RESUMEN
The bicipital aponeurosis (BA) is a fascial expansion which arises from the tendon of biceps brachii and dissipates some of the force away from its enthesis. It helps in dual action of biceps brachii as supinator and flexor of forearm. The aim of the present work was to study the morphology of BA. Thirty cadavericupper limbs (16 right and 14 left side limbs) were dissected and dimensions ofthe BA were noted. The average width of aponeurosis at its commencement on the right was 15.74 mm while on the left it was 17.57 mm. The average angle between tendon and aponeurosis on the right was 21.16° and on the left it was 21.78°. The fibres from the short head of the biceps brachii contributed to the formation of proximal part of aponeurosis. Fascial sheath over the tendon oflong head of biceps brachii was seen to form the distal part of the aponeurosis. In 5 cases, large fat globules were present between the sheath and the tendon. Histologically: The aponeurosis showed presence of thick collagen bundles. Fascials heath covering the tendon of long head extended towards the aponeurosis and passed superficial to the tendon of biceps. Blood vessels and adipose tissue were found to be present between fascial sheath and the tendon. This morphological description of BA may be helpful 1) in elucidating the dynamic role that BA plays in normal functioning and 2) to the surgeons in the repair of ruptured biceps brachii tendon.
Asunto(s)
Fascia/anatomía & histología , Tendones/anatomía & histología , Cadáver , Humanos , Músculo Esquelético/anatomía & histologíaRESUMEN
The vasospastic diseases and chronic pain related to lower limb have been successfully treated by surgical ablation of lumbar sympathetic trunk for last 80 years.Precise knowledge of anatomy of lumbar sympathetic trunk and its adjoining structures is mandatory for safe and uncomplicated lumbar and spinal surgeries.We aim to study the detailed anatomy of entry and exit of lumbar sympathetic trunk, the number, dimensions and location of lumbar ganglia in relation to lumbar vertebra. Thorough dissection was carried out in 30 formalin embalmed cadavers available in the Department of Anatomy, Pravara Institute of Medical Sciences (PIMS), Rural Medical College (RMC), Loni, Maharashtra. A total of 238 ganglia were observed in 60 lumbar sympathetic trunks. The sympathetic trunk traversed dorsal to the crus of diaphragm in 72.6% and in 13.3% it entered dorsal to the medial arcuate ligament. The most common site of the location of lumbar ganglia was in relation to the second lumbar vertebra, sometimes extending up to the L2-L3 vertebral disc. There was a medial shift of sympathetic trunk in lumbar region and it coursed over sacral promontory to reach the pelvic region in 96% of specimens. These variations should be kept in mind in order to prevent hazardous complications like accidental avulsion of first lumbar ganglia and genitofemoral neuritis.
Asunto(s)
Ganglios Simpáticos/anatomía & histología , Vértebras Lumbares/anatomía & histología , Región Lumbosacra/anatomía & histología , Sistema Nervioso Simpático/anatomía & histología , Anciano , Cadáver , Disección , Femenino , Humanos , Vértebras Lumbares/inervación , Masculino , Persona de Mediana EdadRESUMEN
India and other countries in Asia are experiencing rapidly escalating epidemics of type 2 diabetes (T2D) and cardiovascular disease. The dramatic rise in the prevalence of these illnesses has been attributed to rapid changes in demographic, socioeconomic, and nutritional factors. The rapid transition in dietary patterns in India-coupled with a sedentary lifestyle and specific socioeconomic pressures-has led to an increase in obesity and other diet-related noncommunicable diseases. Studies have shown that nutritional interventions significantly enhance metabolic control and weight loss. Current clinical practice guidelines (CPGs) are not portable to diverse cultures, constraining the applicability of this type of practical educational instrument. Therefore, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed and then customized per regional variations in India. The resultant India-specific tDNA reflects differences in epidemiologic, physiologic, and nutritional aspects of disease, anthropometric cutoff points, and lifestyle interventions unique to this region of the world. Specific features of this transculturalization process for India include characteristics of a transitional economy with a persistently high poverty rate in a majority of people; higher percentage of body fat and lower muscle mass for a given body mass index; higher rate of sedentary lifestyle; elements of the thrifty phenotype; impact of festivals and holidays on adherence with clinic appointments; and the role of a systems or holistic approach to the problem that must involve politics, policy, and government. This Asian Indian tDNA promises to help guide physicians in the management of prediabetes and T2D in India in a more structured, systematic, and effective way compared with previous methods and currently available CPGs.
