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1.
Hernia ; 27(2): 273-279, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35312890

RESUMO

PURPOSE: Patient optimization and selecting the proper technique to repair large incisional hernias is a multifaceted challenge. Body mass index (BMI) is a modifiable variable that may infer higher intra-abdominal pressures and, thus, predict the need for component separation (CS) at the time of surgery, but no data exist to support this. This paper assesses if the ratio of anterior-posterior (AP): transverse (TRSV) abdominal diameter, from pre-operative CT imaging, indicates a larger proportion of intra-abdominal fat and correlates with a hernia defect requiring a component separation for successful tension-free closure. METHODS: Ninety patients were identified who underwent either an open hernia repair with mesh by primary closure (N = 53) or who required a component separation at the time of surgery (N = 37). Pre-operative CT images were used to measure hernia defect width, AP abdominal diameter, and TRSV abdominal diameter. Quantitative data, nominal data, and logistic regression was used to determine predictors associated with surgical group categorization. RESULTS: The average hernia defect widths for primary closure and CS were 7.7 ± 3.6 cm (mean ± SD) and 9.8 ± 4.5, respectively (p = 0.015). The average BMI for primary closure was 33.9 ± 7.2 and 33.8 ± 4.9 for those requiring CS (p = 0.924). The AP:TRSV diameter ratios for primary closure and CS were 0.41 ± 0.08 and 0.49 ± 0.10, respectively (p < 0.001). In a multivariate analysis including both defect width and AP:TRSV diameter ratio, only AP:TRSV diameter ratio predicted the need for a CS (p = 0.001) while BMI did not (p = 0.92). CONCLUSION: Intraabdominal fat distribution measured by AP:TRSV abdominal diameter ratio correlates with successful tension-free fascial closure during incisional hernia repair, while BMI does not.


Assuntos
Parede Abdominal , Hérnia Ventral , Hérnia Incisional , Humanos , Parede Abdominal/cirurgia , Índice de Massa Corporal , Herniorrafia/métodos , Telas Cirúrgicas , Hérnia Ventral/cirurgia , Hérnia Incisional/cirurgia
2.
Am J Physiol Regul Integr Comp Physiol ; 313(3): R290-R297, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28701320

RESUMO

Radiation exposure accelerates the onset of age-related diseases such as diabetes, cardiovascular disease, and neoplasia and, thus, lends insight into in vivo mechanisms common to these disorders. Fibrosis and extracellular matrix (ECM) remodeling, which occur with aging and overnutrition and following irradiation, are risk factors for development of type 2 diabetes mellitus. We previously demonstrated an increased incidence of skeletal muscle insulin resistance and type 2 diabetes mellitus in monkeys that had been exposed to whole body irradiation 5-9 yr prior. We hypothesized that irradiation-induced fibrosis alters muscle architecture, predisposing irradiated animals to insulin resistance and overt diabetes. Rhesus macaques (Macaca mulatta, n = 7-8/group) grouped as nonirradiated age-matched controls (Non-Rad-CTL), irradiated nondiabetic monkeys (Rad-CTL), and irradiated monkeys that subsequently developed diabetes (Rad-DM) were compared. Prior radiation exposure resulted in persistent skeletal muscle ECM changes, including a relative overabundance of collagen IV and a trend toward increased transforming growth factor-ß1. Preservation of microvascular markers differentiated the irradiated diabetic and nondiabetic groups. Microvascular density and plasma nitrate and heat shock protein 90 levels were lower in Rad-DM than Rad-CTL. These results are consistent with a protective effect of abundant microvasculature in maintaining glycemic control within radiation-induced fibrotic muscle.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Matriz Extracelular/patologia , Resistência à Insulina/efeitos da radiação , Microvasos/patologia , Microvasos/efeitos da radiação , Músculo Esquelético/patologia , Exposição à Radiação/efeitos adversos , Animais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Relação Dose-Resposta à Radiação , Matriz Extracelular/efeitos da radiação , Feminino , Macaca mulatta , Masculino , Músculo Esquelético/efeitos da radiação , Doses de Radiação , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Lesões por Radiação/fisiopatologia , Espécies Reativas de Oxigênio
3.
Dentomaxillofac Radiol ; 44(2): 20140223, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25352427

