RESUMEN
OBJECTIVES: The purpose of this study was to identify the weak points in the knowledge and attitudes of first-year oral health care and nursing students towards oral health care and to identify the factors associated with their positive willingness to practise oral health care after becoming a health professional in order to develop oral healthcare curricula. MATERIALS AND METHODS: The subjects were 88 first-year dental students (DSs), 64 dental hygiene students (DHSs) and 119 nursing students (NSs) enrolled in schools in Japan, as of April 2017. A questionnaire was distributed to subjects in each school to assess their knowledge and attitudes towards oral health care. RESULTS: Less than half knew that oral health care was also provided in cancer hospitals, hospices, acute care hospitals, maternity wards and psychiatric wards. Only 46.2% knew that oral health care was effective in the prevention of aspiration pneumonia. The level of knowledge and attitudes in NSs regarding oral health care were likely to be lowest amongst the student groups. Only NSs' high interest towards oral health care was associated with their positive willingness to practise oral health care in the future although oral health students' high perceptions and interest regarding oral health care were associated with the willingness. CONCLUSION: This study showed oral healthcare and nursing students' weak points regarding their attitudes and knowledge of oral health care at early stages. Oral health academic staff and professionals should develop effective oral healthcare curricula for oral healthcare students and help nursing staff develop a collaborative nursing oral healthcare curriculum to motivate nursing students.
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Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Motivación , Salud Bucal/educación , Higiene Bucal/educación , Aprendizaje Basado en Problemas , Estudiantes de Odontología/psicología , Estudiantes del Área de la Salud/psicología , Estudiantes de Enfermería/psicología , Adulto , Femenino , Humanos , Masculino , Neumonía por Aspiración/prevención & control , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Objetivo: Identificar los factores de riesgo en la aparición de multidrogo resistencia en pacientes con tuberculosis en el Hospital Regional de Ica, durante los años 2006 al 2012. Materiales y métodos: La muestra estuvo constituida por 41 casos (tratados por tuberculosis multidrogo-resistente [TB-MDR]) y 82 controles (tratados por tuberculosis sensible [TB]), seleccionados mediante muestreo alea-torio sistemático. Resultados: Se halló tuberculosis pulmonar en 92,7% de los casos y 80,5% de los con-troles; extrapulmonar en 22,4% de los casos y 15,9% de los controles y del tipo mixto en 2,4% en igual porcentaje tanto en los casos como en los controles (p>0,05). En 32 casos (78,0%) y 16 controles (19,5%) tenían antecedente de tratamiento antituberculoso (Chi2 =39.36; p=0,000; OR=14.24; IC95%=5,809-37,480). En 9 casos (22,2%) y 1 control (1,2%) se registró contacto previo con paciente diagnosticado de TB-MDR. (Chi2=13,08; p=0,000; OR=22,2; IC95%=3,451-508,8). Conclusiones: La TB-MDR se presenta con mayor probabilidad cuando existe el antecedente de tratamiento antituberculoso y el contacto con un paciente que es portador de TB-MDR. (AU)
