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There is limited evidence supporting the usefulness of endoscopic retrograde pancreatic drainage (ERPD) for symptomatic pancreaticojejunal anastomotic stenosis (sPJS). We examined the usefulness of ERPD for sPJS. We conducted a retrospective analysis of 10 benign sPJS patients. A forward-viewing endoscope was used in all sessions. Following items were evaluated: technical success, adverse events, and clinical outcome of ERPD. The technical success rate was 100% (10/10) in initial ERPD; 9 patients had a pancreatic stent (no-internal-flap: n = 4, internal-flap: n = 5). The median follow-up was 920 days. Four patients developed recurrence. Among them, 3 had a stent with no-internal-flap in initial ERPD, the stent migrated in 3 at recurrence, and a stent was not placed in 1 patient in initial ERPD. Four follow-up interventions were performed. No recurrence was observed in 6 patients. None of the stents migrated (no-internal-flap: n = 1, internal-flap: n = 5) and no stents were replaced due to stent failure. Stenting with no-internal-flap was associated with recurrence (p = 0.042). Mild adverse events developed in 14.3% (2/14). In conclusions, ERPD was performed safely with high technical success. Recurrence was common after stenting with no-internal-flap. Long-term stenting did not result in stent failure.Clinical trial register and their clinical registration number: Nos. 58-115 and R2-9.

Background: Muscle strength around the hip after total hip arthroplasty (THA) is crucial for preventing dislocation and limping. This study aimed to assess and compare muscle volume and degeneration after THA using the posterolateral (PL) and anterolateral (AL) approaches., Methods: Sixty-four hips in 64 patients who underwent primary THA were retrospectively analyzed. Patients were segregated into the PL group (35 hips) and AL group (29 hips) for evaluating pre- and postoperative muscle volumes and degeneration around the hip. Computed tomography (CT) examinations were performed preoperatively and 6 months post THA. The muscle volume and Hounsfield units (HU) of the gluteus maximus (G-max), gluteus medius (G-med), tensor fasciae latae, internal obturator muscle, and external obturator muscle were measured., Results: In the PL group, the postoperative muscle volume of the G-max significantly increased than the preoperative muscle volume. In contrast, the postoperative muscle volume of the internal obturator muscle was significantly lower than the preoperative muscle volume. The postoperative HU of the internal and external obturator muscles were significantly lower than the preoperative HU. In the AL group, the postoperative muscle volumes of the G-max, G-med, and tensor fasciae latae significantly increased than their preoperative muscle volumes. The postoperative HU of the G-med and tensor fasciae latae were significantly higher than the preoperative HU values., Conclusion: The PL approach can lead to degeneration of the internal and external obturator. The AL approach is more beneficial for recovering the G-med, tensor fasciae latae, and internal obturator muscle than the PL approach.

Objective: The efficacy and safety of acute percutaneous transluminal angioplasty or stenting (PTA/PTAS) for vertebrobasilar artery occlusion with atherothrombotic brain infarction (ATBI) have not been confirmed despite the resistance to medical therapy alone. There are few reports about this disease and its treatment. Therefore, the treatment outcomes at our hospital were summarized to evaluate the efficacy and safety., Methods: This was a retrospective study of acute PTA/PTAS for vertebrobasilar artery occlusion due to atherosclerotic change in 19 consecutive patients with a modified Rankin Scale (mRS) score of 0-2 before stroke between March 2010 and December 2018. The factors related to prognosis were investigated. Outcomes were assessed at 90 days of follow-up., Results: Of 19 patients with acute vertebrobasilar artery occlusion treated by PTA/PTAS, 8 had good outcomes (mRS 0-2) and 11 had poor outcomes (mRS 3-6). There were no differences in the clinical or patient background except for the National Institutes of Health Stroke Scale (NIHSS) score between groups. The good outcome group had a lower NIHSS score than the poor outcome group (median: 9.5 vs 35, p <0.001). The Thrombolysis in Cerebral Ischemia (TICI) 2b-3 group had a slightly more favorable outcome than the TICI0-2a group (p = 0.10). There were no differences in outcome between PTA and PTAS groups (p = 0.65)., Conclusion: Reperfusion of the posterior circulation by PTA/PTAS may be necessary for a good outcome. Although acute stenting must be performed under careful observation, a stent can be placed when recurrence in the early phase is estimated with high probability., Competing Interests: Hirotoshi Imamura received rewards as lecture fees from Stryker Japan and Medtronic Japan. Nobuyuki Sakai received research funds from Terumo Corporation, and rewards as lecture fees from Biomedical Solutions, Johnson & Johnson, Medtronic Japan, Penumbra, Stryker Japan, and Terumo Corporation. The remaining authors declare no conflicts of interest regarding the publication of this article., (©2021 The Japanese Society for Neuroendovascular Therapy.)

Anagrelide is widely used for cytoreductive therapy in patients with essential thrombocythemia who are at high risk for thrombosis. The recommended starting dose in the package insert of anagrelide varies by country. A high starting dose leads to an early onset of action, but causes a higher incidence of adverse events. This relationship indicates that both the onset of action and side effects of anagrelide are dose dependent. We retrospectively compared the efficacy and safety of anagrelide as a first-line drug between patients with essential thrombocythemia who started at 0.5 or 1.0 mg/day. Incidence of total adverse events and anagrelide-related palpitation, discontinuation rates, and the median daily dose of anagrelide were lower in the 0.5 mg/day group than in the 1.0 mg/day group; however, comparable platelet-lowering effects were achieved in both groups. These data suggest that a low starting dose of anagrelide followed by dose escalation may result in fewer adverse events and lower discontinuation rates, while providing desirable platelet-lowering effects. Initiating anagrelide at a lower dose may be a useful approach in actual clinical practice.

Objective We aimed to examine the dynamics of serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with acute liver injury. Methods Serum M2BPGi levels at the time of the diagnosis (n=77) and normalization of the serum alanine aminotransferase (ALT) level (n=26) were examined retrospectively. The difference in the serum M2BPGi level according to the etiology, and the correlations with other laboratory parameters were evaluated. Results The serum M2BPGi level at the time of the diagnosis was increased in 59 of 77 patients [2.3 cutoff index (COI); range, 0.31-11.1 COI] and was significantly decreased at the time of serum ALT normalization (0.68 COI; range, 0.15-1.87 COI; p<0.0001). The serum M2BPGi level was positively correlated with the duration for which serum ALT normalization was achieved (n=46, Spearman rho=0.53, p<0.0001). A multivariate analysis identified total bilirubin (T-bil), albumin, ALT, alkaline phosphatase, and etiology (e.g., drug-induced liver injury or etiology unknown) as independent factors for increased serum M2BPGi. In patients with infectious mononucleosis, the serum M2BPGi level was higher relative to the degree of increase of serum ALT or T-bil levels in comparison to other etiologies. Conclusion The serum M2BPGi level in patients with acute liver injury reflects the magnitude and duration of liver injury. However, it should be noted that the degree of increase of serum M2BPGi in patients with acute liver injury may differ according to the etiology.

