Claudin-6 is a single prognostic marker and functions as a tumor-promoting gene in a subgroup of intestinal type gastric cancer

Gastric Cancer - We aimed to identify novel tumor-promoting drivers highly expressed in gastric cancer (GC) that contribute to worsened prognosis in affected patients. Genes whose expression was...     

A case of parathyroid hormone-related peptide producing gallbladder carcinoma presenting humoral hypercalcemia of malignancy]

Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive.     

Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats.

Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP.     

Disposition characteristics of macromolecules in the perfused tissue-isolated tumor preparation.

Disposition characteristics of model macromolecules with different physicochemical characteristics and macromolecular prodrugs of mitomycin C, namely mitomycin C-dextran conjugates, were studied in tissue-isolated tumor preparations of Walker 256 carcinoma with the use of a single-pass vascular perfusion technique. In constant infusion experiments, all radiolabeled macromolecules accumulated in the tumor tissue, but the degree and pattern of distribution greatly varied, depending on their electric charges. Positively charged macromolecules were markedly accumulated compared with those that were neutral or negatively charged. In addition, their concentrations were significantly higher in viable than in necrotic regions, while neutral and negative compounds were distributed in necrotic rather than in viable regions. Pharmacokinetic analysis of tissue concentration-time courses of positively charged diethylaminoethyl and neutral dextrans showed that their movement occurred by convective fluid flow, and that high tissue accumulation of positively charged macromolecules could be explained by strong binding due to electrostatic interaction. For neutral and anionic macromolecules with negligible affinity to the tissue, it was suggested that the final concentration gradient between the viable and necrotic regions was decided by their tissue fluid content. Thus, the present study revealed the basic disposition characteristics of macromolecules in tumor tissue relative to their physicochemical properties.     

Familial spontaneous pneumothorax in three generations and its HLA

We experienced a case of familial spontaneous pneumothorax in three generations. Six of 13 family members had episodes of spontaneous pneumothorax. It is well established that there are some diseases associated with human leukocyte antigen (HLA). We performed HLA phenotyping for HLA of A, B and C. In our study, we detected the HLA haplotype A2, B61 in three of 4 who had episodes of spontaneous pneumothorax. The HLA haplotype A2, B70 were also detected in three of 4 who had episodes. This suggests that familial spontaneous pneumothorax might have hereditary factors.     

Continuous measurement of oxygen consumption using the reversed fick method

We developed a continuous oxygen consumption (Vo₂) measurement system employed the reversed Fick method, in which Vo₂ in computed from continuously measured sured arterial and mixed venous oxygen saturation assed by pulse oximetry and mixed venous oximetry, respectively, and cardiac output by the heat deprivation technique. This system was compared with the conventional intermittent reversed fick method in 7 patients during surgery and with indirect calorimetry in 4 intensive care unit (ICU) patients. The Vo₂ measured by the continuous reversed Fick method showed a high correlation with those simultaneously measured by the intermittent Fick method (r=0.97,P<0.01) and by indirect calorimetry (r=0.74,P<0.01). The 95% confidence limits (bias±2 SD) of the continuous reversed Fick method were −0.6±45 ml·min⁻¹ with the intermittent Fick method and −31±56 ml·min⁻¹ with indirect calorimetry. The continuous Fick method is in satisfactory agreement with the conventional methods for the measured of Vo₂ and potentially allows for convenient assessment of Vo₂ in critically ill patients. This study was supported in part by Grants-in-Aid for the Encouragement of Young Scientists 01771185 and 04857171 from the Ministry of Education, Science and Culture of Japan     

Electron microscopic study of monkey retina after photodynamic treatment

The purpose of this histological study was to determine the effects of photodynamic treatment, using a hematoporphyrin derivative and argon laser, on normal retinas of monkeys. Ten cynomolgus monkeys were treated with a hematoporphyrin derivative, given intravenously at a dose of 2.5 mg/kg. Forty minutes or 1 or 3 days after the injection, argon laser photoradiation was given over a 2.0-mm-diameter with a 10-min exposure and at an intensity of 40, 100, or 200 mW. The eyes were enucleated 1, 3, 4, 15, 18, 21, 35, or 38 days after the photoradiation and tissue samples were observed under a transmission electron microscope. The most fragile regions in the retina were the retinal nerve fibers, the outer segments of the visual cells, and the retinal pigment epithelium. Vascular endothelial cells were also fragile. The retinal capillary was easily obstructed, and the choriocapillaris was also occluded in an animal with severe retinal damage. The Mueller cells had the highest tolerance to the photodynamic treatment. Thus, exposing the normal part of the retina to light during photodynamic therapy should be avoided.