Mutation assay of the novel gene <Emphasis Type="Italic">DOG1</Emphasis> in gastrointestinal stromal tumors (GISTs)

BACKGROUND: Recently, the novel gene DOG1 has been found to be overexpressed in most gastrointestinal stromal tumors (GISTs) specifically within the field of soft tissue tumors. DOG1 might play a role in development of GISTs and have potential as a diagnostic marker and therapeutic target, but the biological function and the overexpression mechanism have not yet been investigated. In this study we examined whether the DOG1 gene mutation occurs as with the KIT gene and PDGFRA gene. METHODS: We investigated ten resected primary GIST tissues. All cases were examined for immunoreactivity for KIT and DOG1 and screened for mutation in the KIT gene (exons 9, 11, 13, and 17) and the PDGFRA gene (exons 12, 14, and 18) by direct DNA sequencing. Four cases with relatively good quality DNA were analyzed for the DOG1 gene (exons 1-26) mutation. RESULTS: All ten GISTs showed immunoreactivity for KIT. Although all cases expressed DOG1 in immunohistochemistry, we could not find any mutations within all 26 exons (a total of 104 exons) of the DOG1 gene in the four analyzed cases. CONCLUSIONS: Based on four cases, the DOG1 gene was found not to be mutated in GISTs.     

Compression of right ventricular out-flow due to localized hematoma after coronary perforation during PCI.

Although coronary perforation can cause tamponade during percutaneous coronary intervention (PCI), this is unusual for patients previously undergoing coronary artery bypass graft surgery (CABG) due to pericardial adhesions. We report here on a rare case of right ventricular out-flow obstruction complicating PCI in a patient with a previous CABG.     

Cytochrome P450 (CYP) 1A2, sulfotransferase (SULT) 1A1, and N-acetyltransferase (NAT) 2 polymorphisms and susceptibility to urothelial cancer

Purpose Arylamines are suspected to be the primary causative agent of urothelial cancer in tobacco smoke. In the human liver, arylamines are N-hydroxylated by a cytochrome P450 (CYP)1A2-catalyzed reaction, which produces a substrate for O-esterification that can be catalyzed by N-acetyltransferases (NAT) or sulfotransferases (SULT). Recently, several polymorphisms of CYP1A2, SULT1A1, and NAT2 that affect their activities have been reported.Methods In this study, 306 Japanese patients with urothelial transitional cell carcinoma and 306 healthy controls were compared for frequencies of CYP1A2, SULT1A1, and NAT2 genotypes.Results The frequencies of NAT2 intermediate or slow acetylator genotype were significantly higher in the urothelial cancer patients than in the healthy control subjects [odds ratio (OR)=1.49, 95% confidence interval (95% CI) 1.06–2.09, OR=3.23, 95% CI 1.72–6.08, respectively]. Stratifying by amount of smoking, among subjects who consumed >33.5 pack-years and carried the SULT1A1 *1/*1 or NAT2 slow acetylator genotype, the OR was 1.73 (95% CI 1.01–2.97) whereas it was 7.31 (95% CI 1.90–28.05) in non-smokers who carried the homozygous wild genotype, respectively. The relationships between CYP1A2, SULT1A1, and NAT2 polymorphisms and clinical findings including tumor differentiation, stage, and recurrence rate were analyzed. Only associations between NAT2 genotype and pathological findings were admitted, and the higher OR of NAT2 intermediate and slow acetylator genotype was more likely to present to a low-grade tumor (G1) among heavy-smokers.Conclusions Our results suggest that SULT1A1 *1/*1 and NAT2 slow acetylator genotypes might modulate the effect of carcinogenic arylamines contained in tobacco smoke, and that the modulation of NAT2 intermediate and slow acetylator genotype has a tendency to present a higher risk for highly differentiated tumors among heavy-smokers.     

Novel technique using intravascular ultrasound-guided guidewire cross in coronary intervention for uncrossable chronic total occlusions.

The experience of using a novel application of intravascular ultrasound (IVUS)-guided percutaneous coronary interventions for chronic total occlusions is reported in 2 cases. In the first case, an IVUS catheter was advanced into a side branch to identify the entry point of the major branch. In the second case, IVUS-guided penetration of the guidewire from the false lumen to the true lumen after causing a dissection was successful.     

A case with life-threatening interstitial pneumonia associated with bucillamine treatment

We report a case of bucillamine-induced interstitial pneumonia accompanied by severe hypoxemia in an 83-year-old woman who had rheumatoid arthritis. Respiratory failure worsened even after withdrawal of bucillamine and administration of high-dose corticosteroids, and mechanical ventilation was required. A review of 15 cases with bucillamine-induced pulmonary injury suggests that advanced age may be associated with the development of severe interstitial pneumonia. Bucillamine can cause corticosteroid-resistant and life-threatening lung injury, especially in the elderly.     

Clinical evaluation of leukotriene receptor antagonists in preventing common cold-like symptoms in bronchial asthma patients.

BACKGROUND: We investigated the possibility of preventing common cold-like symptoms as a previously unknown benefit of leukotriene receptor antagonists (LTRAs). METHODS: A total of 279 adult patients with bronchial asthma referred to our hospital between June and December 2004 were retrospectively analyzed. Patients were divided into LTRA treated and untreated groups. Frequency of acute exacerbations and number of visits to emergency rooms and of hospital admissions were analyzed as indicators of frequency of infections and asthma exacerbation over the previous 12 months. RESULTS: Irrespective of inhaled corticosteroid (ICS) use, frequency of infections was significantly lower in the LTRA treated group (0.3 +/- 0.7 times/year) than in the LTRA untreated group (1.6 +/- 4.2 times/year) (P < 0.05), suggesting that LTRA therapy prevents common cold-like symptoms. Frequency of acute exacerbations and number of hospital admissions were significantly lower in the LTRA treated versus LTRA untreated group (0.4 +/- 0.8 versus 2.7 +/- 4.3 times/year and 0.0 +/- 0.2 versus 0.4 +/- 0.7 times/year, respectively; both P < 0.01). When the patients were divided into ICS treated and untreated groups, none of the parameters analyzed differed significantly between the two groups, although all parameters tended to be lower in the ICS treated group. CONCLUSIONS: Adult asthma patients undergoing treatment with LTRAs exhibit lower incidence rates of common cold-like symptoms than those not receiving LTRAs. LTRAs play an important role in reducing the incidence of common cold-like symptoms among asthma patients and in suppressing exacerbation of asthma symptoms possibly associated with these symptoms.     

The conundrum of hyperuricemia, metabolic syndrome, and renal disease

The level of serum uric acid in human has been increasing over the last decades, and correlates with an increase prevalence of renal disease and metabolic syndrome. Understanding the role of uric acid in these conditions may provide clues for preventing the current epidemic of renal disease. Controversy still remains if hyperuricemia is simply a consequence or a cause of renal disease although epidemiological studies have attempted to resolve this issue. In this review, we discuss the clinical and experimental evidence for a causal role of hyperuricemia in renal diseases and potential relationships of hyperuricemia with metabolic syndrome. Supported by NIH grants HL-68607, DK-52121 and generous funds from Gatorade.