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Beam-column joints are crucial load transmission zones because they face concentrated forces from both the beams and the columns. High shear and axial stresses caused by these concentrated forces in the area of the joint may result in decreased joint strength. This article proposes a new beam-to-column connection developed for precast concrete-resisting frames. Concrete mixtures are enhanced mechanically by adding nano silica as it increases compressive strength, flexural strength, and abrasion resistance. Within the concrete, it creates a solid, gel-like matrix that fills voids and strengthens the whole construction. In this study, three reinforced concrete beam-column joint specimens were cast with fly ash, the other three with nano-silica and fly ash, and one sample with nano-silica and a control mix without admixtures was cast. Specimen cast using fly ash and nano-silica is subjected to cyclic loading after 28 days of curing. A load capacity of 100 kN was imposed on the column during testing. It was observed that a gradual increase in fly ash decreased the compressive and flexural strength of the beam-column joints. This decrease in strength was addressed by adding 2.5% nano-silica. Nano silica acts as a nucleus to bond tightly with cement particles during hydration. The results showed that the flexural strength equivalent to that of a controlled specimen can be achieved by adding nano-silica at 2.5% and fly ash at 60%. The highest loading of 38.1 kN can be applied to the specimen with nano-silica without fly ash. Although a higher axial compression ratio can improve the bearing capacity and initial stiffness, it can also reduce deformation capacity and flexibility.
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CONTEXT: Although antisnake venom (ASV) has been used for many years, selection of an optimal dose is a debated issue due to acute shortage of ASV in India. Despite evidence for smaller doses, most centers still use conventional doses. AIMS: This study aimed to evaluate the effects of two different dosage regimens on the outcome of patients with snake envenomation, using a retrospective descriptive analysis of patient records admitted in our hospital. SETTINGS AND DESIGN: A retrospective descriptive case series study was conducted from hospital records consisting 155 snakebite patients from June 2013 to January 2014. MATERIALS AND METHODS: PATIENTS WERE DIVIDED INTO TWO GROUPS: Low dose ASV group (received <10 vials) and high dose ASV group (received ≥10 vials). Various complications were compared among these two groups. RESULTS: The mean dose of ASV used in high dose, and low-dose group was 14.7 ± 5.3 and 4.2 ± 2.3, respectively. In low dose group, 20.5% of patients had acute kidney injury, whereas it was 10.9% in high dose group. In low dose group, 12.3% patients had neuroparalysis severe enough to require ventilator support and mortality rate was 5.5% which was comparable to the high-dose group (15.8% had neuroparalysis requiring ventilator support and a mortality rate of 8.5%). CONCLUSION: This study demonstrated that the low dose ASV regimen in poisonous snake bites along with supportive treatment as necessary is as efficacious as high dose regimen and has comparable complications.
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Spontaneous uterine scar rupture can be lethal in pregnant women. A spontaneous uterine scar rupture in the early mid-trimester is rare and difficult to diagnose. This is a case of a 30-year-old woman (G2P1L1) at 19 weeks of gestation and having undergone a previous caesarean section presented with acute abdomen in shock. Laparotomy revealed a uterine scar rupture, which was resutured after evacuation of products of conception. This case merits that the uterine rupture should be considered as a differential diagnosis in pregnant women presenting with acute abdomen. In this case, although there was uterine rupture in the second trimester and a complete placental separation, fetus was alive which is quite unusual in patients presenting with rupture uterus.
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Abdomen Agudo/diagnóstico , Cesárea , Cicatriz/patología , Segundo Trimestre del Embarazo , Rotura Espontánea/diagnóstico , Rotura Uterina/diagnóstico , Útero/patología , Abdomen Agudo/etiología , Adulto , Cicatriz/cirugía , Diagnóstico Diferencial , Femenino , Humanos , Placenta , Embarazo , Complicaciones del Embarazo/cirugía , Resultado del Embarazo , Rotura Espontánea/complicaciones , Rotura Espontánea/patología , Rotura Espontánea/cirugía , Rotura Uterina/patología , Rotura Uterina/cirugía , Útero/cirugíaRESUMEN
We report a case of bilateral arterial variation in the upper extremities of a male cadaver. In the left upper extremity, it was observed that the ulnar artery was arising from axillary artery. This ulnar artery was superficial throughout its course at the medial aspect of the arm and forearm. It was highly tortuous and did not have any branches either in the arm or forearm. It ended as the superficial palmar arch in the palm. However the brachial artery entered the cubital fossa and divided into radial and common interosseus arteries. In contrast, the right upper extremity was having normal brachial artery which was terminated into the ulnar and radial arteries at the cubital fossa. However, there was an accessory brachial artery present at the arm and ended at the cubital fossa. We believe that these anatomical variations are because of abnormal developmental vascular pattern in the region. In clinical practice, accurate knowledge of the arterial variations of upper extremity is of considerable importance in case of reparative surgeries and fracture management. They are of interest to the vascular and plastic surgeons.
