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Biomedical subjects

S Paul

Publications and source records attributed to S Paul.

At least 199 records · Page 11Linked to original sources
PubMed1994

Vasoactive intestinal peptide encapsulated in liposomes: effects on systemic arterial blood pressure.

The purpose of this study was to determine whether encapsulation of vasoactive intestinal peptide (VIP) in liposomes enhances its vasoactive effects. Liposomes were formed from a solution of VIP in phospholipids and cholesterol, resulting in incorporation of 0.008 mole peptide/mole phospholipid. Leakage of VIP from the liposomes was undetectable over several days of incubation at 4 degrees C in 0.15 M sodium chloride. Under conditions permitting rapid hydrolysis of VIP by trypsin, there was no breakdown of the encapsulated peptide. Increasing concentrations of the liposome-encapsulated VIP administered intravenously to anesthetized hamsters produced a concentration-dependent decrease in the mean arterial blood pressure. The duration and magnitude of the hypotensive effect of the encapsulated VIP was significantly greater (p < 0.05) compared to equivalent concentrations of the unencapsulated peptide. Infusion of empty liposomes was without significant effect on the mean arterial blood pressure. We conclude that encapsulation of VIP in liposomes potentiates the blood pressure-lowering effect of the peptide.

Animals↗
PubMed1994

Decrease in beta-adrenergic receptors of cerebral astrocytes in hypothyroid rat brain.

Studies on the binding of 3H-dihydroalprenolol (3H-DHA) to astrocytes from cerebra of normal and hypothyroid rats show that hypothyroidism results in a decline in the beta-adrenergic receptors. Ontogenic studies indicated that in normal, euthyroid rats, the maximum binding capacity (Bmax) for 3H-DHA progressively increased with age while the affinity (Kd) remained unaltered. In astrocytes prepared from hypothyroid rats, total number of binding sites for 3H-DHA also increased with age, however, at a given age, the number was significantly lower than that for corresponding euthyroid animals while the affinity for 3H-DHA remained unaffected. Correspondingly, primary cultures of astrocytes from normal and hypothyroid brain when maintained in TH-deficient serum, display a similar reduction of 3H-DHA binding. In the case of astrocytes from hypothyroid brain cultured in TH-deficient serum, the decline can be largely restored by supplementing with normal serum. Results suggest that thyroid hormones (TH) directly or indirectly regulates the level of beta-adrenergic receptors in astrocytes from developing rat brain.

Animals↗
PubMed1994

Combined occurrence of trypanosomal sialidase/trans-sialidase activities and leishmanial metalloproteinase gene homologues in Endotrypanum sp.

Endotrypanum (order Kinetoplastida: family Trypanosomatidae) is a parasite of forest dwelling tree sloths (Edentata: genera Choleopus and Bradypus). Unique among the haemoflagellates, this protozoan has an intraerythrocytic phase in the mammalian host. Nevertheless, many striking similarities exist between Endotrypanum and the human pathogen Leishmania that make it a useful model for epidemiological and evolutionary aspects of the biology of trypanosomatids. Importantly, Endotrypanum species share both the insect vector and host reservoir with certain species of Leishmania (subgenus Viannia). Because mixed infections with Endotrypanum and Leishmania are common in sloths and, therefore, likely to occur in the sandfly vector, there is a need for adequate biochemical markers to distinguish Endotrypanum from Leishmania infections. In this paper we show that Endotrypanum promastigotes possess sialidase and trans-sialidase activities, which are absent from Leishmania, and which are not closely related to the previously described trypanosomal sialidase/trans-sialidase enzyme. We also document the occurrence in Endotrypanum of homologues of the leishmanial surface metalloproteinase gp63 genes. The combined occurrence of sialidase/trans-sialidase activities and gp63 gene homologues in a unique organism has important ramifications for both field and laboratory studies on the biology of trypanosomatids, especially those related to host infection and evolution.

Animals↗
PubMed1994

Learning preferences of medical students.

Learning styles and preferred learning approaches are believed to have an influence on student learning. This study investigated the learning preferences of first-, second- and fourth-year medical students as well as explored differences in learning preferences from first- to fourth-year students. In June 1992, 95 students were administered the learning preferences inventory (LPI) designed by Rezler at the United Arab Emirates University. Analysis of variance (ANOVA) was used to test the significance of the differences of the six LPI mean scores on Abstract/Concrete, Teacher-structured/Student-structured, and Individual/Interpersonal categories across the academic year and sex. The two predominant preferences were concrete and teacher-centred. Results of this study showed students preferred teacher-structured learning experiences dealing with concrete and applied tasks, rather than abstract tasks.

