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BACKGROUND: The histology of the cardiac mucosa at the esophagogastric junction (EGJ) at birth is still a controversy. We conducted a histopathological study of the EGJ to clarify the morphology, and to determine the presence or absence of cardiac mucosa at birth. SUBJECTS: We examined 43 Japanese neonates and infants that are born prematurely or at full term. Death had occurred between 1 and 231 days after birth. RESULTS: Cardiac mucosa without parietal cells showing positivity for anti-proton pump antibody, adjacent to the most distal squamous epithelium, was observed in 32 (74%) of the 43cases. Such mucosa was evident in neonates that were full-term and had died within 14 days after birth. On the other hand, cardiac mucosa with parietal cells adjacent to squamous epithelium was noted in 10 cases (23%); the remaining one (2%) had columnar-lined esophagus. Squamous and columnar islands were observed in a single histological section from the EGJ in 22 (51%) of the 43 cases. Parietal cells were sparsely or densely present in the gastric antral mucosa. CONCLUSIONS: On the basis of these histological findings, we consider that cardiac mucosa exists in neonates and infants and can be defined as such, irrespective of the presence or absence of parietal cells (so-called oxyntocardiac mucosa). Neonates born prematurely or at full-term have cardiac mucosa in the EGJ just after birth, as is the case for Caucasian neonates.
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Esófago de Barrett , Carcinoma de Células Escamosas , Recién Nacido , Humanos , Membrana Mucosa/patología , Unión Esofagogástrica/patología , Esófago de Barrett/patología , Epitelio/patología , Carcinoma de Células Escamosas/patología , Mucosa Gástrica/patologíaRESUMEN
BACKGROUND: We have reported that precancerous conditions and lesions invariably have shorter telomeres and associated chromosomal instability relative to normal tissue. METHODS: Using the Q-FISH method and our original software, Tissue Telo, we estimated telomere lengths in cardiac- and intestinal-type mucosae in 48 cases of Barrett's esophagus (short-segment (SS) n = 18; long-segment (LS) n = 30). RESULTS: There were no significant differences in telomere length between the cardiac and intestinal types in any of the 48 cases, suggesting that the presence or absence of goblet cells in the columnar segments is unrelated to telomere-dependent chromosomal instability in Barrett's esophagus. In LS Barrett's esophagus, telomeres were shorter in cardiac-type than in intestinal-type mucosa, suggesting that the former may play a more important role than the latter as a precancerous lesion in LS. Telomeres in cardiac-type mucosa were longer in SS than in LS, supporting the possibility that cardiac-type LS may pose a higher risk as a precancerous lesion than cardiac-type SS. CONCLUSIONS: Although it has been considered that Barrett's carcinoma arises only from intestinal-type mucosa, our present findings support previous histogenetic studies suggesting that cardiac-type mucosa is more important as a precancerous condition in Barrett's esophagus than anticipated.
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Esófago de Barrett , Lesiones Precancerosas , Esófago de Barrett/genética , Esófago de Barrett/patología , Humanos , Intestinos/patología , Membrana Mucosa/patología , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Telómero/genética , Telómero/patologíaRESUMEN
OBJECTIVES: Periodontal bacteria that have been studied show a strong connection to various vascular diseases. Among the many kinds of periodontal bacteria, Porphyromonas gingivalis (Pg) is well examined in the general aspects and in a rat model. However, whether other periodontal bacteria work or react differently is not studied well. MATERIAL AND METHODS: We chose Aggregatibacter actinomycetemcomitans (Aa) and Prevotella intermedia (Pi) as different types of periodontal bacteria. Low-density and high-density bacterial solutions were injected in the small artery of rats' groins using our rat model. Eighteen limbs of 9 SD male rats (500-650 g) were used. After 7 days, 14-18 days, and 28 days, the rats were sacrificed. A pathological and an immuno-histochemical study was conducted and reported on the low-density group with 12 limbs because the Pi group lacked a high-density study. Immuno-histochemical staining of live Pg was performed on three limbs of three rats at 1 h, 3 h, and 1 week after injection. RESULTS: The appearances from the acute, at 7 days, to chronic phases, at 28 days, were observed. The differences of the species were certainly observed in the internal elastic lamina (IEL), and immuno-histochemical reactions. The inflammatory reactions, such as cellular distribution or intra-thrombus materials, were similar in all. One week later, we could not see any living bacteria in the specimen or immunological observation. CONCLUSIONS: The three species were essentially the same, except for Aa's stronger disruption of IEL, and more CD3 (Pan T cell) in Pi and more CD79a (Pan B cell) in Pg. We propose a new concept of a possible mechanism of vascular diseases, in which the work of LPS (lipopolysaccharides) and a toll-like receptor (TLR) is emphasized.
