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Biomedical subjects

M Chandra

Publications and source records attributed to M Chandra.

At least 37 records · Page 2Linked to original sources
PubMed1999

Expression of cardiac cytokines and inducible form of nitric oxide synthase (NOS2) in Trypanosoma cruzi-infected mice.

Expression of Cardiac Cytokines and Inducible Form of Nitric Oxide Synthase (NOS2) in Trypanosoma cruzi-infected Mice. Journal of Molecular and Cellular Cardiology (1999) 31, 75-88. Both cardiac cytokine and inducible nitric oxide synthase (NOS2) expression have been implicated in the cardiac dysfunction associated with myocarditis and cardiomyopathy. Chagas' disease, caused by Trypanosoma cruzi, is an important cause of cardiomyopathy. We examined the effect of T. cruzi (Brazil strain) infection with or without verapamil treatment on the expression of cytokines and NOS2 in the heart. Messenger RNA for NOS2, IL-1beta, and TNF-alpha was induced in the myocardium of infected mice, and Western blot analysis as well as immunohistochemistry demonstrated a significant increase in NOS2 protein. Verapamil treatment reduced the expression of cardiac NOS2 protein and the mRNAs for NOS2, TNF-alpha, and IL-1beta. Infection-associated increases in cardiac L-citrulline were also reduced by verapamil treatment. Verapamil-treated infected mice that survived for 80 days exhibited less inflammation and fibrosis compared to untreated mice. Gated MRI and echocardiography revealed an increased right ventricular inner diameter (RVID) in untreated but not in verapamil-treated infected CD1 mice. This suggests that the infection-associated expression of cytokines and NOS2 in the heart correlate with the severity of myocarditis and the effect of verapamil. The RVID was significantly increased in infected wild-type (WT) compared to infected syngeneic NOS2 knockout (NOS2-/-) mice. Fractional shortening was decreased and myocardial L-citrulline was increased in infected WT mice. These data suggest that NO generated from cardiac NOS2 may participate in the pathogenesis of murine chagasic heart disease.

Animals↗
PubMed1999

The N-terminal region of troponin T is essential for the maximal activation of rat cardiac myofilaments.

Troponin T (TnT) is an essential protein in the transduction of the Ca2+-binding signal that triggers striated muscle contraction. Functional diversity among various TnT isoforms found in cardiac and skeletal muscles has been correlated with the sequence heterogeneity at the amino (N-) and the carboxyl (C-) terminal regions. The most striking difference between cardiac TnT (cTnT) and skeletal TnT (sTnT) is that cTnT has an extended N-terminus, which is rich in negatively charged amino acids. To investigate the role of this region in cTnT, we deleted the first 76 amino acids in rat cTnT (cTnT77-289) by site-directed mutagenesis. We exchanged the native troponin complex in rat cardiac myofibrillar preparations and detergent skinned cardiac fiber bundles by treatment with excess cTnT or cTnT77-289. After reconstituting the cTnT77-289 containing myofibrils with cardiac troponin I-cardiac troponin C (cTnI-cTnC), the MgATPase activity was 70% of the cTnT treated myofibrils in the relaxed state and 83% of the cTnT treated myofibrils in the maximal Ca2+-activated state. These observations were supported by force measurements in which cTnT and cTnT77-289 were exchanged into skinned fiber bundles. Prior to reconstitution with cTnI-cTnC, the Ca2+-independent maximal force developed by the cTnT77-289 containing fiber was 45% of the force developed by the cTnT containing fiber. After reconstituting with cTnI-cTnC, the Ca2+-activated maximal force of the cTnT77-289 containing fiber was 62% of the force developed by the cTnT containing +cTnI-cTnC reconstituted fiber. In both assays, no significant changes in the normalized Ca2+-activity relation or in co-operativity were observed. Fluorescence experiments using pyrene-labeled Tm demonstrated that the binding of cTnT77-289 to Tm was 3-4 fold stronger than that of cTnT. Our results suggest that strong interactions between cTnT77-289 and Tm stabilize cardiac myofilaments in a sub-maximally activated state. Our findings also indicate that the N-terminus of cTnT is essential for maximal activation of cardiac myofilaments.

Actin Cytoskeleton↗
PubMed1999

Laparoscopic management of benign solid and cystic lesions of the liver.

