Biomedical subjects
Publications and source records attributed to M Chandra.
We describe herein a case of dilated cardiomyopathy. The diagnosis of myocardial sarcoid was suggested by abnormal findings on an MRI of the chest. This was subsequently confirmed by a histology of a subcutaneous nodule. MRI is well suited in imaging myocardial scarring associated with sarcoidosis. Its use should be considered where sarcoidosis is suspected. Early detection and intervention with steroids may improve function.
PURPOSE: We examined data from multiple institutions to determine whether intravesical bladder stimulation therapy is effective in improving bladder compliance by increasing bladder capacity and lowering bladder storage pressures. MATERIALS AND METHODS: The charts of 568 patients from 11 institutions were evaluated. Of the 568 patients 335 had adequate and accurate pretreatment and posttreatment urodynamic studies, and were included in this study. A total of 155 patients was from Children's Memorial Hospital, while the remaining 180 were from 10 other institutions. Bladder capacity and bladder capacity pressure were determined for each patient before and after therapy. RESULTS: Overall, 53% of patients had increased bladder capacity of 20% or greater after treatment (average increase 105 cc), which represents a 63% increase from pretreatment values. This increase occurred in an average of 1.9 years. Further analysis of this subset of patients revealed that in 90% intravesical storage pressures were decreased or maintained within a safe range (less than 40 cm. water). Evaluation of patients who did not respond to bladder stimulation with a 20% or greater increase in bladder capacity revealed that they had nearly normal bladder capacity before therapy. When the data on bladder capacity and bladder capacity pressure from Children's Memorial Hospital were compared to results from the 10 other institutions, there were no appreciable differences. CONCLUSIONS: Bladder stimulation is effective in increasing bladder capacity without significantly elevating storage pressure in a majority of patients. We conclude that this technique is safe and effective in improving bladder compliance, and that it is reproducible elsewhere.
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Urinary tract infection (UTI), vesicoureteral reflux (VUR), and certain voiding disorders result in renal damage. In the past few years, the increasing use of 99mTc-dimercaptosuccinic acid renal scans, urodynamic testing, and antenatal sonography have helped shed light on the interrelationship of these disorders. Renal parenchymal involvement during acute febrile UTI and subsequent renal scarring are quite commonly observed in the absence of VUR, suggesting that the presence of reflux is not a prerequisite for renal damage. In infants with gross VUR, renal damage is often present at birth even before the development of any UTI. High intravesical pressures during bladder filling and voiding are commonly observed in infants with gross VUR, reflecting an underlying voiding dysfunction. High voiding detrusor pressures are also commonly observed in infants presenting with symptomatic UTI who do not have VUR. Children with dysfunctional voiding states are at risk for development of VUR and UTI. Renal damage in these children may occur in the absence of one or the other. This review elucidates how voiding dysfunction predisposes children to bacterial colonization of the bladder, the development or perpetuation of VUR, and renal damage.
BACKGROUND: During the last 12 years, we have used a different approach, arbitrarily designed by us, for treating pemphigus patients that has given us very different and encouraging results. METHOD: The treatment schedule consists of giving 100 mg dexamethasone on 3 consecutive days and 500 mg cyclophosphamide on one day and repeating these pulses (DCPS) every 4 weeks. In between the DCPS, the patient receives only 50 mg cyclophosphamide orally daily and generally no corticosteroids. An essential component of the regimen is to administer a specified amount of the treatment for 1.5 years after achieving clinical remission. RESULTS: Of the 300 patients enrolled for this treatment, 61 patients could not complete the treatment, whereas 12 patients have died, some of them due to unrelated causes. Of the remaining 227 patients, 190 patients (84%) have already completed the treatment and are free of the disease even after complete withdrawal of all treatment, the duration of posttreatment follow-up being more than 5 years in 48 patients, 2 to 5 years in 75 patients, and less than 2 years in 67 patients. The maximum duration of posttreatment follow-up is 9 years. The remaining patients are also showing the same trend. Twenty-four patients are in remission but have not yet completed the treatment schedule, whereas 13 patients are still having evidence of clinically active disease, although it has already become much milder. The blood levels of intercellular antibody also decrease as the treatment progresses. The side effects commonly observed during treatment with corticosteroids are generally absent or insignificant. The relapses of the disease, seen so far in 59 patients, have been observed mostly in those patients who defaulted during the treatment, but a further course of the DCP regimen led again to complete recovery. CONCLUSIONS: If substantiated by further follow-up, this treatment schedule may prove curative in this potentially fatal disease.
