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1.
Arch Orthop Trauma Surg ; 136(6): 873-80, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26969464

RESUMO

INTRODUCTION: The diagnostic value of clinical tests and magnetic resonance (MR) imaging for the investigation of triangular fibrocartilaginous complex (TFCC) lesions is not clear due to a lack of clinical data. MATERIALS AND METHODS: We retrospectively analyzed 908 patients who underwent clinical tests and arthroscopy for suspected TFCC lesions at our institution. Further, MR imaging findings concerning the TFCC were gathered. We correlated clinical tests and MR imaging findings with those obtained during arthroscopy, and we calculated sensitivity, specificity, as well as positive and negative predictive values. RESULTS: In the whole cohort, the positive predictive values of all clinical tests were low, ranging from 0.53 to 0.55. The ulna grinding test had the highest sensitivity, but lowest specificity. Sensitivity and specificity of the ulnar fovea sign and magnetic resonance imaging were similar, ranging from 0.73 to 0.76, and from 0.41 to 0.44, respectively. To some degree, the diagnostic value seemed to depend on the Palmer class of TFCC lesion. CONCLUSIONS: According to this study, clinical tests and MR imaging findings are of very limited diagnostic value for the diagnosis of TFCC lesions.


Assuntos
Imageamento por Ressonância Magnética , Fibrocartilagem Triangular/diagnóstico por imagem , Traumatismos do Punho/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Físico , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
2.
Eur Radiol ; 21(1): 176-81, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20683598

RESUMO

OBJECTIVE: Although in widespread clinical use, evidence of the diagnostic accuracy of radiographic parameters for the diagnosis of scapholunate ligament injuries is scarce. The objective of this study was to evaluate the scapholunate (SL) angle, radiolunate (RL) angle and SL gap as diagnostic parameters for these lesions. METHODS: Eight hundred forty nine patients, who underwent wrist arthroscopy at our institution because of wrist pain were included in a retrospective analysis. In all patients the SL angle, RL angle and SL gap were measured on preoperative radiographs. These parameters were correlated with the actual finding of the SL ligament during arthroscopy. Optimal test thresholds were calculated as well as sensitivity, specificity and the likelihood ratios of each parameter. RESULTS: All three parameters proved useful in statistical analysis. The optimal cut-off points for diagnosing lesions of the SL ligament were calculated as 62.5° for the SL angle, 12.5° for the RL angle and 2.5 mm for the SL gap. SL angles had the greatest specificity (0.93). CONCLUSIONS: We were able to validate plain radiographs as a reliable tool in the work-up of patients with suspected SL ligament injuries. However, wrist arthroscopy remains the gold standard in diagnosing and treating these lesions.


Assuntos
Ligamentos Articulares/diagnóstico por imagem , Traumatismos do Punho/diagnóstico , Articulação do Punho/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Radiografia , Estudos Retrospectivos
3.
J Exp Med ; 192(10): 1501-8, 2000 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-11085751

RESUMO

Hemofiltrate CC chemokine (HCC)-1 is a recently described human chemokine that is constitutively expressed in numerous tissues and is present at high concentrations in normal plasma. Using a cell line expressing CC chemokine receptor (CCR)5 as a bioassay, we isolated from human hemofiltrate an HCC-1 variant lacking the first eight amino acids. HCC-1[9-74] was a potent agonist of CCR1, CCR3, and CCR5 and promoted calcium flux and chemotaxis of T lymphoblasts, monocytes, and eosinophils. It also blocked entry of HIV-1 strains using CCR5 as coreceptor. Limited tryptic digestion of HCC-1 generated the active variant. Conditioned media from several tumor cell lines activated HCC-1 with a high efficiency, and this activity could be inhibited by serine protease inhibitors. Our results indicate that HCC-1 represents a nonfunctional precursor that can be rapidly converted to the active chemokine by proteolytic processing. This process represents an additional mechanism by which tumor cells might generate chemoattractant molecules and recruit inflammatory cells. It might also affect HIV-1 replication in infected individuals and play an important role in AIDS pathogenesis.