OBJECTIVE: The authors present their experience in the laparoscopic management of benign liver disease. The aim of the study is to analyze technical feasibility and evaluate immediate and long-term outcome. SUMMARY BACKGROUND DATA: Indications for the laparoscopic management of varied abdominal conditions have evolved. Although the minimally invasive treatment of liver cysts has been reported, the laparoscopic approach to other liver lesions remains undefined. METHODS: Between September 1990 and October 1997, 43 patients underwent laparoscopic liver surgery. There were two groups of benign lesions: cysts (n = 31) and solid tumors (n = 12). Indications were solitary giant liver cysts (n = 16), polycystic liver disease (n = 9), hydatid cyst (n = 6), focal nodular hyperplasia (n = 3), and adenoma (n = 9). Only solid tumors, hydatid cysts, and patients with polycystic disease and large dominant cysts located in anterior liver segments were included. All giant solitary liver cysts were considered for laparoscopy. Patients with cholangitis, cirrhosis, and significant cardiac disease were excluded. Data were collected prospectively. RESULTS: The procedures were completed laparoscopically in 40 patients. Median size was 4 cm for solid nodules and 14 cm for solitary liver cysts. Conversion occurred in three patients (7%), for bleeding (n = 2) and impingement of a solid tumor on the inferior vena cava (n = 1). The median operative time was 179 minutes. All solitary liver cysts were fenestrated in less than 1 hour. There were no deaths. Complications occurred in 6 cases (14.1%). Two hemorrhagic and two infectious complications were noted after management of hydatid cysts. There were no complications after resection of solid tumors. Three patients received transfusions (7%). The median length of stay was 4.7 days. Median follow-up was 30 months. There was no recurrence of solitary liver or hydatid cysts. One patient with polycystic disease had symptomatic recurrent cysts at 6 months requiring laparotomy. CONCLUSION: Laparoscopic liver surgery can be accomplished safely in selected patients with small benign solid tumors located in the anterior liver segments and giant solitary cysts. The laparoscopic management of polycystic liver disease should be reserved for patients with a limited number of large, anteriorly located cysts. Hydatid disease is best treated through an open approach.

Adult↗
PubMed1999

Spontaneous pericardial mesothelioma in a rhesus monkey.

Spontaneous tumors in nonhuman primates are of great importance. A spontaneous pericardial mesothelioma was observed in an 18-year-old female rhesus monkey. Grossly, the visceral pericardium was multifocally irregular and thickened with tan discoloration and was soft in consistency. Histologically, the pericardium contained highly in-folded branching fronds lined by a single layer of cuboidal cells. Tumor invaded into approximately half of the thickness of the atrial and ventricular muscles. Tumor penetration was not observed into the atrial or ventricular cavity. Within the myocardium, neoplastic cells formed glandular structures which were lined by cuboidal to columnar cells. Neoplastic cells were weakly positive with PAS and strongly positive for colloid iron and alcian blue. Immunohistochemically, neoplastic cells were positive for both vimentin and cytokeratin and negative with CEA and Leu-M1, indicating mesothelial origin. To the best of the authors' knowledge, this is the first report of a spontaneous pericardial mesothelioma in a rhesus monkey.

Aged↗
PubMed1999

Application of cardiac gated magnetic resonance imaging in murine Chagas' disease.

To evaluate the role of gated cardiac magnetic imaging resonance (MRI) in Chagas' disease, we infected mice with Trypanosoma cruzi (Brazil strain). Two models were chosen for study, the CD1 and the inducible nitric oxide synthase knockout (NOS2-/-) mice. Infection of CD1 mice was associated with a significant increase in the right ventricular inner diameter (RVID) that was reversed in some mice by verapamil. Expression of cardiac NOS2 has been associated with myocardial dysfunction. Therefore, we evaluated chagasic cardiomyopathy in NOS2-/- and syngeneic wild type (WT) mice. Infected WT mice exhibited an increase in RVID in the acute phase (< 60 days postinfection) that was more marked during chronic infection (>100 days postinfection). Chronically infected NOS2-/- mice had an increase in RVID. The RVID in infected WT mice was greater than in NOS2-/- mice. These data demonstrate that MRI is a useful tool in the serial evaluation of the heart in murine Chagas' disease. In addition, it supports the notion that the NOS2-/-/NO pathway may contribute to the pathogenesis of murine chagasic cardiomyopathy.

