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Biomedical subjects

M Stapleton

Publications and source records attributed to M Stapleton.

At least 19 recordsLinked to original sources
PubMed2003

Photosensitizers for photodynamic therapy of cutaneous disease.

Photodynamic therapy is a rapidly developing treatment modality in dermatology. A sensitizer drug is activated by light in the presence of oxygen. This results in the release of reactive oxygen species that damage the target tissue. The ideal features of a photosensitizer are that it should be highly selective for lesional tissue, activated by light of a sufficiently long wavelength for tissue penetration, and have a high photodynamic yield (i.e. production of singlet oxygen). A short time interval between administration and its maximal accumulation in tumour tissue, followed by rapid tissue clearance, are also desirable. First-generation sensitizers were complex chemical mixtures, needing parenteral administration and causing troublesome and prolonged photosensitivity. A range of second-generation sensitizers of different chemical families show several advantages including purity, longer activation wavelength and less prolonged photosensitivity, but effective topical formulations have not been developed. Currently, the most convenient and widely practised form of PDT for cutaneous disorders is the topical application of the pro-drug delta-aminolevulinic acid or its methylated ester, which are activated by light following metabolism to the endogenous sensitizer protoporphyrin IX.

Humans↗
PubMed2001

Topical tacrolimus in the management of peristomal pyoderma gangrenosum.

BACKGROUND: Peristomal pyoderma gangrenosum (PPG) is a potentially disabling disease in stoma patients. Topical tacrolimus has been shown to be effective in the management of pyoderma gangrenosum. Unfortunately, greasy topical treatments may be impractical for PPG because of impaired appliance adhesion. OBJECTIVE: The purpose of this open study was to evaluate the therapeutic effectiveness of topical tacrolimus 0.3% formulated in carmellose sodium paste compared with topical corticosteroid preparations in the management of PPG. RESULTS: A total of 11 patients with PPG received treatment with topical tacrolimus 0.3% in Orabase trade mark and 13 with topical clobetasol propionate 0.05% as monotherapy in each case. Seven of the tacrolimus-treated group healed completely (mean time to healing: 5.1 weeks) compared with five of the clobetasol propionate-treated group (mean time to healing: 6.5 weeks). Topical tacrolimus was significantly more effective than clobetasol propionate in managing larger PPG lesions (ulcer diameter > 2 cm). In six patients, who had failed to respond adequately to multiple systemic and topical treatments for PPG, the addition of topical tacrolimus was associated with healing of PPG within 6 weeks. CONCLUSION: These results suggest that topical tacrolimus 0.3% in Orabase trade mark is a more effective and expeditious treatment than clobetasol propionate 0.05% for PPG. It is significantly more effective than clobetasol propionate 0.05% in managing lesions larger than 2 cm in diameter. Topical tacrolimus may be highly effective when other systemic or topical treatments have been unsuccessful.

Abdomen↗
PubMed2001

Polychlorinated biphenyl contamination and minisatellite DNA mutation rates of tree swallows.

The evidence that exposure to polychlorinated biphenyls (PCBs) leads to mutations is equivocal and controversial. Using multilocus DNA fingerprinting, we compared the mutation rate of tree swallows (Tachycineta bicolor) nesting at sites with high and low levels of contamination with PCBs. The upper Hudson River, USA, is highly contaminated with PCBs as a result of releases from two capacitor manufacturing plants in Hudson Falls and Fort Edward, New York, USA. Tree swallows nesting nearby have some of the highest known concentrations of PCBs in their tissues of any contemporary bird population (up to 114,000 ng PCB/g tissue). We found no difference in mutation rates between sites in New York with high PCB contamination and reference sites in Wisconsin, USA, and Ontario and Alberta, Canada, with known or presumably low levels of contamination. Thus, the mechanism behind altered reproductive behavior of tree swallows along the upper Hudson River is most likely physiological impairment, such as endocrine disruption, rather than mutation.

Animals↗
PubMed2000

A Drosophila complementary DNA resource.

Collections of nonredundant, full-length complementary DNA (cDNA) clones for each of the model organisms and humans will be important resources for studies of gene structure and function. We describe a general strategy for producing such collections and its implementation, which so far has generated a set of cDNAs corresponding to over 40% of the genes in the fruit fly Drosophila melanogaster.

3' Untranslated Regions↗
PubMed2000

Topical sucralfate in the management of peristomal skin disease: an open study.

Dermatoses affecting the skin around stoma sites are common and difficult to treat. We have investigated the effectiveness of topical sucralfate in the management of peristomal dermatoses in adults using an open study design. Apart from forming a physical barrier to further irritation, sucralfate binds to basic fibroblast growth factor preventing its degradation and thereby promotes healing. In eight out of nine patients with faecal or urine erosions, daily, topical sucralfate treatment was associated with healing within 4 weeks. There was limited or no response to treatment in a further nine patients with traumatic ulcers, excoriated dermatitis or pyoderma gangrenosum. Topical sucralfate represents a safe, inexpensive and effective therapeutic intervention, particularly for those patients with high output or short stomas where repeated stoma leakage may be unavoidable.

