[MSI-high ascending colon cancer treated with second-line ipilimumab plus nivolumab for conversion surgery:a case report].

A 68-year-old woman with ascending colon cancer was the patient (cT4bN2M1a [LYM] cStage IVA, BRAF V600E mutation-positive, and MSI-high). She was given modified FOLFOXIRI as first-line therapy but did not respond. The infiltration of the primary lesion in the abdominal wall was alleviated, allowing conversion surgery to be performed.

Polyketides from the cultured lichen mycobiont of a Vietnamese Pyrenula sp.

A spore-derived mycobiont of a crustose Pyrenula sp. lichen collected in Vietnam was cultivated on a malt-yeast extract medium supplemented with 10% sucrose. Chemical investigation of the cultivated colonies led to the isolation of eight new alkylated decalin-type polyketides (1-8) along with three known compounds. The structures of these compounds were elucidated by spectroscopic and chemical means. This is the first instance of this type of polyketide being isolated from a cultured lichen mycobiont. The isolated polyketides 1 and 7 exhibited inhibitory activities against mammalian DNA polymerases α and ß with IC50 values ranging from 8.1 to 19.5 µM. Compound 1 showed cytotoxic effects against the HCT116 human colon carcinoma cultured cell line with an IC50 value of 6.4 ± 0.7 µM.

A 14-membered macrolide and isocoumarin derivatives from the cultured lichen mycobionts of Graphis vestitoides.

Spore-derived mycobionts of the crustose lichen Graphis vestitoides collected in Vietnam were cultivated on a malt-yeast extract medium supplemented with 10% sucrose. The investigation of their metabolites resulted in isolation of a novel 14-membered macrolide and a new isocoumarin, together with five known isocoumarin derivatives. Their structures were determined by spectroscopic and chemical means. This is the first instance of isolation of a 14-membered macrolide from a lichen mycobiont.

Molecular characterization and surfactant utilization of Scolecobasidium isolates from detergent-rich indoor environments.

Scolecobasidium, generally found in outdoor samples, were isolated from detergent-rich indoor environments. The isolates from bathrooms and washing machines, because of their exposure to detergents, might be genetically and biologically distinct from outdoor isolates. In this study, 11 Scolecobasidium isolates from detergent-rich indoor environments were examined to find the genetic and biological differences between the indoor and outdoor isolates. One isolate from a wall of a soap factory, showing similar conidia morphology with S. constricta, was phylogenetically distinct from the other Scolecobasidium spp. The 10 isolates from washing machines and bathrooms were identified as S. humicola, but these were classified into 2 groups that differed from the reference strain of S. humicola from leaves. All 11 isolates and the 4 reference strains of S. constricta and S. humicola grew on the medium containing sodium oleate and polyoxyethylene-(9)-lauryl ether, but the reference strains of the other Scolecobasidium spp. grew only on the medium containing sodium oleate. The results showed that S. humicola and S. constricta could utilize both surfactants generally included in soaps or synthetic detergents as nutrients. A further implication is that the genetic variation found in the S. humicola isolates from detergent-rich indoor environments can occur as a result of adaptation to such an environment.

Structure and biosynthesis of lecanopyrone, a naphtho[1,8-cd]pyran-3-one derivative from cultured lichen mycobionts of Lecanora leprosa.

From the cultures of spore-derived mycobionts of the lichen Lecanora leprosa a novel naphtho[1,8-cd]pyran-3-one derivative, lecanopyrone, was isolated. Its structure was determined by spectroscopic methods. The assembly pattern of acetate units in its biosynthesis was verified using sodium [1-13C]-acetate and sodium [1,2-13C2]-acetate.

Comparison of fungi found in bathrooms and sinks.

To identify the pathogenic fungi present in bathrooms, the growth of fungi collected from the drains of bathrooms was studied at various temperatures and compared with that of fungi from kitchen sink drains. Only a small number of fungi from bathrooms and sinks grew on media incubated at 37 degrees C, at which temperature the fungal count was about 1/600 of that at 25 degrees C. Although hot water is used more frequently in bathrooms than in sinks, the fungal counts at 37 degrees C were similar for bathrooms and sinks. Five species of fungus that can grow at 37 degrees C and were found to grow prolifically in bathrooms were identified using DNA and morphological analysis. In both bathrooms and sinks, Exophiala dermatitidis was predominant in culture at 37 degrees C. Moreover, E. dermatitidis grew at 40 degrees C and used surfactant as a nutrient. Thermotolerant fungi appear to inhabit bathrooms and all residential water appliances.

