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L Claudio

Publications and source records attributed to L Claudio.

35 records · Page 2Linked to original sources
PubMed1996

Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer's disease patients.

Alzheimer's disease (AD) is a major cause of dementia. Characteristic neuropathological features of AD include neurofibrillary tangles, senile plaques, amyloid angiopathy and microvascular atrophy. The ultra-structure of the microvascular atrophy in AD and its pathogenetic significance have not been defined. This report presents an analysis of ultrastructural and morphometric features in the cerebral microvasculature of five brain biopsy specimens from AD patients. The cerebral microvasculature normally constitutes the blood-brain barrier (BBB), characterized by interendothelial tight junctions, few pinocytotic vesicles and high mitochondrial content in endothelial cells. In the AD brain biopsy tissue analyzed in the present article, data for endothelial cells were expressed as percentage of cytoplasmic area occupied by the respective organelles. The values for vesicular content ranged from 0.49% to 1.17% and were inversely correlated with mitochondrial content, which ranged from 7.04% to 2.88%. These results indicate decreased mitochondrial content and increased pinocytotic vesicles as compared to values obtained previously in endothelium from multiple sclerosis patients and in laboratory animals. Other findings such as accumulation of collagen in vascular basement membranes and focal necrotic changes in endothelial cells are further indications of BBB disruption. These data, together with earlier reports, suggest that dysfunction of the BBB is a characteristic feature of AD.

Alzheimer Disease↗
PubMed1995

Evidence of persistent blood-brain barrier abnormalities in chronic-progressive multiple sclerosis.

Brain capillaries were analyzed morphometrically for alterations in organelle distribution and density in biopsy samples of central nervous system tissue from seven patients diagnosed as having chronic progressive multiple sclerosis. Data were expressed as percentage of endothelial cytoplasm occupied by the respective organelles. The density of pinocytotic vesicles in endothelium ranged from 0.53% within normal-appearing parenchyma to 1.2% in gliotic areas. For mitochondria the values ranged from 10.87% in normal areas to 4.72% in the same respective samples. Thus, an inverse correlation between vesicular and mitochondrial content was observed. These findings suggest that endothelial cells in gliotic areas are similar to endothelial cells of the systemic circulation in their mitochondrial content and pinocytotic activity. Interendothelial junctions in capillaries of all areas examined appeared normal. Additional evidence for a continuous blood-brain barrier anomaly in multiple sclerosis was the accumulation of perivascular fibrin, suggesting an increase in microvascular permeability. Perivascular collagen deposits, degenerative changes in pericytes and astrocytic swelling were also indicators of an increase in blood-brain barrier permeability. Taken together with previous data from experimental autoimmune encephalomyelitis, the present findings in chronic silent multiple sclerosis lesions suggest that central nervous system endothelial cells show persistent abnormalities of the blood-brain barrier, even in the absence of active inflammation.

Adult↗
PubMed1994

Ultrastructural studies of the blood-retina barrier after exposure to interleukin-1 beta or tumor necrosis factor-alpha.

BACKGROUND: During inflammatory conditions of the central nervous system (CNS), the protective function of the blood-brain barrier (BBB) may be compromised, resulting in CNS edema. However, it is not well understood how inflammatory cells may increase BBB permeability, since increased transendothelial transport of serum proteins is observed in CNS capillaries that are not directly in contact with inflammatory cells. One possible explanation may be that soluble inflammatory factors may cause BBB changes, since pathologic conditions that increase circulating cytokines produce detectable increases in BBB permeability. EXPERIMENTAL DESIGN: To investigate the role of inflammatory cytokines in induction of endothelial cell changes and inflammation in the CNS, we utilized the rabbit retinal system as a model. This system shows vascularization similar to the BBB, and is termed the blood-retina barrier (BRB). The rabbit visual system allows injection of cytokines, causing minimal trauma, and the contralateral eye serves as an intra-animal control. RESULTS: Ultrastructural morphometric analysis of vesicular content in BRB endothelium showed significant increase at 3 hours postintravitreal injection of interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha). Increased transport did not correlate with increased vitreal protein. However, intravascular tracer (horseradish peroxidase) revealed that pericytes, Müller cells, and perivascular microglia accumulate serum proteins, thus acting as sinks for extravasated proteins after BRB disruption. The IL-1 beta-induced inflammatory response was characterized by polymorphonuclear and mononuclear cells, whereas the TNF-alpha-induced response was less intense and comprised monocytes and occasional eosinophils. At the height of inflammation, IL-1 beta produced large gaps between endothelial cells that allowed for extensive cellular inflammation and hemorrhage. TNF-alpha induced necrotic changes on endothelial cells, being most severe at 3 hours postintravitreal injection, revascularization was noted at 24 hours postintravitreal injection. CONCLUSIONS: These results demonstrate that proinflammatory effects of IL-1 beta and TNF-alpha in the BRB initiate many of the changes associated with inflammation of the CNS vasculature, such as those induced during experimental autoimmune encephalitis and multiple sclerosis. Once the permeability of the BRB endothelium is increased, perivascular phagocytic cells such as perivascular, microglia and Müller cells may act as secondary barriers to extravasated proteins.

