RESUMEN
Fanconi's anemia is a rare autosomal recessive disorder associated with variable clinical manifestations. So far, eight complementation groups have been identified, and the genes of four of them have been cloned. Early-onset progressive bone marrow failure and a predisposition to malignancies, particularly acute myelogenous leukemia, liver tumors, and mucocutaneous squamous cell carcinomas, result in a poor prognosis. Additionally, almost all organs can be affected by this defect. Widespread areas of hyper- and hypopigmentation of the skin in a characteristic pattern and café-au-lait spots preceding the manifestation of panmyelopathy can aid early diagnosis. Here we report an 11-year-old boy with Fanconi's anemia presenting with typical cutaneous manifestations. We emphasize the important role of skin abnormalities of Fanconi's anemia as signs enabling early diagnosis. Moreover, we summarize clinical features, course, therapy, and new aspects of the molecular basis of Fanconi's anemia.
Asunto(s)
Manchas Café con Leche/diagnóstico , Anemia de Fanconi/diagnóstico , Hipopigmentación/diagnóstico , Adolescente , Manchas Café con Leche/genética , Niño , Consanguinidad , Diagnóstico Diferencial , Anemia de Fanconi/genética , Estudios de Seguimiento , Humanos , Hipopigmentación/genética , MasculinoRESUMEN
Eotaxin is a potent inducer of eosinophil chemotaxis and was considered as a selective ligand of the CC chemokine receptor 3 (CCR3), which is expressed on eosinophils, basophils, and Th2 lymphocytes. This study shows that eotaxin also interacts with CCR2 and CCR5 and can, thus, affect the responses of monocytes, which express both receptors. In human monocytes pretreatment with eotaxin decreased responsiveness to MCP-1, a selective ligand for CCR2, as well as to RANTES and MIP-1 beta, which bind to CCR5. Similar effects were obtained with transfected cells expressing CCR2 or CCR5, but here a difference became apparent: Eotaxin triggered CCR5 at a concentration of 100 nM but not CCR2 even at 1 microM, suggesting an antagonistic effect on this receptor. In agreement with this observation, eotaxin induced internalization of CCR5 but not of CCR2 in human monocytes and transfected cells. Binding studies showed that eotaxin displaces (125) I-MCP-1 from monocytes in a concentration-dependent manner, and functional experiments showed that eotaxin inhibits MCP-1-induced chemotaxis and enzyme release. The results demonstrate that eotaxin is a CCR5 agonist and a CCR2 antagonist. The present findings suggest a role of eotaxin in the fine-tuning of cellular responses occurring at sites of allergic inflammation, in which both MCP-1 and eotaxin are produced. (Blood. 2001;97:1920-1924)
Asunto(s)
Quimiocinas CC , Citocinas/fisiología , Monocitos/efectos de los fármacos , Receptores CCR5/agonistas , Receptores de Quimiocina/antagonistas & inhibidores , Señalización del Calcio/efectos de los fármacos , Quimiocina CCL11 , Quimiocina CCL2/farmacología , Quimiocina CCL4 , Quimiocina CCL5/farmacología , Quimiotaxis de Leucocito/efectos de los fármacos , Citocinas/farmacología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Endocitosis/efectos de los fármacos , Eosinofilia/fisiopatología , Humanos , Hipersensibilidad/fisiopatología , Inflamación/fisiopatología , Proteínas Inflamatorias de Macrófagos/farmacología , Receptores CCR2 , TransfecciónRESUMEN
BACKGROUND AND OBJECTIVE: Pemphigoid gestationis (PG) is a rare pregnancy-associated autoimmune bullous disease characterized by autoantibodies to the 180 kD bullous pemphigoid antigen (BP180). The clinical spectrum of PG is polymorphic and for diagnostic purposes, a skin biopsy is usually taken demonstrating the deposition of autoantibodies. PATIENTS AND METHODS: From 2 patients, skin biopsies were obtained for histopathologic and immunofluorescence studies. Circulating autoantibodies were characterized by immunoblotting and ELISA using a recombinant form of the immunodominant BP180 NC16 A domain. RESULTS: The 2 PG patients described here did not show blisters but complained about severe itching. In the first case, PG presented in the first trimester of the second pregnancy as an erythema-multiforme-like disease. The second patient developed urticarial plaques a few days after delivery. PG was diagnosed by the detection of autoantibodies against recombinant BP180 NC16 A by immunoblot and ELISA analysis and confirmed by linear deposits of C3 at the cutaneous basement membrane zone on direct immunofluorescence microscopy. Skin lesions healed with oral prednisolone. CONCLUSIONS: In our two patients, non-bullous PG could be diagnosed by serological tests. Immunoblotting and ELISA might be sensitive and specific tools when screening sera of patients with pruritic skin lesions in pregnancy for the presence of autoantibodies to BP180. In some cases, these newer techniques may make a skin biopsy unnecessary.
