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Protective effect of verapamil in ischemic porcine hearts: analysis of ultrastructural and metabolic changes using in vivo 31P-NMR spectroscopy.

To assess the protective effect of verapamil on ischemic myocardium, the changes in high energy phosphates, inorganic phosphate, and intracellular pH were serially and quantitatively measured in ischemic porcine hearts without collateral circulation using 31P-NMR spectroscopy, together with ultrastructural examination. Twenty-six farm pigs weighing 11 to 14 kg were anesthetized with fluothane and were divided into control (C) group and verapamil pretreatment (V) group. In V group 0.2 mg/kg of verapamil was administered for 20 mins before occlusion of the anterior descending coronary artery. 31P-NMR spectra were serially obtained throughout the experiment, and ultrastructural examination was done at 20-min occlusion and at 120-minute occlusion in each group. At 10-min ischemia, creatine phosphate was significantly preserved in V group (C/V = 11 +/- 4%/16 +/- 5% P less than 0.05). At 20 min ischemia, ATP was significantly preserved (C/V = 60 +/- 9%/73 +/- 8% P less than 0.05), and intracellular pH was significantly higher in V group (C/V = 6.4 +/- 0.2/6.6 +/- 0.1 P less than 0.05). Morphologically, clumping of the nuclear chromatin, mitochondrial swelling and decrease in glycogen were milder in V group at 20 min ischemia. However, these beneficial effects disappeared at 120 min ischemia. Thus pretreatment with verapamil attenuated depletion of high energy phosphates, progression of acidosis, and ultrastructural changes. There was no significant difference of rate pressure product and regional blood flow between hearts with and without pretreatment of verapamil. Therefore, this protective effect may be due to the energy sparing effect or other direct subcellular effect of verapamil on ischemic myocyte.

Angiography↗

Brief, intermediate and prolonged ischemia in the isolated crystalloid perfused rat heart: relationship between susceptibility to arrhythmias and degree of ultrastructural injury.

Isolated Langendorff-perfused rat hearts were used to assess susceptibility to reperfusion-induced arrhythmias after different durations of ischemia in relationship to structurally related impairment of heart function, and to examine whether phase two ischemia-induced arrhythmias occur in crystalloid perfused hearts. This was achieved by subjecting the hearts to 5 min reperfusion following either sustained (240 min), intermediate (30 min), or brief (10 min) regional ischemia. Sustained ischemia induced little arrhythmogenesis upon reperfusion (no ventricular fibrillation) and impairment of recovery of coronary flow (approximately 64% of uninvolved zone flow). Electron microscopic investigation of the ischemic region revealed severe degenerative damage of the ultrastructure of cardiac myocytes and capillary endothelial cells. In contrast, reperfusion following brief ischemia caused all hearts to develop ventricular fibrillation (VF), accompanied by a persisting hyperemia throughout the course of reperfusion (flow 149 +/- 33% of that in the uninvolved zone after 1 min of reperfusion). In this group, myocardial ultrastructure exhibited negligible i.e., almost complete reversal of injury, upon reperfusion. Intermediate (30 min) ischemia led to a high incidence of reperfusion arrhythmias (92% of hearts developing VF) and modest hyperemia (flow 111 +/- 22% of that in the uninvolved zone after 1 min of reperfusion). Moderate ultrastructural alterations and their further deterioration upon reperfusion were observed in some but not all hearts in this group. During ischemia, phase 1 arrhythmias were common (57% of hearts developed VF during the first 30 min). However, phase 2 arrhythmias were absent during 120-240 min ischemia in these isolated hearts. In conclusion sustained ischemia in the rat heart renders myocardium unviable with a consequent loss of susceptibility to reperfusion arrhythmias. Phase 2 ischemia-induced arrhythmias do not occur in this model, implicating an intact autonomic nervous system and/or circulating factors from blood (e.g., neutrophils) in phase 2 arrhythmogenesis.

