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S Sundaresan

Publications and source records attributed to S Sundaresan.

50 records · Page 3Linked to original sources
PubMed1994

Differences in early results after single-lung transplantation. Washington University Lung Transplant Group.

Single-lung transplantation is an effective treatment for end-stage pulmonary failure caused by a variety of lung diseases. Although single-lung recipients may undergo a similar operative procedure, physiologic differences in the remaining native lung dictate differences in postoperative management and perhaps outcome. To examine these effects on the early results after single-lung transplantation, we retrospectively reviewed the course of 83 patients undergoing single-lung transplantation from September 1988 through July 1993. The cause of the lung disease was obstructive (OLD) in 43, idiopathic pulmonary fibrosis (IPF) in 16, and primary pulmonary hypertension (PPH) in 24 patients. The hospital mortality was 5% in OLD, 13% in IPF, and 8% in PPH. Gas exchange as demonstrated by alveolar-arterial oxygen gradients was worse after transplantation in patients with IPF (349 +/- 159 mm Hg) or PPH (270 +/- 171 mm Hg) compared with patients with OLD (174 +/- 105 mm Hg; p < 0.05). Mean pulmonary artery pressures were higher in patients with IPF (28 +/- 6 mm Hg) and PPH (26 +/- 7 mm Hg) compared with patients with OLD (22 +/- 5 mm Hg; p < 0.05). Peak airway pressures after transplantation were greater in patients with IPF (36 +/- 6 cm H2O) compared with patients with OLD (28 +/- 6 cm H2O; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Donor lung procurement: assessment and operative technique.

Given the relative scarcity of suitable donors and the widespread application of cardiac and pulmonary transplantation, it is imperative that a heart and two lungs be extracted from each donor. From increasing clinical experience and laboratory investigation in lung preservation, more flexible criteria for the assessment of potential lung donors are emerging. In this communication, we present our current criteria of donor lung suitability, and a simple and reliable technique of combined cardiopulmonary extraction that has provided suitable heart and lung grafts with excellent preservation, used in our last 150 donor organ procurements.

Dissection↗
PubMed1993

Lung preservation with low-potassium dextran flush in a primate bilateral transplant model.

We used a bilateral lung transplant model to confirm, in primates, the results of lung preservation studies previously obtained in a canine single-lung transplant model. The donor lungs were flushed with low-potassium dextran solution and maintained semiinflated with 100% oxygen at 10 degrees C for a planned ischemic time of 12 hours for the lung implanted first. Of eight experiments performed, results in the 6 operative survivors form the basis of this report. After bilateral lung transplantation, animals were maintained on a ventilator for 6 hours; arterial oxygen tension, pulmonary artery pressure, and pulmonary vascular resistance were determined in the recipients at 2, 4, and 6 hours after transplantation and compared with donor values, which served as controls. Arterial oxygen tension in the recipients did not differ from the controls (p = not significant), whereas the pulmonary artery pressure and pulmonary vascular resistance showed significant elevation (p < 0.05 versus control values). After the 6 hours of assessment, the animals were extubated and 3 survived for 48 to 72 hours with a mean arterial oxygen tension of 69 mm Hg on room air. These results demonstrate excellent lung function after a minimum of 12 hours of preservation in a primate model in which the animal is totally dependent on the function of transplanted lung tissue, and confirm the potential for prolonged clinical lung preservation.

Animals↗
PubMed1993

Evaluation of lung metabolism during successful twenty-four-hour canine lung preservation.

