Search

Dendritic cells (DCs) can initiate both naïve and memory T cell activation, as the most potent antigen-presenting cells. For efficient anti-tumor immunity, it is essential to enhance the anti-tumoral activity of tumor-associated DCs (TADCs) or to potently restrain TADCs so that they remain immuno-stimulating cells. Combined phospholipids (cPLs) adjuvant may act through the activation of DCs. This study demonstrated the potential mechanism of tumor growth inhibition of cPLs adjuvant, and confirmed that cPLs adjuvant could induce the maturation and activation (upregulation of MHC-II, CD80, CD40, IL-1β, IL-12, IL-6 expression) of BMDCs in vitro. Then we isolated tumor infiltrating lymphocytes (TILs) from solid tumor and analyzed the phenotype and cytokines of TILs. The examination of the TILs revealed that cPLs adjuvant upregulated the expression of co-stimulatory molecules (MHC-II, CD86), phosphatidylserine (PS) receptor (TIM-4) on TADCs and enhanced the cytotoxic effect (CD107a), as well as pro-inflammatory cytokine production (IFN-γ, TNF-α, IL-2) by the tumor-resident T cells. Taken together, cPLs adjuvant may be an immune-potentiating adjuvant for cancer immunotherapy. This reagent may lead to the development of new approaches in DC-targeted cancer immunotherapy.

Abstract This article reports a clinical and histopathological perspective which noted not only COVID‐19 pneumonia but also exacerbation of chronic renal failure potentially caused by thrombus in the kidney, possibly COVID‐19‐related lesions. The accumulation of autopsy cases will elucidate the pathogenesis of COVID‐19 and aid in the development of effective therapeutics.

Abstract Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative/Ki-67-high (ER+HER2–Ki-67high) luminal breast cancer have a worse prognosis and do not respond to hormonal treatment and chemotherapy. This study sought to identify disease-related protein networks significantly associated with this subtype, by assessing in-depth proteomes of 10 lesions of high and low Ki-67 values (HOT, five; COLD, five) microdissected from the five tumors. Weighted correlation network analysis screened by over-representative analysis identified the five modules significantly associated with the HOT lesions. Pathway enrichment analysis, together with causal network analysis, revealed pathways of ribosome-associated quality controls, heat shock response by oxidative stress and hypoxia, angiogenesis, and oxidative phosphorylation. A semi-quantitative correlation of key-protein expressions, protein co-regulation analysis, and multivariate correlation analysis suggested co-regulations via network-network interaction among the four HOT-characteristic modules. Predicted highly activated master and upstream regulators were most characteristic to ER-positive breast cancer and associated with oncogenic transformation, as well as resistance to chemotherapy and endocrine therapy. Interestingly, inhibited intervention causal networks of numerous chemical inhibitors were predicted within the top 10 lists for the WM2 and WM5 modules, suggesting involvement of potential therapeutic targets in those data-driven networks. Our findings may help develop therapeutic strategies to benefit patients.

