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Biomedical subjects

R R Townsend

Publications and source records attributed to R R Townsend.

At least 73 records · Page 4Linked to original sources
PubMed1991

CT of AIDS-related lymphoma.

A spectrum of CT findings in patients with AIDS-related lymphoma (ARL) is illustrated herein. When a solid mass anywhere in the body is encountered in a patient with AIDS, lymphoma must be considered in the differential diagnosis. Although the CT findings alone generally are not enough for a specific diagnosis of lymphoma, this frequently will be suggested as the most likely diagnosis, facilitating further workup. CT-guided biopsy is useful in providing tissue diagnosis in many cases.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Prenatal diagnosis of urinary tract abnormalities with ultrasound. A review.

The fetal kidneys and bladder are routinely imaged as part of an obstetrical ultrasound examination. The normal appearances of these structures, and how they change through pregnancy, are well documented. Many pathologic conditions, especially hydronephrosis and renal cystic diseases, are easily detectable. In utero diagnosis may facilitate optimal patient counseling, obstetrical management, and postnatal diagnosis and treatment.

Congenital Abnormalities↗
PubMed1990

Structure determination of O-linked glycopeptides by tandem mass spectrometry.

A new method for characterizing O-linked glycopeptides without chemical degradation is presented. Collision-induced dissociation (CID) analysis of intact O-linked glycopeptides containing mono- and disaccharides was performed. For glycopeptides containing one hexose unit, both the peptide sequence and the site of attachment of the sugar moiety were obtained from a single high-energy CID spectrum. However, in a glycopeptide bearing multiple sugar residues per site, the CID spectrum was dominated by fragments resulting from cleavages of the carbohydrate substituents and the gas-phase deglycosylated peptide, thus obviating the concomitant observation of peptide sequence ions. Hence, information on the structures of the carbohydrate substituents was obtained, but not on the sites of attachment of these residues to the peptide. Subsequent CID analysis of the gas-phase deglycosylated peptide ion can be used to obtain the sequence of the peptide backbone from the same sample. This method holds promise for simultaneously determining the carbohydrate structure and the peptide sequence of intact O-linked glycopeptides without chemical degradation.

Amino Acid Sequence↗
PubMed1990

Adaptation of a thermospray liquid chromatography/mass spectrometry interface for use with alkaline anion exchange liquid chromatography of carbohydrates.

An interface is described that allows the direct coupling of high-performance alkaline anion exchange liquid chromatography with thermospray mass spectrometry. A membrane suppressor is used to remove nonvolatile alkaline salts from the mobile phase after the chromatographic process is completed and prior to introduction into the mass spectrometer. Examples are given of both isocratic and gradient separations of a three-component test mixture of N-acetylated mono- and disaccharides, followed by on-line mass spectral data acquisition. Sensitivity studies show minimum detection limits for the test compounds to be in the microgram range.

Carbohydrates↗
PubMed1990

Combined alpha/beta-blockade versus beta 1-selective blockade in essential hypertension in black and white patients.

The purpose of this multicenter investigation was to determine the efficacy and safety of the alpha/beta-blocker labetalol versus the beta 1-selective beta-blocker atenolol in white and black patients with essential hypertension. Equal numbers of black and white patients were enlisted to form four treatment groups (white patients taking either labetalol or atenolol and black patients taking either labetalol or atenolol). Two hundred ninety-two patients (152 white and 140 black patients) with essential hypertension characterized by a standing diastolic blood pressure of 105 to 119 mm Hg (inclusive) were recruited for this trial. Patients were randomized to either labetalol (dosage titrated from 200 to 1600 mg/day) or atenolol (dosage titrated from 50 to 100 mg/day). The therapeutic goal was achievement of a standing diastolic blood pressure of 90 mm Hg or less or a fall of 15 mm Hg in diastolic pressure from baseline value at the end of the placebo run in period. At the end of the study there were no significant differences in blood pressure or heart rate changes in the supine position between the labetalol and atenolol groups. In contrast, labetalol produced greater reduction in both the standing systolic and diastolic blood pressure (-12/-13 mm Hg, respectively) compared with atenolol (-7/-9 mm Hg; p less than 0.05; p less than 0.005, respectively). The greatest decrease in blood pressure was observed in white patients receiving labetalol. In black patients the decrease in blood pressure was greater in those treated with labetalol compared with atenolol, particularly with respect to the systolic blood pressure. We conclude that the alpha 1-blocking property of labetalol provides an additional lowering of the blood pressure over that seen with beta 1-blockade alone, especially in the standing position, and this enhanced efficacy is not confined to one radical group.

