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Biomedical subjects

Noriko Suzuki

Publications and source records attributed to Noriko Suzuki.

At least 37 records · Page 2Linked to original sources
PubMed2003

Site-specific N-glycosylation of chicken serum IgG.

Avian serum immunoglobulin (IgG or IgY) is functionally equivalent to mammalian IgG but has one additional constant region domain (CH2) in its heavy (H) chain. In chicken IgG, each H-chain contains two potential N-glycosylation sites located on CH2 and CH3 domains. To clarify characteristics of N-glycosylation on avian IgG, we analyze N-glycans from chicken serum IgG by derivatization with 2-aminopyridine (PA) and identified by HPLC and MALDI-TOF-MS. There were two types of N-glycans: (1) high-mannose-type oligosaccharides (monoglucosylated 26.8%, others 10.5%) and (2) biantennary complex-type oligosaccharides (neutral, 29.9%; monosialyl, 29.3%; disialyl, 3.7%) on molar basis of total N-glycans. To investigate the site-specific localization of different N-glycans, chicken serum IgG was digested with papain and separated into Fab [containing variable regions (VH + VL) + CH1 + CL] and Fc (containing CH3 + CH4) fragments. Con A stained only Fc (CH3 + CH4) and RCA-I stained only Fab fractions, suggesting that high-mannose-type oligosaccharides were located on Fc (CH3 + CH4) fragments, and variable regions of Fab contains complex-type N-glycans. MS analysis of chicken IgG-glycopeptides revealed that chicken CH3 domain (structurally equivalent to mammalian CH2 domain) contained only high-mannose-type oligosaccharides, whereas chicken CH2 domain contained only complex-type N-glycans. The N-glycosylation pattern on avian IgG is more analogous to that in mammalian IgE than IgG, presumably reflecting the structural similarity to mammalian IgE.

Amino Acid Sequence↗
PubMed2003

Potent estrogenic metabolites of bisphenol A and bisphenol B formed by rat liver S9 fraction: their structures and estrogenic potency.

We previously demonstrated that the estrogenicity of either bisphenol A [BPA; 2,2-bis(4-hydroxyphenyl)propane] or bisphenol B [BPB; 2,2-bis(4-hydroxyphenyl)butane] was increased several times after incubation with rat liver S9 fraction (Yoshihara et al., 2001). This metabolic activation, requiring both microsomal and cytosolic fractions, was observed with not only rat liver, but also human, monkey, and mouse liver S9 fractions. To characterize the active metabolites of BPA and BPB, we investigated the structures of the isolated active metabolites by negative mode LC/MS/MS and GC/MS. The active metabolite of BPA gave a negative mass peak at [M-H](-) 267 on LC/MS and a single daughter ion at m/z 133 on MS/MS analysis, suggesting an isopropenylphenol dimer structure. Finally, this active metabolite was confirmed to be identical with authentic 4-methyl-2,4-bis(p-hydroxyphenyl)pent-1-ene (MBP) by means of various instrumental analyses. The corresponding peaks of the BPB metabolite were [M-H](-) 295 and m/z 147, respectively, suggesting an isobutenylphenol dimer structure. Further, coincubation of BPA and BPB with rat liver S9 afforded an additional active metabolite(s), which gave a negative mass peak at [M-H](-) 281 and two daughter ion peaks at m/z 133 and m/z 147 on MS/MS analysis. These results strongly suggest that the active metabolite of either BPA or BPB might be formed by recombination of a radical fragment, a one-electron oxidation product of carbon-phenyl bond cleavage. It is noteworthy that the estrogenic activity of MBP, the active metabolite of BPA, is much more potent than that of the parent BPA in several assays, including two reporter assays using a recombinant yeast expressing human estrogen receptor alpha and an MCF-7-transfected firefly luciferase plasmid.

3T3 Cells↗
PubMed2003

SH2 domain containing protein tyrosine phosphatase 2 regulates concanavalin A-dependent secretion and activation of matrix metalloproteinase 2 via the extracellular signal-regulated kinase and p38 pathways.