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Aggregatibacter actinomycetemcomitans , Trombosis , Animales , Arterias , Humanos , Masculino , Porphyromonas gingivalis , Prevotella intermedia , RatasRESUMEN
This paper details the first breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) case detected in Japan. The patient, a 67-year-old Japanese woman, was diagnosed with left unilateral breast cancer 17 years ago. Induration and redness presented in the left breast, which had undergone immediate breast reconstructive surgery using a tissue expander, later replaced by a silicone breast implant (SBI). Breast ultrasound showed fluid collection around the SBI. Surgery was performed to remove the left breast implant and the fragmented capsule surrounding the implant. Postoperative pathological findings did not indicate malignancy. Nine months later, a contralateral axillary lymphadenopathy was observed, and an excisional biopsy of the axillary lymph node was performed. The patient was diagnosed with BIA-ALCL and successfully underwent adjuvant CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy.
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Implantes de Mama/efectos adversos , Neoplasias de la Mama/cirugía , Linfoma Anaplásico de Células Grandes/diagnóstico , Mamoplastia/efectos adversos , Neoplasias de la Mama/patología , Femenino , Humanos , Linfoma Anaplásico de Células Grandes/etiología , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: Progressive telomere shortening with age or chronic inflammation may lead to genomic instability that characterizes the early stage of carcinogenesis. Certain risk factors, such as drinking alcoholic beverages or smoking, predispose the oral mucosa to squamous cell carcinoma. The ADH1B and ALDH2 genotypes can influence the risk of cancer due to alcohol drinking. In the present study, we analyzed chromosomal instability due to telomere shortening in the oral mucosa in relation to cancer risk factors. DESIGN: Using our quantitative fluorescence in situ hybridization (Q-FISH) technique, we estimated telomere lengths (TL) in the background mucosa from 23 cases of mucosal carcinoma, 12 cases of oral epithelial dysplasia, and 21 non-neoplasia cases. ALDH2 and ADH1B genotypes were determined using DNA extracted from paraffin sections. We analyzed TL in relation to alcohol drinking, smoking, and cancer multiplicity. RESULTS: Telomeres in the backgrounds of dysplasia and mucosal carcinoma were significantly shorter than in controls. In comparison with adult controls, telomeres were significantly (P = .038) shorter in the ADH1B less-active type (ADH1B*1/*1), but not (P = .841) in the ALDH2 inactive type (ALDH2*1/*2 or *2/*2). Cancer multiplicity and smoking had no significant relationship with TL. CONCLUSION: Telomeres in the oral epithelium are shorter in cases of oral dysplasia or mucosal carcinoma than in non-neoplasia. Unlike the esophageal epithelium of alcoholics, they are also shorter in individuals with the less-active rather than the active ADH1B gene. Telomeres in the oral epithelium may be directly affected by alcohol drinking.
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Alcohol Deshidrogenasa/genética , Aldehído Deshidrogenasa Mitocondrial/genética , Acortamiento del Telómero , Adulto , Consumo de Bebidas Alcohólicas , Genotipo , Humanos , Hibridación Fluorescente in Situ , Polimorfismo GenéticoRESUMEN
Objectives: Our study investigated the pathological outcome of experimental thrombi that incorporate oral bacteria. Material and methods: A small artery and vein in the rats' groins were injected with a solution containing periodontal bacteria Porphyromonas gingivalis and followed up for 28 days. In all, 18 limbs of nine male rats (500-650 g) were used for the arterial study, and eight limbs of four rats were used for the veins. Two densities of the bacterial solution and two arterial thicknesses sizes were used in the arterial study. Both proximal and distal arteries and veins were ligated loosely using a monofilament nylon suture before bacterial suspensions or control solutions were injected into the ligated vessels. Results: After 7, 14-18, and 28 days, the rats were sacrificed. Pathology and immunohistochemistry were performed. All specimens exhibited thrombus formation and an acute inflammation reaction with granulocytes at 7 days and then settled down to chronic fibrous change with plasma cells or macrophages at 28 days in the arterial thrombus. CD3 (Pan T-cells), CD79a (Pan B cells in the rats), and IgG were observed in the process of the healing of the arterial thrombus. Venous changes showed relatively clear recanalization that appeared at 7 days, which is slightly different from the artery. Granulocytes were present from 7 to 28 days. Conclusions: Periodontal bacteria act as an inflammatory core in the vessels, but not as an infectious agent, in our experiments, because of their low ability to invade tissues.