Animals↗
PubMed1992

Effects of prazosin on the blood-brain barrier during experimental autoimmune encephalomyelitis.

Alterations in normal function of the blood-brain barrier (BBB) are important in the pathophysiology of multiple sclerosis and its laboratory counterpart, experimental autoimmune encephalomyelitis (EAE). As part of studies on drugs that affect vascular tone in rats with EAE, we have shown previously that the specific alpha 1-adrenoreceptor antagonist, prazosin, suppressed clinical and pathologic disease. In the present study we used quantitative morphometric analysis of capillary endothelium and the tracer horseradish peroxidase (HRP) to define effects of this drug on vascular events associated with central nervous system edema. In prazosin-treated and saline-treated EAE rats, protein extravasation in the spinal cord correlated with clinical presentation. Consistent with our previous data, the results showed that increased edema was associated with increased vesicular content of capillary endothelium. In prazosin-treated rats with no clinical signs, vesicular content was comparable to that found in normal animals. With increasing severity of disease, vesicular content increased and mitochondrial content decreased. In both prazosin- and saline-treated rats, mitochondrial content was reduced even when clinical signs were slight, and sharply declined when clinical signs increased. These results suggest that damage to mitochondria may be associated with early pathological events. In prazosin-treated animals, HRP accumulated in pericytes, suggesting that these cells were a target for the action of prazosin and may restrict the extravasation of fluid into the perivascular parenchyma. Our results underscore the presence of capillary changes associated with inflammation of the central nervous system, in addition to the well-recognized cellular inflammation that is targeted to the venular bed. The extent of capillary changes was closely associated with extent of tracer leakage in the spinal cord and support the conclusion that transcytotic vesicles are involved in transport of edema fluid during EAE, and that high mitochondrial levels are important for the normal function of BBB endothelium.

Animals↗
PubMed1992

An analysis of the U.S. Environmental Protection Agency neurotoxicity testing guidelines.

Few of the more than 65,000 chemicals listed in the Environmental Protection Agency (EPA) inventory have been tested for neurotoxicity. The nervous system may be especially vulnerable to toxicants because many compounds can cross the blood-brain barrier and induce irreversible damage. Additionally, the young, the elderly, and other sensitive populations may be particularly susceptible to neurotoxic injury. The EPA has developed guidelines including neurobehavioral, neuropathological, and neurochemical tests for the identification of possible neurotoxicants. In the present review, tests included in the current EPA guidelines for neurotoxicity testing are described and evaluated. The main benefit of the tests is that regulators are familiar with them, thus facilitating interpretation. Additionally, validation data on these tests are available for many known neurotoxicants. These factors make it difficult to introduce new methods that may include in vitro and other techniques. The current in vivo tests can be costly and prolonged and can involve the use of many laboratory animals, making them inappropriate for generalized use on existing chemicals. It is suggested that alternative tests be incorporated for screening of large numbers of chemicals and that testing priority be given to chemicals on the basis of structure/activity relationships, lipophilicity, bioaccumulation, and extent of exposure.

Animals↗
PubMed1990

Intraarterial chemotherapy through carotid transposition in advanced head and neck cancer.

We report results of intraarterial chemotherapy (IAC) in patients with advanced unresectable (T4, N0-3, MO) squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the oral cavity, oropharynx, or facial skin, given through a subcutaneously transposed external carotid artery by a fine gauge needle. Forty patients entered the study and 39 were evaluable for clinical response and toxicity. The infusion technique was done in two consecutive series of patients with the same characteristics: 17 had treatment with vincristine, bleomycin, and methotrexate (VBM), and 22 received cisplatin and bleomycin (PB) with a median number of six and five cycles, respectively. The total objective response (OR) rate was 76.9%, which included 12.8% of complete response (CR). A better percentage of OR was attained in BCC than SCC (83.3% versus 75.8%), in tumors of the skin of the face than other sites (87.5% versus 74.2%), and in the group that received PB than the group that received VBM (77.3% versus 76.5%). Our series had an overall technique-related toxicity of 18%; 10.3% with neurologic disturbances and 7.7% with skin inflammation (almost all were reversible). The most common systemic toxic side effects were generally mild and well tolerated (30.8%), whereas major toxicities (severe modifications of the cardiopulmonary function) occurred in four patients (10.3%) in the group that received VBM. After chemotherapy, 28 patients (71.8%) were deemed resectable; 23 of these patients (82.1%) agreed to surgery. Pathologic CR were obtained in 13 patients (56.5%). Our technique has significant advantages over the conventional methods of infusion, because tumor perfusion is feasible and selective, technique-related and catheter-related complications are almost completely eliminated, and fatal drug-related side effects are avoided.

Adult↗
PubMed1990

Mechanisms of autoimmune neuropathies.

