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Biomedical subjects

M Manning

Publications and source records attributed to M Manning.

At least 73 records · Page 4Linked to original sources
PubMed1994

Ureteral stone. Treatment using the Modulith SL 20 and Lithostar plus.

The treatment of ureteric calculi by extra-corporeal shock waves was found to have an 80% success rate by Mannheim authors, regardless of the site of the calculus. The authors compared two 3rd generation apparatuses: 1--the Siemens Lithostar Plus, in which waves are produced by a electromagnetic cylinder and focussed by a parabolic electromagnetic cylinder and focussed by a parabolic reflector: 2--the Storz Medical Modulith SL 10, in which waves produced by an electromagnetic coil are focussed by acoustic lenses. Both apparatuses are based upon image-intensification and ultrasonography concepts. No difference in efficacy was found between the two apparatuses. A second shock wave session was necessary in 16% of cases and some other type of additional treatment in 7% of cases.

Acoustics↗
PubMed1993

Synthesis of paraxanthine analogs (1,7-disubstituted xanthines) and other xanthines unsubstituted at the 3-position: structure-activity relationships at adenosine receptors.

Synthetic procedures for the preparation of various 3-unsubstituted xanthines, including paraxanthine analogs (1,7-disubstituted xanthines) and 1,8-disubstituted xanthines, were developed. Silylation of 1-substituted xanthines followed by alkylation at the 7-position provides a facile route to paraxanthine analogs. Regioselective alkylation of tris(trimethylsilyl)-6-aminouracil provides 3-substituted 6-aminouracils, which are converted to 1,8-disubstituted xanthines by standard procedures. The ring closure of 3-substituted 5-cyclopentanecarboxamido- and 5-(benzoylamino)-6-aminouracils requires drastic reaction conditions. Affinity for brain A1 and A2 adenosine receptors was determined in binding assays for these and other xanthines with substituents in 1-, 3-, 7-, 8-, and 9-positions. Substitution at the 1-position was necessary for high affinity at adenosine receptors. 1,3-Disubstituted xanthines generally had higher affinity than 1,7-disubstituted xanthines. 1,8-Disubstituted xanthines had high affinity for adenosine receptors; some were highly selective for A1 receptors.

Animals↗
PubMed1993

Effect of trifluoromethyl and other substituents on activity of xanthines at adenosine receptors.

An aryl p-(trifluoromethyl) substituent increases the affinity of 1,3-disubstituted 8-phenylxanthines at A2a-adenosine receptors, while having little effect on affinity at A1-adenosine receptors. In contrast, an aryl p-(trifluoromethyl) substituent has little effect on affinity of 3,7-disubstituted and 1,3,7-trisubstituted 8-phenylxanthines. An aryl p-sulfo substituent reduces affinity of all 8-phenylxanthines at A1- and A2a-adenosine receptors. An 8-(trifluoromethyl) substituent markedly reduces affinity of 1,3-dialkylxanthines at both A1- and A2a-adenosine receptors. In contrast, 8-(trifluoromethyl)caffeine retains affinity for A2a-adenosine receptors, but does lose affinity for A1-adenosine receptors. 8-Bromo-, 8-acryl-, and 8-pent-1-enylcaffeines are also selective for A2-adenosine receptors, while 8-cyclobutylcaffeine is nonselective. 8-[trans-2-(tert-butyloxycarbonyl)vinylcaffeine is 20-fold selective for Aza vs A1 receptors.

Acylation↗
PubMed1993

A general correspondence approach to apparent motion.

A general framework is considered for how different features of image parts determine the perceived direction of apparent motion between these parts as a function of their internalized feature weights. It is shown how the compatibility and constraints between pairwise part correspondences also play important roles in the types of perceived motion between parts; this process is modelled via a multivariate constraint-satisfaction procedure.

Adult↗
PubMed1993

Oxytocin receptor subtypes in the pregnant rat myometrium and decidua: pharmacological differentiations.

Oxytocin (OT) has a dual action in the uterus: a uterotonic action on myometrial cells and a prostaglandin (PG)-releasing action on endometrial/decidual cells. It had not been determined whether the OT-binding sites or receptors on the myometrial and the endometrial/decidual membranes are of the same type or may represent two subtypes. Our studies presented in this paper show that isolated day 19-22 pregnant rat uterine horns and myometrial tissues (uterine horns with decidual tissues removed) incubated in Kreb's buffer at 37 C released PGF2 alpha in sustained quantities into the bathing medium. OT stimulated PG release over the basal release rate in a dose-dependent manner in the whole uterine horn but not in the myometrial tissue. Two OT antagonists, P[Phe(Me)2,Thr4]ornithine vasotocin (antagonist A) and desGly-NH2(9),d(CH2)5(1)[Tyr(Me)2,Thr4]ornithine vasotocin (antagonist B) were found to have different effects on the PG-releasing action of OT. At antiuterotonic doses, antagonist A had no antagonism of the PG-releasing action of OT. On the contrary, antagonist A was found to stimulate uterine PG release. Antagonist B was a full OT antagonist. At equivalent antiuterotonic doses, antagonist B inhibited both the uterotonic action and the PG-releasing action of OT. These findings suggest that OT-sensitive PGs are synthesized/released principally in the endometrium/decidua. The myometrial uterotonic OT receptors and the endometrial/decidual PG-releasing OT receptors are two distinct subtypes and can be differentiated. The existence of two OT receptor subtypes in the uterus has important implications in the clinical application of OT antagonists as tocolytics for preterm labor. To be efficacious, OT antagonist therapy needs to block both the uterotonic and the PG-releasing action of OT.