We investigated the role of SH2 domain containing protein tyrosine phosphatase (SHP) 2 in Concanavalin A (Con A) -dependent signaling that leads to the augmented secretion and activation of matrix metalloproteinase (MMP) 2. In cells expressing mutant SHP-2 in which 65 amino acids in the SH2-N domain were deleted, we found that production, secretion, and proteolytic activation of MMP-2 in response to Con A treatment was severely impaired. Under Con A stimulation, complex formation of SHP-2 with SOS-1 and Grb-2 together with the activation of Ras signaling was clearly observed in wild-type cells, but not in SHP-2 mutant cells. In wild-type cells, Con A-treatment activated dual signaling pathways, extracellular signal-regulated kinase (Erk) and p38, in a Ras-dependent manner, whereas Con A-dependent activation of these signaling pathways was absent in SHP-2 mutant cells. In addition, pretreatment of wild-type cells with U0126, a potent inhibitor for mitogen-activated protein/ERK kinase 1, or with SB203580, a specific inhibitor for p38, significantly inhibited the Con A-dependent secretion and activation of MMP-2. However, overexpression of active mitogen-activated protein/ERK kinase 1 in SHP-2 mutant cells could not induce clear activation of MMP-2 secretion, although these cells responded well to the Con A treatment in a p38-dependent manner. Finally, reintroduction of wild-type SHP-2 into SHP-2 mutant cells rescued Erk and p38 activation, and also MMP-2 secretion, whereas dominant-negative SHP-2 could block the Con A-dependent activation of Erk and p38. Taken together, our results strongly suggest that SHP-2 plays a critical role as a positive mediator for Con A-dependent activation of MMP-2 secretion via Ras-Erk and Ras-p38 signalings.

Animals↗
PubMed2003

N-glycan structures of pigeon IgG: a major serum glycoprotein containing Galalpha1-4 Gal termini..

We had shown previously that all major glycoproteins of pigeon egg white contain Galalpha1-4Gal epitopes (Suzuki, N., Khoo, K. H., Chen, H. C., Johnson, J. R., and Lee, Y. C. (2001) J. Biol. Chem. 276, 23221-23229). We now report that Galalpha1-4Gal-bearing glycoproteins are also present in pigeon serum, lymphocytes, and liver, as probed by Western blot with Griffonia simplicifolia-I lectin (specific for terminal alpha-Gal) and anti-P1 (specific for Galalpha1-4Galbeta1-4GlcNAcbeta1-) monoclonal antibody. One of the major glycoproteins from pigeon plasma was identified as IgG (also known as IgY), which has Galalpha1-4Gal in its heavy chains. High pressure liquid chromatography, mass spectrometric (MS), and MS/MS analyses revealed that N-glycans of pigeon serum IgG included (i) high mannose-type (33.3%), (ii) disialylated biantennary complex-type (19.2%), and (iii) alpha-galactosylated complex-type N-glycans (47.5%). Bi- and tri-antennary oligosaccharides with bisecting GlcNAc and alpha1-6 Fuc on the Asn-linked GlcNAc were abundant among N-glycans possessing terminal Galalpha1-4Gal sequences. Moreover, MS/MS analysis identified Galalpha1-4Galbeta1-4Galbeta1-4GlcNAc branch terminals, which are not found in pigeon egg white glycoproteins. An additional interesting aspect is that about two-thirds of high mannose-type N-glycans from pigeon IgG were monoglucosylated. Comparison of the N-glycan structures with chicken and quail IgG indicated that the presence of high mannose-type oligosaccharides may be a characteristic of these avian IgG.

Animals↗
PubMed2003

Effects of the anti-platelet aggregation drug dilazep on cognitive function in Dahl salt-sensitive rats.