Animals↗

Effect of ischemia on axonal transport of choline acetyltransferase and acetylcholinesterase and on ultrastructural changes of isolated segments of rabbit nerves in situ.

Axonal transport of acetylcholinesterase (AChE) and choline acetyltransferase (ChAc) and ultrastructural degenerative changes were compared in isolated nerve segments of rabbit peroneal nerves kept in vivo for 22 h, either with preserved blood supply (control segments) or under conditions of ischemia (ischemic segments). Ischemia abolished the proximo-distal and disto-proximal axonal transport of AChE and the proximo-distal transport of ChAc which, in control segments, were revealed by accumulations of the enzymes at corresponding ends of the segments. Total activities of AChE and ChAc recovered in isolated segments with intact blood supply corresponded to the activities in normal nerves; in ischemic segments, 50% of ChAc activity was lost in 22 h, whereas all AChE activity was preserved. Ultrastructural changes were found in few fibres in control segments and in many fibres in ischemic segments 22 h after nerve interruption. The early changes in control segments correspond to those described in the literature for peripheral stump of severed nerves. The microtubules, neurofilaments and mitochondria were not affected. In ischemic segments, various stages of axoplasmic disintegration occurred in the myelinated and unmyelinated axons:flocculation and clumping of axoplasmic material, decomposition of neurofilaments and microtubules, swelling, formation of amorphous densities and breakdown of mitochondrial cristae. Swelling, amorphous densities, clumping of nuclear chromatin and necrotic mitochondrial changes appeared also in Schwann cells. It is concluded that ischemia blocks axonal transport and brings about, within 22 h, ultrastructural changes both in nerve fibres and in Schwann cells. Cytoplasmic ChAc is affected earlier by necrotic degeneration of the axons than membrane-bound AChE.

Acetylcholinesterase↗

Biochemical and ultrastructural effects of chloroquine on horseradish peroxidase uptake and lysosomal enzyme activities in innervated and denervated mouse skeletal muscle.

The effects of chloroquine treatment on horseradish peroxidase (HRP) uptake and lysosomal enzyme activities in innervated and denervated mouse skeletal muscle have been studied using biochemical, histochemical and ultrastructural techniques. Chloroquine treatment caused a large (59-101%) increase in the activity of cathepsin D in both innervated and denervated muscle. The activity of N-acetyl-beta-D-glucosaminidase also increased slightly in denervated muscle. No effect was observed on acid phosphatase activity. The in vivo uptake of HRP in innervated and denervated muscle was unaffected by chloroquine treatment. The results show that the activities of certain lysosomal enzymes may increase in skeletal muscle without an increase in endocytic activity. This is discussed in comparison to what is seen in denervated and dystrophic muscle. Histochemical and ultrastructural studies showed the HRP uptake to occur segmentally in denervated muscle fibres from untreated as well as chloroquine-treated animals. Ultrastructurally the peroxidase-positive phagosomes occurring in these segments were found to contain increased levels of undegraded material after chloroquine treatment suggesting that these phagosomes are of a lysosomal nature and also participate in autophagic processes.

Animals↗

A qualitative and quantitative study of the ultrastructure of regenerating muscle fibres in Duchenne muscular dystrophy and polymyositis.

Quantitative and qualitative ultrastructural analyses were made of selected small muscle fibres from muscle biopsies from 23 patients with Duchenne muscular dystrophy (DMD) and 10 with polymyositis. It is argued that the fibres selected were regenerating. The myofibrillar content of the fibres was similar in both samples. In both there was considerable misalignment of the myofibrils but their orientation tended to improve as the content increased. The mitochondrial content was similar in the two samples but there were more ultrastructural abnormalities in the DMD population. The concentration of glycogen was elevated and the sarcoplasmic reticulum (SR) was much more commonly dilated in the DMD patients. Dilated SR is the prenecrotic change seen most frequently in mature muscle fibres in DMD and seems to be the first ultrastructural manifestation of the disease process. Its occurrence in the regenerating fibres suggest that the primary genetic lesion is being recapitulated in successive generations of fibres.

