A qualitative and quantitative analysis of the entorhinal cortex in schizophrenia

The entorhinal cortex (ERC) has been implicated in schizophrenia by a number of studies. There is anatomical observation of neuronal heterotopias in the rostral ERC, which is consistent with a hypothesis of neurodevelopmental abnormalities in this disease. In view of the significant cytoarchitectonic variation of the ERC throughout its rostro-caudal extent, we performed a detailed subareal analysis of the rostral two-thirds of the entorhinal cortex (ERCr) in 14 postmortem schizophrenic brains and 14 matched controls (mean ages of 48 and 47 respectively). This systematic evaluation included both a qualitative microscopic analysis of morphogenetic anomalies that would be consistent with neurodevelopmental pathology and quantitative measurements of total neuronal number, average neuronal density, laminar volume and laminar depth from the cortical surface in cytoarchitectonically matched subareas of schizophrenic and control brains. Parcellation of the entire ERC on the basis of cytoarchitectonic criteria identified five distinct regions, similar to those described in the macaque, except that in the human brain three of the regions were further divisible into two or three subareas, yielding nine distinct cellular compartments. Five rostral areas, prorhinal (Pr), lateral (28L), intermediate rostral and caudal (281r and 281c), and sulcal (28S), comprise the ERCr. Gross and microscopic examination of these subdivisions throughout the ERCr failed to reveal laminar disorganization in any of the schizophrenic brains. The brains also did not differ significantly with respect to total neuronal number, total volume and neuronal density per laminar and subareal subdivision, or laminar thickness per entorhinal subarea. However, neuronal number and density were reduced by 12-18% in Pr and 28L, suggesting that mild quantitative abnormalities may exist in the ERCr and might possibly be revealed in a larger sample of schizophrenic brains. We have failed to confirm previous reports of laminar disorganization in the ERCr in brains of patients with schizophrenia; to the extent that this region is implicated in schizophrenia, the structural changes are likely to consist of more subtle cellular disturbances.      

肿瘤坏死因子对牛肺动脉内皮细胞的损伤及蛋白激酶C抑制剂的抑制作用

研究表明:肿瘤坏死因子(TNF)可剂量依赖地引起牛肺动脉内皮细胞乳酸脱氢酶释放率(LDH%)升高,促进中性粒细胞向内皮细胞粘附,并可抑制内皮细胞增殖和DNA合成。蛋白激酶C(PKC)抑制剂1-(5-异喹啉磺酰基)-2-甲基哌嗪(H-7)和槲皮素一方面可剂量依赖地抑制TNF对内皮细胞的直接损伤,另方面又可通过抑制TNF诱导的中性粒细胞对内皮细胞粘附增加,减轻TNF对内皮细胞的间接损伤作用,同时还可抑制TNF对内皮细胞增殖和DNA合成的影响,从而间接加强内皮细胞对损伤的自我修复。     

Transforming growth factor-β (TGF-β) activity in urine of patients with glomerulonephritis is related to their renal functional and structural changes

SUMMARY: Transforming growth factor-β (TGF-β) has been considered the principal cytokine involved in the pathogenesis of renal fibrosis. In the present study, we evaluated TGF-β activity in occasional samples from 22 normal individuals and 29 patients (11 with focal glomerulosclerosis, 11 with membranous nephropathy, five with Berger disease, one with type I membranoproliferative glomerulonephritis and one with postinfectious glomerulonephritis) using a CCL-64 mink lung cell growth inhibition assay.
A significantly increased urinary TGF-β activity (reported in relation to urine creatinine, Ucreat, and median) was observed in patients with glomerulonephritis compared with normal individuals ( P <0.01). the patients with Berger disease [median (Md) = 9.96/10 μg Ucreat.], membranous glomerulonephritis (Md = 7.23/10 μg Ucreat.) and focal glomerulosclerosis (Md = 16.6/10 μg Ucreat.) showed higher urinary TGF-β than normal individuals (Md = 1.09/10 μg Ucreat.) ( P <0.01). We found a positive correlation between the TGF-β activity in the urine of these patients and the incidence of segmental glomerulosclerosis ( r = 0.45, P <0.05) and their plasma creatinine levels ( r = 0.87, P <0.01). A negative correlation was observed between the TGF-β activity in the urine of these patients and their creatinine clearance ( r =−0.75, P <0.01).
Our data suggest that measurement of urinary TGF-β activity could be a useful non-invasive procedure for the evaluation of renal TGF-β production, permitting the assessment of prognosis and the evaluation of therapeutic efficacy in patients with renal disease.     

Subcellular localization of transforming growth factor-alpha in human eosinophil granulocytes

Eosinophils are involved in the inflammatory response seen in allergy and helminthic infestations. Eosinophils synthesize transforming growth factor-alpha (TGF-alpha), which may play a role in the development of the characteristic fibrosis seen in longstanding high eosinophilia. Using immunoelectron microscopic techniques, eosinophils from peripheral blood of healthy individuals and from one patient with high eosinophilia showed presence TGF-alpha in matrix of the specific crystalloid-containing granules. In cryosections, TGF-alpha was also visualized in a vesicular compartment of the cytoplasm. In double- labeling experiments, the TGF-alpha of this latter compartment did not colocalize with CD63, a marker for lysosomes, nor with albumin of secretory vesicles. In extracts from eosinophils, obtained from healthy donors, immunoreactive TGF-alpha could be detected by enzyme-linked immunosorbent assay-technique. In addition, sera from two patients with high eosinophilia showed TGF-alpha concentrations of 1.5 ng/mL and 164 pg/mL, respectively, whereas TGF-alpha could not be detected in serum from healthy controls. In conclusion, TGF-alpha is present in the specific granules, and in an additional vesicular compartment of the cytoplasm of eosinophils.     

Transplantation potential of hematopoietic cells released into the circulation during routine chemotherapy for non-Hodgkin's lymphoma [see comments]

Primitive hematopoietic cells released into the peripheral blood (PB) were studied in 50 patients with high-grade non-Hodgkin's lymphoma enrolled in a phase III trial of intensive weekly chemotherapy (VAPEC- B) alone or with granulocyte colony-stimulating factor (G-CSF). Mononuclear cells numbers were monitored and their in vitro growth potential assessed in clonogenic progenitor cell assays and in long- term culture. Total colony-forming cells (granulocyte-macrophage [GM], burst-forming unit, erythroid [BFU-E], Mix-CFC) were increased 40-fold (median) over baseline with chemotherapy alone and 106-fold with chemotherapy and G-CSF after the final dose. CD34+ cells were increased to a median of 4%, equivalent to that in normal bone marrow (BM) controls. Circulating colony-forming cell levels were maximal when the recovering total white blood cell (WBC) count reached 5 to 10 x 10(9)/L. The timing of the maximum was reproducible in individual patients. Therefore the WBC count can be used as a guide to the timing of leukapheresis. PB cells from normal controls' and patients' prechemotherapy were unable to sustain hemopoiesis in two-stage long- term cultures. In contrast, PB cells collected from patients primed with chemotherapy alone or chemotherapy with G-CSF at the time of predicted maximal colony-forming cell release were able to generate and sustain hematopoiesis in long-term cultures at a level comparable or superior to normal BM. These findings indicate that the use of G-CSF after routine outpatient chemotherapy stimulates maximal release of primitive hemopoietic cells into the circulation, including colony- forming cells and long-term culture-initiating cells. Their numbers are comparable with those in normal BM and are such that a single leukapheresis will usually yield enough cells for hemopoietic reconstitution after myeloablative chemotherapy.