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Biomedical subjects

K S Reddy

Publications and source records attributed to K S Reddy.

At least 73 records · Page 4Linked to original sources
PubMed1999

Allograft pancreatectomy after pancreas transplantation with systemic-bladder versus portal-enteric drainage.

UNLABELLED: From 1989 to 1997, we performed 159 pancreas transplantations (PTXs), including 117 simultaneous kidney PTX (SKPT), 25 PTXs alone (PTA), and 17 sequential PTXs after kidney transplantations (PAKT). A total of 73 PTXs were performed with systemic-bladder (S-B) and 86 with portal-enteric (P-E) drainage. The need for allograft pancreatectomy (PCTY) may be considered as an index of technical morbidity after PTX. A total of 37 PCTYs (23%) were performed at a mean of 4.7 months after PTX. Twenty-seven PCTYs were performed within 1 month, 30 (81%) within 3 months, and the remaining seven more than 6 months after PTX. The incidence of PCTY did not differ according to type of transplantation: simultaneous kidney PTX (SKPT) (23%), PTA (24%), and PAKT (23.5%). Indications for PCTY were thrombosis (23), rejection (9), infection (3), and pancreatitis (2). During the study, a total of 70 pancreas grafts were lost, with PCTY performed in 37 (53%). PCTY was directly related to the timing of graft loss; 77% of grafts lost within 3 months of PTX required PCTY, while 25% of grafts lost after 3 months resulted in PCTY (p < 0.01). The incidence of graft failure resulting in PCTY was similar according to type of transplantation: SKPT (55%), PTA (46%), and PAKT (50%). The incidence of PCTY was also similar according to technique of transplantation: 26% S-B versus 21% P-E, p = NS. However, the incidence of graft failure resulting in PCTY was higher in P-E (69%) versus S-B (43%) (p < 0.05) PTX recipients. Patient and kidney graft survival and pancreas retransplant graft survival rates were higher in PTX recipients with P-E drainage. CONCLUSIONS: PCTY is performed in over half of cases of pancreas allograft loss and is directly related to the timing and cause of graft loss. The incidence of PCTY is neither related to the type nor technique of PTX. The lower overall incidence of graft loss after PTX with P-E drainage is offset by a higher incidence of PCTY in these grafts that fail. These results suggest that whole-organ PTX with P-E drainage does not place the patient at an increased risk for PCTY and does not preclude successful pancreas retransplantation.

Drainage↗
PubMed1999

Evolution in pancreas transplantation techniques: simultaneous kidney-pancreas transplantation using portal-enteric drainage without antilymphocyte induction.

OBJECTIVE: To report initial experience with the combination of a novel technique of portal-enteric pancreas transplantation with newer immunosuppressive strategies that eliminate antilymphocyte induction therapy. BACKGROUND: A new surgical technique of pancreas transplantation has been developed with portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal-enteric). The introduction of potent immunosuppressive agents may allow simultaneous kidney and pancreas transplants (SKPT) to be performed without antilymphocyte induction. METHODS: From September 1996 to November 1998, the authors performed 28 primary SKPTs with portal-enteric drainage and no antilymphocyte induction. All patients received triple immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. The study group had a mean age of 38 years and a mean preoperative duration of diabetes of 25 years. Four patients (14%) had prior kidney transplants. RESULTS: All patients had immediate renal allograft function. Actual patient, kidney, and pancreas graft survival rates were 86%, 82%, and 82%, respectively, after a mean follow-up of 12 months. Four patients died, three as a result of cardiac events unrelated to SKPT. Five kidney and five pancreas grafts were lost, including five deaths with function and three cases of chronic rejection. The mean length of stay and total charges for the initial hospital stay were 12.5 days and $99,517. The mean number of readmissions was 2.9, and 10 patients (36%) had no readmissions. Six patients (21 %) developed acute rejection, with five (18%) receiving antilymphocyte therapy. Seven patients (25%) underwent relaparotomy, including two (7%) for intraabdominal infection. Nine patients (32%) had major infections, including three (11%) with cytomegaloviral infection. Of the 24 surviving patients, 22 (92%) are both dialysis- and insulin-free. CONCLUSION: These preliminary results suggest that SKPT with portal-enteric drainage without antilymphocyte induction can be performed with excellent outcomes.

Adult↗
PubMed1999

Cri du chat and Turner syndrome features in a newborn girl with an unbalanced 45,X,psu dic(5;X)(p15.2;p22.1) karyotype: FISH and replication banding studies.

