Identification of N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo[4,5-f)quinoxaline 3',5'-diphosphate, a major DNA adduct, detected by nuclease P1 modification of the 32P-postlabeling method, in the liver of rats fed MeIQx

The carcinogenic heterocyclic amine 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline(MeIQx) is widely distributed in cooked foods. The nucleaseP1 method increased the sensitivity of the standard ³²P-postlabelinganalysis about 1000-fold for detection of MeIQx-DNA adducts.The recovery of MeIQx-DNA adducts by the nuclease P1 methodwas determined to be about 50% using liver DNA of a rat treatedwith [¹⁴C]MeIQx intragastrically. By the nuclease P1 methodfive adducts were detected in the liver DNA of rats fed MeIQxand two of them, including the most abundant one, were identifiedas MeIQx-deoxyguanosine adducts by comparison with the adductsformed in in vitro reactions of N-acetoxy-2-amino-3,8-dimethylimidazo[4,5-f)quinoxalinewith the four 2'-deoxyribonucleotides. The most abundant adductin vivo was identified as N²-(deoxyguanosin-8-yl)-MeIQx 3',5'-diphosphate(3',5'-pdGp-C8-MeIQx). MeIQx-DNA adduct levels in human tissuescould be determined by the nuclease P1 modification of the ³²P-postlabelingmethod in combination with HPLC, and thus provide informationon the roles of MeIQx in human carcinogenesis.     

Voltage -dependent suppression of calcium current by caffeine in single smooth muscle cells of the guinea-pig urinary bladder

The suppressive action of caffeine on l,-type Ca current (Ica) in smooth muscle cells of the guinea-pig urinary bladder was investigated using the whole-cell patch clamp technique. Caffeine (5–30 mM) suppressed Ica, the effect having two phases: a rapid and transient suppression of Ica, which was followed by a sustained suppression. When intracellular Ca⁺ was strongly buffered by the Ca⁺ chelator EGTA (20 mM) or BAPTA (5 mM) in the patch pipette, the transient suppression of Ica was abolished, whereas the sustained effect remained. Similarly, inclusion of both 10 mM procaine and 1 mg/ml heparin in the patch pipette blocked the transient suppression of Ica, but did not block the sustained effect. The degree of the sustained effect of caffeine on Ica was dose-dependent with a _d of 20 mM. Application of the cyclic AMP analogue, 8-bromo-cyclic AMP (100 M) or forskolin (10 M) to the bath failed to mimick the sustained suppression of Ica, suggesting that inhibition of phosphodiesterase activity was not involved in the caffeine action. The steady-state activation curve remained unchanged by 10 mM caffeine but the steady-state inactivation curve was significantly shifted in the negative direction by 15.6 mV in 1.8 mM Ca²⁺ solution or by 10 mV in 1.8 mM Ba²⁺ solution. From these results it appears that caffeine inhibits L-type Ica via two mechanisms: (1) it releases Ca²⁺ from an internal store causing a transient Ca²⁺-mediated inactivation of the Ca channel; (2) it inhibits Ca channel via a mechanism that does not require such a Ca²⁺ release. It is possible that caffeine suppresses Ica through a preferential binding to the inactivated state of l-type Ca channel.     

Apolipoprotein E ɛ4 allele distribution in Wernicke-Korsakoff syndrome with or without global intellectual deficits

Summary Recent genetic studies show that the apolipoprotein E (ApoE) 4 allele is a risk factor for Alzheimer's disease (AD). Whether this allele is associated with other dementing diseases is the next important question. The information could provide a clue to the pathogenetic role of ApoE. In the present study, patients with Wernicke-Korsakoff syndrome (WKS) of alcoholic etiology were divided into two groups according to the severity of intellectual deficits, i.e., those of classical Korsakoff patients with preserved intellectual function other than amnesia and those with global intellectual deficits. Genotyping showed that the frequency of ApoE 4 allele was significantly higher in the patients with global deficits, suggesting the involvement of this allele in the intellectual decline of WKS. In contrast, distributions of other two markers, 1-antichymotrypsin and presenilin-1, did not differ between the two groups. These results added further support to the notion that the consequence of acute insult to the brain is influenced by the ApoE genotype, and suggested ApoE's role in the development of a certain group of alcoholic dementia.     

