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Biomedical subjects

W Solomon

Publications and source records attributed to W Solomon.

At least 19 recordsLinked to original sources
PubMed2002

Predilection of hemolytic anemia-associated leg ulcers for the medial malleolus.

BACKGROUND: Ischemic ulcers are usually found above the lateral, and venous stasis ulcers at the medial malleoli. Leg ulcers occur in at least 25% of sickle cell disease (SSD) patients in clinic populations, usually in the malleolar region. The function of the large leg veins in most SSD patients is unimpaired. PATIENTS AND METHODS: We determined leg ulcer location in 41 sickle cell anemia (SS), and 4 sickle-beta 0 thalassemic patients with longstanding chronic and/or recurrent leg ulceration, and reviewed published reports of leg ulcers in hereditary spherocytosis and thalassemias. RESULTS: Of the 57 legs of the 45 SSD patients with only 1 ulcer, 42 (74%) were medial and 15 lateral. The difference was significant (p < 0.001). Of patients with only a single ulcer, 22 were medial and 4 lateral. Of 15 reported patients with leg ulcers related to spherocytosis or thalassemia, 20/24 (83%) ulcers were medial. CONCLUSIONS: The medial malleoli are the most common site of leg ulceration in SSD and in other chronic hemolytic anemias. This suggests that stasis may play a role in the leg ulceration associated with chronic hemolytic anemia.

Adult↗
PubMed2001

Response to hypoxia involves transforming growth factor-beta2 and Smad proteins in human endothelial cells.

Oxygen deprivation (hypoxia) is a consistent component of ischemia that induces an inflammatory and prothrombotic response in the endothelium. In this report, it is demonstrated that exposure of endothelial cells to hypoxia (1% O(2)) increases messenger RNA and protein levels of transforming growth factor-beta2 (TGF-beta2), a cytokine with potent regulatory effects on vascular inflammatory responses. Messenger RNA levels of the TGF-beta2 type II membrane receptor, which is a serine threonine kinase, also increased. The stimulatory effect of hypoxia was found to occur at the level of transcription of the TGF-beta2 gene and involves Smad proteins, a class of intracellular signaling proteins that mediates the downstream effects of TGF-beta receptors. Transient transfection studies showed that the region spanning -77 and -40 base pairs within the TGF-beta2 promoter (harboring a Smad-binding "CAGA box") is activated in hypoxic cells compared with nonhypoxic controls (P <.01). Hypoxia also stimulated transcription from another promoter, 3TP-Lux, a reporter construct responsive to Smads and TGF-beta. In addition, specific binding to a Smad-binding oligonucleotide was observed with nuclear extracts from hypoxic endothelial cells but not from nonhypoxic cells. It is concluded that Smad proteins, which can regulate endothelial responses to mechanical and inflammatory stress, also may play an important role in vascular responses to hypoxia and ischemia.

Binding Sites↗
PubMed2001

Impaired venous hemodynamics in a minority of patients with chronic leg ulcers due to sickle cell anemia.

BACKGROUND: Chronic or recurrent leg ulceration occurs in 25% of sickle cell anemia patients, but not in the remaining 75%. Doppler studies of venous function were normal in 16 sickle cell anemia patients with leg ulcers. PATIENTS AND METHODS: Venous Duplex Ultrasound was used to study 33 sickle cell anemia patients with chronic leg ulcers. RESULTS: Six of the 33 patients had venous reflux in at least one leg. CONCLUSIONS: Venous insufficiency may contribute to the development of leg ulcers in a minority of sickle cell anemia patients. A minority of sickle cell anemia patients with chronic leg ulcers can be shown to have leg venous reflux by duplex ultrasound imaging.

Adult↗
PubMed1999

Composite co-activator ARC mediates chromatin-directed transcriptional activation.

Gene activation in eukaryotes is regulated by complex mechanisms in which the recruitment and assembly of the transcriptional machinery is directed by gene- and cell-type-specific DNA-binding proteins. When DNA is packaged into chromatin, the regulation of gene activation requires new classes of chromatin-targeting activity. In humans, a multisubunit cofactor functions in a chromatin-selective manner to potentiate synergistic gene activation by the transcriptional activators SREBP-1a and Sp1. Here we show that this activator-recruited cofactor (ARC) interacts directly with several different activators, including SREBP-1a, VP16 and the p65 subunit of NF-kappaB, and strongly enhances transcription directed by these activators in vitro with chromatin-assembled DNA templates. The ARC complex consists of 16 or more subunits; some of these are novel gene products, whereas others are present in other multisubunit cofactors, such as CRSP, NAT and mammalian Mediator. Detailed analysis indicates that the ARC complex is probably identical to the nuclear hormone-receptor cofactor DRIP. Thus, ARC/DRIP is a large composite co-activator that belongs to a family of related cofactors and is targeted by different classes of activator to mediate transcriptional stimulation.

Amino Acid Sequence↗
PubMed1997

Rhinitis and inhalant allergens.

