RESUMO
We report a unique case of a Japanese woman with herpetiform pemphigus (HP) who had IgG autoantibodies reactive with nondesmosomal sites of keratinocytes and presented characteristic transmission electron microscopic (TEM) findings of various-sized vacuoles in keratinocytes without acantholysis. The patient presented with pruritic annular oedematous erythemas with small blisters lining the margins on the trunk and extremities. Histopathological examinations showed intraepidermal blisters with prominent infiltrations of eosinophils. Direct and indirect immunofluorescence tests revealed the presence of in vivo bound and circulating IgG autoantibodies to the keratinocyte cell surfaces. However, enzyme-linked immunosorbent assays for desmoglein (Dsg) 1, Dsg3 and desmocollins 1-3 showed negative results. Immunoblotting using the full-length human Dsg1 recombinant protein showed a positive band. TEM examination showed various-sized vacuoles squashing the nuclei in many keratinocytes, resulting in rupture of the cells. Immunoelectron microscopic examination revealed IgG deposition over the entire keratinocyte cell surfaces, which spared the desmosomes. IgG antibodies were also present on the inside walls of the vacuoles around the nuclei of keratinocytes and on the cell surfaces of infiltrating eosinophils. This patient also had marked eosinophilia and high levels of thymus and activation-regulated chemokine and interleukin-5 in the serum. These results indicated a novel autoantigen on the nondesmosomal keratinocyte cell surfaces and the pathogenesis of bullous spongiotic change with inflammation in HP.
Assuntos
Dermatite Herpetiforme/diagnóstico , Queratinócitos/ultraestrutura , Pênfigo/diagnóstico , Pele/patologia , Idoso , Dermatite Herpetiforme/patologia , Desmossomos/ultraestrutura , Feminino , Humanos , Queratinócitos/citologia , Microscopia Eletrônica de Transmissão , Pênfigo/patologia , Pele/citologia , Vacúolos/ultraestruturaRESUMO
Phosphorescence lifetime imaging methods using oxygen-sensitive probes are very useful for visualizing the oxygen status of living cells and tissues with high spatial resolution. We aim to develop a useful oxygen detection technique combining a phosphorescent oxygen probe and an optimal detection method. Herein we present a biological oxygen imaging method using a microscope equipped with a gated intensified charge-coupled device (ICCD) camera as a detector and an Ir(iii) complex as a phosphorescent oxygen probe. Microscopic luminescence images of monolayer HT-29 cells (human colorectal adenocarcinoma cells) obtained using the cell-penetrating Ir(iii) complex BTPDM1 and an inverted microscope demonstrated that this method allowed visualization of the oxygen gradient produced in a monolayer of cultured cells when the monolayer is covered with a thin coverslip. Furthermore, combining the IR-emitting Ir(iii) complex DTTPH-PEG24 with a macrozoom microscope equipped with a gated ICCD camera enabled both the visualization of retinal vessels near the optic disc and the monitoring of oxygen level changes in a rabbit retina upon changing the inhaled oxygen content.
RESUMO
Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact. In this study, we identified CNTN5 and CNTN6 deleterious variants in individuals with ASD. Among the carriers, a girl with ASD and attention-deficit/hyperactivity disorder was carrying five copies of CNTN5. For CNTN6, both deletions (6/1534 ASD vs 1/8936 controls; P=0.00006) and private coding sequence variants (18/501 ASD vs 535/33480 controls; P=0.0005) were enriched in individuals with ASD. Among the rare CNTN6 variants, two deletions were transmitted by fathers diagnosed with ASD, one stop mutation CNTN6W923X was transmitted by a mother to her two sons with ASD and one variant CNTN6P770L was found de novo in a boy with ASD. Clinical investigations of the patients carrying CNTN5 or CNTN6 variants showed that they were hypersensitive to sounds (a condition called hyperacusis) and displayed changes in wave latency within the auditory pathway. These results reinforce the hypothesis of abnormal neuronal connectivity in the pathophysiology of ASD and shed new light on the genes that increase risk for abnormal sensory perception in ASD.