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Arteria Axilar/anomalías , Arteria Braquial/anomalías , Arteria Cubital/anomalías , Brazo , Cadáver , Antebrazo , Mano , Humanos , Masculino , Persona de Mediana EdadRESUMEN
It is important to factor-in the characteristics of patients that may affect treatment, outcome and resource when making clinical and administrative decisions, plans or policies. For some two and half decades there have been efforts to construct and refine instruments that endeavour to capture the concept of comorbidity. This paper focuses on such comorbidity measures that are derived from diagnoses information recorded in administrative datasets. The pros and cons of the popular weighted Charlson and Charlson-based indexes are discussed. Means to improve the comorbidity indexes are considered including the very concept and definition of comorbidity.
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Indización y Redacción de Resúmenes/normas , Comorbilidad , Bases de Datos Factuales/normas , Administración Hospitalaria , Australia , Humanos , Clasificación Internacional de EnfermedadesRESUMEN
This study uses hospital administrative data to ascertain the differences in the patient characteristics, process and outcomes of care between the Emergency Department (ED) triage categories of patients admitted from an ED presentation into a large metropolitan teaching hospital with a Stroke Care Unit. Bayesian Networks (BNs) derived from the administrative data were used to provide the descriptive models. Nearly half the patients in each stroke subtype were triaged as 'Urgent' (to be seen within 30 minutes). With a decrease in the urgency of triage categories, the proportion admitted within 8 hours decreased dramatically and the proportion of formal discharge increased. Notably, 45% of transient ischaemic attacks (TIAs) were categorized as 'Semi-urgent' (to be attended within 60 minutes), indicating an opportunity to improve emergency assessment of TIAs. The results illustrate the utility of hospital administrative data and the applicability of BNs for review of the current triage practices and subsequent impact.
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Servicios Médicos de Urgencia/estadística & datos numéricos , Admisión del Paciente , Accidente Cerebrovascular/terapia , Triaje/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia , Teorema de Bayes , Niño , Preescolar , Estudios de Cohortes , Femenino , Hospitales de Enseñanza , Humanos , Lactante , Recién Nacido , Tiempo de Internación , Masculino , Persona de Mediana Edad , Admisión del Paciente/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricos , Accidente Cerebrovascular/epidemiología , Factores de Tiempo , Adulto JovenRESUMEN
Mandatory and standardised administrative data collections are prevalent in the largely public-funded acute sector. In these systems the data collections are used for financial, performance monitoring and reporting purposes. This paper comments on the infrastructure and standards that have been established to support data collection activities, audit and feedback. The routine, local and research uses of these datasets are described using examples from Australian and international literature. The advantages of hospital administrative datasets and opportunities for improvement are discussed under the following headings: accessibility, standardisation, coverage, completeness, cost of obtaining clinical data, recorded Diagnostic Related Groups and International Classification of Diseases codes, linkage and connectivity. In an era of diminishing resources better utilisation of these datasets should be encouraged. Increased study and scrutiny will enhance transparency and help identify issues in the collections. As electronic information systems are increasingly embraced, administrative data collections need to be managed as valuable assets and powerful operational and patient management tools.
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Bases de Datos Factuales/normas , Administración Hospitalaria , Acceso a la Información , Australia , Sistemas de Información en Hospital , Gestión de la Información , Calidad de la Atención de SaludRESUMEN
A delicate balance in estrogen and progesterone signaling through their cognate receptors is characteristic for the physiologic state of the endometrium, and a shift in receptor isotype expression can be frequently found in human endometrial pathology. In this study, using a transgenic mouse model, we examined the mechanisms whereby alterations in progesterone receptor (PR) isotype expression leads to endometrial pathology. For an experimental model, we used transgenic mice (PR-A transgenics) carrying an imbalance in the native ratio of the two PR isoforms A and B (PR-A and PR-B) through the expression of additional A form and examined their uterine phenotype under different hormonal regimens, using various criteria. Uterine epithelial cell proliferation was augmented in PR-A transgenics and was abolished by PR antagonists. In particular, proliferative response to progesterone, independent of signaling through estrogen, was enhanced. Upon continuous exposure to estradiol and progesterone, the uteri in PR-A transgenics displayed gross enlargement, endometrial hyperplasia including atypical lesions, endometritis and pelvic inflammatory disease. Imbalanced expression of the two isoforms of PR in a transgenic model reveals multiple derangements in the regulation of uterine physiology, resulting in various pathologies including hyperplasias.