Choice Behavior↗
PubMed1994

Reversible topology of a bifunctional transmembrane protein depends upon the charge balance around its transmembrane domain.

Hybrid genes were constructed to express bifunctional hybrid proteins in which staphyloccal nuclease A with or without an amino-terminal OmpA signal sequence was fused with TEM beta-lactamase (at the carboxyl terminal side) using the signal peptide of the major outer membrane lipoprotein of Escherichia coli as an internal linker. The hybrid proteins were found to be inserted in the membrane. Orientation of the hybrid protein with the OmpA signal peptide showed that the nuclease was translocated into the periplasm and the beta-lactamase remained in the cytoplasm. This indicates that the cleavable OmpA signal peptide served as a secretory signal for nuclease and the internal lipoprotein signal served as the transmembrane anchor. In the absence of the OmpA signal sequence the topology of the hybrid protein was reversed indicating that the internal lipoprotein signal peptide initially served as the signal peptide for the secretion of the carboxy terminal beta-lactamase domain across the membrane and subsequently as a membrane anchoring signal. The role of charged amino acids in the translocation and transmembrane orientation of membrane proteins was also analysed by introducing charged amino acids to either or both sides of the internal lipoprotein signal sequence in the bifunctional hybrid proteins in the absence of the amino-terminal signal sequence. Introduction of two lysine residues at the carboxy-terminal side of the internal signal sequence reversed the topology of the transmembrane protein by translocating the amino-terminal nuclease domain across the membrane, leaving the carboxyl terminal beta-lactamase domain in the cytoplasm. When three more lysine residues were added to the amino-terminal side of the internal signal sequence of the same construct the membrane topology flipped back to the original orientation. A similar reversion of the topology could be obtained by introducing negatively charged residues at the amino-terminal side of the internal signal sequence. Present results demonstrate for the first time that a bifunctional transmembrane protein can be engineered to assume either of the two opposite orientations and that charge balance around the transmembrane domain is a major factor in controlling the topology of a transmembrane protein.

Amino Acid Sequence↗
PubMed1994

Spontaneous hydrolysis of vasoactive intestinal peptide in neutral aqueous solution.

Hydrolysis of radioiodinated vasoactive intestinal peptide (VIP) was observed in buffered aqueous solution at neutral pH and 38 degrees C. The reaction displayed apparent first-order kinetics at initial peptide concentrations below 3 nM (kobs = 1.5 x 10(-5) s-1), but the rate deviated below predicted values at higher peptide concentrations. The rate constant derived from the reaction progress curve over three half lives, starting at a concentration of 82 pM peptide, was also consistent with a first-order process. The reaction results in several products that were isolated and characterized as peptide fragments. Based on the identity of these fragments, we deduced hydrolysis at five different peptide bonds clustered between residues 17-25 of VIP. Control experiments were devised to eliminate trivial explanations for the peptide hydrolysis. Peptides representing the C-terminal segment 15-28 and the internal segment 14-22 assayed by analogous methods and under identical conditions were not degraded at a measurable rate. Sodium dodecyl sulfate and acetonitrile, agents known to influence the secondary structure of VIP, inhibited its spontaneous hydrolysis, as did chloride salts of sodium and calcium, albumin and a peptide unrelated to VIP. The rate and product distribution are inconsistent with known pathways of peptide degradation involving cyclic imide or anhydride formation at asparagine or aspartate residues. We suggest that the breakdown of VIP in dilute solutions represents an autolytic process.

Amino Acid Sequence↗
PubMed1994

Trauma case review: survival following impalement.

Prehospital care of patients with penetrating wounds must begin within minutes of the injury; definitive treatments should be initiated within an hour. Due to the advanced skills of the paramedics, nurses, doctors, and ancillary personnel, this patient arrived in the operating room within an hour of his accident. Fortunately, the impaled reinforcement rods missed the vital structures within the patient's thoracic and pleural cavities and spared his lower abdominal organs, vascular structures, and skeletal structures in his groin. This case study illustrates the importance of coordinated efforts in caring for this patient from the prehospital setting through the emergency department and operating room.

Adult↗
PubMed1994

Developing a critical pathway for orientation.

