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Biomedical subjects

M Chu

Publications and source records attributed to M Chu.

At least 37 records · Page 2Linked to original sources
PubMed2000

Differential mechanisms mediating descending pain controls for antinociception induced by supraspinally administered endomorphin-1 and endomorphin-2 in the mouse.

We have previously demonstrated that both endomorphin-1 and endomorphin-2 produce their antinociception by the stimulation of mu-opioid receptors. However, the antinociception induced by endomorphin-2 contains an additional component, which is mediated by the release of dynorphin A (1-17) acting on kappa-opioid receptors. These studies were done to determine whether the antinociception induced by endomorphin-1 and endomorphin-2 given supraspinally was mediated by the activation of different descending pain control pathways in the mouse. Specific receptor antagonists or antisera against endogenous opioid peptides were injected intrathecally to block the receptors or bind the released endogenous opioid peptides, and endomorphin-1 or endomorphin-2 was then administered i.c.v. to activate the descending pain control systems to produce antinociception. The tail-flick response was used as antinociceptive test. The blockade of the alpha(2)-adrenoceptors and 5-hydroxytryptamine receptors in the spinal cord by i.t. injection of yohimbine and methysergide, respectively, inhibited the antinociception induced by i.c.v.-administered endomorphin-1 and endomorphin-2. However, the antinociception induced by endomorphin-2 was inhibited by i.t. pretreatment with delta(2)-opioid receptor antagonist naltriben or kappa-opioid receptor antagonist nor-binaltorphimine, but not by the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH(2) or the delta(1)-opioid receptor antagonist 7-benzylidene naltrexamine. Intrathecal pretreatment with antiserum against Met-enkephalin attenuated the antinociception induced by i.c.v.-administered endomorphin-2, but not endomorphin-1. Furthermore, i.t. pretreatment with antiserum against dynorphin A (1-17) also inhibited the antinociception induced by i.c.v.-administered endomorphin-2, but not endomorphin-1. Intrathecal pretreatment with antiserum against Leu-enkephalin or beta-endorphin did not inhibit i.c.v.-administered endomorphin-1- or endomorphin-2-induced antinociception. The results indicate that, like other opioid micro-receptor agonists, morphine, and [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin, endomorphin-1 and endomorphin-2 given i.c.v. produce antinociception by activating spinipetal noradrenergic and serotonergic pathways for producing antinociception. However, the antinociception induced by endomorphin-2 given i.c.v. also contains other components, which are mediated by the release of Met-enkephalin and dynorphin A (1-17) acting on opioid delta(2)- and kappa-receptors, respectively, in the spinal cord.

Adrenergic alpha-Antagonists↗
PubMed2000

[Separation and identification of polyclonal antibodies against type II fimbriae of actinomyces viscosus 5951].

OBJECTIVE: This study was aimed to prepare the polyclonal antibodies against type II fimbriae of actinomyces viscosus 5951. METHODS: Purified type II fimbriae of actinomyces viscosus 5951 were obtained by physical and chemical ways. Then antibodies against type II fimbriae were prepared through immunity of poly ways and tested by double immunodiffusion. RESULTS: The molecular quality of type II fimbriae was 34ku.Concentration of antibodies against type II fimbriae reached 1:64 after immunity of poly ways. CONCLUSION: The molecular quality of type II fimbriae was 34ku.The titre of the antibodies was 1:64, and had mild cross reaction with type I fimbriae.

English Abstract↗
PubMed1999

MRE-Binding transcription factor-1: weak zinc-binding finger domains 5 and 6 modulate the structure, affinity, and specificity of the metal-response element complex.

