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J Antel

Publications and source records attributed to J Antel.

53 records · Page 3Linked to original sources
PubMed1988

Crystal and molecular structure of didemnin B, an antiviral and cytotoxic depsipeptide.

Didemnin B, a highly active depsipeptide isolated from a Caribbean tunicate, crystallizes from chloroform/benzene in the orthorhombic space group C2221, with cell parameters a = 14.990 +/- 0.003 A, b = 22.574 +/- 0.004 A, c = 41.112 +/- 0.009 A, V = 13911.7 A3 at 138 K and a calculated density of 1.143 g/cm3 based on C57H89N7O15, 1.5C6H6.H2O and eight formula units per cell. The overall agreement factor R = 0.052 for 7699 reflections, 20 theta max = 150 degrees, Cu K-alpha radiation. The structure determination revealed that didemnin B contains an isostatine residue instead of a statine residue. The conformation of the 23-membered depsipeptide ring is stabilized by one transannular hydrogen bond. The ring does not show the antiparallel beta-pleated-sheet structure but, instead, has a fold in the shape of a bent figure-eight. The linear peptide moiety, containing N-methylleucine and lactylproline, forms a beta (II)-bend and is folded back toward the cyclic backbone, giving the overall molecule a globular character. Comparison with the structure of cyclosporin A shows distinct stereochemical differences between the two molecules. It is suggested that didemnin B and cyclosporin A are unlikely to have a common receptor binding site.

Antiviral Agents↗
PubMed1987

HLA antigens in narcolepsy.

Eighteen black patients with narcolepsy underwent human leukocyte antigen (HLA) typing. Eleven of the 18 had cataplexy. Twelve patients (66.6%) had HLA-DR2; 7 patients with cataplexy had DR2. All patients had DQw1. In contrast to white and Japanese patients studied to date, not all black narcoleptics have DR2.

Adult↗
PubMed1986

Defective suppressor cell function mediated by T8+ cell lines from patients with progressive multiple sclerosis.

Activated suppressor cell function, induced with either concanavalin A or OKT3 and mediated by either unfractionated mononuclear cells or "panning" enriched T8+ cells, freshly isolated from peripheral blood, is reduced in patients with progressive multiple sclerosis (MS) as compared with control donors. In this study, we generated T8+ cell lines from the peripheral blood of these same patients and controls. Suppressor activity, mediated by T8+ cells exposed to OKT3 on days 1, 7, and 14 of culture and then treated with mitomycin C on day 16, was significantly reduced in the MS group (mean percent suppression 13% +/- 5) as compared with the control group (68% +/- 6, n = 8, p less than 0.001). No differences were noted in [3H]thymidine uptake by the OKT3-stimulated T8+ cell lines of MS and control groups. Mean percent suppression mediated by T4+ cell lines did not differ between MS and control groups (15% +/- 4, n = 3, vs 22% +/- 2, n = 4). These current data suggest that the previously observed defect in T8+ cell-mediated activated suppressor cell function in MS is a persistent one, favoring the postulate that the defect reflects intrinsic alterations in this cell population rather than a transient effect of serum factors on T8+ cell function.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1984

Thalidomide-induced peripheral neuropathy. Effect of serum factor on nerve cultures.

Sensory neuropathies developed in three of four patients with prurigo nodularis who had been treated with thalidomide. The serum samples of the patients who had neuropathy produced morphologic changes in cultured dorsal root ganglion cells. These observed changes support the postulate that thalidomide induces primary neuronal degeneration.

Adult↗
PubMed1982

Eye movements in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of the upper motor neurons in the frontal cortex and the motor neurons of the brain stem and spinal cord. Cranial nerve nuclei III, IV, VI are usually normal histopathologically, as are the eye movements clinically. Using electro-oculography, we found decreased saccadic or smooth pursuit velocities in four of ten patients unidirectional saccadic pursuit in one of these four, and progressively decreasing saccadic velocities in another. We believe the defect is supranuclear and that the ocular motor system is more often abnormal in patients with ALS than previously recognized.

Adult↗
PubMed1982

Modulation of T-lymphocyte differentiation antigens: potential relevance for multiple sclerosis.

Effects of the anti-T-cell monoclonal antibodies OKT3, OKT5, and OKT8 on T-cell surface properties and cell functions were evaluated. Incubation of mononuclear cells isolated from peripheral blood for 48 hr with each monoclonal antibody in the absence of complement resulted in modulation of their respective surface antigens; i.e., the number of cells detected by immunofluorescence as positive for the T3, T5, and T8 surface antigens was reduced. T3, T5, and T8 antigens modulated independently. A radiolabeled second antibody technique confirmed modulation by OKT3 and OKT8 and indicated that T-cell differentiation antigens can regenerate in culture. Incubation of mononuclear cells with OKT3 increased the number of sheep erythrocyte-binding lymphocytes (E+-rosetting cells) and markedly increased the number of avidly E+-rosetting cells. Incubation with OKT8 reduced the number of E+- and of avidly E+-rosetting cells. OKT3 induced both mitogenic reactivity and suppressor cell activity; cells modulated by OKT8 exhibited reduced mitogenic reactivity and reduced suppressor cell function. The decreases in total T cells, in avid T cells, in suppressor cell number, and in suppressor cell function that follow modulation by OKT8 mimic changes observed in multiple sclerosis patients.

Adult↗
PubMedDate not supplied

Crystal and molecular structure of didemnin A, an antiviral depsipeptide.

The molecular structure of didemnin A, the parent compound of a series of antiviral cytotoxic depsipeptides extracted from a marine tunicate Trididemnum solidum of the family of Didemnidae, has been determined by single-crystal X-ray diffraction. In the crystal, didemnin A molecules form pseudo-symmetric dimeric pair. The two molecules in the dimer are held together by strong N--H center dot center dot center dot O and N--H center dot center dot center dot N hydrogen bonds. A chloride ion, placed almost symmetrically between the dimeric pair, forms N--H center dot center dot center dot Cl hydrogen bonds (3.19 and 3.23 Angstrom) with both the molecules. The two independent molecules in the structure have closely similar geometry. For each molecule, the 23-membered depsipeptide ring assumes a folded conformation in the shape of a 'bent figure-of-eight' similar to that observed in the didemnin B crystal structure. The major conformational differences in the macrocycle of didemnin A and didemnin B are around the Hip residue. The root mean-square (RMS) difference of 20 of the 23 endocyclic torsion angles for the two structures is less than 10 degrees, while the three bond torsions in the Hip residue vary by about 50 degrees. The macrocycle conformation is stabilized by a transannular N--H center dot center dot center dot O hydrogen bond linking the isostatine amide group with the leucine carbonyl group. The truncated linear chain is folded back toward the macrocyclic ring and is held by a N--H center dot center dot center dot O hydrogen bond between the leucine amide group and Me-Leu carbonyl group. The transannular hydrogen bond in the didemnin A structure (N4--H center dot center dot center dot O3 = 2.83 Angstrom in both molecule a and molecule b) is noticeably stronger than that observed in the didemnin B structure (3.02 Angstrom). The X-ray structure of didemnin A is generally consistent with that obtained by NMR studies. Within the crystal, the molecules are packed in zig-zag chains formed by intermolecular O--H center dot center dot center dot O hydrogen bonds. The crystal structure and packing of didemnin A are quite different from that of the didemnin B structure.

Antiviral Agents↗