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Biomedical subjects

R Knapp

Publications and source records attributed to R Knapp.

At least 55 records · Page 3Linked to original sources
PubMed1994

[Traumatic lesions of the occipitocervical transition].

The availability of better and quicker resuscitation means that more patients with occipitocervical injuries survive. In view of the complex anatomy and functional capabilities of the upper part of the spine it makes sense to discuss injuries to this part separately from any to the lower cervical and thoracolumbar vertebral column. Computerized tomography with additional multiplanar reconstructions, digital radiography and magnetic resonance imaging early in the diagnostic workup improves the likelihood of a quick and satisfactory diagnosis. Our classification of injuries should enable the radiologist to provide the traumatologist with enough information on the damage to bones and soft tissue to allow an accurate assessment of stability, which is mandatory for the selection of appropriate treatment.

Adult↗
PubMed1994

[Traumatic lesions of the spine below the axis].

Sports activities and traffic accidents are leading to an increasing incidence of spinal injuries. To assist in correct and quick diagnosis of spinal fractures the radiologist such modern diagnostic tools as computerized tomography, magnetic resonance imaging and digital radiography. Nevertheless. The plain film is of major importance for recognition of the type of fracture from its biomechanical pattern. Apart from this, the radiologist should decide individually what other examination(s) are needed for visualization of the full amount of damage. We found the model of Magerl and co-workers for fracture types and the model of Denis for stability the best, covering almost the entire spine from C3 and L5. The different types of fractures and discoligamentous injuries are discussed with reference to the risks attached of neurological complications and stability.

Cervical Vertebrae↗
PubMed1994

Stimulus dose-titration in ECT: a 2-year clinical experience.

One hundred and thirty-four patients referred for electroconvulsive therapy (ECT) over a 2-year period underwent standardized stimulus dose-titration. No significant adverse events were associated with the dose-titration procedure. Our data demonstrate that seizure threshold increases with age (p = 0.0001) and is higher with bilateral electrode placement (p = 0.0001). Contrary to other studies, our data show the effect of gender is not statistically significant (p = 0.54). If consensus regarding optimal dosing strategies relative to seizure threshold can be achieved, dose-titration may be adopted as a clinically useful step in optimizing ECT technique.

Adult↗
PubMed1993

Comparison of ligand-binding sites of modeled apo[a] kringle-like sequences in human lipoprotein[a].

Human lipoprotein[a] contains at least two high-molecular-weight, disulfide-linked apolipoproteins, apo[a] and apo B-100. Apo[a] is a highly glycosylated, hydrophilic apoprotein that somewhat resembles plasminogen by containing an extended kringle domain and a carboxyl-terminal serine protease domain. The apo[a] kringle domain is composed of 11 distinct kringle types. Ten of these display high sequence homology to plasminogen kringle 4 (PGK4). The crystallographic coordinates for PGK4 were used to generate three-dimensional molecular models of the apo[a] kringle types, and the lysine-binding region of PGK4 was used to compare the different potential receptor-ligand and ligand-binding sites contained in each different PGK4-like kringle of apo[a]. A receptor-ligand site can be proposed for each kringle type. Potential serine protease cleavage sites, containing arginine-threonine and threonine-arginine, are located on the surface of the kringles. The ligand-binding site of one apo[a] kringle model is almost identical to that of PGK4 and may be a lysine-binding site of apo[a]. Four other apo[a] kringle models appear to have structurally similar lysine-binding sites, but with differences that may influence ligand-polypeptide specificity. Five apo[a] kringle models have ligand-binding sites that probably do not bind lysine; one of these is the highly repeated kringle in the known apo[a] polymorph.

Amino Acid Sequence↗
PubMed1992

Ring substituted and other conformationally constrained tyrosine analogues of [D-Pen2,D-Pen5]enkephalin with delta opioid receptor selectivity.

