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T Kikuchi

Publications and source records attributed to T Kikuchi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Pentoxifylline improves in vitro fertilization and subsequent development of bovine oocytes.

The purpose of this study was to examine whether pentoxifylline improves in vitro fertilization and developmental rates of bovine oocytes. In the first experiment, we examined the effects on the fertilization rate of various concentrations of pentoxifylline (0-7.5 mM) combined with heparin (10 IU/mL). In the second experiment, we examined fertilization cleavage and blastocyst rates after frozen-thawed spermatozoa, obtained from four different bulls, were incubated with heparin (10 IU/mL) with or without caffeine (5 mM) or pentoxifylline (5 mM). In the first experiment, a significantly higher fertilization rate was obtained in heparin containing 5 mM pentoxifylline compared to that in heparin alone or in heparin containing 7.5 mM pentoxifylline (86% vs 60% vs 64%, respectively). The percentage of monospermy in 5 mM pentoxifylline (81%) was significantly higher than in heparin alone (57%). In the second experiment, the interactions among Bulls A, B, C, and D; between treatments (pentoxifylline-with-heparin, caffeine-with-heparin and heparin alone), and between bulls and treatments were analyzed for the number of oocytes penetrated, monospermic oocytes, cleaved oocytes and blastocysts. Among bulls, there was a significant difference in the number of oocytes penetrated (P < 0.01), monospermic oocytes (P < 0.05), cleaved oocytes (P < 0.001), and blastocysts (P < 0.001). Between treatments, there was a significant difference in the number of oocytes penetrated (P < 0.001), monospermic oocytes (P < 0.01) and cleaved oocytes (P < 0.001). Interaction between bulls and treatments was observed for the number of oocytes penetrated (P < 0.05). Individually, for Bulls A, C and D, the numbers of oocytes penetrated and monospermic oocytes in pentoxifylline-with-heparin were significantly higher than in heparin alone. For Bull D, significantly higher results were obtained for the number of oocytes penetrated, monospermic oocytes, cleaved oocytes and blastocysts in pentoxifylline-with-heparin compared to caffeine-with-heparin and heparin alone (P < 0.05). These results suggest that treating sperm with 5 mM pentoxifylline in combination with heparin is effective for bovine in vitro fertilization and it that this treatment is effective even for bulls that produce low fertilization and blastocysts after sperm treatment with caffeine-with-heparin or heparin alone.

Animals↗
PubMed2001

Cross-strain protection against clinical and laboratory strains of Pseudomonas aeruginosa mediated by dendritic cells genetically modified to express CD40 ligand and pulsed with specific strains of Pseudomonas aeruginosa.

We have shown that dendritic cells (DCs) genetically engineered with a recombinant adenovirus vector (Ad) to express CD40 ligand (CD40L) elicit specific humoral immunity against the Pseudomonas aeruginosa laboratory strain PAO1, without CD4(+) T cell help. In the present study, using several different strains of P. aeruginosa, we examine whether this strategy is generally applicable to enhancing clinically relevant pathogen-specific immunity. Mice immunized with DCs modified with CD40L and pulsed with heat-killed P. aeruginosa clinical strain PA514, originally isolated from the sputum of an individual with cystic fibrosis, survived lethal respiratory challenge with PA514-impregnated agar beads. Consistent with this effective in vivo protection, the immunized mice generated high levels of serum isotype-switched antibodies directed against PA514 without concomitant nonspecific elevations of total serum immunoglobulin levels. The CD40L genetically engineered DCs pulsed with seven of eight different strains of P. aeruginosa afforded significant, albeit variable, cross-protection against lethal respiratory challenge with a clinical (PA514) or laboratory (PAO1) strain of P. aeruginosa. CD40L genetically modified DCs pulsed with a clinical (PA514) or laboratory (PAO1) strain of P. aeruginosa initiated cross-reacting antibody responses against each other, but not against Escherichia coli and vice versa. These observations may be useful in developing vaccines for infectious diseases, including P. aeruginosa infection.

Adenoviridae↗
PubMed2001

Expression of connexin 30 in the developing mouse cochlea.

