A total of 198 patients with dyspeptic symptoms were included in

A total of 198 patients with dyspeptic symptoms were included in the study. A gastric biopsy was collected for histopathology and rapid urease testing. Stool specimens for HpSA testing were also collected. Patients were considered H. pylori positive if two invasive tests (histological and rapid urease tests) were positive. The sensitivity Ponatinib and specificity were 92.2% and 94.4%, respectively, for the Premier Platinum HpSA Plus test; 48.9% and 88.9%, respectively, for the HP Ag test; 86.7% and 88.9, respectively, for the

One Step HpSA test; 68.9% and 92.6%, respectively, for the ImmunoCard STAT! HpSA test; and 78.9% and 87%, respectively, for the H. Pylori fecal antigen test. The Premier Platinum HpSA Plus EIA test was determined to be the most accurate stool test for diagnosing H. pylori infections in adult dyspeptic patients. The currently available ICA-based tests are fast and easy to use but provide less reliable results. “
“The heterogeneity of hepatitis C virus (HCV) infection cannot always be explained by HCV genotypes or

host genetic factors, raising the issue of possible cofactors. A new form of hepatitis leading to liver cancer was discovered in 1992 in mice, owing to an infection by Helicobacter hepaticus. Moreover, several studies showed an association between the presence of HCV and Helicobacter in the liver of patients with severe liver diseases suggesting a possible synergism between Alvelestat manufacturer the two pathogens. In an HCV transgenic mouse model with a B6C3F1 background, selleck compound the combination of H. hepaticus infection and the HCV transgene resulted in a significantly greater incidence and multiplicity of preneoplastic and neoplastic liver foci in males. Because the mouse genetic background is a major determinant in the development of liver disease,

our aim was to test the synergism between HCV and H. hepaticus infection using transgenic mice with a more sensitive genetic background to H. hepaticus infection. For this purpose, four groups of mice were followed up to 14 months, the presence of H. hepaticus was monitored by PCR and hepatic lesions were looked for. We found that H. hepaticus, but not the HCV transgene, increased the number of hepatic lesions. The presence of carcinoma was more likely to occur on a background of hepatitis, and the overall lesions were more frequent in the presence of steatosis. The effect of the mouse genetic background was greater than the effect of the HCV transgene and was sufficient to promote lesions particularly via its sensitivity to H. hepaticus infection. Genetic susceptibility may be a more important factor than expected. Indeed, the synergism between HCV and H. hepaticus infection involved in liver disease may be highly host dependent. “
“Background:  Although gastric cancer (GC) and duodenal ulcer (DU) are both strongly associated with Helicobacter pylori infection, a DU is negatively associated with the risk of GC.

e, three meeting abstracts

were included in the analysis

e., three meeting abstracts

were included in the analysis for China and two in the analysis for Mexico). Seroprevalence using any type of HBsAg assay was allowed (complete criteria are described in Supporting Table 1). Fixed effect (FE) and random effects (RE) meta-analyses of HBsAg seroprevalence rates from studies that met the inclusion criteria were conducted to calculate country-specific pooled CHB prevalence rates. RE analysis, which assumes heterogeneity among surveys, was considered more appropriate based on the nature of the data: HBV was unevenly distributed and we expected different rates from different surveys carried out in different C646 populations in different locations at different times. FE analysis was conducted for comparison. Between-study heterogeneity was assessed for each country dataset using Cochran’s Q test

and the I2 statistic.14, 15 For most countries, data were insufficient for exploration of heterogeneity. Separate pooled rates were calculated for emigrants and for in-country populations for countries for which data were available, and results were compared using a Z test.15 Subgroup analyses were also done by decade of survey and by sex. For the 17 countries with at least 25 surveys, meta-regression analyses, based on the RE models using survey date as the covariate, SAHA HDAC solubility dmso were done using Comprehensive Meta-Analysis software (Biostat, Englewood, NJ). For a few countries with low HBsAg seroprevalence rates (e.g., selleck chemical Japan, Australia, New Zealand, Canada, and northern and western European countries), rates from large, population-based studies were used instead of meta-analysis. Study-quality assessment was done for only a subset of the data (i.e.,

