Case report of de novo dup(18p)/del(18q) and r(18) mosaicism

This is a report of a 27-year-old woman with an unusual de novo chromosomal abnormality. Mosaicism was identified in peripheral blood cells examined by standard G-bands by trypsin using Giemsa (GTG) analysis and fluorescence in situ hybridization (FISH) analysis with chromosome-18 region-specific probes, 46,XX,del(18)(pter → q21.33:)[41], 46,XX,r(18)(::p11.21 → q21.33::)[8], and 46,XX,der(18)(pter → q21.33::p11.21 → pter)[1]. On the other hand, the karyotype of periodontal ligament fibroblasts was nonmosaic, 46,XX, der(18)(pter → q21.33::p11.21 → pter)[50]. All cell lines appeared to be missing a portion of 18q (q21.33 → qter). The pattern of the dup(18p)/del(18q) in the rod configuration raises the possibility of an inversion in chromosome 18 in one of the parents. However, no chromosomal anomaly was detected in either parent. The most probable explanation is that de novo rod and ring configurations arose simultaneously from an intrachromosomal exchange. The unique phenotype of this patient, which included primary hypothyroidism and primary hypogonadism, is discussed in relation to her karyotype.     

Renal function in patients with yusho

Renal functions were examined in 102 patients with yusho in 1988, Frequencies of proteinuria, microhematuria and history of renal diseases were not different from 20 age-matched controls. The means of blood urea nitrogen, serum creatinine and serum uric acid levels of yusho patients did not differ from those of controls. The levels of serum beta 2-microglobulin and its urinary excretion showed no difference between two groups. Serum concentrations of sodium, potassium, chloride, calcium and phosphorus revealed no abnormality in all patients except for one who had hypophosphatemia. Urinary excretions of phosphorus, however, were significantly higher in yusho patients than in controls. Serum PCB levels, which were still higher in yusho patients, did not correlate with urinary excretions of phosphorus. The mechanism and the clinical significance of this phenomenon remain to be elucidated.     

Modified PCR-RFLP method for HLA-DPB1 and -DQA1 genotyping.

We previously developed a new technique for HLA class II genotyping by digestion of polymerase chain reaction-amplified genes with restriction endonucleases (PCR-RFLP method). This PCR-RFLP method is an efficient and convenient typing technique for class II alleles. However, small fragments or bands located close to each other on polyacrylamide gels sometimes prevent precise analysis of the RFLP bands. Furthermore, the restriction enzymes we have reported in the previous papers are not sufficient to identify the genotypes of all heterozygous individuals. Here, we report an improved PCR-RFLP method using some informative restriction enzymes which have either a single cleavage site or, alternatively, no cleavage site in the amplified DNA region, depending on the HLA alleles, making reading of RFLP band patterns much easier. Each second exon of the HLA-DQA1 or -DPB1 gene was selectively amplified from genomic DNAs of 70 HLA-homozygous B-cell lines and 100 healthy Japanese by PCR. Amplified DNAs were digested with restriction endonucleases and then subjected to electrophoresis assaying simply for cutting, or no cutting, of the DNA. ApaLI, HphI, BsaJI, FokI, MboII and Mn1I can discriminate eight alleles of the DQA1 gene. Similarly 19 alleles of the DPB1 gene can be discriminated with Bsp1286I, FokI, DdeI, BsaJI, BssHII, Cfr13I, RsaI, EcoNI, and AvaII enzymes. This modified PCR-RFLP method can be successfully applied to heterozygotes. Thus, the method is technically simpler and more practical for routine HLA typing work than our previous PCR-RFLP method.     

Existence of phenol oxidase in the argasid tick Ornithodoros moubata

Phenol oxidase (PO, EC 1.10.3.1) activity was detected in the hemolymph of the fourth instar nymphs of the argasid tick, Ornithodoros moubata, with peak levels corresponding to the days before the majority of the nymphs had molted, suggestive of a protective role of PO during the ecdysial phase. Higher PO activity was detected in plasma relative to the hemolymph and was negligible in hemocytes. The concentration of the hemolymph and plasma assayed clearly influenced the level of PO activity, and was significantly reduced ( P<0.005) after treatment with 1-phenyl-2 thiourea, a specific PO inhibitor. This is the first report of the existence of PO in the hemolymph and plasma of a soft tick species. The regulation of PO activity and its precise role in soft tick immunity, particularly during the ecdysial phase, are interesting and need to be examined further.     

Isolation of amantadine-resistant influenza a viruses (H3N2) from patients following administration of amantadine in Japan

In Japan, the use of amantadine for treatment of influenza A virus infection was not accepted until November 1998, although it was widely used for treatment of Parkinsonism. Since then, we have monitored the emergence of amantadine-resistant viruses and isolated two viruses from patients on long-term treatment with amantadine.     