OBJECTIVE: A study of the protective efficiency imparted by intermittent warm blood cardioplegia (WBCP) using perfused rat heart model. METHODS: Hemodynamic parameters were monitored simultaneously with metabolic changes in high-energy phosphates using 31P-NMR spectroscopy. Following 30 min perfusion with Krebs-Henseleit (KH) buffer, all hearts were arrested for one hour (G1 and G2) and than reperfused with KH for 30 minutes. A warm oxygenated crystalloid cardioplegia (WCCP, modified St Thomas' hospital solution) was used for the control group (G1). The second group of hearts (G2) were arrested with oxygenated WBCP (K+ = 15 mM; Hct = 15-20%) and the third group (G3), was subjected to a protocol consisting of 4 periods (10 min each) of WBCP interspersed by 10 min of global ischaemia. RESULTS: The post-arrest percentage recoveries of LVDP, +dP/dt and HR were respectively: 88, 93 and 90 for G1 (n = 8); 97, 100 and 98 for G2 (n = 10); 76, 79 and 91 for G3 (n = 12). The corresponding metabolic recoveries of ATP and PCr were respectively, 85 and 90 for G1; 91 and 98 for G2 and 73 and 85 for G3. The PCr level declined during the arrest period in G1 contrasting with elevated PCr level (> 140%) during the WBCP arrest in G2. After an initial rise to approximately 140%, PCr level gradually decreased during the intermittent WBCP interval (G3). CONCLUSIONS: At normothermia, with equal CF rates, continuous WBCP provides better myocardial protection, through an effective oxygen supply, compared with WCCP. During the intermittent periods of ischaemia, certain metabolic and hemodynamic dysfunction occurs.
The authors analyzed 632 consecutive, nontrauma Surgical Intensive Care Unit (SICU) admissions after infra-inguinal arterial surgery over a 3-year period (4/89-3/92) for the need for postoperative SICU care. Group I consisted of 122 patients (58 males, 64 females) with at least one absolute indication for SICU care, including mechanical ventilation, pulmonary artery, catheter monitoring, or intravenous infusion of vasoactive or antiarrythmic drugs. Group II comprised 510 patients (275 males, 235 females) without an absolute indication for SICU care. Data collected included age, first day ICU severity of illness scores (Simplified Acute Physiology Score [SAPS] and Quantitative Therapeutic Intervention Scoring System [QTISS]), preoperative length of stay (LOS), SICU LOS, hospital LOS, and mortality. Ten patients (8.2%) in Group I and ten patients (2.0%) in Group II died in the SICU (P = 0.0004). There was no significant difference in the age of Group I and Group II patients, but Group I patients had a significantly longer preoperative LOS (6.1 +/- 0.7 vs 3.2 +/- 0.3 days, P < 0.0005). In Group II patients there were significant correlations between patient age and postoperative death, as well as between preoperative LOS and SICU LOS > 1 day. Patient age > or = 80 years and preoperative LOS > 3 days are significant preoperative correlates of the need for SICU care following infra-inguinal arterial surgery in patients who do not have an absolute indication for such care.
To assess the structural and functional significance of the N helix (residues 3-13) of avian recombinant troponin C (rTnC), we have constructed NHdel, in which residues 1-11 have been deleted, both in rTnC and in the spectral probe mutant F29W (Pearlstone, J. R., Borgford, T., Chandra, M., Oikawa, K., Kay, C. M., Herzberg, O., Moult, J., Herklotz, A., Reinach, F. C., and Smillie, L. B. (1992) Biochemistry 31, 6545-6553). Comparison of the far- and near-UV CD spectra (+/- Ca2+) of F29W and F29W/NHdel and titration of the Ca(2+)-induced ellipticity and fluorescence changes indicates that the deletion has little effect on the global fold of the molecule but reduces the Ca2+ affinity of the N domain, but not the C domain, by 1.6-1.8-fold. Comparisons of the mutants NHdel, F29W, and F29W/NHdel with rTnC have been made using several functional assays. In reconstituted troponin-tropomyosin actomyosin subfragment 1 and myofibrillar ATPase systems, both F29W and NHdel have significantly reduced Ca(2+)-activated enzymatic activities. These effects are cumulative in the double mutant F29W/NHdel. On the other hand, maximal isometric tension development in Ca(2+)-activated reconstituted skinned fibers is not affected with F29W and NHdel, although the Ca2+ sensitivity of NHdel in this system is markedly reduced. We conclude that both mutations, NHdel and F29W, are functionally deleterious, possibly affecting interactions of the N domain with troponin I and/or T.