Bangladesh, China, India, Iran, Korea, Pakistan, Philippines, Thailand, and Vietnam) to determine whether weighting based on study quality made a difference in the pooled prevalence rates. We developed a three-category scale (Supporting Table 2), scored each study, and calculated the pooled prevalence rates with and without the additional weighting factor, as described by Sutton et al.16 Flow of the systematic review is summarized by world region in Table 1. Results for individual countries are in Supporting Table 3. More than 17,500 articles were identified in PubMed searches; full text of 2,859 articles was assessed and data from 3,276 articles were entered into country-specific databases. In all, we found 1,373 articles reporting data meeting criteria for use in the meta-analyses. Many articles report data for more than one survey (e.g., pregnant women and military recruits) and these were entered separately. A total of 2,053 HBsAg seroprevalence surveys involving 18.6 million subjects were used in the meta-analyses (Table 2; Supporting Table 4).

1F,G) As described above, it has been reported that the scirrhou

1F,G). As described above, it has been reported that the scirrhous find more type of cancers

undergo EMT.11 To evaluate whether or not the EMT-related genes are expressed in S-HCCs, we applied the core EMT interactome genes that have been previously identified elsewhere.19 When we performed the GSEA, significant enrichment of the EMT core gene signature (EMT_CORE_UP; n = 91) was observed in S-HCCs, compared to HCCs (Fig. 4A). This finding was further validated by examining the expression of individual EMT-related genes by the real-time PCR method. The expression of the key EMT molecules, Snail and Twist, was significantly higher in S-HCCs than in HCCs (P < 0.05) (Fig. 4B,C; Supporting Table 3). Protein expression of Snail was significantly more prevalent in S-HCCs (10 of 14; 71%) and CCs (11 of 19; 58%) than in HCCs (6 of 24; 25%) (P =

0.006) (Fig. 4D). In immunohistological evaluation, the expression of Snail protein was mainly localized to the periphery of the tumor nests, next to the fibrous stroma this website (Fig. 4E; Supporting Fig. 2). In addition, Snail and K19/EpCAM expression was colocalized in most S-HCCs (8 of 10 double-positive cases; 80%), which were mainly located on the periphery of the tumor nests, next to the fibrous stroma cells (Fig. 4F). These findings support that the expression of EMT genes are not merely the attributes of fibrotic components, but the results of the cross-talk interaction

between epithelial and fibrotic components within the tumors. We also observed that mRNA levels of Snail and Twist were well correlated with those of SPC markers, including selleckchem K19, EpCAM, cMET, CD133, and Oct3/4, suggesting the distinctive association of EMT with the stem-cell-like features of S-HCC (Supporting Fig. 3). TGF-β binds two types of receptors, TGFβRI and TGFβRII, to form active signaling complexes. The phosphorylated TGFβRI transmits signals intracellularly by phosphorylating the transcription factors, Smad2 and Smad3, which then forms a complex with Smad4. The Smad complex moves into the nucleus, where it regulates the expression of target genes.20 TGF-β is known to promote tumor-cell invasion and metastasis as a potent stimulator of EMT.21-23 With this concern, we next evaluated whether the TGF-β signaling is differentially expressed among tumor subtypes according to the expression of EMT-related molecules. We observed that the expression of TGF-β-signaling molecules, including TGF-β, TGFβRI, and Smad4, was significantly higher in S-HCCs than in HCCs or CCs (P < 0.05) (Fig. 5A-D; Supporting Table 3). Smad4 protein was expressed in most S-HCCs (12 of 14; 86%), but not significantly more than other types (Fig. 5E).

Over the course of healing, the wounds also have abnormal histolo

Over the course of healing, the wounds also have abnormal histological features, including (i) reduced neutrophil influx and delayed macrophage influx; (ii) subcutaneous haematoma formation; (iii) an unexpected increase in wound site angiogenesis and (iv) persistent deposition of iron in

the wound bed and adjacent tissues. We found that temporarily restoring thrombin generation with a single dose of FIX replacement or high dose FVIIa restored neutrophil and macrophage influx. However, it did not correct delayed epithelial closure, excess angiogenesis or late rebleeding [23]. Thus, although formation of an adequate fibrin clot at the time of injury plays a role in tissue repair, the ability to generate thrombin and/or other activated coagulation factors remains important during the later phases of wound healing. Proper haemostatic function later in the healing process prevents bleeding at

