Psoriasis: Ferguson J

Ibbotson SH, Bilsland D, Cox NH, Dawe RS, Diffey B, Edwards C, Farr PM, Ferguson J, Hart G, Hawk J, Lloyd J, Martin C, Moseley H, McKenna K, Rhodes LE, Taylor DK, Anonymous00115. · Pathobiology Unit, Ninewells Hospital and Medical School, Dundee, UK. · Br J Dermatol. · Pubmed #15327535 No free full text.

Abstract: Summary These guidelines for use of narrowband (TL-01) ultraviolet B have been prepared for dermatologists by the British Photodermatology Group on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment of patients with a variety of dermatoses and photodermatoses, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of background photobiology.

Ferguson J. · No affiliation provided · Br J Dermatol. · Pubmed #11069495 No free full text.

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Ferguson J. · No affiliation provided · Arch Dermatol. · Pubmed #10328201 No free full text.

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Dawe RS, Yule S, Cameron H, Moseley H, Ibbotson SH, Ferguson J. · Photobiology Unit, Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Br J Dermatol. · Pubmed #16120152 No free full text.

Abstract: BACKGROUND: Dead Sea (DS) salt solution soaks are used in combination with narrowband ultraviolet B (NB-UVB) to treat psoriasis in many centres, particularly in continental Europe. No previously published controlled study has assessed DS salt + NB-UVB balneophototherapy. OBJECTIVES: To compare DS salt balneophototherapy with NB-UVB monotherapy for chronic plaque psoriasis. METHODS: Sixty patients with chronic plaque psoriasis participated in this paired, controlled study, with pretreatment DS salt soaks randomly allocated to each participant's right or left study limb. Psoriasis severity was assessed with a Scaling, Erythema and Induration score by a blinded observer. Assessments were weekly during the therapy course, and thereafter 8-weekly until relapse or for up to 1 year after clearance. RESULTS: The mean area under the psoriasis severity-time curves during treatment was not detectably lower with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0.099). The psoriasis severity score fell slightly more from beginning to end of courses with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0.019). There was no detectable difference in times to relapse. CONCLUSIONS: In this population the addition of pretreatment DS salt soaks to NB-UVB did not result in a clinically important improvement in clearance of psoriasis.

Dawe RS, Cameron H, Yule S, Man I, Wainwright NJ, Ibbotson SH, Ferguson J. · Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. · Br J Dermatol. · Pubmed #12828749 No free full text.

Abstract: BACKGROUND: In 1991, consensus guidelines recommended psoralen plus ultraviolet A photochemotherapy (PUVA) for those requiring second-line therapy for psoriasis. Narrowband (TL-01) UVB has since become more widely available, replacing the less effective broadband sources. Objectives To compare the efficacy of TL-01 UVB phototherapy and trimethoxypsoralen (TMP) bath-PUVA for chronic plaque psoriasis. PARTICIPANTS AND METHODS: A randomized, observer-masked, intraindividually controlled, paired (half-body) study was done in the Photo(chemo)therapy Unit in Ninewells Hospital and Medical School, Dundee. The study comprised 28 patients (skin phototypes I-III) with chronic plaque psoriasis. Each patient's body halves (sagittal plane) were treated independently, one-half with TL-01 UVB, the other with bath-PUVA. Both treatments were administered according to standard, optimized regimens. Treatment was continued until clearance or minimal residual activity (MRA), or a maximum of 30 treatments. The main outcome measures were treatments and time to clearance/MRA, the proportion reaching clearance/MRA, change in psoriasis severity score (scaling, erythema and induration) and remission durations. RESULTS: Of 18 who completed the study, all reached clearance/MRA with TL-01, but three were still not clear after 30 PUVA exposures. TL-01 achieved clearance/MRA a median of 11 (6.5-25; P = 0.001) days more quickly than PUVA, but required a median of 24.5 compared with 19 exposures [95% confidence interval (CI) for difference 1.5-5.5; P = 0.01]. Ten patients were withdrawn (four because of inadequate response of PUVA-treated halves). Analysed on an intention-to-treat basis, 21 of 28 (75%) of all participants reached clearance/MRA with TL-01 compared with 15 of 28 (54%) with PUVA (95% CI for difference 4-37%; P = 0.03). Remission durations did not differ. CONCLUSIONS: When administered according to these regimens in a skin phototype I-III population, TL-01 UVB is more efficacious than TMP bath-PUVA in the treatment of chronic plaque psoriasis.