Analysis of Variance↗
PubMed1999

Levels of glutathione reductase and glutathione peroxidase of human platelets in unstable angina and myocardial infarction.

Levels of glutathione peroxidase and glutathione reductase were measured in the platelets of 30 patients, 10 of them affected by unstable angina, 10 of them reperfused after myocardial infarction and 10 matched healthy controls. The specific activities of both the enzymes were lowered in both group of patients. Glutathione reductase activity resulted markedly lowered.

Angina, Unstable↗
PubMed1999

Demasking of subclinical left ventricular dysfunction in anemic children.

OBJECTIVE: To study subclinical left ventricular dysfunction in anemic children. SETTING: Hospital. SUBJECTS: The study population consisted of 52 cases of anemia (16 mild, 14 moderate, 22 severe) and 20 normal age and height matched children aged between 7-12 years. METHODS: These children were subjected to Echocardiography on Ascuson XP model using 3.5 MHz Transducer during rest and immediately after maximum tolerated exercise on Quniton Model Q-5000 treadmill using modified Naughton protocol. Left ventricular end diastolic dimensions, left ventricular systolic dimension, fractional shortening, left ventricular end diastolic volume, systolic volume, stroke volume and ejection fraction were studied on M-mode echocardiography, and E/A ratio on doppler mode. RESULTS: Significant differences were observed in resting heart rate, gain in heart rate at peak exercise compared to basal values and double product, total exercise duration and metabolic equivalents at peak exercise in controls and anemic subjects. Left ventricular dysfunction was present in all severely anemic subjects after maximum tolerated exercise on treadmill. The only evidence of left ventricular diastolic dysfunction was in form of decreased left ventricular end diastolic volume after exercise in moderate and severely anemic subjects. CONCLUSIONS: Exercise is helpful in demasking subtle left ventricular dysfunctions in anemic subjects that are not detected during rest.

Anemia↗
PubMed1999

Evaluation of metronidazole toxicity: a prospective study.

Metronidazole is an antimicrobial, antiprotozoal agent that has been widely used in the treatment of a variety of infections. Some therapeutic indications necessitate prolonged treatment with metronidazole. Peripheral neuropathy is a potential metronidazole-induced toxicity, which has been reported in only a few isolated retrospective studies. This prospective study was designed to determine the toxic profile of metronidazole in patients undergoing long-term treatment with this drug. In the present study, 17 patients of both sexes, aged between 20 and 50 years, with body weights ranging from 46 to 62 kg and who were suffering from various medical ailments were recruited. The patients received 400 mg t.i.d. oral metronidazole in a total dose of 16.8-39.6 g for 2-4 weeks. It was found that patients usually suffered from some of the toxic symptoms of metallic taste, headache and dry mouth and to a lesser extent nausea, glossitis, urticaria, pruritus, urethral burning and dark colored urine. Symptoms were irrespective of sex and directly proportional to duration of therapy. Deep tendon ankle jerks were maximally reduced in four patients and sense of vibration at the level of olecranon and patella was affected in two patients. Distal latency and velocity of the sural and posterior tibial nerves were significantly affected (p < 0.01) compared with control values. These results indicate possible motor-sensory neurotoxicity involving the lower limbs due to long-term metronidazole therapy.

Adult↗
PubMed1999

Screening of sputum: an experience in a tertiary care hospital.

In order to reduce the work load on the clinical laboratory, it has been recommended that sputum samples, before accepting for culture, should be looked for the presence of polymorphs and squamous epithelial cells. (An appropriate sample should have more than 25 polymorphs per low power field and less than 10 epithelial cells per low power field; others are labelled as inappropriate). We examined this criteria for it's suitability on 1043 samples received at the clinical bacteriology laboratory at the All India Institute of Medical Sciences (AIIMS) for a period of one year (September, 1996 to August, 1997). Four hundred samples were found appropriate while 643 were inappropriate as per recommended criteria. Amongst the 400 appropriate samples, 215 were culture positive and 185 grew normal flora. However, we found that out of 643 inappropriate samples, 195 were culture positive (p < 0.01, statistically significant). The data was further divided into hospitalized and OPD cases. The distribution of culture positive cases in the appropriate samples was again found to be highly significant. It is apparent from our results that an attempt to process an inappropriate sample does not provide useful information.

Bacteriological Techniques↗
PubMed1998

Comparison of laparoscopic and open staging in Hodgkin disease.

