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1.
J Anim Sci ; 96(4): 1396-1404, 2018 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-29584934

RESUMO

A serial harvest was conducted every 28 d from 254 to 534 d on feed (DOF) to quantify changes in growth and composition of calf-fed Holstein steers (n = 115, initial body weight (BW) = 449.2 ± 19.9 kg). One-half were supplemented with the ß-2 adrenergic agonist zilpaterol hydrochloride (ZH; 8.33 mg/kg 100% dry matter (DM) basis) during the final 20 d followed by a 3-d withdrawal prior to harvest; the remainder was fed a non-ZH control (CON) ration. Five steers were randomly selected and harvested after 226 DOF which served as a reference point for modeling purposes. Fabricated carcass soft tissue was ground, mixed, and subsampled for proximate analysis. Moreover, following the traditional method of rib dissection which includes the 9th, 10th, and 11th rib contained within the IMPS 103 primal, the relationship of carcass chemical composition to 9-10-11 rib composition was evaluated. Carcasses in this investigation had more (P < 0.01) separable lean, fat, ash, and moisture concomitant with less bone and ether extract than rib dissections. However, protein levels were similar (P = 0.27) between carcasses and rib dissections. Using regression procedures, models were constructed to describe the relationship of rib dissection (RD) composition including separable lean (RDSL), separable fat (RDSF), separable bone (RDSB), ether extract (RDEE), protein (RDP), moisture (RDM), and ash (RDA) with carcass composition. Carcass lean (CL), carcass fat (CF), and carcass bone (CB) were correlated (P < 0.01) with RDSL, RDSF, and RDSB with simple r values of 0.41, 0.71, and 0.50, respectively. Chemical composition of the rib and carcass, carcass ether extract (CEE), carcass protein (CP), carcass moisture (CM), and carcass ash (CA) were correlated (P ≤ 0.01) with simple r values of 0.75, 0.31, 0.66, and 0.37, respectively. Equations to predict carcass fatness from rib dissection variables and ZH supplementation status were only able to account for 50 and 56%, of the variability of CF and CEE, respectively. Overall, the relationships quantified and equations developed in this investigation do not support use of 9/10/11 rib dissection for estimation of carcass composition of calf-fed Holstein steers.


Assuntos
Ração Animal/análise , Composição Corporal/efeitos dos fármacos , Bovinos/crescimento & desenvolvimento , Suplementos Nutricionais , Compostos de Trimetilsilil/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Masculino , Carne Vermelha/análise , Costelas/anatomia & histologia
2.
J Anim Sci ; 95(3): 1205-1208, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28380521

RESUMO

Understanding the maximum slaughter size for calf-fed Holstein steers based on hip-height has become a contemporary issue in the beef processing industry. Increased carcass size, in terms of both weight and length, has outpaced the ability of some abattoirs to handle the larger animals. Moreover, some abattoirs have begun rejecting animals that exceed 147.3 cm (58 inches) at the hip, creating a challenge for Holstein cattle feeders. The objective of this study was to quantify the skeletal growth rate of calf-fed Holstein steers fed in confinement. Hip-height of calf-fed Holstein steers ( ≤ 135) was measured every 28 d from 226 to 422 d on feed. Hip-height was a dependent variable modeled via linear regression procedures utilizing days of age and BW as independent variables. Additionally, logistic regression was used to estimate the probability of a steer exceeding a hip-height of 147.3 cm (58 inches) from independent variables of days of age and BW. The linear relationship of BW to hip-height had an adjusted value of 0.7112 (Hip-height, cm = [0.0593 × BW, kg] + 109.00) and on average the calf-fed Holstein steers grew 1.0 cm for each 16.9 kg of BW gain during the finishing phase. The 10%, 50%, and 90% probability of a steer exceeding 147.3 cm (58 inches) of hip-height was achieved at 563, 653, and 743 kg of BW, respectively. The linear relationship of days of age to hip-height had an adjusted value of 0.6687 (Hip-height, cm = [0.0937 × days of age] + 104.4) and the calf-fed Holstein steers grew 1.0 cm for each 10.7 d of age during the finishing phase. The 10%, 50%, and 90% probability of a steer exceeding 147.3 cm (58 inches) of hip-height was estimated to occur at 408, 459, and 510 d of age, respectively. Knowledge of Holstein steer growth rate in relation to BW and age may allow for more accurate sorting to prevent oversized cattle arriving at the abattoir and subsequent discounts or being rejected for slaughter.


