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H N Liu

Publications and source records attributed to H N Liu.

At least 19 recordsLinked to original sources
PubMed2006

Cytokine gene polymorphisms in bullous pemphigoid in a Chinese population.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune bullous disease mostly associated with autoantibodies to the hemidesmosomal BP autoantigens BP180 and BP230. High levels of interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been detected in skin lesions or sera of patients with BP. Cytokine gene polymorphisms may affect cytokine production and contribute to susceptibility to autoimmune diseases. Until now, no cytokine gene polymorphism study has been conducted on patients with BP. OBJECTIVES: We aimed to determine whether the genetic polymorphisms of the cytokine genes might influence the development of BP. METHODS: DNA samples were obtained from 96 BP patients and 174 control subjects. Using direct sequencing and microsatellite genotyping, we examined 23 polymorphisms in 11 cytokine genes including the IL-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, IL-13, IL-4 receptor, TNF-alpha and IFN-gamma genes. RESULTS: Although the BP patients were more likely to carry the -511T and -31C alleles of the IL-1beta gene (P = 0.04), the significance disappeared after correction for multiple testing (Pc). There was complete linkage disequilibrium between the -511T and -31C alleles of the IL-1beta gene. In female patients with BP, the associations with IL-1beta (-511T) and (-31C) alleles were much stronger (68% vs. 40.6%, odds ratio = 3.11, Pc = 0.006). No significantly different allelic and genotypic distributions of other cytokine gene polymorphisms could be found between the patients with BP and controls. Moreover, no association with the extent of disease involvement (localized or generalized) was observed. CONCLUSIONS: The IL-1beta (-511) and (-31) polymorphisms were significantly associated with BP in women. The other genetic polymorphisms of cytokine genes that we analysed do not appear to be associated with BP susceptibility in our Chinese population.

Adult↗
PubMed2006

Psoriasis vulgaris in Chinese individuals is associated with PSORS1C3 and CDSN genes.

BACKGROUND: Besides the HLA-Cw*0602 allele, the psoriasis susceptibility 1 candidate 3 (PSORS1C3) and corneodesmosin (CDSN) genes are two probable psoriasis susceptibility genes in the PSORS1 locus. The -79C, -26C and +246A alleles of the PSORS1C3 gene, the CDSN*971T allele, CDSN*TTC (619T-1236T-1243C) and CDSN*5 (619T-1240G-1243C) are strongly associated with psoriasis in the caucasian population. Until now, no haplotype study of the PSORS1C3 and CDSN genes has been documented in Chinese patients with psoriasis vulgaris. OBJECTIVES: We aimed to determine whether genetic polymorphisms of the PSORS1C3 and CDSN genes were associated with an increased risk of psoriasis vulgaris in Chinese patients in Taiwan. METHODS: We investigated the PSORS1C3 and CDSN genes for disease association by direct sequencing in 178 patients with psoriasis vulgaris and 203 control subjects. Genotyping for HLA-Cw*0602, alpha-helix coiled-coil rod homologue (HCR) gene and single nucleotide polymorphism (SNP) n.9 was also carried out using a sequence-based typing method. RESULTS: The PSORS1C3*582A allele, an SNP in the 3'-untranslated region of the PSORS1C3 gene, was a major psoriasis vulgaris susceptibility allele in the Chinese population, and the association was much stronger in patients with early-onset psoriasis vulgaris (22.3% vs. 6.9%, odds ratio = 3.87, P(c) =0.0000072). The frequencies of CDSN*TTC and CDSN*971T were also significantly increased in patients with early-onset psoriasis vulgaris. Moreover, PSORS1C3*582A, SNP n.9*C, Cw*0602 and HCR*WWCC were in near complete linkage disequilibrium (LD) with each other; in contrast, the LD with the CDSN gene was not so strong. SNP n.9*C-Cw*0602-PSORS1C3*582A-HCR*WWCC was a major susceptibility haplotype in patients with early-onset psoriasis vulgaris (P < 10(-7)) and this risk haplotype also carried CDSN*TTC and CDSN*971T. CONCLUSIONS: The PSORS1C3 and CDSN genes are important psoriasis susceptibility genes in Chinese patients with psoriasis vulgaris.