Growth characteristics of four fungal species in bathrooms.

The growth of four fungal species (four isolates) from bathrooms was examined under various environmental conditions. These fungi were found several times in bathrooms and washing machines, but not in other indoor environments such as house dust or windows. The four species (Ramichloridium strelitziae, Cyphellophora laciniata, Phoma fimeti, and Exophiala sp.) were identified using DNA and morphological analyses. These bathroom fungi were able to consume surfactants, soap and shampoo, but were unable to grow well in high-temperature or dry conditions. Soap and shampoo seem to affect fungal flora in the bathroom.

Fungal growth on anion surfactant medium.

Before the present study, no fungi using anion surfactant as a nutrient had been identified, although some fungi were known to use nonion surfactant. Washing water collected from 63 washing machines was inoculated onto 0.1% LAS (Sodium dodecyl benzenesulfonate) anion surfactant media to identify fungi that can feed on anion-surfactant. Small dark colonies of fungi were found on several of the Petri-dishes from 12 days after inoculation. These were identified as Cladophialophora boppii and Exophiala spinifera using morphological features and rDNA data. A number of the isolates of C. boppii specifically were recognized as using anion surfactant as a nutrient. The growth characteristics of the two fungal species were examined on surfactant media of three kinds. Apart from anion surfactant, the fungi were also able to grow on nonion surfactant and on soap. The application of these fungi for environmental cleansing after detergent pollution is also discussed.

Ochroconis Species Isolated from Limestone Areas as the Origin of Indoor Ochroconis.

The molecular, morphological, and physiological features of 42 strains of Ochroconis collected from many limestone areas were studied. Ochroconis strains are often found in limestone areas, although they have rarely been found in other wild areas, e. g. forests. Moreover, many strains from these areas grew on alkaline media (pH 9.7) and media with soap. They were phylogenetically more variable than Ochroconis strains previously found indoors or at city parks. Thus, the Ochroconis strains are thought to have adapted to the alkaline soil, specifically found in limestones. It is assumed that some strains of Ochroconis originally grew in the limestones and immigrated into park soils with the fine dust of cement and into indoor environments. More species of Ochroconis, with the ability to use surfactants as nutrients, are distributed in limestone areas than indoors or in city parks. Moreover, these fungi were found randomly in the phylogenetic trees of Ochroconis. Although only O. humicola was often found indoors and used surfactants, this fungus was newly found in the limestone areas of Okinawa Prefecture. Ochroconis humicola originally grew outdoors and seems to have immigrated to and propagated indoors. Thus, this species may have originated from the subtropical limestone areas.

Biosynthetic origin of graphenone in cultured lichen mycobionts of Graphis handelii.

The biosynthetic origins of the carbon skeleton in graphenone were verified by feeding the culture of spore-derived mycobionts of the lichen Graphis handelii with sodium [1-13C]-acetate, sodium [1,2-13C2]-acetate, sodium [2-13C]-pyruvate, [1,2,3-13C]-glycerol, [13CH3]-methionine and sodium [1,4-13C2]-succinate.

Molecular and Biological Differences Among Ochroconis Strains Collected from Indoor and Outdoor Environments.

The molecular, morphological, and physiological characters of 55 Ochroconis strains collected from indoor and outdoor environments were studied. In Japan, Ochroconis species are often found in indoor detergent-rich environments, such as bathrooms and washing machines, and the predominant species have been identified as O. humicola, similar to that in other Asian and European countries. Although Ochroconis species have rarely been found in outdoor environments such as mountains, forests, and agricultural fields, in the present study, Ochroconis strains were specifically isolated from the soils of urban city parks. Phylogenetic analysis conducted using the 28S ribosomal RNA (28S rDNA) gene sequence showed that almost all of the Ochroconis strains found in indoor environments (i.e., water supply) were O. humicola. Although city parks were often surrounded by residences, more than half of the Ochroconis strains collected from the soils of city parks examined in this study were different Ochroconis species. The ability to use detergents as nutrients was found in a new genetic group (probably a new species) isolated from the soils of city parks as well as in O. humicola and O. constricta. Ochroconis humicola is assumed to adapt mostly to indoor environments and to penetrate from the outdoors, e.g., soils of urban areas. To elucidate the factors promoting indoor fungal predominance, the ability of using surfactants as nutrients was compared among these three species. Additionally, growth under alkaline and drought conditions, and heat tolerance were examined. Indoor predominance of O. humicola compared to that of the other two species was attributed to the ability of using a non-ionic surfactant as nutrient and to growth under alkaline conditions.