The conformationally restricted, cyclic disulfide-containing delta opioid receptor selective enkephalin analogue [D-Pen2,D-Pen5] enkephalin (DPDPE) was modified by 2' (CH3) and 3' (I, OCH3, NO2, NH2) ring substitutions and by beta-methyl conformationally constrained beta-methyltyrosine derivatives in the 1 position. The potency and selectivity of these analogues were evaluated by bioassay in the mouse vas deference (MVD, delta receptor assay) and guinea pig ileum (GPI, mu receptor assay) assays and by radioreceptor binding assays in the rat brain using [3H]CTOP (mu ligand) and [3H][p-ClPhe4]DPDPE (delta ligand). The analogues showed highly variable potencies in the binding assays and in the bioassays. Aromatic ring substituents with positive Hammett constants had decreased potency, while substituents with negative Hammett constraints has increased potency for the opioid receptor. The most potent and most selective compound based on the binding was [2'-MeTyr1]DPDPE (IC50 = 0.89 nM and selectivity ratio 1310 in the binding assays). The 6-hydroxy-2-aminotetralin-2-carboxylic acid-containing analogue, [Hat1]DPDPE, also was highly potent and selective in both assays, demonstrating that significant modifications of tyrosine in enkephalins are possible with maintenance of high potency and delta opioid receptor selectivity. Of the beta-methyl-substituted Tyr1 analogues, [(2S,3R)-beta-MeTyr1]DPDPE was the most potent and the delta receptor selective. The results with substitution of beta-MeTyr or Hat instead of Tyr also demonstrate that topographical modification in a conformationally restricted ligand can significantly modulate both potency and receptor selectivity of peptide ligands that have multiple sites of biological activity.

Amino Acid Sequence↗
PubMed1992

Synthesis and biological activities of linear and cyclic enkephalin analogues containing a psi (E,CH = CH) or psi (CH2CH2) isosteric replacement.

The peptide CO-NH function was replaced by a trans carbon-carbon double bond or by a CH2-CH2 isostere in enkephalin analogues of DADLE, DCDCE-NH2 or DPDPE. In DADLE the 2-3 and the 3-4 peptide bond was modified, whereas in the cyclic analogues the Gly3-Phe4 bond was replaced by the isosteres Gly psi (E,CH = CH)Phe [5-amino-2-(phenylmethyl)-3(E)-pentenoic acid] or Gly psi (CH2CH2)Phe [5-amino-2-(phenylmethyl)pentanoic acid]. In general, the modification results in a drop in potency which is the largest for the flexible CH2-CH2 replacement. The Gly3 psi (E,CH = CH)Phe4 DCDCE-NH2 analogue retains considerable potency. These results confirm the importance of the peptide function at the 2-3 and 3-4 position in enkephalin analogues for biological potency.

Amino Acid Sequence↗
PubMed1992

Peyronie's disease: MR findings in 28 patients.

Induratio penis plastica (Peyronie's disease) is a chronic fibrotic process involving the penis. Proper treatment of the disease requires assessment of the degree of inflammation preceding or accompanying the fibrous Peyronie's plaques. Owing to its high tissue contrast and its multiplanar capability, MR imaging offers excellent visualization of penile anatomy. To determine the usefulness of MR imaging in the diagnosis and staging of Peyronie's disease, we used MR imaging with a surface coil to examine 28 consecutive patients with clinical evidence of the disease. Eighteen patients had contrast-enhanced MR imaging with gadopentetate dimeglumine. In seven patients who subsequently had surgery or biopsy, MR findings were correlated with histopathologic findings. On unenhanced images, fibrous plaques were shown in 20 patients. Enhanced MR images showed focal contrast enhancement around or within the plaques in seven patients. Images in three patients with plaques showed no enhancement. Images in five patients showed focal areas of contrast enhancement without evidence of plaques. Histologic studies demonstrated that the degree of contrast enhancement correlated with the extent of inflammatory cell infiltration. In two patients with unenhancing plaques on MR, histology confirmed the absence of inflammation. Our results suggest that MR imaging not only depicts the localization and extent of fibrous plaques in patients with Peyronie's disease but also reveals the presence of inflammation. This makes MR imaging the technique of choice for planning therapy and for evaluating the response to conservative treatment.

Adult↗
PubMed1991

Topographically designed analogues of [D-Pen,D-Pen5]enkephalin.