Objective: To identify risk factors in the emergence of multidrug resistance in tuberculosis patients in the Regional Hospital of Ica, during the years 2006 to 2012. Materials and Methods: The sample con-sisted of 41 cases (treated for multidrug-resistant tuberculosis [TB-MDR]) and 82 controls (treated for sensitive tuberculosis [TB]), selected by systematic random sampling. Results: Pulmonary tuberculosis was found in 92.7% of cases and 80.5% of controls; extrapulmonary in 22.4% of cases and 15.9% of controls and mixed type in 2.4% in the same proportion in both cases and controls (p> 0.05). In 32 cases (78.0%) and 16 controls (19.5%) had a history of TB treatment (Chi2 = 39.36; p = 0.000; OR = 14.24; 95% CI = 5.809 to 37.480). In 9 cases (22.2%) and control 1 (1.2%) prior contact with patients diagnosed with MDR-TB was recorded. (Chi2 = 13.08; p = 0.000; OR = 22.2; 95% CI = 3.451 to 508.8). Conclusions: MDR-TB occurs most likely when the history of TB treatment and contact with a patient who is a carrier of MDR-TB exists. (AU)
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Humanos , Masculino , Femenino , Tuberculosis Pulmonar , Factores de Riesgo , Tuberculosis Resistente a Múltiples Medicamentos , Estudios de Casos y ControlesRESUMEN
PURPOSE: To estimate the impact of surgical site infection (SSI) on postoperative resource consumption for colon and rectal open and laparoscopic surgeries after accounting for infection depth and patient characteristics, and to compare these estimates among institutions. METHODS: We collected administrative and SSI-related data from eight Japanese hospitals, and used generalized linear models to estimate excess postoperative length of stay (LOS) and charges attributable to SSI. Covariates included wound class, American Society of Anesthesiologists (ASA) score, operation time, emergency, colostomy, trauma, implant, and comorbidities. RESULTS: We examined 1,108 colon surgery (CS) and 477 rectal surgery (RS) patients. For open surgery, the postoperative LOS in non-SSI patients was 13.5 (CS) and 15.9 days (RS). Compared with non-SSI patients, the postoperative LOS increased by 4.5 (CS) and 2.8 days (RS) for superficial SSI, 6.8 (CS) and 8.5 days (RS) for deep SSI, and 7.8 and 9.5 days for space/organ SSI. For laparoscopic surgery, the postoperative LOS was 9.8 (CS) and 14.6 days (RS). SSI was significantly associated with increased postoperative LOS for superficial SSI [by 4.8 (CS) and 3.6 days (RS)], deep SSI [by 10.3 (CS) and 23.9 days (RS)], and space/organ SSI [by 8.9 days (RS)]. The postoperative LOS among hospitals was 3.8-10.4 days (CS) and 1.3-12.2 days (RS). Postoperative SSI-attributable charges ranged from $386 to $2,873, depending on organ, procedure, and infection depth. CONCLUSION: This study quantified the impact of SSIs on resource consumption and confirmed significant cost variations among hospitals. These variations could not be explained by patient characteristics or infection type.
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Costos de la Atención en Salud , Recursos en Salud/estadística & datos numéricos , Laparoscopía/efectos adversos , Tiempo de Internación/economía , Infección de la Herida Quirúrgica/economía , Colon/cirugía , Femenino , Humanos , Modelos Lineales , Masculino , Periodo Posoperatorio , Recto/cirugía , Índice de Severidad de la Enfermedad , Infección de la Herida Quirúrgica/etiologíaRESUMEN
Transgenerational mass marking of viviparous fish larvae in vivo was validated by intra-muscular injection of elemental strontium chloride (SrCl(2)) in gestating females and detection of the Sr in the otoliths of developing larvae. All otoliths of brown rockfish Sebastes auriculatus larvae produced from SrCl(2)-injected females showed enriched Sr:Ca ratios near the otolith edges, and the signatures did not appear to be affected by the anterior, centre and posterior positions of larvae within the ovary. Results from the present study indicate that transgenerational marking is a highly reliable technique for marking large numbers of extremely small viviparous fish larvae.
