RESUMEN

We report a case of severe central nervous system bleeding in a patient with acute monocytic leukemia. The patient was admitted to our emergency department because of massive back pain and positive meningeal signs. MR imaging yielded a spontaneous epidural hematoma of the thoracic vertebral column. Coagulation studies revealed fibrinogen levels below the linear measuring range and blood smears showed myeloid blast cells in the peripheral blood. The diagnosis of acute monocytic leukemia was confirmed by flow cytometric analysis. Despite of substitution with more than 12 g fibrinogen per day over 3 days plasma fibrinogen levels couldn't be stabilized. After starting the induction chemotherapy with cytarabine, laboratory coagulation test results were improved. Despite all intensive medical efforts, the patient died due to cerebral epidural hematoma.

RESUMEN

Novel drugs like Abiraterone or Enzalutamide, which target androgen receptor (AR) signaling to improve androgen deprivation therapy (ADT), have been developed during the past years. However, the application of these drugs is limited because of occurrence of inherent or acquired therapy resistances during the treatment. Thus, identification of new molecular targets is urgently required to improve current therapeutic prostate cancer (PCa) treatment strategies. PIAS1 (protein inhibitor of activated STAT1 (signal transducer and activator of transcription-1)) is known to be an important cell cycle regulator and PIAS1-mediated SUMOylation is essential for DNA repair. In this context, elevated PIAS1 expression has already been associated with cancer initiation. Thus, in the present study, we addressed the question of whether PIAS1 targeting can be used as a basis for an improved PCa therapy in combination with anti-androgens. We show that PIAS1 significantly correlates with AR expression in PCa tissue and in cell lines and demonstrate that high PIAS1 levels predict shorter relapse-free survival. Our patient data are complemented by mechanistic and functional in vitro experiments that identify PIAS1 as an androgen-responsive gene and a crucial factor for AR signaling via prevention of AR degradation. Furthermore, PIAS1 knockdown is sufficient to decrease cell proliferation as well as cell viability. Strikingly, Abiraterone or Enzalutamide treatment in combination with PIAS1 depletion is even more effective than single-drug treatment in multiple PCa cell models, rendering PIAS1 as a promising target protein for a combined treatment approach to improve future PCa therapies.

Asunto(s)

Retroalimentación Fisiológica , Neoplasias de la Próstata/patología , Proteínas Inhibidoras de STAT Activados/metabolismo , Receptores Androgénicos/metabolismo , Transducción de Señal , Andrógenos/farmacología , Androstenos/farmacología , Benzamidas , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Retroalimentación Fisiológica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Nitrilos , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/farmacología , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas Inhibidoras de STAT Activados/deficiencia , Proteínas Inhibidoras de STAT Activados/genética , Estabilidad Proteica/efectos de los fármacos , Proteolisis/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Androgénicos/genética , Transducción de Señal/efectos de los fármacos , Análisis de Supervivencia , Transcripción Genética/efectos de los fármacos

RESUMEN

PURPOSE: The aim of this study was to assess the indication-related safety, feasibility, and efficacy of laparoscopic Burch colposuspension (LBC), open Burch colposuspension (OB), and midurethral sling (MUS), retropubic vaginal tape (TVT) and transobturator vaginal tape (TOT) procedures for surgical treatment of female stress urinary incontinence (SUI). METHODS: Perioperative outcome was assessed in 321 patients treated for SUI by a single surgeon (LBC, n = 120; OB, n = 23; TVT, n = 129; TOT, n = 49) between April 2001 and December 2007 at a single center. Follow-up was available for 115 patients at 30, 40, and 26 months for LBC, OB, and MUS, respectively. The primary outcome was the objective continence measured by a negative cough stress test. The secondary outcome was the subjective continence measured by subjective perception of cure, the King's Health Questionnaire (KHQ), and visual analog score (VAS). RESULTS: The LBC group had one (0.8%) intra-operative complication (bladder injury) and a mean operation time of 56.5 min. The objective and subjective cure rate associated with LBC was 90.3 and 71%, respectively. The OB group had three (13%) intra-operative complications and a mean procedure time of 44.6 min. The objective and subjective cure rate was 69.2 and 61.5%, respectively. MUS had 7 (TVT, n = 2; retropubic I-STOP, n = 5) procedure-related complications (5.4%) and an operation time of 19.8 min. The objective and subjective efficacy rate for MUS was 84.5 and 62%, respectively. CONCLUSIONS: LBC was shown to be safe and feasible with a high objective and subjective success rate. Use of this minimally invasive procedure should be considered in patients with concomitant intra-abdominal pathology.

