Experimental arthritis induced by continuous infusion of IL-8 into rabbit knee joints.

To determine the roles of IL-8 in inflammatory synovitis, examination was made of the results of continuously injecting human recombinant IL-8 into the knee joints of New Zealand while rabbits. Recombinant human IL-8 was infused continuously into the joint cavity at 75 ng/h for 14 days by a polypropylene catheter connected to a mini-osmotic pump implanted in each rabbit. Infiltration of inflammatory cells into joint cavity and histopathological changes in synovial tissue were examined at 7 and 14 days following the start of infusion. The continuous infusion of IL-8 for 14 days led to severe arthritis characterized by apparent erythema and joint pain, the accumulation of leucocytes, infiltration of mononuclear cells in synovial tissue, and marked hypervascularization in the synovial lining layer. IL-8 may be a factor which can contribute to the inflammatory process of chronic arthritis by mediating leucocyte recruitment and hypervascularization in inflamed joints.     

HeLa cell invasiveness and O antigen of Shigella flexneri as separate and prerequisite attributes of virulence to evoke keratoconjunctivitis in guinea pigs.

Many rough mutants selected from isogenic smooth virulent and avirulent strains of Shigella flexneri were examined for virulence, using tissue culture infection and Sereny tests. Many of the rough mutants isolated from a virulent smooth strain were capable of penetrating tissue culture cells but incapable of producing a positive Sereny test. In contrast, we could not obtain from smooth avirulent strains any rough mutants capable of penetrating HeLa cells. Chemical analysis of lipopolysaccharide of some representative rough strains showed several patterns of sugar composition with a range of from Ra to Re chemotypes. There was no correlation between HeLa cell invasiveness and chemotypes of lipopolysaccharides, thus indicating little significance of oligosaccharides of the rough core as well as O antigens in the ability of S. flexneri to penetrate HeLa cells. When these invasive rough strains were given O antigen genes from a smooth avirulent Shigella Hfr strain, most of the transconjugants that expressed O antigens regained the ability to evoke keratoconjunctivitis in guinea pigs. We also examined the chromosomal loci of HeLa cell invasion by transferring carbohydrate fermentation genes of Escherichia coli K-12 Hfr and found two chromosomal loci, the rha and lac-gal regions, which control the ability to penetrate HeLa cells. These results suggested that O antigens and ability to penetrate tissue culture cells are independent and prerequisite attributes of virulence in Shigella flexneri to evoke keratoconjunctivitis in guinea pigs.     

Human monoclonal anti-nuclear antibodies produced by human-mouse heterohybridomas

To obtain human monoclonal anticentromere antibodies, mouse myelomas were fused with unfractionated mononuclear cells from the peripheral blood of a patient diagnosed as having the CREST variant of scleroderma: with only anticentromere antibodies. After a single fusion an heterohybridoma secreting a human antibody specific for nuclear antigens, as detected by indirect immunofluorescence staining, was isolated. The monoclonal antibody secreted by the clone was of the human IgM class. Indirect immunofluorescence staining of the antibody on HEp-2 cells showed multiple nuclear dots or a discrete speckled pattern resembling that of an anticentromere antibody. Immunoblot analysis showed antibody binding to a 33 kD antigen derived from the nuclear protein fraction. Enzyme-immunoassay results clearly showed that the antibody reacted with the chromosomal protein fraction and not calf thymus DNA.     

Transforming growth factor J3 type II receptor (TGFpRII) mutation in gastric lymphoma without mutator phenotype

A new mutation in the serine-threonine klnase domain of the transforming growth factor β type II receptor (TGFpRII) was found in a case of diffuse, B cell non-Hodgkin's lymphoma of the stomach. A mfssense mutation (ACA to GCA, Thr to Ala) was detected In exon 5, and a wild type allele was also present. This Is the first naturally occurring mutation in the klnase domain of this gene identified in human primary lymphoma. The replication error at three loci was negative, and the poly A tract of exon 3, which is frequently a target of mismatch repair genes, was intact. Malignant lymphoma of B cell origin in the stomach Is an addition to an expanding catalogue of tumors with TGFβRII alterations, and the biological sequelae of the change in the functional domain and the clinical characteristics of the patient in this study are intriguing.     

Electrophysiological comparison between patients with Binswanger's encephalopathy and Alzheimer's disease

Short-latency somatosensory (SSEPs), brainstem auditory evoked potentials (BAEPs) and event-related potentials (ERPs) were studied in 7 patients with Binswanger's encephalopathy, 12 patients with Alzheimer's disease and 17 normal subjects. Patients with Binswanger's encephalopathy showed significantly prolonged central conduction time (CCT) and P300 latency, and prolonged tendency of I-V IPL compared to those of normal subjects. In particular, CCT showed significant prolongation compared to that of patients with Alzheimer's disease. In patients with Alzheimer's disease, I-V IPL and P300 latency were significantly prolonged compared to those of normals although there was no significant difference in CCT between Alzheimer's disease and normal subjects. These results indicate some difference between Binswanger's encephalopathy and Alzheimer's disease from the electrophysiological aspects although both of these entities are characterized by progressive mental deterioration.     

