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Biomedical subjects

R Weiss

Publications and source records attributed to R Weiss.

At least 55 records · Page 3Linked to original sources
PubMed2002

Effects of ketanserin and DOI on spontaneous and 5-HT-evoked peristalsis of the pig ureter in vivo.

1. The influence of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on the ureter motility was investigated in vivo on intact ureters of anaesthetized pigs. Drugs were administered intravenously or topically. 2. 5-HT induced a dose-dependent increase in the frequency of ureter contractions in anaesthetized pigs when given intravenously (0.0001-1 mg kg(-1); ED(50) 0.066 mg kg(-1)) or topically (0.001-1 mg ml(-1); EC(50) 0.043 mg ml(-1)). Significant increases in heart rate and blood pressure were observed when the drug was given intravenously but not topically. 3. The 5-HT(2A) agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) increased the frequency of ureteral contractions in a dose-dependent manner (1-300 microg kg(-1) i.v.). Calculation of ED(50) indicated this compound to be about 1.5 times more potent with an efficacy of 23% compared to 5-HT. 4. The 5-HT(2A/2C) antagonist, ketanserin (0.5 mg kg(-1)) and the 5-HT(2C) antagonist, methysergide (1 mg kg(-1)) antagonized the 5-HT-induced ureter peristalsis when given intravenously. Contraction amplitude, blood pressure and heart rate were not affected by the antagonists. 5. Intravenous (0.0001-1 mg kg(-1)) and topical (0.0001-1 microg ml(-1)) ketanserin significantly decreased the frequency of spontaneous ureteral contractions to about 30% of controls, which could be partly reversed by 5-HT (0.3 mg kg(-1) i.v.). The contraction amplitude, contractions of the contralateral, saline perfused ureter, heart rate and mean arterial blood pressure were not affected. 6. Thus, contractility of porcine ureter is mediated by 5-HT(2) receptors. Their antagonists ketanserin and methysergide seem to be promising drugs for treatment of acute ureteric colic or in preparing the ureter for ureteroscopy.

Animals↗
PubMed2002

Uveal metastatic carcinoma in human immunodeficiency virus infection.

We report the occurrence of uveal metastatic carcinoma in two patients with longstanding HIV infection presenting with decreased visual acuity. In the first case, a 49-year-old man with a 6-year history of HIV infection presented with a 4-5 month history of blurred vision in his right eye. In the second case, a 53-year-old man with a 5-year history of HIV infection presented with a 3-week history of distorted and blurred vision in both eyes. In both cases, a choroidal metastatic carcinoma was ultimately discovered. To our knowledge, these are the first reported cases of metastatic uveal carcinoma in individuals with HIV infection. Currently, there have been dramatic improvements in treatment for HIV infection and longer survival times of infected individuals. This fact, together with reported increased frequencies and aggressiveness of carcinomas in HIV-infected individuals will likely result in increasing occurrences of uveal metastases from primary carcinomas in HIV.

Choroid Neoplasms↗
PubMed2002

5-Hydroxytryptamine mediated contractions in isolated preparations of equine ileum and pelvic flexure: pharmacological characterization of a new 5-HT(4) agonist.

The effects of 5-hydroxytryptamine (5-HT), HTF 919, a new 5-HT(4) agonist, and the antagonists SB 203-186 (5-HT(4)) and tropisetron (5-HT(3)) on intestinal motility were tested in vitro on isolated preparations of horse ileum and pelvic flexure. Concentration-response curves were created by cumulative application of the agonists with or without preincubation of the antagonists. The 5-HT preparation induced a concentration-dependent contraction in equine ileum and pelvic flexure. The results indicate that 5-HT receptors are present in all parts of equine intestine investigated in this study. Tropisetron was found to act as a noncompetitive antagonist in all locations of the equine intestine. SB 203-106 was confirmed as an antagonist to 5-HT in the equine ileum circular muscle, in pelvic flexure circular and longitudinal muscle. Nevertheless, a discernible increase of smooth muscle contractions caused by HTF 919 could only be observed in pelvic flexure. In accordance with an earlier study in the guinea pig, in the equine gut HTF 919 acted as a partial agonist for the 5-HT(4) receptor with an affinity constant in the nanomolar range. It is concluded that 5-HT receptors, and especially their subtypes, may represent a promising target for the treatment and prevention of gastrointestinal (GI) motility disorders in horses.