RESUMO

OBJECTIVES: The aim of this work was to estimate the doses to radiosensitive organs in the head of a young child undergoing panoramic radiography and to establish the effectiveness of a short collimator in reducing dose. METHODS: Thermoluminescent dosemeters were used in a paediatric head phantom to simulate an examination on a 5-year-old child. The panoramic system used was an Instrumentarium OP200 D (Instrumentarium Dental, Tuusula, Finland). The collimator height options were 110 and 140 mm. Organ doses were measured using exposure programmes intended for use with adult and child size heads. The performance of the automatic exposure control (AEC) system was also assessed. RESULTS: The short collimator reduced the dose to the brain and the eyes by 57% and 41%, respectively. The dose to the submandibular and sublingual glands increased by 32% and 20%, respectively, when using a programme with a narrower focal trough intended for a small jaw. The effective dose measured with the short collimator and paediatric programme was 7.7 µSv. The dose to the lens of the eye was 17 µGy. When used, the AEC system produced some asymmetry in the dose distribution across the head. CONCLUSIONS: Panoramic systems when used to frequently image children should have programmes specifically designed for imaging small heads. There should be a shorter collimator available and programmes that deliver a reduced exposure time and allow reduction of tube current. Programme selection should also provide flexibility for focal trough size, shape and position to match the smaller head size.


Assuntos
Cabeça/efeitos da radiação , Imagens de Fantasmas , Doses de Radiação , Proteção Radiológica/normas , Radiografia Panorâmica/instrumentação , Encéfalo/efeitos da radiação , Pré-Escolar , Desenho de Equipamento , Olho/efeitos da radiação , Humanos , Lesões por Radiação/prevenção & controle , Glândulas Salivares/efeitos da radiação
4.
Curr Cancer Drug Targets ; 4(1): 77-84, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14965269

RESUMO

Recent studies have generated sufficient information to warrant a consideration of protein kinase CK2 as a potential target for cancer therapy. CK2 is a ubiquitous and highly conserved protein serine/threonine kinase that has long been considered to play a role in cell growth and proliferation. It is essential for cell survival, and considerable evidence suggests that it can also exert potent suppression of apoptosis in cells. This is important since the cancer phenotype is characterized by deregulation of not only proliferation but also of apoptosis. In normal cells, the level of CK2 appears to be tightly regulated, and cells resist a change in their intrinsic level of CK2. However, in all the cancers that have been examined an elevation of CK2 has been observed. Further, it appears that modest deregulation in the CK2 expression imparts a potent oncogenic potential to the cells. Disruption of CK2 by treatment of cells with antisense CK2 results in induction of apoptosis in a time and dose-dependent manner. Thus, we propose that down-regulation of CK2 by employing specific strategies to deliver antisense CK2 in vivo could have a potential role in cancer therapy.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Neoplasias/terapia , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Caseína Quinase II , Sobrevivência Celular/fisiologia , Proteínas de Ligação a DNA/antagonistas & inibidores , Regulação para Baixo , Inibidores Enzimáticos/farmacologia , Humanos , Neoplasias/enzimologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores
5.
Gynecol Oncol ; 80(3): 350-4, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11263930

RESUMO

OBJECTIVES: The incidence of cervical dysplasia and carcinoma is known to be increased in HIV-infected women. In addition, there is a positive correlation between HIV viral load (VL), CD4+ count, and opportunistic infections, as well as the incidence of various malignancies. This study compares HIV VL and CD4+ count with the presence of cervical dysplasia, as well as with the degree of severity of dysplasia. METHODS: A retrospective chart review of 350 HIV-infected women with polymerase chain reaction (PCR) quantitation of viral load was performed to identify 82 women with biopsy-proven cervical dysplasia and 25 women without any significant cervical pathology. The highest plasma VL within a year of the patients' cervical pathology and corresponding CD4+ count was selected and compared with cervical pathology. Univariate and multivariate statistical analysis using Student's t test and logistic regression analysis was used to analyze the significance of other risk factors such as age, race, smoking history, history of illicit drug use, and prior sexually transmitted disease as well as of viral load and CD4+ count. RESULTS: Of 82 cases of cervical dysplasia, 33 (40.24%) were mild (CIN I), 47 (57.32%) were either moderate or severe (CIN II-III) dysplasia, and 2 demonstrated invasive squamous cell carcinoma (2.44%). A significant statistical difference was found when comparing either HIV plasma VL or CD4+ T-cell counts with the presence of cervical dysplasia on biopsy (P < 0.005). However, only CD4+ count was identified as an independent risk factor for the presence of cervical dysplasia after multivariate analysis. CONCLUSION: In our population, there is a significant correlation between VL and CD4+ count and the presence of cervical dysplasia. However, VL does not appear to be an independent risk factor for cervical dysplasia in this population of HIV-infected women.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Carcinoma de Células Escamosas/virologia , Infecções por HIV/sangue , Infecções por HIV/imunologia , HIV , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/citologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/imunologia , Feminino , HIV/genética , Infecções por HIV/complicações , Humanos , Pessoa de Meia-Idade , Análise Multivariada , RNA Viral/sangue , Análise de Regressão , Estudos Retrospectivos , Displasia do Colo do Útero/sangue , Displasia do Colo do Útero/imunologia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/imunologia , Carga Viral
6.
J Biol Chem ; 276(8): 5992-9, 2001 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-11069898

