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Biomedical subjects

S Subramanian

Publications and source records attributed to S Subramanian.

At least 73 records · Page 4Linked to original sources

Incorporating inheritance into models for understanding ventilatory behavior.

Ventilation and its components (frequency and tidal volume) appear to be determined to a significant extent by inheritance. Gene manipulation, gene identification, and functional genomics now offer powerful tools to identify the strength and mode of inheritance for ventilatory behavior under steady-state and non-steady-state conditions, in health and in disease. Conscious integration of genetic principles into existing explanatory models may increase the likelihood of detecting traits that correlate with protein systems responsible for the structures and the functional components of respiration.

Humans↗

Underlying mechanisms of symmetric calcium wave propagation in rat ventricular myocytes.

Calcium waves in heart cells are mediated by diffusion-coupled calcium-induced calcium release. The waves propagate in circular fashion. This is counterintuitive in view of the accepted ultrastructure of the cardiac myocyte. The density of calcium release sites in the transverse direction is four times higher than in the longitudinal direction. Simulations with release sites localized along Z-lines and isotropic diffusion yielded highly elliptical, nonphysiological waves. We hypothesized that subcellular organelles counteracted the higher release site density along the Z-lines by acting as transverse diffusion barriers and sites of active calcium uptake. We quantified the reduction of transverse diffusion by microinjecting cells with the nonreactive dye fluorescein. The ratio of the radial diffusion coefficient to the longitudinal coefficient was 0.39. Inhibition of mitochondrial uptake by rotenone accelerated the wave in the transverse direction. Simulations with release sites clustered at the Z-lines and a transverse diffusion coefficient 50% of the longitudinal coefficient generated waves of ellipticity 2/1 (major axis along the Z-line). Introducing additional release sites between the Z-lines at a density 20% of that on the Z-lines produced circular waves. The experiments and simulations support the presence of transverse diffusion barriers, additional uptake sites, and possibly intermediate release sites as well.

Animals↗

Outcome and resource use associated with myomectomy.

OBJECTIVE: To evaluate the outcomes and cost of myomectomy through retrospective claims data analysis. METHODS: The study was performed using a retrospective database of private insurance claims from 1995 to 1997. Records were selected for analysis based on the presence of ICD-9-CM procedure and/or CPT-4 codes associated with myomectomy. In addition, diagnosis of uterine leiomyoma and related symptoms for these patients were confirmed through ICD-9-CM diagnosis codes. Inpatient, outpatient, and physician costs were estimated. All cost data were converted into 1997 dollars. RESULTS: A total of 4394 women, between the ages of 14 and 70, were available for analysis. Of these, 3305 were classified by type of myomectomy procedure, and complete data were available on 820 at 1 year and 236 at 2 years. Abdominal myomectomies were the most common procedures, followed by hysteroscopic and laparoscopic myomectomies. Conversion to a more invasive procedure occurred in 5.4% of the patients. The rate of additional surgeries was 8.3% in 6 months, 10.6% in 1 year, and 16.5% in 2 years. Overall cost increased from an initial 6,737 dollars per patient to 7,575 dollars in 1 year and to 8,001 dollars in 2 years. CONCLUSION: The repeat procedures required after the initial myomectomy add significantly to total cost and highlight the importance of assessing post-procedure health care use. This comprehensive analysis facilitates the systematic evaluation of myomectomy with current and emerging alternative treatments for uterine leiomyomas.

Adolescent↗

Depletion of brown fat norepinephrine content by acute cold exposure and adrenoceptor blockade.

