Ultrastructural Changes Associated with Peripheral Neuropathy in HIV/AIDS

Light and electron microscopic studies were performed on neuromuscular biopsy specimens from 12 neurologically affected seropositive patients, 7 with the acquired immune deficiency syndrome (AIDS), 2 with AIDS-related complex, and 3 with no symptoms except for neuropathy. All patients had an axonal injury associated or unassociated with demyelination and peripheral neurogenic atrophy. Capillary lesions were consistently present, which seems to be a new finding. Moreover, tubuloreticular inclusions (TRIs) were found in endomysial (9 of 12 cases) and endoneurial (7 of 12 cases) vessels. Statistical analysis showed that TRIs in more than 20% of endomysial vessels correlated with a survival time shorter than 12 months (P = 0.028). Thus the quantification of TRIs seems to be one of the vital prognostic elements in this patient population.     

用图像分析系统定量研究兔早期缺血心肌细胞超微结构的变化

应用图像分析仪对结扎冠状动脉造成实验性缺血的兔心肌超微结构进行定量检测。结果显示：线粒全和线粒登攀上室的体密度随缺血时间延长而加大，线粒全嵴的体密度随缺血时间的延长而减少，缺血４５ｍｉｎ以后即和正常对照有显著性差别，实践证明，图像分析仪在定量超同结构的变化上，具有高度的精确性，故可早期发现病变。     

Ultrastructural Autoradiographic Studies of the Early Vasoproliferative Response in Tumor Angiogenesis

The early local vasoproliferative response induced by live tumor cells and an extract derived from such cells was studied in rat subcutaneous tissue by means of electron microscopy and ultrastructural autoradiography after local injections of tritium-labeled thymidine. DNA synthesis was localized in endothelial cells, pericytes, and perivascular cells 6 to 8 hours after exposure to 10⁶ live Walker ascites tumor cells. At this time, DNA-synthesizing endothelial cells in parent vessels exhibited a continuous basement membrane and could not be readily differentiated, ultrastructurally, from control endothelium. At 48 to 50 hours, the number of labeled cells increased and there was ultrastructural evidence of regenerating endothelium: marked increase in ribosomes and endoplasmic reticulum, scarce or absent pinocytotic vesicles, attenuated or discontinuous basement membrane and marked irregularities in cytoplasmic surfaces. Labeled endothelial cells were present in parent vessels, as well as along newly formed sprouts. Autoradiographic and ultrastructural findings after tumor extract or live tumor cells at 48 hours were similar. Evidence was also presented that cells which were recognizable as pericytes, by ultrastructural criteria and by their localization within the basement membrane, were capable of DNA synthesis and mitosis.     

Ultrastructural Changes in Muscular Dystrophy: I. Cardiac Tissue of Piglets Deprived of Vitamin E and Selenium

The ultrastructure of cardiac tissue from neonate, 3-, 6-, 8-, and 12-week-old piglets, born of vitamin E- and selenium-deprived sows was studied. A progression of lesions occurred in nonmuscular components of this tissue; the first lesion appeared in connective tissue elements. Fibroblasts and the extracellular compartment appeared most severely altered in the neonate, and progressive vascular damage was very evident from 3 to 12 weeks of age. Similarly, neuronal elements appear altered at 3 weeks and were almost nonevident in areas showing marked lesions at 8 and 12 weeks. Fairly extensive alterations were evident in all of these elements before any marked changes become evident in the muscle. The relevance of these observations is discussed in relation to the etiology of the disease.     

重症急性胰腺炎大鼠肾上腺病理及超微结构变化

目的:观察重症急性胰腺炎(SAP)大鼠肾上腺皮质的病理和超微结构变化。方法:采用5%牛磺胆酸钠逆行胰管注射法建立SAP模型,分别于术后3、12、24h测定血淀粉酶,观察胰腺、肾上腺皮质病理变化,透射电镜观察12h肾上腺皮质束状带细胞超微结构。结果:SAP造模成功后,血淀粉酶、胰腺病理评分进行性升高。3h时肉眼见肾上腺包膜轻度水肿,并逐渐加重,24h最为明显;3h肾上腺组织出现血窦扩张,12h可见肾上腺组织水肿、腺体结构轻度破坏、少量炎性细胞浸润,24h肾上腺皮质部分细胞变性及出血性坏死,腺体结构破坏严重;12hSAP大鼠肾上腺皮质束状带细胞超微结构损伤和分泌功能降低等改变。结论:随着SAP病情进展,肾上腺组织病理及超微结构损害加重。肾上腺功能减退可能与其病理、超微结构损伤有关。     

Specificity of Intertubular Capillary Changes: Comparative Ultrastructural Studies in Renal Allografts and Native Kidneys

