50). In 106 incidences of aggression recorded, 82% of interactions involved a single colony member interacting with the stimulus subject. Both
sexes were equally likely to interact with stimulus subjects: sex ratio of individuals investigating (1) colony R428 member stimulus subjects: 27 females : 23 males; (2) stranger stimulus subjects: 29 females : 27 males. Season × treatment (F1, 18 = 8.03, P = 0.011) was a significant predictor of agonistic interactions when apple was introduced into colonies. Post hoc tests showed that aggression was highest for apple in winter compared with other treatments (Fig. 3). Agonistic interactions consisted mainly of one individual chasing another colony member away from the food. No damaging fights were recorded. Approximately 10% of the apple was consumed aboveground in winter, and all of the remaining food (apple and plants) was carried belowground. Y-27632 in vitro Ice rats consumed and hoarded about 40% of the apple when fresh natural vegetation was abundant in summer; introduced plants were not consumed. Ice rats resumed other activities (including mutual avoidance) after the food was consumed or hoarded. We investigated home-range size and social behaviour of an African alpine rodent, evaluating several functional hypotheses. Because the burrow is a shared resource, we predicted that ice rat colony members would be amicable and/or have reduced
aggression (social tolerance) aboveground, as occurs in mulgara Dasycercus blythi (Körtner, Pavey & Geiser, 2007). However, ice rats of both sexes avoided colony members, and contact was characterized by aggression more often than amicability.
Such spatial organization and social behaviour were 上海皓元医药股份有限公司 consistent between seasons. The potential for aggression possibly results in mutual avoidance between conspecifics (Shier & Randall, 2004). Therefore, the limited occurrence of agonistic interactions within an ice rat colony cannot be used to infer the degree of sociality. Ice rats sharing a burrow system were suspected to be a family group of a founding pair and non-reproductive offspring (Willan, 1990). However, we found that colonies comprised several adult males and females. Although kinship was unknown, all adults were reproductively active in summer, indicating plural breeding. Multi-male and multi-female social groups occur in Gunnison’s prairie dog Cynomys gunnisoni, in which resource availability, not mating strategy, drives sociality (Verdolin, 2007). Therefore, while ice rats may be constrained by their investment in a burrow system, which requires constant maintenance (Schwaibold & Pillay, 2006), our results are consistent with those of other rodents (e.g. lesser cavies Microcavia australis; Taraborelli, 2009) that communal burrowing is unlikely to be the sole driver of sociality.
Fibrosis 4 (FIB4) scoring system based on routine laboratory tests is widely used to estimate the amount of liver fibrosis in NAFLD and help identify patients that would require further evaluation with a liver biopsy. Liver stiffness measurement (LSM) using vibration controlled transient elastography by Fibroscan is a novel non-invasive tool and currently available in the United States for assessment of liver fibrosis in patients with Abiraterone chronic liver disease. Aim: The aim of the current study is to determine the diagnostic accuracy
of FIB4 and LSM for prediction of clinically significant fibrosis in patients with NAFLD and also examine the relationship between FIB4 score and LSM.
Methods: Patients with biopsy proven NAFLD (duration between liver biopsy and Fibroscan <1 year) or NASH related cirrhosis were identified from an IRB approved prospective database of patients undergoing Fibroscan. Clinically significant fibrosis was defined as presence of clinically obvious cirrhosis or METAVIR Fibrosis stage of ≥ 2. Results: A total of 94 patients met study inclusion criteria from a total of 217 NAFLD STI571 in vivo patients that underwent Fibroscan. The mean age of the study cohort was 54 ± 10 years (60% woman; 94% Caucasian) with a BMI of 31 ± 12 kg/m2. The mean ALT was 49 ± 36 U/L. Clinically significant fibrosis was present in 70% (n=66)
of the study cohort. The diagnostic accuracy of LSM for clinically significant fibrosis was good (AUROC=0.81) while the diagnostic accuracy of FIB4 score was poor (AUROC=0.63) (Figure 1). The optimal LSM cut-off value for a diagnosis of clinically significant fibrosis was 10.3 medchemexpress kPa with a sensitivity of 80% and specificity of 75%. The correlation between LSM and FIB score was weak but significant (r=0.35, p-val=0.001). Conclusion: LSM as measured by Fibroscan could be a useful tool for prediction of clinically significant fibrosis and appears to be superior to currently used FIB4 score. AUROC curves for LSM and FIB4 for clinically significant fibrosis in NAFLD Disclosures: Naga P. Chalasani – Consulting: Salix, Abbvie, Lilly, Boerhinger-Ingelham, Aege-rion; Grant/Research Support: Intercept, Lilly, Gilead, Cumberland, Galectin The following people have nothing to disclose: Raj Vuppalanchi, Samer Gaw-rieh, Regina Weber Nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease in Western countries, may progress to cirrhosis, liver failure, and complicated hepatocellular carcinoma.