Assuntos
Bovinos/crescimento & desenvolvimento , Animais , Biometria , Composição Corporal , Peso Corporal , Espaços Confinados , Dieta/veterinária , Masculino
3.
J Anim Sci ; 95(3): 1209-1218, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28380524

RESUMO

Holstein steers ( = 110) were fed zilpaterol hydrochloride (ZH) for 0 or 20 d before slaughter during a 280-d serial harvest study. Cattle were harvested every 28 d beginning at 254 d on feed (DOF) and concluding at 534 DOF. After slaughter, carcasses were chilled for 48 h and then fabricated into boneless closely trimmed or denuded subprimals, lean trim, trimmable fat, and bone. Inclusion of ZH increased cold side weight (CSW) by 10.3 kg ( < 0.01; 212.7 vs. 202.4 kg [SEM 1.96]) and saleable yield by 10.4 kg ( < 0.01; 131.9 vs. 121.5 kg [SEM 1.16]) in calf-fed Holstein steer carcasses. Additionally, saleable yield as a percentage of CSW increased ( ≤ 0.01) by 2.19% (62.64 vs. 60.45% [SEM 0.22]) for cattle supplemented with ZH. Subprimal weights were heavier ( ≤ 0.05) from cattle that received ZH except for the bottom sirloin ball tip, back ribs, and outside skirt regardless of slaughter endpoint. Yield of top round, bottom round, and knuckle was increased ( ≤ 0.01) following ZH supplementation by 0.37, 0.24, and 0.18%, respectively. Yield of the top sirloin butt, strip loin, and tenderloin was increased ( ≤ 0.01) concurrent with ZH supplementation by 0.18, 0.11, and 0.09%, respectively. Regarding the rib primal, the rib eye roll tended ( = 0.08) to had increased yield (2.80 vs. 2.72% [SEM 0.03]) with ZH supplementation; both back ribs and blade meat exhibited increased ( ≤ 0.04) yields of 0.04%. Relative to the chuck primal, increased ( ≤ 0.03) yields of shoulder clod, pectoral meat, and mock tender were observed (0.13, 0.07, and 0.04%, respectively). Yield changes for subprimal brisket, plate, and flank were limited to increased ( < 0.01) proportion of flank steak and elephant ear (cutaneous trunci), 0.07 and 0.04%, respectively. Feeding duration notably altered ( ≤ 0.01) weights and percentages of all subprimals except the brisket. Saleable yield increased ( ≤ 0.01) by 0.192 kg/d with additional DOF. Moreover, trimmable fat and bone increased ( ≤ 0.01) by 0.146 and 0.050 kg/d, respectively. These data illustrate improved saleable meat yields for calf-fed Holstein steers supplemented with ZH and provide the beef industry knowledge of fabrication yield changes throughout a wide range of harvest endpoints.


Assuntos
Bovinos/crescimento & desenvolvimento , Suplementos Nutricionais , Aditivos Alimentares/farmacologia , Carne Vermelha/normas , Compostos de Trimetilsilil/farmacologia , Ração Animal/análise , Animais , Composição Corporal , Peso Corporal , Dieta/veterinária , Masculino
4.
J Anim Sci ; 94(9): 4006-4015, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27898897