Smith G, Wolf CR, Deeni YY, Dawe RS, Evans AT, Comrie MM, Ferguson J, Ibbotson SH. · Biomedical Research Centre, Ninewells Hospital and Medical School, DD1 9SY, Dundee, UK. · Lancet. · Pubmed #12711469 No free full text.

Abstract: BACKGROUND: Treatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemotherapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handling; we investigated whether similar variation in cutaneous gene expression contributes to individuality in response to topical therapies. METHODS: We used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29). We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis. FINDINGS: We found that CYP2S1 is expressed in skin and showed pronounced individuality in constitutive expression of the enzyme and its induction after ultraviolet irradiation or topical drug treatment. Cutaneous expression of CYP2S1 was induced by ultraviolet radiation, PUVA, coal tar, and all-trans retinoic acid; expression was significantly higher in lesional psoriatic skin than in adjacent non-lesional skin (geometric mean 3.38 [95% CI 2.64-4.34] times higher; p<0.0001), which implies that topical drugs are differentially metabolised in psoriatic plaque and non-lesional skin. We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme. INTERPRETATION: These findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis.

Cameron H, Dawe RS, Yule S, Murphy J, Ibbotson SH, Ferguson J. · Photobiology Unit, Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. · Br J Dermatol. · Pubmed #12410709 No free full text.

Abstract: BACKGROUND: The optimum treatment frequency for narrowband (TL-01) ultraviolet B (NB-UVB) in psoriasis is not yet known. We have previously found three times weekly to be preferable to five times weekly treatment in our population. OBJECTIVES: To compare twice weekly with three times weekly NB-UVB phototherapy in chronic plaque psoriasis. METHODS: In an observer-blinded, randomized comparison, patients with chronic plaque psoriasis referred from dermatology out-patient clinics in Tayside for NB-UVB phototherapy received either twice weekly (Monday and Friday) or three times weekly (Monday, Wednesday and Friday) whole-body NB-UVB phototherapy following our standard departmental treatment protocol. Treatment was continued to clearance or until the fourth treatment after minimal residual activity (MRA) was first documented. Number of days in treatment, number of treatments, total dose and time to relapse were recorded. RESULTS: In total, 113 patients were recruited, skin phototypes I-III: 58 in the twice weekly and 55 in the three times weekly group. Forty patients in the twice weekly group reached clearance/MRA, as did 44 in the three times weekly group. It took 1.5 (95% confidence interval 1.3-1.7) times longer to reach clearance/MRA with twice weekly therapy, a geometric mean of 88 vs. 58 days (P < 0.0001). Small differences in numbers of treatments and total dose to reach clearance tended to favour three times weekly therapy, but these were not significant. CONCLUSIONS: Three times weekly NB-UVB clears psoriasis significantly faster than twice weekly treatment, and therefore is preferable for most patients.

Dawe RS, Cameron H, Yule S, Man I, Ibbotson SH, Ferguson J. · Photobiology Unit, Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland. · Arch Dermatol. · Pubmed #12164745 links to  free full text

