RESUMEN
BACKGROUND: Periprosthetic joint infection (PJI) is an extremely damaging complication that can occur after total knee arthroplasty (TKA). There is no study in the literature investigating the relationship between systemic inflammatory response index (SIRI) and systemic inflammation immune index (SII) values and prognosis and infection in patients who have undergone TKA. The aim of the study was to determine the relationship between the inflammatory index values and the rate of PJI in patients who had previously had TKA. METHODS: A total of 187 patients who underwent TKA between 2015 and 2023 years were retrospectively analyzed. RESULTS: The median value of the postoperative SII index was 1862.3 (1146.6-2630.4) in the infected group, while it was 1058.2 (605.0-1762.8) in the non-infected group (p < 0.001). In the infected group, the median value of preoperative SIRI was observed as 2.3 (1.7-3.5), while in the non-infected group it was 0.9 (0.7-1.5) (p < 0.001). The cutoff value for postoperative SIRI was observed to be 2.19, with a sensitivity value of 95%, a specificity value of 46%, the AUC value observed was 65%. The cutoff value for the postoperative SII index was observed to be 1058.96, with a sensitivity value of 100%, a specificity value of 50%. CONCLUSIONS: Our study has associated the inflammatory markers SIRI, SII, neutrophil lymphocyte ratio, and platelet lymphocyte ratio with PJI, which are easy and inexpensive to obtain. There is no widely recognized serum biomarker that can be used alone with good sensitivity and specificity. This study contributes to finding the gold standard inflammatory marker for diagnosing PJI.
RESUMEN
The initial phase of the COVID-19 pandemic changed the nature of course delivery from largely in-person to exclusively remote, thus disrupting the well-established pedagogy of the Genomics Education Partnership (GEP; https://www.thegep.org). However, our web-based research adapted well to the remote learning environment. As usual, students who engaged in the GEP's Course-based Undergraduate Research Experience (CURE) received digital projects based on genetic information within assembled Drosophila genomes. Adaptations for remote implementation included moving new member faculty training and peer Teaching Assistant office hours from in-person to online. Surprisingly, our faculty membership significantly increased and, hence, the number of supported students. Furthermore, despite the mostly virtual instruction of the 2020-2021 academic year, there was no significant decline in student learning nor attitudes. Based on successfully expanding the GEP CURE within a virtual learning environment, we provide four strategic lessons we infer toward democratizing science education. First, it appears that increasing access to scientific research and professional development opportunities by supporting virtual, cost-free attendance at national conferences attracts more faculty members to educational initiatives. Second, we observed that transitioning new member training to an online platform removed geographical barriers, reducing time and travel demands, and increased access for diverse faculty to join. Third, developing a Virtual Teaching Assistant program increased the availability of peer support, thereby improving the opportunities for student success. Finally, increasing access to web-based technology is critical for providing equitable opportunities for marginalized students to fully participate in research courses. Online CUREs have great potential for democratizing science education.
Asunto(s)
Adenocarcinoma/genética , Técnica del Anticuerpo Fluorescente/métodos , Hibridación Fluorescente in Situ/métodos , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/análisis , Femenino , Humanos , MasculinoRESUMEN
To clarify the regulatory mechanism of GW112 gene expression, 5'-flanking region of the human GW112 gene was isolated and characterized in the present study. 5'-RACE analysis showed a single transcription start site, which is located 142 nucleotides upstream of the translation initiation site. Transient transfection studies with serial deletion constructs and close examination of the sequences identified a putative NF kappaB binding sequence between -442 and -430, which could be responsible for efficient expression of the GW112 gene. Indeed, GW112 gene was found to be regulated by NF kappaB signals including overexpressed p65 and I kappaB alpha, IKK inhibitor, and proteasome inhibitor. Binding of NF kappaB to its putative site was confirmed by EMSA and ChIP assays. These results suggest that NF kappaB is an essential regulatory factor for GW112 transcription. Based on this finding, we next confirmed that inhibition of GW112 expression could induce apoptosis in the presence of cytotoxic agent in gastric cancer cells. Furthermore, knocking-down or overexpression of GW112 gene in gastric cancer cells demonstrated that GW112 has an antiapoptotic property against the cytotoxic agents-induced apoptosis. Taken together, these results suggest that GW112 could be an important mediator in NF kappaB-dependent tumorigenesis of digestive tract tissues.
