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Biomedical subjects

J T Henderson

Publications and source records attributed to J T Henderson.

At least 37 records · Page 2Linked to original sources

Localization of CNTF immunoreactivity to neurons and astroglia in the CNS.

Species specific antibodies were raised to a peptide of rat ciliary neurotrophic factor (CNTF-amino acids number 131-147). Following affinity purification, these antibodies were used to determine the pattern of CNTF immunoreactivity in adult rat and mouse brain, spinal cord, and sciatic nerve. Alternate sections stained using neurofilament and the affinity purified anti-CNTF antibody (HARC-1) demonstrate that CNTF immunoreactive neurons are present within the facial nucleus, dentate gyrus, olfactory bulb, basal forebrain, locus coeruleus, cortex and substantia nigra. In addition, neurons throughout the hippocampus, and Purkinje cells within the cerebellum also exhibit CNTF immunoreactivity. CNTF immunopositive neurons demonstrate a preponderance of nuclear staining, with some staining present in the cytoplasm. Alternate sections incubated with glial fibrillary acidic protein (GFAP) antibody also demonstrate glia which are positive for CNTF. In the peripheral nervous system, Schwann cells of the sciatic nerve exhibit strong immunoreactivity for CNTF, however staining is confined to the cytoplasm and is absent from the cell nucleus. These data demonstrate that CNTF immunoreactivity is broadly distributed throughout neurons and glia of the adult rodent nervous system.

Amino Acid Sequence↗

Systemic administration of ciliary neurotrophic factor induces cachexia in rodents.

Ciliary neurotrophic factor (CNTF) has previously been shown to promote the survival of several classes of neurons and glial. We report here that in addition to its effects on the nervous system, CNTF can induce potent effects in extra-neural tissues. Implantation of C6 glioma cells engineered to secrete CNTF either subcutaneously or into the peritoneal cavity of adult mice, or systemic injections of purified rat or human recombinant CNTF, resulted in a rapid syndrome of weight loss resulting in death over a period of 7-10 d. This weight loss could not be explained by a reduction in food intake and involved losses of both fat and skeletal muscle. CNTF also induced the synthesis of acute phase proteins such as haptoglobin. Implantation of C6 lines expressing a nonsecreted form of CNTF, or the parental C6 line itself, did not result in wasting effects. Analysis of this CNTF-induced wasting indicates similarities with the previously described cachectins, tumor necrosis factor, interleukin 6, and leukemia inhibitory factor, but does not involve the induction of these cytokines.

Animals↗

Purification and primary structure of pediocin PA-1 produced by Pediococcus acidilactici PAC-1.0.

The plasmid-encoded bacteriocin pediocin PA-1, produced by the gram-positive bacterium Pediococcus acidilactici strain PAC-1.0, was purified to homogeneity. The purified product exhibited antibacterial activity against several gram-positive bacterial strains, including the food pathogen Listeria monocytogenes. Pediocin PA-1 is a 4629-Da peptide with 44 amino acids and two disulfide bonds. The amino acid sequence and arrangement of the disulfide bonds were determined. Sequence data were used to calculate an isoelectric point of 10.0. The small and basic nature of PA-1 is comparable to several other bacteriocins produced by gram-positive bacteria. Reported sequences of other bacteriocins and of other antimicrobial peptides from diverse origins bear no resemblance to the sequence reported here.

Amino Acid Sequence↗

A semi-micromethod for the determination of the extinction coefficients of duplex and single-stranded DNA.

