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Biomedical subjects

Krishna Kumar

Publications and source records attributed to Krishna Kumar.

At least 19 recordsLinked to original sources
PubMed2006

Bioorthogonal noncovalent chemistry: Fluorous phases in chemical biology.

Chemical entities designed to noncovalently interact with predetermined partners have fashioned a new paradigm in chemical biology. Fluorocarbons are extremely promising as supramolecular synthons toward these objectives. Bioorthogonal noncovalent interactions provide a way to modulate self-assembled systems in environments where such control has hitherto not been possible. Fluorocarbons have now found applications in self-assembly as well as proteomics, biomolecule purification and in the creation of microarray platforms. Other self-assembly motifs with similar attributes might be exploited using the same general approach.

Cell Adhesion↗
PubMed2006

Increased pro-nerve growth factor and p75 neurotrophin receptor levels in developing hypothyroid rat cerebral cortex are associated with enhanced apoptosis.

Thyroid hormone insufficiency adversely affects cortical development; however, its effect on apoptosis modulation during cerebral cortex development is not understood. We investigated the effect of perinatal hypothyroidism on apoptosis and its mechanisms during rat cerebral cortex development. Primary hypothyroidism was induced by feeding methimazole (0.025% wt/vol) in the drinking water to pregnant and lactating rats and continued until the animals were killed (hypothyroid group). Cerebral cortices from pups were harvested at different postnatal ages (postnatal d 0, 8, 16, and 24 and adult), and apoptosis was quantitated by terminal deoxynucleotide transferase-mediated dUTP nick end labeling and cleaved caspase-3 immunoreactivity. Compared with the euthyroid, primary somatosensory cortex (S1) in the hypothyroid group exhibited enhanced apoptosis. In S1 of euthyroid rats, apoptotic cells were mostly found in cortical layers I-III and the proportion of apoptotic cells enhanced significantly in the hypothyroid group (P < 0.001). Most of the apoptotic cells were neurons, as assessed by double immunolabeling. A significantly increased activation of caspase-3 and -7, decreased levels of antiapoptotic proteins Bcl-2 and Bcl-x(L), and increased levels of proapoptotic protein Bax was observed in the developing cerebral cortex of hypothyroid rats, compared with the euthyroid (P < 0.001). In addition, hypothyroidism significantly elevated the levels of 53-kDa pro-nerve growth factor (P < 0.001) and p75 neurotrophin receptor (P < 0.001) and decreased TrkA expression. Taken together, we provide evidence for the possible contribution of pro-nerve growth factor/p75 neurotrophin receptor pathway in hypothyroidism-enhanced apoptosis during rat cortical development. Thus, the present study may help in explaining the mechanism of the deleterious effect of thyroid hormone deficiency on cerebral cortex development in children.

Animals↗
PubMed2006

Selective protein-protein interactions driven by a phenylalanine interface.

Highly specific protein-protein interfaces have been the subject of considerable study for their potential utility in disrupting or interrogating cellular signaling and control networks. We report that coiled-coil sequences decorated with phenylalanine core residues fold into stable alpha-helical bundles and that these self-sort from similar peptide assemblies with aliphatic core side chains. For self-assembled ensembles derived from 30-residue monomeric peptides, the DeltaG of specificity is -1.5 kcal/mol, comparable with earlier self-sorting coiled-coil systems. Intriguingly, although this interface is constructed from canonical amino acids, it does not appear to have been exploited in native proteins.

Amino Acid Sequence↗
PubMed2006

Spinal cord stimulation in treatment of chronic benign pain: challenges in treatment planning and present status, a 22-year experience.