Asunto(s)
Apoptosis , Regulación Neoplásica de la Expresión Génica/fisiología , Factor Estimulante de Colonias de Granulocitos/genética , FN-kappa B/fisiología , Neoplasias Gástricas/genética , Western Blotting , Proliferación Celular , Inmunoprecipitación de Cromatina , Ensayo de Cambio de Movilidad Electroforética , Citometría de Flujo , Humanos , Immunoblotting , Inmunoprecipitación , Luciferasas/metabolismo , Regiones Promotoras Genéticas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Sitio de Iniciación de la Transcripción , Transfección , Células Tumorales Cultivadas , Regulación hacia ArribaRESUMEN
A hallmark of the research experience is encountering difficulty and working through those challenges to achieve success. This ability is essential to being a successful scientist, but replicating such challenges in a teaching setting can be difficult. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-Based Undergraduate Research Experience (CURE). Students participate in genome annotation, generating gene models using multiple lines of experimental evidence. Our observations suggested that the students' learning experience is continuous and recursive, frequently beginning with frustration but eventually leading to success as they come up with defendable gene models. In order to explore our "formative frustration" hypothesis, we gathered data from faculty via a survey, and from students via both a general survey and a set of student focus groups. Upon analyzing these data, we found that all three datasets mentioned frustration and struggle, as well as learning and better understanding of the scientific process. Bioinformatics projects are particularly well suited to the process of iteration and refinement because iterations can be performed quickly and are inexpensive in both time and money. Based on these findings, we suggest that a dynamic of "formative frustration" is an important aspect for a successful CURE.
RESUMEN
Considerable attention has focused on regulation of central tryptophan hydroxylase (TPH) activity and protein expression. At the time of these earlier studies, it was thought that there was a single central TPH isoform. However, with the recent identification of TPH2, it becomes important to distinguish between regulatory effects on the protein expression and activity of the two isoforms. We have generated a TPH2-specific polyclonal antiserum (TPH2-6361) to study regulation of TPH2 at the protein level and to examine the distribution of TPH2 expression in rodent and human brain. TPH2 immunoreactivity (IR) was detected throughout the raphe nuclei, in lateral hypothalamic nuclei and in the pineal body of rodent and human brain. In addition, a prominent TPH2-IR fiber network was found in the human median eminence. We recently reported that glucocorticoid treatment of C57/Bl6 mice for 4 days markedly decreased TPH2 messenger RNA levels in the raphe nuclei, whereas TPH1 mRNA was unaffected. The glucocorticoid-elicited inhibition of TPH2 gene expression was blocked by co-administration of the glucocorticoid receptor antagonist mifepristone (RU-486). Using TPH2-6361, we have extended these findings to show a dose-dependent decrease in raphe TPH2 protein levels in response to 4 days of treatment with dexamethasone; this effect was blocked by co-administration of mifepristone. Moreover, the glucocorticoid-elicited inhibition of TPH2 was functionally significant: serotonin synthesis was significantly reduced in the frontal cortex of glucocorticoid-treated mice, an effect that was blocked by mifepristone co-administration. This study provides further evidence for the glucocorticoid regulation of serotonin biosynthesis via inhibition of TPH2 expression, and suggest that elevated glucocorticoid levels may be relevant to the etiology of psychiatric diseases, such as depression, where hypothalamic-pituitary-adrenal axis dysregulation has been documented.
