RESUMO
BACKGROUND: Detailed morphometric data concentrating on the development of primary ossification centres in human fetuses is critical for the early detection of developmental defects. Thus, an understanding of the growth and development of the parietal bone is crucial in assessing both the normal and pathological development of the calvaria. MATERIALS AND METHODS: The size of the parietal primary ossification centre in 37 spontaneously aborted human fetuses of both sexes (16 males and 21 females) aged 18-30 weeks was studied by means of computed tomography, digital-image analysis and statistics. RESULTS: The numerical data of the parietal primary ossification centre in the human fetus displays neither sex nor laterality differences. With relation to fetal age in weeks, the parietal primary ossification centre grew in sagittal diameter according to the quadratic function: y = 16.322 + 0.0347 × (age)² ± 1.323 (R² = 0.96), in projection surface area according to the cubic function: y = 284.1895 + 0.051 × × (age)³ ± 0.490, while in both coronal diameter and volume according to the quartic functions: y = 21.746 + 0.000025 × (age)4 ± 1.256 and y = 296.984 + + 0.001 × (age)4, respectively. CONCLUSIONS: The obtained morphometric data of the parietal primary ossification centre may be considered age-specific references, and so may contribute to the estimation of gestational ages and be useful in the diagnostics of congenital cranial defects.
Assuntos
Desenvolvimento Fetal , Osso Parietal , Masculino , Feminino , Humanos , Osso Parietal/diagnóstico por imagem , Osteogênese , Feto/diagnóstico por imagem , Idade GestacionalRESUMO
BACKGROUND: The supraspinatus muscle, one of the four rotator cuff muscles, initiates abduction of the arm, simultaneously stretching the articular capsule at the glenohumeral joint, and also contributes to exorotation of the arm. In the present study we aimed to evaluate the age-specific normative values for morphometric parameters of the supraspinatus muscle in human fetuses at varying ages and to elaborate their growth models. MATERIALS AND METHODS: Using anatomical dissection, digital image analysis (NIS Elements AR 3.0) and statistics (Student's t-test, regression analysis), the length, width, circumference and projection surface area of the supraspinatus muscle were measured in 34 human fetuses of both sexes (16 males, 18 females) aged 18-30 weeks of gestation. RESULTS: Neither sex nor laterality differences were found in numerical data of the supraspinatus muscle. In the supraspinatus muscle its length and projection surface area increased logarithmically, while its width and circumference grew proportionately to gestational age. The following growth models of the supraspinatus muscle were established: y = -71.382 + 30.972 × ln(Age) ± 0.565 for length, y = -2.988 + 0.386 × Age ± 0.168 for greatest width (perpendicular to superior angle of scapula), y = -1.899 + 0.240 × Age ± 0.078 for width perpendicular to the scapular notch, y = -19.7016 + 3.381 × Age ± 2.036 for circumference, and y = -721.769 + 266.141 × ln(Age) ± 6.170 for projection surface area. CONCLUSIONS: The supraspinatus muscle reveals neither sex nor laterality differences in its size. The supraspinatus muscle grows logarithmically with reference to its length and projection surface area, and proportionately with respect to its width and circumference.
Assuntos
Manguito Rotador , Articulação do Ombro , Masculino , Feminino , Humanos , Feto/anatomia & histologia , Idade Gestacional , EscápulaRESUMO
BACKGROUND: Frontal sinuses within the frontal bone can be a potential obstacle in neurosurgical approach in this region. Their unintended opening during craniotomy is not beneficial due to the risk of brain infections by bacteria inhabiting the sinus mucosa. Therefore, such opening should be avoided whenever the surgical procedure does not involve the sinus itself. The aim of the study was the morphometric analysis of the frontal sinuses based on computed tomography imaging. MATERIALS AND METHODS: The width, height, projection surface area and location of the highest and most lateral points of the sinuses were determined. RESULTS: The vertical diameter of the sinuses was found to be greater in men compared with women. The most lateral point of the sinuses was located higher in men, and in men was located higher on the left side. The results obtained may indicate that the frontal sinuses tend to be larger in men and that air cells in men extend further in the upper-lateral direction on the left side of the frontal bone. CONCLUSIONS: This may cause an increased risk of unintentional opening of the left frontal sinus during frontal craniotomy or pterional craniotomy with frontal extension.
