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Biomedical subjects

M E Adams

Publications and source records attributed to M E Adams.

At least 109 records · Page 6Linked to original sources
PubMed1991

Functional duality and structural uniqueness of depressant insect-selective neurotoxins.

Depressant insect-selective neurotoxins derived from scorpion venoms (a) induce in blowfly larvae a short, transient phase of contraction similar to that induced by excitatory neurotoxins followed by a prolonged flaccid paralysis and (b) displace excitatory toxins from their binding sites on insect neuronal membranes. The present study was undertaken in order to examine the basis of these similarities by comparing the primary structures and neuromuscular effects of depressant and excitatory toxins. A new depressant toxin (LqhIT2) was purified from the venom of the Israeli yellow scorpion. The effects of this toxin on a prepupal housefly neuromuscular preparation mimic the effects on the intact animal; i.e., a brief period of repetitive bursts of junction potentials is followed by suppression of their amplitude and finally by a block of neuromuscular transmission. Loose patch clamp recordings indicate that the repetitive activity has a presynaptic origin in the motor nerve and closely resembles the effect of the excitatory toxin AaIT. The final synaptic block is attributed to neuronal membrane depolarization, which results in an increase in spontaneous transmitter release; this effect is not induced by excitatory toxin. The amino acid sequences of three depressant toxins were determined by automatic Edman degradation. The depressant toxins comprise a well-defined family of polypeptides with a high degree of sequence conservation. This group differs considerably in primary structure from the excitatory toxin, with which it shares identical or related binding sites, and from the two groups of scorpion toxins that affect sodium conductance in mammals. The two opposing pharmacological effects of depressant toxins are discussed in light of the above data.

Amino Acid Sequence↗
PubMed1991

Quantitative imaging of osteoarthritis.

Plain-film radiography currently remains the mainstay of imaging for diagnosis and follow-up in osteoarthritis (OA). However, recent studies have questioned some aspects of its use, particularly the correlation between radiographically evident joint-space narrowing and articular cartilage loss. The results with imaging modalities such as magnetic resonance imaging and ultrasound suggest that these methods will allow accurate noninvasive definition of the structure of articular cartilage and other soft tissues of joints. Other modalities, including microfocal radiography and high-resolution computed tomography, can produce detailed images of trabecular structure and bony alterations in osteoarthritis. Improvements in image analysis and data manipulation, including three-dimensional reconstruction and digitized storage and measurement of images, will likely enable improved quantitative assessment of the abnormalities demonstrated by these techniques. One can hope that such developments will facilitate not only improved detection and definition of OA, but also better evaluation of the effectiveness of pharmacological and physical therapy in practice and in clinical trials.

Cartilage, Articular↗
PubMed1991

Differential antagonism of transmitter release by subtypes of omega-agatoxins.

1. The omega-agatoxins from Agelenopsis aperta spider venom are a diverse group of voltage-sensitive calcium channel antagonists. Subtypes of omega-agatoxins are distinguished as type I (omega-Aga-IA, omega-Aga-IB, and omega-Aga-IC), type II (omega-Aga-IIA and omega-Aga-IIB), and type III (omega-Aga-IIIA and omega-Aga-IIIB). All except type III toxins block calcium channels in insect motor nerve terminals and in neuronal cell bodies at nanomolar concentrations. 2. The potency and maximum level of block of the excitatory junctional potential (EJP) by omega-agatoxins are dependent on the extracellular calcium concentration ([Ca]o). Saturating concentrations of type I or II omega-agatoxins block 97-99% of the evoked EJP in low [Ca]o (0.75 mM) saline. A remnant of the EJP (1-3%) that persists after toxin exposure suggests that a small amount of voltage-dependent calcium entry is toxin resistant. When [Ca]o is elevated to 5 mM, this resistant component increases dramatically, revealing differences between type I and type II block. Under these conditions, 60-70% of the EJP is resistant to type I toxins and approximately 20% is resistant to type II toxins. 3. Sequential application of type I and II toxins in high [Ca]o leads to enhanced block of the EJP, suggesting that type I and II omega-agatoxins may block calcium channels by different mechanisms. 4. Type I and type II omega-agatoxins also block calcium channels in the somata of locust dorsal unpaired median (DUM) neurons. In agreement with studies on neuromuscular transmission, block of barium action potentials is incomplete after either type I or type II toxin exposure and combined application of the toxins results in enhanced block. 5. Partial calcium channel antagonism by type I and type II toxins could be explained either by altered kinetics of toxin-modified channels or by selectivity for different subtypes of presynaptic calcium channels.