Asunto(s)
5-Hidroxitriptófano/biosíntesis , Dexametasona/análogos & derivados , Lóbulo Frontal/química , Proteínas del Tejido Nervioso/biosíntesis , Núcleos del Rafe/enzimología , Triptófano Hidroxilasa/análisis , Triptófano Hidroxilasa/biosíntesis , 5-Hidroxitriptófano/análisis , Secuencia de Aminoácidos , Animales , Especificidad de Anticuerpos , Dexametasona/farmacología , Inducción Enzimática/efectos de los fármacos , Femenino , Lóbulo Frontal/efectos de los fármacos , Humanos , Sueros Inmunes , Ratones , Ratones Endogámicos C57BL , Mifepristona/farmacología , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/análisis , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/inmunología , Ovariectomía , Fragmentos de Péptidos/inmunología , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , ARN Mensajero/biosíntesis , Núcleos del Rafe/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Triptófano Hidroxilasa/genética , Triptófano Hidroxilasa/inmunologíaRESUMEN
BACKGROUND AND PURPOSE: Consistent and standardized reporting of interval change for certain diagnoses may improve the clinical utility of radiology reports. The purpose of this study was to assess explicitly stated interval change of various findings in noncontrast head CT reports. MATERIALS AND METHODS: A retrospective review was performed on successive noncontrast head CT radiology reports from the first 2 weeks of January 2014. Reports with at least 1 prior comparison CT scan were included. Reports with normal examination findings and those that made comparison with only other types of examinations (eg, MR imaging) were excluded. Descriptive and subgroup statistical analyses were performed. RESULTS: In total, 200 patients with 230 reports and 979 radiographic findings were identified. The average interval between reports was 344.9 ± 695.9 days (range, 0-3556 days). Interval change was mentioned 67.3% (n = 659) of the time for all findings (n = 979). Explicitly stated interval change was significantly associated with nonremote findings (P < .001) and generalized statements of interval change (P < .001). The proportion of interval change reported ranged from 95.3% of the time for hemorrhagic to 36.4% for soft-tissue/osseous categorizations. CONCLUSIONS: Interval change reporting was variable, mentioned for 67.3% of noncontrast head CT report findings with a prior comparison CT scan. Structured radiology reports may improve the consistent and clear reporting of interval change for certain findings.
Asunto(s)
Cabeza/diagnóstico por imagen , Radiología/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Literature review reporting results of salvage brachytherapy and stereotactic body radiotherapy for prostate recurrence only after radiotherapy for prostate cancer. MATERIALS AND METHODS: A total of 38 studies (including at least 15 patients per study) were analysed: 19 using low-dose-rate brachytherapy, nine high-dose-rate brachytherapy and ten stereotactic body radiotherapy. Only five studies were prospective. The median numbers of patients were 30 for low-dose-rate brachytherapy, 34 for high-dose-rate brachytherapy, and 30 for stereotactic body radiotherapy. The median follow-up were 47months for low-dose-rate brachytherapy, 36months for high-dose-rate brachytherapy and 21months for stereotactic body radiotherapy. RESULTS: Late genitourinary toxicity rates ranged, for grade 2: from 4 to 42% for low-dose-rate brachytherapy, from 7 to 54% for high-dose-rate brachytherapy and from 3 to 20% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 24% for low-dose-rate brachytherapy, from 0 to 13% for high-dose-rate brachytherapy and from 0 to 3% for grade 3 or above (except 12% in one study) for stereotactic body radiotherapy. Late gastrointestinal toxicity rates ranged, for grade 2: from 0 to 6% for low-dose-rate brachytherapy, from 0 to 14% for high-dose-rate brachytherapy and from 0 to 11% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 6% for low-dose-rate brachytherapy, and from 0 to 1% for high-dose-rate brachytherapy and stereotactic body radiotherapy. The 5-year biochemical disease-free survival rates ranged from 20 to 77% for low-dose-rate brachytherapy and from 51 to 68% for high-dose-rate brachytherapy. The 2- and 3-year disease-free survival rates ranged from 40 to 82% for stereotactic body radiotherapy. Prognostic factors of biochemical recurrence have been identified. CONCLUSION: Despite a lack of prospective data, salvage reirradiation for prostate cancer recurrence can be proposed to highly selected patients and tumours. Prospective comparative studies are needed.
