RESUMO
Microbial processes are critical to the function of freshwater ecosystems, yet we still do not fully understand the factors that shape freshwater microbial communities. Furthermore, freshwater ecosystems are particularly susceptible to effects of environmental change, including influx of exogenous nutrients such as nitrogen and phosphorus. To evaluate the impact of nitrogen loading on the microbial community structure of shallow freshwater lakes, water samples collected from Lake Shenandoah (Virginia, USA) were incubated with two concentrations of either ammonium, nitrate, or urea as a nitrogen source. The potential impact of these nitrogen compounds on the bacterial community structure was assessed via 16S rRNA amplicon sequencing. At the phylum level, the dominant taxa in Lake Shenandoah were comprised of Actinobacteria and Proteobacteria, which were not affected by exposure to the various nitrogen treatments. Overall, there was not a significant shift in the diversity of the bacterial community of Lake Shenandoah with the addition of nitrogen sources, indicating this shallow system may be constrained by other environmental factors.
Assuntos
Lagos , Nitrogênio , Bactérias , Proteobactérias , RNA Ribossômico 16SRESUMO
Invasive mold infections (IMIs) are a major source of morbidity and mortality among lung transplant recipients (LTRs), yet information regarding the epidemiology of IMI in this population is limited. From 2001 to 2006, multicenter prospective surveillance for IMIs among LTR was conducted by the Transplant-Associated Infection Surveillance Network. The epidemiology of IMI among all LTRs in the cohort is reported. Twelve percent (143/1173) of LTRs under surveillance at 15 US centers developed IMI infections. The 12-month cumulative incidence of IMIs was 5.5%; 3-month all-cause mortality was 21.7%. Aspergillus caused the majority (72.7%)of IMIs; non-Aspergillus infections (39, 27.3%) included Scedosporium (5, 3.5%), mucormycosis (3, 2.1%) and "unspecified" or "other" mold infections (31, 21.7%). Late-onset IMI was common: 52% occurred within 1 year posttransplant (median 11 months, range 0-162 months). IMIs are common late-onset complications with substantial mortality in LTRs. LTRs should be monitored for late-onset IMIs and prophylactic agents should be optimized based on likely pathogen.
Assuntos
Pneumopatias/epidemiologia , Transplante de Pulmão , Micoses/epidemiologia , Estudos de Coortes , Humanos , Pneumopatias/microbiologia , Micoses/microbiologiaRESUMO
BACKGROUND: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of â¼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy. PATIENTS AND METHODS: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. RESULTS: Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively. CONCLUSIONS: Endoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC.
Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Paclitaxel , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Projetos Piloto , GencitabinaRESUMO
Fragments of putative chitin synthase (chs) genes from two filarial species (Brugia malayi and Dirofilaria immitis) were amplified by PCR using degenerate primers. The full genomic and cDNA sequences were obtained for the B. malayi chs gene (Bm-chs-1); the predicted amino acid sequence is highly similar, over a large region, to two CHS sequences of the nematode Caenorhabditis elegans and also to two insect CHS sequences. Bm-chs-1 is abundantly transcribed in B. malayi adult females, independent of their fertilization status, but is also expressed in males and microfilariae. Oocytes and early embryos contain large amounts of Bm-chs-1 transcript by in situ hybridization, but later stage embryos within the maternal uterus show little or no Bm-chs-1 transcript. No specific hybridization could be demonstrated in maternal somatic tissues. Polyclonal antibodies were raised against a peptide expressed from a recombinant cDNA fragment of Bm-chs-1; immunostaining detected CHS protein in oocytes and early to midstage embryos. These studies characterize a gene that is likely to be essential to oogenesis and embryonic development in a parasitic nematode. Because chitin synthesis and eggshell formation begin after fertilization, the presence of CHS protein in early oocytes suggests that the enzyme must be activated as a result of fertilization. These studies also demonstrate that chitin synthesis may not be restricted to eggshell formation in nematodes, as the Bm-chs-1 gene is transcribed in life cycle stages other than adult females.