Assuntos
Seio Frontal , Masculino , Feminino , Humanos , Seio Frontal/diagnóstico por imagem , Seio Frontal/cirurgia , Craniotomia/métodos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Computed tomography (CT)-based quantitative analysis of primary ossification centres in the cranium has not been carried out to date due to the limited availability of the foetal human material. Detailed morphometric data about the development of primary ossification centres in human foetuses may be useful in the early detection of developmental defects. Understanding the growth and development of the occipital bone is crucial in assessing the normal and pathological development of the cranial base, and the cranium as a whole. MATERIALS AND METHODS: The study material comprised 37 human foetuses (16 males and 21 females) aged 18-30 weeks of gestation. Using CT, digital image analysis software, three-dimensional reconstruction and statistical methods, the size of the primary ossification centres of the lateral and basilar parts of the occipital bone was evaluated. RESULTS: The morphometric characteristics of primary ossification centres of the lateral and basilar parts of the occipital bone display neither sex nor laterality differences. These ossification centres grow linearly with respect to their sagittal and transverse diameters, projection surface area and volume. CONCLUSIONS: The obtained morphometric data of primary ossification centres in the lateral and basilar parts of the occipital bone may be considered as normative for their respective prenatal weeks and may contribute to the estimation of gestational ages and the diagnostics of congenital defects.
Assuntos
Desenvolvimento Fetal , Osteogênese , Feminino , Feto/diagnóstico por imagem , Idade Gestacional , Humanos , Masculino , Osso Occipital/diagnóstico por imagem , GravidezRESUMO
Cellular senescence correlates with changes in the transcriptome. To obtain a complete view on senescence-associated transcription networks and pathways, we assessed by deep RNA sequencing the transcriptomes of five of the most commonly used laboratory strains of human fibroblasts during their transition into senescence. In a number of cases, we verified the RNA-seq data by real-time PCR. By determining cellular protein levels we observed that the age-related expression of most but not all genes is regulated at the transcriptional level. We found that 78% of the age-affected differentially expressed genes were commonly regulated in the same direction (either up- or down-regulated) in all five fibroblast strains, indicating a strong conservation of age-associated changes in the transcriptome. KEGG pathway analyses confirmed up-regulation of the senescence-associated secretory phenotype and down-regulation of DNA synthesis/repair and most cell cycle pathways common in all five cell strains. Newly identified senescence-induced pathways include up-regulation of endocytotic/phagocytic pathways and down-regulation of the mRNA metabolism and the mRNA splicing pathways. Our results provide an unprecedented comprehensive and deep view into the individual and common transcriptome and pathway changes during the transition into of senescence of five human fibroblast cell strains.
Assuntos
Senescência Celular/genética , Sequência Conservada , Fibroblastos/citologia , Fibroblastos/metabolismo , Análise de Sequência de RNA , Proliferação de Células , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare entity characterized by a CD4+/CD56+/CD123+ immunophenotype and a fatal clinical course. The average survival of 12-14 months may be prolonged by allogeneic bone marrow transplantation (BMT). OBJECTIVES: We report about a male patient who suffered from BPDCN with a typical histology and co-expression of CD4/CD123 and a CD56 expression by 80% of the tumour cells. The cutaneous tumour relapse after chemotherapy and allogeneic BMT was completely negative for CD56. METHODS: We performed interphase fluorescence in situ hybridization (FISH) analysis of tumour tissue, asserved before and after BMT, using specific probes for chromosome 11, which encompass the CD56 gene region. RESULTS: The tumour cells revealed a partial loss of 11q as well as a monosomy of chromosome 11. CONCLUSION: This case demonstrates for the first time that loss of CD56 expression can also occur as a secondary event after chemotherapy and BMT. In our case, DNA loss of 11q23 could be responsible for the negativity of 20% of tumour cells as observed before chemotherapy. However, the complete loss of CD56 expression in the relapsed tumour cannot be explained by the loss of 11q23 alone. Additional factors such as chemotherapy-induced mutations might also have contributed.