A newborn girl with features of Turner and Cri du chat syndromes was found to have a pseudodicentric 5;X chromosome. Her karyotype was 45,X, psu dic(5;X)(p15.2;p22.1). The net result was monosomy for 5p15.2-pter and Xp22.1-pter. Fluorescence in situ hybridization (FISH) showed the Cri du chat region was deleted. Replication banding studies to assess the X-inactivation pattern found only the X portion of the pseudodicentric chromosome to be late replicating without any apparent spread of inactivation into chromosome 5 segment. There are only two cases reported with a dicentric X; autosome. In this paper, we compare the cytogenetics of the present case and those in the literature.

Chromosome Banding↗
PubMed1999

Effect of flavone in a canine model of myocardial stunning.

Putative cardioprotective action of flavone (10, 20 and 30 mg/kg) was investigated in a canine model of regional ischemia (20 min) followed by 60 min of reperfusion. In animals pretreated with vehicle, myocardial stunning was evidenced by significant changes in hemodynamic parameters (depressed mean arterial pressure, LV peak (+) dP/dt, LV peak (-) dP/dt and elevated LV end-diastolic pressure) and biochemical parameters (decreased myocardial ATP and rise in plasma malondialdehyde or MDA; a marker of free radical-induced injury). A reduction in plasma MDA was noted with 20 and 30 mg/kg flavone, although attenuation of myocardial dysfunction was evident with all the three doses. The results suggest that besides a significant dose-dependent antioxidant effect, flavone may also have some cardioprotective actions per se, which needs to be further investigated.

Adenosine Triphosphate↗
PubMed1998

Trisomy 14 and leukemia.

A total of 11 cases with trisomy 14 as the sole abnormality were found in the database of a large cytogenetic reference laboratory from 1993 to the present. Four of the 11 cases had an isochromosome 14q. In 8 cases, the trisomy 14 was a mosaic cell line. Eight cases were diagnosed with myelodysplasia, 2 cases had both myelodysplastic and myeloproliferative features similar to some atypical chronic myeloid leukemia cases, and 1 case had acute myeloid leukemia of M1 or M2 type. Nine were males and two females. The median age was 77 years. Referring physicians were contacted and clinical information was available in only 8 cases. Survival ranged from 1 month to approximately 3 years. An abnormal red cell morphology, such as elliptocytes or schistocytes or both, was observed in the majority of cases. This study along with the reported cases strengthens the hypothesis that trisomy 14 is a nonrandom cytogenetic abnormality associated with myeloid malignancy.

Aged↗
PubMed1998

Role of beta112 Cys (G14) in homo- (beta4) and hetero- (alpha2 beta2) tetramer hemoglobin formation.

In order to assess the role of beta112 Cys in homo- and hetero-tetrameric hemoglobin formation, we expressed four beta112 variants (beta112Cys-->Asp, beta112Cys-->Ser, beta112Cys-->Thr, and beta112Cys-->Val) and studied assembly with alpha chains in vitro. beta112 Cys is normally present at beta1 beta2 and alpha1 beta1 interaction sites in homo- (beta4) and hetero-tetramers (alpha2 beta2). beta4 formation in vitro was influenced by the amino acid at beta112. beta112 Asp completely inhibited formation of homo-tetramers, whereas beta112 Ser showed only slight inhibition. In contrast, beta112 Thr or Val enhanced homo-tetramer formation compared with betaA chains. Association constants for homo-tetramer formation increased in the order of beta112Cys-->Ser, betaA, beta112Cys-->Thr, and beta112Cys-->Val, whereas the value for beta112Cys-->Asp was zero under the same conditions. These beta112 changes also affected in vitro alpha2 beta2 hetero-tetramer formation. Order of alpha2 beta2 formation under limiting alpha-globin chain conditions showed Hb betaC112S > Hb A > Hb S = Hb betaC112T = Hb betaC112V >>> Hb betaC112D. Hb beta112D can form tetrameric hemoglobin, but this beta112 change promotes dissociation into alpha and beta chains instead of alpha beta dimer formation upon dilution. These results indicate that amino acids at alpha1 beta1 interaction sites such as beta112 on the G helix play a key role in stable alpha beta dimer formation. Our findings suggest, in addition to electrostatic interaction between alpha and beta chains, that dissociation of beta4 homo-tetramers to monomers and hydrophobic interactions of the beta112 amino acid with alpha chains governs stable alpha1 beta1 interactions, which then results in formation of functional hemoglobin tetramers. Information gained from these studies should increase our understanding of the mechanism of assembly of multi-subunit proteins.

Chromatography, Gel↗
PubMed1998

Effect of four helix bundle topology on heme binding and redox properties.