Asunto(s)
Proteínas Portadoras , Proteínas del Citoesqueleto , Proteínas del Tejido Nervioso , Colágenos no Fibrilares , Penfigoide Ampolloso/diagnóstico , Complicaciones del Embarazo/diagnóstico , Adulto , Autoanticuerpos/análisis , Autoantígenos/inmunología , Biopsia , Colágeno/inmunología , Complemento C3/análisis , Distonina , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Recién Nacido , Microscopía Fluorescente , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/patología , Embarazo , Complicaciones del Embarazo/inmunología , Piel/inmunología , Piel/patología , Colágeno Tipo XVIIRESUMEN
An antimicrobial susceptibility surveillance study of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates was performed during the winter of 1996-1997 in order to determine their susceptibilities to 5 fluoroquinolones and 21 other antimicrobial agents. Broth microdilution MICs were determined for 2, 752 isolates from 51 U.S. medical centers. Of the 1,276 S. pneumoniae isolates, 64% were susceptible, 17% were intermediate, and 19% were highly resistant to penicillin. On the basis of the MICs at which 90% of isolates are inhibited and modal MICs, the hierarchy of the five fluoroquinolones from most to least active was grepafloxacin > sparfloxacin > levofloxacin = ciprofloxacin > ofloxacin. For S. pneumoniae isolates for which penicillin MICs were elevated, the MICs of the cephalosporins, macrolides, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole were also elevated, but the MICs of the fluoroquinolones, vancomycin, and rifampin were not. The prevalence of penicillin-susceptible pneumococci varied by U.S. Bureau of the Census region (range, 44% in the East South Central region to 75% in the Pacific region). In addition, S. pneumoniae isolates from blood were significantly more susceptible to penicillin than those from respiratory, ear, or eye specimens, and pneumococci from patients
Asunto(s)
Antibacterianos/farmacología , Haemophilus influenzae/efectos de los fármacos , Moraxella catarrhalis/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Farmacorresistencia Microbiana , Infecciones por Haemophilus/epidemiología , Infecciones por Haemophilus/microbiología , Haemophilus influenzae/enzimología , Haemophilus influenzae/genética , Humanos , Lactante , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/enzimología , Moraxella catarrhalis/genética , Infecciones por Neisseriaceae/epidemiología , Infecciones por Neisseriaceae/microbiología , Fenotipo , Estudios Prospectivos , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , Streptococcus pneumoniae/enzimología , Streptococcus pneumoniae/genética , Estados Unidos/epidemiología , beta-Lactamasas/metabolismoRESUMEN
Due to its high prevalence, atopic dermatitis is an important problem in the dermatologic practice. The chronicity of the disease together with numerous triggering factors of varying individual impact create a complex situation which is difficult to manage under the current circumstances in our health care system. We describe the concept of an outpatient clinic especially for atopic dermatitis as established in our Department of Dermatology. A high degree of standardization is combined with a high measure of individual care. The aims of this clinic are an optimized outpatient management of atopic dermatitis, the gathering of epidemiologic data, the performance of controlled studies, and potentially the reduction of costs.
