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Biomedical subjects

D M Logan

Publications and source records attributed to D M Logan.

At least 37 records · Page 2Linked to original sources
PubMed1987

Fiber-specific cholesterol changes in murine dystrophy.

The cholesterol concentration in dystrophic mouse muscle is reported to be increased compared to normal. The muscles studied are, however, composed in most cases of more than one fiber type. As a result, the observed concentration increase may be due to a general increase or may be due to changes in the proportion of individual fiber types which themselves differ in cholesterol concentration. To decide between these possibilities we have measured the cholesterol concentrations (both free cholesterol and cholesterol esters) in normal and dystrophic whole gastrocnemius muscles and compared the values with the concentrations in fast-glycolytic muscle tissue alone. The cholesterol concentrations in both whole and fast-glycolytic sections of dystrophic muscle are increased compared to normal, with the largest increase in the cholesterol ester fraction. Furthermore, the concentration changes in fast-glycolytic fibers are due mainly to cholesterol ester differences in both membrane and sarcoplasm fractions, with differences in the latter being larger. The data show that changes in whole muscle concentrations cannot be ascribed solely to altered fiber type proportions.

Animals↗
PubMed1986

The importance of dose intensity of doxorubicin administration in non-Hodgkin's lymphoma. A case report.

A 30-year-old woman with Stage IIIA diffuse non-Hodgkins lymphoma was treated with doxorubicin, cyclophosphamide, vincristine, and prednisone (CHOP) every 3 weeks. When the cumulative doxorubicin dosage after nine courses of chemotherapy was 515 mg/m2 (average, 57 mg/m2/course and 19 mg/m2/week), the doxorubicin was discontinued. She relapsed 4.5 months later while receiving vincristine, prednisone, and an escalated dosage of cyclophosphamide (CVP) every 3 weeks. Single-agent chemotherapy consisting of weekly doxorubicin was administered for 15 courses (average dose 29 mg/m2/week) and resulted in a complete remission after nine courses. The cumulative dosage of doxorubicin was 955 mg/m2 at the end of the 15 courses. Mild cardiomyopathy was noted on left ventricular gated scan and electrocardiogram (ECG) at the cessation of therapy. Mild congestive heart failure occurred shortly after the discontinuation of the doxorubicin. It responded to treatment with digoxin and diuretics. At present, she has no dyspnea on exertion and no evidence of cardiomegaly on chest x-ray films; she continues to use digoxin alone. She remains in complete remission 29 months after discontinuation of intensive, weekly, single-agent doxorubicin administration (compared to a remission of only 4.5 months from the end of less intensive administration of doxorubicin every 3 weeks as part of combination chemotherapy). This case illustrates that intensive doxorubicin administration may be superior to conventional doxorubicin administration for the treatment of lymphomas, and raises the possibility that weekly administration could be superior to administration of doxorubicin every 3 weeks. Further studies investigating the efficacy of weekly versus conventional scheduling of doxorubicin are warranted in non-Hodgkin's lymphoma, particularly in light of published evidence that weekly doxorubicin administration is also less cardiotoxic than treatment given every 3 weeks.

Adult↗
PubMed1985

Altered cholesterol ester proportions in embryonic tissues of dystrophic chicken.

The concentrations of cholesterol esters in tissues of dystrophic chicken embryos are altered from normal. These changes are accompanied by significant changes in the proportions of the esterified fatty acids (the fatty acid profile). In serum and pectoral muscles there is a shift to a higher proportion of unsaturated fatty acids (in particular 18:1). Thigh muscle esters are little changed and in liver and brain the proportion of unsaturated fatty acids decreases.

Animals↗
PubMed1983

Aspects of hepatic cholesterol metabolism in normal and dystrophic chicken embryos.