Agatoxins↗
PubMed1991

Evaluation of cartilage lesions by magnetic resonance imaging at 0.15 T: comparison with anatomy and concordance with arthroscopy.

Recent evidence suggests that pharmacological treatment may alter the rate of progression of cartilage damage in osteoarthritis (OA). However, a lack of accurate and precise noninvasive assessments of cartilage structure makes it difficult to answer this question directly with prospective clinical trials, prevents early diagnosis of OA and restricts assessment of treatment to evaluation of symptoms or joint function. It is important, therefore, to develop precise, noninvasive methods both for diagnosis of early OA before damage is extensive and irreversible and for evaluation of therapeutic effectiveness. Magnetic resonance imaging (MRI) allows for noninvasive, multiplanar body imaging which depends on proton density, flow, and the T1 and T2 relaxation times. Because these variables differ markedly among joint tissues, cartilage erosions are visible with MRI and it should be possible to quantify them. Our objective was to compare MRI with arthroscopy for assessing the depth of lesions in the articular cartilage of human knees to help develop and validate MRI for use in clinical trials designed to assess the effect of therapy on cartilage structure. In the first part of our study, the effect of the MRI pulse sequence variables on the images was evaluated by varying them systematically and comparing the anatomy seen with MRI with that seen at arthroscopy or arthrotomy and with the histology. In the second part, 31 patients were assessed with MRI before arthroscopy. The MRI were graded on a 4-point ordinal scale by 2 observers who were unaware of the clinical diagnosis and compared with findings at arthroscopy which were graded using the same scale.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthroscopy↗
PubMed1991

Hypertrophic repair of canine articular cartilage in osteoarthritis after anterior cruciate ligament transection.

Transection of the anterior cruciate ligament in the dog is used frequently to produce a model of osteoarthritis (OA). Although it results in metabolic, biochemical, biomechanical and morphological changes in the articular cartilage of the unstable knee which resemble those in human OA, it rarely results in full thickness cartilage loss. The lack of progression of the cartilage lesions in this model has generally been attributed to stabilization of the joint by osteophytes and capsular fibrosis which develop following transection of the ligament. In our study transection of the anterior cruciate ligament of adult foxhounds and mongrels resulted in a progressive increase in the amount of articular cartilage in the unstable knee. In articular cartilage from the medial femoral condyle of the unstable knee the total amount of proteoglycan, as assessed by hexuronic acid analysis, and, often, the proteoglycan concentration were increased. Furthermore, the rate of proteoglycan synthesis was commonly elevated, in comparison with that from the contralateral knee. Thus, in these animals knee instability did not lead to loss of cartilage but to an active synthetic response by the chondrocytes resulting in hypertrophic cartilage repair which was sustained for up to 64 weeks of observation.

Animals↗
PubMed1991

Measurement of proteoglycan mRNA in articular cartilage--preliminary investigations.

Measurement of mRNA in adult articular cartilage could define whether treatment with nonsteroidal antiinflammatory drugs affects the rate of proteoglycan synthesis in vivo in osteoarthritis. We studied a variety of extraction and isolation methods to obtain a high yield of pure mRNA from adult articular cartilage. By combining a single step extraction procedure, precipitation in 0.8 M LiCl and poly d-T affinity isolation, we obtained pure mRNA that hybridized with a cDNA probe for the large aggregating proteoglycan. Thus, it should be feasible to assess the level of message using polymerase chain reaction technology; it is unlikely that northern blots, slot blots, or RNA protection assays can be performed directly on the small specimens of articular cartilage that are available from experimental model studies or from surgical specimens.