RESUMO

Protein kinase CK2 (CK2) has long been implicated in the regulation of cell growth and proliferation. Its activity is generally elevated in rapidly proliferating tissues, and nuclear matrix (NM) is an important subnuclear locale of its functional signaling. In the prostate, nuclear CK2 is rapidly lost commensurate with induction of receptor-mediated apoptosis after growth stimulus withdrawal. By contrast, chemical-induced apoptosis in prostate cancer and other cells (by etoposide and diethylstilbestrol) evokes an enhancement in CK2 associated with the NM that appears to be because of translocation of CK2 from the cytoplasmic to the nuclear compartment. This shuttling of CK2 to the NM may reflect a protective response to chemical-mediated apoptosis. Supporting evidence for this was obtained by employing cells that were transiently transfected with various expression plasmids of CK2 (thereby expressing additional CK2) prior to treatment with etoposide or diethylstilbestrol. Cells transfected with the CK2alpha or CK2alphabeta showed significant resistance to chemical-mediated apoptosis commensurate with the corresponding elevation in CK2 in the NM. Transfection with CK2beta did not demonstrate this effect. These results suggest, for the first time, that besides the commonly appreciated function of CK2 in cell growth, it may also have a role in protecting cells against apoptosis.


Assuntos
Apoptose , Matriz Nuclear/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , Adenocarcinoma/tratamento farmacológico , Animais , Caseína Quinase II , Domínio Catalítico , Compartimento Celular , Citoproteção , Citosol/enzimologia , DNA de Neoplasias/análise , Dietilestilbestrol/farmacologia , Etoposídeo/farmacologia , Feminino , Humanos , Masculino , Neoplasias Mamárias Animais/tratamento farmacológico , Camundongos , Neoplasias da Próstata/tratamento farmacológico , Proteínas Serina-Treonina Quinases/genética , Transporte Proteico , Proteínas Recombinantes/metabolismo , Frações Subcelulares/enzimologia
7.
Head Neck ; 22(4): 341-6, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10862016

RESUMO

BACKGROUND: Human squamous cell carcinomas of the head and neck (SCCHN) overexpress the protein kinase CK2, and elevated CK2 activity correlates with aggressive tumor behavior and poor clinical outcome. We therefore investigated whether interference with CK2 expression would inhibit SCCHN cell growth in vitro. METHODS: We targeted the catalytic (alpha) subunit of CK2 using an antisense oligodeoxynucleotide (ODN) strategy. Human Ca9-22 cells derived from SCCHN were transfected with CK2-alpha sense, nonsense, or antisense ODN; CK2 activity was measured; and the effect on CK2 activity and on cell growth was determined. RESULTS: Transfection of Ca9-22 cells with antisense CK2-alpha ODN resulted in significantly decreased CK2 kinase activity associated with nuclear chromatin and in dose-dependent growth inhibition of Ca9-22 cells in vitro. CONCLUSIONS: Interference with the protein kinase CK2 signal in SCCHN cells may offer a novel anticancer strategy for this malignancy.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Neoplasias de Cabeça e Pescoço/enzimologia , Oligonucleotídeos Antissenso/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Sequência de Bases , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Caseína Quinase II , Divisão Celular/efeitos dos fármacos , Divisão Celular/genética , Códon sem Sentido , Relação Dose-Resposta a Droga , Regulação para Baixo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Neoplasias Gengivais/enzimologia , Neoplasias Gengivais/genética , Neoplasias Gengivais/terapia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Oligonucleotídeos Antissenso/genética , Probabilidade , Proteínas Serina-Treonina Quinases/biossíntese , Valores de Referência , Sensibilidade e Especificidade , Transfecção , Células Tumorais Cultivadas
8.
Semin Hematol ; 37(4 Suppl 7): 34-42, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11147488