Calcineurin Inhibitor–Induced Pain Syndrome in ABO-Incompatible Living Kidney Transplantation: A Case Report

Background

Calcineurin-inhibitor–induced pain syndrome (CIPS) was used as a reference in the literature as reflex sympathetic dystrophy syndrome related to calcineurin inhibitors. Much of the literature describes CIPS that occurred after kidney and bone marrow transplantation. We describe a rare case of CIPS in induction immunosuppression before kidney transplantation, under administration of an anti-rheumatoid drug.

Development and evaluation of the ambulatory relative metabolic rate (RMR) realtime monitoring system

Development of an ambulatory RMR monitoring system for evaluating the physical work-load is presented. This system can be used under special conditions where it is difficult to use the traditional "Douglas" method. The main features of this system are: Using an improved turbin-spirometer to measure expiratory gas volume, data-processing procedure is simplified by converting a 0.1 iota expiratory gas volume to an electric pulse signal. Utilizing a Galvanic-cell type sensor, a kind of porlarograph electrode, to measure oxygen concentration in expiratory gas, the temperature of the electrode is maintained constantly at 40 degrees C in order to stabilize the output of the sensor against change in environmental and expiratory gas temperature. To improve the accuracy measurement of oxygen concentration and to prevent the teflon membrane at the top of the electrode from chilling and vibrating by direct expiratory gas flow, the bypass stream line is led to the electrode and a small portion of expiratory gas is introduced to measure oxygen concentration. It is possible to measure the time-sequential RMR value for several hours by minimizing and lightening the measuring instruments. It is possible to measure the time-sequential changing characteristics of the physical work-load (RMR), heart rate, breathing rate, and skin temperature under the actual work environment by a telemetring or portable recording method.     

Extranodal NK/T-cell lymphoma of the nasal cavity developed in a patient with intestinal Epstein–Barr virus-positive T/NK-cell lymphoproliferative disorder

Extranodal NK/T cell lymphoma, nasal type (ENKL) developed in a patient with intestinal Epstein-Barr virus (EBV)-positive T/NK-cell lymphoproliferative disorder (LPD). The patient was a 46-year-old Chinese man who complained of diarrhea and abdominal pain without immune-deficiency. Endoscopy demonstrated ileum ulcers like Crohn’s disease, without histological granulomas. His symptoms continued waxing and waning for 3 years until he developed overt lymphoma (ENKL) in the nasal cavity. The ileum lesions exacerbated into a large deep ulcer, and the biopsy specimens from the ileum, including the one 3 years ago, showed infiltration of small lymphocytes containing many EBV-positive T/NK cells without atypia. Thus, the patient illness of intestine was revealed as intestinal EBV-positive T/NK-cell LPD, which might be closely associated with development of ENKL in this patient. In cases of inflammatory bowel disease without typical clinical courses and histological findings, check-up of EBV in the biopsy might help correct diagnosis.     

Wound,pressure ulcer and burn guidelines – 1: Guidelines for wounds in general,second edition

The Japanese Dermatological Association prepared the clinical guidelines for the “Wound, pressure ulcer and burn guidelines”, second edition, focusing on treatments. Among them, “Guidelines for wounds in general” is intended to provide the knowledge necessary to heal wounds, without focusing on particular disorders. It informs the basic principles of wound treatment, before explanations are provided in individual chapters of the guidelines. We updated all sections by collecting references published since the publication of the first edition. In particular, we included new wound dressings and topical medications. Additionally, we added “Question 6: How should wound-related pain be considered, and what should be done to control it?” as a new section addressing wound pain, which was not included in the first edition.