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Biomedical subjects

P Natarajan

Publications and source records attributed to P Natarajan.

At least 19 recordsLinked to original sources
PubMed2006

The changing prevalence of drug-resistant Escherichia coli clonal groups in a community: evidence for community outbreaks of urinary tract infections.

A multidrug-resistant clonal group (CgA) of Escherichia coli was shown to cause half of all trimethoprim-sulphamethoxazole (TMP-SMZ)-resistant urinary tract infections (UTIs) in a college community between October 1999 and January 2000. This second study was conducted to determine the fate of CgA. Urine E. coli isolates from women with UTI, collected between October 2000 and January 2001, were tested for antibiotic susceptibility, O serogroup, ERIC2 PCR and DNA macrorestriction patterns using pulsed-field gel electrophoresis. The proportion of UTIs caused by CgA declined by 38% (P<0.001) but the prevalence of resistance to TMP-SMZ did not change. Six additional clonal groups were identified and these were responsible for 32% of TMP-SMZ-resistant UTIs. The temporal decline in the proportion of UTIs caused by CgA provides evidence that CgA caused a community outbreak of UTI. The fluctuation and occurrence of other E. coli clonal groups in this community suggest that a proportion of community-acquired UTIs may be caused by E. coli disseminated from one or more point sources.

Adolescent↗
PubMed2005

Rosai-Dorfman disease of the central nervous system.

Rosai-Dorfman disease (RDD) is an idiopathic, non-neoplastic, lymphoproliferative disorder characterized by sinus histiocytosis and massive lymphadenopathy. When RDD involves the central nervous system the lesion simulates a meningioma. Histological and immunohistochemical confirmation is essential for a definitive diagnosis. In this paper, ten cases of RDD confined to the central nervous system are reported. Another case with orbital RDD was excluded. Nine cases involved the cranial cavity alone; in one, the cervical extradural region was also involved. Treatment consisted of surgical excision or biopsy. Histology and immunohistochemistry revealed a mixed cell population of predominantly mature histiocytes with evidence of emperipolesis and strong positivity for S100 protein in all cases. No recurrence was observed during follow up ranging from three months to eight years.

Adolescent↗
PubMed2002

Di- and tetranuclear ruthenium(II) and/or osmium(II) complexes of polypyridyl ligands bridged by a fully conjugated aromatic spacer: synthesis, characterization, and electrochemical and photophysical studies.

A series of mono-, di-, and tetranuclear homo/heterometallic complexes of Ru(II) and Os(II) based on the bridging ligand dppz(11-11')dppz (where dppz = dipyrido[3,2-a:2',3'-c]phenazine) (BL) have been synthesized and characterized. This bridging ligand is a long rigid rod with only one rotational degree of freedom and provides complete conjugation between the chromophores. The complexes synthesized are of general formula [(bpy)(2)Ru-BL](2+), [(phen)(2)/(bpy)(2)M-BL-M(bpy)(2)/(phen)(2)](4+) (M = Ru(II) and Os(II)), [(bpy)(2)Ru-BL-Os(bpy)(2)](4+), and [((bpy)(2)Ru-BL)(3)M](8+). Detailed (1)H NMR studies of these complexes revealed that each chiral center does not influence its neighbor because of the long distance between the metal centers and the superimposed resonances of the diastereoisomers, which allowed the unambiguous assignment of the signals, particularly for homonuclear complexes. Concentration-dependent (1)H NMR studies show molecular aggregation of the mono- and dinuclear complexes in solution by pi-pi stacking. Electrospray mass spectrometry data are consistent with dimerization of mono- and dinuclear complexes in solution. Electrochemical studies show oxidations of Ru(II) and Os(II) in the potential ranges +1.38 to +1.40 and +0.92 to +1.01 V, respectively. The bridging ligand exhibits two one-electron reductions, and it appears that the added electrons are localized on the phenazene moieties of the spacer. All of these complexes show strong metal-to-ligand charge-transfer (MLCT) absorption and (3)MLCT luminescence at room temperature. Quantum yields have been calculated, and the emission lifetimes of all complexes have been measured by laser flash photolysis experiments. The luminescence intensity and lifetime data suggest that the emission due to the Ru center of the heteronuclear complexes is strongly quenched (>90%) compared to that of the corresponding model complexes. This quenching is attributed to intramolecular energy transfer from the Ru(II) center to the Os(II) center (k = (3-5) x 10(7) s(-1)) across the bridging ligand.