Relationship between immediate hypersensitive reactions by buckwheat ingestion and specific IgE for rice in subject with positive IgE-RAST for buckwheat]

IgE-mediated mechanisms are important in immediate hypersensitive reactions (IHR) to buckwheat. However, a part of subjects with high IgE for buckwheat show no IHR to buckwheat ingestion. Inspite of cross-allergenicity between buckwheat and rice, rice ingestion rarely induces IHR even in subjects with high IgE for rice unlike buckwheat-induced IHR. We speculated that there were some relationships between the presence of IHR to buckwheat and recognition of cross-allergenic determinants on buckwheat components with rice components. We examined IgE-RAST for rice in 58 subjects with positive IgE-RAST for buckwheat. IgE-RAST for Dermatophagoides pteronyssinus (Dp), egg white and cow's milk as unrelated antigens with rice were also assessed for a comparison. Subjects (n = 33) without IHR to buckwheat showed higher IgE-RAST values for rice than those (n = 25) with IHR, whereas there were no differences in IgE-RAST values for Dp, egg white and cow's milk between two groups with and without IHR. IgE-RAST values for buckwheat showed significant close correlations to those for rice in subjects without IHR to buckwheat but not in those with IHR. There were no significant correlations between IgE-RAST values for buckwheat and for Dp, egg white or cow's milk in both groups with and without IHR. These results suggested that the IgE from subjects without IHR to buckwheat recognized cross-allergenic determinants with rice on the buckwheat components.     

TCR repertoire in early fetal mouse thymus

We investigated the rearrangement and expression of TCR genesin mouse fetal thymus organ culture, a system that avoids subsequententry of hematopoietic precursor cells. The first observablerearranged TCR gene was homogeneous V2-J2, detectable as earlyas fetal day 11 (d11) in the thymic primordla. The productiveTCR was homogeneous V5-J1, first detectable in d13 thymocytes,followed by adult-type TCR (V4 and V7). Sequence analysis ofTCR revealed five types of V-J junctional sequences. In thevery early stage, a homogeneous V-J junction is generated viaa short homology sequence in the coding region (Type I), whilea short homology sequence in the P-nucleotlde rather than thecoding region is used in the following stage (Type II). In thelater embryonic stages, diverse V-J junctions are generatedby well-known mechanisms, such as P-nucleotide (Type III), N-regioninsertion (Type IV) or trimming of the coding ends (Type V).These findings suggest that the generation of homogeneous TCR (V2 and V5) in the early fetal stages is due to the intrinsicrearrangement mechanisms and is in stage specific manner.     

Restriction site polymorphism at the LPA (Lp(a) apoliprotein; apoliprotein(a)) locus

A restriction site polymorphism in the Lp(a) apolipoprotein gene (the LPA gene) is reported. The basis for the polymorphism is presence or absence of an MspI restriction site that appears to be 3' to the last kringle IV structure of the gene. The "1" gene (presence of the restriction site) has a frequency of 0.316 and the "2" gene (absence of the restriction site) has a frequency of 0.684. Both members of each of 67 monozygotic (MZ) twin pairs had the same genotype and there was Mendelian segregation of the DNA variants in 40 families with a total of 75 children. There was a lower proportion of people with genotype 1-1 in the top quartile than in the 3 bottom quartiles of the population distribution of Lp(a) lipoprotein levels but the difference did not reach statistical significance.     

Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization

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Undifferentiated (embryonal) sarcoma of the liver in middle-aged adults: smooth muscle differentiation determined by immunohistochemistry and electron microscopy

Undifferentiated (embryonal) sarcoma of the liver (UESL) is a rare pediatric liver malignancy that is extremely uncommon in middle-aged individuals. We studied 2 cases of UESL in middle-aged adults (1 case in a 49-year-old woman and the other in a 62-year-old man) by histology, immunohistochemistry, and electron microscopy to clarify the cellular characteristics of this peculiar tumor. One tumor showed a mixture of spindle cells, polygonal cells, and multinucleated giant cells within a myxoid matrix and also revealed focal areas of a storiform pattern in a metastatic lesion. The other tumor was composed mainly of anaplastic large cells admixed with few fibrous or spindle-shaped components and many multinucleated giant cells. In both cases, some tumor cells contained eosinophilic hyaline globules that were diastase resistant and periodic acid-Schiff positive. Immunohistochemically, the tumor cells showed positive staining for smooth muscle markers, such as desmin, alpha-smooth muscle actin, and muscle-specific actin, and also for histiocytic markers, such as alpha-1-antitrypsin, alpha-1-antichymotrypsin, and CD68. Electron microscope examination revealed thin myofilaments with focal densities and intermediate filaments in the cytoplasm of tumor cells. Our studies suggest that UESL exhibits at least a partial smooth muscle phenotype in middle-aged adults, and this specific differentiation may be more common in this age group than in children. Tumor cells of UESL with smooth muscle differentiation in middle-aged adults show phenotypic diversity comparable to those of malignant fibrous histiocytoma with myofibroblastic differentiation.