Allergic rhinitis affects about 20% of the US population. The diagnosis is based on patterns of symptoms, physical examination, and assessment of IgE antibodies by skin or in vitro testing. The most common offending allergens are pollens of grasses, trees, and weeds; fungi; animal allergens; and dust mites. In an individual with nasal allergy, exposure leads to rapid release of mast cell-derived mediators. This immediate response is followed by a cell-dominated response, including eosinophils and lymphocytes. Cytokines from T(H)2 lymphocytes, such as interleukin 4 and interleukin 5, orchestrate allergic inflammation. Resulting tissue changes produce symptoms of the disease and augment responses on subsequent exposure to allergens and irritants. Strategies for avoiding offending agents are important in management. In intermittent disease, antihistamines and/or decongestants are first prescribed. More continuous symptoms may mandate intranasal steroids. Immunotherapy is often helpful for patients who respond poorly to pharmacotherapy and avoidance.

Allergens↗
PubMed1996

An incremental dosing protocol for women with severe vaginal trichomoniasis and adverse reaction to metronidazole.

OBJECTIVE: Our purpose was to develop and test an incremental dosing protocol for women with adverse reaction to metronidazole and severe symptomatic Trichomonas vaginitis. STUDY DESIGN: Two women with documented Trichomonas infection and presumed metronidazole allergy were initially treated with a number of alternative methods without success. With persistent severe symptoms associated with their infection, these women were admitted to the hospital and underwent an intravenous incremental metronidazole dosing protocol. RESULTS: Both patients were successfully treated without adverse event. They are both symptom-free and apparently cured several months after treatment. CONCLUSION: This protocol offers a new therapeutic option to women with adverse metronidazole reactions and severe symptomatic Trichomonas vaginitis resistant to treatment with nonmetronidazole therapy.

Antitrichomonal Agents↗
PubMed1996

The viewing wand--its introduction and uses.

The Innovated Systems Group (ISG) Viewing Wand was developed in Toronto, Canada, for use in Neurosurgery. In June 1992, Frenchay Hospital was the first centre in Europe to pioneer the use of the ISG Viewing Wand, which is an intraoperative image display system. This equipment has in the main replaced stereotaxic surgery by removing the need for a cumbersome frame and intra-operative scanning. However, there is still a need for stereotaxic surgery for point source localisation of small deep seated targets e.g. thalamotomy and pallidotomy. The aim of this article is to explain what the Viewing Wand is, what it does and the effect this hi-tech equipment has had on theatre nursing practice.

Equipment Design↗
PubMed1995

Maduropeptin: an antitumor chromoprotein with selective protease activity and DNA cleaving properties.

Maduropeptin (MDP) is a recently isolated antitumor antibiotic, consisting of an enediyne-containing chromophore embedded in a highly acidic protein. This holoantibiotic damages duplex DNA in vitro, producing a mixture of single- and double-strand breaks at selected sites. The chromophore, isolated as the methanol adduct from the protein-containing holoantibiotic, exhibits the same selectivity and cleavage chemistry as the chromoprotein complex. Preliminary evidence suggests that the primary DNA breaks involve 4'-H abstraction from the deoxyribose sugars at the cleavage sites. Unlike most other enediyne antitumor antibiotics, DNA strand scission is not bioreductively induced by MDP or the methanol adduct of the chromophore. This was also observed for the C1027 chromophore. DNA cleavage is inhibited in the presence of certain cations (Ca2+, Mg2+) as was observed with the kedarcidin chromophore. 1H NMR spectroscopy studies on the methanol adduct of the maduropeptin chromophore in the presence of calcium chloride provide clues regarding its activation and give insight as to the regions of the chromophore important for DNA binding. Our results suggest that the solvent artifact of the chromophore may in essence be a prodrug and it regenerates the parent chromophore as in the holoantibiotic prior to cleaving DNA. As with kedarcidin and neocarzinostatin, maduropeptin exhibits a high affinity for histones, in vitro, cleaving them to low molecular mass peptides. Histone H1, the most opposite in net charge, is cleaved most readily. This latter activity may serve to disrupt the chromatin superstructure in vivo, prior to exposing the DNA to the chromophore.

Alkynes↗
PubMed1993

Selective proteolytic activity of the antitumor agent kedarcidin.

Kedarcidin is a potent antitumor antibiotic chromoprotein, composed of an enediyne-containing chromophore embedded in a highly acidic single chain polypeptide. The chromophore was shown to cleave duplex DNA site-specifically in a single-stranded manner. Herein, we report that in vitro, the kedarcidin apoprotein, which lacks any detectable chromophore, cleaves proteins selectively. Histones that are the most opposite in net charge to the apoprotein are cleaved most readily. Our findings imply that the potency of kedarcidin results from the combination of a DNA damaging-chromophore and a protease-like apoprotein.

Amino Acid Sequence↗
PubMed1993

Kedarcidin chromophore: an enediyne that cleaves DNA in a sequence-specific manner.

