Search PubMed⌕ Search

Biomedical subjects

M Saha

Publications and source records attributed to M Saha.

At least 55 records · Page 3Linked to original sources

The impact of cardiac index on cerebral hemodynamics.

BACKGROUND AND PURPOSE: Current noninvasive testing allows accurate assessment of cerebrovascular hemodynamics. The cardiovascular influence on the noninvasive assessment of cerebrovascular studies has not been defined. This study was designed to determine the effect of cardiac index (CI) on cerebral blood flow velocities, ocular pulse amplitude, ophthalmic systolic pressure, and ocular blood flow (OBF) as currently estimated by noninvasive laboratories. METHODS: Based on a retrospective study of 181 patients, we prospectively evaluated 45 patients undergoing right heart catheterization for hemodynamic monitoring to correlate the relation between CI, transcranial Doppler sonography, and ocular pneumoplethysmography. Patients with hemodynamic instability, severe carotid stenoses, massive cerebral infarct, or sepsis were ineligible for the study. Simultaneous recordings of systemic blood pressure, ophthalmic systolic pressure, heart rate, ocular pulse amplitude, middle cerebral artery blood flow velocities, and cardiac output were obtained on all patients. OBF was calculated from the heart rate and ocular pulse amplitude. RESULTS: The relation between OBF and CI is expressed by the equation CI = 2.36 + 0.61 x OBF (r = .47, P = .0010). The middle cerebral artery peak systolic velocities and CI had a correlation of .36 (P = .0181). The equation, derived from the linear relation between OBF and CI, was then validated on a sample of 15 patients. With the apparent linear relation between OBF and CI, we used the derived equation to predict CI from OBF. The OBF determination predicted CI within 30% in all patients and within 20% in 53.3% of the patients. CONCLUSIONS: We demonstrated that OBF and middle cerebral artery systolic velocity decrease with diminishing CI. Our findings suggest that CI may be potentially estimated in selected patients by noninvasive assessment of OBF using ocular pneumoplethysmography.

Blood Pressure↗

Interphotoreceptor retinoid-binding protein (IRBP), a major 124 kDa glycoprotein in the interphotoreceptor matrix of Xenopus laevis. Characterization, molecular cloning and biosynthesis.

We have demonstrated that the neural retina of Xenopus laevis secretes into the extracellular matrix surrounding the inner and outer segments of its photoreceptors a glycoprotein containing hydrophobic domains conserved in mammalian interphotoreceptor retinoid-binding proteins (IRBPs). The soluble extract of the interphotoreceptor matrix contains a 124 kDa protein that cross-reacts with anti-bovine IRBP immunoglobulins. In vitro [3H]fucose incorporation studies combined with in vivo light and electron microscopic autoradiographic analysis, showed that the IRBP-like glycoprotein is synthesized by the neural retina and secreted into the interphotoreceptor matrix. A 1.2 kb Xenopus IRBP cDNA was isolated by screening a stage 42 (swimming tadpole) lambda Zap II library with a human IRBP cDNA under low-stringency conditions. The cDNA hybridizes with a 4.2 kb mRNA in adult Xenopus neural retina, tadpole heads as well as a less-abundant mRNA of the same size in brain. During development, IRBP and opsin mRNA expression correlates with photoreceptor differentiation. The translated amino acid sequence of the Xenopus IRBP clone has an overall 70% identity with the fourth repeat of the human protein. Sequence alignment with the four repeats of human IRBP showed three highly conserved regions, rich in hydrophobic residues. This focal conservation predicts domains important to the protein's function, which presumably is to facilitate the exchange of 11-cis retinal and all-trans retinol between the pigment epithelium and photoreceptors, and to the transport of fatty acids through the hydrophilic interphotoreceptor matrix.

Amino Acid Sequence↗

Studies on phospholipids of different mutants of Salmonella minnesota.

Lipid composition of the cells of smooth (S form) and core-defective rough mutants (Ra, Rb & Re) of Salmonella minnesota has been studied. The readily-extractable lipids (RELs), acid-extractable lipids, and polar and nonpolar phospholipids have been analysed. Fatty acid composition of the different fractions containing phospholipids and other neutral lipids have been determined by GLC and GC-MS techniques. Phosphatidyl glycerol (PG), phosphatidylethanolamine (PE) and diphosphatidyl glycerol (DPG) were the major phospholipids present in all the strains. The major saturated fatty acid found was C16:0, and unsaturated fatty acids were, C16:1 and C18:1. Cyclopropane fatty acids, C17cy and C19cy, were also present in small amounts. Increased amounts of REL and unsaturated fatty acids were found in the mutants compared with the smooth strain. The amount of PG and PE decreased and DPG increased in the mutant strains.

Fatty Acids↗

Preparation of electrophoric derivatives of N7-(2-hydroxyethyl)guanine, an ethylene oxide DNA adduct.