RESUMO

A 2 × 11 factorial treatment structure was applied in a completely randomized experimental design to investigate differences in noncarcass tissue among serially harvested Holstein steers. Steers ( = 110) were randomly assigned to 1 of 2 dietary treatments: a ration supplemented with zilpaterol hydrochloride (ZH) fed at a rate of 8.3 mg/kg DM for 20 d followed by a 3-d withdrawal or a control ration with no ZH included in the diet. Within treatment, steers were assigned to harvest groups of 254, 282, 310, 338, 366, 394, 422, 450, 478, 506, or 534 d on feed (DOF) prior to initiation of the trial. Cattle fed ZH realized an empty BW (EBW) increase ( ≤ 0.03) of 2.8% (644.2 vs. 626.4 kg [SEM 5.4]) and a HCW increase of 5.0% (429.1 vs. 408.4 kg [SEM 4.0]) with a concomitant 12% reduction (45.1 vs. 51.2 kg [SEM 3.1]) in gastrointestinal contents and 2.1 percentage unit increase in dressed carcass yield (62.1 vs. 60.0% [SEM 0.01]). Additionally, ZH supplementation decreased (P ≤ 0.03) the absolute weight of the liver and kidneys by 0.3 and 0.1 kg, respectively. When noncarcass components were expressed on an empty body basis (g/kg EBW), reductions ( ≤ 0.01) in the limbs (18.8 vs. 19.5 g/kg EBW [SEM 0.1]), hide (81.1 vs. 78.1 g/kg EBW [SEM 0.7]), liver (14.2 vs. 13.2 g/kg EBW [SEM 0.2]), kidneys (2.6 vs. 2.3 g/kg EBW [SEM 0.04]), small and large intestines (74.9 vs. 69.6 g/kg EBW [SEM 1.2]), and gastrointestinal tract (119.8 vs. 113.4 g/kg EBW [SEM 1.3]) were observed with ZH supplementation. Additionally, there was a tendency ( = 0.07) for the proportion of total offal to be reduced (253.2 vs. 247.4 g/kg EBW [SEM 2.5]) with ZH supplementation. Empty BW and HCW linearly increased ( < 0.01) by 1.16 and 0.758 kg/d ( < 0.01), respectively, with additional DOF. The weight of the liver and intestines linearly increased ( < 0.01) by 0.007 and 0.133 kg/d ( < 0.01), respectively, with additional DOF. These data indicate the magnitude of change in noncarcass tissues that can be expected when calf-fed Holstein steers are supplemented with ZH.


Assuntos
Composição Corporal/efeitos dos fármacos , Bovinos/fisiologia , Compostos de Trimetilsilil/farmacologia , Adrenérgicos/farmacologia , Ração Animal/análise , Animais , Composição Corporal/fisiologia , Peso Corporal , Dieta/veterinária , Suplementos Nutricionais , Masculino , Aumento de Peso
5.
J Anim Sci ; 94(5): 2139-50, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27285710

RESUMO

This experiment was designed to study the effect of days on feed (d 225-533) and zilpaterol hydrochloride (ZH) supplementation on Holstein steer ( = 110) performance and feeding behavior as part of a serial slaughter trial. Steers were randomly assigned to 1 of 11 harvest groups with 10 steers ( = 5 control and = 5 ZH; ZH at 8.33 mg/kg diet) harvested each 28 d. Steers were weighed every 28 d (d 225, 253, 281, 309, 337, 365, 393, 421, 449, 477, 505, and 533); individual daily meal consumption data for each steer were recorded using GrowSafe technology. In the pretreatment period, dry matter intake expressed a negative quadratic relationship with days on feed (DOF) {DMI = -5.7120 + (0.08370 x DOF)- (0.00011 x DOF); Adj. = 0.2574; RMSE = 0.25 75; 0.01}. A linear increase in BW ( < 0.01) occurred during the pretreatment 308 d period from 466 to 844 kg, {BWend = 137.61 + (1.4740 x DOF); Adj. = 0.8819; RMSE = 37.06; < 0.01}, whereas ADG and G:F decreased linearly. Dry matter intake per meal exhibited a quadratic relationship over days on feed and peaked ( < 0.01) during d 365 to 392 at 1.065 kg coinciding with the highest numerical daily DMI (11.19 kg). Daily consumption visit duration differed ( < 0.01) during the 308 d period, with a low of 52.29 min (d 337-364) and a high of 55.59 min (d 365-392). Consumption rate peaked at 714 g/min (d 337-364) and exhibited a quadratic relationship to DOF. The difference ( < 0.04) in DMI between control and ZH treated cattle across all 11 harvest groups averaged 0.575 kg. Moreover, ZH treatment resulted in decreased ( 0.01) DMI per meal event of 0.093 kg. Gain to feed tended to improve ( = 0.06) with ZH treatment by 0.017 kg gain per kg feed relative to the control cattle. Daily bunk, consumption, and meal visit durations were influenced by ZH during the 20 d treatment period ( = 0.01); the average difference between control and ZH supplemented cattle over the 308 d trial was 9.09, 8.71, and 11.39 min per d, respectively. The data collected in this trial indicate live growth performance and feeding behavior were impacted by both DOF and ZH supplementation.