BACKGROUND: Staging laparotomy provides useful information for management of Hodgkin disease but has fallen into disfavor because procedure-related morbidity exceeds that of new chemotherapeutic regimens. OBJECTIVE: To determine the feasibility, effectiveness, and safety of laparoscopic staging for Hodgkin disease compared with those of open staging. PATIENTS: Fifty-five patients with Hodgkin disease of cell types including nodular sclerosis in 43 (78%), mixed cellularity in 9 (16%), and lymphocyte predominance in 3 (5%). STUDY DESIGN: Concurrent evaluation of laparoscopic staging (n = 15) and retrospective review of open staging (n = 40). INTERVENTIONS: Laparoscopic and open techniques of surgical staging for Hodgkin disease, including splenectomy, liver biopsies, and lymph node sampling. MAIN OUTCOME MEASURES: Operative time, duration of postoperative ileus and of postoperative hospitalization, morbidity, number of lymph nodes retrieved, alteration in pathologic stage, recurrence, and survival. RESULTS: For laparoscopic staging vs open staging groups, mean operative time was 202 vs 144 minutes (P=.001); mean postoperative ileus was 1.9 vs 3.2 days (P<.001); mean postoperative hospitalization was 4.4 vs 6.7 days (P<.001); complications occurred in 3 patients (20%) vs 11 patients (28%) (P=.57); and mean number of lymph nodes retrieved was 8.5 vs 4.6 (P=.05). In the laparoscopic staging group, 2 cases (13%) were upstaged and 2 cases (13%) were downstaged. In the open staging group, 6 cases (15%) were upstaged and 3 cases (7.5%) were downstaged. Follow-up data were available for all patients in the laparoscopic staging group, at a mean of 23.5 months postoperatively. All were alive, none had recurrent disease below the diaphragm, and 2 (13%) had residual mediastinal disease. Follow-up data were available for 31 patients (78%) in the open staging group at a mean of 52.5 months postoperatively. All were alive, 27 (87%) were disease free, 3 (10%) had had relapses above the diaphragm, and 1 (3%) had residual mediastinal disease. CONCLUSIONS: Compared with open staging, laparoscopic staging of Hodgkin disease is oncologically equivalent and functionally superior. These data should encourage reappraisal of the role of operative staging in the management of Hodgkin disease.

Adolescent↗
PubMed1998

Laparoscopic splenectomy: outcome and efficacy in 103 consecutive patients.

OBJECTIVE: To study the safety and efficacy of laparoscopic splenectomy (LS) in patients with predominantly benign hematologic disorders. SUMMARY BACKGROUND DATA: The technical feasibility of LS has been recently established. However, data regarding the efficacy of the procedure in a large cohort of patients are scarce. METHODS: One hundred three consecutive patients underwent LS between June 1992 and October 1997. Data were collected prospectively on all patients. RESULTS: Indications were idiopathic thrombocytopenic purpura (ITP), hereditary spherocytosis, autoimmune hemolytic anemia, thrombotic thrombocytopenic purpura, and others. Mean spleen size was 14 cm and mean weight was 263 g. Accessory spleens were found in 12 patients with ITP and in 5 patients without ITP. There were no deaths. Complications occurred in six patients, one requiring a second procedure for small bowel obstruction. Six patients received transfusions, and four procedures were converted to open splenectomy for bleeding. Mean surgical time was 161 minutes and was greater in the first 10 cases than the last 10. Mean postsurgical stay was 2.5 days. Thrombocytopenia resolved after surgery in 84% of patients with ITP, and hematocrit levels increased significantly in 70% of patients with chronic hemolytic anemias. A positive response was noted in 92% of patients with hereditary spherocytosis, without relapse for the duration of the observation. ITP relapsed in four patients during follow-up, three within 12 months. CONCLUSIONS: LS can be performed safely and effectively in a teaching institution. Rigorous technique will minimize capsular fractures, reducing the risk of splenosis. Accessory spleens can be successfully localized, thus improving response and limiting recurrence of ITP. LS should become the technique of choice for treatment of intractable benign hematologic disease.

Adult↗
PubMed1998

Nocturnal enuresis in children.

