PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

Leukocyte-Endothelium Interaction in the Rat Mesenteric Microcirculation during Halothane or Sevoflurane Anesthesia

Background: The effects of inhalational anesthetics on the microcirculation, including leukocyte dynamics, remain to be clarified. The authors investigated halothane and sevoflurane anesthesia to determine if these agents evoked leukocyte adhesion through endothelial cell-dependent mechanisms involving such adhesion molecules.

Methods: Rats were anesthetized with halothane or sevoflurane in 100% oxygen and the lungs were mechanically ventilated. Leukocyte behavior in mesenteric venules was recorded through intravital video microscopy under monitoring microvascular hemodynamics. To examine the mechanisms for leukocyte rolling and adhesion, these studies were repeated after animals were pretreated with a monoclonal antibody against P-selectin (MAb PB1.3) or against intracellular adhesion molecule-1 (ICAM-1; MAb 1A29): P-selectin required for rolling of circulating leukocytes and ICAM-1 for firm adhesive interactions with leukocyte integrins.

Results: Under baseline anesthetic conditions (1 minimum alveolar concentration [MAC]), venular wall shear rates, an index of the disperse force on marginating leukocytes, in the sevoflurane-treated rats were about two times higher than those with halothane. At 2 MAC, halothane caused a marked arteriolar constriction and decreasing shear rates concurrent with an increasing density of venular leukocyte adhesion. Sevoflurane at 2 MAC induced leukocyte rolling and adhesion, which were attenuated by PB1.3 and 1A29, without alterations in the wall shear rates. Halothane-induced leukocyte adhesion was not prevented by PB1.3 but it was by 1A29.     

Response of Müller cells following experimental lensectomy-vitrectomy

We used morphological, biochemical and immunohistochemical methods to assess the response of Müller cells after experimental lensectomy-vitrectomy in rabbits. We observed widened intercellular spaces between the Müller cells and nerve fibers of ganglion cells, and increased electron opacity in the Müller cells of eyes injected with silicone oil. No apparent morphological changes were detected in the Müller cells of air-injected eyes. The specific and total activities of Müller cell-marker enzymes (glucose 6-phosphatase and glutamine synthetase) showed an initial increase, followed by a decrease. Glial fibrillary acidic protein immunoreactivity was not found in the Müller cells of the normal rabbit retina but was exhibited after surgery. Our results showed that markers of Müller cells associated with glycogenolysis and/or gluconeogenesis, glutamate-glutamine cycle and cytoskeletal protein metabolism were affected by the experimental lensectomy-vitrectomy.     

Early seizures after acute ischemic stroke]

In order to determine predictive factors of early seizures (ES) after acute stroke and to estimate prognosis, we retrospectively examined clinical data of 1,743 consecutive patients with acute ischemic stroke. The subjects were divided into two groups; an ES group (19 patients) and a non-ES group (1,724 patients). Multivariate statistical analysis revealed that the NIH-Stroke Scale score on admission (/10, OR, 1.1: 95% CI 1.04 to 1.13) and positive past history of cerebrovascular disease or brain injury (OR, 3.85: 95% CI 1.49 to 9.95) are significant factors to predict ES. There was no significant difference in the outcome between the two groups. A recurrence of seizures, after follow up for 4 to 40 months, was observed only in one patient with a history of ES.     

Association of BRCA2 polymorphism at codon 784 (Met/Val) with breast cancer risk and prognosis.

