实验猪小肠移植后急性排异反应的形态计量学研究

本文以猪小肠移植为模型，应用图像分析仪显微形态测量观察测量了移植前后肠粘膜结构。定量评价小肠急性排异反应的形态变化，评价免疫抑制剂对急排的作用。结果显示：小肠急排发生在术后５天，排异反应中肠粘膜形态、炎症程度及类型均有显著变化。免疫抑制剂可显著减轻急排，但不能防止排异反应的发生。形态计量检测结果可作为排异反应的早期指标，并可动态地监测排异反应的发展，指导免疫抑制剂的应用。     

Lactation-induced plasticity in the supraoptic nucleus augments axodendritic and axosomatic GABAergic and glutamatergic synapses: an ultrastructural analysis using the disector method

The disector, an unbiased stereological method for evaluation of synaptic densities, was used to analyse putative GABA and glutamate innervations of the supraoptic nucleus of virgin and lactating rats. The analysis was performed on ultrathin sections labelled for either of the amino acids with a postembedding immunogold technique. Our observations showed that the volume of the nucleus increased by 40% in lactating animals, an increase due to a significant enlargment of dendritic and somatic, but not vascular, volumes. Nevertheless, values of overall synaptic densities in the whole nucleus remained as high as those in virgin rats (37–40×10⁶ synapses/mm³). About 45% of all synapses were immunoreactive for GABA and 25% for glutamate; there were twice as many GABA- and glutamate-positive synapses on dendrites as on somata. When we estimated synaptic densities in relation to the neuropil (by subtracting the proportion of sampled areas occupied by somatic profiles), we found a significant increase in synaptic density in lactating animals. This affected axodendritic as well as axosomatic synapses, immunopositive and immunonegative for GABA or glutamate. The disector also allowed us to determine that the number of synapses from terminals making contacts on several somata and/or dendrites simultaneously constituted about 9% of all synapses in virgin rats, a proportion which more than doubled in lactating rats. About 50% were immunopositive for GABA and 30% for glutamate.

Our data offer further evidence of physiologically-linked structural synaptic plasticity in the supraoptic nucleus and clearly demonstrate that it affects both inhibitory and excitatory inputs on dendrites, as well as on somata, throughout the nucleus.     

Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.     

The Glutamatergic Innervation of Oxytocin- and Vasopressin-secreting Neurons in the Rat Supraoptic Nucleus and its Contribution to Lactation-induced Synaptic Plasticity

The present ultrastructural study analysed the distribution of glutamatergic synapses on oxytocin- and vasopressin-secreting neurons in the rat supraoptic nucleus (SON) after post-embedding immunogold labelling for glutamate and GABA, oxytocin or vasopressin. About 20% of SON axo—somatic synapses were enriched in glutamate immunoreactivity, visible over synaptic-like vesicles, mitochondria and synaptic densities. Double labelling for glutamate and GABA showed that putative glutamatergic terminals were distinct from GABAergic terminals. In ultrathin sections stained for glutamate and either oxytocin or vasopressin, the proportion of glutamatergic synapses was similar on oxytocinergic and vasopressinergic somata in virgin rats under basal conditions of peptide release as well as in lactating rats, in which oxytocin secretion is enhanced. Cross-sectional soma areas were significantly increased in lactating rats: oxytocinergic profiles were, on average, ˜40% larger than in virgin rats. However, the incidence of axo—somatic glutamatergic synapses (assessed as mean number of synapses per 100 μm of plasmalemma or proportion of somatic surface apposed to synaptic active zones) did not diminish, indicating that there was a compensatory increase of synapses during lactation. Also, we found an increase in the number of glutamatergic terminals making synaptic contact simultaneously onto two or more oxytocinergic elements in the same plane of section. Our observations therefore indicate that SON oxytocinergic and vasopressinergic neurons are innervated to a similar extent by a relatively large proportion of glutamatergic synapses. They reveal, moreover, that glutamatergic afferents participate in the lactation-induced synaptic plasticity of the oxytocinergic system.     

Correlation of Nuclear Morphometry and Immunostaining for p53 and Proliferating Cell Nuclear Antigen in Transitional Cell Carcinoma of the Bladder

Background :
In an attempt to determine the biological significance of nuclear morphometric findings, measurements of mean nuclear volume (MNV) and nuclear roundness factor (NRF) were compared to the immunoreactivityof p53 expression and proliferating cell nuclear antigen (PCNA) in human bladder cancer.
Methods :
MNV and NRF were measured using stereological methods. Expression of p53 and PCNA were determined by immunohistochemical staining. Specimens from 111 patients with previously untreated bladder cancer were analyzed.
Results :
The mean MNV was 235.8 ± 1 33.6 μm³ for the 81 patients with p53-labeling index (LI) less than 10% and 337.2 ± 141.0 μn³ for the 30 patients with p53 LI greater than 10% (P = 0.008). There was Resign if icant correlation between NRF and expression of p53. The mean MNV was 220.1 ± 1 20.5 μm³ for the 67 patients with PCNA LI less than 28% (the mean value of PCNA LI) and 328.9 ± 149.2 μm³ in 44 patients with PCNA LI greater than 28% (P= 0.0001). The mean NRF was 80.7 ± 4.2 for the 67 patients with PCNA LI less than 28%, and 82.3 ± 3.4 for the 44 patients with PCNA LI more than 28% (P= 0.04). Conclusion: Nuclear morphometric findings may reflect the proliferative potential of cancer eel Is of the bladder, as indicated by findings of immunostaining for p53 and PCNA.     