Asunto(s)

Laparoscopía , Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Cavidad Abdominal , Adulto , Anciano , Estudios de Factibilidad , Femenino , Humanos , Complicaciones Intraoperatorias/etiología , Tiempo de Internación , Persona de Mediana Edad , Tempo Operativo , Satisfacción del Paciente , Diafragma Pélvico/cirugía , Calidad de Vida , Cabestrillo Suburetral/efectos adversos , Encuestas y Cuestionarios , Resultado del Tratamiento

RESUMEN

Shoulder dystocia is the term used to describe failure to progress in labour after the head has been delivered due to insufficient rotation of the shoulders. It is unpredictable and cannot be prevented by the midwife or the obstetrician. We report here on a severe case of shoulder dystocia, where delivery of the shoulder was finally achieved through direct pressure on the anterior shoulder after laparotomy and uterotomy with concurrent vaginal Woods screw manoeuvre and was followed by vaginal delivery. The patient presented risk factors like maternal obesity and administration of labour-inducing drugs. After different manoeuvres like McRoberts manoeuvre and several manoeuvres for internal rotation were carried out unsuccessfully, an emergency laparotomy was performed. The newborn was in need for reanimation and artifical ventilation postpartum but recovered fast during the following days. An Erb's palsy of the posterior arm improved during the hospital stay. The German Guideline of the DGGG 8 recommends a risk management plan and regular training to all birth attendants for obstetric clinics. Beside the vaginal manoeuvres one should have at least theoretical expertise in operative manoeuvres to be able to perform them in emergency cases.

RESUMEN

PURPOSE: To report acute toxicity and to evaluate the relationship between dose-volume effects and acute toxicity in patients with localized prostate cancer, treated with intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Acute toxicity (both lower gastrointestinal [GI] and genito-urinary [GU]) in 100 patients treated with IMRT definitively to a prescribed dose of 70 Gy were assessed using RTOG scoring criteria. A rectal balloon was used for prostate immobilization. Mean doses to seminal vesicles, prostate, bladder, and rectum were recorded. Average irradiated bladder and rectal volumes above 65, 70, and 75 Gy were assessed. A relationship between dose volume and clinical toxicity was evaluated. All patients completed the full duration of acute toxicity assessment. RESULTS: Mean doses to the prostate and seminal vesicles were 75.8 and 73.9 Gy. This represents a moderate dose escalation. Acute GI toxicity profile was very favorable. Eleven percent and 6% of the patients had grade 1 and 2 GI toxicity, respectively, while 83% had no GI complaint. For GU complaints, 38% and 35% had grade 1 and 2 toxicity, respectively, while 27% had no complaints. There was no grade 3 or higher acute GI or GU toxicity. Mean doses to the bladder were 22.8, 23.4, and 26.1 Gy for grade 0, 1, and 2 GU toxicity, respectively (p = 0.132). There is no statistically significant relationship between acute GU toxicity and the bladder volume receiving > 65 Gy, > 70 Gy, or > 75 Gy. In evaluating acute GI toxicity, there are very few grade 1 and 2 events. No relationship was found between acute rectal toxicity and mean rectal dose or irradiated rectal volumes receiving more than 65, 70, and 75 Gy. CONCLUSION: The findings are important with regard to the safety of IMRT, especially in reducing acute GI toxicity. Dose escalation with IMRT using a prostate immobilization technique is feasible. The findings are also important because they contribute to the clinical and dosimetric correlation aspect in the use of IMRT to treat prostate cancer. A larger cohort may be needed to determine if there is a relationship between acute GU toxicity and (a) mean bladder dose and (b) irradiated bladder volume receiving > 65 Gy, > 70 Gy, or > 75 Gy. A larger cohort of patients treated to a higher dose may be needed to show a relationship between dose volume and acute GI toxicity.