Central venous catheter (CVC) insertion is an essential medical procedure in patients with hematologic disorders. Recently, the use of peripherally inserted central venous catheters (PICCs) for CVC insertion has been increasing. However, the suitable arm for PICC insertion has not been fully discussed. This study retrospectively examined catheter-related complications on the insertion side of PICC in patients with hematologic disorders. Total 809 PICCs were inserted in 316 patients with hematologic disorders. The insertion side was the right upper arm for 515 PICCs and the left upper arm for 294 PICCs. In a direct comparison between the insertion side groups, there was no obvious difference in the basic demographic characteristics of the patients except the age at the time of insertion. Moreover, there was no significant difference in the reasons for PICC removal, and the incidence of catheter-related bloodstream infection was similar and low in both the study groups. During the selection of the insertion side for PICC, it may be possible to consider the side that seems more suitable for insertion by confirming the vessels in both upper arms with ultrasonography, and, if the conditions are equivalent, to consider the side where the patient wishes to insert the PICC.

We experienced a pregnant woman with superior vena cava syndrome at 15 weeks of pregnancy who was diagnosed with primary mediastinal large B-cell lymphoma and given chemotherapy. In this case, the clinical courses of both the mother and infant were favorable without any serious complications because of close multidisciplinary cooperation. Based on a retrospective review of this case, the administration of CHOP-like regimens during the second and third trimesters appears relatively safe. Because pregnancy and continuation of pregnancy are rare in patients with hematopoietic malignancies, the accumulation of detailed information is important.

Objective: This study aimed to retrospectively assess the efficacy and safety of anagrelide in cytoreduction therapy-naïve essential thrombocythemia (ET) patients in a real-world setting., Method: Data from 53 ET patients who received anagrelide as a first-line therapy were reviewed for patient characteristics, antiplatelet status, cytoreduction status, therapeutic effects, adverse events, thrombohemorrhagic event development, progression to myelofibrosis or acute leukemia, and cause of death., Results: The rate of achieving a platelet count of <600 × 10 9 /L during anagrelide monotherapy was 83.0%. Adverse events occurred in 32 of 53 patients, and tended to be slightly more severe in patients with cardiac failure; however, they were mostly tolerable. The therapeutic effect of anagrelide was consistent, regardless of genetic mutation profiles. The incidence of anemia as an adverse event was significantly higher in the CALR mutation-positive group. Favorable platelet counts were also achieved in patients for whom hydroxyurea was introduced as a replacement for anagrelide or in addition to anagrelide because of unresponsiveness or intolerance to treatment., Conclusion: In Japanese cytoreduction therapy-naïve ET patients, anagrelide administration as a first-line therapy demonstrated favorable effects in reducing platelet counts, and its safety profile that was generally consistent with those in previous reports., (© 2019 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.)

Hepatitis C virus (HCV) cell culture systems have facilitated the development of efficient direct-acting antivirals against HCV. Huh-7.5, a subline of the human hepatoma cell line Huh-7, has been used widely to amplify HCV because HCV can efficiently replicate in these cells due to a defect in innate antiviral signalling. Recently, we established a novel cell line, KH, derived from human hepatocellular carcinoma, which showed atypical uptake of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) in a Gd-EOB-DTPA-enhanced magnetic resonance imaging study. KH cells expressed hepatocyte markers including microRNA-122 (miR-122) at a lower level than Huh-7.5 cells. We demonstrated that KH cells could support the entire life cycle of HCV; however, HCV replicated at a lower rate in KH cells compared to Huh-7.5 cells, and virus particles produced from KH cells seemed to have some disadvantages in viral assembly compared with those produced from Huh-7.5 cells. KH cells had more robust interferon-stimulated gene expression and induction upon HCV RNA transfection, interferon-α2b addition, and HCV infection than Huh-7.5 cells. Interestingly, both miR-122 supplementation and IRF3 knockout in KH cells boosted HCV replication to a similar level as in Huh-7.5 cells, suggesting that intact innate antiviral signalling and lower miR-122 expression limit HCV replication in KH cells. KH cells will enable a deeper understanding of the role of the innate immune response in persistent HCV infection.

Patients infected with hepatitis C virus (HCV) have an increased risk of developing type 2 diabetes. HCV infection is linked to various liver abnormalities, potentially contributing to this association. We show that HCV infection increases the levels of hepatic selenoprotein P (SeP) mRNA (SEPP1 mRNA) and serum SeP, a hepatokine linked to insulin resistance. SEPP1 mRNA inhibits type I interferon responses by limiting the function of retinoic-acid-inducible gene I (RIG-I), a sensor of viral RNA. SEPP1 mRNA binds directly to RIG-I and inhibits its activity. SEPP1 mRNA knockdown in hepatocytes causes a robust induction of interferon-stimulated genes and decreases HCV replication. Clinically, high SeP serum levels are significantly associated with treatment failure of direct-acting antivirals in HCV-infected patients. Thus, SeP regulates insulin resistance and innate immunity, possibly inducing immune tolerance in the liver, and its upregulation may explain the increased risk of type 2 diabetes in HCV-infected patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A 60-year-old man with an unruptured cerebral aneurysm and family history of moyamoya disease was admitted to our hospital with epigastric pain since the previous day. Serum levels of pancreatic enzyme were elevated and abdominal contrast-enhanced computed tomography showed localized enlargement of the pancreatic tail in the arterial phase and revealed numerous areas of fine mesh-like vascular hyperplasia consistent with an enlarged pancreatic tail. We diagnosed pancreatic arteriovenous malformation (P-AVM) with acute pancreatitis. Furthermore, in the pancreatic body, endoscopic ultrasonography showed lobularity (honeycombing type) and hyperechoic foci (non-shadowing), which suggests chronic pancreatitis. Acute management was performed with conservative treatment including administration of replacement fluids and proteolytic enzyme inhibitor. Distal pancreatectomy for P-AVM was performed because P-AVM is associated with acute pancreatitis recurrence, development of portal hypertension, progression of chronic pancreatitis, and refractory duodenal bleeding. Histological findings on the resected specimens revealed the anastomosis of abnormal arteries and veins, which suggested P-AVM. In addition, inflammation accompanied by fat necrosis due to ischemic infarction in the pancreatic tail, which suggested acute pancreatitis, and mild fibrosis in the pancreatic body, which suggested chronic pancreatitis, were shown. Although P-AVM is associated with various complications, symptomatic P-AVM should be considered a chronic and progressive disease.

