Metabolic alterations in the synoviocytes in chronically inflamed knee joints in immune arthritis in the rabbit: comparison with rheumatoid arthritis

The metabolism of the synovial lining cells of the normal and chronically inflamed joints of rabbits, in the Dumonde and Glynn model of rheumatoid arthritis, has been examined by quantitative cytochemistry. Significant alterations in metabolic activity were found in the synovial lining cells of the chronically inflamed joints. These alterations in metabolic activity closely resemble the pattern of metabolic changes found in human synovial lining cells in rheumatoid arthritis.     

Metabolic alterations in the synoviocytes in chronically inflamed knee joints in immune arthritis in the rabbit: comparison with rheumatoid arthritis.

The metabolism of the synovial lining cells of the normal and chronically inflamed joints of rabbits, in the Dumonde and Glynn model of rheumatoid arthritis, has been examined by quantitative cytochemistry. Significant alterations in metabolic activity were found in the synovial lining cells of the chronically inflamed joints. These alterations in metabolic activity closely resemble the pattern of metabolic changes found in human synovial lining cells in rheumatoid arthritis.     

Topographical changes along the neural fold associated with neurulation in the hamster and mouse

The topography of the ectoderm was examined by scanning electron microscopy during neurulation in hamster and mouse embryos. Stages from the appearance of the neural folds to closure of the posterior neuropore were studied. Progressive development of a zone of altered cellular morphology was observed along the crests of the neural folds. This zone evolved from and abrupt transition between surface and neural regions of the ectoderm to a narrow band of flattened cells which exhibited numerous membranous “ruffles” in the mouse, or blebs and presumably degenerating cells in the hamster, immediately prior to contact between the folds. These alterations were more prominent along the anterior than the posterior portions of the folds. Contact of the folds occurred first between the flattened cells with subsequent union of the surface cells. Stages of neural crest cell formation were observed subjacent to the zone of alterations in histological sections. It is suggested that the observed surface alterations may reflect changes in the membrane properties of the altered cells which are correlated with both neural crest formation and initial adhesion between the folds.     

A sequential ultrastructural study of different arteries in the hypertensive rat

Hypertensive vascular disease was induced in rats using weekly injections of deoxycorticosterone and substituting 1% sodium chloride for tap water to drink. The emphasis of the study was on the progression and comparative aspects of alterations produced in the large clastic vessels and the coronary artery.One of the carliest alterations was observed in the intima of all vascular segments. These were characterized by endothelial cell enlargement and a gradual subendothelial accumulation of granular material leading to intimal thickening. In the later stages of the disease, mononuclear cells, fibrin and smooth muscle cells were present within the intima, with the exception of the coronary artery; only smooth muscle cells were seen in the intimal portion of this vessel.Early changes in the media consisted of smooth muscle hypertrophy and widened lamellar units, resulting in increased thickness of the vessel wall. These alterations progressed to include variation in the shape of smooth muscle cells, increasing disorganization of the cellular arrangement, focal cytoplasmic necrosis, and the loss of entire smooth muscle cells.A definite regional difference in susceptibility of individual mural components to hypertensive damage was noted. The most striking feature of this difference was demonstrated by the relatively early, severe involvement of the media of the coronary artery, in contrast to the other arteries examined.These alterations may be initiated by increased intraluminal pressure. In the case of the coronary artery, failure of this vessel to adapt effectively to increased mural tension by structural re-modelling of the arterial wall, may exacerbate these alterations.     

Fibromatosis of the breast and mutations involving the APC/beta-catenin pathway

Fibromatoses of the breast are nonmetastasizing tumors, but can be infiltrative and locally recurrent. Breast fibromatoses are rare, and their specific genetic alterations have not been elucidated. However, their occasional occurrence in patients with familial adenomatous polyposis (FAP) and their morphologic identification with other deep fibromatoses (desmoid tumors) suggest that alterations of the APC/beta-catenin pathway might be involved in the pathogenesis of sporadic and FAP-associated breast fibromatoses. We analyzed somatic beta-catenin and APC gene mutations in 33 breast fibromatoses (32 sporadic and 1 FAP-associated) using immunohistochemistry for beta-catenin, 5q allelic loss assays, and direct DNA sequencing for exon 3 of the beta-catenin gene and the mutation cluster region of the APC gene. Nuclear accumulation of beta-catenin was present in the stromal tumor cells in most (82%) cases but not in normal stroma or mammary epithelial cells. Somatic alterations of the APC/beta-catenin pathway were detected in 79% of breast fibromatoses, including activating beta-catenin gene mutations in 15 cases and somatic APC alterations (mutation or 5q allelic loss or both) in 11. These findings indicate that alterations of the APC/beta-catenin pathway with resultant nuclear translocation of beta-catenin are important in the pathogenesis of both sporadic and FAP-associated breast fibromatosis. The spectrum of beta-catenin and APC alterations is similar to that described for desmoid tumors of the abdomen, paraspinal region, and extremities.     