Assuntos
Bovinos/crescimento & desenvolvimento , Comportamento Alimentar/efeitos dos fármacos , Compostos de Trimetilsilil/farmacologia , Aumento de Peso/efeitos dos fármacos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Composição Corporal/efeitos dos fármacos , Bovinos/fisiologia , Dieta/veterinária , Suplementos Nutricionais , Masculino , Compostos de Trimetilsilil/administração & dosagem
6.
J Anim Sci ; 94(12): 5129-5136, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28046164

RESUMO

Serial harvests were conducted using Holstein steers ( = 110) fed zilpaterol hydrochloride (ZH) for 0 or 20 d prior to harvest. Steers were harvested in 28-d increments beginning at 254 d on feed (DOF) and ending at 534 DOF. After harvest and a 36-h chill period, carcasses were evaluated using grading methods standard for the United States (USDA), Canada (Canadian Beef Grading Association [CBGA]), and Japan (Japanese Meat Grading Agency [JMGA]). No ZH treatment differences ( = 0.81) were detected for 12th-rib fat thickness; however, additional DOF resulted in a daily linear increase ( < 0.01) of 12th-rib fat thickness by 0.004 cm/d. Longissimus muscle area was increased ( < 0.01) by 8.7 cm with ZH supplementation and linearly increased ( < 0.01) 0.08 cm2/d with additional DOF. Calculated USDA yield grade (YG) decreased ( < 0.01) 0.33 units due to ZH treatment and linearly increased ( < 0.01) 0.009 units/d. Steers supplemented with ZH exhibited increased ( < 0.01) CGBA LM width; however, no difference ( = 0.37) was detected in CGBA LM length. No ZH treatment differences ( = 0.64) were observed for CBGA fat class; however, CGBA fat class linearly increased ( < 0.01) by 0.01 units/d. No ZH differences ( ≥ 0.17) were detected for the CBGA estimated lean percentage or YG equations. Evaluation for JMGA occurs at the sixth and seventh rib interface; LM area was 4.6 cm2 greater ( = 0.02) for cattle supplemented with ZH and linearly increased ( < 0.01) by 0.07 cm2/d with additional DOF. Subcutaneous fat thickness was not different among ZH treatments ( = 0.10) but linearly ( < 0.04) increased ( < 0.01) by 0.005 cm/d with additional DOF using the JMGA grading method. No difference ( ≥ 0.21) was calculated between ZH treatments or DOF for JMGA estimated yield. No ZH treatment differences ( = 0.85) were detected in USDA marbling score; however, marbling linearly increased ( < 0.01) 0.07 units/d. These data illustrate the impact of ZH and increasing DOF on economically important carcass grading outcomes used in the USDA, CBGA, and JMGA grading programs.


Assuntos
Adrenérgicos/farmacologia , Composição Corporal/efeitos dos fármacos , Carne/normas , Compostos de Trimetilsilil/farmacologia , Adrenérgicos/administração & dosagem , Animais , Canadá , Bovinos/fisiologia , Esquema de Medicação , Japão , Masculino , Compostos de Trimetilsilil/administração & dosagem
7.
Langmuir ; 28(4): 2281-7, 2012 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-21506526

RESUMO

Poly(N-isopropyl acrylamide) or pNIPAM is a thermoresponsive polymer that is widely studied for use in bioengineering applications. The interest in this polymer lies in the polymer's unique capability to undergo a sharp property change near physiological temperature, which aids in the spontaneous release of biological cells from substrates. Currently, there are many methods for depositing pNIPAM onto substrates, including atom-transfer radical polymerization (ATRP) and electron beam ionization. Each method yields pNIPAM-coated substrates with different surface characteristics that can influence cell behavior. In this work, we compare two methods of pNIPAM deposition: plasma deposition and codeposition with a sol-gel. The resulting pNIPAM films were analyzed for use as substrates for mammalian cell culture based on surface characterization (XPS, ToF-SIMS, AFM, contact angles), cell attachment/detachment studies, and an analysis of exocytosis function using carbon-fiber microelectrode amperometry (CFMA). We find that although both methods are useful for the deposition of functional pNIPAM films, plasma deposition is much preferred for cell-sheet engineering applications because of the films' thermoresponse, minimal change in cell density, and maintenance of supported cell exocytosis function.