Journal Article↗
PubMed2000

Effects of cytochalasin H, a potent inhibitor of cytoskeletal reorganisation, on platelet function.

Platelets contain a well-developed and dynamic cytoskeleton composed mainly of actin and actin-associated proteins. Upon platelet activation there is rapid polymerisation of actin and a marked reorganisation of the platelet cytoskeleton. Cytochalasins are agents that interfere with the polymerisation of actin, and it has recently been discovered that cytochalasin H (CyH) is particularly effective as an inhibitor of the cytoskeletal reorganisation that occurs in platelets following activation by adenosine diphosphate (ADP). Here we have used CyH to inhibit platelet cytoskeletal reorganisation and to determine its effects on various aspects of platelet function. Experiments were performed in hirudinized platelet-rich plasma (PRP) or whole blood obtained from human volunteers. PRP was treated with 10 microM CyH or vehicle, then activated by ADP. The effect of CyH on cytoskeletal reorganisation was determined by SDS-PAGE of the Triton X-100 insoluble cytoskeletons and quantitated by densitometry. Platelet aggregation and aggregate stability in PRP were measured by monitoring changes in light absorbance; aggregation was measured in whole blood via platelet counting. Shape change, P-selectin expression and changes in intracellular calcium were measured using flow cytometry. CyH prevented the normal incorporation of actin, alpha-actinin and actin-binding protein into the cytoskeleton that occurred following ADP activation, and incorporation of myosin was markedly reduced. Aggregation was only partially inhibited but, more dramatically, the rate of disaggregation following addition of certain agents that interfere with fibrinogen binding to glycoprotein IIb/IIIa on the surface of platelets was markedly increased. The ADP-induced shape change was also inhibited. CyH had no effect on calcium mobilisation. Curiously, expression of P-selectin was potentiated by CyH, suggesting a modulatory role of the cytoskeleton in platelet secretory activity. The results suggest that cytoskeletal reorganisation plays an important role in platelet shape change and aggregation and contributes in a major way to the stability of the aggregates that form.

Adenosine Diphosphate↗
PubMed2000

Reexamination of the effect of endotoxin on cell proliferation and transfection efficiency.

Plasmid DNA purified from bacterial cells can be contaminated with endotoxin to different extents, depending on the purification method. Earlier reports indicate that endotoxin can decrease transfection efficiency in many eukaryotic cell lines; however, the amount of endotoxin required for inhibition is unclear. We determined endotoxin effects in several cell lines and observed that endotoxin levels greater than or equal to 10,000 endotoxin units (EU) were needed to significantly affect cell proliferation and viability; levels greater than 2000 EU/mu g DNA were required to significantly inhibit transfection for all but one (Huh-7) of the cell lines tested. These endotoxin levels are significantly higher than endotoxin contamination in plasmid DNA purified by anion exchange, CsCl2 gradient and endotoxin-free purification technology, but not as high as a crude alkaline lysis preparatory method. Plasmid DNA prepared using anion exchange technology was comparable to endotoxin-free technology in terms of transfection efficiency. Even Huh-7 cells, which are markedly more sensitive to endotoxins, have comparable transfection efficiencies using plasmid DNA purified by either of these two methods. We conclude that for those cell lines commonly used for transfection studies, endotoxin-free, quality DNA is not necessary because significantly higher levels of bacterial endotoxins are required to inhibit either cell proliferation or transfection.

Animals↗
PubMed2000

Paper-based archiving of mammalian and plant samples for RNA analysis.