Asunto(s)
Braquiterapia , Recurrencia Local de Neoplasia/radioterapia , Neoplasias de la Próstata/radioterapia , Radiocirugia , Reirradiación/métodos , Terapia Recuperativa/métodos , Braquiterapia/estadística & datos numéricos , Humanos , Masculino , Recurrencia Local de Neoplasia/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico por imagen , Radiocirugia/estadística & datos numéricos , Reirradiación/estadística & datos numéricos , Terapia Recuperativa/estadística & datos numéricosRESUMEN
OBJECTIVES: The medially spherical GMK Sphere (Medacta International AG, Castel San Pietro, Switzerland) total knee arthroplasty (TKA) was previously shown to accommodate lateral rollback while pivoting around a stable medial compartment, aiming to replicate native knee kinematics in which some coronal laxity, especially laterally, is also present. We assess coronal plane kinematics of the GMK Sphere and explore the occurrence and pattern of articular separation during static and dynamic activities. METHODS: Using pulsed fluoroscopy and image matching, the coronal kinematics and articular surface separation of 16 well-functioning TKAs were studied during weight-bearing and non-weight-bearing, static, and dynamic activities. The closest distances between the modelled articular surfaces were examined with respect to knee position, and proportions of joint poses exhibiting separation were computed. RESULTS: Overall, 1717 joint poses were analyzed. At a 1.0 mm detection threshold, 37 instances of surface separation were observed in the lateral compartment and four medially (p < 0.001). Separation was activity-dependent, both laterally and medially (p < 0.001), occurring more commonly during static deep flexion in the lateral compartment, and during static rotation in the medial compartment. Lateral separation occurred more frequently than medial during kneeling (7/14 lateral vs 1/14 medial; p = 0.031) and stepping (20/1022 lateral vs 0/1022 medial; p < 0.001). Separation varied significantly between individuals during dynamic activities. CONCLUSION: No consistent association between closest distances of the articular surfaces and knee position was found during any activity. Lift-off was infrequent and depended on the activity performed and the individual knee. Lateral separation was consistent with the design rationale. Medial lift-off was rare and mostly in non-weight-bearing activities.Cite this article: S. Key, G. Scott, J.G. Stammers, M. A. R. Freeman, V. Pinskerova, R. E. Field, J. Skinner, S. A. Banks. Does lateral lift-off occur in static and dynamic activity in a medially spherical total knee arthroplasty? A pulsed-fluoroscopic investigation. Bone Joint Res 2019;8:207-215. DOI: 10.1302/2046-3758.85.BJR-2018-0237.R1.
RESUMEN
Individual members of the E2F/DP protein family control cell cycle progression by acting predominantly as an activator or repressor of transcription. In Drosophila melanogaster the E2f1, E2f2, Dp, and Rbf1 genes all contribute to replication control in ovarian follicle cells, which become 16C polyploid and subsequently undergo chorion gene amplification late in oogenesis. Mutation of E2f2, Dp, or Rbf1 causes ectopic DNA replication throughout the follicle cell genome during gene amplification cycles. Here we show by both reverse transcription-PCR and DNA microarray analysis that the transcripts of prereplication complex (pre-RC) genes are elevated compared to the wild type in E2f2, Dp, and Rbf1 mutant follicle cells. For some genes the magnitude of this transcriptional derepression is greater in Rbf1 than in E2f2 mutants. These differences correlate with differences in the magnitude of the replication defects in follicle cells, which attain an inappropriate 32C DNA content in both Rbf1 and Dp mutants but not in E2f2 mutants. The ectopic genomic replication of E2f2 mutant follicle cells can be suppressed by reducing the Orc2, Orc5, or Mcm2 gene dose by half, indicating that small changes in pre-RC gene expression can affect DNA synthesis in these cells. We conclude that RBF1 forms complexes with both E2F1/DP and E2F2/DP that cooperate to repress the expression of pre-RC genes, which helps confine DNA synthesis to sites of gene amplification. In contrast, E2F1 and E2F2 repressors function redundantly for some genes in the embryo. Thus, the relative functional contributions of E2F1 and E2F2 to gene expression and cell cycle control depends on the developmental context.