Assuntos
Percepção Auditiva/genética , Transtorno do Espectro Autista/genética , Contactinas/genética , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Espectro Autista/metabolismo , Criança , Contactinas/metabolismo , Variações do Número de Cópias de DNA , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Mutação , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Although a number of pathological processes resulting in amyloid deposition have been described in lichen amyloidosus (LA), no attention has been paid to the involvement of sweat glands/ducts in the pathogenesis of LA. According to recent studies, follicular structures are usually spared in serial histological sections of LA, and deposits of amyloid are likely to be confined to areas that display xerosis, suggesting that decreases in skin wetness by sweating disturbance seem to initiate LA. OBJECTIVES: To investigate whether sweating disturbance could represent an early event that triggers LA, and whether resolution of LA could be induced by restoring the sweating disturbance. METHODS: By using the impression mould technique, which allows an accurate quantification of individual sweat glands/ducts actively delivering sweat, we examined sweat responses to thermal stimulus in LA lesions before and after treatment with a moisturizer. RESULTS: Sweating disturbance was most profoundly detected in the 'hub' structure of the LA papule, and this disturbance due to leakage of sweat could be restored by short-term treatment with a moisturizer, particularly when used under occlusion. CONCLUSIONS: This study was limited by the relatively small sample size. Treatment of LA should be primarily directed at preventing leakage of sweat into the dermis or epidermis and therefore sweat delivery to the skin surface could be made easier.
Assuntos
Amiloidose/etiologia , Líquen Plano/etiologia , Doenças das Glândulas Sudoríparas/complicações , Glândulas Sudoríparas/fisiologia , Sudorese/fisiologia , Adulto , Idoso , Fármacos Dermatológicos/uso terapêutico , Feminino , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
The gene encoding the neural cell adhesion molecule Cntn5 (a.k.a. NB-2) has been put forward as a candidate in neurodevelopmental disorders, like autism spectrum disorder (ASD), by recent genetic findings. Little is known about the expression pattern and function of the gene, and its functional involvement in brain development has remained elusive. So far, most research has focused on its early postnatal expression in the auditory system, where the absence of Cntn5 causes abnormal responses to acoustic stimuli and a decrease in fiber density. The current study shows that the Cntn5 gene is expressed in forebrain structures during embryonic development, starting at E15.5, and that it continues to be expressed into adulthood. Sites of strong expression included the thalamus, the caudate putamen (CPu) and to a lesser extent layer Va of the cerebral cortex. Cntn5-positive thalamic nuclei include the laterodorsal (LD), ventrolateral (VL) and posterior group (Po), which contain glutamatergic neurons. Visualization of the expression pattern through the Tau-LacZ fusion protein coded by an insert in the Cntn5 gene, demonstrated that Cntn5-positive nuclei of the thalamus project to the cortex, based on co-localization with thalamocortical markers L1 and Calretinin. These results indicate that the cell adhesion functions of Cntn5 are exploited for circuit formation and connectivity in early development and for synaptic maintenance during adulthood. Subtle alterations in the formation of the thalamocortical circuit may contribute to neurodevelopmental disorders, such as ASD.
Assuntos
Córtex Cerebral , Contactinas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Neurônios/metabolismo , Tálamo , Animais , Animais Recém-Nascidos , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Córtex Cerebral/embriologia , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/metabolismo , Misturas Complexas/metabolismo , Contactinas/genética , Embrião de Mamíferos , Camundongos , Camundongos Transgênicos , Vias Neurais/fisiologia , Tálamo/embriologia , Tálamo/crescimento & desenvolvimento , Tálamo/metabolismo , Fatores de Transcrição/metabolismo , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , beta-Galactosidase/genética , beta-Galactosidase/metabolismoRESUMO
Brownian dynamics simulation on model electrolyte solutions in our previous work [T. Yamaguchi et al., J. Chem. Phys. 134, 244506 (2011)] is extended to include the hydrodynamic interaction between ions, in order to examine its effects on ionic mobility in solvents of low dielectric constant. The effects of the hydrodynamic interaction are rather small as a whole, and the equivalent conductivity minimum is observed in systems with the hydrodynamic interaction. The hydrodynamic interaction increases the self-diffusion coefficient while decreases the equivalent conductivity, thereby increases the deviation from the Nernst-Einstein relationship. Based on the analysis of the time-dependent ionic mobilities, these changes are elucidated in terms of the electrophoretic and relaxation effects. It is also demonstrated that the concentration dependence of the ionic mobilities with the hydrodynamic interaction is reproduced fairly well by a theoretical calculation.
