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.     

Analysis of long-term social rehabilitation of brain contusion]

164 patients with brain contusion were evaluated with respect to social rehabilitation. 70 out of 134 patients (66.7%), said to have had good recovery or moderate disability by the Glasgow Outcome Scale (GOS), returned to full or partial employment. Factors such as age, Glasgow Coma Scale (GCS) at admission, duration of unawareness, fibrin and fibrinogen degradation product (FDP) were the most important in predicting social recovery. The Wechsler Adult Intelligence Scale (WAIS) was applied in 33 patients. The IQs of the patients who returned to their job fully tended to be higher than those who could not. In the majority of patients, impaired capacity for work was caused not only by physical deficits, but by mental retardation described as such as IQ score.     

Study on the extent of peritumoral edema in glioma: its correlation with the proliferative potential and tumor-infiltrating mononuclear cells]

The correlation between the extent of peritumoral edema and the proliferative potential or the infiltration of mononuclear cells was studied in 17 gliomas. The peritumoral edema was evaluated on contrast enhanced CT scan as the ratio of the low density area around the tumor to the enhanced high density area. The proliferative potential and the infiltration of mononuclear cells into the tumor were investigated immunohistochemically using monoclonal antibody (MAb) against DNA polymerase alpha and anti-Leu MAb's respectively. There was a significant correlation between the extent of the peritumoral edema and the percentage of DNA polymerase alpha positive cells. The degree of the infiltration of mononuclear cells into the tumor tissue also correlated with the extent of peritumoral edema. In gliomas with high proliferative potential and/or severe infiltration of mononuclear cells, the peritumoral edema may be aggravated by disruption of the blood-brain-barrier and increased vascular permeability.     

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.     

Anti-pruritic effect of nemolizumab in hemodialysis patients with uremic pruritus: a phase II,randomized, double-blind,placebo-controlled clinical study

Clinical and Experimental Nephrology - The pathophysiology of uremic pruritus (UP), which is characterized by systemic and intractable itching, remains unclear. As interleukin (IL)-31 may be...     

Immunohistochemical demonstration of DNA polymerase alpha in human brain-tumor cells

The proliferative capacity of brain-tumor cells was analyzed in vitro and in situ using monoclonal antibody (MAb) against deoxyribonucleic acid (DNA) polymerase alpha. For the in vitro studies, two cultured human glioma cell lines were investigated using MAb against DNA polymerase alpha, the MAb Ki-67, a serum against proliferating cell nuclear antigen (PCNA/cyclin), bromodeoxyuridine (BUdR), and an anti-BUdR MAb. During exponential growth of the cells, the percentage of polymerase alpha-positive cells (the "polymerase alpha score") ranged from 72.0% to 77.1%, the Ki-67-positive cells (the "Ki-67 score") ranged from 43.4% to 59.4%, the PCNA/cyclin-positive cells from 30.9% to 41.4%, and the BUdR labeling index from 28.6% to 39.3%. For the in situ studies, tissue from 60 human brain tumors and from two normal human brains was investigated and the polymerase alpha scores and Ki-67 scores were compared. In normal brain tissue, no immunostaining was found by either method. In brain tumors, both the polymerase alpha scores and the Ki-67 scores correlated with the histological grade of malignancy. Polymerase alpha scores were generally higher than Ki-67 scores in the same specimen, especially in malignant brain tumors. These findings suggest that immunostaining of DNA polymerase alpha is a convenient and important new method by which to estimate the cellular proliferation rate of brain tumors. Polymerase alpha scores may be closer to the growth fraction of the individual tumor than the MAb Ki-67 or other scores.