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T A Hamilton

Publications and source records attributed to T A Hamilton.

At least 55 records · Page 3Linked to original sources
PubMed1996

IL-4-induced expression of the IL-1 receptor antagonist gene is mediated by STAT6.

IL-4 alone or in cooperation with LPS can induce the expression of the gene encoding the secreted-type IL-1 receptor antagonist (sIL-1ra) in mononuclear phagocytes. To determine the nuclear signaling mechanisms involved in this response, the region flanking the transcription start site of the human sIL-1ra gene was placed upstream of the luciferase reporter gene, and the function of specific sequence elements was analyzed following transient transfection in the macrophage-like cell line RAW264.7. A region located between -250 and -200 bases relative to the transcription start site was necessary for response to IL-4 alone and for cooperation between IL-4 and LPS. This 50-bp region contains two inverted repeat elements that represent potential binding sites for members of the signal transducer and activator of transcription (STAT) gene family (STAT-binding elements (SBEs)). Site-directed mutagenesis of the distal SBE abolished IL-4 responsiveness, and multiple copies of this motif were able to confer IL-4 sensitivity to luciferase expression in the context of a heterologous (herpes virus thymidine kinase) promoter. Mutation of the proximal SBE in the intact IL-1ra promoter had little or no effect on response to IL-4, and this sequence motif was inactive when examined alone. Electrophoretic mobility shift assays using an oligonucleotide corresponding to the distal SBE identified a single binding activity that was detected in nuclei within 15 min of IL-4 treatment and that was recognized by Ab to STAT6. These results indicate that IL-4-induced STAT6 is required for IL-4-induced transcriptional activation of the sIL-1ra gene.

Animals↗
PubMed1996

LPS does not directly induce STAT activity in mouse macrophages.

Induction of gene expression in cytokine-treated cells involves the protein tyrosine kinase-dependent activation of members of the STAT family of transcription factors. To determine if lipopolysaccharide (LPS) might activate one or more STAT factors, nuclear extracts from LPS-treated RAW264.7 macrophages were assayed for STAT-like DNA binding activity using oligonucleotides recognized by different members of this protein family. Within 30 min a single LPS-inducible DNA-protein complex was detected using three separate oligonucleotides. This activity was not reactive with anti-STAT antibodies and was subsequently identified as composed of the NF kappa B components NF kappa B1 and Rel-A. Thus, LPS does not directly stimulate STAT factors with known sequence-specific DNA binding activity.

Animals↗
PubMed1996

Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites.

Pentraxins, which include C reactive protein (CRP) and serum amyloid P component (SAP), are prototypic acute phase reactants that serve as indicators of inflammatory reactions. Here we report genomic and cDNA cloning of mouse ptx3 (mptx3), a member of the pentraxin gene family and characterize its extrahepatic expression in vitro and in vivo. mptx3 is organized into three exons on chromosome 3: the first (43 aa) and second exon (175 aa) code for the signal peptide and for a protein portion with no high similarity to known sequences the third (203 aa) for a domain related to classical pentraxins, which contains the "pentraxin family signature." Analysis of the N terminal portion predicts a predominantly alpha helical structure, while the pentraxin domain of ptx3 is accommodated comfortably in the tertiary structure fold of SAP. Normal and transformed fibroblasts, undifferentiated and differentiated myoblasts, normal endothelial cells, and mononuclear phagocytes express mptx3 mRNA and release the protein in vitro on exposure to interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF)alpha. mptx3 was induced by bacterial lipopolysaccharide in vivo in a variety of organs and, most strongly, in the vascular endothelium of skeletal muscle and heart. Thus, mptx3 shows a distinct pattern of in vivo expression indicative of a significant role in cardiovascular and inflammatory pathology.

3T3 Cells↗
PubMed1996

Cytokine and chemokine expression in tumors of mice receiving systemic therapy with IL-12.

