Heterotransplantation of experimentally induced dog stomach adenocarcinoma to nude mice.

Heterotransplantation of gastric adenocarcinoma, induced in dog by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) has been attempted to nude mouse. Biopsied materials from Borrmann 3 type carcinoma, which showed signet-ring cell carcinoma at the subcardiac region of a beagle dog, were inoculated into the muscles of the hind legs of BALB/c-nu/nu nude mice. Serial transmission was obtained in 2 lives, so far 4-5 passages. The histological findings of the grafts were mainly poorly differentiated adenocarcinomas.     

Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.     

Characterization of [3H]brevetoxin binding to voltage-dependent sodium channels in adrenal medullary cells

We have previously reported that in bovine adrenal chromaffin cells Ptychodiscus brevis toxin-3 (PbTx-3) does not alter the veratridine-induced ²²Na influx when given alone, but increases the influx of ²²Na when co-applied with either - or -scorpion venom (Wada et al. 1992). In the present study, we characterized [³H]PbTx-3 binding in bovine adrenal chromaffin cells. [³H]PbTx-3 binding was saturable, reversible and of high-affinity with an equilibrium dissociation constant (K_d) of 32.0±4.9 nmol/1 and a maximum binding capacity B_max of 6.2 ± 1.2 pmol/4 × 10⁶ cells (4.5 ± 0.9 pmol/mg cell protein). A Hill plot revealed the lack of cooperative interaction among the binding sites. Unlabelled PbTx-3 inhibited [³H]PbTx-3 binding with an IC₅₀ of 31 nmol/l. However, tetrodotoxin, veratridine, - and -scorpion venom, or veratridine in combination with either - or -scorpion venom did not alter [³H]PbTx-3 binding. All these results suggest that PbTx-3 binds to a site (site 5) distinct from the previously known four toxin binding sites, which does not gate voltage-dependent Na channels by itself, but is specifically involved in the allosteric modulation of Na channels in adrenal medullary cells. Correspondence to: A. Wada at the above address     

Internal mammary artery embolization for hemoptysis

PURPOSE: The purpose of this study was to determine the factors influencing development of blood supply from the internal mammary artery and to discuss the value of embolization of the abnormal branches from this vessel using small particles following occlusion of the normal distal branches using microcoils in treating hemoptysis. MATERIAL AND METHODS: Five patients with hemoptysis underwent internal mammary artery embolization with coaxial microcatheter systems. Bronchoscopy, chest radiographs, and CT were performed to determine the site and extent of the basic disease before embolotherapy in all patients. RESULTS: In all patients, pulmonary lesions had extended from the lung to the adjacent pleural surface at the anterior lung field. Four patients underwent embolization from the proximal portion of the internal mammary artery following distal coil embolization. One patient who underwent only proximal embolization had recurrent bleeding. CONCLUSION: The internal mammary artery contributes to the perfusion of lesions responsible for hemoptysis when the basic lesion involves the pulmonary parenchyma adjacent to the anterior pleural surface. Initial distal occlusion of the internal mammary artery may improve the efficacy of embolization of this artery for hemoptysis.     

Endosonography during endoscopic mucosal resection to enhance its safety

BACKGROUND: We have performed endoscopic mucosal resection of the esophagus (172 cases), stomach (102 cases), and colon (28 cases) using a transparent plastic cap. Because the lesion-bearing mucosa is suctioned up inside the cap under endoscopic suction, the mucosa should be dissected sufficiently from the proper muscle layer to prevent perforation. METHODS: To avert the risk of perforation, we introduced endosonographic assessment of submucosal dissection (47 cases). In all cases, just keeping the ultrasonic probe on the surface of the mucosa allowed us to evaluate whether the mucosal lesion was lifted up sufficiently from the proper muscle layer after local saline injection. RESULTS: It was possible to confirm that the muscle layer was kept outside the strangulating snare by the same procedure (32 of 37 cases, 86.5%). CONCLUSIONS: We experienced five muscular resections in cases without the ultrasonic probe and no muscular resection with the ultrasonic probe. Thus we recommend endosonographic assessment during endoscopic mucosal resection to enhance its safety.     

