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Biomedical subjects

O Prakash

Publications and source records attributed to O Prakash.

At least 55 records · Page 3Linked to original sources
PubMed1996

Angiotensin II increases left ventricular mass without affecting myosin isoform mRNAs.

We studied the effect of chronic (7 days) angiotensin II (Ang II) infusion in nonpressor and pressor doses on cardiovascular mass and expression of alpha- and beta-myosin heavy chain genes in the left ventricle in normotensive Wistar rats. An increased left ventricular mass was observed in rats receiving non-pressor and pressor doses of Ang II, but only high doses increased arterial pressure. Normalization of arterial pressure during Ang II infusion by losartan, a specific Ang II receptor antagonist, or hydralazine had different effects on left ventricular mass. Losartan prevented the increased left ventricular mass, and hydralazine did not affect left ventricular mass. Northern blot analysis showed that the switch in left ventricular myosin isoform mRNA from the adult to the fetal pattern occurred only in rats given the pressor Ang II dose. Both losartan and hydralazine, in parallel with the normalization of arterial pressure, prevented this myosin isoform switch. Thus, these data suggest that the Ang II-induced increase in left ventricular mass was not dependent on pressure overload, but the switch in myosin isoform mRNA from the adult to the fetal pattern was dependent on pressure overload.

Angiotensin II↗
PubMed1995

Reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor-V: function, thermodynamic stability, and NMR solution structure.

Reactive-site (Lys44-Asp45 peptide bond) hydrolyzed Cucurbita maxima trypsin inhibitor-V (CMTI-V*) was prepared and characterized: In comparison to the intact form, CMTI-V* exhibited markedly reduced inhibitory properties and binding affinities toward trypsin and human blood coagulation factor XIIa. The equilibrium constant of trypsin-catalyzed hydrolysis, Khyd, defined as [CMTI-V*]/[CMTI-V], was measured to be approximately 9.4 at 25 degrees C (delta G degrees = -1.3 kcal.mol-1). From the temperature dependence of delta G degrees, the following thermodynamic parameters were estimated: delta H degrees = 1.6 kcal.mol-1 and delta S degrees = 9.8 eu. In order to understand the functional and thermodynamic differences between the two forms, the three-dimensional solution structure of CMTI-V* was determined by a combined approach of NMR, distance geometry, and simulated annealing methods. Thus, following sequence-specific and stereospecific resonance assignments, including those of beta-, gamma-, delta-, and epsilon-hydrogens and valine methyl hydrogens, 809 interhydrogen distances and 123 dihedral angle constraints were determined, resulting in the computation and energy-minimization of 20 structures for CMTI-V*. The average root mean squared deviation in position for equivalent atoms between the 20 individual structures and the mean structure obtained by averaging their coordinates is 0.67 +/- 0.15 A for the main chain atoms and 1.19 +/- 0.23 A for all the non-hydrogen atoms of residues 5-40 and residues 48-67.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1995

Decapeptide agonists of human C5a: the relationship between conformation and neutrophil response.

A series of decapeptide analogues corresponding to the C-terminal region of the human C5a anaphylatoxin (C5a65-74) was synthesized with residue substitutions to restrict conformational flexibility in the C-terminal region (residues 71-74). These analogues behaved as full agonists of natural C5a in their ability to induce shape change (polarization) and the release of enzyme (beta-glucuronidase) from human neutrophils (PMNs). There was a significant pharmacological correlation between the polarization and enzyme-release assays, suggesting similarities in PMN responsiveness toward these constrained peptides. Good correlations were also observed between these two PMN responses and spasmogenic activity (smooth muscle contraction of human fetal artery). A structure-function analysis for PMN polarization and enzyme release led to the identification of the following preferred backbone conformations: a twisted, helix-like conformation for residues 65-69, an extended conformation for residues 70-71, and a beta-turn of type V for residues (71)72-74. The existence of a C-terminal, type V beta-turn is supported by the NOE (nuclear Overhauser effect) results of two peptides from this series. These conformational features are reminiscent of those that were shown to correlate with the expression of spasmogenic and platelet aggregatory activities in an earlier investigation (Sanderson, S.D.; et al. J. Med. Chem. 1994, 37, 3171). These results suggest that PMNs and the cells responsible for smooth muscle contraction possess C5a receptors that respond to similar topochemical features presented by the agonist peptide ligand.

Amino Acid Sequence↗
PubMed1995

A study of spontaneous echo contrast in patients with rheumatic mitral stenosis and normal sinus rhythm: an Indian perspective.

