndrome is characterised by arthralgia, myalgia, pleurisy, rash and fever in association with antinuclear antibodies in the serum. The clinical and laboratory manifestations of drug-induced SLE are similar to those of idiopathic SLE, but central nervous system and renal involvement are rare in DILE. Recognition of DILE is important because it usually reverts within a few weeks after stopping the drug. This review discusses the general issues in DILE, such as pathogenic mechanisms, clinical forms and diagnostic criteria, and provides more detailed information for some of the most recent implicated drugs: minocycline, statins, anti-TNF-alpha agents.     

Preliminary Evaluation of the Safety and Efficacy of Standard Intravenous Immunoglobulins in Pregnant Women with Primary Cytomegalovirus Infection

Hyperimmune globulins were reported to prevent and treat fetal cytomegalovirus (CMV) infection during pregnancy. Here, we report that infusions of standard human intravenous immunoglobulin significantly increase CMV IgG titers and avidity indexes in pregnant women, paving the way to their use for passive transfer of maternal CMV humoral immunity to fetuses. Preliminary data on perinatal outcomes of the first 67 newborns are encouraging.     

A Computerized System to Study Masticatory Function

This article describes a system that allows for simultaneous analysis of subjects' mandibular movements and electromyographic activity during chewing. The authors examined clockwise and counterclockwise movements separately, using the following parameters for the opening and closing strokes at 20 different degrees of jaw separation: 1. Number of times the movement occurred.

2. Mean displacement values.

3. Actual velocity.

4. Velocity values on the three coordinates X, Y, and Z.

A plotter was used for a graphic analysis of the movements. The system recorded electromyographic activity from both masseters with a two-channel electromyograph. (However, the system can record up to eight channels at once.) After the data was collected, the mean electrical activity for each degree of jaw separation during opening and closing was calculated. The system used for this study seems to be a reliable and comprehensive means of assessing masticatory activity in function and dysfunction.     

Addition of platelet‐rich plasma supports immune modulation and improved mechanical integrity in Alloderm mesh for ventral hernia repair in a rat model

The recurrence of ventral hernias continues to be a problem faced by surgeons, in spite of efforts toward implementing novel repair techniques and utilizing different materials to promote healing. Cadaveric acellular dermal matrices (Alloderm) have shown some promise in numerous surgical subspecialties, but these meshes still suffer from subsequent failure and necessitation of re‐intervention. Here, it is demonstrated that the addition of platelet rich plasma to Alloderm meshes temporally modulates both the innate and cytotoxic inflammatory responses to the implanted material. This results in decreased inflammatory cytokine production at early time points, decreased matrix metalloproteinase expression, and decreased CD8+ T cell infiltration. Collectively, these immune effects result in a healing phenotype that is free from mesh thinning and characterized by increased material stiffness.