RESUMEN
In order to learn more on the occurrence of pains and motor deficit in severe diabetic polyneuropathy we reviewed the data of a series of 30 diabetic patients with an uncommonly severe length-dependent diabetic polyneuropathy (LDDP). Extensive sensory loss predominated with pains and temperature sensations and affected all four limb extremities, anterior trunk in all, plus the top of the scalp in 9 patients and the cauda equina territory in 2. Twenty patients had neuropathic pains. Symptomatic autonomic dysfunction was present in 28/30 patients, mild distal motor deficit in 12 patients, severe in only one. Vibratory sensation was impaired in the lower limbs in 18 patients; position sense in 8. In the 10 nerve biopsy specimens, the density of myelinated axons was reduced to 23 % and that of unmyelinated axons to 8.5 % of control values. Regenerating axons accounted for 32.4 +/- 19.8 % of the myelinated fibres. On teased fibre preparations 13.9 % of fibres were undergoing axonal degeneration, while 29.4 % of fibres showed focal abnormalities of the myelin sheath.We conclude that distal motor deficit occurs only after major loss of sensory fibres in LDDP; the unmyelinated axons are predominantly affected; absence of clinical improvement contrasts with the high proportion of regenerating axons; detection of alteration of pain and temperature sensation in the feet seems the best method for neuropathy screening in diabetic patients.
Asunto(s)
Axones/fisiología , Neuropatías Diabéticas/fisiopatología , Actividad Motora/fisiología , Regeneración Nerviosa , Dolor/fisiopatología , Trastornos de la Sensación/fisiopatología , Adulto , Anciano , Axones/ultraestructura , Neuropatías Diabéticas/patología , Femenino , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Fibras Nerviosas Mielínicas/ultraestructura , Conducción Nerviosa , Estimulación Física , Nervio Sural/patología , Nervio Sural/fisiopatología , Adulto JovenRESUMEN
It is considered that refractory dissolved organic substances have caused an increase in the COD concentration in Lake Biwa in recent years. We investigated the organic matter in the first flush of stormwater runoff from a road in the watershed area of the lake, and studied the possibility of improvement in the water environment from that aspect. After percolating the stormwater through soil, we analyzed organic substances fractionated by using GPC-TC. And we examined the effect of removal of organic substances by comparing the peak height before and after percolation. In the result of the experiments, we found that soil infiltration reduced the refractory dissolved organic substance and we successfully designed a system for a simple and easy experimental facility to treat urban runoff.
Asunto(s)
Monitoreo del Ambiente/métodos , Compuestos Orgánicos/análisis , Contaminantes Químicos del Agua/análisis , Biodegradación Ambiental , Cromatografía , Ciudades , Japón , Lluvia , Suelo , Agua , Movimientos del Agua , Contaminantes del Agua , Abastecimiento de AguaRESUMEN
The present study examined the relationship between methylation of five genes (p16(INK4a), RASSF1A, APC, RARbeta and CDH13) and patient survival in 351 cases of surgically resected lung cancers. While there was no relationship between the other genes and survival, p16(INK4a) methylation was significantly related to unfavourable prognosis in lung adenocarcinomas.
Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Metilación de ADN , ADN de Neoplasias/metabolismo , Genes p16 , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Epidermal growth factor (EGF) comprises a structurally related family of proteins containing heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor alpha (TGFalpha) that regulates the development of dopaminergic neurons as well as monoamine metabolism. We assessed the contribution of EGF to schizophrenia by measuring EGF family protein levels in postmortem brains and in fresh serum of schizophrenic patients and control subjects. EGF protein levels were decreased in the prefrontal cortex and striatum of schizophrenic patients, whereas the levels of HB-EGF and TGFalpha were not significantly different in any of the regions examined. Conversely, EGF receptor expression was elevated in the prefrontal cortex. Serum EGF levels were markedly reduced in schizophrenic patients, even in young, drug-free patients. Chronic treatment of animals with the antipsychotic drug haloperidol had no influence on EGF levels in the brain or serum. These findings suggest that there is abnormal EGF production in various central and peripheral tissues of patients with both acute and chronic schizophrenia. EGF might thus provide a molecular substrate for the pathologic manifestation of the illness, although additional studies are required to determine a potential link between impaired EGF signaling and the pathology/etiology of schizophrenia.
