Treatment of hepatic amyloid light‐chain amyloidosis with bortezomib and dexamethasone in a liver transplant patient

Hepatic amyloid light‐chain (AL) amyloidosis is characterized by abnormal deposition of amyloid fibrils in the liver. As this precursor protein is produced by a proliferative plasma cell clone in the bone marrow, liver transplantation (LT) does not affect the disease's progression. Here, we describe the successful treatment using bortezomib‐ and dexamethasone‐based chemotherapy, following LT, of hepatic AL amyloidosis in a 65‐year‐old woman with progressive liver failure. The patient presented with progressive hepatic dysfunction accompanied by hepatorenal syndrome requiring hemodialysis, and living donor LT was successfully performed. Histology revealed amyloid deposits in the liver and stomach, and serum immunofixation revealed AL amyloidosis (κ‐type). The patient began chemotherapy on day 45 after the LT, and remission was achieved after one course. She was subsequently discharged 83 days after the LT, with normal liver and renal function, and no clinical evidence of recurrent disease was observed at the latest follow up (22 months post‐LT).     

Functional polymorphisms in the promoter region of macrophage migration inhibitory factor and chronic gastritis

Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator, which plays a pivotal role in inflammatory and immune diseases. We attempted to clarify associations of the functional polymorphisms of the MIF gene promoter with the development of chronic gastritis. The study was performed with 290 stocked DNAs from subjects with no evidence of gastric malignancy. We employed the PCR-SSCP method to detect gene polymorphisms. The severity of histological chronic gastritis in antral biopsy specimens was classified according to the updated Sydney system. Both the 7/7-CATT repeat at position -794 and the -173 C/C genotypes were significantly associated with a risk of developing severe gastric mucosal atrophy (OR, 9.69; 95% CI, 1.29-72.5; and OR, 4.60; 95% CI, 1.05-20.2, respectively). In subjects younger than 60 years old, the number of 7-CATT alleles was significantly correlated with both the activity and inflammation scores (p=0.0079 and 0.0080, respectively). Our results suggested that functional promoter polymorphisms of the MIF gene might be associated with the severity of gastric mucosal inflammation in younger subjects and with the subsequent development of mucosal atrophy.     

Immunologic benefits of longer graft in rat allogenic small bowel transplantation

BACKGROUND: The effect of graft length on rejection reaction in small bowel transplantation (SBT), which is poorly understood, is tested using rat allogenic SBT models with a short course of tacrolimus. MATERIALS AND METHODS: Inbred Brown Norway rats (major histocompatibility complex: RT1) and Lewis rats (RT1) were used as donors and recipients, respectively. The intestinal tract of the recipient was partially or totally replaced by segmental (15 cm) or whole (70 cm) donor intestine, using two different SBT models. With tacrolimus treatment (0.64 mg/kg per day, 0-13 postoperative days, intramuscularly), recipients' body weights and their survival were evaluated. To compare the extent of peripheral chimerism, donor passenger leukocytes were followed using flow cytometry with a donor-specific monoclonal antibody, OX-27. For the periodical histologic analysis, heterotopic SBT and protocol biopsies of the graft were also performed with short or long intestinal grafts. RESULTS: In a classical Monchik and Russell orthotopic SBT model, whole SBT recipients survived more than 60 days. However, all of the allogenic segmental SBT recipients died within 14 days without histologic sign of graft rejection. In the modified orthotopic SBT model using a cuff technique without systemic clamping, all recipients with segmental allograft survived longer than 29 days. However, recipients with whole graft tended to survive longer than those with segmental graft. The suffering period, lasting from the onset of rejection to death, was significantly shorter in the segmental group than in the whole group. Flow cytometric analysis showed that recipients with whole intestinal grafts had significantly higher ratio of donor passenger leukocytes in peripheral blood. Histologic studies of the protocol biopsies showed that the shorter graft tended to be more severely rejected than the longer graft. CONCLUSIONS: We have demonstrated experimentally that long intestinal grafts have immunologic advantage over short grafts.     

Primary hepatic presentation of Hodgkin's lymphoma: A case report

Hodgkin's lymphoma (HL) is in general a lymph node‐based disease. Hepatic involvement usually occurs in the advanced disease. Primary and prominent manifestation of the disease in the liver is extremely rare. We report magnetic resonance imaging leading to diagnosis in a rare case of liver involvement as the first sign of HL.     