We have developed a rapid and convenient procedure for the determination of concentrations and extinction coefficients of oligo- and polynucleotides. It offers significant advantages over other methods in terms of precision and the ability to detect artifactual or erroneous results. Samples are first completely digested with appropriate enzymes to mononucleotides and nucleosides. Using the multicomponent linear regression capabilities of commonly available spreadsheet programs, the absorbance spectrum of the digest can be analyzed as a linear combination of the contribution of the possible constituent monomers. If all the spectral components present have been included, the analysis yields the concentration of each of the monomer species whose sum is the concentration (in monomer units) of the original undigested sample. When combined with the predigest absorbance spectrum, the extinction coefficients of the intact sample can then be calculated. The analysis also yields the fractional base composition of the oligomer or polymer. The extensive spectral data provided by digital read-outs of modern spectrophotometers permit the application of sensitive tests of the goodness of fit, thus facilitating the detection of artifacts and sample inhomogeneity. Both single-strand and duplex structures can be analyzed comfortably in sample sizes of 25 to 35 nmol (total) of mononucleotides with a precision of 1%. The concentrations obtained by this method agree, on the average, within 0.2% with those determined by phosphate analysis of the same sample. The method also yields the base composition with an accuracy of ca. 5% for high-molecular-weight polymers and 2% for short oligomers (15-20 bp) when compared to the predicted values.

Base Composition↗

Chemical cross-linking of bovine retinal transducin and cGMP phosphodiesterase.

The bifunctional reagents para-phenyldimaleimide and maleimidobenzoyl-N-hydroxysuccinimide ester were used to chemically cross-link the subunits of the transducin and cGMP phosphodiesterase (PDE) complexes of bovine rod photoreceptor cells. The cross-linked products were identified by Western immunoblotting using antisera against purified subunits of transducin (T alpha and T beta gamma) and PDE. Oligomeric cross-linked products of transducin subunits as large as (T alpha beta gamma)3 were observed in the latent form of transducin with bound GDP. In addition to the expected T alpha beta and T beta gamma cross-linked products, a (T alpha gamma)2 structure was detected. The close proximity of T alpha and T gamma suggests that T gamma may play a role in conferring the specificity of the interaction between T alpha and rhodopsin. Most of the oligomeric cross-linked structures between T alpha and T beta gamma were diminished in the activated form of transducin, with guanosine 5'-(beta, gamma-imidotriphosphate) (Gpp(NH)p) bound. However, cross-linking between T beta and T gamma was not altered. These results suggest that transducin exists as an oligomer in solution which dissociates upon the binding of Gpp(NH)p. To identify the possible interacting domains between the T alpha, T beta, and T gamma subunits, the cross-linked products were subjected to limited tryptic proteolysis. Several cross-linked tryptic peptides of transducin subunits were found and include the cross-linked products of the N terminus 15-kDa fragment of T beta and the C terminus 5-kDa fragment of T alpha, T gamma and the 12-kDa fragment of T alpha, T gamma and the 15-kDa as well as the 23-kDa fragments of T beta, and an intra-T alpha cross-linked product of the 2- and 21-kDa fragments. These results have allowed the construction of a topographical model for the transducin subunits. The organization of the subunits of PDE (P alpha, P beta, and P gamma) was also studied. The formation of the high molecular size cross-linked products of PDE resulted in the concurrent loss of the P beta and P gamma subunits, suggesting that they are in close proximity. Finally, the interaction between transducin and PDE was examined by chemical cross-linking of transducin-Gpp(NH)p and PDE. Two additional cross-linked products of 180 and 210 kDa were obtained which could be due to the cross-linking of T alpha or T beta with P alpha beta subunits.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases↗

Assignment of the aromatic 1H-NMR resonances of myotoxin a isolated from the venom of Crotalus viridis viridis.

The 400 MHz 1H-NMR spectrum of myotoxin a from the venom of Crotalus viridis viridis is described. The identification of spin systems in the aromatic region corresponding to the six aromatic residues of myotoxin a was completed using both one- and two-dimensional NMR spectroscopy and the pH dependence of chemical shifts. Assignments of these spin systems to specific residues was possible for the singly occurring amino acids Tyr-1 and Phe-12. Resonances from Tyr-1, His-5 and His-10 were shifted significantly from their random coil values in a pH-dependent manner. These shift perturbations were deemed evidence of a helical arrangement of the amino terminal region which placed these residues in close proximity to each other.