Assuntos
Fármacos Anti-HIV/farmacologia , Proteínas Sanguíneas/metabolismo , Quimiocinas CC/metabolismo , Receptores CCR5/agonistas , Receptores de Quimiocinas/agonistas , Adulto , Sequência de Aminoácidos , Bioensaio , Sinalização do Cálcio , Fatores Quimiotáticos/farmacologia , Quimiotaxia de Leucócito , Meios de Cultivo Condicionados/metabolismo , Endopeptidases/metabolismo , Humanos , Dados de Sequência Molecular , Fragmentos de Peptídeos/farmacologia , Processamento de Proteína Pós-Traducional , Receptores CCR1 , Receptores CCR3
5.
Curr Drug Targets Infect Disord ; 2(1): 9-16, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12462149

RESUMO

Highly active inhibitors of human immunodeficiency virus (HIV) reverse transcriptase and protease have made it possible to dramatically reduce virus load in HIV-positive individuals. However, the presence of viral reservoirs, the emergence of drug-resistant HIV variants and the side effects of these compounds call for research into new drugs that target different stages of the viral life cycle. One attractive target is the first step in HIV replication: entry of virus into cells. HIV entry is initiated by the attachment of the virus to the host cell membrane, which is some cases involves binding to attachment factors such as DC-SIGN. Subsequent interaction of the envelope protein (Env) with the CD4 receptor causes conformational changes that enable Env to interact with a coreceptor, generally the chemokine receptors CCR5 or CXCR4. Coreceptor engagement triggers the final conformational changes in Env, which mediate lipid mixing between the viral and cellular membranes. All of these steps are potential targets for therapeutic intervention: targeting proteins that mediate viral attachment may reduce HIV transmission, while receptor blockade will inhibit virus entry. Highly conserved domains in Env which bind to CD4 and coreceptor are promising targets for broadly neutralizing antibodies, and peptide inhibitors that bind to Env and that block membrane fusion are in advanced clinical trials. These new approaches may supplement current HIV therapy and may assist in the development of an HIV vaccine.


Assuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/prevenção & controle , Receptores Virais/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Produtos do Gene env/fisiologia , Infecções por HIV/virologia , Humanos , Fusão de Membrana/efeitos dos fármacos
6.
Toxicon ; 26(5): 453-8, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-2460973

RESUMO

One monovalent (habu-antivenom) and five polyvalent antivenoms (Crotalidae; Orient, North, Central and South Africa) were tested for their ability to neutralize the hemorrhagic activity of 12 snake venoms (Agkistrodon, Bothrops, Crotalus, Sistrurus, Trimeresurus, Bitis, Echis spp.) when mixed prior to injection into the hind leg of mice. Considerable cross-neutralization was observed: antivenoms prepared against African snake venoms were equally or more potent in neutralizing the hemorrhagic activity of Crotalidae venoms. The same applies to Crotalidae antivenom which neutralized the activity of African snake venoms. Anti-hemorrhagic antibodies were isolated from a polyvalent antivenom by affinity chromatography using purified hemorrhagins from Bitis arietans and Crotalus adamanteus venom as ligands. These antibodies neutralized the activity of both hemorrhagins indicating common antigenic determinants in these molecules.


Assuntos
Anticorpos/isolamento & purificação , Antivenenos/normas , Endopeptidases , Venenos de Serpentes/toxicidade , Animais , Reações Cruzadas , Endopeptidases/imunologia , Epitopos/imunologia , Camundongos , Testes de Neutralização
7.
Accid Anal Prev ; 26(6): 689-702, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7857486

RESUMO

Forty-eight drivers of different ages (35-50 years old, 61 years and older) took part in our study, which tested a marketable navigation system (TRAVELPILOT IDS). Driving and navigation performance, as well as mental workload and the acceptance of innovative technology, were investigated. A limited range of findings will be presented in this paper. The results show that older and middle-aged drivers differ in only a few aspects. Both age groups reveal comparable results in driving. However, regarding the operation of the navigation system and concerning its effectiveness, older drivers performed worse. Age-related differences being rather small, analyses revealed significant global differences between the navigation system and a common road map: usage of the TRAVELPILOT influenced driving behavior negatively with respect to traffic safety. Also, the drivers' orientation was not any better using the navigation system. Based on this experimental work and on results derived from the literature, conclusions are drawn regarding future navigation systems in general and with respect to needs of elderly drivers.