The ability to archive biological samples for subsequent nucleic acid analysis is essential for tissue specimens and forensic samples. FTA Card is a chemically treated filter paper designed for the collection and room temperature storage of biological samples for subsequent DNA analysis. Its usefulness for the preservation of biological samples for subsequent RNA analysis was tested. Here, we demonstrate that RNA in biological samples stored on FTA Cards is stable and can be used successfully for RT-PCR and northern blot analysis. RNA stability depends on the storage temperature and the type of biological specimen. RNA in mammalian cells stored on FTA Cards is stable for over one year at temperatures at or below -20 degrees C and for two to three months in samples stored at room temperature. For plant leaf, longer storage times (> 5 days) require temperatures at or below -70 degrees C following sample application. FTA Cards may constitute a method not only for convenient collection and storage of biological samples but also for rapid RT-PCR analysis of tissue and cell samples.

Animals↗
PubMed2000

Macrophage colony stimulating factor (M-CSF) within cord blood sera may be partially responsible for the reduced proliferation of cord blood T cells.

We show that there are differences in the soluble factors in cord blood (CB) and adult serum and that these differences play a role in T cell function. Thus, the mitogen and alloantigen-specific proliferative response of adult T cells was enhanced with increasing concentrations of adult serum and CB serum, but to a lesser extent with CB serum. In addition, proliferation of T cells induced by stimulation through the T cell receptor alone (via CD3 stimulation), could be enhanced with adult but not CB serum. However, CB serum enhanced the IL-2-specific proliferative response of pure T cells whereas adult serum did not. To determine whether there was an anti-inflammatory cytokine within CB serum which could induce these results, we assayed our serum samples for anti-inflammatory cytokines. IL-13 could not be detected in any serum sample, whereas IL-10 could be detected in adult but not CB serum (P < 0.002). However, there was a significant difference in the levels of macrophage colony stimulating factor (M-CSF) detected in adult and CB serum samples (P < 0.01). M-CSF was detected in 6/7 CB serum samples (mean +/- SD was 3.8 +/- 2.3 ng/ml) and 0/5 adult serum samples. Furthermore, anti-M-CSF antibody restored the reduced allo-response of T cells incubated in CB serum. Thus, M-CSF may act as a suppressor factor in CB serum. Whether this is sufficient to explain the lack of an allo-response by the foetus to the mother, or the reduced graft-versus-host disease when CB is used instead of bone marrow in stem cell transplantation, is yet to be determined.

Adult↗
PubMed1999

Comparison of auscultatory and oscillometric automated blood pressure monitors in the setting of preeclampsia.

OBJECTIVE: The aim of this study was to compare the accuracy of 2 automated blood pressure monitors against mercury sphygmomanometry and intra-arterial blood pressure determination in women with preeclampsia. STUDY DESIGN: The auscultatory and oscillometric monitors were compared with mercury sphygmomanometry according to the British Hypertension Society protocol and criteria of the Association for the Advancement of Medical Instrumentation in a group of 30 women with proteinuric preeclampsia. In addition both monitors were compared with intra-arterial blood pressure measurements in a group of 6 women with severe preeclampsia. The mean (+/- SD) of the differences was calculated and a paired t test was used to compare values obtained with each monitor with intra-arterial measurements. RESULTS: Compared with mercury sphygmomanometry the auscultatory QuietTrak monitor markedly underestimated systolic and diastolic blood pressure by 13 +/- 15 mm Hg. The oscillometric SpaceLabs 90207 monitor also underestimated systolic pressure by 10 +/- 10 mm Hg and diastolic pressure by 8 +/- 7 mm Hg. According to the British Hypertension Society grading criteria both monitors achieved the lowest grade (D) for recording systolic and diastolic pressure. The 2 monitors also did not meet the accuracy criteria stipulated by the Association for the Advancement of Medical Instrumentation. Compared with intra-arterial readings the SpaceLabs monitor significantly underestimated systolic and mean arterial pressures (by 19 and 7 mm Hg, respectively, P <. 01). The QuietTrak monitor significantly underestimated systolic, diastolic, and mean arterial pressures (by 25 mm Hg, P <.05, 18 mm Hg, P <.01, and 20 mm Hg, P <.01, respectively). CONCLUSION: Neither monitor can be recommended for clinical use in women with proteinuric preeclampsia.