OBJECTIVE: To study the incidence of spontaneous echo contrast in left atrium of Indian patients with rheumatic mitral stenosis in normal sinus rhythm and to define its relations. SUBJECTS: Transthoracic and multiplane transoesophageal echocardiographic studies were performed in 89 consecutive patients with rheumatic mitral stenosis who were in normal sinus rhythm. RESULTS: Spontaneous echo contrast in the left atrium was seen in 57.3% of patients on multiplane transoesophageal echocardiography and in only 5.6% on transthoracic echocardiography. The mean mitral valve area was 1.07 (SD 0.33) cm2 and 1.32 (0.45) cm2 (P = 0.004), mean left atrial size was 4.27 (0.67) cm and 3.91 (0.5) cm (P = 0.029), mean diastolic pressure gradient was 12.64 (5.69) mm Hg and 10 (5.5) mm Hg (P = 0.049), and absence of mitral regurgitation was seen in 45% and 23% of patients respectively (P = 0.1). Among patients with spontaneous echo contrast, 31% had either left atrial/appendage thrombus or a history of embolism, upsilon 0% in patients without spontaneous echo contrast (P < 0.0001). CONCLUSIONS: There is a high incidence of spontaneous echo contrast in the left atrium in Indian patients with rheumatic mitral stenosis in normal sinus rhythm on multiplane transoesophageal echocardiography. These patients are likely to embolise or form thrombi in the left atrium. The presence of spontaneous echo contrast is also associated with significantly smaller mitral valve area, larger left atrium, and higher mean diastolic mitral pressure gradient.

Adult↗
PubMed1995

Early genes induction in spontaneously hypertensive rats left ventricle with angiotensin-converting enzyme inhibitors but not hydralazine.

Spontaneously hypertensive rats were given an angiotensin-converting enzyme (ACE) inhibitor (benazepril or quinapril) or hydralazine and were left for up to 6 hr. To examine whether administration of antihypertensive agents affects expression of immediate early genes in left ventricular myocardium, groups of rats were sacrificed at 1, 3, and 6 hr after dosing; total RNA was extracted from left ventricular tissue and analyzed by blot hybridization technique using labeled probes for c-myc, c-fos, and GAPDH mRNA. All three antihypertensive agents reduced pressure similarly, and treatment with the two ACE inhibitors increased c-fos and c-myc mRNA expression in left ventriculum. By contrast, hydralazine did not increase steady-state mRNA expression of either proto-oncogene. Thus, in parallel with the pressure fall, acute administration of the ACE inhibitors induced expression of c-fos and c-myc mRNAs in the left ventricle. Since the equidepressor dose of hydralazine did not affect expression of these proto-oncogenes, this effect of ACE inhibitors is independent of their hemodynamic action.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Immunologic characterization of TAT72-transgenic mice: effects of morphine on cell-mediated immunity.

The immunosuppressive effect of morphine in an HIV-1 transactivator of transcription (TAT)-transgenic mouse model was investigated in order to elucidate possible mechanisms of human immunodeficiency virus (HIV)-1 disease progression. The TAT72 transgene (1-72 amino acids) was placed under the control of SV40 viral promoter to provide systemic expression. Mice were treated daily for 5 days with morphine (50.0 mg/kg) or vehicle following alloantigen immunization. In TAT-transgenic mice, morphine modestly reduced mitogen-induced IL-2 production, which correlated with reduced percentages of CD4+ and CD8+ splenic lymphocytes. TAT-transgenic animals displayed reduced splenic natural killer (NK) and peritoneal cytotoxic T-lymphocyte (CTL) activities irrespective of morphine treatment. In addition, the effect of morphine on splenic NK and CTL activity was shown to be stereospecific as defined using (+)-morphine (50 mg/kg). Pretreatment of mice with the mu-selective opioid receptor antagonist beta-funaltrexamine (40.0 mg/kg) blocked morphine-induced modulation of splenic CTL activity. Since elevated corticosterone levels have previously been associated with immunosuppression following prolonged morphine exposure, serum corticosterone levels were assessed. Reduced serum corticosterone levels were found to be associated with morphine treatment in non-transgenic mice as well as vehicle- or morphine-treated mice. Collectively, the data suggest that the presence of TAT72 compromises splenic NK activity as well as peritoneal CTL activity and leads to a reduction in serum corticosterone levels. Also, morphine-mediated modulation of the immune system in non-transgenic mice is stereoselective and due in part to mu-opioid receptors.

