Crystal-storing histiocytosis: a disorder occurring in plasmacytic tumors expressing immunoglobulin kappa light chain

Intracellular immunoglobulin crystal formation within plasma cells is an uncommon finding in multiple myeloma and other lymphoplasmacytic tumors. We present 12 cases of plasmacytic tumors with prominent crystal formation, including myeloma (5 cases), lymphoplasmacytic lymphoma (6 cases), and a nonneoplastic plasma cell proliferation. In all cases, crystal formation was associated with the proliferation of variable numbers of histiocytes containing similar inclusions. These cases showed a variety of appearances, sometimes obscuring the underlying plasma cell tumor and raising the differential diagnosis of a storage disorder, hemophagocytosis, or a mesenchymal lesion. In cases of lymphoplasmacytic lymphoma, patients typically presented with marked paraproteinemia and symptoms of hyperviscosity. Crystal-storing histiocytosis was not associated with other immunoglobulin deposition disorders, including amyloidosis, Mott cell tumors, or kappa-light chain deposition. In our cases and those previously reported, we found an overwhelming association of crystal-storing histiocytosis (CSH) with tumors expressing immunoglobulin kappa light chain with no consistent association with a particular heavy chain. These results suggest that CSH results from the ingestion of crystals produced by plasma cell tumors that either overproduce kappa light chain or express a structurally aberrant molecule. CSH persists in the marrow and other sites throughout the course of the disease and in our series was not highly associated with development of the adult Fanconi syndrome or rapid clinical deterioration.     

Polymorphisms of tumor necrosis factor receptor 2 are not associated with insulin-dependent diabetes mellitus or Graves' disease

Insulin-dependent diabetes mellitus (IDDM) and Graves' disease (GD) are autoimmune endocrinopathies and associated with distinct HLA-DR and -DQ alleles as well as several tumor necrosis factor a (TNF-α) and β (TNF-β) alleles. TNF-α and TNF-β interact with TNF receptor (TNF-R), of which two subtypes have been described: TNF-R1 and TNF-R2. We investigated TNF-R2 alleles in 90 patients with IDDM, 101 with GD and 70 healthy controls. Genomic DNA was amplified with specific flanking primers for the untranslated 3 region of TNF-R2. SSCP analysis revealed two alleles by different fragment patterns: TNF-R2*1 and TNF-R2*2. Patients with IDDM or Graves' disease and controls did not differ significantly: TNF-R2*1/*1:IDDM(8%)/GD(2%)/KO(4%); TNF-R2*2/*2:IDDM(34%)/GD(48%)/KO(42%), heterozygosity TNF-R2*1/*2:IDDM(58%)/GD(50%)/KO(54%) (IDDM vs KO: P =0.46, χ²=1.57; GD vs KO: P =0.59, χ²=1.05). In conclusion, the studied polymorphism of TNF-R2 was associated with neither IDDM nor GD in a German population.     

Neonate blood IgE levels on filter paper as indicators of atopic disease

Measurements of IgE levels in the blood of neonates were investigated using filter paper for blood collection in mass screening of congenital metabolic disorders. Time-resolved fluoroimmunometric assay system for the measurement of filter paper blood IgE levels was also studied. In an analysis of the present results, IgE values of at least 0.015U/ml, the measurement limit, were considered as high. High IgE levels in filter paper blood were seen in 28 (7.2%) of the 389 cases. When the relation with serum IgE levels at 18 months of age was investigated in 134 of 389 subjects, high serum IgE levels were also found in about 86.7% of the subjects with high IgE levels in filter paper blood. In addition, when the relation between family history of atopic disease and presence of atopic disease in the first 18 months of age was investigated in 203 of the 389 subjects, about 90% of the subjects with a family history of atopic disease and high IgE levels in filter paper blood developed atopic disease. Since filter paper blood is routinely collected in Japan, IgE levels in this blood should be widely checked for the prediction of onset of atopic disease in infants.     

Immunoglobulins, cognitive status and duration of illness in alzheimer''s disease

Immunologic changes have been reported in the dementing illnesses of mid and late life. The results of two studies of drug-free males meeting research diagnostic criteria for primary neuronal degeneration of the Alzheimer's type suggest that serum IgG levels decrease with the progression of dementia. Serum IgG levels were inversely correlated with duration of illness and the levels of psychiatric symptomatology. Performance on the mini-mental status examination was positively associated with serum IgG concentrations.     