Asunto(s)
Replicación del ADN/fisiología , Proteínas de Drosophila/fisiología , Drosophila melanogaster/fisiología , Regulación del Desarrollo de la Expresión Génica , Silenciador del Gen/fisiología , Oogénesis/fisiología , Folículo Ovárico/citología , Factores de Transcripción/fisiología , Transcripción Genética/fisiología , Alelos , Animales , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/fisiología , Proteínas de Drosophila/genética , Drosophila melanogaster/citología , Drosophila melanogaster/embriología , Factores de Transcripción E2F , Factor de Transcripción E2F1 , Factor de Transcripción E2F2 , Embrión no Mamífero/metabolismo , Femenino , Perfilación de la Expresión Génica , Sustancias Macromoleculares , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Oogénesis/genética , Fenotipo , Proteína de Retinoblastoma , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transactivadores/genética , Transactivadores/fisiología , Factores de Transcripción/genéticaRESUMEN
AIMS: Hip hemiarthroplasty is a standard treatment for intracapsular proximal femoral fractures in the frail elderly. In this study we have explored the implications of early return to theatre, within 30 days, on patient outcome following hip hemiarthroplasty. PATIENTS AND METHODS: We retrospectively reviewed the hospital records of all hip hemiarthroplasties performed in our unit between January 2010 and January 2015. Demographic details, medical backround, details of the primary procedure, complications, subsequent procedures requiring return to theatre, re-admissions, discharge destination and death were collected. RESULTS: A total of 705 procedures were included; 428 Austin Moore and 277 Exeter Trauma Stems were used. A total of 34 fractures (in 33 patients) required early return to theatre within 30 days. Age, gender, laterality, time from admission to primary procedure, American Society of Anesthesiologists grade, and implant type were similar for those requiring early return to theatre and those who did not. Early return to theatre was associated with a significantly higher length of stay (mean 33.6 days (7 to 107) versus 18.6 days (0 to 152), p < 0.001), re-admission rate (38.2% versus 8.6%, p < 0.001), and subsequent revision rate (17.6% versus 1.3%, p < 0.001). We found no difference in level of care required on discharge or mortality. CONCLUSION: Proximal femoral fractures are common in the elderly population, with far-reaching medical and economic implications. Factors such as infection or dislocation may require early return to theatre, and this is associated with outcomes which may be both medically and economically detrimental. This illustrates the importance of avoiding early complications to improve longer term outcome. Return to theatre within 30 days is associated with longer length of stay, higher re-admission rate, and higher subsequent revision rate. It may be a useful short-term quality indicator for longer term outcome measures following hip hemiarthroplasty for intracapsular fractures of the proximal femur. Cite this article: Bone Joint J 2017;99-B:958-63.
Asunto(s)
Fracturas del Cuello Femoral/cirugía , Hemiartroplastia , Reoperación/estadística & datos numéricos , Anciano de 80 o más Años , Femenino , Fracturas del Cuello Femoral/epidemiología , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
CRF-containing parvocellular axons in the external zone of the rat median eminence were classified as vasopressin-containing (CRF+/AVP+) and vasopressin-deficient (CRF+/AVP-) subpopulations based on post-embedding electron microscopic immunocytochemical staining of serial ultrathin sections for CRF, AVP and the other peptides derived from the AVP precursor: AVP-associated neurophysin (NP-AVP) and the C-terminal glycopeptide (GP). In normal animals, the CRF+/AVP+ and CRF+/AVP- subpopulations were approximately equal in terms of detectable axonal swellings. Three to 14 days after adrenalectomy (ADX), the CRF+/AVP+ and CRF+/AVP- subpopulations represented about 95% and 5%, respectively, of total CRF+ swellings. This change was due to a 90% decrease in the absolute number of detectable CRF+/AVP- swellings after ADX, whereas the absolute number of detectable CRF+/AVP+ swellings rose by less than 20%. These changes were completely blocked by administering the glucocorticoid agonist dexamethasone throughout the period after ADX. The results suggest that the CRF+/AVP+ and CRF+/AVP- subpopulations of neurosecretory axons in the external zone of the median eminence respond differently to ADX, indicating that they are independently regulated by glucocorticoids.