the wound find more site and at adjacent sites of angiogenesis. This prevents deposition of additional iron in the wound area, which can promote inflammation that impedes healing [37]. Our data suggest that sites of angiogenesis are at high risk of rebleeding during wound healing [14]. Inhibition of angiogenesis does not further impair wound healing in haemophilia. Celecoxib, a non-steroidal anti-inflammatory agent, reduced angiogenesis in healing wounds in the haemophilia B mouse model, but did not further delay healing [4]. Inflammation alone does not seem to provoke R788 manufacturer bleeding in haemophilic mice [38]. However, certain inflammatory mediators can drive angiogenesis and may possibly provoke bleeding at sites where inflammation is secondarily associated with angiogenesis. Although our studies have been conducted using skin wounds, we feel that they reveal general principles that likely apply to bleeding and healing in other tissues, such as joints. We believe that modulators of angiogenesis and inflammation hold promise as adjunctive therapies to reduce joint and soft tissue bleeding in haemophilia. Cartilage is composed of chondrocytes embedded in an extracellular

matrix. Chondrocytes are responsible for maintenance of the matrix. The cartilage matrix consists of two major components: collagen, which provides shape and tensile strength, and proteoglycans, which are responsible for the negative selleck screening library charge. This causes high osmotic pressure, thereby attracting water and with that resisting compressive forces in a joint. Previous in vitro research showed that a single blood-exposure of cartilage leads to persistent damage [39]. It was demonstrated that monocytes/macrophages and red blood cells, as present in blood, are responsible for the irreversible inhibition of cartilage matrix synthesis [40]. This is caused by induction of chondrocyte apoptosis due to formation of hydroxyl radicals in the vicinity of chondrocytes [41]. Small amounts of interleukin (IL)-1β, produced by activated monocytes/macrophages, increase production of hydrogen peroxide by chondrocytes.

[37] In an attempt to address the inadequacies of the ICHD-1, Sil

[37] In an attempt to address the inadequacies of the ICHD-1, Silberstein and Lipton (S-L criteria) proposed draft operational criteria for TM in 1994 (Table 2).[37] Considered a subset of migraine, TM was defined by headaches for at least 4 hours a day on at least 15 days a month. A history of migraine and increasing headache frequency were also required to establish a link to migraine. Headache on ≥15 days/month for 3 months Occurring in a patient who has had at least 5 attacks fulfilling criteria for 1.1 Migraine without aura On ≥8 days per month, for at least 3 months, headache fulfills criteria for migraine C1 and/or C2 below, that is, has fulfilled criteria for pain and associated

symptoms of migraine without aura Has at least 2 of a-d: a)  Unilateral location Treated or relieved with triptans or ergotamine before the expected development of C1 check details above No medication overuse and not attributable to other causative disorder The 1994 draft criteria required a history of transformation. Silberstein and Lipton elected not to require particular characteristics for the daily or near-daily headaches in part because these headaches are pleiomorphic; daily headaches may be unilateral or bilateral, mild to severe in intensity, with or without associated migrainous features. Furthermore, while patients with TM often continue to have episodes of headaches that fulfill ICHD-1 criteria for migraine

(1.1 or 1.2), ICHD-1-defined migraine attacks may cease in ALK inhibitor a small minority of patients. To address medication overuse, S-L criteria defined 2 subtypes of TM, 1 with medication overuse and 1 without, using a consensus of published reports to define medication overuse. In field tests, approximately 40% of daily headache sufferers could not be classified using the 1994 S-L draft criteria,[2, 32] most often because they had difficulty recalling and

reporting a history of headache escalation. The criteria were modified to eliminate the requirement for transformation, requiring instead either a history of escalation over 3 months or a current headache that, except for duration, met the ICHD-1 criteria for migraine.[2] The S-L draft criteria continued to distinguish 2 forms of TM, 1 with medication overuse and the other without, selleck chemicals and defined requisite levels of use for each. They did not attempt to define the causal role of medication-taking in the progression of headache but instead identified it as a modifier of TM. Further, to avoid more than 1 diagnosis for a single headache type, they imposed a hierarchical diagnostic rule whereby patients could not be diagnosed with chronic tension-type headache if they met the criteria for TM. The 1996 S-L criteria have been used around the world in clinic-based and population-based studies as well as in clinical trials.[3-6, 38-40] ICHD-2,[1] published in 2004, provided operational diagnostic criteria for CM (Table 2) as a complication of migraine.