The cellular and molecular mechanisms of IL-12-mediated anti-tumor activity have been examined. BALB/c mice bearing established s.c. RENCA or CT26 tumors that were treated daily with IL-12 showed essentially complete tumor regression while tumors in untreated animals grew progressively. Examination of inflammatory gene expression in tumor tissue from treated vs untreated mice revealed the selective expression of IFN-gamma and the IFN-gamma-inducible CXC chemokine IP-10. Immunohistologic analysis demonstrated that tumors from treated mice were heavily infiltrated with CD8+ T cells and Mac-1+ mononuclear cells. Tumor regression in IL-12-treated mice was associated with expression of the lytic effector molecules perforin and granzyme B. These findings support the hypothesis that the anti-tumor function of IL-12 treatment depends upon the induced expression of IFN-gamma by T cells and/or NK cells, the amplification of the immune response mediated by IFN-gamma-induced expression of chemoattractant cytokines, and the IL-12-dependent potentiation of the cytolytic effector function of recruited CD8+ T cells.

Adenocarcinoma↗
PubMed1996

Oxidized LDL potentiates LPS-induced transcription of the chemokine KC gene.

Oxidized low-density lipoprotein (LDL) has been shown to modulate the expression of multiple gene products associated with inflammation in several different cell types including mononuclear phagocytes. The reported effects vary dramatically, however, depending upon cell type, stimulus, and degree of LDL oxidation. In the present report, oxidized LDL has been found to markedly potentiate expression of the KC chemokine gene in lipopolysaccharide (LPS)-stimulated macrophages. Pretreatment of elicited mouse peritoneal macrophages with oxidized LDL but not native LDL produced a significant enhancement of LPS-induced KC mRNA expression, whereas levels of IP-10 mRNA, another CXC chemokine, were altered in opposite fashion. The alteration in KC mRNA expression was dependent upon the dose, exposure time, and extent of LDL oxidation. Oxidized LDL selectively prolonged the expression of KC mRNA. Surprisingly this was not a consequence of altered mRNA stability, but rather of prolonged transcription. These effects on KC gene transcription were in marked contrast to previous reports demonstrating inhibitory effects of oxidized LDL on LPS-induced macrophage chemokine expression. Thus extensively oxidized LDL acts on the transcriptional control process in macrophages in both positive and negative fashion on separate members of the same gene family.

Animals↗
PubMed1996

A comparison of wire brush and diamond fraise superficial dermabrasion for photoaged skin. A clinical, immunohistologic, and biochemical study.

BACKGROUND: Superficial dermabrasion has a proven beneficial effect on photoaged skin, but little is known about the differences between the two major modalities used in dermabrasion, the diamond fraise (DF) and the wire brush (WB). OBJECTIVE: We compared the clinical, immunohistologic, and biochemical changes after superficial dermabrasion with DF and WB. METHODS: Eight photoaged patients (mean age, 68 years; range, 49 to 80 years) underwent facial dermabrasion to the level of the papillary dermis. Clinical assessments were performed at baseline and at 3 and 12 weeks after dermabrasion. Biopsy specimens were taken from both dermabraded halves at the same time points and assessed by routine histologic and immunohistologic examinations, western blot analysis, and radioimmunoassay. Scoring of intracellular and extracellular transforming growth factor-beta 1 was based on a semiquantitative ordinal scale (0 = no staining to 4 = maximum staining) in half-unit increments. The score for each specimen represents the average of values obtained from four high-power fields. RESULTS: Both methods of dermabrasion resulted in significant resolution of actinic keratoses, lentigines, and wrinkling. No statistical significance was noted between the two methods in regard to clinical efficacy. Significantly fewer milia occurred after DF than after WB. Solar elastosis decreased with both the WB and DF. Immunohistologic examination demonstrated a highly significant increase in papillary dermal fibroblast staining for amino terminal procollagen I (type I pN-collagen) at 3 weeks for both DF and WB compared to baseline. Staining at 12 weeks had decreased from the peak noted at week 3, but was still significantly increased from baseline. Western blotting of type I pN-collagen demonstrated a 5.4-fold (p = 0.01) increase from baseline at 3 weeks and a 4.9-fold (p = 0.002) increase at 12 weeks after dermabrasion with the WB. Similarly, the DF produced a 4.9-fold (p = 0.006) increase at 3 weeks and a 5.1-fold (p = 0.008) increase at 12 weeks after dermabrasion. Western blotting of amino terminal procollagen III (type III pN-collagen) showed a 6.1-fold (p = 0.07) increase from baseline at 3 weeks and a 3.9-fold (p = 0.04) increase at 12 weeks after dermabrasion with the DF. The WB showed a 3.8-fold (p = 0.07) increase from baseline at 3 weeks and a 5.1-fold (p = 0.05) increase at 12 weeks. Transforming growth factor-beta 1 demonstrated a significant increase in extracellular staining with DF (3.3 +/- 0.2) and WB (3.7 +/- 0.2) from baseline (1.2 +/- 0.2, p < 0.001) at 3 weeks. CONCLUSION: Superficial dermabrasion with DF and WP appears to be similarly efficacious in the treatment of photoaged skin. Significant increases in type I pN-collagen, type III pN-collagen, and TGF-beta 1 occurred in the papillary dermis after both types of dermabrasion. These results suggest that increased fibroblast activity and consequent collagen I and III synthesis underlie the clinical improvement.

