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Biomedical subjects

M Erman

Publications and source records attributed to M Erman.

8 recordsLinked to original sources
PubMed1992

Inhibition of Streptomyces hydrogenans 3 alpha,20 beta-hydroxysteroid dehydrogenase by licorice-derived compounds and crystallization of an enzyme-cofactor-inhibitor complex.

Streptomyces hydrogenans 3 alpha,20 beta-hydroxysteroid dehydrogenase reduces the C20 ketone on glucocorticoids and progestins. We find that two licorice-derived compounds, glycyrrhizic acid and carbenoxolone, inhibit this enzyme with microM Kis. Inhibition is competitive, indicating that these compounds are binding at or close to the catalytic site. Carbenoxolone's high aqueous solubility and affinity for 3 alpha,20 beta-hydroxysteroid dehydrogenase enabled us to prepare crystals of a carbenoxolone-NADH-enzyme ternary complex, which preliminary X-ray analysis indicates has a crystal structure that is significantly different from that of the 3 alpha,20 beta-hydroxysteroid dehydrogenase-NADH complex. A comparison of the tertiary structures of these two complexes should prove useful in understanding this enzyme's catalytic mechanism, as well as those of two homologous enzymes, mammalian 11 beta-hydroxysteroid dehydrogenase and 15-hydroxyprostaglandin dehydrogenase that also are inhibited by carbenoxolone.

Binding Sites↗
PubMed1992

Anti-lymphocyte, anti-monocyte, and anti-endothelial cell antibodies in chronic haemodialysis patients.

Patients receiving chronic haemodialysis treatment are known to have a high prevalence of anti-panel antibodies (anti-lymphocyte, anti-monocyte, and anti-endothelial cell) originating from a number of different possible sensitizing events such as blood transfusions, multiparity, or renal transplantation. In this study the prevalence of these antibodies in 123 chronic haemodialysis patients was evaluated. Anti-lymphocyte antibodies and anti-monocyte antibodies were found in 27.6% and 21.9% of the patient group respectively. Following exclusion of twelve patients within the study population with a history of previous graft rejection, anti-monocyte antibodies were encountered more frequently in transfused patients than those never having been transfused (22.4% versus 0%, P less than 0.05), whilst the prevalence of anti-lymphocyte antibodies was similar in both groups (28.2% versus 19.2%). Multiparity, patient age, or duration of dialysis treatment could not be demonstrated to significantly alter the prevalence of either of these antibodies. Of 12 patients with an episode of previous graft rejection, eight were positive for anti-monocyte antibodies and five for anti-lymphocyte antibodies. Anti-endothelial cell antibodies were common in patients in this group, being present in seven of eight individuals investigated.

Adolescent↗
PubMed1991

Three-dimensional structure of holo 3 alpha,20 beta-hydroxysteroid dehydrogenase: a member of a short-chain dehydrogenase family.

The x-ray structure of a short-chain dehydrogenase, the bacterial holo 3 alpha,20 beta-hydroxysteroid dehydrogenase (EC 1.1.1.53), is described at 2.6 A resolution. This enzyme is active as a tetramer and crystallizes with four identical subunits in the asymmetric unit. It has the alpha/beta fold characteristic of the dinucleotide binding region. The fold of the rest of the subunit, the quaternary structure, and the nature of the cofactor-enzyme interactions are, however, significantly different from those observed in the long-chain dehydrogenases. The architecture of the postulated active site is consistent with the observed stereospecificity of the enzyme and the fact that the tetramer is the active form. There is only one cofactor and one substrate-binding site per subunit; the specificity for both 3 alpha- and 20 beta-ends of the steroid results from the binding of the steroid in two orientations near the same cofactor at the same catalytic site.

Amino Acid Sequence↗
PubMed1991

Crystallization and preliminary diffraction analysis of cholesterol esterase from Candida cylindracea.

Cholesterol esterase (EC 3.1.1.13) from the microorganism Candida cylindracea has been crystallized in two forms. Crystals, typically 0.30 x 0.15 x 0.10 mm in size, diffract rotating anode generated x-rays to beyond 3 A are suitable for data collection for an x-ray crystallographic investigation. A monoclinic crystal form in the space group P2(1) was found to have cell dimensions of a = 122.9 A, b = 101.0 A, c = 95.2 A and beta = 108.3 degrees. The asymmetric unit of the cell contains two dimers of 129 kDa each. A second crystal form, in the triclinic space group P1, has cell dimensions of a = 58.6 A, b = 88.7 A, c = 58.6 A, alpha = 93.3 degrees, beta = 113.8 degrees and gamma = 96.0 degrees, and has one dimer per asymmetric unit.

Candida↗
PubMed1990

Narcolepsy.

Narcolepsy is a neurological condition with a prevalence of up to 1 per 1,000 that is characterized by irresistible bouts of sleep. Associated features include the pathological manifestations of rapid-eye-movement (REM) sleep: cataplexy, sleep paralysis, hypnagogic hallucinations, and abnormal sleep-onset REM periods and disturbed nocturnal sleep. The condition is strongly associated with the HLA-DR2 and DQw1 phenotype. The phenomenology of narcolepsy is discussed, and diagnostic procedures are reviewed. Treatment modalities involving central nervous system stimulants for somnolence and tricyclic drugs for REM-sleep abnormalities are discussed. Sleep laboratory studies on the treatment efficacy of methylphenidate, pemoline, dextroamphetamine, protriptyline, and viloxazine are presented. Data suggest that: (1) methylphenidate and dextroamphetamine objectively improve somnolence; (2) pemoline, at doses up to 112.5 mg, is less effective in controlling somnolence but may improve certain aspects of performance; and (3) protriptyline and viloxazine are effective anticataplectic agents that produce little improvement in somnolence.

Adult↗
PubMed1989

Extrapyramidal reactions. Neuropsychiatric mimics in patients with AIDS.

The use of neuroleptic medication as antiemetics, or in the treatment of neuropsychiatric disorders in patients with AIDS, may be associated with extrapyramidal side effects and lead to difficulty with diagnosis and management. Two cases are presented that describe severe extrapyramidal syndromes occurring in two patients with AIDS, one treated with prochlorperazine and the other with prochlorperazine and metoclopropramide. It is possible that the neuropathologic lesions found in patients with the AIDS dementia complex may pre-dispose to extrapyramidal side effects of neuroleptic medication. The differential diagnosis and treatment of delirium, dementia, depression, and extrapyramidal reactions in patients with AIDS is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1977

Conformations of prostaglandin F 2alpha and recognition of prostaglandins by their receptors.

The conformation of prostaglandin F 2alpha (PGF 2alpha) has been determined by x-ray diffraction techniques. Two independent conformers of PGF 2alpha, studied as the tris(hydroxymethyl)methylamine salt, are observed to adopt the familiar "hairpin" conformation with the alpha and omega chains aligned roughly parallel. The conformers differ in ring conformation and at the C(17)-C(18) bond, one adopting a C(9) envelope ring conformation and a trans geometry at the C(17)-C(18) bond, while the other adopts a C(8) envelope ring conformation and a novel gauche geometry about C(17)-C(18). Comparison of the conformation of PGF 2alpha with that of prostaglandin E2 suggests a recognition mechanism which would permit PGF 2alpha and prostaglandin E receptors to distinguish between the two potent prostaglandins. The recognition model explains much of the binding data for the PGF 2alpha receptor in the corpus luteum and predicts the existence of an interesting PGF 2alpha analog.

Molecular Conformation↗