Animals↗
PubMed2001

Alkyl and aryl substituted corroles. 1. Synthesis and characterization of free base and cobalt containing derivatives. x-ray structure of (Me(4)Ph(5)Cor)Co(py)(2).

The synthesis, spectroscopic properties, and electrochemistry of six different alkyl- and aryl-substituted Co(III) corroles are presented. The investigated compounds contain methyl, ethyl, phenyl, or substituted phenyl groups at the eight beta-positions of the corrole macrocycle and four derivatives also contain a phenyl group at the 10-meso position of the macrocycle. Each cobalt corrole undergoes four reversible oxidations in CH(2)Cl(2) containing 0.1 M tetra-n-butylammonium perchlorate and exists as a dimer in its singly and doubly oxidized forms. The difference in potential between the first two oxidations is associated with the degree of interaction between the two corrole units of the dimer and ranges from an upper value of 0.62 V, in the case of (Me(6)Et(2)Cor)Co, to a lower value of about 0.17 V, in the case of four compounds which have a phenyl group located at the 10-meso position of the macrocycle. These Co(III) corroles strongly coordinate two pyridine molecules or one carbon monoxide molecule in CH(2)Cl(2) media, and ligand binding constants were evaluated using spectroscopic and electrochemical methods. The structure of (Me(4)Ph(5)Cor)Co(py)(2) was also determined by X-ray diffraction. Crystal data: (Me(4)Ph(5)Cor)Co(py)(2).3CH(2)Cl(2).H(2)O, orthorhombic, a = 19.5690(4) A, b = 17.1070(6) A, c = 15.9160(6) A, V = 5328.2(5) A(3), space group Pna2(1), Z = 2, 35 460 observations, R(F) = 0.069.

Journal Article↗
PubMed2001

Alkyl and aryl substituted corroles. 2. Synthesis and characterization of linked "face-to-face" biscorroles. X-ray structure of (BCA)Co(2)(py)(3), where BCA represents a biscorrole with an anthracenyl bridge.

The synthesis, spectroscopic properties, and electrochemistry of (BCA)Co(2) and (BCB)Co(2) are described where BCA and BCB represent biscorroles linked by an anthracenyl (A) or a biphenylenyl (B) bridge. The pyridine and CO binding properties of (BCA)Co(2) and (BCB)Co(2) are also presented, and one of the compounds in its pyridine-ligated form, (BCA)Co(2)(py)(3), is structurally characterized. The data on the biscorroles are compared on one hand to the monocorrole having the same substitution pattern and on the other hand to bisporphyrins having two Co(II) ions and the same anthracenyl or biphenylenyl linkers in order to better understand the interaction which occurs between the two corrole macrocycles. A parallel study on five different Co(III) phenyl-substituted corroles showed that bis-pyridine and mono-CO adducts are readily formed from the complexes in CH(2)Cl(2). This present paper examines how the ligand binding properties and electrochemistry of these Co(III) corroles are modified by the anthracenyl or biphenylenyl bridge which links the two macrocycles in a face to face orientation. An X-ray crystal structure was obtained for the tris-pyridine adduct of the anthracenyl bridged derivative, (BCA)Co(2)(py)(3), and gives the following results: C(127)H(99)Co(2)N(11).2CHCl(3), M = 2135.90, triclinic, space group P&onemacr;, a = 13.2555(5) A, b = 18.6406(8) A, c = 22.2140(9) A, alpha = 94.186(9) degrees, beta = 102.273(9) degrees, gamma = 94.205(9) degrees, V = 5326.8(4) A(3), 9293 independent reflections collected, R(F) = 0.066.