Adolescent↗
PubMed2006

No association of cytokine gene polymorphisms in Chinese patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronically relapsing skin disease associated with the activation of T-helper 2 cells. Recent studies have shown that polymorphisms in the genes for interleukin (IL)-4, the IL-4 receptor, IL-13, and signal transducer and activator 6 (STAT6) may contribute to susceptibility of AD. To date, no cytokine gene polymorphism study has been conducted on Chinese patients with AD. AIMS: To determine whether genetic polymorphisms of the cytokine genes might influence the development of AD. METHODS: DNA samples were obtained from 94 patients and 186 control subjects. Using direct sequencing and microsatellite genotyping, we examined 22 polymorphisms in eight cytokine genes including the genes for IL-4, -10, -12B and -13, the IL-4 receptor, tumour necrosis factor (TNF)-alpha, STAT6, and interferon (IFN)-gamma. RESULTS: No significantly different allelic and genotypic distributions of the cytokine gene polymorphisms could be found between patients and controls. Moreover, no association was observed with disease onset, gender, the presence of elevated serum total IgE level or blood eosinophilia. CONCLUSION: Our study suggests that the analysed genetic polymorphisms of cytokine genes do not appear to be associated with AD susceptibility in our Chinese population.

Adolescent↗
PubMed2005

A study of PSORS1C1 gene polymorphisms in Chinese patients with psoriasis.

BACKGROUND: Although genetic analyses have identified the HLA-Cw*0602 allele as the major risk allele for chronic plaque psoriasis in various ethnic groups, it has been proposed that the association of Cw*0602 is due to linkage disequilibrium and that other nearby genes are involved in susceptibility to psoriasis. The psoriasis susceptibility 1 candidate 1 (PSORS1C1, formerly SEEK1) gene, located 127 kb telomeric to the HLA-C locus, is considered to be one of the potential candidate genes of psoriasis. Up to the present, no association study of the PSORS1C1 gene has been conducted on Chinese patients with psoriasis. OBJECTIVES: We aimed to determine whether the genetic polymorphisms of the PSORS1C1 gene were associated with an increased risk of psoriasis in Chinese patients. METHODS: We investigated the PSORS1C1 gene for disease association by direct sequencing of the PSORS1C1 gene in 143 Chinese patients with chronic plaque psoriasis and 188 control subjects. Genotyping for HLA-Cw*0602 and the alpha-helix coiled-coil rod homologue (C6orf18, formerly HCR) gene was also carried out using a sequence-based typing method. RESULTS: We identified 10 single nucleotide polymorphisms (SNPs) on the PSORS1C1 gene in our subjects; four of these SNPs cause amino acid change. We also detected poly(C) repeat variants from nucleotide positions 386-392 (poly(C)6-8). The poly(C) repeat polymorphisms cause a frame shift mutation. Another poly(C) repeat variant was also found at nucleotide positions 748-751. No significantly different allelic distributions of the PSORS1C1 SNPs or poly(C) repeat polymorphisms could be found between the patients with chronic plaque psoriasis and controls after correction for multiple testing. However, a significant increase of the Cw*0602 allele and tryptophan-tryptophan allele of the C6orf18 gene (HCR*WW) was found in patients with early onset psoriasis (21.9% vs. 4.8%, P < 10(-7)). Haplotype-based association analysis also showed a susceptibility haplotype carrying Cw*0602 and HCR*WW alleles in early onset Chinese patients. CONCLUSIONS: Our results indicate that the PSORS1C1 gene might not play an important role in the causation of chronic plaque psoriasis in Chinese people.

Adolescent↗
PubMed2004

A study of cytokeratin profiles in localized cutaneous amyloids.