Animals↗
PubMed1994

Solvent effects on the conformation of cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu-). An NMR spectroscopy and molecular modeling study.

The conformations of cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu-) in dimethyl sulfoxide-d6 (DMSO-d6) and water were determined using two-dimensional nuclear magnetic resonance spectroscopy and restrained molecular dynamics. Comparisons were made between conformations of the cyclic pentapeptide in both solvents. The NMR study revealed that, while the backbone remained relatively unchanged in both solvents, the side-chains adopted distinctly different orientations in DMSO-d6 vs. H2O. A modeling study, minus NOE constraints, produced a set of low-energy conformers possessing agreement in backbone conformation with the NMR-derived structures; however, lowest-energy conformers did not have this agreement. These results show that different solvents can significantly affect the preferred side-chain conformation of small cyclic peptides in solution. This finding will impact the selection of solvent when determining structures for use as templates in rational drug design.

Amino Acid Sequence↗
PubMed1993

Expression of viral T-antigen in pathological tissues from transgenic mice carrying JC-SV40 chimeric DNAs.

Immunostaining methods were used to detect viral T-antigen and the cellular protein p53 in pathological tissues obtained from transgenic mice carrying JC-SV40 hybrid viral DNAs. A transgenic mouse carrying the SV40 regulatory region and JC virus (JCV) T-antigen-coding sequences exhibited an SV40-characteristic choroid plexus papilloma that expressed JCV T-antigen and p53. JCV-associated pathology was observed in two other mice in which the JCV regulatory signals directed SV40 T-antigen-induced adrenal neuroblastomas and brain neoplastic cells. However, these mice also exhibited an SV40-characteristic osteosarcoma and abdominal lymphoma that contained SV40 T-antigen and p53-positive cells. Contrasting thymic pathology was observed in the two types of mice where the SV40 regulatory region directed a JCV T-antigen-induced thymoma in one mouse, and the JCV regulatory region directed SV40 T-antigen-induced thymic hypoplasia in two other mice.

Adrenal Gland Neoplasms↗
PubMed1993

The use of murine polyclonal anti-idiotypic antibodies as surrogate allergens in the diagnosis of Parthenium hypersensitivity.

BACKGROUND: Anti-idiotypic antibodies (Ab-2), which are the mirror images of idiotypic antibodies (Ab-1), may be useful as diagnostic reagents and for use as immunogen to induce antigen-specific immune responses. METHODS AND RESULTS: To explore the biologic potential of Ab-2 as diagnostic reagents in allergic diseases, murine mouse (m) Ab-2 were raised by immunizing Balb/c mice with affinity purified rabbit (r) Ab-1 specific for the pollen of Parthenium hysterophorus, an allergenic weed that grows wild on the Indian subcontinent and in Australia, Mexico, and the southern United States. Affinity purified Parthenium-specific human (h)AB-1 could successfully inhibit the binding of mAb-2 to immobilized rAb-1. Further, Balb/c mice immunized with mAb-2 induced Parthenium-specific anti-anti-idiotypic IgE and IgG antibodies. Specificity of the Ab-2 was confirmed by the ability of Parthenium pollen extracts to inhibit the binding of allergen-specific IgE and IgG Ab-1 in the sera of patients with rhinitis to immobilized mAb-2. Parthenium-sensitive patients with rhinitis who had positive results on skin prick tests to Parthenium pollen extracts also responded with a positive skin reaction to mAb-2. CONCLUSION: Our data demonstrate that Parthenium-specific mAb-2 may be of value as surrogate allergens in allergen standardization and for in vitro diagnosis.

Allergens↗
PubMed1993

Standardization of pollen allergens of Parthenium hysterophorus and selection of an in-house reference extract.

A standardized in-house reference extract from the pollen of Parthenium hysterophorus, which is responsible for the high incidence of allergic rhinitis in India, was generated and examined by skin test, radio-allergosorbent test inhibition and isoelectric focusing. Parthenium reference allergen discs and positive reference serum were also generated. These reference reagents could not only be used for the quantitation of Parthenium-specific IgE in the sera of rhinitis patients but also for the evaluation of allergenic activity (relative potency and lot-to-lot variation) of different batches of Parthenium pollen.

Adult↗
PubMed1993

Significance of serum immunoglobulin levels in conglomeration with trans-sternal phlebography in the phlebography management of breast cancer.