Although hematopoietic stem cell transplantation (HSCT) may increase the curability of refractory hematologic diseases, it requires complication management due to a long-term immunocompromised state. We experienced a case who received an autologous peripheral blood stem cell transplantation (Auto-PBSCT) for POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) and developed cutaneous Mycobacterium chelonae infection. It is clear that attention needs to be paid to prevent bacterial, fungal and viral infection after HSCT. It is also important to keep in mind that tuberculous and nontuberculous mycobacteria (NTM), in rare cases, lead to lethal complications., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A 37-year-old obese man who was a social drinker was admitted to our hospital to undergo a detailed examination for liver injury with anti-mitochondrial antibody positivity. Abdominal ultrasonography revealed moderate fatty liver. A histological analysis showed steatosis of approximately 30% of the hepatocytes, focal necrosis, a few ballooning hepatocytes and lobular inflammation suggestive of steatohepatitis, epithelioid granuloma and irregularity of the sequence of the bile duct epithelium accompanied by lymphocyte infiltration suggestive of chronic cholangitis. He was diagnosed with non-alcoholic steatohepatitis complicated with primary biliary cholangitis. His liver injury was improved by weight loss and high-dose ursodeoxycholic acid treatment.

Since diffuse hepatic hemangiomatosis (DHH) is an extremely rare disease especially in adults, the etiology and natural course of adult-onset DHH has not been well understood. We report a case of DHH complicated with multiple organic dysfunction and Kasabach-Merritt syndrome (KMS) in an 83-year-old female. She presented with mild abdominal distension and laboratory findings revealed thrombocytopenia and abnormal coagulation, indicating disseminated intravascular coagulation (DIC). Enhanced computed tomography revealed diffuse, hypodense hepatic nodules with delayed enhancement involving the whole liver, and multiple hypodense splenic legions. To obtain a definitive diagnosis, laparoscopic-guided biopsy was performed. Histological findings revealed irregularly dilated non-anastomotic vascular spaces, which were lined with flat endothelial cells without cellular atypia. We diagnosed this as DHH complicated with splenic lesions and KMS. Although the patient was treated with symptomatic treatment, such as anti-coagulation therapy, hemangiomatous lesions, especially in the spleen, progressed rapidly, leading to worsening of DIC. Finally, the patient died of multiple organ failure at 12 months after diagnosis. A postmortem examination demonstrated diffuse hemangiomatosis of not only the liver and spleen, but also the adrenal glands and bone marrow. Despite no malignant histologically, DHH can be fatal if it progresses rapidly within a short period of time.

Objective: We examined the prognostic factors to validate previous prognostic models for survival and thrombosis with large-scale data on Japanese patients with essential thrombocythemia (ET)., Method: We conducted a study in 352 patients with ET to validate previous prognostic models and search for new prognostic factors., Results: The International Prognostic Score for essential thrombocythemia (IPSET), the conventional risk classification and the International Prognostic Score for thrombosis in essential thrombocythemia (IPSET-T) were confirmed to be reproducible in Japanese patients. However, no significant difference was observed between the low-risk and intermediate-risk categories according to the revised IPSET-T, which does not allow direct comparison of the four risk groups. We reevaluated the risk using a modified revised IPSET-T, which was derived from the revised IPSET-T by scoring the factors as follows: one point for age > 60 years, two points for past history of thrombosis, two points for JAK2 gene mutation-positive; total points of 0 = very low risk, 1 =  low risk, 2 =  intermediate risk, 3 and above = high risk, with significantly different thrombosis-free survival., Conclusion: The modified revised IPSET-T has been useful for 4-group stratification to predict a population that requires therapeutic intervention, irrespective of the treatment regimens., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Simeprevir is a novel NS3/4A protease inhibitor (PI) of hepatitis C virus (HCV). The baseline polymorphism NS3-Q80K is frequently observed in genotype (GT) 1a HCV and often associated with treatment failure in simeprevir-containing regimens. We aimed to elucidate mechanisms of treatment failure due to NS3-Q80K. We included a Q80R mutation in our study and generated a series of Huh-7.5 cell lines, each of which harbored either wild-type GT 1a strain H77S.3 or the Q80K or Q80R variant. The cells were cultured with increasing concentrations of simeprevir, and NS3 domain sequences were determined. The mutations identified by sequence analyses were subsequently introduced into H77S.3. The sensitivity of each mutant to the NS3/4A PIs simeprevir, asunaprevir, grazoprevir, and paritaprevir was analyzed. We introduced the mutations into GT 1b strain N.2 and compared the sensitivity to simeprevir with that of GT 1a strain H77S.3. While simeprevir treatment selected mutations at residue D168, such as D168A/V in the wild-type virus, an additional mutation at residue R155, R155K, was selected in Q80K/R variants at simeprevir concentrations of <2.5 μM. Sensitivity analyses showed that simeprevir concentrations of <1 μM significantly boosted the replication of Q80K/R R155K variants. Interestingly, this boost was not observed with the other NS3/4A PIs or in Q80R R155Q/G/T/W variants or GT 1b isolates. The boosted replication of the Q80K+R155K variant by simeprevir could be related to treatment failure in simeprevir-containing antiviral treatments in GT 1a HCV-infected patients with the NS3-Q80K polymorphism. This result provides new insight into how resistance-associated variants can cause treatment failure., (Copyright © 2018 American Society for Microbiology.)