The morphological changes in the pulmonary resistive vessels in the development of high-altitude pulmonary arterial hypertension

The structural alterations of pulmonary resistance vessels in rabbits during short-term adaptation to the high altitude were studied. As an example of ecological adaptation the structural alterations of pulmonary vessels in yaks living at altitudes above 3000 m were analyzed. Considerable structural alterations of endotheliocytes and blood cells were found that promote the appearance and development of high-altitude pulmonary hypertension. In yaks the adaptive alterations of pulmonary resistance vessels take place in the process of evolution. These alterations ensure, first, low resistance of pulmonary vessels when the volume of the vessel bed increases and, second, high functional activity of endotheliocytes. The changes are considered as a structural basis of ecological adaptation of pulmonary vessels providing a new level of homeostasis in pulmonary circulation.     

Electron microscopic study on the injurious effects of chlorpromazine on rat liver cells.

The authors examined the effect of chlorpromazine administration on rat liver cells. The early alterations were limited to the pericanalicular region, but the dilatation of bile canaliculi and the destruction of canalicular microvilli, both characteristic of rats with cholestasis were not observed. It is suggested that beside the Golgi apparatus, the smooth surfaced endoplasmic reticulum, the plasma membranes of liver cells also have an important role in the formation of vesicles and vacuoles in the pericanalicular region. The progressive proliferation of the smooth surfaced endoplasmic reticulum is thought to be related to an increased overburdening of the biotransformation system of liver cells, which is the result of chronic drug administration. In the last period of the experiment there was a decrease in the quantity of rough surfaced endoplasmic reticulum and increased fatty infiltration, mitochondrial alterations in some liver cells and simultaneously numerous regenerating liver cells were observed. All these alterations are attributed by the authors to the direct liver injuring effect of chlorpromazine.     

Age-related alterations in the signal transduction pathways of the elastin-laminin receptor.

With aging we assist to alterations in the vascular structure and function. One important factor in these vascular wall changes is the degradation of the elastin fibre major protein: elastin. Elastin peptides derived from the degradation are present in human sera. Elastin peptides induce on fibroblasts, phagocytic cells, lymphocytes, smooth muscle cells and endothelial cells, a variety of biological effects mediated by the elastin-laminin receptor which has been demonstrated to be present on the membrane of these cells. The transduction pathway of the ELR receptor involves the activation of phospholipase C (PLC) by a pertussis toxin sensitive G-protein. PLC induces the production of inositol trisphosphate (IP3) leading to the increase of the intracellular free calcium on one hand, and of diacylglycerol (DAG) which stimulates the translocation to the membrane of PKC leading to the phosphorylation of members of the MAPK family, such as p42/p44 MAPK. A progressive age dependent uncoupling of the elastin-laminin receptor occurs impairing its transduction pathway and which results in alteration of the calcium signaling and loss in calcium homeostasis of the cells. These alterations in the signal transduction of the elastin-laminin receptor result in modified activities of parenchymal and phagocytic cells with aging, such as free radical production and elastase release. Thus, these age-related alterations in the elastin-laminin receptor signal transduction may be involved in the atherogenesis.     

The effect of the duodenal ulcerogen cysteamine on somatostatin and gastrin cells in the rat

Previous studies showed a rapid decrease of somatostatin concentration in the gut and an increase in serum gastrin levels after a single dose of the duodenal ulcerogen cysteamine. An attempt was made to identify morphologic changes that would correlate with these functional changes. Rats were killed 1, 4, 8 or 24 hr after a single dose of cysteamine and sections of gastric mucosa and pancreas were processed for electron and light microscopy. Subtle ultrastructural alterations were seen in D cells of the stomach (e.g., dilation of mitochondrial cristae and endoplasmic reticulum, and apparent increase in electron density of secretory granules) after cysteamine administration. The number of somatostatin-positive cells visualized by the immunoperoxidase technique using light microscopy was decreased in 1–4 hr but returned to normal by 24 hr. The alterations observed in the G cells after cysteamine administration are consistent with release of gastrin from mature granules and increased synthesis of the hormone. The lack of major morphologic changes in the D cells suggests that cysteamine affects somatostatin without causing cell necrosis or alteration in lysosome formation. The effect of the drug may thus be mediated at the biochemical level without marked morphologic alterations.     