Aged↗
PubMed1996

Interferon-inducible protein-10 is highly expressed in rats with experimental nephrosis.

Interferon-inducible protein (IP)-10 is a small glycoprotein member of a family of chemotactic cytokines structurally related to interleukin-8. We have recently described the induction of IP-10 mRNA in mouse mesangial cells stimulated with lipopolysacharide, interferon-gamma, and tumor necrosis factor-alpha. To further evaluate a possible role for this chemokine in renal injury, we have studied IP-10 in an experimental model of nephrosis induced in rats by adriamycin. High levels of glomerular IP-10 mRNA expression and glomerular and tubulointerstitial IP-10 protein were seen on day 21, coinciding with maximal proteinuria, glomerular tumor necrosis factor mRNA expression, and interstitial cellular infiltrates. Maintenance on a low protein diet not only delayed the appearance of proteinuria and interstitial cellular infiltrate but also decreased glomerular IP-10 mRNA expression. Isolated normal glomeruli and cultured glomerular epithelial and mesangial cells from normal rats expressed IP-10 mRNA upon stimulation with 100 U/ml interferon or 1 microgram/ml lipopolysaccharide for 3 hours. IP-10 mRNA expression was also inducible by lipopolysaccharide and cytokines in NRK 49F renal interstitial fibroblasts and, to a lesser extent, in NRK 52E tubular epithelial cells. Furthermore, IP-10 protein was inducible in murine mesangial cells. We conclude that IP-10 is highly inducible in vitro and in vivo in resident glomerular and tubulointerstitial cells. IP-10 may participate in the modulation of renal damage in experimental nephrosis.

Animals↗
PubMed1996

Topical tretinoin (retinoic acid) improves early stretch marks.

BACKGROUND AND DESIGN: Stretch marks are disfiguring lesions usually caused by excessive stretching of skin. We investigated the response of early, clinically active stretch marks to topical 0.1% tretinoin (retinoic acid) cream. In a double-blind, randomized, vehicle-controlled study, 22 patients applied either 0.1% tretinoin (n = 10) or vehicle (n = 12) daily for 6 months to the affected areas. Patients were evaluated by physical examination monthly and by analysis of biopsy specimens of stretch marks obtained before and at the end of therapy in comparison with untreated normal skin. RESULTS: After 2 months, patients treated with tretinoin had significant improvements in severity scores of stretch marks compared with patients who received vehicle (P < .05). After 6 months, eight (80%) of the 10 tretinoin-treated patients had definite or marked improvement compared with one (8%) of the 12 vehicle-treated patients (P = .002). Targeted stretch marks in patients treated with tretinoin had a decrease in mean length and width of 14% and 8%, respectively, compared with an increase of 10% (P < .001) and 24% (P = .008), respectively, in patients who received vehicle. There were no significant differences in various measures of quality and quantity of dermal collagen and elastic fibers in stretch marks when tretinoin and vehicle treatments were compared. CONCLUSIONS: Topical application of tretinoin significantly improves the clinical appearance of early, active stretch marks. The processes that are responsible for the clinical improvement remain unknown.

Administration, Cutaneous↗
PubMed1996

Concurrent application of tretinoin (retinoic acid) partially protects against corticosteroid-induced epidermal atrophy.