Animals↗
PubMed1990

Nucleotide sequence and expression of a cDNA encoding chick brain actin depolymerizing factor.

Chick brain actin depolymerizing factor (ADF) is a 19-kDa protein that severs actin filaments and binds actin monomers. We have obtained a cDNA encoding ADF by screening a chick embryo lambda gt11 cDNA library with both a rabbit anti-ADF antiserum and two oligonucleotide probes. Several non-full-length clones of 636 bases and one full-length clone of 1886 bases were isolated and sequenced. The full-length cDNA encodes a protein of 165 amino acids with a calculated molecular weight of 18,520. The deduced amino acid sequence shows 73% identity with the porcine brain actin binding protein cofilin. The coding region of the ADF cDNA has been placed in an expression vector, and the resulting protein shows immunoreactivity with an anti-ADF antiserum but not with an anti-cofilin antibody. The expressed ADF has been purified and has an actin depolymerizing activity identical with that of brain ADF. Like cofilin, ADF contains a sequence similar to the nuclear transport signal sequence of the SV40 large T antigen and a calcium/calmodulin-dependent protein kinase II phosphorylation consensus sequence. Northern blots of both embryonic chick brain and muscle RNA revealed two ADF mRNAs of length 2.1 and 0.9 kilobases. Southern blots suggest that the ADF gene is present in a single copy within the chicken genome. ADF contains regions of homology with other actin binding proteins including tropomyosin, gelsolin, and depactin.

Actin Depolymerizing Factors↗
PubMed1990

Omega-agatoxins: novel calcium channel antagonists of two subtypes from funnel web spider (Agelenopsis aperta) venom.

A new series of polypeptide presynaptic antagonists ("omega-agatoxins") was purified from venom of the funnel web spider Agelenopsis aperta. Physiological data indicate that all of these peptides are antagonists of voltage-sensitive calcium channels. Although all three omega-agatoxins (Aga) described here (omega-Aga-IA, omega-Aga-IB, and omega-Aga-IIA) block insect neuromuscular transmission presynaptically, biochemical data permit their subclassification as Type I and Type II toxins. Type I toxins (omega-Aga-IA and -IB) are 7.5 kDa, have closely related amino acid sequences, and exhibit characteristic tryptophan-like UV absorbance spectra. Complete Edman sequencing of omega-Aga-IA reveals it to be a 66-amino acid polypeptide containing 9 cysteines and 5 tryptophan residues. omega-Aga-IIA, a Type II toxin, is 11 kDa, shows limited amino acid sequence similarity to the Type I toxins, and exhibits mixed tryptophan- and tyrosine-like absorbance. Nanomolar concentrations of omega-Aga-IIA inhibit the specific binding of 125I-labeled omega-conotoxin GVIA to chick synaptosomal membranes while omega-Aga-IA and -IB have no effect under identical conditions. The omega-agatoxins thus are defined as two subtypes of neuronal calcium channel toxins with different structural characteristics and calcium channel binding specificities.

Agatoxins↗
PubMed1990

A meta-analysis of alcoholic beverage consumption in relation to risk of colorectal cancer.