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Arterias/inmunología , Arterias/patología , Infecciones por Bacteroidaceae/complicaciones , Trombosis/inmunología , Trombosis/patología , Venas/inmunología , Venas/patología , Animales , Arterias/microbiología , Infecciones por Bacteroidaceae/microbiología , Masculino , Porphyromonas gingivalis/aislamiento & purificación , Ratas , Trombosis/microbiología , Venas/microbiologíaRESUMEN
Background: Prostaglandin E2 (PGE2) is metabolized to prostaglandin E-major urinary metabolite (PGE-MUM). Enhanced cyclooxygenase-2 (COX-2) expression demonstrated in lung adenocarcinoma indicates increased PGE-MUM levels in patients with lung adenocarcinoma. Objectives: We aimed to elucidate the clinical usefulness of measuring PGE-MUM as an indicator of tumor burden in patients with lung adenocarcinoma. Methods: PGE-MUM was measured by a radioimmunoassay in control healthy volunteers (n = 124) and patients with lung adenocarcinoma (n = 54). Associations between PGE-MUM levels and clinical characteristics of the patients (including lung cancer stage and TNM factors (T: Tumor, N: Node, M: Metastasis) were examined. Results: PGE-MUM levels were significantly elevated in patients with lung adenocarcinoma. A PGE-MUM level of 14.9 µg/gâCr showed 70.4% sensitivity and 67.7% specificity for the diagnosis of lung adenocarcinoma. PGE-MUM levels tended to be positively correlated with cancer progression as determined by the TNM staging system. Advanced stage (stage III, stage IV, and recurrence) was significantly associated with high PGE-MUM levels by logistic regression analysis. No apparent correlation was demonstrated between PGE-MUM and carcinoma embryonic antigen (CEA) levels. Conclusions: PGE-MUM can be a promising biomarker reflecting the systemic tumor burden of lung adenocarcinoma.
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BACKGROUND: Early definitive diagnosis of necrotizing enterocolitis (NEC) based on Bell's staging criteria is difficult because there are few observable changes on abdominal imaging and blood chemistry tests at the onset of the disease. PURPOSE: To investigate whether prostaglandin E-2 major urinary metabolite (PGE-MUM) can be a useful surrogate marker reflecting the disease state and severity of NEC in infants. METHODS: Infants were enrolled in this study between January 2014 and December 2016. NEC diagnosis was based on Bell's staging criteria > Stage II or necrotic bowel observed at surgery. After diagnosis, PGE-MUM level was measured and compared with that of the other disease and healthy infant groups. RESULTS: Median PGE-MUM value was highest in the NEC group (576 [65-3672] µg/gâ¢Cre/BSAâ¯×â¯1000), followed by the other disease group (94 [57-296] µg/gâ¢Cre/BSAâ¯×â¯1000) and the healthy infant group (19 [10-44] µg/gâ¢Cre/BSAâ¯×â¯1000) (sensitivity: 92.3%, specificity: 81.5%, accuracy: 85.0%; pâ¯<â¯0.01). PGE-MUM level correlated with improved status of NEC, length of necrotic intestine, and Bell's staging criteria. CONCLUSIONS: PGE-MUM level may be a useful surrogate biomarker reflecting the disease state of NEC. The method of urine sample collection is also advantageous, being noninvasive for infants. This is the first study reporting PGE-MUM level in NEC. TYPE OF STUDY: Study of diagnostic test. LEVEL OF EVIDENCE: LEVEL II.