Biopsy↗

Tridimensional ultrastructure of glomerular capillary endothelium revealed by high-resolution scanning electron microscopy.

Recent advances in specimen preparation techniques and scanning electron microscope (SEM) design have permitted ultrastructural examination of the glomerular capillary wall in three dimensions using high-resolution scanning electron microscopy (HRSEM). Specimens in which the cytosol and cytoskeleton have been extracted, but cell membranes nuclear structures and organelles left in place, were studied using a Hitachi SEM with a resolution of approximately 3 nm. Each HRSEM micrograph displayed a depth of field and information content equivalent to 15-30 consecutive, ultrathin, transmission electron microscope (TEM) sections viewed simultaneously in perfect serial alignment. The results have confirmed previous ultrastructural observations obtained by use of TEM and, in addition, have revealed new ultrastructural features of the normal rat glomerulus. A morphometric analysis of glomerular endothelium carried out using the HRSEM micrographs revealed that the endothelial cell processes, which lie between the fenestrae, are nearly circular in cross section and that they, as well as the fenestrae, have a diameter of approximately 60 nm. The potential functional role of the fenestrae in controlling access to the underlying basement membrane requires further study.

Animals↗

Endocrine dependency of endometriosis: an ultrastructural study.

The comparison of the ultrastructural features of endometriotic implants in 96 patients before and after suppressive therapy by danazol showed that the glands of the ectopic endometrium had a wide range of morphologic development. In about one-third of the pretreatment biopsies significantly different ultrastructural patterns were observed in the same specimen, ranging from poorly to highly differentiated endometrial glands. Adequate morphological changes during the menstrual cycle were found in implants only in 14 patients during the proliferative phase, but adequate, homogeneously performed secretory changes were completely missing during the luteal phase. Besides incomplete or delayed secretory changes the majority was proliferative rather than secretory. After 6 months of endocrine suppression laparoscopic biopsies of endometriosis were repeated, and the ultrastructural findings lead to three conclusions. 1. Poorly differentiated endometriotic foci do not respond to danazol. 2. Endometriotic implants consisting of highly differentiated epithelium with adequate cyclic variations respond well to danazol and disappear in nearly 80% of cases. 3. In endometriosis with mixed areas consisting of various degrees of glandular differentiation the hormonal suppression can eliminate endometriotic implants or arrest them at a proliferative stage. If the morphological appearance of the ectopic implants depends not simply upon the endocrine stimulus, but primarily on the degree of differentiation and maturity of the cell, then perhaps cyclic modulation is only a secondary phenomenon, and hormones play only a secondary role in therapy. If this hypothesis is correct, only complete elimination of endocrine influence can cure endometriosis. Transient or incomplete suppression may lead only to partial regression.

Cell Differentiation↗

Odontogenic myxoma. Surgical management and an ultrastructural study.

Odontogenic myxoma is a tumor of primitive mesenchyme, probably derived from the dental apparatus. Surgical management of this benign but locally aggressive tumor is either by curettage or en bloc resection. Two cases of odontogenic myxoma of the mandible are reported. In one case, en bloc resection. Two cases of odontogenic myxoma of the mandible are reported. In one case, en block resection with immediate reconstruction was undertaken. In the second case, the neoplasm was thoroughly curetted. The first case was studied by electron microscopy. Six ultrastructural studies of seven odontogenic myxomas have been previously reported. The ultrastructural features of odontogenic epithelium that may be present in myxomas of the jaws have been examined by electron microscopy once before. Our observations are in agreement with those of other workers who suggest that the connective tissue cell is the proliferating component of the tumor and is very similar to a fibroblast but has enough ultrastructural and functional features to deserve the term myxoblast. The majority of the tumor cells are metabolically active and secretory and there is adequate evidence that the tumor matrix consists of large amounts of mucopolysaccharides. It is reasonable, therefore, to conclude that myxoblasts secrete the mucoid matrix that is so characteristic of odontogenic myxomas. Unlike normal or neoplastic fibroblasts, the myxoblasts are not engaged in abundant synthesis of banded collagen throughout the entire lesion.