RESUMO
We study the phase diagram of composite fermions (CFs) in the presence of spin and pseudospin degrees of freedom in the bilayer nu=2/3 quantum Hall (QH) state. Activation studies elucidate the existence of three different QH states with two different types of hysteresis in the magnetotransport. While a noninteracting CF model provides a qualitative account of the phase diagram, the observed renormalization of tunneling gap and a non-QH state at high densities are not explained in the noninteracting CF model, and are suggested to be manifestations of interactions between CFs.
RESUMO
We produced NB3C4, a novel monoclonal antibody specific for oligodendrocytes, using human neuroblastoma IMR-32 cells. NB3C4 specifically recognized oligodendrocytes in the CNS, although it bound to neuroblastoma IMR-32 cells and oligodendrocytes in vitro. Double immunofluorescence staining of rat brain using NB3C4 and anti-GST-pi, anti-glial fibrillary acidic protein (GFAP), or anti-neurofilament 200 (NF) antibody revealed that anti-GST-pi antibody identified an oligodendrocyte marker recognizing NB3C4-positive cells, while both anti-GFAP and anti-NF antibody did not. Western blotting of rat brain homogenates showed that NB3C4 bound three proteins of 22-28 kDa, while the anti-GST-pi recognized a 27 kDa protein. Therefore, antigens recognized by NB3C4 could be novel markers for oligodendrocytes.
Assuntos
Anticorpos Monoclonais/farmacologia , Especificidade de Anticorpos , Oligodendroglia/imunologia , Animais , Biomarcadores , Encéfalo/citologia , Feminino , Humanos , Imunização , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neuroblastoma , Gravidez , Ratos , Ratos Wistar , Células Tumorais CultivadasRESUMO
The Lewis X (Le(x)) bearing glycolipids were noticeably increased in amounts during the course of neural differentiation of P19 EC cells induced by retinoic acid (RA, all-trans form). Applying neoglycolipid technology and in situ TLC-LSIMS, the oligosaccharide chains of these scarce Le(x) bearing glycolipids were partially characterized after released by endoglycoceramidase and subsequent conversion into neoglycolipids. In order to understand the enzymatic basis for the expression of Le(x) bearing glycolipids, we measured glycolipid, glycoprotein and oligosaccharide fucosyltransferase (Fuc-T) activities using appropriate substrates in P19 EC cells with or without RA treatment. All three Fuc-Ts were increased after RA treatment and the highest activity was in the differentiated neural cells. We then investigated the two possible Fuc-T genes that might be responsible for these changes using RT-PCR analysis. Mouse Fuc-TIX (mFuc-TIX) transcript was detected in all cell types but it was only strongly expressed in RA-induced aggregates and neural cells. In the case of mouse Fuc-TIV (mFuc-TIV) gene, its transcript was only detectable in RA-induced aggregates and not found in either undifferentiated or RA-induced neural cells. These results strongly support that RA induces only a transient expression of the mFuc-TIV gene in cell aggregates but a more persistent expression of the mFuc-TIX gene at the transcription level throughout neural cell differentiation. The mFuc-TIX gene is probably the main cause for the increased expression of Le(x) glycoconjugates during neural differentiation of P19 EC cells.
Assuntos
Diferenciação Celular , Epitopos/biossíntese , Antígenos CD15/biossíntese , Neurônios/citologia , Neurônios/metabolismo , Animais , Western Blotting , Sequência de Carboidratos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Indução Enzimática/efeitos dos fármacos , Epitopos/química , Epitopos/imunologia , Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Glicolipídeos/análise , Glicolipídeos/química , Antígenos CD15/química , Antígenos CD15/imunologia , Espectrometria de Massas , Camundongos , Dados de Sequência Molecular , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Oligossacarídeos/análise , Oligossacarídeos/química , RNA Mensageiro/análise , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tretinoína/farmacologiaRESUMO
We describe magnetic resonance imaging findings in a 37-year-old man with a rare entity of isolated polyarteritis nodosa of the epididymis, which correlated well with the histopathologic findings.
