RESUMO
The need for consortial programs to provide advanced education in food animal veterinary production medicine has been recognized and lauded for nearly three decades. This article describes one effort to create a dairy production medicine curriculum funded by a United States Department of Agriculture (USDA) Higher Education Challenge Grant. This National Center of Excellence in Dairy Production Medicine Education for Veterinarians is housed at the Dairy Education Center of the University of Minnesota and the project was a collaboration of the University of Minnesota, the University of Illinois, the University of Georgia, and Kansas State University. The article reviews the need for innovative ways to educate students who will optimally serve the dairy industry, provides a broad overview of the process of developing and delivering the eight-week dairy production medicine curriculum, and describes the challenges faced and lessons learned as a result of offering such a program.
Assuntos
Indústria de Laticínios/educação , Educação em Veterinária , Médicos Veterinários , Animais , Currículo , Humanos , Kansas , Estudantes , Estados UnidosRESUMO
Fast, label-free optical identification and quantification of biomolecules and other relevant biological materials in microfluidic devices and the vascular system will play a major role in liquid biopsy and related diagnoses. An optical microscope probing simultaneously non-linear coherent anti-Stokes Raman scattering (CARS) and linear scattering (LS) was used to probe microparticles in aqueous solutions flowed unconstrained in microfluidic channels. Despite the optical complexity of these systems, where out-of-focus microparticles randomly impede CARS and LS, and where water CARS generates a substantial background, we demonstrate that in-focus microparticles can be individually and unambiguously detected when CARS and LS are co-analyzed. The ability to chemically discriminate microscale features in optically realistic flows supports the relevance of multimodal CARS platforms for liquid biopsy.
Assuntos
Micropartículas Derivadas de Células/química , Microfluídica , Análise Espectral Raman/instrumentaçãoRESUMO
PR1, an HLA-A2-restricted peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes (CTLs) that preferentially kill leukemia and contribute to cytogenetic remission. To evaluate safety, immunogenicity and clinical activity of PR1 vaccination, a phase I/II trial was conducted. Sixty-six HLA-A2+ patients with acute myeloid leukemia (AML: 42), chronic myeloid leukemia (CML: 13) or myelodysplastic syndrome (MDS: 11) received three to six PR1 peptide vaccinations, administered subcutaneously every 3 weeks at dose levels of 0.25, 0.5 or 1.0 mg. Patients were randomized to the three dose levels after establishing the safety of the highest dose level. Primary end points were safety and immune response, assessed by doubling of PR1/HLA-A2 tetramer-specific CTL, and the secondary end point was clinical response. Immune responses were noted in 35 of 66 (53%) patients. Of the 53 evaluable patients with active disease, 12 (24%) had objective clinical responses (complete: 8; partial: 1 and hematological improvement: 3). PR1-specific immune response was seen in 9 of 25 clinical responders versus 3 of 28 clinical non-responders (P=0.03). In conclusion, PR1 peptide vaccine induces specific immunity that correlates with clinical responses, including molecular remission, in AML, CML and MDS patients.
Assuntos
Vacinas Anticâncer/imunologia , Antígeno HLA-A2/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Peptídeos/imunologia , Biomarcadores , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/efeitos adversos , Epitopos de Linfócito T/imunologia , Feminino , Antígeno HLA-A2/química , Humanos , Memória Imunológica , Imunofenotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Análise de Sobrevida , Especificidade do Receptor de Antígeno de Linfócitos T , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Resultado do Tratamento , VacinaçãoRESUMO
Chronic kidney disease has multiple etiologies, but its single, hallmark lesion is renal fibrosis. CD39 is a key purinergic enzyme in the hydrolysis of ATP and increased CD39 activity on regulatory T cells (Treg) is protective in adriamycin-induced renal fibrosis. We examined the effect of overexpression of human CD39 on the development of renal fibrosis in the unilateral ureteric obstructive (UUO) model, a model widely used to study the molecular and cellular factors involved in renal fibrosis. Mice overexpressing human CD39 (CD39Tg) and their wild-type (WT) littermates were subjected to UUO; renal histology and messenger RNA (mRNA) levels of adenosine receptors and markers of renal fibrosis were examined up to 14 days after UUO. There were no differences between CD39Tg mice and WT mice in the development of renal fibrosis at days 3, 7, and 14 of UUO. Relative mRNA expression of the adenosine A2A receptor and endothelin-1 were higher in CD39Tg than WT mice at day 7 post UUO, but there were no differences in markers of fibrosis. We conclude that human CD39 overexpression does not attenuate the development of renal fibrosis in the UUO model. The lack of protection by CD39 overexpression in the UUO model is multifactorial due to the different effects of adenosinergic receptors on the development of renal fibrosis.