Assuntos
Resinas Acrílicas/química , Resinas Acrílicas/farmacologia , Células Cromafins/citologia , Células Cromafins/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Temperatura , Animais , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Exocitose/efeitos dos fármacos , Camundongos , Microeletrodos , Gases em Plasma/química , Polimerização , Propriedades de Superfície
8.
J Appl Biomater Biomech ; 6(2): 81-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-20740450

RESUMO

The thermoresponsive properties of poly(N-isopropyl acrylamide) (pNIPAM) have led to its wide use in bioengineering applications, including the reversible adhesion of mammalian cells. The groups performing this research have used different solutions to initiate cell release and have varied the temperature of the solution during detachment. To our knowledge, there has been no direct correlation between the solution identity or temperature on the efficiency of cell release from pNIPAM films. In this work, we present a study of the effect of the solution type and temperature used to initiate detachment on the time required to achieve 100% detachment of bovine aortic endothelial cells (BAECs) from pNIPAM. The pNIPAM films used in this work were obtained using a novel technique using a spin-coated solution containing pNIPAM (spNIPAM). We found that the fastest, most reliable release of cells occurred below the LCST of the polymer at 4 degrees C in serum free media (SFM). As it is sometimes desirable to stop cell metabolism at the time of detachment (e.g., to "freeze" protein expression prior to subsequent analysis), the use of extremely cold SFM would be ideal in such cases.

9.
J Med Genet ; 45(2): 87-92, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17932119

RESUMO

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting up to 4% of children worldwide. Familial inheritance of AIS is now recognised and several potential candidate loci have been found. METHODS: We studied 25 multi-generation AIS families of British descent with at least 3 affected members in each family. A genomewide screen was performed using microsatellite markers spanning approximately 10-cM intervals throughout the genome. This analysis revealed linkage to several candidate chromosomal regions throughout the genome. Two-point linkage analysis was performed in all families to evaluate candidate loci. After identification of candidate loci, two-point linkage analysis was performed in the 10 families that segregated, to further refine disease intervals. RESULTS: Significant linkage was obtained in a total of 10 families: 8 families to the telomeric region of chromosome 9q, and 2 families to the telomeric region of 17q. A significant LOD score was detected at marker D9S2157 Z(max) = 3.64 ( theta= 0.0) in a four-generation family (SC32). Saturation mapping of the 9q region in family SC32 defined the critical disease interval to be flanked by markers D9S930 and D9S1818, spanning approximately 21 Mb at 9q31.2-q34.2. In addition, seven other families segregated with this locus on 9q. In two multi-generation families (SC36 and SC23) not segregating with the 9q locus, a maximum combined LOD score of Z(max) = 4.08 ( = 0.0) was obtained for marker AAT095 on 17q. Fine mapping of the 17q candidate region defined the AIS critical region to be distal to marker D17S1806, spanning approximately 3.2 Mb on chromosome 17q25.3-qtel. CONCLUSION: This study reports a common locus for AIS in the British population, mapping to a refined interval on chromosome 9q31.2-q34.2 and defines a novel AIS locus on chromosome 17q25.3-qtel.


Assuntos
Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 9/genética , Genes Dominantes , Escoliose/genética , Adolescente , Mapeamento Cromossômico , Feminino , Genótipo , Humanos , Escore Lod , Masculino , Fenótipo , Escoliose/patologia
11.
Br J Cancer ; 92(1): 55-9, 2005 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-15611797

RESUMO

Wide variation in the surgical management of breast cancer exists at hospital, regional, national and international level. To demonstrate whether variation in surgical practice observed at aggregate level between breast units persists following adjustment for case-mix, individual patient-level data from the Trent Breast Screening Programme Quality Assurance database (1997-2003) was analysed. Expected case-mix adjusted mastectomy rates were derived by logistic regression using the variables tumour size, site and grade, patient age and year of presentation, employing the region's overall case-mix adjusted practice as the reference population. The region's 11 breast screening units detected 5109 (3989 invasive) surgically managed primary breast cancers over the 6-year period. A total of 1828 mastectomies (Mx) were performed (Mx rate 35.8%, 95% confidence interval: 34.5-37.1%). Significant variation in mastectomy rates were observed between units (range 25-45%, P<0.0001), and persists following case-mix adjustment (P<0.0001). Two-fold variation in observed to expected unit mastectomy rate coefficient is demonstrated overall (range 0.66-1.36), increasing to almost four-fold variation in cancers less than 15 mm diameter (range 0.55-1.95). Significant variation in surgery for screen-detected primary breast cancer is not explained by case-mix. Further research is required to investigate potential patient and professional causative factors.