Asunto(s)
Factor de Crecimiento Epidérmico/análisis , Receptores ErbB/análisis , Prosencéfalo/química , Esquizofrenia/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Factor de Crecimiento Epidérmico/sangre , Receptores ErbB/sangre , Femenino , Factor de Crecimiento Similar a EGF de Unión a Heparina , Humanos , Péptidos y Proteínas de Señalización Intercelular , Masculino , Persona de Mediana Edad , Ratas , Ratas Wistar , Factor de Crecimiento Transformador alfa/análisis , Factor de Crecimiento Transformador alfa/sangreRESUMEN
Recently DNA microarray technology has been introduced into analyses of comprehensive biological functions. This DNA microarray is a new technology for simultaneous analysis to examine expression patterns of thousands of genes. It was thought that this technique should be very useful for examination of cellular and molecular mechanisms of drugs of abuse: cocaine, amphetamine, and others. This technology was therefore applied for the rapid analysis of gene expression in the brain from phencyclidine-treated mice. Mainly mouse DNA microarray was examined by using labeled cDNAs produced from a control mouse brain mRNA and from brain mRNA of mouse exposed to drugs as probes. Some changes in a probe from brain mRNA of drug-treated mouse could be observed, but it was necessary to examine another DNA microarray, including more samples from the brain.
Asunto(s)
Encéfalo/fisiología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Fenciclidina/farmacología , Animales , Encéfalo/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , Transcripción Genética/efectos de los fármacosRESUMEN
We investigated the aberrant promoter methylation profile of bladder cancers and correlated the data with clinicopathological findings. The methylation status of 10 genes was determined in 98 surgically resected bladder cancers, and we calculated the median methylation index (MI), a reflection of the methylated fraction of the genes tested. Methylation frequencies of the genes tested in bladder cancers were 36% for CDH1, 35% for RASSF1A and APC, 29% for CDH13, 16% for FHIT, 15% for RAR beta, 11% for GSTP1, 7% for p16(INK4A), 4% for DAPK, and 2% for MGMT. Methylation of four of the individual genes (CDH1, RASSF1A, APC, and CDH13) and the MI were significantly correlated with several parameters of poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, and ploidy pattern). Methylation of CDH1, FHIT, and a high MI were associated with shortened survival. CDH1 methylation positive status was independently associated with poor survival in multivariate analyses. Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in bladder cancer.
Asunto(s)
Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/patología , Metilación de ADN , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Transicionales/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Regiones Promotoras Genéticas , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
We report a 73-year-old woman with intravascular malignant lymphomatosis (IML) who showed generalized telangiectasia as well as various neurological symptoms. In July 1998, she developed fever, dizziness, and confusion followed by left hemiparesis, and was admitted to our hospital on August 11, 1998. Laboratory tests indicated a normochromic normocytic anemia, thrombocytopenia, elevated serum lactic dehydrogenase (LDH), C-reactive protein (CRP), and cerebrospinal fluid protein. Magnetic resonance imaging (MRI) of the brain revealed an infarct-like lesion in the left frontal lobe and multiple white matter lesions. After admission, her neurological status deteriorated and lapsed into coma and quadriplegia. At the end of September 1998, generalized telangiectasia appeared, and she was diagnosed as IML on skin biopsy. Although combination chemotherapy failed to improve her neurological symptoms, telangiectasia disappeared in a few days, and the infarct-like lesion on MRI decreased in size. Serum LDH, CRP, and thrombocyte counts were normalized. Autopsy findings revealed perivascular clustering of B cell type lymphoma cells in the left frontal lobe where abnormal signal intensity was found on MRI, as well as the spleen and the bone marrow. This case emphasizes the importance of early diagnosis and treatment in IML.