Novel mutations in type 2 Gaucher disease in Chinese and their functional characterization by heterologous expression

We investigated 10 unrelated Chinese patients with type 2 Gaucher disease and performed ex vivo expression for the novel mutations to characterize their functional defects. These patients were diagnosed by enzymatic assays and clinicopathologic features over the past five years in a national centre in China. Genomic DNA was sequenced by a two-stage PCR approach for mutations in the functional GBA gene. Novel mutations were expressed with baculovirus-transfected Sf21 cells. Six novel mutations were found (in traditional nomenclature): P122L, Y363C, N382K, L383R, L385P, and M416V. Review of reported mutations indicated clustering of type 2 mutations in three regions of the GBA gene. Expression of novel mutations revealed that the enzyme defect could arise from one of two mechanisms: loss of catalytic activity (Y363C and M416V) or enzyme instability (P122L and N382K).     

Histological score for cells with irregular nuclear contours for the diagnosis of reflux esophagitis in children

Histological criteria for the diagnosis of reflux esophagitis include basal zone hyperplasia, stromal papillae elongation, and inflammatory infiltrate. However, endoscopic esophageal biopsy specimens may include little or no lamina propria. Intraepithelial T lymphocytes, seen in hematoxylin and eosin-stained sections as cells with irregular nuclear contours (CINC), may have a higher density in children with esophagitis. We evaluated the diagnostic accuracy of a numerical score built up by grading the "classical" parameters and its correlation with CINC density in grasp biopsy specimens obtained from children undergoing esophagogastroduodenoscopy with and without esophagitis. We analyzed esophageal biopsy specimens from 349 children (median age, 5 years) subdivided in 4 groups according to the previous routine histology report: group 1, 144 children with esophagitis; group 2, 65 controls; group 3, 51 children with dubious esophagitis; and group 4, 75 children with esophagitis on endoscopy but a normal histology report. A numerical value was assigned to each parameter; the sum of these values represented the histological score. We also evaluated intraepithelial CINC density (ie, number of CINC per high-power field). We separately analyzed histological sections with and without lamina propria. For both total score and for CINC density, we calculated a cutoff using a receiver operating characteristic curve. Cutoffs of 6 for score and of 4 for CINC density provided the best sensitivity and specificity. Sensitivity of the histological score was better in biopsy specimens containing lamina propria (94%) than in those without lamina propria (4%). Sensitivity of CINC density was satisfactory in both specimens with (78%) and without (75%) lamina propria. Specificity was satisfactory for both parameters. In conclusion, when lamina propria was present in sections of endoscopic esophageal biopsy specimens, histological score provided a better diagnostic accuracy for the diagnosis of esophagitis. However, when no lamina propria was present, as was the case in 67% of our children, CINC density had better sensitivity. In addition, this latter parameter showed esophageal mucosa damage in 34% of previously dubious cases or cases with esophagitis at endoscopy but a previous routine histology report of normal mucosa.     

Fusion and Matrix Protein Gene Sequence Analysis of Paramyxoviruses of Type 1(PMV-1) Isolated from Pigeons in Slovenia

Paramyxoviruses of type 1 (PMV-l) isolated from pigeons were genetically analyzed. A part of the fusion and the matrix protein genes were amplified and sequenced, Typical amino acid sequences associated with virulence were determined at the fusion protein cleavage site in all PMV-1 isolates. All Slovene pigeon PMV-1 strains share high amino acid sequence similarity with other pigeon strains. In the phylogenetic tree, they are clustered together with pigeon PMV-1 isolates with moderate pathogenicity. Phylogenetic analysis obtained from the fusion and the matrix protein gene alignments showed the same branching order. Viruses circulating among pigeons were found to form quite unique lineage of virulent NDV strains.     

Complete Nucleotide Sequence of the Rice Tungro Spherical Virus Genome of the Highly Virulent Strain Vt6

The complete nucleotide sequence of rice tungro spherical virus (RTSV) strain Vt6, originally from Mindanao, the Philippines, with higher virulence to resistant rice cultivars, was determined and compared with the published sequence for the Philippine-type strain A (RTSV-A-Shen). It was reported that RTSV-A was not able to infect a rice resistant cultivar TKM 6 (10). RTSV-Vt6 and RTSV-A-Shen share 90% and 95% homology at nucleotide and amino-acid levels, respectively. The N-terminal leader sequence of RTSV-Vt6 contained a 39-amino acids-region (positions 65 to 103) which was totally different from that of RTSV-A-Shen; the difference resulted from frame shifting by nucleotide insertions and deletions. To confirm the amino-acid sequence differences of the leader polypeptide, the same region was cloned and sequenced using a newly obtained variant of RTSV-type 6, which had been collected in the field of IRRI, and seven field isolates from Mindanao, the Philippines. Since all the sequences of the target region are identical to that of the Vt6 leader polypeptide, the sequence difference in the leader region seems not to correlate with the virulence of Vt6.