Assuntos
Brugia Malayi/embriologia , Brugia Malayi/enzimologia , Quitina Sintase/genética , Quitina Sintase/metabolismo , Sequência de Aminoácidos , Animais , Southern Blotting , Brugia Malayi/crescimento & desenvolvimento , Quitina Sintase/química , Dirofilaria immitis/embriologia , Dirofilaria immitis/enzimologia , Filariose Linfática/parasitologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Genes de Helmintos , Gerbillinae , Imuno-Histoquímica , Hibridização In Situ , Masculino , Dados de Sequência Molecular , Óvulo/enzimologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNARESUMO
Mesenchymal stem cells (MSCs) have been used to repair connective tissue defects in several animal models. Compared to "natural healing" controls (no added cells), MSC-collagen gel constructs in rabbit tendon defects significantly improve repair biomechanics. However, ectopic bone forms in 28% of MSC-treated rabbit tendons. To understand the source of bone formation, three studies were performed. In the first study, the hypothesis was tested that MSCs delivered during surgery contribute to bone formation in the in vivo repair site. Adjacent histological sections in the MSC-treated repair tissue were examined for pre-labeled MSCs and for cells showing positive alkaline phosphatase (ALP) activity. Both cells were observed in serial sections in regions of ectopic bone. Contralateral "natural healing" tendons lacked both markers. In the other two studies, the effects of osteogenic supplements and construct geometry (monolayer vs. 3-D) on ALP activity were studied to test three hypotheses: that rabbit MSCs increase ALP activity over time in monolayer culture conditions; that adding osteogenic inducing supplements to the culture medium increases cellular protein in monolayer culture; and that rabbit MSCs increase ALP activity both in monolayer and in 3-D constructs, with and without media supplements. Culture in monolayer under similar conditions to in vivo (as in the first study) did not increase ALP at 2 or 4 weeks. Medium designed to increase osteogenic activity significantly increased cell numbers (cellular protein increased by 260%) but did not affect ALP activity either in monolayer or 3-D constructs (p>0.12). However, MSCs in 3-D constructs exhibited higher ALP activity than cells in monolayer, both in the presence (p<0.045) and absence of supplement (p<0.005). These results suggest that in vitro conditions may critically influence cell differentiation and protein expression. Mechanisms responsible for these effects are currently under investigation.
Assuntos
Fosfatase Alcalina/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Osteogênese , Tendões/cirurgia , Animais , Diferenciação Celular , Feminino , Células-Tronco Mesenquimais/enzimologia , CoelhosRESUMO
The mesenteric circulation is acutely sensitive to processes that affect the entire body. Such systemic diseases and syndromes are reviewed with particular emphasis on the mechanisms by which they influence the mesenteric vasculature and blood flow.