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Enterocolitis Necrotizante/orina , Prostaglandinas E/orina , Biomarcadores/orina , Enterocolitis Necrotizante/diagnóstico , Enterocolitis Necrotizante/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios RetrospectivosRESUMEN
In order to investigate the population dynamics of telomere status, we measured the telomere lengths of glandular cells in the adenohypophysis (AH) and pituicytes, a type of glial cell, in the neurohypophysis (NH) of 128 autopsied humans (65 men, 63 women, 0 and 102 years) using our original quantitative fluorescence in situ hybridization (Q-FISH) method. Telomeres in the AH shortened with aging in both men and women, but those of pituicytes did not. Pituicyte telomeres were significantly longer in women than in men. The data suggest that telomeres shorten with age in the AH, whereas those in pituicytes maintain a constant length throughout life. Comparison of pituicyte telomere lengths among 5 generations, <18, 18-69, 70-79, 80-89, and >90â¯years, revealed a tendency for telomeres to be longer in individuals in their 80â¯s and 90â¯s than in those in their 70â¯s. These findings lend support to the widely held notion that humans with longer telomeres may have a longer life span, and shed light on the biology of pituitary gland in terms of telomere length dynamics, as well contributing to the development of bioengineered hormone-producing cell replacement strategies and regenerative therapies.
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Envejecimiento/metabolismo , Hibridación Fluorescente in Situ , Hipófisis/metabolismo , Homeostasis del Telómero/fisiología , Telómero/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Autopsia , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana EdadRESUMEN
AIM: The telomere is a structure present at the ends of chromosomes, and is known to shorten with aging and successive rounds of cell division. However, very little is known about telomere attrition in post-mitotic cells, such as neurons. METHODS: Using our originally developed quantitative fluorescence in situ hybridization method, we analyzed age-dependent alterations of telomere length in three types of cells in the human cerebrum: neurons and glial cells in both the gray and white matter. RESULTS: In adults, telomeres were significantly longer in neurons than in glial cells, whereas in infants, telomere lengths did not differ among the three cell types. No aging-related telomere attrition was evident in neurons. However, the telomeres of glial cells were shorter in older individuals than in younger individuals, and attrition was more rapid in the white matter than in the gray matter. CONCLUSIONS: The present results suggest that the telomeres of neurons remain stable throughout life, whereas telomeres in white matter glial cells become significantly shorter with age. Examination of adults showed no significant correlation between telomere length and age in the three cell types. Although the present study was cross-sectional, the results suggest that telomere shortening before adolescence contributes to the significant decrease of telomere length in white matter glial cells. The present findings in normal cerebral tissues will be informative for future studies of telomere stability in the diseased brain. Geriatr Gerontol Int 2018; 18: 1507-1512.
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Envejecimiento/genética , Longevidad/genética , Neuroglía/patología , Neuronas/patología , Telómero/patología , Factores de Edad , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Células Cultivadas , Preescolar , Estudios Transversales , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , Masculino , Factores de Riesgo , Sensibilidad y Especificidad , Técnicas de Cultivo de TejidosRESUMEN
BACKGROUND: The diversity and composition of the gut microbiota may affect breast cancer risk by modulating systemic levels of oestrogens and inflammation. The current investigation tested this hypothesis in postmenopausal women by identifying breast cancer associations with an inflammation marker, oestrogen levels, and faecal microbes that were or were not coated with mucosal immunoglobulin A (IgA). METHODS: In this population-based study, we compared 48 postmenopausal breast cancer cases (75% stage 0-1, 88% oestrogen-receptor positive) to 48 contemporaneous, postmenopausal, normal-mammogram, age-matched controls. Microbiota metrics employed 16S rRNA gene amplicon sequencing from IgA-coated and -noncoated faecal microbes. High-performance liquid chromatography/mass spectrometry (HPLC/MS) and radioimmunoassay were used to quantify urine prostaglandin E metabolite (PGE-M), a possible marker of inflammation; urine oestrogens and oestrogen metabolites were quantified by HPLC/MS-MS. RESULTS: Women with pre-treatment breast cancer had non-significantly elevated oestrogen levels; controls' (but not cases') oestrogens were directly correlated with their IgA-negative microbiota alpha diversity (P=0.012). Prostaglandin E metabolite levels were not associated with case status, oestrogen levels, or alpha diversity. Adjusted for oestrogens and other variables, cases had significantly reduced alpha diversity and altered composition of both their IgA-positive and IgA-negative faecal microbiota. Cases' faecal microbial IgA-positive imputed Immune System Diseases metabolic pathway genes were increased; also, cases' IgA-positive and IgA-negative imputed Genetic Information Processing pathway genes were decreased (P⩽0.01). CONCLUSIONS: Compared to controls, breast cancer cases had significant oestrogen-independent associations with the IgA-positive and IgA-negative gut microbiota. These suggest that the gut microbiota may influence breast cancer risk by altered metabolism, oestrogen recycling, and immune pressure.