The spot sign persisted in all patients, none had high-grade inte

The spot sign persisted in all patients, none had high-grade internal carotid artery stenosis, stroke or transient ischemic attacks. Four patients were completely blind, 3 patients were able to recognize hand movements. OCT demonstrated retinal atrophy, and fundoscopy revealed only minimal arterial perfusion. The hyperechoic spot sign may be an important predictive prognostic marker for persistent loss of vision.

Its persistence may indicate calcified or cholesterol emboli and may explain the low therapeutic success rate to thrombolysis. Further studies on their origin and significance in atherosclerotic disease are warranted. “
“In this work, we demonstrate oxygen extraction fraction (OEF) measurement using 7T MRI with susceptibility-weighted imaging (SWI), in sedated and

nonsedated adults. Ten healthy subjects RGFP966 mouse (30.3 ± 4.5 years, 9 men, 1 woman) formed control (n = 5) and sedation groups (n = 5). Midazolam and propofol injection was administered to the same sedation group subjects during 2 different scanning sessions. Two-dimensional SPGR imaging was performed before, during, and twice after (propofol, +10, +30 minutes; midazolam, +10, +40 minutes) conscious sedation. The equivalent procedure was performed with the control group without sedation. After SWI analysis, change in OEF between scans was quantified, and parcelated ΔOEF maps were generated with 77 gray matter (GM)-containing volumes-of-interest (VOIs). Significant decreases in OEF were shown in 14 GM VOIs during sedation relative to the control group, most notably during midazolam see more sedation (P < .05). In contrast, no significant decrease BAY 57-1293 was observed after 10 minutes and in only 4 VOIs after 40 minutes recovery. Significant change in ΔOEF during conscious sedation using midazolam and propofol could be measured using SWI

at 7T in vivo. This may be a potentially useful approach for the noninvasive assessment of OEF in the brain on a clinical basis. “
“Multipurpose ultrasound probes combined with ultra-mobile ultrasound instrumentation have the potential to increase the availability and use of ultrasound examinations in the assessment of atherosclerotic burden and cardiac disease. The aim of this study was to compare the agreement of a newly developed multipurpose probe to a standard linear carotid probe in detection of atherosclerosis of the precerebral arteries. We examined 103 patients with a multipurpose probe (General Electric, G9L MPP-9 MHz) and a standard linear probe (General Electric, Vivid 7-M12L-14 MHz). Measurements included intima-media thickness (IMT) in the common carotid arteries (CCA), carotid bifurcations (BIF), internal carotid arteries (ICA), and detection of carotid plaques and stenoses. We found a significant level of agreement between the two probes for all IMT measurements with intraclass correlation coefficients (ICC) of: left CCA .91, left BIF .68, left ICA .75, right CCA .84, right BIF .74, and right ICA .59.

34, P < 0001) In particular, kudus were captured significantly

34, P < 0.001). In particular, kudus were captured significantly later than impala (Tukey's test, P < 0.001), showing a genuine prey selection related to hunt timing, which would have been overlooked using clock time. These results thus highlight that even at low latitudes (18°S), the truer significances will be lost in noise if clock rather than sun are used to measure find more event sequences. First, all controlled studies (i.e. as opposed to field studies) unsurprisingly indicate the exact variation in the daylight cycle. This may reflect and acknowledge the importance of light as a ‘zeitgeber’. Among the field studies, only 33% used the actual variation of sunset and sunrise to characterize daily activity patterns.

In contrast, 38% of field studies ACP-196 order used clock time and finally 29% divided the study period

monthly or seasonally, leading to difficulties of interpretation of the effect of change in the sun’s position at a set clock time. Consequently, two-thirds of the ‘field’ studies we reviewed could be subject to misinterpretation caused by an inappropriate handling of time data. This is illustrated in Fig. 6, which accounts for the proportion of field studies that used the different measurement methods according to the latitude, duration of the study and taxa investigated. Tropical studies are more likely to use ‘clock time’ probably because changes in sunrise and sunset are seemingly less marked there (χ2, P = 0.001). Yet, two-thirds of the studies conducted between 30° and 60° used

