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Biomedical subjects

S Paul

Publications and source records attributed to S Paul.

At least 127 records · Page 7Linked to original sources
PubMed1998

Video recording feedback: a feasible and effective approach to teaching history-taking and physical examination skills in undergraduate paediatric medicine.

Medical educators have always recognized the need to teach and train medical graduates and undergraduates the skills of conducting a consultation. Several authors have established the efficacy of using constructive feedback on videotape of each student's interaction with a patient to teach and enhance such skills. This study reports 'students' perceptions' of the feedback process used in the Junior Paediatric Clerkship at the Faculty of Medicine of the United Arab Emirates University. An unexpected 73% of the respondents believed that self-observation influenced development of their clinical skills. More than 80% said that the feedback from instructors and peers helped them to improve their clinical skills, but they would have liked to have more than one of their consultations recorded and reviewed. It was found that 75% of the students felt that self-critique of their performance made them aware of their strengths and weaknesses and their skills in analysing and evaluating consultations had been enhanced. It was found from Kruskal Wallis one-way ANOVA that the students' professional attitude, empathy, and warmth towards the patients differed highly significantly (P = 0.0062, 0.0089, 0.0007, respectively) from self-assurance, self-confidence and competence. They were also deficient in certain areas of history-taking, interviewing skills, and physical examination techniques and perceived they needed more training in order to be proficient.

Clinical Competence↗
PubMed1998

Validity of visual stabilization conditions used with computerized dynamic platform posturography.

Temporal and spatial relationships between head motion and tilt of a visual surround were evaluated in conditions 3 and 6 of the sensory organization test (SOT) to determine the validity of visual stabilization during computerized dynamic platform posturography (CDP). Seven healthy subjects participated (mean age 42.4 years, SD = 19 years, range 25-72 years). Sagittal head translation and head pitch were evaluated separately with respect to displacement of the visual surround. Overall, the mean correlation between sagittal head motion and surround tilt was r = 0.68 for C3 and r = 0.93 for C6. The average phase (aggregate findings supported with trial-by-trial analysis), however, showed that sagittal head displacement leads motion of the visual surround ( + 452 ms for C3 and + 250 ms for C6). The mean correlation between head pitch and surround tilt was r = -0.30 for C3 and r = -0.72 for C6. Head pitch also leads visual surround motion (+567 ms for C3 and +539 ms for C6), but with greater variability than sagittal head translation. The results showed that visual stabilization was not consistently achieved during SOT conditions 3 and 6. The fundamental assumption that posture behaves as an inverted pendulum, with control of equilibrium originating in the lower extremities, does not appear to be applicable to the voluntary corrections of sway required during the SOT.

Adult↗
PubMed1998

Transurethral prostate ablation using saline-liquid electrode introduced via flexible cystoscope.

An interstitial saline-electrode has been developed to couple radiofrequency (RF) energy to prostate tissue in order to produce large lesions quickly and controllably. In this study, we attempted to produce similar results using a flexible catheter introduced transurethrally via a flexible cystoscope. An insulated 4F catheter with an extendable needle electrode (26-gauge, 5-mm exposed metal tip) was introduced through a port of a flexible cystoscope into the urethra of 10 dogs via a small perineal incision (required for the canine U-shaped urethra). Under visual endoscopic guidance, the electrode was placed in the center of the prostate and the needle electrode extended at an angle into the prostate, one lobe at a time. Hypertonic saline (14.6% NaCl) was infused at 2 mL/min through the needle electrode into the tissue for 30 seconds before and during RF application. The energy (50 W, 475 kHz) was delivered for 30, 45, 60, or 90 seconds (RFT System; U.S. Surgical Corporation). Prostate and urethral temperatures were monitored using thermocouples mounted on the catheter. There was an automatic high-temperature shut-off if the urethra reached >42 degrees C or if impedance reached >300 omega during RF energy application. Prostate sizes ranged from 1.4 x 2.0 x 1.4 cm to 5.0 x 4.5 x 4.2 cm. In this group, there were no automatic shut-offs at any of the energy durations, and the lesions produced ranged from 1.3 x 1.3 x 1.1 cm (0.99 cm3) to 1.6 x 2.7 x 2.2 cm (5.03 cm3). The average ablation volumes produced were 1.76 cm3 at 30 seconds' RF application, 2.42 cm3 at 45 seconds, 3.96 cm3 at 60 seconds, and 5.03 cm3 at 90 seconds. Histologic examination revealed typical coagulation necrosis in the treatment zone without tissue desiccation. Introduction of the saline-electrode through a flexible cystoscope provides a minimally invasive procedure that quickly and controllably produces large lesions that may provide effective treatment for benign prostatic hyperplasia with less patient discomfort.