Cutaneous atrophy arising from prolonged use of potent topical corticosteroids has long been a concern. Thus, it would be advantageous to find an agent which protects against atrophy produced by corticosteroids but at the same time does not impair their anti-inflammatory effects. Recent work shows that topical all-trans retinoic acid (tretinoin) prevents skin atrophy in mice treated with topical corticosteroids, but such studies have not been performed in humans. We performed an 8-week clinical, histological and biochemical study to test the ability of tretinoin to enhance efficacy and inhibit atrophogenicity of topical corticosteroids, when used in the treatment of psoriasis. In each of 20 psoriasis patients, one plaque, and its perilesional skin, was treated once daily with betamethasone dipropionate and tretinoin 0.1%, and one plaque, and its perilesional skin, treated with once daily betamethasone dipropionate and tretinoin vehicle. There was no difference in the speed or degree of improvement in plaques treated with either the topical corticosteroid/tretinoin combination or with corticosteroid alone. Light microscopy revealed a 19% reduction in epidermal thickness, in corticosteroid-treated perilesional skin, as compared with a slight (1%) increase in corticosteroid/tretinoin-treated perilesional areas (P = 0.067). Western blot analysis showed a 55% reduction in procollagen I aminopropeptide in perilesional skin treated corticosteroid alone, as compared with a 45% reduction in corticosteroid/tretinoin-treated perilesional skin. These data indicate that the addition of tretinoin does not impair the efficacy of a topical corticosteroid, in the treatment of psoriasis, and partially ameliorates epidermal atrophy produced by the topical corticosteroid.

Administration, Topical↗
PubMed1995

Two structurally distinct kappa B sequence motifs cooperatively control LPS-induced KC gene transcription in mouse macrophages.

The mouse KC gene is an alpha-chemokine gene whose transcription is induced in mononuclear phagocytes by LPS. DNA sequences necessary for transcriptional control of KC by LPS were identified in the region flanking the transcription start site. Transient transfection analysis in macrophages using deletion mutants of a 1.5-kb sequence placed in front of the chloramphenicol acetyl transferase (CAT) gene identified an LPS-responsive region between residues -104 and +30. This region contained two kappa B sequence motifs. The first motif (position -70 to -59, kappa beta 1) is highly conserved in all three human GRO genes and in the mouse macrophage inflammatory protein-2 (MIP-2) gene. The second kappa B motif (position -89 to -78, kappa B2) was conserved only between the mouse and the rat KC genes. Consistent with previous reports, the highly conserved kappa B site (kappa B1) was essential for LPS inducibility. Surprisingly, the distal kappa B site (kappa B2) was also necessary for optimal response; mutation of either kappa B site markedly reduced sensitivity to LPS in RAW264.7 cells and to TNF-alpha in NIH 3T3 fibroblasts. Although both kappa B1 and kappa B2 sequences were able to bind members of the Rel homology family, including NF kappa B1 (P50), RelA (65), and c-Rel, the kappa B1 site bound these factors with higher affinity and functioned more effectively than the kappa B2 site in a heterologous promoter. These findings demonstrate that transcriptional control of the KC gene requires cooperation between two kappa B sites and is thus distinct from that of the three human GRO genes and the mouse MIP-2 gene.

Animals↗
PubMed1995

The interferon-stimulated response element and a kappa B site mediate synergistic induction of murine IP-10 gene transcription by IFN-gamma and TNF-alpha.

The present study investigates mechanisms involved in cooperation between IFN-gamma and TNF-alpha to promote transcription from the IP-10 gene in NIH 3T3 cells. IFN-gamma synergistically enhanced TNF-alpha-induced levels of IP-10 mRNA, whereas levels of JE (MCP-1) or KC (GRO/MGSA) mRNA induced by TNF-alpha were unaffected by IFN-gamma. The cooperation between IFN-gamma and TNF-alpha for induction of IP-10 mRNA was independent of de novo protein synthesis and mediated at least in part by increased transcription. Transient transfection analysis with a 243-bp fragment flanking the transcription start site of the murine IP-10 gene indicated that synergy between the two stimuli was dependent upon occupancy of at least two of three critical regulatory sequence elements: an IFN-stimulated response element (ISRE) and one of two kappa B sites. IFN-gamma and TNF-alpha independently activated nuclear factors capable of specific interaction with the ISRE and kappa B sites, respectively. IFN-gamma induced two ISRE binding complexes, one of which was protein synthesis independent, appeared within 15 min of stimulation, and contained p91 or signal transducer and activator of transcription (STAT) 1. TNF-alpha induced only one ISRE binding activity, which was dependent upon protein synthesis. TNF-alpha also induced kappa B binding activity that was composed of NF-kappa B1 (p50) and RelA (p65) whereas IFN-gamma had no detectable effect on kappa B binding activity. Together these results indicate that the highly synergistic transcriptional activation of the IP-10 gene by IFN-gamma and TNF-alpha involves the cooperation between factors that are independently activated by the two stimuli and that bind to independent sites.