The major component of localized cutaneous amyloids may be derived from cytokeratin (CK). However, the CK profiles of primary cutaneous amyloidosis (PCA) and secondary cutaneous amyloidosis (SCA) remain obscure. Paraffin-embedded sections of skin tissue from 64 patients with PCA, 111 with SCA and 3 with systemic amyloidosis were analyzed immunohistochemically using 12 different polyclonal or monoclonal anti-CK antibodies (34betaE12, MNF116, LP34, AE1/AE3, anti-CK1, CK5, CK6, CK7, CK10, CK14, CK16 and CK17). In addition, frozen skin tissues from 12 patients with PCA were analyzed for comparison with the paraffin-embedded tissue. In all 64 PCA paraffin sections, the amyloid deposits were immunopositive for anti-CK5 antibody and 34betaE12. In all 12 frozen sections of PCA, the amyloid deposits were immunopositive for anti-CK5 antibody, 34betaE12, MNF116 and LP34, and seven (58.3%), three (25%) and one (8.3%) were immunopositive for anti-CK1, CK14, and CK10 antibodies, respectively. In all SCA sections, the amyloid deposits were immunopositive for CK5 and 34betaE12. In addition, MNF116 immunolabeled amyloids of all sections from patients with basal cell carcinoma and trichoepithelioma, and MNF116 and LP34 immunolabeled amyloids of sections from patients with porokeratosis. Our results indicate that CK5 is the major CK present in the amyloid deposits of PCA and SCA, and "amyloid-K" is mainly derived from basal keratinocytes.

Adult↗
PubMed2004

Genetic polymorphisms of the HCR gene and a genomic segment in close proximity to HLA-C are associated with patients with psoriasis in Taiwan.

BACKGROUND: Although psoriasis vulgaris (PV) is strongly associated with HLA-Cw*0602, it has been proposed that the association of Cw*0602 is due to linkage disequilibrium and that other nearby genes are involved in PV susceptibility. The alpha-helix coiled-coil rod homologue (HCR) gene, located 110 kb telomeric to the HLA-C locus, is presumed to be one of the PV candidate genes. Recently, a 10-kb genomic segment, centromeric to HLA-C, defined by two new single nucleotide polymorphisms (SNPs) n.7*A and n.9*C, was found to have a stronger association with psoriasis than the HCR gene. Until now, no study of the association of the HCR gene, SNPs n.7, and n.9 has been conducted on Chinese patients with psoriasis. OBJECTIVES: We aimed to determine whether the genetic polymorphisms of the HCR gene, SNPs n.7*A, and n.9*C were associated with an increased risk of psoriasis in Chinese patients. METHODS: Using direct sequencing of the HCR gene and the genomic region containing SNPs n.7 and n.9, we investigated the HCR gene, SNPs n.7, and n.9 for disease association in 115 Chinese patients with psoriasis and 103 control subjects. The HCR SNPs were confirmed by denaturing high performance liquid chromatography. Genotyping for HLA-Cw*0602 was also carried out using sequence-based typing. RESULTS: We observed a different allelic distribution between patient and control groups at nucleotide positions 386, 404, 1802 and 2406 of the HCR gene, and SNPs n.7, and n.9. The associations were much stronger in early onset PV patients (for HCR-386*T and HCR-404*T, odds ratio = 5.63, Pc < 0.0001). The HLA-Cw*0602 also displayed a similar association with PV (odds ratio = 5.4, Pc < 0.0001). Moreover, SNP n.7*A, SNP n.9*C, Cw*0602, HCR-386*T, HCR-404*T and HCR-1802*T were in linkage disequilibrium with each other. Haplotype-based association analysis showed SNP n.7*A-SNP n.9*C-Cw*0602-HCR-386*T-HCR-404*T-HCR-1802*T-HCR-2406*G as a major susceptibility haplotype in this Chinese population (for early onset patients, odds ratio = 5.15, Pc < 0.0001). CONCLUSIONS: Our results indicate that the HCR gene, SNP n.7*A, and SNP n.9*C as well as Cw*0602 are major susceptibility markers for psoriasis in Chinese patients.

Adolescent↗
PubMed2003

SPR1 gene near HLA-C is unlikely to be a psoriasis susceptibility gene.