Assuntos
Transplante de Medula Óssea , Antígeno CD56/metabolismo , Cromossomos Humanos Par 11/genética , Células Dendríticas/patologia , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/terapia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno CD56/genética , Cromossomos Humanos Par 11/efeitos dos fármacos , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Evolução Fatal , Neoplasias Hematológicas/patologia , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Masculino , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prednisolona/administração & dosagem , Pele/metabolismo , Pele/patologia , Neoplasias Cutâneas/patologia , Transplante Homólogo , Vincristina/administração & dosagemRESUMO
We describe a 79-year-old patient who presented with fatigue, weight loss, pancytopenia and a papular exanthem. Previous attempts to taking bone-marrow biopsies had resulted in a 'dry tap', with no material collected, suggesting idiopathic myelofibrosis. Histological examination of skin biopsies showed dermal infiltration of monocytoid cells, resulting in a diagnosis of acute myeloid leukaemia (French-American-British M5 morphology) with leukaemia cutis (LC). Numerous abnormalities of chromosome 8 (trisomy or tetrasomy) have been identified in association with LC. We performed fluorescent in situ analysis on cutaneous tissue using directly labelled probes for various gene loci often involved in patients with AML; these tests showed deletion of p53 and excluded trisomy 8. However, application of probes for AML/ETO, MYC and telomere 8q revealed a gain at 8q22/8q24/8q telomere in a significant number of infiltrating cells. We hypothesize that a partial gain at 8q rather than trisomy of the whole chromosome 8 exhibits an association with LC in AML.
Assuntos
Cromossomos Humanos Par 8/genética , Genes p53/genética , Hibridização in Situ Fluorescente/métodos , Leucemia Mieloide Aguda/genética , Trissomia/genética , Idoso , Aberrações Cromossômicas , Humanos , Interfase , Leucemia Mieloide Aguda/patologia , MasculinoRESUMO
BACKGROUND: Giardiasis is a common, potentially zoonotic disease, and dogs often harbor and shed cysts without showing clinical signs. Treatment with the probiotic Enterococcus faecium SF68 has been shown to stimulate mucosal and systemic immunity in a variety of animal models and in young dogs, and to reduce giardial cyst and antigen shedding in rodents. HYPOTHESIS: Adult dogs with chronic naturally acquired giardiasis will have decreased giardial fecal cyst and antigen shedding and increased innate and adaptive immunity after 6 weeks probiotic treatment with E. faecium SF68. ANIMALS: Twenty adult dogs. METHODS: After a 6-week dietary equilibration period, dogs were randomized to receive E. faecium SF68 or placebo for 6 weeks, and then crossed over to the alternate treatment. We measured cyst shedding, fecal giardial antigen, fecal immunoglobulin A (IgA) concentration, and circulating leukocyte phagocytic activity at multiple timepoints to determine the effect of E. faecium SF68 on giardiasis and immune responses in these dogs. RESULTS: No differences were observed between placebo or E. faecium SF68 treatment for giardial cyst shedding, fecal antigen shedding, fecal IgA concentration, or leukocyte phagocytic activity. CONCLUSIONS: Short-term treatment with E. faecium SF68 of dogs with chronic naturally acquired subclinical giardiasis fails to affect giardial cyst shedding or antigen content and does not alter innate or adaptive immune responses.