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Peces/crecimiento & desarrollo , Membrana Otolítica/crecimiento & desarrollo , Animales , Femenino , Larva/crecimiento & desarrollo , Estroncio/análisisRESUMEN
Extensive collections were made of the larvae of the temperate Japanese eel Anguilla japonica and the tropical giant mottled eel Anguilla marmorata in an overlapping area of the North Equatorial Current region of the western North Pacific Ocean. Collections of 189 A. marmorata and > 2500 A. japonica larvae during nine surveys from 1991 to 2007 showed that these two anguillid eels have similar spawning areas just west of the southern West Mariana Ridge. In July to August 2006 and August 2007, morphologically and genetically identified A. marmorata preleptocephali were mainly collected between 14.5-15 degrees N and 142-142.5 degrees E, where A. japonica preleptocephali were also caught in some of the same net tows. Fewer A. marmorata preleptocephali, however, were collected (n = 31) compared to those of A. japonica (n = c. 165), and fewer small larvae of A. marmorata were collected per tow than A. japonica (n = 1-10 and 1-294, respectively), suggesting relatively smaller spawning aggregations of A. marmorata. The distribution of preleptocephali and small larvae was wider in longitude in A. marmorata (131- 143 degrees E) than in A. japonica (137-143 degrees E), while the latitudinal range was almost the same (12-17 degrees N). Although spawning by these two species overlaps both spatially and temporally, the tropical eels of the North Pacific population of A. marmorata probably have a much longer spawning season with fewer spawners, at least in summer, and recruit to a much wider latitudinal range of growth habitats.
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Anguilla/fisiología , Reproducción , Animales , Larva/fisiología , Océano PacíficoRESUMEN
The influences of water temperature and feeding regime on otolith growth in Anguilla japonica glass eels and elvers were investigated using individuals reared at 5, 10, 15, 20, 25 and 30 degrees C and in fed or unfed conditions at salinity 32 after their otoliths were marked with alizarin complexone (ALC). To eliminate the difficulty of observing the edges of otoliths with optical (OM) or scanning electron (SEM) microscopes, three to 10 individuals were sampled from each tank at 10, 20 and 30 days during the experiment and reared for an additional 10 days at 25 degrees C after their otoliths were marked a second time. Otolith growth and the number of increments were measured using both OM and SEM. Most A. japonica commenced feeding after 10 days at 20-30 degrees C or after 20 days at 15 degrees C, but no feeding occurred at 5 and 10 degrees C. No otolith growth occurred at 5 and 10 degrees C except in two individuals with minimal increment deposition at 10 degrees C. Otolith growth was proportional to water temperature within 15-25 degrees C and not different between 25 and 30 degrees C. At 15, 25 and 30 degrees C, the mean otolith growth rate in fed conditions was higher than in unfed conditions. The number of increments per day was significantly different among water temperatures (0.00-0.01 day(-1) at 5 and 10 degrees C, 0.43-0.48 day(-1) at 15 degrees C and 0.94-1.07 day(-1) at 20-30 degrees C). These results indicated that otolith growth in A. japonica glass eels and elvers was affected by temperature and ceased at < or =10 degrees C under experimental conditions. Hence, future studies analysing the otoliths of wild-caught A. japonica glass eels and elvers need to carefully consider the water temperatures potentially experienced by the juveniles in the wild.
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Anguilla/fisiología , Frío , Conducta Alimentaria , Membrana Otolítica/crecimiento & desarrollo , Anguilla/crecimiento & desarrollo , Animales , Membrana Otolítica/ultraestructuraRESUMEN
Irinotecan (CPT-11) is a key drug for the treatment of various cancers. CPT-11 can be considered to be a prodrug, since it needs to be activated into the toxic drug SN-38 by the enzyme carboxylesterase. However, CPT-11 may induce severe diarrhea and bone marrow suppression as adverse effects, thus leading to treatment interruption. The tumor-specific activation of CPT-11 is a possible strategy to avoid the severe toxicities by reducing the serum concentration of CPT-11. In this study, we constructed human liver carboxylesterase-2 fused with anticarcinoembryonic antigen (CEA) scFv as a targeting molecule. The recombinant enzyme anchors onto the tumor cell surface CEA, and thus metabolize CPT-11 extracellularly. In addition a secreted tumor-targeted form of carboxylesterase should help prevent the leakage of the enzyme from the site of the tumor into the circulation. This fusion protein showed CPT-11 activation to SN-38 and specific binding to CEA-expressing cells. In combination with CPT-11, the recombinant carboxylesterase protein exerted antiproliferative effects on human cancer cells. This recombinant enzyme is, therefore, a promising new tool in enzyme prodrug therapy for the treatment of carcinoma with CPT-11.