The phenotype of Maid KO mice is normal. We therefore added 3 month repeated CCl4 injection (0.5mg/kg body) into Maid KO mice and wild type mice, and then analyzed liver fibrosis and hepatocarcinogenesis. We did DNA chip analysis and Ingenuity pathway analysis using 3 month CCl4 injected Maid KO and wild type livers and control no damage. We used 20 nM Bortezomib on HepG2 cells and human hepatocytes, and analyzed cell proliferation and HHM Selleckchem Z VAD FMK expression. (Results) CCl4 injected Maid KO mice accelerated to induce liver fibrosis compared with wild type mice (p<0.05), and had AFP positive-HCC (25%).
DNA chip analysis revealed that “”Cell cycle”" related genes such as Cyclin A2, Cyclin E1, Cyclin B and CDC25c were increased. We also found that these genes related with “”double strand DNA break repair”" such as RAD51, RAD54L and RAD50 were also increased. DNA repair genes such as BLM, MSH2, MHH1, RAD50 and MRE1 1 were also activated in Maid KO livers. Moreover, we found that TGF-beta 3, Collagen 1A Neratinib chemical structure and Collagen 3A were significantly increased. In vitro analysis, Bortezomib
specifically inhibited HepG2-proliferation with up-regulated HHM expression. (Discussion) We found that Maid KO mice itself activated DNA damage related and cell cycle related genes. Concerning with TGF-beta signaling, Maid disruption does not stop TGF-beta related cell inhibition and ECM production. From these systems, Maid KO mice induced both liver fibrosis and generation of HCC. Bortezomib induced HHM expression with inhibition of cell proliferation in HepG2 but not hepatocyte. These results indicated that Maid specifically 上海皓元医药股份有限公司 regulate DNA damage and progression of liver fibrosis and hepatocarcinogenesis. (Conclusion) Maid is a specific guardian gene to regulate DNA damage in liver fibrosis and hepatocarcinogenesis. Disclosures: Tomoaki Murata – Board Membership: Naoki Yamamoto, Taro
Takami, Issei Saeki, Koichi Fujisawa, Hiroshi Nishina, Isao Sakaida; Speaking and Teaching: Shuji Terai The following people have nothing to disclose: Shuji Terai, Naoki Yamamoto, Taro Takami, Issei Saeki, Koichi Fujisawa, Hiroshi Nishina, Isao Sakaida Tivantinib has been tested in clinical trials as c-MET inhibitor and demonstrated clinical benefit as a second line treatment of hepatocellular carcinoma (HCC). Since its efficacy was predicted by elevated expression of c-MET in previous phase-2 and -3 randomized trials, a phase-3 trial in HCC patients selected according to c-MET expression has been initiated. Unexpectedly, recent in vitro studies challenged the notion of tivantinib as a selective c-MET inhibitor. To provide a possible explanation for these conflicting data, we investigated the molecular mechanisms of action of tivantinib and whether their regulation is influenced by c-MET by using a panel of 8 cell lines showing different c-MET expression status.