Auscultation↗
PubMed1998

Molecular packing in virus crystals: geometry, chemistry, and biology.

An automated procedure was developed to determine the geometrical and chemical interactions of crystalline virus particles using the crystal parameters, particle position, orientation, and atomic coordinates for an icosahedral asymmetric unit. Two applications of the program are reported: (1) An analysis of a novel pseudo-rhombohedral (R32) symmetry present in the monoclinic crystal lattices of both Nodamura Virus (NOV) and Coxsackie virus B3 (CVB3). The study shows that in both cases the interactions between particles is substantially increased by minor deviations from exact R32 symmetry and that only particles with the proper ratio of dimensions along twofold and fivefold symmetry axes (such as southern bean mosaic virus) can achieve comparable buried surface area in the true R32 space group. (2) An attempt was made to correlate biological function with remarkably conserved interparticle contact regions found in different crystal forms of three members of the nodavirus family, NOV, Flock House Virus (FHV), and Black Beetle Virus (BBV). Mutational evidence implicates the quasi-threefold region on the viral surface in receptor binding in nodaviruses and this region is dominant in particle contacts in all three virus crystals. Examination of particle contacts in numerous crystal structures of viruses in the picornavirus super-family showed that portions of the capsid surface known to interact with a receptor or serve as an epitope for monoclonal antibodies frequently stabilize crystal contacts.

Computer Simulation↗
PubMed1998

Particle polymorphism caused by deletion of a peptide molecular switch in a quasiequivalent icosahedral virus.

The capsid of flock house virus is composed of 180 copies of a single type of coat protein which forms a T=3 icosahedral shell. High-resolution structural analysis has shown that the protein subunits, although chemically identical, form different contacts across the twofold axes of the virus particle. Subunits that are related by icosahedral twofold symmetry form flat contacts, whereas subunits that are related by quasi-twofold symmetry form bent contacts. The flat contacts are due to the presence of ordered genomic RNA and an ordered peptide arm which is inserted in the groove between the subunits and prevents them from forming the dihedral angle observed at the bent quasi-twofold contacts. We hypothesized that by deleting the residues that constitute the ordered peptide arm, formation of flat contacts should be impossible and therefore result in assembly of particles with only bent contacts. Such particles would have T=1 symmetry. To test this hypothesis we generated two deletion mutants in which either 50 or 31 residues were eliminated from the N terminus of the coat protein. We found that in the absence of residues 1 to 50, assembly was completely inhibited, presumably because the mutation removed a cluster of positively charged amino acids required for neutralization of encapsidated RNA. When the deletion was restricted to residues 1 to 31, assembly occurred, but the products were highly heterogeneous. Small bacilliform-like structures and irregular structures as well as wild-type-like T=3 particles were detected. The anticipated T=1 particles, on the other hand, were not observed. We conclude that residues 20 to 30 are not critical for formation of flat protein contacts and formation of T=3 particles. However, the N terminus of the coat protein appears to play an essential role in regulating assembly such that only one product, T=3 particles, is synthesized.

Amino Acid Sequence↗
PubMed1997

Resolution of space-group ambiguity and structure determination of nodamura virus to 3.3 A resolution from pseudo-R32 (monoclinic) crystals.