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Proliferación Celular , Hiperplasia Endometrial/patología , Endometrio , Isoformas de Proteínas/metabolismo , Receptores de Progesterona/metabolismo , Animales , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/fisiopatología , Endometrio/citología , Endometrio/patología , Endometrio/fisiología , Estradiol/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Humanos , Ratones , Ratones Transgénicos , Ovariectomía , Progesterona/metabolismo , Isoformas de Proteínas/genética , Receptores de Progesterona/antagonistas & inhibidores , Receptores de Progesterona/genética , Útero/anomalías , Útero/anatomía & histología , Útero/metabolismoRESUMEN
BACKGROUND: Perinatal viral infections of fetus are among the leading causes of congenital cataract and identifying the viral etiology is important. OBJECTIVES: To detect the presence of Rubella virus (RV), herpes simplex virus (HSV) and cytomegalovirus (CMV) in lens aspirate specimens obtained from patients with congenital cataract and relate the results with serology. SETTING AND DESIGN: Prospective study carried out in tertiary care hospital. MATERIALS AND METHODS: Fifty lens aspirates from 50 infants with congenital cataract were subjected to HSV, RV isolation and polymerase chain reaction (PCR) for detection of HSV and CMV. Reverse transcription polymerase chain reaction (RT-PCR) was applied for RV detection. Peripheral blood specimens were screened for anti-HSV, RV and CMV antibodies by enzyme-linked immunosorbant assay (ELISA). RESULTS: Rubella virus was detected in nine (18%) lens aspirates, by nRT-PCR which includes six positive by culture. HSV-2 DNA was detected in nine other lens aspirates, while CMV was not detected by PCR. Serological results did not correlate with the presence of viruses in the lens aspirates. This is the first report of detection of HSV-2 DNA in cases of congenital cataract. CONCLUSIONS: Cytomegalovirus may not be playing a significant role in causation of congenital cataract. The role of serology in identifying causative viral infection for congenital cataract needs to be re-evaluated.
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Catarata/congénito , Catarata/virología , Citomegalovirus/aislamiento & purificación , Infecciones Virales del Ojo/virología , Virus de la Rubéola/aislamiento & purificación , Simplexvirus/aislamiento & purificación , Citomegalovirus/genética , Citomegalovirus/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Reacción en Cadena de la Polimerasa/métodos , Estudios Prospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Virus de la Rubéola/genética , Virus de la Rubéola/inmunología , Simplexvirus/genética , Simplexvirus/inmunologíaRESUMEN
PURPOSE: To detect T. gondii DNA and specific antibodies in lens aspirates (LA) and peripheral blood leucocytes (PBL) of congenital cataract patients. METHODS: ELISA for T. gondii antibodies on sera nPCR for T. gondii DNA (B1 gene) on LA and PBL were performed for 52 patients. RESULTS: T. gondii DNA was detected in 29 (55.8%) of the 52 patients (LA-14, PBL-13, LA and PBL-2, and specific IgM in 2 sera). nPCR in PBL was more sensitive than ELISA (p<0.005). CONCLUSION: nPCR is a sensitive technique to detect T. gondii from LA and PBL in congenital cataract patients.
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Catarata/congénito , Cristalino/parasitología , Leucocitos/parasitología , Toxoplasma/genética , Toxoplasmosis Congénita/diagnóstico , Toxoplasmosis Ocular/diagnóstico , Animales , Anticuerpos Antiprotozoarios/análisis , Catarata/sangre , Extracción de Catarata , ADN Protozoario/análisis , Ensayo de Inmunoadsorción Enzimática , Hospitales Especializados , Humanos , India , Lactante , Oftalmología , Reacción en Cadena de la Polimerasa/métodos , Toxoplasma/inmunologíaRESUMEN
Being an intracellular parasite, Chlamydia pneumoniae disseminates to organs outside the respiratory tract and causes chronic diseases in human. Nucleic acid-based method such as polymerase chain reaction (PCR) as diagnostic test has greater sensitivity and specificity than conventional microbiological techniques. The PCR protocol consisting of touchdown technique to detect C. pneumoniae DNA using major outer membrane protein gene (MOMP) was carried out in our laboratory as described in reference paper, but analytical sensitivity reported in it was not reproducible. Hence, the PCR was optimized after modifications in annealing temperature and magnesium ion concentrations. First round PCR profile with annealing at 56 degrees C for 8 cycles followed by 32 cycles with annealing temperature maintained at 54 degrees C and second round profile modified with annealing temperature maintained at 49 degrees C had resulted in 3-fold increase in clinical sensitivity. The present work highlights the importance of optimization of PCR in laboratory settings.