RESUMO

Although exciting advances in monoclonal antibody therapy have already occurred, a review of agents in earlier stages of development reveals that many new agents may be approaching the clinic in the years to come. A look at the horizon of monoclonal antibody therapy reveals the following: novel strategies for augmenting the efficacy of monoclonal antibodies with which many clinicians are already familiar; novel antibodies with activity against lymphoma cells; novel technologies for generating and humanizing monoclonal antibodies; novel types of antibody-based therapeutics; and novel uses for these agents as modulators of the host immune system or other aspects of host-tumor interaction. Research in each of these areas will be reviewed.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Linfoma/terapia , Alemtuzumab , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/uso terapêutico , Antígenos CD/imunologia , Humanos , Doenças do Sistema Imunitário/terapia , Linfoma/tratamento farmacológico
9.
J Cell Biochem Suppl ; Suppl 35: 130-5, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11389542

RESUMO

Many stimuli play a role in influencing the structure and function of chromatin and nuclear matrix through post-translational modifications of the component proteins in these dynamic structures. We propose that the protein serine/threonine kinase CK2 (formerly casein kinase II) is one such agent that is involved in signal transduction in the nuclear matrix and chromatin in response to a variety of stimuli. Protein kinase CK2 appears to undergo rapid modulations in its association with nuclear matrix and nucleosomes in response to mitogenic signals and is involved in the phosphorylation of a variety of intrinsic proteins in these structures depending on the state of genomic activity. In addition, its association or loss from the nuclear matrix may also influence the apoptotic activity in the cell. CK2 has been found to be dysregulated in virtually all the neoplasias examined and nuclear association appears to be an important facet of its expression in tumor cells. We hypothesize that CK2 provides a functional paradigm linking the nuclear matrix and chromatin structures. Identification of precise loci of action of CK2 in these structures and how they influence the morphological appearance of the nucleus under normal and abnormal growth conditions would be an important future direction of investigation. J. Cell. Biochem. Suppl. 35:130-135, 2000. Published 2001 Wiley-Liss, Inc.


Assuntos
Núcleo Celular/metabolismo , Neoplasias/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Animais , Caseína Quinase II , Divisão Celular , Humanos , Células Tumorais Cultivadas
10.
J Cell Biochem ; 74(1): 127-34, 1999 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10381269

RESUMO

Modest dysregulation of CK2 has been shown to enhance the oncogenic potential in transgenic models of cancer. Since nuclear matrix serves as an anchor for CK2 and plays a key role in growth-related activities, we examined the effects of CK2 overexpression on its signaling to the nuclear matrix. Expression plasmids pCI-CK2alpha, pCI-CK2beta, and the bicistronic pCI-CK2alphabeta containing full length cDNAs encoding the various subunits were employed to transiently transfect two cell lines, BPH-1 and COS-1. Cytosol from transfected BPH-1 cells containing alpha or beta or alpha + beta or alphabeta showed a modest increase in CK2 activity by 26%, 1%, 20%, and 17%, respectively, over that in the controls transfected with pCI vector. However, the corresponding increase in CK2 activity in the NM fraction was 156%, 8%, 147%, and 152%, respectively. Immunoblot analysis of the CK2 in the NM accorded with these data. Similar results were obtained with COS-1 cells or other expression vectors. The results suggest that moderate overexpression of CK2 in the cells evokes a differential several-fold enhancement in NM associated CK2 relative to that in the cytosol. This process may have a bearing on the functional signaling of this kinase in relation to its possible role in oncogenesis.