The effects of Ca2+, Mg2+, and troponin I (TnI) inhibitory peptide (Ip) binding on the spectral properties of a Phe-154 to Trp mutant (F154W) of chicken recombinant troponin C (rTnC) have been examined. Residue 154 is positioned in the final flanking helix H of metal binding site IV. Since there are no other Tyr or Trp residues in the protein, spectral properties can be unambiguously assigned. No significant differences in the far UV CD spectra of rTnC and F154W were observed in either the absence or presence of Ca2+. When reconstituted into whole Tn the ATPase specific activities (+/- Ca2+) of the troponin-tropomyosin-actomyosin subfragment 1 system were the same for both proteins. A 2-fold reduction in Ca2+ affinity of C domain sites III/IV but not of N domain sites I/II in isolated F154W is explicable in terms of the environment of residue 154 in the relatively disordered apo-C domain and its buried position in the known ordered 2Ca2+ crystal structure. Filling of sites III/IV by divalent cations was accompanied by a number of spectral changes which were different for Ca2+ and Mg2+. Binding of Ip peptides (residues 96-116 and 104-115(116)) elicited fluorescence emission spectral alterations in the presence of Ca2+. These were not observed in its absence nor in the presence of Mg2+ even though binding occurs under these conditions. Since Ca2+ affinity to C domain but not to N domain sites was increased by Ip at the low concentrations of protein and Ip tested, Ip binding appears to be stronger with C domain.(ABSTRACT TRUNCATED AT 250 WORDS)
The two globular N and C domains of chicken troponin C (TnC) are connected by an exposed alpha-helix (designated D/E; residues 86-94). Recombinant N (residues 1-90) and C (residues 88-162) domains containing either F29 or W29 and F105 or W105 have been engineered and expressed in Escherichia coli. These termination and initiation sites were chosen to minimize disruption of side-chain interactions between the D/E helix and other residues. W29 and W105 served as useful spectral probes for monitoring Ca(2+)-induced structural transitions of the N and C domains, respectively [Pearlstone et al. (1992) Biochemistry 31, 6545-6553; Trigo-Gonzalez et al. (1992) Biochemistry 31, 7009-7015]. By all criteria tested, the properties of the isolated F29W/N domain (1-90) were identical to those of the N domain in intact F29W. These included fluorescence emission spectra in the absence and presence of Ca2+/Mg2+, far-UV CD spectra, and Ca2+ affinity as monitored by fluorescence and ellipticity at 221 nm. Similar but not identical properties were observed for isolated F105W/C domain (88-162) and intact F105W. A summation of the far-UV CD spectra (+/- Ca2+) of the two domains was virtually superimposable on that of the intact protein. Of the total Ca(2+)-induced ellipticity change at 221 nm, 27% could be assigned to the N domain and 73% to the C domain. The data suggest a significant Ca(2+)-induced transition involving secondary structural elements of the N domain.(ABSTRACT TRUNCATED AT 250 WORDS)
The backbone resonance assignments have been completed for the apo (1H and 15N) and calcium-loaded (1H, 15N, and 13C) regulatory N-domain of chicken skeletal troponin-C (1-90), using multidimensional homonuclear and heteronuclear NMR spectroscopy. The chemical-shift information, along with detailed NOE analysis and 3JHNH alpha coupling constants, permitted the determination and quantification of the Ca(2+)-induced secondary structural change in the N-domain of TnC. For both structures, 5 helices and 2 short beta-strands were found, as was observed in the apo N-domain of the crystal structure of whole TnC (Herzberg O, James MNG, 1988, J Mol Biol 203:761-779). The NMR solution structure of the apo form is indistinguishable from the crystal structure, whereas some structural differences are evident when comparing the 2Ca2+ state solution structure with the apo one. The major conformational change observed is the straightening of helix-B upon Ca2+ binding. The possible importance and role of this conformational change is explored. Previous CD studies on the regulatory domain of TnC showed a significant Ca(2+)-induced increase in negative ellipticity, suggesting a significant increase in helical content upon Ca2+ binding. The present study shows that there is virtually no change in alpha-helical content associated with the transition from apo to the 2Ca2+ state of the N-domain of TnC. Therefore, the Ca(2+)-induced increase in ellipticity observed by CD does not relate to a change in helical content, but more likely to changes in spatial orientation of helices.