The overlap of multiple liver diseases can cause the disease activity and severity to worsen rapidly in some cases. We rarely see patients with non-alcoholic steatohepatitis (NASH) with overlapping autoimmune hepatitis (AIH). A 64-year-old woman who had been prescribed oral drugs to treat diabetes and hypertension (metformin 500 mg/day and voglibose 0.9 mg/day, and termisartan 40 mg/day and amlodipine 5 mg/day, respectively) was diagnosed with NASH with histological confirmation. At 68 years of age, her liver injury worsened with an IgG of 2,871 mg/dL and a high serum anti-nuclear antibody (ANA) level of 2,560. We repeated the liver biopsy, which revealed NASH and mild interface hepatitis with some lobular focal necrosis consisting of overlapping AIH. Therefore, she was treated with 30 mg of prednisolone daily. The treatment led to an improvement in her IgG levels and ANA in the serum and an improvement in the histology results.

Although the life expectancy if patients with essential thrombocythemia (ET) is considered to be almost similar to that of the general population, advanced age, leukocytosis, and a previous history of thrombosis are poor prognostic factors, and it is important to prevent thrombohemorrhagic events, leukemic transformation, and secondary malignancies. We report an 85-year-old ET patient with a history of asymptomatic lacunar infarction, who developed symptomatic cerebral infarction and even chronic subdural hematoma. It is necessary to follow patients who have asymptomatic cerebral infarction or chronic ischemic change and to examine the necessity of brain imaging and treatment intervention at the time of diagnosis.

Background: White globe appearance (WGA) refers to a small white lesion of globular shape underneath cancerous gastric epithelium that can be clearly visualized by magnifying endoscopy with narrowband imaging (M-NBI). WGA has been reported to be a novel endoscopic marker that is highly specific in differentiating early gastric cancer (GC) from low-grade adenoma, and has a significantly higher prevalence in early GCs than in noncancerous lesions. However, interobserver agreement in detecting WGA and whether training intervention can improve diagnostic accuracy are unknown., Methods: Twenty sets of M-NBI images were examined by 16 endoscopists. The endoscopists attended a lecture about WGA, and examined the images again after the lecture. Interobserver agreement in detecting WGA in the second examination and increases in the proportion of correct diagnoses and the degree of confidence of diagnoses of cancerous lesions were evaluated., Results: The kappa value for interobserver agreement in detecting WGA in the second examination was 0.735. The proportion of correct diagnoses was significantly higher in the second examination compared with the first examination when WGA was present (95.5% vs 55.4%; P < 0.001), but not when WGA was absent (61.6% vs 52.7%; P = 0.190). The proportion of correct diagnoses with a high degree of confidence was significantly higher in the second examination, both with WGA (91.1% vs 29.5%; P < 0.001) and without WGA (36.6% vs 20.5%; P = 0.031)., Conclusions: The detection of WGA by endoscopists was highly reproducible. A brief educational lecture about WGA increased the proportion of correct diagnoses and the degree of confidence of diagnoses of GC with WGA.

The innate immune system functions as the first line of defense against invading bacteria and viruses. In this context, the cGAS/STING [cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase/STING] signaling axis perceives the nonself DNA associated with bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. In this pathway, the noncanonical cyclic dinucleotide 2',3'-cyclic GMP-AMP (2',3'-cGAMP) functions as a second messenger for signal transduction: 2',3'-cGAMP is produced by the enzyme cGAS upon its recognition of double-stranded DNA, and then the 2',3'-cGAMP is recognized by the receptor STING to induce the phosphorylation of downstream factors, including TBK1 (TANK binding kinase 1) and IRF3 (interferon regulatory factor 3). Numerous crystal structures of the components of this cGAS/STING signaling axis have been reported and these clarify the structural basis for their signal transduction mechanisms. In this review, we summarize recent progress made in the structural dissection of this signaling pathway and indicate possible directions of forthcoming research.

A three-year-old spayed domestic short-haired cat presented for evaluation of weight loss, cardiomegaly and pleural effusion. Echocardiographic examination demonstrated a thickened pericardium with mild pericardial effusion and a large volume of pleural effusion characterized by exudate. Although the cat was treated with antibiotics, the clinical symptoms did not improve. The cat developed dyspnea and died on day 7. Necropsy revealed a large amount of modified transudates ascites, pleural effusion and markedly dilated pericardium. Histopathological examination revealed severe exudation of fibrin and granulation tissue in a thick layer of the epicardium. The cat was diagnosed with fibrinous pericarditis secondary to bacterial infection.

A 75-year-old woman was referred to our hospital with suspected leukemia. Complete blood count demonstrated WBC 3,810/µl with 26% blasts, Hb of 11.7 g/dl and Plt of 18.0×10 4 /µl. Bone marrow aspiration revealed blasts (86.3%) with expressions of CD34, CD7, TdT, CD33, and CD117. MPO was negative. Chromosomal analysis of the bone marrow showed isolated trisomy 10 in all leukemic cells (20/20). Swelling of superficial lymph nodes was also observed. Cervical lymph node biopsy revealed leukemic blasts which had the same phenotype as those in the bone marrow except that proliferation of Langerhans cell-like cells (LCs) was observed in the paracortex. LCs had pale cytoplasm and grooved nuclei, and were positive for both CD1a and S100 protein. Trisomy 10 was detected in both the leukemic blasts and the LCs by fluorescence in situ hybridization. This rare case strongly suggests leukemic cells to differentiate into LCs.

Background: Recently, morbidities due to primary cytomegalovirus (CMV) infection have increased in young Japanese adults because of decreased anti-CMV antibodies in them. CMV infections are typically resolved naturally in immunocompetent individuals, and complications rarely occur. Here we present the case of an immunocompetent adult with CMV infection complicated by splenic infarctions and an esophageal ulcer., Case Report: A 37-year-old male complaining of a prolonged fever and liver injury was admitted to hospital for a closed examination. The patient had general malaise and mild appetite loss but no abdominal pain. Symptoms of infectious mononucleosis, including liver injury, appearance of atypical lymphocytes in the blood, and hepatosplenomegaly, were observed. A primary CMV infection was confirmed by CMV-IgM positive and CMV-IgG negative serological tests. Enhanced abdominal computed tomography confirmed hepatitis and splenic infarction, and an upper gastrointestinal endoscopy revealed an esophageal ulcer. The patient exhibited no predisposing risk factors for thrombosis, and he was diagnosed with splenic infarctions associated with CMV infection. Because the patient was immunocompetent, he underwent symptomatic therapy without antiviral or anticoagulant therapies. The treatment improved his overall condition. Including the present case, only 11 cases of CMV infections with splenic infarction in immunocompetent individuals have been reported. Contrary to what is observed in immunocompromised hosts, upper gastrointestinal lesions with CMV infection are rare in immunocompetent individuals. The esophageal lesion observed in our patient was a typical punched-out ulcer. The immunohistochemical staining of the tissue biopsies revealed that the ulcer was associated with CMV., Conclusion: Although splenic infarctions and esophageal ulcers are rare, they should be considered as potential complications accompanying CMV infection in immunocompetent individuals. The administration of symptomatic therapy should be considered even when the patient is immunocompetent.