Assuntos
Antígenos CD/genética , Apirase/genética , Fibrose/patologia , Rim/patologia , Insuficiência Renal Crônica/patologia , Animais , Antígenos CD/metabolismo , Apirase/metabolismo , Modelos Animais de Doenças , Fibrose/genética , Fibrose/metabolismo , Rim/metabolismo , Camundongos , Camundongos Transgênicos , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/metabolismoRESUMO
The PR1 peptide, derived from the leukemia-associated antigens proteinase 3 and neutrophil elastase, is overexpressed on HLA-A2 in acute myeloid leukemia (AML). We developed a high-affinity T-cell receptor-like murine monoclonal antibody, 8F4, that binds to the PR1/HLA-A2 complex, mediates lysis of AML and inhibits leukemia colony formation. Here, we explored whether 8F4 was active in vivo against chemotherapy-resistant AML, including secondary AML. In a screening model, coincubation of AML with 8F4 ex vivo prevented engraftment of all tested AML subtypes in immunodeficient NSG (NOD scid IL-2 receptor γ-chain knockout) mice. In a treatment model of established human AML, administration of 8F4 significantly reduced or eliminated AML xenografts and extended survival compared with isotype antibody-treated mice. Moreover, in secondary transfer experiments, mice inoculated with bone marrow from 8F4-treated mice showed no evidence of AML engraftment, supporting the possible activity of 8F4 against the subset of AML with self-renewing potential. Our data provide evidence that 8F4 antibody is highly active in AML, including chemotherapy-resistant disease, supporting its potential use as a therapeutic agent in patients with AML.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Antígeno HLA-A2/imunologia , Humanos , Elastase de Leucócito/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Pessoa de Meia-Idade , Mieloblastina/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Long-term renal allograft survival has not improved despite improvements in short term outcomes. Graft loss is characterized histologically by the development of interstitial fibrosis and tubular atrophy (IFTA). Mechanisms underlying the development of IFTA are multifactorial and include ischemia-reperfusion injury (IRI). Therapeutic options to reduce IFTA include management of immunologic causes, such as rejection, but despite these efforts IFTA can still occur and leads to the inexorable destruction of the transplanted kidney. The adenosine A2B receptor (A2BR) has recently been implicated in the development of renal fibrosis. We performed an observational study to examine the mRNA expression of the adenosine receptors after renal ischemia up to the development of renal fibrosis in a mouse model of unilateral IRI. A2BR was the only adenosine receptor that showed elevated expression following ischemia until the development of renal fibrosis 4 weeks after injury. At 2 weeks after ischemia, increased expression of the fibrotic markers transforming growth factor ß and Collagen-1α was observed. Expression of hypoxia inducible factor 1α and endothelin-1, which lie downstream of A2BR activation and have been recognized to promote renal fibrosis, were also significantly up-regulated at 2 weeks after ischemia. Expression of fibrotic markers returned to baseline by 4 weeks after ischemia, indicating resolution of injury with the concurrent development of renal fibrosis and reduced renal function. Our data suggest that A2BR may be a therapeutic target in reducing the development of renal fibrosis after ischemia.
