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J Partin

Publications and source records attributed to J Partin.

12 recordsLinked to original sources
PubMed1999

Evidence for mitochondrial control of neuronal polarity.

An early and essential step in the formation of functional neuronal circuits is the establishment of cell polarity, a process involving the morphological and functional differentiation of the axon (axonogenesis). We now report that treatment of cultured embryonic hippocampal neurons with ethidium bromide (EtBr; an agent that depletes mitochondrial DNA), prior to the establishment of cell polarity, prevents axon formation while permitting outgrowth of minor processes. The polarity-suppressing action of EtBr occurs under conditions of maintained cellular ATP levels, and is not mimicked by ATP-depleting agents (iodoacetate, p-(trifluoromethyoxy)phenylhydrazone [FCCP], and cyanide). Levels of tau, a microtubule-associated protein involved in axonogenesis, were not decreased in neurons treated with EtBr. Electron and confocal microscope analyses showed that EtBr treatment altered mitochondrial ultrastructure and subcellular localization. Basal levels of intracellular calcium were elevated 2- to 3-fold, intramitochondrial calcium levels were greatly increased, and mitochondrial transmembrane potential was decreased in EtBr-treated neurons. Exposure of neurons to a calcium ionophore prevented axonogenesis. Confocal images of intracellular calcium levels and mitochondrial localization in the same cells revealed congregations of mitochondria at the base of the axon associated with local reductions of intracellular calcium levels. When taken together with previous data indicating important roles for calcium in regulating neurite outgrowth, the present findings suggest critical roles for mitochondrial function and modulation of calcium homeostasis in the establishment of neuronal polarity.

Adenosine Triphosphate↗
PubMed1998

Amyloid beta-peptide induces apoptosis-related events in synapses and dendrites.

Synapse loss in cerebral cortex and hippocampus is a prominent feature of Alzheimer's disease (AD) that is correlated with cognitive impairment. Postsynaptic regions of dendrites are subjected to particularly high levels of calcium influx and oxidative stress as a result of local activation of glutamate receptors, and are therefore likely to be sites at which neurodegenerative processes are initiated in AD. Data suggest that neurons may die in AD by a process called apoptosis which involves a stereotyped series of biochemical changes that culminate in nuclear fragmentation, and that amyloid beta-peptide (Abeta) may play a role in such apoptosis. We now report that Abeta induces apoptosis-related biochemical changes in cortical synaptosomes, and in dendrites of cultured hippocampal neurons. Exposure of synaptosomes to Abeta resulted in loss of membrane phospholipid asymmetry, caspase activation, and mitochondrial membrane depolarization. Cytosolic extracts from synaptosomes exposed to Abeta induced chromatin condensation and fragmentation in isolated nuclei indicating that signals capable of inducing nuclear apoptosis can be generated locally in synapses. Exposure of cultured hippocampal neurons to Abeta resulted in caspase activation and mitochondrial membrane depolarization in dendrites and cell bodies. A caspase inhibitor prevented Abeta-induced mitochondrial membrane depolarization in synaptosomes, and mitochondrial membrane depolarization and nuclear apoptosis in cultured hippocampal neurons. Collectively, the data demonstrate that apoptotic biochemical cascades can be activated in synapses and dendrites by Abeta, and suggest that such 'synaptic apoptosis' may contribute to synaptic dysfunction and degeneration in AD.

Amyloid beta-Peptides↗
PubMed1987

Association of reovirus proteins with the structural matrix of infected cells.

The interaction of reovirus with the cytoskeleton was investigated. The soluble components of infected cells were extracted with the nonionic detergent NP-40 in a physiological buffer, and a cytoskeletal extract was prepared from the detergent-insoluble fraction. We observed a selective association of viral-specified products with the cytoskeleton that was temporally controlled. Viral dsRNA appeared first on the framework but after several hours was found also in the soluble phase, encapsidated in mature virions. The initial viral translation products were associated exclusively with the soluble fraction, but concomitant with the appearance of dsRNA, viral proteins microNS and sigma 3 were detected on the cytoskeleton. Several hours later, all viral proteins were detected on the framework. Viral polypeptide microNS exhibited unique spatial distribution patterns that correlated with viral assembly: Before dsRNA replication, it appeared as diffusely distributed protein; a few hours later, it was detected in punctate foci interconnected by tiny filaments; several hours later, it appeared as an extensive fiber network that traversed the foci. The other viral proteins were detected only within viral foci. MicroNS remained bound to the matrix fraction after treatment with DNase, Mg2+, and high salt, treatments that released other viral proteins. This distribution pattern was virus-directed because passage of virus at high multiplicity of infection induced mutations that prevented assembly of the microNS-coated filament organization. A small fraction of the viral-specified products that included polypeptide microNS, but not viral dsRNA, was coprecipitated from cytoskeletal extracts with proteins of mol wt approximately 55K by monoclonal antibodies that recognized tubulin and vimentin. Disruption of this interaction by long exposure to colchicine did not prevent association of viral proteins or RNA with the matrix, indicating that viral products were not transported through these interactions. The results indicate that reovirus morphogenesis includes temporal and spatial controls not described previously.