A direct correlation exists between job satisfaction and employee retention with an organized and compassionate orientation process for new employees on a nursing unit. It is generally recognized that preceptorship/mentoring is the most desirable orientation modality; however, situations occasionally require orientees to work with several preceptors with varying levels of proficiency. A program based upon a framework designated "critical pathway" was established in a coronary care unit and a cardiac progressive care unit to organize orientation information into weekly segments, with each week's content building upon the previous week's information. Because the critical pathway clearly delineates the orientation content, all necessary information is imparted to the orientee in an organized fashion without omitting pertinent details. Problems with orientation are documented as variances on the critical pathway, and are discussed between the preceptor and orientee during weekly evaluation sessions. This article reports the procedure for developing a critical pathway for orientation using the critical pathway concept, which is adapted from the nursing case management practice model.

Coronary Care Units↗
PubMed1993

Identification of vasoactive intestinal polypeptide (VIP) binding protein in bovine pineal gland.

Vasoactive intestinal polypeptide (VIP) containing nerves are present in close proximity to epithelial, endocrine, and vascular smooth muscle cells. The pineal gland, known also as a "neuroendocrine transducer organ" contains a high content of VIP which prompted us to characterize the binding sites for VIP in this organ. [Tyr10-125I]VIP was bound selectively and specifically to pineal membrane preparations in a time-dependent fashion. Scatchard analysis demonstrated a single class of high affinity binding sites with a dissociation constant (Kd) value of 5.7 +/- 0.52 nmol/1 and a receptor density (Bmax) value of 440 +/- 35 fmol/mg protein. A Hill Plot with a slope of 1.013 indicated the absence of cooperativity. Covalent crosslinking with [Tyr10-125I]VIP followed by SDS electrophoresis and autoradiography, revealed that the VIP binding protein exhibited a molecular weight of 51.8 +/- 0.5 kDa. The precise function of pineal VIP binding protein remains to be delineated.

Animals↗
PubMed1993

Nursing grand rounds: Wolff-Parkinson-White syndrome: a challenging case study.

Wolff-Parkinson-White (WPW) syndrome involves connections of myocardial fibers between the atrium and ventricle that can carry electrical impulses outside of the normal conduction system. Treatment options include pharmacologic management, surgical interruption, antitachycardia devices, or transvenous catheter ablation. This is a case study of a patient who underwent surgical ablation of an accessory pathway and reoperation because of continued abnormal conduction. She had tachypalpitations after both procedures and later underwent radiofrequency ablation. Nursing care was complicated because she spoke very little English and was extremely anxious about her illness.

Adult↗
PubMed1993

Ability of clinical laboratories to detect antimicrobial agent-resistant enterococci.

To test the ability of clinical laboratories to detect antimicrobial resistance among enterococci, we sent four vancomycin-resistant enterococcal strains and one beta-lactamase-producing enterococcus to all 93 nongovernment, hospital-based clinical laboratories in New Jersey; 76 (82%) participated in the study. Each organism was tested by the laboratory's routine antimicrobial susceptibility testing method. The proportion of laboratories that correctly reported that an isolate was resistant to vancomycin varied according to the resistance level of the isolate: high-level resistance (MIC for Enterococcus faecium = 512 micrograms/ml), 96% of laboratories correct; moderate-level resistance (MIC for E. faecium = 64 micrograms/ml), 27% correct; low-level resistance (MIC for Enterococcus faecalis = 32 micrograms/ml), 16% correct; and intrinsic low-level resistance (MIC for Enterococcus gallinarum = 8 micrograms/ml), 74% correct. The beta-lactamase-producing E. faecalis isolate was identified as resistant to penicillin and ampicillin by 66 and 8% of laboratories, respectively, but only three laboratories recognized that it was a beta-lactamase producer. This survey suggests that many laboratories may fail to detect antimicrobial agent-resistant enterococci.

Ampicillin Resistance↗
PubMed1993

Gene deletion suggests a role for Trypanosoma cruzi surface glycoprotein GP72 in the insect and mammalian stages of the life cycle.