We used a canine left lung allotransplantation model to evaluate 24-hour lung preservation with two different electrolyte solutions, low-potassium dextran and low-potassium dextran with 1% glucose. To investigate changes in the energy status during preservation, we analyzed the lungs for adenosine triphosphate, phosphocreatine, and several metabolites of the glycolysis pathway and the citric acid cycle: glucose, glucose-6-phosphate, lactate, citrate, and malate. We also devised and evaluated a pulmonary cooling jacket to prevent rewarming of the lung during implantation. The lungs were divided into four groups. Groups I (n = 10) and II (n = 6) were flushed with low-potassium dextran and groups III (n = 6) and IV (n = 6) were flushed with low-potassium dextran solution with 1% glucose. The cooling jacket was used for groups II and IV only. After 24-hour preservation at 10 degrees C, the left lungs were implanted into the recipient animals. Function of the transplanted left lung was assessed during temporary (10 minutes) occlusion of the contralateral pulmonary artery while both lungs were ventilated with 100% oxygen. This assessment was performed at 1 hour and at 3, 8, and 22 days after transplantation. Immediately after transplantation the arterial oxygen tension was 279 +/- 70 mm Hg in group I, 376 +/- 56 mm Hg in group II, 523 +/- 41 mm Hg in group III, and 518 +/- 50 mm Hg in group IV. The arterial oxygen tension in groups III and IV were significantly greater than in group I (p < 0.05). Of the lungs preserved with low-potassium dextran solution with 1% glucose solution, 11 of 12 (92%) showed excellent lung function (arterial oxygen tension > 300 mm Hg) at 3 days; only 10 of 16 lungs preserved with low-potassium dextran achieved this level of function. Glucose, glucose-6-phosphate, lactate, citrate and malate levels decreased significantly during 24-hour preservation with low-potassium dextran solution; they were stable with low-potassium dextran solution with 1% glucose. Adenosine triphosphate and phosphocreatine were stable for 24 hours with both low-potassium dextran and low-potassium dextran solution with 1% glucose. The cooling jacket provided uniform cooling of the lung parenchyma during implantation, and significant increase in temperature was observed in its absence, with topical cooling by cold saline solution.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1993

Profound systemic hypothermia protects the spinal cord in a primate model of spinal cord ischemia.

Spinal cord ischemia with resultant paraplegia or paraparesis remains an important clinical problem after operations on the thoracoabdominal aorta. Because hypothermia has a protective effect on ischemic neural tissue, we developed a baboon model of spinal cord ischemia to simulate the situation encountered clinically for resection of aneurysms of the thoracoabdominal aorta and to determine whether profound hypothermia produced by hypothermic cardiopulmonary bypass has a protective effect on spinal cord function. After cardiopulmonary bypass was established, the aorta was clamped distal to the left subclavian artery and proximal to the renal arteries for 60 minutes. Group I animals (n = 9) underwent aortic clamping at normothermia (37 degrees C), and group II animals (n = 9) were cooled to a rectal temperature of 15 degrees C before aortic clamping and underwent cardiopulmonary bypass at this temperature until the aorta was unclamped. Of the eight operative survivors in group I, six animals were paraplegic and two were paraparetic, whereas all six group II animals that survived the procedure were neurologically intact (p = 0.0002). The protective effect of hypothermia was associated with blunting of the hyperemic response of spinal cord blood flow (determined by the radioactive microsphere technique) in the lower thoracic and the lumbar segments of the spinal cord after unclamping of the aorta. Profound hypothermia produced by hypothermic cardiopulmonary bypass may be an effective method of protection of the spinal cord in patients undergoing repair of aneurysms of the thoracoabdominal aorta and may reduce the prevalence of ischemic injury to the spinal cord.

Animals↗
PubMed1992

"Central" and "peripheral" benzodiazepine receptors: opposite changes in human epileptogenic tissue.

We measured the density of two benzodiazepine (BZ) receptor subtypes in neurosurgically obtained hippocampal tissue from the seizure focus of patients with temporal lobe epilepsy (TLE) showing mesial temporal sclerosis, the most common pathologic finding in TLE. We performed quantitative in vitro receptor autoradiography with [125I]Ro 16-0154, a probe for the central-type BZ receptor and with [3H]PK 11195, a probe for the peripheral-type BZ receptor. In comparison with autopsy and neurosurgical control groups, patients with mesial temporal sclerosis had regionally selective decreased central-type and increased peripheral-type BZ receptors. These changes paralleled regional losses of neurons and proliferation of glia. Decreases of the inhibitory central-type BZ receptor may be a component of the enhanced excitability of the seizure focus and also may allow localization of the focus by in vivo neuroreceptor imaging. Single photon emission computed tomography (SPECT) imaging of two TLE patients with [123I]Ro 16-0154 suggests that this technique may provide a more sensitive means of localizing the seizure focus than current imaging methods relying on changes in blood flow or glucose metabolism.

