Hans Gerhard Creutzfeldt (1885-1964): a life in neuropathology.
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Biomedical subjects
Publications and source records attributed to J H Wolf.
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Infusion of phenol into peripheral nerves is used clinically to manage spasticity. It produces relief of symptoms by chemical denervation. We simulated the clinical procedure by bathing the lateral plantar nerve of rats in 7% phenol solution for 20 min. We studied the innervation of muscle spindles in the plantar lumbrical muscles of untreated rats and in rats 4 and 6 weeks after a single phenol block. Spindles were identified by the immunoreactivity of nuclear bag(1) fibers to slow tonic myosin (antibody ALD 19). The integrity of the sensory and motor reinnervation of spindles was evaluated using a monoclonal antibody specific for a high molecular weight neurofilament protein. Four weeks after phenol block, muscle spindles were difficult to find, as their immunoreactivity to antibody ALD 19 was reduced. In those spindles studied, most (>80%) were completely denervated. The remainder of which were innervated by afferents only. None received efferent (gamma) innervation. After 6 weeks, spindles were readily identified and nearly all (>90%) received recognizable afferent innervation. A much smaller number (38%) received gamma innervation. Phenol block thus results in a complete denervation of muscle spindles, followed by a fairly rapid sensory reinnervation. Reinnervation by gamma motor neurons is either incomplete or significantly delayed.
Beginning in the 1880s, many mothers reported breastfeeding difficulties. Doctors blamed the stress of urban life. The "bad" human milk invariably produced by the mammary glands of urban women, some physicians charged, harmed babies as surely as the dirty and adulterated cow's milk common to the late nineteenth-century city. Mothers and pediatricians proved unusually susceptible to believing this allegation. Mothers, just learning about the germ theory of disease and anxious about protecting their babies from unseen microbes, found themselves gratefully relying on "scientific" food rather than on their own, apparently faulty, bodies. And pediatricians no longer had to defend their new specialty. Now they could point to the need for improved artificial food-given women's growing inability to lactate-as one justification for their specialty's existence. Under the influence of these mothers and doctors, the notion that human lactation is an unreliable body function became a cultural truth that has persisted unabated to the present day.
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An automated method is described to couple carboxyl-containing metabolites to the fluorophore 2-aminoanthracene in aqueous solution (containing 75% methanol) in the presence of N,N-dicyclohexylcarbodiimide. The reaction was optimized for N-acetylaspartate (N-Ac-Asp) and N-acetylaspartylglutamate (N-Ac-Asp-Glu). The reactions occurred within 5 min at room temperature in the presence of 0.5-2 mM HCl. At concentrations of electrolytes exceeding 10 mM the coupling reaction became suboptimal. Derivatization was performed in a commercial precolumn derivatization unit. Additional tubing was needed to provide the reagents prior to reversed-phase HPLC and fluorescence detection. The assay is linear over at least three orders of magnitude; as little as 1 pmol could reproducibly be assayed in 100 micrograms wet weight brain tissue extracted with a mixture of methanol and 4 mM HCl (9:1, v/v). N-Ac-Asp and N-Ac-Asp-Glu levels in several brain regions and spinal cord were similar to those so far reported. The compounds could not be detected in peripheral tissue. The advantages, prospects and limitations of the present approach over existing methods to estimate water-soluble carboxylic acids is discussed.
The cellular and extracellular brain concentration of valproic acid in freely moving rats has been estimated after intravenous injection of sodium valproate. Some rats were provided with a stereotaxically implanted dialysis probe in the striatum and a cannula in the heart through which the drug was injected and which allowed regular removal of blood. In other rats tissue levels of valproic acid were determined 5 and 90 min after drug injection. Valproic acid was determined by an automated precolumn derivatization procedure followed by HPLC separation and fluorimetric detection. Extracellular concentration was proportional to the blood concentration at every time interval, indicating rapid exchange of the drug between the two compartments. About 50% of the striatal content of valproate was in extracellular space. The experiments demonstrated the usefulness of microdialysis to estimate both the extracellular concentration and the average cellular drug levels, provided a sensitive analysis procedure is available.
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A method is described to automate the solid phase catalyzed reaction of a carbonyl group with labels containing a bromomethyl group. The acids to be determined must be soluble in an aprotic, non-aqueous reaction medium, such as acetonitrile. Special emphasis is placed on the solubility of the base, which serves as a catalyst. A suspension of potassium carbonate was prepared in acetonitrile. In this way, the effective surface area of the base is drastically enlarged resulting in faster reaction kinetics. The procedure is illustrated with the detection of fatty acids in serum and rat brain tissue with bromomethylmethoxycoumarin as label. The generality of our approach for HPLC determination of carbonyl compounds is discussed.
The carbohydrate moiety of mouse submandibular mucin (MSM) contains mainly D-mannose and 2-acetamido-2-deoxy-D-glucose together with sialic acid, D-galactose, and 2-acetamido-2-deoxy-D-galactose. O-Glycosylically bound saccharides, obtained by treatment of MSM with alkaline borohydride, were shown by methylation analysis to have the structure: alpha-NeuAc-(2----3)-beta-Gal-(1----3)-GalNAc-ol. N-Glycosylically bound saccharides obtained from MSM by hydrazinolysis, and analysed by 500-MHz 1H-n.m.r. spectroscopy, were shown to have the following comprehensive structures. (Formula: see text).
A method using HPLC has been developed for the detection of choline (Ch) and acetylcholine (ACh) using an immobilized enzyme reactor which converts Ch and ACh into hydrogen peroxide and betaïne. The formed H(2)O(2) is quantified by means of a solid-state peroxyoxalate chemiluminescence detector based on an immobilized fluorophore and addition of oxalate from a solid bed. The conditions necessary for chemiluminescence detection are obtained by using a make-up flow of acetonitrile after the enzyme reactor. Precipitation problems due to the poor solubility of salts in the final acetonitrile-water mixture are circumvented by adding a crown ether to the make-up flow. The reproducibility of the method was calculated to be 3.4-3.7% RSD. Detection limits are in the sub-picomole range and a linear range of at least three orders of magnitude is found. Measurements in urine and serum reveal no matrix effects.
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Distance is the major factor determining the frequency of social interaction with family and friends for elderly whites. Age, sex, marital status, length of residence, and income also affect the number of social contacts. These relationships have not been studied for elderly blacks. Utilizing data from a survey of 655 black urban residents 60 years old and older, this study investigated contacts with family and friends. The major finding was that the neighborhood is an important place for socializing with both family and friends for this population as is the case for working-class white elderly adults. A surprising finding is that, whereas social contacts increase with higher income for working-class elderly whites, for these black elderly adults who are of the working class and poor, social contacts decrease with higher income.