Among the consequences of the increasing prolongation of lifespan is a worldwide increase in the number of cases of dementia or impaired cognition. In the present study, to test the hypothesis that mechanisms independent of high blood pressure are involved in maintaining cognitive function, we assessed the effects of long-term dilazep treatment on cognitive dysfunction in normotensive Dahl salt-sensitive (Dahl S) rats fed a low-salt diet, using the standard passive avoidance test. Normotensive Dahl S rats fed a 0.3% NaCl diet were treated for 6 months with low-dose dilazep (2.5 microg/ml in drinking water) or high-dose dilazep (12.5 microg/ml). Systolic blood pressure was within normotensive range throughout the study and did not differ among the experimental groups. The results of the passive avoidance test revealed that dilazep treatment attenuated the decline of latency time relative to that in the untreated control rats (control latency time, 235 s; low-dilazep group, 389 s; high-dilazep group, 397 s), suggesting that the cognitive function of normotensive Dahl S rats was improved by dilazep treatment. This improvement of cognition was associated with significant increases in the number of neuronal cells in the hippocampal region and with an increase in capillary length in dilazep-treated Dahl rats. In addition, the dilazep treatments significantly attenuated arteriolar injury of glomeruli in the kidney. These data suggest that dilazep treatment, through vascular and non-vascular effects, maintains the brain function in Dahl S rats susceptible to vascular injury and organ dysfunction.

Animals↗
PubMed2003

Physiologic role of decidual beta1 integrin and focal adhesion kinase in embryonic implantation.

Implantation refers to a series of interactions between embryo and endometrium including hatching, attachment, and outgrowth. We investigated the expression and function of beta1 integrin and focal adhesion kinase (FAK) in human decidual cells during implantation. Immunofluorescent staining localized beta1 integrin to surfaces of cultured decidual cells. Double staining for beta1 integrin and mediators of intracellular signaling involving beta1 integrin, such as FAK and vinculin, colocalized beta1 integrin with these substances, suggesting that human decidual cells express beta1 integrin in the focal adhesion region. We next investigated the actions of beta1 integrin and FAK in implantation by co-culturing mouse embryos and human decidual cells. Mouse blastocysts attached to cultured decidual cells after embryo hatching, usually within 24 h of culture initiation. Blastocysts attached to decidual cells exhibited extensive outgrowth at 48 h. Treatment of decidual cells with an antibody against beta1 integrin or with an antisense FAK oligonucleotide did not affect hatching or attachment of blastocysts, but either one could inhibit outgrowth. Thus, it was concluded that human decidual beta1 integrin and FAK participate in this final step of implantation.

Animals↗
PubMed2003

Blood test values and Community Periodontal Index scores in medical checkup recipients.

BACKGROUND: We examined the blood test values of people who received general medical checkups and their Community Periodontal Index (CPI) score. METHODS: A total of 7,452 persons (5,742 males and 1,710 females), who had general medical and dental checkups, were the subjects of the study. Many were people who worked for companies in and around Nagoya and their family members, ranging in age from 16 to 80 years. The blood test in our study consisted of 37 items used in general blood tests. Partial-mouth recordings were used to measure CPI scores. The highest CPI score for each subject was used for analysis. Odds ratios and confidence interval values were obtained using the Mantel-Haenszel method to analyze the results. RESULTS: CPI scores of 3 and 4 were related to the test values of high-density-lipoprotein cholesterol, serum iron, white blood cell count, fasting blood sugar, glycosylated hemoglobin A1, glycosylated hemoglobin A1c, and C-reactive protein. CONCLUSION: Blood test values tended to show correlations with CPI scores, more clearly seen in males than in females.

Adolescent↗
PubMed2002

Increasing the conformational stability by replacement of heme axial ligand in c-type cytochrome.

To investigate the role of the heme axial ligand in the conformational stability of c-type cytochrome, we constructed M58C and M58H mutants of the red alga Porphyra yezoensis cytochrome c(6) in which the sixth heme iron ligand (Met58) was replaced with Cys and His residues, respectively. The Gibbs free energy change for unfolding of the M58H mutant in water (DeltaG degrees (unf)=1.48 kcal/mol) was lower than that of the wild-type (2.43 kcal/mol), possibly due to the steric effects of the mutation on the apoprotein structure. On the other hand, the M58C mutant exhibited a DeltaG degrees (unf) of 5.45 kcal/mol, a significant increase by 3.02 kcal/mol compared with that of wild-type. This increase was possibly responsible for the sixth heme axial bond of M58C mutant being more stable than that of wild-type according to the heme-bound denaturation curve. Based on these observations, we propose that the sixth heme axial ligand is an important key to determine the conformational stability of c-type cytochromes, and the sixth Cys heme ligand will give stabilizing effects.

