Expression of blood group antigens including HLA markers in human adult liver

The localisation of the principal blood group antigens has been studied in human liver. These blood group antigens included the erythrocyte antigens and the antigen of the major histocompatibility complex. This study was performed by the indirect immunofluorescence technique using polyclonal antibodies of human or animal origin and monoclonal antibodies from hybridomas. This study has shown that the normal hepatocyte is lacking in blood group antigens. On the contrary, the biliary cell was rich in antigenic markers: the main antigens expressed were Lewis, Pr, HLA-A and B antigens. In Kupffer cells, only i and HLA-DR antigens were clearly expressed. The endothelial cells of blood vessels mainly show A, B, H, HLA-A and B antigens; HLA-DR and Pr are slightly expressed. HLA-DR antigens were more strongly expressed on veins than on arteries. Dendritic cells have been identified in the portal space of human liver. They bore i and HLA-DR antigens.     

CM1 ligation initiates apoptosis in a caspase 8-dependent manner in Ramos cells and in a mitochondria-controlled manner in Raji cells

Burkitt lymphoma (BL) is a tumor with the characteristics of germinal center B cells. We previously reported that the CM1 (centrocyte/-blast marker 1) molecule is expressed only in germinal center B cells, specifically, in a subpopulation of centroblasts and centrocytes. In the present study, we investigated the apoptosis induced by anti-CM1 in the Ramos and Raji human BL cell lines. The Ramos is protected from apoptosis by the crosslinking of sIgM and the calcium ionophore by the ligation of CD40 with anti-CD40 monoclonal antibodies (mAb) or soluble CD40 ligand (sCD40L). In this investigation on the effect of CM1 on apoptosis in BL cell lines, we found that cellular signaling by CM1 induces apoptosis and decreases cell viability, in BL cell lines cultured for 24 hours with protein-G agarose beads conjugated anti-CM1 mAb. Stimulation by CD40 ligated with sCD40L protected Raji cells from CM1-induced apoptosis, but did not protect Ramos cells. Furthermore, after anti-CM1 mAb stimulation, CD95 expression was upregulated and CD40 expression was unaltered or slightly decreased in Ramos cells, whereas CD95 was downregulated and CD40 was slightly upregulated in Raji cells. The engagement of CD40 by sCD40L enhanced CD95 expression, but the level of CM1 expression was unchanged in Ramos. However, sCD40L downregulated both CD95 and CM1 expression in Raji. In addition, the caspase-8 specific inhibitor blocked CM1-induced apoptosis in Ramos cells, but not in Raji cells. Increased mitochondrial membrane permeabilization was observed only in Raji cells. Moreover, the effector caspase inhibitor, z-DEVD, blocked CM1-mediated apoptosis in both cell lines. We found that CM1-induced apoptosis is achieved via different initiation pathways, which are cell-type dependent.     

Altered p53 expression in Epstein Barr virus positive T cell lymphomas.

Recent studies have suggested a probable association between Epstein-Barr virus (EBV) and nasal/nasopharyngeal T cell lymphomas but the role of oncogenes or tumor suppressor genes is poorly understood. We have studied the frequency of p53 expression and its relation to the EBV infection in 33 Korean patients with head and neck (H&N) lymphomas. All cases (23 B cell & 10 T cell) were immunostained for p53 protein using the mAb D07 (Novocastra) and the avidin biotin peroxidase method. EBER in situ hybridization was performed using a fluorescein conjugated EBV oligonucleotide probe (Dako). Among 33 lymphomas, 16 cases stained positively for p53 protein. P53 expression was frequent both in higher grade lymphomas and in advanced stage. Nine cases were EBER positive, EBER was more commonly found in T cell lymphomas than in B cell lymphomas (70% vs 8.7%). EBER positive lymphomas showed a higher frequency of p53 positivity than EBER negative lymphomas (78% vs 38%), although the difference was not statistically significant (p = 0.095). These findings indicate altered expression of p53 protein occurs in H&N lymphomas, especially in late event lymphoma progression and appears to play a role in the development of EBER positive T cell lymphomas.     