Kedarcidin chromophore is a 9-membered enediyne, recently isolated from an actinomycete strain. In vivo studies show this molecule to be extremely active against P388 leukemia and B16 melanoma. Cytotoxicity assays on the HCT116 colon carcinoma cell line result in an IC50 value of 1 nM. In vitro experiments with phi X174, pM2 DNA, and 32P-end-labeled restriction fragments demonstrate that this chromophore binds and cleaves duplex DNA with a remarkable sequence selectivity producing single-strand breaks. The cleavage chemistry requires reducing agents and oxygen similar to the other naturally occurring enediynes. Certain cations (Ca2+ and Mg2+) prevent strand cleavage. High-resolution 1H NMR studies on the chromophore in the presence of calcium chloride implicate the 2-hydroxynaphthoyl moiety in DNA binding. Interestingly, the kedarcidin chromophore appears structurally related to neocarzinostatin yet recognizes specific DNA sequences in a manner similar to calicheamicin gamma 1I, an enediyne with a significantly different structure. Moreover, kedarcidin and calicheamicin share a DNA preferred site, the TCCTN-mer. These observations indicate that the individual structural features of these agents are not solely responsible for their DNA selectivity. Rather, a complementarity between their overall tertiary structure and the local conformation of the DNA at the binding sites must play a significant role in the recognition process.

Alkynes↗
PubMed1992

Altered interleukin-2 production in schizophrenia: association between clinical state and autoantibody production.

Mitogen-stimulated interleukin-2 (IL-2) production was measured in 122 patients who met Research Diagnostic Criteria for schizophrenia and 98 normal control subjects. The presence of autoantibodies against seven common antigens was also determined. There was no relationship between the presence of circulating autoantibodies and IL-2 production in control subjects. In patients, however, autoantibody-positive, acutely ill patients had significantly lower IL-2 production as compared with other patients and control subjects. Never-medicated patients showed the same trends for decreased IL-2 production in association with autoantibodies. These data suggest that decreased IL-2 production is associated with acute illness in schizophrenic patients who produce autoantibodies, a trait known to be associated with increased vulnerability to autoimmune disease.

Adult↗
PubMed1989

Stimulation of the human heat shock protein 70 promoter in vitro by simian virus 40 large T antigen.

Simian virus 40 large tumor (T) antigen stimulates transcription from the SV40 late promoter and some cellular genes. We report here the novel finding that purified T antigen preferentially stimulates transcription from the human heat shock protein 70 promoter in an in vitro transcription system. T antigen is thus capable of stimulating transcription by a process that does not require synthesis of other proteins and that may involve a direct interaction with preexisting cellular factors.

Animals↗
PubMed1987

Epicoccum allergy: skin reaction patterns and spore/mycelium disparities recognized by IgG and IgE ELISA inhibition.

Comparable degrees of skin reactivity were observed towards spore and mycelium extracts from two isolates of Epicoccum and to one preparation of Alternaria in 35 rural and 120 university patients. The best experimental extracts detected Epicoccum sensitivity in 70% of the group tested while the commercial extract detected sensitivity in only 6%. Skin reaction correlations were greatest within isolates (eg, spore-A/mycelium-A), then for specific fungus parts (eg, spore-A/spore-B), then between isolates and parts (spore-A/mycelium-B). High correlations were found between individual IgG and IgE ELISA values for all antigens using serum from Epicoccum skin-reactive patients. ELISA inhibition results suggested that significant cross-reactivity exists between Epicoccum and Alternaria antigens recognized by IgG but not by IgE. ELISA inhibition cross-reaction patterns among Epicoccum antigens were comparable to skin reactions while IgG patterns showed little variability. Further characterization of spore/mycelium and interstrain recognition patterns among different immunoglobulin isotypes will be necessary before complete standardization of extracts from different parts of fungi will be possible. The use of spore material for skin testing and treatment of Epicoccum sensitivity appears to be both premature and unnecessary at this time.

Enzyme-Linked Immunosorbent Assay↗
PubMed1985

The "beta-like-globin" gene domain in human erythroid cells.

We have mapped the distribution of the major and minor DNase I-hypersensitive sites in the human "beta-like-globin" gene domain. The minor DNase I-hypersensitive sites map close to the 5' end of each of the beta-like-globin genes. Their presence is specifically associated with the transcription of the immediate downstream beta-like-globin genes. The major DNase I-hypersensitive sites map in what appear to be the 5' and 3' boundary areas of the human beta-like-globin gene domain, a region estimated to span at least 90 kilobases of DNA. These major sites are present in various erythroid cells, which express predominantly either the embryonic, the fetal, or the adult beta-like-globin genes, and seem to be involved in defining the active beta-like-globin genes domain in cells of erythroid lineage. The four major DNase I-hypersensitive sites in the 5' boundary area, when correlated with sequencing data, are shown to be located in DNA regions containing enhancer core-like sequences and alternating purine and pyrimidine bases.

Base Sequence↗