We have designed two alternative four helix bundle protein scaffold topologies for maquette construction to examine the effect of helix orientation on the heme binding and redox properties of our prototype heme protein maquette, (alpha-SS-alpha)2, previously described as H10H24 [Robertson, D. E., Farid, R. S., Moser, C. C., Mulholland, S. E., Pidikiti, R., Lear, J. D., Wand, A. J., DeGrado, W. F., and Dutton, P. L. (1994) Nature 368, 425]. Conversion of the disulfide-bridged di-alpha-helical monomer of (alpha-SS-alpha)2 into a single polypeptide chain results in topological reorientation of the helix dipoles and side chains within a 62 amino acid helix-loop-helix monomer, (alpha-l-alpha), which self-associates to form (alpha-l-alpha)2. Addition of an N-terminal cysteine residue to (alpha-l-alpha) with subsequent oxidation yields a 126 amino acid single molecule four helix bundle, (alpha-l-alpha-SS-alpha-l-alpha). Gel permeation chromatography demonstrated that (alpha-SS-alpha)2 and (alpha'-SS-alpha')2, a uniquely structured variant of the prototype, as well as (alpha-l-alpha)2 and (alpha'-l-alpha')2 assemble into distinct four helix bundles as designed, whereas (alpha-l-alpha-SS-alpha-l-alpha) elutes as a monomeric four alpha-helix bundle. Circular dichroism (CD) spectroscopy proves that these peptides are highly alpha-helical, and incorporation of four hemes has little effect on the helical content of the secondary structure. Four heme dissociation constants were evaluated by UV-visible spectroscopy and ranged from the 15 nM to 25 microM range for each of the peptides. The presence of Cotton effects in the visible CD illustrated that the hemes reside within the protein architecture. The equilibrium redox midpoint potentials (Em8) of the four bound hemes in each peptide are between -100 and -280 mV, as determined by redox potentiometry. The heme affinity and spectroelectrochemical properties of the hemes bound to (alpha-l-alpha)2 and (alpha-l-alpha-SS-alpha-l-alpha) are similar to those of the prototype, (alpha-SS-alpha)2, and to bis-histidine ligated b-type cytochromes, regardless of the global architectural changes imposed by these topological rearrangements. The hydrophobic cores of these peptides support local electrostatic fields which result in nativelike heme chromophore properties (spectroscopy, elevated reduction potentials, heme-heme charge interaction, and reactivity with exogenous diatomics) illustrating the utility of these non-native peptides in the study of metalloproteins.

Amino Acid Sequence↗
PubMed1998

A designed cavity in the hydrophobic core of a four-alpha-helix bundle improves volatile anesthetic binding affinity.

The structural features of protein binding sites for volatile anesthetics are being explored using a defined model system consisting of a four-alpha-helix bundle scaffold with a hydrophobic core. Earlier work has demonstrated that a prototype hydrophobic core is capable of binding the volatile anesthetic halothane. Exploratory work on the design of an improved affinity anesthetic binding site is presented, based upon the introduction of a simple cavity into a prototype (alpha 2)2 four-alpha-helix bundle by replacing six core leucines with smaller alanines. The presence of such a cavity increases the affinity (Kd = 0.71 +/- 0.04 mM) of volatile anesthetic binding to the designed bundle core by a factor of 4.4 as compared to an analogous bundle core lacking such a cavity (Kd = 3.1 +/- 0.4 mM). This suggests that such packing defects present on natural proteins are likely to be occupied by volatile general anesthetics in vivo. Replacing six hydrophobic core leucine residues with alanines results in a destabilization of the folded bundle by 1.7-2.7 kcal/mol alanine, although the alanine-substituted bundle still exhibits a high degree of thermodynamic stability with an overall folded conformational delta GH2O = 14.3 +/- 0.8 kcal/mol. Covalent attachment of the spin label MTSSL to cysteine residues in the alanine-substituted four-alpha-helix bundle indicates that the di-alpha-helical peptides dimerize in an anti orientation. The rotational correlation time of the four-alpha-helix bundle is 8.1 +/- 0.5 ns, in line with earlier work on similar peptides. Fluorescence, far-UV circular dichroism, and Fourier transform infrared spectroscopies verified the hydrophobic core location of the tryptophan and cysteine residues, showing good agreement between experiment and design. These small synthetic proteins may prove useful for the study of the structural features of small molecule binding sites.

Amino Acid Sequence↗
PubMed1998

Interstitial deletion of chromosome 4, del(4)(q12q21.1), in a mentally retarded boy with a piebald trait, due to maternal insertion, ins(8;4).