Animals↗
PubMed1998

Vasodilation elicited by liposomal VIP is unimpeded by anti-VIP antibody in hamster cheek pouch.

The purpose of this study was to determine whether a monoclonal anti-vasoactive intestinal peptide (VIP) antibody, which binds VIP with high affinity and specificity and catalyzes cleavage of the peptide in vitro, attenuates VIP vasorelaxation in vivo and, if so, whether insertion of VIP on the surface of sterically stabilized liposomes (SSL), which protects the peptide from trypsin- and plasma-catalyzed cleavage in vitro, curtails this response. Using intravital microscopy, we found that suffusion of monoclonal anti-VIP antibody (clone c23.5, IgG2ak), but not of nonimmune antibody (myeloma cell line UPC10, IgG2ak) or empty SSL, significantly attenuates VIP-induced vasodilation in the in situ hamster cheek pouch (P < 0.05). By contrast, anti-VIP antibody has no significant effects on vasodilation elicited by isoproterenol, nitroglycerin, and calcium ionophore A-23187, agonists that activate intracellular effector systems in blood vessels that mediate, in part, VIP vasoreactivity. Suffusion of VIP on SSL, but not of empty SSL, restores the vasorelaxant effects of VIP in the presence of anti-VIP antibody. Collectively, these data suggest that VIP catalysis by high affinity and specific VIP autoantibodies displaying protease-like activity constitutes a novel mechanism whereby VIP vasoreactivity is regulated in vivo.

Animals↗
PubMed1998

Reproductive endocrine and endometrial effects of raloxifene hydrochloride, a selective estrogen receptor modulator, in women with regular menstrual cycles.

Previous studies of raloxifene conducted in animal models and postmenopausal women have demonstrated antiestrogenic action on the endometrium. The purpose of this first study of raloxifene in women with normal menstrual cycles was to determine its reproductive endocrine and endometrial effects. In part I, raloxifene (400 mg) was administered for 5 days in the follicular, periovulatory, or luteal phase of the menstrual cycle (n = 12). In part II, women were randomized to receive raloxifene (100 or 200 mg) for 28 days beginning on day 3 of the cycle (n = 19). All women ovulated in both parts of the study. Raloxifene did not alter the length of the menstrual cycle or the day of the LH surge. A 5-day course of raloxifene administered in any phase of the cycle elevated FSH area under the curve (AUC) for the entire cycle and estradiol AUC for the second half of the cycle compared with those in control cycles. In part II, raloxifene also appeared to increase the FSH AUC and estradiol AUC. Raloxifene decreased the number of gland mitoses in follicular phase endometrial biopsies. Subtle effects suggestive of gland-stromal dysynchrony were noted in a limited number of the secretory phase endometrial biopsies. This study has demonstrated that 1) raloxifene does not prevent ovulation in women with normal menstrual cycles; 2) ovarian estrogen production will continue, and in some cases increase, in response to raloxifene; and 3) antiestrogenic effects of raloxifene on the endometrium are subtle in the endocrine milieu of normal to high circulating estradiol concentrations.

Adult↗
PubMed1998

Induction of apoptosis in Neuro-2A cells by Zn2+ chelating.

Metal ions such as Ca2+, Mg2+, or Zn2+, are important for many cell functions, for example, signal transduction and the modulation of enzyme activity. The relationship between apoptosis and metal cations, especially Ca2+, has been described in many reports. We have investigated the role of metal cations in the regulation of apoptosis in the mouse neuroblastoma cell line, Neuro-2A. When Neuro-2A cells were treated with ethylene diaminetetraacetic acid (EDTA), apoptosis was detected as growth inhibition, DNA fragmentation with a ladder pattern in agarose gel electrophoresis, and nuclear decomposition. However, in case of the treatment with ethylene glycol bis- (beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), which has a higher chelating specificity for Ca2+ than EDTA, DNA fragmentation was not detected. Moreover, the apoptosis induced by EDTA was inhibited by exogenous Zn2+. The membrane permeable Zn2+ chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) also induced apoptosis of the Neuro-2A cells, and addition of equimolar exogenous Zn2+ or Cu2+, but not Mn2+ or Fe2+, prevented TPEN-induced apoptosis. The results suggest that Zn2+ may be a key regulator of apoptosis in Neuro-2A cells.

Animals↗
PubMed1998

Stabilization of vasoactive intestinal peptide by lipids.

