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1.
Org Lett ; 3(22): 3557-9, 2001 Nov 01.
Article in English | MEDLINE | ID: mdl-11678707

ABSTRACT

[reaction: see text]. We report the synthesis of cyclic sulfates by halocyclization. The resulting cyclic sulfate products can be opened selectively with sodium azide to transform them into highly functionalized compounds that contain azide, alcohol, and halide groups.


Subject(s)
Sulfuric Acid Esters/chemical synthesis , Cyclization , Indicators and Reagents , Oxidation-Reduction , Sodium Azide/chemistry
2.
J Chromatogr Sci ; 39(7): 273-9, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11471989

ABSTRACT

This article presents a case study in dealing with robustness investigations and attempts by our analytical laboratory to address these issues without sacrificing valuable time in revamping the method validation prior to submission. A liquid chromatographic method is developed for the analysis of a novel triazinetrione anticoccidial product. The method effectively separates the active pharmaceutical ingredient (API), impurities, and preservatives in the API and product formulation. For much of the validation, the method holds up to the rigorous guidelines of the International Conference of Harmonization, the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products, and the Good Manufacturing Practices. However, in analyzing a base-degraded sample one of the impurity peaks yields inconsistent retention times (RTs) during a series of injections. When switching the system to another analytical column from the same supplier, this impurity peak elutes at a different retention window and the remaining peaks in the chromatographic profile remain essentially the same. This RT variation of a single peak in the chromatographic profile is observed with additional columns from the same supplier and from different manufacturing lots. This suitability problem is not encountered with the columns used in the method development stage. The method no longer meets the robustness criteria established for pharmaceutical methods. An investigation is commenced and it is discovered that with the addition of tetrabutylammonium hydroxide to the mobile phases, the impurity peak gives a consistent RT in relation to the active peak. The peak shows comparable RTs relative to that of the API peak with columns of different silica lots and bond lots. All peaks, including the aforementioned impurity peak, are well-resolved under the revised high-performance liquid chromatographic conditions. This temporary solution enables continued submission work for FDA, but the robustness of this method is still a concern. After further investigation, it is determined that inhomogeneity of the active sites on the column's stationary phase is the likely culprit. Fortunately, a new column is found to be more suitable for this method and a column qualification study is initiated.

3.
J Biol Chem ; 274(9): 5271-8, 1999 Feb 26.
Article in English | MEDLINE | ID: mdl-10026133

ABSTRACT

Synthetic carbohydrate and glycoprotein mimics displaying sulfated saccharide residues have been assayed for their L-selectin inhibitory properties under static and flow conditions. Polymers displaying the L-selectin recognition epitopes 3',6-disulfo Lewis x(Glc) (3-O-SO3-Galbeta1alpha4(Fucalpha1alpha3)-6-O-SO3-Glcbeta+ ++-OR) and 3',6'-disulfo Lewis x(Glc) (3, 6-di-O-SO3-Galbeta1alpha4(Fucalpha1alpha3)Glcbeta-OR) both inhibit L-selectin binding to heparin under static, cell-free binding conditions with similar efficacies. Under conditions of shear flow, however, only the polymer displaying 3',6-disulfo Lewis x(Glc) inhibits the rolling of L-selectin-transfected cells on the glycoprotein ligand GlyCAM-1. Although it has been shown to more effective than sialyl Lewis x at blocking the L-selectin-GlyCAM-1 interaction in static binding studies, the corresponding monomer had no effect in the dynamic assay. These data indicate that multivalent ligands are far more effective inhibitors of L-selectin-mediated rolling than their monovalent counterparts and that the inhibitory activities are dependent on the specific sulfation pattern of the recognition epitope. Importantly, our results indicate the L-selectin specificity for one ligand over another found in static, cell-free binding assays is not necessarily retained under the conditions of shear flow. The results suggest that monovalent or polyvalent carbohydrate or glycoprotein mimetics that inhibit selectin binding in static assays may not block the more physiologically relevant process of selectin-mediated rolling.


Subject(s)
Glycoproteins/pharmacology , L-Selectin/drug effects , Leukocytes/drug effects , Animals , Carbohydrate Sequence , Cell Line , Glycoproteins/chemistry , Glycoproteins/metabolism , L-Selectin/metabolism , Leukocytes/cytology , Lewis X Antigen/chemistry , Ligands , Mice , Molecular Mimicry , Molecular Sequence Data
4.
Circulation ; 98(15): 1495-503, 1998 Oct 13.
Article in English | MEDLINE | ID: mdl-9769302