Asunto(s)

Cateterismo/métodos , Inmovilización , Neoplasias de la Próstata/radioterapia , Radioterapia Conformacional/métodos , Anciano , Anciano de 80 o más Años , Sistema Digestivo/efectos de la radiación , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Dosificación Radioterapéutica , Recto/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Sistema Urogenital/efectos de la radiación

RESUMEN

PURPOSE: To report our initial experience on postprostatectomy IMRT (PPI), addressing acute genitourinary (GU) toxicity in comparison to primary IMRT (PI) for prostate cancer. METHODS AND MATERIALS: From April 1998 to December 1999, 40 postprostatectomy patients were treated with intensity modulated radiation therapy (IMRT) to a median prescribed dose of 64 Gy (mean dose of 69 Gy). The Radiation Therapy Oncology Group (RTOG) scoring system was used to assess acute GU toxicity. Target volume and maximum and mean doses were evaluated. The mean doses to the bladder and irradiated bladder volume receiving >65 Gy were assessed. These were compared to those of 125 patients treated with PI to a prescribed dose of 70 Gy (mean dose of 76 Gy). RESULTS: The acute GU toxicity profile is more favorable in the PPI group with 82.5% of Grade 0-1 and 17.5% of Grade 2 toxicity compared to 59.2% and 40.8%, respectively, in the PI group (p < 0.001). There was no Grade 3 or higher toxicity in either group. The target volume was larger in the PPI group, while the maximum and mean doses to the target were higher in the PI group. The mean dose delivered to the bladder was higher in the PPI group. The irradiated bladder volume receiving >65 Gy was significantly larger in the PI group (p < 0.001). CONCLUSIONS: PPI can be delivered with acceptable ute GU toxicity. The larger PPI target volume may be related to the difficulty in delineating prostatic fossa. Despite a larger target volume and a higher mean dose to the bladder, PPI produced a more favorable acute GU toxicity profile. This may be related to a combination of lower mean and maximum doses and smaller bladder volumes receiving >65 Gy in the PPI group, as well as urethral rather than bladder irradiation. The findings have implications in the evaluation of IMRT treatment plan for prostate cancer, whereby the irradiated bladder volumes above 65 Gy may be more meaningful than the mean dose to the bladder. Longer term toxicity results are awaited.

Asunto(s)

Prostatectomía , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Radioterapia Conformacional/métodos , Vejiga Urinaria/efectos de la radiación , Anciano , Anciano de 80 o más Años , Terapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Postura , Radiometría , Dosificación Radioterapéutica , Radioterapia Adyuvante , Recto/efectos de la radiación , Terapia Recuperativa , Factores de Tiempo