Experiments were conducted to characterize the effects of acute cold exposure, with and without adrenoceptor blockade, on intrascapular brown adipose tissue (IBAT) and adrenal catecholamine content in male Sprague-Dawley rats. Groups of animals with indwelling temperature transmitters were tested following treatment with saline, the alpha-adrenoceptor blocker phentolamine, the beta-adrenoceptor blocker propranolol, combined blockade with phentolamine plus propranolol, and the ganglionic blocker chlorisondamine. IBAT norepinephrine (NE) content was not affected in animals tested at 22 degrees C, but was reduced in 4 degrees C-exposed animals treated with phentolamine (-57%), phentolamine plus propranolol (-97%), and chlorisondamine (-42%). Adrenal NE and epinephrine (EPI) content were not altered by the treatments at 4 degrees C or 22 degrees C. None of the treatments affected the temperature of animals at 22 degrees C, but significant hypothermia occurred at 4 degrees C after chlorisondamine (-2.3+/-0.3 degrees C) and the combination of phentolamine and propranolol (-1.5+/-0.4 degrees C). These results suggest that cold exposure alone did not affect IBAT NE content, but when cold exposure was combined with adrenoceptor blockade, the sympathetic activation was sufficient to cause a reduction in IBAT NE content. In addition, alpha- and beta-adrenoceptor-mediated mechanisms contribute to the maintenance of core temperature. However, both alpha- and beta-receptor mechanisms had to be interrupted before a deficit in body temperature was detected.

Adipose Tissue, Brown↗

Uterine artery embolization for leiomyomata: resource use and cost estimation.

PURPOSE: The objective of this study is to provide an assessment of the facility cost associated with uterine artery embolization (UAE) for leiomyomata and to provide a basis for the estimation of cost so as to compare UAE with surgical approaches. MATERIALS AND METHODS: Information was gathered from the clinical/accounting system for 23 patients who had UAE performed at a single institution. Cost-to-charge ratios and microcosting were employed to derive cost estimates. A detailed meta-analysis was also performed on the resource use parameters reported in the literature. RESULTS: Facility costs range from 2,058 dollars to 4,951 dollars and the mean total cost is 3,080 dollars. The radiology procedure and observation stay are the largest contributors to facility cost. The average length of stay is 21.5 hours with a range from 8 hours to 48 hours. The estimates from this analysis provide a good approximation of facility cost; there are no significant differences in resource use between this study and the meta-analysis. CONCLUSIONS: The facility cost of UAE (3,080 dollars) compares favorably with hysterectomy, the cost of which ranges from 3,100 dollars to 4,900 dollars depending on the type of procedure performed. This cost information can be used to analyze the cost effectiveness of UAE compared to alternate therapies.

Arteries↗

Fourier transform infrared and Raman spectral analysis of trans-1,4-polyisoprene.

Polyisoprene is the most widely used polymer in industry and commerce. Fourier transform infrared (FTIR) and Raman spectra of trans-1,4-polyisoprene have been recorded in the range of 4000-400 and 4000-100 cm(-1), respectively. In the present investigation, detailed assignments of the observed fundamental bands of trans-1,4-polyisoprene has been analysed in terms of peak positions and relative intensities. With the hope of providing more and effective information on the fundamental vibrations, a normal co-ordinate analysis has been performed on trans-1,4polyisoprene, by assuming Cs symmetry. The simple general valance force field (SGVFF) method has been employed in normal co-ordinate analysis and to calculate the potential energy distribution (PED) for each fundamental vibration. The PED contribution corresponding to each of the observed frequencies shows the reliability and accuracy of the spectral analysis. The validity of the SGVFF method as a practical tool for complete analysis of vibrational spectra, even for a polymer of this complexity, is confirmed in the present work.

Hemiterpenes↗

Modulation of abscisic acid signal transduction and biosynthesis by an Sm-like protein in Arabidopsis.

The phytohormone abscisic acid (ABA) regulates plant growth and development as well as stress tolerance. The Arabidopsis sad1 (supersensitive to ABA and drought) mutation increases plant sensitivity to drought stress and ABA in seed germination, root growth, and the expression of some stress-responsive genes. sad1 plants are also defective in the positive feedback regulation of ABA biosynthesis genes by ABA and are impaired in drought stress induction of ABA biosynthesis. SAD1 encodes a polypeptide similar to multifunctional Sm-like snRNP proteins that are required for mRNA splicing, export, and degradation. These results suggest a critical role for mRNA metabolism in the control of ABA signaling as well as in the regulation of ABA homeostasis.