Adult↗

Ultrastructural alterations in Tetrahymena pyriformis induced by growth on saturated phospholipids at 40.1 degrees C.

Structural changes in Tetrahymena pyriformis, strain WH-14, induced by growth on saturated phospholipids at 40.1 degrees C, uere studied by electron microscopy. Alterations in the ultrastructural organizations of the cell membrane and surface regions were common. These alterations were characterized in the displacement of kinetosomes, the spatial disorientation and disorganization of cortical ridges and grooves, and the spatial disorientation of longitudal and transverse microtubular ribbons. Irregular surface protrusions and multiple invaginations of alveolar membranes were among the most common features encountered. Disorganization of longitudinal microtubular ribbons was also a frequent encounter. The integrity of the ultrastructure of cell surface membranes and of the internal organization and ultrastructure of the kinetosomes, however, appeared to be unaltered. Other alterations included those of a number of cytoplasmic organelles (e.g. mitochondria and endoplasmic reticulum), which showed characteristic changes in the structural patterns.

Animals↗

Time course of cadmium-induced ultrastructural changes in rat liver.

Ultrastructural changes in rat liver were studied 1, 2, 4, 6, 8, and 10 hr after administration of a single, high dose of Cd (3.9 mg Cd/kg, iv) or after repeated administration of a lower dose (0.5 mg Cd/kg, sc, 6 days/week for 6 months). These dosing regimens have been previously shown to produce hepatotoxicity and result in large accumulations of Cd in liver. In addition to light and electron microscopy, plasma enzyme activities indicative of liver injury, namely alanine (ALT) and aspartate (AST) aminotransferase, were determined at the aforementioned times. One hour after an acute dose of Cd, electron photomicrographs of liver showed dilation of the rough endoplasmic reticulum with concomitant loss of membrane-associated ribosomes, nucleolar condensation, and an increase in the number of perichromatin granules. At later times (4 and 6 hr), ultrastructural changes included mitochondrial swelling associated with matrical inclusions, further dilation and vesiculation of rough endoplasmic reticulum, and presence of a fibrillar material within cytoplasm. In contrast to changes observed after single administration of Cd, the predominant hepatic lesions in rats injected repeatedly with the metal over 6 months were interstitial fibrosis, nuclear enlargement, and an increase in number and predominance of nucleoli. Ultrastructural evidence of nuclear alterations included condensation of nucleoli and an increase in the number of perichromatin granules. These results indicate that Cd interferes with hepatic protein synthesis early after injection of a large dose, and that further degenerative changes occur later and possibly in response to protein inhibition. Although severe degenerative changes in liver were not evident in rats chronically exposed to the metal, Cd-induced changes in nuclei and nucleoli also indicate the likelihood of altered protein synthesis.

Alanine Transaminase↗

Triphenyl phosphite-induced ultrastructural changes in bovine adrenomedullary chromaffin cells.