Our studies have focused on the mechanisms involved in blood-brain barrier and blood-nerve barrier alterations in inflammatory demyelinating diseases. The results support the conclusion that these diseases are initiated by delayed hypersensitivity reactions. They further demonstrate a role for mast cell degranulation and vasoactive amines in the peripheral nerve. In the central nervous system, our studies have documented both active and passive mechanisms of edema formation and support the conclusion that cytokines may be involved in altered blood-brain barrier permeability and inflammation. We conclude that several mechanisms of barrier breakdown are activated in the inflammatory demyelinating diseases and that alteration in endothelial cell function is a major component of disease induction.

Blood-Brain Barrier↗
PubMed1990

Mechanisms of edema formation in experimental autoimmune encephalomyelitis. The contribution of inflammatory cells.

Most of the central nervous system (CNS) endothelium regulates the passage of solutes and functions as a blood-brain barrier (BBB). During experimental autoimmune encephalomyelitis (EAE), an inflammatory demyelinating disease of the CNS, loss of BBB function occurs. The authors have previously shown an increase in endothelial transcytotic activity associated with decreased mitochondrial content as evidence of BBB dysfunction in EAE. These changes occurred in the capillary bed and correlated with CNS edema and clinical signs. In the present report, a fixation procedure before infusion of the intravascular tracer horseradish peroxidase (HRP) in rats at the height of clinical EAE has been used. In these animals, tracer leakage was only noted in inflamed venules with diameters of 12 to 19 mu. The authors detected several mechanisms of passive leakage: 1) increased junctional permeability; 2) increased interendothelial space; 3) leakage alongside migrating inflammatory cells. Some small capillaries showed necrotic changes with minimal tracer leakage. This report demonstrates that BBB disruption also occurs via nonendocytic mechanisms that may be induced by inflammatory cells.

Animals↗
PubMed1989

Increased vesicular transport and decreased mitochondrial content in blood-brain barrier endothelial cells during experimental autoimmune encephalomyelitis.

Mechanisms involved in the loss of blood-brain barrier function in Lewis rats with experimental autoimmune encephalomyelitis (EAE) were examined using horseradish peroxidase (HRP) as a tracer. In animals injected with HRP before fixation, tracer was observed in two intracytoplasmic compartments: multivesicular bodies (presumably secondary lysosomes) and transcytotic vesicles. Quantitative morphometry of electron micrographs of capillary endothelial cells demonstrated a 5.2-fold increase in these vesicles. This increase in vesicular transport was associated with a decrease in mitochondrial content from 13.7% of the endothelial cytoplasmic area in the normal rat to 4.2% in EAE rats at the height of clinical disease. These alterations correlated with the clinical course of EAE. In animals infused with tracer after fixation, tracer was restricted to areas of cellular inflammation. Immunogold staining of endogenous albumin demonstrated the presence of albumin in cytoplasmic vesicles and in channel-like tubular structures adjacent to endothelial cell junctions. These results indicate that there is a role for vesicles in transendothelial cell transport and edema formation in animals with EAE.

Animals↗
PubMed1988

Coexpression of glial fibrillary acidic protein and vimentin in the central and peripheral nervous systems of the twitcher mutant.

A method to purify glial fibrillary acidic protein (GFAP) from mouse spinal cord is described, which permits the measurement of GFAP in the sciatic nerve of the twitcher mutant and control mouse. Cytoskeletal proteins from sciatic nerves and purified GFAP standards were electrophoresed on gel, transferred to nitrocellulose paper, and immunostained with anti-GFAP antibody. From the immunostained, 51,000-dalton band, we estimated about 200 ng GFAP per 50 micrograms of cytoskeletal protein in the twitcher sciatic nerve. The control nerve showed no detectable GFAP. Double-labeled fluorescence immunocytochemistry showed that in the brainstem of twitcher mutant, GFAP and vimentin were coexpressed in the majority of astrocytes.

Animals↗
PubMedDate not supplied

[Role of crural inguinal lymphadenectomy and dynamic sentinel lymph node biopsy in lymph node staging in squamous-cell carcinoma of the penis. Our experience].

PURPOSE: We determine the value of dynamic sentinel node biopsy for staging squamous cell carcinoma of the penis. MATERIALS AND METHODS: During a period of 2 years 17 patients with penile cancer was performed after lymphoscintigraphy pre and intraoperatively with gamma ray detection probe at biopsy of the sentinel node with the aid of perilesional administered patent blue dye. After 20 days regional lymph node dissection was performed in all patients. RESULTS: Sentinel node metastasis was found in 5 patients; in one case lymphoscintigraphy not visualized sentinel node. All negative node biopsy was confirmed with the regional lymph node dissection. No major complication did occur after sentinel node biopsy. CONCLUSIONS: Occult lymph node metastases can be detected by dynamic sentinel node biopsy including preoperative lymphoscintigraphy, vital dye and gamma ray detection probe with a sensitivity of 78%, predictive negative value of 100% and with low morbidity.

Aged↗