Asunto(s)
Adrenalectomía , Arginina Vasopresina/metabolismo , Axones/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Eminencia Media/ultraestructura , Animales , Dexametasona/farmacología , Histocitoquímica , Inmunoensayo , Masculino , Eminencia Media/efectos de los fármacos , Microscopía Electrónica , Ratas , Ratas EndogámicasRESUMEN
Inhibition of the LHRH system appears to play an important role in preventing precocious activation of the hypothalamic-pituitary-gonadal axis. Evidence points to gamma-aminobutyric acid (GABA) as the major negative regulator of postnatal LHRH neuronal activity. Changes in LHRH messenger RNA (mRNA) levels after alterations of GABAergic activity have been reported in vivo. However, the extent to which GABA acts directly on LHRH neurons to effect LHRH mRNA levels has been difficult to ascertain. The present work evaluates the effect of GABAergic activity, via GABA(A) receptors, on LHRH neuropeptide gene expression in LHRH neurons maintained in olfactory explants generated from E11.5 mouse embryos. These explants maintain large numbers of primary LHRH neurons that migrate from bilateral olfactory pits in a directed manner. Using in situ hybridization histochemistry and single cell analysis, we report dramatic alterations in LHRH mRNA levels. Inhibition of spontaneous synaptic activity by GABA(A) antagonists, bicuculline (10(-5) M) or picrotoxin (10(-4) M), or of electrical activity by tetrodotoxin (TTX, 10(-6) M) significantly increased LHRH mRNA levels. In contrast, LHRH mRNA levels decreased in explants cultured with the GABA(A) receptor agonist, muscimol (10(-4) M), or KCl (50 mM). The observed responses suggest that LHRH neurons possess functional pathways linking GABA(A) receptors to repression of neuropeptide gene expression and indicate that gene expression in embryonic LHRH neurons, outside the CNS, is highly responsive to alterations in neuronal activity.
Asunto(s)
Técnicas Citológicas , Hormona Liberadora de Gonadotropina/genética , Hormona Liberadora de Gonadotropina/metabolismo , Neuronas/metabolismo , Mucosa Olfatoria/fisiología , ARN Mensajero/metabolismo , Receptores de GABA-A/fisiología , Animales , Antagonistas del GABA/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Ratones/embriología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Cloruro de Potasio/farmacología , Tetrodotoxina/farmacologíaRESUMEN
In adult rodents, the peptide galanin is expressed in a subpopulation of hypothalamic luteinizing hormone-releasing hormone (LHRH) neurones in an activity-dependent manner. In this investigation, we examined whether galanin mRNA expression in mice was activated coincident with LHRH mRNA expression, as LHRH neurones differentiate from the olfactory placode. Using in situ hybridization, we show (i) that galanin mRNA is coexpressed in LHRH neurones prenatally, (ii) that there is a decrease in galanin mRNA expression relative to LHRH mRNA expression once LHRH mRNA positive/galanin mRNA positive neurones migrate out of the olfactory pit and into the nasal septum, and (iii) the presence of a novel population of galanin mRNA positive/LHRH mRNA negative expressing neurones in the olfactory pit/vomeronasal organ which do not migrate into the central nervous systenm (CNS). This study demonstrates that there are at least two populations of galanin mRNA expressing neurones arising from the olfactory placode; one that remains in nasal regions, is LHRH mRNA negative and whose function is unknown, and one which is coexpressed with LHRH. In addition, the temporal expression of galanin mRNA in LHRH cells indicates that initial activation and subsequent inactivation of galanin mRNA expression is independent of synaptic CNS connections.
Asunto(s)
Galanina/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Neuronas/metabolismo , Vías Olfatorias/embriología , Órgano Vomeronasal/embriología , Animales , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario y Fetal/fisiología , Galanina/genética , Hormona Liberadora de Gonadotropina/genética , Ratones , Vías Olfatorias/citología , ARN Mensajero/metabolismo , Órgano Vomeronasal/citologíaRESUMEN
Trophozoites and cysts of amebas were found within the necrotic cornea of an enucleated eye. The organism was identified, by indirect immunofluorescent staining using specific antiserum, to be Acanthamoeba castellani. This case report illustrates the difficulty of clinical diagnosis and typical inefficacy of medical therapy shown in other reports of this rare keratitis.