Ethylene oxide, a potential human carcinogen, mainly damages DNA by reacting at guanine sites to form N7-(2-hydroxyethyl)guanine. In order to determine this DNA adduct with high sensitivity by gas chromatography, we have prepared, for comparison purposes, four electrophoric derivatives. The two that are most promising to date are bis- and tris-pentafluorobenzyl products prepared by first chemically transforming the N7-(2-hydroxyethyl)guanine to a corresponding xanthine, and then reacting the latter with pentafluorobenzyl bromide. These two derivatives are obtained in good yields and give molar responses of 0.6 and 0.5, respectively, relative to that of lindane by gas chromatography with electron-capture detection.

Chromatography, Gas↗

Ester and related derivatives of ring N-pentafluorobenzylated 5-hydroxymethyluracil. Hydrolytic stability, mass spectral properties, and trace detection by gas chromatography-electron-capture detection, gas chromatography-electron-capture negative ion mass spectrometry, and moving-belt liquid chromatography-electron-capture negative ion mass spectrometry.

One consequence of radiation damage to DNA is the conversion of thymine to 5-hydroxymethyluracil (HMU). In order to sensitively detect this DNA adduct by gas chromatography (GC) or high-performance liquid chromatography (HPLC) with electron-capture detection techniques, it is necessary to derivatize it. This study was designed to select an optimum ester derivative of the aliphatic hydroxyl group on HMU. N1, N3-Bis(pentafluorobenzyl)-HMU was formed as a parent derivative, and from this a series of esters. Also O-pentafluorobenzyl and O-tetrafluorobenzyl ether derivatives were prepared. Of the esters the pivalyl derivative was the best choice because it formed easily, was relatively stable to aqueous hydrolysis (t 1/2 = 9.8 days at pH 11.5, 24 degrees C) and gave a response at fmol levels by GC and LC comparable to that of the ethers. Unanticipated was a good response as well for the parent derivative, a free hydroxyl compound, by GC and LC at this level. The work also demonstrates a high performance by LC-electron-capture negative ion mass spectrometry with a belt interface for the trace detection of derivatives of this type.

Chemical Phenomena↗

Preparation and mass spectral characterization of pentafluorobenzyl derivatives of alkyl and hydroxyalkyl-nucleobase DNA adducts.

Pentafluorobenzyl (PFBz) derivatives of the following nucleobases were prepared: cytosine, 5-methylcytosine, O2-methylcytosine, O2-ethylthymine, O4-ethylthymine, 5-hydroxymethyluracil, N6-methyladenine, O6-methylguanine, O6-hydroxyethylguanine and O6-hydroxyethylpurine. 13C nuclear magnetic resonance was diagnostic for O- versus N-attachment of the PFBz moiety: the resonance of the methylene carbon appeared in the range 29.15-42.13 ppm for NCH2C6F5, and 58.45-69.01 for OCH2C6F5. Considerable structural information was provided by mass spectrometry with ionization by electron impact. All of the derivatives were detected with high sensitivity and specificity by gas chromatography with detection by electron capture negative ion mass spectrometry, reflecting not only their chemical and physical stability, but also their strong tendency to form a structurally diagnostic anion, [M - PFBz]-, in high yield under these ionization conditions. PFBz derivatives are therefore attractive forms of alkyl-substituted nucleobases for analysis by mass spectrometry.

DNA↗

Pentafluorobenzylation of alkyl and related DNA base adducts facilitates their determination by electrophore detection.

The DNA adduct O4-ethylthymine can be alkylated under mild conditions with pentafluorobenzyl bromide. The product has good gas chromatographic characteristics and also forms a structurally characteristic anion in high yield when subjected to electron capture mass spectrometry. Related adducts for other DNA bases behave similarly. These properties stimulated us to develop a general analytical method based on the derivatization reaction. Important for this method is an oxidation-elimination reaction that mildly releases a base from a nucleoside. Thus, a general analytical method based on pentafluorobenzylation is now available for determining many alkyl and related DNA adducts.

Alkylation↗

Replacement of aromatic fluorine by a methoxy group during reaction with methyl iodide in N,N-dimethylformamide solvent.

The DNA base uracil was derivatized with pentafluorobenzoyl chloride, followed by methylation with methyl iodide in the presence of N,N-dimethylformamide (DMF). In addition to a 3-pentafluorobenzoyl-1-methyl derivative of uracil, GC/MS analysis of the reaction mixture revealed the formation of an unusual product, whose molecular weight was 12 U higher than that of the prior derivative. This unexpected product has been identified as the 3-(para-methoxytetrafluorobenzoyl)-1-methyl derivative of uracil. Isotopic labeling and related experiments have revealed that the DMF solvent contributes the oxygen atom of the methoxy group that replaces the para fluorine atom. This work allowed a single derivative to be obtained for the methylation reaction by changing the solvent to acetonitrile.

Acylation↗