Assuntos
Doenças do Tecido Conjuntivo/complicações , Doenças Hematológicas/complicações , Intestinos/irrigação sanguínea , Isquemia/etiologia , Doenças Metabólicas/complicações , Humanos , Neoplasias/complicações , Circulação Esplâncnica/efeitos dos fármacos , Circulação Esplâncnica/efeitos da radiaçãoRESUMO
In otherwise healthy individuals, disease caused by the fungus Histoplasma capsulatum manifests itself as a self-limiting pulmonary infection. Dissemination of the organisms may occur in a setting of compromised cellular immunity. Gastrointestinal involvement occurs in many such cases, but rarely it is clinically obvious and the disease seldom comes to the attention of the general surgeon. However, with the increasing incidence of acquired immunodeficiency syndromes, general surgeons are managing more of these patients than in the past. In our report, we describe a patient with acquired immunodeficiency syndrome who presented with gastrointestinal histoplasmosis.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Gastroenteropatias/complicações , Gastroenteropatias/microbiologia , Histoplasmose/complicações , Adulto , Feminino , Gastroenteropatias/diagnóstico , Histoplasmose/diagnóstico , HumanosRESUMO
BACKGROUND: A prosthetic device must be used to repair ventral hernias in patients with insufficient tissue for a tension-free primary closure. Several prosthetic materials have been employed for this purpose, with varying results. We here review a long experience with the use of expanded polytetrafluoroethylene (ePTFE) patches in the open repair of large abdominal wall defects. METHODS: Demographic, operative, follow-up, and histologic data were recorded and analyzed for all patients in a surgical practice who were treated for large abdominal wall defects with open repair using ePTFE patches between November 1983 and March 1996. RESULTS: Ventral hernia repairs using an ePTFE patch were performed in 98 patients. In 48 (49%), the patient had already undergone at least one previous ventral hernia repair. Of the 98 operations, 78 were full-thickness repairs, 11 were Rives-Stoppa procedures, and 9 were onlay operations. Complications included 5 seromas, 3 fistulas related to removal of a previously implanted prosthesis, and 9 infections. In addition, 10 patients developed recurrent hernias not related to explantation of the patch because of infection or fistula. In 3 patients, infections were treated successfully without removal of the patch. There were no complications related to adhesions, erosion of the patch into the viscera, or bowel obstruction. Histologic studies of longterm ePTFE implants showed excellent fibrous tissue ingrowth and minimal foreign body response. CONCLUSIONS: Our long-term clinical experience indicates that prosthetic patches of ePTFE are safe and effective when used in the repair of large abdominal wall defects that cannot be closed primarily. Operative complications were within acceptable limits, as was the reherniation rate.
Assuntos
Hérnia Ventral/cirurgia , Politetrafluoretileno , Telas Cirúrgicas , Adulto , Idoso , Colágeno/ultraestrutura , Feminino , Hérnia Ventral/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Recidiva , Técnicas de Sutura , Resultado do TratamentoRESUMO
BACKGROUND: The use of prosthetic materials in tension-free incisional hernia repairs has diminished reherniation rates markedly; however, infection, intestinal fistulization, and seroma formation have been reported after repairs. Use of the Rives-Stoppa procedure for incisional hernia repair, in which the prosthesis is placed between the rectus abdominis muscle and the posterior sheath, may reduce occurrence of these problems. METHODS AND MATERIALS: Over a 6-year period 57 open abdominal wall incisional hernia repairs were performed using the Rives-Stoppa technique; 15 (26.3%) had previously undergone incisional hernia repair. The prosthetic materials used were polypropylene, expanded polytetrafluoroethylene (ePTFE), and ePTFE with perforations. The prosthesis size ranged from 8x8 cm to 20x28 cm (mean area 199.6 cm(2)). Follow-up consisted of an office visit 12 months postoperatively and at least one subsequent office visit or telephone interview; mean follow-up time was 34.9 months (range 11.7-81.9). RESULTS: There were no hernia recurrences (except in one patient whose prosthesis was removed), gastrointestinal complications, fistulas, or deaths. Seromas occurred postoperatively in seven patients (12.3%). Two patients (3.5%) had wound infections that required removal of the prosthesis. CONCLUSIONS: In this series the Rives-Stoppa technique had excellent long-term results, with minimal morbidity, in patients with large primary or recurrent incisional hernias. The absence of serious complications and hernia recurrences in patients with grafts in place suggests that the Rives-Stoppa procedure is the repair of choice in such patients.