Asunto(s)
Amebiasis/diagnóstico , Queratitis/etiología , Adulto , Amebiasis/inmunología , Amoeba/clasificación , Amoeba/inmunología , Córnea/patología , Humanos , Queratitis/diagnóstico , Queratitis/patología , Masculino , SerotipificaciónRESUMEN
The eyes of three patients followed clinically for many years with a diagnosis of macular disciform scarring, secondary to ocular histoplasmosis, were studied histopathologically. A fibrovascular scar interposed between the choroid and retina was observed in all cases. Vessels passing from the choroid through defects in Bruch's membrane into the nodule were demonstrated. Theories of the pathogenesis of the lesion are discussed.
Asunto(s)
Oftalmopatías/patología , Histoplasmosis/patología , Mácula Lútea/patología , Adulto , Coroides/patología , Oftalmopatías/etiología , Oftalmopatías/terapia , Femenino , Histoplasmosis/complicaciones , Humanos , Fotocoagulación , Masculino , Persona de Mediana Edad , Retina/patología , SíndromeRESUMEN
Antisera against partially processed, unamidated forms of AVP and OT were raised and characterized by radioimmunoassay and immunocytochemistry. These antibodies, and antibodies that recognize fully processed, amidated forms of AVP and OT, were used together with various fractionation methods to study the content of prohormones, partially processed and fully processed forms of AVP and OT in the hypothalamo-neurohypophysial system of adult and fetal (E21) rats. The levels of cleaved AVP and OT in the fetus were lower than those of the adult (1 to 3 orders of magnitude for brain and pituitary, respectively), and the detection of cleaved OT in brain and pituitary was delayed compared to that of AVP. Pro-AVP cleavage efficiency in the adult and the fetus was high (99 and 95% cleavage, respectively) resulting in formation of fully processed amidated forms of AVP, with no detectable partially processed peptides. Pro-OT processing in the adult was very similar (over 99% cleavage) resulting in formation of fully processed amidated OT. However, Pro-OT processing efficiency in the fetus was very low and incomplete, resulting in 40% unprocessed precursor and the accumulation of C-terminally extended unamidated intermediate forms (OT-Gly, OT-Gly-Lys, and OT-Gly-Lys-Arg).
Asunto(s)
Arginina Vasopresina , Neurofisinas , Oxitocina/análogos & derivados , Precursores de Proteínas/metabolismo , Procesamiento Proteico-Postraduccional , Vasopresinas/metabolismo , Animales , Anticuerpos/inmunología , Cromatografía en Gel , Reacciones Cruzadas , Electroforesis , Sistema Hipotálamo-Hipofisario/inmunología , Sistema Hipotálamo-Hipofisario/metabolismo , Inmunohistoquímica , Masculino , Oxitocina/inmunología , Oxitocina/metabolismo , Precursores de Proteínas/inmunología , Radioinmunoensayo , Ratas , Ratas Endogámicas , Núcleo Supraóptico/inmunología , Núcleo Supraóptico/metabolismo , Núcleo Supraóptico/ultraestructura , Vasopresinas/inmunologíaRESUMEN
Vasopressin and its carrier protein, vasopressin-associated neurophysin, are co-packaged together with an opioid peptide, dynorphin, into 160 nm diameter neurosecretory vesicles in the normal rat hypothalamo-neurohypophysial system. The homozygous Brattleboro rat lacks vasopressin and vasopressin-associated neurophysin, but contains substantial amounts of dynorphin in the vasopressin-deficient neurosecretory cells. We used post-embedding electron microscopic immunocytochemistry to determine the subcellular location of dynorphin in Brattleboro rats. The results show that dynorphin is present within 100 nm neurosecretory vesicles in homozygous Brattleboro cell bodies and axons, and within 160 nm vesicles in heterozygous (control) neurosecretory cell bodies and axons. Oxytocin-associated neurophysin is present in a separate population of magnocellular neurons in both homozygous and heterozygous rats, and is contained within 160 nm vesicles in both cases. Therefore, the absence of synthesis of the vasopressin prohormone results in a dramatic reduction of neurosecretory vesicle size, despite the continued synthesis and packaging of dynorphin peptides.