Atenolol↗
PubMed1990

Sonographic diagnosis of perforation in patients with acute appendicitis.

The sonographic diagnosis of appendicitis can be challenging in patients with perforation. In order to detect the accuracy of specific sonographic features of appendiceal perforation, graded compression sonograms in 100 patients with surgically confirmed acute appendicitis were reviewed retrospectively. Twenty-two of these patients had perforation. A statistically significant association was found between three sonographic findings and perforation: loculated pericecal fluid, prominent pericecal fat, and circumferential loss of the submucosal layer of the appendix. No single finding had a specificity greater than 59%. By using a combination of one or more findings, the overall sensitivity of sonography for the diagnosis of perforation was 86%. The specificity, however, was only 60%. Our results suggest that in patients without a sonographically visible appendix, recognition of loculated pericecal fluid and prominent pericecal fat may be a useful indirect clue to the diagnosis of perforating appendicitis.

Acute Disease↗
PubMed1990

Combined Doppler and morphologic sonographic evaluation of renal transplant rejection.

We sought to evaluate whether results of Doppler ultrasound alone or in combination with morphologic sonographic evaluation could predict acute renal transplant rejection accurately enough to avoid biopsy. Seventy-one patients were evaluated at time of biopsy. A resistive index greater than 0.90 was 100% predictive of acute rejection, but sensitivity was only 26%. Resistive indices in acute and chronic rejection were often similar. When all morphologic features were abnormal (11%), acute rejection was uniformly present. Regression analysis selected resistive index over morphologic features for ability to predict acute rejection. When resistive index is greater than 0.90 or all morphologic features are abnormal, acute rejection can be predicted with high accuracy, but biopsy remains necessary in many cases.

Adolescent↗
PubMed1990

Combination of converting enzyme inhibitor with diuretic for the treatment of hypertension.

In recent years there has been increased discussion about goals of antihypertensive therapy other than blood pressure reduction. The development of angiotensin-converting enzyme inhibitors has provided a class of drugs with a very low side-effect profile. However, single-drug therapy is effective in only about half of hypertensive patients. In the past, diuretics have traditionally been used as the initial or second antihypertensive. Increasingly, diuretic therapy is being avoided, and other antihypertensive combinations are being used. In controlled trials, combination converting enzyme inhibitor-diuretic therapy is effective in about 85% of patients. This synergistic combination allows the diuretic dose to be reduced so that the adverse effects and metabolic complications are minimized. At this time, the combination of converting enzyme inhibitor and diuretic provides an ideal choice in terms of efficacy, compliance, side effects, and cost.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Separation of fucosylated oligosaccharides using high-pH anion-exchange chromatography with pulsed-amperometric detection.

Fucosylated oligosaccharides of the beta Gal(1----4)GlcNAc-, beta Gal(1----4)Glc-, and beta Gal(1----3)GlcNAc-series were chromatographed on a high-performance anion-exchange pellicular resin under alkaline conditions (pH congruent to 13). Fucosylation of either lactose, lactosamine (Type II chains), or lacto-N-biose (Type I chains) oligosaccharides markedly decreased the retention time (10-38 min) of the non-fucosylated form. The magnitude of the reduction was related to whether fucose replaced Gal [alpha Fuc(1----3)----GlcNAc], whether fucose was alpha-(1----2)-linked to Gal at the end of a chain, or whether fucose was linked in a subterminal position [alpha(1----3) or alpha (1----4)] to Gal or GlcNAc. The results suggest that the decreases in retention times of fucosylated oligosaccharides (10-38 min) is not attributable to the absence of a 6-OH in Fuc but instead to steric and substitution effects which affect the interaction of the most readily ionizable groups of Fuc (2-OH), Gal (2-OH), and GLcNAc (3-OH) with the stationary phase. We show that high-pH anion-exchange chromatography can effectively separate 1----2, 1----3, and 1----4 fucose positional isomers in a single chromatographic step.

Carbohydrate Conformation↗
PubMed1989

The major subunit of the rat asialoglycoprotein receptor can function alone as a receptor.