Quantitative methods were used to review epidemiologic data relating consumption of alcoholic beverages to risk of colorectal cancer. The data (27 studies) supported the presence of a weak association. For consumption of two alcoholic beverages daily, on average the relative risk of colorectal cancer was 1.10 (95% confidence interval 1.05-1.14). Other findings were: (1) the association did not vary according to gender or site within the large bowel; (2) results from follow-up studies (relative risk 1.32, 95% confidence interval 1.16-1.51) suggested a stronger relationship than those from case-control studies (relative risk 1.07, 95% confidence interval 1.02-1.12); and (3) the evidence supporting beverage specificity was not conclusive, although the results were consistent with a stronger association with consumption of beer (relative risk 1.26, 95% confidence interval 1.13-1.41) than with consumption of wine (relative risk 1.11, 95% confidence interval 0.91-1.36) or liquor (relative risk 1.13, 95% confidence interval 0.99-1.29). Because the magnitude of the association between alcohol consumption and risk of colorectal cancer was small, the findings regarding a causal role of alcohol were inconclusive.

Alcohol Drinking↗
PubMed1990

Adrenal cortical adenoma in the spinal canal of an 8-year-old girl.

An ectopic adrenal cortical adenoma containing high levels of androstenedione but without clinically detectable virilizing effects was found in the spinal intradural space of an 8-year-old girl. The tumor, which was located at the L2 level, manifested itself clinically by a short history of bilateral leg pain. It was well encapsulated; therefore, total surgical removal was accomplished. The light microscopic appearance of the tumor was typical of adenomatous adrenal cortical tissue. Ultrastructurally, it also showed characteristic features of steroid-producing tumors, including very abundant smooth endoplasmic reticulum and giant mitochondria with tubulovesicular and circular cristae. Frozen tissue analyzed by radioimmunoassay was found to contain almost 20 times the normal tissue level of androstenedione. There was no elevation of cortisol or aldosterone levels in the tumor. Postoperative magnetic resonance imaging (MRI) scan of the retroperitoneum showed no abnormalities in the patient's adrenal glands. Serum androstenedione levels were normal. We postulate that the adenoma developed from congenital ectopic rests of intraspinal adrenal tissue. Although ectopic occurrence of adrenal cortical tissue has been recorded in other areas, neither such rests nor tumors developing from them have been previously reported within the spinal canal.

Adenoma↗
PubMed1990

Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc.

A five-category grading scheme for assessing the gross morphology of midsagittal sections of the human lumbar intervetebral disc was developed. The ability of three observers to categorize a series of 68 discs with a wide spectrum of morphologies established the comprehensiveness of the classification. Three independent observers tested the reproducibility of the procedure by assignment of grades blindly to duplicate images of 68 discs taken from 15 spines. The intraobserver agreement ranged from 87 to 91%. The interobserver agreement was 61, 64, and 88% for the three pairs, the two low values being attributable to the bias of one observer. The agreement between the assigned and average grades was 85, 92, 68, 90, and 76% for Grades I through V, respectively. Except for Grade III, the disagreements were attributable mainly to the bias of one observer. Both the increase in the grade with age and the finding that all the discs within 14 of 15 spines had a narrow range of grades demonstrated the biologic credibility of the scheme.

Adult↗
PubMed1990

Inhibition of neuronal Ca2+ channel currents by the funnel web spider toxin omega-Aga-IA.

Ca2+ channel currents were recorded from cultured rat dorsal root ganglion neurons and cerebellar granule cells using the whole-cell recording variant of the patch clamp technique. omega-Aga-IA, a toxin purified from the venom of the American funnel web spider, Agelenopsis aperta, markedly inhibited high threshold barium currents (lBa) when applied at 10 nM concentration. The low threshold T-type current activated at Vc = -30 mV and the outward (Ca2+ channel) current activated at +120 mV were significantly less sensitive to omega-Aga-IA, omega-Conotoxin GVIA (1 microM) inhibited IBa irreversibly. In contrast, the action of omega-Aga-IA was partially reversed 5 min after its removal. The voltage-activated calcium current (ICa) was inhibited by omega-Aga-IA in a manner different from IBa. ICa measured at the end of a 100-msec voltage step command was reduced to a greater extent than the peak current. The residual ICa following application of omega-Aga-IA was a fast transient current. omega-Aga-IA did not inhibit voltage-activated sodium currents from dorsal root ganglion neurons in the absence of tetrodotoxin. omega-Aga-IA abolished the dihydropyridine (+)-202-791-sensitive L-type current component of IBa. We conclude that omega-Aga-IA is a very potent inhibitor of neuronal voltage-activated Ca2+ channel currents and that it may prove to be a useful tool in the characterization and isolation of Ca2+ channels.