Assuntos
Doenças do Cão/prevenção & controle , Enterococcus faecium , Giardíase/veterinária , Probióticos , Ração Animal , Animais , Dieta/veterinária , Suplementos Nutricionais , Doenças do Cão/microbiologia , Cães , Feminino , Giardíase/prevenção & controle , MasculinoRESUMO
BACKGROUND: The results of studies examining the role of Helicobacter spp. in the pathogenesis of canine and feline gastritis are inconclusive. Furthermore, data evaluating the effectiveness of medical therapy for eradication of Helicobacter infection are limited. AIM: To detect Helicobacter spp. in mucosal biopsies of dogs and cats diagnosed with gastritis, with fluorescence in situ hybridization (FISH). ANIMALS: Three dogs and 2 cats with signs of chronic gastrointestinal disease. METHODS: Dogs and cats infected with Helicobacter spp. were treated with triple antimicrobial therapy and fed an elimination diet for 21 days. Helicobacter spp. status in endoscopic (3 dogs, 1 cat) or surgical biopsies (1 cat) of gastric mucosa was compared pre- and posttreatment in each animal by histology, FISH analysis, and polymerase chain reaction (PCR). RESULTS: Gastritis of varying severity with intraglandular spiral bacteria was observed in all animals. Pretreatment diagnostic tests confirmed the presence of mucosal Helicobacter spp. in all animals by FISH and histopathology and in 4/5 animals by PCR. Rapid resolution of vomiting episodes was observed in all animals. Gastric biopsies performed after triple therapy revealed clearance of visible Helicobacter spp. by histopathology and negative FISH analysis, as well as PCR in all animals. CONCLUSIONS AND CLINICAL IMPORTANCE: Application of FISH to routine biopsy specimens enabled rapid and specific identification of Helicobacter spp. within the gastric mucosa of dogs and cats. Although medical therapy was useful in resolution of clinical signs and clearance of visible Helicobacter spp. in gastric biopsies, gastric inflammation persisted.
Assuntos
Antibacterianos/uso terapêutico , Doenças do Gato/microbiologia , Doenças do Cão/microbiologia , Gastrite/veterinária , Infecções por Helicobacter/veterinária , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Animais , Antibacterianos/administração & dosagem , Bismuto/administração & dosagem , Bismuto/uso terapêutico , Doenças do Gato/tratamento farmacológico , Gatos , Doenças do Cão/tratamento farmacológico , Cães , Quimioterapia Combinada , Gastrite/tratamento farmacológico , Hibridização in Situ Fluorescente/veterinária , Metronidazol/administração & dosagem , Metronidazol/uso terapêutico , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/uso terapêutico , Salicilatos/administração & dosagem , Salicilatos/uso terapêuticoRESUMO
Feline inflammatory bowel disease (IBD) is the term applied to a group of poorly understood enteropathies that are considered a consequence of uncontrolled intestinal inflammation in response to a combination of elusive environmental, enteric microbial, and immunoregulatory factors in genetically susceptible cats. The present study sought to examine the relationship of mucosal bacteria to intestinal inflammation and clinical disease activity in cats with inflammatory bowel disease. Duodenal biopsies were collected from 27 cats: 17 undergoing diagnostic investigation of signs of gastrointestinal disease, and 10 healthy controls. Subjective duodenal histopathology ranged from normal (10), through mild (6), moderate (8), and severe (3) IBD. The number and spatial distribution of mucosal bacteria was determined by fluorescence in situ hybridization with probes to 16S rDNA. Mucosal inflammation was evaluated by objective histopathology and cytokine profiles of duodenal biopsies. The number of mucosa-associated Enterobacteriaceae was higher in cats with signs of gastrointestinal disease than healthy cats (P<0.001). Total numbers of mucosal bacteria were strongly associated with changes in mucosal architecture (P<0.001) and the density of cellular infiltrates, particularly macrophages (P<0.002) and CD3(+)lymphocytes (P<0.05). The number of Enterobacteriaceae, E. coli, and Clostridium spp. correlated with abnormalities in mucosal architecture (principally atrophy and fusion), upregulation of cytokine mRNA (particularly IL-1, -8 and -12), and the number of clinical signs exhibited by the affected cats. These data establish that the density and composition of the mucosal flora is related to the presence and severity of intestinal inflammation in cats and suggest that mucosal bacteria are involved in the etiopathogenesis of feline IBD.
Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/veterinária , Doenças do Gato/microbiologia , Doenças Inflamatórias Intestinais/veterinária , Mucosa Intestinal/microbiologia , Animais , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Biópsia/veterinária , Doenças do Gato/patologia , Gatos , Citocinas/análise , Citocinas/biossíntese , Citocinas/genética , Duodeno/microbiologia , Duodeno/patologia , Feminino , Inflamação/microbiologia , Inflamação/veterinária , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Densidade Demográfica , Análise de Componente Principal , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , RNA Ribossômico 16S/genética , Regulação para CimaRESUMO
Smokeless tobacco (ST) products have the potential to be used as a harm reduction method for cigarette smokers. These products can deliver significantly less toxicants than cigarettes, although they are not toxicant free nor harmless. It is important to examine potential health risks and benefits of these products. These two small pilot studies examined the effects of two different ST products (Exalt and Ariva) compared with medicinal nicotine, another potential harm reduction product. Dependent, healthy adult cigarette smokers, who were motivated to quit smoking, underwent 1 week of baseline smoking measurement. They were then asked to quit smoking and were randomly assigned to use either an ST product or a medicinal nicotine lozenge (MNL, Commit) for 2 weeks, then crossed over to use the other product for 2 weeks. In the last week, following the sampling phase, subjects could choose the product they wished to use. Assessments were made repeatedly during baseline cigarette use and throughout the 5 weeks of treatment. Outcome measures included biomarkers for tobacco exposure and subjective, physiological, and behavioral responses. Tobacco-specific carcinogen uptake was greater from Exalt than from the MNL, and was comparable between the MNL and Ariva. Physiological effects and subjective effects on withdrawal and craving were comparable among Exalt, Ariva, and the MNL. Ariva was preferred over the MNL, which was preferred over Exalt. With the exception of medicinal nicotine products, low-nitrosamine ST products have the greatest potential to result in reduced toxicant exposure compared with other combustible reduced exposure products and have promise for reducing individual risk for disease. However, the population effect of marketing of such products as reduced exposure/reduced risk is unknown. The need for further research in this area and regulation of tobacco products is evident.
Assuntos
Estimulantes do Sistema Nervoso Central/administração & dosagem , Nicotina/análogos & derivados , Nicotina/administração & dosagem , Nitrosaminas/urina , Ácidos Polimetacrílicos/administração & dosagem , Polivinil/administração & dosagem , Abandono do Hábito de Fumar/métodos , Tabaco sem Fumaça , Adulto , Biomarcadores/urina , Monóxido de Carbono/urina , Cotinina/urina , Estudos Cross-Over , Feminino , Redução do Dano , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/efeitos adversos , Nicotina/farmacocinética , Projetos Piloto , Ácidos Polimetacrílicos/efeitos adversos , Ácidos Polimetacrílicos/farmacocinética , Polivinil/efeitos adversos , Polivinil/farmacocinética , Projetos de Pesquisa , Dispositivos para o Abandono do Uso de Tabaco , Tabaco sem Fumaça/farmacocinéticaRESUMO
OBJECTIVE: To compare nicotine pharmacokinetics and subjective effects of three new smokeless tobacco potential reduced exposure products (PREPs; Ariva, Revel and Stonewall) with moist snuff (Copenhagen) and medicinal nicotine (Commit lozenge). METHODS: 10 subjects completed a randomised, within-subject, crossover study. Subjects used one product for 30 min at each of the five laboratory sessions. Maximal nicotine concentration (Cmax) was determined and area under the concentration time curve (AUC) was calculated for a 90-min period (during use and 60 min after use). Nicotine craving, withdrawal symptoms and ratings of product effects and liking were measured during product use. RESULTS: Nicotine AUC and Cmax were higher for Copenhagen than for any other product (p<0.002) and higher for Commit than for either Ariva or Revel (p<0.001). Cmax for Commit was also higher than for Stonewall (p = 0.03). Craving was lowest during use of Copenhagen (p<0.03). Craving during use of Stonewall, Ariva and Commit was lower than during use of Revel (p<0.05). Withdrawal symptom score during use of Copenhagen was lower than during use of Revel (p = 0.009). Copenhagen scores were higher (p<0.005) than all other products in several measures of drug effects and liking (feel good effects, satisfaction, liking and desire for product, and strength of product). CONCLUSION: The new smokeless tobacco PREPs result in lower nicotine concentrations and equivalent or lower reductions in subjective measures compared with medicinal nicotine. Since health effects of PREPs are largely unknown, medicinal nicotine should be preferentially encouraged for smokers or smokeless tobacco users wishing to switch to lower-risk products.
