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Biomedical subjects

S Chandra

Publications and source records attributed to S Chandra.

At least 109 records · Page 6Linked to original sources
PubMed1996

The Pto kinase mediates a signaling pathway leading to the oxidative burst in tomato.

The Pto gene encodes a serine/threonine kinase that confers resistance in tomato to Pseudomonas syringae pv. tomato strains that express the avirulence gene avrPto. Partial characterization of the Pto signal transduction pathway and the availability of transgenic tomato lines (+/- Pto) make this an ideal system for exploring the molecular basis of disease resistance. In this paper, we test two transgenic tomato cell suspension cultures (+/-Pto) for production of H2O2 following independent challenge with two strains of P. syringae pv. tomato (+/-avrPto). Only when Pto and avrPto are present in the corresponding organisms are two distinct phases of the oxidative burst seen, a rapid first burst followed by a slower and more prolonged second burst. In the remaining three plant-pathogen interactions, we observe either no burst or only a first burst, indicating that the second burst is correlated with disease resistance. Further support for this observation comes from the finding that both resistant and susceptible tomato lines produce the critical second oxidative burst when challenged with P. syringae pv. tabaci, a nonhost pathogen that elicits a hypersensitive response on both tomato lines. The Pto kinase is not required, however, for the oxidative burst initiated by non-specific elicitors such as oligogalacturonides or osmotic stress. A model describing a possible role for the Pto kinase in the overall scheme of oxidative burst signaling is proposed.

Journal Article↗
PubMed1996

Ion microscopy imaging of 10B from p-boronophenylalanine in a brain tumor model for boron neutron capture therapy.

Boron neutron capture therapy (BNCT), a binary treatment modality that can potentially irradiate tumor tissue within cellular dimensions, is critically dependent on the preferential delivery of 10B to individual neoplastic cells. In this study, ion microscopy was used to quantitatively evaluate the selectivity of p-boronophenylalanine-fructose (BPA-F) in the rat 9L gliosarcoma brain tumor model. With a spatial resolution of approximately 0.5 microm, ion microscopy images show that BPA-F delivers 3.5 times more boron to the main tumor mass [99 +/- 36 microg/g tissue (mean +/- SD)] than to the contiguous normal brain (27 +/- 12 microg/g tissue). A similar, but lower, accumulation was observed away from the main tumor mass in small clusters of neoplastic cells (47 +/- 15 microg/g tissue) invading the surrounding brain (16 +/- 8 microg/g tissue). These findings establish for the first time the selectivity of BPA-F to the neoplastic cells invading the normal brain and provide a much-needed baseline measurement of the distribution of a clinically approved BNCT drug. Given the propensity for malignant brain tumors to infiltrate the surrounding normal brain, these observations have particular significance for clinical trials of BNCT for human glioblastoma multiforme using the drug BPA-F.

Animals↗
PubMed1996

Electro-physiological evaluation of nerves during reactions in leprosy.

Forty-two patients with leprosy (7 with tuberculoid type, 30 borderline, 5 lepromatous) were studied electrophysiologically during reactions. Thirty-three had type I reactions while 9 had type II reactions. Each patient received 60 mg/day prednisolone tapered over a 6-week period. Motor conduction studies were performed on one clinically affected and one unaffected nerve and were repeated 12 weeks after the beginning of steroid therapy. Significant motor conduction abnormalities were observed in 14 affected (33.3%) and 8 unaffected nerves (19.1%). The majority of these nerves were in patients with borderline leprosy having type I reactions. Following steroid therapy, nerve function improved in 14 affected (33.3%) and 20 unaffected nerves (47.66%). However, 5 affected (10.2%) and 12 unaffected nerves (28.5%) showed a worsening of nerve function following steroid therapy. The majority of the nerves that showed improvement with steroid therapy had type I reactions, while those that showed deterioration had type II reactions. Steroids improved nerve function mainly in patients with type I reactions. Their role in patients with type II reactions remains debatable.

Adolescent↗
PubMed1996

Ion microscopic imaging of calcium during 1,25-dihydroxyvitamin D-mediated intestinal absorption.

