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Biomedical subjects

H M Wu

Publications and source records attributed to H M Wu.

At least 91 records · Page 5Linked to original sources

[Studies on the chemical constituents of Dendrobium loddigesii rolfe].

According to IR, UV, MS and NMR spectra of the compounds isolated from the fresh stem of Dendrobium loddigesii Rolfe (a Chinese medicine), 3 constituents were identified. They are shihunidine, shihunine and dendrophenol (4,4'- dihydroxy-3,3',5-trimethoxybibenzyl). Chemical reactions showed that shihunidine was derived from shihunine during isolation. Shihunidine and shihunine were shown to be inhibitors of Na+, K+-ATPase of the rat kidney.

Animals↗

Chemical and physiochemical comparison of advanced atherosclerotic lesions of similar size and cholesterol content in cholesterol-fed New Zealand White and Watanabe Heritable Hyperlipidemic rabbits.

Watanabe Heritable Hyperlipidemic (WHHL) and cholesterol-fed New Zealand White (CH-FED NZW) rabbits were sacrificed at 15 months of age or after 16 weeks of cholesterol feeding, respectively. During the experimental period, the arterial walls of both the CH-FED NZW and WHHL rabbits were exposed to similar amounts of cholesterol and the lesions which developed at the aortic arch had similar intimal thicknesses, total lipid and cholesterol content. However, the lesions of the WHHL rabbits morphologically resembled human plaques, and contained lipid in the form of smectic liquid crystalline droplets and cholesterol monohydrate crystals. The CH-FED NZW rabbits had lesions which were fatty streak-like, containing liquid crystalline cholesteryl ester droplets but few crystals. The aortic arch intimas of the CH-FED NZW rabbits contained significantly more cholesteryl ester, and less unesterified cholesterol and triglyceride, than those of the WHHL rabbits. The intimal compositions of the two rabbit models did not overlap. Analysis of the compositions predicted precipitation of cholesterol monohydrate crystals in the WHHL but not the CH-FED NZW. The physical state of the deposited cholesterol esters was similar in both with about half being in smectic liquid crystalline form at body temperature. Since the size and total lipid content of the lesions of the CH-FED NZW and WHHL rabbits were similar, we suggest that the greater time of exposure to hypercholesterolemia was important in the formation of cholesterol monohydrate crystal-containing plaques in the aortic arch of the WHHL rabbits.

Animals↗

Monoclonal antibody-mediated protection and neutralization of motility in experimental Proteus mirabilis infection.

A panel of monoclonal antibodies with specificity for a wound isolate of Proteus mirabilis was established. Of nine antibodies studied in detail, three were broadly reactive with various Proteus isolates, while six reacted in a serotype-specific fashion with the strain used for immunization. Five of the six serotype-specific antibodies were reactive with lipopolysaccharide. The sixth serotype-specific antibody, 4-F (immunoglobulin G1 [IgG1]), was potently protective in a burn wound sepsis model and recognized a protein antigen. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) analysis were used to determine that 4-F was reactive with flagellar protein. Approximately 1.3 micrograms of the antibody was sufficient to provide protection against 8 50% lethal doses of wound isolate, and approximately 26 micrograms provided full protection against challenge with 333 50% lethal doses. In vitro test results indicated that 4-F inhibited the motility of the wound isolate, and in vivo testing showed that it inhibited dissemination of the inoculum from the burn site to the liver and spleen. Whereas the antibody was highly effective in preventing the death of mice subsequent to challenge at a burn site, no protection was seen following an intraperitoneal challenge. These results may therefore indicate that the protection observed in the burn model is solely a reflection of the capacity of 4-F to neutralize bacterial motility.

Animals↗

Mode of inhibition of brain Na+,K+-ATPase by agelasidines and agelasines from a sea sponge.