Mutations in the GJB6 gene encoding connexin 30 (Cx30) can cause dominant forms of nonsyndromic deafness. By studying immunohistochemical localization of Cx30 in the mouse cochlea at different ages from 0 to 30 days after birth, we found that the expression of Cx30 is nearly the same as that of Cx26. These findings suggest that as well as Cx26, Cx30 may also contribute to the generation and maturation of endocochlear potential.

Age Factors↗
PubMed2001

NF-kappa B and STAT5 play important roles in the regulation of mouse Toll-like receptor 2 gene expression.

Toll-like receptor 2 (TLR2) is involved in the innate immunity by recognizing various bacterial components. We have previously reported that TLR2 gene expression is rapidly induced by LPS or inflammatory cytokines in macrophages, and by TCR engagement or IL-2/IL-15 stimulation in T cells. Here, to investigate the mechanisms governing TLR2 transcription, we cloned the 5' upstream region of the mouse TLR2 (mTLR2) gene and mapped its transcriptional start site. The 5' upstream region of the mTLR2 gene contains two NF-kappa B, two CCAAT/enhancer binding protein, one cAMP response element-binding protein, and one STAT consensus sequences. In mouse macrophage cell lines, deletion of both NF-kappa B sites caused the complete loss of mTLR2 promoter responsiveness to TNF-alpha. NF-kappa B sites were also important but not absolutely necessary for LPS-mediated mTLR2 promoter activation. In T cell lines, mTLR2 responsiveness to IL-15 was abrogated by the 3' NF-kappa B mutation, whereas 5' NF-kappa B showed no functional significance. The STAT binding site also seemed to contribute, as the deletion of this sequence significantly reduced the IL-15-mediated mTLR2 promoter activation. EMSAs confirmed nuclear protein binding to both NF-kappa B sites in macrophages following LPS and TNF-alpha stimulation and to the 3' NF-kappa B site in T cells after IL-15 treatment. Thus, NF-kappa B activation is important but differently involved in the regulation of mTLR2 gene expression in macrophages and T cells following LPS or cytokine stimulation.

5' Untranslated Regions↗
PubMed2001

Cloning and DNA sequencing of the surface protein antigen I/II (PAa) of Streptococcus cricetus.

We have cloned and sequenced the gene encoding the surface protein antigen PAa (antigen I/II family) from Streptococcus cricetus E49 (serotype a) using degenerate PCR. The deduced amino acid sequence of PAa reveals two repeating regions (A region; alanine-rich region, P region; proline-rich region). Two additional tandem repeats were found in the A region and part of the P region was deleted compared to antigen I/II. Homology and phylogenetic analyses reveal that PAa is homologous to Streptococcus sobrinus PAg rather than Streptococcus mutans PAc. Using degenerate PCR a gene homologous to PAc was identified in Streptococcus intermedius, but not found in Streptococcus rattus or Streptococcus anginosus.

Animals↗
PubMed2001

Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors.

Osteoclast differentiation factor (ODF), a recently identified cytokine of the TNF family, is expressed as a membrane-associated protein in osteoblasts and stromal cells. ODF stimulates the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. Here we investigated the effects of LPS on the gene expression of ODF in mouse osteoblasts and an osteoblast cell line and found that LPS increased the ODF mRNA level. A specific inhibitor of extracellular signal-regulated kinase or protein kinase C inhibited this up-regulation, indicating that extracellular signal-regulated kinase and protein kinase C activation was involved. A protein synthesis inhibitor, cycloheximide, rather enhanced the LPS-mediated increase of ODF mRNA, and both a neutralizing Ab of TNF-alpha and a specific inhibitor of PGE synthesis failed to block the ODF mRNA increase by native LPS. Thus, LPS directly induced ODF mRNA. Mouse osteoblasts and an osteoblast cell line constitutively expressed Toll-like receptor (TLR) 2 and 4, which are known as putative LPS receptors. ODF mRNA increases in response to synthetic lipid A were defective in primary osteoblasts from C3H/HeJ mice that contain a nonfunctional mutation in the TLR4 gene, suggesting that TLR4 plays an essential role in the process. Altogether, our results indicate that ODF gene expression is directly increased in osteoblasts by LPS treatment via TLR, and this pathway may play an important role in the pathogenesis of LPS-mediated bone disorders, such as periodontitis.

Animals↗
PubMed2001

Use of a new ICG-dye-enhanced diode laser for percutaneous laser disc decompression.