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Antineoplásicos Fitogénicos/farmacología , Camptotecina/análogos & derivados , Carboxilesterasa/genética , Antígeno Carcinoembrionario/genética , Región Variable de Inmunoglobulina/genética , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/toxicidad , Camptotecina/farmacocinética , Camptotecina/farmacología , Camptotecina/toxicidad , Carboxilesterasa/antagonistas & inhibidores , Carboxilesterasa/metabolismo , Antígeno Carcinoembrionario/inmunología , Antígeno Carcinoembrionario/metabolismo , Relación Dosis-Respuesta Inmunológica , Marcación de Gen , Células HeLa , Humanos , Región Variable de Inmunoglobulina/fisiología , Irinotecán , Proteínas Recombinantes de Fusión/genéticaRESUMEN
BACKGROUND: The present study has been performed to evaluate the expression of MK-1 in schistosomiasis-associated squamous cell carcinoma of the urinary bladder and to correlate this new marker with the conventional histopathological parameters. PATIENTS AND METHODS: Paraffin sections of 5-microm thickness from 81 cases were prepared for hematoxylin and eosin staining and immunohistochemical analysis of MK-1 expression was carried out. RESULTS: Forty-six cases (56.8%) were positive for MK-1 protein expression. Significant correlations between MK-1 expression and tumor grade (p=0.004), schistosoma (p=0.031), DNA ploidy (p=0.001), and tumor recurrence (p<0.001) were observed. MK-1, sex, tumor grade, stage, schistosoma, DNA ploidy, and recurrence were evaluated in relation to outcome. Univariate and multivariate analysis of survival were performed. The overall 5-year survival was 51.85%. In univariate analysis, MK-1 expression, tumor grade, DNA ploidy, and recurrence had a significant impact on the survival of these patients. In a Cox proportional hazards model, recurrence maintained its significant impact on survival. CONCLUSIONS: These findings suggest that MK-1 is a prognostic marker for recurrence: 34 (87.2%) of 39 recurrent cases were positive for MK-1 expression. However, only recurrence was an independent prognostic factor in patients with schistosomiasis- associated squamous cell carcinoma of the bladder.
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Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/diagnóstico , Moléculas de Adhesión Celular/análisis , Neoplasias de la Vejiga Urinaria/diagnóstico , Adulto , Carcinoma de Células Escamosas/química , Molécula de Adhesión Celular Epitelial , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Neoplasias de la Vejiga Urinaria/químicaRESUMEN
A small lesion showing ground-glass opacity (GGO) by preoperative computed tomography (CT) is sometimes difficult to detect after lobectomy when it locates in the central part of the lobe. In order to facilitate to identify the lesion for marking pathological specimen, we developed a new method using CT. After surgery, the resected pulmonary lobe was expanded with airflow through the bronchial stump and the target lesion was examined with CT. The laser beam of the CT on the surface of the lung is used as a guiding line for cutting. Through the application of this method for 2 clinical cases, it was found to be possible to exactly identify the GGO lesion from the surface of the resected lung enabling to visualize a fresh surface of the lesion like a CT image with minimal destruction of the structure.
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Neoplasias Pulmonares/patología , Pulmón/diagnóstico por imagen , Pulmón/patología , Tomografía Computarizada por Rayos X , Anciano , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , NeumonectomíaRESUMEN
The purpose of this study is to investigate the expression of thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein, during re-epithelialization in wounded corneas of vitamin A-deficient mice. Epithelial defects were created in the corneas of normal and Vitamin A-deficient mice with a microgrinder. Wounded corneas were stained with fluorescein and photographed for evaluation of re-epithelialization. Histological examination and immunohistochemical analysis of TSP-1 expression were also performed on the specimens from wounded corneas. In vitamin A-deficient mice, re-epithelialization of the wounded corneal epithelium was significantly delayed compared with that in normal mice. TSP-1 was detectable neither in the unwounded corneal epithelium of normal mice nor in that of vitamin A-deficient mice. In normal mice, linear staining of TSP-1 was observed on the wounded corneal surface and stroma at 30 min and 8 h to 16 h, respectively, after abrasion, and this TSP-1 expression disappeared at 36 to 48 h, when re-epithelialization was completed. In contrast, no TSP-1 staining was observed in the wounded corneas of vitamin A-deficient mice, except for the endothelial cells, throughout the wound healing process. Histological examination revealed a progressive increase in polymorphonuclear neutrophil infiltration in the stroma of the corneas of vitamin A-deficient mice during the healing process. These findings suggest that vitamin A may modulate the expression of TSP-1 in the corneas to accelerate the re-epithelialization of wounded corneas.