Although genetics analyses have identified the HLA-Cw6 allele to be the major risk allele for psoriasis vulgaris (PV) in many racial groups, it has been proposed that other putative genes near the HLA-C locus are involved in PV susceptibility and that the association of Cw6 is a result of linkage disequilibrium. The SPR1 gene, a predicted gene located 128 kb telomeric to the HLA-C locus, is considered to be one potential candidate gene of PV. Until now, no association study of the SPR1 gene has been conducted on psoriasis patients. We investigated the SPR1 gene for disease association by direct sequencing of the SPR1 gene in 116 Chinese patients with PV and 116 normal subjects. Genotyping for HLA-Cw6 was also carried out using polymerase chain reaction/restriction fragment length polymorphism. Significant increase of the HLA-Cw6 allele was found in psoriasis patients (32.8% vs. 13.8%, P = 0.001). We found that the SPR1 gene is a highly polymorphic gene containing 13 single nucleotide polymorphisms (SNPs), two of which have not been previously reported, and four SNPs cause amino acid change. No significantly different allelic distribution of 13 SPR1 SNPs could be found between the patients with PV and controls after correction for multiple testing. If the frequencies of SPR1 SNPs were compared between the early onset psoriatics and control subjects, early onset patients were more likely to have G allele at position 988 (60% vs. 35.3%, P = 0.001). However, the significance disappeared upon stratification for the Cw6 status. Haplotype-based association analysis showed two susceptibility haplotypes (types 8 and 19) in early onset psoriasis patients. Nonetheless, the significance also disappeared after stratification of the Cw6 status. Our results suggest that HLA-Cw6 remains the major risk allele in Chinese psoriatics, and that the SPR1 gene might not play an important role in the causation of PV.

Adult↗
PubMed2003

A study of candidate genes for psoriasis near HLA-C in Chinese patients with psoriasis.

BACKGROUND: Genetic analyses have identified the HLA-Cw6 allele as the major risk allele for psoriasis in many racial groups. However, by serological typing, HLA-Cw6 is not considered a risk factor in Chinese psoriatics. There are several susceptibility genes for psoriasis residing in chromosome 6p near the HLA-C locus, including the corneodesmosin (CDSN) gene, the octamer transcription factor-3 (POU5F1) gene, the major histocompatibility complex class I chain-related gene A (MICA), and the gene for tumour necrosis factor (TNF)-alpha. However, the information about their role in psoriasis in Chinese patients is limited. OBJECTIVES: We aimed to determine whether Cw6 and the genetic polymorphism of the CDSN gene, POU5F1 gene, MICA gene and the gene for TNF-alpha promoter region were associated with an increased risk of psoriasis in Chinese patients. METHODS: We conducted a case-control association study in 105 Chinese patients with psoriasis vulgaris and 160 control subjects of similar ages. Genotypes of Cw6, the CDSN gene, the POU5F1 gene, and the gene for the TNF-alpha promoter region were determined by polymerase chain reaction (PCR) followed by restriction enzyme digestion. Genotyping of MICA was determined by PCR combined with fluorescent-based automated fragment detection technology. Results The allele frequencies showed no differences between patients and controls for the POU5F1 gene, MICA gene and the gene for TNF-alpha promoter region. The frequency of the HLA-Cw6 allele in the psoriasis group was significantly higher than that in the control group (18.6% vs. 6.56%, P < 0.00005). For the CDSN gene, patients were more likely to have C allele at position +619 (P = 0.006) and C allele at position +1243 (P = 0.007), but the significance disappeared after correction for multiple testing (Pc > 0.05). CONCLUSIONS: HLA-Cw6 remains the most significant susceptibility gene in Chinese patients with psoriasis. However, the role of the CDSN gene in the pathogenesis of psoriasis deserves further scrutiny.

Adolescent↗
PubMed2001

Pharmacological and functional characterization of muscarinic receptor subtypes in developing oligodendrocytes.

This study focused on the molecular and pharmacological characterization of muscarinic acetylcholine receptors expressed by progenitors and differentiated oligodendrocytes. We also analyzed the role of muscarinic receptors in regulating downstream signal transduction pathways and the functional significance of receptor expression in oligodendrocytes. RT-PCR analysis revealed the expression of transcripts for M3, and to a lesser extent M4, followed by M1, M2 and M5 receptor subtypes in both progenitors and differentiated oligodendrocytes. Competition binding experiments using [(3)H]N-methylscopolamine and several antagonists, as well as inhibition of carbachol-mediated phosphoinositide hydrolysis, showed that M3 is the main subtype expressed in these cells. In progenitors the activation of p42/44-mitogen-activated protein kinase (MAPK) and cAMP-response element binding protein (CREB) as well as c-fos mRNA expression were blocked by the M3 relatively selective antagonist, 4-DAMP, and its irreversible analogue, 4-DAMP-mustard. Carbachol increased proliferation of progenitors, an effect prevented by atropine and 4-DAMP, as well as by the MAPK kinase inhibitor PD98059. These results indicate that carbachol modulates oligodendrocyte progenitor proliferation through M3 receptors, involving activation of a MAPK signaling pathway. Receptor density and phosphoinositide hydrolysis are down-regulated during oligodendrocyte differentiation. Functional consequences of these events are a reduction in carbachol-stimulated p42/44(MAPK) and CREB phosphorylation, as well as induction of c-fos.