Abscisic Acid↗

Magnetic resonance imaging for in vivo assessment of tissue oxygen concentration.

Magnetic resonance imaging (MRI) provides high-resolution morphological images useful in diagnostic radiology to differentiate normal from abnormal/pathological states. More recently, emerging developments in MRI seek to add a functional/physiological dimension to the anatomic images to provide better understanding of the physiology of pathological conditions. Three MRI methods offer the promise of providing important physiologic information, such as oxygen status and redox capability of tissues, and these are discussed in the context of their potential usefulness to radiation oncology. The techniques include blood oxygen level-dependent (BOLD) MRI, Overhauser enhanced MRI (OMRI), and electron paramagnetic resonance imaging (EPRI). BOLD MRI provides information of tumor oxygen status by using the differences in MRI images from tumors obtained when breathing air or carbogen. Deoxyhemoglobin serves as an endogenous BOLD MRI contrast agent. OMRI utilizes the enhancement of proton MRI images by a nontoxic free radical contrast agent. The advantages of this technique are the very low magnetic fields used and its capability to provide quantitative information of tissue oxygen concentration. EPRI also uses free radical contrast agents and can provide redox and oxygen status differences between tumor and normal tissues. Some of the contrast agents used in EPRI have been identified as radiation protectors. The images obtained from each of the technologies may ultimately be used to overlay their respective views (containing spatial tissue physiology information) onto detailed anatomic maps.

Humans↗

Electron paramagnetic resonance for small animal imaging applications.

Magnetic resonance imaging (MRI) provides high-resolution morphological images useful in diagnostic radiology to differentiate between normal and abnormal/pathological states in tissues. More recently, emerging developments in MRI have added a functional/physiological dimension to anatomical images. Electron paramagnetic resonance (EPR), a magnetic resonance technique similar to nuclear magnetic resonance, detects paramagnetic species such as free radicals. Like MRI, EPR can be implemented as an imaging technique for small animals and potentially human applications. Because of the low abundance of naturally occurring paramagnetic species, exogenous paramagnetic species are needed for in vivo EPR imaging (EPRI). The image data from EPRI contain both spatial distribution of paramagnetic species and spectral information. Hence, spatially encoded functional information such as tissue oxygen status and redox status can be extracted and coregistered with the spatial distribution of the spin probe, to the anatomy, or both by suitable means. Ultimately, the images obtained from EPRI may be used to overlay the functional information (containing spatial tissue physiology information) onto detailed anatomical maps. With its ability to enable whole animal imaging in mice, EPRI will be a useful imaging technique that complements other techniques such as MRI and positron emission tomography in obtaining valuable functional/physiological images.

Anatomy, Cross-Sectional↗

Ventilatory behavior after hypoxia in C57BL/6J and A/J mice.

Given the environmental forcing by extremes in hypoxia-reoxygenation, there might be no genetic effect on posthypoxic short-term potentiation of ventilation. Minute ventilation (VE), respiratory frequency (f), tidal volume (VT), and the airway resistance during chemical loading were assessed in unanesthetized unrestrained C57BL/6J (B6) and A/J mice using whole body plethysmography. Static pressure-volume curves were also performed. In 12 males for each strain, after 5 min of 8% O2 exposure, B6 mice had a prominent decrease in VE on reoxygenation with either air (-11%) or 100% O2 (-20%), due to the decline of f. In contrast, A/J animals had no ventilatory undershoot or f decline. After 5 min of 3% CO2-10% O2 exposure, B6 exhibited significant decrease in VE (-28.4 vs. -38.7%, air vs. 100% O2) and f (-13.8 vs. -22.3%, air vs. 100% O2) during reoxygenation with both air and 100% O2; however, A/J mice showed significant increase in VE (+116%) and f (+62.2%) during air reoxygenation and significant increase in VE (+68.2%) during 100% O2 reoxygenation. There were no strain differences in dynamic airway resistance during gas challenges or in steady-state total respiratory compliance measured postmortem. Strain differences in ventilatory responses to reoxygenation indicate that genetic mechanisms strongly influence posthypoxic ventilatory behavior.