RESUMEN

PURPOSE: To report the initial experience in the definitive treatment of head and neck carcinomas using SMART (Simultaneous Modulated Accelerated Radiation Therapy) boost technique. Radiation was delivered via IMRT (Intensity Modulated Radiotherapy). The following parameters were evaluated: acute toxicity, initial tumor response, clinical feasibility, dosimetry and cost. METHODS AND MATERIALS: Between January 1996 and December 1997, 20 patients with primary head and neck carcinomas were treated with SMART boost technique. The treatment fields encompassed two simultaneous targets. The primary target included palpable and visible disease sites. The secondary target included regions at risk for microscopic disease. Daily fractions of 2.4 Gy and 2 Gy were prescribed and delivered to the primary and secondary targets to a total dose of 60 Gy and 50 Gy, respectively. Lower neck nodes were treated with a single conventional anterior portal. This fractionation schedule was completed in 5 weeks with 5 daily fractions weekly. Toxicity was evaluated by RTOG acute toxicity grading criteria, evidence of infection at immobilization screw sites, subjective salivary function, weight loss, and the need for treatment split. Mean follow-up was 15.2 months. Initial tumor response was assessed by clinical and radiographical examinations. Clinical feasibility was evaluated by the criteria: time to treat patient, immobilization, and treatment planning and QA time. In dosimetry, we evaluated the mean doses of both targets and normal tissues and percent targets' volume below goal. To evaluate cost, Medicare allowable charge for SMART boost was compared to those of conventional fractionated and accelerated radiotherapy. RESULTS: ACUTE TOXICITY: None of the patients had a screw site infection and all patients healed well after completion of radiotherapy. Sixteen of 20 patients (80%) completed the treatment within 40 days without any split. Sixteen patients (80%) had RTOG Grade 3 mucositis while 10 patients (50%) had Grade 3 pharyngitis. Three of 20 patients (15%) had weight loss greater than 10% of their pretreatment weight. Ten patients (50%) required intravenous fluids, tube feeding or both. Nine patients (45%) reported moderate xerostomia with significant relief reported within 6 months. INITIAL TUMOR RESPONSE: 19 patients (95 %) had complete response (CR) while one had partial response (PR). The patient with PR had stable disease on imaging at 12 months follow-up. Two patients were found to have lung metastases at 2 months and 5 months follow-up. To date, there have been two local recurrences in the complete responders. Both patients had nasopharyngeal primary; one was retreated with radioactive Cesium-137 implant and the other died from the disease. CLINICAL FEASIBILITY: The average treatment time for a three-arc treatment was 17.5 minutes and 2.5 minutes for each additional arc. Eleven patients (55%) had four-arc treatment while six patients (30%) had five-arc treatment and three patients (15%) had three-arc treatment. Immobilization was reproducible within less than 2 mm. The treatment planning, QA and documentation prior to treatment averaged 2 days. DOSIMETRY: The mean doses to the primary and secondary targets were 64.4 Gy and 54.4 Gy, respectively; 8.9% of the primary target volume and 11.6% of the secondary target volume were below prescribed dose goal. The mean dose delivered to the mandible was 30 Gy, spinal cord 17 Gy, ipsilateral parotid 23 Gy, and contralateral parotid 21 Gy. COST: Total Medicare allowable charge for SMART boost was $7000 compared to $8600 (conventional) and $9400 (accelerated fractionation). CONCLUSIONS: SMART boost technique is an accelerated radiotherapy scheme that can be delivered with acceptable toxicity. It allows parotid sparing as evidenced both clinically and by dosimetry. Initial tumor response has been encouraging. It is clinically feasible and cost saving. A larger population of patients and a long-term fol

Asunto(s)

Carcinoma Adenoide Quístico/radioterapia , Carcinoma de Células Escamosas/radioterapia , Fraccionamiento de la Dosis de Radiación , Neoplasias de Cabeza y Cuello/radioterapia , Radioterapia Conformacional/métodos , Anciano , Estudios de Factibilidad , Femenino , Humanos , Inmovilización , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/etiología , Radioterapia Conformacional/efectos adversos , Factores de Tiempo

RESUMEN

Advances in imaging technology and implant technique have led to the resurgent interest and practice of brachytherapy for the treatment of prostate cancer. Brachytherapy is a form of radiation treatment in which radioactive sources are placed directly into the tumor; it offers the advantage of maximizing the radiation dose delivered to the tumor while sparing the adjacent normal tissue. Permanent implants have become an important component of radiation delivery. Interstitial gold radioisotope (Au-198) implants for prostate cancer were introduced at Baylor College of Medicine in 1965. The rationale for using Au-198, instead of the two most commonly used radioisotopes, Palladium-103 (Pd-103) and Iodine-125 (I-125), is discussed, and the Baylor implant technique is compared to that used in other centers. Retrospective review divides the patient population into pre-ultrasound versus post-ultrasound eras. Dosimetric calculation and disease control with the Au-198 seed implant for prostatic cancer are reviewed for the two different eras; toxicity is evaluated in the post-ultrasound era only. In the pre-ultrasound era, 510 patients were treated with pelvic lymph node sampling and gold seed insertion of the prostate followed by external beam radiation. In the post-ultrasound era, 54 patients were treated definitively with ultrasound-guided transperineal Au-198 implant followed by external beam irradiation. A small group of 30 patients in the post-ultrasound era were evaluated for the efficacy of Au-198 re-implantation for locally recurrent disease.

Asunto(s)

Braquiterapia , Radioisótopos de Oro/uso terapéutico , Neoplasias de la Próstata/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Radioisótopos de Oro/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/mortalidad , Dosificación Radioterapéutica , Radioterapia de Alta Energía , Estudios Retrospectivos , Tasa de Supervivencia , Ultrasonografía

RESUMEN

In order to evaluate the relation between costs and benefit of the use of a temporary shunt during surgery of the carotid artery, we analysed 356 patients undergoing 401 operations of the carotid artery in a period from January 1991 to August 1995 in a retrospective study. The morbidity and mortality during hospital stay were 1.75% respectively 0.75% referring to neurological outcome and death. The potential to economize surgery of the carotid artery by recording the somatosensory evoked potentials in order to select the patients requiring a temporary shunt would be 4.1% of the payment which will be payed from 1996 by the social insurance for carotid endarterectomy. These savings can be realized without loss of quality or higher risk for the patient.