Expression of estrogen receptor-alpha protein in the rat digestive tract.

The current study evaluates the expression of estrogen receptor-alpha (ER-alpha) protein in the digestive tract and other organs using immunohistochemistry in male and female intact rats. As a result, the expression of ER-alpha protein was intensively immunoreactive in the nuclei of squamous epithelium of the forestomach connected to the limiting ridge and the anus connected to the anorectal junction. Rat ER-alpha mRNA signals were also detected in the epithelium of the limiting ridge using in situ hybridization. The incidence of ER-alpha protein in the limiting ridge decreased with age in both males and females. The incidence of ER-alpha protein in the anorectal junction strongly decreased with age in males, although the incidence did not decrease with age in females. In conclusion, it was suggested that estrogen may be involved in the proliferation and differentiation of these cells in the limiting ridge of the stomach and anorectal junction of rats.

Porcine model of auxiliary partial orthotopic liver transplantation for acute liver failure.

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has been an effective alternative in acute liver failure (ALF), but clinically several problems remain to be resolved. Thus, we attempt to establish an APOLT model for ALF using a large animal and demonstrate the validity of our model. METHODS: In experiment 1, we created an animal model of ALF using pig. ALF was induced by resection of 70% of the whole liver under total hepatic vascular exclusion (THVE). The duration of ischemia was 90 minutes. In experiment 2, we tried to make an APOLT model by using this ALF model as a recipient. That is, during 90 minutes of THVE, 70% hepatectomy and subsequent partial orthotopic transplantation was completed. RESULTS: In experiment 1, six of seven pigs died within three days with jaundice and massive ascites. Based on microcirculatory disturbance of the remnant liver and hepatocellular necrosis, 70% hepatectomy with 90 minutes of THVE was considered a proper model of ALF. In experiment 2, six out of seven APOLT model animals survived more than four days. T. Bil levels in the APOLT model remained consistently within the normal range throughout the observation period. In immunohistochemistry, several labeled nuclei stained with Ki67 were identified in native liver of the APOLT model. CONCLUSIONS: This APOLT procedure provided temporary liver function support and enabled the recipient to survive until the failing native liver had regenerated. Our APOLT model could be suitable and useful for understanding the role of APOLT in ALF.

Monomeric and dimeric dibenzofurans from cultured mycobionts of Lecanora iseana.

Spore-derived mycobionts of the lichen Lecanora iseana were cultivated on a malt-yeast extract medium supplemented with 10% sucrose and their metabolites were investigated. Four 3,7-dihydroxy-1,9-dimethyldibenzofuran derivatives along with the known 3,7-dihydroxy-1,9-dimethyldibenzofuran and five norlichexanthone derivatives were isolated. Their structures were determined by spectroscopic methods.

Influence of preoperative administration of omega-3 fatty acid-enriched supplement on inflammatory and immune responses in patients undergoing major surgery for cancer.

OBJECTIVE: Polyunsaturated fatty acid supplementation may produce beneficial effects after surgery. We investigated the influence of preoperative administration of a supplement rich in arginine, omega-3 fatty acids, and RNA, Impact (Japan), on inflammatory and immune responses in patients undergoing major surgery for cancer. METHODS: Patients in the supplement group (n = 12) received 1 L/d of Impact (Japan) for 5 d before surgery, and those in the control group (n = 14) received an ordinary diet without Impact (Japan) before surgery. Plasma levels of omega-3 and omega-6 fatty acids, thromboxane B(2), prostaglandin E(2), inflammatory markers, nutritional markers, cytokines, and cytokine receptors were obtained 5 d before the operation at the starting point of supplementation in the supplement group. Samples were collected on postoperative days (PODs) 0, 1, 3, and 7. RESULTS: After taking the supplement, significant increases in omega-3 fatty acids and rapid turnover proteins were found the day after ending supplementation (POD-0), whereas thromboxane B(2) levels and the ratio of omega-6 fatty acids to omega-3 fatty acids were significantly lower than before supplementation (P < 0.001). On POD-0 only, inflammatory markers and cytokine receptors in the supplement group showed low levels in comparison with the control group (P < 0.05). On POD-1 and POD-3, remarkable decreases in polymorphonuclear leukocyte-elastase and interleukin-8 in the supplement group were observed. CONCLUSION: Our findings suggest that oral administration of a supplement rich in omega-3 fatty acids for 5 d before surgery may improve not only preoperative nutritional status but also preoperative and postoperative inflammatory and immune responses in patients who have cancer.