Assuntos
Regulação da Expressão Gênica , Transplante de Rim , Rim/patologia , Receptores Purinérgicos P1/genética , Traumatismo por Reperfusão/genética , Animais , Fibrose/genética , Fibrose/metabolismo , Fibrose/patologia , Rim/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptores Purinérgicos P1/biossíntese , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante HomólogoRESUMO
To enhance the therapeutic index of allogeneic hematopoietic SCT (HSCT), we immunized 10 HLA-matched sibling donors before stem cell collection with recipient-derived clonal myeloma Ig, idiotype (Id), as a tumor antigen, conjugated with keyhole limpet hemocyanin (KLH). Vaccinations were safe in donors and recipients. Donor-derived KLH- and Id-specific humoral and central and effector memory T-cell responses were detectable by day 30 after HSCT and were boosted by post-transplant vaccinations at 3 months in most recipients. One patient died before booster vaccinations. Specifically, after completing treatment, 8/9 myeloma recipients had persistent Id-specific immune responses and 5/9 had improvement in disease status. Although regulatory T cells increased after vaccination, they did not impact immune responses. At a median potential follow-up period of 74 months, 6 patients are alive, the 10 patients have a median PFS of 28.5 months and median OS has not been reached. Our results provide proof of principle that neoantigen and tumor antigen-specific humoral and cellular immunity could be safely induced in HSCT donors and passively transferred to recipients. This general strategy may be used to reduce relapse of malignancies and augment protection against infections after allogeneic HSCT.
Assuntos
Antígenos de Neoplasias/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Imunização/métodos , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Doadores de Tecidos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Epitopos , Feminino , Antígenos HLA/imunologia , Hemocianinas/administração & dosagem , Hemocianinas/imunologia , Humanos , Imunidade Celular/imunologia , Idiótipos de Imunoglobulinas/administração & dosagem , Idiótipos de Imunoglobulinas/imunologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Imunologia de Transplantes , Transplante HomólogoRESUMO
We have shown that CD39 and CD73 are coexpressed on the surface of murine CD4+ Foxp3+ regulatory T cells (Treg) and generate extracellular adenosine, contributing to Treg immunosuppressive activity. We now describe that CD39, independently of CD73, is expressed by a subset of blood-derived human CD4+ CD25+ CD127lo Treg, defined by robust expression of Foxp3. A further distinct population of CD4+ CD39+ T lymphocytes can be identified, which do not express CD25 and FoxP3 and exhibit the memory effector cellular phenotype. Differential expression of CD25 and CD39 on circulating CD4+ T cells distinguishes between Treg and pathogenic cellular populations that secrete proinflammatory cytokines such as IFNγ and IL-17. These latter cell populations are increased, with a concomitant decrease in the CD4+ CD25+ CD39+ Tregs, in the peripheral blood of patients with renal allograft rejection. We conclude that the ectonucleotidase CD39 is a useful and dynamic lymphocytes surface marker that can be used to identify different peripheral blood T cell-populations to allow tracking of these in health and disease, as in renal allograft rejection.
Assuntos
Antígenos CD/biossíntese , Apirase/biossíntese , Antígenos CD4/imunologia , Linfócitos T CD4-Positivos/imunologia , Pirofosfatases/imunologia , Linfócitos T Reguladores/imunologia , Rejeição de Enxerto/imunologia , Humanos , Memória Imunológica , Interferon gama/biossíntese , Interleucina-17/biossíntese , Subunidade alfa de Receptor de Interleucina-2/imunologia , Falência Renal Crônica/imunologia , Transplante de Rim , Fenótipo , Pirofosfatases/biossíntese , Subpopulações de Linfócitos T/imunologia , Células Th17/imunologiaRESUMO
The vascular ectonucleotidases CD39[ENTPD1 (ectonucleoside triphosphate diphosphohydrolase-1), EC 3.6.1.5] and CD73[EC 3.1.3.5] generate adenosine from extracellular nucleotides. CD39 activity is critical in determining the response to ischemia-reperfusion injury (IRI), and CD39 null mice exhibit heightened sensitivity to renal IRI. Adenosine has multiple mechanisms of action in the vasculature including direct endothelial protection, antiinflammatory and antithrombotic effects and is protective in several models of IRI. Mice transgenic for human CD39 (hCD39) have increased capacity to generate adenosine. We therefore hypothesized that hCD39 transgenic mice would be protected from renal IRI. The overexpression of hCD39 conferred protection in a model of warm renal IRI, with reduced histological injury, less apoptosis and preserved serum creatinine and urea levels. Benefit was abrogated by pretreatment with an adenosine A2A receptor antagonist. Adoptive transfer experiments showed that expression of hCD39 on either the vasculature or circulating cells mitigated IRI. Furthermore, hCD39 transgenic kidneys transplanted into syngeneic recipients after prolonged cold storage performed significantly better and exhibited less histological injury than wild-type control grafts. Thus, systemic or local strategies to promote adenosine generation and signaling may have beneficial effects on warm and cold renal IRI, with implications for therapeutic application in clinical renal transplantation.
