bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential correlation between interleukin patterns in disseminated and chronic human paracoccidioidomycosis
Authors: SILVA C L , SILVA M F , FACCIOLI L H , PIETRO R C L , CORTEZ S A E , FOSS N T 
Published: November 2013

SUMMARYIn an attempt to understand better the immunoregulatory disorders in paracoccidioidomycosis (PCM), the possible correlation between interleukin pattern, lymphoproliferation, C-reactive protein (CRP) and specific antibody levels was investigated in the polarized clinical forms of this disease. We studied 16 PCM patients, eight with the disseminated disease (four under treatment and four non-treated) and eight with the chronic disease. The patients with disseminated disease exhibited high antibody titres specific to Paracoccididoides brasiliensis antigen compared with patients with the chronic form of disease. Tumour necrosis factor (TNF), IL-1, IL-6 and CRP in the serum of non-treated disseminated PCM patients were increased, which correlated positively with the low mitogenic response of peripheral blood mononuclear cells (PBMC) to phytohaemagglutinin (PHA) (P &lt; 0·01) and with the high antibody titres (P &lt; 0·001) of these patients. Moreover, we found in the disseminated PCM patients positive correlations between IL-1 and IL-6 (P = 0·0007); IL-1 and TNF (P = 0·0045); IL-1 and IL-6 with the high antibody titres (P = 0·0834 and P = 0·0631, respectively); IL-1, IL-6 and TNF with CRP levels. By contrast, no correlations were found with those interleukins in the treated disseminated and chronic patients or in controls. It was interesting to find an inverse correlation between IL-4 and antibody production in non-treated disseminated PCM (r = −0·4770); moreover, a significant correlation (P = 0·0820) was found in chronic PCM patients with respect to the low level of either IL-4 and antibody titres against fungus antigen. Chronic PCM patients also had IL-2 levels inversely correlated with antibody production (r = −0·6313; P = 0·0628). Inverse correlations were also observed between IL-2 and IL-6 levels in non-treated disseminated patients (P = 0·0501) and between IL-2 and IL-4 in chronic patients (P = 0·0131). The inflammatory cytokines might have a pivotal role in the genesis and in control of some aspects of the disease, such as granulomatous reaction, hypergammaglobulinaemia and depression of T cell-mediated immunity in PCM.
The role of somatic structure of the fungusParacoccidioides brasiliensisupon B cell activation in experimental paracoccidioidomycosis
Authors: SILVA M F , SILVA C L 
Published: November 2013

SUMMARYIn this study, we report an increase of the number of antibody-secreting cells and the augmentation of antibody production against unrelated antigens in mice infected with the fungus P. brasiliensis, as well as in mice inoculated with cell wall preparation isolated from P. brasiliensis (CW). The immunomodulatory effect of the live fungus and the CW preparation was dose-dependent, and their actions were mainly restricted to the i.v. or i.p. inoculation simultaneously with the sheep erythrocyte challenge by the i.v. route or restricted to i.p. inoculation of CW when bovine serum albumin (BSA) antigen was used. The dependence of antibody production on different routes of CW inoculation was correlated with the number of antigen-specific B cells in the spleen as determined by direct and reverse plaque-forming cell assays. The immunization schedules using CW preparation caused a preferential production of IgM and IgG3 antibodies. The results also showed that the hyperactive humoral immune response of mice induced by i.p. inoculation of CW was devoid of polyclonal B cell activation compared with the effects observed for the lipopolysaccharide (LPS)-treated groups. Paracoccidioides brasiliensis CW components may have potent immunological properties related to the non-specific B cell activation found in paracoccidioidomycosis.
Interaction of the cell-binding domain of fibronectin with VLA-5 integrin induces monokine production in cultured human monocytes
Authors: TAKIZAWA T , NISHINARITA S , KITAMURA N , HAYAKAWA J , KANG H , TOMITA Y , MITAMURA K , YAMAGAMI K , HORIE T 
Published: November 2013