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Epitelio Corneal/lesiones , Epitelio Corneal/metabolismo , Trombospondina 1/metabolismo , Deficiencia de Vitamina A/metabolismo , Cicatrización de Heridas/fisiología , Animales , Epitelio Corneal/patología , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Factores de Tiempo , Deficiencia de Vitamina A/patologíaRESUMEN
OBJECTIVE: N-(2-hydroxyethyl)-nicotinamide nitrate (nicorandil) is a unique anti-anginal agent, reported to act as both an ATP-sensitive K(+) channel opener (PCO) and a nitric oxide donor. It also has an anti-oxidant action. We examined the effects of nicorandil on streptozotocin (STZ)-induced islet beta-cell damage both in vivo and in vitro. DESIGN AND METHODS: STZ-induced diabetic Brown Norway rats (STZ-DM) were fed with nicorandil-containing chow from day 2 (STZ-DM-N48), 3 (STZ-DM-N72), and 4 (STZ-DM-N96) to day 30. Body weight, blood glucose, and plasma insulin were measured every week. For the in vitro assay, neonatal rat islet-rich cultures were performed and cells were treated with nicorandil from 1 h before to 2 h after exposure to STZ for 30 min. Insulin secretion from islet cells was assayed after an additional 24 h of culture. We also observed the effect of nicorandil on the generation of reactive oxygen species (ROS) from rat inslinoma cells (RINm5F). RESULTS: Body weight loss and blood glucose levels of STZ-DM-N48 rats were significantly lower than those of STZ-DM rats. Immunohistochemical staining of insulin showed preservation of insulin-secreting islet beta-cells in STZ-DM-N48 rats. Nicorandil also dose-dependently recovered the insulin release from neonatal rat islet cells treated with STZ in in vitro experiments. Nicorandil did not act as a PCO on neonatal rat islet beta-cells or RINm5F cells, and did not show an inhibitory effect on poly(ADP-ribose) polymerase-1. However, the drug inhibited the production of ROS stimulated by high glucose (22.0 mmol/l) in RINm5F cells. CONCLUSIONS: These results suggested that nicorandil improves diabetes and rat islet beta-cell damage induced by STZ in vivo and in vitro. It protects islet beta-cells, at least partly, via a radical scavenging effect.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Nicorandil/farmacología , Vasodilatadores/farmacología , Animales , Glucemia , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Depuradores de Radicales Libres/farmacología , Glucagón/metabolismo , Técnicas In Vitro , Insulina/sangre , Insulina/metabolismo , Secreción de Insulina , Masculino , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Poli(ADP-Ribosa) Polimerasas/metabolismo , Ratas , Ratas Endogámicas BN , Especies Reactivas de Oxígeno/metabolismo , Superóxidos/metabolismoRESUMEN
AIM: To report a new form of retinopathy that was observed in patients who had undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (AMI). METHODS: Serial ophthalmological examinations were conducted in 40 patients who underwent PCI. Thirty patients were diagnosed with AMI, and another 10 had stable angina pectoris. RESULTS: Cotton wool spots developed in 17 (57%) patients from the group with AMI undergoing PCI (n = 30) within 2 months. Of these, 41% (seven patients) also developed superficial haemorrhages. Retinopathy was most prominent 1-2 months after AMI and then tended to become quiescent afterwards, without treatment. CONCLUSION: We have identified a new form of retinopathy in patients with AMI that spontaneously subsides without treatment.