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Antígenos CD/biossíntese , Apirase/biossíntese , Traumatismo por Reperfusão/prevenção & controle , Adenosina/metabolismo , Animais , Isquemia Fria , Humanos , Necrose do Córtex Renal/prevenção & controle , Camundongos , Camundongos Transgênicos , Modelos AnimaisRESUMO
We reviewed 131 consecutive primary total hip replacements implanted into 127 patients between 1995 and 1997. Surgery was performed through a Hardinge approach using the Exeter universal stem in combination with the Ogee Elite acetabular component.Five of 131 hips have required revision. The ten year survival analysis demonstrates: 95.3% survival with revision for any cause as the end point; 98.9% with revision for aseptic loosening of the stem as the endpoint, 98.1% revision for aseptic loosening of the acetabular component as the endpoint. There were no cases of dislocation.Our findings show that the Exeter universal stem in combination with the Ogee Elite acetabular component can be inserted through a Hardinge approach in a district general setting with results comparable to surgery performed in a specialist unit and through a posterior approach.
Assuntos
Artroplastia de Quadril/instrumentação , Artroplastia de Quadril/métodos , Prótese de Quadril , Osteoartrite do Quadril/cirurgia , Desenho de Prótese , Acetábulo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Prótese , Reoperação , Estudos RetrospectivosRESUMO
The intensity and duration of host responses are determined by protective mechanisms that control tissue injury by dampening down inflammation. Adenosine generation and consequent effects, mediated via A2A adenosine receptors (A2AR) on effector cells, play a critical role in the pathophysiological modulation of these responses in vivo. Adenosine is both released by hypoxic cells/tissues and is also generated from extracellular nucleotides by ecto-enzymes e.g. CD39 (ENTPD1) and CD73 that are expressed by the vasculature and immune cells, in particular by T regulatory cell. In general, these adenosinergic mechanisms minimize the extent of collateral damage to host tissues during the course of inflammatory reactions. However, induction of suppressive pathways might also cause escape of pathogens and permit dissemination. In addition, adenosinergic responses may inhibit immune responses while enhancing vascular angiogenic responses to malignant cells that promote tumor growth. Novel drugs that block A2AR-adenosinergic effects and/or adenosine generation have the potential to boost pathogen destruction and to selectively destroy malignant tissues. In the latter instance, future treatment modalities might include novel 'anti-adenosinergic' approaches that augment immune clearance of malignant cells and block permissive angiogenesis. This review addresses several possible pharmacological modalities to block adenosinergic pathways and speculates on their future application together with impacts on human disease.
Assuntos
Antagonistas do Receptor A2 de Adenosina , Adenosina/fisiologia , Linfócitos T Reguladores/efeitos dos fármacos , Adenosina/antagonistas & inibidores , Adenosina/metabolismo , Animais , Espaço Extracelular/metabolismo , Humanos , Imunoterapia , Inflamação/imunologia , Inflamação/patologia , Receptores Acoplados a Proteínas G/efeitos dos fármacos , Linfócitos T Reguladores/imunologiaRESUMO
Supramaximal stimulation of the rat pancreas with CCK, or its analog caerulein, triggers acute pancreatitis and a number of pancreatitis-associated acinar cell changes including intracellular activation of digestive enzyme zymogens and acinar cell injury. It is generally believed that some of these various acinar cell responses to supramaximal secretagogue stimulation are interrelated and interdependent. In a recent report, Lu et al. showed that secretin, by causing generation of cAMP and activation of PKA, sensitizes acinar cells to secretagogue-induced zymogen activation, and, as a result, submaximally stimulating concentrations of caerulein can, in the presence of secretin, trigger intracellular zymogen activation. We found that secretin also sensitizes acinar cells to secretagogue-induced cell injury and to subapical F-actin redistribution but that it did not alter the caerulein concentration dependence of other pancreatitis-associated changes such as the induction of a peak plateau intracellular [Ca(2+)] rise, inhibition of secretion, activation of ERK1/2, and activation of NF-kappaB. The finding that secretin sensitizes acinar cells to both intracellular zymogen activation and cell injury is consistent with the concept that these two early events in pancreatitis are closely interrelated and, possibly, interdependent. On the other hand, the finding that, in the presence of secretin, caerulein can trigger subapical F-actin redistribution without inhibiting secretion challenges the concept that disruption of the subapical F-actin web is causally related to high-dose secretagogue-induced inhibition of secretion in pancreatic acinar cells.
