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.     

Double-crush nerve compression in thoracic-outlet syndrome

We studied 165 cases of thoracic-outlet syndrome in 142 patients in whom resection of the first rib had been performed. In seventy-three cases (44 per cent), there was compression of a nerve distally, as shown by electromyography and conduction studies. The most common secondary compression was carpal tunnel syndrome (forty-one cases). Thirteen patients needed an operation at three sites or more. Our results show that proximal compression of a nerve lessens its ability to withstand more distal compression. Once the diagnosis of thoracic-outlet syndrome has been made, the possibility of an additional distal compression neuropathy should be investigated.     

Intranasal steroid reduces exhaled bronchial cysteinyl leukotrienes in allergic patients

BACKGROUND: Allergic rhinitis (AR) precedes and is often associated with bronchial asthma. Indeed, local and systemic inflammations in both conditions are very similar. Cysteinyl-leukotrienes (cys-LTs) are generated during early- and late-phase allergic reactions and induce smooth-muscle contraction, microvascular leakage, and mucous hypersecretion. Cys-LTs are detected in exhaled breath condensate (EBC) of asthmatics and regardless of bronchial symptoms, they are also found in EBC of rhinitic patients. OBJECTIVE: To evaluate cys-LTs in EBC of allergic patients and to assess the activity of nasal fluticasone propionate (FP) on EBC cys-LTs levels. METHODS: Cys-LTs coefficient of variation (CV) was evaluated from different EBC in 5 healthy volunteers. Cys-LTs levels from EBCs in 13 healthy controls and 56 allergic rhinitic (n=31) and rhinitic/asthmatic (n=25) patients were also evaluated at baseline. Subsequently patients were randomized to receive either FP 100 microg/day per nostril or placebo for 2 weeks and then re-evaluated for EBC cys-LTs. RESULTS: The CV was 14.12%. EBC cys-LTs in allergic patients were significantly higher than in healthy subjects (70.9 vs. 20.6 pg/mL (median), P<0.05), while it did not differ between asthmatic/rhinitic and purely rhinitic patients. Treatment significantly reduced cys-LTs (from 93.6 to 19.9 pg/mL, P<0.001). This effect was evident both in asthmatic/rhinitic and in rhinitic patients. CONCLUSION: Treatment of AR with FP significantly reduces the levels of cys-LTs, major noninvasive markers of lower airway inflammation, suggesting that upper and lower airway inflammation is present and should be thus treated as a whole in subjects with AR with and without asthma.     

Spindle and EEG sleep alterations in subjects affected by cortical cerebellar atrophy

All-night polygraphic records (EEG, EOG and ECG) were performed on 9 subjects. Four of them were affected by Familiar Cerebellar Atrophy (FCA) whereas the others were their blood relatives without clinical signs of cerebellar deficit. In the former FCA was diagnosed clinically and the cerebellar atrophy was confirmed by computer tomography (CT). In all the latter except one who showed slight cerebellar atrophy, the CTs were negative. The EEG sleep records of the FCA patients were characterized by slowly changing phases between synchronized and desynchronized sleep, instability of the synchronized sleep with frequent modifications of EEG activity, subnormal measurement of both REM and slow-wave sleep and presence of spindles in REM sleep (only in 2 patients). The spindle activity was reduced in two FCA subjects. The electroencephalographic sleep records of two BRs, one of which with small cerebellar atrophy, showed qualitative and quantitative alterations similar to those of FCA patients, even if marked to a lesser degree. Increased spindle densities were present in the same BRs who showed sleep abnormalities. The EEG alterations observed in the two BR subjects could show small cerebellar injuries which would be insufficient to induce clinical signs.     

Role of Th1 and Th2 Cytokines in Immune Response to Uncomplicated Plasmodium falciparum Malaria

The relative balance between Th1 and Th2 cytokines appears crucial, since the role of cytokines has been evaluated in several studies by comparison of clinically heterogeneous groups of patients. The aim of this study is to determine the role of proinflammatory Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-γ), and anti-inflammatory Th2 cytokines, IL-4 and IL-10, in a homogeneous group of patients with uncomplicated Plasmodium falciparum malaria. Levels of IL-12, IFN-γ, Il-4, and IL-10 in serum for 20 adult patients and 15 healthy control subjects were determined by an immunoenzymatic assay. Serum levels of Th1 cytokines, IL-12 (8.6 ± 2.8 pg/ml; controls, 3.2 ± 0.7 pg/ml) and IFN-γ (39.2 ± 67.6 pg/ml; controls, 8.4 ± 6.3 pg/ml), were significantly increased at admission; 3 days later, levels of IL-12 in serum remained significantly high (8.8 ± 2.6 pg/ml), whereas IFN-γ levels returned to control values. The anti-inflammatory response of Th2 cytokines (IL-10 and IL-4) was distinct. Levels of IL-10 in serum were not significantly increased at day 0 and day 3 (306.6 ± 200.4 pg/ml and 56.6 ± 38.4 pg/ml, respectively; controls, 17.4 ± 9.0 pg/ml). In contrast, levels of IL-4 in serum were not increased on admission (3.4 ± 1.2 pg/ml; controls, 2.4 ± 0.8 pg/ml), but at day 3 a moderate and significant increase of IL-4 levels was observed (4.5 ± 1.7 pg/ml). In conclusion, the increase of Th1 cytokine IL-12 and IFN-γ levels during the acute phase of uncomplicated P. falciparum malaria may reflect an early and effective immune response regulated by proinflammatory Th1 cytokines, and in particular IFN-γ may play a role in limiting progression from uncomplicated malaria to severe and life-threatening complications.     