Abstract: OBJECTIVE: To determine if UV-B phototherapy clears psoriasis through systemic effects. DESIGN: Randomized, within-subject comparison of change in psoriasis in 3 plaques in patients attending for whole-body UV-B therapy. Change in patients' psoriasis plaques covered during UV-B treatment was compared with plaques in an untreated control group. SETTING: University hospital phototherapy unit. PATIENTS: The study population comprised 17 patients with chronic plaque psoriasis treated with UV-B and 24 psoriasis control patients awaiting UV-B phototherapy. INTERVENTIONS: Treatment with a standard 3-times weekly narrowband TL-01 UV-B regimen. Three similar plaques were randomly allocated to be covered every treatment, covered for 2 of 3 weekly treatments, and exposed to local UV-B every treatment. Similar plaques were selected in control patients (awaiting but not yet started UV-B therapy). Severity of psoriasis plaques was assessed using a scaling, erythema, and induration (SEI) scoring system. MAIN OUTCOME MEASURES: Change in SEI score of the selected plaques over the complete treatment course for UV-B-treated patients and change over 3 weeks in SEI score of plaques covered during UV-B treatment compared with that of plaques in controls. RESULTS: There was a significant (P<.001) difference in how much the SEI score changed in the 3 plaques in UV-B-treated patients. It fell by a mean of 7.6 for uncovered plaques compared with 3.2 for plaques covered during each UV-B exposure (95% confidence interval for difference, 3.0 to 5.8). In patients awaiting UV-B, SEI score of plaques fell by a mean of 0.4 over 3 weeks, compared with a mean fall of 1.4 for covered plaques in UV-B-treated patients (95% confidence interval for difference in means, 0.1 to 2.0). CONCLUSIONS: If UV-B therapy has any systemic effect capable of improving psoriasis, this effect is small and unlikely to be of clinical importance. It is insufficient to alter interpretation of findings of within-subject comparative phototherapy studies. UV-B phototherapy works for chronic plaque psoriasis through local effects.

Smith G, Wilkie MJ, Deeni YY, Farr PM, Ferguson J, Wolf CR, Ibbotson SH. · Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Br J Dermatol. · Pubmed #17916200 No free full text.

Abstract: BACKGROUND: The melanocortin 1 receptor (MC1R) is a highly polymorphic G protein-coupled receptor. Inheritance of various MC1R alleles has been associated with a red hair/fair skin phenotype, increased incidence of skin cancer and altered sensitivity to ultraviolet (UV) radiation. OBJECTIVES: To investigate whether MC1R genotype influences erythemal sensitivity to psoralen-UVA photochemotherapy (PUVA) in patients with psoriasis and other common skin diseases. METHODS: Patients (n = 111) about to start PUVA were recruited to the study. Erythemal responses were assessed visually at 72 h and 96 h following PUVA by assessment of the minimal phototoxic dose (MPD). MC1R genotype was determined by direct sequencing. RESULTS: Inheritance of the MC1R Arg(151)Cys allele was associated with a red hair phenotype (odds ratio 25.19, P = 0.0004). In contrast, inheritance of the Val(60)Leu and Arg(163)Gln SNPs was associated with increased PUVA erythemal sensitivity (reduced MPD) 72 h following treatment in all patients (n = 111; Val(60)Leu chi(2) = 5.764, P = 0.016; Arg(163)Gln chi(2) = 5.469, P = 0.019) and in a subset of patients with psoriasis (n = 55; Val(60)Leu chi(2) = 4.534, P = 0.033; Arg(163)Gln chi(2) = 7.298, P = 0.007). Inheritance of two or more MC1R SNPs was also associated with increased PUVA erythemal sensitivity (reduced MPD) in both patient groups (n = 111; chi(2) = 8.166, P = 0.017; n = 55; chi(2) = 10.303, P = 0.016). CONCLUSIONS: Our data demonstrate that MC1R genotype influences PUVA erythemal sensitivity in patients with psoriasis and other common skin diseases.

Smith G, Ibbotson SH, Comrie MM, Dawe RS, Bryden A, Ferguson J, Wolf CR. · Biomedical Research Centre and Photobiology Unit, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Br J Dermatol. · Pubmed #16882163 No free full text.

