Reconstitution of recombinant N-formyl chemotactic peptide receptor with G protein

A recombinant human neutrophil N-formyl peptide receptor (rFPR) expressed in transfected mouse fibroblasts (TX2 cells) was analyzed for its ability to couple physically with the heterotrimeric G protein, Gi. Immunoprecipitation of photoaffinity-labeled rFPR and endogenous neutrophil formyl peptide receptor (nFPR) with an anti-FPR peptide antibody demonstrated that the receptors were identical in both size and extent of glycosylation. Coupling of rFPR with endogenous TX2 Gi was demonstrated by coimmunoprecipitation of the two proteins with an anti-Gi antibody. Moreover, rFPR was able to form a physical complex with purified Gi in a soluble reconstitution system. We observed similar affinities of rFPR and nFPR for Gi. This report provides the first direct evidence that rFPR associates physically with Gi and provides a foundation for analysis of the G protein coupling capacity of mutant rFPRs.     

Humor in the helping relationship

BACKGROUND: Our aim was to determine the frequency, survival and symptomatic local recurrence rate of patients with a positive proximal resection margin in a series of patients having a resection for carcinoma of the oesophagus or stomach. METHODS: A retrospective study of pathology reports and case notes. Survival and data on local recurrence were obtained from the patient or general practitioner. RESULTS: Ten (11.5%) of 87 patients having a gastric or oesophageal resection for carcinoma had a positive proximal resection margin. All 10 patients underwent a palliative resection for late-stage disease. Nine were dead at an average 8.3 months (range 2-20 months) post-resection and one patient remains alive at 9 months. Only one of these 10 patients had evidence of a local recurrence with recurrent dysphagia prior to death at 11 months. CONCLUSION: A high incidence of a positive proximal resection margin was found. This occurred in patients who underwent a palliative resection for late-stage disease, most of whom died before local recurrence became a problem. For patients recognized as having late-stage disease, surgery for symptom palliation need not be aggressive (such as to include a thoracotomy) because achieving microscopic clearance is unlikely to affect the long-term outcome.     

Magnetic resonance imaging and magnetic resonance angiography in long term survivors of acute lymphoblastic leukemia treated with cranial irradiation

BACKGROUND: Successful treatment of acute lymphoblastic leukemia (ALL) has resulted in an increasing number of patients whose disease is cured. This treatment includes cranial irradiation as prophylaxis against central nervous system relapse. The late effects of irradiation are well documented, but their incidence is unknown. The authors investigated the late effects of this treatment modality further by scanning 35 long term survivors of ALL who received cranial irradiation. METHODS: Thirty-five survivors of ALL with no known complication of treatment were included in this study. They were examined with magnetic resonance imaging (MRI) of the brain and magnetic resonance angiography (MRA) of the circle of Willis. A control group of 24 patients who were cured of other childhood malignancies without exposure to cranial irradiation also were scanned. RESULTS: Fifteen of 35 (43%) abnormalities were found in the study group versus 4/24 (17%) in the control group. Excluding minor atrophic changes that are known to be produced by irradiation and chemotherapy, there were 9/35 (26%) abnormalities in the study group and 1/24 (4%) in the control group (P < 0.05). These abnormalities included three tumors, a meningioma, a paranasal sinus rhabdomyosarcoma, and an anaplastic astrocytoma. In addition, there were two cases of large vessel vasculopathy, two small cystic infarcts, one diffuse white matter abnormality, and one cryptic vascular malformation. The abnormal control patient had a cerebellar infarct. CONCLUSION: Complications of cranial irradiation in the treatment of ALL appear to be more frequent than currently are appreciated. That these complications include tumors that are potentially treatable suggests that screening may be valuable for these patients.     

Preventing perinatal transmission of HIV--costs and effectiveness of a recommended intervention

OBJECTIVE: To calculate the national costs of reducing perinatal transmission of human immunodeficiency virus through counseling and voluntary testing of pregnant women and zidovudine treatment of infected women and their infants, as recommended by the Public Health Service, and to compare these costs with the savings from reducing the number of pediatric infections. METHOD: The authors analyzed the estimated costs of the intervention and the estimated cost savings from reducing the number of pediatric infections. The outcome measures are the number of infections prevented by the intervention and the net cost (cost of intervention minus the savings from a reduced number of pediatric HIV infections). The base model assumed that intervention participation and outcomes would resemble those found in the AIDS Clinical Trials Group Protocol 076. Assumptions were varied regarding maternal seroprevalence, participation by HIV-infected women, the proportion of infected women who accepted and completed the treatment, and the efficacy of zidovudine to illustrate the effect of these assumptions on infections prevented and net cost. RESULTS: Without the intervention, a perinatal HIV transmission rate of 25% would result in 1750 HIV-infected infants born annually in the United States, with lifetime medical-care costs estimated at $282 million. The cost of the intervention (counseling, testing, and zidovudine treatment) was estimated to be $ 67.6 million. In the base model, the intervention would prevent 656 pediatric HIV infections with a medical care cost saving of $105.6 million. The net cost saving of the intervention was $38.1 million. CONCLUSION: Voluntary HIV screening of pregnant women and ziovudine treatment for infected women and their infants resulted in cost savings under most of the assumptions used in this analysis. These results strongly support implementation of the Public Health Service recommendations for this intervention.