Biomedical subjects

R S Fischer

Publications and source records attributed to R S Fischer.

25 records · Page 2Linked to original sources

PubMed1991

Reversed lateralization of cognitive functions in right handers. Exceptions to classical aphasiology.

Most current and past research on the cerebral organization of cognitive functions has presupposed certain specialized hemisphere operations. At least for right handers, language and praxis are to be organized in the left hemisphere, while affective prosody, configurational spatial capacity, and global attention are lateralized in the right hemisphere. Deviations from these presuppositions, as in crossed aphasics and perhaps left handers, are generally considered to be 'exceptions' and either to disprove the rules or to be irrelevant to the rule. We report 4 very 'exceptional' cases, right handers with almost entirely reversed lateralization of functions. Analysis of the intrahemispheric relationships between functions suggests that there may be a specific neurobiology to the interrelationships between and among cognitive functions, handedness, and the intrahemisphere localization of the function.

Adult↗

PubMed1990

Remnants of an ancient pathway to L-phenylalanine and L-tyrosine in enteric bacteria: evolutionary implications and biotechnological impact.

The pathway construction for biosynthesis of aromatic amino acids in Escherichia coli is atypical of the phylogenetic subdivision of gram-negative bacteria to which it belongs (R. A. Jensen, Mol. Biol. Evol. 2:92-108, 1985). Related organisms possess second pathways to phenylalanine and tyrosine which depend upon the expression of a monofunctional chorismate mutase (CM-F) and cyclohexadienyl dehydratase (CDT). Some enteric bacteria, unlike E. coli, possess either CM-F or CDT. These essentially cryptic remnants of an ancestral pathway can be a latent source of biochemical potential under certain conditions. As one example of advantageous biochemical potential, the presence of CM-F in Salmonella typhimurium increases the capacity for prephenate accumulation in a tyrA auxotroph. We report the finding that a significant fraction of the latter prephenate is transaminated to L-arogenate. The tyrA19 mutant is now the organism of choice for isolation of L-arogenate, uncomplicated by the presence of other cyclohexadienyl products coaccumulated by a Neurospora crassa mutant that had previously served as the prime biological source of L-arogenate. Prephenate aminotransferase activity was not conferred by a discrete enzyme, but rather was found to be synonymous with the combined activities of aspartate aminotransferase (aspC), aromatic aminotransferase (tyrB), and branched-chain aminotransferase (ilvE). This conclusion was confirmed by results obtained with combinations of aspC-, tyrB-, and ilvE-deficient mutations in E. coli. An example of disadvantageous biochemical potential is the presence of a cryptic CDT in Klebsiella pneumoniae, where a mutant carrying multiple enzyme blocks is the standard organism used for accumulation and isolation of chorismate.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Dicarboxylic↗

PubMed1989

Distributed anatomy of transcortical sensory aphasia.

We examined four patients with transcortical sensory aphasia and eight with milder language disturbances but with similar thalamic and/or temporo-occipital lesions. Specific attention was paid to differentiation of the computed tomographic lesion site of the milder cases from the transcortical sensory aphasia cases. The critical lesion for transcortical sensory aphasia in these patients involved pathways in the posterior periventricular white matter adjacent to the posterior temporal isthmus, pathways that are probably converging on the inferolateral temporo-occipital cortex. Analysis of the language function of these patients, of the influence of sensory modalities on language function, and of the interaction between semantic memory and semantic lexical functions suggests the existence of a specific brain system for semantic functions. This semantic system has a particular distributed anatomy. We propose that damage to this system may have a variety of clinical manifestations in language and in memory, depending on the exact lesion configuration.

Aged↗

PubMed1989

Crossed aphasias can be mirror image or anomalous. Case reports, review and hypothesis.

Individual cases of crossed aphasia (aphasia after a right hemisphere lesion in a right-hander) have often been reported. A number of theories have been proposed as to the neuropsychological and/or nerobiological mechanisms that might underlie this phenomenon, but there is still disagreement about its language phenomenology and possible significance. We report 2 cases of crossed aphasia after stroke and review 34 cases from the literature with anatomical documentation of lesion site. Analysis of this material suggests that they represent at least two populations. There may be general conclusions concerning mechanisms of cerebral lateralization to be learned from the investigation of anomalous groups such as crossed aphasics.