Assuntos
Epididimo/irrigação sanguínea , Imageamento por Ressonância Magnética , Poliarterite Nodosa/diagnóstico , Adulto , Diagnóstico Diferencial , Epididimo/cirurgia , Humanos , Masculino , Poliarterite Nodosa/patologia , Poliarterite Nodosa/cirurgiaRESUMO
We examined the localization of the pituitary adenylate cyclase-activating peptide (PACAP) receptor (PAC1-R) and its mRNA with immunocytochemistry and in situ hybridization, respectively. PAC1-R immunoreactivity and its transcript were detected in both chromaffin cells and ganglion cells but not detected in the adrenal cortex. In addition, strong PAC1-R immunoreactivity was found beneath the plasma membrane of the immunoreactive medullary cells. Electron microscopic immunocytochemistry revealed that PAC1-R was predominantly expressed in adrenaline-containing cells. This report supports the notion that PACAP is an activator and modulator of catecholamine secretion as well as synthesis in the adrenal medulla.
Assuntos
Medula Suprarrenal/metabolismo , Neuropeptídeos/metabolismo , Receptores do Hormônio Hipofisário/metabolismo , Medula Suprarrenal/ultraestrutura , Animais , Masculino , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Receptores do Hormônio Hipofisário/genética , Transdução de Sinais/fisiologiaRESUMO
Both leptin and orexin have been recently discovered as peptides involved in feeding regulation. The morphological evidence of neural interaction between leptin and orexin, one considered to inhibit food intake and the other to stimulate it in the central nervous system (CNS), was studied by use of double immunostaining method. The leptin receptor-like immunoreactive (LR-LI) neurons in the hypothalamic arcuate nucleus and ventromedial nucleus were innervated by orexin-like immunoreactive (OX-LI) neurons. The distribution of LR-LI neurons in the hypothalamus was very similar to that of OX-LI neurons. These results may suggest that leptin and orexin are intimately correlated with each other and that they reciprocally regulate feeding at the hypothalamic level.
Assuntos
Proteínas de Transporte/metabolismo , Hipotálamo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Leptina/metabolismo , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Receptores de Superfície Celular , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Núcleo Arqueado do Hipotálamo/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Hipotálamo/patologia , Masculino , Receptores de Orexina , Orexinas , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G , Receptores para Leptina , Receptores de Neuropeptídeos , Núcleo Hipotalâmico Ventromedial/metabolismo , Núcleo Hipotalâmico Ventromedial/patologiaRESUMO
HNK-1 epitope is a cell-surface carbohydrate mediating various cell-cell or cell-substrate interactions. We found HNK-1 epitope in longitudinally arrayed fibers in the subpopulation of the epaxial myotome, and hypaxial myoblasts migrating into the limb bud in the rat embryo. We next investigated the expression patterns of genes encoding two glucuronyltransferases (GlcAT-P, GlcAT-D) and sulfotransferase (Sul-T), which are required for biosynthesis of HNK-1 epitope. GlcAT-P gene was expressed in the non-migrating longitudinal fibers, whereas GlcAT-D gene was expressed in the migrating myoblasts in the limb bud. Sul-T gene expression was ubiquitously observed in all these myogenic populations. Thus, differential expression of GlcAT genes may relate to the epaxial/hypaxial or migrating/non-migrating myoblast lineages.
Assuntos
Antígenos CD57/biossíntese , Glucuronosiltransferase/genética , Animais , Epitopos/biossíntese , Regulação da Expressão Gênica no Desenvolvimento , Glucuronosiltransferase/metabolismo , Hibridização In Situ , Músculos/embriologia , Músculos/enzimologia , Músculos/imunologia , Ratos , Ratos Sprague-Dawley , Células-Tronco/enzimologia , Células-Tronco/imunologia , Sulfotransferases/genéticaRESUMO
To evidence the notion that gangliosides involve neuronal cell interactions in the brain, we surveyed the presence of ganglioside-binding proteins in membrane lysates of adult rat cerebellum. Three proteins (p58, p90, and p160) were identified as GT1b-binding proteins by incubation of the blot of the membrane lysate with GT1b micelles. We generated a monoclonal antibody (mAb) specific to the polypeptide portion of the GT1b-binding proteins (YAK-2). The YAK-2 mAb specifically reacted with all three proteins on blots of proteins pretreated under nonreducing conditions for SDS-PAGE, but reacted mainly with p58 under reducing conditions, showing that p90 and p160 are oligomeric forms of p58. The binding activity of the YAK-2 mAb was completely inhibited by the presence of GT1b micelles, indicating the specificity of YAK-2 mAb for p58 and its oligomers. Immunohistochemical investigations revealed that both p58 and GT1b colocalize within the granular layer of adult rat cerebellum. Expression cloning of p58 cDNA was performed using YAK-2 mAb, and five putative clones were obtained. Among them, the nucleotide sequence of one cDNA completely matched that of rat brain-specific sodium-dependent inorganic phosphate cotransporter (rBNPI), a 61 kDa membrane protein. COS7 cells were transfected with a Flag-chimeric construct containing the rBNPI/p58 cDNA, and the membrane lysate was subjected to immunoprecipitation with anti-Flag antibody. One protein (64 kDa) was detected only with YAK-2 mAb, and the membrane lysate specifically bound to GT1b micelles. Taking together, we propose that rBNPI/p58 functions as a GT1b-binding protein in neuronal cells.