Histological alterations in the testicular tissue induced by sildenafil overdoses

Twenty adult male rabbits (Oryctolagus cuniculus) received sildenafil (0, 1, 3, 6, 9 mg/kg/day) for 4 weeks to investigate the testicular histological alterations induced by overdoses of this drug. Exposure to overdoses of sildenafil had provoked tubular and interstitial histological alterations. Abnormality in the germinal epithelium of the seminiferous tubules included spermatocytes karyopyknosis, spermatocytes degeneration, desquamation, spermatid giant cells and arrest of spermatogenesis. Additionally, increased Leydig cells cellularity, tubular degeneration, thickening of the interstitium were also observed. The encountered histological findings indicate that chronic exposure to sildenafil overdoses produces significant morphological and histological alterations in the testes which finally might lead to complete arrest of spermatogenesis.     

The twitcher mouse. An alteration of the unmyelinated fibers in the PNS.

The twitcher is an authentic murine model of globoid cell leukodystrophy (GLD) in man. Extensive demyelination of the central and peripheral nervous systems (CNS and PNS) characterizes the neuropathologic features of GLD. In the common peroneal nerve of the twitcher, where demyelination was extensive, pronounced morphologic and quantitative alterations were noted in the unmyelinated fibers. They were 1) a large number of long and attenuated cellular processes of Schwann cells, which often enclosed only one or two axons; and 2) a threefold increase in the number of Schwann cell-axon units with reduced numbers of axons per unit. These results suggested increased branching of unmyelinated Schwann cells. Mild increase in unmyelinated fibers and mild decrease in myelinated fibers were additional features. In contrast, the sympathetic nerve trunk, which had only small numbers of myelinated and rare or no demyelinated fibers, showed much milder alterations in the unmyelinated fibers. Thus, the results of our study suggest that the alterations of the Schwann cells of the unmyelinated fibers in the twitcher are secondary to or in association with the chronic demyelinating process.     

Anemia causes erythropoiesis and increased antibody synthesis in the spleen of the pregnant mouse

The role of anemia in the induction of splenic alterations during pregnancy has been studied in mice and rats. The enlarged spleens of 12 day pregnant CBA mice typically showed 1) dramatic increase in numbers of esterase-positive cells (mainly erythroblasts) and 2) increase in numbers of immunoglobulin-secreting cells. Pregnant Sprague-Dawley rats showed slight enlargement of the spleen, no change in the content of esterase-positive cells, but a clearcut increase in numbers of Lepehne-stained erythroblasts and immunoglobulin-secreting spleen cells. Virgin mice and rats were made anemic by bleeding or phenylhydrazine-treatment. These animals showed very much the same splenic alterations as those of pregnant mice and rats. In a final experiment pregnant CBA mice were subjected to transfusion of washed syngeneic red blood cells in order to normalize their erythrocyte counts. These mice showed 1) reduced splenomegaly, 2) reduced increase in numbers of esterase-positive cells and 3) reduced numbers of immunoglobulin-secreting cells. It was concluded that pregnancy-associated anemia (erythropenia) is a major reason to the gross change in size and cell content of the maternal spleen.     

Effects of repeated deprivation of drinking water on the structure of renal medulla of rats.

Rats were exposed to repeated episodes of hydropenia for periods of 5 and 16 weeks, and structural alterations of renal medulla were investigated by light and electron microscopy. The hydropenia induced, within the inner medulla, focally severe structural changes in the tubular and endothelia and loss of interstitial cells. The findings present evidence that repeated episodes of hydropenia are capable of inducing cellular alterations of the renal medulla, particularly in the interstitial cells.     

Redox control of red blood cell biology: the red blood cell as a target and source of prooxidant species

Red blood cells may exert both an antioxidant and a prooxidant activity. The first is exerted in physiologic conditions, whereas the second can be detected in several human pathologies. These opposite characteristics can depend on the environmental milieu as well as on intrinsic alterations. Both these aspects are summarized in this brief review that takes into account the possible implications of redox-associated alterations of red blood cells in determining their function and fate.     

Sequential morphologic alterations in the bronchial epithelium of Syrian golden hamsters during N-nitrosomorpholine-induced pulmonary tumorigenesis.