Primary cultures of bovine adrenomedullary chromaffin cells were treated with the phosphorus acid ester triphenyl phosphite (TPP), a chemical capable of producing Type II organophosphorus compound-induced delayed neurotoxicity (OPIDN), and the morphological changes were assessed by transmission electron and scanning microscopy. Following a 24-hr incubation with 100 microM TPP nearly all mitochondria were either disrupted or swollen and glycogen buildup within the cytoplasm was evident. The viability of cells treated with TPP and cultured on coverslips for scanning electron microscopy was very low. By scanning electron microscopy, the filopodia of these cells appeared contracted. The surface texture was very irregular and giant globular bodies were evident. Parallel studies were carried out with the cholinergic compound O,O-diethyl 4-nitrophenyl phosphate (paraoxon) and the Type I delayed neurotoxicant O,O-diisopropylphosphorofluoridate (DFP). Transmission and scanning electron microscopy revealed that treatment with these organophosphorus compounds did not produce the ultrastructural effects that were seen with TPP. The morphological data were confirmed biochemically by assessing the viability of the mitochondria via measurement of [3H]adenosine incorporation into ATP. Treatment with 100 microM TPP for 4 or 24 hr caused a marked inhibition (90% relative to controls) of adenosine incorporation. Neither 100 microM paraoxon nor 100 microM DFP had an inhibitory effect on incorporation. The effect of TPP was time-dependent with significant biochemical effects as early as 60 min. In contrast, ultrastructural changes were not seen until 24 hr. Morphologically, the 60-min incubations showed no perturbation in mitochondrial integrity. Our results support a specific effect of the triphenylphosphite, TPP, a Type II OPIDN compound, not a general toxic effect of organophosphorus compounds since the cholinergic agent paraoxon and the Type I delayed neurotoxic compound DFP did nto alter the cells ultrastructurally or compromise the mitochondria biochemically. The apparent target for TPP toxicity is the mitochondria.

Adenosine↗

Brenner tumor of the ovary: a correlative histologic, histochemical, immunohistochemical, and ultrastructural investigation.

The histologic, histochemical, immunohistochemical, and ultrastructural features of Brenner tumor (BT) were studied. BT was compared with transitional bladder cells, and close similarities between the two tissues were identified. Abundant glycogen in all cellular layers, an alcianophilic/sialomucinic surface mucous coat, and argyrophilic cells characterized both BT and bladder epithelium. Immunohistochemically, chromogranin and neuron-specific enolase reactivity was observed in all cases examined. An additional relevant finding was the presence of serotonin-storing cells in both BT and urothelium. Moreover, carcinoembryonic antigen, epithelial membrane antigen, and keratin reaction were found in BT and urothelium, indicating an additional antigenic similarity. Additionally, malignant Brenner tumor was ultrastructurally found to share many common features with the bladder tissue. The distinct histochemical, ultrastructural, and antigenic pattern of BT, primarily of the transitional type, is emphasized.

Brenner Tumor↗

Epithelioid hemangioendothelioma of the liver: an ultrastructural study.

Epithelioid hemangioendotheliomas are uncommon vascular tumors, mainly observed in lung and soft tissues. Liver involvement is infrequent and, in contrast to the extrahepatic localizations of the tumor, has not been subjected to detailed ultrastructural analysis. This prompted us to report the results of the ultrastructural study of three cases of epithelioid hemangioendothelioma of the liver. Neoplastic proliferation was heterogeneous. Most of neoplastic cells presented features suggestive of endothelial differentiation, including presence of Weibel-Palade bodies and evidence of vasoformative properties demonstrated by formation of both intra- and extracellular vascular channels resembling the normal structures successively observed during embryogenesis and tissue regeneration. A minor cell population, unreported so far, exhibited ultrastructural characters resembling those of pericytes and presented organoid relationship to neoplastic endothelial cells. Tumor spreading along sinusoids induced pseudopeliotic dilatations and led to a progressive disruption of normal liver architecture. In conclusion, the three cases of hepatic epithelioid hemangioendothelioma examined in this work assume many organoid features mimicking the successive steps of normal angioformation and indicative of a high degree of morphological differentiation.

Adult↗

The extracellular matrix in large-cell lymphomas: a histopathologic, immunohistochemical, and ultrastructural study.

