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Biomedical subjects

M G Hamilton

Publications and source records attributed to M G Hamilton.

At least 55 records · Page 3Linked to original sources

Spontaneous disappearance of an intracranial aneurysm after subarachnoid hemorrhage.

Spontaneous disappearance of an intracranial aneurysm after subarachnoid hemorrhage is an uncommon event and usually associated with severe cerebral vasospasm, giant aneurysms or the use of antifibrinolytics. We present a young woman who suffered a grade 5 subarachnoid hemorrhage with severe vasospasm caused by a small anterior communicating artery aneurysm. The patient underwent a slow recovery and two years later requested surgery. Angiography demonstrated complete disappearance of the aneurysm. The neurosurgeon should be aware that spontaneous thrombosis of cerebral aneurysms can occur and ensure that angiography is repeated when surgery is significantly delayed.

Adult↗

Pharmacological evidence for an omega-conotoxin, dihydropyridine-insensitive neuronal Ca2+ channel.

Inactivation of N-type voltage-sensitive Ca2+ channels (VSCC) with omega-conotoxin (omega-CgTx) in tissue obtained from chicken brain produces a concentration dependent (0.01-0.1 microM) inhibition of K(+)-stimulated Ca2+ influx (delta K+), the rise in [Ca2+]i and acetylcholine (ACh) release. In identical preparations from rat brain, Ca2+ influx and the rise in [Ca2+]i were only marginally affected by much higher (1-10 microM) concentrations of omega-CgTx. The release of ACh, however, was inhibited to the same degree with similar amounts of omega-CgTx as those used in chicken brain. An L-type VSCC inhibitor failed to affect any of these parameters alone, or to augment the effect of omega-CgTx. The results suggest that almost all the VSCC in chicken brain are of the N type and that these channels regulate neurotransmitter release. In rat brain, on the other hand, Ca2+ channels resistant to N- or L-type blockers account for almost 75% of the measurable Ca2+ influx and rise in [Ca2+]i. The conspicuous dissociation between the regulation of Ca2+ influx and ACh release demonstrated in rat brain by using omega-CgTx, suggest that neurotransmitter release is governed by only a small proportion of strategically located N-type, omega-CgTx sensitive, VSCC in the presynaptic terminal.

Acetylcholine↗

The stabilizing influence of divalent ions and Na+ on the di-decameric structure of Yoldia limatula hemocyanin.

The stabilizing influence of Ca2+, Mg2+, Ba2+ and Na+ on the di-decameric structure of the hemocyanin of the bivalve, Yoldia limatula has been investigated by light-scattering molecular weight measurements and by analytical ultracentrifugation. The molecular weight (Mw) data, examined as a function of decreasing divalent ion and sodium ion concentrations at pH 8.0 and at a constant hemocyanin concentration of 0.10 g.l-1, show biphasic transition profiles, with a sharp initial decline in Mw as the concentration of the stabilizing cations is reduced. The analysis of the molecular weight data is best described in terms of the four-species, di-decamer-decamer-dimer-monomer scheme of association-dissociation equilibria. About 25 to 35 bound divalent ions and about 10 bound Na+ ions per half-molecule or decamer are required in order to account for the initial step of the observed transitions. The subsequent transitions representing the decamer to dimer and the dimer to monomer steps of the reaction account for the additional binding of three to four and two to four cations per dimer and per monomer, respectively. The relatively large number of divalent ions per decamer suggests strong ionic stabilization of the decamer to decamer contacts within the parent di-decameric assembly of Yoldia hemocyanin. This is consistent with earlier observations showing relatively few hydrophobic groups at the decamer to decamer contact areas.

Animals↗

Higher order assemblies of molluscan hemocyanins.