Asunto(s)
Algoritmos , Enfermedades Cardiovasculares/dietoterapia , Diabetes Mellitus Tipo 2/dietoterapia , Angiopatías Diabéticas/dietoterapia , Promoción de la Salud , Terapia Nutricional , Obesidad/dietoterapia , Pueblo Asiatico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/prevención & control , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/prevención & control , Dieta , Femenino , Predisposición Genética a la Enfermedad , Guías como Asunto , Disparidades en Atención de Salud , Humanos , India/epidemiología , Estilo de Vida , Masculino , Terapia Nutricional/métodos , Obesidad/epidemiología , Obesidad/prevención & control , Factores de RiesgoRESUMEN
The size and shape of the thyroid gland is subject to much variation, as stated by Wood Jones. Literature is replete with a large number of variations of the gland. By utilizing various techniques like gross dissection, histology, developmental anatomy, and recently thyroid scans and scintigraphy, some common and certain rare anomalies of the thyroid with their possible developmental bases are described in the literature. An attempt has been made to study the thyroid glands in 90 male cadavers available in our department, with ages ranging from 60 to 75 years with mean height of 5'4". The parameters that were observed included the length and width of lobes, presence or absence of pyramidal lobe, levator glandulae thyroideae, and isthmus with its relation to the tracheal rings. The average length of the right lobe was 4.32 cm, and the left lobe was 4.22 cm. The thickness of the right lobe was 1.13 cm, and the left lobe was 1.18 cm. Pyramidal lobe was present in 34 (37.77%) cases, frequently arising from the left lobe, while the levator glandulae thyroideae was present in 27 (30%) instances, mostly attached superiorly to the body of the hyoid bone. The isthmus was absent in 15 (16.66%) cases; its relation with the tracheal rings greatly varied from the cricoid cartilage to the fourth tracheal ring. Knowledge of variations of the thyroid assumes significance as this has relevance in the resection of thyroid, tumours, and tracheostomy.
Asunto(s)
Glándula Tiroides/anatomía & histología , Tráquea/anatomía & histología , Anciano , Cadáver , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Glándula Tiroides/fisiología , Tráquea/fisiologíaRESUMEN
Endoscopic injection treatment for VUR appears to have less success rate than open surgical treatment, even in Gr 3 VUR. Economics of use of deflux injection and its success rate do not suit Indian milieu. To achieve high success rate of Atlanta group in endoscopic injection treatmnent , requires a longer learning curve and yet it has not achieved success rate of 96-98% achieved by open surgical techniques. Recent addition of modified extravesical reimplantation technique has reduced significantly the post operative pain and patient can be discharged within 2 days from the hospital.
RESUMEN
BACKGROUND: Staphylococcus aureus infective endocarditis (IE) associated with injection of new psychoactive substances (NPS) in Edinburgh from 2014 to 2016 was observed. We compared these infections with a series of S. aureus IE cases in a non-injecting population within Edinburgh. METHODS: NPS-associated S. aureus IE diagnosed between 1 January 2014 and 31 May 2016 in persons who inject drugs (PWID) were compared with a series of S. aureus IE cases from non-PWID. RESULTS: There was a fourfold increase in the annual incidence of S. aureus IE, mainly due to NPS use in PWID. A larger vegetation diameter was seen on echocardiogram in PWID vs non-PWID (median 1.7 cm vs 0.65 cm; p = 0.009) with more embolic complications in PWID (15 PWID vs 1 non-PWID; p = 2.1 x 10-7) but no difference in 90-day mortality (2 PWID vs 4 non-PWID; p = 0.39). CONCLUSIONS: NPS-associated S. aureus IE correlated with complications, such as deep organ embolic abscesses, that were different from non-PWID S. aureus IE. The alarming increase in incidence resolved with targeted public health and legislative measures.