3T3 Cells↗
PubMed1995

Anomalous effects of losartan on aminopeptidase-induced reductions of blood pressure in SHR.

The present investigation initially determined that a commercially available aminopeptidase M (AmM, Sigma Chemical) can lower blood pressure when intracerebroventricularly (ICV) infused in spontaneously hypertensive rats (SHR). Pretreatment with the angiotensin II (AngII) receptor subtype 1 (AT1) antagonist, DuP 753 (losartan) significantly attenuated this hypotensive effect, in a dose-dependent manner, while pretreatment with the AngII receptor subtype 2 (AT2) antagonist, PD123177, did not influence AmM-induced hypotension. These results suggest that AT1 receptors may be involved in the hypotension accompanying the ICV infusion of AmM; however, the relationship among available AT1 sites, angiotensin ligands, and peptidase activity appears to be complicated with the likely involvement of additional, as yet unspecified, brain peptide systems possessing cardiovascular action.

Angiotensin Receptor Antagonists↗
PubMed1995

Reduced type I and type III procollagens in photodamaged adult human skin.

We have quantitatively assessed the relation between type I and type III procollagen precursor levels and the severity of clinical photodamage in human skin. Levels of procollagen, pN collagen (collagen without the carbroxypropeptide), and/or pC collagen (collagen without the aminopropeptide) were determined by radioimmunoassay, Western blot, and immunohistology in punch biopsy specimens from mildly and severely photodamaged forearm skin and from sunprotected underarm and buttock skin of the same subjects. Collagen precursor levels in forearm and underarm skin were expressed relative to buttock levels for comparison. In the mildly photodamaged group, collagen precursors in the forearm did not differ from those in the underarm by any measurement, except for type I collagen precursors measured by radioimmunoassay, which were reduced 16%. In severely photodamaged forearm skin, both type I and type III collagen precursor levels, measured by radioimmunoassay, were significantly reduced (approximately 40%). Western analysis revealed similar significant reductions in type I and type III collagen precursor levels in severely photodamaged forearm skin compared with the sun-protected underarm. Immunohistology localized both type I and III pN collagens predominantly to the extracellular papillary dermis. Relative staining intensities of type I and type III pN collagen were also significantly reduced in severely photodamaged forearm skin. Multiple linear regression modeling of all data demonstrated that reductions in collagen precursor levels were significantly correlated (p < 0.03) with the severity of photodamage, but not with chronologic age. These data demonstrate, by three independent methods, coordinate reductions of both type I and type III collagen precursors in photodamaged human skin, and the degree of reduction correlated with the degree of photodamage. It is likely that such changes in collagen precursors lead to reduced levels and/or altered organization of fibrillar collagen, and thus may contribute to the wrinkled appearance of photodamaged human skin.

Adult↗
PubMed1995

The effects of oxidized low density lipoproteins on inducible mouse macrophage gene expression are gene and stimulus dependent.

Oxidized LDL has been previously reported to suppress the expression of genes induced in mononuclear phagocytes by inflammatory stimuli. In this study we extend these findings to demonstrate that the suppressive effects of oxidized LDL vary depending upon the gene being monitored and the stimulus being used to induce or enhance its expression. The expression of a selection of LPS-inducible genes exhibited differential sensitivity to pretreatment with oxidized LDL. Furthermore, the ability of oxidized LDL to suppress gene expression varied markedly with the inducing stimulus used. TNF alpha and IP-10 mRNA expression induced by IFN gamma and IL-2 was markedly more sensitive to suppression by oxidized LDL than that induced by LPS. The cooperative effects of IFN gamma and LPS on the expression of the inducible nitric oxide synthase gene were suppressed by oxidized LDL while the antagonistic effect of IFN gamma on LPS-induced expression of the TNF receptor type II mRNA was not altered. The suppressive activity of LDL was acquired only after extensive oxidation and was localized in the extractable lipid component. These results suggest a potent and direct connection between the oxidative modification of LDL and the chronic inflammation seen in atherogenic lesions. Furthermore, the appreciable selectivity of oxidized LDL in mediating secondary control of cytokine gene expression demonstrates that the active material(s) is targeted to disrupt specific intracellular signaling pathways.