Assuntos
Condução de Veículo , Sistemas Homem-Máquina , Orientação , Adulto , Fatores Etários , Idoso , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Zoonoses Public Health ; 59 Suppl 2: 116-31, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22958256

RESUMO

Zoonotic transmission of Ebola virus (EBOV) to humans causes a severe haemorrhagic fever in afflicted individuals with high case-fatality rates. Neither vaccines nor therapeutics are at present available to combat EBOV infection, making the virus a potential threat to public health. To devise antiviral strategies, it is important to understand which components of the immune system could be effective against EBOV infection. The interferon (IFN) system constitutes a key innate defence against viral infections and prevents development of lethal disease in mice infected with EBOV strains not adapted to this host. Recent research revealed that expression of the host cell IFN-inducible transmembrane proteins 1-3 (IFITM1-3) and tetherin is induced by IFN and restricts EBOV infection, at least in cell culture model systems. IFITMs, tetherin and other effector molecules of the IFN system could thus pose a potent barrier against EBOV spread in humans. However, EBOV interferes with signalling events required for human cells to express these proteins. Here, we will review the strategies employed by EBOV to fight the IFN system, and we will discuss how IFITM proteins and tetherin inhibit EBOV infection.


Assuntos
Ebolavirus/fisiologia , Interferons/antagonistas & inibidores , Interferons/metabolismo , Proteínas Virais/metabolismo , Proteínas Virais Reguladoras e Acessórias/metabolismo , Animais , Humanos , Zoonoses
9.
Dtsch Med Wochenschr ; 133(46): 2377-82, 2008 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-18988129

RESUMO

BACKGROUND AND OBJECTIVE: Myasthenia gravis in the majority of patients is a well treatable neurological autoimmune disorder with a prevalence of 60-150 per million. For the treatment of myasthenic crisis in the intensive care unit the use of therapeutic apheresis, e. g. immunoadsorption or plasma exchange, is well established due to its rapid therapeutic effect, whereas the necessity in long term treatment is still questioned. Aim of this retrospective cohort-study was the assessment of patients with refractory myasthenia gravis in Germany treated by regular immunoadsorption, the characterization of previous therapies and the efficacy of long-term treatment. PATIENT AND METHODS: In total 14 patients (9 women, 5 men, mean age: 40.5 years) were identified in Germany using regular therapeutic apheresis. 13 were treated with different modes of immunoadsorption (10 yen l-tryptophan-adsorption, 2 yen epitope-specific adsorption, 1 yen polyclonal sheep antibody on sepharose) and 1 with plasma exchange. Mean duration of standard treatment of myasthenia gravis before initiation of regular apheresis was 7.8 years. RESULTS: Average duration of analyzed apheresis treatment was 6.4 years, with a mean treatment-interval of 1.1 per week. Mean reduction rate of autoantibodies against acetylcholine-receptor-protein was 50-60 % per session. After initiation of immunoadsorption the mean time of hospitalisation decreased significantly by app. 60 %. In particular the number of myasthenic crises could be reduced by 89 % per year. Tolerability of immunoadsorption was very good, no severe adverse events occurred. CONCLUSION: In conclusion, for the treatment of the subgroup of myasthenia gravis patients becoming refractory to standard treatment immunoadsorption should be regarded as integral part of the therapeutic armamentarium to stabilize and optimize the state of neurologic rehabilitation. This evaluation should be also carefully considered by carriers of health care cost as currently best available evidence to decide on appropriate treatment regimens for these rare patients.


Assuntos
Remoção de Componentes Sanguíneos , Técnicas de Imunoadsorção , Miastenia Gravis/terapia , Troca Plasmática , Adulto , Autoanticorpos/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Receptores Colinérgicos/imunologia , Estudos Retrospectivos , Fatores de Tempo
10.
Vet Comp Oncol ; 4(4): 218-31, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19754806

RESUMO

This prospective study describes the feasibility and toxicity of (192)Iridium high-dose-rate (HDR) brachytherapy as an alternative strategy for the treatment of canine intranasal tumours. Fifteen dogs with malignant intranasal tumours were treated twice weekly using a hypofractionated protocol with eight fractions, 5 Gy per fraction, resulting in a total dose of 40 Gy. Acute and chronic adverse side-effects appeared to be rare. Only 7% of the acute side-effects and 5% of the chronic were classified as severe (grade 3). Eight dogs showed clinical complete remission, and five dogs had partial remission, with a resolution of tumour-related symptoms. Magnetic resonance imaging showed a reduced tumour mass in 12 cases. Median survival time was 17 months (range 4-48 months), with four dogs (three without disease) still alive. Median time to recurrence of these dogs was 14 months. In nine dogs, progression or recurrence of the tumour was the cause of death. This study suggests that HDR brachytherapy is feasible and well tolerated.