Assuntos
Músculos Abdominais/cirurgia , Hérnia Ventral/cirurgia , Complicações Pós-Operatórias , Telas Cirúrgicas , Procedimentos Cirúrgicos Operatórios/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polipropilenos/uso terapêutico , Politetrafluoretileno/uso terapêutico , Recidiva , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Resultado do TratamentoRESUMO
29Si NMR, small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) are used to monitor the synthesis of silica nanoparticles from the base-catalyzed hydrolysis of TEOS in methanol and ethanol. The reactions are conducted at a [TEOS] =0.5 M, low concentrations of ammonia ([NH(3)] =0.01-0.1 M), and [H(2)O] =1.1-4.4 M to resolve the initial size of the first nuclei and to follow their structural evolution. It is found that after an induction period where there is a buildup of singly hydrolyzed monomer, the first nuclei are fractal and open in structure. Interestingly, the nuclei are twice as large in ethanol (R(g) approximately 8 nm) as those in methanol (R(g) approximately 4 nm). The data suggest that the difference in primary particle size is possibly caused by a higher supersaturation ratio of the singly hydrolyzed monomer in methanol than in ethanol if it is assumed that the surface energy of the first nuclei is the same in methanol and ethanol. The particle number concentration and the volume fraction of the silica particles are calculated independently from the SAXS, DLS, and 29Si NMR results. Finally, the rate of nucleation is obtained from the particle number concentrations.
RESUMO
Temozolomide has an evolving role in the treatment of high grade gliomas. Recent studies suggest that temozolomide is well tolerated and efficacious. This study retrospectively analysed the activity and toxicity associated with temozolomide at two Australian centres over a 24 month period. Fifty-six patients with recurrent high grade gliomas were treated with temozolomide. Patients received temozolomide orally at 150-200mg/m(2)daily, days 1-5, every 4 weeks. The median number of treatment cycles was 4 (1-12). Of the 56 patients, 15 (27%) achieved complete or partial response and 18 (32%) achieved minor response or stable disease. There were no episodes of febrile neutropenia and temozolomide was generally well tolerated. In conclusion, temozolomide is an active therapy in patients with recurrent high grade glioma and our results concord with published studies.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Glioma/tratamento farmacológico , Adulto , Idoso , Austrália , Neoplasias Encefálicas/mortalidade , Dacarbazina/análogos & derivados , Intervalo Livre de Doença , Feminino , Glioma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Temozolomida , Resultado do TratamentoRESUMO
Glycolysis is an important metabolic pathway for most organisms, including protozoan parasites. Many of these primitive eukaryotes have streamlined their metabolism, favoring glycolysis for generating ATP in the glucose-rich environments in which they reside. Therefore, the enzymes involved in hexose metabolism could prove to be attractive targets for therapeutic development. This hypothesis is supported by a number of chemical and genetic validation studies. Additionally, the peculiar biochemistry of many of the components, along with limited protein sequence identity emphasizes the likelihood of developing compounds that selectively inhibit the parasite enzymes. In this review, we examine the status of target validation at the genetic and/or chemical levels from the protozoan parasites. While the proteins from some species have been interrogated to the point that well-defined lead compounds have been identified with activities against both enzyme and parasite growth, progress in other systems has to date been limited.
