Unilateral acute eosinophilic pneumonia on the operative side: A case 9 years after lung lobectomy.

The typical clinical manifestation of acute eosinophilic pneumonia is acute onset of respiratory symptoms due to smoking or medication use, accompanied by bilateral ground-glass opacity with consolidations on chest radiography. However, differential diagnosis with acute eosinophilic pneumonia should not be excluded in cases of unilateral pneumonia of postoperative lung.

A Nano-Emulsion Containing Ceramide-like Lipo-Amino Acid Cholesteryl Derivatives Improves Skin Symptoms in Patients with Atopic Dermatitis by Ameliorating the Water-Holding Function.

Because ceramide-like lipo-amino acid cholesteryl derivatives can exert a bound water-holding function due to their lamellae-forming properties, in this study, we determined if topical application of those derivatives to atopic dry skin would elicit an ameliorative effect on skin symptoms, at least on its water-holding function. In this clinical study, daily treatment with a nano-emulsion containing 10% phytosteryl/octyldodecyl lauroyl glutamate (POLG) significantly (p < 0.0001) improved skin symptoms, including dryness/scaling, itchiness and stimulus sensations, in the non-lesional skin of patients with atopic dermatitis (AD) at 3 and at 6 weeks compared with week 0. Those significant improvements in skin symptoms were accompanied by a significantly enhanced water content (conductance) and a significant improvement of roughness (SESC) and smoothness (SESM) values measured using a Visioscan at 3 and 6 weeks. Those effects appeared concomitant with a significantly increased corneocyte size, a significantly down-regulated degree of thick abrasions, and a significant impairment of the corneocyte lipid envelope at 6 weeks. Thus, our clinical study suggests, for the first time, that topical application of the POLG nano-emulsion has the distinct potential to ameliorate atopic dry skin symptoms, particularly scaling and itchiness, in the skin of patients with AD. Those effects result from alleviation of the disrupted water-holding function probably due to the increased supply of lamellae structures into the stratum corneum despite the failure to improve barrier function.

The Attenuated Secretion of Hyaluronan by UVA-Exposed Human Fibroblasts Is Associated with Up- and Downregulation of HYBID and HAS2 Expression via Activated and Inactivated Signaling of the p38/ATF2 and JAK2/STAT3 Cascades.

Little is known about the effects on hyaluronan (HA) metabolism of UVA radiation. This study demonstrates that the secretion of HA by human dermal fibroblasts (HDFs) is downregulated by UVA, accompanied by the down- and upregulation of mRNA and protein levels of the HA-synthesizing enzyme (HAS2) and the HA-degrading protein, HYaluronan Binding protein Involved in HA Depolymerization(HYBID), respectively. Signaling analysis revealed that the exposure distinctly elicits activation of the p38/MSK1/CREB/c-Fos/AP-1 axis, the JNK/c-Jun axis, and the p38/ATF-2 axis, but downregulates the phosphorylation of NF-kB and JAK/STAT3. A signal inhibition study demonstrated that the inhibition of p38 significantly abrogates the UVA-accentuated mRNA level of HYBID. Furthermore, the inhibition of STAT3 significantly downregulates the level of HAS2 mRNA in non-UVA exposed HDFs. Analysis using siRNAs demonstrated that transfection of ATF-2 siRNA but not c-Fos siRNA abrogates the increased protein level of HYBID in UVA-exposed HDFs. An inhibitor of protein tyrosine phosphatase but not of protein serine/threonine phosphatase restored the diminished phosphorylation level of STAT3 at Tyr 705, accompanied by a significant abolishing effect on the decreased mRNA expression level of HAS2. Silencing with a protein tyrosine phosphatase PTP-Meg2 siRNA revealed that it abrogates the decreased phosphorylation of STAT3 at Tyr 705 in UVA-exposed HDFs. These findings suggest that the UVA-induced decrease in HA secretion by HDFs is attributable to the down- and upregulation of HAS2 and HYBID expression, respectively, changes that are mainly ascribed to the inactivated signaling of the STAT3 axis due to the activated tyrosine protein phosphatase PTP-Meg2 and the activated signaling of the p38/ATF2 axis, respectively.

Comparison of the effects of pachymic acid, moronic acid and hydrocortisone on the polysome loading of RNAs in lipopolysaccharide-treated THP-1 macrophages.

