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Biomedical subjects

W L Parker

Publications and source records attributed to W L Parker.

At least 19 recordsLinked to original sources

Physicochemical characterization of a ouabain isomer isolated from bovine hypothalamus.

Recent reports have shown the presence of a ouabain-like inhibitor of Na+/K(+)-ATPase in humans. We have purified a bovine hypothalamic Na+/K(+)-ATPase inhibitory factor (HIF) by using affinity chromatography combined with HPLC. This inhibitor has a molecular weight of 584 as determined by ion-spray mass spectrometry, making it isobaric with ouabain. Glycosidase treatment or acid hydrolysis of HIF released only L-rhamnose, the hexose isomer found in ouabain, as detected by chiral GC/MS. Additionally, enzymatically generated desrhamnosyl HIF was found to have a molecular weight of 438, as does ouabagenin, the aglycone of ouabain. HIF and its aglycone were indistinguishable from ouabain and ouabagenin, respectively, by reversed-phase HPLC retention times. However, derivatization with naphthoylimidazole followed by HPLC revealed different retention times for naphthoylation products of HIF and ouabain. Subsequent CD spectroscopy on isolated naphthoylation products of HIF and ouabain confirmed that they were different. This study provides chromatographic and spectroscopic evidence that ouabain and HIF are isomeric cardenolides. The structural difference is presumed to account for the significant differences in biological properties observed for HIF and ouabain.

Animals

Hypothalamic Na+,K(+)-ATPase inhibitor constricts pulmonary arteries of spontaneously hypertensive rats.

Hypothalamic inhibitory factor (HIF) is an endogenous high-affinity inhibitor of Na+,K(+)-ATPase with ouabain-like properties and has been implicated in the pathogenesis of genetic systemic hypertension. We wondered whether HIF might also be associated with the recently demonstrated pulmonary hypertension of spontaneously hypertensive rats (SHRs). We compared HIF effects on the contractility of isolated 2- to 3-mm pulmonary artery (PA) rings from SHRs and age-matched normotensive Sprague-Dawley (SD) rats. HIF caused a reversible, concentration-dependent increase in tension in PA rings of SHR and SD rats, whereas ouabain did not. PA tension development with HIF (4 nM final concentration) was significantly higher in SHRs than in SD rats: 308 +/- 56 mg (mean +/- SE) vs. 137 +/- 26, respectively, p < 0.05. Abdominal aortic contractions induced by HIF did not differ between SHRs and SD rats. In SHRs, but not SD rats, the effect on PA rings was significantly greater than on aortic rings. In all cases, contraction was abolished by phentolamine but was unaffected by calcium-channel blockade using verapamil. HIF-induced tension development required external Ca2+. We conclude that PA rings from SHRs are more sensitive to Na+,K(+)-ATPase inhibitory effects of HIF than PA rings from SD rats, which may contribute to the observed pulmonary hypertension in SHR. Local modulation of the Na+,K(+)-ATPase-adrenergic neuroeffector interaction may be the vasoconstrictive mechanism of action of HIF in these vessels.

Animals

Aloe vera as a biologically active vehicle for hydrocortisone acetate.

Aloe vera, as a biological vehicle for hydrocortisone 21-acetate, was tested topically and systemically against acute inflammation. Systemically, the combination of A. vera and hydrocortisone produced a maximum 88.1% inhibition of edema. Polymorphonuclear leukocyte infiltration was reduced 91.1%. The topical inhibition of edema peaked at 97%. The possibility that A. vera has significant potential as a biologically active vehicle for steroids is discussed.

Acute Disease

The isolation of an active inhibitory system from an extract of aloe vera.

An Aloe vera extract was prepared with 50% ethanol. The resultant supernatant and precipitate were tested for anti-inflammatory activity using the croton oil-induced ear-swelling assay. The supernatant fraction decreased inflammation, when applied topically, by 29.2%, and the precipitate decreased inflammation by 12.1%. The authors have shown that the anti-inflammatory activity (inhibitory system) resides in the supernatant of a 50% ethanol extract.

Aloe

Isolation of a stimulatory system in an Aloe extract.

The authors' previous work on a 50% ethanol extract of Aloe vera was done to evaluate anti-inflammatory activity using the croton oil-induced ear swelling assay. The anti-inflammatory activity was found in the supernatant fraction. The supernatant fraction decreased inflammation, when applied topically, by 29.2%, and the precipitate decreased inflammation by 12.1%. However, in the present work, the precipitate fraction decreased the wound diameter by an average of 47.1% (stimulatory system). Little or no wound healing activity was found in the supernatant. Aloe vera appears to act as a modulatory system toward wounds and inflammation and is a potentially valuable tool for managing lower extremity conditions.

Adult

Aerocyanidin, a new antibiotic produced by Chromobacterium violaceum.

Aerocyanidin, a new antibiotic containing an isonitrile group, has been isolated from fermentations of Chromobacterium violaceum ATCC 53434. Structure 1 was assigned on the bais of spectroscopic characterization of the antibiotic and of a degradation product that results from treatment with base. The antibiotic is primarily active against Gram-positive bacteria.

Anti-Bacterial Agents

Xylocandin: a new complex of antifungal peptides. II. Structural studies and chemical modifications.

Xylocandins A1, A2, B1, B2, C1, C2, D1 and D2 are new antifungal peptides isolated from Pseudomonas cepacia ATCC 39277. The molecular weights of the xylocandins were determined by fast atom bombardment mass spectrometry (A1 m/z 1,215; A2 1,199; B1 1,229; B2 1,213; C1 1,097; C2 1,081; D1 1,083; D2 1,067). Each xylocandin is a cyclic peptide containing glycine, serine, asparagine (1-3 residues), beta-hydroxytyrosine, and an unusual amino acid with the formula C18H37NO5. Additionally A1, A2, D1 and D2 contain 2,4-diaminobutyric acid; A1, B1, C1 and D1 contain erythro-beta-hydroxyasparagine; and A1, A2, B1 and B2 contain xylose. For each xylocandin pair, an erythro-beta-hydroxyasparagine residue in the first component of the pair is thus replaced by an asparagine in the second component, accounting for the 16 dalton mass difference for each pair. Chemical modification of A1 and A2 at the diaminobutyric acid and beta-hydroxytyrosine residues was used to probe structural requirements for activity.

Anti-Bacterial Agents

Phenacein--an angiotensin-converting enzyme inhibitor produced by a streptomycete. II. Isolation, structure determination and synthesis.

Phenacein, an inhibitor of angiotensin-converting enzyme, has been isolated from the fermentation broth of a Streptomyces species belonging to the Streptomyces tanashiensis-zaomyceticus group. The inhibitor was shown to be 3,6-dihydroxy-1-phenazinecarboxylic acid by spectroscopic, degradative and synthetic methods.

Angiotensin-Converting Enzyme Inhibitors

Cepacin A and cepacin B, two new antibiotics produced by Pseudomonas cepacia.

Two new acetylenic antibiotics, cepacins A and B, have been isolated from the fermentation broth of Pseudomonas cepacia SC 11,783 and assigned structures 1 and 2. Cepacin A has good activity against staphylococci (MIC 0.2 micrograms/ml) but weak activity against streptococci (MIC 50 micrograms/ml) and the majority of Gram-negative organisms (MIC values 6.3 approximately greater than 50 micrograms/ml). Cepacin B has excellent activity against staphylococci (MIC less than 0.05 micrograms/ml) and some Gram-negative organisms (MIC values 0.1 approximately greater than 50 micrograms/ml).

Anti-Bacterial Agents