ABSTRACT Pathogenic intracellular mycobacteria, such as Mycobacterium tuberculosis and Mycobacterium avium, which cause lung diseases, can grow in macrophages. Extracellular mycobacteria have been reported in the lungs, blood, and sputum of patients, indicating the involvement of these pathogens in disease progression. Erythrocytes are involved in the symptoms associated with pulmonary mycobacterial diseases, such as bloody sputum and hemoptysis; however, little attention has been paid to the role of erythrocytes in mycobacterial diseases. Herein, we found that Mycobacterium avium subsp. hominissuis (MAH) and Mycobacterium intracellulare colocalized with erythrocytes at the sites of lung infection, inside capillaries and necrotic areas of granulomas, using histopathological examinations. Electron microscopy showed that MAH adhered and entered human erythrocytes when they were cocultured in vitro. MAH adhered to erythrocytes through complement receptor 1 and cell-surface sialo-glycoproteins. Importantly, MAH grew vigorously without causing any pronounced damage to erythrocytes. This erythrocyte-mediated enhancement of MAH growth occurred extracellularly depending on its direct attachment to erythrocytes. In contrast, MAH failed to multiply inside erythrocytes. Similarly, erythrocytes augmented the growth of other pathogenic mycobacteria, such as M. intracellulare and M. tuberculosis. THP-1 cell-derived human macrophages preferentially phagocytosed erythrocytes that were attached to mycobacteria (compared to bacteria alone), suggesting that erythrocyte-attached mycobacteria are an efficient infectious source for macrophages. Our findings provide new insights into the pathogenesis of mycobacterial diseases and offer an alternative and useful strategy for treating mycobacterial disease. IMPORTANCE Pathogenic mycobacteria, such as Mycobacterium tuberculosis, Mycobacterium avium subsp. hominissuis (MAH), and Mycobacterium intracellulare, cause pulmonary infections as intracellular parasites of lung macrophages and epithelial cells. Here, using histopathological examinations we found that MAH and M. intracellulare colocalized with erythrocytes in lung infection sites. Subsequent studies demonstrated that direct interaction with erythrocytes enhances the extracellular proliferation of mycobacteria based on the following results: 1. MAH adhered and invaded human erythrocytes upon coculture in vitro; 2. MAH adhered to erythrocytes through complement receptor 1 and cell-surface sialo-glycoproteins; 3. MAH rapidly proliferated when directly attached to erythrocytes but not within them; 4. other mycobacteria, such as M. intracellulare and M. tuberculosis, also proliferated in the same way as MAH. The finding that pathogenic mycobacteria grow extracellularly in an erythrocyte-dependent manner is of considerable clinical importance for understanding disease progression and latent infection.

Abstract Background Idiopathic portal hypertension (IPH) generally has a good prognosis and rarely results in liver transplantation. Furthermore, there are few reports of living donor liver transplantation (LDLT) for IPH with extrahepatic portal vein stenosis. Case presentation We report the case of a 51-year-old female patient diagnosed with IPH more than 20 years ago. She suffered severe jaundice, massive ascites, and encephalopathy at the time of her visit to our hospital. The patient’s extrahepatic portal vein showed a scar-like stenosis, and the portal flow was completely hepatofugal. Collateral circulation such as the splenorenal shunt was well developed, and multiple splenic artery aneurysms up to 2 cm were observed in the splenic hilum. Her Model for End-Stage Liver Disease score increased to over 40 because of renal dysfunction, requiring temporary dialysis. We performed LDLT using her husband’s right lobe graft and splenectomy. The extrahepatic stenotic portal vein was completely resected, and the superficial femoral vein (SFV) graft collected from the recipient’s right leg was used for portal reconstruction as an interposition graft. Although the clinical course after LDLT had many complications, the patient was discharged on postoperative day 113 and has been fine for 2 years after LDLT. Histopathologically, the explanted liver had obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal cirrhosis. Conclusion This case showed that severe IPH is occasionally associated with extrahepatic portal vein stenosis and can be treated with LDLT with portal vein reconstruction using an interposition graft. It was also suggested that the SFV is a useful choice for the interposition graft.

Abstract Background Granulosa cell tumor (GCT) is a type of ovarian sex cord-stromal tumor with low-grade malignancy, which can recur long after primary resection. All reports on GCTs in the liver describe cases of metastases, while there are no previous reports of primary GCTs originating from the liver. We report a case of GCT, with recurrence of liver metastasis long after ovariectomy, which was subsequently resected by a right trisectionectomy. Case presentation A 76-year-old woman presented with a history of surgical resection of an ovarian tumor performed 30 years previously; no details of the tumor were available. When she was 68 years old, an abdominal ultrasound revealed a small liver mass, which was diagnosed as a hepatic hemangioma with slow growth. Outpatient follow-up was discontinued for 5 years, and the patient was not examined again until the age of 76 years. At this point, the tumor had substantially increased in size, and surgical resection was required owing to suspicion of malignancy. The patient was then referred to our hospital. Contrast-enhanced computed tomography (CT) showed a large tumor, approximately 18 cm in size, occupying the right lobe and medial section of the liver. After percutaneous transhepatic portal vein embolization, a right trisectionectomy was performed. The histopathological findings of the resected specimen showed that the tumor cells had “coffee bean-like” nuclear grooves, which are characteristic of a GCT. Acidophilic non-structural Call-Exner bodies were also observed. Inhibin-α, CD99, and CD56 markers of sex cord-stromal tumors were detected on immunohistological examination; all pathology suggested a GCT. We considered the tumor to be a liver metastasis of a previous ovarian GCT that was resected 30 years prior by ovariectomy. There was no recurrence for > 15 months after the hepatectomy. Conclusions We report a case of a GCT in the liver, which was identified to be a liver metastasis. Right trisectionectomy was subsequently performed for tumor resection. Clinicians should be aware that ovarian GCTs may recur in the liver, and that GCT recurrence may occur long after ovariectomy of the primary ovarian GCT.