Assuntos
Matriz Nuclear/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteína de Ligação a Androgênios/genética , Animais , Western Blotting , Caseína Quinase II , Linhagem Celular , Complemento C3/genética , Citosol/enzimologia , DNA Complementar , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Transfecção
11.
Cancer Res ; 59(5): 1146-51, 1999 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10070976

RESUMO

Protein kinase CK2, a messenger-independent serine/threonine kinase, has been implicated in cell growth. Androgenic stimulus in rat prostate modulates its association with nuclear matrix (NM) and chromatin. Because the growth of human prostate carcinoma cells is influenced by androgens and/or growth factors, we determined the nature of CK2 signaling in the NM in response to androgen and growth factor stimuli. Androgen-sensitive LNCaP and androgen-insensitive PC-3 cells were cultured in media to regulate their growth in the presence of 5alpha-dihydrotestosterone (5alpha-DHT) or growth factors (epidermal growth factor, keratinocyte growth factor, and transforming growth factor alpha). The activity of CK2 was measured in the cytosolic and NM fractions isolated from these cells after treatment with growth stimuli. The changes in CK2 in various fractions were also confirmed by immunoblotting with a specific antibody. LNCaP cells responded to both 5alpha-DHT and growth factors for growth. The presence of these agents in the culture medium evoked a translocation of CK2 to the NM from the cytosol. The PC-3 cells did not respond to 5alpha-DHT for growth but did respond to growth factors. Under these conditions, there was also a translocation of CK2 to the NM concomitant with a decrease in the cytosolic fraction. These results suggest that CK2 translocation to the NM occurs in response to various growth stimuli in cells in culture. Thus, CK2 is a common downstream signal transducer in response to diverse growth stimuli that may relate to the pathobiology of prostate cancer cells.


Assuntos
Di-Hidrotestosterona/farmacologia , Fatores de Crescimento de Fibroblastos , Substâncias de Crescimento/farmacologia , Matriz Nuclear/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/fisiologia , Adenocarcinoma , Animais , Caseína Quinase II , Divisão Celular/efeitos dos fármacos , Cromatina/fisiologia , Citosol/fisiologia , Proteínas de Ligação a DNA/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Fator 10 de Crescimento de Fibroblastos , Fator 7 de Crescimento de Fibroblastos , Humanos , Cinética , Masculino , Neoplasias da Próstata , Ratos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador alfa/farmacologia , Células Tumorais Cultivadas
12.
Oral Oncol ; 35(3): 290-5, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10621850

RESUMO

Overexpression of the epidermal growth factor (EGF) receptor, a hallmark of aerodigestive squamous cell carcinoma of the head and neck (SCCHN), correlates with aggressive tumor behavior. There is evidence that SCCHN cells auto-activate their EGF receptors. The receptor has therefore attracted interest as a potential therapeutic target. We tested the in vitro therapeutic efficacy of PD153035--a potent, specific inhibitor of the tyrosine kinase intrinsic to the EGF receptor--by employing a well-characterized cell line derived from human gingival SCCHN. DNA-synthesis and cell number were assayed for growth-inhibitory effects, phosphorylation of the EGF receptor was quantitated by immunoblot, and cell apoptosis was detected by terminal deoxytransferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) in situ assay. PD153035, at nanomolar concentrations, inhibited autophosphorylation of the EGF receptor induced by EGF stimulation and the inhibition occurred in a dose-dependent manner. Under the same conditions, PD153035 inhibited cell growth, and induced apoptosis of SCCHN cells in vitro. We conclude that selective inhibition of the EGF receptor tyrosine kinase completely abolishes EGF receptor phosphorylation resulting from receptor stimulation, and results in growth inhibition and apoptosis of SCCHN cells in vitro. By inducing cytostasis and apoptosis, this new class of inhibitors may be of therapeutic value against SCCHN.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Receptores ErbB/metabolismo , Neoplasias Gengivais/tratamento farmacológico , Quinazolinas/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Neoplasias Gengivais/enzimologia , Neoplasias Gengivais/patologia , Humanos , Células Tumorais Cultivadas
13.
Int J Gynecol Pathol ; 17(4): 312-9, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9785131

RESUMO

The identification of prognostic variables is an important aspect of managing and counseling women with endometrial adenocarcinoma. The surgical stage, age, cell type, depth of myometrial invasion, and histologic grade have all been previously demonstrated to be related to prognosis. Several reports have indicated that tumor ploidy as determined by flow cytometry with fresh or fixed cells removed from paraffin blocks of endometrial adenocarcinomas can contribute to the assessment of prognosis. To verify the significance of DNA content in endometrial adenocarcinoma, we conducted an historical cohort study on a subgroup of women from a Gynecologic Oncology Group (GOG) protocol of early clinical stage disease. Flow cytometry was performed at one facility on cells extracted from blocks obtained from several GOG member institutions. Blocks were submitted for 293 of 933 eligible patients. Ninety-two histograms were of good quality, with 55 interpreted as diploid and 37 as aneuploid. One hundred sixty-two histograms were technically suboptimal, of which 137 were considered probably diploid, 13 probably aneuploid, and 12 unacceptable due to high background noise. Of the commonly accepted prognostic variables, only depth of invasion was significantly related to the ploidy status. There was no discernable difference in survival between patients with diploid and patients with probable diploid and probable aneuploid tumor types. Incorporation of the flow cytometry data into a proportional hazards regression model adjusted for age and surgical stage revealed a significant increased risk of disease-related death (relative risk, 4.1; 95% confidence interval, 2.3 to 7.3) for patients with aneuploid tumor type as compared to patients with diploid tumor type. This study confirms the prognostic significance of ploidy determination by flow cytometry and also indicates some of the difficulties of retrospectively applying this technology to cooperative group studies.