The Na+,K+-ATPase from brain or kidney and sarcoplasmic reticulum (SR) Ca2+-ATPase were inhibited potently by agelasidine C (Agd-C) and agelasine B (Ags-B), the bioactive principles of sea sponge, while Agd-C and Ags-B exerted less potent inhibition of heart Na+,K+-ATPase. The ionized moiety in Agd-C and the long nonpolar side chains in Ags-B play important roles in their inhibitory action. The inhibition of Na+,K+-ATPase by Agd-C or Ags-B was virtually reversed by diluting with the inhibitor-free solution. Kinetic analysis of the inhibitory effects of Agd-C and Ags-B indicates that the inhibition of pig brain Na+,K+-ATPase is parabolic and noncompetitive with respect to ATP. This may indicate that the inhibition of Na+,K+-ATPase results from the binding of two molecules of Agd-C or Ags-B to one enzyme. The sigmoidal behavior (n = 1.3-1.4) in the K+ activation curve for Na+,K+-ATPase was strikingly intensified (n = 2.1) by Agd-C, whereas it was almost eliminated (n = 1.1) by Ags-B. These results suggest that the cooperative interaction between K+-binding sites on the enzyme was dramatically altered.

Animals↗

Bending and flexibility of kinetoplast DNA.

We have evaluated the extent of bending at an anomalous locus in DNA restriction fragments from the kinetoplast body of Leishmania tarentolae using transient electric dichroism to measure the rate of rotational diffusion of DNA fragments in solution. We compare the rate of rotational diffusion of two fragments identical in sequence except for circular permutation, which places the bend near the center in one case and near one end of the molecule in the other. Hydrodynamic theory was used to conclude that the observed 20% difference in rotational relaxation times is a consequence of an overall average bending angle of 84 +/- 6 degrees between the end segments of the fragment that contains the bending locus near its center. If it is assumed that bending results from structural dislocations at the junctions between oligo(dA).oligo(dT) tracts and adjacent segments of B DNA, a bend angle of 9 +/- 0.5 degrees at each junction is required to explain the observations. The extent of bending is little affected by ionic conditions and is weakly dependent on temperature. Comparison of one of the anomalous fragments with an electrophoretically normal control fragment leads to the conclusion that they differ measurably in apparent stiffness, consistent with a significantly increased persistence length or contour length in the kinetoplast fragments.

Animals↗

CAP binding to B and Z forms of DNA.

We have examined the interaction between the cyclic AMP receptor protein (CAP) and a small DNA fragment containing its specific recognition sequence by circular dichroism spectroscopy. The binding of CAP to this fragment induces a B to "C-like" change in the CD spectrum, which is different from that observed for non-specific binding. A one-to-one (CAP dimer to DNA) binding stoichiometry was deduced from spectroscopic titration data, as was a non-specific binding site size of 17 bp/dimer. In addition, we have compared the non-specific binding affinity of CAP for the B and Z forms of synthetic DNA copolymers. A slight preference for the B form was found. These results do not support the recent specific suggestion that CAP binds to a left-handed form of DNA (1), but indicate more generally that an optically detectable conformational change takes place in DNA on binding CAP.

Base Composition↗

A retrospective survey on side effects of praziquantel among 25,693 cases of schistosomiasis japonica.

A retrospective survey involving 25,693 persons was carried out in four provinces and the city of Shanghai, China between December 1981 until May 1982 to document relatively serious side effects of praziquantel used in a mass treatment programme for schistosomiasis japonica. Only 122 or 0.47% of those participating in the study had experienced relatively serious side reactions to the drug. Most had only one kind of side effects but two or more were recorded in a few patients. Neuropsychiatric reactions were seen in 39 persons (0.15%,) cardiovascular reactions in 37 (0.14%), hepatic changes in four (0.02%), dermatological reactions in 18 (0.07%) and delayed reactions resulting in fatigue and inability to work in 29 (0.11%). Praziquantel remains the drug of choice for the treatment of oriental schistosomiasis, it is highly effective and although side effects are minimal, caution should be taken in the treatment of chronic disease with heart failure, ascites, poor hepatic compensation and renal failure.

Adolescent↗

Stability of carbohydrate-modified vesicles in vivo: comparative effects of ceramide and cholesterol glycoconjugates.

The stability and tissue distribution of lipid vesicles modified at the surface by the incorporation of either a galactosyl ceramide (GalCer) or a galactosyl cholesterol (GalChol) glycoconjugate have been studied in mice by measuring the release of vesicle-entrapped 111In. Although the tissue distributions of both vesicle types were similar, the GalCer-containing vesicles were markedly less stable than those prepared with GalChol, whether administered orally or by intraperitoneal injection. Physical characterization of the vesicles in vitro suggests that the increased disruption rate for GalCer vesicles in vivo is related to structural instabilities induced by the cerebroside, which can then result in either an increased rate of vesicle uptake by tissues or a greater susceptibility to lysis. These studies demonstrate the importance of the nonpolar anchoring groups in determining the fate of surface-modified vesicles in vivo.

