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M Tolar

Publications and source records attributed to M Tolar.

13 recordsLinked to original sources
PubMed1999

Truncated apolipoprotein E (ApoE) causes increased intracellular calcium and may mediate ApoE neurotoxicity.

Apolipoprotein E (apoE)-related synthetic peptides, the 22 kDa N-terminal thrombin-cleavage fragment of apoE (truncated apoE), and full-length apoE have all been shown to exhibit neurotoxic activity under certain culture conditions. In the present study, protease inhibitors reduced the neurotoxicity and proteolysis of full-length apoE but did not block the toxicity of truncated apoE or a synthetic apoE peptide, suggesting that fragments of apoE may account for its toxicity. Additional experiments demonstrated that both truncated apoE and the apoE peptide elicit an increase in intracellular calcium levels and subsequent death of embryonic rat hippocampal neurons in culture. Similar effects on calcium were found when the apoE peptide was applied to chick sympathetic neurons. The rise in intracellular calcium and the hippocampal cell death caused by the apoE peptide were significantly reduced by receptor-associated protein, removal of extracellular calcium, or administration of the specific NMDA glutamate receptor antagonist MK-801. These results suggest that apoE may be a source of both neurotoxicity and calcium influx that involves cell surface receptors. Such findings strengthen the hypothesis that apoE plays a direct role in the pathology of Alzheimer's disease.

Animals↗
PubMed1998

Sympathetic neurite outgrowth is greater on plaque-poor vs. plaque-rich regions of Alzheimer's disease cryostat sections.

Senile plaques are a characteristic histopathological feature of Alzheimer's disease (AD) and are associated with altered neuritic morphology. Numerous individual plaque components, most notably beta-amyloid, have been studied for their possible effects on neurite outgrowth in culture. However, the effect of senile plaques on neuronal morphology and function is difficult to assess. In the present study, the effect of senile plaques on neurite outgrowth was studied by culturing embryonic chick sympathetic neuronal explants on Alzheimer's tissue sections. Explants were cultured for 3 days on amygdala tissue sections from AD as well as non-AD patients in serum-free medium. Neurite outgrowth on plaque-rich regions was compared with outgrowth on plaque-poor regions of the same tissue section, and with outgrowth on non-AD tissue, through colocalization of the living explants and the underlying plaques. Explants growing on plaque-rich regions showed significantly less neurite outgrowth compared with those on plaque-poor regions in the same section or on control brain tissue. These results suggest that plaques are poor substrates for neurite outgrowth as compared with non-plaque areas of the same tissue sections, and support the hypothesis that components of the senile plaques may inhibit neurite outgrowth.

Aged↗
PubMed1998

Flexor tendon repair using a stainless steel internal anchor. Biomechanical study on human cadaver tendons.

We have developed a stainless steel internal tendon anchor that is used to strengthen a tendon repair. This study tested its use in vitro to produce a repair that can withstand the tensile strength demands of early active flexion. Fresh human cadaver flexor digitorum profundus tendons were harvested, divided, and then repaired using four different techniques: Kessler, Becker or Savage stitches, or the internal tendon anchor. The internal splint repairs demonstrated a 99-270% increase in mean maximal linear tensile strength and a 49-240% increase in mean ultimate tensile strength over the other repairs. It is hoped that this newly developed internal anchor will provide a repair that will be strong enough to allow immediate active range of motion.

Cadaver↗
PubMed1997

Neurotoxicity of the 22 kDa thrombin-cleavage fragment of apolipoprotein E and related synthetic peptides is receptor-mediated.

Potent neurotoxicity is associated with both apolipoprotein E (apoE)-related synthetic peptides and the 22 kDa N-terminal thrombin-cleavage fragment of apoE. Furthermore, the E4 isoform of the 22 kDa fragment is significantly more toxic than the same fragment derived from the E3 isoform, suggesting the possibility of a direct role of apoE-associated neurotoxicity in the pathophysiology of Alzheimer's disease. In the present study, the potential role of cell surface receptors in mediating neurotoxicity was assessed by using a variety of agents that should block the heparin-binding and receptor-binding activity of apoE. Effective inhibitors of neurotoxicity of both the apoE peptides and the apoE fragment include heparin, heparan sulfate, sodium chlorate and heparinase, the low-density lipoprotein (LDL) receptor-related protein receptor-associated protein, and a polyclonal anti-LDL receptor-related protein antibody. These results suggest that the neurotoxicity of the 22 kDa thrombin cleavage fragment of apoE and related peptides is receptor-mediated, and that the most likely candidate receptor is a heparan sulfate proteoglycan-LDL receptor-related protein complex.

Animals↗
PubMed1996

A thrombin cleavage fragment of apolipoprotein E exhibits isoform-specific neurotoxicity.