11.
Virology ; 213(1): 263-70, 1995 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-7483273

RESUMO

The paramyxovirus hemagglutinin-neuraminidase (HN) is a type II homotetrameric integral membrane glycoprotein composed of a pair of disulfide-linked dimers that are held together by noncovalent bonds. To determine the role of the internal uncleaved signal-anchor (S/A) domain in stable tetramer formation, cDNA-derived HN mutants containing S/A substitutions were expressed in HeLa cells. The assembly into tetramers and ER-to-Golgi transport of the proteins were examined by sucrose gradient sedimentation and by endoglycosidase treatment. A leucine-scanning substitution analysis of the 19-residue S/A identified 2 polar residues (Ser 31 and Tyr 36) in the C-terminal end of the S/A that were important for the formation of a stable tetramer. While Ala, Cys, and Gly could functionally replace Ser 31 in the formation of a stable tetramer, substitution with Leu or Phe resulted in mutants that were detected as disulfide-linked dimers. These results indicate that a small amino acid in position 31, rather than a specific residue per se, is an important assembly requirement in the S/A. In contrast to the size requirement for position 31, the conservative substitution of Tyr 36 with Phe produced an HN mutant that sedimented as a mixture of dimers, tetramers, and higher order oligomers, suggesting that proper assembly requires a Tyr in this position. The S/A mutants that were detected as disulfide-linked dimers showed only a slight reduction in ER-to-Golgi transport (approximately 50% of WT), consistent with the proposal that the S/A substitutions had affected tetramer stability and not the formation of a transport-competent oligomer. These data indicate that there are different structural requirements for two positions in the C-terminal region of the HN S/A for the assembly of a stable tetramer.


Assuntos
Proteína HN/química , Proteínas de Membrana/química , Paramyxoviridae/química , Sequência de Aminoácidos , Aminoácidos , Centrifugação com Gradiente de Concentração , DNA Viral , Complexo de Golgi/metabolismo , Proteína HN/genética , Proteína HN/fisiologia , Células HeLa , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Paramyxoviridae/genética , Paramyxoviridae/fisiologia , Processamento de Proteína Pós-Traducional , Relação Estrutura-Atividade
12.
Strahlenther Onkol ; 171(11): 641-5, 1995 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-7502227

RESUMO

AIMS: The classic continuous low dose rate (LDR) brachytherapy was very important in such cases with a higher risk of severe especially late radiation reactions. From clinical experiences and radiobiological considerations it is known, that the therapeutic ratio of LDR is higher than HDR. Another way to combine the therapeutic ratio of LDR and the possibility of optimisation is the use of pulse dose rate (PDR) technique. The PDR-technique is a method, which can be compared with continuous LDR-therapy. PDR should have biological effects equivalent to conventional LDR. MATERIAL AND METHODS: We have tried to compare the classic continuous LDR-technique with 2 PDR-regimes by means of the guinea pig skin model. In this test series we involved 20 female animals with an initial weight of 400 to 500 g. We compared radiation reactions of following regimes: 1. Continuous LDR regimen with a cobalt-60 source with an activity of 5.5 mCi 30 Gy in 60 hours. 2. PDR regimen 0.5 Gy hourly, pulse length minimal 10 minutes, 30 Gy in 60 hours with an Ir-192 source with an activity of nearly 40 mCi. 3. PDR-regimen 0.8 Gy hourly with 9 hours night break (10.00 p. m. to 7.00 a. m.). The radiation reaction was controlled by the help of an evaluation table in which the criteria of radiation reaction were classified according to the degree of seriousness. The observation time is now minimal 14 and maximal 24 months. RESULTS: The findings shows a significant coincidence of early and late radiation reactions of the skin fields irradiated with the continuous LDR-technique and fields irradiated with the PDR-technique. There was not a difference of the radiation reactions between PDR-irradiation with and without night break. CONCLUSIONS: Generally it is possible to compare the radiation reactions of PDR-irradiation and the classic continuous LDR-brachytherapy. It is also possible to use a PDR-regimen with a night break of 9 hours. But results must be calculated for each tissue of interest, in our test consequently for guinea pig skin.