Animals↗
PubMed1986

Characterization and functional studies of rheumatoid synovial mast cells. Activation by secretagogues, anti-IgE, and a histamine-releasing lymphokine.

Microscopic analysis of synovial specimens from 35 patients with rheumatoid arthritis (RA) and 7 patients with osteoarthritis revealed mast cell hyperplasia in perivascular regions, in fibrous interstitial areas, and clustered around the periphery of lymphoid aggregates. Metachromatic staining, immunofluorescence studies, and ultrastructural analysis revealed a single population of connective tissue-type mast cells with surface IgE receptors. Total extractable histamine of synovial tissue was 4.15 +/- 2.30 micrograms/gm (n = 8) for RA synovium and 0.53 +/- 0.23 microgram/gm (n = 7) for OA synovium. Mast cell secretion was assessed and specific release of histamine from RA synovial mast cells was observed following stimulation with anti-IgE (32.3%), compound 48/80 (40.1%), calcium ionophore A23187 (25.2%), and a partially purified lymphokine with histamine-releasing activity (23.9%).

Antibodies, Anti-Idiotypic↗
PubMed1983

Reversal of neutropenia with intravenous gammaglobulin in autoimmune neutropenia of infancy.

Intravenous gammaglobulin (IVIgG) was used to treat autoimmune neutropenia of infancy in two males with repeated infections. The neutrophil count increased significantly in both patients with the initial IVIgG therapy; 1 patient went into remission. The neutrophil count in the other remained above baseline for 3 wk, and a subsequent booster infusion also caused the neutrophil count to increase. The patients have remained clinically well since their treatment began. Serial studies of antineutrophil antibody and serum lysozyme, performed to elucidate the mechanism of action, suggested decreased neutrophil destruction, perhaps by Fc receptor blockade, as well as decreased synthesis of antineutrophil antibody. Neutrophil function was not impaired after the neutrophil count increased. Many patients with immune neutropenia have a benign course, but those who have significant infections could be treated, acutely or prophylactically, with intravenous gammaglobulin.

Agranulocytosis↗
PubMed1981

Asterixis and encephalopathy following metrizamide myelography: investigations into possible mechanisms and review of the literature.

Marked asterixis occurred in two patients following metrizamide myelography. One also suffered generalized seizures and the other had severe stuttering speech for seven days. The spectrum of toxic manifestations of metrizamide is reviewed with emphasis on the unusual lethargy and other depressive effects seen with this relatively safe agent. The hypothesis that metrizamide exerts a ouabain-like effect on the cortical surface was tested. Metrizamide in concentrations as high as 20 mM had no inhibitory effect on rat cerebral K+-para-nitrophenylphosphatase, a partial reaction of (Na+K+)-adenosine triphosphatase. Because metrizamide is a 2-deoxyglucose analogue, a competitive inhibition of hexokinase at the first step in glycolysis was also postulated. Metrizamide was found to competitively inhibit commercial (microbial) hexokinase. The Michaelis constant for glucose rises from 0.13 to 0.25 to 0.33 to 0.91 mM in the presence of 0, 0.4, 1.0, and 2.0 mM metrizamide, respectively. Since the concentration of metrizamide over the cerebral cortex after routine myelography may be approximately 50 mM compared with a glucose concentration of only 3.6 mM (65 mg/dl), it is postulated that impaired brain glucose metabolism may be responsible for some of the toxic effects of metrizamide.

Animals↗
PubMed1981

Hypocomplementemia in Reye syndrome: relationship to disease stage, circulating immune complexes, and C3b amplification loop protein synthesis.