The pathophysiology of chronic rejection of renal allografts is poorly understood and specific morphologic markers are being sought for its diagnosis. Ultrastructural splitting and reduplication of the basal lamina of the intertubular capillaries (ITCs) have been shown to be consistently associated with transplant glomerulopathy (TG) in renal allografts and have been used as a marker of chronic allograft rejection. Although the presence of ITC abnormalities is extremely helpful diag-nostically and has been considered a surrogate for the diagnosis of TG when glomeruli are not available for examination, their specificity has not been tested. This study examined 135 biopsy specimens from renal allografts and native kidneys and categorized the ITC basal lamina alterations into 5 patterns. The results showed that although marked ITC basal lamina abnormalities are characteristically seen in association with TG, lesser degrees of these changes may also be found in native kidneys and in transplants with other types of glomerulopathies. In native kidneys, splitting and reduplication of the ITC basal lamina were observed in cases of active lupus nephritis, membranoproliferative glomerulonephritis type I, crescentic glomerulonephritis, cryoglobulinemia, and hypertension. In allografts, ITC changes were seen in postinfectious proliferative glomerulonephritis, acute cyclosporin toxicity, and hemolytic uremic syndrome, in addition to cases with TG. The histopathologic diagnosis in renal diseases relies heavily on clinical, immunofluorescence, and ultrastructural findings. Therefore, in the transplantation setting, with other less common pathological processes ruled out, the presence of abnormalities of the ITC basal lamina is highly indicative of TG. This association is particularly true for cases with severe ITC abnormalities.     

Early Ultrastructural Changes in the Central Nervous System in Fukuyama Congenital Muscular Dystrophy

Electron microscopy of the central nervous system surface structure is described in two fetuses with Fukuyama congenital muscular dystrophy (FCMD). In addition to relatively large surface defects, many minute defects less than several micrometers in size associated with protrusion of glial cytoplasm were observed in the cerebrum. These findings were considered to represent early changes prior to cortical dysplasia. The basement membrane adjacent to the defects showed amorphous, wavy, or whorled configurations, and gradually disappeared. The glial cytoplasmic membrane seemed to be relatively well preserved in some areas where the basement membrane disappeared. On the other hand, both the basement membrane and cytoplasmic membrane became indistinct irregularly in areas without defects, including the spinal cord; similar lesions were found in the skeletal muscle. These observations confirm previous observations concerning defects of the pial-glial barrier of the brain surface, and may suggest the involvement of abnormal basement membrane or related structures, or both, in the genesis of the brain lesions of FCMD.     

Developmental Changes in Early Sharp Waves in the Hippocampus of Neonatal Rats

Neuroscience and Behavioral Physiology - Synchronized activity the hallmark of neural networks. Early sharp waves (eSPW) form one type of synchronized activity – these are synchronized...     

Artocarpus Communis Forst. Root-Bark Aqueous Extract- and Streptozotocin-Induced Ultrastructural and Metabolic Changes in Hepatic Tissues of Wistar Rats

Decoctions and infusions of Artocarpus communis (Forst.) (family: Moraceae) root-bark are commonly used traditionally among the Yoruba-speaking people of Western Nigeria as folk remedies for the management, control and/or treatment of an array of human diseases, including type 2, adult-onset diabetes mellitus. Although numerous bioactive flavonoids have been isolated from the roots, stem-bark and leaves of A. communis, to the best of our knowledge, the effects of the plant''s root-bark extract on animal model of diabetes mellitus and on liver tissues have hitherto, not been reported in the biomedical literature. In view of this, the present study was undertaken to investigate the glycaemic effect of, and hepatic tissue ultrastructural, morphological and metabolic changes induced by, A. communis root-bark aqueous extract (ACE) in Wistar rats. The ultrastructural, morphological and metabolic effects of ACE have been compared with those induced by streptozotocin (STZ) in rat experimental paradigms. Four groups (A, B, C and D) of Wistar rats, each group containing 10 rats, were used. Diabetes mellitus was induced in the diabetic groups B and C animals by intraperitoneal injections of STZ (75 mg/kg body weight), while group A rats received A. communis root-bark aqueous extract (ACE, 100 mg/kg body weight, i.p.) alone. Control group D rats received distilled water in quantities equivalent to the volume of ACE administered intraperitoneally. The rats in group C were additionally treated with ACE (100 mg/kg body weight i. p.) daily from day 3 to day 10 after STZ treatment. Hepatic glucokinase, hexokinase, glutamate dehydrogenase, succinate dehydrogenase, β-hydroxybutyrate dehydrogenase, serum insulin and blood glucose levels of the animals were measured and recorded before and after ACE, STZ and STZ+ACE treatments. Hepatic tissues were also processed for transmission electron microscopy. Electron microscopic examinations showed toxic, deleterious alterations in the ultrastructures of groups A, B and C hepatic cells, the most prominent deleterious effects being on the hepatocytes. Ultrastructural changes observed within the hepatocytes of groups A, B and C rats include disrupted mitochondria with increase in lipid droplets, extensive hepatocellular vacuolation, scanty rough endoplasmic reticulum (RER) and ribosomes. Large glycogen clusters were also noticed displacing the mitochondria and RER in group A rats. Group A rats also developed significant hyperglycemia (p<0.05) immediately after ACE administration, while groups B and C rats developed hyperglycemia 24 hours after STZ treatment. When compared with the control group D rats, the activities of all the three subsystems were disrupted, leading to overall inhibition of oxidative phosphorylation of the liver mitochondria in groups A, B and C rats, but remain normal in the untreated group D control rats. The findings of the present study indicate that A. communis root-bark aqueous extract induces hyperglycaemia in the experimental animal model used, and that the plant''s extract disrupts the ultrastructural characteristics and architecture of hepatocytes as well as oxidative energy metabolism.     