Adult↗
PubMed1989

Genes for HMG-CoA reductase and serotonin 1a receptor are on mouse chromosome 13.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is the key regulatory enzyme for cholesterol biosynthesis. The human gene (HMGCR) has been assigned to the q13.3-q14 region of chromosome 5 (HSA5). We have now mapped the mouse gene Hmgcr to mouse chromosome 13 by Southern analysis of somatic cell hybrids. We also report the mapping to mouse chromosome 13 of the murine homolog of the gene for an intronless beta 2-adrenergic-like receptor, which is also located on human chromosome 5 region q11.2-q13 and has recently been identified as the serotonin 1a receptor. Our results confirm the existence of an evolutionarily conserved syntenic group of genes on the proximal long arm of HSA5 and on MMU13 that also includes the loci for arylsulfatase B, hexosaminidase B and dihydrofolate reductase.

Animals↗
PubMed1989

Gene for alpha 2(I) collagen is on mouse chromosome 6 not 16.

Collagen is the most abundant protein in the animal world and a principal component, of the extracellular matrix of tissues. Type I collagen is composed of two alpha 1 chains and one alpha 2 chain. The human alpha 2(I) locus (COL1A2) has been assigned to human chromosome 7q21.3-q22.1. Here, we report the mapping of its murine counterpart Colla-2 to mouse chromosome 6 (MMU6) by Southern blotting using somatic cell hybrids. This result disagrees with the previously reported mapping of Colla-2 to MMU16 by immunochemical techniques. Our results are supported by comparative mapping data showing conserved homology between regions of human chromosome 7 and mouse chromosome 6.

Animals↗
PubMed1989

Genes for beta 2-adrenergic receptor and platelet-derived growth factor receptor map to mouse chromosome 18.

The beta 2-adrenergic receptor (ADRB2R) mediates the response of various cel types to neurotransmitters, hormones, and drugs. The platelet-derived growth factor (PDGF) interacts with its receptor (PDGFR) to stimulate mesenchymal cell proliferation. In the human, ADRB2R and PDGFR have been mapped to the q31--q32 region of chromosome 5 (HSA5). Here we report the mapping of Pdgfr and Adrb2r to mouse chromosome 18 (MMU18) using somatic cell hybrid mapping techniques. Together with previous mapping of genes for the glucocorticoid receptor (human locus GRL; mouse locus Gr1-1), the class II HLA invariant chain (human locus PHLAG; mouse locus Ii) and the FMS protooncogene to HSA5 and MMU18, the assignment of both Pdgfr and Adrb2r to MMU18 expands the conserved autosomal syntenic group.

Animals↗
PubMed1989

Insulin-like growth factor I receptor gene is concordant with c-Fes protooncogene and mouse chromosome 7 in somatic cell hybrids.

The insulin-like growth factor I (IGF-1) mediates the actions of pituitary growth hormone in a variety of tissues. Its receptor (IGF1R) displays considerable structural similarity to the insulin receptor. In humans, the IGF1R gene has been mapped near FES, the cellular counterpart of the feline sarcoma virus transforming gene v-fes, at the q25-q26 region of human chromosome 15 (HSA15). Here, we report the mapping of mouse Igf1r to mouse chromosome 7 (MMU7) by somatic cell hybrid analysis. This result, along with the prior assignment of the loci for mitochondrial isocitrate dehydrogenase and FES to human chromosome 15 and mouse chromosome 7, suggest a conserved autosomal synteny group on the distal long arm of HSA15 and in the center of MMU7.

Animals↗
PubMed1988

Chromosome localization and expression pattern of Lmyc and Bmyc in murine embryonal carcinoma cells.