Measurement of C1q, C2, C4, C5, C6, factor B, properdin, beta1H, and C3bINA were made in acute sera from 31 patients with Reye syndrome. Abnormalities were found in 18 patients. The magnitude of the complement component depression correlated with disease severity. Sera from patients with stage IV illness had significantly lower complement levels than did sera from patients with state I (P less than 0.001), II (P less than 0.05), and III (P less than 0.05) disease. Circulating immune complex measurements were performed on all 31 acute sera and were present in six (19%). However, from the results of the present study, it would appear that in the majority of the patients circulating immune complexes are not the cause of the lowered levels of, at least, C3 and factor B. Rather, these low levels could be explained as secondary to reductions in the levels of the C3b amplification loop control proteins beta1H and C3bINA.

Antigen-Antibody Complex↗
PubMedDate not supplied

Morphology of acute myopathy associated with influenza B infection.

Calf muscle samples were obtained from 12 children with transient incapacitating myalgia and proved infection of the upper respiratory tract with influenza virus, type B. In all except one, light microscopy revealed isolated segmental muscle fiber degeneration and necrosis without frank myositis. Ultrastructural studies revealed that in zones of segmental necrosis, the sarcolemma was lysed but the basement membrane was intact. Focal degenerative changes included myofibrillar disarray with disruption/loss of the sarcoplasmic reticulum, glycogen depletion accompanied by mitochondriopathy, subsarcolemmal mitochondrial aggregates, activation of satellite cells, and focal filopodial transformation of the sarcolemma. The primary event in the pathogenesis of focal muscle fiber necrosis is likely to be biochemical and was not elucidated, but the focal sarcolemmal and T-tubule changes and mitochondriopathy suggest that destabilization of cell membranes may play a critical role. Sarcolemmal filopodia may be a marker for a specific type of membrane injury, but we were unable to establish that influenza virus has a direct role in its genesis.

Child↗
PubMedDate not supplied

Use of a soft catheter for acute peritoneal dialysis in infants and children.

Acute peritoneal dialysis in 49 infants and children is described comparing the use of the conventional hard Trocath catheter and the soft catheter. The mean age of the patients was 3.6 years (range 1 day--17 years). Sixteen were treated using the hard Trocath catheter and 33 were treated using a soft catheter. Overall mortality for the total patient population was 43%. Twenty-three neonates were included in the series with an overall mortality of 61%. Significantly less mortality was observed in the 26 patients older than two months of age (31%). Major complications of the dialysis procedure included viscus perforation in three neonatal patients and subcutaneous extravasation of dialysate in two older patients. These major complications occurred only with the use of the Trocath. Two episodes of peritonitis occurred in two adolescent patients and were associated with an interruption of the sterile system. Peritonitis was not specifically related to the type of catheter used. We conclude that major complications associated with the use of the hard catheter for peritoneal dialysis in neonates precludes its continued use in this population. The alternative use of a soft catheter is recommended in neonates. Elective use of a soft catheter for acute peritoneal dialysis in older patients would also seem to be indicated.

Abdominal Injuries↗
PubMedDate not supplied

Changes in laminin during recovery from postischemic acute renal failure in rats.

Changes in the immunoreactivity of laminin have been demonstrated in a variety of tissues undergoing injury-regeneration process and during nephrogenesis. Studies in vitro revealed that laminin is important in many cellular functions such as growth, differentiation, and cell communication. This study examined the changes of laminin in the extracellular matrix (ECM) of proximal straight tubules (PST) in the outer stripe of the outer medulla after renal ischemia, an area where most morphological damage occurred. Anesthetized male Sprague-Dawley adult rats underwent a 30-min temporary occlusion of the left renal artery. The inulin clearance (Cin) of the postischemic left kidneys was significantly decreased at 30 min, 1 day, 2 days, and 5 days after the injury, and at 7 and 10 days after the injury it rose to a level not significantly different from the sham-operated controls. Using immunogold electron microscopy, the density of immunoreactive laminin (gold-conjugated laminin grains/micron2 ECM area) in PST where flattened PST cells were present was decreased at 1 day and 2 days, and at 5 days, a time when the renal function was still depressed, it returned to a level not significantly different from that in controls. These changes were not observed in those PST or proximal convoluted tubules in which morphology was intact. Further studies are needed to determine if these changes in laminin of damaged PST cells have any significant role during their recovery from the ischemic injury.

Acute Kidney Injury↗