Biomedical subjects

C L Klein

Publications and source records attributed to C L Klein.

45 records · Page 3Linked to original sources

PubMed1994

Comparative studies on vascular endothelium in vitro. I. Cytokine effects on the expression of adhesion molecules by human umbilical vein, saphenous vein and femoral artery endothelial cells.

Endothelial cells (ECs) are very responsive to proinflammatory cytokines. ECs are stimulated by these substances to increase expression of cell surface adhesion molecules, leading to dramatically altered interactions with leukocytes. In these interactions, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are suggested to play the most important role. Recent evidence has suggested diversity in the responses of ECs from different regions of the vascular system. Human umbilical vein ECs (HUVECs) are the most often used EC culture model, although there are few studies comparing their response with other human EC types from the adult organism. In this study the expression of E-selectin, ICAM-1 and VCAM-1 on cultured human adult ECs from the saphenous vein (HSVECs) and from the femoral artery (HAFECs), as well as HUVECs was studied. Using a cell enzyme immunoassay as well as immunoelectron microscopical methods, we found that both HSVECs and HAFECs respond in a similar way to HUVECs to exogenous stimulation by IL-1 beta, TNF alpha or LPS. IL-1 beta and TNF alpha increased the expression of E-selectin on the cytoplasmic membranes of HUVECs, HSVECs and HAFECs and elicited even similar absolute quantities of this molecule, comparing the different cell types. ICAM-1 and VCAM-1 appeared to be regulated dose dependently by IL-1 beta, independent of the EC type. HUVECs as well as HSVECs and HAFECs gave a reproducible constitutive ICAM-1 expression, whereas E-selectin and VCAM-1 were absent on nonstimulated ECs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

cis-1,2,3a,4,5,9b-hexahydro-3H-benz[e]indoles: synthesis and in vitro binding affinity at dopamine D1 and D2 receptors.

cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e]indoles were synthesized and evaluated for in vitro dopamine D1 and D2 receptor binding affinity. The target compounds 21-25 were readily prepared by reduction of the air-sensitive tricyclic enamines 10-14. Reduction of 10-14 with sodium borohydride, sodium cyanoborohydride, palladium on carbon in ethanol, and platinum oxide in ethanol or acetic acid gave only the cis (3a,9b) 1,2,3a,4,5,9b-hexahydro-3H-benz[e]indoles. The stereochemistry was confirmed by single-crystal X-ray analysis. In the 6-hydroxy series, the binding affinity at D1 and D2 receptors was of the order 22 (N-n-butyl) > 21 (N-n-propyl) > 23 (N-H). The compounds demonstrated greater binding affinity at D2 receptors than at D1 binding sites. In contrast, 8-OH derivatives exhibited affinity only for D2 receptors, with 25 (N-n-butyl) having slightly greater affinity than 24 (N-n-propyl).

Animals↗

PubMed1993

Intracavernosal kinetics of eicosanoids and endothelin during erection. Data from human and animal studies on intrapenile and systemic prostaglandins.

The release of mediator substances of the arachidonic acid cascade is closely related to the functional state of the endothelium. A significant lower prostacyclin/thromboxane A2 ratio in penile plasma of organogenic impotent patients in comparison to patients with psychogenic erectile dysfunction has been described in the literature. We observed the time-related liberation of prostacyclin, thromboxane A2 and the vasoactive peptide endothelin for 16 minutes of a drug-induced erection. We compared kinetics of patients with penile deviation and transsexualism, to patients suffering from severe organogenic impotence. We assessed the usefulness of the prostacyclin-to-thromboxane A2 ratio as a possible indicator of corporal degeneration. An animal model has been created to observe differences between rabbits under 100 days of standard diet alimentation, rabbits under cholesterol enriched diet and rabbits with hereditary hyperlipidemia type II A. Hyperlipidemia is suspected to be one possible factor causing organogenic impotence. Enzyme-immuno-assays were used for the determination of all substances. The systemic prostacyclin-to-thromboxane A2 ratio differed significantly between control rabbits and rabbits with hyperlipidemia. Prostacyclin, thromboxane A2 and endothelin in corpus cavernosum plasma showed a typical profile during spontaneous and drug-induced erection. A significant difference between groups of patients suffering from organogenic or psychogenic impotence could not be found. The value of the determination of the studied substances in differential diagnosis seems to be dubious.

Alprostadil↗

PubMed1991

Structure of L-prolyl-L-tyrosine monohydrate.

C14H18N2O4.H2O, Mr = 296.32, triclinic, P1, a = 5.524 (3), b = 6.621 (2), c = 10.307 (2) A, alpha = 78.82 (3), beta = 86.82 (4), gamma = 84.96 (4) degrees, V = 368.11 A3, Z = 1, Dx = 1.34 g cm-3, lambda(Mo K alpha 1) = 0.70930 A, mu = 1.10 cm-1, F(000) = 158, T = 298 K, final R = 0.044 for 2182 observed reflections. The molecule crystallizes as a zwitterion with the peptide backbone folded and a water molecule of hydration. The water molecule and the dipeptide molecule are involved in an extensive hydrogen-bond network.

Dipeptides↗

PubMed1991

Structure of nortriptyline hydrochloride.

C19H22N+.Cl-, Mr = 299.84, monoclinic, P2(1)/c, a = 5.070 (2), b = 34.088 (5), c = 9.976 (1) A, beta = 90.74 (2) degrees, V = 1724.0 A3, Z = 4, Dx = 1.16 g cm-3, lambda (Mo K alpha 1) = 0.70930 A, mu = 2.2 cm-1, F(000) = 640, T = 295 K, final R = 0.046 for 1381 observed reflections. The nortriptyline molecule crystallized with a 'butterfly' fold angle of 124.3 (2) degrees and an extended propylamino side chain. The amino nitrogen is involved in hydrogen bonds to two different chloride ions.