Morphological Changes in Varicocele Veins: Ultrastructural Study

Background: Varicocele consists of dilatation of the pampiniform venous plexus and the internal spermatic veins. It is present in 15% of male population and is a common cause of male infertility. Objective: To describe the normal structure of the internal spermatic vein and the morphological changes in grade 3 varicocele. Methods: The authors dissected and analyzed a 2- to 3-cm tract of the pampiniform venous plexus of 20 patients undergoing varicocelectomy for left varicocele and of 10 consecutive patients undergoing surgery for left inguinal hernia. The histological examination was performed with hematoxylin–eosin and Masson trichrome stains. The ultrastructural evaluation was done using both scanning and transmission electron microscopy. Results: Compared with normal internal spermatic veins, varicocele veins showed narrowing and/or obliteration of the lumens, destruction of the endothelial cells, invagination of the intima, and deposition of collagen bundles in the media (light microscopy). The ultrastructural changes in varicocele veins included elongation of the endothelial cells with features of cellular damage, loss of the internal elastic lamina, and the appearance of ghost bodies and degenerative vacuoles in the subendothelial layer. Conclusions: The authors believe this is the first report analyzing ultrastructual changes in normal human internal spermatic vein samples and in varicocele. The underlying molecular mechanisms of these changes await further studies.     

Endothelial Proliferation in Inflammation: I. Autoradiographic Studies Following Thermal Injury to the Skin of Normal Rats

Endothelial prolifertion was studied in sites of acute inflammation induced by necrotizing (60 C for 20 seconds) or mild (54 C for 20 seconds) thermal injury to the skin of rsts. DNA synthesis in endothelial cells was assayed 6 hours to 10 days following injury by quantitation of the ³H-thymidine labeling indices on 2-μ Epon section autoradiographs. In lesions induced at 60 C for 20 seconds, increase in DNA synthesis in small vessels around the necrotic tissue began at 1 day and became significant at 2 and 3 days (10 to 12% for endothelial cells, 9% for perivascular cells). This increased endothelial replication resulted in the formation of new blood vessels by 5 to 7 days. Endothelial labeling diminished progressively after 3 days, as the epidermis regenerated. Foci completely covered by new epidermis consistently showed lower labeling indices than those which were not reepithelialized. Mild thermal injury (54 C for 20 seconds) also resulted in significant increases in endothelial labeling (6%), but the labeling was present mainly in superficial vessels and was not followed by neovascularization. The findings with mild injury are consistent with data that vascular leakage from superficial vessels is due to direct, albeit delayed, endothelial damage. Electron microscopic studies confirmed labeling in endothelial cells and indicated that ultrastructural alterations that were previously ascribed to activation, recovery, or regenerative transformation of endothelium represent, in the main, endothelial proliferation.     

Prion Protein with an Insertional Mutation Accumulates on Axonal and Dendritic Plasmalemma and Is Associated with Distinctive Ultrastructural Changes