Journal Article↗
PubMed2001

The Fe-only nitrogenase from Rhodobacter capsulatus: identification of the cofactor, an unusual, high-nuclearity iron-sulfur cluster, by Fe K-edge EXAFS and 57Fe Mössbauer spectroscopy.

Samples of the dithionite-reduced FeFe protein (the dinitrogenase component of the Fe-only nitrogenase) from Rhodobacter capsulatus have been investigated by 57Fe Mössbauer spectroscopy and by Fe and Zn EXAFS as well as XANES spectroscopy. The analyses were performed on the basis of data known for the FeMo cofactor and the P cluster of Mo nitrogenases. The prominent Fourier transform peaks of the Fe K-edge spectrum are assigned to Fe-S and Fe-Fe interactions at distances of 2.29 A and 2.63 A, respectively. A significant contribution to the Fe EXAFS must be assigned to an Fe backscatterer shell at 3.68 A, which is an unprecedented feature of the trigonal prismatic arrangement of iron atoms found in the FeMo cofactor of nitrogenase MoFe protein crystal structures. Additional Fe...Fe interactions at 2.92 A and 4.05 A clearly indicate that the principal geometry of the P cluster is also conserved. Mössbauer spectra of 57Fe-enriched FeFe protein preparations were recorded at 77 K (20 mT) and 4.2 K (20 mT, 6.2 T), whereby the 4.2 K high-field spectrum clearly demonstrates that the cofactor of the Fe-only nitrogenase (FeFe cofactor) is diamagnetic in the dithionite-reduced ("as isolated") state. The evaluation of the 77 K spectrum is in agreement with the assumption that this cofactor contains eight Fe atoms. In the literature, several genetic and biochemical lines of evidence are presented pointing to a significant structural similarity of the FeFe, the FeMo and and the FeV cofactors. The data reported here provide the first spectroscopic evidence for a structural homology of the FeFe cofactor to the heterometal-containing cofactors, thus substantiating that the FeFe cofactor is the largest iron-sulfur cluster so far found in nature.

Ferredoxins↗
PubMed2001

Evidence of infectious diseases in harbour porpoises (Phocoena phocoena) hunted in the waters of Greenland and by-caught in the German North Sea and Baltic Sea.

The pathological, microbiological and serological findings in harbour porpoises hunted in Greenlandic waters were compared with the findings in animals accidentally caught in fishing gear in the German North Sea and Baltic Sea. The body condition of the Greenlandic animals was good, whereas nine of 23 German harbour porpoises were moderately to markedly emaciated. Both groups were infested with parasites. In the Greenlandic animals parasitism of the aural peribullar cavity with Stenurus minor, of the liver and pancreas with Orthosplanchnus mironovi, of the lungs with Halocercus species and of the subcutaneous and mammary tissue with Crassicauda species was generally associated with a mild inflammatory response. No diseases associated with bacteria were identified in any of the Greenlandic harbour porpoises. In the porpoises from the German North Sea and Baltic Sea, parasites were present in the aural peribullar cavity (S minor), liver (Campula oblonga), first and second gastric compartment (Anisakis simplex) and in the lungs (Pseudalius inflexus and Torynurus convolutus). Moderate to marked pulmonary parasitism and suppurative pneumonia, not observed in the Greenlandic porpoises, were present in 11 and 10, respectively, of the 23 German porpoises. The suppurative pneumonia was attributed to bacterial infection with beta-haemolytic streptococci and Escherichia coil var haemolytica. Four Greenlandic and 10 German porpoises had positive porpoise morbillivirus-specific antibody titres suggesting that the virus was circulating in both populations.

Animals↗
PubMed2001

Seroepidemiology and molecular epidemiology of Kaposi's sarcoma-associated herpesvirus among Jewish population groups in Israel.

