The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus

Administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on embryonic day 17 (E17) produces behavioral and anatomical brain abnormalities, which model some aspects of schizophrenia. This has lead to the premise that MAM rats are a neurodevelopmental model for schizophrenia. However, the underlying molecular pathways affected in this model have not been elucidated. In this study, we investigated the molecular phenotype of adult MAM rats by focusing on the frontal cortex and hippocampal areas, as these are known to be affected in schizophrenia. Proteomic and metabonomic analyses showed that the MAM treatment on E17 resulted primarily in deficits in hippocampal glutamatergic neurotransmission, as seen in some schizophrenia patients. Most importantly, these results were consistent with our finding of functional deficits in glutamatergic neurotransmission, as identified using electrophysiological recordings. Thus, this study provides the first molecular evidence, combined with functional validation, that the MAM-E17 rat model reproduces hippocampal deficits relevant to the pathology of schizophrenia.     

Plasma iron status and lipid peroxidation following thrombolytic therapy for acute myocardial infarction

Summary— Free radical species have been implicated as important agents involved in myocardial ischemic and reperfusion injuries. Superoxide is capable of mobilizing iron from ferritin and the released iron can cause hydroxyl formation from H₂O₂. The aim of this study was to evaluate the time-dependent increase in lipid peroxidation assessed by plasma thiobarbituric acid reactive substances (TBARS) and the relationship between lipid-peroxidation and the iron status. Peripheral venous blood samples were obtained from 17 men with acute myocardial infarction (AMI) before thrombolytic treatment (T0***) and 1, 2, 3, 4, 8, 12, 16, 20, 24 and 48 hours after commencing fibrinolytic treatment. The concentration of TBARS, the parameters of iron metabolism, serum myoglobin, creatine kinase, and creatine kinase-MB were measured. Early reperfusion was judged by regression of sinus tachycardia (ST) elevation and reduction of chest pain. Recanalization of coronary artery was evaluated by a late coronary angiography 24–96 hours after thrombolysis. After thrombolytic therapy, the TBARS level was raised from 2.98 ± 0.80 (T0***) to 4.57 ± 1.24 (peak), and decreased to 2.96 ± 0.40 nmol/mL plasma at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, TO vs T48: NS). The mean time of the peak was observed at 9.7 ± 7.5 hours. The iron increased significantly from 0.67 ± 0.34 (T0) to 1.15 ± 0.52 mg/L (peak), and returned to the pre-reperfusion to levels: 0.53 ± 0.28 UI/L at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, TO vs T48: NS). The mean time of the peak was observed at 9.4 ± 7.3 hours. In return, no correlation was found between the increase of plasma creatine-kinase activity, myoglobin and iron or between the biochemical markers and time of fibrinolytic therapy. The results confirmed the importance of the temporal relationship between lipid peroxidation and iron status after thrombolytic therapy. Our results are in agreement with the concept that antioxidant agents used in association with thrombolytic therapy might be useful.     

Direct demonstration that autologous bone marrow transplantation for solid tumors can return a multiplicity of tumorigenic cells

Patients with solid tumors are increasingly being treated by autologous bone marrow transplantation (BMT). Although response rates appear to be increased, disease recurrence is the commonest cause of treatment failure. Whether relapse is entirely due to residual disease in the patient or arises also from infiltrating malignant cells contained in the autologous marrow transplant has not been resolved. If the latter explanation is correct, then purging would be required as part of the transplantation procedure. We used retrovirally mediated transfer of the neomycin-resistance gene to mark BM harvested from eight patients with neuroblastoma in clinical remission. The marked marrow cells were subsequently reinfused as part of an autologous BMT. At relapse, we sought the marker gene in malignant cell populations. Three patients have relapsed, and in each the marker gene was detected by phenotypic and genetic analyses of resurgent malignant cells at medullary and extramedullary sites. Analysis of neuroblast DNA for discrete marker gene integration sites suggested that at least 200 malignant cells, each capable of tumor formation, were introduced with the autologous marrow transplant and contributed to relapse. Thus, autologous BMTs administered to patients with this solid tumor may contain a multiplicity of malignant cells that subsequently contribute to relapse. The marker-gene technique we describe should permit evaluation of the mechanisms of relapse and the efficacy of purging in patients receiving autologous marrow transplantation for other solid tumors that infiltrate the marrow.     

Ultrasound‐guided percutaneous tenotomy for the treatment of iliopsoas impingement: A description of technique and case study

Iliopsoas impingement is a commonly recognised source of groin pain following total hip replacement. When conservative measures fail, open or arthroscopic iliopsoas tendon release can reliably alleviate pain and improve function. This article describes an alternative ultrasound‐guided percutaneous technique, achieving iliopsoas tenotomy utilising a modified 18G coaxial needle and thus minimising the morbidity and cost associated with an open or arthroscopic procedure. This method proved successful with resultant complete resolution of patient symptoms. To the knowledge of the authors, this is the first case of ultrasound‐guided percutaneous iliopsoas tenotomy for iliopsoas impingement post total hip replacement.     

5-羟色胺对气道平滑肌细胞增生的影响及c-fos的表达

５－羟色胺对气道平滑肌细胞增生的影响及ｃ－ｆｏｓ的表达刘振千梁凤珍马军红戚好文为了探讨哮喘气道平滑肌层增厚的机制，考察哮喘的炎性介质５－羟色胺（５－ＨＴ）对兔气道平滑肌细胞（ＡＳＭＣ）增生的影响及原癌基因ｃ－ｆｏｓ的表达。新西兰大白兔，抗α－肌动蛋白...     

Deposition of autofluorescent eosinophil granules in pathologic bone marrow biopsies

Eosinophil granules are intensely autofluorescent when excited by green light. To determine if eosinophils degranulate in the bone marrows of patients with a variety of diseases, we used green light epifluorescence microscopy to examine deparaffinized and dezenkerized sections of 49 bone marrow core biopsies. In 14 of the biopsies, there was striking extracellular deposition of intensely autofluorescent eosinophil granules in addition to numerous intact eosinophils. Among the 14 specimens with extracellular autofluorescence were seven cases of leukemia, four cases of non-Hodgkin's lymphoma, two cases of myelofibrosis, and one case of pancytopenia with eosinophilia. In the remaining 35 specimens, only intact eosinophils were identifiable. There was no extracellular autofluorescence in three normal marrows, four marrows from AIDS patients, or three biopsies from patients with idiopathic thrombocytopenic purpura (ITP). We conclude that green light epifluorescence microscopy identifies extracellular deposits of eosinophil granules in bone marrow biopsies of some neoplastic disorders and in diseases associated with reticulin fibrosis.