Abstract: BACKGROUND: Individuality in the expression and regulation of hepatic drug-metabolizing enzymes (DMEs) and cytoprotective (CP) genes is an important determinant of treatment response. There is increasing evidence that many DMEs and CP genes are also expressed in human skin. Responses to topical drugs used to treat common skin diseases, such as psoriasis, are unpredictable and may potentially be rationalized, at least in part, by interindividual differences in cutaneous DME and CP gene expression. OBJECTIVES: We investigated whether three topical drugs [coal tar, all-trans retinoic acid (atRA) and clobetasol 17-propionate] used in routine clinical practice modulated the expression of a variety of DME and CP genes [cytochrome P450s, glutathione S-transferases (GSTs) and drug transporters] in healthy human skin in vivo. METHODS: Healthy adult volunteers (n = 30) were invited to participate in the study. Each subject was randomly allocated to receive two of the three study chemicals and one control site application. Crude coal tar (n = 13), atRA (n = 14) or clobetasol 17-propionate (n = 10) was applied under occlusion to photoprotected buttock skin for 96 h. A vehicle control (white soft paraffin) was also applied under the same conditions at an adjacent site in all subjects. Full-thickness punch biopsies (4-mm diameter) were then taken from treated and control sites. Total RNA was extracted and reverse transcribed into cDNA, which was used as a template in subsequent real-time polymerase chain reaction analysis, where fluorescent output was directly proportional to input cDNA concentration. Triplicate measurements of skin mRNA expression were made from each sample, and the arithmetic mean values taken. After logarithmic transformation, the paired t-test was used to compare values between treated and control skin. RESULTS: Cytochrome P450s CYP1A1, CYP1A2, CYP1B1, CYP2C18, quinone reductase (NQO-1), GSTP1, gamma-glutamyl cysteine synthetase (gamma-GCS), glutathione peroxidase-1 (GPx-1), cyclooxygenase-2 (COX-2) and haem oxygenase-1 (HO-1) were induced by coal tar; CYP26, NADPH P450 reductase (CPR), GSTP1 and HO-1 by atRA; and CYP3A5 by clobetasol 17-propionate. In contrast, CYP1A1 and CYP1A2 expression was suppressed by atRA, and gamma-GCS and MRP1 by clobetasol 17-propionate. Marked interindividual variation in gene regulation by topical drugs was seen for the majority of genes examined. CONCLUSIONS: These data demonstrate that topical drugs can modulate DME gene expression in human skin in vivo and indicate that variation in the expression and regulation of these genes may be a determinant of individuality in response to topical therapies for common skin diseases.

Beattie PE, Dawe RS, Ferguson J, Ibbotson SH. · No affiliation provided · Clin Exp Dermatol. · Pubmed #15347356 No free full text.

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Dawe RS, Ferguson J. · Photobiology Unit, Department of Dermatology, Ninewells Hospital and Medical School, Dundee, Scotland. · Clin Exp Dermatol. · Pubmed #15245544 No free full text.

Abstract: We prospectively asked 146 consecutive patients starting narrow-band UVB (NB-UVB) for psoriasis about the effects of sunlight on their psoriasis. Eighty-eight (60%) patients reported improvement with sunlight, six (4%) reported worsening, and 52 (36%) had not noted any change in their psoriasis with sunlight exposure. Overall, 101 (69%) were recorded to reach clearance or minimal residual activity (MRA), 24 (16.5%) to achieve moderate improvement, and 21 (14.5%) had other recorded outcomes (mainly 'did not attend'), with UVB phototherapy. Forty-two (72%) of the 58 who did not report improvement with sunlight went on to clearance/MRA with UVB compared to 59/88 (67%) of those who did report improvement (95% confidence interval for difference in percentage improving, -10% to 20%, P = 0.49). Patients' replies to questions about how their psoriasis responds to sunlight do not appear to predict response to UVB phototherapy in our patient population.

Smith G, Dawe RS, Clark C, Evans AT, Comrie MM, Wolf CR, Ferguson J, Ibbotson SH. · Biomedical Research Center, Photobiology Unit, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK. · J Invest Dermatol. · Pubmed #12880432 links to  free full text