BACKGROUND: The incidence of classic Kaposi's sarcoma among Jews in Israel is among the highest in the developed world. Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) is causally linked to Kaposi's sarcoma. Very little is known about the prevalence of KSHV in the Middle East or about the modes of transmission in Mediterranean countries. METHODS: From 1992 through 1995, sera were obtained from 1648 adults who had tested positive for hepatitis B virus (HBV) surface antigen 20 years earlier at blood donations; sera were also obtained from 2403 of their family members. All sera were tested for anti-KSHV antibodies with the use of an indirect immunofluorescence assay. To analyze the effects of various factors on the risk of KSHV infection for both the HBV-positive cohort and their families, logistic regression for cluster data and generalized estimating equations were used. All statistical tests were two-sided. RESULTS: Among family members, the seroprevalence of antibodies against KSHV was 9.9% (95% confidence interval [CI] = 8.7% to 11.1%); among the former blood donors who had tested positive for hepatitis B, it was 22% (95% CI = 19.9% to 24.1%). Overall, the best predictor of KSHV status was the place of birth. The most important risk factors found for both husband and wife to test KSHV positive were their own places of birth and their spouse's seropositivity. For a child to test positive, the most important risk factor was maternal seropositivity. CONCLUSIONS: The crude prevalence rate of KSHV among the Jewish population in Israel is 9.9%. Important routes of KSHV transmission in the families studied are spouse to spouse and mother to child. The presence of KSHV in Jews in Israel of all ethnic origins and their high incidence of reported Kaposi's sarcoma suggest that KSHV was introduced into the Jewish population prior to the major Diaspora.

Adolescent↗
PubMed2001

Removal of the circumsporozoite protein (CSP) glycosylphosphatidylinositol signal sequence from a CSP DNA vaccine enhances induction of CSP-specific Th2 type immune responses and improvesprotection against malaria infection.

The C terminus of the circumsporozoite protein (CSP) is anchored to the parasite cell membrane by a glycosylphosphatidylinositol (GPI) glycolipid. This GPI signal sequence functions poorly in heterologous eukaryotic cells, causing CSP retention within internal cell organelles during genetic immunization. Cellular location of antigen has quantitative and qualitative effects on immune responses induced by genetic immunization. Removal of the GPI signal sequence had a profound effect on induction and efficacy of CSP-specific immune response after genetic immunization of BALB/c mice with a gene gun. The CSP produced from the plasmid lacking the GPI anchor signal sequence (CSP-A) was secreted and soluble, but that produced by the CSP+A plasmid was not. The CSP-A plasmid induced a highly polarized Th2 type response, in which the CSP-specific IgG antibody titer was three- to fourfold higher, and the protective effect was significantly greater than that induced by the CSP+A plasmid. Thus, these two physical forms of CSP induced quantitatively and qualitatively different immune responses that also differed in protective efficacy. Engineering plasmid constructs for proper cellular localization of gene products is a primary consideration for the preparation of optimally efficacious DNA vaccines.

Animals↗
PubMed2001

High lane density slab-gel electrophoresis using micromachined instrumentation.

In this paper, micromachined pipette arrays (MPAs) and microcombs were studied as a means of enabling high lane density gel electrophoresis. The MPA provide a miniaturized format to interface sub-microliter volumes of samples between macroscale sample preparation formats and microscale biochemical analysis systems. The microcombs provide a means of creating sample loading wells in the gel material on the same center-to-center spacing as the MPAs. Together, the two micromachined instruments provide an alternative to current combs and pipetting technologies used for creating sample loading wells and sample delivery in gel electrophoresis systems. Using three designs for the microcomb-MPA pair, center-to-center spacings of 1.0 mm, 500 microm, and 250 microm are studied. The results demonstrate an approximate 10-fold increase in lane density and a 10-fold reduction in sample size from 5 microL to 500 pL. As a result, the number of theoretical plates has increased 2.5-fold, while system resolution has increased 1.5-fold over the conventional agarose gel systems. An examination of changes in resolution across the width of individual separation lanes in both systems revealed dependence in the case of the conventional gels and no dependence for the gels loaded with the micromachined instrumentation.

Bromphenol Blue↗
PubMed2001

Production of correctly folded Fab antibody fragment in the cytoplasm of Escherichia coli trxB gor mutants via the coexpression of molecular chaperones.