Monoclinic crystals of nodamura virus (NOV) have two virus molecules per asymmetric unit. Packing analysis reveals a pseudo-rhombohedral (pseudo-C2 monoclinic) arrangement of particles in the actual P2(1) space group (a = 562.1, b = 354.1, c = 612.8 A, beta = 110.9 degrees ). The R32 symmetry is broken rotationally and translationally. The pseudo-symmetry of the unit cell results in three possible monoclinic origins and also restrains the four particles in the unit cell to similar orientations. NOV particles deviate by less than 3 degrees from the ideal orientations, causing overlap of peaks in the rotation function and the generation of peaks that were not interpretable as particle symmetry elements. The space-group ambiguity was resolved by analysing the relationship between the particle orientations determined by high-resolution rotation functions and the attenuation of peak heights in native Patterson maps. Particles were centered less than 1 A from the R32 special positions. Three different approaches were required to identify the correct particle center. Following the solutions of the rotation and translation problems, phases were computed using the coordinates of flock house virus (FHV), another member of this virus family. The phases were improved by real-space molecular averaging with a 120-fold non-crystallographic symmetry and by solvent flattening with a spherical mask. The final model for the NOV structure was built using the 3.3 A averaged map. While the overall subunit structure was very similar to that of other nodaviruses, FHV and black beetle virus, NOV showed distinct structural features near particle threefold and quasi-threefold axes and at the protein-RNA interfaces that are consistent with phenotype differences among the related viruses.

Journal Article↗
PubMed1997

Systemic and regional (including superior mesenteric) haemodynamic responses during supine exercise while fasted and fed in normal man.

The systemic and regional (including superior mesenteric artery, SMA) responses to exercise in the fasting and fed state were studied in ten normal subjects before, during and after 9 min of graded supine bicycle exercise on two separate occasions, when fasted and after a liquid meal. During exercise, blood pressure (BP) and cardiac index rose similarly in both states. Resting SMA blood flow was higher when fed (519 (282-619) versus 240 (133-255) ml/min, p < 0.01). SMA blood flow fell during exercise in both states, to 98 (63-154) ml/min, p < 0.01 when fasted and to 55 (42-149) ml/min, p < 0.01 when fed. SMA vascular resistance rose during exercise in both states, but rose less when fasted by 36 (6-57)% versus 143 (36-240)% (NS). Resting forearm and leg blood flow (FBF and LBF) and vascular resistance (FVR and LVR) were similar fasted and fed. FBF and FVR did not change after exercise in either state. LBF rose and LVR fell similarly in both states. We conclude that in normal subjects, although splanchnic oxygen demand is likely to be greater after food, during light to moderate exercise splanchnic vasoconstriction contributes to maintenance of BP.

Aged↗
PubMed1997

Haemodynamic and hormonal effects of two different oral glucose loads in normal human subjects.

Systemic and regional haemodynamics and hormonal responses to two isovolaemic, iso-osmotic solutions of 0.5 and 1.0 g/kg of glucose were compared in ten normal young subjects (mean age 24 +/- 3 years). Measurements were made while subjects were supine before glucose and every 15 min for 60 min after ingestion of each solution. Superior mesenteric artery (SMA) blood flow rose similarly after each dose. There were corresponding reductions in SMA vascular resistance after each dose but no difference between doses. Pulsatility index of the SMA was lower after 1.0 g/kg. There was no change in blood pressure, heart rate, cardiac index or forearm muscle blood flow after either dose. Plasma glucose levels rose after each dose and were higher after 1.0 g/kg. There was no difference in the plasma insulin rise between doses. Plasma levels of noradrenaline and adrenaline did not change after either dose. These results suggest that with glucose loads within the ranges we used, changes in SMA blood flow are not dose-related and larger increases in SMA blood flow or in plasma insulin than we observed are needed to reflexly activate cardiac output and raise plasma noradrenaline levels in young normal subjects.

Adult↗
PubMed1995

Crystallization and preliminary X-ray analysis of the cytoplasmic domain of human erythrocyte band 3.

A cytoplasmic domain of the human erythrocyte membrane protein band 3 (M(r) = 42,500), residues 1-379, expressed in and purified from E. coli, has been crystallized by the method of vapor diffusion in sitting drops with subsequent streak-seeding at room temperature. Initial crystals were grown from solutions containing 65-68% saturated ammonium sulfate at pH 4.9 and 2 mg/ml protein. Subsequent streak-seeding into solutions of 50-53% ammonium sulfate at pH 4.9 and 7 mg/ml protein produced single crystals suitable for X-ray analysis, which contained pure protein as revealed by gel electrophoresis. The crystals belong to the monoclinic space group C2 with cell dimensions of a = 178.8 A, b = 90.5 A, c = 122.1 A, and beta = 131.3 degrees and diffract at least to 2.7 A resolution (at 100 K). A self-rotation function shows the presence of approximate 222 local symmetry.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1986

[Effects of elastase on experimentally induced aneurysms in rats].