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Angioplastia Coronaria con Balón/efectos adversos , Infarto del Miocardio/complicaciones , Enfermedades de la Retina/etiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Angiografía con Fluoresceína , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/terapia , Remisión EspontáneaRESUMEN
To characterize antigenic sites in carcinoembryonic antigen (CEA) further and to investigate whether there are differences between colon tumor CEA and meconium CEA (NCA-2) that can be detected by anti-CEA monoclonal antibodies (MAb), 19 new anti-CEA MAb were analyzed with respect to specificity, epitope reactivity and affinity. Their reactivities were compared with 10 anti-CEA MAb with known CEA-domain binding specificity that have previously been classified into five nonoverlapping epitope groups, GOLD 1-5. Cross-inhibition assays with antigen-coated microtiter plates and immunoradiometric assays were performed in almost all combinations of MAbs, using conventionally purified CEA (domain structure: N-A1B1-A2B2-A3B3-C) from liver metastasis of colorectal carcinomas, recombinant CEA, meconium CEA (NCA-2), truncated forms of CEA and NCA (CEACAM6) as the antigens. The affinity of the MAbs for CEA was also determined. The new MAbs were generally of high affinity and suitable for immunoassays. Three new MAbs were assigned to GOLD epitope group 5 (N-domain binding), 3 MAbs to group 4 (A1B1 domain), 1 to group 3 (A3B3 domain), 3 to group 2 (A2B2 domain) and 3 to group 1 (also the A3B3 domain). Three MAbs formed a separate group related to group 4, they were classified as GOLD 4' (A1B1 domain binding). The remaining 3 MAbs appear to represent new subspecificities with some relationship to GOLD groups 1, 2 or 4, respectively. Five MAbs, all belonging to epitope group 1 and 3, reacted strongly with tumor CEA but only weakly or not at all with meconium CEA, demonstrating that the two products of the CEA gene differ from each other, probably due to different posttranslational modifications.
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Antígeno Carcinoembrionario/química , Antígeno Carcinoembrionario/inmunología , Animales , Anticuerpos Monoclonales/química , Afinidad de Anticuerpos , Educación , Mapeo Epitopo , Epítopos , Humanos , Cinética , Ratones , Unión Proteica , Estructura Terciaria de Proteína , Radioinmunoensayo , Proteínas Recombinantes/metabolismoRESUMEN
BACKGROUND: A possible relation between maternal-fetal microchimerism and autoimmune diseases with some similarities to chronic graft versus host disease (cGVHD) has been reported. OBJECTIVE: To investigate whether cells with male DNA exist in female patients with Sjögren's syndrome (SS) as SS has clinical features similar to those of cGVHD. METHODS: DNA was extracted from 27 samples of peripheral blood mononuclear cells (PBMC), 42 biopsy samples of labial salivary glands (LSG), and nine samples of bronchoalveolar lavage fluid (BALF) cells from 56 female patients with SS. The presence of male DNA was determined by nested polymerase chain reaction (PCR) and by fluorescence in situ hybridisation (FISH). RESULTS: Among 56 female patients with SS, 42 patients had at least one male child. Among those 42 patients, none of the 22 PBMC but 10/28 (36%) LSG samples tested positive by PCR for the Y chromosome-specific sequence (p=0.0013). The Y chromosome-specific sequence was not detected in the samples of LSG in 10 patients without SS. In the BALF samples 2/9 (22%) patients with SS tested positive by PCR. Cells containing the Y chromosome were shown to exist in all the LSG specimens from three female patients with SS by FISH. CONCLUSIONS: Maternal-fetal microchimerism was shown for the first time to exist in the salivary glands and lungs of female patients with SS in this study. The presence of non-host cells in the inflammatory lesions but not in the peripheral blood suggests a possible role for maternal-fetal microchimerism in the pathogenesis of SS.