Assuntos
Modelos Animais de Doenças , Pele/efeitos da radiação , Animais , Braquiterapia , Radioisótopos de Cobalto/administração & dosagem , Relação Dose-Resposta à Radiação , Feminino , Cobaias , Radioisótopos de Irídio/administração & dosagem , Método de Monte Carlo , Radiobiologia , Dosagem Radioterapêutica , Fatores de Tempo
13.
Strahlenther Onkol ; 168(12): 711-5, 1992 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-1481121

RESUMO

Since the introduction of the high-dose rate afterloading therapy a higher biological effectivity of this method has been well known in comparison with the low-dose contact therapy. This will practically taken into account by reducing the dose and more fractionating of the total dose. With our test we want: firstly to prove the influence of the therapy break on the duration of the radiation reaction. Secondly we want to prove the influence of the dose rate on the efficiency of the radiation reaction. We have tried to answer the question by the animal model guinea pig skin. We examined early reactions as well late reactions.


Assuntos
Radioisótopos de Irídio/uso terapêutico , Animais , Relação Dose-Resposta à Radiação , Feminino , Cobaias , Radioisótopos de Irídio/efeitos adversos , Radiodermite/etiologia , Radiodermite/patologia , Dosagem Radioterapêutica , Pele/patologia , Pele/efeitos da radiação , Fatores de Tempo
14.
Stem Cells ; 15 Suppl 1: 31-8; discussion 38-9, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9368322

RESUMO

The kinetics of blood and organ engraftment following transplants of defined populations of hematopoietic stem/progenitor cells were investigated utilizing cell populations defined by surface antigen and rhodamine-123 staining. While long-term repopulating stem cells, short-term multipotent progenitors and committed progenitors all reconstituted peripheral blood red cells and splenic cellularity, only the population of cells that includes highly enriched long-term repopulating stem cells (Thy-1.1lowLinnegSca-1+Rh123low) reconstituted marrow cellularity. In addition, peripheral blood platelet and nucleated cell count increased only after transplant of the long-term repopulating population. These results argue that the major cell population that functions to reconstitute hematopoiesis after bone marrow transplantation is a primitive, marrow-homing stem cell. Transplantation of highly enriched multipotent progenitors that lack long-term reconstituting potential had no impact on hematopoietic recovery, apart from a transient increase in circulating erythrocytes. These results suggest that the primary cell population that functions to reconstitute hematopoiesis in a transplant setting is the long-term repopulating stem cell. This observation is discussed in the context of the normal hematopoietic process.


Assuntos
Hematopoese/fisiologia , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Animais , Antígenos de Diferenciação/análise , Plaquetas , Células da Medula Óssea , Eritrócitos , Células-Tronco Hematopoéticas/química , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos , Baço/citologia
15.
Strahlenther Onkol ; 175(4): 170-4, 1999 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-10230459

RESUMO

BACKGROUND: In our department we have developed a standardized applicator for HDR brachytherapy of surface lesions, the so called Leipzig-applicator. We have used this method since September 1987, initially with a Decatron remote afterloading machine, but more recently from November 1990 with a microSelectron-HDR. We report about our experience of 10 years. PATIENTS AND METHOD: Since 1987 we treated 520 patients in 3,026 fractions with this method. In most of the cases we irradiated tumors of the skin of the face, but we also treated tumors of the mouth, of the tongue, of the perianal region and the external genitalia. The histological types were in most of the cases squamous cell carcinomas and basal cell carcinomas, but we also treated tumors like Kaposi-sarcomas, melanomas and skin manifestations of lymphomas and solid organ tumors. We also irradiated benign lesions like keloids after excision. We use single doses between 5 and 10 Gy once to twice a week. The isodose distribution was depending of the tissue infiltration of the tumor. The total dose was 30 to 40 Gy. RESULTS: In 91% of the cases we obtained a complete remission of the tumor, in 6% a partial remission. Recurrences appeared in 8% of the patients. In most cases the reason of the recurrence was a lower brachytherapy dose because of a prior radiotherapy. We didn't observe any severe late radiation reaction. CONCLUSION: We consider that our series of patients treated with HDR brachytherapy and a range of standardized applicators demonstrates that this is a successful method of treating surface lesions.