Assuntos
Nicotina/sangue , Agonistas Nicotínicos/farmacocinética , Abandono do Hábito de Fumar/métodos , Tabaco sem Fumaça/farmacocinética , Adolescente , Adulto , Idoso , Estudos Cross-Over , Redução do Dano , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Nicotina/uso terapêutico , Síndrome de Abstinência a Substâncias/sangue , Síndrome de Abstinência a Substâncias/reabilitação , ComprimidosRESUMO
PURPOSE: To determine if measurement of lens protein in serum is a feasible means to gain information on the physiologic status of the lens in human subjects. METHODS: The gamma-crystallin concentration was measured by a sandwich radioimmunoassay in the sera of 280 subjects aged 25-94 years. Medical records were reviewed for diagnoses of cataract and aphakia. RESULTS: There was no effect of age or sex on the serum gamma-crystallin concentration. There were 57 subjects with cataract and 27 with aphakia. gamma-Crystallin was higher in all cataract groups and lower in aphakia. The mean gamma-crystallin concentrations for selected subject groups were as follows: clear lens 301 pg/ml; pure nuclear cataract 344 pg/ml; pure cortical cataract 439 pg/ml and aphakia 255 pg/ml. CONCLUSIONS: This is the first published report to show that lens protein is measurable in serum and to demonstrate the feasibility of using serum assays of lens proteins to gain information on the physiological status of the lens. Our results confirm the hypothesis that molecular and cellular events leading to cataract cause increased leakiness of lens cell membranes with release of lens proteins appearing in the blood. It is conceivable that measurement of lens proteins in serum might find future use in the evaluation of cataract risk, potentially cataractogenic and anticataractogenic agents, retained lens fragments after phacoemulsification, secondary cataract, phacolytic glaucoma, anaphylactic endophthalmitis, eye injuries, and other eye diseases.
Assuntos
Extração de Catarata , Catarata/sangue , Cristalinas/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Afacia/sangue , Catarata/fisiopatologia , Feminino , Humanos , Cristalino/fisiopatologia , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Fatores SexuaisRESUMO
Bifunctional peptidylglycine alpha-amidating enzyme (alpha-AE) catalyzes the O2-dependent conversion of C-terminal glycine-extended prohormones to the active, C-terminal alpha-amidated peptide and glyoxylate. We show that alpha-AE will also catalyze the oxidative cleavage of N-acylglycines, from N-formylglycine to N-arachidonoylglycine. N-Formylglycine is the smallest amide substrate yet reported for alpha-AE. The (V/K)app for N-acylglycine amidation varies approximately 1000-fold, with the (V/K)app increasing as the acyl chain length increases. This effect is largely an effect on the KM,app; the KM,app for N-formylglycine is 23 +/- 0.88 mM, while the KM,app for N-lauroylglycine and longer chain N-acylglycines is in the range of 60-90 microM. For the amidation of N-acetylglycine, N-(tert-butoxycarbonyl)glycine, N-hexanoylglycine, and N-oleoylglycine, the rate of O2 consumption is faster than the rate of glyoxylate production. These results indicate that there must be the initial formation of an oxidized intermediate from the N-acylglycine before glyoxylate is produced. The intermediate is shown to be N-acyl-alpha-hydroxyglycine by two-dimensional 1H-13C heteronuclear multiple quantum coherence (HMQC) NMR.