Base Sequence↗
PubMed2002

Human cytomegalovirus immediate-early protein IE2-86, but not IE1-72, causes graft coronary arteriopathy in the transplanted rat heart.

BACKGROUND: Graft coronary arteriopathy (GCA) after heart transplantation is a major factor limiting the long-term survival of the recipients. Human cytomegalovirus (HCMV) infection is a possible cause of this disease which is characterized by diffuse intimal thickening resulting from smooth muscle cell migration and proliferation. It has been reported that HCMV immediate-early (IE) proteins, IE1 and IE2, could play an important role in the development of this disease; however, the precise in vivo role of these proteins in causing GCA has not been clarified. METHODS AND RESULTS: Excised Lewis rat hearts were transfected with HCMV IE1-72, IE2-86 or control plasmid by intra-coronary infusion of Hemagglutinating Virus of Japan-liposome, and transplanted into syngeneic recipients' abdomens. All cardiac grafts continued to beat well throughout the incubation period in the absence of immunosuppression. Exclusive expression of IE1-72 or IE2-86 protein in coronary artery walls was demonstrated after IE1-72 or IE2-86 gene transfection, respectively. Luminal occlusion as a consequence of intimal thickening of graft coronary arteries developed in the IE2-86 transfected hearts at day 21 after transplantation (30.1+/-3.4% occlusion, P<0.0001), compared with the IE1-72 and control transfected ones (8.2+/-1.6 and 6.8+/-1.1%, respectively). In contrast, there was no significant difference in luminal occlusion between the IE1-72 and control transfected hearts. CONCLUSIONS: We have demonstrated that expression of IE2-86 alone, but not IE1-72, causes intimal hyperplasia after cardiac transplantation. IE2-86 protein may therefore prove to be a useful target in therapies aimed at preventing HCMV-related GCA and improving the long-term result of cardiac transplantation.

Animals↗
PubMed2002

Development of an in vivo ischemia-reperfusion model in heterotopically transplanted rat hearts.

BACKGROUND: Heart transplantation has been extensively used in animal models, including studies on gene therapy for myocardial preservation. We investigated the feasibility of in situ left coronary artery (LCA) ligation as a physiological system for the examination of strategies to modulate myocardial tolerance against ischemia-reperfusion injury, such as gene therapy, using heterotopically transplanted rat hearts. METHODS: Lewis rat hearts that had been transplanted into syngeneic recipients' abdomens were subjected to 30-min ischemia, by occluding the LCA, and subsequent blood reperfusion by releasing the suture in situ (I/R group). Transplanted hearts in the sham group underwent laparotomy only. RESULTS: At 24 hr of reperfusion, the size of the ischemic region was 40.1+/-3.1% of the total left ventricular mass, and the infarct size was 47.5+/-3.3% of the area at risk in the I/R group. Cardiac function was reduced in the I/R group compared with the sham group, associated with higher myeloperoxidase activity (5.12+/-1.35 vs. 0.97+/-0.33 U/g wt) and higher incidence of apoptosis as defined by TUNEL (29.8+/-3.2 vs. 3.8+/-0.7%) and DNA ladder. In the I/R group, up-regulation of Bax, Bak, and caspase-3 was observed. CONCLUSIONS: These data on myocardial damage of transplanted hearts are consistent and equivalent to those of the usual LCA occlusion model, suggesting that this method is useful to investigate strategies for modulating myocardial tolerance against ischemia-reperfusion injury using heterotopically transplanted rat hearts in a more physiological blood-perfused model.

Animals↗
PubMed2002

The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic cells.