Asunto(s)
Endocarditis Bacteriana/epidemiología , Infecciones Estafilocócicas/epidemiología , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Anciano , Ecocardiografía , Embolia/microbiología , Endocarditis Bacteriana/diagnóstico por imagen , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/mortalidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Psicotrópicos , Escocia/epidemiología , Infecciones Estafilocócicas/etiología , Staphylococcus aureusRESUMEN
Earlier reports from our laboratory showed that Abelson virus-induced, highly malignant and liver metastatic RAW117-H10 cells, but not the parental, less metastatic RAW117-P cells, inhibited both T-cell and B-cell mitogen-induced proliferation of syngeneic normal murine spleen cells. Similar inhibition was also noted when RAW117-H10 cell surface molecules extracted with butanol were used instead of whole tumor cells. In this report we describe the suppressive properties of the butanol-extracted RAW117-H10 cell surface molecules on other immune functions and the isolation/purification of a molecule from RAW117-H10 cell butanol extract which shows inhibitory activity. The immunosuppressive molecules also inhibit natural killer cell-mediated cytotoxicity, lymphokine-activated killer cell-mediated cytotoxicity, and bone marrow colony-forming unit-granulocyte-macrophage colony formation, but not colony-forming unit-fibroblast colony formation. The suppressive molecules inhibit interleukin 2 production by the T-lymphocytes. One of the molecules responsible for some of the immunosuppressive activity has been isolated and purified from butanol extracts of the metastatic RAW117-H10 cells by preparative isoelectrofocusing techniques. The suppressive molecule has an isoelectric point of 4.3 with an approximate molecular weight of 70,000. Metastatic RAW117-H10 lymphoma cells therefore express immunosuppressive molecules, which may facilitate their growth and metastasis in vivo.
Asunto(s)
Inmunosupresores/aislamiento & purificación , Linfoma/inmunología , Animales , Citotoxicidad Inmunológica/efectos de los fármacos , Inmunosupresores/farmacología , Interleucina-2/biosíntesis , Células Asesinas Activadas por Linfocinas/inmunología , Células Asesinas Naturales/inmunología , Virus de la Leucemia Felina/patogenicidad , Ratones , Ratones Endogámicos BALB C , Peso Molecular , Metástasis de la Neoplasia , Células Tumorales CultivadasRESUMEN
The highly malignant and metastatic RAW117-H10 cell line was developed by in vivo selection from the Abelson leukemia virus induced parental RAW117-P lymphoma. In this study we have characterized these cell lines with regard to their expression of lymphocyte and macrophage differentiation antigens, adherence, phagocytic properties, binding of various lectins, binding of antibodies to glycolipid asialo-monoganglioside, and the role of butanol extractable cell surface molecules to determine if any of these cell surface properties are associated with the malignant potential of RAW117-H10 cells. The only major difference in immunological phenotypes between RAW117-P and RAW117-H10 cells was an increased expression of Thy-1 molecules by the latter. However, the highly malignant RAW117-H10 cells bound significantly less concanavalin A, Ricinia communis agglutinin, succinylated wheat germ agglutinin, and particularly anti-asialomonoganglioside than their parental counterpart and were resistant to natural killer cell mediated cytolysis. Removal of butanol extractable cell surface molecules significantly decreased the malignancy of RAW117-H10 cells and increased their susceptibility to natural killer cell mediated cytolysis. The butanol treated RAW117-H10 cells regained high in vivo malignancy when recultured for 3 days to permit regeneration of their cell surface components. The butanol extracted RAW117-H10 cells still expressed high levels of Thy-1 indicating that this most probably represented "inappropriate" antigen expression. Since the expression of lymphocyte differentiation antigens did not correlate with the malignant behavior of the cells, we postulate that these antigenic differences merely represent phenotypic variation. The decreased malignant potential of the butanol treated RAW117-H10 cells did correlate with increased cell surface anti-asialomonoganglioside binding (glycolipid) and increased natural killer cell susceptibility.