Blotting, Northern↗
PubMed2001

Effect of diabetes and insulin treatment on nitric oxide synthase content in rat corpus cavernosum.

AIM: To study the effect of diabetes mellitus and insulin treatment on rat penile nitric oxide synthase content. METHODS: Male Wistar rats were divided at random into two groups: the Control (n = 8) and the Diabetic (n = 17). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The diabetic animals were then randomly divided into two subgroups: diabetic rats without insulin treatment (n = 7) and diabetic rats with insulin treatment (n = 10). The neuronal nitric oxide synthase (nNOS) in the penile corpus cavernosum were assayed by immumohistochemical staining with specific antibody to nNOS and the nNOS-positive nerve fibers were counted semiquantitatively under a high power microscope. RESULTS: The nNOS- positive nerve fibres in diabetic rats with treatment was higher than that in diabetic rats without treatment (P < 0.05) and lower than that in the controls (P < 0. 01). The nNOS-positive nerve fibres in diabetic rat without treatment were also lower than that in the controls (P < 0. 01). CONCLUSION: In streptozotocin-induced diabetic rats, the nNOS content in the penile corpus cavernosum was significantly decreased. Insulin treatment at the dose level employed partially restores the penile nNOS content in these rats.

Animals↗
PubMed2000

Exposure of developing oligodendrocytes to cadmium causes HSP72 induction, free radical generation, reduction in glutathione levels, and cell death.

Primary cultures of oligodendrocytes were used to study the toxic effects of cadmium chloride. Cell viability was evaluated by the mitochondrial dehydrogenase activity and confirmed by propidium iodide (PI) fluorescence staining. The expression of the 72 kDa stress protein, HSP72, was assayed by Western blot analysis. The results showed that Cd(2+)-induced toxicity was dependent on the time and dose of exposure, as well as on the developmental stage of the cultures. Oligodendrocyte progenitors were more vulnerable to Cd(2+) toxicity than were mature oligodendrocytes. Mature oligodendrocytes accumulated relatively higher levels of Cd(2+) than did progenitors, as determined by (109)CdCl(2) uptake; treatment with the metal ion caused a more pronounced reduction in intracellular glutathione levels and significantly higher free radical accumulation in progenitors. The latter could explain the observed differences in Cd(2+) susceptibility. HSP72 protein expression was increased both in progenitors and in mature cells exposed to Cd(2+). Pretreatment with N-acetylcysteine, a thiocompound with antioxidant activity and a precursor of glutathione, prevented Cd(2+)-induced (i) reduction in glutathione levels and (ii) induction of HSP72 and diminished (i) Cd(2+) uptake and (ii) Cd(2+)-evoked cell death. In contrast, buthionine sulfoximine, an inhibitor of gamma-glutamyl-cysteine synthetase, depleted glutathione, and potentiated the toxic effect of Cd(2+). These results strongly suggest that Cd(2+)-induced cytotoxicity in oligodendrocytes is mediated by reactive oxygen species and is modulated by glutathione levels.

Acetylcysteine↗
PubMed1999

Molecular pathways mediating activation by kainate of mitogen-activated protein kinase in oligodendrocyte progenitors.