Lectins on antigen presenting cells are potentially involved in the antigen uptake and the cellular recognition and trafficking. Serial analysis of gene expression in monocyte-derived dendritic cells (DCs), monocytes, and macrophages revealed that 7 of the 19 C-type lectin mRNA were present in immature DCs. Two of these, the macrophage mannose receptor and the macrophage lectin specific for galactose/N-acetylgalactosamine (MGL), were found only in immature DCs, as confirmed by reverse transcriptase-PCR and flow cytometric analysis. By subcloning and sequencing the amplified mRNA, we obtained nucleotide sequences encoding seven different human MGL (hMGL) subtypes, which were apparently derived from alternatively spliced mRNA. In addition, the hMGL gene locus on human chromosome 17p13 contains one gene. A single nucleotide polymorphism was identified at a position in exon 3 that corresponds to the cytoplasmic region proximal to the transmembrane domain. Of all the splicing variants, the hMGL variant 6C was expressed at the highest levels on immature DCs from all donors tested. Immature DCs could incorporate alpha-GalNAc-modified soluble acrylamide polymers, and this was significantly inhibited by pretreatment of the cells with an anti-hMGL monoclonal antibody that blocks the lectin-carbohydrate interaction. We propose that hMGL is a marker of imDCs and that it functions as an endocytic receptor for glycosylated antigens.

Acetylgalactosamine↗
PubMed2002

The variable stiffness colonoscope: assessment of efficacy by magnetic endoscope imaging.

BACKGROUND: Variable-stiffness colonoscopes combine the flexibility of pediatric instruments for negotiation of the sigmoid colon with the ability to stiffen the insertion tube to prevent or control looping after straightening. Previous studies have found wide variation in the efficacy of the stiffening mechanism. Thus, two studies were conducted to assess the potential benefit of the stiffening device and its optimal use. METHODS: In study 1, the effect of routinely stiffening the straightened variable-stiffness colonoscopes in the mid-descending colon was determined in 82 patients. Two insertions were performed (mid-descending colon to cecum) in each patient with and without application of the stiffening device (randomized). The time to negotiate the proximal colon (mid-descending to cecum), time to pass the variable-stiffness colonoscopes across the splenic flexure into the transverse colon, time to pass the right colon, and ancillary maneuvers used were recorded for each insertion. In study 2, consecutive patients, excluding any with previous colonic resection, were examined by using standard adult variable-stiffness colonoscopes. Real-time views of the procedure with magnetic endoscope imaging were recorded for all examinations, but procedures were randomized to be done either with (n = 88), or without (n = 87) the endoscopist viewing the magnetic endoscope imaging display. Whenever stiffening was applied, the anatomic location of the colonoscope tip and stiffness efficacy were recorded. RESULTS: In study 1, time taken to negotiate the proximal colon (p = 0.0041) and time to negotiate the splenic flexure (p = 0.006) were significantly shorter and ancillary maneuvers performed were fewer (p = 0.0014) with the stiffening device activated. In study 2, stiffening was used with similar frequency in patients examined with and without the magnetic endoscope imaging view, most commonly for passing the splenic flexure (71%), but also in the transverse colon (12%), right colon (9%), and sigmoid/descending colon (8%). Stiffening was significantly more effective when used in combination with magnetic endoscope imaging (69% with imager vs. 45% without imager; p = 0.0102). CONCLUSIONS: Overall, the variable-stiffness device used was effective in controlling looping 57% of the time. Activating maximum stiffness appears to be effective once the sigmoid colon has been negotiated and the colonoscope straightened with the tip in the proximal colon, reducing the number of ancillary maneuvers and shortening the insertion time through the proximal colon. Routine magnetic endoscope imaging further enhances the efficacy of the variable-stiffness colonoscopes by helping to identify the optimal time for stiffening.

Colon↗
PubMed2002

Effects of combined pioglitazone and metformin on diabetes and obesity in Wistar fatty rats.