Asunto(s)
Dermatitis Atópica/terapia , Grupo de Atención al Paciente , Atención Ambulatoria/economía , Control de Costos/tendencias , Estudios Transversales , Dermatitis Atópica/economía , Dermatitis Atópica/etiología , Alemania , Humanos , Incidencia , Grupo de Atención al Paciente/economía , Garantía de la Calidad de Atención de Salud/economíaRESUMEN
We describe a 30-year-old man presenting with congenital widespread unilateral hyperpigmented areas on the right side of the face and limbs that were studded with multiple blue nevi. There was nevus of Ota-like scleral involvement of the right eye. Histologic examination showed common blue nevi, one in association with lentigo. For this unusual type of dermal melanocytosis we propose the term, congenital unilateral speckled lentiginious blue nevi. In addition, the patient had monomelic spinal muscular atrophy of his right shoulder girdle and arm.
Asunto(s)
Lentigo/patología , Atrofia Muscular Espinal/complicaciones , Nevo Azul/patología , Neoplasias Cutáneas/patología , Adulto , Neoplasias del Ojo/complicaciones , Neoplasias del Ojo/patología , Humanos , Lentigo/complicaciones , Lentigo/congénito , Masculino , Nevo de Ota/complicaciones , Nevo de Ota/patología , Nevo Azul/complicaciones , Nevo Azul/congénito , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/congénitoRESUMEN
Strains of Streptococcus pneumoniae from the United States that were susceptible, intermediately resistant, or highly resistant to penicillin were tested for susceptibility to 26 antimicrobial agents that have been used or considered for the treatment of patients with pneumococcal infections. The drugs tested included penicillins, one penicillin/beta-lactamase inhibitor combination, cephalosporins, macrolides, a lincosamide, fluoroquinolones, and four miscellaneous drugs (vancomycin, rifampin, tetracycline, and trimethoprim-sulfamethoxazole). The activities of the penicillins and macrolide agents were similar, but the activities within the cephalosporin and fluoroquinolone classes were often dissimilar. For the fluoroquinolones, the order of in vitro activity, from most to least active, was grepafloxacin, sparfloxacin, levofloxacin, ciprofloxacin, and ofloxacin. Increased resistance to penicillin in the pneumococcal isolates studied correlated with increased resistance to other penicillins, cephalosporins, macrolides, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole but did not correlate with increased resistance to the fluoroquinolones, rifampin, or vancomycin. These findings may be helpful to health professionals selecting empiric therapy for respiratory tract infections involving S. pneumoniae.
Asunto(s)
Antiinfecciosos/farmacología , Fluoroquinolonas , Resistencia a las Penicilinas , Piperazinas/farmacología , Quinolonas/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Estreptocócicas/microbiologíaRESUMEN
A U.S. surveillance study of antimicrobial resistance in respiratory tract pathogens in the respiratory season (1996-1997) is reported that included 11,368 isolates from 434 institutions in 45 states and the District of Columbia. beta-lactamase was produced by 33.4% of Haemophilus influenzae and 92.7% of Moraxella catarrhalis. Of the 9,190 Streptococcus pneumoniae isolates tested, 33.5% were not susceptible to penicillin (MIC > or = 0.12 microgram/mL), with 13.6% having high-level resistance (MICs > 1 microgram/mL). For H. influenzae, the most active antimicrobials (based on percent of strains susceptible) were levofloxacin (100%) and ceftriaxone (99.9%); the least active were ampicillin (67.2%) and clarithromycin (58.1%). For M. catarrhalis, the most active drugs were amoxicillin-clavulanate, ceftriaxone, and levofloxacin (100%); the least active was ampicillin. The order of the activity of the drugs against S. pneumoniae were levofloxacin (97.3%) > ceftriaxone (87.1%) > amoxicillin-clavulanate (81.7%) = clarithromycin (80.9%) > cefuroxime (74.5%) > penicillin (66.5%). The activity of the beta-lactams and clarithromycin against isolates of S. pneumoniae was closely associated with the resistance to penicillin. Levofloxacin was more active against S. pneumoniae overall, because it exhibited no cross-resistance. These data indicate that the incidence of beta-lactamase production in H. influenzae (33.4%) and M. catarrhalis (92.7%) is similar to other recent studies, and that the incidence of penicillin-intermediate and -resistant S. pneumoniae is increasing, particularly the high-level penicillin-resistant (MICs > 1 microgram/mL) strains, which were often multi-resistant.