MRE-binding transcription factor-1 (MTF-1) contains six Cys(2)-His(2) zinc finger sequences, and it has been suggested that the zinc finger domain itself may function as a zinc sensor in zinc-activated expression of metallothioneins (MTs). Previous work has shown that a subset ( approximately 3-4) of the zinc fingers in MTF-zf play a structural role in folding and high-affinity metal-response element (MREd) binding, while one or more other fingers have properties consistent with a metalloregulatory role (weak zinc binding affinity in the absence of DNA). We show here that zinc fingers 5 and 6 correspond to the weak zinc-binding fingers in MTF-zf. Limited trypsinolysis of a Zn(6)-MTF-zf:MREd complex gives rise to a highly protease-resistant core fragment corresponding to amino acids 137-260 or N-terminal zinc fingers 1-4 of MTF-zf. Characterization of a collection of broken-finger (His --> Asn) and missing-finger mutants of MTF-zf reveals that deletion of zinc fingers 5 and 6 to create MTF-zf14 attenuates MREd binding affinity ( approximately 20-fold), while deletion of fingers 4-6 (MTF-zf13) results in a further 20-fold reduction of binding affinity with a nearly complete loss of specificity. Circular dichroism studies reveal that the binding of MTF-zf to the MREd induces a dramatic alteration of the structure of the MREd from a B-form to a double-helical conformation with A-like features. Formation of stoichiometric complexes with MTF-zf14, H279N (Deltazf5) MTF-zf, and MTF-zf13 induces comparatively less A-like structure. Steady-state fluorescence resonance energy transfer (FRET) spectroscopy has been used to globally define the orientation of the multifinger MTF-zf on the MREd. These experiments suggest that fingers 1-4 are oriented on the highly conserved TGCRCnC side of the MREd with fingers 5-6 bound at or near the gGCCc sequence. These findings are consistent with a model in which the N-terminal zinc fingers in MTF-zf are required for high affinity and specific binding to the consensus TGCRCnC core in a way which is subjected to structural and allosteric modulation by the weak zinc-binding C-terminal zinc fingers.

Amino Acid Sequence↗
PubMed1999

Isolation and structure of SCH 351633: a novel hepatitis C virus (HCV) NS3 protease inhibitor from the fungus Penicillium griseofulvum.

A new hepatitis C virus (HCV) protease inhibitor designated as Sch 351633 (1) was isolated from the fungus, Penicillium griseofulvum. Structure elucidation of 1 was accomplished by analysis of spectroscopic data, which determined compound 1 to be a bicyclic hemiketal lactone. Compound 1 exhibited inhibitory activity in the HCV protease assay with an IC50 value of 3.8 microg/mL.

Antiviral Agents↗
PubMed1999

Phenolic aporphine-benzylisoquinoline alkaloids from Thalictrum faberi.

From the roots of Thalictrum faberi, six new phenolic aporphine-benzylisoquinoline alkaloids, 3-hydroxy-6'-desmethyl-9-O-methylthalifaboramine (1), 3-hydroxythalifaboramine (2), 6'-desmethylthalifaboramine (3); 3,5'-dihydroxythalifaboramine (4), 5'-hydroxythalifaboramine (5) and 3-hydroxy-6'-desmethylthalifaboramine (6) were isolated. Their structures were established through the use of one- and two-dimensional NMR techniques. All of the tested alkaloids showed potent cytotoxic and antimalarial activities.

Alkaloids↗
PubMed1999

Immature thymocytes employ distinct signaling pathways for allelic exclusion versus differentiation and expansion.

T cell receptor (TCR) beta chain allelic exclusion occurs at the thymocyte CD4- 8- (double-negative, or DN) to CD4+ 8+ (double-positive, or DP) transition, concurrently with differentiation and cellular expansion, and is imposed by a negative feedback loop in which a product of the first rearranged TCRbeta allele arrests further recombination in the TCRbeta locus. All of the major events associated with the development of DP cells can be induced by the introduction of TCRbeta or activated Lck transgenes. Here, we present evidence that the signaling pathways that promote thymocyte differentiation and expansion of RAG-deficient DN cells but not those that suppress rearrangements of endogenous TCRbeta genes in normal DN cells are engaged by activated Ras. We propose that TCRbeta allelic exclusion is mediated by effector pathways downstream of Lck but independent of Ras.

Alleles↗
PubMed1999

PCR detection of Yersinia pestis in fleas: comparison with mouse inoculation.