Assuntos
Adenocarcinoma/genética , DNA de Neoplasias/análise , Neoplasias do Endométrio/genética , Adenocarcinoma/cirurgia , Aneuploidia , Estudos de Coortes , Diploide , Neoplasias do Endométrio/cirurgia , Feminino , Citometria de Fluxo , Humanos , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico
14.
Artigo em Inglês | MEDLINE | ID: mdl-9720095

RESUMO

Three adenoid cystic carcinomas and two epithelial-myoepithelial carcinomas, which focally shared common histologic features, were studied to examine the common differentiation pathways manifested by these tumors and to discuss criteria for hybrid salivary gland tumors. Regions of the adenoid cystic carcinomas had cellular features ranging from simple clear cell change of basal/myoepithelial cells to combined clear cells and prominent ductal structures mimicking epithelial-myoepithelial carcinoma. Conversely, two epithelial-myoepithelial carcinomas had adenoid cystic carcinoma-like regions caused by the formation of "pseudocysts"; this resulted in a focal cribriform pattern. Electron microscopy of two additional but typical epithelial-myoepithelial carcinomas revealed both excess basal lamina at the margins of cellular nests and widened intercellular spaces containing reduplicated basal lamina and accumulations of glycosaminoglycans; these ultrastructural features were identical to those seen in adenoid cystic carcinomas. The five current cases are not examples of hybrid tumors, but they demonstrate the effects of gene expression and the resulting differentiation of synthetic products and tumor cells that are generally restricted to one or the other of these two tumor types by as-yet-unknown means. To avoid misdiagnosis and its prognostic implications, adenoid cystic carcinoma-like regions in epithelial-myoepithelial carcinoma and epithelial-myoepithelial-like regions in adenoid cystic carcinoma should be recognized simply as anomalous differentiation.


Assuntos
Carcinoma Adenoide Cístico/patologia , Carcinoma/patologia , Neoplasias das Glândulas Salivares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Basal/ultraestrutura , Diferenciação Celular/genética , Linhagem da Célula/genética , Células Epiteliais/patologia , Espaço Extracelular , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Glicosaminoglicanos/ultraestrutura , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Prognóstico , Ductos Salivares/patologia
15.
Neurosurgery ; 42(5): 1153-5; discussion 1155-6, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9588562

RESUMO

OBJECTIVE AND IMPORTANCE: Hemangioendothelioma is an uncommon vascular neoplasm, and its intracranial occurrence is extremely rare. The occurrence of such a tumor within the cavernous sinus has not been reported previously. CLINICAL PRESENTATION: We report a 36-year-old woman who presented with right-sided retro-orbital pain and diplopia caused by a right sixth nerve paresis. Magnetic resonance imaging revealed a lesion within the right inferior cavernous sinus. INTERVENTION: The tumor was excised completely via an orbitozygomatic approach. CONCLUSION: Hemangioendothelioma is a rare, indolent vascular tumor, and its characteristics are reviewed. The need for complete excision is emphasized, and the advantages of the orbitozygomatic approach for the removal of tumors of the cavernous sinus is discussed.