Abdomen↗
PubMed2000

TAK1 participates in c-Jun N-terminal kinase signaling during Drosophila development.

Transforming growth factor beta (TGF-beta)-activated kinase 1 (TAK1) is a member of the MAPKKK superfamily and has been characterized as a component of the TGF-beta/bone morphogenetic protein signaling pathway. TAK1 function has been extensively studied in cultured cells, but its in vivo function is not fully understood. In this study, we isolated a Drosophila homolog of TAK1 (dTAK1) which contains an extensively conserved NH(2)-terminal kinase domain and a partially conserved COOH-terminal domain. To learn about possible endogenous roles of TAK1 during animal development, we generated transgenic flies which express dTAK1 or the mouse TAK1 (mTAK1) gene in the fly visual system. Ectopic activation of TAK1 signaling leads to a small eye phenotype, and genetic analysis reveals that this phenotype is a result of ectopically induced apoptosis. Genetic and biochemical analyses also indicate that the c-Jun amino-terminal kinase (JNK) signaling pathway is specifically activated by TAK1 signaling. Expression of a dominant negative form of dTAK during embryonic development resulted in various embryonic cuticle defects including dorsal open phenotypes. Our results strongly suggest that in Drosophila melanogaster, TAK1 functions as a MAPKKK in the JNK signaling pathway and participates in such diverse roles as control of cell shape and regulation of apoptosis.

Amino Acid Sequence↗
PubMed1998

HMG-17, a chromosomal non-histone protein, shows developmental regulation during organogenesis.

We used the differential hybridization technique for isolating developmentally regulated genes from the mouse metanephric kidney. In this screening, we identified the cDNA encoding high-mobility-group protein 17 (HMG-17), a chromosomal non-histone protein which modulates the conformation of transcriptionally active chromatin. Using Northern blot analysis, the HMG-17 mRNA was strongly expressed during embryogenesis and downregulated in various adult murine organs. At the histological level, the transcript localized to differentiating tissue regions and was apparently downregulated in mature structures indicating that HMG-17 expression is linked to cell differentiation. HMG-17 can thus be regarded as a general marker for tissues or cells undergoing differentiation during organogenesis.

Animals↗
PubMed1996

MADR1, a MAD-related protein that functions in BMP2 signaling pathways.

Components of the signaling pathways that lie downstream of Ser/Thr kinase receptors and are required for signaling by the TGF beta superfamily have been poorly defined. The Drosophila gene Mothers against dpp (MAD) and the C. elegans sma genes are implicated in these signaling pathways. We show that MAD functions downstream of DPP receptors and is required for receptor signaling. Phosphorylation of MADR1, a human homolog of MAD, is tightly regulated and rapidly induced by BMP2, but not TGF beta or activin. This phosphorylation is necessary for function, since a point mutant that yields a null phenotype in Drosophila is not phosphorylated. BMP2 treatment results in accumulation of MADR1 in the nucleus. MAD proteins may thus define a novel class of signaling molecules with nuclear function in Ser/Thr kinase receptor signaling pathways.

Activins↗
PubMed1995

Communitywide shigellosis: control of an outbreak and risk factors in child day-care centers.

OBJECTIVES: The study's objectives were to assess (1) control of a community outbreak of shigellosis through the promotion of handwashing, (2) risk factors in day-care centers, and (3) shigellosis attributable to attendance at a day-care center. METHODS: In 1991, an outbreak of Shigella sonnei infections occurred in Lexington-Fayette County, Ky; 14 licensed child day-care centers were involved. Communitywide promotion of hand washing was instituted along with diarrhea surveillance. A case-control study compared day-care centers that had confirmed cases of shigellosis with centers that had none. A family transmission study determined those cases attributable to attendance at day-care centers. RESULTS: The outbreak abated 3 weeks after the interventions' initiation. Day-care centers with outbreaks were more likely than those with no cases to have a food handler who changed diapers and to provide transportation for children from their homes to the center. These centers also had a higher toddler-to-toilet ratio than control centers (21 vs 12). In 58% of families with shigellosis, the first person with diarrhea during the outbreak was a child younger than 6 years; 92% of diarrheal illnesses among these children were attributable to day-care attendance. CONCLUSIONS: Community involvement in increasing hand washing most likely resulted in control of this shigellosis outbreak. Diarrhea prevention strategies in day-care centers could prevent substantial communitywide disease.

Case-Control Studies↗
PubMed1992

Adjuvanticity and ISCOM formation by structurally diverse saponins.

Adjuvant activity and immunostimulating complex (ISCOM) formation by a series of saponins and glycoalkaloids differing in the structures of their aglycones and sugar chains were examined. The only two saponins apart from Quillaia that were adjuvant-active were Gypsophila and Saponaria, which resemble Quillaia in that they contain saponins with branched sugar chains attached to positions 3 and 28 of the aglycone. Glycoalkaloids with a branched sugar chain lacked adjuvant activity. Saponaria saponins formed irregular ISCOM-like structures, and Gypsophila produced a sheet of joined pore-like structures. The alfalfa hederagenin saponin and Quinoa also formed pore-sheets, despite lacking adjuvanticity.