Induction of Thymus-Derived γδ T Cells by Escherichia coli Enterotoxin B Subunit in Peritoneal Cavities of Mice

We examined the activation of intraperitoneal T cells in BALB/c mice by the Escherichia coli enterotoxin B subunit, which induced a specific Th2 type of T-cell response to intraperitoneally coadministered bovine immunoglobulin G. The numbers of both γδ and αβ T cells increased significantly after intraperitoneal administration of the B subunit in a time-dependent manner; these numbers were not affected by the B-subunit G33D mutant, which is defective in GM₁ ganglioside-binding ability. Early after administration a small number of γδ T cells produced either interleukin-4 (IL-4) or gamma interferon, while late after administration primarily IL-10-producing γδ T cells were detected. γδ T cells induced by the B subunit did not express a characteristic V gene over the time course of the study. The induction of γδ T cells did not occur in athymic nu/nu mice but could be induced upon transplantation of fetal AKR thymus-like αβ T cells. γδ T cells in athymic nu/nu mice with a fetal thymic graft predominantly expressed the donor Thy-1.1 antigen but not the host Thy-1.2 antigen. The induction of these T cells, however, could not be restored by coadministration of the B subunit with peritoneal cells from normal mice. These results suggest that the B subunit activates intraperitoneal γδ and αβ T cells in a manner dependent upon its ability to bind to GM₁ ganglioside. γδ T cells induced by the B subunit are Th2-type cells derived from the thymus. These γδ T cells may be functionally involved in specific Th2 responses to the B subunit, which possibly acts as an adjuvant through the influence of αβ T cells.     

IgG heavy chain allotypes (Gm) in autoimmune diseases.

Serum samples from 100 patients with myasthenia gravis, 322 with Graves' disease, 113 with Hashimoto's disease, 132 with systemic lupus erythematosus (SLE), 192 with insulin-dependent juvenile diabetes mellitus, 83 with Behçet's syndrome, 73 with psoriasis vulgaris, 258 with leprosy, 112 with Duchenne progressive muscular dystrophy and 343 non-related normal controls were studied for Gm allotypes. The incidence of Gm phenotypes with Gm(2) was significantly increased in patients with myasthenia gravis. Graves' disease, Hashimoto's disease, and high in SLE patients. The Gm1,2,21 haplotype was increased in patients with myasthenia gravis (chi 2 = 34 . 08, corrected P less than 0 . 001), Hashimoto's disease (chi 2 = 12 . 39, corrected P less than 0 . 05), Graves' disease (chi 2 = 8 . 65, corrected P less than 0 . 05), and SLE (chi 2 = 6 . 41, 0 . 1 greater than corrected P greater than 0 . 05). The total chi-square for the four different Gm haplotypes was significantly increased in patients with myasthenia gravis (chi 2 = 44 . 46, corrected P less than 0 . 001), SLE (chi 2 = 20 . 70, corrected P less than 0 . 005), Hashimoto's disease (chi 2 = 17 . 03, corrected P less than 0 . 025), and Graves' disease (chi 2 = 11 . 87, corrected P less than 0 . 025). Our data suggest the presence of Gm-associated pathogenic polygenes in certain autoimmune disorders.     

Congenital aplasia of the extensor muscles of the fingers and thumb associated with generalized polyneuropathy: an autosomal recessive trait

Three sibs born to normal but consanguinous parents had flexion deformities of the thumb and fingers on one hand and sensory deficit in the other hand. Extensor muscles were absent or vestigial in all of them. Polyneuropathic electrophysiological findings were detected in 4 limbs. This is an apparently autosomal recessive trait previously unreported.     

Soluble intercellular adhesion molecule-I levels in sera of patients with Kawasaki disease]

We investigated whether serum levels of soluble ICAM-1 antigens increases during acute Kawasaki disease (KD). We also compared levels in acute KD with those in anaphylactoid purpura (AP) and in measles. Serum soluble ICAM-1 levels were measured by a double determinant immunoassay using two monoclonal antibodies in the FAST system. Serum levels of tumor necrosis factor-alpha (TNF-alpha) were measured by a specific and sensitive sandwich enzyme immunoassay. Patients with KD, but not with AP or measles, had increased ICAM-1 levels in serum during the acute stage. In addition, during the acute stage, KD patients with coronary-artery lesions (CAL) were found to have increased ICAM-1 levels in serum compared to patients without CAL. We found a positive correlation between serum levels of ICAM-1 and levels of TNF-alpha during acute KD. Our results suggest that the serum level of soluble ICAM-1 is an important immunologic parameter for determining the severity of vascular damage during acute KD.