An anionic phospholipid, phosphatidylglycerol (PG), induced vasoactive intestinal peptide (VIP) to adopt a helical conformation, determined by circular dichroism studies. PG inhibited the trypsin-catalyzed, antibody-catalyzed and uncatalyzed cleavage of VIP, measured by radiometric and HPLC methods. Phosphatidylcholine, a neutral lipid, did not alter the circular dichroism spectra of VIP, and it was without detectable effect on the rates of VIP cleavage. Trypsin-catalyzed cleavage of Boc-Ile-Glu-Arg-methylcoumarinamide, a substrate unrelated in sequence to VIP, proceeded at equivalent rates in the absence and presence of PG, which suggests that the phospholipid did not exert a nonspecific inhibitory effect on the enzyme. Study of the kinetics of antibody-catalyzed VIP cleavage indicated that the inhibition by PG was due to decreased affinity for VIP, suggested by observations of increased K(m) values and unaltered Vmax values. Incorporation of VIP in the liposomes and the liposomal surface permitted maintenance of the peptide in essentially undegraded form at 37 degrees C for 8 days. The longevity of liposomal VIP administered i.v. to mice was increased by about 5-fold compared with aqueous VIP. These observations indicate that certain phospholipids and liposomes can be applied to circumvent the rapid loss of VIP in vitro and in vivo due to degradative processes.

Amino Acid Sequence↗
PubMed1997

A novel juxtamembrane domain isoform of HER4/ErbB4. Isoform-specific tissue distribution and differential processing in response to phorbol ester.

Human epidermal growth factor receptor 4 (HER4) is a member of the epidermal growth factor (EGF) receptor subfamily of receptor tyrosine kinases that is activated by neuregulins (NRG), betacellulin (BTC), and heparin-binding EGF-like growth factor. Sequencing of full-length human HER4 cDNAs revealed the existence of two HER4 isoforms that differed by insertion of either 23 or 13 alternative amino acids in the extracellular juxtamembrane (JM) region. The 23-amino acid form (HER4 JM-a) and the 13-amino acid form (HER4 JM-b) were expressed in a tissue-specific manner, as demonstrated by reverse transcriptase-polymerase chain reaction analysis of mouse and human tissues. Both isoforms were expressed in neural tissues such as cerebellum, whereas kidney expressed HER4 JM-a only and heart HER4 JM-b only. In situ hybridization using specific oligonucleotides demonstrated transcription of both JM-a and JM-b isoforms in the mouse cerebellum. Tyrosine phosphorylation analysis indicated that both receptor isoforms were activated to the same extent by NRG-beta1 and BTC, and to a lesser extent by NRG-alpha1 and heparin-binding EGF-like growth factor. A functional difference was found, however, in response to phorbol ester treatment. Stimulation of cells with phorbol ester resulted in a loss of 125I-NRG-beta1 binding and in a reduction of total cell-associated HER4 protein in HER4 JM-a transfectants but not in HER4 JM-b transfectants. It was concluded that novel alternatively spliced isoforms of HER4 exist, that they are distributed differentially in vivo in mouse and human tissues, that they are both activated by HER4 ligands, and that they may represent cleavable and noncleavable forms of HER4.

Amino Acid Sequence↗
PubMed1997

Cleavage specificity of a proteolytic antibody light chain and effects of the heavy chain variable domain.

The recombinant light chain (L chain) of an antibody raised by immunization with vasoactive intestinal polypeptide (VIP) cleaved this peptide on the C-terminal side of basic residues. The major sites of cleavage in VIP were two adjacent peptide bonds, Lys20-Lys21 and Lys21-Tyr22. Lower levels of cleavage were evident at Arg14-Lys15 and Lys15-Gln16. Hydrolysis of radiolabeled VIP by the L chain was inhibited by two serine protease inhibitors, diisopropylfluorophosphate and aprotinin, but not by soybean or lima bean trypsin inhibitors or inhibitors of other classes of proteases. To probe the role of the VH domain, single chain Fv constructs composed of the VL domain of the anti-VIP L chain linked via a 14-residue peptide to its natural VH domain partner or an irrelevant anti-lysozyme VH domain (hybrid Fv) were prepared. The anti-VIP Fv hydrolyzed VIP with Ks 21.4-fold lower than the L chain and 250-fold lower than the hybrid Fv, suggesting increased affinity for the substrate ground state due to the anti-VIP VH domain. The kinetic efficiency (kcat/Ks) of the anti-VIP Fv was 6.6-fold greater compared to the L chain and 29.4-fold greater compared to the hybrid Fv. Peptide-MCA substrates unrelated in sequence to VIP were hydrolyzed by the anti-VIP Fv and L chain at equivalent rates. These observations lead to a model of catalysis by the anti-VIP Fv in which the essential catalytic residues are located in the VL domain and additional residues from the VH domain are involved in high affinity binding of the substrate.

Amino Acid Sequence↗
PubMed1997

Characterization of thyroglobulin-directed and polyreactive catalytic antibodies in autoimmune disease.