Amino Acid Oxidoreductases↗
PubMed1995

Angioleiomyoma of the nasopharynx in a dog.

A polypoid angioleiomyoma was surgically removed from the nasopharynx of a 1-year-old, male golden retriever. The polypoid mass recurred 4 months later and was again excised. There was no sign of regrowth 13 months postoperatively. This is, apparently, the first reported angioleiomyoma occurring in the dog.

Angiomyoma↗
PubMed1995

Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams.

BACKGROUND AND DESIGN: The efficacy of topical tretinoin (all-trans-retinoic acid) in treating photoaging is well established. Questions that remain are (1) whether irritation causes all or part of the improvement; (2) the concentration of tretinoin that maximizes clinical response with minimal side effects; and (3) the effects of long-term treatment on components of the cutaneous immune system. To address these issues, 99 photoaged patients completed a 48-week study using 0.1% tretinoin cream (n = 32), 0.025% tretinoin (n = 35), or vehicle (n = 32) once daily in a double-blind manner. Before and after treatment, we assessed histologic features, keratinocyte expression of HLA-DR and intercellular adhesion molecule-1, numbers of epidermal Langerhans' cells and epidermal and dermal T lymphocytes, and vascularity as measured by dermal endothelial cell area. RESULTS: Both 0.1% and 0.025% tretinoin produced statistically significant overall improvement in photoaging of the face compared with vehicle; there were no clinically or statistically significant differences in efficacy between the two concentrations of tretinoin. After 48 weeks, 0.1% and 0.025% tretinoin produced similar statistically significant epidermal thickening (by 30% and 28%, respectively) compared with vehicle (11% decrease) and increased vascularity (by 100% and 89%, respectively) compared with vehicle (9% decrease). By various analyses, irritant side effects (erythema and scaling) were statistically significantly greater with 0.1% tretinoin than with 0.025% tretinoin. No significant changes occurred in any immunologic markers when tretinoin and vehicle treatments were compared. CONCLUSIONS: Tretinoin 0.1% and 0.025% produce similar clinical and histologic changes in patients with photoaging, despite significantly greater incidence of irritation with the higher concentration. The separation between clinical improvement and irritation suggests that mechanisms other than irritation dominate tretinoin-induced repair of photoaging in humans.

Aged↗
PubMed1995

Duration of remission during maintenance cyclosporine therapy for psoriasis. Relationship to maintenance dose and degree of improvement during initial therapy.

BACKGROUND: Cyclosporine therapy is highly effective in the treatment of psoriasis. To minimize side effects, the lowest effective dosage for maintenance therapy should be sought. METHODS: We selected 61 patients who had achieved clearing or near-clearing of psoriasis during an induction phase of cyclosporine therapy. We then randomly assigned them in a double-blind fashion to receive one of two dosages of cyclosporine (1.5 or 3 mg/kg per day) or placebo for maintenance treatment. For each patient, the time to relapse was the time from the start of maintenance therapy until the patient showed a two-point worsening of psoriasis on a seven-point scale, up to a maximum of 4 months, when the study ended. RESULTS: Sixty patients completed the maintenance study. The mean time to relapse was significantly longer in the 3-mg/kg group (12 +/- 1 weeks) than in the 1.5-mg/kg group (9 +/- 1 weeks; P = .04) and the placebo group (7 +/- 1 weeks; P = .002); the latter two groups were not significantly different (P = .3). When the study ended, 57% of the 3-mg/kg group had not relapsed, compared with 21% and 5% of the 1.5-mg/kg and placebo groups, respectively. The following factors were associated with longer remissions: less psoriasis at the start of maintenance dosing (r = .40, P = .002); lower dosage of cyclosporine to achieve clearing or near-clearing during induction (r = -.30, P = .02); higher maintenance dosing (r = .38, P = .004); and smaller differences between the induction and maintenance dosages (r = -.41, P = .002). Patients' laboratory values improved compared with those at induction, and no patient experienced important clinical side effects during maintenance dosing. CONCLUSIONS: After clearing or near-clearing is achieved in patients with severe psoriasis, 3 mg/kg per day is a reasonable dosage to choose for maintenance. Patients who are more responsive to cyclosporine (as measured by greater clearing of psoriasis at lower induction dosages) tend to have longer remissions.

Adult↗