The purpose is to study the potentiality of Elastase in preventing the development of experimentally induced aneurysms in rats. 64 Sprague-Dawly male rats of 5 months age were used. Unilateral common carotid artery ligation was done to effect hemodynamic changes in intracranial vessels. Posterior renal artery was ligated to induce hypertension which was further augmented by feeding with 1% saline and 0.1% BAPN, separately and in combination. The rats were divided into two equal groups of 32 and 32. The second group was in addition treated with intra-muscular injection of Elastase at a dose of 10 mg/kg/day for 6 days in a week. The rats were sacrificed at the end of 18 weeks to study the development of intracranial aneurysm and the effect of Elastase. There were 5 aneurysms in the first group comparing with 2 aneurysms in second group. The histopathology showed thickening of the intima and breakdown of elastic lamina at the site of the aneurysm. The effect of Elastase on these pathological changes is discussed.

Animals↗
PubMed1983

Surgical treatment of 200 consecutive patients with left main coronary artery disease.

Two hundred consecutive patients underwent myocardial revascularization for left main coronary artery disease between January, 1975, and December, 1981. The mean age of this group was 64 +/- 8 years, and 78.5% of the patients were men. The anginal pattern was chronic stable in 6% of the patients and progressive or unstable in the remainder. Resting electrocardiograms showed prior myocardial infarction in 45.5%. Left ventricular end-diastolic pressure was elevated in 145 patients, and ejection fraction was less than 50% in 40 patients. The mean number of bypass grafts per patient was 3.2 +/- 1.4 (standard deviation). Seventeen patients underwent major concomitant cardiovascular procedures. The operative mortality was 3.5%, and the incidence of perioperative infarction was 3%. Factors associated with reduced operative survival were increased age; unstable angina, or acute myocardial infarction, or both; female sex; circumflex-dominant circulation; and major concomitant procedures. Late mortality at a mean follow-up of 33.5 months was 6%, and 91% of the surviving patients assessed their quality of life as "excellent" or "good."

Adult↗
PubMed1983

Surgical treatment of mitral valve disease: pathologic findings and atrial dysrhythmia.

One hundred fifty patients underwent surgery for mitral valve disease between January 1974 and May 1981. There were 98 female and 52 male patients with a mean age of 57 years (+/- 18.6). One hundred forty-six patients were in New York Heart Association functional class III or IV. Pathologic diagnoses included 67% rheumatic (55 calcified), 27% degenerative and fibrotic, 3.3% prosthetic valve malfunctions, and 2.6% acute papillary muscle dysfunction. Atrial biopsy material was normal in 72% (37/51) and Aschoff's bodies were present in 2% (1/51). Preoperative cardiac rhythm was regular sinus in 40%, atrial fibrillation in 59%, and pacemaker-induced in 1%. Valve replacement was performed in 119 patients, commissurotomy in 26, and annuloplasty in five. Left atrial thrombus was removed from 21 patients. Hospital mortality was 10%. The 135 survivors have been followed up for an average of 30.4 months. Of patients who were in regular sinus rhythm preoperatively, 90.7% maintained it postoperatively, and 9.3% converted to atrial fibrillation. Of patients in atrial fibrillation preoperatively, 33.8% converted to regular sinus rhythm postoperatively and 66.2% remained in atrial fibrillation. These data indicate that rheumatic mitral valve disease is still the most common finding in patients coming to surgery, followed by degenerative and fibrotic mitral valve disease. Acute papillary muscle dysfunction is uncommon. The chance of preserving preoperative regular sinus rhythm postoperatively is excellent (90.7%), and a 33% conversion rate of preoperative atrial fibrillation to postoperative regular sinus rhythm is encouraging.

Adult↗