Systemic and local evidence of increased Fas-mediated apoptosis in ulcerative colitis

BACKGROUND AND AIMS: Recent studies suggest that Fas-mediated apoptosis is involved in the pathogenesis of inflammatory bowel disease (IBD). This study was conducted to clarify whether soluble forms of Fas (sFas) and Fas ligand (sFasL) are concerned with inflammation in IBD. METHODS AND PATIENTS: Concentration of serum sFas and sFasL was measured by enzyme-linked immunosorbent assay in 10 patients with ulcerative colitis (UC), 10 with Crohn's disease (CD) in both active and remission stages, and 20 controls. Expression of Fas and sFas in colonic mucosa was examined by western blot. Distribution of Fas and FasL in colonic mucosa was examined by immunohistochemistry in 20 UC, 20 CD, and 10 non-IBD colitis patients and in 10 controls. Apoptotic cells were examined by TUNEL. RESULTS: Concentration of systemic sFas was significantly lower in active UC than controls. The number of FasL-containing cells was significantly higher in active UC than in remission UC, non-IBD colitis, and controls. Apoptotic cells were increased in active UC. CONCLUSIONS: Our results demonstrate that systemic and local Fas-mediated apoptosis is promoted in UC, which might be involved in the pathogenesis in UC.     

Chronic hepatitis C associated with anti-liver/kidney microsome-1 antibody is not a subgroup of autoimmune hepatitis

To determine whether “autoimmune hepatitis type IIb” should be categorized as a subgroup of autoimmune hepatitis, we conducted a clinicopathological study of 25 adult Japanese patients who were positive for anti-liver/kidney microsome-1 (anti-LKM-1) antibody and infected with the hepatitis C virus (HCV). Anti-LKM-1 was determined by indirect immunofluo-rescence and by the double immunodiffusion assays we have developed. Twenty-two patients did not present any unusual symptoms or any associated diseases during the course of their chronic HCV infection. The spectrum of HCV genotypes of these patients did not significantly differ from that of anti-LKM-1-negative Japanese patients with chronic hepatitis C. Histological examination of liver biopsy specimens showed the usual characteristics of chronic hepatitis C and lack of characteristics of autoimmune hepatitis type I. No disease-specific HLA haplotypes were noted, and HLA-DR4, which is detectable in 88.7% of Japanese patients with autoimmune hepatitis type I, was detected in only 50.0% of our group, the same rate as the background frequency. Prednisolone was effective in none of the six patients treated, but interferon was effective in six of ten treated patients (60%). From these results, we conclude that “autoimmune hepatitis type IIb” should not be categorized as autoimmune hepatitis, and that this subgroup is essentially chronic hepatitis C in which an autoantibody has been produced during the course of chronic HCV infection.     

Case of pneumothorax associated with pulmonary Mycobacterium fortuitum infection

A 39-year-old man with dyspnea was revealed to have severe pneumothorax and received partial resection of the left upper lobe after unsuccessful drainage. Necrotizing epitheloid granuloma was found in the resected lung and Mycobacterium fortuitum was detected from the lesion. Chemotherapy with levofloxacin and clarithromycin was started one year after surgery because of the newly found nodular shadow near the lesion. The case experienced pyothorax due to pulmonary tuberculosis three years before and Mycobacterium avium pleuritis one year before this episode. Three-time mycobacterial pleural infection in three years seems to be uncommon. Furthermore this is the first report of pneumothorax associated with pulmonary Mycobacterium fortuitum infection.     

A case of liver abscess co-infected with Desulfovibrio desulfuricans and Escherichia coli and review of the literature

A 73-year-old woman was admitted with consciousness disturbance following a fever. Abdominal computed tomography revealed a large liver abscess with which the presence of Desulfovibrio desulfuricans and Escherichia coli was confirmed by thorough blood and abscess content culture. Empiric meropenem treatment was switched to cefoperazone/sulbactam, followed by ampicillin/sulbactam based on susceptibility testing. Desulfovibrio desulfuricans is a common bacterium that rarely causes liver abscess and may be overlooked during co-infection due to overgrowth of the accompanying bacteria. Clinicians should bear Desulfovibrio desulfuricans in mind and select the appropriate antibiotics according to susceptibility testing when anaerobic bacteria are detected in a liver abscess.     

Pharmacological characterization of the voltage-dependent calcium channel of pancreatic B-cell

Pharmacological characteristics of the voltage-dependent calcium channel (VDCC) of the pancreatic B-cell were studied using omega-conotoxin (omega CgTX) and dihydropyridine (DHP) calcium channel blockers. High glucose and potassium (K+) depolarization were employed as the stimulant of insulin release. omega CgTX (greater than 50 nM), a blocker of neural, but not muscular, Ca2+ channels, partially blocked (27%) the second, but not the first, phase of glucose-induced insulin release without a significant effect on K+ depolarization-induced insulin release. The DHP Ca2+ channel blocker nifedipine inhibited both phases of glucose-induced insulin release (ED50 = 200 nM) and completely abolished both phases of response at 10 microM. In contrast, the DHP Ca2+ channel blocker only partially suppressed (75% at 10 microM) K+ depolarization-induced insulin release with an ED50 of 100 nM. We conclude that pancreatic B-cell possesses at least two classes of VDCCs; one is DHP sensitive, and the other DHP insensitive. Partial suppression of the second phase of glucose-induced insulin release by a high concentration of omega CgTX may be due to its toxic effect on the secretory machinery other than VDCC.     

The possible novel treatment of achondroplasia, C-type natriuretic peptide (CNP)

C-type natiruetic peptide (CNP) showed a potent effect on the elongation of the tibial organ culture system. CNP also corrected the dwarfing phenotype of the CNP knockout mice. These results suggest that CNP is the novel promoter of the endochondral ossification, and that CNP/GC-B activation is possible target of the treatment of the achondroplasia.