Polyreactive and thyroglobulin (Tg)-directed proteolytic activities present in the serum IgG of healthy controls and patients with autoimmune disease were studied by electrophoretic separation of 125I-labeled Tg reaction products and spectrofluorometric measurement of Pro-Phe-Arg-methylcoumarinamide cleavage at the Arg-methylcoumarinamide bond. A decrease of the polyreactive proteolytic activity accompanying an increase of the Tg-cleaving activity in IgG from autoimmune thyroiditis (ATh) and systemic lupus erythematosus (SLE) patients was evident. The Tg, a known target of autoimmune reactions in ATh, was cleaved at lower levels by Abs from patients with this disease than from SLE patients. The Tg-cleaving and Tg-binding activities of the autoantibody preparations were not correlated. Enhanced rates of cleavage at saturating substrate concentrations (Vmax), not increased Tg-binding affinities, were evident in IgG preparations with the greatest Tg-cleaving activity. Similarly, diminution of the polyreactive proteolytic activity in IgG from the autoimmune disease patients was due to decreased Vmax values, not decreased substrate-binding affinities. No cleavage of Tg by IgG from subjects with HIV-1 infection, or from mice hyperimmunized with an albumin-hapten conjugate was evident, suggesting that generation of Tg-cleaving Abs does not accompany V region affinity maturation in response to unrelated Ags. These observations establish Tg as a target of catalytic autoantibodies in SLE and ATh, suggest a transition from polyreactive proteolytic activity to autoantigen-directed activity in autoimmune disease, and open the possibility that combining site chemical reactivity is a factor driving the expression of catalytic activity by autoantibodies.

Autoantibodies↗
PubMed1997

Altered cleavage site preference of a proteolytic antibody light chain induced by denaturation.

A recombinant antibody light chain (L chain) maintained under non-denaturing conditions displayed preferential cleavage of synthetic peptides conjugated to methylcoumarinamide (MCA) on the C-terminal side of Arg and Lys residues. The same L chain renatured from a denaturing solvent (guanidine hydrochloride) acquired the capability of cleaving Tyr-MCA and Leu-MCA bonds, and its ability to cleave MCA linked to basic residues was decreased. The altered cleavage preference was accompanied by a conformational transition in the protein, evident from the fluorescence emission spectra. These observations suggest the feasibility of redirecting the cleavage specificity via alterations in the conformation of proteolytic antibody combining sites.

Amino Acid Sequence↗
PubMed1997

Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent mitogen and chemotactic factor for fibroblasts, smooth muscle cells and keratinocytes. It is demonstrated that HB-EGF is not only a ligand for HER1, as previously reported, but for HER4 as well. HB-EGF binds to NIH 3T3 cells overexpressing either HER1 or HER4 alone, but not HER2 or HER3 alone. Binding to HER4 is independent of HER1. The ability of HB-EGF to bind to two different receptors is in contrast to EGF which binds to HER1, but not to HER4, and heregulin-beta1 which binds to HER4, but not to HER1. Besides binding, HB-EGF activates HER4. For example (i) it induces tyrosine phosphorylation of HER4 in cells overexpressing this receptor and of endogenous HER4 in MDA-MB-453 cells and astrocytes; (ii) it induces association of phosphatidylinositol 3-kinase (PI3-K) activity with HER4; and (iii) it is a potent chemotactic factor for cells overexpressing HER4. Chemotaxis is inhibited by wortmannin, a PI3-K inhibitor, suggesting a possible role for PI3-K in mediating HB-EGF-stimulated chemotaxis. On the other hand, HB-EGF is not a mitogen for cells expressing HER4, in contrast to its ability to stimulate both chemotaxis and proliferation in cells expressing HER1. It was concluded that HER4 is a newly described receptor for HB-EGF and that HB-EGF can activate two EGF receptor subtypes, HER1 and HER4, but with different biological responses.

3T3 Cells↗
PubMed1997

Allogeneic transplantation after a conditioning regimen with ifosfamide, carboplatin and etoposide (ICE).

Successful allogeneic hematopoietic transplants require conditioning regimens with sufficient immunosuppression to allow acceptance of the allograft. Cyclophosphamide, in combination either with TBI or with chemotherapeutic drugs, is the keystone of commonly used regimens. The toxicities of TBI and tumor resistance to cyclophosphamide create a niche for alternative, chemotherapy-based conditioning regimens. We report successful allogeneic stem cell transplantation after an ifosfamide-based regimen with ifosfamide 20 g/m2, carboplatin 1.8 g/m2 and etoposide 3 g/m2 (ICE) in divided doses over 6 days. Engraftment was prompt with neutrophils > or = 20 x 10(9)/l on day +10 and platelets > 20 x 10(9)/l on day +18. Engraftment of donor cells was documented by chromosome analysis and by VNTR analysis. An ifosfamide-based regimen provides sufficient immunosuppression for hematopoietic allograft acceptance in the absence of cyclophosphamide or of TBI.

Antineoplastic Agents, Phytogenic↗