A combination of ion microscopic and conventional radionuclide techniques was employed to investigate the temporal-spatial dynamics of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-stimulated intestinal calcium (Ca) absorption. At varying times following the administration of a single intravenous dose of 1,25(OH)2D3 to vitamin D-deficient chicks, transepithelial transport and tissue retention of Ca were quantitated in vivo, using the ligated duodenal loop technique and 47Ca as the tracer. The localization of Ca in the intestinal tissue during absorption was monitored by ion microscopy, using the stable Ca isotope, 44Ca, as the absorbed species. There was little transepithelial absorption of Ca in the vitamin D-deficient animals despite a substantial tissue accumulation of luminally derived Ca, the latter localizing predominantly in the brush border region of the enterocyte, as shown by the 44Ca-ion microscopic images. The early (30 min-1 h) response to 1,25(OH)2D3 was an increased tissue uptake of luminal 47Ca, which also primarily associated with the brush border region, again as shown by ion microscopy. At 2-4 h after the 1,25(OH)2D3 dose, there was a progressive redistribution of Ca from the brush border region throughout the cytoplasm and into the lamina propria. At 8-16 h, 47Ca absorption was maximal and 44Ca was sparsely distributed in the intestinal tissue. 47Ca absorption gradually declined and reached pre-dose levels by 72 h. At this time, tissue 44Ca was again largely limited to the brush border region. These results provide support for the multiple actions of 1,25(OH)2D3 on the intestinal Ca absorption process. The ion microscopic images provided unique information on the specific time-dependent changes in the tissue localization of Ca during the process of its intestinal absorption as affected by 1,25(OH)2D3.

Animals↗
PubMed1996

Integrated backscatter for quantification of left atrial spontaneous echo contrast.

OBJECTIVES: This study was designed to develop a quantitative method of spontaneous echo contrast (SEC) assessment using integrated backscatter and to compare integrated backscatter SEC measurement with independent qualitative grades of SEC and clinical and echocardiographic predictors of thromboembolism. BACKGROUND: Left atrial SEC refers to dynamic swirling smokelike echoes that are associated with low flow states and embolic events and have been graded qualitatively as mild or severe. METHODS: We performed transesophageal echocardiography in 43 patients and acquired digital integrated backscatter image sequences of the interatrial septum to internally calibrate the left ventricular cavity and left atrial cavity under different gain settings. Patients were independently assessed as having no, mild or severe SEC. We compared intensity of integrated backscatter in the left atrial cavity relative to that in the left ventricular as well as to the independently assessed qualitative grades of SEC. Fourier analysis characterized the temporal variability of SEC. The integrated backscatter was compared with clinical and echocardiographic predictors of thromboembolism. RESULTS: The left atrial cavity integrated backscatter intensity of the mild SEC subgroup was 4.7 dB higher than that from the left ventricular cavity, and the left atrial intensity of the severe SEC subgroup was 12.5 dB higher than that from the left ventricular cavity. The left atrial cavity integrated backscatter intensity correlated well with the qualitative grade. Fourier transforms of SEC integrated backscatter sequences revealed a characteristic dominant low frequency/high amplitude spectrum, distinctive from no SEC. There was a close relationship between integrated backscatter values and atrial fibrillation, left atrial size, left atrial appendage flow velocities and thrombus. CONCLUSIONS: Integrated backscatter provides an objective quantitative measure of SEC that correlates well with qualitative grade and is closely associated with clinical and echocardiographic predictors of thromboembolism. The relationship between integrated backscatter measures and cardioembolic risk will be defined in future multicenter studies.

Aged↗
PubMed1996

Characterization of left atrial appendage Doppler flow in atrial fibrillation and flutter by Fourier analysis.