but remained significant; however, NAFLD was not statistically significantly associated with CAC scores ≥100 (OR, 1.30; 95% CI, 0.94-1.80). The main finding of this large population-based study was a strong relationship between NAFLD and CAC, the latter being an established surrogate marker for coronary atherosclerosis. Importantly, this association was independent of the traditional risk factors for coronary artery disease as well as visceral adiposity. The association of NAFLD with CAC may be indirect and due to generalized obesity or ectopic fat, including VAT. However, CT examination revealed learn more that visceral adiposity attenuated but did not eliminate the relationship between
NAFLD and CAC. This study gave us the unique opportunity to assess the relationship between NAFLD and subclinical coronary atherosclerosis above and beyond VAT. An increasing number of studies have suggested that NAFLD is an independent risk factor for coronary artery disease and mortality.3, 5, 6, 9 This hypothesis has been supported by community-, population-, and hospital-based studies.29-31 Recent large prospective cohort study reported that in patients with clinical indications for coronary angiogram, NAFLD is associated with coronary artery disease independently of other metabolic factors.32 However, most of the previous studies that have suggested an independent NU7441 chemical structure association between NAFLD and coronary artery disease did not directly measure abdominal VAT. Most of these studies indirectly measured VAT using waist circumference, which has been shown to be more closely correlated with subcutaneous adipose tissue than with VAT.33 Because of this, multivariable analysis adjusted for waist circumference is not sufficient to demonstrate an independent relationship between NAFLD and coronary
artery disease above and beyond VAT. Recent studies have reported that the VAT is the abdominal fat that is most intimately associated with metabolic disease, myocardial infarction, stroke, and overall mortality.34-36 The cardiovascular risk in NAFLD may be attributed in part to underlying VAT.37 Therefore, we examined the relative contributions of hepatic fat MCE and VAT to subclinical coronary atherosclerosis. Multivariable regression analysis proved that the relationship between NAFLD and CAC score was significant, even after adjusting for age, sex, traditional coronary risk factors, and VAT. Therefore, we suggest that NAFLD might be an independent risk factor for subclinical coronary atherosclerosis. In addition, NAFLD together with elevated ALT, which might indicate suspected nonalcoholic steatohepatitis, was more associated with CAC than NAFLD with normal ALT in a dose-dependent manner. These findings suggest that CAC is associated with both nonalcoholic steatohepatitis and NAFLD.
1D and Supporting Table 2). We confirmed these results via real-time qRT-PCR and found that coculture
with HMs for 24 hours or for 5 days increased the expression of known NF-κB–regulated genes, including Il6, Saa3, Cxcl5, Cxcl14, Serpinb2, Ch25h, and Mmp13 (Fig. 2A,C). Surprisingly, HMs did not induce classical HSC activation markers such as Col1a1, Col1a2, or Acta2 messenger RNA (mRNA) and did not change α-smooth muscle actin (α-SMA) protein levels in HSCs (Fig. 2C). We confirmed that all NF-κB–dependent genes, including Timp1, were suppressed in the presence of adenoviral IκB superrepressor (Fig. 2A) or by short-term treatment with IKK inhibitor Bay 11-7085 at very low nontoxic concentrations (Supporting Fig. 3). NF-κB activation was further confirmed via Selleck LY294002 p65 immunohistochemistry (Fig. 2D) and immunoblot (Fig. 2E) demonstrating p65 translocation, p65-S536 phosphorylation, and IκBα degradation in HSCs treated with conditioned media from HMs but not after treatment with control media. Similar observations were made in an NF-κB reporter assay, in which coculture with HMs induced a >15-fold increase in NF-κB–driven luciferase activity (Fig. 2F). Based on these results, we focused on the NF-κB pathway in subsequent analyses of mechanisms by which HMs affect HSCs and fibrogenesis. Next, we determined whether HMs alter NF-κB–dependent
gene expression in HSCs in the fibrotic liver by employing a depletion approach. MCE公司 For this purpose, we analyzed gene expression in fluorescence-activated Selleck Kinase Inhibitor Library cell sorting (FACS) ultrapure HSCs isolates that were immediately lysed after isolation and thus provide a “snapshot” of HSC gene expression in the fibrotic liver. NF-κB–dependent gene expression was highly up-regulated in HSCs activated in vivo compared with quiescent HSCs (Fig. 2G). Macrophage depletion by repeated liposomal clodronate injection efficiently reduced F4/80-positive and CD11b- and F4/80-double positive macrophages and ameliorated liver fibrosis following BDL and CCl4 treatment (Supporting
Fig. 4). Notably, macrophage depletion strongly suppressed the expression of the NF-κB–dependent genes that were up-regulated by HMs in our coculture system (Fig. 2G). We further excluded that liposomal clodronate directly affects NF-κB via NF-κB reporter assay and or cell death in cultured HSCs (Fig. 2H,I). Next, we investigated mechanisms through which HMs induce NF-κB activation in HSCs. First, we tested the contribution of interleukin (IL)−1 and TNF to HM-induced NF-κB in HSCs based on their known potent activation of NF-κB, the presence of the IL-1 receptor in the NF-κB network identified by IPA analysis (Fig. 1C), and up-regulated M1 markers inducible nitric oxide synthase and Cox2 in HMs from BDL mice (Supporting Fig. 1C). HMs induced NF-κB to the same degree as rmIL-1β, and to a higher degree than rmTNFα (Fig. 3A).