OBJECTIVE: To present an in-depth analysis of clinical predictors of outcome including age, sex, etiology of pain, type of electrodes used, duration of pain, duration of treatment, development of tolerance, employment status, activities of daily living, psychological status, and quality of life. Suggestions for treatment of low back pain with a predominant axial component are addressed. We analyzed the complications and proposed remedial measures to improve the effectiveness of this modality. METHODS: Study group consists of 410 patients (252 men, 58 women) with a mean age of 54 years and a mean follow-up period of 97.6 months. All patients were gated through a multidisciplinary pain clinic. The study was conducted over 22 years. RESULTS: The early success rate was 80% (328 patients), whereas the long-term success rate of internalized patients was 74.1% (243 patients) after the mean follow-up period of 97.6 months. Hardware-related complications included displaced or fractured electrodes, infection, and hardware malfunction. Etiologies demonstrating efficacy included failed back syndrome, peripheral vascular disease, angina pain, complex regional pain syndrome I and II, peripheral neuropathy, lower limb pain caused by multiple sclerosis. Age, sex, laterality of pain or number of surgeries before implant did not play a role in predicting outcome. The percentage of pain relief was inversely related to the time interval between pain onset and time of implantation. Radicular pain with axial component responded better to dual Pisces electrode or Specify-Lead implantation. CONCLUSION: Spinal cord stimulation can provide significant long-term pain relief with improved quality of life and employment. Results of this study will be effective in better defining prognostic factors and reducing complications leading to higher success rates with spinal cord stimulation.

Adult↗
PubMed2006

Complications of spinal cord stimulation, suggestions to improve outcome, and financial impact.

OBJECT: The long-term success of spinal cord stimulation is impeded by the high incidence of adverse events. The cost of complications to the healthcare budget is influenced by the time course needed to reverse the effect, and by the type of corrective measures required. Understanding the mechanism of complications and reducing them can improve the overall success rate and the cost factor. METHODS: The authors performed a retrospective analysis of data obtained in 160 patients treated during a 10-year period. For each category of complication, the level of healthcare resource use was assessed for each case and a unit cost was applied. The total cost of each complication was determined by summing across healthcare resource headings. All cost calculations were performed in Canadian dollars at 2005 prices. To understand the mechanics of various hardware-related complications and how to avoid them, the authors have utilized the results of bench tests conducted at Medtronic, Inc. Fifty-one adverse events occurred in 42 of the 160 patients. The complications were classified as either hardware related (39 events) or biological (12 events). The mean cost of complications during the 10-year study period was dollar 7092 (range dollar 130 - dollar 22,406). CONCLUSIONS: Complications not only disrupt the effect of pain control but also pose an added expense to the already high cost of therapy. It is possible to reduce the complication rate, and thus improve the long-term success rate, by following the suggestions made in this paper, which are supported by the biomechanics of the human body and the implanted material.

Adult↗
PubMed2005

Controlling association of vesicle embedded peptides by alteration of the physical state of the lipid matrix.

We report here the reversible association of a designed peptide embedded in a lipid membrane through a stimulus-sensitive trigger that changes the physical state of the bilayer matrix. A peptide designed with the classical 4-3 heptad repeat of coiled coils, equipped with leucine residues at all canonical interface positions, TH1, was rendered membrane soluble by replacement of all exterior residues with randomly selected hydrophobic amino acids. Insertion of TH1 into large unilamellar phosphatidylcholine vesicles was followed by monitoring tryptophan fluorescence. Peptide insertion was observed when the lipids were in the liquid-crystalline state [1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)] but not when they were in the crystalline phase [1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)]. Formation of a trimeric alpha-helical bundle in lipid bilayers was followed by fluorescence resonance energy transfer. Global fit analysis revealed a monomer--trimer equilibrium with a dissociation constant of around 10(-5) [corrected] MF(2). A lipid mixture composed of DPPC and POPC exhibiting a phase transition at 34 degrees C between a crystalline/liquid-crystalline coexistence region and a completely miscible liquid-crystalline phase was used to control the formation of the trimeric peptide bundle. TH1 is phase excluded in crystalline DPPC domains below 34 degrees C, leading to a larger number of trimers. However, when the DPPC domains are dispersed at temperatures above 34 degrees C, the number of trimers is reduced.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2005

Vertebroplasty in osteoporotic spine fractures: a quality of life assessment.