The receptor for the bee venom derived neurotoxin, apamin, is widely believed to be an integral component of the small conductance calcium-activated potassium channel in many excitable cells. By affinity chromatography on immobilized apamin, a 78 kD apamin binding protein of the bovine brain synaptosomes was isolated. Antibodies were elicited against this protein and used to clone a cDNA from a porcine vascular smooth muscle expression library. This gene (Kcal 1.8) codes for a 438 amino protein with four potential transmembrane domains, one putative calcium binding site, a protein kinase C phosphorylation site, and a leucine zipper motif. Kcal 1.8 encoded protein has no significant sequence homologies with any known ion channels or receptors. Kcal 1.8 is likely to encode a protein associated with the small conductance calcium-activated potassium channel in vascular smooth muscle.
The present work was conducted to evaluate the oxygen free radical system in 29 patients and comparing them with nine matched healthy controls of acute and chronic myocardial ischemic syndromes. The parameters assessed for oxidative stress were superoxide anion and malonyldialdehyde, and for the antioxidant defence system were superoxide dismutase, catalase and glutathione reductase. Both oxidative stress and the antioxidant defence system were altered in myocardial ischemia. Subset analysis revealed that in unstable angina and acute myocardial infarction, superoxide anion, malonyldialdehyde and glutathione reductase were elevated while superoxide dismutase and catalase levels were reduced. In stable angina only increased levels of superoxide anion and decreased levels of superoxide dismutase were found. However, this alteration was less marked than in unstable angina and acute myocardial infarction. In the post myocardial infarction group there was no alteration in any of these parameters.
Testicular tumors are not uncommon in aging rats. However, metastasis from these neoplasms to several distant visceral organs has not been reported. Testicular tumors were observed in a total of 18 (1.34%) Sprague-Dawley rats out of 1340 males examined. Out of these 18 neoplasms, interstitial tumors were observed in 12 rats, of which 11 were benign and one malignant. Spermatic seminomas were observed in two (0.15%) cases (one benign and one malignant). Both rats with malignant testicular neoplasms were sacrified in extremis. Remaining four tumors were classified as mesotheliomas. Detailed gross, histopathologic and electron microscopic features of primary testicular neoplasms with metastases to several distant visceral organs are described and discussed.
Incidence and pathology of naturally occurring renal lesions in CD-1 and B6C3F1 mice are evaluated, tabulated, and discussed. In CD-1 mice, most frequent non-neoplastic renal lesion was interstitial nephritis (72.6%) followed by amyloidosis (40.6%), mononuclear cell infiltration (23.6%), tubular mineralization (12.8%), cortical cysts (8.2%), hydronephrosis (6.7%), tubular dilatation (5.9%), and tubular degeneration/regeneration (4.7%). Cortical epithelial origin renal cell carcinomas were observed in one male (0.13%) and one female mice (0.13%). In B6C3F1 mice, most commonly occurring non-neoplastic renal lesion was mononuclear cell infiltration (29.8%) followed by tubular mineralization (11.3%), interstitial nephritis (6.8%), tubular vacuolization (4.5%), tubular degeneration/regeneration (2.5%), and cortical cysts (1.3%). Cortical cell adenoma was the only primary renal neoplasm which was observed in one female mice (0.16%). In both strains, other renal lesions were less frequent.