Adjuvants, Immunologic↗
PubMed1992

The control of the antibody isotype response to recombinant human immunodeficiency virus gp120 antigen by adjuvants.

Both saponin and muramyl dipeptide (MDP) formulated with a squalane-in-water emulsion of large particle size prepared with a vortex mixer were superior to Al(OH)3 as adjuvants for HIV gp120 in mice. All the adjuvants induced IgG1 antibody, but saponin elicited the highest titers of IgG2a. The secretion of interleukin-5 (IL-5) and interferon gamma (IFN gamma) by lymph node cells cultured in vitro with gp120 was studied. All the cultures secreted IL-5, but only those from saponin-immunized mice produced IFN gamma, suggesting that saponin is capable of activating both the Th1 and TH2 T-cell subsets. The titers of neutralizing antibodies were low with both MDP and saponin, and they occurred in mice which were also positive for antibodies against a V3 loop peptide. Glucosaminylmuramyl dipeptide (GMDP) which is less pyrogenic than MDP and a nonpyrogenic analog GMDPA, displayed equivalent adjuvant activity to MDP. The level and isotype composition of antibodies induced by GMDP in combination with squalane emulsions depended on the dimension of the emulsion particles. With a large (2500 nm) particle size the response was confined to IgG1 in Balb/c mice, but when this was reduced to 150 nm by sonication the antibody response was increased and relatively high levels of IgG2a appeared in some mice.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Dithranol allergy: fact or fiction?

A case of a psoriatic patient allergic to dithranol and coal tar is described. It is suggested that dithranol 0.001% pet. is a suitable concentration to test for dithranol allergy, as higher concentrations may produce irritant reactions. The literature on dithranol allergy is reviewed and the frequent simultaneous reactions to dithranol and coal tar discussed.

Anthralin↗
PubMed1992

Survival of persons with AIDS in Kentucky.

Of all reported Kentucky adult/adolescent cases of AIDS (124) with diagnosis dates from July 1, 1990, through June 30, 1991, 33% died within three months of diagnosis. To discern possible reasons for these very short survival times, information was analyzed from the CDC AIDS Confidential Case Report of the 124 patients and from the hospital charts of the 29 patients who were reported as having died within the month of or the month following diagnosis. Data suggested that survival for three months appears to be less likely for blacks, for males, and for those 30 through 34 years old. In the cohort the first diagnosis of AIDS was made at 40 different hospitals and the patients presented to 77 different physicians. Of chart-reviewed patients, 16 of the 29 (55.1%) were previously known to be HIV-positive. The most commonly identified likely reason for short survival time from AIDS diagnosis to death was that the diagnosis had been previously missed (10 of the 29 patients--34%). The study showed that many known to be HIV-positive for some time had apparently received little or no care for their infection from testing until diagnosis with AIDS. Medical review of patient charts suggested that scatter of caregivers may have resulted in some errors in diagnosis and treatment decisions. Also, considerable numbers of persons with HIV infection are either not utilizing the existing HIV counseling, testing, and follow-up systems or are not receiving medical care for their infection once it is identified.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Genomic structure of Chlamydomonas caltractin. Evidence for intron insertion suggests a probable genealogy for the EF-hand superfamily of proteins.

A clone containing the gene locus for Chlamydomonas caltractin, a 20,000 Mr calcium-binding protein that is a member of the EF-hand superfamily of calcium-modulated proteins, was isolated and the structural organization of the gene was determined. The intron-exon organization was resolved by direct comparison of the genomic sequence with a caltractin cDNA. The promoter region does not contain the typical TATA or CCAAT boxes, but the sequences at the splice junctions are similar to those of other eukaryotes. The positions of the six introns in the caltractin gene do not typically define unit structures, nor do they coincide with those in genes for other members of the EF-hand superfamily. An analysis of exon sequences at the splice junctions in the genes of this multigene family was undertaken; evidence was obtained that supports the hypothesis that introns arose at proto-splice sites. A probable evolutionary history for the EF-hand superfamily based on intron insertion is offered.

Amino Acid Sequence↗
PubMed1982

Serum elevation of high density lipoprotein (HDL) cholesterol in epileptic patients taking carbamazepine or phenytoin.

Serum lipids and the cholesterol concentration in the high density lipoprotein (HDL) fraction were measured in epileptic patients taking either carbamazepine or phenytoin as single drug treatment. There was a significant increase in HDL-cholesterol levels in patients taking both phenytoin and carbamazepine. Serum total-cholesterol concentrations in patients taking both drugs did not differ significantly from those of controls. The ratio of HDL-cholesterol/total cholesterol was increased in both drugs and the increase reached significance in patients taking phenytoin. There was a significant increase in serum triglycerides in females taking carbamazepine.

Adolescent↗