1. The effects of combined treatment with pioglitazone.HCl and metformin on diabetes and obesity were investigated in Wistar fatty rats, which are hyperglycaemic and hypertriglyceridaemic and have higher plasma levels of total ketone bodies than lean rats. 2. Plasma glucose was significantly decreased when pioglitazone.HCl or metformin was administered alone and combined treatment accentuated this decrease. The administration of pioglitazone.HCl, but not metformin, also decreased plasma levels of triglyceride and total ketone bodies. 3. The glycogen content of skeletal muscle was not increased by pioglitazone.HCl or metformin alone, but was increased by combined treatment (P=0.003, ANOVA). 4. Pioglitazone.HCl produced increased food intake and bodyweight in hyperphagic Wistar fatty rats; however, concurrent administration of metformin significantly ameliorated these pioglitazone.HCl-induced increases. 5. These results indicate that combined treatment with pioglitazone.HCl and metformin induces a marked hypoglycaemic effect accompanied by a reduction in plasma levels of total ketone bodies and prevention of excessive bodyweight gain in Wistar fatty rats. These favourable effects suggest that the combination would be beneficial in treating patients with type 2 diabetes.

Adipose Tissue↗
PubMed2002

Treatment with argon plasma coagulation reduces recurrence after piecemeal resection of large sessile colonic polyps: a randomized trial and recommendations.

BACKGROUND: Recurrence is frequent after piecemeal snare resection of large sessile colorectal polyps. The aim of this study was to evaluate the safety and efficacy of argon plasma coagulation (APC) in preventing recurrence when applied to the edge and base of the polypectomy site after apparently complete piecemeal resection. METHODS: Patients with large (>1.5 cm) sessile polyps removed by piecemeal snare cautery were placed into 2 groups. The first consisted of patients with polyps believed by the endoscopist to be completely excised. These patients were randomized to either no further therapy (control) or to APC of the rim and any residual mucosal or submucosal tissue in the base of the polypectomy site. The second group comprised patients in whom polyps, as judged by the endoscopist, were incompletely excised by snare polypectomy; APC was routinely applied without randomization to all visible remaining adenomatous tissue. Follow-up colonoscopy was performed within 3 months and 1 year; biopsy specimens were taken routinely from the resection site and further polypectomy was performed as indicated. RESULTS: There were fewer recurrences after APC in the randomized group (1/10 APC, 7/11 no APC; p = 0.02). In the group with initial incomplete snare polypectomy, recurrence was detected at 3 months in 6 of 13 despite APC. One patient was hospitalized with abdominal pain and minor rectal bleeding but required no intervention. There were no other episodes of significant late bleeding caused by piecemeal polypectomy. One patient was referred for surgery after unsuccessful endoscopic management. CONCLUSIONS: In patients with apparent complete endoscopic snare resection of large adenomas, postpolypectomy application of APC reduces adenomatous recurrence.

Aged↗
PubMed2002

Effect of magnetic endoscope imaging on patient tolerance and sedation requirements during colonoscopy: a randomized controlled trial.

BACKGROUND: Pain during colonoscopy is primarily related to mesenteric stretching from looping of the colonoscope insertion tube. Prompt recognition and removal of loops reduces patient discomfort and may lessen sedation requirements. Magnetic endoscope imaging allows real-time visualization of the colonoscope during insertion. The effect of magnetic endoscope imaging on patient pain and sedation requirements was assessed in a prospective randomized controlled trial. METHODS: A total of 122 consecutive patients undergoing routine colonoscopy by a single experienced endoscopist were randomized to have the procedure performed either with the endoscopist viewing the imager display (n = 62), or without the imager view (n = 60). Procedures began with administration of hyoscine-N-butylbromide alone, and sedative medications (midazolam and meperidine) were self-administered by the patient with a patient-controlled analgesia pump. Cardiorespiratory parameters were recorded and patient pain was assessed with a 100-mm visual analogue scale. RESULTS: The number of attempts at straightening the colonoscope was fewer (median 8 [0-66] vs. 15 [0-87], p = 0.0076) and the duration of looping less (median 4.5 min [0-27.3 min] vs. 6.4 min [0-29.4 min]), when the endoscopist was able to see the imager view. The total number of patient demands (by patient-controlled analgesia) for medication (median 1 vs. 2.5) and total doses of midazolam (median 0.44 mg vs. 0.88 mg) and meperidine (median 16.75 mg vs. 32.5 mg) administered did not significantly differ between patients examined with or without the imager. Patient pain scores were also similar. CONCLUSIONS: Magnetic endoscope imaging allows accurate assessment and straightening of loops during colonoscopy, but without a significant reduction in patient requirements for sedative medication or improvement in patient tolerance. However, the dosages of sedation drugs used were small.