Asunto(s)
Infarto Cerebral/etiología , Linfoma de Células B/patología , Telangiectasia/etiología , Neoplasias Vasculares/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Encéfalo/patología , Infarto Cerebral/patología , Femenino , Humanos , Linfoma de Células B/complicaciones , Linfoma de Células B/tratamiento farmacológico , Imagen por Resonancia Magnética , Cuadriplejía/etiología , Piel/irrigación sanguínea , Telangiectasia/patología , Neoplasias Vasculares/complicaciones , Neoplasias Vasculares/tratamiento farmacológicoRESUMEN
OK-432 has been used clinically as a biological response modifier for cancer therapy. We investigated here the protective effects of OK-432 against endotoxic shock and infectious death caused by Pseudomonas aeruginosa and Salmonella enteritidis in mice and proposed a possible mechanism. Pretreatment of OK-432 reduced the lethality of lipopolysaccharide (LPS)-induced endotoxic shock in D-(+)-galactosamine-sensitized C3H/HeN mice. OK-432 did not affect the TNFalpha production in blood, but it did decrease the susceptibility to TNFalpha. Furthermore, an acceleration of LPS clearance from blood was detected. The pretreatment of OK-432 also decreased the lethality of mice in bacterial infection caused by P. aeruginosa and S. enteritidis. The rapid decrease of the viable bacteria from the circulating blood and in spleen and liver in mice was observed in a manner similar to LPS clearance. These findings indicate that the protective effect of OK-432 against the endotoxemia and bacteremia may depend on an up-regulation of clearance of LPS and bacteria and the augmented resistance to TNFalpha.
Asunto(s)
Bacteriemia/tratamiento farmacológico , Endotoxemia/tratamiento farmacológico , Picibanil/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Infecciones por Salmonella/tratamiento farmacológico , Salmonella enteritidis , Animales , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Relación Dosis-Respuesta Inmunológica , Femenino , Lipopolisacáridos/efectos adversos , Lipopolisacáridos/sangre , Masculino , Ratones , Ratones Endogámicos C3H , Picibanil/farmacología , Infecciones por Pseudomonas/sangre , Pseudomonas aeruginosa/efectos de los fármacos , Infecciones por Salmonella/sangre , Salmonella enteritidis/efectos de los fármacos , Choque Séptico/sangre , Choque Séptico/inducido químicamente , Choque Séptico/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Aberrant promoter methylation and resultant silencing of several genes plays an important role in the pathogenesis of many tumor types. We compared the methylation profile of 66 malignant mesotheliomas (MMs) and 40 lung adenocarcinomas using methylation-specific PCR for seven genes frequently methylated in lung cancer. We also compared the methylation frequencies of these genes as well as the methylation index, a reflection of all of the gene frequencies, with the presence of SV40 large T-antigen (Tag) sequences, histological subtype, and patient survival. Our major findings are: (a) with the exception of the RASSF1A promoter of the RASSF1 gene, frequencies of aberrant methylation were significantly lower in MMs than in adenocarcinomas; (b) the frequency of RASSF1A aberrant methylation and the value of the methylation index were significantly higher in SV40 sequence positive MM than in negative MM; and (c) the methylation index was higher in epithelial MM than in sarcomatous/mixed MM. Our results demonstrate a relationship between SV40 and aberrant methylation in MMs.