Animals↗
PubMed1993

Design, synthesis and some uses of receptor-specific agonists and antagonists of vasopressin and oxytocin.

Selective agonists and antagonists are powerful tools for studies on AVP and OT receptors and on the physiological and pathophysiological roles of AVP and OT. Here we show how some of these peptides and their radiolabelled derivatives were designed. We also present examples of the currently available cyclic and linear OT and AVP agonists and antagonists from our laboratories.

Amino Acid Sequence↗
PubMed1992

Potent V2/V1a vasopressin antagonists with C-terminal ethylenediamine-linked retro-amino acids.

We report the solid-phase synthesis and antagonistic potencies of 25 analogues (1-25) of [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O-ethyl-D-tyrosine,4-valine]arginine-vasopressin (d(CH2)5D-Tyr(Et)2-VAVP) (A) and of the related Ile4 (D) and [D-Phe2,Ile4] (E) analogues, potent antagonists of the antidiuretic (V2-receptor) and of the vasopressor (V1a-receptor) responses to arginine-vasopressin (AVP). Six of these peptides (1, 13, 17, 19, 21, and 23) have the Pro-Arg-Gly-NH2 tripeptide side chain fully or partially replaced or extended by ethylenediamine (Eda). The remaining 19 peptides have L- or D-amino acids retrolinked to these six C-terminal Eda peptides. Peptides 1, 13, 17, and 19 all have the ring structure of (A). Their side-chain structures are as follows: 1, Eda; 13, Pro-Eda; 17, Pro-Arg-Eda; 19, Arg-Gly-Eda. Peptide 21 is the Pro-Arg-Eda analogue of D; peptide 23 is the Pro-Arg-Gly-Eda analogue of E. Peptide 2 is the retro-Arg analogue of 1. Its side-chain structure is Eda<--Arg. Peptides 3-6 are analogues of 2 which have the D-Tyr-(Et)2 residue replaced by L-Tyr(Et)2 (3), D-Phe2 (4), D-Ile2 (5), or D-Leu2 (6), respectively. Peptides 7-12 are analogues of 2 which have the C-terminal retro-Arg replaced in retrofashion by D-Arg (7), Gly (8), Orn (9), D-Orn (10), D-Lys (11), or Arg-Arg (12). Peptides 14-16 have D-Orn (14), D-Lys (15), and D-Arg (16) retrosubstituted to peptide 13. Peptides 18, 20, and 22 are the retro-Arg-substituted analogues of 17, 19, and 21, respectively. Peptides 24 and 25 have Val and D-Val in retrolinkage with 23, respectively. All 25 peptides were examined for agonistic and antagonistic potencies in AVP V2/V1a assays. With the exception of peptides 5 and 6, all exhibit potent anti-V1a antagonism, with anti-V1a pA2 values in the range 7.64-8.33.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1992

Synthesis and some pharmacological properties of potent and selective antagonists of the vasopressor (V1-receptor) response to arginine-vasopressin.

We report the solid-phase synthesis of eight position-9-modified analogues of the potent V1-receptor antagonist of arginine-vasopressin, [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O-methyltyrosine]arginine-vasopressin (d(CH2)5Tyr(Me)AVP) (1-8) and five position-9-modified analogues of the closely related beta,beta-dimethyl less potent V1 antagonist, [1-deaminopenicillamine,2-O-methyltyrosine]arginine-vasopressin (dPTyr(Me)AVP) (9-13). In d(CH2)5Tyr(Me)AVP the C-terminal Gly-NH2 was replaced by (1) ethylenediamine (Eda), (2) methylamine (NHMe), (3) Ala-NH2, (4) Val-NH2, (5) Arg-NH2, (6) Thr-NH2, (7) Gly-Eda, (8) Gly-N-butylamide (Gly-NH-Bu); in dPTyr(Me)AVP the C-terminal Gly-NH2 was replaced by (9) Ala-NH2, (10) Val-NH2, (11) Thr-NH2, (12) Arg-NH2, and (13) Tyr-NH2. All 13 analogues were tested for agonistic and antagonistic activities in in vivo rat vasopressor (V1-receptor) and rat antidiuretic (V2-receptor) assays. They exhibit no evident vasopressor agonism. All modifications in both antagonists were well-tolerated with excellent retention of V1 antagonism and striking enhancements in anti-V1/anti-V2 selectivity. With anti-V1 pA2 values of 8.75, 8.73, 8.86, and 8.78, four of the analogues of d-(CH2)5Tyr(Me)AVP (1-3 and 6) are equipotent with d(CH2)5Tyr(Me)AVP (anti-V1 pA2 = 8.62) but retain virtually none of the V2 agonism of d(CH2)5Tyr(Me)AVP. They are in fact weak V2 antagonists and strong V1 antagonists with greatly enhanced selectivity for V1 receptors relative to that of d(CH2)5Tyr(Me)AVP. With anti-V1 pA2 values respectively of 8.16, 8.05, 8.04, 8.52, and 8.25, all five analogues (9-13) of dPTyr(Me)AVP are at least as potent V1 antagonists as dPTyr(Me)AVP (pA2 = 7.96) and three of these (9, 12, 13) actually show enhanced V1 antagonism over that of dPTyr(Me)AVP. In fact, the Arg-NH2(9) analogue (12) is almost equipotent with d(CH2)5Tyr(Me)AVP. These new V1 antagonists are potentially useful as pharmacological tools for studies on the cardiovascular roles of AVP. Furthermore the analogues of dPTyr(Me)AVP may be useful in studies on the role(s) of AVP in the V1b-receptor-mediated release of ACTH from corticotrophs.