1. The hemocyanins of the Fissurellidae, Naticidae and Melongenidae families of marine gastropods as well as some other molluscs including some members of the Opistobranchia and Bivalvia groups have hemocyanins which exist in solution as tri-decameric and mixed, multi-decameric aggregates characterized by sedimentation coefficients close to 100 S, 130 S, 150 S, 170 S and 200 S to 230 S. 2. The particle masses of the molluscan hemocyanins appear to be integral multiples close to 4.4 x 10(6) daltons. Thus, particle mass values of 4.47 x 10(6), 8.67 x 10(6) and 13.40 x 10(6) daltons were obtained for representative decameric, di-decameric, and tri-decameric components of Stenoplax conspicua, Fasciolaria tulipa and Euspira (Lunatia) heros hemocyanins. For Busycon contrarium, a gastropod with a mixed multidecameric hemocyanin, scanning transmission electron microscopic (STEM) measurements gave particle masses ranging from 8.89 x 10(6) and 13.20 x 10(6) for the di- and tri-decameric components to 38.87 x 10(6) and 43.40 x 10(6) daltons for highest nano- and deca-decameric aggregates. 3. The electron microscopic images of both uranyl acetate-stained and unstained specimens of hemocyanin aggregates indicate a non-random mode of assembly of the multi-decameric particles. This is most apparent from the electron micrographs of the moon snail hemocyanins. The tri-decameric and tetra-decameric particles seem to be assembled from a single di-decameric unit of the Mellema and Klug arrangement, with the collar ends facing outward, to which decameric units have been added from one or both ends, in a unidirectional tail-to-head to tail-to-collar manner. Consequently, all the aggregates including the higher, Melongenidae polymers have the appearance of closed cylinders terminating with the collar ends. 4. The radial distribution of the end-on views of the hemocyanin of the moon-snail Calinatioina oldroydii, show that the radial mass drops to zero at the center of the cylindrical particles consisting of one, two, or three decamers. This suggests that no caps are present at the ends of the hemocyanin particles which would inhibit or terminate their linear assembly. 5. The light-scattering behavior of B. contrarium and Marisa cornarietis hemocyanins examined as a function of increasing reagent concentration using the hydrophobic urea and Hofmeister salt series of reagents, show distinct aggregation and increase in molecular weights at low concentrations of reagent. Together with the stabilizing influence of Mg2+ and Ca2+ ions, this suggests polar and ionic stabilization of the inter-decameric contacts between the central di-decamers and the added decameric units of the higher aggregates of molluscan hemocyanins.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Subunit structure of the hemocyanins of some of the Muricidae and Fasciolariidae families: Chicoreus florifer dilectus (A. Adams), Muricanthus fulvescens (Sowerby), Urosalpinx cinerea (Say), Fascilaria lilium hunteria (Perry), and Pleuroploca gigantea (Kiener).

1. The hemocyanins of the Muricidae and Fasciolariidae families of marine gastropods: Chicoreus florifer dilectus, Muricanthus fulvescens, Urosalpinx cinerea, Fasciolaria lilium hunteria, and Pleuroploca gigantea were investigated by sedimentation velocity, scanning transmission electron microscopy, light-scattering, and other physical techniques. 2. The hemocyanins of these species are characterized by sedimentation coefficients close to 100 S and molecular weights of 8.2 x 10(6)-9.0 x 10(6). 3. The hemocyanins have di-decameric structures, with tail-to-tail arrangement of the decameric halves of the cylindrical particles. Only the hemocyanin of U. cinerea was found to contain about 30% higher, tri-, and tetra-decameric particles, with one or two decameric units added in a tail-to-head manner to a central di-decameric particle of the Mellema and Klug tail-to-tail arrangement. 4. The influence of pH, and the urea and Hofmeister salt series of reagents on the subunit structure and denaturation of P. gigantea hemocyanin were also investigated.

Animals↗

Alteration of calcium influx in rat cortical synaptosomes by soman.