N-nitrosomorpholine (NM)-induced pulmonary carcinogenesis was examined by light and electron microscopy in a 20-week serial sacrifice study using Syrian golden hamsters. First to be observed were a proliferation of endocrine APUD cells and a formation of lamellated inclusion bodies in the cytoplasm of Clara cells. After continued NM treatment, APUD cells underwent squamous metaplasia and Clara cells invaded the pulmonary tissues adjacent to the bronchi. Lung tumors consisted of cells possessing numerous lamellated inclusion bodies in their cytoplasm and a few squamous metaplastic and APUD cells. The observed pathologic alterations closely resembled those found after treatment with N-diethylnitrosamine (DEN) and N-dibutylnitrosamine (DBN) but were completely different from the cellular reactions induced by polycyclic aromatic hydrocarbons. It is concluded that the observed alterations of APUD cells and Clara cells are specific to nitrosamines.     

Influence of the intramural innervation on the morphogenesis of the enteroendocrine cells and the genetic construct involved (review)

The influence of intramural intestinal innervation on the morphogenesis of the mucosa and in particular of the enteroendocrine cells (EECs) has been studied on male Wistar rats with morphometric, autoradiographic and immuno-histochemical methods in the duodenum, proximal and distal jejunum and ilium before and after myenteric ablation with benzalkonium chloride (BAC). Twenty-one days after denervation alterations were observed in the mucosal structure with thickening of the mucosa, increase in the proliferation rate and with changes in numerical and spatial distribution of D-cells, I-cells, N-cells, glucagon and glicentin i.r. L-cells and 5-HT i.r. cells which myenteric ablation caused. Analysis of the genetic constructs involved in the alterations of EECs on the EECs provide evidence for the cAMP responsive elements as the main mediator.     

Lesions of the Islets of Langerhans in Encephalomyocarditis Virus-Infected Mice with Diabetes Mellitus-Like Disease: I. Acute Lesions

Mice infected with the M variant of the encephalomyocarditis (EMC) virus develop lesions of the islets of Langerhans associated with a diabetes mellitus-like disease. Ultrastructural alterations become evident in capillaries and beta cells at a time when large amounts of virus are present in the pancreatic tissue. Although some beta cells become necrotic, degranulation and contraction of intact cells is the prominent lesion. Changes in the capillaries appear early in the course of the infection and later are associated with interstitial fibrosis in and around the islets. During early convalescence, beta cells are degranulated and exhibit striking alterations of cytoplasmic organelles. These changes appear to be consequent to increased metabolic activity by the residual insular tissue. Interestingly enough, specific lesions of the alpha cells are not observed.     

Morphological changes in the kidney glomeruli in gout

Kidney biopsies from 18 patients with primary gout were studied. Glomerular changes were found in all cases along with alterations in tubuli and vessels and stromal sclerosis. They were characterized by local thickening of basal membranes of capillaries, increase in the mesangial matrix, focal or diffuse proliferation of mesangial and endothelial cells of various degree of severity. Proliferation and activation of endothelial cells, mesangiocytes, podocytes, signs of podocyte damage, were found electron-microscopically. Subendothelial lucid zones were observed in the basal membrane, possibly at the site of uric acid deposits. The above described alterations resemble those in focal mesangio-capillary or mesangial proliferative glomerulonephritis.     

Ultrastructural studies of the myotendonous junction of selenium-deficient ducklings.

An ultrastructural study was made of the changes occurring within the gastrocnemius insertion of normal and selenium-deficient ducklings from 1 to 12 days of age. The cytologic characteristics of the fibroblasts, vessels, collagen, and muscle cells are described. Those exposed to the selenium deficiency showed major alterations of all components. The fibroblasts showed changes ranging from collapsed cisternae and degenerating mitochondria to rupture. The capillary endothelium was abnormal, as was the smooth muscle of arteriolar walls. The collagen sizes were altered, and the muscle cell termini showed major pathologic changes. The above alterations occurred within 4 days of exposure of the deficiency. The muscle cells of the body portion of the gastrocnemius showed no alterations until Day 8. The observations present evidence that indicates that connective-tissue-vascular abnormalities precede myopathic changes in nutritionally induced dystrophy. The significance of these findings is discussed with respect to the etiology of nutritionally induced dystrophy.     

Effects of taipoxin on the ultrastructure of cholinergic axon terminals in the mouse adrenal medulla.

Intravenous injection of the neurotoxin, taipoxin, to adult mice caused conspicuous alterations in the ultrastructure of axon terminals upon chromaffin cells in the adrenal gland. The alterations were in several respects similar to those previously described at the neuromuscular junction. The electron density of the axoplasm was greatly increased and the mitochondria swollen. In many instances the number of synaptic vesicles was reduced. The alterations were more marked the longer the period of toxin action.It is suggested that the toxin molecule, which has phospholipase A₂ activity, enters the axoplasm before exerting a hydrolytic and thereby neurotoxic action on cholinergic nerve terminals.