Using Southern blot analysis of DNA from mouse-hamster somatic cell hybrids, we have mapped Lmyc and Bmyc, two members of the myc family of genes, to mouse chromosomes 4 and 2, respectively. Furthermore, we have compared the regulation of Lmyc and Bmyc expression under different growth conditions and during in vitro differentiation of the murine EC line F9 and considered the findings in relation to our previous studies on Nmyc and c-myc expression in the same line (Sejersen et al., 1987). Lmyc was down-regulated at an early stage of visceral endoderm differentiation, similarly to c-myc and Nmyc, while Bmyc was expressed at a constant low level at all stages. Lmyc, but not c-myc and Nmyc, was upregulated in terminally differentiated visceral endoderm cells. Inhibition of protein synthesis by cycloheximide for 4 h induced a 70% increase in Lmyc and 30% increase in Bmyc transcript levels, indicating that the expression of these genes is negatively regulated by a short-lived protein. Mitogenic stimulation with insulin and transferrin did not affect Lmyc and Bmyc mRNA levels. Lmyc transcripts have a half life of 30 min, whereas the Bmyc transcript is highly stable, with a half life of 6 h. The half-lives of the c-myc and Nmyc transcripts have been estimated previously as 40 and 130 min, respectively.

Animals↗
PubMedDate not supplied

Spectrophotometric determination of cyanoglucosides in cassava.

A new method is reported for determination of cyanoglucosides in cassava. The method is simple, rapid, and sensitive. Ten g cassava tuber is homogenized with warm (65-70 degrees C) 80% ethanol (1 + 6, w/v) to extract cyanoglucosides (CNG). The ethanol is evaporated, and an aliquot of the extract (0.1-0.2 mL) is incubated with added linamarase in pH 6.0 phosphate buffer for 15 min at 30 degrees C. The reaction is stopped by adding 0.2 N sodium hydroxide, the solution is neutralized, and cyanide is estimated by adding chloramine T and barbituric acid-pyridine reagent and measuring the absorbance at 570 nm. Complete CNG extraction and rapid inactivation of endogenous linamarase is possible with 80% ethanol. There is no interference from extractives in the linamarase reaction or in the estimation of cyanide. Recovery of added linamarin (as cyanide) is 98% by this assay. The minimum detection limit of cyanide in the assay is 0.1 micrograms/mL.

Glycosides↗
PubMedDate not supplied

Cytokine gene transcripts for tumor necrosis factor-alpha, interleukin-2, and interferon-gamma in human pulmonary allografts.

BACKGROUND: Cytokines participate in host responses to allografts, largely through recruiting and activating various regulatory and effector cells. We performed this study to determine the feasibility of using polymerase chain reaction methodology to define the expression of three important cytokines (tumor necrosis factor-alpha, interleukin-2, and interferon-gamma) in human pulmonary allografts. METHODS: Twenty-six graft-derived samples (11 transbronchial biopsy and 8 macrophage and 7 lymphocyte cell pellets isolated from bronchoalveolar lavage) were obtained from 13 lung transplant recipients and treated as follows: extraction of RNA; reverse transcription of RNA to complementary DNA; polymerase chain reaction amplification of cDNA with oligonucleotide primers specific for the three cytokines; gel electrophoresis of the polymerase chain reaction products; and verification of correct cytokine message by Dot blot technique (with specific 32P-labeled oligonucleotide probes). RESULTS: Concomitant pathologic evaluation of biopsy specimens from these 13 recipients showed five diagnostic groups: "normal" (no rejection/infection), n = 2; acute rejection, n = 4; nonspecific inflammation, n = 3; infection, n = 3; and obliterative bronchiolitis, n = 1. Interleukin-2 was expressed predominantly in acute rejection and infection (seven of ten and five of six samples positive, respectively), whereas tumor necrosis factor-alpha was expressed mainly in nonspecific inflammation (four of five samples) and somewhat less in rejection (six of ten). Interferon-gamma was expressed less frequently (in two of six samples with infection, but in none of ten with rejection and none of five with nonspecific inflammation). Serial data from one patient (6 months apart) showed considerable increase in interleukin-2 and interferon-gamma expression as she progressed from normal histologic status to obliterative bronchiolitis. CONCLUSIONS: Cytokine gene transcripts can be determined from minute samples derived directly from pulmonary allografts. Although our data are insufficient to make definitive conclusions, the suggestion of trends of cytokine expression in different posttransplantation pathologic conditions may indicate a useful role for this approach in the clinical evaluation of the lung transplant recipient.

Adult↗