A 22 kDa fragment of apoE containing a putative cytotoxi domain was identified in postmortem human brain tissue and fresh CSF. This fragment is apparently equivalent to the major apoE thrombin cleavage product. In vitro toxicity assays demonstrate that the corresponding fragment derived from recombinantly expressed human apoE is toxic to primary neurons in culture and that the E4-derived fragment is significantly more toxic than the fragment derived from the E3 isoform. These results suggest that proteolytic fragments of apoE may play a direct role in the pathology associated with AD and other diseases in which apoE has been implicated.

Apolipoproteins E↗
PubMed1994

Neurite degeneration elicited by apolipoprotein E peptides.

Apolipoprotein E (apoE) has been localized to the neurofibrillary tangles and beta-amyloid-containing plaques found in the cortex of patients with Alzheimer's disease (AD) (14, 28), suggesting that apoE may play a role in this disorder. Recently, synthetic peptides containing a sequence within apoE (amino acids 141-155) were found to be cytotoxic to T lymphocytes in culture. In the present study, tandem presentation of the apoE sequence E141-155, as well as longer monomeric peptides that include this domain, was found to cause extensive and specific degeneration of neurites from embryonic chick sympathetic ganglia in vitro. These results, together with the observation of strong beta A4/apoE binding in vitro and the disproportionate occurrence of the epsilon 4 allele in both familial and sporadic AD patients, suggest that peptide sequences associated with apoE may contribute directly to neurodegenerative processes.

Animals↗
PubMed1989

Single K+ currents during differentiation of embryonic muscle cells in vitro.

After 3-7 days in culture, chicken myotubes possess five types of K+ channel: two high-conductance channels of 195 and 105 pS which are sensitive to tetraethylammonium (TEA), an ATP-sensitive channel of 64 pS and two low-conductance channels of 40 and 15 pS which are insensitive to TEA and ATP. The same population of channels is to be found in EGTA-treated muscle cells with blocked fusion and, with the exception of the ATP-sensitive channel, also in 1-day-old myoblasts. There are differences between myoblasts and myotubes in the percentage of incidence of individual channel types. High-conductance K+ channels are most frequently to be observed in myotubes, but they are rare in myoblasts and EGTA-treated cells where low-conductance K+ channels predominate.

Adenosine Triphosphate↗
PubMed1987

Effect of exercise on muscle fibre composition and enzyme activities of skeletal muscles in young rats.

Young Wistar rats underwent dynamic (D) or static (S) exercise from the 5th to 35th day after birth. Histochemical and biochemical analysis were performed in the extensor digitorum longus (EDL) and the soleus muscle (SOL). Lactate dehydrogenase (LDH) (regulating anaerobic metabolism) and citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase (HAD) (both regulating aerobic metabolism) activities were determined spectrophotometrically. An increase of the fast oxidative-glycolytic (FOG) muscle fibres was found in the slow SOL muscle in both trained groups, i.e. by 10% in group D and by 7% in group S in comparison with the C group. The EDL muscle fibre distribution did not differ from those of control animals in respect to the slow oxidative (SO) fibre type. A higher percentage of FOG fibres by 19% was found in group D contrary to a decreased number of the fast glycolytic (FG) muscle fibres in this trained group. The greatest increase of CS (EDL 185%, SOL 176%) and HAD (EDL 83%, SOL 178%) activities were found in group D as compared with control group (C). Only small differences were observed in LDH activity. The values of characteristic enzyme activity ratios show that dynamic training resulted in an elevation of oxidative capacity of skeletal muscle, while the static load led preferentially along the glycolytic pathway. It may be concluded that an adaptive response to the training load during early postnatal development is different due to the type of exercise (dynamic or static) and/or the type of skeletal muscle (fast or slow).

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1985

Poly(2-hydroxyethyl methacrylate)--collagen composites which promote muscle cell differentiation in vitro.

A new simple method has been developed which allows the mixing of poly(2-hydroxyethyl methacrylate)--polyHEMA--and fibrillar collagen in any desired ratio. PolyHEMA alone was shown to be an unsuitable cultivation substrate for primary cultures of chicken embryonic skeletal muscle cells. Composites containing polyHEMA and 50% (w/w) or more collagen supported myogenesis. Such layers, firmly adhered to the bottom of plastic Petri dishes, were mechanically stable and biologically active, thus favourably combining properties of both the original materials. It is suggested that polyHEMA-collagen composite layers may be used for cultivation of differentiating cells in vitro.

Animals↗
PubMed1980

Cultivation conditions influencing de novo development of nerve-muscle junctions in vitro.

A variety of cultivation conditions was tested with respect to the formation of nerve-muscle junctions in vitro. The long-term maintenance and survival of innervated muscle fibres was achieved under these conditions: The myoblasts from 11 to 12-day-old chicken embryos were added to a section of the spinal cord with meninges, which was taken from 7 to 9-day-old chicken embryos and cultivated three days in advance in Maximow's assemblies. The myoblasts were prepared from pectoral or leg muscles. The spinal cord sections of the cervical, throacic and lumbar levels were equally successful in inducing the development of nerve-muscle junctions.

Animals↗