Asunto(s)

Estenosis Carotídea/cirugía , Endarterectomía Carotidea/economía , Monitoreo Intraoperatorio/economía , Anciano , Estenosis Carotídea/economía , Estenosis Carotídea/mortalidad , Análisis Costo-Beneficio , Potenciales Evocados Somatosensoriales/fisiología , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud/economía , Garantía de la Calidad de Atención de Salud/economía , Estudios Retrospectivos , Tasa de Supervivencia

RESUMEN

In the microenvironment of many solid tumors the pH is considerably lower (mean pH between 6.6 to 7.2) than the pH in normal tissue (pH 7.0-7.5). Therefore, the influence of acidic pH on the cytotoxic activity of lymphokine-activated killer cells (LAK cells) after different culture periods was tested. K-562 human erythroleukemia cells were selected as target cells. Cell killing was measured using a two-color flow cytometric method. At physiological pH of 7.4, LAK cell-mediated cytotoxicity ranged from 15 to 48% (E:T ratio = 50:1). The specific lysis of target cells was considerably reduced (up to 70% inhibition of specific lysis) under acidic conditions (pH 6.8, 6.3, 5.8). This effect was independent of donors, duration of the culture period, and the E:T ratio in the cytotoxic assay. As pH gradients surrounding tumor cells may reach values below pH 6.0 at the cell surface, the pH-dependence of LAK cell cytotoxicity could at least partially explain the inhibition of the natural immune response in solid tumors. Therapeutic immunological strategies concerning the enhancement of the natural immune response like LAK cell and IL-2 immunotherapy including IL-2 gene therapy may only be successful if a simultaneous inhibition of the acidification process and an elevation of tumor pH is achieved.

Asunto(s)

Citotoxicidad Inmunológica , Concentración de Iones de Hidrógeno , Células Asesinas Activadas por Linfocinas/inmunología , Línea Celular , Células Cultivadas , Humanos , Cinética , Leucemia Eritroblástica Aguda , Factores de Tiempo , Células Tumorales Cultivadas

RESUMEN

Synthetic lipopeptide analogues of the N-terminal region of bacterial lipoprotein are potent activators of macrophages. In a previous study we showed that within minutes after their addition to macrophage cultures, lipopeptides were found attached to the plasma membranes and within different compartments of the cells. Their rapid interaction with the plasma membrane is thought to occur via the insertion of their three fatty acids. We used the freeze-fracture technique to study the influence of lipopeptides on the architecture of plasma membranes. Fifteen to thirty seconds after addition of the lipopeptides, the freeze-fractured plasma membranes show a rapid decrease in the particle density. This effect is not due to a loss of proteins, but is caused by lateral diffusion of single particles, which subsequently aggregate. These alterations are transient, temperature-sensitive and disappear 20 min after stimulation. At 4 degrees C, no change is found in the architecture of the plasma membranes. Using electron energy loss spectroscopy (EELS), lipopeptides can neither be detected on the membrane nor within the cells when incubated at this temperature. Our findings suggest that membrane protein aggregation is involved in the rapid uptake of lipopeptides into macrophages after their interaction with the plasma membranes.

Asunto(s)

Membrana Celular/ultraestructura , Citotoxinas/farmacología , Lipoproteínas/farmacología , Activación de Linfocitos/fisiología , Macrófagos/efectos de los fármacos , Secuencia de Aminoácidos , Animales , Células de la Médula Ósea , Membrana Celular/efectos de los fármacos , Técnica de Fractura por Congelación , Macrófagos/ultraestructura , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Rastreo , Datos de Secuencia Molecular , Análisis Espectral , Temperatura