Herein, we report a case of an occult thyroid cancer that was not detected as a primary tumor on preoperative ultrasonography or postoperative pathological examination, although a diagnosis of papillary thyroid carcinoma metastasis was made owing to the presence of a mass in the right upper neck. Needle biopsy of the mass in the right upper neck revealed positive results for thyroglobulin and TTF-1 on immunostaining, and a papillary thyroid carcinoma was observed with papillary and follicular patterns. We suspected papillary thyroid carcinoma (T0N1bM0) or ectopic papillary thyroid carcinoma. Accordingly, we performed total thyroidectomy, central lymph node dissection, right lateral neck dissection, and resection of the superficial lobe of the right parotid. A postoperative pathological examination of 5-mm slices of the specimen revealed no primary tumor in the thyroid. However, a hyalinized image of the thyroid indicated that a micropapillary thyroid carcinoma might have spontaneously disappeared. As there was no normal thyroid tissue in the metastasis to the superior internal jugular lymph node, the tumor was unlikely to be an ectopic papillary thyroid carcinoma. Therefore, we made a diagnosis of a papillary thyroid carcinoma (pT0N1bM0). After surgery, we determined that the tumor belonged to a high-risk group of papillary thyroid carcinomas and a poor-prognosis group of symptomatic papillary thyroid microcarcinomas; accordingly, ablation was performed with 30 mCi iodine-131. There was no recurrence or metastasis 24 months after the first surgery.

A 57-year-old man who received a kidney transplant 4 years previously owing to unknown underlying disease presented with thrombocytopenia and fever. Hepatosplenomegaly and lymphadenopathy were observed, and development of prominent anasarca and worsening of renal function yielded the diagnosis of TAFRO syndrome. He was treated with high-dose steroids and plasmapheresis, and a thrombopoietin receptor agonist was administered for refractory thrombocytopenia. However, his general condition worsened, and he died on day 92. Histopathological analysis of a kidney autopsy specimen showed thrombotic microangiopathy characterized by glomerular endothelial swelling, mesangiolysis, and double contours of the glomerular capillary walls. His bone marrow showed megakaryocytic hyperplasia with mild reticulin fibrosis. Interestingly, these clinical and pathological features were remarkably similar to those the patient demonstrated before the kidney transplant, suggesting the recurrence of TAFRO syndrome. TAFRO syndrome is a rare systemic disorder whose concept has recently been established, but information on its long-term outcome is scarce. To our knowledge, this is the first case of TAFRO syndrome developing in a kidney transplant recipient, which suggests that disease recurrence occurs many years after the kidney transplant.

Abstract Background Pancreatic vascular malformation causes epigastric pain, pancreatitis, portal vein hypertension, bleeding, and rupture. It is a rare disease, with most pancreatic vascular malformations being arteriovenous malformations (AVMs) and the other types of malformations being rare. We report a case of capillary lymphatic malformation (CLM) in the pancreatic uncinate process. Case presentation A 74-year-old woman, who presented with complaints of repeated upper abdominal pain, was admitted to our institution. Contrast-enhanced dynamic computed tomography (CT) scan revealed that the tumor in the pancreatic uncinate process had a poor contrast effect in the arterial phase and a small contrast effect in the equilibrium phase, which are suggestive of a benign disease-like vascular malformation. However, we suspected that it could possibly be a malignant tumor because the tumor size tended to increase over time; thus, we decided to perform a surgery. We resected the tumor through a partial resection of the pancreas. Macroscopically, the cut surface of the tumor had a spongioid appearance. Histopathological examination findings showed a mixed shape of small capillaries and lymphatic ducts. The patient was diagnosed with CLM according to the International Society for the Study of Vascular Anomalies (ISSVA) classification, based on the histological appearance and immunostaining findings. The postoperative course of the patient was uneventful. Conclusions We reported a case of pancreatic vascular malformation, specifically a CLM, which was completely resected through a partial pancreatectomy.