Influence of MDR1 Polymorphism on <Emphasis Type="Italic">H. pylori</Emphasis>-Related Chronic Gastritis

Background  

There is evidence that changes in MDR1 function and/or expression contribute to the pathogenesis of inflammatory disorders of the gastrointestinal tract.     

Promoter methylation of protease-activated receptor (PAR2) is associated with severe clinical phenotypes of ulcerative colitis (UC)

Tryptase acting at protease-activated receptor 2 (PAR2) contributes to the pathogenesis of Inflammatory bowel diseases (IBDs). DNA methylation has been shown to be an important mechanism in gene silencing. We attempted to clarify the relationship between the promoter methylation of PAR2 and ulcerative colitis (UC). 84 UC patients enrolled in the study. UC patients were classified by disease behavior, severity and extent of disease. For rectal inflammatory mucosal specimens from all the patients, and normal terminal ileum from 23 patients, promoter methylation of PAR2 gene was quantified by digital densitographic analysis following to methylation-specific polymerase chain reaction (MSP). The mean methylation levels of the PAR2 gene in all 84 subjects was 38.4 ± 19.6%. Although mean methylation levels in rectal inflammatory mucosa, and paired normal terminal ileum did not vary, methylation levels of PAR2 gene was significantly higher in total colitis than rectal colitis (total colitis vs. rectal colitis; 42.9 ± 19.6% vs. 34.5 ± 18.9%, P = 0.046). The higher methylation levels were also associated with Steroid-dependent (P = 0.002) and refractory (P = 0.007) UC. Our data suggest that PAR2 methylation status in rectal mucosa correlates with more severe disease phenotypes of UC.     

Usefulness of transnasal endoscopy where endoscopic submucosal dissection is difficult

Background  

Early gastric cancer located from the pyloric ring to inside the duodenal bulb (DB) is not easily treated by endoscopic submucosal dissection (ESD). The endoscope needs to be reversed inside the DB to set the resection line at a safe distance from the anal side. Because of the space limitations and limited flexibility of conventional endoscopy (CE), there have been increasing possibilities of complications. Here we report a new ESD technique using a transnasal endoscope (TN-E) that is reversed inside the DB.     

Association of polymorphism of TLR4 and CD14 genes with gastroduodenal diseases in Japan

Background: Host genetic factors may play a key role in determining the long-term outcome of the Helicobacter pylori infection. Toll like receptor 4(TLR4) and CD14-mediated recognition of lipo-polysaccharide (LPS) is required for efficient recognition of Gram-negative bacterial infections. Aims: We investigated the effects of common polymorphisms of TLR4 Asp299Gly, Thr399Ile and CD14 promoter –C159T on the risk of gastric cancer including its subtypes and clinicopathologic features. We also investigated the effects of these polymorphisms on histologic degree of H. pylori induced gastritis. Subjects: The study was performed in 149 gastric cancer(GC) cases [mean age 64.0 ±12.4, M:F = 109:40] and 94 patients without evidence of GC (mean age 64.1 ±12.3, M:F = 65:25, Peptic ulcer diseases = 43.6 %, gastritis = 56.4 %) as the control group. Methods: TLR4 Asp299Gly, Thr399Ile and CD14 promoter – C159T were determined by PCR-RFLP in all the patients. Gastritis scores of non-cancerous gastric mucosa were assessed according to the updated Sydney system in H. pylori-positive subjects(n = 174). Results: The frequencies of CD14-260 TT and T carrier were significantly lower in patents with intestinal type gastric cancer than in controls (OR = 0.31;95 % CI = 0.12–0.78, OR = 0.38; 95 % CI = 0.18–0.81, respectively) Compared with patients older than 61 years, the atrophy score in antrum was significantly lower in TT and CT patients.TLR4 Asp299Gly, Thr399Ile were not detected in all the patients. Conclusion: Our data suggest that CD14 promoter-159TT and T carrier were associated with lower risk of developing gastric mucosal atrophy in H. pylori infected patients more than 61 years of age, and these genotypes may reduce the risk of intestinal type gastric cancer and TLR4 Asp299Gly, Thr399Ile are very rare in the Japanese population. Received 12 July 2006; accepted 17 August 2006