Asunto(s)
Gránulos Citoplasmáticos/ultraestructura , Dinorfinas/análisis , Neurohipófisis/ultraestructura , Núcleo Supraóptico/ultraestructura , Animales , Heterocigoto , Homocigoto , Técnicas para Inmunoenzimas , Masculino , Microscopía Electrónica , Ratas , Ratas BrattleboroRESUMEN
BACKGROUND: Recently we demonstrated that gastric mucosa of rats can synthesize, store and release dopamine. Out of five different subtypes, mRNA of D5 (=D1b) dopamine receptor is very abundant in the gastric epithelium. D1 receptor selective dopamine agonists have been shown to protect against experimental gastro-duodenal lesions. AIMS: To test the hypothesis that protective effects of dopamine involve D5 receptors, mucosal lesions were induced in D5 receptor deficient (KO) and wild-type (WT) mice using cysteamine. Morphology and gastric acid secretion of D5 KO mice were also studied. METHODS: Single doses of 600 mg/kg, 300 mg/kg cysteamine or vehicle were administered subcutaneously to fasted animals. After 24 h, number and severity of gastro-duodenal lesions were analyzed. Basal and histamine-induced maximal gastric acid output were measured by a stomach-sac wash-through method. RESULTS: All the KOs in the 600 mg/kg cysteamine group died within 4 h showing symptoms of toxicity while three out of four WTs survived (P<0.05). Mortality after 300 mg/kg cysteamine was significantly higher in KOs versus the WTs: 6/14 versus 2/11, P<0.05. Gastric lesion-index was also significantly higher in KOs (median, middle quartile): four (3-9) versus 0 (0-0), P<0.05. Duodenal lesions did not develop from this single dose of cysteamine in either genotype. Basal and histamine-induced maximal gastric acid output were comparable in the two genotypes. CONCLUSIONS: This study demonstrates that loss of D5 receptor causes mucosal vulnerability and increased toxicity of cysteamine in genetically manipulated mice. Thus, D5 receptor subtype is indeed likely to be involved in protective effects of dopamine in the stomach.
Asunto(s)
Cisteamina/farmacología , Citoprotección/fisiología , Receptores de Dopamina D1/fisiología , Animales , Ácido Gástrico/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Inmunohistoquímica , Masculino , Ratones , Ratones Noqueados/genética , Receptores de Dopamina D1/deficiencia , Receptores de Dopamina D1/genética , Receptores de Dopamina D5 , Valores de ReferenciaRESUMEN
BACKGROUND: Changes in right ventricular mass and ejection fraction after single-lung transplantation for pulmonary hypertension are poorly understood. METHODS: To complement functional data provided by echocardiography, radionuclide ventriculography, and right heart catheterization, magnetic resonance imaging was used to assess right ventricular function in 5 single-lung transplant recipients with preoperative pulmonary hypertension and right ventricular dysfunction (right ventricular ejection fraction, 0.21 +/- 0.09). The right and left ventricular mass, ejection fraction, and mass ratio (left ventricular mass/right ventricular mass) were calculated from the magnetic resonance images. RESULTS: The mean pulmonary artery pressure fell from 72 +/- 18 to 21 +/- 8 mm Hg after transplantation. At 3 months after transplantation both the left ventricular and right ventricular ejection fractions approached normal values, as shown by both radionuclide ventriculography and magnetic resonance imaging, but the right ventricular mass remained abnormally high with slightly low mass ratios. By 1 year both the left ventricular and right ventricular masses had regressed to normal with near-normal mass ratios. CONCLUSIONS: Right ventricular performance returns to nearly normal early after transplantation, but the right ventricular mass regresses over a more prolonged time. Cine magnetic resonance imaging provides a noninvasive means of assessing changes in right ventricular function and mass after lung transplantation.