Assuntos
Ceruletídeo/farmacologia , Pâncreas/efeitos dos fármacos , Secretina/farmacologia , Actinas/metabolismo , Amilases/antagonistas & inibidores , Amilases/metabolismo , Animais , Morte Celular/efeitos dos fármacos , AMP Cíclico/fisiologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Precursores Enzimáticos/farmacologia , Isoquinolinas/farmacologia , MAP Quinase Quinase 2/fisiologia , Masculino , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , NF-kappa B/fisiologia , Ratos , Ratos Sprague-Dawley , Estimulação Química , Sulfonamidas/farmacologiaRESUMO
BACKGROUND: Laparoscopic repair of a right paraduodenal hernia has never been described in the literature. A 24-year-old woman was admitted after 2 weeks of intermittent abdominal pain associated with nausea and vomiting. Physical examination was normal. Laboratory studies and upper endoscopy were normal. Computed tomography revealed that the small bowel was on the right side of the abdomen and the colon on the left, suspicious for malrotation. Subsequent upper gastrointestinal series with small bowel follow-through revealed the ligament of Treitz on the right with the small bowel encased within a probable hernia sac. A presumptive diagnosis of a right paraduodenal hernia was made. METHODS AND RESULTS: Initial access was obtained with a 10-mm infraumbilical port followed by placement of 5-mm ports in the right and left upper and lower quadrants. The duodenum was identified and the small bowel was found encased within a hernia sac, which was opened widely from the duodenum to the pelvis. The hernia sac was opened laterally to avoid injury to the superior mesenteric vessels. The small bowel was then released from the sac into the peritoneal cavity. The entire bowel was inspected and no other abnormalities were noted. The patient had resolution of her abdominal pain and her postoperative course was uncomplicated. She was discharged home on postoperative day 3 and has since done exceptionally well. CONCLUSIONS: Paraduodenal hernia, a rare cause of small bowel obstruction, can present a diagnostic challenge. However, when the diagnosis is made preoperatively, a laparoscopic repair is a feasible and practical option.
Assuntos
Duodenopatias/cirurgia , Laparoscopia/métodos , Dor Abdominal/etiologia , Adulto , Duodenopatias/complicações , Duodeno/embriologia , Feminino , Hérnia/complicações , Herniorrafia , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Mesentério/embriologia , RotaçãoRESUMO
Striking cell losses occur during late B lymphocyte maturation, reflecting BcR-mediated selection coupled with requisites for viability promoting signals. How selection and survival cues are integrated remains unclear, but a key role for B lymphocyte stimulator (BLyS(TM); trademark of Human Genome Sciences, Inc.) is suggested by its marked effects on B cell numbers and autoantibody formation as well as the B lineage-specific expression of BLyS receptors. Our analyses of the B cell-deficient A/WySnJ mouse have established Bcmd as a gene controlling follicular B cell life span, and recent reports show Bcmd encodes a novel BLyS receptor. Here we show that A/WySnJ B cells are unresponsive to BLyS, affording interrogation of how Bcmd influences B cell homeostasis. Mixed marrow chimeras indicate A/WySnJ peripheral B cells compete poorly for peripheral survival. Moreover, in vivo BrdU labeling shows that (A/WySnJ x BALB/c)F(1) B cells have an intermediate but uniform life span, indicating viability requires continuous signaling via this pathway. Together, these findings establish the BLyS/Bcmd pathway as a dominant mediator of B cell survival, suggesting competition for BLyS/Bcmd signals regulates follicular B cell numbers.