The conformationally restricted, cyclic disulfide-containing delta opioid receptor selective enkephalin analogue [D-Pen2,D-Pen5]enkephalin (1, DPDPE) was systematically modified topographically by addition of a methyl group at either the pro-S or pro-R position of the beta carbon of an L-Phe4 or D-Phe4 residue to give [(2S,3S)-beta-MePhe4]DPDPE (2), [(2R,3R)-beta-MePhe4]DPDPE (3), [(2S,3R)-beta-MePhe4]DPDPE (4), and [(2R,3S)-beta-MePhe4]DPDPE (5). The four corresponding isomers were prepared in which the beta-methylphenylalanine residue was p-nitro substituted, that is with a beta-methyl-p-nitrophenylalanine (beta-Me-p-NO2Phe) residue, to give [(2S,3S)-beta-Me-p-NO2Phe4]DPDPE (6), [(2R,3R)-beta-Me-p-NO2Phe4]DPDPE (7), [(2S,3R)-beta-Me-p-NO2Phe4] DPDPE (8), and [(2R,3S)-beta-Me-p-NO2Phe4]DPDPE (9), respectively. The potency and selectivity (delta vs mu opioid receptor) were evaluated by radioreceptor binding assays in the rat brain using [3H]CTOP (mu ligand) and [3H]DPDPE (delta ligand) and by bioassay with mouse vas deferens (MVD, delta receptor assay) and guinea pig ileum (GPI, mu receptor assay). The eight analogues of DPDPE showed highly variable binding and bioassay activities particularly at the delta opioid receptor (4 orders of magnitude), but also at the mu opioid receptor, which led to large differences (3 orders of magnitude) in receptor selectivity. For example, [(2S,3S)-beta-MePhe4]DPDPE (2) is 1800-fold selective in binding to the delta vs mu receptor, making it one of the most selective delta opioid receptor ligands in the enkephalin series as assessed by the rat brain binding assay, whereas the corresponding (2R,3R)-beta-Me-p-NO2Phe-containing analogue 9 is only 4.5-fold selective (nonselective) in this same assay. On the other hand, in the bioassay systems, [(2S,3S)-beta-Me-p-NO2Phe4]DPDPE (5) is more potent than DPDPE and 8800-fold selective for the MVD (delta receptor) vs the GPI (mu receptor), making it the most highly selective ligand in this series for the delta opioid receptor on the basis of these bioassays. In these assay systems, the (2R,3S)-beta-MePhe4-containing analogue 5 had very weak potency and virtually no receptor selectivity (4.4-fold). These results demonstrate that topographical modification alone in a conformationally restricted peptide ligand can significantly modulate both potency and receptor selectivity of peptide ligands that have multiple sites of biological activity and suggest that this approach may have general application to peptide ligand design.

Amino Acid Sequence↗
PubMed1990

[D-Pen2,D-Pen5]enkephalin analogues with increased affinity and selectivity for delta opioid receptors.

The conformationally restricted, cyclic disulfide-containing enkephalin analogue [D-Pen2,D-Pen5]enkephalin (DPDPE) was modified by halogenation (F, Cl, Br, I) of the phenylalanine-4 residue in the para position. The potency and selectivity of these analogues for the delta opioid receptor was greater than that of the parent peptide. The analogues possessed greater potency and affinity for the delta receptors than DPDPE in the mouse vas deferens assay and in radioreceptor assays (against [3H]DPDPE), respectively. [p-ClPhe4]DPDPE was the most selective in the radioligand binding assays (IC50(mu)/IC50(delta) = 574), being about 5-fold more delta opioid receptor selective than DPDPE in this assay, whereas [p-IPhe4]DPDPE was the most selective in the classical bioassay systems using the mouse vas deferens and guinea pig ileum assays (IC50(GPI)/IC50(MVD) = 17,374), making it nearly 9-fold more selective than DPDPE in direct comparisons using the same assay conditions.

Amino Acid Sequence↗
PubMed1990

Cholecystokinin analogues with high affinity and selectivity for brain membrane receptors.