Assuntos
Braquiterapia/instrumentação , Queloide/radioterapia , Paroniquia/radioterapia , Neoplasias Cutâneas/radioterapia , Adulto , Idoso , Braquiterapia/métodos , Braquiterapia/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Cuidados Pós-Operatórios , Dosagem Radioterapêutica , Resultado do Tratamento
16.
Radiobiol Radiother (Berl) ; 30(6): 515-20, 1989.
Artigo em Alemão | MEDLINE | ID: mdl-2608891

RESUMO

First results of high-dose-rate afterloading therapy in the head-neck area are encouraging. The procedure is not very invasive and is suitable especially for older patients, not tolerating much, who can be hardly submitted another therapeutic method. The limited spatial dose distribution allows a careful treatment of the surrounding tissue in spite of the application of high single doses, however limits the size of tumors too, that the afterloading therapy is possible in (max. 2 cm). The method represents an alternative of the much more complicated procedure of the low-dose contact therapy, that affects the patients in a stronger way like interstitial therapy and moulage treatment. No tumor recurrences or metastasis were seen in our patients. Influence of alteration in fractionation rhythm and of application of sources with very high dose capacity will be the subject of further studies.


Assuntos
Braquiterapia/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica
17.
Strahlenther Onkol ; 170(5): 264-8, 1994 May.
Artigo em Alemão | MEDLINE | ID: mdl-8197548

RESUMO

PURPOSE: The frequency and the poor therapeutic results in advanced cervical cancer establish the demand for effectiveness of treatment. Recent clinical data have shown that simultaneous radiochemotherapy may yield high remission rates in squamous cell carcinomas of other organs. PATIENTS AND METHODS: In our Department of Radiotherapy and Radiooncology of the University of Leipzig we treated since 1.6.1991 17 patients with advanced cancer of the uterine cervix with a simultaneous radiochemotherapy with carboplatin. RESULTS: The rate of complete remission was 76%. Follow-up is available from six to 24 months. Severe or toxic side effects of the treatment we didn't observe. Eight (47%) patients live relapse-free. CONCLUSIONS: In our opinion randomized studies are required to determine: What is better? Simultaneous radiochemotherapy or radiotherapy?


Assuntos
Carboplatina/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adolescente , Adulto , Idoso , Carboplatina/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia/efeitos adversos , Indução de Remissão , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
18.
J Virol ; 72(7): 5589-98, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9621017

RESUMO

Large deletions of the upstream U3 sequences in the long terminal repeats (LTRs) of human immunodeficiency virus and simian immunodeficiency virus (SIV) accumulate in vivo in the absence of an intact nef gene. In the SIV U3 region, about 65 bp just upstream of the single NF-kappaB binding site always remained intact, and some evidence for a novel enhancer element in this region exists. We analyzed the transcriptional and replicative capacities of SIVmac239 mutants containing deletions or mutations in these upstream U3 sequences and/or the NF-kappaB and Sp1 binding sites. Even in the absence of 400 bp of upstream U3 sequences, the NF-kappaB site and all four Sp1 binding sites, the SIV promoter maintained about 15% of the wild-type LTR activity and was fully responsive to Tat activation in transient reporter assays. The effects of these deletions on virus production after transfection of COS-1 cells with full-length proviral constructs were much greater. Deletion of the upstream U3 sequences had no significant influence on viral replication when either the single NF-kappaB site or the Sp1 binding sites were intact. In contrast, the 26 bp of sequence located immediately upstream of the NF-kappaB site was essential for efficient replication when all core enhancer elements were deleted. A purine-rich site in this region binds specifically to the transcription factor Elf-1, a member of the ets proto-oncogene-encoded family. Our results indicate a high degree of functional redundancy in the SIVmac U3 region. Furthermore, we defined a novel regulatory element located immediately upstream of the NF-kappaB binding site that allows efficient viral replication in the absence of the entire core enhancer region.


Assuntos
Elementos Facilitadores Genéticos , NF-kappa B/metabolismo , Vírus da Imunodeficiência Símia/genética , Fator de Transcrição Sp1/metabolismo , Replicação Viral , Animais , Sequência de Bases , Células COS , Dados de Sequência Molecular , Proto-Oncogene Mas , Sequências Repetitivas de Ácido Nucleico
19.
Virology ; 284(2): 287-96, 2001 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-11384227