We studied the histopathologic, immunohistochemical, and ultrastructural features of the extracellular matrix (ECM) in 20 immunologically defined large-cell lymphomas, including immunoblastic sarcoma of B cells (three patients), peripheral T cell lymphoma (five patients), large non-cleaved follicular center cell (FCC) lymphoma (nine patients), and non-marking large-cell lymphoma (three patients). Immunohistochemical studies were performed with antibodies to laminin, fibronectin, and collagen types I, III, IV, and V. The immunologically defined subgroups demonstrated characteristic differences in ECM in light microscopic appearance, composition, and ultrastructural features. Immunoblastic sarcomas of B cells showed delicate intercellular bands that were apparent only at high power but were distinct in exhibiting focal staining for basement membrane elements (laminin and type IV collagen) in addition to type I collagen and fibronectin. Electron microscopically, no basal lamina were apparent, although the collagen fibers were embedded in a dense matrix not seen in the other lymphomas. All peripheral T cell lymphomas exhibited a packeting pattern of intercellular bands and were distinguished by the frequent presence of intense pericellular staining for type V collagen as well as by focal pericellular staining for types I and III collagen. The latter finding corresponded to extensive areas of direct contact between tumor cells and the ECM by electron microscopy. The large non-cleaved FCC lymphomas and the non-marking large-cell lymphomas demonstrated both diffuse and compartmentalizing arrangements of intercellular bands that frequently coexisted and stained predominantly for fibronectin and types I and III collagen. All groups demonstrated myofibroblasts and fibroblasts partially or completely separating the ECM from tumor cells, suggesting that most of the ECM is part of a reaction to these lymphomas. These studies show more variation in light microscopic appearance, composition, and ultrastructural relationships of the intercellular and pericellular ECM than was apparent in earlier studies of cleaved FCC lymphomas.

Aged↗

The ultrastructure of small-cell osteosarcoma, with a review of the light microscopy and differential diagnosis.

Small-cell osteosarcoma is a rare form of osteosarcoma and often poses difficulty in differential diagnosis when tissue samples do not include any diagnostic osteoid. By light microscopy, it may be difficult to distinguish small-cell osteosarcoma from other small-cell neoplasms, especially Ewing's sarcoma and mesenchymal chondrosarcoma. Relatively little has been reported about the ultrastructural characteristics of small-cell osteosarcoma, whereas electron microscopic examination has proven very useful in the diagnosis of most other small-cell neoplasms. We have studied four proven small-cell osteosarcomas in detail at the electron microscopic level and found their common features to be a high nucleocytoplasmic ratio, poorly differentiated cytoplasm, numerous free ribosomes and mitochondria as the next most prevalent organelle, small junctions, and envelopment of individual and groups of cells by matrix. Beyond these characteristics, cytoplasmic organelles and nuclear features varied, and no single pathognomonic ultrastructural picture was observed. However, within the range of possible ultrastructure of small-cell osteosarcoma, most small-cell neoplasms can be ruled out. Only certain examples of Ewing's sarcoma and mesenchymal chondrosarcoma may be indistinguishable from it when osteoid is not present in the sample.

Adolescent↗

Leiomyosarcoma of somatic soft tissues in childhood: an immunohistochemical analysis of six cases with ultrastructural correlation.