Asunto(s)
Antígenos Transformadores de Poliomavirus/genética , Metilación de ADN , Genes Supresores de Tumor , Mesotelioma/genética , Proteínas Supresoras de Tumor , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Anciano , Femenino , Gutatión-S-Transferasa pi , Glutatión Transferasa/genética , Humanos , Isoenzimas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Mesotelioma/patología , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Regiones Promotoras Genéticas/genética , Células Tumorales CultivadasRESUMEN
alpha-Amylase is expressed in cotyledons of germinated Vigna mungo seeds and is responsible for the degradation of starch that is stored in the starch granule (SG). Immunocytochemical analysis of the cotyledon cells with anti-alpha-amylase antibody showed that alpha-amylase is transported to protein storage vacuole (PSV) and lytic vacuole (LV), which is converted from PSV by hydrolysis of storage proteins. To observe the insertion/degradation processes of SG into/in the inside of vacuoles, ultrastructural analyses of the cotyledon cells were conducted. The results revealed that SG is inserted into LV through autophagic function of LV and subsequently degraded by vacuolar alpha-amylase. The autophagy for SG was structurally similar to micropexophagy detected in yeast cells. In addition to the autophagic process for SG, autophagosome-mediated autophagy for cytoplasm and mitochondria was detected in the cotyledon cells. When the embryo axes were removed from seeds and the detached cotyledons were incubated, the autophagosome-mediated autophagy was observed, but the autophagic process for the degradation of SG was not detected, suggesting that these two autophagic processes were mediated by different cellular mechanisms. The two distinct autophagic processes were thought to be involved in the breakdown of SG and cell components in the cells of germinated cotyledon.
Asunto(s)
Autofagia/fisiología , Cotiledón/metabolismo , Rosales/metabolismo , Almidón/metabolismo , Fraccionamiento Celular , Cotiledón/ultraestructura , Gránulos Citoplasmáticos/metabolismo , Inmunohistoquímica , Microscopía Confocal , Modelos Biológicos , alfa-Amilasas/metabolismoRESUMEN
Expression of some members of the cadherin family is reduced in several human tumors, and CDH13 (H-cadherin), located on chromosome 16q24.2-3, may function as a tumor suppressor gene. In human tumors, loss of expression of many tumor suppressor genes occurs by aberrant promoter region methylation. We examined the methylation status of the CDH13 promoter in breast and lung cancers and correlated it with mRNA expression using methylation-specific PCR and reverse transcription-PCR. Methylation was frequent in primary breast tumors (18 of 55, 33%) and cell lines (7 of 20, 35%). In lung cancers, methylation was present more frequently in non-small cell lung cancer tumors (18 of 42, 43%) and cell lines (15 of 30, 50%) than in small cell lung cancer cell lines (6 of 30, 20%; P = 0.03). Only the methylated or unmethylated forms of the gene were present in most (73 of 80, 91%) tumor cell lines. CDH13 expression was present in 24 of 30 (80%) of nonmethylated tumor lines. All 18 methylated lines tested lacked expression irrespective of whether the unmethylated form was present, confirming biallelic inactivation in methylated lines. Gene expression was restored in all five methylated cell lines tested after treatment with the demethylating agent 5'-aza-2-deoxycytidine. Our results demonstrate frequent aberrant methylation of CDH13 in breast and lung cancers accompanied by loss of gene expression, although expression may occasionally be lost by other mechanisms.
Asunto(s)
Neoplasias de la Mama/genética , Cadherinas/genética , Metilación de ADN , Neoplasias Pulmonares/genética , Neoplasias de la Mama/metabolismo , Cadherinas/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Células Pequeñas/genética , Carcinoma de Células Pequeñas/metabolismo , ADN de Neoplasias/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Genes Supresores de Tumor , Humanos , Pérdida de Heterocigocidad , Neoplasias Pulmonares/metabolismo , Reacción en Cadena de la Polimerasa/métodos , Regiones Promotoras Genéticas , Análisis de Secuencia de ADN , Células Tumorales CultivadasAsunto(s)
Aire/análisis , Cuidado Intensivo Neonatal/normas , Monitoreo del Ambiente , Humanos , Recién Nacido , JapónRESUMEN
The possible involvement of vacuolar cysteine proteinases in degradation of ribulose-bisphosphate carboxylase (Rubisco) in senescing French bean leaves was studied by ultrastructural and immunocytochemical analyses with antibodies raised against the large subunit (LSU) of Rubisco and SH-EP, a cysteine proteinase from Vigna mungo that is immunologically identical to one of the major proteinases of French bean plants. Primary leaves of 10-day-old plants were detached and placed at 25 degrees C in darkness for 0, 4, and 8 days to allow their senescence to proceed. The leaves at each senescence stage were subjected to the conventional electron microscopic and immunocytochemical studies. The results indicated that the chloroplasts of senescing French bean leaves were separated from the cytoplasm of the cell periphery and taken into the central vacuole and that the Rubisco LSU in the chloroplasts was degraded by vacuolar enzymes such as an SH-EP-related cysteine proteinase that developed in senescing leaves. The present results together with the results of previous biochemical studies using vacuolar lysates support the view that Rubisco is degraded through the association of chloroplasts with the central vacuole during the senescence of leaves that were detached and placed in darkness.