RESUMO

In contrast to human immunodeficiency viruses type 1 and type 2 (HIV-1 and HIV-2, respectively), simian immunodeficiency virus (SIVmac) rarely uses CXCR4 (X4) for efficient entry into target cells. Basic amino acid residues in the V3 loop of HIV Env allow efficient coreceptor utilization of X4. Therefore, we investigated if similar changes in the SIVmac Env protein also mediate a coreceptor switch from CCR5 (R5) to X4. Functional analysis revealed that none of eight SIVmac variants, containing V3 regions with an overall charge between +4 and +10, efficiently utilized X4 as entry cofactor. Nonetheless, these alterations had differential effects on SIV coreceptor tropism and on Env expression levels. A single amino acid substitution of L328R, located near the tip of the V3 loop, resulted in grossly reduced Env expression levels and impaired viral infectivity. Notably, additional basic residues restored efficient Env expression and virion incorporation but not infectivity. In comparison to the L328R mutation, changes of P334K and D337K had little disruptive effects on SIVmac entry and replication. Interestingly, mutation of L320K and P321R disrupted coreceptor usage of GPR15 but not R5. These changes also impaired SIVmac replication in peripheral blood mononuclear cells (PBMC) derived from a Delta32/Delta32 donor but not in R5-expressing human or simian PBMC. Our results show that positively charged amino acid residues in the V3 loop affect SIVmac coreceptor tropism and infectivity but do not allow efficient utilization of X4.


Assuntos
Receptores CXCR4/metabolismo , Receptores Virais/metabolismo , Vírus da Imunodeficiência Símia/genética , Proteínas do Envelope Viral/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Células Cultivadas , Humanos , Leucócitos Mononucleares/virologia , Dados de Sequência Molecular , Mutação , Ligação Proteica , Vírus da Imunodeficiência Símia/patogenicidade , Tropismo , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/metabolismo , Replicação Viral
20.
Blood ; 96(1): 41-9, 2000 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10891428

RESUMO

CCR5 and CXCR4 are the major coreceptors that mediate human immunodeficiency virus 1 (HIV-1) infection, while most simian immunodeficiency virus (SIV) isolates use CCR5. A number of alternative coreceptors can also mediate infection of some virus strains in vitro, although little is known about their in vivo relevance. Therefore, we characterized the expression pattern and coreceptor activity of one of these alternative coreceptors, STRL33/Bonzo, using a newly developed monoclonal antibody. In addition to being highly expressed (approximately 1000-7000 STRL33 ABS [antibody binding sites]) on specific subsets of natural killer cells (CD3(-)/CD16(-/low)/CD56(+) and CD3(-)/CD16(low)/CD56(-)) and CD19(+) B lymphocytes (approximately 300-5000 STRL33 ABS), STRL33 was expressed at levels sufficient to support virus infection on freshly isolated, truly naive CD4(+)/CD45RA(+)/CD62L(+) cells (6000-11 000 ABS). STRL33 expression on peripheral blood mononuclear cells (PBMCs) was increased by mitogenic stimulation (OKT3/IL-2 [interleukin-2] had a greater effect than phytohemaglutinin (PHA)/IL-2), but it was dramatically decreased upon Ficoll purification. Infection of CCR5(-) human peripheral blood lymphocytes (PBLs) showed that 2 different SIV envelope (Env) proteins mediated entry into STRL33(+) cells. More importantly, the preferential infection of STRL33(+) cells in CCR5(-) PBLs by an R5/X4/STRL33 HIV-1 maternal isolate in the presence of a potent CXCR4 antagonist (AMD3100) suggests that STRL33 can be used as a coreceptor by HIV-1 on primary cells. Rhesus macaque (rh) STRL33 was used less efficiently than human STRL33 by the majority of SIV Env proteins tested despite similar levels of expression, thereby making it less likely that STRL33 is a relevant coreceptor in the rhesus macaque system. In summary, the expression pattern and coreceptor activity of STRL33 suggest its involvement in trafficking of tumor-infiltrating lymphocytes and indicate that STRL33 may be a relevant coreceptor in vivo.


Assuntos
Linfócitos B/imunologia , Células Matadoras Naturais/imunologia , Receptores de Citocinas/fisiologia , Receptores Acoplados a Proteínas G , Receptores Virais/fisiologia , Animais , Antígenos CD/fisiologia , Linhagem Celular , Células Cultivadas , Citometria de Fluxo , Genes Reporter , Vetores Genéticos , Proteínas de Fluorescência Verde , Humanos , Proteínas Luminescentes/análise , Proteínas Luminescentes/genética , Macaca mulatta , Receptores CCR5/deficiência , Receptores CCR5/genética , Receptores CCR5/fisiologia , Receptores CXCR6 , Receptores de Quimiocinas , Receptores de Citocinas/genética , Receptores Virais/genética , Transfecção
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