clock time (Fig. 6a). The method used did not differ according to the duration of the study (χ2, P = 0.981), despite the fact that long-term studies are more affected by the change in day length. In all cases, more than two-thirds of the studies failed to record time properly (Fig. 6b). There was a trend for mammal and reptile studies to use the clock time more than studies of other taxa (χ2, P = 0.016). Studies on reptiles, which are poikilothermic animals, would be expected to take account for sun’s position when recording time, but systematically used clock times (Fig. 6c). This short review shows that even if the behaviour is recorded in high latitude, during a prolonged study selleckchem and/or on poikilothermic taxa, a significant number of studies still use clock time, despite the risk of errors and misinterpretation due to changes in the sun’s position. With a mathematical model based on astronomical parameters, we demonstrated that recording behavioural data in the field using the time given by a clock can generate substantial errors compared with the real time of events, as given by the position of the sun in the sky. These errors increase with both latitude and duration of the study. The analysis of African wild dog hunting behaviour data shows that using clock time would have generated a false pattern, suggesting that all three prey species were killed within the same time windows.

5) Further testing indicated a significant difference in the ang

5). Further testing indicated a significant difference in the angular standard deviation of the Δheading data, with the SD of the Δheading distribution after the playback significantly lower than would be predicted from rotated data (Fig. 6). This indicates that the whale maintained a more directed course after the cessation of the killer whale playback (Fig. 2, 3). The whale’s course heading was centered on a northerly direction (Fig. 7), which took it directly away from the source of the playback, and towards the only deep-water exit of the TOTO canyon. It should be noted that, while the experiment was designed to test for a change www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html in movement patterns, as measured by heading, the angular standard deviation

test was developed post hoc. The NLR tests for any change in the Doxorubicin order distribution of the Δheading data. Once it was determined that there was a significant difference between the distribution of the whale’s heading before and after the killer whale playback, we then chose to focus on the variation in heading, as measured by the angular standard deviation. This decision was influenced by the observed results, and ideally, the test developed after this examination of the data would be utilized to confirm these findings

in future playback experiments. However, the difficulty involved in finding and tagging beaked whales made this unfeasible in this case. One goal for this paper is to encourage similar future playback experiments to use this method to test for similar responses. This prolonged, directed avoidance in reaction to the killer whale playback put increasing distance between

the whale and the location of the playback, similar to that seen in predation avoidance by other species. Minke and sei whales, which employ this flight strategy, have been observed to beach themselves while being chased by killer whales (Ford et al. 2005, Ford and Reeves 2008). The reaction observed here may be an antipredator response similar to the flight reaction of baleen whales to killer whale predators (Ford et al. 2005, Ford and Reeves 2008) and it is possible that this sustained directed flight puts beaked whales at risk for stranding as well. It is not apparent whether the strandings of baleen whales were the result of an intentional avoidance find more strategy, or if the whales inadvertently ran into the shallows due to their fixed course, or were perhaps driven ashore by the pursuing whales (Ford et al. 2005, Ford and Reeves 2008). Regardless of the reason for stranding, in only one observed case was a minke whale able to work its way off the beach after the killer whales departed. Therefore, if it is an intentional strategy, it must be a last ditch very high risk effort, motivated by extreme predation pressure. If Blainville’s beaked whales utilize a similar strategy, then in extreme cases this may put them at risk for stranding.

On the other hand, autophagy inhibition could also evolve as a th

On the other hand, autophagy inhibition could also evolve as a therapeutic concept for liver diseases in which its activation is associated with cellular senescence or transdifferentiation.14 “
“The results of independent genome-wide association studies have recently been reported, describing the identification of single-nucleotide polymorphisms (SNPs) strongly associated with natural hepatitis C virus (HCV) clearance during acute infection and cure of chronic HCV infection on antiviral therapy with pegylated interferon (IFN)-α and ribavirin.1-4