Asunto(s)
Fabaceae/enzimología , Hojas de la Planta/enzimología , Ribulosa-Bifosfato Carboxilasa/metabolismo , Vacuolas/enzimología , Envejecimiento/fisiología , Cloroplastos/metabolismo , Cloroplastos/ultraestructura , Cisteína Endopeptidasas/inmunología , Cisteína Endopeptidasas/metabolismo , Fabaceae/citología , Fabaceae/ultraestructura , Inmunohistoquímica , Microscopía Electrónica , Hojas de la Planta/citología , Hojas de la Planta/ultraestructura , Ribulosa-Bifosfato Carboxilasa/inmunología , Vacuolas/ultraestructuraRESUMEN
SH-EP is a vacuolar cysteine proteinase from germinated seeds of Vigna mungo. The enzyme has a C-terminal propeptide of 1 kDa that contains an endoplasmic reticulum (ER) retention signal, KDEL. The KDEL-tail has been suggested to function to store SH-EP as a transient zymogen in the lumen of the ER, and the C-terminal propeptide was thought to be removed within the ER or immediately after exit from the ER. In the present study, a protease that may be involved in the post-translational processing of the C-terminal propeptide of SH-EP was isolated from the microsomes of cotyledons of V. muno seedlings. cDNA sequence for the protease indicated that the enzyme is a member of the papain superfamily. Immunocytochemistry and subcellular fractionation of cotyledon cells suggested that the protease was localized in both the ER and protein storage vacuoles as enzymatically active mature form. In addition, protein fractionations of the cotyledonary microsome and Sf9 cells expressing the recombinant protease indicated that the enzyme associates with the microsomal membrane on the luminal side. The protease was named membrane-associated cysteine protease, MCP. The possibility that a papain-type enzyme, MCP, exists as mature enzyme in both ER and protein storage vacuoles will be discussed.
Asunto(s)
Cisteína Endopeptidasas/metabolismo , Gránulos Citoplasmáticos/enzimología , Retículo Endoplásmico/enzimología , Proteínas de la Membrana/metabolismo , Vacuolas/enzimología , Secuencia de Aminoácidos , Animales , Línea Celular , Centrifugación por Gradiente de Densidad , Clonación Molecular , Cisteína Endopeptidasas/química , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/aislamiento & purificación , Gránulos Citoplasmáticos/ultraestructura , Retículo Endoplásmico/química , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/ultraestructura , Fabaceae/citología , Fabaceae/enzimología , Aparato de Golgi/enzimología , Aparato de Golgi/ultraestructura , Inmunohistoquímica , Membranas Intracelulares/metabolismo , Membranas Intracelulares/ultraestructura , Proteínas de la Membrana/química , Proteínas de la Membrana/aislamiento & purificación , Microscopía Electrónica , Datos de Secuencia Molecular , Peso Molecular , Oligopéptidos , Papaína/metabolismo , Filogenia , Plantas Medicinales , Precursores de Proteínas/química , Precursores de Proteínas/metabolismo , Procesamiento Proteico-Postraduccional , Señales de Clasificación de Proteína , Proteínas Recombinantes/metabolismo , Alineación de Secuencia , Vacuolas/ultraestructuraRESUMEN
Aberrant methylation of CpG islands in promoter regions of tumor cells is one of the major mechanisms for silencing of tumor suppressor genes. We determined the frequency of aberrant promoter methylation of the p16, adenomatous polyposis coli (APC), H-cadherin (CDH13), glutathione S-transferase P1 (GSTP1), O6-methylguanine-DNA-methyltransferase (MGMT), retinoic acid receptor beta-2 (RAR beta), E-cadherin (CDH1), and RAS association domain family 1A (RASSF1A) genes in 198 tumors consisting of small cell lung cancers [SCLCs (n = 43)], non-small cell lung cancers [NSCLCs (n = 115)], and bronchial carcinoids (n = 