Nocturnal enuresis (NE) can result from an interaction of unstable detrusor contractions, delayed arousal from sleep, and nocturnal polyuria. Some children with NE can hold urine well for several hours during the day and have isolated nocturnal enuresis, while others manifest diurnal voiding symptoms (DVS) as well, including urinary frequency, urgency, urge incontinence, and pelvic withholding. The pathogenesis of NE in patients with isolated NE may be different than in those with NE and DVS. In children with NE and DVS, detrusor instability may play a major role in the causation of their voiding problems, whereas delayed arousal from sleep in response to a full bladder may be a major contributor to NE in patients with isolated NE. The treatment should address the underlying pathogenic factors. The commonly used treatment regimens are described. Motivation and efforts of the child in training the bladder are vital to achieving cure of enuresis.

Antidepressive Agents, Tricyclic↗
PubMed1998

Absence of Helicobacter pylori in oral mucosal lesions.

A prospective study was conducted in 26 patients with benign oral ulcers and oral carcinoma and 26 age and sex matched controls to determine the prevalence of Helicobacter pylori in oral mucosal biopsies. Oral mucosal biopsies were subjected to rapid urease test, campylobacter like organism (CLO) test, histopathological examination and bacteriological culture for demonstration of H pylori. Urease test was positive for H pylori in 3 (11.4%) out of 26 cases and CLO test in 2 (14%) out of 14 cases. On histology, H pylori was identified in 4 (15.38%) out of 26 cases. The spiral organism was universally absent in culture of both patients and controls. These pilot data negate the casual association of H pylori in oral mucosal lesions.

Biopsy, Needle↗
PubMed1997

Effects of protein kinase A phosphorylation on signaling between cardiac troponin I and the N-terminal domain of cardiac troponin C.

During beta-adrenergic stimulation of the heart, there is a decrease in myofilament Ca2+ sensitivity mediated by the protein kinase A-(PKA-) induced phosphorylation of troponin I (cTnI). Phosphorylation, which occurs at Ser 23 and Ser 24 in an amino-terminal extension unique to cTnI, decreases the Ca2+ affinity of the amino-terminal regulatory site of cardiac troponin C (cTnC). In view of the antiparallel organization of the cTnI-cTnC complex [Krudy, G. A., Kleerekoper, Q., Guo, X., Howarth, J. W., Solaro, R. J., and Rosevear, P. R. (1994) J. Biol. Chem. 269, 23731-23735], it is not clear how the phosphorylation signal at one end of the complex affects the Ca2+ binding site at the other end. To address this question, we probed the interaction between cTnI and cTnC fragments, cTnC1-89 and cTnC90-162 (recombinant peptides corresponding to the N- and C-domains of cTnC). cTnI-Cys 5 mutant (S5C/C81I/C98S) and cTnC1-89 were fluorescently labeled with IAANS. When cTnI was phosphorylated, the affinity of Ca2+ for the cTnI-cTnC1-89 complex decreased significantly as indicated by a shift in the pCa50 value from 6.65 to 5.25. Upon phosphorylation, the affinity of cTnI for cTnC1-89 decreased by 3.8-fold in the absence of Ca2+ and 1.7-fold in the presence of Ca2+. In contrast to the case with full-length cTnC, neither cTnC1-89 nor cTnC90-162 induced significant structural changes in cTnI-Cys 5 as determined from intersite distance measurements between Cys 5 and Trp 192. Moreover, neither fragment of cTnC could significantly restore Ca2+ regulation of force generation, when exchanged into fiber bundles from which cTnC had been extracted. Our findings indicate that the transduction of PKA-induced phosphorylation signal from cTnI to the regulatory site of cTnC involves a global change in cTnI structure.

Animals↗
PubMed1997

NMR studies of Ca2+ binding to the regulatory domains of cardiac and E41A skeletal muscle troponin C reveal the importance of site I to energetics of the induced structural changes.