These SNPs, in chromosomal region 19q13 buy Fludarabine upstream of the interleukin-28B (IL28B; IFN-λ3) gene, appear to be markers of cell responsiveness to type 1 IFNs. Nevertheless, the underlying mechanisms remain unknown. Several articles have been subsequently published that confirmed the association and provided valuable information on the predictive value of the so-called “IL28B genotype”

on the outcomes of acute HCV infection, antiviral treatment of chronic infection, and recurrence of HCV infection after liver transplantation. These findings have been recently reviewed by Afdhal et al.5 To date, most of the current knowledge on HCV biology and new HCV drug development is based on in vitro studies using hepatoma cell lines, principally Huh7 cells and their derivatives. These cells are permissive for HCV entry, and harbor replication of subgenomic and genomic replicons of various

genotypes, as well as the full life cycle of the selleck compound genotype 2a JFH1 (Japanese fulminant hepatitis 1) infectious clone and Selleck GSI-IX derivatives. Nevertheless, their IL28B genotype remains uncharacterized, despite its likely effects on numerous intracellular biological processes relevant to HCV infection. We therefore genotyped the IL28B rs12979860 SNP of hepatoma cell lines used in HCV research, including Huh7, Huh7.5, Huh7.5.1, and HepG2 cells, as well as the commonly used non-hepatoma HEK293 (human embryonic kidney 293) and Hela cell lines. We used ultra-deep pyrosequencing to sequence 292 nucleotides flanking the rs12979860 locus, using a GS FLX Titanium Sequencing Kit in conjunction with a Genome Sequencer FLX (Roche Molecular Systems, Pleasanton, CA). Data was analyzed using two original in-house softwares: Pyroclass and Pyromute, with the results shown in Table 1. Huh7 cells and derivatives, and even two Huh7 cell lines originating from different laboratories, demonstrated different allelic frequencies. The “non-Mendelian” distribution of these polymorphisms is likely a consequence of the polyploidal nature of hepatoma cells, but may indicate the presence of multiple clonal populations arising under different environmental pressures. Data obtained from in vitro cell culture systems may often be related to the genetic background of the cell line(s) used.

Similar results were recently obtained with ubiquitous Hjv−/− mic

Similar results were recently obtained with ubiquitous Hjv−/− mice.34 These results are consistent with the restoration of hepcidin expression HIF inhibitor and normalization of iron parameters upon reintroduction of Hjv to hepatocytes of Hjv−/− mice by an adenoviral system,34 and highlight the importance of the liver in body iron metabolism as a site of both hepcidin production and regulation by Hjv. Our data support the hypothesis that Hjv may constitute part of an “iron sensing complex” (possibly together with HFE, TfR2, and further molecules) that responds to alterations

in transferrin saturation and/or BMP6 levels, and transmits signals for hepcidin transcriptional activation by way of the BMP/SMAD pathway.40, 41 According to this model, Hjv would be expected to operate in a cell-autonomous fashion at the sites of hepcidin production in the liver. Although hepcidin appears to be predominantly expressed in periportal hepatocytes,20, 42 discordant results have been published about the site of hepatic Hjv expression. By measuring lacZ activity in liver sections of Hjv−/− mice where lacZ was introduced from the targeting vector, Niederkofler et al.6 reported a patterned distribution of Hjv around periportal hepatocytes. However, by in situ hybridization of Hjv mRNA and immunohistochemical staining with an Hjv antibody, Lee at al.20 concluded that Hjv is mostly expressed MAPK inhibitor around

the central vein of the liver. Certainly, more work is required to clarify this important issue. Periportal expression of Hjv would support a cell-autonomous activity of this protein on hepcidin regulation. Nevertheless, if the majority of hepatic Hjv is concentrated around perivenous areas, an activity of Hjv in trans would be conceivable. We also show here that mice with specific ablation of Hjv in skeletal muscles and cardiomyocytes do not develop iron overload and do not exhibit any apparent phenotypic abnormalities. This finding is intriguing, considering that skeletal muscles express substantially higher levels of Hjv compared to the liver,5, 13 and suggests that muscle see more Hjv is not involved

in the regulation of systemic iron homeostasis, at least under standard laboratory conditions. The absence of cardiac iron overload in muscle-specific Hjv−/− mice appears to exclude the possibility for a local iron regulatory function of this protein Nevertheless, it will be interesting to evaluate iron metabolism in Hfe2f/f:MCK-Cre mice subjected to stress, such as strenuous physical exercise or hypoxia. Moreover, it will be important to examine whether these mice exhibit any possible phenotype in muscles, unrelated to iron metabolism. In light of the high abundance of Hjv in skeletal muscles and the capacity of differentiating muscle cells to release sHjv,15, 17 it is reasonable to speculate that circulating sHjv may primarily derive from muscle tissue.