Immunohistologic analysis of a human pulmonary alveolar macrophage antigen

PAM1 is a 200-kDa polypeptide antigen present on lavaged human alveolar macrophages but not on monocytes, peritoneal macrophages, breast milk macrophages, or other normal hematopoietic cells studied by flow cytometry. We have characterized the distribution of expression of this antigen by cells in tissues by using immunohistologic techniques. Normal and diseased lung as well as lymph nodes, spleen, kidney, liver, GI tract, and skin were studied. PAM1 was expressed strongly on the surface and weakly in the cytoplasm of most alveolar macrophages in all 15 of the lung specimens. Occasional interstitial macrophages had weak to moderate staining for this antigen but the majority did not stain. The distribution, pattern, and intensity of staining for PAM1 was the same in normal lung specimens and those with interstitial pneumonitis, despite the increase in mononuclear cells in the latter. Dermal histiocytes and Kuppfer cells expressed PAM1 weakly. Sinus histiocytes in lymph nodes were moderately to strongly positive. Although lymphoid cell suspensions (tonsil) were negative by flow cytometry, five of six lymph nodes had positive cells by immunohistology. PAM1 was also detected on endothelial cells of splenic sinusoids in all 6 specimens but not on any other endothelium. Hence, while PAM1 is expressed most strongly on alveolar macrophages, it can also be demonstrated in other locations using sensitive immunohistologic techniques. Since circulating monocytes are antigen negative and some lung interstitial macrophages bear antigen, PAM1 may be a useful marker for studies of the differentiation of mononuclear cells in the lung.     

Psychopathological dimensions of depression: a factor study of the 17-item Hamilton depression rating scale in unipolar depressed outpatients

BACKGROUND: Agreement on the factor structure of the Hamilton Depression Rating Scale (HDRS) has not been consistent among studies, and some investigators argued that the scale's factor structure is not reliable. This study aimed at shedding more light on this debated issue. METHODS: We studied 186 adults with unipolar depression (Major Depressive Disorder, n=80; Dysthymic Disorder, n=71; Depressive Disorder Not Otherwise Specified, n=25; Adjustment Disorder, n=10). They had no comorbid DSM-IV axis I or axis II disorders, and had received no treatment with antidepressant drugs in the previous 2 months. The factor structure of the scale was studied using the principal factor method, followed by oblique rotation. Factor scores were computed for each subject using the regression method. RESULTS: Using the scree-test criterion for factor extraction, we obtained a four-factor solution, explaining 43.8% of total variance. The four factors extracted were identified as (1) somatic anxiety/somatization factor; (2) a psychic anxiety dimension; (3) a pure depressive dimension; and (4) anorexia factor. Patients with Major Depressive Disorder scored significantly higher than patients with other diagnoses on the pure depressive dimension. LIMITATIONS: These results need to be replicated in different cultures, using analogous factoring techniques. CONCLUSIONS: Though not exhibiting factorial invariance in the stricter sense of the term, the 17-item HDRS did exhibit a relatively reliable factor structure. Our analysis provides further evidence that the scale is multidimensional. However, as long as the multidimensional character of the scale is taken into account the scale should be able to play a useful role in clinical research.     

Gene conversion is a likely cause of mutation in PKD1

Approximately 70% of the gene responsible for the most common form of autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in several highly homologous copies located more proximally on chromosome 16. We recently have described a novel technique for mutation detection in the duplicated region of PKD1 that circumvents the difficulties posed by these homologs. We have used this method to identify two patients with a nearly identical cluster of base pair substitutions in exon 23. Since pseudogenes are known to be reservoirs for mutation via gene conversion events for a number of other diseases, we decided to test whether these sequence differences in PKD1 could have arisen as a result of this mechanism. Using changes in restriction digest patterns, we were able to show that these sequence substitutions are also present in N23HA, a rodent-human somatic cell hybrid that contains only the PKD1 homologs. Moreover, these changes were also detected in total DNA from several affected and unaffected individuals that did not harbor this mutation in their PKD1 gene copy. This is the first example of gene conversion in PKD1 , and our findings highlight the importance of using gene-specific reagents in defining PKD1 mutations.