Leiomyosarcoma (LMS) of soft tissue is a rare tumor in children. Although LMS may exhibit clinical and histologic features that are typical of smooth muscle neoplasms in adults, they may often be confused with or resemble tumors of presumed fibroblastic, myofibroblastic, or rhabdomyoblastic differentiation. As a result, the diagnosis of LMS in children is often difficult to establish with confidence. To address this problem, we analyzed the immunohistochemical features of six LMS in children (one of deep soft tissue of an extremity, one of paravertebral tissue, one of the retroperitoneum, two of oropharyngeal soft tissue, and one of subcutis); the ultrastructural features of four of these tumors were also studied. Histologically, each of the three tumors of deep soft tissue and one of the retromolar trigone were composed of pleomorphic spindle cells arranged in interweaving fascicles. In contrast, the subcutaneous tumor and the lesion of the hard palate had an epithelioid appearance. Ultrastructural features were typical of adult type LMS. Immunohistochemically, these neoplasms were diffusely reactive for vimentin, while each was negative for cytokeratin, epithelial membrane antigen, and S-100 protein. Desmin was present in all cases, but was expressed only focally in three; a similar pattern of staining was noted for muscle-specific actin, although staining was generally noted in a larger population of cells. alpha-1-Antichymotrypsin was found in five tumors, and cathepsin B reactivity was encountered in four cases. Leu-7 antigen and myelin basic protein were coexpressed by one tumor, but neither was found in the remaining cases. These results indicate that immunohistochemical detection of desmin and muscle-specific actin may be useful in the differential diagnosis of spindle or epithelioid cell proliferations in childhood when ultrastructural analysis in unavailable.

Adolescent↗

Neuronal involution during ageing. Ultrastructural study in the rat cerebellum.

Involutive phenomena have been investigated by electron microscopy in the Purkinje Pk neuron of the cerebellar cortex of the aging rat. The still limited number of specimens available to date, however, suggest an age-related progression of morphological and functional deteriorations involving particularly the intraneuronal "nucleus-ribosome system" (NRS). The impairments are characterized by changes in the nucleolar texture. These alterations are accompanied by modifications in the repartition and relative proportion of RNP components of the nucleolus. In addition, other nuclear elements such as interchromatin and perichromatin granules may vary in importance with age. Recognizable changes in the ribosomal constituents of the NRS are evidenced by modifications in the density and distribution of free ribosomes. An altered structure and organization of GER cisternae are also evident. Furthermore, "light" cytoplasmic areas, an increased evidence of neurotubules and the gradual congestion of the pericaryon by age pigments are other valuable ultrastructural features that may be regarded as part of the sequence of morphologic events occurring during neuonal ageing. The above ultrastructural data will subsequently form the basis of a model of ageing in the nerve cell, which will complete the previously proposed model of neuronal maturation. Therefore, this long-term study essentially purports the investigation of subcellular events taking place in the Pk neuron all along the normal life span in rats. This model will also be used to evaluate the changes in the sequence and the reinforcement of the processes of evolution versus involution as affected by certain xenobiotics, such as abused drugs(alcohol and narcotics). The intraneuronal modifications found in the nuclear and cytoplasmic structures of the NRS could possibly reflect the molecular dysfunction related to the production of various types of RNA and neuronal proteins. This hypothesis is supported by biochemical data obtained from analysis of the brain of aged animals. Ultrastructural and biochemical data appear to be in good agreement with the neurophysiologic interpretation of a slow-down and reduced efficiency of the CNS during the progressive development of senescence in human and animal subjects.

Age Factors↗

On the ultrastructural diversity and essence of residual bodies in neuronal ceroid-lipofuscinosis.

In 4 patients with neuronal ceroid-lipofuscinoses (NCL) (3 patients with the junvenile type, 1 patient with the late infantile type), the ultrastructural spectrum of residual bodies in the central and peripheral nervous system presented curvilinear profiles in all cases and regions investigated and many more ultrastructural patterns within and beyond regions commonly accessible to biopsy, probably due to age dependence, local tissue and cellular biochemical factors. Sampling from basal ganglia especially yielded combined curvilinear-fingerpint bodies, from peripheral ganglia additional membranous bodies. Residual bodies in NCL were present in almost every cell type, similar to the distribution of regular lipofuscin. Although the classical subgroups of NCL contain electronmicroscopically well defined residual bodies, permitting distinction of the late infantile type from the juvenile type, the ultrastructural differences are more of a quantitative than of a qualitative nature. However, they are not pathognomonic. N.m.r. spectra of ceroid and lipofuscin support the concept of their biochemical similarity, and argue against the proposition that they contain a single major component.

Brain↗