Abstract: There are unpredictable inter-individual differences in response to ultraviolet radiation, used in the treatment of psoriasis and other common skin diseases. It is therefore essential that we attempt to identify phenotypic markers that correlate with individual treatment outcomes. Exposure of human skin to ultraviolet radiation results in the generation of reactive intermediates and oxidative stress. Hepatic drug metabolizing and cytoprotective genes are induced as an adaptive response to xenobiotics and reactive intermediates; as several of these genes are present in skin, we hypothesized that their cutaneous expression and regulation may be implicated in responses to ultraviolet radiation. We used quantitative real-time reverse transcription-polymerase chain reaction to investigate interindividual differences in the cutaneous expression of a variety of drug metabolizing and cytoprotective genes, including cytochrome P450s, glutathione S-transferases and drug transporters, and investigated the regulation of gene expression by ultraviolet radiation and in lesional psoriatic skin. We confirmed significant induction of cyclooxygenase 2 (mean 3.63-fold, range 0.14-22.6, p<0.0001) by ultraviolet radiation and showed more modest (approximately 2-fold) inductions of glutathione peroxidase, and novel inductions of glutathione S-transferase P1 and the drug transporter multidrug resistance associated protein-1. Glutathione S-transferase P1 (3.74-fold, 1.3-33.1, p<0.0001) and multidrug resistance associated protein-1 (4.06-fold, 1.3-24.8, p<0.0001) were also significantly increased in psoriatic plaque, as were P450 CYP2E1 (3.64-fold, 1-28.9 p<0.0001) and heme oxygenase-1 (10.19-fold, 2.9-49.7, p<0.0001), implying a differential adaptive response to oxidant exposure in lesional psoriatic skin. We found considerable interindividual variation in constitutive gene expression and inducibility, indicating that these genes may be associated with individuality in response to ultraviolet radiation.

Cameron H, Yule S, Moseley H, Dawe RS, Ferguson J. · Photobiology Unit, Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. · Br J Dermatol. · Pubmed #12410707 No free full text.

Abstract: BACKGROUND: While most patients requiring phototherapy can attend for hospital-based out-patient ultraviolet (UV) B therapy, a significant number cannot attend because of geographical, work, economic and other reasons. OBJECTIVES: To determine whether there was a need for home phototherapy in the Tayside area and, if so, to establish protocols and then to assess if such a service would be workable. METHODS: Patients referred from dermatology out-patient clinics in Tayside for narrow-band UVB (TL-01) phototherapy completed a pilot questionnaire that was followed by a two-phase project. In phase 1, patients with psoriasis were trained to use the home phototherapy equipment (HoPE) within the hospital department under nursing supervision while a teaching package and protocols were developed. In phase 2, home phototherapy was made available for patient use in the community, supported by a specialist home phototherapy nurse. Waldmann UV100 home therapy units were used, with accurate dosimetry. Detailed treatment records were kept and questionnaires were used to assess acceptability and costs of therapy. RESULTS: Fifty-two pilot questionnaires were completed. Forty-two per cent of respondents found hospital phototherapy inconvenient and 75% felt phototherapy at home would be helpful. In phase 1, seven of 10 patients trained to use the HoPE completed therapy with the HoPE unit alone, reaching minimal residual activity (MRA) or clearance in a median of 18 exposures (median dose 10.38 J cm-2). In phase 2, 32 courses of home phototherapy were given to 30 patients. Of 23 with psoriasis, 18 reached clearance or MRA in a median of 22.5 exposures (median dose 9.84 J cm-2). Although self-reported erythema rates appeared higher than expected, all post-treatment questionnaire respondents would choose home phototherapy over hospital therapy if required in the future. CONCLUSIONS: UVB (TL-01) home phototherapy is a useful practical development that has fulfilled a need in our catchment area. Where appropriate training and support teams are available it appears to be similar in effectiveness to hospital therapy, to be safe and to be cost-effective for patients.

Ferguson J. · Photobiology Unit, Ninewells Hospital and Medical School, Dundee, DD1 9SY Scotland. · Photodermatol Photoimmunol Photomed. · Pubmed #11982921 No free full text.

This publication has no abstract.