Asunto(s)
Antibacterianos/farmacología , Haemophilus influenzae/efectos de los fármacos , Moraxella catarrhalis/efectos de los fármacos , Infecciones del Sistema Respiratorio/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Combinación Amoxicilina-Clavulanato de Potasio/farmacología , Ceftriaxona/farmacología , Cefuroxima/farmacología , Claritromicina/farmacología , Estudios de Cohortes , Farmacorresistencia Microbiana , Haemophilus influenzae/enzimología , Haemophilus influenzae/patogenicidad , Humanos , Levofloxacino , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/enzimología , Moraxella catarrhalis/patogenicidad , Ofloxacino/farmacología , Infecciones del Sistema Respiratorio/epidemiología , Streptococcus pneumoniae/patogenicidad , Estados Unidos/epidemiología , beta-Lactamasas/biosíntesisRESUMEN
In the adult central nervous system, nitric oxide (NO) is formed from L-arginine by the so-called constitutive or type I NO synthase (NOS-I155). However, expression of NOS-I155 immunoreactivity and activity was low or not detectable in developing mouse and rat brain. NOS-I155 was sharply induced coincident with the onset of synaptogenesis in specific brain regions. This was followed by a second phase in which total NOS-I155 expression decreased both in specific cell populations and in the total synaptosomal subcellular fraction.Furthermore, two putative variants of NOS-I were transiently observed: an NOS-I-immunoreactive protein with increased electrophoretic mobility (NOS-I144) and a transient hypersensitivity of NOS-I155 to the competitive substrate inhibitor N omega-nitro-L-arginine. It is concluded that NOS-I expression is not constitutive but locally induced. In the central nervous system, this regionally specific, biphasic pattern of postnatal NOS-I induction is consistent with a role for NO in synaptogenesis and synaptic plasticity.
Asunto(s)
Aminoácido Oxidorreductasas/biosíntesis , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Neuronas/enzimología , Sinapsis/enzimología , Aminoácido Oxidorreductasas/clasificación , Animales , Secuencia de Bases , Western Blotting , Encéfalo/enzimología , Fraccionamiento Celular , Inducción Enzimática , Femenino , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Óxido Nítrico Sintasa , Reacción en Cadena de la Polimerasa , Empalme del ARN , ARN Mensajero/análisis , ARN Mensajero/genética , Ratas , Ratas Sprague-DawleyAsunto(s)
Aminoácido Oxidorreductasas/metabolismo , Aminoácido Oxidorreductasas/química , Aminoácido Oxidorreductasas/genética , Animales , Regulación Enzimológica de la Expresión Génica , Humanos , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Estructura Molecular , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa , Procesamiento Proteico-PostraduccionalRESUMEN
Bone marrow ablation using combined whole body hyperthermia (WBH), total body irradiation (TBI), and cyclophosphamide (Cy) was investigated in C3H f/Sed mice to demonstrate cytotoxic synergism between the three modalities. TBI was given on day 0. WBH treatment was for 1 hr at 41.8 degrees C, given in daily sessions for 1, 2 or 3 modalities. TBI was given on day 0. WBH treatment was for 1 hr at 41.8 degrees C, given in daily sessions for 1, 2 or 3 consecutive days following TBI. Total cyclophosphamide doses were 160 and 240 mg/kg given in 2 daily injections on days 1 and 2 following TBI. Polymorphonuclear leukocyte and lymphocyte numbers were determined by differential cell counts. The total peripheral blood cell counts were also determined. WBH alone, given in daily sessions for 3 days, did not reduce the total peripheral blood cell counts. However, when WBH was added to TBI (6.3 Gy) peripheral blood cellularity was reduced on day 2, but no significant heat/radiosensitization was evident after day 2. WBH (3 daily sessions) significantly reduced the peripheral blood cellularity and resulted in bone marrow ablation when it was combined with TBI and Cy. CY (160-240 mg/kg) combined with TBI (5.4 Gy) resulted in bone marrow ablation and subsequent death in 14-22% of mice treated; 60-100% of mice died from bone marrow ablation when WBH was added to TBI (5.4 Gy) and Cy (160-240 mg/kg). Femoral and vertebral tissue sections showed total loss of progenitor cells when WBH, TBI (5.4 Gy), and Cy (240 mg/kg) were combined whereas lessor treatment was associated with histologically verified reconstitution of progenitor cells inside the marrow cavities. These studies indicate that bone marrow ablation can be achieved when using WBH in combination with lower doses of TBI and Cy.