Several aspects of hepatic cholesterol metabolism have been studied in normal and dystrophic chicken embryos (12 days in ovo). Dystrophic embryo livers weigh the same and have the same total protein content as their normal counterparts. However, the total cholesterol content of dystrophic embryo livers is significantly decreased compared with the content of normal embryo livers. This decrease in total cholesterol is due mainly to a large decrease in the amount of cholesterol esters, although the free cholesterol content is also decreased. The proportions of free cholesterol and cholesterol esters are 43 and 57%, respectively, in normal embryo livers, but this proportion is essentially reversed in dystrophic embryo livers (i.e., 56 and 44%). The decreased total cholesterol content of dystrophic embryo livers is not apparently due to a decrease in the rate of free cholesterol de novo biosynthesis or to a decrease in the rate of free cholesterol esterification. However, the decrease in cholesterol ester content may be due to an increase in the rate of its hydrolysis, as a result of increased levels of sterol ester hydrolase in dystrophic livers. These data are consistent with the proposal that membranes in dystrophic tissues are altered as a result of altered cholesterol metabolism and utilization.

Animals↗
PubMed1982

Neurotoxins from Bungarus fasciatus venom: a simple fractionation and separation of alpha- and beta-type neurotoxins and their partial characterization.

The crude venom of Bungarus fasciatus has been fractionated by column chromatography, and the fractionation characteristics of three different resins have been compared. A minimum of 21 fractions can be identified under optimum conditions on Bio-Gel CM-30. Of the major fractions tested for neurotoxic activity, three showed postsynaptic (alpha) and four showed presynaptic (beta) neurotoxic activity. The major protein component (an alpha-neurotoxin) has an isoleucyl N terminus and a calculated molecular weight of 14 200 based on amino acid composition. This main component contains 127 amino acid residues including 16 cysteine residues. A second less abundant alpha-neurotoxin of similar molecular weight has a methionyl N terminus. The isoelectric points of these toxins are 9.1 and 8.8, respectively. A third fraction also has postsynaptic (alpha) activity. Four other, very basic proteins have presynaptic (beta) activity. Their apparent molecular weights are approximately 10 800 (two fractions), 13 100, and 19 100 as determined by sodium dodecyl sulfate gel electrophoresis. All alpha-toxin fractions showed a high tendency to aggregate in aqueous media; however, the presence of L-cysteine in molar excess prevents dimer formation. In the absence of L-cysteine, freeze/thaw cycling of aqueous solutions of alpha-toxins invariably leads to the formation of dimers which can be dissociated only under reducing conditions (beta-mercaptoethanol). Conversely, only one out of four beta-toxins examined tended to form dimers.

Amino Acid Sequence↗
PubMed1981

Altered acetylcholinesterase isozyme patterns in mice with hereditary muscular dystrophy.

Normal and dystrophic mouse muscles were separated into a predominantly white muscle fraction (gastrocnemius, extensor digitorum longus) and a predominantly red muscle fraction (diaphragm). Acetylcholinesterase (AChE) was extracted from each muscle fraction using a Triton X-100/NaCl buffer. Six forms of AChE were separated from each muscle homogenate by velocity sedimentation on linear sucrose gradients. Their apparent sedimentation coefficients in each case were 19.7S, 16.0S, 13.3S, 10.4S, 7.6S, and 3.9S. Gel electrophoresis of crude muscle homogenates under nondenaturing conditions (native gels) and of ech separate isozyme fraction gave one band of AChE activity with a consistent Rf (relative mobility) value. Reelectrophoresis of native gel bands on SDS/acrylamide slab gels revealed a similar monomeric subunit protein from either crude muscle homogenates or isozyme fractions with an apparent molecular weight of approximately 69,000 daltons. Our results indicate that the AChE distribution and activity are severely affected in dystrophic "white" muscles (anaerobic) but much less so in "red" muscles (aerobic). Dystrophic predominantly white muscles weigh less, contain less protein, and have a decreased total AChE activity in comparison with their normal counterparts. Furthermore, the relative proportions of AChE activity in each isozyme fraction is altered between normal white and dystrophic white muscle fractions: i.e., dystrophic white muscle contains a decreased proportion of a low molecular weight form (7.6S) and increased proportions of higher molecular weight forms (16.0S, 19.7S). In contrast, no significant differences occur in AChE activity or distribution between normal and dystrophic predominantly red muscle. The changes in white muscle AChE are toward a pattern common to red muscle. This suggests that the effect of muscular dystrophy and its related stress on mouse white muscle is at least in part a shift from a predominantly anaerobic, fatigable metabolism to an aerobic, fatigue-resistant metabolism.