Assuntos
Neoplasias Encefálicas/patologia , Seio Cavernoso , Hemangioendotelioma/patologia , Adulto , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Seio Cavernoso/patologia , Seio Cavernoso/cirurgia , Diagnóstico Diferencial , Diplopia/etiologia , Feminino , Hemangioendotelioma/complicações , Hemangioendotelioma/diagnóstico , Hemangioendotelioma/cirurgia , Hemangioma/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico
16.
J Cell Biochem ; 69(2): 211-20, 1998 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-9548568

RESUMO

Nuclear matrix (NM) appears to be an intranuclear locale for significant and dynamic association of the ubiquitous multifunctional messenger-independent serine/threonine protein kinase CK2 that has been implicated in growth control [Tawfic et al. (1996): J Cell Biochem 61:165-171]. We have examined the nature of the association of CK2 with the NM. Nuclei prepared in the presence of a sulfhydryl-blocking reagent such as iodoacetamide demonstrate a reduction in the amount of CK2 associated with the NM to less than 5% of the control. On the other hand, when nuclei are treated with the sulfhydryl crosslinking reagent sodium tetrathionate, NM-associated CK2 increases severalfold. Treatment of nuclei with sodium tetrathionate followed by 2-mercaptoethanol blocks this increase. Nuclei isolated from rat liver and prostate behaved similarly, suggesting an identical mode of association of CK2 with the NM regardless of the organ. These results indicate a role of sulfhydryl interactions such that NM anchoring of CK2 occurs via its beta subunit, which contains several vicinal cysteine residues. Further, various sulfhydryl-blocking reagents inhibited CK2 activity in a concentration-dependent manner, and the inhibitory effect was reversed by agents such as dithiothreitol, implying that cysteine residues in the CK2 play a role in its catalytic activity.


Assuntos
Dissulfetos/metabolismo , Matriz Nuclear/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Caseína Quinase II , Ditiotreitol/farmacologia , Ativação Enzimática/efeitos dos fármacos , Indicadores e Reagentes , Masculino , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/metabolismo , Compostos de Sulfidrila/metabolismo
17.
Arch Otolaryngol Head Neck Surg ; 123(3): 283-8, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9076234

RESUMO

OBJECTIVE: To test the hypothesis that transformation of normal upper aerodigestive mucosa to squamous cell carcinoma of the head and neck (SCCHN) is associated with specific changes in nuclear matrix (NM) proteins. DESIGN: Retrospective, nonrandomized investigation using a cellular fractionation sequence followed by 2-dimensional gel electrophoresis analysis of NM proteins. SUBJECTS: Nuclear matrix proteins were extracted from a cohort of 12 pathologic SCCHN specimens and 5 normal specimens of oropharyngeal mucosa. RESULTS: All SCCHN specimens examined expressed 11 NM proteins that were not detected in normal mucosa. Conversely, at least 4 NM proteins that were expressed by all specimens of normal mucosa were absent from all SCCHN tumors. Seven NM proteins were common to carcinomas and normal specimens. Spindle cell histological variants of squamous cell carcinoma had distinct NM patterns. CONCLUSIONS: Malignant transformation of normal upper aerodigestive mucosa to SCCHN is associated with specific changes in NM composition. These data suggest that different NM proteins might serve as specific tumor markers.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Proteínas Nucleares/análise , Antígenos Nucleares , Biomarcadores/análise , Carcinoma de Células Escamosas/química , Eletroforese em Gel Bidimensional , Neoplasias de Cabeça e Pescoço/química , Humanos , Mucosa/química , Orofaringe/química , Estudos Retrospectivos
18.
J Cell Biochem ; 64(3): 499-504, 1997 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-9057107

RESUMO

Nuclear matrix (NM) plays a role of fundamental structural and functional significance as the site of replication, transcription, and RNA processing and transport, acting as an anchor or attachment site for a variety of enzymes and other proteins involved in these activities. We have previously documented that protein kinase CK2 translocates from the cytosol to the nucleus, where it associates preferentially with chromatin and NM, in response to certain growth stimuli. Considering that characteristics of the isolated NM can depend on the procedural employed for its isolation, we compared three standard methods for NM preparation to confirm the association of intrinsic CK2 with this structure. Our data suggest that the method used for isolating the NM can qualitatively influence the measurable NM-associated CK2. However, all three methods employed yielded qualitatively similar results with respect to the stimulus-mediated modulation of NM-associated CK2, thus further supporting the notion that NM is an important site for physiologically relevant functions of CK2. In addition, core filaments and cytoskeleton that were isolated by two of the preparative methods had a small but significant level of associated CK2 activity.