BACKGROUND AND OBJECTIVE: The lasers used today for Percutaneous Laser Disc Decompression (PLDD) can not selectively ablate the nucleus pulposus (NP). We hypothesized that if indocyanine green dye were injected into the NP, 805 nm diode laser irradiation would result in selective and safe removal of NP tissue without damaging nearby tissues. STUDY DESIGN/MATERIALS AND METHODS: Twelve beagle dogs were used for three experiments, i.e., determination of attenuation coefficients of NP and AF, determination of weight of NP before and after laser irradiation, and histopathological study. RESULTS: The attenuation coefficient at 805 nm of NP which had been homogenized in the presence of ICG was 2521.3/cm. Upon application of the diode laser at a power of 1, 3, or 5 W (the intensity of laser irradiation: 0.353, 1.061, or 1.768 x 10(3) W/cm(2)) to NPs into which ICG had been injected, the weight of the NPs decreased by a mean 20, 45, and 65%, respectively. Macroscopic and microscopic examination of the discs after PLDD showed that only the NP where the tissues were stained by ICG were removed. CONCLUSIONS: These results indicated that the combined use of ICG and diode laser irradiation effectively and selectively ablates the NP with low laser power.

Animals↗
PubMed2001

Large amounts of apicoplast nucleoid DNA and its segregation in Toxoplasma gondii.

Apicoplasts (apicomplexan plastids) are nonphotosynthetic, secondary endosymbiotic plastids that are found in most apicomplexans. Although these organelles are essential for parasite survival, their functions, activities, and structures are not well understood. We examined the apicoplast nucleoid of Toxoplasma gondii from a morphological aspect by high-resolution epifluorescence microscopy and electron microscopy. We found unexpectedly large amounts of DNA in the nucleoid and the presence of several division-related structures. Initially, we identified the organellar nucleoids by staining with the DNA-specific dye 4',6-diamidino-2-phenylindole. A single nucleoid was observed per apicoplast, and the fluorescent spot representing the nucleoid was bright and spherical in contrast to the weak and filamentous spot representing the mitochondrial nucleoid. We also measured the DNA content of each apicoplast nucleoid by a video-intensified microscope photon-counting system and determined that the genomic copy number was at least 25, a figure over four times greater than that reported previously. Moreover, several groups of apicoplasts had significantly higher genomic copy numbers. The DNA molecules were accurately divided into two daughter apicoplasts just before nuclear division. In addition, we examined nucleoid segregation and the division apparatus using electron microscopy. However, we failed to observe nucleoid structures, suggesting that the apicoplasts are predominantly composed of nucleoid material. In addition, we observed "cap" structures at the termini of dividing apicoplasts, a possible plastid-dividing ring, and a microbody-like granule around the constriction. These structures may be involved in apicoplast division.

Animals↗
PubMed2001

Twenty-four-hour Tl-201 delayed scan underestimates myocardial viability in patients with acute myocardial infarction after percutaneous transluminal coronary angioplasty.

BACKGROUND: Myocardial viability in area at risk of acute myocardial infarction (AMI) after reperfusion therapy may be underestimated by the 24-hour images due to reverse redistribution (r-RD). METHODS: Subjects were 37 AMI patients in whom Tc-99m pyrophosphate (PYP)/Tl-201 dual-isotope SPECT was positive. The 24-hour delayed scan was performed with only a Tl window. One month later, follow up rest Tl SPECT was performed to evaluate myocardial viability. In early (at PYP/Tl-201 dual-isotope SPECT), 24-hour, and one month follow up Tl studies, Tl uptake in the area of AMI was scored into four grades: 3 as normal to 0 as severely reduced. The scores were evaluated. RESULTS: Among the 37 AMI lesions, there were 16 r-RD, 3 RD, 16 fixed defect (FD) and 2 normal (positive PYP and normal Tl). Mean Tl scores were early; 1.4 +/- 1.1, 24-hr; 0.9 +/- 0.9 and one month; 1.3 +/- 1.1. The 24-hour Tl score was lower than the early and one month Tl scores (p < 0.01). CONCLUSION: Reverse redistribution is frequently observed in an area at risk where PYP SPECT was positive. Nuclear medicine physicians should be aware of the existence of frequent r-RD in Tl scan to avoid the underestimation of myocardial viability in the acute phase after PTCA.

