Peripheral Lymphocyte Subpopulations in Patients with Herpes Genitalis

Peripheral blood samples from 52 women including 16 with herpes genitalis and 36 healthy persons were studied to enumerate subpopulations of lymphocytes. T lymphocyte counts were done by SRBC rosette tests and B lymphocytes by immunobead rosette tests using antibody-coated polyacrylamide beads. It was found that the mean percentage of «active T lymphocytes was significantly less in the patients with herpes genitalis than in the controls (herpes genitalis; 13.9 ± 6.8%, controls; 25.0 ± 8.3%, p < 0.001). No difference was noted in the percentage of «total» T lymphocytes, «total» B lymphocytes and subsets of B lymphocytes (IgG-, IgA- and IgM-bearing lymphocytes) between the patients and controls. The present findings suggest that cell-mediated immune function associated with «active» T lymphocytes is suppressed in patients with herpes genitalis.     

αN-catenin expression in the normal and regenerating chick sciatic nerve

Summary The Ca²⁺-dependent intercellular adhesion molecule cadherin is known to be linked to the cytoskeleton by the protein catenin, an association of which appears to be important for the cell-adhesion function of cadherin. Catenin consists of three subtypes-, , and . In our previous study, N-cadherin was shown to be localized on the plasmalemma of normal and regenerating chick peripheral nerve. Thus, as N-catenin is a subtype of -catenin (which is specifically associated with N-cadherin), we investigated the immunolocalization of N-catenin in normal and regenerating chick sciatic nerve. In normal nerve, unmyelinated axons exhibited either intense or weak N-catenin immunoreactivity throughout the axoplasm, whereas myelinated axons were completely immunonegative. Regenerating axons, including those derived from parent myelinated axons, showed N-catenin immunoreactivity of variable intensities in growth cones and axon shafts. Schwann cells were invariably devoid of immunoreactivity. Thus N-catenin is not necessarily bound to the surface plasmalemma, but is distributed throughout the cytoplasm, suggesting that most N-catenin molecules are dissociated from N-cadherin.     

Molecular mechanism for connective tissue destruction by dipeptidyl aminopeptidase IV produced by the periodontal pathogen Porphyromonas gingivalis

Porphyromonas gingivalis is a pathogen associated with adult periodontitis. It produces dipeptidyl aminopeptidase IV (DPPIV), which may act as a virulence factor by contributing to the degradation of connective tissue. We investigated the molecular mechanism by which DPPIV contributes to the destruction of connective tissue. DPPIV itself did not show gelatinase or collagenase activity toward human type I collagen, but it promoted the activity of the host-derived matrix metalloproteinase 2 (MMP-2) (gelatinase) and MMP-1 (collagenase). DPPIV bound to fibronectin and mediated the adhesion of P. gingivalis to fibronectin. Mutant DPPIV with catalytic Ser mutagenized to Ala (DPPSA) did not accelerate the degradation of collagen and gelatin by MMPs but retained fibronectin-binding activity. The adhesion of human gingival fibroblasts and NIH 3T3 cells to fibronectin was inhibited by DPPIV. Strain 4351ADPPSA exhibited an intermediate level of virulence in mice, between that of the strain expressing wild-type DPPIV (4351ADPP) and that of the strain harboring only the plasmid vector (4351AVEC). It is suggested that both activity promoting the degradation of collagen and gelatin and binding to fibronectin are required for full virulence. These results reveal novel biological functions of DPPIV and suggest a pathological role in the progression of periodontitis.     

Sequence analysis of two serological variants, HLA-A2K and HLA-A9HH, detected in Japanese

Two rare variants of HLA-A locus antigens, tentatively called HLA-A2K and HLA-A9HH, were serologically identified in the Japanese population. A2K and A9HH showed short reaction patterns of a series of anti-A2 and anti-A9 sera, respectively. The latter variant also reacted with some anti-A2 sera. Nucleotide sequences of full-length cDNAs for A2K and A9HH were determined. The results revealed that both antigens are encoded by previously undescribed alleles. The nucleotide sequence of the allele for A2K was identical to that of A^*0207 except for a single nucleotide difference in exon 3. The nucleotide sequence of the allele for A9HH was identical to that of A^*2402 except for two nucleotides in exon 2. These two nucleotides are shared by all the reported A2 alleles. These sequencing results the allele for A9HH were consistent with the serological cross-reactivity of A9HH with some anti-A2 sera.     

Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3

The pathogenesis of hepatitis C virus (HCV)-associated insulin resistance remains unclear. Therefore, we investigated mechanisms for HCV-associated insulin resistance. Homeostasis model assessment for insulin resistance was increased in patients with HCV infection. An increase in fasting insulin levels was associated with the presence of serum HCV core, the severity of hepatic fibrosis and a decrease in expression of insulin receptor substrate (IRS) 1 and IRS2, central molecules of the insulin-signaling cascade, in patients with HCV infection. Down-regulation of IRS1 and IRS2 was also seen in HCV core-transgenic mice livers and HCV core-transfected human hepatoma cells. Carbobenzoxy-l-leucyl-l-leucyl-l-leucinal, a potent proteosomal proteolysis inhibitor, blocked down-regulation of IRS1 and IRS2 in HCV core-transfected hepatoma cells. In human hepatoma cells, HCV core up-regulated suppressor of cytokine signaling (SOCS) 3 and caused ubiquitination of IRS1 and IRS2. HCV core-induced down-regulation of IRS1 and IRS2 was not seen in SOCS3(-/-) mouse embryonic fibroblast cells. Furthermore, HCV core suppressed insulin-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase and Akt, activation of 6-phosphofructo-2-kinase, and glucose uptake. In conclusion, HCV infection changes a subset of hepatic molecules regulating glucose metabolism. A possible mechanism is that HCV core-induced SOCS3 promotes proteosomal degradation of IRS1 and IRS2 through ubiquitination.     

Studies on fine structure and location of lipids in quick-freeze replicas of atherosclerotic aorta of WHHL rabbits

Summary The fine structure of intracellular and extracellular lipids in the atherosclerotic aorta of Watanabe-heritable hyperlipidemic (WHHL) rabbits was demonstrated by a quick-freeze etching technique. Many lipid droplets, with and without a membrane, were observed in the foam cells. Membrane-free droplets were observed as onionlike structure with a concentric lamellar structure surrounded by 10 nm filaments. Droplets surrounded by a limited membrane probably correspond to lipid-laden lysosomes.In the extracellular connective tissue space, marked accumulation of lipids with a vesicular structure was seen among collagen fibers. The appearance of these lipids was similar to that of lipids in lysosomes of foam cells.     

Percutaneous transluminal angioplasty against arteriosclerosis obliterans in dialysis patients

The incidence of peripheral arteriosclerosis is on the increase in chronic hemodialysis patients. Recently, the intervention (IV) treatment is conducted to deal with this problem. IV was performed in 4 dialysis patients against the complication of arteriosclerosis obliterans (ASO) but the result was unsuccessful in 3 of them. These 3 failure cases were investigated to find the problems associated with percutaneous transluminal angioplasty (PTA). Cases 1, 2 and 3 had intermittent claudication while case 4 had gangrenous toes as the major complaint. The symptoms in these cases were attributable to 90-100% stenosis and occlusion of superficial femoral artery, bilateral iliac arteries, bilateral superficial femoral-popliteal artery, branch of right iliac artery and left iliac artery region, respectively. IV was successful in case 1 but failed in cases 2 and 4 because the catheter itself did not go through due to the severe stenosis of vessel or the procedure of forcefully dilating the vessel caused dispersion of minute thrombi. In case 3, acute myocardial infarction occurred at 10 h after successful IV, resulting in sudden death. In view of the extent of invasion, IV is a treatment method selected against ASO in dialysis patients. However, the method has a high risk of causing thrombus formation, vessel rupture and organ failure. In this regard, it is advisable to evaluate the systemic condition and conduct IV if the extent of stenosis is mild.     

Anti-beta(2)-glycoprotein I antibodies in children with atopic dermatitis

beta(2)-Glycoprotein I (beta(2)GPI) appears to be the major antigen for antiphospholipid antibodies (aPL) in patients with antiphospholipid syndrome (APS). In early infancy, virtually all children initiate transient immune response to non-pathogenic nutritional antigens, which fails to terminate in children with atopic diseases. To examine the possibility that a prolonged immune response to beta(2)GPI could also spread to the human protein, antibodies against human beta(2)GPI (anti-beta(2)GPI) were determined in 93 randomly selected children with different allergic diseases. A high frequency (42%) of IgG anti-beta(2)GPI was found in children with atopic dermatitis (AD), but not in those with other allergic diseases. Anti-beta(2)GPI in children with AD were exclusively of the IgG1 subclass and bound to bovine beta(2)GPI as well, but not to either beta(2)GPI combined with the phospholipid cardiolipin. The epitopes were identified in domain V of beta(2)GPI and the antibody binding was abolished upon the specific proteolytic cleavage of the phospholipid-binding C-terminal loop in domain V of beta(2)GPI. These results indicated that the epitopes for anti-beta(2)GPI in children with AD most likely resided in close vicinity of the phospholipid-binding site of beta(2)GPI. The epitopic difference from anti-beta(2)GPI in APS may explain presumed non-thrombogenicity of anti-beta(2)GPI in children with AD.     

Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia

Mixed-lineage leukemia (MLL) fusion proteins are potent inducers of leukemia, but how these proteins generate aberrant gene expression programs is poorly understood. Here we show that the MLL-AF4 fusion protein occupies developmental regulatory genes important for hematopoietic stem cell identity and self-renewal in human leukemia cells. These MLL-AF4-bound regions have grossly altered chromatin structure, with histone modifications catalyzed by trithorax group proteins and DOT1 extending across large domains. Our results define direct targets of the MLL fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in cancer.