Lung cancer is one of the most common malignancies with a high rate of mortality. Lung cancer stem-like cells (CSCs)/ cancer-initiating cells (CICs) play major role in resistance to treatments, recurrence and distant metastasis and eradication of CSCs/CICs is crucial to improve recent therapy. Cytotoxic T lymphocytes (CTLs) are major effectors of cancer immunotherapy, and CTLs recognize antigenic peptides derived from antigens that are presented by major histocompatibility complex (MHC) class I molecules. In this study, we analyzed the potency of a cancer-testis (CT) antigen, brother of the regulator of the imprinted site variant subfamily 6 (BORIS sf6), in lung CSC/CIC immunotherapy. BORIS sf6 mRNA was expressed in lung carcinoma cells (9/19), especially in sphere-cultured lung cancer stem-like cells, and in primary lung carcinoma tissues (4/9) by RT-PCR. Immunohistochemical staining using BORIS sf6-specific antibody revealed that high expression of BORIS sf6 is related to poorer prognosis. CTLs could be induced by using a human leukocyte antigen, (HLA)-A2 restricted antigenic peptide (BORIS C34_24(9)), from all of 3 HLA-A2-positive individuals, and CTL clone cells specific for BORIS C34_24(9) peptide could recognize BORIS sf6-positive, HLA-A2-positive lung carcinoma cells. These results indicate that BORIS sf6 is a novel target of lung cancer immunotherapy that might be useful for targeting treatment-resistant lung cancer stem-like cells.

Objective: Rare co-existance of disease or pathology Background: Currently, 3 molecular targeted drugs are available for the treatment of unresectable and recurrent gastrointestinal stromal tumors (GISTs), and result in improved prognoses and rare occurrence of bone metastases. However, there is no established treatment guideline for bone metastases of GIST. Case Report: The patient was a 56-year-old male who was diagnosed with leiomyosarcoma in 1997. Partial resection of the small bowel was performed. As part of post-operative follow-up in 2004, a computed tomography scan showed metastatic lesions in the liver and the right femoral neck. Accordingly, partial hepatectomy was performed, followed by artificial femoral head replacement. In 2006, bone metastases were detected in the sternum, cervical and thoracic vertebra, and the right upper arm; therefore, the patient was subjected to radiotherapy. However, further histopathological examination revealed positive findings for CD34+ and KIT cells, prompting a diagnosis of GIST. Imatinib was started. The disease remained stable. However, in 2010, metastasis to the right ilium was detected, after which there was an increase in metastatic lesions in the thoracic vertebra, prompting a diagnosis of progressive disease. Thus, treatment with sunitinib was initiated. In 2012, the patient experienced spinal paralysis due to metastasis in the eighth thoracic vertebra. In 2013, metastases in the right ilium, lungs, and liver were detected. In 2014, the patient died. Conclusions: Multidisciplinary treatment via radiotherapy and surgery for GIST with bone metastases indicates the possibility of extending the overall survival further. [ABSTRACT FROM AUTHOR]

Background: Uterine sarcoma is a rare tumor that is often difficult to classify based on morphological and immunohistochemical analysis alone. Limited access to molecular biological analysis in routine practice would hinder making a definitive diagnosis. Case Presentation: In this report, we describe a case of a mesenchymal tumor arising from the uterine cervix in a 52-year-old woman. From microscopic morphology of the resected specimen, epithelioid leiomyosarcoma, high-grade endometrial stromal sarcoma, or uterine gastrointestinal stromal tumor (GIST) were considered as differential diagnoses. The immunophenotype of the tumor featured smooth muscle differentiation and hormone receptor expression. The cell membrane and cytoplasm were positive for c-kit, although no mutation was found in the c-kit or PDGFRA gene. Fluorescence in situ hybridization (FISH) analysis revealed a relatively low frequency of YWHAE rearrangement, whereas there were few NUTM2A and NUTM2B split signals. Conclusions: In this case, the tumor was not typical of any three of the differential diagnoses mentioned above. However, insufficient frequency of YWHAE, NUTM2A, and NUTM2B gene rearrangement and absence of mutation in both the c-kit and PDGFRA genes suggested that this tumor should be categorized as epithelioid leiomyosarcoma. This is an instructive case showing a potential diagnostic pitfall of uterine sarcoma. Comprehensive approaches including molecular biological techniques are required for definitive diagnosis. [ABSTRACT FROM AUTHOR]