We have proposed that analysis of ribosome-loaded mRNAs (i.e., the translatome) is useful for elucidation of pharmacological effects of phytocompounds in immune cells, regarding the involvement of post-transcriptional regulation mechanisms. In the present study, we compared the effects of pachymic acid from Poria cocos fungus and moronic acid from propolis with those of hydrocortisone on the translatomes of THP-1 macrophages exposed to bacterial lipopolysaccharide (LPS) to find clues to their biological effects. Polysome-associated RNAs collected from cells treated for 3 h with LPS plus each of the compounds were analyzed by DNA microarray followed by analyses of pathways/gene ontologies (GO). Upregulated mRNAs in enriched pathways that were found to contain AUUUA (AU)-rich motifs were checked by real-time PCR, and expression of candidate RNA-binding proteins stabilizing/destabilizing such AU-rich mRNAs was checked by Western blotting. The numbers of upregulated and downregulated genes (fold-changes ± 2.0 versus vehicle-control) were, respectively, 209 and 125 for moronic acid, 23 and 2 for pachymic acid, and 214 and 59 for hydrocortisone treatment. Overlapping with hydrocortisone treatment for upregulation were 158 genes in moronic acid and 17 in pachymic acid treatment; of these, 16 overlapped within all treatments (C-X-C motif chemokine ligands, interferon-induced protein with tetratricopeptide repeats, etc.). Pathway analyses showed GO enrichments such as 'immune response', 'receptor binding', 'extracellular space' etc. The pachymic acid-upregulated mRNAs (highly overlapped with the other 2 treatments) showed the presence of signal peptides and AU-rich motifs, suggesting regulation by AU-rich element (ARE)-binding proteins. The expression of ARE-binding protein HuR/ELAV-1 was increased by the 3 compounds, and AUF1/hnRNP D was decreased by pachymic acid. These results suggested that pachymic acid and moronic acid effects may involve as yet unknown post-transcriptional modulation via ARE-binding proteins resembling that of glucocorticoids.

Starfish Apaf-1 activates effector caspase-3/9 upon apoptosis of aged eggs.

Caspase-3-related DEVDase activity is initiated upon apoptosis in unfertilized starfish eggs. In this study, we cloned a starfish procaspase-3 corresponding to mammalian effector caspase containing a CARD that is similar to the amino terminal CARD of mammalian capsase-9, and we named it procaspase-3/9. Recombinant procaspase-3/9 expressed at 15 °C was cleaved to form active caspase-3/9 which has DEVDase activity. Microinjection of the active caspase-3/9 into starfish oocytes/eggs induced apoptosis. An antibody against the recombinant protein recognized endogenous procaspase-3/9 in starfish oocytes, which was cleaved upon apoptosis in aged unfertilized eggs. These results indicate that caspase-3/9 is an effector caspase in starfish. To verify the mechanism of caspase-3/9 activation, we cloned starfish Apaf-1 containing a CARD, a NOD, and 11 WD40 repeat regions, and we named it sfApaf-1. Recombinant sfApaf-1 CARD interacts with recombinant caspase-3/9 CARD and with endogenous procaspase-3/9 in cell-free preparations made from starfish oocytes, causing the formation of active caspase-3/9. When the cell-free preparation without mitochondria was incubated with inactive recombinant procaspase-3/9 expressed at 37 °C, DEVDase activity increased and apoptosome-like complexes were formed in the high molecular weight fractions containing both sfApaf-1 and cleaved caspase-3/9. These results suggest that sfApaf-1 activation is not dependent on cytochrome c.

[A case of gallbladder carcinoma following cholecystogastric fistula].

A 79-year-old woman with pneumobilia and liver dysfunction was admitted to our hospital. ERCP and gastrointestinal endoscopy revealed choledochal stones and a cholecystogastric fistula at the greater curvature of the gastric antrum. The risk of cholecystectomy and fistulectomy appeared to be extremely high for this patient because of her advanced age and low respiratory function due to interstitial pneumonia. Therefore, only an endoscopic lithotomy was performed, and the cholecystogastric fistula remained. However, after 2 years of follow-up, she developed an advanced gallbladder carcinoma. This finding suggests that cholecystogastric fistula is a risk factor for gallbladder carcinoma. Because of the difficulty of early detection of gallbladder carcinoma associated with cholecystogastric fistula, both fistulectomy and cholecystectomy are necessary when cholecystogastric fistula is diagnosed.