Disulfide bonds are normally formed after a polypeptide has been exported from the reducing environment of the cytoplasm into a more oxidizing compartment, such as the bacterial periplasm. Recently, we showed that in Escherichia coli trxB gor mutants, in which the reduction of thioredoxin and glutathione is impaired, the redox potential of the cytoplasm becomes comparable to that of the mammalian endoplasmic reticulum, thus allowing the formation of disulfide bonds in certain complex proteins (P. H. Bessette et al., 1999, Proc. Natl. Acad. Sci. USA 96, 13703-13708]. Here, we investigate the expression of a Fab antibody fragment in the bacterial cytoplasm. The effect of coexpressing cytoplasmic chaperones (GroEL/ES, trigger factor, DnaK/J), as well as signal sequenceless versions of periplasmic chaperones (DsbC and Skp), was examined. Skp coexpression was shown to have the most significant effect (five- to sixfold increase) on the yield of correctly folded Fab. A maximum yield of 0.8 mg Fab/L/OD(600) Fab was obtained, indicating that cytoplasmic expression may be a viable alternative for the preparative production of antibody fragments.

Amino Acid Sequence↗
PubMed2001

Valence-tautomerism in high-valent iron and manganese porphyrins.

Iron and manganese hemes are "high-valent" when the valence state of the metal exceeds III. Redox chemistry of the high valent metal complexes involves redistribution of holes and electrons over the metal ion and the porphyrin and axial ligands, defined as valence tautomerism. Thus, catalytic pathways of heme-containing biomolecules such as peroxidases, catalases and cytochromes P450 involve valence tautomerism, as do pathways of biomimetic oxygen transfer catalysis by manganese porphyrins, robust catalysts with potential commercial value. Determinants of the site of electron abstraction are key to understanding valence tautomerism. In model systems, metal-centered oxidation is supported by hard anionic axial ligands that are also strongly pi-donating, such as oxo, aryl, bix-methoxy and bis-fluoro groups. Manganese(IV) is more stable than iron(IV) and metal-centered one-electron oxidations occur with weaker pi-donating axial ligands such as bisazido, -isocyanato, -hypochlorito and bis chloro groups. Virtually all known high-valent iron porphyrin complexes oxidized by two-electrons above the ferric state are coordinated by the strongly pi-donating oxo or nitrido ligands. In all well-characterized oxo complexes, iron is in the ferryl state and the second oxidizing equivalent resides on the porphyrin. Complexes with iron(V) have not been definitively characterized. One-electron oxidation of oxomanganese(IV) porphyrin complexes gives the oxomanganese(IV) porphyrin pi-cation redicals. In aqueous solution, oxidation of Mn(III) complexes of tetra cationic N-methylpyridiniumylporphyrin isomers by monooxygen donors yields a transient oxomanganese(V) species.

Catalase↗
PubMed2001

Systemic and topical drug administration in the pig ureter: effect of phosphodiesterase inhibitors alpha1, beta and beta2-adrenergic receptor agonists and antagonists on the frequency and amplitude of ureteral contractions.