Asunto(s)
Antígenos de Neoplasias/análisis , Antígenos de Superficie/análisis , Gangliósido G(M1) , Linfocitos/fisiología , Linfoma/fisiopatología , Animales , Butanoles , Línea Celular , Citotoxicidad Inmunológica , Glicoesfingolípidos/análisis , Células Asesinas Naturales/inmunología , Linfoma/patología , Ratones , Metástasis de la Neoplasia , Fagocitosis , Receptores de Antígenos de Linfocitos B/análisis , Receptores Mitogénicos/análisis , Formación de Roseta , Propiedades de SuperficieRESUMEN
AIMS: Patent foramen ovale (PFO) has been implicated in the etiology of a number of different pathologies, including cryptogenic stroke, decompression sickness in divers, etc. It can act as a channel for paradoxical embolism. PFO is not an uncommon condition, with a probe-patency in 15-35% population. The fossa ovalis (FOv) varies in size and shape from heart to heart; the prominence of annulus FOv also varies. The entire FOv may be redundant and aneurysmal. The anatomico-functional characterization of interatrial septum seems to be of paramount importance for both atrial septal defect (ASD) and PFO, not only for the device selection, but also for the evaluation of the outcome of this procedure. METHOD: This study was conducted in 50 apparently normal hearts available in Department of Anatomy. After opening the right atrium, the shape of FOv was observed. The size was measured with the digital vernier caliper; the prominence and extent of limbus, and the redundancy or otherwise of FOv were noted; probe patency was confirmed. RESULTS: In the majority, FOv was oval (82%); average transverse diameter was 14.53mm and vertical 12.60mm. In 90%, the rim of the annulus was raised; in 20%, a recess was found deep to the margin of the annulus; and 18% showed probe patency. CONCLUSION: As no study of this nature has been carried out in the Indian population, this provides pertinent information on the morphology of FOv, which may be useful for device selection in treating ASD and PFO.
Asunto(s)
Ecocardiografía Transesofágica/métodos , Foramen Oval Permeable/diagnóstico , Foramen Oval/anatomía & histología , Tabique Interatrial/anatomía & histología , Cadáver , Humanos , Valores de ReferenciaRESUMEN
In this report we describe the characteristics of an immunosuppressive molecule from an Abelson Leukemia Virus transformed highly malignant and metastatic RAW117-H10 murine large cell lymphoma cells. Our studies have shown that the mitomycin-c treated or irradiated RAW117-H10 cells very significantly (p < 0.001) inhibited the nitrogen induced proliferation of normal Balb/c splenocytes. The cell surface extracts from the immunosuppressive RAW117-H10 lymphoma cells significantly inhibited the in vitro T cell or NK/LAK cell functions. Our in vivo studies demonstrated that there was a significant suppression of immune response in the Balb/c mice bearing RAW117-H10 cells when compared with mice bearing low metastatic parental RAW117-P cells or control mice. Subsequently we isolated and purified the main molecule responsible for this immunosuppression and found that the molecule is a glycoprotein with a molecular weight of 70 kD with an isoelectric point of 4.3, which cross reacted with antibodies to murine leukemia virus envelope gp70 molecules. Further analysis using immunoelectrophoresis, molecular probing techniques, and mannose specific lectin binding assay revealed that the immunosuppressive 70 kD molecule, is different from the wild type MLV envelope gp70 molecule and thus appears to be an altered gp70 molecule. These studies demonstrate that the metastatic lymphoma associated immunosuppression may facilitate the growth and metastasis of tumor cells. Our results also elucidate the possible mechanism(s) of retrovirus induced immunosuppression and the molecular basis of this retroviral envelope-mediated process in viral pathogenesis and tumor progression.