PURPOSE: The association of BRCA2 polymorphisms at codon 372 [Asn (N)/His (H)]and codon 784 [Met (M)/Val (V)] with breast cancer risk was evaluated in Japanese women. In addition, the prognostic significance of these polymorphisms was studied in breast cancer patients. EXPERIMENTAL DESIGN: A case-control study was conducted to examine the association of the BRCA2 N/H372 polymorphism and M/V 784 polymorphism with breast cancer risk (cases = 149, controls = 154). The prognostic significance of these polymorphisms was evaluated in 139 patients with primary breast cancer. RESULTS: No significant association was observed between the N/H372 polymorphism and breast cancer risk. In contrast, a significant increase in breast cancer risk (odds ratio, 2.03; 95% confidence interval, 1.07-3.87) was observed in carriers of the variant allele (V784) of the M/V784 polymorphism as compared with noncarriers after adjustment for the classical risk factors, age, family history, parity, body mass index, and so forth. Among breast cancer patients, various clinicopathological parameters including menopausal status, tumor size, lymph node status, histological grade, and estrogen-receptor status were not significantly different between the carriers and noncarriers of the variant allele with regard to both N/H372 and M/V784 polymorphisms. The N/H 372 polymorphism was not significantly associated with patient prognosis. On the other hand, breast cancer patients carrying the variant allele of M/V784 polymorphism showed a significantly (P = 0.014) lower 3-year disease-free survival rate (63%) than noncarriers (92%). Multivariate analysis has revealed that the M/V784 polymorphism is a significant prognostic factor, being independent of the other conventional prognostic factors such as lymph node status and estrogen receptor status. CONCLUSION: These results suggest that the M/V784 polymorphism, but not the N/H372 polymorphism, would be useful in the selection of women at high risk for developing breast cancer and would also serve as a clinically useful prognostic factor in breast cancer patients.     

Acute type a aortic dissection complicated with acute inferior myocardial infarction following aortic valve replacement

Acute aortic dissection complicated with acute myocardial infarction (AMI) is the most fatal situation. We experienced the successful treatment for acute type A aortic dissection complicated with inferior AMI following aortic valve replacement (AVR). A 60-year-old man had had AVR for aortic regurgitation. Sixteen months after the AVR, he had a sudden onset of severe chest pain with complete atrioventricular block. Immediately, temporary pacing and cardiac catheterization were conducted, showing the occlusion of the right coronary artery due to acute type A aortic dissection. On his way to our hospital, direct current shock was conducted 3 times for ventricular fibrillation. We replaced the ascending aorta combined with coronary artery bypass grafting and the postoperative course was uneventful. The key to treat acute aortic dissection complicated with AMI is early accurate diagnosis, prompt temporary pacing for bradycardia, defibrillation for lethal arrhythmia and insertion of a perfusion catheter if possible. These preoperative hemodynamic stabilization gives us the chance to save these patients.     

Neutrophil elastase inhibitor reduces hepatic metastases induced by ischaemia-reperfusion in rats.

OBJECTIVE: To investigate the possibility in rats that ONO-5046 Na, a new recombinant inhibitor of neutrophil elastase, can reduce hepatic metastases induced by ischaemia-reperfusion. DESIGN: Laboratory experimental study. SETTING: Research laboratory, Japan. SUBJECTS: Male Fischer rats. INTERVENTIONS: Rats underwent 60 min of 70% partial hepatic ischaemia, after which rat colon adenocarcinoma cells (RCN-H4) were injected into the spleen. The animals were divided into two test groups and a control group. One group was given ONO-5046 Na intravenously at 10 mg/kg/hour. A second group was given a saline solution for the same period, while the controls were not made ischaemic. MAIN OUTCOME MEASURES: Three weeks after inoculation, the number of tumour nodules on the liver surface was counted. The anti-cancer effect of ONO-5046 Na was measured by monotetrazolium assay. RESULTS: Hepatic ischaemia-reperfusion increased the number of liver metastases of RCN-H4 in both clamped and unclamped hepatic lobes. ONO-5046 Na significantly inhibited this in unclamped lobes, but had no anti-cancer effect. CONCLUSION: Neutrophil elastase may have an important role in increasing haematogenous liver metastases by ischaemia-reperfusion, particularly in unclamped lobes.     

Alternative Expression of a Chitosanase Gene Produces Two Different Proteins in Cells Infected withChlorellaVirus CVK2

SeveralChlorellavirus CVK2 proteins had chitosanase and/or chitinase activities. A gene coding for an ORF of 328 amino acids (aa) with a predicted molecular mass of 36,769 Da was cloned from the viral genome. The predicted amino acid sequence of an N′-portion (174 aa) of this gene product (vChta-1) showed 22 to 25% identity with various bacterial chitosanases. A glutathioneS-transferase (GST)–vChta-1 fusion protein had strong chitosanase activity. Western blot analysis with antisera raised against the vChta-1 protein identified two proteins of 37 and 65 kDa in virus-infectedChlorellacells beginning at 240 min postinfection and continuing until cell lysis. The larger protein was packaged in the virion, while the smaller one remained in the cell lysate. Both chitosanase proteins were produced from the single gene,vChta-1,by a mechanism of alternative gene expression.