Background: Pseudomyogenic hemangioendothelioma (PHE) is an unusual vascular tumor of intermediate malignancy that rarely metastasizes and tends to arise in the lower limbs of young adults and children. Histologically, PHE shows fascicular proliferation of eosinophilic spindle cells and/or epithelioid cells showing "pseudomyogenic" morphology. Immunohistochemically, PHE is usually positive for vimentin, cytokeratin, CD31 and ERG. Method: We examined FOSB immunohistochemistry (IHC) in 27 cases consisting of 4 PHE and its histologic mimics including 6 epithelioid hemangioendotheliomas (EHE), 8 angiosarcomas (AS), 4 Kaposi sarcomas (KS) and 5 epithelioid sarcomas (ES). In addition, we performed IHC of CAMTA1 which has recently been established as a useful marker of EHE. We elucidated the diagnostic utility of FOSB IHC in the differential diagnosis of PHE and its histological mimics and also examined the usefulness of FOSB and CAMTA1 IHC combination in the differential diagnosis of the tumors. Results: IHC revealed diffuse and strong FOSB expression in all PHE cases, while the other tumor types demonstrated limited, weak or no FOSB expression. All EHE cases exhibited diffuse and moderate to strong expression of CAMTA1. All tumor types except for EHE showed limited, weak or no CAMTA1 reactivity. Conclusions: Diffuse and strong FOSB expression was specific for PHE in the current series and FOSB IHC is an effective tool for differentiating between PHE and its histological mimics. Moreover, the combination of FOSB and CAMTA1 IHC is useful for distinguishing PHE from EHE. [ABSTRACT FROM AUTHOR]

Background: Exogenous lipoid pneumonia is a rare disease caused by aspiration or inhalation of oily substances.Case Presentation: A 66-year-old male with dry cough (Case 1) and a 38-year-old female with shortness of breath (Case 2) demonstrated ground-glass opacities on chest computed tomography and were diagnosed with lipoid pneumonia based on the confirmation of lipid-laden alveolar macrophages. Both patients habitually performed sesame oil pulling via nasal or mouth washing for several months prior to the diagnosis.Conclusion: Steroid therapy and bronchoalveolar lavage resulted in improvement in Case 1, and no intensive therapy was required for Case 2. Sesame oil pulling has been rarely been reported to cause lipoid pneumonia. [ABSTRACT FROM AUTHOR]

Survivin is expressed in the nucleus and/or cytoplasm of various malignant cells. Nuclear survivin is critical for the completion of mitosis, while cytoplasmic survivin functions as an inhibitor of apoptosis. The expression of survivin has been reported to be associated with the aggressiveness of certain types of cancer. The present study examined the association between cigarette smoking history and the expression of survivin and Ki-67 in lung adenocarcinomas of pathological (p) stages I, II and III. The expression of survivin and Ki-67 in adenocarcinomas was also compared with that of other p-stage I lung cancers, including squamous cell carcinoma (SqCC), large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SmCCs), of patients with a smoking history. In adenocarcinomas at p-stage I, labeling indices (LIs) of nuclear survivin and Ki-67 were significantly higher in tissue samples from smokers than those from non-smokers; however, the nuclear survivin and Ki-67 LIs in p-stage II and III adenocarcinomas from non-smokers and smokers were similar to those in p-stage I adenocarcinomas of smokers. The nuclear survivin and Ki-67 LIs in adenocarcinomas of smokers at p-stage I were lower than those in SqCCs, LCNECs and SmCCs of smokers at the same stage. Smokers with adenocarcinoma also exhibited a higher survival rate compared with that of smokers with SqCCs, LCNECs and SmCCs. The present results indicated that a history of smoking is associated with increased nuclear survivin and Ki-67 expression in lung adenocarcinomas of p-stage I, but not p-stages II or III. In addition it was revealed that, in smokers, the nuclear survivin and Ki-67 expression in p-stage I adenocarcinomas was lower than that of other p-stage I lung cancer types, and was associated with an enhanced survival rate. In conclusion, smoking is associated with the histogenesis of lung adenocarcinoma but not with the development of lung adenocarcinoma, based on the nuclear expression levels of Ki-67 and survivin. [ABSTRACT FROM AUTHOR]