Amino Acid Sequence↗
PubMed1992

Extracorporeal shock wave lithotripsy of ureteric stones with the Modulith SL 20.

A series of 138 patients with ureteric calculi was treated by in situ extracorporeal shock wave lithotripsy (ESWL) during the clinical introduction of the Modulith SL 20. This machine represents a newly developed lithotriptor with an electromagnetic cylinder as shock wave source and a dual localisation system consisting of in-line ultrasound and an integrated fluoroscope C-arm. During the first 2 months, 12 patients (phase 1) were treated under ultrasound localisation alone; during the next 5 months, 37 patients (phase 2) were treated using dual imaging modalities with reduced peak pressure (max. 18 kV = 800 bar); during the final 7 months, 89 patients (phase 3) were treated under ultrasonic and fluoroscopic localisation combined with an increased maximal shock wave pressure (20 kV = 1024 bar). The introduction of fluoroscopic targeting (phases 2 and 3) resulted in satisfactory localisation of calculi in the mid-ureter, previously limited by use of only coaxial ultrasound. The extension of stone localisation to the whole length of the ureter was associated with a marked decrease in treatment time, reflecting the easy handling of the dual localisation system. The rise in generator voltage (phase 3) improved the disintegration rate from 81% (phase 2) to 85%, whereas the number of impulses remained unchanged. However, the rate of auxiliary procedures following ESWL (adjuvant and curative) was reduced from 33% (phase 2) to 24.5%. Thus the Modulith SL 20 in its final design enables in situ ESWL to be the treatment of choice for all ureteric calculi, rendering special positioning techniques or multiple treatment unnecessary.

Humans↗
PubMed1991

A radioiodinated linear vasopressin antagonist: a ligand with high affinity and specificity for V1a receptors.

A linear vasopressin antagonist, Phaa-D-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-Tyr-NH2 (Linear AVP Antag) (Phaa = Phenylacetyl), was monoiodinated at the phenyl moiety of the tyrosylamide residue at position 9. This antagonist appeared to be a highly potent anti-vasopressor peptide with a pA2 value in vivo of 8.94. It was demonstrated to bind to rat liver membrane preparations with a very high affinity (Kd = 0.06 nM). The affinity for the rat uterus oxytocin receptor was lower (Ki = 2.1 nM), and affinities for the rat kidney- and adenohypophysis-vasopressin receptors were much lower (Ki = 47 nM and 92 nM, respectively), resulting in a highly specific vasopressin V1a receptor ligand. Autoradiographical studies using rat brain slices showed that this ligand is a good tool for studies on vasopressin receptor localization and characterization.

Amino Acid Sequence↗
PubMed1991

Cyclic and linear vasopressin V1 and V1/V2 antagonists containing arginine in the 4-position.

Substitution of arginine for glutamine in the 4-position of a vasopressin V1 antagonist has been reported to turn it into an agonist. We resynthesized this 4-arginine analog and synthesized additional cyclic and linear vasopressin antagonists containing a 4-arginine. The presence of a 4-arginine in the resynthesized and new analogs had relatively minor effects on their antivasopressin V1 and V2 antagonistic potencies.

Amino Acid Sequence↗
PubMed1990

Invertebrate neuropeptides resembling vasotocin and some analogues: synthesis and pharmacological properties.

The solid phase synthesis of three invertebrate vasopressin-oxytocin homologs: AVP-like factor, F1(1), ([Leu2, Thr4] AVT)2 isolated from subesophageal and thoracic ganglia of Locusta migratoria3, Arg-conopressin-S4. ([Ile2, Arg4] AVT), Lys-conopressin-G4 ([Phe2, Arg4] LVT), both isolated from the venom of fish-hunting marine snails of the genus Conus and six of their analogues is reported. These analogues are: [Arg4] AVT, [Ile2] AVT, [Leu2] AVT, [Phe2, Arg4] AVT, [Arg4] LVT and [Ile2, Arg4] LVT. All peptides were tested for antidiuretic and vasopressor activities.

Animals↗