[Double esophageal carcinosarcomas showing rapid growth of a new polypoid tumor after sloughing of another polypoid tumor].

A 55-year-old man presented at our hospital with a large polypoid esophageal tumor. Initial upper gastrointestinal endoscopy revealed that this tumor had sloughed off to be replaced with ulceration in the thoracic esophagus. However, after the tumor at the thoracic esophagus sloughed off, a semi-circular, superficial, flat squamous cell carcinoma was observed adjacent to the ulceration. In addition, a separate carcinosarcoma, 2cm in diameter, was found at the esophagogastric junction. Approximately one month later, endoscopic re-examination revealed a new polypoid tumor approximately 4cm in diameter that was growing rapidly in the center of the superficial thoracic esophageal carcinoma lesion. Standard subtotal esophagectomy was performed. Histopathological examination revealed that both lesions were esophageal carcinosarcomas. This is a rare case of double esophageal carcinosarcoma associated with rapid polypoid tumor growth from a superficial squamous cell carcinoma lesion.

[Eosinophilic cholangitis from almost normal appearance to the bile duct sclerosis similar to primary sclerosing cholangitis].

A 48-year-old man was admitted to our hospital because of eosinophilia and liver dysfunction. Initial abdominal CT and MRI (MRCP) finding showed almost normal liver and bile duct. Liver biopsy demonstrated mild portal infiltration of lymphocytes and eosinophils. Definitive diagnosis was difficult, but we suspected autoimmune disease. Oral steroid administration was started, which led to a rapid improvement of eosinophilia and liver dysfunction. Dose reduction of steroid administration resulted in exacerbation of eosinophilia and liver dysfunction. Follow-up MRCP and ERCP study revealed biliary strictures similar to primary sclerosing cholangitis (PSC). A second liver biopsy revealed dense infiltration composed of lymphocytes and eosinophils in the portal area. Therefore we diagnosed eosinophilic cholangitis. This is the first case of eosinophilic cholangitis, observed after changes of the bile duct from an almost normal appearance to diffuse sclerosing and narrowing similar to PSC by imaging and pathological studies.

[A case of combined syndrome of juvenile polyposis and hereditary hemorrhagic telangiectasia associated with SMAD4 mutation].

A 47-year-old man was found to have abnormal findings on chest radiography. Chest computed tomography (CT) and magnetic resonance imaging (MRI) showed that he had a pulmonary arteriovenous malformation. He had experienced epistaxis when he was a junior high school student, and since then, the symptom had frequently recurred. Further, he had telangiectasia on the lips. Thus, he was given a diagnosis of hereditary hemorrhagic telangiectasia (HHT). Endoscopy revealed gastric telangiectasia, and in addition, his colon had many juvenile polyps. When he was 49 years of age, he underwent genetic analysis for HHT. A diagnosis of juvenile polyposis-HHT combined syndrome (JP-HHT) was made since a heterozygous germline 4-base deletion in exon 9 of SMAD4 was detected. To the best of our knowledge, this is the first case of JP-HHT associated with SMAD4 mutation in Japan.

Gastrointestinal follicular lymphoma: review of the literature.

Gastrointestinal follicular lymphoma (GI-FL) is a relatively rare disease, accounting for only 1%-3.6% of gastrointestinal non-Hodgkin's lymphoma. Although the duodenum and terminal ileum are considered to be the most common sites of origin, the development of wireless capsule endoscopy and double-balloon enteroscopy has increased the detection of GI-FL in every part of the small intestine. Approximately 70% of patients with GI-FL are estimated to have multiple lesions throughout the entire gastrointestinal tract. FL is a low-grade lymphoma that usually develops very slowly. If the lymphoma causes no symptoms, immediate treatment may not be necessary. Standard therapy has not yet been established for GI-FL, but chemotherapy, radiotherapy, monoclonal antibody therapy, or a combination of these therapies, is sometimes performed based on the therapeutic regimens for nodal FL. Regimens including conventional chemotherapy with rituximab, which achieve high response rates in nodal FL, are commonly used for GI-FL. The long-term clinical outcome of GI-FL is unclear. The results of a few series on the long-term outcomes of patients with GI-FL treated with conventional therapy indicate a median relapse-free time ranging from 31 to 45 months. On the other hand, in patients with GI-FL who were followed without treatment, the median time to disease progression was 37.5 months. Thus, whether to initiate aggressive therapy or whether to continue watchful waiting in patients with GI-FL is a critically important decision. Ongoing research on biomarkers to guide individualized GI-FL therapy may provide invaluable information that will lead to the establishment of a standard therapeutic regimen.