PURPOSE: We searched for compounds that are pharmacologically active on ureteral motility for treating ureteral colic to ease retrograde access into the ureter and improve the clearance of stones or stone particles from the ureter. The effects of the alpha1-adrenergic receptor agonist phenylephrine, the nonselective beta and beta2-adrenergic receptor agonists isoproterenol and fenoterol, and the phosphodiesterase inhibitors papaverine (nonspecific) and rolipram (type IV) on the frequency and amplitude of ureteral contractions when administered intravenously or topically were investigated in pigs. MATERIALS AND METHODS: A total of 52 pigs were anesthetized. A double lumen 6Fr catheter was inserted through each renal pelvis and into the ureter, allowing perfusion of saline or drug solution into the renal pelvis and the recording of contractions from the mid portion of the ureter. RESULTS: The alpha1 and beta-adrenergic receptors of the ureter are not tonically activated by endogenous epinephrine or norepinephrine. Phenylephrine administered intravenously at a dose of 0.01 to 3 mg./kg. and topically at 0.1 to 3 mg./ml. per minute increased contraction frequency 10 and 4-fold, respectively, and contraction amplitude 2-fold each in a dose dependent manner. Arterial blood pressure increased markedly during intravenous administration of phenylephrine but was minimally affected during topical application. The phenylephrine effects were reversed by the antagonist prazosin. Isoproterenol administered intravenously at a dose of 0.01 to 10 mg./kg. and topically at 0.1 to 200 microg./ml. per minute decreased contraction frequency to 13% and 31% of controls, respectively. Contraction amplitude was not affected by intravenous administration but decreased to 59% of controls when applied topically. These effects were also observed with a slight delay in the saline perfused contralateral ureter. The heart rate also increased, suggesting absorption of the drug by the urothelium. The isoproterenol effects were blocked by the antagonist propranolol. Fenoterol administered intravenously at a dose of 0.1 to 30 microg./kg. and topically at 0.003 to 1 mg./ml. per minute decreased contraction frequency to 14% and 10% of controls, and contraction amplitude to 84% and 65%, respectively. These effects on the drug perfused ureter were also observed on the contralateral saline perfused ureter but to a lesser extent. The fenoterol effects were blocked by the antagonist propranolol. Papaverine administered intravenously at a dose of 0.001 to 3 mg./kg. decreased contraction frequency to 33% of controls. Topically administered papaverine as well as intravenous and topically administered rolipram had no relevant effect on ureteral motility. CONCLUSIONS: Intravenous phenylephrine increases, and isoproterenol and fenoterol decrease the frequency and amplitude of ureteral contractions in the pig. The same effects are observed with the topical administration of phenylephrine, which causes a significant local but not systemic side effect. Topical administration of isoproterenol and fenoterol produced local as well as systemic effects, suggesting absorption by the urothelium. However, to our knowledge a drug that relaxes ureteral peristalsis in pigs without causing systemic side effects has not yet been identified.

Administration, Topical↗
PubMed2001

Singer's formant in sopranos: fact or fiction?

Although it is generally agreed that the singer's formant (F(S)) is a prerequisite for successful stage performance, the results of this research do not support its presence in the soprano voices of trained female singers. Results are based on a recent investigation testing 10 advanced/professional sopranos in two groups singing sustained vowels at three frequencies: high (932 Hz), mid (622 Hz), and low (261 Hz). Spectrographic analysis shows that the nature of harmonic energy varies in relation to pitch. A resonance band somewhat resembling the tenor F(S) was usually evident in vowels sung at low and mid pitch. However, unlike the F(S) of typically less than 1 kHz bandwidth associated with tenors, sopranos singing similar pitches produced corresponding bandwidths which were significantly broader, usually at least 2-kHz wide. Vowels sung by sopranos at high-pitch levels exhibited strong fundamental frequency production with strong reinforcement of adjacent harmonics extending to 5 kHz and beyond. This type of production in essence nullifies the necessity for a typical F(S). Absence of the F(S) in strong soprano voices might also imply the adaptation of a sufficiently different overall vocal tract configuration, so that techniques geared to developing maximal projection should not be the same as those developed to maximize the F(S) in other voices.

Adult↗
PubMed2001

Molecular imprinting and solid phase extraction of flavonoid compounds.

Molecularly imprinted polymers (MIPs) for quercetin have been successfully prepared by a thermal polymerization method using 4-vinylpyridine (4-VP) and ethylene glycol dimethacrylate (EDMA) as functional monomer and cross-linker, respectively. The obtained molecularly imprinted polymers were evaluated by HPLC using organic eluents, with respect to their selective recognition properties for quercetin and related compounds of the flavonoid class. Two equivalent control polymers, a blank polymer and a polymer imprinted with a structural analogous template, were synthesized, in order to confirm the obtained results. Furthermore, preliminary experiments confirm the applicability of the prepared MIPs for solid phase extraction (SPE), as rapid and facile clean-up of wine samples for HPLC analysis is an envisaged field of application. The successful preparation of molecularly imprinted polymers for flavones provides an innovative opportunity for the development of advanced separation materials, with applications in the field of wine and fermentation analysis.

Chromatography, High Pressure Liquid↗