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Bacterias/clasificación , Neoplasias de la Mama/microbiología , Estrógenos/orina , Inmunoglobulina A/farmacología , Posmenopausia/metabolismo , Análisis de Secuencia de ADN/métodos , Anciano , Bacterias/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/orina , Cromatografía Líquida de Alta Presión , ADN Bacteriano/genética , ADN Ribosómico/genética , Heces/microbiología , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Espectrometría de Masas , Persona de Mediana Edad , Posmenopausia/inmunología , Posmenopausia/orina , Prostaglandinas E Sintéticas/orina , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: The 99th percentile of cardiac troponin I level in the general population is accepted as the cut-off for the diagnosis of acute myocardial infarction (AMI). However, it is not clear whether the cut-offs derived in racially and geographically different populations are applicable in Japan. METHODS: Troponin I was determined using the Abbott ARCHITECT STAT high-sensitive troponin I immunoassay in 698 apparently healthy individuals who visited the Japanese Red Cross Medical Center for a health checkup. RESULTS: The 99th percentile of the hsTnI in the overall population was 22.5 (95% confidence interval (CI), 16.8-36.6) pg/mL, 17.7 (95% CI 12.0-22.8) pg/mL for females and 30.6 (95% CI 17.1-53.4) pg/mL for males. The median of the hsTnI in the overall population was 3.2 (95% CI, 3.0-3.3) pg/mL, 2.6 (95% CI 2.4-2.8) pg/mL for females and 4.0 (95% CI 3.8-4.3) pg/mL for males. The age and gender had a significant influence on these values. The troponin I level also showed significant associations with the body mass index (BMI), the gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), estimated glomerular filtration rate (eGFR), and cardiac abnormalities by electrocardiography (ECG) but not with the high-sensitive C-reactive protein (hsCRP) level. CONCLUSIONS: The 99th percentiles of the troponin I measured in the general population in Japan were comparable as the ones derived in the US, Germany, and Singapore. The troponin I level was dependent on the gender, age, BMI, and cardiac abnormalities found by ECG but not by the hsCRP level.
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Troponina I/sangre , Adulto , Femenino , Humanos , Inmunoensayo/normas , Japón/epidemiología , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Valores de ReferenciaRESUMEN
Epithelial-mesenchymal transition (EMT) is a significant process in the invasion and metastasis of cancers including oral squamous cell carcinoma (OSCC), and the cadherin switch has been identified as one of the hallmarks of EMT. The aim of the present study was to evaluate the significance of the cadherin switch in the prognosis of OSCC and generate a model for prognostic predictions. Seventy-six biopsy and/or initial surgical specimens from OSCC patients were immunohistochemically analyzed for the expression of E-cadherin and N-cadherin in either overall OSCC cells in tumor nests or in OSCC cells at the invasive front. Among 76 OSCC cases, overall OSCC cells in tumor nests were negative for the expression of E-cadherin in 10 cases and positive for that of N-cadherin in 53 cases. Among 10 cases negative for the expression of E-cadherin, 4 cases were positive for that of N-cadherin. In OSCC cells at the invasive front, the expression of E-cadherin was negative in 62 cases, while that of N-cadherin was positive in 39 cases. Among 62 cases negative for the expression of E-cadherin, 33 cases were positive for that of N-cadherin. A logistic regression analysis showed that a model using the evaluation of N-cadherin expression in overall OSCC cells in tumor nests with a cut-off point of 70 years old was the best fit model. These results suggest that N-cadherin has significant value in prognostic predictions for OSCC patients.
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Postprandial glucose level is an independent risk factor for cardiovascular disease that exerts effects greater than glucose levels at fasting state, whereas increase in serum triglyceride level, under both fasting and postprandial conditions, contributes to the development of arteriosclerosis. Insulin resistance is a prevailing cause of abnormalities in postabsorptive excursion of blood glucose and postprandial lipid profile. Excess fat deposition renders a vicious cycle of hyperglycemia and hypertriglyceridemia in the postprandial state, and both of which are contributors to atherosclerotic change of vessels especially in patients with type 2 diabetes mellitus. Several therapeutic approaches for ameliorating each of these abnormalities have been attempted, including various antidiabetic agents or new compounds targeting lipid metabolism.