Assuntos
Neoplasias da Mama/cirurgia , Grupos Diagnósticos Relacionados , Mastectomia/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Feminino , Humanos , Modelos Logísticos , Mamografia , Mastectomia Segmentar/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Reino Unido
12.
J Cutan Pathol ; 31(9): 625-9, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15330995

RESUMO

Carcinoma exhibiting thymus-like differentiation (CASTLE) is a rare, distinct tumor of the thyroid gland or soft tissue of the head and neck that may simulate primary squamous cell carcinoma or lymphoepithelioma, and which contains features reminiscent of thymic differentiation including Hassall's corpuscles, occasional perivascular spaces, and the presence of lymphocytes. Ectopic thymic tissue may result from incomplete descent or persistence of the cervical portion of the thymus and may occur anywhere along the course of the embryonic descent from the angle of the mandible to the sternal notch. Herein, we report two cases of dermal extrathyroidal CASTLE. The differential diagnosis of squamoid carcinoma with features of thymic differentiation includes extrathyroidal CASTLE, a primary squamous cell carcinoma with thymic differentiation, lymphoepithelioma-like carcinoma of the skin, and metastatic squamous cell carcinoma of unknown primary. It is essential that the latter two be ruled out before accepting the diagnosis of an extrathyroidal carcinoma with thymus-like differentiation.


Assuntos
Carcinoma/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Antígenos CD5/metabolismo , Antígenos CD57/metabolismo , Carcinoma/metabolismo , Carcinoma de Células Escamosas/patologia , Diagnóstico Diferencial , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Neoplasias de Tecidos Moles/metabolismo , Timo/patologia
14.
Cancer Res ; 61(22): 8074-8, 2001 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11719430

RESUMO

The oncogenic protein Ski associates with Smad proteins and counteracts their activation of gene expression and growth inhibition in response to transforming growth factor beta (TGF-beta). Here we show that Ski protein levels are increased in all 44 human melanoma tumor tissues analyzed in vivo. In addition, Ski subcellular localization changes from nuclear, in preinvasive melanomas (melanomas in situ), to nuclear and cytoplasmic in primary invasive and metastatic melanomas. Furthermore, Ski/Smad association in the cytoplasm seems to prevent Smad3 nuclear translocation in response to TGF-beta. The biological significance of Ski overexpression in melanomas was established by showing that down-regulation of Ski levels, by antisense Ski vectors, restored TGF-beta-mediated growth inhibition. Such inhibition is apparently mediated by up-regulation of the cyclin-dependent kinase-I p21(Waf-1) and inhibition of cyclin-dependent kinase 2 activity. Our results suggest that high levels of Ski in human melanomas produce a disruption of TGF-beta signaling phenotypically similar to that in cells harboring mutations in TGF-beta receptors or Smad proteins, and this may represent a significant event in the progression of melanomas in vivo.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Melanoma/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Cutâneas/metabolismo , Fator de Crescimento Transformador beta/fisiologia , Divisão Celular/fisiologia , Citoplasma/metabolismo , Proteínas de Ligação a DNA/biossíntese , Humanos , Melanoma/patologia , Proteínas Proto-Oncogênicas/biossíntese , Transdução de Sinais/fisiologia , Neoplasias Cutâneas/patologia , Proteína Smad3 , Transativadores/metabolismo , Células Tumorais Cultivadas
16.
Melanoma Res ; 11(4): 355-69, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11479424

RESUMO

As with most cancers, the aetiology of human cutaneous melanoma is likely to be multifactorial and to include the accumulation of irreversible alterations in an unknown number of genes. Elucidating this molecular progression necessitates both the identification of genetic perturbations at each clinically relevant stage, and the assessment of their impact on the normal melanocyte. The observation that the epidermal melanocyte, in contrast to metastatic melanoma cells, requires activation of the protein kinase C (PKC) pathway to facilitate growth in vitro indicates that one or more isoforms (or substrates) of this large and complex family of proteins are among those that undergo alteration during the development of malignant melanoma. Consequently, a number of studies have investigated the expression of various PKC family members in both melanocyte and melanoma cell lines, without a consensus of opinion as to which isoforms are of biological significance in melanoma development and progression. The present study involved a comprehensive evaluation of the PKC profile in normal melanocytes and in 16 metastatic melanoma cell lines. The results show that the major difference in isoform expression between epidermal melanocytes and melanoma cells is the loss of PKCbeta protein expression in 90% of melanoma cell lines. Examination of PKCbeta in benign and malignant melanocytic lesions revealed that this protein is either downregulated or absent in both naevi and metastatic melanomas. We conjecture that, although the loss of PKCbeta expression is a common phenomenon in malignant melanocytes, it may be related more to a normal process of melanocytic differentiation than to malignant transformation.