Adult↗
PubMed2002

Use of video and magnetic endoscope imaging for rating competence at colonoscopy: validation of a measurement tool.

BACKGROUND: Counting the number of procedures performed provides at best a crude measure of technical competence in colonoscopy. The aim of this study was to develop and validate a qualitative and a quantitative score for measuring technical competency in colonoscopy using videotape evaluation. METHODS: Eighteen endoscopists with varying levels of experience were prospectively videotaped during colonoscope insertion. The following were recorded simultaneously: a closed circuit television view showing instrument handling, the endoscopic luminal view, and a continuous display of the colonoscope configuration (magnetic endoscope imaging). Videotapes were reviewed blindly and in random order by 3 experts. Performance in 3 categories was evaluated: (1) manipulation of instrument controls (0-10), (2) manipulation of the insertion tube (0-6) and (3) depth of insertion (0-4). A global assessment of competence was given for each endoscopist. RESULTS: Comparing the total scores as assessed by the 3 blinded experts, for each individual endoscopist, there were significant differences. However, there was good interobserver agreement and correlation between the individual scores and global assessment ratings of competence (p < 0.0001). CONCLUSIONS: The video assessment tool described appears to measure technical competence at colonoscopy, although in its present form it lacks reliability. Refinement of the score may improve reliability and deserves further evaluation.

Clinical Competence↗
PubMed2002

Single fibers of skeletal muscle as a novel graft for cell transplantation to the heart.

OBJECTIVE: Skeletal myoblast transplantation is a promising alternative to treat heart failure. A single fiber, the minimal functional unit of skeletal muscle, retains skeletal myoblasts beneath the basal lamina. When surrounding muscle is injured, myoblasts migrate from the fiber into the damaged area to regenerate muscle. We hypothesized that such isolated fibers could be used as an efficient vehicle to deliver myoblasts into damaged myocardium, resulting in improved cardiac function. METHODS: Living single fibers of rat skeletal muscle were isolated, and their behavior was characterized in vitro. Single fibers were injected into the myocardium (at 4 sites, each receiving a single fiber) of rats in 2 models of heart failure induced either by means of doxorubicin administration or left coronary artery occlusion. RESULTS: Skeletal myoblasts dissociated from an isolated single fiber, proliferated, and differentiated into multinucleated myotubes in vitro. Within 3 days after grafting in vivo, original fibers provided putative myoblasts and disappeared. At 4 weeks, discrete loci consisting of several multinucleated myotubes were observed. Furthermore, single-fiber transplantation significantly improved cardiac function compared with the control treatment in either doxorubicin-treated hearts (maximum dP/dt, 4013.9 +/- 96.1 vs 3603.1 +/- 102.3 mm Hg/s; minimum dP/dt, -2313.7 +/- 75.1 vs. -2057.1 +/- 52.4 mm Hg/s) or ischemic hearts (maximum dP/dt, 3905.6 +/- 103.0 vs 3572.6 +/- 109.7 mm Hg/s; minimum dP/dt, -2336.1 +/- 69.7 vs -2106.4 +/- 74.2 mm Hg/s). CONCLUSION: Single-fiber transplantation acts as a vehicle for delivering putative skeletal myoblasts that appear to differentiate into myotubes within the myocardium. This was associated with improved function of failing hearts, suggesting its efficacy as a novel graft for cellular cardiomyoplasty.

Animals↗