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A novel system auxiliary to the Union for International Cancer Control classification may allow the prognosis of patients with malignant tumors at similar stages to be predicted, as currently this is challenging. The present study generated a novel system to predict populations at low risk among patients with stage III/IV oral squamous cell carcinoma (OSCC). A total of 41 patients who were diagnosed at stages III/IV OSCC and underwent surgical tumor resection were analyzed. Band-like or follicular lymphocyte infiltration, intraepithelial micro-abscess formation and natural killer (NK) cell infiltration were histopathologically evaluated. Cox's proportional hazards regression model was used to identify prognostic factors, and a set of factors was selected from a combination of those prognostic factors to create a logic covariate model. A logic regression analysis for 41 patients with OSCC revealed that the presence of intraepithelial micro-abscesses and a lower density of NK cells were significantly associated with a favorable prognosis among patients with stage III/IV OSCC. These results suggested that the host innate immune responses, including neutrophil and NK cell infiltrations, are useful for prognostic prediction in patients with advanced malignant tumors.
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Autoanticuerpos/inmunología , Desmogleína 3/inmunología , Inmunoglobulina G/inmunología , Pólipos Nasales/inmunología , Rinitis/inmunología , Sinusitis/inmunología , Adulto , Autoanticuerpos/sangre , Enfermedad Crónica , Humanos , Masculino , Pólipos Nasales/sangre , Rinitis/sangre , Sinusitis/sangreRESUMEN
Past, present, and future research into hepatic stellate cells (HSCs, also called vitamin A-storing cells, lipocytes, interstitial cells, fat-storing cells, or Ito cells) are summarized and discussed in this review. Kupffer discovered black-stained cells in the liver using the gold chloride method and named them stellate cells (Sternzellen in German) in 1876. Wake rediscovered the cells in 1971 using the same gold chloride method and various modern histological techniques including electron microscopy. Between their discovery and rediscovery, HSCs disappeared from the research history. Their identification, the establishment of cell isolation and culture methods, and the development of cellular and molecular biological techniques promoted HSC research after their rediscovery. In mammals, HSCs exist in the space between liver parenchymal cells (PCs) or hepatocytes and liver sinusoidal endothelial cells (LSECs) of the hepatic lobule, and store 50-80% of all vitamin A in the body as retinyl ester in lipid droplets in the cytoplasm. SCs also exist in extrahepatic organs such as pancreas, lung, and kidney. Hepatic (HSCs) and extrahepatic stellate cells (EHSCs) form the stellate cell (SC) system or SC family; the main storage site of vitamin A in the body is HSCs in the liver. In pathological conditions such as liver fibrosis, HSCs lose vitamin A, and synthesize a large amount of extracellular matrix (ECM) components including collagen, proteoglycan, glycosaminoglycan, and adhesive glycoproteins. The morphology of these cells also changes from the star-shaped HSCs to that of fibroblasts or myofibroblasts.
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Células Estrelladas Hepáticas , Hígado/citología , Vitamina A/metabolismo , Animales , Separación Celular , Colágeno/metabolismo , Técnicas Citológicas , Matriz Extracelular/metabolismo , Glicoproteínas/metabolismo , Glicosaminoglicanos/metabolismo , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Técnicas Histológicas , Humanos , Proteoglicanos/metabolismoRESUMEN
OBJECTIVES: Prostaglandin E-major urinary metabolite (PGE-MUM) is a useful biomarker for adult ulcerative colitis (UC) activity. In the present study, we evaluated whether PGE-MUM can also be a biomarker of pediatric UC activity and compared its efficacy in predicting UC activity with that of C-reactive protein and erythrocyte sedimentation rate. METHODS: Twenty-nine pediatric patients with UC (8-18 years) and 29 healthy age- and sex-matched subjects were enrolled. UC activity was evaluated using the Pediatric Ulcerative Colitis Activity Index, highest Mayo endoscopic scoring (Mayo), and Matts grading (Matts) for histologic scoring, and the sum of Mayo (total of 6 segments) and Matts in all patients with UC. PGE-MUM levels were measured using a radioimmunoassay. RESULTS: PGE-MUM levels were elevated in endoscopically and histologically active UC patients, but not in patients with endoscopic and histologic remission or controls. PGE-MUM levels positively and significantly correlated with UC activity. PGE-MUM levels were positively correlated with Pediatric Ulcerative Colitis Activity Index (râ=â0.594), highest Mayo (râ=â0.462), the sum of Mayo (râ=â0.694), and the sum of Matts (râ=â0.613), but not with highest Matt (râ=â0.352). The sum of Mayo and the sum of Matts, which reflect total colon inflammation, showed highest correlation with PGE-MUM. C-reactive protein levels did not correlate with any UC activity scores. Erythrocyte sedimentation rate exhibited correlation (râ=â0.490) with the sum of Mayo only. CONCLUSIONS: PGE-MUM is a reliable biomarker that reflects both the endoscopic and histologic activity of the entire colon in pediatric UC.