SUMMARYThe effect of fibronectin on IL-1α, IL-1β, tumour necrosis factor-alpha (TNF-α), and IL-6 production was investigated with cultured monocytes isolated from human peripheral blood. Monokine concentrations were determined by both ELISA and bioassay. Fibronectin markedly stimulated the secretion of IL-1α, IL-1β, TNF-α and IL-6 from cultured monocytes in a dose-dependent manner, with the maximal effect apparent within 24 h. Northern blot analysis revealed a marked increase in the abundance of mRNA specific for each monokine on exposure of monocytes to fibronectin. Monoclonal antibodies to the α chain of very late antigen (VLA)-5, the β1 integrin, the α chain of Mac-1, and the β2 integrin, as well as the synthetic peptide of GRGDSP (which corresponds to the cell-binding domain of fibronectin), inhibited (&gt;50%) fibronectin-induced monokine production. Monoclonal antibodies to the α chain of VLA-4, and the α chain of LFA-1, as well as the synthetic peptide CS-1 (which corresponds to the alternatively spliced connecting segment of fibronectin) and the control peptide GRADSP, had no inhibitory effect on monokine production. A MoAb, R60, that recognizes an epitope of the fibronectin molecule that includes the RGD sequence, inhibited monokine production, whereas the MoAb Y16, which recognizes another epitope of fibronectin not including RGD, did not. These results indicate that fibronectin-induced production of IL-1α, IL-1β, TNF-α and IL-6 from cultured monocytes is mediated predominantly by interaction of the cell-binding domain of fibronectin with VLA-5, although Mac-1 also may contribute to this effect of fibronectin. Our results indicate that the interaction of fibronectin with integrins may contribute to the cytokine network in inflammatory response.
COMBINED INTRAARTERIAL CISPLATIN INFUSION AND RADIATION THERAPY FOR INVASIVE BLADDER CANCER
Authors: Mizoguchi Hiroaki , Nomura Yoshio , Terada Katsuhiko , Nakagawa Masayuki , Ogata Jiro 
Published: November 2013

Combined intraarterial cisplatin infusion and radiation therapy were performed as the initial treatment for 23 patients (mean age: 70 years) with invasive bladder cancers (T2 in 17, T3 in 6) who were suitable for total cystectomy. Of these patients, five who had multiple invasive cancers without laterality had their intrapelvic hemodynamics altered by embolizing a contralateral internal iliac artery. Cisplatin (50 mg) was infused into the internal iliac artery through a subcutaneous reservoir twice a week over three weeks while concurrent radiation therapy with 30 Gy, delivered in 15 fractions, was performed. Additional cisplatin infusions were given in six patients. After this combined therapy, total cystectomy and ileal conduit was performed in six patients and transurethral resection of bladder tumor (TURBT) in 17. Two of the patients who underwent total cystectomy were found to exhibit a complete response. Therefore, the overall response rate was 87%, including 13 complete responses and seven partial responses. The complete response rates in patients with clinical stage T2 and T3 disease were 53 and 67%, respectively. The complete response rate was slightly higher in patients with a non‐papillary cancer than in those with a papillary one. Toxic reactions included a decrease in bladder capacity in two patients and severe diarrhea due to methicillin‐resistant Staphylococcus aureus colitis in one. Other forms of toxicity, including nausea, vomiting, neurotoxicity in the gluteal region, nephrotoxicity and myelosuppression, were tolerable. All but one of the patients are alive. This patient died of distant metastasis and seven other patients had a local recurrence of bladder cancer. One patient who developed invasive bladder cancer reaching the prostatic urethra underwent total cystectomy and ileal conduit. One who had a recurrence at the same site as the previous tumor underwent partial cystectomy. Five patients who had superficial bladder cancer were easily controlled by TURBT. Finally, bladder function was preserved in 65% of all patients in this study at a mean follow‐up time of 29 months.We conclude that combined intraarterial cisplatin infusion and radiation therapy is useful for the initial treatment of invasive bladder cancer because this combined therapy provides a favorable quality of life with the preservation of bladder function.Further detailed follow‐up is necessary to determine whether this therapy also has a prophylactic effect on the recurrence of bladder cancer.
Lysophosphatidic acid accelerates lung fibrosis by inducing differentiation of mesenchymal stem cells into myofibroblasts
Authors: Tang Na , Zhao Yanxia , Feng Ruopeng , Liu Yinan , Wang Shuling , Wei Wanguo , Ding Qiang , An Michael (Songzhu) , Wen Jinhua , Li Lingsong 
Published: November 2013