Airway Resistance↗

Impact of global bundled payments on hospital costs of coronary artery bypass grafting.

The Health Care Financing Administration began the Medicare Participating Heart Bypass Center Demonstration in 1991, in which hospitals and physicians are paid a single negotiated global price for all inpatient care for heart bypass patients. This article analyzed the changes in total and departmental direct variable costs during the 1991-1993 period using micro-cost data. The results indicate that all participating hospitals had significant reductions in total direct variable costs, after controlling for preoperative risk factors and postoperative outcomes. However, the patterns in cost reductions across major departments were different across hospitals. The cost reductions primarily came from nursing intensive care unit, routine nursing, pharmacy, and catheter lab.

Boston↗

Immunocontraceptive potential of major antigenic determinants of chicken riboflavin carrier protein in the female rat.

Earlier investigations have demonstrated that antibodies generated against the N-terminal (10-17) and C-terminal (200-207) ends of chicken riboflavin carrier protein (RCP; 219 AA), but not towards the internal region (172-179), curtail pregnancy establishment in rodents and sub-human primates. In those studies, epitope peptides conjugated to diphtheria toxoid were used as immunogens. In the present study, linkage of these sequences to extraneous carriers was avoided to rule out the possibility of carrier-mediated suppression of hapten-specific antibody production in long-term immune response. The ability of these three free peptides to function as minivaccines was examined and the functional importance of these sequences in pregnancy establishment in rodents were evaluated. The results obtained reveal that the peptides YGC (residues 3-24) and HAC (residues 200-219) serve as immunocontraceptive vaccines.

Amino Acid Sequence↗

Surface Chemical Studies on Pyrite in the Presence of Polysaccharide-Based Flotation Depressants.

The interaction of dextrin and guar gum with pyrite has been investigated through adsorption, flotation, and electrokinetic measurements. The adsorption densities of the polysaccharides onto pyrite reveal a region of higher adsorption density in the pH range 7.5-11, with a maximum around pH 10 for both polymers. The isotherms exhibit Langmuirian behavior. The adsorption density of guar gum onto pyrite is higher than that of dextrin. Electrokinetic measurements indicate a decrease in the electrophoretic mobility values in proportion to the concentration of the polymer added. Co-precipitation tests confirm polymer-ferric species interaction in the bulk solution, especially in the pH range 5.5-8.5. The pH range for higher adsorption, significant co-precipitation, and appreciable depression of pyrite encompass each other. XPS and FTIR spectroscopic studies provide evidence in support of chemical interaction between hydroxylated pyrite and the hydroxyl groups of the polymeric depressants. Copyright 2000 Academic Press.

Journal Article↗

Three-dimensional whole body imaging of spin probes in mice by time-domain radiofrequency electron paramagnetic resonance.

Imaging of stable paramagnetic spin probes in phantom objects and in vivo was evaluated using a RF time domain EPR spectrometer/imager operating at 300 MHz. Projections were collected using static magnetic field gradients and images were reconstructed using filtered back-projection techniques. Results from phantom objects containing approximately 10(17) spins of stable paramagnetic probes with single narrow EPR spectra provide three-dimensional spatial images with resolution better than 2 mm. When the spin probe was administered to mice, the spin probe accumulation was temporally observed in the thoracic, abdominal, and pelvic regions. A three-dimensional image (from 144 projections) from a live mouse was collected in 5 min. Using fiducial markers, the spin probe accumulation in organs such as liver, kidney, and bladder could be observed. Differences in the oxygen status between liver and kidney were observed from the EPR images from mice administered with spin probe, by treating the time-domain responses with convolution difference approach, prior to image reconstruction. The results from these studies suggest that, with the use of stable paramagnetic spin probes and time-domain RF EPR, it is possible to perform in vivo imaging on animals and also obtain important spatially resolved physiologic information.