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Colitis Ulcerosa/diagnóstico , Ácidos Prostanoicos/orina , Índice de Severidad de la Enfermedad , Adolescente , Biomarcadores/orina , Estudios de Casos y Controles , Niño , Preescolar , Colitis Ulcerosa/patología , Colitis Ulcerosa/orina , Colonoscopía , Femenino , Humanos , Lactante , Masculino , Estudios Prospectivos , Análisis de Regresión , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Dysregulation of the prostaglandin E2 (PGE2) signaling pathway has been implicated in interstitial pneumonia (IP) pathogenesis. Due to the unstable nature of PGE2, available detection methods may not precisely reflect PGE2 levels. We explored the clinical usefulness of measuring stable prostaglandin E-major urinary metabolite (PGE-MUM) with respect to pathogenesis and extent of chronic fibrosing IP (CFIP), including idiopathic pulmonary fibrosis (IPF), as PGE-MUM is reflective of systemic PGE2 production. METHODS: PGE-MUM was measured by radioimmunoassay in controls (n = 124) and patients with lung diseases (bronchial asthma (BA): n = 78, chronic obstructive pulmonary disease (COPD): n = 33, CFIP: n = 44). Extent of lung fibrosis was assessed by fibrosing score (FS) of computed tomography (CT) (FS1-4). Immunohistochemical evaluation of COX-2 was performed to find PGE2 producing cells in IPF. Human bronchial epithelial cells (HBEC) and lung fibroblasts (LFB) were used in in vitro experiments. RESULTS: Compared to control, PGE-MUM levels were significantly elevated in CFIP. PGE-MUM levels were positively correlated with FS, and inversely correlated with %DLCO in IP (FS 1-3). COX-2 was highly expressed in metaplastic epithelial cells in IPF, but lower expression of EP2 receptor was demonstrated in LFB derived from IPF. TGF-ß induced COX-2 expression in HBEC. CONCLUSIONS: PGE-MUM, elevated in CFIP, is a promising biomarker reflecting disease activity. Metaplastic epithelial cells can be a source of elevated PGE-MUM in IPF.
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Fibrosis Pulmonar Idiopática/metabolismo , Enfermedades Pulmonares Intersticiales/metabolismo , Pulmón/metabolismo , Ácidos Prostanoicos/análisis , Orina/química , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Ciclooxigenasa 2/metabolismo , Células Epiteliales/metabolismo , Femenino , Fibroblastos/metabolismo , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Fibrosis Pulmonar Idiopática/patología , Japón/epidemiología , Pulmón/patología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Prostaglandinas/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Endoscopic retrograde cholangiopancreatography (ERCP) brushing cytology often cannot distinguish adenocarcinoma from reactive epithelial changes. We attempted to improve the diagnostic sensitivity of ERCP using the following methods: systematic cytological evaluation, immunocytochemical examination of minichromosome maintenance proteins (MCM) 2 and p53, and a combination of these methods. ERCP specimens from 53 patients (13 benign and 40 malignant cases) were studied. First, we reclassified the cases into three categories according to the systematic cytological evaluation: negative, suspicious, and positive. Secondly, immunocytochemistry was performed for MCM 2 and p53. The cut-off values were set at 25% labeling index (LI) for MCM 2 and 10% LI for p53, respectively. We evaluated the sensitivity, specificity, and diagnostic accuracy. The sensitivity of the systematic cytological evaluation alone did not improve significantly, compared with the original screening examination (77% vs. 68%). The sensitivity of immunocytochemistry for MCM 2 and p53 was 90% (P < 0.05) and 68%, respectively. Applying only the suspicious or positive categories, the sensitivity improved significantly to 93% for the combination of systematic cytological evaluation and immunocytochemistry for MCM 2 and p53 (P < 0.01). In conclusion, the combination of morphology and immunocytochemistry for MCM 2 and p53 may help to overcome the diagnostic cytological difficulties of pancreaticobiliary adenocarcinoma.