In the protected forest, dietary breadths were low for jaguars and pumas and showed little overlap. In this habitat each relied heavily on a single medium-sized (5–10 kg) prey species: armadillos Dasypus novemcinctus for jaguars, and pacas Agouti paca for pumas. Both cats also took larger prey (>10 kg), mainly
white-lipped peccaries Tayassu pecari by jaguars and red brocket deer Mazama americana by pumas. In unprotected fragmented lands, jaguar scats rarely contained large wild prey species; rather, a diet of relatively small wild prey was supplemented with larger domestic species. buy JQ1 Pumas did not take domestic species and were scarce outside the protected forest, possibly indicating competition with humans for pacas and deer, which are also prized game species in the region. This study is the largest analysis to date of sympatric jaguar and puma diets in both forest and farmland. We suggest that jaguar predation on cattle may be reduced by ensuring that game hunting is sustainable and potentially by augmenting forests within the human matrix with large wild ungulates. The supplementation could benefit both of the cat species, and the local game hunting economy. ”
“The time it takes seeds to pass
through the gut of vertebrates is an important aspect of endozoochorous seed dispersal because it influences seed dispersal distance. The physical characteristics of 上海皓元医药股份有限公司 seeds (e.g. dry seed weight, volume and specific gravity) LEE011 supplier vary among plant species, which might cause a difference in seed movement through the gastrointestinal system. We conducted feeding experiments with captive female Japanese macaques Macaca fuscata (n=5) using eight different types of seeds to evaluate the effects of the physical characteristics of seeds on their passage time. The median seed recovery percentage for the real seeds was 35.5% (range, 24–78%). Among three passage time variables examined, the mean retention time (MRT) (37–54 h) and time of last appearance of a seed (TLA) (53–109 h) differed significantly among seed types, and the former differed significantly
among individuals. Transit time (TT) (22–35 h) did not. The generalized linear models (GLM) selected dry seed weight as the most important factor affecting MRT, and specific gravity of seeds as the most important factor affecting TLA. This implies that (1) heavier seeds and (or) seeds with greater specific gravity remain in the gut longer and are likely to be dispersed farther from the parent plant; (2) the lighter seeds and (or) seeds with lower specific gravity are dispersed nearer the parent. Our study demonstrated the importance of considering the effects of the physical characteristics of seeds on the manner in which primates disperse plant species, although we should consider the effect of the individual variation in the passage time, too.
 For example, passive transfer of AMA or immunization selleck kinase inhibitor with target antigens of AMA cannot induce the disease in animal models, and reduction of the titers of AMA does not improve the disease. Therefore, some researchers suppose that AMA does not seem to have an etiopathogenic role in PBC. In addition, because these M2 antigens are ubiquitously expressed in almost all cells of the body, AMA does not explain the organ-specificity of PBC. In contrast, it has been proposed that the cross-interaction of AMA with the epitheliocytic antigens of bile cholangioles may damage the epithelium of ductules, resulting in their obliteration.