Mammalian hepatic asialoglycoprotein receptors (ASGP-R) are composed of two unique, but closely related polypeptides, which in the rat are designated rat hepatic lectins 1 and 2/3 (RHL 1, RHL 2/3). Despite numerous studies, the composition of a functional ASGP-R has remained unclear. We examined this question in rat hepatoma tissue culture (HTC) cells (which lack endogenous ASGP-R) that were co-transfected with cDNAs for both RHL 1 and RHL 2/3. The original population was cloned, but derivatives were unstable. We therefore used fluorescence-activated cell sorting to separate a subpopulation of cells (positive) that specifically endocytosed fluoresceinated asialoorosomucoid (ASOR) from one that did not (negative). We then used indirect immunofluorescence with polypeptide-specific ASGP-R antibodies, immunoanalysis, and binding and uptake studies with two Gal ligands (ASOR and NAc-galactosylated poly-L-lysine (Gal-Lys] to further define the ASGP-R status in these two populations. As reported by others, we found that expression of both RHL 1 and RHL 2/3 in the positive cells resulted in binding, uptake and degradation of ASOR, the most commonly used ASGP-R ligand. The negative cells expressed only RHL 1 and neither bound nor processed ASOR. However, the presence of RHL 1 was sufficient for specific high affinity binding and processing of the synthetic ligand, Gal-Lys, by negative cells. These results show that RHL 1 can function as an ASGP-R, given a highly galactosylated ligand, and that RHL 2/3 must play an important role in the organization of native ASGP-R in the membrane.

Animals↗
PubMed1989

Separation of branched sialylated oligosaccharides using high-pH anion-exchange chromatography with pulsed amperometric detection.

Ten characterized sialylated oligosaccharides from bovine fetuin (B. Bendiak, M. Harris-Brandts, S. W. Michnick, J. P. Carver, and D. A. Cumming, Biochemistry, in press; and D. A. Cumming, C. G. Hellerqvist, M. Harris-Brandts, S. W. Michnick, J. P. Carver, and B. Bendiak, Biochemistry, in press) were chromatographed using high-performance anion-exchange chromatography with pulsed amperometric detection. At near neutral pH values, oligosaccharides were separated according to their number of formal negative charges from sialic acid; however, at alkaline pH, the neutral portion of the oligosaccharides enhanced resolution due to oxyanion formation. Specifically, trisialylated triantennary oligosaccharides containing a Gal-beta(1,3)GlcNAc sequence were more retained and could be completely separated from those having only Gal-beta(1,4)GlcNAc units. Oligosaccharides containing the same number of sialic acids were separated according to the combination of alpha(2,6)- and alpha(2,3)-linked sialic acids (alpha(2,6)-linked sialic acid reduced retention time). The relative molar electrochemical responses for di-, tri-, tetra-, and pentasialylated oligosaccharides were found to be similar (4.8 +/- 14% relative to glucose). Coelution studies were performed with each of the characterized oligosaccharides and the mixture of oligosaccharides which were released from fetuin with N-glycanase. The relative proportion of the major classes of sialylated oligosaccharides (bi-, tri-, tetra-, and penta-) varied significantly in bovine fetuin from different sources.

Chromatography, Ion Exchange↗
PubMed1989

Abdominal lymphoma in AIDS: evaluation with US.

The sonographic findings in 38 patients with abdominal lymphomas related to acquired immunodeficiency syndrome (AIDS) were reviewed. Thirty-three patients had non-Hodgkin lymphoma, and five had Hodgkin disease. Abnormal masses were detected with sonography in 33 patients (87%). Focal hypoechoic liver lesions up to 10 cm in diameter were visible in 17 patients. Several lesions were anechoic and septated, mimicking fluid. Adenopathy (at the retroperitoneum, mesentery, or porta hepatis) was seen in 15 patients. Other involved areas included bowel, omentum, spleen, kidney, and adrenal gland. AIDS-related abdominal lymphomas frequently cause extranodal masses that can be readily imaged with ultrasound. Ultrasound-guided fine needle aspiration biopsy allows a specific diagnosis to be made in many cases.

Abdominal Neoplasms↗
PubMed1989

Sonography in patients with suspected acute appendicitis: value in establishing alternative diagnoses.

We reviewed the clinical and sonographic findings in 297 patients who had graded compression sonography for suspected acute appendicitis. The purpose of the study was to determine the accuracy of sonography in detecting other diseases in the 174 patients in this group who proved not to have acute appendicitis. Of the 174 patients without acute appendicitis, 93 patients (53%) were ultimately discharged with a diagnosis of abdominal pain of unknown origin. Of the 81 patients in whom specific diagnoses were established, sonography suggested the correct diagnosis in 57 patients (70%). A broad spectrum of diseases was detected, including: gynecologic diseases (35); visceral diseases, including hollow viscera and diseases of liver, pancreas, or spleen (18); and urinary tract abnormalities (four). This study suggests that sonography is useful in establishing alternative diagnoses in patients undergoing sonography for suspected acute appendicitis.