OBJECTIVE: Our goal was to perform a quantitative evaluation of the improvement in functional capacity, quality of life, mental function, reduction in drug intake and impact on hospital admissions after vertebroplasty in the treatment of osteoporotic compression fractures. The efficacy of vertebroplasty in relief of pain has been addressed in previous publications but the quantitative evaluation of improvement in quality of life has not been addressed before. METHODS: This is a prospective study of 42 patients with 83 symptomatic vertebral fractures treated by vertebroplasty with a mean follow-up of 9.1 months. The outcome was measured by pre and postoperatively utilizing the Visual Analogue Scale, the Oswestry Disability Index, the Rolland Morris Scale for Back Pain and EuroQol-5D questionnaire (EQ-5D). The postoperative evaluations were performed at one week, one month, three month, and six month intervals thereafter. RESULTS: In 34 out of 39 active patients, marked pain relief was noted (87%). The Visual Analogue Scale score improved from a mean preoperative score of 8.2 to a mean postoperative score of 2.9 (p=0.0000003) at one week follow up and 3.9 at the last follow-up. The Rolland Morris Scale for Back Pain showed a drop from a mean preoperative rating of 13 to a mean postoperative rating of 10, showing a 25% improvement (p= 0.0207). The Oswestry Disability Index preoperatively was 64.4 which improved to 43.8 postoperatively, showing a 32% improvement (p= 0.0207). The EQ-5D showed a mean preoperative index value of 0.097 and mean postoperative index value of 0.592 (p = 0.0000003). All p-values were determined by the Willcoxin sign-ranked test. CONCLUSION: Vertebroplasty is a safe and efficacious procedure with a resulting improvement in pain and quality of life.

Adult↗
PubMed2005

Spinal epidural abscess.

INTRODUCTION: The incidence of spinal epidural abscesses (SEAs) is rising. Although increased awareness has led to decreased mortality, morbidity remains unacceptably high, with rapid deterioration of neurological status when there is a delay in initiation of treatment. Therefore, we need to build a better understanding of prognostic factors and management strategies. The goal of this article is to identify various prognostic factors, the role of inflammatory markers, optimal management strategies, and the relationship between timing of intervention and outcome. METHODS: A computer search of health records in our institution revealed 20 cases of spinal epidural abscess over the past 5 years. A retrospective analysis of clinical, radiological, laboratory, and surgical findings was performed. A scoring system ranging from 1 (complete neurological recovery) to 5 (dead) was used to assess outcomes. We also analyzed the prognostic value of several factors, including demographics, clinical presentation, comorbidities, inflammatory markers, imaging findings, and timing of intervention. RESULTS: Fifteen of 20 patients had a good outcome (score of 1 or 2) in this series. Erythrocyte sedimentation rate, muscle strength at time of admission, and timing of intervention were found to have a statistically significant relationship with outcome. C-reactive protein, comorbidities, age, sex, and degree of thecal sac compression were found to have no prognostic value. CONCLUSION: Although many prognostic factors have been suggested and analyzed, the most important contributor to outcome in SEA remains a high clinical suspicion, prompt investigation, and immediate intervention.

Adult↗
PubMed2004

De novo design of defined helical bundles in membrane environments.

Control of structure and function in membrane proteins remains a formidable challenge. We report here a new design paradigm for the self-assembly of protein components in the context of nonpolar environments of biological membranes. An incrementally staged assembly process relying on the unique properties of fluorinated amino acids was used to drive transmembrane helix-helix interactions. In the first step, hydrophobic peptides partitioned into micellar lipids. Subsequent phase separation of simultaneously hydrophobic and lipophobic fluorinated helical surfaces fueled spontaneous self-assembly of higher order oligomers. The creation of these ordered transmembrane protein ensembles is supported by gel electrophoresis, circular dichroism spectroscopy, equilibrium analytical ultracentrifugation, and fluorescence resonance energy transfer.