Assuntos
Anticorpos Monoclonais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Cerebelo/metabolismo , Gangliosídeos/imunologia , Gangliosídeos/metabolismo , Fosfatos/metabolismo , Sódio/metabolismo , Simportadores , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/química , Células COS , Proteínas de Transporte/biossíntese , Clonagem Molecular , Feminino , Micelas , Peso Molecular , Ratos , Ratos Wistar , Proteínas Cotransportadoras de Sódio-Fosfato , TransfecçãoRESUMO
Medullary neurons containing pituitary adenylate cyclase-activating polypeptide (PACAP) and noradrenalin (NA) project to the hypothalamus and they are involved in the regulation of arginine vasopressin (AVP) neurons. At the ultrastructural level, PACAP immunoreactivity was detected in the granular vesicles in catecholaminergic nerve terminals that made synaptic contact with AVP neurons. Both PACAP (at least 1 nM) and NA (at least 1 microM) induced large increases in the cytosolic Ca2+ concentration ([Ca2+]i) in isolated AVP cells. PACAP at 0.1 nM and NA at 0.1 microM had little effects, if any, on [Ca2+]i. However, when 0.1 nM PACAP and 0.1 microM NA were combined, they evoked large increase in [Ca2+]i in AVP neurons. An inhibitor of protein kinase A (PKA) completely inhibited the PACAP-induced increase in [Ca2+]i, but only partly inhibited the NA-induced increase in [Ca2+]i. In AVP cells that were prelabeled with quinacrine, PACAP and NA acted synergistically to induce a loss of quinacrine fluorescence, indicating secretion of neurosecretory granules in AVP neurons. The results suggest that PACAP and NA, coreleased from the same nerve terminals, act in synergy to evoke calcium signaling and secretion in AVP neurons, and that the synergism is mediated by the interaction between cAMP-PKA pathway an as yet unidentified factor "X" linked to L-type Ca2+ channels. The synergism between PACAP and NA may contribute to the regulation of AVP secretion under physiological conditions.
Assuntos
Terminações Nervosas/metabolismo , Neuropeptídeos/metabolismo , Norepinefrina/metabolismo , Animais , Arginina Vasopressina/metabolismo , Sinalização do Cálcio , Imuno-Histoquímica , Masculino , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Ratos , Ratos Sprague-Dawley , Núcleo Supraóptico/metabolismoRESUMO
We isolated a cDNA encoding a novel glucuronyltransferase, designated GlcAT-D, involved in the biosynthesis of the HNK-1 carbohydrate epitope from rat embryo cDNA by the degenerate polymerase chain reaction method. The new cDNA sequence revealed an open reading frame coding for a protein of 324 amino acids with type II transmembrane protein topology. The amino acid sequence of GlcAT-D displayed 50.0% identity to rat GlcAT-P, which is involved in the biosynthesis of the HNK-1 epitope on glycoproteins. Expression of GlcAT-D in COS-7 cells resulted in the formation of the HNK-1 epitope on the cell surface. The enzyme expressed in COS-7 cells transferred a glucuronic acid (GlcA) not only to asialo-orosomucoid, a glycoprotein bearing terminal N-acetyllactosamine structure, but also to paragloboside (lacto-N-neotetraosylceramide), a precursor of the HNK-1 epitope on glycolipids. Furthermore, substrate specificity analysis using a soluble chimeric form of GlcAT-D revealed that GlcAT-D transfers a GlcA not only to Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc-pyridylamine++ + but also to Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc-pyridylamine++ +. Enzymatic hydrolysis and Smith degradation of the reaction product indicated that GlcAT-D transfers a GlcA through a beta1,3-linkage to a terminal galactose. The GlcAT-D transcripts were detected in embryonic, postnatal, and adult rat brain. In situ hybridization analysis revealed that the expression pattern of GlcAT-D transcript in embryo is similar to that of GlcAT-P, but distinct expression of GlcAT-D was observed in the embryonic pallidum and retina. Regions that expressed GlcAT-D and/or GlcAT-P were always HNK-1-positive, indicating that both GlcATs are involved in the synthesis of the HNK-1 epitope in vivo.