Asunto(s)
Virus de la Leucemia Murina de Abelson/genética , Transformación Celular Neoplásica , Productos del Gen env/inmunología , Glicoproteínas/inmunología , Activación de Linfocitos , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/virología , Linfocitos T/inmunología , Proteínas del Envoltorio Viral/inmunología , Animales , Línea Celular , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/efectos de la radiación , Terapia de Inmunosupresión , Células Asesinas Activadas por Linfocinas/inmunología , Células Asesinas Naturales/inmunología , Linfoma de Células B Grandes Difuso/patología , Macrófagos/efectos de los fármacos , Macrófagos/efectos de la radiación , Ratones , Ratones Endogámicos BALB C , Mitomicina/farmacología , Metástasis de la NeoplasiaRESUMEN
Thirty-one cases of acute leukemia with blast cells greater than or equal to 70% positive for the hematopoietic stem cell Ag, CD34 (MY10, HPCA-1), were identified from the University of Nebraska Medical Center and The Johns Hopkins Oncology Center over an 18-month period. Fourteen of the cases were classified as early B-lineage ALL, 3 cases were other ALL subtypes, and 14 of the cases were ANLL. Five of the 17 cases of ALL expressed one or more myeloid-associated surface Ags, 3 ANLL cases expressed CD10 (CALLA, J5), and T-lymphoid Ags were present in 12 of 31 cases (1 T-cell ALL, 3 of 16 B-lineage ALL cases, and 8 of 14 ANLL cases). Eleven of 12 CD34+ ALL cases studied had abnormal karyotypes; only 7 of 12 CD34+ ANLL cases studied had abnormal karyotypes, and 3 of these were CD10+ ANLL. Six cases were Ph1 positive, including the one mature B cell ALL, 4 early B-lineage ALL, and 1 CD10+ ANLL case. Good and poor prognosis subgroups of high frequency of expression of CD34 leukemias could be identified, generally, as would have been predicted by previously defined criteria. Thus, of the 10 Ph1-negative early B-lineage ALL patients, 9 achieved CR (90%). At the other extreme, the CR rate of CD10- ANLL was 4 of 11 (36%). The leukemias characterized by greater than or equal to 70% of cells positive for CD34 form a relatively undifferentiated subset of the leukemias which may show features associated with more than one lineage, and if CD10- and myeloid morphology, may respond poorly to therapy.
Asunto(s)
Antígenos de Diferenciación/análisis , Antígenos de Neoplasias/análisis , Leucemia Mieloide Aguda/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Antígenos CD34 , ADN de Neoplasias/genética , Genes de Inmunoglobulinas , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia Mieloide Aguda/clasificación , Leucemia Mieloide Aguda/patología , Glicoproteínas de Membrana/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/clasificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Receptores de Antígenos de Linfocitos T/genéticaRESUMEN
In this study, in vitro and in vivo antitumor effects of mononuclear cells from human umbilical cord blood cells (UCBCs) and peripheral blood stem cells (PBCs) harvest obtained by leukapheresis were compared. Interleukin 2 (IL-2)-activated mononuclear cells from UCBCs showed increased cytotoxicity against K562 and Raji hematopoietic malignant cells compared with PBCs (P < 0.05). After IL-2 activation, both UCBCs and PBCs showed significant cytotoxicity against MDA-231 human breast cancer cells. The UCBC population involved in this antitumor activity appeared to be CD56+ natural killer precursors. The cytotoxicity of UCBCs was inhibited in the absence of Ca2+ (P < 0.05), supporting a perforin/granzyme-mediated target of cell lysis. In addition, antibodies to Fas ligand blocked cytotoxic activity, suggesting that some of the antitumor cytotoxicity was Fas ligand mediated. In vivo antitumor effects of UCBCs and PBCs were studied using a human leukemic cell-bearing severe combined immunodeficient mouse model. There was a significant increase in the survival of K562 leukemia-bearing mice that also received 5 million in vitro IL-2-activated UCBCs or PBCs i.v. on days 3 and day 5 after tumor transplantation compared with untreated mice (P < 0.01). Similar antitumor cytotoxicity of UCBCs and PBCs was also observed against MDA-231 human breast cancer grown in severe combined immunodeficient mice (P < 0.01). These studies suggest that IL-2-activated UCBCs may be a useful source of cellular therapy for patients with hematological malignancies and breast cancer.