Asunto(s)
Trasplante de Médula Ósea , Ciclofosfamida/farmacología , Hipertermia Inducida/métodos , Irradiación Corporal Total , Animales , Médula Ósea/patología , Terapia Combinada , Recuento de Leucocitos/efectos de los fármacos , Recuento de Leucocitos/efectos de la radiación , Ratones , Ratones Endogámicos C3HRESUMEN
The protective effect of Mr 70,000 heat shock protein (HSP-70) during thermotolerance has been previously observed. However, it is not known what cellular processes or components may be protected by this protein during the tolerance state. In the studies reported here, the protective effects of purified HSP-70, the nonspecific heat-stable proteins fetuin and trypsin inhibitor (ovomucoid), and other proteins and agents such as bovine serum albumin, D2O, or glycerol on protein and DNA synthesis during heating were investigated in vitro. In vitro protein synthesis at 30, 40, and 42 degrees C was measured by globin mRNA translation. Protein synthesis was inhibited 40 to 70% when incubated for 60 min at 40 and 42 degrees C. However, protein synthesis was protected when either fetuin or ovomucoid was present during protein synthesis at elevated temperatures. The protection was concentration dependent. The HSP-70 purified from Chinese hamster (HA-1) cells was also able to confer protection to the translation system, but at much lower concentrations than either fetuin or ovomucoid. Other proteins, such as bovine serum albumin, or other agents, such as D2O or glycerol which are known protectors of cellular survival during heating, did not protect the translation system. Similar experiments were performed with DNA synthesis in vitro. Purified DNA polymerase alpha was added to the activated calf thymus DNA in an in vitro replication system. A temperature of 46 degrees C for 60 min inhibited replication by 40%. Addition of heat-stable proteins, purified HSP-70, bovine serum albumin, D2O, or glycerol did not confer protection to the replication system. These studies provide new evidence that HSP-70 may confer protection to a component of the protein synthesis machinery during thermotolerance.
Asunto(s)
ADN/biosíntesis , Proteínas de Choque Térmico/farmacología , Calor , Biosíntesis de Proteínas , Animales , Células Cultivadas , Cricetinae , Deuterio/farmacología , Óxido de Deuterio , Glicerol/farmacología , Agua/farmacología , alfa-Fetoproteínas/farmacologíaRESUMEN
Oxygen-producing electron transport reactions of a photosystem II preparation are described. The preparation has six major peptides with apparent molecular weights of 36,000, 31,000, 28,000, 27,000, 25,000, and 21,000. Sucrose density gradient centrifugation indicates that the preparation is more homogeneous and more dense than control thylakoid membranes. The preparation photoreduces a number of known photosystem II oxidants including the Class I acceptor, ferricyanide; the Class II acceptor, 2,6-dichloroindophenol; and the Class III acceptor, 2,6-dichlorobenzoquinone. However, quinonediimines such as phenylenediimine are not reduced, suggesting that these substances are reduced at sites in the thylakoid membrane which are not found in the photosystem II preparation. All the oxygen-producing reactions are sensitive to inhibition by 3-(3,4-dichlorophenyl)-1,1-dimethylurea.