Acetylcholinesterase↗
PubMed1980

Noradrenaline and cyclic AMP--independent growth stimulation in newt limb blastemata.

Adult newts regenerate functional limbs after amputation. This process normally depends on the trophic influence of nerves on the regenerating limbs, particularly in the early stages before differentiation of the regeneration blastema, when it stimulates growth by maintaining high rates of macromolecular synthesis. The sequence of biochemical events involved is unknown, but it has been suggested that intracellular cyclic AMP may be a second messenger within the blastema. Many studies have indicated that the neural agent(s) involved might be protein. The recent finding that blastemata contain high levels of catecholamines, however, has implicated noradrenaline (NA) as the neurotrophic agent, and suggested that it works via stimulation of beta-adrenergic receptors on the blastemal cells, thereby raising the intracellular concentrations of cyclic AMP. To test this hypothesis we studied the ability of NA alone and in combination with alpha-and beta-adrenergic antagonists to increase cyclic AMP levels and to mimic the effects of nerves by maintaining high rates of protein synthesis and high mitotic indices (MI) in denervated blastemata in organ culture. We find that although NA raises cyclic AMP levels through a beta-adrenergic effect, it does not maintain high rates of protein synthesis or high MI in cultured blastemata. It is unlikely therefore, that this hypothesis applies.

Animals↗
PubMed1978

Nerve trophic effects: an in vitro assay for factors involved in regulation of protein synthesis in regenerating amphibian limbs.

We have developed a rapid sensitive test for factors that mimic the trophic effects of nerves by maintaining normal rates of protein synthesis in denervated forelimb blastemata of adult newts (Notophthalmus viridescens). Rates of protein synthesis in secondary blastemata are similar. However, after they are denervated and explanted into organ culture the rates of protein synthesis first increase and later fall below control values. Similar changes occur after denervation in vivo. The alterations in the rates of protein synthesis are prevented by adding to the culture medium aqueous extracts from brains of adult newts or chicken embryos. The active material is either a peptide or a protein.

Animals↗
PubMed1977

A kinetic analysis of the processive enzyme Lactobacillus plantarum exoribonuclease.

Oligonucleotide chains consisting of adenosine residues and ranging from 1 to 70 residues in length have been tested as substrates or inhibitors with Lactobacillus plantarum exoribonuclease (EC3.1.4.20). The kinetic constants V, Km, and Ki are all chain-length dependent. Ki decreases with increasing chain length to a minimum for oligonucleotides seven residues in length and then begins to increase slightly. Kinetic plots indicate that the oligonucleotides are almost all competitive inhibitors of poly A hydrolysis. However, the oligonucleotide (Ap)3A greater than p probably leads to mixed inhibition. The enzyme is unable to retain its processivity when it hydrolyzes short oligonucleotides such as (Ap)2A and (Ap)3A. It is proposed that L. plantarum exoribonuclease possesses seven binding sites for the polynucleotide. When the enzyme is bound to a long-chain-length substrate the complex is stabilized by a binding energy of about 8 Kcal/mol. After cleavage of the terminal nucleotide the remaining binding energy is still sufficient to maintain an enzyme-substrate complex. The shortened nucleotide chain is moved relative to the enzyme to re-form the seven-bond association by a gradient of energy of about 1.7 Kcal/mol for the change from six to seven bonds.

Adenosine↗
PubMed1972

Thermal and pH stability of 2 -isopentenyl pyrophosphate.

The isoprenoid precursors Delta(3)-isopentenyl pyrophosphate and gamma,gamma-dimethylallyl pyrophosphate (Delta(2)-isopentenyl pyrophosphate) have been separated by thin-layer chromatography. The products from Delta(2)-isopentenyl pyrophosphate incubated under various conditions of pH and temperature have been separated, and the survival of Delta(2)-isopentenyl pyrophosphate under these conditions has been calculated. The acid-labile Delta(2)-isopentenyl pyrophosphate can be stored indefinitely at pH 11.5 and -100 degrees C.

Alkenes↗