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Biomedical subjects

M Erman

Publications and source records attributed to M Erman.

At least 55 records · Page 3Linked to original sources

Monomeric and dimeric forms of cholesterol esterase from Candida cylindracea. Primary structure, identity in peptide patterns, and additional microheterogeneity.

Cholesterol esterase from Candida cylindracea was separated into two fractions, corresponding to a dimeric and a monomeric form. Fingerprint analysis after lysine cleavages shows identical patterns, suggesting lack of primary differences. Crystals obtained from the two proteins differ and suggest the possibility of an equilibrium between the two forms, influenced by the substrate cholesterol linoleate, which appears to stabilize the more active, dimeric form. All crystals have dimers as the asymmetric unit. The primary structure of the enzyme was determined at the peptide level and shows only one difference, Leu-350 instead of Ile, from a DNA-deduced amino acid sequence, and conservation of features typical for cholesterol esterases characterized.

Amino Acid Sequence↗

Crystallization and preliminary X-ray diffraction studies of a mammalian steroid dehydrogenase.

20 beta-Hydroxysteroid dehydrogenase from the cytosolic fraction of neonatal pig testis is a NADPH-dependent enzyme that catalyzes the reduction of the C-20 ketone of C21-steroids. It is 85% homologous in amino acid sequence to the human enzyme, carbonyl reductase. The enzyme has been crystallized from 36% saturated ammonium sulfate in 10 mM 2-[N-Morpholino]ethanesulfonic acid buffer. The size and the quality of nicely formed square bi-pyramidal crystals were improved by using a "seeding" technique. The crystals diffract X-rays to at least 2.5 A resolution. The space group is P4(1)2(1)2 (or P4(3)2(1)2) and the unit-cell dimensions are a = b = 58.53 A, c = 165.64 A. There is one molecule (M(r) = 30.5 kDa; 289 amino acid residues) in the asymmetric unit. An intensity data set to 2.5 A has been collected with an overall Rmerge of 6.6% for all reflections.

Animals↗

The treatment of excessive somnolence with stimulant drugs.

Controlling the symptom of excessive sleepiness is an important responsibility of sleep medicine. Our group has reported that methamphetamine, given in the morning at doses of 40-60 mg, allowed narcoleptics to function throughout the day at normal levels of sleep tendency and psychomotor functioning as measured by multiple sleep latency and performance testing. These findings are important because they are the first to show normalization of function in narcolepsy with pharmacotherapy and because the dose of stimulant utilized was more than twice the maximum recommended by the manufacturer. Because it is possible to essentially eliminate the disabling sleepiness of narcolepsy, at least in the short term, we suggest that the following principles be applied in the therapeutic use of stimulant drugs: 1) Pathological sleepiness warrants aggressive treatment when sustained alertness is necessary for individual or public safety; 2) Stimulant drugs are important in the therapeutic approach to patients with pathological sleepiness; 3) The prime goal, although sometimes unachievable, should be symptom-free daytime functioning. It is important that, during therapy, a period of symptom-free daytime functioning be achieved for a frame of reference for evaluating future treatments; 4) Treatment efficacy should be assessed periodically with objective techniques such as the multiple sleep latency test or the maintenance of wakefulness test; 5) In some cases, stimulant doses may exceed the manufacturer's recommendations. However, the clinician should be guided by the prime goal of therapy, the patient's needs and the patient's ability to tolerate the chosen therapy.

Central Nervous System Stimulants↗

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↗

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↗

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↗

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↗

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↗

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↗

Evidence for a directional correspondence between eye movements and dream imagery in REM sleep.

We examined the relationship between eye movement direction in REM sleep recorded by electrooculograph (EOG) and gaze direction in dream imagery. In a double-blind protocol, carefully screened and trained subjects were awakened subsequent to direct coupled EOG activity that was either predominantly horizontal or vertical. Following a target eye movement that fulfilled predetermined amplitude and directional criteria, a brief period of ocular quiescence was allowed to transpire before the subject was awakened. The dream narratives and EOG activity occurring prior to the REM awakenings were each reduced to a series of quantitatively scaled ratings. Analyses of variance demonstrated that when the confidence level of the experimenters' prediction is taken into account, statistically significant relationships exist between the number and direction of shifts of gaze in the dream report and scaled measurements of the corresponding EOG. When given dream narratives and the corresponding EOG recordings in sets of four, judges were unable to match them correctly better than by chance. However, in the above matching, judges significantly paired the dream narratives with EOG recordings that were in the same axis of gaze.

Adult↗

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↗

Alprazolam in bipolar-I depressions.

In an open-label study of alprazolam in five bipolar-I depressed patients, three patients remitted completely, one failed to respond, and one responded transiently, based on the Hamilton Rating Scale and Beck Depression Inventory scores. Further studies of alprazolam as an antidepressant are warranted.

Adult↗

Coincidental detection of T-cell rich B-cell lymphoma in the paraaortic lymph nodes of a woman undergoing lymph node dissection for cervical cancer.

The diagnosis of cervical squamous cell carcinoma with concurrent T-cell rich B-cell lymphoma in dissected lymph nodes has not been reported to our knowledge. We report such a case. The biopsy of an exophytic lesion at the uterine cervix showed squamous cell carcinoma in a 50-year-old woman presenting with postcoital bleeding. Type III hysterectomy, bilateral salpingo-oophorectemy, bilateral pelvic, paraaortic lymph node dissections were performed. Pathologic examination revealed a T-cell rich B-cell lymphoma in some lymph nodes beside squamous cell carcinoma in several of others. ELISA for human immuno-deficiency virus (HIV) was negative. The cervical carcinoma was staged as FIGO clinical stage IB1 and the lymphoma as Ann Arbor IIA. Six cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) chemotherapy for the lymphoma and concomitant pelvic chemo-radiotherapy with cisplatin for cervical cancer were given. In this rare coincidence; the best available therapy for each of the diseases should be considered individually. We also suggest that HIV screening test be carried out, because both diseases may be related to human immuno-deficiency virus, although our patient was HIV-negative.

Antineoplastic Combined Chemotherapy Protocols↗

Coincidental detection of T-cell rich B cell lymphoma in the para-aortic lymph nodes of a woman undergoing lymph node dissection for cervical cancer: a case report.

The diagnosis of cervical squamous cell carcinoma with concurrent T-cell rich B cell lymphoma in dissected lymph nodes has not been reported to our knowledge. In our case, the biopsy of an exophytic lesion at the uterine cervix showed squamous cell carcinoma in a 50-year-old woman presenting with postcoital bleeding. Type III hysterectomy, bilateral salpingo-oophorectemy, bilateral pelvic, para-aortic lymph node dissections were performed. Pathologic examination revealed a T-cell rich B cell lymphoma in some lymph nodes beside squamous cell carcinoma in several of others. ELISA for human immuno-deficiency virus (HIV) was negative. The cervical carcinoma was staged as FIGO clinical stage IB1 and the lymphoma as Ann Arbor IIA. Six cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolon) chemotherapy for the lymphoma and concomitant pelvic chemoradiotherapy with cisplatin for cervical cancer were given. In this rare coincidence, the best available therapy for each of the diseases should be considered individually. We also suggest that HIV screennig test be carried out, because both diseases may be related to human immuno-deficiency virus, although our patient is HIV-negative.

Antineoplastic Combined Chemotherapy Protocols↗