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Quimera , Cromosomas Humanos Y , Intercambio Materno-Fetal , Síndrome de Sjögren/patología , Adolescente , Adulto , Anciano , Secuencia de Bases , Biopsia/métodos , Líquido del Lavado Bronquioalveolar/citología , Niño , ADN/análisis , Femenino , Humanos , Hibridación Fluorescente in Situ , Leucocitos Mononucleares , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Embarazo , Glándulas Salivales/inmunología , Síndrome de Sjögren/genéticaRESUMEN
AIMS/HYPOTHESIS: Early stage leukocyte entrapment in the retinal microcirculation (retinal leukostasis) is considered to be one of the important pathogenetic events in diabetic retinopathy. Gliclazide, a sulphonylurea, was reported to reduce leukocyte adhesion to endothelial cells in hyperglycaemia in vitro, thus suggesting possible selective efficacy of this sulphonylurea in preventing leukostasis in diabetic patients. This study evaluated the effectiveness and selectivity of gliclazide treatment on retinal leukostasis of diabetic rats in vivo. METHODS: Streptozotocin (STZ) (65 mg/kg)-induced diabetic rats were divided into three groups (n = 8 each): an untreated diabetic group, a gliclazide-treated diabetic group, and a glibenclamide-treated diabetic group. Gliclazide or glibenclamide was administered orally during a 3-week period. Non-diabetic rats were used as a control (n = 8). Retinal leukostasis was quantitatively evaluated in vivo by acridine orange leukocyte fluorography using a scanning laser ophthalmoscope. RESULTS: The number of leukocytes trapped in the area around the optic disc in the untreated diabetic group (36.9 +/- 5.1 cells) increased significantly compared with the non-diabetic control group (21.9 +/- 2.9 cells; p = 0.0007). The number of leukocytes trapped in the gliclazide-treated diabetic group (23.5 +/- 4.0 cells) decreased significantly compared with untreated diabetic group ( p = 0.0008). In contrast, no reduction of retinal leukostasis was found in the glibenclamide-treated diabetic group (37.8 +/- 5.8 cells; p = 0.7923). CONCLUSION/INTERPRETATION: This suggests that gliclazide could directly improve abnormalities in the retinal microcirculation independent of blood glucose control and possibly have selective therapeutic benefits in preventing early, critical events in diabetic retinopathy compared with other sulphonylurea drugs.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Retinopatía Diabética/prevención & control , Gliclazida/uso terapéutico , Hipoglucemiantes/uso terapéutico , Leucostasis/prevención & control , Animales , Adhesión Celular , Leucocitos/efectos de los fármacos , Leucocitos/fisiología , Masculino , Ratas , Ratas Endogámicas BNRESUMEN
A pronase resistant 85-kd glycoprotein in the Concanavalin A-binding fraction (CABF) of biliary glycoproteins has been reported to act as a promotor of cholesterol crystallization. De Bruijn et al. (Gastroenterology 1996;110:1936-1944) found this protein in a low-density protein-lipid complex (LDP) with potent cholesterol crystallization promoting activity. This study identifies and characterizes this protein. An LDP was prepared from CABF by discontinuous gradient ultracentrifugation. Proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), blotting and immunochemical staining with anti-carcinoembryonic antigen, CEA-related adhesion molecule 1 (CEACAM1) cross-reacting antibodies. Biliary concentrations of CEA cross-reacting proteins were determined in patients with and without gallstones. Two isoforms of CEACAM1 (85- and 115-kd bands), CEA and 2 CEA cross-reacting protein bands of 40 and 50 kd were found in human bile. All bands were also present in CABF, but only a subfraction of the 85-kd band found in the LDP was resistant to digestion with pronase. CEACAM1-85 exhibited potent cholesterol crystallization promoting activity in vitro and accounted for most of the activity in CABF. Total CEA cross-reacting protein concentrations were the same in gallbladder biles from patients with cholesterol and pigment gallstones but only half of those in biles from nongallstone subjects. In conclusion, we have identified the protein component of the cholesterol crystallization promoting LDP to be CEACAM1-85.