The cancer cells of lung adenocarcinoma with a micropapillary pattern (MPP) have been found to frequently invade lymphatic vessels, and the prognosis of patients with lung adenocarcinoma with an MPP is poor. In the present study, the cancer cells of lung adenocarcinomas containing an MPP were found to express vimentin more extensively than those in lung adenocarcinoma without an MPP. The contribution of cancer cells in the MPP component to adenocarcinoma lymphatic invasion was assessed using vimentin as a marker. Vimentin expression was analyzed in the cancer cells present in each lymphatic vessel and compared with the expression of vimentin in the cancer cells in the adenocarcinomas without an MPP component. The results showed that the cancer cells in the lymphatic vessels expressed vimentin more extensively than those in the adenocarcinoma components without an MPP, suggesting that cancer cells derived from an MPP component are present in the lymphatic vessels. By contrast, the area of the MPP component in each adenocarcinoma was <25%. These findings suggest that cancer cells in MPP components have a high capacity to invade lymphatic vessels and that their high invasive capacity may be associated with a poor prognosis in patients with adenocarcinoma with an MPP component. [ABSTRACT FROM AUTHOR]

Abstract  Hyperplastic polyps (HPs) of the stomach have been reported to be mostly benign. However, in rare cases, carcinomas have been found in HPs. We treated a 59-year-old Japanese male who underwent a total gastrectomy, and a gross examination of the resected stomach revealed a 4.8 � 3.8-cm polyp on the greater curvature of the antrum and multiple small polyps in the whole gastric mucosa. Histologically, the large polyp consisted mainly of hyperplastic foveolar epithelium, while the presence of variously colored lobules demonstrated a poorly differentiated adenocarcinoma mixed with signet-ring cell carcinoma. Hyperplastic polyps should therefore be carefully examined microscopically as a polypectomy specimen and in resected stomach specimens. [ABSTRACT FROM AUTHOR]

Many nuclear and cytoplasmic proteins are O-glycosylated on serine or threonine residues with the monosaccharide β-N-acetylglucosamine, which is then termed O-linked N-acetylglucosamine (O-GlcNAc). It has been shown that abnormal O-GlcNAc modification (O-GlcNAcylation) of proteins is one of the causes of insulin resistance and diabetic complications. In this study, in order to examine the relationship between O-GlcNAcylation of proteins and glucose-stimulated insulin secretion in noninsulin-dependent type (type 2) diabetes, we investigated the level of O-GlcNAcylation of proteins, especially that of PDX-1, and the expression of O-GlcNAc transferase in Goto–Kakizaki (GK) rats, which are an animal model of type-2 diabetes. By immunoblot and immunohistochemical analyses, the expression of O-GlcNAc transferase protein and O-GlcNAc-modified proteins in whole pancreas and islets of Langerhans of 15-week-old diabetic GK rats and nondiabetic Wistar rats was examined. The expression of O-GlcNAc transferase at the protein level and O-GlcNAc transferase activity were increased significantly in the diabetic pancreas and islets. The diabetic pancreas and islets also showed an increase in total cellular O-GlcNAc-modified proteins. O-GlcNAcylation of PDX-1 was also increased. In the diabetic GK rats, significant increases in the immunoreactivities of both O-GlcNAc and O-GlcNAc transferase were observed. PUGNAc, an inhibitor of O-GlcNAcase, induced an elevation of O-GlcNAc level and a decrease of glucose-stimulated insulin secretion in isolated islets. These results indicate that elevation of the O-GlcNAcylation of proteins leads to deterioration of insulin secretion in the pancreas of diabetic GK rats, further providing evidence for the role of O-GlcNAc in the insulin secretion. [ABSTRACT FROM AUTHOR]