Morphometric study of nucleolar organizer regions in human oral normal mucosa, papilloma and squamous cell carcinoma

A morphometric study of nucleolar organizer regions (NOR) was performed to analyze their distribution, volume, number and shape in the different strata of human normal oral mucosa epithelium and papilloma and in squamous cell carcinoma employing microphotographs of silver-stained paraffin sections. The different NOR-related parameters evidenced significant differences between normal mucosa, papilloma and squamous cell carcinoma. The functional polarity of normal mucosa epithelium and of papilloma is also evidenced in terms of NOR-related parameters. The discriminative value of certain NOR parameters was demonstrated.     

Neuropathology of schizophrenia: A mini review

The neuropathology of schizophrenia remains obscure despite the fact that many neuropathologists have investigated this area for over 100 years. While remarkable progress has been made in the neuropathological study of neurodegenerative diseases including Alzheimer's disease, progress in studying the neuropathological entity of schizophrenia has not kept pace; the phrase “schizophrenia is the graveyard of neuropathologists” has been stated in the field. Since the 1980s, the morphological or functional abnormalities in the brains of schizophrenia patients have been reported by means of CT or MRI and with advanced functional brain image technology such as positron emission tomography or single photon emission computed tomography. Results from such imaging studies have led to neuropathological examination of the post mortem brains of schizophrenia patients being undertaken again. These neuroimaging studies have influenced the neuropathological investigation of the schizophrenic brain. Not only the classical microscopic observation of neuropathology, but also measurement and statistical analysis using computer imaging software or using immunohistological techniques has been performed. Based on the neuropathological studies of schizophrenia over the last 20 years, it is clear that schizophrenia is not a pure functional disease without organic factors. Reports of neuropathological abnormalities in the post mortem schizophrenic brain indicated they were found in almost all areas of the brain, but there are more reports describing the temporal lobe and frontal lobe compared to those describing other areas of the brain. These observed neuropathological abnormalities are explained rationally by the hypothesis of a neurodevelopmental disorder in this disease. In recent molecular biology studies, several putative candidate genes were reported, and some of these genes might have the function of neurodevelopment or making neuronal networks. It is important to consider together these findings with morphometric studies in neuropathological observation, neuroimaging studies and genome studies to pursue the etiology of schizophrenia from various perspectives.     

A method to quantitate axonal injury

The quantitation of diffuse axonal injury provides a more objective approach to the assessment of tissue damage in head injuries. The method designed in this study takes into account the anisotropy and structural inhomogeneity of the brain, and the distribution of lesions in diffuse axonal injury. The number of counts required for the statistical analysis is inversely proportional to the square of the desired accuracy, specified as the percentage of the mean value of the axonal balloons since the true mean is unknown from the outset. The number of fields are examined using an indexed-squares graticule in 10 different areas of the brain. Silver-stained sections from the brains of head injured patients that survived longer than 12 h must be used with this method. Difficulties may arise when patients of different survival times are compared since it takes some time for the axonal balloons to develop. A correlation with the survival time can be established with the quantitative data collected. The morphometric principles and the statistical rationale on which this methodology is based are briefly presented.     

Analysis of the conducting airway system in the lung: A new method combining morphometry with mathematical modeling for airway classification

Although the lung is structurally complex, it is suitable for morphometric analysis of the structural determinants of lung function in health and disease. Analysis of the organized branching airways has been problematic because of the need to identify and classify airways before structural characteristics of different‐order branches can be determined. Airway casts have been used to identify relationships between branches, measure some structural features, and develop mathematical models that describe simply the relationships between generations. However, cast preparation destroys surrounding tissue, including the airway wall, thus precluding analysis of these structural elements. We describe a new approach using tissue sections which combines the classification of airways into Strahler order (SO) with tissue structural analysis. Lung‐tissue sections are prepared, and outer (OD) and inner (ID) diameters are determined over a wide range of airways. The line equation relating log OD vs. SO is determined using measured values for SO1 (terminal bronchioles) and SO8 (first branch bronchi). Mean ODs can then be calculated for each of the other SO groups, and measurements can be classified. Calculations can be made for the mean number of branches and airway lengths (given the log linear relationship of these factors with SO and morphometrically determined volume densities for airway lumen), and for individual airway resistance and total resistances for each SO. For an example, mean data are presented for airways in the adult sheep (n = 13). The methodology presented allows identification of subtle alterations in airway structures which may be affecting selected orders of airways, with specific implications for changes in lung function. Anat Rec 266:51–57, 2002. © 2002 Wiley‐Liss, Inc.