Assuntos
Matriz Nuclear/enzimologia , Proteínas Serina-Treonina Quinases/isolamento & purificação , Animais , Caseína Quinase II , Cromatina , Citoesqueleto , Citosol/enzimologia , Humanos , Masculino , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Células Tumorais Cultivadas
19.
Pediatr Emerg Care ; 12(3): 166-8, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8806137

RESUMO

The objective of this study was to describe the use of a pediatric emergency department (PED) by children with chronic conditions. The study design was retrospective and descriptive in an urban tertiary care pediatric hospital setting. We reviewed 8561 visits to a PED over a three-month time period. Two thousand twenty-four (24%) of the visits were by children with one or more chronic conditions. There were no interventions. The mean age of the patients was 4.9 years, and 61% were male. Thirty-one percent of the patients sought care between 8 AM and 5 PM Monday through Friday. Five subspecialty areas accounted for 86% of the chronic conditions seen: asthma (43%), neurology (15%), hematology/oncology (14%), neurosurgery (10%), and cardiology (4%). Twenty-eight percent of the chronically ill patients were admitted as compared to 11% of the nonchronically ill patients (P < 0.001). One percent of the chronically ill patients were admitted to the intensive care unit as compared to 0.03% of the nonchronically ill patients (P < 0.0001). It was concluded that children with chronic conditions account for one-quarter of all PED visits. Sixty-nine percent of those visits were made during evening/ nighttime hours or on the weekend. A relatively large percentage of these children were admitted. The pediatric emergency physicians provide an important service to both the children with chronic conditions and the subspecialists who care for them. PEDs may need to refine emergency department systems to serve this group of patients as efficiently and effectively as possible.


Assuntos
Doença Crônica/terapia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adolescente , Adulto , Asma/terapia , Criança , Pré-Escolar , Feminino , Infecção Focal/terapia , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Admissão do Paciente , Estudos Retrospectivos , Tempo , População Urbana
20.
Ann Surg ; 221(2): 171-5, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7857144

RESUMO

BACKGROUND: Although early resumption of enteral feeding after gastrointestinal surgery results in improved nitrogen balance and lower infectious complications, no postoperative nutritional data after laparoscopic-assisted colectomy exists. OBJECTIVE: The authors prospectively compared nitrogen balance after laparoscopic-assisted colectomy versus open colectomy. METHODS: This is a series of colon resections (open, N = 10; laparoscopic-assisted, N = 9) at the Ferguson-Blodgett Hospital, Grand Rapids, Michigan, between January and March 1993. Nitrogen intake and 24-hour urine collections were performed on postoperative days 1, 3, and 7 for the analysis of total urinary nitrogen and urinary 3 methylhistidine-(3mH). RESULTS: The time to passage of flatus (4.7 +/- 0.6; 2.0 +/- 0.2), resumption of oral intake (6.1 +/- 0.7; 1.4 +/- 0.2; p < 0.05, Student's test), first bowel movement (5.2 +/- 1.0; 3.0 +/- 0.3; p < 0.05, Student;s t test), and discharge (10.3 +/- 1.3; 4.1 +/- 1.8; p < 0.05, Student's t test) occurred significantly earlier in the laparoscopic-assisted colectomy group. Overall hospital charges were lower in the laparoscopic-assisted colectomy group ($11,572 +/- $823 vs. $13,961 +/- $1050). The operative time was higher in the laparoscopic-assisted colectomy group (176 +/- 12 hours vs. 105 +/- 17 hours, p < 0.05,Student's test). Blood loss was higher in the open group (805 +/- 264 mL vs 217 +/- 32 mL, p < 0.05, Student's test). Urinary nitrogen losses were similar between the two groups; however, significantly more patients in the laparoscopic-assisted colectomy group achieved net positive nitrogen on day 3 (6/9; 0/10; p < 0.05, Fisher's exact test), and day 7 (9/9; 4/10; p < 0.05, Fisher's exact test). Infectious complications occurred less frequently in the laparoscopic-assisted colectomy group (0/9 vs. 4/10; p < 0.05, Fisher's exact test). CONCLUSIONS: Patients undergoing laparoscopic-assisted colectomy can achieve early resumption of enteral nutrition with earlier return to positive nitrogen balance compared with open colectomy. This may offer benefits of fewer infectious complications and lower cost of care.


Assuntos
Colectomia/métodos , Laparoscopia , Nitrogênio/metabolismo , Colectomia/economia , Nutrição Enteral , Feminino , Preços Hospitalares/estatística & dados numéricos , Humanos , Incidência , Laparoscopia/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Metilistidinas/urina , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório , Fatores de Tempo
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