A 40-year-old man complaining of abdominal distention was referred to our hospital. Computed tomography of the abdomen demonstrated a very large abdominal mass with fat and calcification. The size of the mass rapidly increased from 30cm to 40cm over two weeks. The tumor was removed and diagnosed by pathological examination to be a retroperitoneal mature cystic teratoma that contained a 40-cm long, mature intestinal tract-like cyst, together with bone marrow and fat. The rapid growth of the tumor may have been caused by an increased secretion in the cyst.

Objective Although use of the peripherally inserted central venous catheter (PICC) has become increasingly common, there are few reports of PICCs used for patients with hematologic diseases. In this study, we analyzed the safety of PICC placement in patients with hematologic diseases where PICCs had been placed to perform blood collection, blood transfusion, drug administration, and hematopoietic stem cell transplantation. Methods This study included 142 PICCs placed in 95 patients managed at our department from November 2013 to December 2015. The PICCs used were the Groshong ® Catheter (NXT single-lumen; BARD Inc.). Results A total of 95 patients underwent the placement of 142 PICCs. The mean patient age was 65.5 years. The total duration of catheterization was 8,089 days, with a mean duration of 57.0 days. Chemotherapy was administered through 107 catheters. Stem cells were injected through 12 catheters. Although a fever was observed in association with 103 catheters, it was generally controlled by antimicrobial therapy. There were 18 catheter-related bloodstream infection (CRBSI) cases, an incidence equivalent to 2.1 cases per 1,000 catheter-days. Conclusion The present study demonstrated a low CRBSI incidence rate and found no evidence of serious complications with PICC placement. PICCs can be used for blood collection, blood transfusion, drug administration, and hematopoietic stem cell transplantation without problems. Thus, PICC placement appears to be a safe procedure for patients with hematologic diseases. Safe catheters are therefore urgently needed for these patients. We expect that PICCs will be widely adopted in Japan in the near future.

In the innate immune system, pattern recognition receptors (PRRs) specifically recognize ligands derived from bacteria or viruses, to trigger the responsible downstream pathways. DEAD box protein 41 (DDX41) is an intracellular PRR that triggers the downstream pathway involving the adapter STING, the kinase TBK1, and the transcription factor IRF3, to activate the type I interferon response. DDX41 is unique in that it recognizes two different ligands; i.e., double-stranded DNA (dsDNA) and cyclic dinucleotides (CDN), via its DEAD domain. However, the structural basis for the ligand recognition by the DDX41 DEAD domain has remained elusive. Here, we report two crystal structures of the DDX41 DEAD domain in apo forms, at 1.5 and 2.2 Å resolutions. A comparison of the two crystal structures revealed the flexibility in the ATP binding site, suggesting its formation upon ATP binding. Structure-guided functional analyses in vitro and in vivo demonstrated the overlapped binding surface for dsDNA and CDN, which is distinct from the ATP-binding site. We propose that the structural rearrangement of the ATP binding site is crucial for the release of ADP, enabling the fast turnover of DDX41 for the dsDNA/CDN-induced STING activation pathway.

We report a 67-year-old woman with essential thrombocytosis who developed cerebral infarction and heparin-induced thrombocytopenia during treatment for the cerebral infarction. She developed additional cerebral infarcts, acute femoral artery occlusion, and thrombophlebitis of her lower extremities. She was successfully treated with argatroban. This is the first report of a patient with essential thrombocytosis who developed heparin-induced thrombocytopenia and serious conditions, which included multiple thromboembolisms and coagulation disorders mimicking disseminated intravascular coagulation., (Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

We performed surgical resection of synchronous multiple primary lung cancer, comprising adenocarcinoma and carcinoid components. The latter tumor was located within the central scar tissue formed by the adenocarcinoma (cancer-in-cancer). The patient was a 67-year-old Japanese woman who had a nodular lesion in the right S1 on chest computed tomography. Lung cancer was diagnosed intraoperatively by rapid needle aspiration cytology, and right upper lobectomy with mediastinal lymph node dissection was performed. Histological examination of the resected specimen revealed cancer-in-cancer, consisting of adenocarcinoma and a carcinoid tumor. The carcinoid component was localized within the central fibrous scar of the dominant adenocarcinoma component.

Adults of Papilio protenor demetrius emit a faint odour; the male odour is notably stronger than that of the females. The extracts of whole individuals of each sex comprised 53 compounds regarded as cuticular lipid components, of which the 17 major compounds were straight-chain alkanes and alkenes with 23-31 carbon atoms, higher fatty acids, long-chain aliphatic ketones, squalene, and cholesterol. However, highly volatile compounds were not detected in the whole individual extracts. Eight of the 17 major compounds showed a significant sex difference in relative abundance per individual. Principal component analysis, using the major compounds as variables, revealed a marked sexual dimorphism in the chemical composition of cuticular lipids. From the extracts of 10 dissected individuals of each sex, 21 highly volatile compounds were identified in amounts of less than 200 ng/individual. Among them, linalool and 2,3-butanediol showed a significantly larger amount in males than in females, indicating that the adult odour is also sexually dimorphic. Moreover, both sexes shared several odoriferous compounds, such as heptanal, nonanal, methyl salicylate, benzyl alcohol, and benzoic acid. The faint odour of P. protenor adults, perceivable by the human nose, appears to originate from these volatile compounds.

In the United States and European countries, Mycobacterium immunogenum has been identified in metalworking fluids and is reported to be a causative agent of metalworking fluid-associated hypersensitivity pneumonitis. However, in Japan, there has been no reports of M. immunogenum isolated from metalworking fluids. This is the first report of isolation of the microorganism from the sputum of a metal-grinding machine worker in Japan. We should consider the possibility of M. immunogenum infection in case of non-tuberculosis mycobacteriosis and hypersensitivity pneumonitis in metalworkers.