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Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/aislamiento & purificación , ADN Bacteriano/análisis , ADN Bacteriano/genética , Reacción en Cadena de la Polimerasa/métodos , Proteínas de la Membrana Bacteriana Externa/genética , Infecciones por Chlamydophila/diagnóstico , Humanos , Sensibilidad y Especificidad , TemperaturaRESUMEN
BACKGROUND & OBJECTIVE: Rubella virus (RV) is one of the leading causes of childhood blindness in India. In this study we applied an optimized nested reverse transcription polymerase chain reaction (nRT-PCR) to detect RV in clinical specimens. METHODS: nRT-PCR was optimized using total RNA extracted from standard strain of RV using nested sets of primers specific for E1 open reading frame. nRT-PCR was applied onto 30 lens aspirates and corresponding peripheral blood leucocytes of 30 infants with congenital (29)/ developmental (01) cataract. Serology for anti-RV IgG and IgM antibodies was done. RV isolation was attempted using Vero and SIRC cell cultures. RESULTS: Optimized nRT-PCR was specific for RV and sensitive to detect 10 fg of RV RNA. Among 30 patients, nRT-PCR detected presence of RV in lens aspirates of 6 (20%) and 4 corresponding leucocytes. RV was isolated from 3 (10%) lens aspirates (nRT-PCR positive) of the 30 patients. Sera of these 6 patients showed presence of anti-RV IgG and IgM in one, only anti-RV IgG in 3 others and none in the other two. Of the remaining 24 patients, anti-RV IgG was detected in 3 and no anti-RV IgM antibodies in others. INTERPRETATION & CONCLUSION: Findings of our study showed that the nRT-PCR was a more sensitive and rapid technique to detect RV from lens aspirates compared to conventional methods of virus isolation and serology.
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Cristalino/virología , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Virus de la Rubéola/aislamiento & purificación , Animales , Catarata/congénito , Catarata/virología , Chlorocebus aethiops , Humanos , Lactante , Recién Nacido , ARN Viral/análisis , Rubéola (Sarampión Alemán)/congénito , Rubéola (Sarampión Alemán)/virología , Virus de la Rubéola/genética , Células VeroRESUMEN
Transforming growth factor (TGF)-beta1 is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor (ER)-alpha cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF-beta1 is necessary for the quiescence of ER-alpha-positive populations, we examined mouse mammary epithelial glands at estrus. Approximately 35% of epithelial cells showed TGF-beta1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF-beta signaling is autocrine. Nuclear Smad co-localized with nuclear ER-alpha. To test whether TGF-beta inhibits proliferation, we examined genetically engineered mice with different levels of TGF-beta1. ER-alpha co-localization with markers of proliferation (ie, Ki-67 or bromodeoxyuridine) at estrus was significantly increased in the mammary glands of Tgf beta1 C57/bl/129SV heterozygote mice. This relationship was maintained after pregnancy but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF-beta1 via the MMTV promoter suppressed proliferation of ER-alpha-positive cells. Thus, TGF-beta1 activation functionally restrains ER-alpha-positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF-beta1 dysregulation may promote proliferation of ER-alpha-positive cells associated with breast cancer risk in humans.
