Regulation of substrate oxidation in isolated myocardial cells by beta-hydroxybutyrate

The role of ketone bodies in myocardial substrate oxidation was examined using freshly isolated Ca2+-tolerant heart myocytes, beta-hydroxybutyrate (beta OHB) inhibited lactate oxidation by the myocytes by 30-60%, and the inhibition was concentration dependent. Palmitate oxidation was also markedly decreased, whereas octanoate oxidation was only minimally affected by the presence of beta OHB. Lactate, octanoate, or palmitate had little, if any, effect on beta OHB oxidation. beta OHB oxidation was reduced by 22-28% in myocytes isolated from chronically diabetic rats, whereas the oxidation of palmitate remained similar to the controls. However, beta OHB still inhibited palmitate oxidation to the same extent as in the control cells. Our data support the role of beta OHB as a physiologic regulator of myocardial substrate metabolism.     

Immunoglobulin light chains in chronic lymphocytic leukemia and related diseases

The combination of two-dimensional mini gel electrophoresis with the 'western blot' technique proves to be a powerful tool in characterizing lymphoid cells. By testing for kappa and lambda immunoglobulin light chains we were able to differentiate between mono-, oligo-, and polyclonal B-cell diseases. The distribution of the lambda isotypes of 24 cases with chronic lymphocytic B-cell leukemia (B-CLL) tested was not random when compared to the distribution of the lambda light chains in B-lymphocytes of normal persons. This might implicate a genetic link between the lambda loci (chromosome 22) and the development of the lambda-CLL.     

Cytokinin-induced switch in development in excised cotyledons of radiata pine cultured in vitro

Cotyledons of Pinus radiata D. Don were cultured under shoot-forming (plus cytokinin) and elongating (minus cytokinin) conditions. Using. autoradiographic and precursor incorporation techniques, the sites and rate of macromolecular synthesis were examined during the first five days in culture. Active incorporation of ³H-thymidine, ³ H-uridine and ³H-leucine occurred. In shoot-forming cotyledons the incorporation became preferentially located in the epidermal and sub-epidermal cell layers in contact with the medium. In elongating cotyledons, in contrast, incorporation was randomly distributed, and the amount of incorporation declined with time. Biochemically, differences in DNA, RNA and total protein synthetic patterns were observed. In elongating cotyledons the rates of RNA and protein synthesis were higher during the first 48 h than in shoot-forming tissues, after which the synthetic rates were similar. Two peaks of newly formed DNA were observed in both tissues. These findings indicate that the cytokinin-induced changes in developmental pathways began within 24 h in culture.     

Organization of the ribosomal ribonucleic acid genes in various wild-type strains and wild-collected strains of Neurospora

Summary The organization of the ribosomal DNA (rDNA) repcat unit in the standard wild-type strain of Neurospora crassa, 74-OR23-1A, and in 30 other wild-type strains and wild-collected strains of N. crassa, N. tetrasperma, N. sitophila, N. intermedia, and N. discreta isolated from nature, was investigated by restriction enzyme digestion of genomic DNA, and probing of the Southern-blotted DNA fragments with specific cloned pieces of the rDNA unit from 74-OR23-1A. The size of the rDNA unit in 74-OR23-1A was shown to be 9.20 kilobase pairs (kb) from blotting data, and the average for all strains was 9.11+0.21 kb; standard error=0.038; coefficient of variation (C.V.)=2.34%. These data indicate that the rDNA repeat unit size has been highly conserved among the Neurospora strains investigated. However, while all strains have a conserved HindIII site near the 5 end of the 25 S rDNA coding sequence, a polymorphism in the number and/or position of HindIII sites in the nontranscribed spacer region was found between strains. The 74-OR23-1A strain has two HindIII sites in the spacer, while others have from 0 to at least 3. This restriction site polymorphism is strain-specific and not species-specific. It was confirmed for some strains by restriction analysis of clones containing most of the rDNA repeat unit. The current restriction map of the 74-OR23-1A rDNA repeat unit is presented.     