Assuntos
Antiprotozoários/farmacologia , Proteínas de Protozoários/metabolismo , Animais , Glicólise , Humanos , Terapia de Alvo MolecularAssuntos
Doença de Crohn/cirurgia , Veias Mesentéricas , Veia Porta , Complicações Pós-Operatórias/cirurgia , Protrombina/genética , Trombectomia/instrumentação , Trombose Venosa/cirurgia , Adulto , Doença de Crohn/complicações , Feminino , Humanos , Complicações Pós-Operatórias/etiologia , Reoperação , Trombectomia/métodos , Trombose Venosa/etiologia , Trombose Venosa/genéticaRESUMO
Type 2 diabetes is associated with normal-to-higher bone mineral density (BMD) and increased rate of fracture. Hyperinsulinemia and hyperglycemia may affect bone mass and quality in the diabetic skeleton. In order to dissect the effect of hyperinsulinemia from the hyperglycemic impact on bone homeostasis, we have analyzed L-SACC1 mice, a murine model of impaired insulin clearance in liver causing hyperinsulinemia and insulin resistance without fasting hyperglycemia. Adult L-SACC1 mice exhibit significantly higher trabecular and cortical bone mass, attenuated bone formation as measured by dynamic histomorphometry, and reduced number of osteoclasts. Serum levels of bone formation (BALP) and bone resorption markers (TRAP5b and CTX) are decreased by approximately 50%. The L-SACC1 mutation in the liver affects myeloid cell lineage allocation in the bone marrow: the (CD3(-)CD11b(-)CD45R(-)) population of osteoclast progenitors is decreased by 40% and the number of (CD3(-)CD11b(-)CD45R(+)) B-cell progenitors is increased by 60%. L-SACC1 osteoclasts express lower levels of c-fos and RANK and their differentiation is impaired. In vitro analysis corroborated a negative effect of insulin on osteoclast recruitment, maturation and the expression levels of c-fos and RANK transcripts. Although bone formation is decreased in L-SACC1 mice, the differentiation potential and expression of the osteoblast-specific gene markers in L-SACC1-derived mesenchymal stem cells (MSC) remain unchanged as compared to the WT. Interestingly, however, MSC from L-SACC1 mice exhibit increased PPARgamma2 and decreased IGF-1 transcript levels. These data suggest that high bone mass in L-SACC1 animals results, at least in part, from a negative regulatory effect of insulin on bone resorption and formation, which leads to decreased bone turnover. Because low bone turnover contributes to decreased bone quality and an increased incidence of fractures, studies on L-SACC1 mice may advance our understanding of altered bone homeostasis in type 2 diabetes.
Assuntos
Densidade Óssea/fisiologia , Antígeno Carcinoembrionário/metabolismo , Diferenciação Celular/fisiologia , Insulina/metabolismo , Fígado/metabolismo , Osteoclastos/metabolismo , Análise de Variância , Animais , Composição Corporal/fisiologia , Reabsorção Óssea/metabolismo , Antígeno Carcinoembrionário/genética , Moléculas de Adesão Celular/metabolismo , Citometria de Fluxo , Hiperinsulinismo/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Camundongos Transgênicos , Obesidade/metabolismo , Osteogênese/fisiologia , Ligante RANK/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Campylobacter species are known to cause infectious abortion in domestic animals. In humans, Campylobacter are an important cause of enteritis, an occasional cause of systemic infection and have had a rare association with abortion and perinatal infection. A case history of spontaneous abortion, at 26 weeks' duration, associated with maternal bacteraemia, due to Campylobacter coli is presented. Transmission, pathogenesis, treatment, and the need for further investigation are discussed.
Assuntos
Bacteriemia , Infecções por Campylobacter , Campylobacter coli , Morte Fetal/etiologia , Complicações Infecciosas na Gravidez , Adulto , Feminino , Humanos , GravidezRESUMO
Colonic anastomoses are frequently encountered, but their endoscopic features have never been adequately characterized. Results of 117 consecutive colonoscopies in patients with colonic anastomoses were prospectively studied during a 12-month period. Anastomoses were photographed, videotaped, and reviewed by the authors. The age range of patients was 18 to 87 years, and interval from surgery extended to 42 years. An equal number of right and left colonic resections were encountered; 9 patients had subtotal colectomies. Ninety-two anastomoses were hand-sewn, and 25 were stapled. Ileal pouch-anal anastomoses were not included. Nine common anastomotic features were identified with the following frequency of occurrence: neovascularity, 105 (89.7%); white anastomotic edge, 64 (54.7%); disruption of haustral pattern, 64 (54.7%); radial suture tracks, 35/92 (38.0%); exposed suture, 11/92 (11.9%); exposed staples, 6/25 (24%); scar tissue adjacent to anastomotic line, 8 (6.8%); nondistensibility of anastomosis, 5 (4.3%); blind colonic pouch, 10 (8.5%). No recurrent carcinomas were noted. The site of seven anastomoses (5.5%) could not be identified. Six of these patients underwent endoscopy more than 8 years postoperatively. Of the remaining 110 patients, 94 (85.5%) had between two and four of the above features identified. In three of four patients who required dilation because of strictures, neovascularity was not seen. We conclude that colonic anastomoses have characteristic endoscopic features. These features can be used as landmarks for definitive identification of anastomotic sites at colonoscopy. The lack of neovascularity at a colonic anastomosis may be an indicator of relative ischemia, predisposing to stricture formation.