This study evaluated the effects of hinokitiol (a natural antibacterial compound extracted from Thujopsis dolabrata var. hondai) and an organic acid mixture (citrate content 50%) on ruminal fermentation. Antibacterial properties were examined by measuring minimal inhibitory concentration. Hinokitiol at 1.56µg/mL or an organic acid mixture at 1600µg/mL inhibited Streptococcus bovis growth. The combination of 0.78µg/mL hinokitiol and 200µg/mL of an organic acid mixture also inhibited S. bovis growth. Both hinokitiol and the hinokitiol and an organic acid mixture combination showed strong antibacterial properties on Gram-positive bacteria such as S. bovis, but relatively weak antibacterial activities on Gram-negative bacteria such as Megasphaera elsdenii. Three ruminally cannulated heifers were fed a bloat-producing diet containing barley, pelleted alfalfa meal, soybean meal and salt without long-cut roughage to investigate the ruminal characteristics in vivo. Feeding to heifers a bloat-producing diet containing 7.8mg/kg hinokitiol and 0.2% of an organic acid mixture significantly decreased the increase in stable ingesta volume. Hinokitiol or an organic acid mixture did not affect ruminal volatile fatty acids, protozoa and bacteria. These results suggest that a combination of hinokitiol and an organic acid mixture might reduce frothy bloat in cattle fed high-grain diets., (© 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.)

A 71-year-old male underwent an upper gastrointestinal endoscopy ; as a result of a biopsy, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was suspected. Abdominal computed tomography scan disclosed an approximately 4-cm-large mass in the ileocecal region. After ileocecal resection, the patient was diagnosed with MALT lymphoma (CD79a(+), CD20(+), CD3(-), CD5(-), CD10(-), and cyclin D1(-)). He achieved complete remission after receiving chemotherapy. However, four years after the primary onset, he was diagnosed with recurrence. Although he achieved remission again by salvage therapy, six years after the primary onset, he was referred to our hospital with second recurrence. Colonoscopy revealed the appearance of multiple lymphomatous polyposis and biopsy specimens showed monotonous proliferation of centrocyte-like cells (CD79a(+), CD20(+), CD3(-), CD5(-), CD10(-), and cyclin D1(+)), which were consistent with mantle cell lymphoma (MCL) except for CD5. The result of reactivity to cyclin D1 was different from that at initial diagnosis, so we reexamined the initial surgical specimens, the histological and histochemical features of which were proven to be the same as those of colonic biopsy specimens. Finally, the patient was diagnosed with CD5-negative MCL (marginal zone-like variant). As MALT lymphoma and MCL sometimes show similar histological features, they are difficult to distinguish from each other. It is necessary to take the possibility of this rare phenotype of MCL into consideration and to reexamine the initial diagnosis, especially if the clinical course is unusual for MALT lymphoma. This case is very interesting in view of its indolent clinical feature and phenotype.

Papilio maackii females prefer a rutaceous plant, Phellodendron amurense, for oviposition, whereas another semi-sympatric Rutaceae feeder, Papilio protenor, never exploits this plant as a host in nature. However, the larvae of both species perform well on this plant in the laboratory. Phellamurin, a flavonoid present in the organic fraction from P. amurense inhibits egg laying by P. protenor. We examined whether phellamurin is involved in the differential acceptance of P. amurense by the two butterflies. The ovipositing females of P. maackii readily accepted P. amurense and a methanolic extract of the foliage, while P. protenor rejected them entirely. However, the aqueous fraction derived from the extract elicited significant oviposition responses of similar levels from the two species. Phellamurin did not induce oviposition behavior in P. protenor females. In contrast, P. maackii was stimulated to oviposit by phellamurin at concentrations exceeding 0.2%. The response was dose-dependent and reached ca. 70% at 2% phellamurin, which is approximately equivalent to its natural abundance in young leaves of P. amurense. Since the aqueous fraction was very stimulatory to both species, the combined effect of phellamurin and the aqueous fraction on oviposition was tested. The addition of phellamurin to the aqueous fraction enhanced the ovipositional activity of P. maackii, but dramatically suppressed the oviposition response of P. protenor even at 0.1% concentration. These results, taken together with those obtained from electrophysiological recordings with foretarsal chemosensilla, indicate that phellamurin acts as an oviposition stimulant for P. maackii, and as a potent deterrent for P. protenor. The results suggest that host range expansion or host shifts may be made by ovipositing females that overcome phytochemical barriers.

Paradoxical reaction in tuberculosis treatment is not generally fatal. On rare occasion it can lead a patient with diminished lung function and poor general condition to death. A 60-year-old man with history of left upper lobe resection from tuberculosis was referred to our hospital due to the recurrence of tuberculosis. Sputum examination showed a positive smear with a Gaffky score of 10, and the chest X-ray and CT revealed pulmonary infiltrate with many cavities (bII2) on the whole left lung field. Anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) were administered, but his high fever persisted, and the infiltrate on the chest X-ray deteriorated. While the positive sputum smear persisted, the culture became negative after one month. The tuberculous bacilli were susceptible to all anti-tuberculosis drugs in vitro. Though we performed examinations and trial treatments for non-tuberculous conditions such as pneumonia and drug-induced pneumonia, the patient died after 6 months. A necropsy specimen taken from the worsening lesion (the right upper lobe) as shown on the chest X-ray revealed many epithelioid granulomas. The patient had malnutrition, diabetes, alcoholic hepatic disorder, and insanity. It is supposed that although antituberculosis drugs were effective, a large quantity of killed organisms was continuously excreted from many cavities in the left lung toward the right lung. Lesions in the right lung thus newly produced in this paradoxical reaction seemed to reduce the remaining lung function. In addition, poorly controlled diabetes caused deteriorated heart function. These multiple factors contributed to the poor prognosis of the patient and his ultimate death.

Objective: With the progress of anti-tuberculous therapy, tuberculous peritonitis (TBP) has become a rare manifestation of active tuberculosis. Its early diagnosis is difficult due to lack of pathognomonic findings and specific symptoms. However, early diagnosis is important for effective treatment and for reducing fatality., Materials and Method: We retrospectively reviewed medical records of eight patients who were hospitalized with TBP in National Hospital Organization Omuta National Hospital during the periods between 2001 and 2009., Results: Three patients were males and five were females. The age of the patients ranged between 28 and 80 years old (average 67.3 years). The most common presenting findings were abdominal distention seen in four patients and loss of appetite in five patients. Blood examination suggested that most patients were in poor nutrition. Three patients were diagnosed based on bacteriological examination, two based on histopathological findings of caseating granulomas, two based on the elevation of adenosine deaminase activity in ascitic fluid and one based on clinical diagnosis. The most common CT findings were thin lines along mesenteric vessels representing thickened mesenteric leaves and smooth uniform peritoneal thickening. Most patients were treated with isoniazid, rifampicin and ethambutol for 9 months with/without pyrazinamide initially. Seven patients completed anti-tuberculous therapy successfully and were cured. However, one patient died of the deterioration of tuberculosis., Conclusion: TBP should be considered for diagnosis, in patients with non-specific abdominal symptoms. Adenosine deaminase activity in ascitic fluid and CT images are considered to be useful for the diagnosis of TBP in patients in whom bacteriological and histopathological examinations are difficult to perform.