Clark C, Dawe RS, Evans AT, Lowe G, Ferguson J. · Department of Dermatology, Ninewells Hospital and Medical School, Dundee, Scotland. · Arch Dermatol. · Pubmed #10871938 links to  free full text

Abstract: BACKGROUND: Although patch-stage mycosis fungoides (MF) has a generally good prognosis, and long-term survival rates with current therapies (UV-B, photochemotherapy, topical nitrogen mustards, electron-beam therapy) are similar, there is concern regarding their potential adverse effects. Narrowband or TL-01 UV-B phototherapy (311 nm), in use for more than 10 years, is more effective than broadband UV-B for the treatment of psoriasis, with an efficacy approaching that of psoralen UV-A. This open study assesses TL-01 as an alternative therapy for patch-stage MF. OBSERVATIONS: Eight white patients (4 men, 4 women; age range, 66-83 years) with histologically proven patch-stage MF received TL-01 phototherapy 3 times weekly using a standard protocol. Complete clearance of MF was achieved in 6 cases in a mean of 9 weeks or 26 treatments (range, 20-37 weeks) and 4 patients have had prolonged remissions. Mean duration of clinical improvement has been 20 months (range, 11-40 months). Partial response to TL-01 or poor histologic improvement was associated with rapid relapse. CONCLUSIONS: TL-01 is an effective, convenient therapy that may have less risk of long-term adverse effects than current alternatives. Although larger prospective studies are necessary, for some patients intermittent courses of TL-01 may offer effective long-term therapy.

Halpern SM, Anstey AV, Dawe RS, Diffey BL, Farr PM, Ferguson J, Hawk JL, Ibbotson S, McGregor JM, Murphy GM, Thomas SE, Rhodes LE. · Dermatology Unit, University Clinical Departments, University of Liverpool, Liverpool L69 3GA, UK. · Br J Dermatol. · Pubmed #10651690 No free full text.

Abstract: Psoralen photochemotherapy [psoralen ultraviolet A (PUVA)] plays an important part in dermatological therapeutics, being an effective and generally safe treatment for psoriasis and other dermatoses. In order to maintain optimal efficacy and safety, guidelines concerning best practice should be available to operators and supervisors. The British Photodermatology Group (BPG) have previously published recommendations on PUVA, including UVA dosimetry and calibration, patient pretreatment assessment, indications and contraindications, and the management of adverse reactions.1 While most current knowledge relates to oral PUVA, the use of topical PUVA regimens is also popular and presents a number of questions peculiar to this modality, including the choice of psoralen, formulation, method of application, optimal timing of treatment, UVA regimens and relative benefits or risks as compared with oral PUVA. Bath PUVA, i.e. generalized immersion, is the most frequently used modality of topical treatment, practised by about 100 centres in the U.K., while other topical preparations tend to be used for localized diseases such as those affecting the hands and feet. This paper is the product of a recent workshop of the BPG and includes guidelines for bath, local immersion and other topical PUVA. These recommendations are based, where possible, on the results of controlled studies, or otherwise on the consensus view on current practice.

Turner FB, Andreassi 2nd JL, Ferguson J, Titus S, Tse A, Taylor SM, Moran RG. · Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA. · Cancer Res. · Pubmed #10626793 links to  free full text

Abstract: Folates and folate antimetabolites are metabolically trapped in mammalian cells as polyglutamates, a process catalyzed by folylpoly-gamma-glutamate synthetase (FPGS). Using 5'-rapid amplification of cDNA ends, RNase protection assays, transfection of cDNAs into FPGS-deficient cells, and kinetic analysis of recombinant enzymes expressed in insect cells, it was determined that the species of active FPGS in mouse liver and kidney was different from that in mouse tumor cells, bone marrow, and intestine. The NH2-terminal peptide of hepatic enzyme contained 18 amino acids not found in enzyme from dividing tissues, and the specificity of the two isoforms for antifolates also differed, suggesting different architecture of the active sites. In most tissues, the expression of one isozyme or the other was an all-or-nothing event. The exclusive use of one of two alternative sets of initial coding exons in different tissues underlies this phenomenon, suggesting the design of antifolates specific for activation by individual FPGS isoforms and hence tissue-selective targeting of antifolate therapy for cancer, arthritis, or psoriasis.

Dawe RS, Arseculeratne G, Ferguson J. · No affiliation provided · Photodermatol Photoimmunol Photomed. · Pubmed #15752132 No free full text.

This publication has no abstract.