The aim of this study was to characterize left atrial appendage mechanical function in atrial fibrillation and flutter by Fourier analysis to analyze frequency and regularity of flow. Left atrial appendage function is central to a patient's risk for thromboembolism. Although the function of the appendage can be analyzed by Doppler echocardiography in sinus rhythm, its mechanical function in atrial fibrillation and flutter has not been well characterized. This lack of adequate definition is caused by the complexity and temporal variability of the Doppler flow profiles. We assessed left atrial appendage function in 21 cases of atrial fibrillation (n - 11) and flutter (n = 10) and five in sinus rhythm with transesophageal Doppler echocardiography. Doppler profiles were examined by Fourier analysis, and the power spectra compared and analyzed between patients with atrial fibrillation and flutter. Left atrial appendage Doppler flow in atrial fibrillation produced Fourier spectra over a narrow band of frequencies with a peak frequency of 6.2 +/- 1.0 Hz, significantly higher than in atrial flutter (3.9 +/- 0.6 Hz, p < 0.00001). Additionally, a significant difference in subharmonic modulation (spectral power below the peak frequency) was observed between atrial appendage flow in atrial fibrillation and flutter, because 37% +/- 16% of the total spectral power was achieved before the dominant frequency in atrial fibrillation compared with 20% +/- 14% in atrial flutter (p = 0.02). Conversely, patients in sinus rhythm exhibited broad-banded Fourier spectra with most of the power in discrete frequency spikes at harmonics above the fundamental frequency with very little subharmonic modulation (1% +/- 0.05%). Left atrial appendage function in atrial fibrillation and flutter can be well characterized by Fourier analysis of Doppler flow. Atrial fibrillation has higher dominant frequencies and greater subharmonic modulation compared with flutter. Moreover, atrial fibrillation demonstrated quasiperiodic contraction patterns typically found in chaotic systems. Fourier analysis of left atrial appendage contraction patterns may therefore have significant promise in providing insights into mechanisms of atrial fibrillation and thromboembolism.

Aged↗
PubMed1996

Nutritional modulation of the final outcome of hepatotoxic injury by energy substrates: an hypothesis for the mechanism.

Survival after hepatocellular injury and necrosis may depend on the ability of the remaining hepatocytes to divide and restore an adequate population of functioning cells. Although adequate nutritional support is necessary for liver regeneration after severe liver damage, much is yet to be discovered concerning which nutritional factors are critical for liver regeneration. Clinically, nutritional substances are administered only from the energy aspect, without regard to whether or how these substrates may facilitate or impede liver tissue repair processes. Glucose is used as principal source of energy in liver damage because of accompanying marked hypoglycemia. But the contribution of glucose to compensatory liver regeneration and/or survival is unclear. This paper advances the hypotheses that: (1) glucose increases the toxicity of centrilobular hepatotoxicants by inhibiting hepatic cell division and tissue repair allowing unrestrained progression of injury; (2) fatty acids facilitate hepatic-cell division permitting hepatolobular restoration to occur thus preventing death from even a lethal dose. If hepatic tissue repair can be stimulated by some therapeutically compatible mechanism, then it might be possible to prevent death from even massive hepatocellular injury. In addition to nutritional manipulation, it should be possible to exploit molecular mechanisms that regulate organized cell division (tissue repair) to increase survival rates of patients suffering from fulminant hepatic failure. These findings have significant impact on tissue repair in a variety of other organs and tissues, particularly in diabetes-like conditions.

Animals↗
PubMed1995

Adjunctive magnesium infusion therapy in acute myocardial infarction.

Intravenous magnesium therapy in acute myocardial infarction (MI) has been shown to be beneficial in many studies. However, these effects are not consistent from one trial to another, and their clinical significance is often questionable. A total of 78 consecutive patients were included in a prospective placebo controlled, randomized study of the effects of intravenous magnesium sulfate infusion in acute MI. Of these, 52 (66%) received intravenous streptokinase and the rest belonged to a non-thrombolysed group. These patients were randomized to receive magnesium sulfate infusion (8 mmol over 5 min followed by 65 mmol over 24 h) or placebo. The end points were serious arrhythmias, left ventricular ejection fraction (LVEF) and death during hospital stay and at the end of 28 days. LVEF measured by radionuclide ventriculography at discharge (9 +/- 5 days) was similar in two groups (41 +/- 11 vs. 39 +/- 10; magnesium vs. placebo respectively, P = 0.40). However, the LVEF of the placebo-treated thrombolysed group was higher than the non-thrombolysed group (42 +/- 10 vs. 37 +/- 0, P = 0.02). Incidence of nonsustained ventricular tachycardia (NSVT) was higher with placebo than with magnesium (50% vs. 23% respectively, P < 0.02, odds ratio = 0.29; 95% confidence intervals (CI) 0.1-0.85). Mortality during hospital stay and at the end of 28 days was also similar in both the groups. Thus, the administration of magnesium infusion as an adjunct to thrombolytic therapy remains to be of questionable benefit.

Anti-Arrhythmia Agents↗