Assuntos
Diferenciação Celular/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Isoenzimas/genética , Melanoma/enzimologia , Proteína Quinase C/genética , Western Blotting , Extratos Celulares , Linhagem Celular , Membrana Celular/enzimologia , Tamanho Celular , Citosol/enzimologia , Regulação para Baixo , Perfilação da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Humanos , Imuno-Histoquímica , Isoenzimas/metabolismo , Melanócitos/citologia , Melanócitos/enzimologia , Melanócitos/metabolismo , Melanócitos/patologia , Melanoma/genética , Melanoma/patologia , Invasividade Neoplásica/genética , Proteína Quinase C/metabolismo , Proteína Quinase C beta , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
17.
J Cutan Pathol ; 28(8): 393-9, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11493376

RESUMO

BACKGROUND: Melanocytic nevi typically show a morphologic sequence of maturation from epithelioid "type A" cells to fusiform, Schwann cell-like "type C" cells with dermal descent. Nevi may also produce Wagner-Meissner-like structures (nevic corpuscles). Previous studies have shown that this maturation of intradermal nevi recapitulates intermediate stages in Schwann cell development. In intradermal nevi, we have evaluated the pattern of S100A6 protein, a form of S100 found in Schwann cells. METHODS: Formalin-fixed, paraffin-embedded archival tissues were evaluated by immunohistochemistry using antibodies specific for S100A6 and S100B in 38 intradermal nevi (IDN). Ten neurofibromas (NF), 3 Schwannomas (SCH), 2 palisaded and encapsulated neuromas (PEN), and 2 granular cell tumors (GCT) were included as positive controls since these lesions have large numbers of Schwann cells. RESULTS: Melanocytic nevi demonstrated preferential anti-S100A6 staining of "type C" cells (36/38; 28 strong, 8 weak) and nevic corpuscles (25/38; 19 strong, 6 weak) compared to "type A" cells (17/38; 17 weak) and "type B" cells (17/38; 4 strong, 13 weak). All NF, SCH, and PEN stained strongly with anti-S100A6. Both GCT were negative with anti-S100A6 but positive with anti-S100B. CONCLUSIONS: The pattern of S100A6 expression in intradermal nevi further supports the hypothesis that maturation in these lesions recapitulates features of Schwann cell differentiation. The lack of S100A6 expression by both GCT suggests that these lesions have lost this feature of Schwann cells, which may play a role in their peculiar phenotypic appearance.


Assuntos
Proteínas de Ciclo Celular , Nevo Intradérmico/metabolismo , Nevo Pigmentado/metabolismo , Proteínas S100/metabolismo , Células de Schwann/metabolismo , Neoplasias Cutâneas/metabolismo , Transformação Celular Neoplásica , Humanos , Técnicas Imunoenzimáticas , Nevo Intradérmico/patologia , Nevo Pigmentado/patologia , Proteína A6 Ligante de Cálcio S100 , Células de Schwann/patologia , Neoplasias Cutâneas/patologia
18.
J Cutan Pathol ; 28(5): 229-34, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11401666