Poisoning by soman causes changes in brain activity leading to neuronal death in several brain areas. We investigated whether disruption of normal Ca2+ homeostasis was sufficient to account for at least some of the OP-induced neurotoxicity. Beginning 24 h after a challenge with soman (1 or 4 LD50) K(+)-stimulated synaptosomal Ca2+ influx was significantly elevated above that in control animals. Neuronal Ca2+ influx remained elevated for two days after 1 LD50 of soman and at least 7 days after 4 LD50. The effect was specific for depolarization induced influx as there was no effect on resting (5 mM K+) Ca2+ accumulation. These results suggest that increased intracellular Ca2+ may contribute to the neuronal degeneration and neurotoxicity observed after poisoning with soman.

Animals↗

Distribution of the bispyridinium oxime [14C] HI-6 in male and female rats.

Female rats poisoned with multiple LD50s of soman or tabun have been shown previously to respond to the protective effects of HI-6 more positively than male rats. This present study was designed first to determine the distribution pattern and concentration of [14C] HI-6 in rats, and secondly, to determine the possibility that HI-6 might be located in high concentrations in critical tissues in the female as opposed to the male. To these ends, [14C] HI-6 was administered to groups of male and female rats and its radiolabelled distribution determined by whole body autoradiography and/or by measurement of its actual concentration, by scintillation spectrometry. The experiments were repeated in the presence of 2 x LD50 soman and supporting therapy with atropine. In both sexes, HI-6 levels were highest in the kidney, followed in order by cartilage greater than plasma greater than liver greater than heart greater than or equal to lung greater than or equal to diaphragm greater than brain and spinal cord. The relative distribution in the two sexes was confirmed by both methods and was not significantly altered in the presence of soman and atropine. The lack of a measurable difference in tissue distribution of [14C] HI-6 derived radioactivity between males and females suggested that the hormone-dependent difference in the protective effects previously observed was not due to selective accumulation of [14C] HI-6 in organs believed to be important in its therapeutic activity, such as brain or diaphragm.

Animals↗

Light-scattering and scanning transmission electron microscopic investigation of the hemocyanin of the bivalve, Yoldia limatula (Say).

1. The hemocyanin of the bivalve, Yoldia limatula (Say) was found by light-scattering to have a mol. wt of 8.0 +/- 0.6 x 10(6). Mass measurements by scanning transmission electron microscopy (STEM) gave a particle mass of 8.25 +/- 0.42 x 10(6) for the native particle and 4.09 +/- 0.20 x 10(6) for the half-molecule. 2. The hemocyanin subunits fully dissociated in 8.0 M urea and 6.0 M GdmCl at pH 8.0, and at pH 11.0, 0.01 M EDTA have mol. wts of 4.38 x 10(5), 4.22 x 10(5) and 4.71 x 10(5), close to one-twentieth of the parent molecular weight of Y. limatula hemocyanin and most gastropod hemocyanins. 3. Analyses of the urea dissociation transitions studied at pH 8.0, 1 x 10(-2) M Mg2+, 1 x 10(-2) M Ca2+ and pH 8.0, 3 x 10(-3) M Ca2+ suggest few hydrophobic amino acid groups, of the order of 10 to 15 at the contact areas of each half-molecule or decamer. 4. The further dissociation of the decamers to dimers and the dimers to monomers indicates the presence of a larger number of amino acid groups of ca 35-40/dimer and 100-120/monomer. 5. This suggests hydrophobic stabilization of the dimer to dimer and monomer to monomer contacts within the decamers, as observed with other molluscan hemocyanins.

Animals↗

The hemoglobin of the aquatic snail, Planorbella duryi (Wetherby).