Cellular immune mechanisms involving T-cell reaction are thought to participate in the pathogenesis of PBC, especially CNSDC and bile duct loss. T-helper 1 type CD4+ T cells expressing γ-interferon or CXCR3 have been check details reported to play important roles in progressive bile duct damage of PBC. Moreover, both CD4+ and CD8+ autoreactive T cells that specifically target PDC-E2 self-antigen, were detected in both peripheral blood and liver tissues of patients with PBC. The presence of anti-M3R antibodies
in patients with PBC should be significant both clinically and pathologically. First, anti-M3R antibodies could be useful as diagnostic markers for PBC. Antibodies reactive to the first loop had the highest diagnostic value for PBC
with moderate sensitivity (73.3%), and with both high specificity (80.0–100.0%) and high accuracy (74.0–84.6%) between PBC and CHC, NASH, PSC, obstructive jaundice, drug-induced liver injury and controls. Moreover, we could raise the sensitivity to 93.3% by analyzing anti-M3R antibodies against at least one epitope. Therefore, the combination of anti-M3R antibodies reactive to these epitopes could be a useful tool for the differential 上海皓元 diagnosis of PBC from CHC, NASH, PSC, obstructive jaundice, drug-induced liver injury and HC. Importantly, all 19 patients with PBC negative for antimitochondria M2 subunit antibody carried anti-M3R antibodies reactive to at least one extracellular domain of M3R, and 17 out of these 19 patients (89.5%) with PBC carried anti-M3R antibodies reactive to the first loop. Thus, anti-M3R antibodies could be useful as a new diagnostic marker for especially AMA negative patients with PBC. Second, we focused on the relationship between anti-M3R antibodies and clinicopathological features of PBC, including histopathological findings and various other autoantibodies. Unfortunately, we could not detect any difference between anti-M3R antibody positive and negative patients with PBC.
Several studies that looked at the frequency of development of overt HE in cirrhotic
patients found that those with MHE developed overt HE more often during follow up than those without MHE (Table 4).4,15,17,20,48,88,89 In addition, some studies have shown an increased risk of death in patients with liver cirrhosis and MHE compared to those without MHE (Table 4).20,22,88 However, patients with MHE had poorer liver function Midostaurin solubility dmso than those without MHE in these studies, making it difficult to ascribe the poor outcome to the presence of MHE. Das et al.4 studied the relationship of progression of MHE to overt HE in relation to the severity of liver dysfunction and found that the rate of progression to overt HE was much higher in patients with MHE and a CTP score > 6 than in those with MHE and a CTP score ≤ 6. Amodio et al.88 found that the presence of MHE and that of liver dysfunction were both associated with mortality on univariate analysis; however, on multivariate analysis, liver functional status was the only independent predictor of mortality. In another study, progression of MHE to overt HE was associated with abnormal response to oral glutamine challenge, which in turn CCI-779 mouse was associated with poor liver function.90 Furthermore, MHE in patients with preserved liver function but large portal-systemic shunts (congenital
shunts, non-cirrhotic portal hypertension and cirrhosis with preserved liver function) appears to have a good outcome, even though these data are based on a small number of patients.10 Thus, it appears that the higher risk of overt HE or death in patients with MHE may not be related to MHE per se but to the poorer liver
function in patients with MHE. 42 Patients with liver cirrhosis and MHE have a higher rate of subsequent development of HE than those with cirrhosis but no MHE. (1b) Treatment of MHE is primarily directed towards reduction of ammonia and includes non-absorbable disaccharides, prebiotics/probiotics and LOLA. Treatment of MHE improves psychometric performance and quality of life (Table 5). However, several issues regarding therapy remain unsettled. The effects of treating MHE on driving, complex occupational tasks, development MCE公司 of overt HE, and on survival have not been studied. Duration of therapy for achieving these end-points, choice of therapeutic agents and the role of combinations of therapies have also not been adequately studied and further research is needed to clarify these issues. Lactulose decreases blood ammonia levels, and improves psychometric performance and HRQOL (Table 5).3,59,62,64,67,91–95 Using cerebral diffusion tensor imaging, Kale et al.59 showed that interstitial brain edema observed in patients with MHE resolves after treatment for 3 weeks with lactulose in parallel with improvements in neuropsychiatric performance. Prasad et al.