Molecular Conformation↗

PubMed1989

Structure of droperidol-ethanol (1/1).

1-(1-[4-(4-Fluorophenyl)-4-oxobutyl]-1,2,-3,6-tetrahydro-4-pyridyl)-1,3- dihydro-2H-benzimidazol-2-one ethanol solvate, C22H22FN3O2.C2H6O, Mr = 426.3, triclinic, P1, a = 6.083 (3), b = 10.296 (1), c = 16.018 (2) A, alpha = 100.93 (1), beta = 92.72 (2), gamma = 96.27 (2) degrees, V = 976.7 A3, Z = 2, Dx = 1.45 g cm-3, Mo K alpha, lambda = 0.71073 A, mu = 0.97 cm-1, F(000) = 452, T = 90 (2) K, final R = 0.046 for 2261 observed reflections. The title compound crystallizes with the droperidol skeleton extended and a solvated ethanol molecule disordered about an inversion center. The ethanol molecule forms a hydrogen bond to the droperidol skeleton at ketone atom O(1) on the imidazole ring.

Chemical Phenomena↗

PubMed1987

7,12-Dimethylbenz[a]anthracene: refined structure, electron density distribution and endo-peroxide structure.

The crystal structure of 7,12-dimethylbenz[a]anthracene (DMBA) has been refined from new X-ray diffraction data collected at low temperature (180 K). This has allowed the location of the hydrogen atom positions not previously reported in earlier structure determinations and refinements; a more precise molecular geometry is therefore now presented. In addition, an analysis of the electron density in this carcinogenic molecule has been made by multipole refinement. These two types of studies give information on the amount of strain in the bay region and the distribution of electron density in the molecule. The molecule is highly distorted in the bay region as a result of steric overcrowding between hydrogen atoms (minimum H ... H 2.06 A) so that torsion angles of 18 degrees and 22 degrees occur in this area. The bonds in the bay region and to the two methyl groups appear to be electron-rich; however, while the K-region of DMBA has a high pi-bond density computed from interatomic distances, the multipole analysis does not indicate that it is highly electron-rich. The 7- and 12-positions (equivalent to the 9- and 10-positions of anthracene) are highly reactive and appear to show a deficiency of electron density. Molecular dioxygen can add across these positions to give a peroxy compound. The crystal structure of such an endo-peroxide of DMBA has also been studied at 180 K although not to the high precision obtained for the parent compound. Some distortions are apparent in this molecule; in particular small CH3-C-O angles (101-104 degrees) are observed, indicative of some strain in the molecule. A computer graphics analysis of the diol epoxides of DMBA, generated from X-ray coordinates of DMBA and reported values for a diol epoxide of benzo[a]pyrene, show that steric overcrowding may affect the conformation of certain isomers of the diol epoxides.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1985

Molecular structure of two conformationally restrained fentanyl analogues: cis- and trans-isomers of N-(3-methyl-1-[2-(1,2,3,4-tetrahydro)naphthyl] -4-piperidinyl)-N-phenylpropanamide.

The X-ray crystallographic structures of two analogues of the potent analgetic fentanyl in which the N-phenethyl substituent is restrained through incorporation into a tetrahydronaphthyl ring system are reported. The tetrahydronaphthyl moiety exists in an equatorial conformation with respect to the piperidine ring which exists in the chair conformation. The propanilido group is also equatorial and antiperiplanar. The orientation of the N-phenyl group with respect to the N-acyl moiety is essentially invariant with an approximately 90 degrees dihedral angle. The implications of these conformations in the interaction of fentanyl-type analgetics with opiate receptors are discussed. The following data were obtained: cis-[C25H33N2O+]Cl- . 1/2 C2O4H2, triclinic, P-1; a = 7.005(7), b = 13.189(2), c = 14.312(4)A, alpha = 111.27(2), beta = 99.15(5), gamma = 93.52(4)0, V = 1205.9A, Z = 2, T = 110K, R = 0.0596, Rw = 0.0760; trans-[C25H33N2O+] C2O4H- . 1/2 C2O4H2 . 2 H2O, triclinic, P-1, a = 8.235(6), b = 10.546(8), c = 17.108(9)A, alpha = 107.72(5), beta = 95.73(5), gamma = 90.63(6)0, V = 1406.8A3, Z = 2, T = 110K, R = 0.0737, Rw = 0.0934.

Chemical Phenomena↗

PubMed1984

Molecular structure of anti-3,4-dihydroxy-1,2,3,4-tetrahydronaphthalene 1,2-oxide.

The molecular structure and conformation of anti-3,4-dihydroxy-1,2,3,4-tetrahydronaphthalene 1,2-oxide have been determined by X-ray crystallographic techniques. This compound has been identified as a urinary metabolite of naphthalene and also mimics various metabolites of carcinogenic polyaromatic hydrocarbons. The compound crystallizes in space group Pca2(1) with cell dimensions a = 8.120(3), b = 8.656(2), and c = 23.729(5) A. There are two unique molecules in the asymmetrical unit with similar conformations. The major difference between the two molecules is in the epoxide ring. One molecule shows symmetrical C--O bond lengths and the other shows unsymmetrical C--O bond lengths, due to steric variations in the environments of the epoxide oxygen atoms. Both molecules show a "twist-boat" conformation in the saturated portion of the carbon skeleton. Packing of the molecules in the unit cell results in alternate layers of hydrophobic and hydrophilic regions and an extensive intermolecular hydrogen bond network.

Carcinogens↗