Asunto(s)
Neoplasias de la Mama/terapia , Sangre Fetal/inmunología , Trasplante de Células Madre Hematopoyéticas , Leucemia/terapia , Animales , Antígeno CD56/análisis , Citotoxicidad Inmunológica , Proteína Ligando Fas , Femenino , Humanos , Inmunofenotipificación , Células Asesinas Naturales/inmunología , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/fisiología , Ratones , Ratones SCID , Perforina , Proteínas Citotóxicas Formadoras de Poros , Linfocitos T/inmunología , Células Tumorales CultivadasRESUMEN
Cell-surface molecules, particularly glycoconjugates, appear to be involved in the in vivo homing of hematopoietic stem and progenitor cells and in their interactions with hematopoietic stromal cells. To study the role of cell-surface molecules of hematopoietic stem cells, the expression of some surface molecules was altered using n-butanol treatment. We examined the in vivo and in vitro colony-forming abilities, in vivo homing patterns, and cell-surface lectin receptor expression of butanol-treated bone marrow cells (BMC) from BDF1 mice. The butanol-treated/-modified BMC formed an increased number of significantly larger spleen colonies (CFU-S) in lethally irradiated (1050 rad) mice. The butanol-treated BM formed significantly larger in vitro granulocyte-macrophage progenitor cell colonies (CFU-C) and in vitro fibroblastic colonies (CFU-F), although the number of such colonies was not significantly altered. The homing pattern of butanol-treated BMC was studied by comparing the distribution in lethally irradiated mice of intravenously injected 51Cr-labeled butanol-treated BMC with that of untreated cells. The butanol treatment altered the in vivo homing pattern of these cells, with increased homing to liver, spleen, and bone marrow and decreased homing to thymus, lung, and mesenteric lymph nodes. Flow-cytometric analyses of butanol-treated BMC showed an increased expression of receptors for the lectins concanavalin A (conA) and wheat germ agglutinin (WGA), indicating an increased expression of mannosyl and galactosyl residues, which are known sugar moieties in hematopoietic stem/progenitor cell homing. These results indicate that cell surface modifications can influence homing and growth of transplanted BMC and that butanol treatment is a useful tool for studying the mechanisms of hematopoietic stem/progenitor cell homing in vivo and for further characterizing the molecules involved in this process.
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Células de la Médula Ósea , Médula Ósea/efectos de los fármacos , Butanoles/farmacología , Animales , Radioisótopos de Cromo , Ensayo de Unidades Formadoras de Colonias , Femenino , Citometría de Flujo , Células Madre Hematopoyéticas/citología , Hígado/citología , Macrófagos/citología , Ratones , Bazo/citología , Irradiación Corporal TotalRESUMEN
Sleep perturbations including fragmented sleep with frequent night-time awakenings and daytime naps are common in patients with Alzheimer's disease (AD), and these daily disruptions are a major factor for institutionalization. The objective of this study was to investigate if sleep-wake patterns are altered in 5XFAD mice, a well-characterized double transgenic mouse model of AD which exhibits an early onset of robust AD pathology and memory deficits. These mice have five distinct human mutations in two genes, the amyloid precursor protein (APP) and Presenilin1 (PS1) engineered into two transgenes driven by a neuron-specific promoter (Thy1), and thus develop severe amyloid deposition by 4 months of age. Age-matched (4-6.5 months old) male and female 5XFAD mice were monitored and compared to wild-type littermate controls for multiple sleep traits using a non-invasive, high throughput, automated piezoelectric system which detects breathing and gross body movements to characterize sleep and wake. Sleep-wake patterns were recorded continuously under baseline conditions (undisturbed) for 3 days and after sleep deprivation of 4h, which in mice produces a significant sleep debt and challenge to sleep homeostasis. Under baseline conditions, 5XFAD mice exhibited shorter bout lengths (14% lower values for males and 26% for females) as compared to controls (p<0.001). In females, the 5XFAD mice also showed 12% less total sleep than WT (p<0.01). Bout length reductions were greater during the night (the active phase for mice) than during the day, which does not model the human condition of disrupted sleep at night (the inactive period). However, the overall decrease in bout length suggests increased fragmentation and disruption in sleep consolidation that may be relevant to human sleep. The 5XFAD mice may serve as a useful model for testing therapeutic strategies to improve sleep consolidation in AD patients.
Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Privación de Sueño/fisiopatología , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Homeostasis/fisiología , Humanos , Masculino , Ratones Transgénicos , Presenilina-1/genética , Presenilina-1/metabolismo , Caracteres Sexuales , Sueño/fisiología , Factores de TiempoRESUMEN
Smoking is an established risk factor for pancreatic cancer (PC), but late diagnosis limits the evaluation of its mechanistic role in the progression of PC. We used a well-established genetically engineered mouse model (LSL-K-ras(G12D)) of PC to elucidate the role of smoking during initiation and development of pancreatic intraepithelial neoplasia (PanIN). The 10-week-old floxed mice (K-ras(G12D); Pdx-1cre) and their control unfloxed (LSL-K-ras(G12D)) littermates were exposed to cigarette smoke (total suspended particles: 150 mg/m(3)) for 20 weeks. Smoke exposure significantly accelerated the development of PanIN lesions in the floxed mice, which correlated with tenfold increase in the expression of cytokeratin19. The systemic accumulation of myeloid-derived suppressor cells (MDSCs) decreased significantly in floxed mice compared with unfloxed controls (P<0.01) after the smoke exposure with the concurrent increase in the macrophage (P<0.05) and dendritic cell (DCs) (P<0.01) population. Further, smoking-induced inflammation (IFN-γ, CXCL2; P<0.05) was accompanied by enhanced activation of pancreatic stellate cells and elevated levels of serum retinoic acid-binding protein 4, indicating increased bioavailability of retinoic acid which contributes to differentiation of MDSCs to tumor-associated macrophages (TAMs) and DCs. TAMs predominantly contribute to the increased expression of heparin-binding epidermal growth factor-like growth factor (EGFR ligand) in pre-neoplastic lesions in smoke-exposed floxed mice that facilitate acinar-to-ductal metaplasia (ADM). Further, smoke exposure also resulted in partial suppression of the immune system early during PC progression. Overall, the present study provides a novel mechanism of smoking-induced increase in ADM in the presence of constitutively active K-ras mutation.
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Carcinoma in Situ/patología , Factor de Crecimiento Similar a EGF de Unión a Heparina/biosíntesis , Macrófagos/citología , Células Mieloides/citología , Neoplasias Pancreáticas/patología , Fumar/efectos adversos , Células Acinares/patología , Animales , Carcinoma Ductal Pancreático/patología , Diferenciación Celular/genética , Quimiocina CXCL2/biosíntesis , Células Dendríticas/citología , Progresión de la Enfermedad , Genes ras/genética , Inflamación/inducido químicamente , Interferón gamma/biosíntesis , Queratina-19/biosíntesis , Macrófagos/metabolismo , Metaplasia/inducido químicamente , Ratones , Ratones Transgénicos , Conductos Pancreáticos/patología , Células Estrelladas Pancreáticas/metabolismo , Receptores de Ácido Retinoico/metabolismo , Transducción de Señal/genética , Humo/efectos adversos , Tretinoina/metabolismoRESUMEN
Anticancer chemotherapeutic agents are effective in inhibiting growth of cancer cells in vitro and in vivo, however, toxicity to normal cells is a major problem. In this study, we assessed the effect of a novel IH636 grape seed proanthocyanidin extract (GSPE) to ameliorate chemotherapy-induced toxic effects in cultured Chang epithelial cells, established from nonmalignant human tissue. These cells were treated in vitro with idarubicin (Ida) (30 nM) or 4-hydroxyperoxycyclophosphamide (4HC) (1 microg/ml) with or without GSPE (25 microg/ml). The cells were grown in vitro and the growth rate of the cells was determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; thiazolyl blue] assay. Our results showed that GSPE decreased the growth inhibitory and cytotoxic effects of Ida as well as 4HC on Chang epithelial cells in vitro. Because these chemotherapeutic agents are known to induce apoptosis in the target cells, we analyzed the Chang epithelial cells for apoptotic cell population by flow cytometry. There was a significant decrease in the number of cells undergoing apoptosis following treatment with GSPE. We also found increased expression of the anti-apoptotic protein Bcl-2 in GSPE-treated cells using western blot techniques. Thus, these results indicate that GSPE can be a potential candidate to ameliorate the toxic effects associated with chemotherapeutic agents and one of the mechanisms of action of GSPE includes upregulation of Bcl-2 expression.