RESUMO

BACKGROUND: S100A6, an S100 calcium-binding protein, has been found in a variety of cutaneous and extracutaneous lesions including: melanocytic nevi, melanoma, some salivary gland and epithelial tumors, and malignant fibrous histiocytoma (MFH). Dermal dendrocytes (DD) in the papillary dermis of skin also express S100A6 protein. We evaluated a variety of cutaneous fibrohistiocytic lesions to determine if the immunophenotype of S100A6 positivity can be expanded to include some or all of these lesions. METHODS: Formalin-fixed, paraffin-embedded tissues from fibrous papules (FP, 20), dermatofibromas (DF, 20), dermatofibrosarcoma protuberans (DFSP, 5), atypical fibroxanthomas (AFX, 5), oral fibromas (3), digital fibroma (1), and dermatomyofibroma (1) were evaluated with antibodies to S100A6, S100B, factor XIIIa, and MAC387 using a one-hour capillary action-based immunohistochemical procedure. RESULTS: DD in 20/20 FP, 19/20 DF, and 4/4 fibromas stained positively with anti-S100A6 in a pattern similar to anti-factor XIIIa. No DFSP cases stained with anti-S100A6. Anti-S100A6 showed superior staining to anti-factor XIIIa in 4/5 AFX cases. CONCLUSIONS: The immunophenotypes of some fibrohistiocytic lesions can be expanded to include S100A6 protein. With the exception of AFX, the use of anti-S100A6 does not appear to offer added benefit over anti-factor XIIIa in the differential diagnosis of fibrohistiocytic lesions.


Assuntos
Proteínas de Ciclo Celular , Histiocitoma Fibroso Benigno/metabolismo , Proteínas S100/metabolismo , Neoplasias Cutâneas/metabolismo , Anticorpos Monoclonais/metabolismo , Dermatofibrossarcoma/metabolismo , Dermatofibrossarcoma/patologia , Derme/inervação , Derme/metabolismo , Derme/patologia , Diagnóstico Diferencial , Histiocitoma Fibroso Benigno/patologia , Humanos , Imuno-Histoquímica , Mecanorreceptores/metabolismo , Mecanorreceptores/patologia , Proteína A6 Ligante de Cálcio S100 , Proteínas S100/análise , Dermatopatias Papuloescamosas/metabolismo , Dermatopatias Papuloescamosas/patologia , Neoplasias Cutâneas/patologia , Transglutaminases/metabolismo , Xantomatose/metabolismo , Xantomatose/patologia
19.
Cutis ; 67(3): 217-9, 220, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11270294

RESUMO

Acantholytic dermatosis of the vulvocrural area is a rare skin disorder characterized by solitary or multiple skin-colored to white, smooth papules or plaques. Histopathological features of both Hailey-Hailey disease and Darler's disease are present. There is acantholysis, which may involve the full thickness of the epidermis, and dyskeratosis with corps ronds and grains. There may be marked hyperkeratosis and focal parakeratosis. We report a case of this rare disease and discuss its differential diagnosis and treatment.


Assuntos
Acantólise/diagnóstico , Doenças da Vulva/diagnóstico , Acantólise/patologia , Acantólise/cirurgia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Doenças da Vulva/patologia , Doenças da Vulva/cirurgia
20.
Am J Physiol Lung Cell Mol Physiol ; 280(3): L379-86, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11159019

RESUMO

Metabolism of surfactant protein (SP) A and dipalmitoylphosphatidylcholine (DPPC) was assessed in alveolar macrophages isolated from granulocyte-macrophage colony-stimulated factor (GM-CSF) gene-targeted [GM(-/-)] mice, wild-type mice, and GM(-/-) mice expressing GM-CSF under control of the SP-C promoter element (SP-C-GM). Although binding and uptake of (125)I-SP-A were significantly increased in alveolar macrophages from GM(-/-) compared with wild type or SP-C-GM mice, catabolism of (125)I-SP-A was markedly decreased in GM(-/-) mice. Association of [(3)H]DPPC with alveolar macrophages from GM(-/-), wild-type, and SP-C-GM mice was similar; however, catabolism of DPPC was markedly reduced in cells from GM(-/-) mice. Fluorescence-activated cell sorter analysis demonstrated decreased catabolism of rhodamine-labeled dipalmitoylphosphatidylethanolamine by alveolar macrophages from GM(-/-) mice. GM-CSF deficiency was associated with increased SP-A uptake by alveolar macrophages but with impaired surfactant lipid and SP-A degradation. These findings demonstrate the important role of GM-CSF in the regulation of alveolar macrophage lipid and SP-A catabolism.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Metabolismo dos Lipídeos , Macrófagos Alveolares/metabolismo , Proteínas/metabolismo , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , Animais , Corantes Fluorescentes , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Transgênicos/genética , Proteolipídeos/metabolismo , Proteína A Associada a Surfactante Pulmonar , Proteínas Associadas a Surfactantes Pulmonares , Surfactantes Pulmonares/metabolismo , Rodaminas
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