AbstractLung fibrosis is characterized by vascular leakage and myofibroblast recruitment, and both phenomena are mediated by lysophosphatidic acid (LPA) via its type‐1 receptor (LPA1). Following lung damage, the accumulated myofibroblasts activate and secrete excessive extracellular matrix (ECM), and form fibrotic foci. Studies have shown that bone marrow‐derived cells are an important source of myofibroblasts in the fibrotic organ. However, the type of cells in the bone marrow contributing predominantly to the myofibroblasts and the involvement of LPA‐LPA1 signalling in this is yet unclear. Using a bleomycin‐induced mouse lung‐fibrosis model with an enhanced green fluorescent protein (EGFP) transgenic mouse bone marrow replacement, we first demonstrated that bone marrow derived‐mesenchymal stem cells (BMSCs) migrated markedly to the bleomycin‐injured lung. The migrated BMSC contributed significantly to α‐smooth muscle actin (α‐SMA)‐positive myofibroblasts. By transplantation of GFP‐labelled human BMSC (hBMSC) or EGFP transgenic mouse BMSC (mBMSC), we further showed that BMSC might be involved in lung fibrosis in severe combined immune deficiency (SCID)/Beige mice induced by bleomycin. In addition, using quantitative‐RT‐PCR, western blot, Sircol collagen assay and migration assay, we determined the underlying mechanism was LPA‐induced BMSC differentiation into myofibroblast and the secretion of ECM via LPA1. By employing a novel LPA1 antagonist, Antalpa1, we then showed that Antalpa1 could attenuate lung fibrosis by inhibiting both BMSC differentiation into myofibroblast and the secretion of ECM. Collectively, the above findings not only further validate LPA1 as a drug target in the treatment of pulmonary fibrosis but also elucidate a novel pathway in which BMSCs contribute to the pathologic process.
Colon epithelial proliferation and carcinogenesis in diet‐induced obesity
Authors: Takahashi Hirokazu , Hosono Kunihiro , Endo Hiroki , Nakajima Atsushi 
Published: November 2013

AbstractColorectal cancer is the third leading cause of cancer death in Japan and the United States and is strongly associated with obesity, especially visceral obesity. Several metabolic mediators, such as adiponectin, have been suspected to play a role in obesity‐related carcinogenesis. In a previous human study, the existence of a significant correlation between the number of human dysplastic aberrant crypt foci (ACF) and the visceral fat area was demonstrated, and also that of a significant inverse correlation between the number of dysplastic ACF and the plasma adiponectin level. Other studies have investigated the effect of adiponectin under the normal and high‐fat diet conditions in a mouse model of azoxymethane‐induced colon cancer. Enhanced formation of both ACF and tumors was observed in the adiponectin‐deficient mice, as compared with that in the wild‐type, under the high‐fat diet condition but not under the normal diet condition. Furthermore, that the 5′‐AMP‐activated kinase/mammalian target of rapamycin pathway is involved in the promotion of colorectal carcinogenesis in adiponectin‐deficient mice under the high‐fat diet condition was shown. Therefore, that the 5′‐AMP‐activated kinase/mammalian target of rapamycin signaling pathway may play an important role in colorectal carcinogenesis was speculated. Metformin, a biguanide derivative widely used in the treatment of diabetes mellitus, has been shown to exert a suppressive effect on ACF formation in both mouse models and humans. Therefore, metformin might be a promising candidate as a safe drug for chemoprevention of colorectal carcinogenesis. Further studies with high evidence levels, such as randomized, controlled studies, are needed to clarify these relationships.
Non‐alcoholic fatty liver disease: Factors associated with its presence and onset
Authors: Miyake Teruki , Kumagi Teru , Furukawa Shinya , Tokumoto Yoshio , Hirooka Masashi , Abe Masanori , Hiasa Yoichi , Matsuura Bunzo , Onji Morikazu 
Published: November 2013

AbstractNon‐alcoholic fatty liver disease (NAFLD) may progress to cirrhosis, liver failure, and complicated hepatocellular carcinoma. In addition, NAFLD is a risk factor for the development of other serious diseases, such as diabetes or cardiovascular disease. Therefore, the detection of early‐stage NAFLD is important. Many studies have described the factors that predict the presence of NAFLD and its onset, and several markers have been identified. These markers have enabled the identification of high‐risk patients and have improved routine medical practice. To prevent advanced disease, clinicians need to have simple markers that predict the onset of NAFLD so that interventions can be started at much earlier stages of disease. This review summarizes the current state of knowledge regarding independent factors, as reported in large studies, that predict the presence of NAFLD and its onset, especially markers that can be used in daily medical practice, such as physical measurements and blood tests.
Nutritional components regulate the gut immune system and its association with intestinal immune disease development
Authors: Lamichhane Aayam , Kiyono Hiroshi , Kunisawa Jun 
Published: November 2013