RESUMEN

Synthetic lipopeptides, structurally derived from the N-terminal part of bacterial lipoprotein, constitute macrophage and B-lymphocyte activators. The molecular mechanism of macrophage activation by lipopeptides still remains unclear. The purpose of our study was to determine the route and kinetics of lipopeptide distribution in bone marrow-derived macrophages. The intracellular localization of the C-terminally biotinylated lipodipeptide Pam3Cys-Ser was investigated on ultrathin cryosections using the biotinstreptavidin-gold system. Our findings indicate that the lipopeptide penetrates the plasma membrane and can already be found within the cytoplasm, the nuclear membrane, and within the nucleus after 2 min of stimulation. The pattern of lipopeptide distribution obtained 2 min after stimulation resembles that obtained after longer incubation times (8 and 20 min). Correlating distribution patterns were observed when using the method of electron energy loss spectroscopy (EELS). These findings are a clear indication for the rapid uptake of lipopeptides into eukaryotic cells, and are of importance for further studies of the immunostimulating properties of the bacterial lipopeptides and vaccines derived therefrom.

Asunto(s)

Lipoproteínas/análisis , Factores Activadores de Macrófagos/análisis , Macrófagos/química , Fragmentos de Péptidos/análisis , Animales , Células de la Médula Ósea , Inmunohistoquímica , Macrófagos/ultraestructura , Ratones , Ratones Endogámicos BALB C , Análisis Espectral

RESUMEN

The lipopeptide Pam3Cys-Ser, a synthetic analogue of the N-terminal part of bacterial lipoprotein, constitutes a potent activator for B lymphocytes, monocytes/macrophages and several lymphoid cell lines. We applied the novel method of electron energy loss spectroscopy (EELS) to determine, after stimulation, the distribution of the activator within the cell compartments of the lipopeptide sensitive cell line BCL1. Our results show that the lipopeptide, 20 min after the addition to the cell culture, was found at different locations within the cell: A major amount of the mitogen was found in the plasma membrane. Remarkably, considerable amounts of the activator were also found on the cytoplasm, the nuclear membrane, and the nucleus. After 24 h, a substantial amount of the lipopeptide was still present within the cells. These findings should help to elucidate the molecular mechanism of lymphocyte stimulation by lipopeptides. The novel method of EELS, which was demonstrated here using lipopeptides as examples, constitutes a valuable tool of localizing any given compounds such as growth factors or drugs within cells.

Asunto(s)

Dipéptidos/metabolismo , Lipoproteínas/metabolismo , Linfocitos/metabolismo , Secuencia de Aminoácidos , Animales , Proteínas Bacterianas , Línea Celular , Dipéptidos/síntesis química , Congelación , Lipoproteínas/síntesis química , Linfocitos/ultraestructura , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Análisis Espectral/métodos , Bazo/metabolismo

RESUMEN

Synthetic lipopeptide analogues of bacterial lipoprotein constitute potent polyclonal activators for monocytes/macrophages and B lymphocytes. However, the fate of the lipopeptides after their interaction with target cells is as yet unknown. In order to follow the routes and to determine the distribution of the lipopeptide within macrophages after stimulation, we investigated lipopeptide-stimulated bone marrow-derived macrophages using the novel method of electron energy loss spectroscopy (EELS). Our results show that the lipopeptide was present in different compartments of the cell. The major amount of the activator was located within the cytoplasm and the plasma membrane, and minor quantities were detected within the nuclear membrane and the nucleus. The distribution of the lipopeptides varied depending on the duration of stimulation. Our results should help to elucidate the molecular mechanisms of macrophage stimulation by lipopeptides or other cell activators.

Asunto(s)

Lipoproteínas/metabolismo , Macrófagos/inmunología , Animales , Médula Ósea/inmunología , Médula Ósea/metabolismo , Compartimento Celular , Histocitoquímica , Activación de Macrófagos , Macrófagos/metabolismo , Ratones , Ratones Endogámicos BALB C , Análisis Espectral/métodos

RESUMEN

A 23-year-old patient with chronic rhinitis suffered from attacks of asthma. We found positive reactions in the prick test and rubbing test to the scales of the lizard Egernia cunninghami and others, which the patient kept as house-pets at this time or earlier. The bronchial function test showed bronchial obstruction after the patient had been at home with the lizards.

Asunto(s)

Alérgenos , Asma/etiología , Lagartos , Adulto , Animales , Animales Domésticos , Humanos , Masculino , Prueba de Radioalergoadsorción , Pruebas Cutáneas