Biomedical subjects
Publications and source records attributed to S Hammer.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
High affinity receptors (VDR) for 1,25-dihydroxycholecalciferol (calcitriol) are expressed in HL60 human leukemia cells and in low numbers in peripheral blood lymphocytes (PBL). HL60 cells, expressing some characteristics of promyelocytes, can be induced to monocytoid differentiation by calcitriol. Specific nuclear translocation of [3H]calcitriol/VDR was examined after exposure of whole cells to 10(-9) M/l calcitriol in the presence and absence of a 500-fold excess of unlabeled ligand and subsequent isolation of nuclei. Specific nuclear translocation of [3H]calcitriol/VDR was found to be time dependent reaching a maximum of approximately 2100 binding sites/nucleus after 3 h of incubation in HL60 cells, whereas a maximum of approximately 310 binding sites/nucleus was found after 3 h in PBL. Pulse exposure of HL60 to radiolabeled hormone for 3 h followed by culture in medium without serum and calcitriol lead to nuclear retention of approximately 1600 radiolabeled VDR by 8 h and approximately 1000 VDR by 24 h. Radiolabeled VDR disappeared from the nuclear compartment with a halflife of approximately 30 min if cells were cultured with identical concentrations of unlabeled hormone after the pulse (pulse/chase-experiments). No difference of VDR retention in pulse and pulse/chase-experiments was seen in PBL, where VDR halflife was approximately 30 min. No specific translocation into the nuclear compartment was seen when isolated nuclei were incubated in [3H]calcitriol. Radiolabeled hormone/receptor complexes of nuclei isolated from cells exposed for 3 h to radiolabeled hormone--in contrast to identical experiments with intact cells--did not disappear from the nuclear compartment upon incubation of nuclei with identical concentrations of the unlabeled compound. The activity of DNA relaxing enzymes (e.g. topoisomerases I and II) in nuclear extracts was measured using a PBR 322-relaxation-assay. Enhanced overall enzyme activity was found in nuclear extracts by 1 h after incubation with calcitriol (final ethanol concentration 0.0001% v/v) in HL60 and PBL. The enhanced activity disappeared after 2 h in PBL, whereas it was still enhanced by 4 h in HL60. No effect was seen in ethanol treated controls. We conclude that a specific nuclear translocation mechanism exists for calcitriol in both cell types examined, most likely due to translocation of receptor proteins after hormone binding. Translocated hormone/receptor complexes compete for a limited number of specific nuclear binding sites. Enhanced activity of topoisomerases in nuclear extracts upon translocation of VDR might reflect interaction of both within the nuclear compartment, thus initiating DNA-unwinding, a prerequisite of transcription initiation.
Explore the source record for details and available documents.
The three major areas of concern which impact the automation of today's hospital pharmacy send a clear message to vendors. The message is that vendors need to offer an integrated pharmacy management system on the hospital's central computer to offer significant department functionality. The system must have a consistent fit into the technological direction of information systems at the hospital. Such a system provides the ability to gather and access information for numerous hospital departments to support the delivery of high quality clinical care and to support the decision-making process. This provides the hospital the best chance to compete effectively. The hospital's objective must continue to be the main thrust of software development efforts.
This case report documents a perforation of the terminal ileum in a 40-year-old white male homosexual with the acquired immunodeficiency syndrome. The perforation occurred at a site that had severe cytomegalovirus infection and was in close proximity to multiple nodules of Kaposi's sarcoma. The ileum showed multiple deep ulcers with large numbers of cytomegalovirus inclusions and vasculitis with infected endothelial cells, small-vessel thrombosis, focal disruption, and hemorrhage. We review the evidence that cytomegalovirus infection--and not Kaposi's sarcoma--was responsible for this perforation and, in light of the new medical therapy for such infections, should be regarded as an important cause of gastrointestinal perforation in patients with the acquired immunodeficiency syndrome.
Interocular differences in tonic accommodation were assessed before and after a 10 minute period of sustained monocular fixation. The fixation task was carried out once for each eye using a high-contrast target at near, and once for each eye using an empty illuminated field. Tonic accommodation increased significantly as a result of fixating the high contrast target at near, but remained stable when viewing the empty field. Close correspondence was found between the two eyes with respect to both prefixation tonic level and magnitude of tonic after-effect. Absence of interocular differences clearly demonstrates the consensuality of accommodative hysteresis.
Explore the source record for details and available documents.
Pulmonary reactions may follow therapy with nitrogen mustard, vincristine, procarbazine, and prednisone. Two patients with Hodgkin's disease are described who were treated with nitrogen mustard, vincristine, procarbazine, and prednisone and developed diffuse lung disease. Their disease processes were evaluated with serial pulmonary function studies, chest radiography, and open lung biopsy. Hypersensitivity reactions appeared to be responsible, and treatment with corticosteroids was successful. Procarbazine may have been the responsible agent.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
As compared to standard glucocorticoids (GC), prednicarbate (PC) is favorable in the treatment of eczema due to its high benefit/risk ratio. The remarkable anti-inflammatory effects of PC are in strong contrast to its reported low glucocorticoid receptor (GR) binding affinity. In transfected COS-7 cells we related the transcriptional potencies of PC, its metabolites and conventional GC to their receptor binding properties. Moreover, the expression pattern of the human GR isoform hGRalpha and its mutual dominant negative inhibitor hGRbeta in skin cells have been investigated as well as the influence of hGRbeta on receptor binding and transactivation. hGRalpha mRNA and protein was largely overexpressed in skin cells. hGRbeta showed no influence on hGRalpha binding and transactivation. Concentration response curves indicated the greater transactivation potency of betamethasone 17-valerate followed by dexamethasone and prednisolone 17-ethylcarbonate. Native PC appeared almost as potent as dexamethasone. With both a strong correlation was observed between transactivation and GR binding.
Since the limited knowledge of cutaneous drug metabolism can impair the development of specifically acting topical dermatics and transdermal application systems, the cell-type-specific androgen metabolism in human skin and its inhibition by drugs were investigated. Cultured human foreskin and scalp skin keratinocytes and fibroblasts as well as occipital scalp dermal papilla cells (DPC) were incubated with testosterone 10(-6) and 10(-8)M alone and in the presence of 17alpha-estradiol, 17beta-estradiol or dutasteride for 24 h. Androgens extracted from culture supernatants were subjected to thin-layer chromatography and quantified by beta-counting. In keratinocytes and DPC, dihydrotestosterone (DHT) was only formed to a low extent while androstenedione was the main metabolite. In fibroblasts, DHT formation was pronounced following 10(-8)M testosterone. Dutasteride 10(-8)M completely suppressed 5alpha-dihydro metabolite formation. 17alpha-Estradiol and 17beta-estradiol at nontoxic concentrations decreased 17-ketometabolites. Human skin regulates testosterone action by cell-type-specific activation or deactivation. Effects of 17alpha-estradiol in androgenetic alopecia are not due to 5alpha-reductase inhibition. Dutasteride may be useful in acne and androgenetic alopecia.