Assuntos
Amidas/metabolismo , Ácidos Graxos/biossíntese , Glicina/análogos & derivados , Glicina/metabolismo , Oxigenases de Função Mista/metabolismo , Complexos Multienzimáticos , Ácidos Oleicos/metabolismo , Adulto , Animais , Catálise , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Ácidos Graxos/metabolismo , Feminino , Glicina/farmacologia , Glioxilatos/metabolismo , Humanos , Cinética , Oxigenases de Função Mista/antagonistas & inibidores , Oxigenases de Função Mista/sangue , Ácidos Oleicos/farmacologia , RatosRESUMO
Protective/suppressive major histocompatibility complex (MHC) class II alleles have been identified in humans and mice where they exert a disease-protective and immunosuppressive effect. Various modes of action have been proposed, among them differential expression of MHC class II genes in different types of antigen-presenting cells impacting on the T helper type 1 (Th1)-Th2 balance. To test this possibility, the expression of H-2 molecules from the four haplotypes H-2(b), H-2(d), H-2(k), and H-2(q) was determined on bone marrow-derived macrophages (BMDMs) and splenic B cells. The I-Ab and I-Ek molecules, both well characterized as protective/suppressive, are expressed at a high level on almost all CD11b+ BMDMs for 5-8 days, after which expression slowly declines. In contrast, I-Ad, I-Ak, and I-Aq expression is lower, peaks over a shorter period, and declines more rapidly. No differential expression could be detected on B cells. In addition, the differential MHC class II expression found on macrophages skews the cytokine response of T cells as shown by an in vitro restimulation assay with BMDMs as antigen-presenting cells. The results indicate that macrophages of the protective/suppressive haplotypes express MHC class II molecules at a high level and exert Th1 bias, whereas low-level expression favors a Th2 response. We suggest that the extent of expression of the class II gene gates the back signal from T cells and in this way controls the activity of macrophages. This effect mediated by polymorphic nonexon segments of MHC class II genes may play a role in determining disease susceptibility in humans and mice.
Assuntos
Regulação da Expressão Gênica/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Macrófagos/imunologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Linhagem Celular , Citocinas/imunologia , Ativação Linfocitária , Ativação de Macrófagos , CamundongosRESUMO
The intestinal epithelium contains a distinct group of lymphocytes (iIEL). The majority of iIEL are T cells characterized by a phenotype different from PBL. This phenotypic peculiarity has led to the hypothesis that iIEL, develop in a thymus-independent fashion, that they may develop locally in the gut epithelium itself and that they have the distinct function of providing a first line of defense in the gut. We looked at the expression of the gut-associated surface molecule alpha E beta 7 on T cells in inflamed tissues outside the gut epithelium. The already high frequency of 41.8% alpha E beta 7+ T cells in bronchoalveolar lavage from healthy lungs rises to a median of 61% in a fibrotic lung. In synovial fluid the percentage of T cells expressing alpha E beta 7 was diverse; it was not as high as in the lung but was elevated compared to PBL levels. In both tissues, the increase in alpha E beta 7 expression correlated with an increase in CD8+ cells. We discuss our data in the context of a model in which iIEL can leave the gut epithelium and become involved in inflammatory processes, possibly related to autoimmune disease.