Aged↗
PubMed2001

Lack of association of mutations of the bestrophin gene with age-related macular degeneration in non-familial Japanese patients.

BACKGROUND: Heterozygous mutations of the bestrophin gene are associated with Best macular dystrophy (BMD). The bestrophin gene is specifically expressed in the retinal pigment epithelium. BMD is a hereditary form of macular degeneration that may develop subretinal neovascularisation similar to the wet type of age-related macular degeneration (AMD). PURPOSE: To study whether mutations of the bestrophin gene occur in non-familial Japanese AMD patients. METHODS: A total of 85 non-familial AMD patients (average age 67.5 years; 71 male, 14 female) diagnosed by indocyanine green angiography were screened. Among them, 69 patients (81 %) were classified as having wet type AMD. Genomic DNA was purified from the total blood and used as the template for polymerase chain reaction (PCR). All the exons of bestrophin gene were amplified by PCR. Mutation analysis was performed by SSCP using the ABI Prism 310 Genetic Analyzer (Perkin Elmer). Nucleotide sequence was determined by direct sequencing of the PCR amplicons. As the control, 105 non-AMD patients (average age 62.0 years; 52 male, 53 female) were screened by the same method. RESULTS: Only one AMD patient had a specific polymorphism in exon 2, but no mutations leading to amino acid substitutions were found. In exon 2 and 3, two further polymorphisms were detected in all AMD patients as well as normal controls. CONCLUSION: No mutations were found in the bestrophin gene in nonfamilial Japanese patients with AMD or in normal controls.

Aged↗
PubMed2001

Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells.

Several reports of clinical trials of immunotherapy using dendritic cells have been published to date. In this study, we investigated the safety and clinical response of immunotherapy with fusions of dendritic and glioma cells for the treatment of patients with malignant glioma. Eight patients with malignant glioma, ranging in age from 4 to 63 years old, participated in this study. Dendritic cells were generated from peripheral blood. Cultured autologous glioma cells were established from surgical specimens in each case. Fusion cells of dendritic and glioma cells were prepared with polyethylene glycol, and the fusion efficiency ranged from 9.2 to 35.3% (mean, 21.9%). All patients received the fusion cells every three weeks for a minimum of 3, and a maximum of 7, immunizations. Fusion cells were injected intradermally, close to a cervical lymph node. The percentage of CD16- and CD56-positive cells in peripheral blood lymphocytes slightly increased after immunization in 4 out of 5 cases investigated. Peripheral blood mononuclear cells were incubated with irradiated autologous glioma or U87MG cells and supernatants were harvested. In 6 cases analyzed, the concentration of interferon-gamma in the supernatant increased after immunization. Clinical results showed that there were no serious adverse effects and two partial responses. Although the results of the phase I clinical trial of fusion cells indicated that this treatment safely induced immune responses. we were unable to establish a statistically significant treatment-associated response rate, due to the limited sample population. Therefore, further evaluation of the role of adjuvant cytokines is necessary.

Adult↗
PubMed2001

Comparative in-vitro activity of carbapenem antibiotics against respiratory pathogens isolated between 1999 and 2000.

We investigated the antibacterial activity of 12 antibiotics, inclusive of four carbapenems, against 167 strains of respiratory pathogens isolated between 1999 and 2000. Thirty strains of methicillin-susceptible Staphylococcus aureus (MSSA), 28 strains of methicillin-resistant S. aureus (MRSA), 11 strains of penicillin-susceptible Streptococcus pneumoniae (PSSP), 29 strains of penicillin-resistant S. pneumoniae (PRSP), 30 strains of Pseudomonas aeruginosa, 14 strains of Moraxella catarrhalis, and 25 strains of Haemophilus influenzae were examined. The minimum inhibitory concentration (MICs)50/90 (microg/ml) of imipenem, panipenem, meropenem, and biapenem against the clinical isolates obtained between 1999 and 2000 were: 0.06/0.25, 0.12/0.25, 0.12/0.25, and 0.12/0.25, respectively, against MSSA; 16/32, 16/32, 16/32, and 8/32 against MRSA; < or = 0.015/0.06, < or = 0.015/0.03, 0.03/0.12, and < or = 0.015/0.06 against PSSP; 0.12/0.25, 0.03/0.06, 0.25/0.5, and 0.12/0.25 against PRSP; 1/8, 2/8, 0.5/2, and 2/16 against P. aeruginosa; 0.06/0.06, 0.03/0.06, < or = 0.015/0.06, and 0.06/0.12 against M. catarrhalis; and 1/4, 1/4, 0.12/0.25, and 2/4 against H. influenzae. A comparison of the antibacterial activity of the four carbapenems with that found in our previous studies showed no significant difference in the susceptibility of clinical isolates, except for a slight decrease in the susceptibility of MSSA. Carbapenems have remained effective for severe infections. The MIC data showed that imipenem and panipenem were more active than meropenem and biapenem against gram-positive bacteria, and that meropenem and biapenem were more active than imipenem and panipenem against gram-negative bacteria. As only meropenem had an MIC90 below the breakpoint of pneumonia against all species except MRSA, meropenem was considered to be the most potent of the four carbapenems studied.