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Proliferación Celular , Células Epiteliales/patología , Receptor alfa de Estrógeno/metabolismo , Glándulas Mamarias Animales/patología , Factor de Crecimiento Transformador beta/fisiología , Animales , Cruzamientos Genéticos , Proteínas de Unión al ADN/metabolismo , Células Epiteliales/metabolismo , Estro/metabolismo , Femenino , Heterocigoto , Glándulas Mamarias Animales/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Fosforilación , Proteína Smad2 , Transactivadores/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta1RESUMEN
Polymerase chain reaction (PCR) was evaluated to detect Adenoviruses and Chlamydia trachomatis on nasopharyngeal aspirates (NPA) obtained 4-5 days after the onset of lower respiratory tract illness in children. Forty-five nasopharyngeal aspirates (NPA) from 45 children with lower respiratory tract infections were processed for the detection of C. trachomatis and Adenovirus by Fluorescent antibody test (FAT), culture and PCR for the cryptic plasmid of C. trachomatis and the gene coding for hexon of Adenoviruses. Seven (13.3%) and 4 (6.6%) of the 45 specimens were positive for C. trachomatis and adenovirus by PCR respectively, which included one specimen each positive for these agents. Cultures were negative for both the organisms. PCRs showed a statistically significant (McNemar test--p= 0.004) higher sensitivity. PCR test is necessary to detect C. trachomatis and adenovirus in nasopharyngeal aspirates obtained 4-5 days after the onset of illness.
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Adenovirus Humanos/aislamiento & purificación , Chlamydia trachomatis/aislamiento & purificación , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virología , Infecciones por Adenovirus Humanos/diagnóstico , Adenovirus Humanos/genética , Secuencia de Bases , Preescolar , Infecciones por Chlamydia/diagnóstico , Chlamydia trachomatis/genética , ADN Bacteriano/genética , ADN Viral/genética , Humanos , Lactante , Nasofaringe/microbiología , Nasofaringe/virología , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/estadística & datos numéricos , Sensibilidad y Especificidad , SucciónRESUMEN
Since susceptibility of a cell line is an important factor for cultivation of Chlamydia trachomatis, McCoy, HeLa, BHK-21, HEp-2, Vero and A549 cell lines were tested for this characteristic. These were inoculated with 150 infection-forming units (IFU) of C. trachomatis A, B, Ba and C serovars. Growth was graded according to the number of IFUs per microscopic field (100X). A549-cell line was not susceptible to infection by any of the serovars. The growth of C. trachomatis was good to very good in McCoy and HeLa cell lines. Vero, BHK-21 and HEp-2 cell lines varied considerably in the susceptibility to infection.
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The FVB/N mouse strain is widely used in the generation of transgenic mouse models. We have observed that mammary glands of wild-type virgin female FVB/NCr mice frequently have the morphologic and histologic appearance of a gland during pregnancy. By 13 months of age, the mammary glands of more than 40% of the mice examined had lobuloalveolar hyperplasia that was characterized by the presence of secretory alveoli and distended ducts apparently containing secretory material. The prevalence of this phenotype further increased with age. The mammary phenotype was highly correlated with the presence of proliferative, prolactin-secreting lesions in the pituitary gland. In mice aged 18 to 23 months, hyperplasia of the pars distalis was seen in 11 of 21 mice (52%), and a further 4 of 21 mice (19%) had pituitary adenomas. Pituitary hyperplasia was already evident in some mice as young as nine months. The pituitary phenotype was also associated with high prevalence (4/6 mice) of spontaneous mammary tumors in aged multiparous, but not virgin FVB/NCr mice. This high prevalence of pituitary abnormalities and their effects on the mammary gland have important consequences for the interpretation of new phenotypes generated in transgenic models using this mouse substrain.
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Glándulas Mamarias Animales/patología , Ratones Endogámicos , Enfermedades de la Hipófisis/veterinaria , Hipófisis/patología , Animales , Modelos Animales de Enfermedad , Femenino , Hiperplasia , Neoplasias Mamarias Animales/etiología , Neoplasias Mamarias Animales/patología , Ratones , Ratones Transgénicos , Enfermedades de la Hipófisis/complicaciones , Enfermedades de la Hipófisis/patologíaRESUMEN
The inbred FVB/N mouse strain is widely used for creating transgenic mice. Over the past decade, persistent mammary hyperplasia has been detected in many multiparous FVB/N female mice sent to the University of California, Davis (UCD) Mutant Mouse Pathology Laboratory (MMPL) by a number of different laboratories. However, the experimental details concerning most specimens were not always available. To confirm these empiric findings, experiments were carried out to evaluate the mammary glands of FVB/N mice under controlled conditions. Persistent mammary hyperplasia that related to parity was found. Weeks after their first to fourth pregnancy, 10 FVB/N female mice from the Lawrence Berkeley National Laboratory (LBNL) colony were studied and the mammary glands were evaluated. The percentage of fat pad filled was estimated, using image analysis. Serum samples and the pituitary gland from other FVB/N mice from the LBNL were assayed for prolactin concentration. Multiparous FVB/N females consistently had persistent mammary hyperplasia. Four of seven females in the LBNL colony had hyperplasia after three pregnancies. A few foci of squamous nodules and sporadic carcinomas also were observed. Thus, some FVB/N females may have persistent mammary hyperplasia after three pregnancies without detectable pituitary abnormalities. Mammary carcinomas also may develop sporadically. These background phenotypes must be considered when interpreting the effect of genetic manipulation in FVB/N mice.