Agatoxins↗
PubMed1989

Argiotoxin-636 blocks excitatory synaptic transmission in rat hippocampal CA1 pyramidal neurons.

Argiotoxin 636, (AR636), a synaptic antagonist from orb weaver spider venom, is shown to produce reversible blockade of excitatory transmission in CA1 pyramidal neurons of the in vitro rat hippocampus. Microtopical application of AR636 (5-50 nM) resulted in a concentration-dependent suppression of the amplitude of the dendritic field EPSP recorded from stratum radiatum, and the amplitude of the population spike recorded from stratum pyramidale in response to stimulation of the Schaffer collaterals. The maximum effect of AR636 occurred at about 15-25 min. These effects were reversible after washing with toxin-free physiological solution with the rate of recovery having an inverse relationship to the concentration of AR636. In contrast to the effects observed with orthodromic stimulation, the amplitude of the antidromic spike was not affected by exposure to AR636. The temporal pattern of GABAergic paired-pulse inhibition was unaffected by exposure to AR636. Neuronal discharge elicited by pressure ejection of L-glutamate was abolished by AR636, whereas, responses to L-aspartate were not significantly affected. These data suggest that AR636 functions as a selective antagonist of glutamate-mediated synaptic transmission in rat hippocampus.

Action Potentials↗
PubMed1989

Purification and characterization of two classes of neurotoxins from the funnel web spider, Agelenopsis aperta.

Two classes of paralytic toxins were isolated from the venom of Agelenopsis aperta and their chemical and larvicidal properties characterized. Five acylpolyamine toxins (alpha-agatoxins) of molecular masses 452, 488, 489, 504, and 505 Da produce immediate but reversible paralysis in Manduca sexta following injection. Six insecticidal peptides (mu-agatoxins) produce a gradual but irreversible paralysis. The complete amino acid sequences (36-38 residues) of the mu-agatoxins are presented. These peptides contain eight half-cystines and are quite similar in sequence. At least four of these toxins are amidated at the carboxyl terminus. The secondary structure of one of these toxins (mu-Aga V) was investigated.

Amino Acid Sequence↗
PubMed1989

Production of catabolin by synovium from an experimental model of osteoarthritis.

Catabolic factors from synovium, or catabolins, may be important in the pathogenesis of osteoarthritis. The synovial production of catabolin in osteoarthritis was studied using the experimental model of osteoarthritis induced by section of the anterior cruciate ligament. At 1, 4, and 32 weeks after operation, the synovium was harvested, cultured, and the synovial conditioned medium assayed for catabolic activity. The synovial conditioned medium from the operated joints was significantly more capable of inducing cartilage destruction (p less than 0.05) than was the synovial conditioned medium from the unoperated knees. However, when the results were expressed relative to the weight of synovium, the differences were not significant. These results suggest that the increased production of catabolic synovial factors in early experimental osteoarthritis is probably a result of the synovial hypertrophy.

Animals↗
PubMed1989

omega-Aga-I: a presynaptic calcium channel antagonist from venom of the funnel web spider, Agelenopsis aperta.

Spider venoms are proving to be important sources of specific ion channel toxins. Venom of Agelenopsis aperta, a funnel web spider, contains a class of polypeptide toxins which blocks neuromuscular synapses at nanomolar concentrations. Detailed physiological analyses of block caused by one of these toxins, omega-Aga-I, show that it suppresses transmitter release at insect and frog neuromuscular junctions and blocks calcium spikes in insect neuronal cell bodies. omega-Aga-I may define a binding site on neuronal calcium channels which is common to both vertebrates and invertebrates.

Agatoxins↗