Linear programming analysis of VA/Q distributions: average distribution

The defining equations of the multiple inert gas elimination technique are underdetermined, and an infinite number of VA/Q ratio distributions exists that fit the same inert gas data. Conventional least-squares analysis with enforced smoothing chooses a single member of this infinite family whose features are assumed to be representative of the family as a whole. To test this assumption, the average of all ventilation-perfusion ratio (VA/Q) distributions that are compatible with given data was calculated using a linear program. The average distribution so obtained was then compared with that recovered using enforced smoothing. Six typical sets of inert gas data were studied. In all sets but one, the distribution recovered with conventional enforced smoothing closely matched the structure of the average distribution. The single exception was associated with the broad log-normal VA/Q distribution, which is rarely observed using the technique. We conclude that the VA/Q distribution conventionally recovered approximates a simple average of all compatible distributions. It therefore displays average features and only that degree of fine structural detail that is typical of the family as a whole.     

Interactions of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with monoamine oxidases.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a thermal breakdown product of a meperidine-like narcotic used by drug abusers as a heroin substitute, produces Parkinsonian symptoms in humans and primates. The nigrostriatal toxicity is not due to MPTP itself but to one or more oxidation products resulting from the action of monoamine oxidase (MAO) on this tertiary allylamine. Both MAO A and B catalyse the oxidation of MPTP to the 1-methyl-4-phenyl-2,3-dihydropyridinium species (MPDP+), which undergoes further oxidation to the fully aromatic 1-methyl-4-phenylpyridinium species (MPP+). These bio-oxidations are blocked by selective inhibitors of MAO A and B. Additionally, MPTP, MPDP+ and MPP+ are competitive inhibitors of MAO A and B. The A form of the enzyme is particularly sensitive to this type of reversible inhibition. Both MAO A and B also are irreversibly inactivated by MPTP and MPDP+, but not by MPP+. This inactivation obeys the characteristics of a mechanism-based or 'suicide' process. The inactivation, which is accompanied by the incorporation of radioactivity from methyl-labelled MPTP, is likely to result from covalent modification of the enzyme.     

The innervation of the pyloric region of the crab,Cancer borealis: Homologous muscles in decapod species are differently innervated

Summary The muscles of the pyloric region of the stomach of the crab,Cancer borealis, are innervated by motorneurons found in the stomatogastric ganglion (STG). Electrophysiological recording and stimulating techniques were used to study the detailed pattern of innervation of the pyloric region muscles. Although there are two Pyloric Dilator (PD) motorneurons in lobsters, previous work reported four PD motorneurons in the crab STG (Dando et al. 1974; Hermann 1979a, b). We now find that only two of the crab PD neurons innervate muscles homologous to those innervated by the PD neurons in the lobster,Panulirus interrruptus. The remaining two PD neurons innervate muscles that are innervated by pyloric (PY) neurons inP. interruptus. The innervation patterns of the Lateral Pyloric (LP), Ventricular Dilator (VD), Inferior Cardiac (IC), and PY neurons were also determined and compared with those previously reported in lobsters. Responses of the muscles of the pyloric region to the neurotransmitters, acetylcholine (ACh) and glutamate, were determined by application of exogenous cholinergic agonists and glutamate. The effect of the cholinergic antagonist, curare, on the amplitude of the excitatory junctional potentials (EJPs) evoked by stimulation of the pyloric motor nerves was measured. These experiments suggest that the differences in innervation pattern of the pyloric muscles seen in crab and lobsters are also associated with a change in the neurotransmitter active on these muscles. Possible implications of these findings for phylogenetic relations of decapod crustaceans and for the evolution of neural circuits are discussed.Abbreviations ACh acetylcholine - Carb carbamylcholine - cpv muscles of the cardio-pyloric valve - cpv7n nerve innervating muscle cpv7 - cv muscles of the ventral cardiac ossicles - cv1n nerve innervating muscle cvl - cv2n nerve innervating muscle cv2 - EJP excitatory junctional potential - IC inferior cardiac neuron - IV inferior ventricular neuron - IVN inferior ventricular nerve - LP lateral pyloric neuron - LPG lateral posterior gastric neuron - lvn lateral ventricular nerve - mvn medial ventricular nerve - p muscles of the pylorus - PD pyloric dilator neuron - PD _in intrinsic PD neuron - PD _ex extrinsic PD neuron - pdn pyloric dilator nerve - PY pyloric neuron - pyn pyloric nerve - STG stomatogastric ganglion - VD ventricular dilator neuron