A case report: Severe bone marrow suppression caused by 6-mercaptopurin in Crohn's disease patient]

A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and perianal abscess caused by Crohn's disease. After incision and drainage of the abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced. His white blood cell (WBC) count on day 12 after initiation of 6-MP was not decreased. However, on day 24 he was re-admitted because of severe myelosuppression (WBC: 300/microl), which was complicated by the recurrence of the perianal abscess. Myelosuppression was prolonged and required the administration of granulocyte colony stimulating factor (G-CSF). G-CSF was continued for 17 days to achieve recovery of his WBC count to a normal level.     

Case of severe ulcerative colitis successfully treated with intravenous cyclosporine without high dose corticosteroid]

A 44-year-old women developed marked myopathy one year earlier, when she was treated with intravenous prednisolone for acute severe exacerbation of ulcerative colitis. When she was admitted to our hospital for another severe exacerbation, intravenous cyclosporine A was administered as monotherapy because she could not tolerate corticosteroid. The treatment was successful and she obtained complete remission. Cyclosporine A monotherapy is considered to be a valuable alternative to proctocolectomy for severe ulcerative colitis patients who cannot tolerate corticosteroid.     

Pemphigoid Nodularis: A Case with 230 kDa Hemidesmosomes Antigen Associated with Bullous Pemphigoid Antigen

We report a 73-year-old woman with typical clinical, histological and immunofluorescence features of pemphigoid nodularis. Direct immunofluorescence studies of prurigo nodularis-like lesions and peribullous skin showed the linear deposition of IgG and C3 at the basement membrane zone. Circulating IgG against the basement membrane was also detected by indirect immunofluorescence. The serum from the patient was shown to contain the autoantibody against 230 kDa hemidesmosomal antigen associated with bullous pemphigoid antigen.     

Expression of Lewis Y (Ley) Antigen in Human Anagen Hair Follicles

Lewis Y (Le^y) antigen, a difucosylated tetrasaccharide found on type 2 blood group oligosaccharides of glycolipids and glycoproteins, is thought to be a phenotypic marker predictive of cell differentiation. The distribution of this antigen in human anagen hair follicles was examined by immunohistochemical staining using a monoclonal antibody (AH-6) to Le^y. In the bulbar and suprabulbar portion of anagen hair follicles, Le^y antigen was detected in the three layers of the inner root sheath. Subsequently, the positive staining became translocated to the innermost layer of the outer root sheath in the middle part of the hair follicles. In the upper portion of the hair follicles, Le^y antigen was found in the outer cells of the outer root sheath. These findings suggested that the expression of Le^y antigen in the anagen hair follicles was correlated with the processes of keratinization or terminal differentiation.     

Improved high performance liquid chromatography determination of hippuric acid and methylhippuric acid isomers in urine

A study was made on the effect of detection wavelength and separation mode of HPLC on determination of urinary hippuric acid (HA) and three isomers of methylhippuric acid (MHA). The interference of other constituents of urine in the determination was effectively decreased by detection at a short wavelength of 227.6 nm. Meta and para MHAs were separated by the addition of beta-cyclodextrine to the mobile phase. Four metabolites were successfully separated from other components of urine by the combination of ODS-silica packed-column and mobile phase (method F). The detection limits were found to be 50 and 5 mg/l for HA and MHAs, respectively. MHAs could not be detected in the non-exposed subjects. Average levels (+/- SD) of HA in non-exposed males and females were 272.2 (+/- 210.8) and 393.0 (+/- 269.8) mg/l, respectively. The urinary levels of HA in females were significantly higher than those in males.     

Death of a classified worker probably caused by overexposure to gamma radiation.

This paper describes the case of an industrial radiographer who was seriously overexposed to gamma radiation. The exact circumstances of this exposure were not established but it was concluded that he was repeatedly irradiated probably to a total average whole body dose of at least 10 Gy over several years. Also, a much larger dose to a hand required its partial amputation. He developed myelodysplasia, which progressed to acute myeloid leukaemia from which he died. Karyotypic examination of the leukaemic blasts showed changes very similar to those associated with secondary leukaemia that may develop after radio or chemotherapy. The paper describes his medical case history, the investigation of his workplace, and the attempts to estimate his radiation dose by chromosomal analysis of blood lymphocytes and electron spin resonance of dental enamel and bone.     

Fatal necrotic enteritis associated with Clostridium perfringens in wild crows (Corvus macrorhynchos)

Sporadic outbreaks of fatal enteritis occurred among free-living wild crows (‘large billed’ or ‘wok’ crow; Corvus macrorhynchos) in an open-air park in Japan in 2002. Eight crows were found dead during February, followed by two more in September, and five of the eight were examined histopathologically. At necropsy, all cases showed a markedly dilated small intestine, especially the jejunum and ileum, with large amounts of gas, and dark red to greenish–brown soft content. The necrotic intestinal wall was markedly thickened with multifocal haemorrhages. All cases had multifocal white foci in the liver, and four cases showed marked splenomegaly. Histologically, there was severe necrotic enteritis characterized by extensive mucosal necrosis and multifocal haemorrhages, as well as inflammatory cell infiltrations. A prominent pseudo-membrane formation was noted in the affected intestine. Severe adhesive peritonitis was also observed in three cases. Gram-positive bacilli were present in large numbers in the lumen, and in and around necrotic lesions in the affected intestine. The bacilli were positive for Clostridium perfringens enterotoxin type A by immunohistochemistry, and were also positive for C. perfringens type A using the immunofluorescence method. C. perfringens was isolated by anaerobic culture from the intestinal contents. The present enteritis was thought to be induced by proliferated C. perfringens in the intestine, and to be the cause of death.     

Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation

Accumulation of unfolded and malfolded proteins causes endoplasmic reticulum (ER) stress, stimulating unfolded protein response (UPR) and c-Jun N-terminal kinase (JNK) activation and activating caspase-12 located on the ER. Little is known about the relationship between the ER stress and polyglutamine [poly(Q)] aggregates. Poly(Q)72 repeats [poly(Q)(72)] induced the stimulation of ER stress signals such as JNK activation, upregulation of Grp78/Bip and caspase-12 activation in C2C5 cells. We prepared antiserum against the cleavage site of mouse caspase-12 at D(318) (anti-m12D318), and showed that poly(Q)(72) with perinuclear aggregates, cytoplasmic inclusions and nuclear inclusions stimulated JNK activation and anti-m12D318 immunoreactivity, but poly(Q)(72) with dispersed aggregates and small nuclear aggregates showed a significantly less effect. Poly(Q)(72) and poly(Q)(11) dispersed in cytoplasm did not. Anti-m12D318-positive cells showed apoptotic features. Unlike anti-m8D387 immunoreactivity, the anti-m12D318 immunoreactivity was not coaggregated with poly(Q). Ac-IETD-fmk (caspase-8 inhibitor) and Ac-DEVD-CHO (caspase-3 inhibitor) did not prevent the anti-m12D318 immunoreactivity induced by poly(Q)(72) aggregates. Anti-m12D318 immunoreactivity was detected in caspase-8(-/-) and caspase-3(-/-) mouse embryonic fibroblasts expressing poly(Q)(72) aggregates. Thus, caspase-12 was activated by poly(Q)(72) aggregates via a pathway independent of caspase-8 and caspase-3 activation, and caspase-12 activation was closely associated with poly(Q) aggregate-mediated cell death. Stimulation of ER stress signals may be involved in the pathogenesis of neurodegenerative disorders with poly(Q) expansion.     

Gastric motility in patients with recurrent gastric ulcers.

The existence of abnormal gastric motility in gastric ulcer disease remains controversial. The aim of this study was to characterize gastric motility in patients with recurrent gastric ulcers. Studies were performed in 10 control subjects and in 24 patients with recurrent active gastric ulcer disease as diagnosed by gastrointestinal endoscopy. Gastric motility was evaluated by cutaneous electrogastrography (EGG) and by gastric semi-liquid meal emptying. The EGG was recorded before and after ingestion of a test meal containing 20 mg/kg of acetaminophen. Patients with a dominant EGG frequency of greater than 0.06 Hz were defined as tachygastria, while those with a frequency of less than 0.04 Hz were defined as bradygastria. A transient frequency decrease, called postprandial dip (PD), was identified visually. The degree of gastric emptying was determined from the serum acetaminophen concentration 45 minutes after the meal. Control subjects showed no irregularity in their dominant EGG frequency in tither fasting or postprandial states. PD was observed in 8 control subjects. In patients presenting with active gastric ulcers, abnormal patterns in the dominant EGG frequency (either as tachygastria or bradygastria) were observed in 14 of the 24 patients when fasting and in 15 of them in the postprandial state. After successful treatment, the number of patients with abnormal patterns in their dominant EGG frequency remained unchanged, while PD was observed in 11 patients. No significant difference was observed in the EGG power ratio as a result of successful treatment. Gastric emptying was significantly delayed compared with controls in both the active and healed stages. These findings suggest that abnormal gastric motility, including gastric electrical abnormalities and delayed gastric emptying, plays an important role in the pathophysiology of recurrent gastric ulcers.     

Association of single nucleotide polymorphisms of the interleukin-10 promoter gene and susceptibility to primary biliary cirrhosis: immunogenetic differences in Italian and Japanese patients

Several lines of data suggest that genetic factors play an important role in the onset and/or progression of primary biliary cirrhosis (PBC). Since PBC is an autoimmune disease, it is reasoned to assume that genes encoding cytokines may confer susceptibility to disease. Amongst these factors, interleukin-10 (IL-10) has received significant attention. The promoter region of IL-10 gene has three single nucleotide polymorphisms (SNPs) at positions -1082, -819 and -592. To elucidate the association of the three SNPs of IL-10 promoter region with susceptibility of PBC in two different genetic populations, 159 unrelated patients with PBC (94 Italian and 65 Japanese) and 143 local controls (72 Italian and 71 Japanese) were enrolled. SNPs were determined using allele-specific PCR/RFLP. In Italian PBC patients, the frequency of homozygosity for G/G at position -1082 was significantly higher than that of local controls (p < 0.041, OR = 2.44, 95% C.I.; 1.02-5.86). The frequencies of haplotype GCC in PBC patients, possibly linked to higher IL-10 production, were also significant higher than local controls (p < 0.033). However, in Japanese population, there were no significant differences in the three SNPs and haplotypes between PBC patients and controls. Excessive production of IL-10 may play an important role in some populations in modulating the onset of PBC. Further, immunogenetic studies of PBC should take into account ethnic and geographic variations; this makes such studies in heterogeneous population, like the USA, more difficult.