Anti-Bacterial Agents↗
PubMed2001

Antidepressant-like responses to the combined sigma and 5-HT1A receptor agonist OPC-14523.

The antidepressant-like activity of a novel compound, OPC-14523, was investigated in comparison with the conventional antidepressants, fluoxetine and imipramine. OPC-14523 bound with nanomolar affinities to sigma receptors (IC(50)=47-56 nM), the 5-HT(1A) receptor (IC(50)=2.3 nM), and the 5-HT transporter (IC(50)=80 nM). OPC-14523 inhibited the in vitro reuptake of 3H-5-HT (IC(50)=27 nM), but it showed very weak inhibitory activity on 3H-NE and 3H-DA reuptake. OPC-14523 did not inhibit MAO A or B activities or muscarinic receptors. A single oral administration of OPC-14523 produced a marked antidepressant-like effect in the forced swimming test (FST) with rats (ED(50)=27 mg/kg) and mice (ED(50)=20mg/kg) without affecting the general locomotor activity. In contrast, fluoxetine and imipramine each required at least four days of repeated dosing to show this activity. The acute activity of OPC-14523 was blocked by pretreatment with the sigma receptor antagonist NE-100 or the selective 5-HT(1A) receptor antagonist WAY-100635. The induction of flat body posture by OPC-14523 was blocked by the selective 5-HT(1A) receptor antagonist NAN-190, and forebrain 5-HT biosynthesis was attenuated by OPC-14523 at behaviorally effective doses. In contrast, OPC-14523, unlike fluoxetine, failed to inhibit 5-HT reuptake at oral doses below 100mg/kg. Thus, the acute antidepressant-like action of OPC-14523 is achieved by the combined stimulation of sigma and 5-HT(1A) receptors without inhibition of 5-HT reuptake in vivo.

Animals↗
PubMed2001

Membrane localization and demonstration of isoforms of nucleoside triphosphate hydrolase from Toxoplasma gondii.

Toxoplasma gondii has a unique enzyme, a NTPase, which has a wide specificity toward NTP. In the present study, we produced a monoclonal antibody (IgG1, 6C6) against the enzyme which could recognize NTPase isozymes among several strains of T. gondii. Three avirulent strains of T. gondii, ME49, Beverley and Nakayama, were found to have 1 NTPase (63 kDa, pI 6.0), while a virulent strain RH and an avirulent strain Fukaya had 2 isozymes (63 kDa) with different pIs (pIs 6.0 and 6.5 for the former, and pIs 6.2 and 6.4 for the latter, respectively), suggesting that this monoclonal antibody recognizes a common epitope of NTPase among T. gondii strains. Furthermore, 6C6 could inhibit NTPase activity in the presence of dithiothreitol in a dose-dependent manner, and immuno-EM study of NTPase revealed that this molecule is located on the surface membrane of T. gondii tachyzoites. When Vero cells were co-cultured with tachyzoites pre-treated with 6C6, the number of infected cells significantly decreased, suggesting that 6C6 inhibits invasion of the parasites to host cells. These data suggest that the molecule recognized by 6C6 might be considered a potential candidate antigen for vaccines against T. gondii tachyzoites.

Acid Anhydride Hydrolases↗
PubMed2001

Transcripts of the MHM region on the chicken Z chromosome accumulate as non-coding RNA in the nucleus of female cells adjacent to the DMRT1 locus.