1. The hemoglobin of the pond snail, Planorbella duryi has a molecular weight of 1.64 x 10(6) to 1.77 x 10(6) as determined by light-scattering at 630 nm and a sedimentation coefficient of 36 S. 2. The analysis of the circular dichroism spectrum obtained in the 190-250 nm region suggests a high degree of helical folding of the polypeptide chains of P. duryi hemoglobin analogous to human hemoglobin and myoglobin, with estimates of alpha-helical folding of about 60-65%, 0-5% beta-structure, and the remaining portion of the chains in unordered form. 3. The dissociated subunits in 6.0 M GdmCl, in the absence and in the presence of reducing reagent (0.1 M dithiothreitol), have a molecular weight of 3.73 +/- 0.23 x 10(5) and 1.93 +/- 0.04 x 10(5), suggesting a di-decameric assembly of the parent hemoglobin organized in the form of five dimers held together by disulfide-linkages. 4. The native hemoglobin is strongly resistant to both pH dissociation and dissociation by urea and such salts as NaCl and NaClO4. Dissociation and denaturation could only be effected in concentrated GdmCl solutions. 5. The influence of the various dissociating agents on the quaternary structure suggest ionic stabilization of the decameric assembly, which is stabilized by salt bridges between the subunits.

Animals↗

The hemocyanin of the ramshorn snail, Marisa cornuarietis (Linné).

1. The hemocyanin of the freshwater snail, Marisa cornuarietis exists predominantly as a di-decamer with the approximate mol. wt of 8.5 x 10(6) and a sedimentation coefficient of 100 S. Sedimentation and scanning transmission electron microscopy experiments indicate that about 15-20% of the hemocyanin forms tri-decameric and possibly higher aggregates with mol. wts of 12.5 x 10(6) and 130 S. 2. The fully dissociated subunits in 8.0 M urea and 6.0 M GdmCl have mol. wts of 4.1 to 4.7 x 10(5) which is close to one-twentieth of the major di-decameric component of the native hemocyanin. 3. Subunit dissociation by the urea series and the Hofmeister salt series of reagents suggests hydrophobic stabilization of the decamers or half-molecules of the parent hemocyanin. As with the other molluscan hemocyanins the order of effectiveness of the ureas as dissociating agents shows increased efficacy with increasing hydrophobicity or chain-length of the urea substituents. 4. Denaturation of the hemocyanin subunits by the ureas and Hofmeister salt series, investigated by circular dichroism measurements, essentially follow the same trend in effectiveness as observed by changes in subunit dissociation followed by light-scattering mol. wt measurements. 5. The observed denaturation transitions are shifted to much higher ranges of reagent concentration than the concentrations required for the dissociation of the hemocyanin subunits.

Animals↗

Subunit structure and higher order assembly of the hemocyanins of five members of the Naticidae family of marine gastropods: Calinaticina oldroydii (Dall), Euspira heros (Say), Neverita duplicata (Say), Polinices draconis (Dall), and Polinices lewisii (Gould).

1. The hemocyanins of the Naticidae family, E. heros, N. duplicata, P. draconis, P. lewisii and C. oldroydii were investigated by sedimentation velocity and scanning transmission electron microscopy. 2. At pH 8.0, 0.05 M Mg2+ E. heros hemocyanin is found to be predominantly in the tri-decameric state with a sedimentation coefficient (So20,w) of 131.3 (+/- 0.6) S. While the hemocyanin of N. duplicata is also mainly in the 130 S form, the hemocyanin of C. oldroydii is largely in the di-decameric form with a sedimentation coefficient close to 100 S. Other Naticidae hemocyanins, those of P. lewisii and P. draconis, have mixtures of the 100 S and 130 S di- and tri-decamers, and minor amounts of 150 S and faster sedimenting components. 3. The average particle masses based on STEM measurements are 8.85 x 10(6), 1303 x 10(6), and 17.1 x 10(6) da for the di-, tri-, and tetra-decameric assemblies of hemocyanin. 4. The subunit mol. wts of C. oldroydii hemocyanin and the published values for E. heros hemocyanin at alkaline pHs and in the presence of 8.0 M urea range from 4.2 x 10(5) to 4.8 x 10(5), suggesting the same decameric organization of the sub-assemblies of the Naticidae hemocyanins as for other molluscan hemocyanins. 5. The appearance of the larger hemocyanin particles in the electron micrographs support the hypothesis for their assembly that was based on similar studies of the hemocyanins of the Melongenidae family. According to this scheme the formation of higher aggregates is accomplished by the tail-to-head addition of each decameric unit to a central di-decamer which itself has the tail-to-tail Mellema and Klug arrangement of decamers. In this model all the higher aggregates terminate from either end with the same "collar" ends.