Assuntos
Linfócitos B/citologia , Contagem de Linfócitos , Proteínas de Membrana , Receptores do Fator de Necrose Tumoral/fisiologia , Transdução de Sinais/fisiologia , Animais , Receptor do Fator Ativador de Células B , Sobrevivência Celular/fisiologia , Heterozigoto , Camundongos , Camundongos Endogâmicos BALB C , Receptores do Fator de Necrose Tumoral/genéticaRESUMO
Better knowledge of peripheral B lymphocyte homeostasis is needed to address the human hypogammaglobulinemia diseases. A defect in the Bcmd gene shortens the B cell life span and causes B cell deficiency in A/WySnJ mice. Previous genetic mapping placed Bcmd near Srebf2 on chromosome 15. Inspection of the human chromosome 22 syntenic region identified the proapoptotic Bik gene as a candidate. Two mapping methods placed the homologous mouse gene, Blk, near Srebf2. The Blk genomic structure was highly homologous to BIK: Sequence analysis ruled out coding region mutations, but Blk transcripts were overly abundant in sorted A/WySnJ T1 B cells. Moreover, enriched transitional B cells showed a cell-autonomous defect leading to excessive apoptosis. Thus, Bcmd may be a direct mutation in Blk, or in a gene involved in Blk regulation, such that excess expression pushes the A/WySnJ transitional B cells past the apoptosis checkpoint to cell death.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Apoptose/genética , Subpopulações de Linfócitos B/citologia , Subpopulações de Linfócitos B/metabolismo , Proteínas de Transporte/biossíntese , Proteínas de Transporte/genética , Regulação da Expressão Gênica , Proteínas Mitocondriais , Proteínas Proto-Oncogênicas c-bcl-2/genética , Animais , Apoptose/imunologia , Proteínas Reguladoras de Apoptose , Subpopulações de Linfócitos B/patologia , Células Cultivadas , Regulação da Expressão Gênica/imunologia , Humanos , Camundongos , Camundongos Endogâmicos A , Polimorfismo Genético/imunologia , Mapeamento de Híbridos Radioativos , Recombinação Genética/imunologiaRESUMO
OBJECTIVES: To describe reproductive health issues in women with end-stage renal disease (ESRD) treated with haemodialysis. STUDY DESIGN: Cross-sectional survey based on structured interviews. SETTING: Nephrology units of two major metropolitan tertiary referral hospitals in Victoria and their satellite dialysis centres between 1 November 1998 to 30 June 1999. METHODS: Women aged 20 years or over in haemodialysis programs. OUTCOME MEASURES: Menstrual status; prevalence of menstrual and climacteric symptoms; use of gynaecological screening; and prevalence of comorbidities that may benefit from hormone replacment therapy. RESULTS: 48 women completed the survey. They were similar to the 485 women undergoing haemodialysis in Victoria in age (mean age, 55.5 years; range, 20-84 years), years on dialysis (mean age, 3.9 years; range, 1 month-17 years) and primary diagnosis. Eleven of the 15 premenopausal women reported menstrual cycles of 22-35 days, 13 reported common premenstrual symptoms, and six reported dysmenorrhoea that interfered with daily activities. Average age at menopause was 47.7 years (95% CI, 45.6-49.9 years), and six of the 31 postmenopausal women underwent menopause before 45 years. Eight had ever been prescribed hormone replacement therapy (oral in all cases). Over half the women (26) had not had a Pap smear in the last two years, and 12 of those aged over 50 (38%) had not had a mammogram in the same period. CONCLUSION: Despite their risk of early menopause, cardiovascular disease and bone fracture, few women undergoing haemodialysis were offered hormone replacement therapy. Nor were they adequately screened for gynaecological cancers. Women's health issues seem to be neglected among haemodialysis patients.