Animals↗

Antigenic relationships between Mojave toxin subunits, Mojave toxin and some crotalid venoms.

Immunochemical responses of a number of pit viper venoms to antibodies derived separately from the acidic and basic subunits were investigated by enzyme linked immunosorbent assay (ELISA) and Ouchterlony immunodiffusion. The polyclonal antisera to the basic subunit were generated in rabbits, whereas mouse hybridoma cell cultures were used to produce antibodies to the acidic subunit. The immunochemical response of a venom correlated well with published values for LD50 dose for the test venom. Many venoms that elicited a positive response with antiserum to the basic subunit also reacted strongly with the hybridoma derived antibodies to the acidic subunit. The data support the conclusion that crotalid venoms which are more lethal have in common a potent venom component that is immunochemically related to Mojave toxin.

Animals↗

Tioconazole in the treatment of fungal infections of the skin. An international clinical research program.

In 32 studies involving 1,304 patients tioconazole 1% dermal cream has been shown to be effective and safe in the treatment of a wide variety of superficial fungal infections of the skin and erythrasma. Tioconazole cream is more effective than miconazole nitrate 2% cream in the treatment of pityriasis versicolor and in infections with Trichophyton rubrum and Trichophyton mentagrophytes which cause 70% of dermatophyte infections in man. Data from comparisons with econazole and clotrimazole are too few to allow conclusions to be drawn on relative efficacy. All the creams were easy to apply and there were no serious adverse reactions, local or systemic.

Adolescent↗

Smoking and risk factors in deep vein thrombosis.

The incidence of deep vein thrombosis (DVT) as diagnosed by the 125I fibrinogen test (125IFT) was determined in a series of 300 newly admitted medical and 201 surgical patients. 6 medical patients died before 125IFT screening could be completed. The incidence of DVT was 14% in medical patients and 18% in surgical patients. Increasing age, a malignant condition and a past history of thromboembolism all increased the risk of DVT. Increasing levels of cigarette smoking were found to be associated with a reduced incidence of DVT. Although statistical significance was achieved at only the 10% level for this finding it is in agreement with the results from studies on patients with myocardial infarction. The protective effect of cigarrette smoking was observed at all ages, and in both medical and surgical patients.

Adult↗

Managed care and women's health: access, preventive services, and satisfaction.

This paper examines insured women's access to health care, receipt of preventive services, and satisfaction with care by the types of health plans in which they are enrolled. Three types of plans are compared: managed care (HMOs and PPOs), fee-for-service with utilization controls, and traditional fee-for-service. For women who have been enrolled in their plans for at least one year, we find the same or better access to care in managed care plans as compared with other plans; receipt of more gender-specific clinical preventive services in managed care plans, but no differences among types of plans for non-gender-specific preventive services or counseling services; and lower satisfaction with care in managed care plans. The implications for practice and policy are discussed.

Adult↗

Gender and patient satisfaction in managed care plans: analysis of the 1999 HEDIS/CAHPS 2.0H Adult Survey.

This paper investigates gender differences in satisfaction, and in the variables associated with satisfaction, using the Consumer Assessment of Health Plans Study (CAHPS) adult questionnaire administered by the National Committee for Quality Assurance (NCQA) as part of HEDIS 1999. Data represent 97,873 men and women enrolled in 206 commercial managed care plans nationwide. Mean plan-level gender differences in satisfaction measures are small, with no consistent pattern of one gender being more satisfied than the other. Controlling for health plan, member, utilization, and selected HEDIS performance indicators, health plan characteristics account for the largest proportion of variance explained in satisfaction. Not-for-profit status and lower turnover of primary care providers are stronger determinants of women's than men's satisfaction. We conclude that it can be useful to analyze CAHPS scores by gender to identify areas for quality improvement in women's health care.

Adolescent↗