Prion diseases are fatal neurological diseases characterized by central nervous system deposition of abnormal forms of a membrane glycoprotein designated PrP (prion protein). Tg(PG14) transgenic mice express PrP that harbor a nine-octapeptide insertional mutation homologous to one described in a familial prion disease of humans. Tg(PG14) mice spontaneously develop a fatal neurological illness accompanied by massive apoptosis of cerebellar granule neurons and accumulation of an aggregated and weakly protease-resistant form of PrP that is not infectious. Previous light microscopic analyses of these mice left open questions regarding the subcellular distribution of the mutant protein and the nature of the neuropathological lesions produced. To address these questions, we undertook an immunogold electron microscopic study of Tg(PG14) mice. We found that mutant PrP is localized primarily on the plasma membrane of dendrites and unmyelinated axons in the hippocampus and cerebellum, with little labeling of either neuronal cell bodies or intracellular organelles. PrP deposits were shown to be associated with degenerative changes in dendritic structure. We also describe for the first time marked pathology in myelinated axons, and alterations in the axon/oligodendrocyte interface. Taken together, our results suggest cellular mechanisms by which mutant PrPs produce pathology. In addition, they highlight distinctions between familial and infectious prion disorders at the ultrastructural level that correlate with differences in cellular trafficking of the disease-associated PrP forms.Transmissible spongiform encephalopathies, or prion diseases, are fatal neurological disorders of humans and animals that occur in sporadic, contagious and familial forms.¹ A key molecular event in all prion diseases is the conversion of a normal cell-surface sialoglycoprotein (PrP^C) into a conformationally altered isoform (PrP^Sc) that is enriched in β-sheet structure.² PrP^Sc, which is typically identified by its increased resistance to protease digestion, has been claimed to be infectious in the absence of nucleic acid.³ However, there is evidence that some pathogenic forms of PrP are not infectious, and that some may be protease sensitive.^4,5,6Immunohistochemical methods have been used to visualize disease-specific accumulations of PrP (PrP^d), encompassing both protease-resistant and protease-sensitive forms, in tissues of infected animals.⁷ These studies have shown that accumulations of PrP^d occur predominantly on the perikaryonal and dendritic plasma membranes of neurons, and within lysosomes.^8,9,10 Such PrP^d accumulations specifically co-localize with several kinds of cellular pathology, including abnormal endocytic structures, microfolding of the plasma membrane, and excess lysosomes.⁹ In several murine scrapie models (eg, ME7), there is also conspicuous synaptic loss (not co-localized with PrP^d), as well as marked degeneration of axons.¹¹Tg(PG14) mice express the murine homologue of PrP carrying a nine-octapeptide insertional mutation described in human patients with an inherited prion disease.¹² These mice spontaneously develop a fatal, ataxic, neurological illness, and they accumulate in their brains an insoluble and weakly protease-resistant form of the mutant protein that shares certain biochemical similarities with abnormal PrP derived from infectious prion sources.¹³ However, PrP from Tg(PG14) mice is not infectious in transmission experiments or in cell-free amplification reactions.^5,13 Tg(PG14) mice therefore provide an ideal model for investigation of PrP pathogenic mechanisms independent of mechanisms of prion infectivity.The neuropathological features of Tg(PG14) mice have been previously characterized by light microscopy.^12,14 These animals display a marked cerebellar cortical atrophy associated with apoptosis of granule neurons and thinning of the synapse-rich molecular layer. Immunohistochemistry shows accumulation of PG14 PrP in neuropil regions throughout the brain as diffuse, non-amyloid deposits previously characterized as “synaptic-like.” In addition, prominent intra-axonal deposits of the mutant protein have been described in Tg(PG14-EGFP) mice that express PG14 PrP fused to enhanced green fluorescent protein.¹⁵The Tg(PG14) mouse represents a model of inherited prion disease in which the neuropathology induced by a mutant prion protein can be studied in detail. However, previous light microscopic analyses of Tg(PG14) brains left open several important questions. Most importantly, what is the subcellular distribution of PG14 PrP deposits, and are such deposits associated with degenerative morphological changes in neurons or other cell types? To address this question, and to compare the lesions associated with PG14 PrP to those associated with PrP^d accumulations in infectious prion diseases, we have undertaken an immunogold electron microscopic analysis of the brains of Tg(PG14) mice. Our results significantly extend previous understanding of the neuropathology of Tg(PG14) mice, providing insight into cellular mechanisms operative in familial prion diseases and how these compare to the processes underlying infectious prion diseases.     

A Case of Acute Motor and Sensory Axonal Neuropathy Following Hepatitis A Infection

Acute motor and sensory axonal neuropathy (AMSAN) are recently described subtypes of Guillain-Barre syndrome characterized by acute onset of distal weakness, loss of deep tendon reflexes, and sensory symptoms. A 21-yr-old male was transferred to our hospital due to respiration difficulties and progressive weakness. In laboratory findings, immunoglobulin M antibodies against hepatitis A were detected in blood and cerebrospinal fluid. The findings of motor nerve conduction studies showed markedly reduced amplitudes of compound muscle action potentials in bilateral peroneal, and posterior tibial nerves, without evidence of demyelination. Based on clinical features, laboratory findings, and electrophysiologic investigation, the patient was diagnosed the AMSAN following acute hepatitis A viral infection. The patient was treated with intravenous immunoglobulin and recovered slowly. Clinicians should consider this rare but a serious case of AMSAN following acute hepatitis A infection.