Ca2+ binding to the N-domain of skeletal muscle troponin C (sNTnC) induces an "opening" of the structure [Gagné, S. M., et al. (1995) Nat. Struct. Biol. 2, 784-789], which is typical of Ca2+-regulatory proteins. However, the recent structures of the E41A mutant of skeletal troponin C (E41A sNTnC) [Gagné, S. M., et al. (1997) Biochemistry 36, 4386-4392] and of cardiac muscle troponin C (cNTnC) [Sia, S. K., et al. (1997) J. Biol. Chem. 272, 18216-18221] reveal that both of these proteins remain essentially in the "closed" conformation in their Ca2+-saturated states. Both of these proteins are modified in Ca2+-binding site I, albeit differently, suggesting a critical role for this region in the coupling of Ca2+ binding to the induced structural change. To understand the mechanism and the energetics involved in the Ca2+-induced structural transition, Ca2+ binding to E41A sNTnC and to cNTnC have been investigated by using one-dimensional 1H and two-dimensional {1H,15N}-HSQC NMR spectroscopy. Monitoring the chemical shift changes during Ca2+ titration of E41A sNTnC permits us to assign the order of stepwise binding as site II followed by site I and reveals that the mutation reduced the Ca2+ binding affinity of the site I by approximately 100-fold [from KD2 = 16 microM [sNTnC; Li, M. X., et al. (1995) Biochemistry 34, 8330-8340] to 1.3 mM (E41A sNTnC)] and of the site II by approximately 10-fold [from KD1 = 1.7 microM (sNTnC) to 15 microM (E41A sNTnC)]. Ca2+ titration of cNTnC confirms that cNTnC binds only one Ca2+ with a determined dissociation constant KD of 2.6 microM. The Ca2+-induced chemical shift changes occur over the entire sequence in cNTnC, suggesting that the defunct site I is perturbed when site II binds Ca2+. These measurements allow us to dissect the mechanism and energetics of the Ca2+-induced structural changes.

Animals↗
PubMed1997

Calcium-induced structural transition in the regulatory domain of human cardiac troponin C.

While calcium binding to troponin C (TnC) triggers the contraction of both skeletal and cardiac muscle, there is clear evidence that different mechanisms may be involved. For example, activation of heart myofilaments occurs with binding to a single regulatory site on TnC, whereas activation of fast skeletal myofilaments occurs with binding to two regulatory sites. The physiological difference between activation of cardiac and skeletal myofilaments is not understood at the molecular level due to a lack of structural details for the response of cardiac TnC to calcium. We determined the solution structures of the apo and calcium-saturated regulatory domain of human cardiac TnC by using multinuclear, multidimensional nuclear magnetic resonance spectroscopy. The structure of apo human cardiac TnC is very similar to that of apo turkey skeletal TnC even though there are critical amino acid substitutions in site I. In contrast to the case with the skeletal protein, the calcium-induced conformational transition in the cardiac regulatory domain does not involve an "opening" of the regulatory domain, and the concomitant exposure of a substantial hydrophobic surface area. This result has important implications with regard to potential unique aspects of the interaction of cardiac TnC with cardiac troponin I and of modification of cardiac myofilament regulation by calcium-sensitizer drugs.

Calcium↗
PubMed1997

Conformation of the N-terminal segment of a monocysteine mutant of troponin I from cardiac muscle.

A monocysteine mutant of cardiac muscle troponin I, cTnI(S5C/C81I/C98S), was generated from a mouse cTnI cDNA clone and expressed in a bacterial system. Cys-5 was modified with the fluorescent sulfhydryl reagent IAANS to probe the conformation of the N-terminal extension of the mutant and the mutant complexed with cardiac muscle troponin C. Our emphasis was on the effect of phosphorylation of Ser-23 and Ser-24 by protein kinase A on the conformation of the N-terminal segment. Phosphorylation resulted in an 8-nm red-shift of the emission spectrum of the attached IAANS probe and a reduction of its quantum yield by a factor of 4-5. The intensity decay of nonphosphorylated IAANS-labeled mutant was complex and had to be described by a sum of three exponential terms, with lifetimes in the range 0.1-5 ns. A fourth component in the range 7-9 ns was required to describe the intensity decay of the phosphorylated mutant. Phosphorylation also reduced the weighted mean lifetime, consistent with the changes observed in the steady-state fluorescence parameters and a 33% decrease in the global rotational correlation time calculated from anisotropy decay data. This change in correlation time suggested a decrease in the axial ratio of the protein. The fluorescence changes of the labeled mutant induced by phosphorylation were carried over to its complex with troponin C. The Stern-Volmer plots of acrylamide quenching of the steady-state fluorescence were essentially linear for nonphosphorylated mutant but displayed pronounced concave downward curvatures for the phosphorylated protein under all conditions studied. The present results are interpreted in terms of a more compact hydrodynamic shape of the phosphorylated cTnI mutant and are consistent with a folded conformation of the N-terminal extension induced by phosphorylation of the two serines. These conformational changes may play a role in the modulation of cardiac muscle contractility by troponin I phosphorylation.

Animals↗