Administration, Oral↗

Solution structural studies of the A and Z forms of DNA.

We report transient electric dichroism studies of short double-helical DNA and poly[d(G-C)] fragments in alcohol/water mixtures. The limiting reduced dichroism and the rotational correlation time changed abruptly in the alcohol concentration range expected for the DNA B-to-A and poly[d(G-C)] B-to-Z transitions. The Z form of poly[d(G-C)] was also induced by mitomycin C crosslinking in aqueous solution. The rotational correlation times observed for A- and Z-DNA were approximately consistent with dimensions determined by crystallographic and fiber diffraction analysis: the estimated rise per base pair was 2.8 A for A-DNA and 3.7 A for Z-DNA in solution. In addition, the observed limiting reduced dichroism values for A- and Z-DNA were close to the theoretical limit of -1.5, requiring a structure in which the base transition moments are effectively perpendicular to the double-helix axis. This is the result expected for any DNA double helix having dyad symmetry in which the base pairs are flat and the base transition moments lie predominantly in the short axis of the base pair and therefore close to a helix dyad axis. Only B-DNA deviates from this rule, strongly reinforcing our earlier conclusion that the base pairs in B-DNA are not flat but are propeller twisted, either statically or as a dynamic average.

Animals↗

Kin preference in infant Macaca nemestrina.

The ability to recoginize conspecifics is a prerequisite for many types of social behaviour, including, for example, parent-offspring relation, mate selection and recognition, territorial defence and dominance coalitions. This ability is of special importance to Hamilton's kin selection hypothesis, which predicts that an individual's behaviour towards a conspecific will depend on the degree of genetic relatedness between them. Although recognition depends on previous experience between individuals in some species, this does not precluded the possibility that recognition could occur in its absence. For example, juveniles who disperse before nonlittermate siblings are born or adult males who do not participate in rearing their young might benefit from recognition abilities that are independent of prior association between the individuals. Here we show that young pigtail macaques prefer to interact with a related over an unrelated monkey in a laboratory test. Because subjects were separated from their dams at birth and reared apart from all other relatives, results suggest that kin recognition can occur in the absence of prior association with relatives.

Age Factors↗

Unfolding of nucleosomes by ethidium binding.

We report spectroscopic, hydrodynamic, and biochemical studies on the complex of ethidium bromide with 140 base pair nucleosomal core particles. Fluorescence titration indicates a greater intrinsic affinity of ethidium for nucleosomes than for DNA, and fluorescence depolarization measurements imply increased immobilization of ethidium bound to nucleosomes, but with more extensive dye-dye energy transfer compared to DNA-bound dye. Ethidium intercalated into DNA in nucleosomes has a limiting reduced linear dichroism of -0.45 at 320 nm and -0.25 at 530 nm. Both the energy transfer and dichroism results are consistent with clustering of the nucleosome-bound dye molecules. Electric dichroism measurements and ultracentrifugation studies reveal that structural distortion of the nucleosome accompanies ethidium binding, occurring in the range of r (ethidium residues per base pair) values from 0.02 to 0.06. The distortion transition is characterized by an increase in the negative limiting reduced dichroism from 0.29 to 0.45 at 265 nm, an increase in the field-induced viscosity-limited rotational orientation time from 0.8 to 3 mus, and a decrease in sedimentation coefficient from 10.5 to 8.2 S. The complex was modeled hydrodynamically as a cylinder of 335-A length and 67-A diameter, containing 1.4 superhelical turns of DNA. Dimethylsuberimidate cross-linked nucleosomes, or native nucleosomes in the presence of Mg2+, bind ethidium weakly and are not distorted. The periodicity of cutting sites produced by DNase II digestion of nucleosomes remains constant as ethidium is added, but the bandwidth increases. A thermodynamic model is proposed to interpret the binding isotherm, based on enhancement of drug binding affinity due to release of superhelical stress in the nucleosome-ethidium complex.

Base Composition↗