Adult nymphalid butterflies possess sensilla trichodea (ST) that perceive taste in their walking legs. We examined whether the gustatory responses to mid-leg tarsal stimulation were different between Vanessa indica (rotting-food feeder) and Argyreus hyperbius (flower-nectar feeder). Sucrose, fructose, and glucose elicited behavioral responses (proboscis extension reflex: PER) and electrophysiological responses (spikes) from ST. Sugar responsiveness was similar in both species, where sucrose was the most stimulatory. Two fermentation products, ethanol and acetic acid, never induced PERs but elicited large-amplitude spikes at a concentration of >1% (w/v). The two species significantly differed in responsiveness to the binary mixtures of sucrose and the fermentation products. Ethanol enhanced the sugar responses of V. indica but slightly inhibited those of A. hyperbius. Although acetic acid suppressed the sugar responses of both species, V. indica was less susceptible than A. hyperbius. When concentration of the fermentation products increased, binary mixtures evoked large spikes together with small ones regarded as the sucrose responses. Unlike the proboscal sensilla in our previous study, the tarsal ST of both species unambiguously responded to fermentation products. These results demonstrate that the tarsal gustatory sense of V. indica is adaptive to the use of rotting foods., (2010 Elsevier Ltd. All rights reserved.)

A 76-year-old woman was admitted because of respiratory failure with bilateral multiple interstitial shadows and mediastinal adenopathy on chest CT images. Blood examination revealed eosinophilia without leukocytosis and elevated C-reactive protein levels. Corticosteroids were administered before diagnosis because of rapid respiratory failure. Although her symptoms and pulmonary lesions disappeared with steroid therapy, they recurred 4 days later. A definitive diagnosis was not obtained until bronchofiberoptic examination. At the time of recurrence 6 months later, angioimmunoblastic T-cell lymphoma (AITL) was diagnosed with axillary lymph node biopsy. AITL is rare, and shows rapid deterioration of respiratory failure with poor prognosis. Lymph node biopsy is necessary to establish a definitive diagnosis.

Background: The remodeling of arterial extra-cellular matrix induced by hemodynamic stimuli is involved in the process of atherosclerosis in the carotid and cerebral arteries. Scarce information is available on the relationship between atherosclerotic changes in brain aneurysms itself and its intra-aneurysmal hemodynamics., Methods: Surgical exploration of a large MCA aneurysm depicted extensive atherosclerotic changes in the aneurysm wall. Computational tomographic angiography of this aneurysm was used to create an in vitro aneurysm model. This model was used to perform intra-aneurysmal flow measurement using particle imaging velocimetry and LDV. Intra-aneurysmal hemodynamic pattern with wall shear stress distribution was compared between areas with and without atherosclerotic changes., Results: No high oscillation of wall shear stress was observed on the atherosclerotic plaque area. However, the magnitude of wall shear stress tended to be higher in the area without atherosclerotic changes than the area with those changes (P < .001). There was no atherosclerotic change at the aneurysm inflow zone, where relatively fast flow velocity and higher magnitude of wall shear stress was noted., Conclusions: This single case of atherosclerosis in an aneurysm shows some similarity in hemodynamic values observed in cases of carotid atherosclerotic plaques.

Adult Vanessa indica and Argyreus hyperbius frequently forage on flower nectar, but the former also utilizes tree sap and rotting fruits. Compared to flower nectar, these rotting foods are characterized by low sugar concentrations and the presence of fermentation products (ethanol and acetic acid). We suspected that gustatory responses by the receptors on the proboscis might differ in these species. Among the three sugars tested, sucrose elicited the greatest probing (behavioral) responses and was followed by fructose and glucose. A. hyperbius showed higher sugar sensitivity than V. indica in probing responsiveness. In electrophysiological responses of the proboscis sensilla, V. indica was slightly more sensitive than A. hyperbius to glucose and lower concentrations of the other sugars. The sugar reception in A. hyperbius was strongly inhibited by fermentation products, particularly acetic acid at natural concentrations. In contrast, V. indica was noticeably less susceptible to them than A. hyperbius, and its behavioral and sensory responses to sucrose were enhanced by 5-20% (w/v) ethanol. Thus, V. indica not only possesses tolerance to fermentation products but may perceive them as synergists for sugar reception. To utilize rotting foods, such tolerance might be more necessary than high sugar sensitivity.

Benzimidazolone derivatives were discovered as novel CB2 selective agonists. Structure Activity Relationship (SAR) studies around them were examined to improve metabolic stability. Compound 39 exhibited excellent metabolic stability in human liver microsomes (HLM) and significant attenuation of the chronic colonic allodynia in the TNBS-treated rats by po administration.

Previous studies have shown that cannabinoid 2 (CB(2))-receptor agonists might have analgesic effects on visceral hypersensitivity. To extend these results, we have determined the pharmacological characteristics of a newly designed CB(2) ligand, N-[(1S)-1-(aminocarbonyl)-2,2-dimethylpropyl]-3-(3-hydroxy-3-methylbutyl)-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxamide (PF-03550096), in vitro and in vivo. PF-03550096 showed high affinity to human (K(i) = 7.9 +/- 1.7 nM) and rat CB(2) receptors (K(i) = 47 +/- 5.6 nM). In a cell-based functional assay, PF-03550096 behaved as a full agonist and showed high selectivity for human CB(2) receptors. Orally administered PF-03550096 (3, 10 mg/kg) inhibited the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced decrease in colonic pain threshold with statistical significance. The inhibitory effect of PF-03550096 (10 mg/kg) was significantly reversed by a selective CB(2) antagonist, N-(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl-5-(4-chloro-3-methylphenyl)-1(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528), while SR144528 itself did not modify colonic pain threshold. These results indicate that PF-03550096 is a potent CB(2) agonist and possesses efficacy in a rat model of visceral hypersensitivity.