The study was conducted on 63 patients with breast lump and twenty normal healthy females. In benign breast disease, a significant (P < 0.001) rise in serum IgA, significant (P < 0.001) decrease in IgG and no change in IgM levels was seen before operation. A significant decrease (P < 0.001) in serum IgA and significant increase in IgG and IgM was observed post operatively. In carcinoma breast, a significant (P < 0.001) elevation in IgA, IgG and IgM levels was found pre-operatively with a concomitant decrease in serum IgA and IgG and increase in serum IgM levels, post operatively. Trans-sternal phlebography (TSP) carried out with 95.23% success has revealed significant (P < 0.001) change in the staging of carcinoma breast. The increased levels of serum immunoglobulins associated with the patients of carcinoma breast with metastasis has led to conclude that these levels, if punctuated with TSP findings can lead to better assessment of the staging of carcinoma breast and thereby its management.

Biomarkers, Tumor↗
PubMed1992

Continuous intra-arterial PO2 monitoring during thoracic surgery.

Intermittent blood gas sampling has several disadvantages, the most important being that samples are usually taken at set intervals, or when changes in oxygenation are suspected--when it is too late. Another problem is inaccuracy caused by careless blood sample handling. Continuous intravascular PaO2 monitoring eliminates these problems. This study shows that the Continucath sensor is an easy-to-use and reliable monitor, with specific early warning capabilities for hypoxia, thereby improving anesthetic and intensive care management. Its characteristics are: a stabilization period of 10 minutes, a 90% response time of 90 seconds, temperature dependence of 4% per degree celsius, a flow dependence of less than 1% if the flow is more than 5 cm/sec, a drift of less than 0.7% per hour, a correlation coefficient of 0.92 when compared to blood gas analysis during surgery.

Adult↗
PubMed1992

Real-time respiratory monitoring workstation--software and hardware engineering aspects.

We have applied advanced real-time techniques in software, that are intensively used in critical areas like space research and defence applications, to realise an Integrated Real-Time Respiratory Monitoring System at the Thorax Anesthesiology, Academic Hospital Rotterdam. The system is called the 'SERVO WINDOW'--a window to the servo ventilator. The heart of the system is a real-time kernel that uses preemptive scheduling to achieve multitasking on a IBM PC compatible hardware platform. To the clinician this means that he gets all relevant information from one source i.e. the Respiratory Workstation. The waveforms of the airway pressure, airway flow and the expired CO2 curve are displayed continuously on the screen. The Vector Loops like Pressure Volume, Flow Pressure and Flow Volume loops are also available in addition to the lung mechanics parameters like Expiratory and Inspiratory Resistances, Compliances, Peak Pressure, PEEP, etc. The Single Breath Diagram i.e. expired CO2 concentration versus volume and dead space ventilation is also calculated. The blood gas analysis data is plotted in convenient diagrams like the O2-CO2 diagram, Oxygen Chart, etc. The trend of all these parameters are available with a granularity of one minute. An industry standard laser printer is used for report generation to produce reports of the real-time waveforms, parameter values and the trends. User interface is through easy menus with the traditional keyboard, touchscreen including keyboard on screen for data entry and the mouse.

Computer Systems↗
PubMed1992

Comparison of ketorolac and morphine for postoperative pain after major surgery.

This study was designed to determine the relative analgesic efficacy and safety of single intramuscular injections of ketorolac (10 mg or 30 mg) and morphine (10 mg) in patients of either sex with moderate to severe pain after major surgery. In a single-dose, randomised, double-blind study of parallel design, pain was assessed immediately before injection of test medication and at regular intervals for 8 h thereafter. One hundred and seventeen patients (109 undergoing cardiac surgery; 8 lung surgery) were randomized to one of the three treatment groups. Pain intensity was assessed using a 5-point verbal scale before administration of study drugs. Postadministration, at 30 min and hourly for 8 h, pain intensity and pain relief were assessed, again using the 5-point verbal scale. Additionally, as a measure of analgesia, forced expiratory volume (FEV1) was obtained in all patients. Vital signs including blood pressure, pulse, temperature, respiratory rate and blood gases (PaCO2) were recorded prior to and after study medication. Based on hourly pain intensity differences and hourly pain relief observations, ketorolac 10 mg was generally more effective than morphine 10 mg, and ketorolac 30 mg was generally more effective than ketorolac 10 mg. The results of this study show that ketorolac is an effective and safe (with regard to arterial pressure, blood gases and lung function) analgesic for relief of postoperative pain after major surgery in stable patients. No clinically significant adverse effects occurred during the study. One cannot exclude an influence on patients with organ system dysfunction or on parameters not measured in this study.

Adult↗