ABSTRACT

BACKGROUND: The validity of quantitative coronary angiography (QCA) after stent placement has been questioned because the optical density of a metallic stent, added to the density of a contrast-filled lumen, could affect border definition. METHODS AND RESULTS: We deployed 3.0- and 4.0-mm Palmaz-Schatz, Wiktor, Multilink, NIR, and InStent stents in precision-cast phantoms. Central lumens of 2.0 mm were created. There was no difference between the "true" diameters of any stented lumen by both QCA and quantitative ultrasonic (QCU) measurement poststenting. QCA systematic error (SE) varied from 0.01 for the Wiktor stents to 0.14 mm for the Palmaz-Schatz stents; the random error (RE) was 0.03 to 0.14 mm. QCU SE varied from 0.05 to 0.11 mm, and RE ranged from 0.01 to 0.07 mm. At the next stage, 4.0-mm Wiktor and Palmaz-Schatz stents were deployed into the phantom lumens; 1.5-, 2.0-, 2.5- and 3.0-mm lumens were created inside the stents. QCA and QCU measurements of 1.5- to 2.5-mm residual lumens were overestimated by 0.1 to 0.3 mm. In the 3. 0-mm residual lumen within the Wiktor stent, QCA underestimated the luminal size by -0.1 mm. There was no QCA inaccuracy for a 3.0-mm lumen within the Palmaz-Schatz stent. In patients, in 25 stented segments in both the Palmaz-Schatz and Wiktor groups, there was no difference between QCA and QCU diameters. CONCLUSIONS: QCU is sufficiently precise for the assessment of the coronary lumen after stenting. QCA can be used as an accurate method of poststent assessment, except when a very mild recurrence within a highly opaque stent is measured. In that instance, QCA may underestimate the luminal diameter.


Subject(s)
Stents , Coronary Angiography/instrumentation , Coronary Disease/diagnostic imaging , Coronary Vessels/diagnostic imaging , Humans , Phantoms, Imaging , Ultrasonography
5.
J Hum Evol ; 34(3): 249-302, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9547457

ABSTRACT

Lower spinal structure correlates well with positional behavior among mammals. Nonetheless, the functional morphology of the axial post-crania of australopithecines has received less attention than their appendicular skeletons. This paper presents a detailed description and comparative morphometric analysis of the australopithecine thoracolumbar vertebral series Stw-H8/H41, and examines spinal mechanics in early hominids. Stw-H8/H41 is an important specimen, as the australopithecine vertebral sample is small, and vertebral series are more useful than isolated elements for the interpretation of spinal function. Results of the study support the interpretation that australopithecine species are highly sexually dimorphic. The study also reveals a considerable amount of morphometric variation other than size among australopithecine vertebrae, though the sample is too small and incomplete to ascertain whether this indicates significant interspecific differences in spinal function. Most importantly, structural and metric observations confirm that the morphology of the lower spine in australopithecines has no modern analogue in its entirety. Aspects of zygapophyseal structure, numerical composition of the lumbar region, and centrum wedging suggest that the australopithecine vertebral column was adapted to human-like intrinsic lumbar lordosis and stable balance of the trunk over the pelvis in sustained bipedal locomotion. However, relative centrum size in australopithecines indicates that either they had a different mechanism for channeling vertical forces through the vertebral column than humans, or differed behaviorally from humans in ways that produced smaller increments of compression across their centra. These findings have important implications for hypotheses of australopithecine positional behavior, and demonstrate that larger samples and more complete vertebral series are needed to improve our understanding of australopithecine spinal function.


Subject(s)
Cercopithecidae/anatomy & histology , Fossils , Hominidae/anatomy & histology , Lumbar Vertebrae/anatomy & histology , Thoracic Vertebrae/anatomy & histology , Adult , Animals , Biological Evolution , Female , Humans , Male
7.
Biochemistry ; 35(47): 14862-7, 1996 Nov 26.
Article in English | MEDLINE | ID: mdl-8942649

ABSTRACT

Protein-carbohydrate interactions are known to mediate cell-cell recognition and adhesion events. Specifically, three carbohydrate binding proteins termed selectins (E-, P-, and L-selectin) have been shown to be essential for leukocyte rolling along the vascular endothelium, the first step in the recruitment of leukocytes from the blood into inflammatory sites or into secondary lymphoid organs. Although this phenomenon is well-established, little is known about the molecular-level interactions on which it depends. All three selectins recognize sulfated and sialylated derivatives of the Lewis x [Le(x):Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc] and Lewis a [Le(a): Gal beta 1-->3(Fuc alpha 1-->4)GlcNAc] trisaccharide cores with affinities in the millimolar range, and it is believed that variants of these structures are the carbohydrate determinants of selectin recognition. Recently it was shown that the mucin GlyCAM-1, a secreted physiological ligand for L-selectin, is capped with sulfated derivatives of sialyl Lewis x [sLe(x): Sia alpha 2-->3Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc] and that sulfation is required for the high-affinity interaction between GlyCAM-1 and L-selectin. To elucidate the important sites of sulfation on Le(x) with respect to L-selectin recognition, we have synthesized six sulfated Le(x) analogs and determined their abilities to block binding of a recombinant L-selectin-Ig chimera to immobilized GlyCAM-1. Our results suggest that 6-sulfo sLe(x) binds to L-selectin with higher affinity than does sLe(x) or 6'-sulfo sLe(x) and that sulfation of sLe(x) capping groups on GlyCAM-1 at the 6-position is important for L-selectin recognition.