A novel potent NMDA-NR2B selective antagonist without the reactive metabolites formation issue was identified. Through this study, a close correlation between reactive metabolites formation and calculated HOMO energies of parent compounds was found.

Background and Purpose: The role of blood-flow biomechanics on the size, morphology, and growth of cerebral aneurysms is poorly known. The purpose of this study was to evaluate intra-aneurysmal hemodynamics before and after aneurysm growth., Materials and Methods: A flow-simulation study was performed in a middle cerebral artery (MCA) aneurysm with a bleb that grew after 1-year follow-up. Geometrically realistic in vitro models before and after aneurysm growth were constructed on the basis of CT angiograms. Blood-flow velocity, vorticity, and wall shear stress were obtained by using particle imaging velocimetry and laser Doppler velocimetry., Results: No significant quantitative differences were noted among the overall flow structures before and after aneurysm growth, with the exception of less vorticity in the bleb after aneurysm growth. A circulating flow pattern was seen within the aneurysm domes. A blood-flow separation was observed at the margins of the bleb. No impingement of inward flow into the enlarging bleb was noted. Before the aneurysm growth, the wall shear stress was high at the aneurysm neck and also at the margin of the bleb. The value of wall shear stress decreased in the deeper part of the bleb. This value decreased even more after the aneurysm growth., Conclusions: Intra-aneurysmal hemodynamic structures before and after the growth of an MCA aneurysm were compared. Further investigation with a similar approach is mandatory to obtain a firm conclusion.

One strain of Antarctic bacteria, Flavobacterium xanthum IAM12026, has a highly active antifreeze protein (AFP) in the intracellular space. The cell-free extract from strain IAM12026 after culturing at 4 degree C for 7 days in TSB medium, had activity of 0.04 degree C at a concentration of 0.7 mg/ml. The ice crystals formed do not have distinct facets without typically rounded shape and the changes of their morphology during the course of the thermal hysteresis (TH) measurement. The ice crystal 'burst' occurring at the end-point of the TH is dendritic with hexagonal symmetry. Also, this activity was not affected by the treatment of dialysis and the addition of EDTA. Furthermore, this cell-free extract had high levels of ice recrystallization-inhibiting (RI) activity like those of Fish AFPs. The AFP (FlAFP) was homogeneity purified using chromatography. A relative molecular mass of approximately 59,000 was calculated from gel filtration and SDS-PAGE data. The thermal stability of FlAFP was below 50 degree C, and TH value was absent above 60 degree C. The TH value of FlAFP was activated at 5.2 degree C by the addition of 0.5 M malate. This activation was decreased with increasing protein concentration. To our knowledge this is the first report on the high level of TH and RI activities of bacterial intracellular AFP.

Two compounds, 9,10-epoxytetrahydroedulan (ET) and viridiflorine beta-lactone (VL), were identified as major components from the hairpencils of field-caught males of a danaid butterfly, Euploea mulciber. By contrast, laboratory-reared males entirely lacked VL, but possessed a significant quantity of ET. Various feeding experiments with larvae and indoor adult males strongly suggested that ET is biosynthesized de novo only after eclosion from nutrients ingested during the larval development. Since VL was suspected to be derived from pyrrolizidine alkaloids (PAs) acquired as an adult, tests for feeding response to and oral administration of four PAs (a 4:1 mixture of intermedine/lycopsamine, heliotrine, monocrotaline, and retronecine) were conducted. When the tarsi or proboscis were stimulated with PA solutions, males showed positive feeding responses (proboscis extension and sucking movements) to intermedine/lycopsamine, heliotrine, and retronecine in decreasing order of responsiveness, thereby providing evidence that male adults are endowed with taste receptor(s) specific to PAs on the legs as well as on the proboscis. Differently from gustatory responsiveness, only males fed with intermedine/lycopsamine produced a significant quantity of VL (ca. 35 microg/male), whereas those that ingested heliotrine or monocrotaline hydrochloride produced traces of VL (<0.18 microg/male). Uptake of retronecine did not lead to VL formation at all. In behavioral bioassays to test the attractivity of PAs to males, all individuals tested were attracted exclusively to intermedine/lycopsamine. This shows that certain PA(s) per se serve as attractant(s) for males in locating PA sources, and further suggests that in the field, males will seek particular PA(s) that are indispensable as precursors for the efficient biosynthesis of VL.

We compared the chemical compositions of the osmeterial secretions of fourth and fifth (last) instars of eight swallowtail species of the tribe Papilionini. Four species (Papilio demoleus, P. polytes, P. paris, and P. macilentus) are Asian Rutaceae-feeding swallowtails. The other four (Chilasa epicydes, C. agestor, P. troilus, and P. glaucus) represent more distant clades within the Papilionini and species with larval hosts in other plant families. We conducted a quantitative analysis for six species, but only qualitative analysis for P. glaucus and C. agestor. In all eight species, regardless of larval host plant, secretions of the fourth instar principally consisted of mono- and sesquiterpene hydrocarbons, whereas those of the fifth instar comprised aliphatic acids and their esters. Consistent with earlier findings, our results suggest that this "heterogeneous" pattern of osmeterial chemistry, not seen in other tribes, may characterize the Papilionini as a whole. Unlike those of most Papilio species, the fourth and fifth instars of Chilasa species resemble each other in body coloration. Thus, the heterogeneous osmeterial pattern is not necessarily associated with color change in papilionid larvae. The major terpenoids identified in fourth instar larval secretions from the six species were alpha-pinene, sabinene, beta-myrcene, limonene, beta-phellandrene, (Z)-beta-ocimene, (E)-beta-ocimene, p-mentha-1,4(8)-diene, beta-elemene, beta-caryophyllene, (E)-beta-farnesene, (3Z,6E)-alpha-farnesene, (Z)-alpha-bisabolene, germacrene-A, (E)-alpha-bisabolene, and germacrene-B. The profiles for individual species differed both qualitatively and quantitatively from one another, and certain species also secreted methyl 3-hydroxy-n-butyrate and oxygenated sesquiterpenes in relatively large proportions. Secretions from fifth instars were composed of varying proportions of isobutyric, 2-methylbutyric, and acetic acids, and methyl and ethyl (minor) esters of both isobutyric and 2-methylbutyric acids. The heterogeneity of osmeterial chemistry in the tribe Papilionini may represent fine-tuning of chemical defense in response to shifting predation pressures as the larvae age and grow.