Assuntos
Unidades Hospitalares de Hemodiálise/normas , Falência Renal Crônica/terapia , Nefrologia/normas , Avaliação de Resultados em Cuidados de Saúde , Administração dos Cuidados ao Paciente , Serviços de Saúde da Mulher/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Fidelidade a Diretrizes , Pesquisas sobre Atenção à Saúde , Humanos , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Vitória/epidemiologia , Serviços de Saúde da Mulher/organização & administraçãoAssuntos
Erros de Diagnóstico , Neoplasias da Próstata/complicações , Stents/efeitos adversos , Ureter/lesões , Obstrução Ureteral/cirurgia , Idoso , Serviço Hospitalar de Emergência/normas , Evolução Fatal , Humanos , Masculino , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , RupturaRESUMO
As a starting point for a phylogenetic study of self-incompatibility (SI) in crucifers and to elucidate the genetic basis of transitions between outcrossing and self-fertilizing mating systems in this family, we investigated the SI system of Arabidopsis lyrata. A. lyrata is an outcrossing close relative of the self-fertile A. thaliana and is thought to have diverged from A. thaliana approximately 5 million years ago and from Brassica spp 15 to 20 million years ago. Analysis of two S (sterility) locus haplotypes demonstrates that the A. lyrata S locus contains tightly linked orthologs of the S locus receptor kinase (SRK) gene and the S locus cysteine-rich protein (SCR) gene, which are the determinants of SI specificity in stigma and pollen, respectively, but lacks an S locus glycoprotein gene. As described previously in Brassica, the S haplotypes of A. lyrata differ by the rearranged order of their genes and by their variable physical sizes. Comparative mapping of the A. lyrata and Brassica S loci indicates that the S locus of crucifers is a dynamic locus that has undergone several duplication events since the Arabidopsis--Brassica split and was translocated as a unit between two distant chromosomal locations during diversification of the two taxa. Furthermore, comparative analysis of the S locus region of A. lyrata and its homeolog in self-fertile A. thaliana identified orthologs of the SRK and SCR genes and demonstrated that self-compatibility in this species is associated with inactivation of SI specificity genes.
Assuntos
Arabidopsis/genética , Brassica/genética , Proteínas de Plantas/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Brassicaceae/genética , Mapeamento Cromossômico , Clonagem Molecular , Troca Genética , Regulação da Expressão Gênica de Plantas , Biblioteca Gênica , Genes de Plantas , Glicoproteínas , Haplótipos , Região de Controle de Locus Gênico , Dados de Sequência Molecular , Pólen/fisiologia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Proteínas Quinases , Proteínas Recombinantes , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Especificidade da EspécieAssuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/diagnóstico , Idoso , Biomarcadores/sangue , Biópsia , Diagnóstico Diferencial , Glomerulonefrite Membranosa/imunologia , Humanos , Masculino , Vasculite/complicações , Vasculite/diagnóstico , Vasculite/imunologiaRESUMO
The A/WySnJ mouse, but not the related A/J strain, has peripheral B-lymphocyte deficiency and mastocytosis. Minimally, two quantitative trait loci (QTLs) control the B-cell deficiency in (A/WySnJ x CAST/Ei)F2 intercross mice; one of them, Bcmd-1, mapped to Chromosome (Chr) 15. Several QTLs controlled the mastocytosis in this intercross, and it was not possible to determine whether any of them co-segregated with Bcmd-1. We have now mapped a second QTL controlling the B-cell deficiency, Bcmd-2, to Chr 4. Furthermore, we narrowed the map position of Bcmd-1 to <2.0 cM. Both QTLs have been confirmed through the construction of AW. Bcmd-1(c), AW. Bcmd-2(c), and AW. Bcmd-1(c)Bcmd-2(c) recombinant congenic strains. The Bcmd-1 locus is the major regulator of B-cell homeostasis, while Bcmd-2 is the minor regulator, and their effects are additive, as shown by splenic B-cells analysis in these congenic strains. In addition, Bcmd-2 or a linked locus controls mastocytosis, while Bcmd-1 does not, as indicated by splenic mast cell analysis in the congenic strains. Thus, the major genetic controls on B-cell homeostasis and mast cell homeostasis in A/WySnJ mice are asserted by distinct genes.