Villous adenoma of the bile ducts: a case report and a review of the reported cases in Korea

Villous adenomas are benign epithelial lesions with malignant potential which can occur at any site in the gastrointestinal tract. They are usually encountered in the rectum and colon, less frequently in the small bowel and very rarely in the biliary trees. Nine cases of bile duct villous adenomas have been reported in the literature. However, 4 cases of bile duct villous adenomas have been reported in the Korean literature. Recently, we experienced a case of villous adenoma in the common hepatic duct in a 77-year-old man presenting with obstructive jaundice in which preoperative histologic diagnosis of villous adenoma played a critical role in managing this patient. Herein, we present a case report of bile duct villous adenoma and a review of the reported cases in Korea to help define and manage this rare disease entity in the bile ducts. In addition, confusing nomenclature of bile duct adenomas is discussed.     

Activation of Src tyrosine kinase in microglia in the rat hippocampus following transient forebrain ischemia

To better understand the pathophysiological role of Src protein, a non-receptor protein tyrosine kinase of 60kDa, in the ischemic brain, we investigated the time course and regional distribution of active Src expression by using a specific antibody against Tyr416 phosphorylated Src (phospho-Src) in the rat hippocampus after transient forebrain ischemia. In the hippocampus of the control animals, active Src expression was too low to be detected by immunolabeling. Beginning 4h after reperfusion, active Src expression became evident and, after 1 day, had increased preferentially in the CA field of the hippocampus proper and the dentate gyrus. By day 3, active Src expression markedly increased in the pyramidal cell layer of CA1 and the dentate hilar region in temporal correlation with neuronal cell death occurring in these areas, where cells typical of phagocytic microglia showed phospho-Src immunoreactivity. Double-labeling experiments revealed that cells expressing active Src were microglia that stained for biotinylated lectin derived from Griffonia simplicifolia (GSI-B4). Active Src expression began to decline at day 7 and returned to the basal level by day 14 after reperfusion. These results demonstrate increased phosphorylation of Src in activated microglia of the post-ischemic hippocampus, indicating that Src signaling may be involved in the microglial reaction to an ischemic insult.     

PCR-RFLP based molecular typing of enteroviruses isolated from patients with aseptic meningitis in Korea

Summary.  We have evaluated PCR–RFLP as a practical method for rapid typing of enteroviruses causing aseptic meningitis in Korea. Through blind examination of 80 clinical isolates from patients with aseptic meningitis, we have compared the results of conventional serotyping with PCR–RFLP based genotyping, which was developed for this study. Among the 80 case isolates, which had been previously typed by routine neutralization test, only 42 cases (52.5%) were matched with typing by PCR–RFLP. The result clearly demonstrated that the enterovirus serotype does not coincide with the genotype. Therefore, the classification of enteroviruses by genotyping with PCR–RFLP, although rapid and simple, may be complicated by regional or seasonal differences. However, the PCR–RFLP method developed in this study is applicable to the epidemiological study of enteroviruses when regional or seasonal differences exist, and is useful in identifying the source of an infection. Received August 6, 2001; accepted April 15, 2002 Published online July 10, 2002     

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.     

Reduced mitochondrial coupling in vivo alters cellular energetics in aged mouse skeletal muscle

The mitochondrial theory of ageing proposes that the accumulation of oxidative damage to mitochondria leads to mitochondrial dysfunction and tissue degeneration with age. However, no consensus has emerged regarding the effects of ageing on mitochondrial function, particularly for mitochondrial coupling (P/O). One of the main barriers to a better understanding of the effects of ageing on coupling has been the lack of in vivo approaches to measure P/O. We use optical and magnetic resonance spectroscopy to independently quantify mitochondrial ATP synthesis and O₂ uptake to determine in vivo P/O. Resting ATP demand (equal to ATP synthesis) was lower in the skeletal muscle of 30-month-old C57Bl/6 mice compared to 7-month-old controls (21.9 ± 1.5 versus 13.6 ± 1.7 nmol ATP (g tissue)⁻¹ s⁻¹, P = 0.01). In contrast, there was no difference in the resting rates of O₂ uptake between the groups (5.4 ± 0.6 versus 8.4 ± 1.6 nmol O₂ (g tissue)⁻¹ s⁻¹). These results indicate a nearly 50% reduction in the mitochondrial P/O in the aged animals (2.05 ± 0.07 versus 1.05 ± 0.36, P = 0.02). The higher resting ADP (30.8 ± 6.8 versus 58.0 ± 9.5 μmol g⁻¹, P = 0.05) and decreased energy charge (ATP/ADP) (274 ± 70 versus 84 ± 16, P = 0.03) in the aged mice is consistent with an impairment of oxidative ATP synthesis. Despite the reduced P/O, uncoupling protein 3 protein levels were not different in the muscles of the two groups. These results demonstrate reduced mitochondrial coupling in aged skeletal muscle that alters cellular metabolism and energetics.     

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.