Oligodendroglial cells express ionotropic glutamate receptors of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid hydrobromide (AMPA) and kainate (KA) subtypes. Recently, we reported that AMPA receptor agonists increased 45Ca2+ uptake and phospholipase C (PLC) activity. To further elucidate the intracellular signaling mechanisms, we examined the effects of AMPA and KA on mitogen-activated protein kinase (MAPK). KA caused a time- and concentration-dependent increase in MAPK activity (predominantly the p42mapk or ERK2) and the effect was blocked by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), a competitive AMPA/KA receptor antagonist. Furthermore, the noncompetitive antagonists of AMPA receptor GYKI 52466 and LY 303070 prevented the actions of the agonists, indicating that the effect of KA on MAPK activation is mediated through AMPA receptors in oligodendrocyte progenitors. Chelation of extracellular Ca2+ by EDTA or inhibition of PLC with U73122 abolished MAPK activation by KA. In addition, KA-stimulated MAPK activation was reduced by the protein kinase C (PKC) inhibitors, H7 and bisindolylmaleimide, as well as downregulation of PKC by prolonged exposure to phorbol esters. The involvement of PKC in the signal transduction pathways was further supported by the ability of KA to induce translocation of PKC measured by [3H]PDBu binding. Interestingly, a wortmannin-sensitive phosphatidylinositol 3-kinase and a pertussis toxin (PTX)-sensitive G protein form part of the molecular pathways mediating MAPK activation by AMPA receptor. A specific inhibitor of MAPK kinase, PD 098059, blocked MAPK activation and reduced KA-induced c-fos gene expression. All together, these results indicate that MAPK is implicated in the transmission of AMPA signaling to the nucleus and requires extracellular Ca2+, and PLC/PKC activation.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1998

Detection of Epstein-Barr virus and HTLV-I in T-cell lymphomas of skin in Taiwan.

Viral etiology has been associated with the pathogenesis of T-cell lymphomas of skin (TCLS). Therefore, we studied the presence of Epstein-Barr virus (EBV) and type I human T-cell lymphotropic virus (HTLV-I) in tumor cells of TCLS to determine the significance of these viruses with the disease. A retrospective study was conducted on the skin tissues from 28 Chinese patients with TCLS. We used in situ hybridization, immunohistochemistry, and polymerase chain reaction to determine the presence of viruses. Among the 28 cases, HTLV-I was only detected in two cases with adult T-cell leukemia/lymphoma, not in other cases of TCLS. This suggests that HTLV-I may not play a significant role in the oncogenesis of TCLS in Chinese patients. Conversely, EBV was detected in 12 cases (42.9%), including the secondary TCLS, large cell lymphoma, mycosis fungoides, adult T-cell leukemia/lymphoma, and angiocentric lymphoma. Nevertheless, latent membrane protein 1 was not detected in any of the EBV-positive cases. Neither was any correlation found between the presence of EBV in TCLS and the prognosis or the severity of the skin lesion. Although there is a close association of EBV with a portion of TCLS, its pathogenic role needs further investigation.

Adolescent↗
PubMed1997

Glutamate-stimulated production of inositol phosphates is mediated by Ca2+ influx in oligodendrocyte progenitors.

The effect of glutamate on the accumulation of [3H]inositol phosphates was examined in oligodendrocyte progenitor cultures prepared from rat brains. Glutamate, and the analogues alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate, caused a concentration- and time-dependent increase in [3H]inositol trisphosphate (IP3) formation and the effect was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a competitive AMPA and kainate receptor antagonist. Similarly, the more selective, noncompetitive antagonist of AMPA receptors, 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), significantly reduced the effect of both AMPA and kainate. In contrast, antagonists of N-methyl-D-aspartate (NMDA) receptor, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5, 10-imine (MK-801) and R(-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), and antagonists of metabotropic receptors, L(+)-2-amino-3-phosphono-propanoic acid (L-AP3) and alpha-methyl-4-carboxyphenylglycine (MCPG), were ineffective. These results suggest that the effect of glutamate on [3H]IP3 accumulation is mediated through ionotropic AMPA receptors. Cyclothiazide, an inhibitor of AMPA receptor desensitization, strongly potentiated the AMPA and kainate-stimulated [3H]IP3 formation as well as the uptake of 45Ca2+ in line with the previous findings. 45Ca2+ uptake evoked by AMPA or kainate, in combination with cyclothiazide, was also prevented by both CNQX and GYKI 52466. Glutamate-stimulated [3H]IP3 accumulation was prevented by EGTA, suggesting a requirement for extracellular calcium. Pre-incubation with the voltage-gated Ca2+ channel blockers, diltiazem, nifedipine and CdCl2, partially prevented the glutamate-induced [3H]IP3 accumulation as well as 45Ca2+ uptake. Similarly, the Na+/Ca2+ exchanger blockers benzamil and 3,4-dichlorobenzamil reduced significantly kainate-stimulated 45Ca2+ uptake. These data indicate that glutamate-induced [3H]IP3 accumulation is triggered by calcium influx via AMPA receptors, voltage-gated calcium channels and the Na+/Ca2+ exchanger operating in reverse mode.