Aged↗

PubMed1987

Glyphosate sensitivity of 5-enol-pyruvylshikimate-3-phosphate synthase from Bacillus subtilis depends upon state of activation induced by monovalent cations.

The 5-enol-pyruvylshikimate-3-phosphate (EPSP) synthase from Bacillus subtilis was activated by monovalent cations, catalytic activity being negligible in the absence of monovalent cations. The order of cation effectiveness (NH4+ greater than K+ greater than Rb+ greater than Na+ = Cs+ = Li+) indicated that the extent of activation was directly related to the unhydrated cation radius. Ammonium salts, at physiological concentrations, were dramatically more effective than other cations. Activation by ammonium was instantaneous, was not influenced by the counter ion, and gave a hyperbolic saturation curve. Hill plots did not show detectable cooperativity in the binding of ammonium. Double-reciprocal plots indicated that ammonium increases the maximal velocity and decreases the apparent Michaelis constants of EPSP synthase with respect to both phosphoenol pyruvate (PEP) and shikimate 3-phosphate (S3P). A direct relationship between sensitivity to inhibition by glyphosate and the activation state of EPSP synthase was demonstrated. Hill plots indicated a single value for glyphosate binding throughout the range of ammonium activation. Double-reciprocal plots of substrate saturation data obtained with ammonium-activated enzyme in the presence of glyphosate showed glyphosate to behave as a competitive inhibitor with respect to PEP and as a mixed-type inhibitor relative to S3P. The increased glyphosate sensitivity of ammonium-activated EPSP synthase is attributed to a lowering of the inhibitor constant of glyphosate with respect to PEP. Erroneous underestimates of sensitivities of some bacterial EPSP synthases to inhibition by glyphosate may result from failure to recognize cation requirements of EPSP synthases.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗

PubMed1986

Comparative action of glyphosate as a trigger of energy drain in eubacteria.

Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa, each possessing a 5-enolpyruvylshikimate 3-phosphate synthase that is sensitive to inhibition by glyphosate [N-(phosphonomethyl)glycine], provide a good cross-section of organisms exemplifying the biochemical diversity of the aromatic pathway targeted by this potent antimicrobial compound. The pattern of growth inhibition, the alteration in levels of aromatic-pathway enzymes, and the accumulation of early-pathway metabolites after the addition of glyphosate were distinctive for each organism. Substantial intracellular shikimate-3-phosphate accumulated in response to glyphosate treatment in all three organisms. Both E. coli and P. aeruginosa, but not B. subtilis, accumulated near-millimolar levels of shikimate-3-phosphate in the culture medium. Intracellular backup of common-pathway precursors of shikimate-3-phosphate was substantial in B. subtilis, moderate in P. aeruginosa, and not detectable in E. coli. The full complement of aromatic amino acids prevented growth inhibition and metabolite accumulation in E. coli and P. aeruginosa where amino acid end products directly control early-pathway enzyme activity. In contrast, the initial prevention of growth inhibition in the presence of aromatic amino acids in B. subtilis was succeeded by progressively greater growth inhibition that correlated with rapid metabolite accumulation. In B. subtilis glyphosate can decrease prephenate concentrations sufficiently to uncouple the sequentially acting loops of feedback inhibition that ordinarily link end product excess to feedback inhibition of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase by prephenate. The consequential unrestrained entry is an energy-rich substrates into the aromatic pathway, even in the presence of aromatic amino acid end products, is an energy drain that potentially accounts for the inability of end products to fully reverse glyphosate inhibition in B. subtilis. Even in E. coli after glyphosate inhibition and metabolite accumulation were allowed to become fully established, a transient period where end products were capable of only partial reversal of growth inhibition occurred. The distinctive metabolism produced by dissimilation of different carbon sources also profound effects upon glyphosate sensitivity.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗

PubMed1981

Regulation of glutamate dehydrogenase in Bacillus subtilis.

The activity of the nicotinamide adenine dinucleotide-dependent glutamate dehydrogenase in Bacillus subtilis was influenced by the carbon source, but not the nitrogen source, in the growth medium. The highest specific activity for this enzyme was found when B. subtilis was grown in a minimal or rich medium that contained glutamate as the carbon source. It is proposed that glutamate dehydrogenase serves a catabolic function in the metabolism of glutamate, is induced by glutamate, and is subject to catabolite repression.

Alanine Dehydrogenase↗