AbstractThe gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases.
Characteristics and diagnosis of NAFLD/NASH
Authors: Hashimoto Etsuko , Taniai Makiko , Tokushige Katsutoshi 
Published: November 2013

AbstractNon‐alcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome. NAFLD has become an important public health issue because of its high prevalence. NAFLD consists of two clinicopathological entities: simple steatosis, which generally follows a benign non‐progressive clinical course, and non‐alcoholic steatohepatitis (NASH), which may progress to cirrhosis and hepatocellular carcinoma. The diagnosis of NAFLD is based on the following three criteria: non‐alcoholic, detection of steatosis either by imaging or by histology, and appropriate exclusion of other liver diseases. Alcoholic liver disease can occur when daily alcohol consumption exceeds 20 g in women or 30 g in men. Thus, non‐alcoholic indicates lower levels of these alcohol consumptions. However, there is still no clear consensus regarding the threshold alcohol consumption for defining non‐alcoholic liver disease. Then, there is the strong recommendation for a change in the nomenclature, such as use of the term metabolic fatty liver and metabolic steatohepatitis. NASH has emerged as a clinicopathological entity, and even now, a liver biopsy remains the gold standard for making a definitive diagnosis. However, liver biopsy has several drawbacks. In general practice, NAFLD is a convenient‐to‐use term for the diagnosis and management of these patients, and serum biomarkers that indicate the severity of fibrosis serve as clinically useful tools for the identification of NAFLD in patients with bridging fibrosis or cirrhosis. In the future, improved understanding of the pathogenesis of NASH and new technologies may contribute to the diagnostic process and provide reliable, non‐invasive alternatives to liver biopsy.
Response to nutritional support and therapeutic approaches of amino acid and protein metabolism in surgical patients
Authors: Sakurai Yoichi 
Published: November 2013

AbstractThe response to critical illness involves alterations in all aspects of metabolic control, favoring catabolism of body protein. In particular, body protein loss occurring as a result of the alteration of protein metabolism has been reported to be inversely correlated with the survival of critically ill patients. Despite the availability of various therapeutic modalities aiming to prevent loss of the body protein pool, such as total parenteral nutrition, enteral nutrition designed to provide excessive calories as a form of energy substrate, and protein itself, the loss of body protein cannot be prevented by any of these. Loss of the boyd protein store occurs as a consequence of the alteration of the intermediate metabolism that works for the production of energy substrate. This alteration of substrate metabolism may be linked to the alteration of protein metabolism. However, no specific factors regulating amino acid and protein metabolism have been identified. Thus, further investigations evaluating amino acid and protein metabolism are required to obtain better understanding of metabolic regulation in the body, which may lead to the development of novel and more effective therapeutic modalities for nutrition in the future.
Maldigestion from pancreatic exocrine insufficiency
Authors: Pongprasobchai Supot 
Published: November 2013

AbstractPancreatic exocrine insufficiency (PEI) is one of the long‐term consequences of chronic pancreatitis (CP). Majority of patients with PEI were undiagnosed or undertreated. Inadequately treated or subclinical severe PEI causes malnutrition and may pose the patients at risk of premature atherosclerosis and cardiovascular events. Indication of pancreatic enzyme replacement therapy (PERT) is patients with severe PEI, as indicated by the presence of steatorrhea, diarrhea, weight loss, fecal fat > 7 g/day, 13C‐mixed triglyceride breath test < 29%, fecal elastase < 100 ug/g stool, imaging or endoscopic findings of pancreatic ductal dilatation or calculi, and eight endosonographic criteria of CP. The mainstay treatment of PEI is PERT. Dietary fat restriction is unnecessary. PERT with lipase > 40 000 U per meal is recommended. Enteric‐coating may be preferred to conventional enzymes because of the availability of high‐dose preparations and no need of acid suppression co‐therapy. Administration of enzymes with meals is proven to be the most effective regimen. Response to PERT should be measured by the improvement of patients' symptoms, nutritional status, and, in selected cases, by fecal fat or 13C‐mixed triglyceride breath test. Patients unresponsive to PERT should be checked for compliance, increase the dose of lipase to 90 000 units/meal or co‐therapy with proton pump inhibitor. In patient with previous gastrointestinal surgery that may interfere enzyme‐food mixing, opening the capsules and administering the enzyme granules with meals. Finally, search for small intestinal bacterial overgrowth syndrome and other causes of small bowel malabsorption.
The relationship between pretreatment dietary composition and weight loss during a randomised trial of different diet approaches
Authors: McVay M. A. , Jeffreys A. S. , King H. A. , Olsen M. K. , Voils C. I. , Yancy W. S. 
Published: November 2013