Amino Acid Sequence↗
PubMed2004

Just add water: a new fluorous capping reagent for facile purification of peptides synthesized on the solid phase.

A novel fluorous capping reagent is introduced to facilitate purification during solid-phase peptide synthesis (SPPS). Reagent 1 is a trivalent iodonium salt that reacts vigorously with free amines to deliver a long-chain fluoroalkyl group. It has been used to tag all unreacted amines following the peptide coupling step in SPPS. The resulting fluoroalkylated amine is no longer able to couple in further peptide coupling steps and is also stable to standard peptide synthesis conditions. Deletion products are removed using flash fluorous chromatography to yield the pure, full-length peptide.

Chromatography, High Pressure Liquid↗
PubMed2004

A Highly stereospecific and efficient synthesis of homopentafluoro- phenylalanine.

A short and efficient synthesis of homopentafluorophenylalanine (6) from oxazolidine aldehyde 1 in 57% overall yield and in > 98% ee is described. The enantiomeric excess of the product was determined by 19F NMR analysis of the coupling product derived from 5 and L-Ser(O-t-Bu)-OCH3, by comparison to a dipeptide obtained from racemic 5.

Catalysis↗
PubMed2004

Neonatal Kawasaki disease.

The authors report a case of Kawasaki disease that manifested in a newborn and presented at the age of 6 weeks of age with coronary artery aneurysms.

Coronary Vessels↗
PubMed2004

Langerhans cell histiocytosis presenting as a limbal nodule in an adult patient.

PURPOSE: To report a case of Langerhans cell histiocytosis presenting as a limbal nodule. DESIGN: Observational case report. METHOD: A 26-year-old man presented with a superior limbal mass. On clinical examination, an infiltrative/neoplastic lesion was suspected, and a differential diagnosis of limbal amyloidosis, limbal fibrous histiocytoma, lymphoma, and juvenile xanthogranuloma was made. There was no other associated ocular or systemic abnormality. An excision biopsy was performed. RESULTS: The histopathology and immunohistochemical staining examination established the diagnosis of limbal Langerhans cell histiocytosis. CONCLUSION: To the best of our knowledge, this is an unusual presentation of Langerhans cell histiocytosis, and although rare, Langerhans cell histiocytosis should be included in the differential diagnosis of a limbal mass.

Adult↗
PubMed2004

Free flap neovascularization: myth or reality?

The blood supply of 17 free flaps was studied several months after surgery. The aim was to see whether or not the free flaps acquired blood flow through vessels across the flap inset independently of the main vascular anastomoses. A color Doppler flowmeter was used to identify the original arterial and venous anastomoses, the vessels in the margin of the flap, and also across the flap inset. The main vascular pedicle was then manually compressed for 2 min and blood flow was again examined in the vessels at the margin of the flap. The flap vessels (post-anastomotic), the anastomoses, and the recipient vessels (pre-anastomotic) could be identified in every case. There was no evidence of anastomotic stenosis. No vessels (neo-vascularization) greater than 0.5 mm could be identified across the flap inset. Small arteries could be identified in the flap near the inset. These vessels emptied completely on manual compression of the vascular pedicle for 2 min and did not refill until the compression was released. This evidence suggests that the free flaps do not receive significant blood flow through vessels across the flap inset, and are therefore significantly dependent for vascularity on the original anastomoses even 1 year after surgery.

Anastomosis, Surgical↗
PubMed2004

Effect of precocene on development of ovarian follicles in flesh fly, Sarcophaga ruficornis F.

Administration of precocene II (6,7-dimethoxy-2, 2-dimethyl chromene) to freshly emerged virgin female flies of S. ruficornis adversely affected the development and differentiation of ovarian follicles leading to a number of morphological abnormalities. Precocene treatment resulted into suppression of development of egg chamber, differentiation of follicular epithelium, degeneration of nurse cells, growth of oocyte and uptake of yolk granules by oocytes. The results suggest that precocene induced effects are due to deficiency of juvenile hormone.

Animals↗