Assuntos
Antígenos CD57/biossíntese , Epitopos/biossíntese , Glucuronosiltransferase/metabolismo , Glicoproteínas/biossíntese , Oligossacarídeos/biossíntese , Sequência de Aminoácidos , Animais , Sequência de Bases , Encéfalo/embriologia , Encéfalo/metabolismo , DNA Complementar/genética , Globosídeos/metabolismo , Glucuronatos/metabolismo , Ácido Glucurônico , Glucuronosiltransferase/genética , Glucuronosiltransferase/isolamento & purificação , Glicoproteínas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Dados de Sequência Molecular , Família Multigênica , Conformação Proteica , Ratos , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Especificidade por Substrato , Distribuição TecidualRESUMO
Cytochrome P450IID6 (CYP2D6) plays an important role in the hepatic metabolism of various psychotropic drugs. We detected a mutation of the CYP2D6 gene in two patients who previously had episodes of neuroleptic malignant syndrome (NMS). They were homozygous for a mutated CYP2D6J allele conferring a poor-metabolizer phenotype. Possession of this trait may contribute to susceptibility to NMS.
Assuntos
Antipsicóticos/efeitos adversos , Citocromo P-450 CYP2D6/genética , Síndrome Maligna Neuroléptica/genética , Alelos , Substituição de Aminoácidos , Antipsicóticos/farmacocinética , Citocromo P-450 CYP2D6/fisiologia , Análise Mutacional de DNA , Predisposição Genética para Doença , Homozigoto , Humanos , Inativação Metabólica/genética , Masculino , Microssomos Hepáticos/enzimologia , Pessoa de Meia-Idade , Síndrome Maligna Neuroléptica/enzimologia , Mutação PuntualRESUMO
Three patients presented with a non-thrombocytopenic purpuric rash on their upper and lower limbs, abdominal pain, diarrhoea, and arthralgia. Grey scale ultrasound showed abnormally thickened walls of the small bowel. Colour Doppler showed blood flow signals in the diseased bowel wall in all patients. Subsequent barium and endoscopic studies showed oedematous bowel loops with petechial lesions. Biopsy from the purpuric rash of the skin demonstrated vasculitis of subdermal small vessels. The clinical diagnosis of Henoch-Schönlein purpura was made in each case. This paper describes the efficacy of grey scale and colour Doppler ultrasonography in the assessment of the small bowel involvement of Henoch-Schönlein purpura.
Assuntos
Vasculite por IgA/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Adulto , Idoso , Feminino , Humanos , Enteropatias/diagnóstico por imagem , MasculinoRESUMO
OBJECTIVE: The molecular basis of neuroleptic malignant syndrome is unclear, but studies suggest that genetic factors are involved in its pathogenesis. Considering possible involvement of the serotonergic system in neuroleptic malignant syndrome, the authors examined the association between neuroleptic malignant syndrome and polymorphisms of the 5-HT1A and 5-HT2A receptor genes. METHOD: The authors examined the frequencies of gene polymorphisms in the 5-HT1A (Arg219Leu) and 5-HT2A (Thr25Asn and His452Tyr) receptor genes in 29 patients previously diagnosed with neuroleptic malignant syndrome, 94 neuroleptic-treated patients with schizophrenia who had no history of neuroleptic malignant syndrome, and 94 healthy comparison subjects. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to screen gene mutations. RESULTS: No polymorphic allele was detected in the patients who had experienced the neuroleptic malignant syndrome. CONCLUSIONS: The authors cannot conclude that polymorphisms in the 5-HT1A and 5HT2A receptor genes are factors determining susceptibility to the neuroleptic malignant syndrome.