Subject(s)
Carbohydrate Metabolism , L-Selectin/metabolism , Lewis X Antigen/metabolism , Trisaccharides/metabolism , Carbohydrate Sequence , Ligands , Mucins/metabolism , Sulfuric Acid Esters/metabolism
8.
Am Heart J ; 131(4): 639-48, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8721633

ABSTRACT

One hundred twenty-three patients treated with high-speed rotational atherectomy (HSRA) were restudied 6.9 +/- 1.2 months later. At the follow-up, the number of focal concentric lesions increased from 32.2 percent to 63.0 percent, p<0.01, with decrease of type C lesions from 54.8 percent to 30.8 percent, p<0.05. Comparison of the degree of the net gain (NG) showed more severe baseline lesions in the high-gain group (NG >20 percent) compared with the moderate-gain group (20 percent > NG > 0 percent) and to the loss group (minimal luminal diameter [MLD] 0.8 +/- 0.4 mm vs 1.0 +/ 0.4 mm, p<0.05; and 1.2 +/- 0.5 mm; p<0.01, respectively). Highest initial gain (36.5 percent +/- 26.2 percent vs 24.5 percent +/- 18.1 percent; p<0.015; and 19.0 percent +/- 23.2 percent; p<0.001) as well as lowest late loss (1.8 percent +/- 21.7 percent vs 14.0 percent +/-18.4 percent; p<0.01 and 28.1 percent +/- 25.0 percent; p<0.01) were found in the high NG group. A higher interaction between burr and atheroma resulted in the lowest restenosis rate of 6 percent.


Subject(s)
Atherectomy, Coronary , Coronary Angiography , Coronary Disease/diagnostic imaging , Coronary Disease/surgery , Aged , Atherectomy, Coronary/methods , Female , Follow-Up Studies , Humans , In Vitro Techniques , Male , Middle Aged , Treatment Outcome
9.
Comput Healthc ; 7(7): 22-4, 1986 Jul.
Article in English | MEDLINE | ID: mdl-10278858
12.
Am J Cardiol ; 49(5): 1208-15, 1982 Apr 01.
Article in English | MEDLINE | ID: mdl-6978060

ABSTRACT

A computer-assisted method for reporting coronary arteriographic findings has been developed. A videographic display with a touch input system permits finger pointing to designate arterial segments, lesion locations, graft insertion points and collateral vessels. The coronary diagram is flexible to accommodate variations in dominance and in the size and length of the left coronary system branches. Lesion severity, type and length of lesions, distal vessel anatomy, collateral circulation and coronary bypass grafts (including Y or jump grafts) are displayed pictographically. A tabular summary and graphic output provide a completed coronary report eliminating the need for narrative dictation. An edit mode provides capability for teaching and review. The computer-assisted reporting method has the advantage of automatic data encoding in formats suitable for data base storage and subsequent retrieval.


Subject(s)
Angiography , Coronary Angiography , Collateral Circulation , Computers , Coronary Artery Bypass , Coronary Circulation , Data Display , Humans , Information Systems
13.
Antimicrob Agents Chemother ; 18(4): 529-31, 1980 Oct.
Article in English | MEDLINE | ID: mdl-7447416

ABSTRACT

The in vitro susceptibilities of 16 Mycobacterium marinum strains to eight antimicrobial agents were determined by the agar dilution technique. The most active drugs were amikacin and kanamycin. Tetracycline, doxycycline, and minocycline were inhibitory, predominantly at concentrations slightly below the expected blood and tissue levels. Trimethoprim-sulfamethoxazole and erythromycin demonstrated activity only at concentrations greater than those usually attained in serum and tissues. Gentamicin was relatively inactive.


Subject(s)
Anti-Bacterial Agents/pharmacology , Mycobacterium/drug effects , Amikacin/pharmacology , Erythromycin/pharmacology , Kanamycin/pharmacology , Microbial Sensitivity Tests , Tetracyclines/pharmacology
14.
Med Instrum ; 11(5): 265-7, 1977.
Article in English | MEDLINE | ID: mdl-916919

ABSTRACT

During the past several decades, cardiovascular monitoring has been used with increasing frequency. Measurement of pressures, flows, cardiac rhythm, and blood gases permits the physician and surgeon to apply physiological concepts for treating patients with disease. More complex surgical procedures are now possible. Higher postoperative survival rates have resulted directly from careful monitoring and treatment in the postoperative care units. Operations may be performed with greater safety because of cardiovascular monitoring in the operating room. The relationship between the respiratory system and the circulatory system in managing patients with disease and in patients who are postoperative has been elucidated by new monitoring techniques. The value of extending monitoring to ambulatory patients is just being appreciated, and techniques to do so have been developed. The future offers much promise for an improved quality of medical care, with advanced techniques in cardiovascular monitoring that will be developed for use in the very near future. It is our hope that this symposium will provide useful information for those responsible for selecting such systems in future years.


Subject(s)
Cardiovascular System/physiopathology , Monitoring, Physiologic , Arrhythmias, Cardiac/diagnosis , Computers , Humans , Monitoring, Physiologic/instrumentation
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