Assuntos
Colo/cirurgia , Colonoscopia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica , Colo/patologia , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The results of a home-based preoperative bowel preparation, with and without the support of home care services, are compared with hospital-based preoperative bowel preparation. Length of stay, morbidity, and mortality rates; issues of patient satisfaction; and demographics are reported. The method and tools used in planning, implementing, and evaluating the home preoperative bowel preparation program are also shared. Other issues discussed are the healthcare market forces that promote an increased value of care. Economic and patient satisfaction considerations by employers, payers, and patients; the increasing influence of patient choice on healthcare provider selection and care setting preferences; the nursing workforce issues related to the impending shortage; and issues of regulatory and accrediting agencies are also discussed.
Assuntos
Administração de Caso/organização & administração , Serviços de Assistência Domiciliar/organização & administração , Enteropatias/cirurgia , Satisfação do Paciente , Cuidados Pré-Operatórios/enfermagem , Cuidados Pré-Operatórios/psicologia , Gestão da Qualidade Total/organização & administração , Adulto , Redução de Custos , Feminino , Humanos , Masculino , Marketing de Serviços de Saúde , Pessoa de Meia-Idade , Pesquisa em Avaliação de Enfermagem , Planejamento de Assistência ao Paciente , Educação de Pacientes como Assunto , Cuidados Pré-Operatórios/economia , Avaliação de Programas e Projetos de Saúde , Encaminhamento e ConsultaRESUMO
In an attempt to clarify the restriction of asialo GM1 expression, the presence of asialo GM1 positive cells in the lymphoid tissues of normal and athymic mice was examined using affinity-purified monospecific anti-asialo GM1 antibodies and a FACS-II. The results presented herein demonstrate that a significant frequency of asialo GM1-positive cells can be detected in the primary lymphoid tissues (bone marrow and thymus) as well as in the secondary lymphoid tissues (spleen and lymph nodes). The observed expression of asialo GM1 within the T-cell lineage is, in general, consistent with the previously proposed restriction of asialo GM1 expression to mature T cells. However, the demonstration that a significant frequency of asialo GM1-positive cells is detectable in bone marrow of normal mice, as well as in spleen and bone marrow of athymic mice, establishes that a substantial number of lymphocytes not committed to the T-cell lineage and/or pre-T cells also express the asialo Gm1 antigen. These results indicate that the asialo GM1 marker may be an important tool for following T differentiation from the multipotential stem cell to the functionally mature T cell.
Assuntos
Gangliosídeo G(M1) , Glicoesfingolipídeos/imunologia , Linfócitos/imunologia , Camundongos Nus/imunologia , Animais , Células da Medula Óssea , Diferenciação Celular , Epitopos/imunologia , Feminino , Citometria de Fluxo , Técnicas Imunológicas , Linfonodos/citologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C/imunologia , Camundongos Endogâmicos C57BL/imunologia , Baço/citologia , Linfócitos T/imunologia , Timo/citologiaRESUMO
In order to determine the extent to which Thy-1-positive and Thy-1-negative lymphocytes express the asialo GM1 antigen, lymphocytes in normal spleen and lymph node were examined for simultaneous expression of the asialo GM1 and Thy-1.2 determinants. The results presented herein demonstrate that 55-57% of Thy-1.2-positive cells in spleen and 61-70% of Thy-1.2-positive cells in lymph node express asialo GM1. Furthermore, a significant frequency of Thy-1-negative cells in spleen (12-19%) and in lymph node (28-32%) also express asialo GM1. Since asialo GM1 has previously been shown to be absent on Ig-positive lymphocytes [9], these results establish that asialo GM1 is a marker shared by lymphocytes belonging to the T-cell lineage and lymphocytes apparently not committed to the T-cell to the T-cell lineage, most probably including natural killer (NK) cells. The implication of this finding as to the controversy regarding the possible relation of NK cells to T cells is discussed. Pretreatment of lymphocytes from spleen, thymus and lymph node with neuraminidase resulted in subsequent reactivity of 80-90% of these cells with anti-asialo GM1 anti-bodies. A smaller increase in asialo GM1 detection after neuraminidase treatment was seen with bone-marrow cells (65%). Protease treatment did not affect the subsequent reactivity of lymphocytes with anti-asialo GM1 antibodies. It is concluded that in situ enzymatic modification of asialo GM1 by the addition of sialic acid may be an important regulatory event in lymphocyte differentiation.