Animals↗

Intradural herniation of a thoracic disc presenting as flaccid paraplegia: case report.

A case of intradural herniation of a thoracic disc in a patient with a flaccid paraplegia is described. Intradural herniation of a thoracic disc is considered a rare event. A review of the relevant patient literature revealed 14 other reports involving 28 patients. No other report has described a patient with an intradural thoracic disc herniation who developed a flaccid paraplegia.

Aged↗

Effect of endothelin on Ca2+ influx, intracellular free Ca2+ levels and ligand binding to N and L type Ca2+ channels in rat brain.

The actions of endothelin, an endogenous vasoconstrictor compound with potent effects on various parameters of Ca2+ metabolism in peripheral tissue, were studied in several neuronal preparations. Endothelin, by itself, did not alter resting intracellular free Ca2+ levels or Ca2+ influx in either rat or chicken brain preparations; nor did it affect depolarization (K+) induced changes in these parameters. Endothelin also had no effect on the binding of [3H]-nitrendipine or [125I]-omega-conotoxin to "L " or "N" type channels respectively nor did it induce the release of endogenous acetylcholine from brain slices. The results show that, despite the proposed role of endothelin on voltage sensitive Ca2+ channels in peripheral tissue and despite the existence of endothelin binding sites on both smooth muscle and neurons, endothelin has no measurable effects on Ca2+ metabolism in neural tissue of central origin.

Acetylcholine↗

HI-6 therapy of soman and tabun poisoning in primates and rodents.

The bis-pyridinium oxime HI-6, in conjunction with atropine, was found to offer significant protection against multiple LD50 challenges with the organophosphorus compounds soman and tabun. In adult rhesus macaques, the therapeutic administration of HI-6 with atropine and diazepam protected three of four animals from the lethal effects of 5 x LD50 of soman and three of three animals from 5 x LD50 of tabun. However, when toxogonin was substituted for HI-6 in the therapeutic mixture, all three animals poisoned with 5 x LD50 of soman died. In rats, the 24 h protective ratios against tabun and soman with HI-6 were 2 and 3.5, respectively, whereas in guinea pigs these values were between 4 and 6 for both agents. No evidence was obtained for acetylcholinesterase (AChE) reactivation by HI-6 in tissue from tabun-poisoned rodents or following soman or tabun in primate plasma. The results underscore the significant therapeutic benefit of HI-6 in primates, a species specific efficacy against tabun, and argue for some mechanism of action of HI-6 at least partly unrelated to AChE reactivation.

Acetylcholinesterase↗

The haemocyanin of the whelk, Busycon contrarium (Conrad): aggregation states and subunit structure.