Assuntos
Artrite Reumatoide/metabolismo , Integrinas/análise , Integrinas/biossíntese , Doenças Pulmonares Intersticiais/metabolismo , Pulmão/metabolismo , Nódulos Linfáticos Agregados/metabolismo , Líquido Sinovial/imunologia , Linfócitos T/metabolismo , Artrite Reumatoide/imunologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/biossíntese , Líquido da Lavagem Broncoalveolar/imunologia , Epitélio/imunologia , Epitélio/metabolismo , Citometria de Fluxo , Humanos , Doenças Pulmonares Intersticiais/imunologiaRESUMO
BACKGROUND: Bile acids may stimulate the movement of hepatocyte vesicles and enhance their fusion with the biliary canaliculus. The present study examined the effects of various bile acids on the exocytosis of the contents of hepatocyte lysosomes into the biliary canaliculus. METHODS: The effects of various bile acids on hepatocyte lysosome movement and on exocytosis of the contents of hepatocyte lysosomes into the biliary canaliculus were determined from the distribution of fluorescein isothiocyanate-dextran--labeled lysosomes in hepatocyte couplets and by quantitating biliary lysosomal enzyme output in rats. RESULTS: Hydrophobic as well as hydrophilic and nonmicellar bile acids were found to stimulate to a similar degree the output of lysosomal enzymes into bile, indicating that bile acid-induced change of canalicular or lysosomal membrane fluidity is not responsible for enhanced exocytosis. The taurocholate-dependent increase in lysosomal enzyme excretion was completely blocked by either microtubule or microfilament inhibition, suggesting that these subcellular structures are involved in bile acid-dependent vesicular transport. Fluorescent microscopy studies showed that taurocholate causes a microtubule-dependent translocation of lysosomes towards the canaliculus in hepatocyte couplets, which occurred at the same time as increased output of lysosomal enzymes into bile. CONCLUSIONS: The results suggest that bile acids modulate vesicle traffic towards the canaliculus by a mechanism unrelated to bile acid interaction with the vesicle membrane.
Assuntos
Ácidos e Sais Biliares/fisiologia , Bile/enzimologia , Membranas Intracelulares/fisiologia , Lisossomos/enzimologia , Citoesqueleto de Actina/fisiologia , Animais , Transporte Biológico/fisiologia , Colchicina/farmacologia , Exocitose/fisiologia , Fluoresceína-5-Isotiocianato , Infusões Intravenosas , Membranas Intracelulares/ultraestrutura , Lisossomos/ultraestrutura , Masculino , Fluidez de Membrana/fisiologia , Microscopia de Fluorescência , Microtúbulos/fisiologia , Faloidina/farmacologia , Ratos , Ratos Sprague-Dawley , Ácido Taurocólico/administração & dosagem , Ácido Taurocólico/farmacologia , Vimblastina/farmacologiaRESUMO
Infant research addresses the question of how subjective structures are objectively established during early development and what biological and psychological preconditions must be met. By contrast, psychoanalytic-developmental research explores how the child processes what it experiences within its relationships. Despite these differences in topic and method, the two research programs complement one another and can be related to each other on the basis of a psychoanalytic theory of socialization.
Assuntos
Desenvolvimento da Personalidade , Teoria Psicanalítica , Psicologia da Criança , Socialização , Humanos , Lactente , PesquisaRESUMO
The contribution of the hepatocyte vacuolar apparatus to bile fluid formation was assessed by studying the transcellular transport and biliary excretion of the fluid-phase marker sucrose. In rats sucrose-loaded by IP administration of sucrose, electron microscopy showed expansion of the vacuolar apparatus and numerous large lysosomelike structures in hepatocytes. Subcellular distribution studies showed that sucrose was sequestered in lysosomes. Compared with controls, sucrose-loaded rats had a 30% higher (P less than 0.01) bile flow with no change in biliary bile acid or electrolyte concentrations. Administration of colchicine ablated the sucrose-induced choleresis and resulted in parallel changes in biliary secretions of sucrose and lysosomal enzymes. Our data suggest that in the sucrose-loaded rat, the hepatocyte vacuolar apparatus may contribute significantly to bile formation by microtubule-dependent release of fluid into bile by exocytosis.
Assuntos
Bile/metabolismo , Fígado/ultraestrutura , Sacarose/farmacocinética , Animais , Transporte Biológico , Exocitose , Lisossomos/metabolismo , Masculino , Microscopia Eletrônica , Ratos , Ratos Endogâmicos , Vacúolos/metabolismoRESUMO
The influence of pilocarpine gel 4% and pilocarpine eye drops 4% or 2% on the optical and ophthalmological parameters pupil diameter, intraocular pressure, ametropia and visual acuity, range of accommodation, and nocturnal visual acuity with and without blinding was investigated. The tendency to amplify the myopia and impair nocturnal vision acuity with and without blinding was greater with eye drops than with gel. There was no significant difference between gel and eye drops as regards their effect on other parameters.