Acute Disease↗
PubMed1988

High-performance anion-exchange chromatography of oligosaccharides using pellicular resins and pulsed amperometric detection.

High-performance liquid chromatography using pellicular quaternary amine-bonded resins was used to separate a variety of neutral, sialylated, and phosphorylated oligosaccharides. At pH 4.6, sialylated compounds were separated according to number of negative charges, sialic acid linkage [alpha(2,3) compared to alpha(2,6)], and position of sialic acid linkage along a linear saccharide chain. At pH 13, the neutral sugar portion of the sialylated chain had a significant effect on the separation, due to oxyanion formation. Specifically, sialylated tetrasaccharides containing the Gal beta(1,3)GlcNAc sequence were retained much more than their Gal beta(1,4)GlcNAc- or Gal-beta(1,4)GalNAc-sialylated counterparts. Linear phosphorylated oligosaccharides could be completely separated according to number of charges and net carbohydrate content. Partial separation of linear-chain positional isomers, differing in either location of Man-6-PO4 in the chain or linkage position of Man or Man-6-PO4, was accomplished. Branched-chain phosphorylated compounds could be completely separated according to which antennae contained the Man-6-PO4. The electrochemical current generated by oxidation of sialylated, phosphorylated, and neutral oligosaccharides was compared to that of a glucose. The relative molar response factors for neutral, sialylated, and phosphorylated oligosaccharides ranged from 0.2 to 3.2. Neutral oligosaccharides gave the following molar responses for each group of structurally related compounds: (1) mono- and disaccharide, 1-1.3; (2) linear tri- and tetrasaccharides, 1.5-2.0; and (3) branched pentasaccharide-nonasaccharides, 2.4-3.1. Response factors for the sialyated compounds were not as consistent and were affected by linkage position of sialic acid. For oligosaccharides of the same size, increasing phosphorylation resulted in a twofold decrease in response factor for each added phosphate group. Therefore, conversion of sialylated and phosphorylated oligosaccharides to their neutral counterparts, using alkaline phosphatase or neuraminidase, respectively, was required for quantitative analysis of oligosaccharide mixtures using electrochemical response. Using this approach, complete separation of the parent neutral structures was obtained, the relative proportions of the neutral species were quantified, and the amount of sialic acid released was easily determined in a neuraminidase digest.

Anion Exchange Resins↗
PubMed1988

Chromatography of carbohydrates.

The coupling of high-performance anion-exchange chromatography with pulsed amperometric detection provides a much needed analytical tool for the analysis of the carbohydrates of glycoconjugates.

Carbohydrates↗
PubMed1988

Assessment of glycosylation-site heterogeneity using plasma desorption mass spectrometry.

Plasma desorption mass spectrometry (PD-MS) was used to assess the molecular weight heterogeneity of glycopeptides (6-12 amino acids) from each of the three N-linked glycosylation sites of bovine fetuin (R.G. Spiro (1962) J. Biol. Chem. 237, 382-388). The glycopeptides were purified by a combination of anion exchange chromatography and reverse-phase HPLC. Since no detectable fragmentation was observed in the PD-MS of these asialoglycopeptides, the observation of multiple molecular ions could be attributed to either carbohydrate or peptide heterogeneity. Assignment of molecular ions, within 3 to 5 amu of the theoretical mass, of glycopeptides from each glycosylation site was made from amino acid composition, peptide sequence around the glycosylation sites, and previously reported triantennary oligosaccharide structures (B. Nilsson, N.E. Nordén, and S. Svensson (1979) J. Biol. Chem. 254, 4545-4553). Ion groups differing in mass by one N-acetyllactosamine unit were observed in glycopeptides from the Asn-Asp and Asn-Cys sites, localizing these previously observed biantennary oligosaccharide structures (R.R. Townsend, M.R. Hardy, T.C. Wong, and Y.C. Lee (1986) Biochemistry 25, 5716-5725; S. Takasaki and A. Kobata (1986) Biochemistry 25, 5709-5715) to these two sites. The presence of biantennary oligosaccharides at the Asn-Asp sites could be substantiated using 1H NMR but were not detected in the Asn-Cys glycopeptides. PD-MS was also implemented in the purification protocol for these glycopeptides and proved to be useful in assessing purity of chromatographic fractions which were mixtures of glycopeptides displaying both carbohydrate and peptide heterogeneity. A preparation scheme was developed to obtain molecular ions of desialylated glycopeptides by PD-MS.

Amino Acids↗