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Adenosina Trifosfatasas/metabolismo , Bilis/metabolismo , Moléculas de Adhesión Celular/metabolismo , Colesterol/fisiología , Lípidos/fisiología , Pronasa/fisiología , Proteínas/fisiología , Adenosina Trifosfatasas/química , Adenosina Trifosfatasas/aislamiento & purificación , Adenosina Trifosfatasas/fisiología , Antígenos CD , Moléculas de Adhesión Celular/química , Moléculas de Adhesión Celular/aislamiento & purificación , Moléculas de Adhesión Celular/fisiología , Colelitiasis/metabolismo , Cristalización , Resistencia a Medicamentos , Vesícula Biliar/metabolismo , Glicoproteínas/metabolismo , Humanos , Peso Molecular , Valores de ReferenciaRESUMEN
CEACAM6 (CD66c) and CEACAM8 (CD66b) are cell-adhesion proteins on neutrophils that belong to the human carcinoembryonic antigen (CEA) family. CEACAM6 reveals homophilic adhesion and heterophilic adhesion to other CEACAM family antigens including CEACAM8, CEACAM1, and CEA, whereas CEACAM8 exhibits only heterophilic adhesion to CEACAM6. Here, we investigated and compared structural requirements for the homophilic adhesion of CEACAM6 and heterophilic adhesion between CEACAM6 and CEACAM8 at the amino acid level by using CHO transfectants expressing their mutant and chimeric proteins. The NH(2)-terminal domain (N-domain) of CEACAM6 expressed on a CHO cell was suggested to bind the N-domain of CEACAM6 or CEACAM8 on the opposing cell. By homologue-scanning mutagenesis, we found that the locations of the sequences critical for the adhesion of CEACAM6 to itself and to CEACAM8 are overlapped and that they are highly similar but not identical to the locations of the residues previously shown to be essential for the binding of CEACAM antigens to Opa proteins of pathogenic NEISSERIAE: Our findings imply that subtle differences in the N-domain sequences determine the specificity of the CEACAM antigens on neutrophils for interaction with the same or different CEACAM antigens and the bacterial proteins.
Asunto(s)
Antígenos de Neoplasias , Moléculas de Adhesión Celular , Adhesión Celular , Glicoproteínas de Membrana/fisiología , Neutrófilos/inmunología , Secuencia de Aminoácidos , Animales , Antígenos CD , Células CHO , Cricetinae , Proteínas Ligadas a GPI , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/genética , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Mutación , Estructura Terciaria de Proteína , Relación Estructura-Actividad , TransfecciónRESUMEN
Carcinoembryonic cell adhesion molecule 1 (CEACAM1) is a human membrane glycoprotein belonging to the carcinoembryonic antigen (CEA) family and to the immunoglobulin superfamily. It is expressed in apical membranes of many epithelial cells in gastrointestinal and urogenital tract and also in granulocytes and lymphocytes, and its biological effect in human tissues has recently been discussed in literature. The purpose of this study was to isolate CEACAM1 glycoprotein from bile and characterize its purity and recovery which has not been described before. Affinity chromatography of CEACAM1 on hydrazide-activated cellulose with immobilized monoclonal anti-CEA F34-187 antibody is described. The immunoglobulin carbohydrate moiety was oxidized by periodate and then bound to hydrazide-activated matrix. Crude protein fraction from bile was applied on the affinity column and after extensive washing of non-bound proteins CEACAM1 was eluted with 6 M guanidine-HCl. A single immunopositive 85 kDa band was detected on Western blots with anti-CEA antibody after SDS-PAGE. We found out that CEACAM1 was not stainable with any common method of protein staining and the only non-specific method which could detect the 85 kDa band was a lectin staining.