We have explored the biological function of a surface glycoprotein (GP72) of Trypanosoma cruzi by studying a null mutant parasite, generated by targeted gene deletion. GP72 deletion affected parasite morphology in several stages of the life cycle. Insect midgut (epimastigote) forms had a detached flagellum (apomastigote) in the null mutant. The abnormal flagellar phenotype persisted during development of the infective (metacyclic) forms but there was no impairment in the acquisition of complement resistance, sialidase expression or cell infectivity. The GP72 null mutant could efficiently infect and proliferate in mouse macrophages and non-phagocytic L6E9 cells. The mammalian stages of the life cycle also showed major morphological abnormalities. During early subcultures in L6E9 cells, few extracellular fully flagellated forms, expressing markers characteristic of trypomastigotes, were seen. The extracellular population consisted almost exclusively of rounded forms with short flagella (micromastigote), which expressed an amastigote-specific surface marker and no sialidase. The propagation of the parasite was not affected, despite the apparent lack of the trypomastigote forms, which are thought to be primarily responsible for cell invasion. After some subcultures, the extracellular population changed to about equal numbers of micromastigotes and a range of flagellated forms that still did not include true trypomastigotes. Instead, the kinetoplast remained close to the nucleus and the flagellum emerged from the middle of the cell (mesomastigote). Half of the flagellum adhered to the cell body and the remainder was free at the anterior end. In Triatoma infestans, the survival of the mutant was dramatically reduced, suggesting that either GP72 itself, or the altered properties of the flagellum, were critical for establishment in the insect vector.

Animals↗
PubMed1993

Caffeine withdrawal: apparent heterologous sensitization to adenosine and prostacyclin actions in human platelets.

Chronic exposure to caffeine increases the number of adenosine receptors (up-regulation) but these observations have been mostly limited to animal models that study A1 adenosine receptors. The regulation of adenosine receptors by caffeine in humans and, in particular A2 receptors, remains largely unexplored. The purpose of this study was to test the hypothesis that withdrawal from chronic caffeine administration results in up-regulation of A2 adenosine receptors in humans. The authors also wanted to determine whether caffeine induces homologous or heterologous up-regulation. Caffeine 250 mg three times daily was given orally to a total of 19 normal volunteers for 7 days. Platelets were obtained at base line and 12 and 60 hr after the last dose of caffeine and the antiaggregation responses to adenosine and prostacyclin receptors were evaluated ex vivo. Plasma caffeine levels remained elevated at 22 microM 12 hr after the last dose but decreased to 0.6 microM at 60 hr. Adenosine receptor activation with the agonist 5'-N-ethylcarboxamidoadenosine and prostacyclin receptor activation with iloprost or prostaglandin E1 produced a greater antiaggregation effect at 60 hr postcaffeine. Increased responsiveness to both receptors could also be demonstrated at 12 hr after removal of caffeine by washing the platelets. Sensitization to the actions of prostacyclin, however, was reversed if caffeine was added ex vivo. These results support the hypothesis that chronic caffeine exposure induces heterologous up-regulation of adenosine and prostacyclin receptors in humans and implies that endogenous adenosine normally modulates platelet adenosine receptors in vivo. These findings may be relevant to the caffeine withdrawal syndrome observed in humans.

Adenosine↗
PubMed1992

Identity of a membrane-bound vasoactive intestinal peptide-binding protein with calmodulin.

A vasoactive intestinal peptide (VIP)-binding protein purified from guinea pig lung membranes (p18) was digested with trypsin, and the amino acid sequence of the peptide fragments was determined. The sequence of six tryptic fragments of p18 was identical with subsequences present in mammalian calmodulin. Authentic porcine brain calmodulin and p18 co-migrated on an sodium dodecyl sulfate-electrophoresis gel and displayed identical chromatographic behavior on a reverse phase high performance liquid chromatography column. The VIP-binding properties of p18 and calmodulin were indistinguishable. Both proteins displayed saturable and apparent high affinity binding of VIP, evidenced by potent inhibition of complexation with [Tyr10-125I]VIP by unlabeled VIP (IC50 = 6.0-8.1 nM). Rat growth hormone releasing factor and a C terminally extended form of VIP ([Leu17]VIP-GKR) also displayed potent inhibition of the binding (IC50 = 6.4 and 4 nM, respectively). These neuropeptides are potential modulators of calmodulin function.

Amino Acid Sequence↗
PubMed1992

Peptidolytic monoclonal antibody elicited by a neuropeptide.

We report evidence that a monoclonal antibody raised by immunization with a vasoactive intestinal peptide (VIP)-carrier protein conjugate selectively hydrolyzes VIP and a fluorescence quenched decapeptide (FQ14-22D), representing the region of VIP most susceptible to autoantibody-mediated cleavage (residues 14-22). A high affinity of the antibody for VIP and a lower affinity for FQ14-22D were revealed by kinetic studies and further substantiated by potent inhibition of FQ14-22D cleaving activity by full-length VIP. Sequencing of FQ14-22D hydrolysis products indicated selective cleavage at one peptide bond. These observations suggest that antibodies induced against naturally occurring polypeptide antigens can express peptidolytic activity targeted for specific sequences in the recognition epitope.

Amino Acid Sequence↗