[A case report of renal cell carcinoma with metastatic intraductal tumor thrombus of the common bile duct].

We present a case of liver metastasis of renal cell carcinoma (RCC) presenting as an intraductal tumor thrombus of the common bile duct. A 62-year-old man was admitted with jaundice. He had undergone right nephrectomy for RCC 8 years previously, and had been administered interferon alfa for lung, bone, and liver metastases for these 3 years. Abdominal enhanced computerized tomography (CT) disclosed the progression of liver metastasis to the common bile duct and the dilated bilateral bile ducts. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a smooth filling defect in an upper portion of the common bile duct, suggesting an intraductal RCC tumor thrombus of the common bile duct. He died 4 months later despite the percutaneous biliary drainage. Liver metastasis of RCC proceeding to the common bile duct is extremely rare, and this is the 8th case. We should be aware of the fact that metastatic intraductal tumor thrombus of the common bile duct can cause obstructive jaundice.

Spontaneous Yersiniosis due to Yersinia pseudotuberculosis serotype 7 in a squirrel monkey.

A captive male Bolivian squirrel monkey (Saimiri boliviensis) of less than 1 year of age died following diarrhea and debilitation on the day of death. At necropsy, necrotizing enteritis accompanied with enlarged Peyer's patches, solitary lymphatic follicles and mesenteric lymph nodes, and multiple yellowish-white nodules in the spleen and liver were found. Histopathologically, these lesions were necrotizing inflammation containing Gram-negative bacilli. Yersinia pseudotuberculosis serotype 7 was isolated from the spleen and liver. The virF gene, which is an essential virulent plasimid (pYV) in pathogenic Y. pseudotuberculosis isolates, and the ypmA gene, which is a superantigenic toxin, were detected in the isolates. This is the first report of a fatal case of Yersinia pseudotuberculosis 7 infection in the world.

[Case of ruptured gastroduodenal arterial pseudoaneurysm with penetration to the duodenum, successfully treated with transcatheter arterial embolization].

A 77-year-old man, who underwent segmental pancreatectomy for intraductal papillary mucinous adenoma in 2001, was referred to our hospital with complaints of hematemesis and melena on January, 2004. Emergency upper gastrointestinal endoscopy showed a pulsating submucosal protrusion in the duodenal bulb, which was identified as a gastroduodenal arterial aneurysm measuring 1.5cm on abdominal CT imaging. Transcatheter arterial embolization of the aneurysm with metallic coils was successfully performed. Periodically repeated endoscopic examination has revealed the coils protruding into the duodenal lumen without any serious complication.

High incidence of the gullet worm, Gongylonema pulchrum, in a squirrel monkey colony in a zoological garden in Japan.

Histological examination revealed the gullet worm (Gongylonema pulchrum) embedded in the lingual mucosa of two of four dead Bolivian squirrel monkeys (Saimiri boliviensis) from a zoological garden in Kyushu, Japan. The zoo had kept the monkeys as a colony of approximately 80-100 individuals in a moated, open ground since 1981. To assess the incidence of G. pulchrum infection in this colony, lingual scraping with disposable plastic sticks was conducted in February during 2 consecutive years (2003 and 2004). The oval, thick-shelled egg containing a larva was found in 15 of 27 arbitrarily-chosen adult monkeys (55.5%) in 2003, and 27 of 106 monkeys (25.5%) in 2004. Infection of other zoo-kept mammals with G. pulchrum was not assessed. Since the gullet worm infects a variety of mammals including primates as natural definitive hosts, and dung beetles and cockroaches as intermediate hosts, the zoological garden may provide an ideal environment for the parasite. Zoo veterinarians should be aware of this disease in kept mammals, and should consider in the case of primates, monthly or bimonthly prophylactic anthelmintic treatment.