Interdependent effect of angiotensin-converting enzyme and platelet-activating factor acetylhydrolase gene polymorphisms on the progression of immunoglobulin A nephropathy

In order to investigate the interdependent action of the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene and polymorphism in exon 11 (C1136-->T; Ala379Val) of the platelet-activating factor acetylhydrolase (PAF-AH) gene, which encodes a functional antagonist of PAF, on the progression of immunoglobulin A (IgA) nephropathy, we analysed both polymorphisms in patients with primary IgA nephropathy, who were followed-up for longer than 3 years. During the follow-up (87.3 +/- 50.0 months), the disease progressed in 38 of the 191 patients (19.9%). The D allele of the ACE gene in the absence of the T allele of the PAF-AH gene did not affect the prognosis [odds ratio (OR), 3.6; 95% confidence interval (CI), 0.8-16.4] and neither did the T allele in the absence of the D allele (OR, 3.0; 95% CI, 0.4-24.2). However, the presence of both was a significant prognostic factor (OR, 6.6; 95% CI, 1.4-31.3). After adjusting for other risk factors, the presence of both proved to be an independent risk factor (OR, 4.5; 95% CI, 1.6-12.7). These results suggest that the interdependent effects of ACE and PAF-AH polymorphisms on the progression of IgA nephropathy might be more important than the effect of the individual polymorphisms.     

Molecular targets of dietary polyphenols with anti-inflammatory properties

There is persuasive epidemiological and experimental evidence that dietary polyphenols have anti-inflammatory activity. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have long been used to combat inflammation. Recently, cyclooxygenase (COX) inhibitors have been developed and recommended for treatment of rheumatoid arthritis (RA) and osteoarthritis (OA). However, two COX inhibitors have been withdrawn from the market due to unexpected side effects. Because conventional therapeutic and surgical approaches have not been able to fully control the incidence and outcome of many inflammatory diseases, there is an urgent need to find safer compounds and to develop mechanism-based approaches for the management of these diseases. Polyphenols are found in many dietary plant products, including fruits, vegetables, beverages, herbs, and spices. Several of these compounds have been found to inhibit the inflammation process as well as tumorigenesis in experimental animals; they can also exhibit potent biological properties. In addition, epidemiological studies have indicated that populations who consume foods rich in specific polyphenols have lower incidences of inflammatory disease. This paper provides an overview of the research approaches that can be used to unravel the biology and health effects of polyphenols. Polyphenols have diverse biological effects, however, this review will focus on some of the pivotal molecular targets that directly affect the inflammation process.     

X-linked severe combined immunodeficiency syndrome: the first Korean case with gamma c chain gene mutation and subsequent genetic counseling

X-linked severe combined immunodeficiency (X-SCID) is a rare, life-threatening immune disorder, caused by mutations in the gamma c chain gene, which encodes an essential component of the cytokine receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. A 13-month-old boy with recurrent infections who had reduced serum immunoglobulin levels and decreased numbers of CD3, CD16/56 cells was evaluated for gamma c chain gene mutation and protein expression. The patient had a C-to-T point mutation at nucleotide position 690, one of the hot spots, resulting in a single amino acid substitution of cysteine for arginine (R226C), as determined by direct sequencing and PCR-RFLP. The patient's mother was a heterozygous carrier. Percutaneous umbilical cord blood sampling was performed at the 6-month of gestation in a subsequent pregnancy. As the immunophenotype of the fetus showed an identical pattern, the pregnancy was terminated and genetic analysis of the abortus confirmed recurrence. This is the first report of the molecular diagnosis of X-SCID in Korea. Genetic analysis of the gamma c chain gene is useful for definite diagnosis and genetic counseling for X-SCID.     