Animals↗
PubMed1997

In vitro immunosuppressive effects of methotrexate and azathioprine on Langerhans cells.

The long-term use of immunosuppressive agents may cause profound suppression of the cutaneous immune function. Because epidermal Langerhans cells (LC) play an important role in the cutaneous immune system, they could be the target of immunosuppressants. Since little information is available about the direct immunosuppressive effects of methotrexate (MTX) and azathioprine (AZA) on LC, we studied the viability and immunostimulatory effects of purified LC after pulsation with MTX or AZA at various concentrations. Both MTX and AZA started to suppress the mixed LC-T lymphocyte reaction (MLCLR) significantly at a concentration of 1 microgram/ml. However, the suppressive effect of MTX was not dose-dependent; no further suppression was seen up to a concentration of 1 mg/ml. MTX showed no inhibitory effect on the viability of LC even at concentrations as high as 1 mg/ml. In contrast, the suppressive effect of AZA on the MLCLR was dose-dependent and AZA at a concentration of 500 micrograms/ml or higher markedly decreased the viability of LC. Our study confirmed the immunosuppressive effect of MTX and AZA on epidermal LC. In comparison to MTX, AZA at pharmacological levels showed stronger inhibitory effects on alloantigen-presenting capacity of human epidermal LC and was more cytotoxic to LC. In the therapeutic range, however, MTX and AZA probably have no direct effect on epidermal LC. Our study supports the notion that long-term immunosuppressants deplete cutaneous LC by bone marrow suppression.

Azathioprine↗
PubMed1997

Uremic pruritus: roles of parathyroid hormone and substance P.

BACKGROUND: Most patients receiving maintenance hemodialysis have pruritus, but its underlying mechanism remains unknown. Secondary hyperparathyroidism is another common problem in these patients, but its role in uremic pruritus is controversial. Capsaicin can deplete substance P from the peripheral neurons and is known to be effective in the treatment of pain and itching. OBJECTIVE: Our purpose was to evaluate the role of parathyroid hormone (PTH) and substance P in uremic pruritus and to elucidate the underlying mechanisms. METHODS: The study contained two phases. In phase I, we analyzed the correlation between the intensity of itching and serum levels of intact PTH. In phase II, patients with moderate to severe pruritus were placed into two groups: one with high PTH levels and one with low levels. A double-blind, placebo-controlled study of capsaicin 0.025% cream was conducted in phase II. RESULTS: Serum levels of intact PTH did not correlate with the intensity of pruritus and did not significantly change during treatment with capsaicin or placebo. Capsaicin was significantly more effective in alleviating uremic pruritus than the placebo, and no serious side effects were noted. CONCLUSION: Uremic pruritus is not related to PTH. Substance P may act as a neurotransmitter in uremic pruritus and topical capsaicin can be used in the treatment of localized pruritus.

Calcium↗
PubMed1997

Primary papular xanthoma of children: a clinicopathologic, immunohistopathologic and ultrastructural study.

Papular xanthoma (PX) is a very rare skin disorder. We describe a typical case of PX in a 13-month-old Chinese boy who presented with numerous yellow-red papulonodules, 2-8 mm in diameter, mainly on the face, both upper extremities, and abdomen of 10 months duration. Histologic studies showed a diffuse monomorphous infiltrate of foamy cells in the upper dermis. The foamy cells stained positively with oil red O and CD68. The periodic acid Schiff (PAS) stain, S-100 protein, CD1a, CD56, lysozyme, alpha1-antitrypsin, and factor XIIIa were all negative in the foamy cells. The electron microscopic (EM) studies revealed the morphologic features of macrophages with electron-dense, membrane-limited lipid vacuoles in the cytoplasm. After 14 months, neither spontaneous regression nor anetoderma-like scars were noted. Our immunohistochemical and ultrastructural studies support the notion that the origin of the foamy cells is the macrophage rather than the factor XIIIa (+) dermal dendrocyte. There was no associated or underlying disease in this case. We suggest the term primary PX for cases such as this one.

Foam Cells↗