6H-dibenzo[b,d]pyran-6-one derivatives from the cultured lichen mycobionts of Graphis spp. and their biosynthetic origin.

The spore-derived mycobionts of the lichen Graphis prunicola, G. cognata and G. scripta were cultivated on a malt-yeast extract medium supplemented with 10% sucrose and their metabolites were investigated. Graphislactones A-D were isolated from the cultures of G. prunicola, while alternariol and graphislactones A and C were isolated from those of G. cognata. From the cultured mycobionts of G. scripta, a new 6H-dibenzo[b,d]pyran-6-one derivative, graphislactone E with graphislactones A and C was obtained. On the other hand, cultivation of the mycobionts of G. prunicola on a malt-yeast extract medium supplemented with 2.5% sucrose and 0.25% sodium acetate produced two new metabolites, graphislactones E and F. Their structures were determined by spectroscopic methods. The biogenetic origin of the carbon skeleton in both compounds was verified by administering sodium [1-13C]-acetate and sodium [1,2-13C(2)]-acetate.

Three isocoumarins and a benzofuran from the cultured lichen mycobionts of Pyrenula sp.

The spore-derived mycobionts of the lichen Pyrenula sp. were cultivated on a malt-yeast extract medium supplemented with 10% sucrose. The investigation of their metabolites resulted in isolation of four compounds, three isocoumarins and a biogenetically related benzofuran; their structures were determined by spectroscopic methods.

Recurrent nonocclusive mesenteric ischemia after resection of iliac artery aneurysm.

A case of recurrent nonocclusive mesenteric ischemia in a patient with isolated internal iliac artery aneurysm penetrating the sigmoid colon is described. On the day after the aneurysm and the sigmoid colon had been resected, the patient developed necrosis of the left hemicolon. Fourteen and nineteen days after left hemicolectomy, massive intestinal bleedings occurred, requiring ileectomy. On the basis of operative findings of good pulsation of visceral arterial branches; angiography showing patent mesenteric vessels with some spasms; and pathological findings suggesting mesenteric ischemia, these ischemic events were diagnosed as nonocclusive mesenteric ischemia. Low-output syndrome induced by massive intestinal bleeding and atrial fibrillation and sepsis were responsible for the establishment of the nonocclusive mesenteric ischemia. Development of disseminated intravascular coagulation and continuous administration of diuretics for acute renal failure seemed to have further perturbed the mesenteric circulation. The patient died of subsequent multiple organ failure 4 months after the first operation. We should pay more attention to nonocclusive mesenteric ischemia in patients with mesenteric ischemia, and strict circulatory management during the perioperative period is essential in these patients.

Serotonin activity and liver dysfunction following hepatic ischemia and reperfusion.

Serotonin (5-hydroxytriptamine; 5-HT), which is stored in platelets, is known to induce vasoconstriction and promote platelet aggregation. More recent studies suggest that serotonin also plays a role in organ injury after ischemia and reperfusion. The purpose of this study was to characterize the role of 5-HT and platelet function in the pathogenesis of hepatic ischemia-reperfusion injury. Under the portocaval shunt, 60 or 90 min of complete warm ischemia of canine liver was induced by Pringle's maneuver, followed by reperfusion for 120 min. Time-matched, sham-operated animals served as controls. Hepatic tissue blood flow and various parameters of hepatic vein blood (ALT, LDH, platelet count and platelet aggregation) were measured before and after reperfusion. 5-HT levels in portal vein and hepatic vein were also assayed. Hepatic ischemia and reperfusion resulted in liver hypoperfusion, hepatocellular dysfunction, increased platelet aggregation, increased 5-HT levels, and hepatic microcirculation injury. These results suggest that the endogenous 5-HT released from platelet may contribute to liver tissue hypoperfusion following hepatic ischemia-reperfusion.

A rare case of gastric lipoma with early gastric cancer.

An 84-year-old man was admitted to our hospital with a 1-month history of epigastralgia. Upper gastrointestinal endoscopy revealed gastric cancer and a gastric submucosal tumor (SMT) on the greater curvature of the gastric body. By endoscopic ultrasonography, SMT was demonstrated as a well-circumscribed, smooth-bordered and hypoechoic mass localized in the submucosal layer. Total gastrectomy was performed. The histology of the resected specimen revealed a gastric lipoma and an early gastric cancer widespread to the surface on the lipoma. Two lesions were present in the same lesion, but not linked. We report a rare case of gastric lipoma complicated with early gastric cancer.