Assuntos
Gangliosídeo G(M1) , Glicoesfingolipídeos/imunologia , Linfócitos/imunologia , Ácidos Siálicos/farmacologia , Linfócitos T/imunologia , Animais , Diferenciação Celular , Epitopos/imunologia , Feminino , Citometria de Fluxo , Células Matadoras Naturais/imunologia , Linfonodos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Neuraminidase/farmacologia , Baço/citologia , Timo/citologiaRESUMO
PURPOSE: Inflammatory bowel disease surveillance strategies are designed to identify patients at greater than average risk for the development of invasive colonic carcinoma. Colonoscopic detection of mucosal dysplasia is considered the best available surveillance tool. However, the usefulness of dysplasia as a marker for cancer is uncertain. Furthermore, when dysplasia is found some suggest immediate colectomy, whereas others opt for continued surveillance. The aim of this study is to determine whether an association between dysplasia grade and cancer exists in patients with chronic ulcerative colitis, to ascertain the sensitivity, specificity, and positive predictive value of dysplasia as a cancer marker, and to clarify what action to take once dysplasia is discovered. METHODS: The pathology reports of 590 patients who underwent total proctocolectomy or restorative proctocolectomy for chronic ulcerative colitis were reviewed for dysplasia, grade of dysplasia, presence of carcinoma, and tumor stage. One hundred sixty of these patients had undergone colonoscopic examination within the year before surgery. Findings from these studies were also reviewed. RESULTS: Seventy-seven specimens (13.1 percent) contained at least one focus of dysplasia. Invasive cancers were found in 38 specimens (6.4 percent). Cancers were significantly more common among specimens with dysplastic changes (33/77 vs. 5/513; P < 0.001). Specimens with dysplasia of any grade were 36 times more likely to harbor invasive carcinoma. Stage III disease was found in association with indefinite or low-grade dysplasia in 5 of 26 (19.2 percent) of cases. Tumor stage did not correlate with dysplasia grade. Preoperative colonoscopy identified neoplastic changes in 57 (69.5 percent) cases. Dysplasia, cancer or both were missed in 25 cases. Lesions were correctly identified in only 31 (39.7 percent) of cases. Colonoscopically diagnosed dysplasia as a marker for synchronous cancer had a sensitivity of 81 percent and a specificity of 79 percent. The positive predictive value of a finding of preoperative dysplasia of any grade was 50 percent. The positive predictive value of a finding of low-grade dysplasia was 70 percent. CONCLUSIONS: Dysplasia is an unreliable marker for the detection of synchronous carcinoma. However, when dysplasia of any grade is discovered at colonoscopy, the probability of a coexistent carcinoma is relatively high. Colonoscopic evidence of low-grade dysplasia has a higher positive predictive value than either dysplasia associated mass or lesion or high-grade dysplasia. Dysplasia grade does not predict tumor stage. Because advanced cancer can be found in association with dysplastic changes of any grade, confirmed dysplasia of any grade is an indication for colectomy.