1. The haemocyanin of the left-handed whelk Busycon contrarium (Conrad) exists largely as six or more multi-decameric aggregates characterized by sedimentation coefficients of approximately 105S, 132S, 155S, 170S, 185S and about 200-220S. 2. These aggregates represent di- to hepta- or octa-decameric assemblies of the basic haemocyanin decamer having a mol. wt of 4.3 x 10(6)-4.5 x 10(6). 3. The fully dissociated subunits in 8.0 M urea (pH 8.5) and at pH 11.1, 0.01 M EDTA have mol. wts of 4.78 x 10(5) and 4.62 x 10(5), close to one-tenth of the mol. wt of the basic decameric unit of most gastropod haemocyanins. 4. The pH dependence of the mol. wts (Mw), studied by light-scattering at the constant protein concentration of 0.010%, exhibit bell-shaped pH transition profiles with mol. wt values of about 16 x 10(6) in the presence of 0.01 M Mg2+, in the pH region from about pH 4.5-8.0; in the absence of stabilizing divalent ions the observed mol. wt is about 10 x 10(6) at pH 4.5-7.0. Below pH 4.5 and above 7.0-8.0 there is a sharp drop in mol. wt to about 4 x 10(5)-4.5 x 10(5). 5. The transition profiles observed with both the urea and salt series of probes investigated at concentration = 0.010% are found to produce aggregation at low reagent concentrations with mol. wt changes from about 9 x 10(6)-12 x 10(6)-14 x 10(6), followed by a decrease in mol. wt below 4.3 x 10(6)-4.5 x 10(6) of the haemocyanin decamers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Subunit structure and higher order assembly of the hemocyanins of the Melongenidae family: Melongena corona (Gmelin), Busycon canaliculatum (Linné), B. carica (Gmelin), B. contrarium (Conrad), and B. spiratum (Lamarck).

1. The hemocyanins of the Melongenidae family of marine gastropods: Melongena corona, Busycon canaliculatum, B. carica, B. contrarium, and B. spiratum exist in solution as multi-decameric aggregates characterized by sedimentation coefficients of approximately 105 S, 130 S, 150 S, 170 S, and higher values, corresponding to di-, tri-, tetra-, penta-, and larger multi-decameric particles. 2. The hemocyanins of B. contrarium and B. carica seem to form the largest decameric aggregates with the tri- to penta-decamers respresenting the major constitutents. Scanning transmission electron microscopy (STEM), both of unstained, freeze-dried and negatively-stained specimens, shows the presence of discrete aggregates consisting of up to ten decameric units. 3. The particle masses as determined by STEM mass measurements for individual molecules gave integral multiples of from 4.2 x 10(6) to 4.4 x 10(6) daltons ranging from about 8.2 x 10(6) daltons for the typical di-decamer of B. canaliculatum hemocyanin to as high as about 39 x 10(6) and 43 x 10(6) for the nano-and deca-decamers of B. contrarium hemocyanin. 4. The appearance of the higher multi-decamers in both negatively-stained and freeze-dried specimens suggest that they are formed by the addition of decameric units to a single di-decameric unit "tail-wise" in both directions. The higher aggregates formed seem to terminate with a closed head or collar at both ends of the assembly.

Animals↗

Scanning transmission electron microscopic study of molluscan hemocyanins in various aggregation states: comparison with light scattering molecular weights.

The masses of individual particles of the hemocyanins of six members of two molluscan classes, Polyplacophora and Gastropoda, have been determined by scanning transmission electron microscopy (STEM) of unstained specimens dried from the frozen state. The decameric hemocyanins of two chitons, Mopalia muscosa and Stenoplax conspicua, had masses of 4.20 +/- 0.18 and 4.47 +/- 0.56 MDa, respectively; the didecameric hemocyanins of two gastropods, Fasciolaria tulipa and Pleuroploca gigantea, had masses of 8.67 +/- 0.44 and 8.96 +/- 0.39 MDa, respectively; and the tridecameric hemocyanin of Lunatia heros had a mass of 13.50 +/- 0.44 MDa. The STEM values were in close agreement with those obtained by light scattering measurements of the same samples in solution. For Busycon contrarium, a gastropod with a multidecameric hemocyanin, nine size classes from didecamers to decadecamers with masses that corresponded to multiples of a basic decamer (4.4 MDa) were detected. The appearance of unstained specimens of the cylindrical particles differs from negatively stained specimens. Viewed end-on the cylinders show no internal structure, but in well-preserved specimens cavities are apparent in the side views of the cylinders that resemble those seen in negatively stained specimens. Although they lack the characteristic "tiered" appearance, the number of decameric units can be counted and their arrangement within the particle seen.

Animals↗