40). The profile of methylated genes in the two neuroendocrine tumors (SCLC and carcinoids) were very different from that of NSCLC. However, whereas the overall pattern of aberrant methylation of carcinoids was similar to that of SCLC, carcinoids had lower frequencies of methylation for some of the genes tested. There were also significant differences in the methylation profiles between the two major types of NSCLC, adenocarcinoma and squamous cell carcinoma. We performed cluster analysis and found that SCLCs clustered with other SCLCs and carcinoids but not with NSCLCs, whereas the NSCLCs tended to cluster together. Within NSCLCs, adenocarcinomas and squamous cell carcinomas clustered with their respective histological types. Finally, we compared the methylation profiles of SCLC and NSCLC tumors and their respective cell lines (n = 44). In general, methylation frequencies were higher in tumor cell lines, but these differences were seldom significant. Thus, tumor cell lines appear to be suitable models to study aberrant DNA methylation. We conclude that SCLC, carcinoids, squamous cell carcinomas, and adenocarcinomas of the lung have unique profiles of aberrant methylation. Our findings should help us understand differences in the pathogenetic mechanisms of lung cancers.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Metilación de ADN , ADN de Neoplasias/genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Proteínas Supresoras de Tumor , Proteína de la Poliposis Adenomatosa del Colon/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Bronquios/genética , Cadherinas/genética , Tumor Carcinoide/genética , Carcinoma de Células Pequeñas/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Femenino , Genes Supresores de Tumor , Gutatión-S-Transferasa pi , Glutatión Transferasa/genética , Humanos , Isoenzimas/genética , Masculino , Persona de Mediana Edad , O(6)-Metilguanina-ADN Metiltransferasa/genética , Reacción en Cadena de la Polimerasa , Receptores de Ácido Retinoico/genéticaAsunto(s)
Brotes de Enfermedades , Desinfección/normas , Unidades de Cuidado Intensivo Neonatal , Resistencia a la Meticilina , Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus/genética , Dermatoglifia del ADN/métodos , ADN Bacteriano/química , Desinfección/métodos , Electroforesis en Gel de Campo Pulsado/métodos , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
Previous neuropathological studies have revealed that the corticolimbic system of schizophrenic patients expresses abnormal levels of various synaptic molecules, which are known to be influenced by the neuronal differentiation factors, neurotrophins. Therefore, we determined levels of neurotrophins and their receptors in the postmortem brains of schizophrenic patients and control subjects in relation to molecular impairments in schizophrenia. Among the neurotrophins examined, levels of brain-derived neurotrophic factor (BDNF) were elevated specifically in the anterior cingulate cortex and hippocampus of schizophrenic patients, but levels of nerve growth factors and neurotrophin-3 showed no change in any of the regions examined. In parallel, the expressions of TrkB receptor and calbindin-D, which are both influenced by BDNF, were reduced significantly in the hippocampus or the prefrontal cortex. However, neuroleptic treatment did not appear to mimic the neurotrophic change. Neither withdrawal of drug treatment in patients nor chronic administration of haloperidol to rats altered levels of BDNF. These findings suggest that neurotrophic abnormality is associated with the corticolimbic structures of schizophrenic patients and might provide the molecular substrate for pathological manifestations of the illness.