A 17-year-old boy who was diagnosed with "Waardenburg syndrome" showed moderate growth and mental retardation. Chromosome analysis showed an apparent interstitial deletion 4q12q21.1. The mother had a direct insertion of the deleted segment into a chromosome 8. The rearrangement was confirmed to be nonreciprocal and an insertion by in situ hybridization using whole chromosome 4 and 8 painting probes. The mother's karyotype is 46,XX,ins(8;4)(q21.2;q12q21.1); that of the propositus is 46,XY, der(4)ins(8;4)(q21.2;q12q21.1)mat. This is the first report of an inherited proximal 4q deletion.

Adolescent↗
PubMed1998

Clinical management of a rare de novo translocation 46,X,t(Y;15) (p11.2 approximately 11.3;q11.2).ish t(Y;15)(DYZ3+,AMELY+,SNRPN+;D15Z+) found prenatally.

A 40-year-old woman had amniocentesis at 16 weeks' gestation. Chromosome studies based on 15 colonies showed a de novo 46,X,t(Y;15)(p11.2 approximately 11.3;q11.2) karyotype. Using C- and Q-banding, the additional material on 15 appeared to be Yqh heterochromatin. The satellite on the small derivative chromosome was positive by AgNOR staining. Fluorescence in situ hybridization (FISH) studies using Y and 15 alpha satellite centromeric probes (DYZ3 and D15Z) showed that the derivative chromosome that resembled 15p+ had a Y centromere and that the satellited derivative had a 15 centromere. The break on Y was distal to the amelogenin locus and on 15 it was shown to be proximal to the Prader Willi/Angelman region by using the SNRPN probe. DNA studies ruled out uniparental disomy of chromosome 15 and a SRY deletion. The pregnancy was continued and a normal baby boy without any discernible abnormalities was born.

Adult↗
PubMed1998

The mobile nature of acrocentric elements illustrated by three unusual chromosome variants.

Variant chromosomes are polymorphic in areas that are rich in repeat sequences such as the pericentromeric regions or in the acrocentric short arm regions. The dynamic nature of these regions is evident in the polymorphisms they exhibit. In this paper three unusual variants are described: a chromosome 21 with additional material on its short arm, a chromosome 7 with an insertion in the short arm and a chromosome 2 with satellites at the end of the long arm. All three variants were shown to involve acrocentric elements using special banding techniques and fluorescence in situ hybridization. The 21 variant was found to be a tricentric with a 21 and two 15 alpha-, two classical and three acrocentric beta-satellite signals interspersed by AgNOR-positive regions. The telomeres were present at the two terminal ends. The insertion on chromosome 7 was found to be C-band positive and to contain acrocentric beta-satellite DNA. However, acrocentric alpha-satellite, classical satellite, whole-chromosome-painting or all-telomeres sequence probes did not hybridize to the insertion. The satellited region of chromosome 2 had two C-bands, a small positive all-centromeres probe signal, and two signals for the beta-satellite probe. Sandwiched between the beta-satellite sequences was an AgNOR-positive region. The telomeres were present at the two ends of the satellited chromosome 2. Chromosome 2 subtelomeric probes hybridized to the terminal ends of the short and long arm of chromosome 2. The common thread in these three variants is the involvement of acrocentric short arm elements. The acrocentric short arm elements are shown to move to other acrocentric or nonacrocentric chromosomes and relocate to both terminal and interstitial positions. The integrations are stable and heritable.

Abnormalities, Multiple↗
PubMed1998

A Philadelphia-negative chronic myeloid leukemia with a BCR/ABL fusion gene on chromosome 9.

A 40-year-old man had chronic myeloid leukemia (CML) and an apparently normal karyotype. Fluorescence in situ hybridization with a BCR/ABL1-S probe, which is formatted to display a BCR/ABL fusion signal on chromosome 22, gave a positive fusion signal on a chromosome 9. Therefore this patient has a BCR/ABL fusion gene on chromosome 9. The BCR/ABL1-D probe, formatted to display a fluorescent signal for both the reciprocal products of a 9/22 rearrangement, gave a positive fusion signal on the derivatives 9 and 22. These findings favor either a cryptic reciprocal exchange between BCR and ABL loci or the reversal of a Philadelphia translocation. An insertion of BCR next to ABL is ruled out. The reverse-transcriptase polymerase chain reaction provided molecular evidence that a typical CML chimeric product resulting from a fusion of BCR exon 2 with C-ABL exon II, a2b2, is present.

Adult↗