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Glándulas Mamarias Animales/patología , Ratones Endogámicos , Animales , Femenino , Hiperplasia , Ratones , Ratones Transgénicos , Paridad , Hipófisis/química , Embarazo , Prolactina/análisis , Prolactina/sangreRESUMEN
Expression of the 'A' and 'B' forms of progesterone receptor (PR), in an appropriate ratio is critical for normal mammary development. As such, mammary glands of PR-A transgenic mice, carrying additional 'A' form of PR as transgene, exhibit morphological and histological characteristics associated with transformation. Accordingly, in the present studies, we analyzed these mammary glands for the presence of transformed epithelial cells by examining for alterations in gene expressions and growth potential, known to be associated with different stages of transformation. These studies reveal that, in the aberrant mammary epithelial structures, there is a decrease in p21 expression, an increase in cyclin D1 expression accompanied by an increase in cell proliferation, and a decrease in estrogen receptor alpha (ER alpha). In mammary ducts with normal histology, there is a decrease in p21 expression without an elevation in cyclin D1 expression or cell proliferation or a decrease in ER alpha expression. Treatment of PR-A transgenics with anti-progestin, mifepristone, has no effect on cell proliferation, cyclin D1 or ER alpha expression in the aberrant epithelial structures. In contrast, mifepristone restored the loss of p21 expression in the epithelial cells of both the ducts with normal histology and aberrant structures. Parallel studies reveal no apparent differences between the mammary glands of wild-type and PR-B transgenic mice, which carry additional PR 'B' form. Accordingly, we conclude that (i) mammary glands of PR-A transgenics contain at least two distinct populations of transformed epithelial cells, (ii) the epithelial cell population in the ducts with normal histology contain presumptive immortalized cells, indicative of early stages of transformation, (iii) the aberrant epithelial structures contain later stages of transformation associated with hyperplasias/pre-neoplasias and (iv) the transformation of mammary epithelial cells in PR-A transgenics might be due to a misregulation in progesterone action resulting from overexpression of PR 'A' form.
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Transformación Celular Neoplásica/genética , Regulación de la Expresión Génica , Glándulas Mamarias Animales/citología , Receptores de Progesterona/genética , Animales , Células Epiteliales/citología , Células Epiteliales/metabolismo , Glándulas Mamarias Animales/metabolismo , Ratones , Ratones TransgénicosRESUMEN
To study phenotype-genotype correlations, ErbB/Ras pathway tumors (transgenic for ErbB2, c-Neu, mutants of c-Neu, polyomavirus middle T antigene (PyV-mT), Ras, and bi-transgenic for ErbB2/Neu with ErbB3 and with progesterone receptor) from four different institutions were histopathologically compared with Wnt pathway tumors [transgenes Wnt1, Wnt10b, dominant-negative glycogen synthase kinase 3-beta, beta-Catenin, and spontaneous mutants of adenomatous polyposis coli gene (Apc)]. ErbB/Ras pathway tumors tend to form solid nodules consisting of poorly differentiated cells with abundant cytoplasm. ErbB/Ras pathway tumors also have scanty stroma and lack myoepithelial or squamous differentiation. In contrast, Wnt pathway tumors exhibit myoepithelial, acinar, or glandular differentiation, and, frequently, combinations of these. Squamous metaplasia is frequent and may include transdifferentiation to epidermal and pilar structures. Most Wnt pathway tumors form caricatures of elongated, branched ductules, and have well-developed stroma, inflammatory infiltrates, and pushing margins. Tumors transgenic for interacting genes such as protein kinase CK2alpha (casein kinase IIalpha), and the fibroblast growth factors (Fgf) Int2/Fgf3 or keratinocyte growth factor (Kgf/Fgf7) also have the Wnt pathway phenotype. Because the tumors from the ErbB/Ras and the Wnt pathway are so distinct and can be readily identified using routine hematoxylin and eosin sections, we suggest that pathway pathology is applicable in both basic and clinical cancer research.