AbstractBackgroundIdentifying pretreatment dietary habits that are associated with weight‐loss intervention outcomes could help guide individuals' selection of weight‐loss approach among competing options. A pretreatment factor that may influence weight‐loss outcomes is macronutrient intake.MethodsOverweight and obese Durham Veterans Affairs outpatients were randomised to a weight‐loss intervention with a low‐carbohydrate diet (n = 71) or orlistat medication therapy plus a low‐fat diet (n = 73). Percentage fat, carbohydrate and protein intake prior to treatment were measured using 4‐day food records. Linear mixed‐effects models were used to determine whether pretreatment percentage macronutrient intake influenced weight trajectories and weight loss in each weight‐loss condition.ResultsParticipant's mean age was 53 years, baseline body mass index was 39.3 kg m–2 and 72% were male. A higher pretreatment percentage carbohydrate intake was associated with less rapid initial weight loss (P = 0.02) and less rapid weight regain (P = 0.03) in the low‐carbohydrate diet condition but was not associated with weight trajectories in the orlistat plus low‐fat diet condition. In both conditions, a higher pretreatment percentage fat intake was associated with more rapid weight regain (P < 0.01). Pretreatment percentage protein intake was not associated with weight trajectories. None of the pretreatment macronutrients were associated with weight loss on study completion in either condition.ConclusionsSelection of a weight‐loss approach on the basis of pretreatment macronutrient intake is unlikely to improve weight outcomes at the end of a 1‐year treatment. However, pretreatment macronutrient intake may have implications for tailoring of interventions to slow weight regain after weight loss.
In routine clinical practice, few physicians use early viral kinetics to guide HCV dual therapy treatment decisions
Authors: Mangia Alessandra , Bányai Tivadar , De Bartolomeo Giuseppe , Gervain Judit , Habersetzer François , Mulkay Jean‐Pierre , Ouzan Denis , Parruti Giustino , Passariello Nicola , Remy Andre‐Jean , Rizzetto Mario , Shiffman Mitchell L. , Tice Alan D. , Schmitz Manuela , Tatsch Fernando , Rodriguez‐Torres Maribel 
Published: November 2013

AbstractBackground & AimsPROPHESYS is a large, multinational, non‐interventional prospective cohort study of chronic hepatitis C patients treated with peginterferon alfa/ribavirin. This subanalysis assesses rates of premature treatment discontinuation stratified by on‐treatment virological response (VR).MethodsThis PROPHESYS subanalysis is restricted to treatment‐naive, hepatitis C virus (HCV) genotype (G)1/2/3 mono‐infected patients who received peginterferon alfa‐2a (40KD)/ribavirin with intended treatment duration of 48 (G1) or 24 weeks (G2/3). Early virological responses were classified into four mutually exclusive categories [rapid VR (RVR), complete early VR (cEVR), partial EVR (pEVR), no RVR/EVR], using standard criteria.ResultsThe likelihood for shortening treatment owing to good efficacy was highest among patients with an RVR and HCV RNA ≤400 000 IU/ml (G1 10.0%; G2/3 5.8%) whereas for poor efficacy, it was highest in G1 non‐RVR/EVR patients with HCV RNA >400 000 IU/ml (56.6%). Factors significantly associated with early treatment discontinuation as a result of good efficacy in G1 patients included RVR vs. no RVR/EVR and, at baseline, lower HCV RNA, lower FIB‐4 score, HCV infection via injection drug use. For G2/3 patients, factors included lower baseline HCV RNA and G2 vs. G3 infection. Most patients started with the recommended peginterferon alfa‐2a dose, but a high proportion received a higher‐than‐recommended ribavirin dose.ConclusionsDespite international guidelines, few physicians used early viral kinetics to abbreviate treatment. Therefore, relatively few patients with an RVR and low baseline HCV RNA abbreviated treatment. In addition, there were deviations in ribavirin starting doses, suggesting that physicians tailor treatment according to local guidelines or previous experience.