Animals↗

Parallel coil resonators for time-domain radiofrequency electron paramagnetic resonance imaging of biological objects.

Resonators suitable for time-domain electron paramagnetic resonance spectroscopy and imaging at a radiofrequency capable of accommodating experimental animals such as mice are described. Design considerations included B(1) field homogeneity, optimal Q, spectral bandwidth, resonator ring-down, and sensitivity. Typically, a resonator with 25-mm diameter and 25-mm length was constructed by coupling 11 single loops in parallel with a separation of 2.5 mm. To minimize the resonator ring-down time and provide the necessary spectral bandwidth for in vivo imaging experiments, the Q was reduced predominantly by overcoupling. Capacitative coupling was utilized to minimize microphonic effects. The B(1) field in the resonator was mapped both radially and axially and found to be uniform and adequate for imaging studies. Imaging studies with phantom objects containing a narrow-line spin probe as well as in vivo objects administered with the spin probe show the suitability of these resonators for valid reproduction of the spin probe distribution in three dimensions. The fabrication of such resonators is simple and can be scaled up with relative ease to accommodate larger objects as well.

Animals↗

What is the optimal distal resection margin for esophageal carcinoma?

BACKGROUND: Whereas a proximal resection margin of 12 cm is recommended for complete resection of esophageal cancer, the extent of distal resection is unclear. METHODS: We examined distal resection margins in a consecutive series of patients who underwent esophagectomy for squamous cell carcinomas (n = 50), primary esophageal adenocarcinomas (n = 100), and adenocarcinomas of the cardia (n = 39), in whom all macroscopic tumor was judged to be completely resected. RESULTS: Microscopic tumor was found at a 3-cm distal resection margin for one multifocal squamous cell carcinoma. Positive distal resection margins were seen in 12% (12 of 100 patients) of primary esophageal adenocarcinomas (median, 2 cm versus 4 cm if negative; p = 0.002, Wilcoxon) and 28% (11 of 39 patients) of cardia adenocarcinomas (median, 1 cm versus 3 cm if negative; p = 0.02, Wilcoxon). Although pathologic stage was shown to be the only significant predictor of overall survival (Hazard ratio [HR] 1.8; 95% confidence interval 1.2 to 2.6; p = 0.007), there was a trend toward reduced postoperative survival for patients with histologically positive distal resection margins, in particular for patients with cardia adenocarcinomas (median, 15.4 months versus 5.7 months if negative; p = 0.0001). CONCLUSIONS: To achieve consistently negative distal resection margins, we recommend resection of at least 5 cm of macroscopically normal foregut below the distal margin of the primary tumor.

Adenocarcinoma↗

Inhibition of Ca(2+) sparks by ruthenium red in permeabilized rat ventricular myocytes.

We have compared the effects of the sarcoplasmic reticulum (SR) Ca(2+) release inhibitor, ruthenium red (RR), on single ryanodine receptor (RyR) channels in lipid bilayers, and on Ca(2+) sparks in permeabilized rat ventricular myocytes. Ruthenium red at 5 microM inhibited the open probability (P(o)) of RyRs approximately 20-50-fold, without significantly affecting the conductance or mean open time of the channel. At the same concentration, RR inhibited the frequency of Ca(2+) sparks in permeabilized myocytes by approximately 10-fold, and reduced the amplitude of large amplitude events (with most probable localization on the line scan) by approximately 3-fold. According to our theoretical simulations, performed with a numerical model of Ca(2+) spark formation, this reduction in Ca(2+) spark amplitude corresponds to an approximately 4-fold decrease in Ca(2+) release flux underlying Ca(2+) sparks. Ruthenium red (5 microM) increased the SR Ca(2+) content by approximately 2-fold (from 151 to 312 micromol/l cytosol). Considering the degree of inhibition of local Ca(2+) release events, the increase in SR Ca(2+) load by RR, and the lack of effects of RR on single RyR open time and conductance, we have estimated that Ca(2+) sparks under normal conditions are generated by openings of at least 10 single RyRs.

Animals↗