A series of CCK analogues in which positions 28 and 31 have been replaced by N-methylnorleucine residues have been synthesized. It has been found that most of these N-methylnorleucine containing analogues of CCK are highly potent and some are extraordinarily selective for the central vs. peripheral receptor in two animal models (guinea pig and rat). [N-MeNle28,31]CCK26-33 nonsulfated exhibited both high potency (IC50 = 0.13 nM) and selectivity for central vs. peripheral receptors. The pancrease to brain cortex binding affinity ratio for this analogue is 5100 in the rat model. NMR studies reveal that there is cis/trans isomerism about the N-methylnorleucine residue that may be related to high selectivity.

Amino Acid Sequence↗
PubMed1990

Intravenous gamma-globulin: clinical applications in pediatric care.

Intravenous gamma-globulin is being used with increasing frequency in the care of children. This article reviews the physiology of the immune system, the pharmacology of intravenous gamma-globulin, and presents four case studies. Administration guidelines, adverse reactions, and appropriate interventions are discussed. A table comparing four commonly used products is presented.

Adolescent↗
PubMed1989

Beta-carboline interactions at the BZ-GABA receptor chloride-ionophore complex in the rat cerebral cortex.

beta-Carboline congeners can act at the benzodiazepine (BZ) recognition site of the BZ-GABA receptor complex to increase GABA-stimulated chloride conductance (agonist effect), inhibit this conductance (inverse agonist effect) or block the actions of agonists and inverse agonists (antagonist effect). In this communication we describe the effects of several beta-carbolines (ZK 93423, ZK 91296, ZK 93426, and DMCM) on GABA-stimulated chloride influx into vesicles prepared from rat cerebral cortex. ZK 93423 produces an approximate 2-fold left-shift of the GABA dose-response curve at a concentration of 1.0 microM consistent with its full agonist activity (positive intrinsic efficacy), while the same concentration of ZK 91296 produces over a 1-fold left-shift consistent with its partial agonist activity. At higher concentrations (0.1 mM), ZK 91296 inhibits GABA-stimulated chloride influx which appears to be mediated through a non-BZ receptor mechanism since this effect is not reversed by the BZ antagonist ZK 93426. The augmenting effect of both ZK 93423 and ZK 91296 on GABA-stimulated chloride flux was reduced by the antagonist ZK 93426 in a dose-dependent manner and reached GABA-stimulated control levels at a ZK 93426 concentration of 1.0 microM. Interestingly, there was a further inhibition of the GABA-stimulated chloride influx at higher concentrations of ZK 93426 which is not seen when ZK 93426 is used in the absence of BZ agonists. The inverse agonist activity of DMCM was incompletely blocked by the antagonist ZK 93426. These data show that ZK 93426 can antagonize the effects of the full agonist ZK 93423 and partial agonist ZK 91296 at the BZ receptor. Furthermore, the interaction of the agonists with ZK 93426 results in the appearance of inverse agonist-like activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Chorea and dystonia: a remote effect of carcinoma.

A 45-year-old woman with an acquired multifocal neurologic syndrome, including chorea, dystonia, cerebellar dysfunction, multiple cranial neuropathies, and pure sensory neuropathy, was found at autopsy to have oat cell carcinoma. Neuropathologic examination revealed several features typically associated with remote effects of malignancy on the nervous system. We believe that this is the first described case of chorea as a remote effect of malignancy.

Carcinoma, Small Cell↗
PubMed1988

Subclinical left ventricular abnormalities in young diabetics.

Twenty young asymptomatic diabetic patients were evaluated for left ventricular dysfunction by determining the radionuclide ejection fraction response to supine bicycle ergometry. The double product at peak exercise (28,743 +/- 3,314 vs 29,007 +/- 3,625, p greater than .05) was not significantly different between the two groups. Seven of 20 diabetics had either no change or a drop in their ejection fraction during exercise while 1 of 20 control subjects had no change in ejection fraction. There was no correlation between the FBS (r = .26) and HbA1c (r = .32) and ejection fraction change during exercise, although those diabetics with LV dysfunction tended to have a higher HbA1c level as compared to diabetics with a normal response (16.8 +/- 3.1 percent vs 12.5 +/- 3.8 percent respectively, p greater than .05). The LV systolic dysfunction in young asymptomatic diabetic subjects does not appear to correlate with the degree of acute or chronic hyperglycemia, and therefore, is not a direct function of the dynamic metabolic state of diabetes.

Adult↗