Asunto(s)
Antocianinas/farmacología , Antineoplásicos/efectos adversos , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Ciclofosfamida/análogos & derivados , Proantocianidinas , Rosales/química , Semillas/química , Antibióticos Antineoplásicos/farmacología , Apoptosis/fisiología , Western Blotting , Línea Celular , Supervivencia Celular , Ciclofosfamida/farmacología , Células Epiteliales , Citometría de Flujo , Genes bcl-2/fisiología , Humanos , Idarrubicina/farmacologíaRESUMEN
In the present study, the immune status of syngeneic Balb/c animals bearing a poorly metastatic RAW117-P lymphoma and the highly malignant liver metastatic variant RAW117-H10 lymphoma were measured and compared to control animals with no known tumor. The immune status was evaluated by performing various analyses of spleen cells for the frequencies of immune cells using flow cytometry, in vitro mitogen response and in vitro NK cell-mediated cytotoxicity assays on days 6, 9 and 12 after tumor transplantation. The results of these studies indicated that from day 9 onwards, some of the immune response of the RAW117 lymphoma-bearing animals appeared to decrease compared to control animals. In order to boost the immune response of the tumor-bearing immunosuppressed animals, recombinant interleukin-2 (rIL-2) was administered to RAW117-H10 lymphoma-bearing animals. The immune status of tumor-bearing animals treated with rIL-2 was evaluated on days 5, 10 and 15 after tumor transplantation using similar analyses of spleen cells as described above. The results of these experiments indicated that IL-2 treatment increased splenic levels of cytotoxic cells, and decreased the in vivo tumorigenicity/metastasis of metastatic RAW117-H10 lymphoma cells. rIL-2 administration resulted in a significant increase in survival of tumor-bearing animals, and histological studies showed significantly lower tumor burdens in treated animals: it appears that rIL-2 has a beneficial therapeutic effect on immunosuppressive metastatic RAW117 lymphoma.
Asunto(s)
Tolerancia Inmunológica , Interleucina-2/uso terapéutico , Linfoma/terapia , Animales , Femenino , Citometría de Flujo , Activación de Linfocitos , Linfoma/inmunología , Ratones , Ratones Endogámicos BALB C , Metástasis de la Neoplasia , Proteínas Recombinantes/uso terapéutico , Células Tumorales CultivadasRESUMEN
A syngeneic murine model system was used to study the immunobiology of metastasis. The highly malignant RAW117-H10 cell line was compared to the less malignant parental RAW117-P cell line from which it was derived, for expression of cell surface antigens. Using rabbit antisera, two major glycoprotein antigens were detected on the tumor cell surfaces. Antigen-I was uniformly distributed over the surface of these cells whereas antigen-II had a patchy, punctate distribution. Antigen-I was displayed less on RAW117-H10 cells than on RAW117-P cells, while the expression of the other serologically distinct antigen (antigen-II) was increased on RAW117-H10 cells compared to the less malignant parental (RAW117-P) cells. This differential antigen expression was assessed by immunodiffusion, a 125I-labeled protein-A binding assay, flow cytometry and rocket immunoelectrophoresis. Both these antigens had a molecular weight of 70,000 daltons. Antigen-I bound the lectin concanavalin-A whereas antigen-II did not, suggesting that antigen-I might be the viral envelope glycoprotein gp70. The identity of antigen-II is presently unknown. Syngeneic Balb/c mice injected with highly malignant and metastatic RAW117-H10 cells coated with antiserum to antigen-I were protected from early death; this effect was not seen with RAW117-H10 cells coated with antiserum to antigen-II. The opsonizing qualities of these antisera may be different due to antibody to antigen-II being shed more rapidly than antibody to antigen-I.