Cholangitis is a careful complication after stone extraction. Endoscopic biliary stenting (EBS) after incomplete www.selleckchem.com/products/acalabrutinib.html extraction of stones is sometimes performed in patients with comorbidities and poor performance status. We retrospectively investigated the risk factors for cholangitis after biliary stone extraction and the characteristics of patients who underwent EBS due to residual stones. Methods: Between October 2011 and January 2014, 130 consecutive patients
underwent endoscopic extraction of bile duct stones. Risk factors for cholangitis after biliary extraction were investigated. The number and diameter of biliary stones, number of ERCP sessions, and duration of hospital stay were compared in patients whose stones were completely extracted (Group A) and those who underwent EBS due to residual stones (Group B). In Group B, the incidence of cholangitis in patients treated with single plastic stenting (SPS) versus multiple plastic stenting (MPS) was compared. Results: Multivariate analysis revealed that EBS was a significant Selleck ALK inhibitor risk factor for cholangitis after biliary stone extraction (odds ratio, 5.4; 95% confidence interval, 1.9–15.1; p < 0.01). There were 103 patients in Group A (mean age, 74 years; 51 males and
52 females) and 27 in Group B (83 years; 7 males and 20 females). Patients in Group A 上海皓元 required more sessions of ERCP (1.4
vs. 1.1, p < 0.01) and longer hospital stays (17.5 vs. 10.8, p = 0.07). Patients in Group B had more stones on average (2.7 vs. 3.7, p < 0.01) and stones with a significantly greater diameter (10.6 mm vs. 16.1 mm, p = 0.03) than patients in Group A. In Group B, MPS tended to be associated with a lower incidence of cholangitis than SPS (p = 0.09). Conclusion: EBS is a risk factor for cholangitis after stone extraction, even though EBS is usually performed in high-risk patients as a palliative procedure. Multiple biliary stenting is effective for reducing the risk of cholangitis in patients with residual biliary stones. Key Word(s): 1. biliary stenting bile duct stone cholangitis Presenting Author: GUNAWAN JEFFRI Additional Authors: RANGGA RABBINU, ALBAR ZULJASRI, SYAM ARI FAHRIAL, SANITYOSO ANDRI, WIDHANI ALVINA, LUBIS ANNA MIRA Corresponding Author: GUNAWAN JEFFRI Affiliations: University of Indonesia, University of Indonesia, University of Indonesia, University of Indonesia, University of Indonesia, University of Indonesia Objective: Portal vein thrombosis considered as the primary cause of adults portal hypertension. Commonly occurs in patient with cirrhosis, this entity could manifest as asymptomatic and symptomatic forms (portal hypertensive bleeding, abdominal pain, and intestinal infarction).
It has been a unique experience of which I am immensely proud.
I wish the journal every success in the future. ”
“Summary. There is a considerable number of anti-CTLA-4 antibody women with inherited bleeding disorders in Iran. von Willebrand disease, Glanzman thrombasthenia and factor XIII deficiency are the most common coagulation disorders. The main cause of this high rate of coagulation disorders is attributed to a high rate of consanguineous marriages in Iran. Medical care continues to improve for individuals affected with coagulation disorders in Iran. However, these disorders continue to have a significant impact on the affected Iranian women. As a result of the hereditary nature of these disorders, the impact extends to the psychosocial dimension of the lives of the women. Therefore it is recommended that women with coagulation disorders are provided with psychological and social support along with coagulation therapy. ”
“Patients with bleeding disorders may be exposed
to ionizing radiation during medical care. We hypothesized that children with severe haemophilia may have higher radiation exposure than those with mild bleeding disorders (MBDs). To compare medical radiation exposure rates between children with severe haemophilia and MBDs. Selleck Metformin Charts of 35 pediatric patients with severe haemophilia were randomly selected from a database of active male patients followed in our bleeding disorders clinic from 2000 to 2010. Case patients were age and sex matched with two control patients with MBDs [Type 1 von Willebrand disease (VWD) or mild platelet function defect (PFD)]. By retrospective review, data on radiation exposure in millisieverts (mSv) was collected from radiological studies performed within Emory/CHOA. The rates of exposure between cohorts were compared using the Mann–Whitney Test. Case patients had a mean of 11.3 (median 8, IQR = 29) radiographic studies compared with 1.8 (median 1, IQR = 11) for controls (P < 0.001). The mean effective dose of radiation per patient per year of study was medchemexpress two
mSv for case patients (median 0.4, IQR = 3) and 0.4 mSv for control patients (median 0.01, IQR = 0.3) (P < 0.001). Overall, 1.4% of controls and 31.4% of cases accumulated high to very high levels of exposure ( > 20 mSv). Case patients with severe hemophilia accumulated significantly more medical radiation exposure than controls. While the use of ionizing radiation is often necessary for management of these patients, avoidance of unnecessary exposure along with exploration of alternative imaging techniques and low dose protocols should be considered whenever possible. ”
“Summary. Haemorrhagic manifestations in patients with haemophilia A and B are considered quite similar for comparable level of factor deficiency. We investigated the bleeding frequency and factor usage between HA and HB patients with comparable disease severities.