Isometric and isokinetic torque curves at the knee joint

Isometric and isokinetic torques of bilateral quadriceps and hamstrings were measured with Isokinetic Rehabilitation and Testing System (Model No. Cybex 340) on 40 normal untrained subjects, 20 males and 20 females, ranging between the ages of 23 and 35 years. The mean peak isometric and isokinetic torque values of both muscle groups showed no significant differences between dominant (right) and nondominant (left) limbs in both sexes; however there were significant differences between the male and the female. As the angular velocity increased, the peak torque significantly decreased, and the point of peak torque output occurred significantly later in the range of motion for quadriceps and hamstrings (p less than 0.01). There were no significant changes in the hamstrings to quadriceps (H/Q) ratios as the angular velocity increased. However, there were significant differences of mean H/Q ratio between male and female (p less than 0.01). Height had significant positive correlation with peak isometric and isokinetic torques for both quadriceps and hamstrings (p less than 0.01). Weight was found to correlate significantly with peak isometric and isokinetic torques (p less than 0.01). The mean isometric torques were significantly higher than the mean isokinetic torques for any joint angles in both sexes (p less than .01).     

Amino acid differences in capsid protein, VP1, between diabetogenic and nondiabetogenic variants of encephalomyocarditis virus

The genes for the major capsid protein, VP1(1D), of both diabetogenic D variant (EMC-D) and nondiabetogenic B variant (EMC-B) of encephalomyocarditis virus were cloned by using two synthetic primers which are common to both EMC-D and EMC-B. The cloned genes were mapped for major restriction enzyme sites including AccI, BamHI, EcoRI, HincII, KpnI, PvuII, SstI, TaqI, and XbaI. Among those nine restriction enzyme sites, only the TaqI site distinguished EMC-D genome from the counterpart of EMC-B genome. The complete nucleotide sequences (831 bases) of the VP1 genes revealed five amino acid differences between the two variants. Three of the changes, at positions 41, 58, and 152, were Thr (EMC-B) to Ala (EMC-D). The additional two changes occurred at positions 63 [Gln (EMC-B) to Glu (EMC-D)] and 181 [Thr (EMC-B) to Ser (EMC-D)]. All of these amino acid changes were due to point mutations at the first base of each codon.     

Cytokine secretion induced by superantigens in peripheral blood mononuclear cells, lamina propria lymphocytes, and intraepithelial lymphocytes.

Superantigens are potent inducers of T-cell proliferation and induce a broad range of cytokines, including tumor necrosis factor (TNF), gamma interferon, and interleukin 2 (IL-2). In the present study, we compared the abilities of different staphylococcal superantigens (staphylococcal enterotoxin B [SEB], staphylococcal enterotoxin E [SEE], and toxic shock syndrome toxin 1 [TSST-1]) to stimulate distinct cytokine profiles in peripheral blood mononuclear cells (PBMC), lamina propria lymphocytes (LPL), and intraepithelial lymphocytes (IEL). One million PBMC, LPL, and IEL were stimulated with various concentrations of superantigen (10 to 0.001 ng/ml) for 24, 48, and 72 h. Maximum cytokine production by PBMC, LPL, and IEL was observed for all three superantigens at 48 h at a concentration of 1 ng/ml. In PBMC, SEE and TSST-1 stimulated more IL-2 and gamma interferon than SEB. SEE and TSST-1 also stimulated more TNF and IL-4 production than SEB. In contrast, SEB stimulated more IL-6 than either SEE or TSST-1. In LPL, there was no SEE-induced IL-2 or IL-4 production, but IL-6, TNF, and gamma interferon were induced. SEB similarly induced no IL-2 or gamma interferon from the LPL, but IL-4, IL-6, and TNF were detected. TSST-1 stimulation of LPL resulted in IL-2 and TNF production but no IL-4, IL-6, or gamma interferon. In IEL, SEE induced no IL-2, IL-4, or gamma interferon but produced IL-6 and TNF, while SEB stimulation resulted in no IL-2 or gamma interferon but did result in detectable IL-4, IL-6, and TNF. Taken together, these data indicate that there are significant differences in the cytokine profiles induced by superantigens in LPL and IEL compared with those in PBMC, and these differences may relate to differences in activation requirements.