Handlebar hernia with intra-abdominal extraluminal air presenting as a novel form of traumatic abdominal wall hernia: Report of a case

An 18-year-old male was admitted to our Emergency Department with a traumatic abdominal wall hernia (TAWH) of the left lower quadrant (LLQ) after suffering hypogastric blunt injury and urogenital lacerations in a motorcycle accident. Upright chest X-ray showed a small amount of right infradiaphragmatic free air, and a computed tomographic (CT) scan demonstrated an abdominal wall hernia. At surgery, no impairment was found in the digestive tract, and an abdominal herniorrhaphy was performed. It is suggested that the free air had passed through a connection between the scrotal laceration and the contralateral abdominal defect via the subcutaneous space and was palpated as emphysema. This is a new type of TAWH, which suggests that blunt abdominal trauma may result in negative pressure in the subcutaneous and peritoneal cavity, and this could reflect the pathophysiology of TAWH.     

Modification of low density lipoprotein potentiates its inhibitory effect on catecholamine secretion in cultured bovine adrenal medullary cells

Low density lipoprotein (LDL) and lipoprotein(a) suppress catecholamine secretion in cultured adrenal medullary cells. Modification of LDL by oxidation or acetylation potentiates various atherogenic actions of LDL. In the present study, we investigated whether the modification of LDL influences catecholamine secretion in cultured bovine adrenal medullary cells. The exposure of LDL to CuSO₄ caused a time-dependent oxidation of LDL. Maximal oxidation of LDL was observed after exposure to CuSO₄ for 24 h. Native LDL inhibited catecholamine secretion induced by carbachol to 68.5% of control. Oxidized LDL caused further inhibition of carbachol-evoked secretion to 37.6% of control. Acetylated LDL inhibited it to 41.0% of control. There was a good correlation between the extent of LDL oxidation and the inhibition of catecholamine secretion. These results suggest that oxidation or acetylation of LDL augments its inhibitory effect on the secretion of catecholamines. Since catecholamines are a risk factor of atherosclerosis, the inhibitory effect by such modified LDL may be a mechanism inhibiting atherosclerotic progression. Received: 29 January 1999 / Accepted: 19 April 1999 / Published online: 22 June 1999     

A mild transient decrease of peripheral red blood cell counts induced by a suprapharmacological dose of pegylated human megakaryocyte growth and development factor in rats.

Previous studies have shown that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) at suprapharmacological dose induces a mild transient decrease of red blood cell counts according to thrombopoiesis in normal mice. To unravel the mechanism underlying this mild transient decrease of red blood cells, we have studied the effect of PEG-rHuMGDF on the circulating plasma and blood volume, and the serum biochemical parameters of anaemia and splenectomy. Also, we have performed histological studies of the bone marrow and the spleen of PEG-rHuMGDF-treated rats. PEG-rHuMGDF (300 microg kg(-1)]) or vehicle was subcutaneously administered to rats once a day for up to five days. From day 6 after the start of PEG-rHuMGDF administration, the platelet counts and plateletcrit levels were significantly increased, reaching peak values on day 10, and recovering to normal by day 20. The red blood cell counts and the haematocrit levels were significantly decreased on day 6 to 13. The decreases in red blood cell levels and haematocrit produced by PEG-rHuMGDF treatment were mild and had recovered by day 15. The plasma and blood volumes were significantly increased on day 10 in PEG-rHuMGDF-treated rats. No alteration of the serum biochemical parameters for anaemia, iron or total bilirubin, were observed on day 10. The histological examination on day 10 revealed a marked increase in megakaryocytes and a slight decrease in erythropoiesis in the bone marrow of rats that received PEG-rHuMGDF (300 microg kg(-1)). There was also a slight increase in splenic megakaryocytes and erythropoiesis. The decrease of red blood cells by PEG-rHuMGDF was not affected by splenectomy. These results suggest that the mild transient decrease of red blood cells induced by PEG-rHuMGDF treatment for up to five days is based mainly on the increases in the plasma and blood volume. These events are secondary changes due to the regulation of the excess production of megakaryocytes in the marrow and the peripheral platelets.