The male hypermethylated (MHM) region, located near the middle of the short arm of the Z chromosome of chickens, consists of approximately 210 tandem repeats of a BamHI 2.2-kb sequence unit. Cytosines of the CpG dinucleotides of this region are extensively methylated on the two Z chromosomes in the male but much less methylated on the single Z chromosome in the female. The state of methylation of the MHM region is established after fertilization by about the 1-day embryonic stage. The MHM region is transcribed only in the female from the particular strand into heterogeneous, high molecular-mass, non-coding RNA, which is accumulated at the site of transcription, adjacent to the DMRT1 locus, in the nucleus. The transcriptional silence of the MHM region in the male is most likely caused by the CpG methylation, since treatment of the male embryonic fibroblasts with 5-azacytidine results in hypo-methylation and active transcription of this region. In ZZW triploid chickens, MHM regions are hypomethylated and transcribed on the two Z chromosomes, whereas MHM regions are hypermethylated and transcriptionally inactive on the three Z chromosomes in ZZZ triploid chickens, suggesting a possible role of the W chromosome on the state of the MHM region.

Animals↗
PubMed2001

Potential role of the chemokine receptors CXCR3, CCR4, and the integrin alphaEbeta7 in the pathogenesis of psoriasis vulgaris.

Various adhesion molecules have been implicated in T lymphocyte binding to dermal vascular endothelium in psoriasis vulgaris, but the chemotactic signals that promote subsequent homing into the adjacent dermis and overlying epidermis are poorly defined. We studied chemokine receptor (CCR1-CCR5, CXCR1-CXCR3), chemokine (interferon-gamma inducible protein 10 [IP-10]), monokine induced by interferon-gamma (MIG), thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), and adhesion molecule (cutaneous lymphocyte antigen [CLA], E-selectin, lymphocyte function-associated antigen-1 [LFA-1], intercellular adhesion molecule-1 [ICAM-1], very late antigen 4 [VLA-4], vascular cell adhesion molecule-1 [VCAM-1], alphaEbeta7, and E-cadherin) expression in psoriasis by immunohistology, flow cytometry, and molecular techniques. CXCR3 and CCR4 were expressed by dermal CD3+ lymphocytes, and their chemokine ligands, IP-10, MIG, TARC, and MDC, were up-regulated in psoriatic lesions. Keratinocytes stimulated with tumor necrosis factor-alpha and interferon-gamma up-regulated expression of IP-10, MIG, and MDC mRNA, whereas dermal endothelial cells, similarly stimulated, up-regulated expression of IP-10, MDC, and TARC mRNA, suggesting that these cell types were sources of the chemokines detected in biopsies. There was enhanced expression of E-selectin, CLA, LFA-1, ICAM-1, VLA-4, VCAM-1, and alphaEbeta7 in psoriatic lesions versus nonlesional skin. Finally, intra-epidermal CLA+ and alphaEbeta7+ T lymphocytes selectively expressed the chemokine receptor CXCR3. Collectively, these data suggest that CXCR3 and CCR4 may be involved in T lymphocyte trafficking to the psoriatic dermis and that CXCR3 is selectively involved in subsequent T cell homing to the overlying epidermis.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2001

Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling.

Psoriasis is recognized as the most common T cell-mediated inflammatory disease in humans. Genetic linkage to as many as six distinct disease loci has been established but the molecular etiology and genetics remain unknown. To begin to identify psoriasis disease-related genes and construct in vivo pathways of the inflammatory process, a genome-wide expression screen of multiple psoriasis patients was undertaken. A comprehensive list of 159 genes that define psoriasis in molecular terms was generated; numerous genes in this set mapped to six different disease-associated loci. To further interpret the functional role of this gene set in the disease process, a longitudinal pharmacogenomic study was initiated to understand how expression levels of these transcripts are altered following patient treatment with therapeutic agents that antagonize calcineurin or NF-KB pathways. Transcript levels for a subset of these 159 genes changed significantly in those patients who responded to therapy and many of the changes preceded clinical improvement. The disease-related gene map provides new insights into the pathogenesis of psoriasis, wound healing and cellular-immune reactions occurring in human skin as well as other T cell-mediated autoimmune diseases. In addition, it provides a set of candidate genes that may serve as novel therapeutic intervention points as well as surrogate and predictive markers of treatment outcome.

Adult↗