Pink-flowered gentian plants (Gentiana scabra) have been bred from spontaneous mutations of blue-flowered gentian plants, but the formation mechanism(s) is unknown so far. To investigate the process, two independent pink-flowered gentian plant lines were analyzed by a molecular biological approach. HPLC analysis showed that petals of the blue-flowered cultivar contained a small amount of cyanidin derivatives and major delphinidin derivatives, whereas pink petals had only a small amount of cyanidin derivatives. To find the causal factor(s) of this change, we focused on flavonoid 3′,5′-hydroxylase (F3′,5′H), which is a key enzyme for delphinidin biosynthesis in the flavonoid biosynthetic pathway. Molecular analyses confirmed that the loss of delphinidin synthesis could be attributed to the insertions of different transposable elements in the F3′,5′H gene in each independent pink-flowered gentian plant. Sequence analysis showed that these transposable elements were classified into an hAT superfamily and terminal-repeat retrotransposon in miniature (TRIM), by which normal F3′,5′H transcripts were interrupted. Southern blot analysis indicated that they belong to high copy number elements and are also found in a related gentian species (G. triflora). These results suggest that the transposable elements inserted in F3′,5′H are the source of the mutations and may also play a substantial role in the genomic evolution of the genus Gentiana. [ABSTRACT FROM AUTHOR]

The occurrence of pleural malignant mesothelioma (MM) is unusual and the cases that appear as a localized tumor are extremely rare. A case of localized pleural MM including immunohistochemical findings is presented. A 70-year-old man had an abnormal shadow found during a routine roentgenogram at an annual health checkup and was admitted to Toneyama National Hospital (Toyonaka, Osaka, Japan) for detailed examinations. Chest X-rays showed a 2 × 5 cm-sized nodule with relatively smooth margins in the right segment three. Computed tomography (CT) showed an extrapleural mass with a smooth surface and a thickened parietal pleura, and results of a biopsy performed under CT scanning yielded MM. Systematic examinations did not show any metastasis and the patient underwent surgery for removal of the mass. The resected tumor, measuring 3.2 × 3.1 cm, was firm, partially encapsulated, and irregularly shaped. Pathological examinations revealed that it consisted of large polygonal cells, partially showing myxoid patterns, which led to a diagnosis of localized pleural MM. Tumor recurrence was seen, and the duration between initial symptoms and death was 29 months. This case suggests that localized pleural MM has a high proliferative potential and aggressive course, and is considered an early stage of diffuse pleural MM. [ABSTRACT FROM AUTHOR]

In suspension cultures of Phytolacca americana, betacyanin accumulation was reduced when cell division was inhibited by treatment with various inhibitors of DNA synthesis or anti-microtubule drugs. Aphidicolin (APC), an inhibitor of DNA synthesis, reduced the incorporation of radioactivity from labeled tyrosine into betacyanin, but the incorporation of radioactivity from labeled 3,4-dihydroxyphenylalanine (DOPA) into betacyanin was not affected by similar treatments. Propyzamide, another anti-microtubule drug, reduced incorporation of radioactivity from tyrosine and DOPA into betacyanin. However, the rate of incorporation from DOPA was higher than that from tyrosine. The results suggest that inhibition of betacyanin accumulation in Phytolacca americana cells by APC and propyzamide is due to suppression of the reaction converting tyrosine to DOPA, which may be closely related to cell division. [ABSTRACT FROM AUTHOR]

2,4-Dichlorophenoxyacetic acid (2,4-D) strongly promoted betacyanin accumulation in suspension cultures of Phytolacca americana L. The betacyanin accumulation attained a maximum al 5 μM 2,4-D, when betacyanin content per cell reached 252% as compared to the control (2,4-D free). 2,4-D elevated the level of free tyrosine, which is tine precursor of betacyanin. The addition of 1 mM tyrosine tö the medium partially reversed the reduction of betacyanin accumulation caused by the removal of 2,4-D. Tracer experiments using labelled tyrosine showed that 2,4-D activated the biosynthetic pathway from tyrosine to betacyanin. These results indicate that a sufficient supply of tyrosine and the activation of biosynthesis of betacyanin from tyrosine by 2,4-D elevate the level of betacyanin [ABSTRACT FROM AUTHOR]