The "gold standard" for identifying Yersinia pestis-infected fleas has been inoculation of mice with pooled flea material. Inoculated mice are monitored for 21 days, and those that die are further analyzed for Y. pestis infection by fluorescent-antibody assay and/or culture. PCR may provide a more rapid and sensitive alternative for identifying Y. pestis in fleas. To compare these assays, samples were prepared from 381 field-collected fleas. Each flea was analyzed individually by both PCR and mouse inoculation. Sixty of the 381 flea samples were positive for Y. pestis by PCR; 48 of these PCR-positive samples caused death in mice (80.0% agreement). None of the 321 PCR-negative samples caused death. Among the 12 mice that survived inoculation with PCR-positive samples, 10 were later demonstrated by serology or culture to have been infected with Y. pestis. This suggests that death of inoculated mice is less reliable than PCR as an indicator of the presence of Y. pestis in flea samples. Mouse inoculation assays produce results that are comparable to PCR only when surviving as well as dead mice are analyzed for infection. The rapidity and sensitivity (10 to 100 CFU of Y. pestis) of PCR suggest that it could serve as a useful alternative to mouse inoculation for routine plague surveillance and outbreak investigations.

Animals↗
PubMed1998

Pregnancy outcome following maternal organic solvent exposure: a meta-analysis of epidemiologic studies.

BACKGROUND: Evidence of fetal damage or demise from occupational organic solvent levels that are not toxic to the pregnant woman is inconsistent in the medical literature. The risk for major malformations and spontaneous abortion from maternal inhalation of organic solvent exposure during pregnancy was summarized using meta-analysis. METHODS: Medline, Toxline, and Dissertation Abstracts databases were searched to locate all research papers published in any language from 1996 to 1994. Included were studies that were case-control or cohort in design and indicated first trimester (or up to 20 weeks gestation for spontaneous abortion) maternal solvent exposure. A summary odds ratio (ORs) with 95% confidence intervals (CI) was calculated from research results combined by the Mantel-Haenszel method. RESULTS: In total, 559 studies were obtained from the literature search. Five studies for each outcome of interest qualified for inclusion in the analysis. The ORs for major malformations from five studies (n = 7,036 patients) was 1.64 (CI 1.16-2.30) and for spontaneous abortion from five studies (n = 2,899 patients) was 1.25 (CI 0.99-1.58). CONCLUSIONS: Maternal occupational exposure to organic solvents is associated with a tendency toward an increased risk for spontaneous abortion and additional studies may affect the trend. There is a statistically significant association with major malformations which warrants further investigation.

Abnormalities, Drug-Induced↗
PubMed1998

The effect of blood in the oral cavity on breath alcohol analysis.

The theory that blood (containing alcohol) present in the oral cavity may falsely increase breath analysis recently led to a successful appeal against a drink driving conviction. Subjects who had previously consumed vodka (37.2% alc/vol), at 30 ml/10 kg and reached a BAC (blood alcohol concentration) of between 0.05 and 0.10% were then given four oral solutions consisting of a control (distilled water), and 0.05, 0.10 and 0.15% aqueous alcohol (ethanol) solutions, administered in coded form. A four-way cross-over, blind, randomized assay was conducted with the solutions, with breath analyses conducted in the presence or absence of solution in the mouth. The first trial group (n = 18) received 2 ml of solution, and we found that the simulated 0.15, 0.10 and 0.05% alcohol solutions in the mouth produced BAC reading increases of 0.0088 +/- 0.0014, 0.0062 +/- 0.0008 and 0.0055 +/- 0.0010% respectively (p < 0.001). The second trial group (n = 20) received 1 ml of solution and produced BAC reading increases of 0.0047 +/- 0.0011 (p < 0.001), 0.0023 +/- 0.0008 (p < 0.01) and 0.0020 +/- 0.0006% (p < 0.05) respectively. In conclusion, these studies indicate that small volumes of blood (containing alcohol) in the mouth would not have a practical effect on breath analysis readings.

Clinical Trial↗
PubMed1998

Turnover of thrombomodulin at the cell surface occurs at a similar rate to receptors that are not actively internalized.

Loss of thrombomodulin (TM) from the endothelial cell surface is thought to contribute to thrombosis encountered in malignant and inflammatory disease. Internalization or endocytosis of TM from the cell surface has been proposed to be one mechanism by which TM levels are reduced. Previous work has led to a view that TM is rapidly internalized using a non-conventional pathway, under the direction of a signal motif in its extracellular domain. This is contrary to the clathrin-dependent route taken by most rapidly internalized receptors that possess signals in their cytoplasmic domains. However the internalization rate of TM has never been directly compared to known internalizing or non-internalizing molecules. Here we show that the rate and amount of uptake of TM (5-10% per hour) is indistinguishable from the non-internalizing influenza virus haemagglutinin (HA), and is considerably less than the actively internalizing low density lipoprotein receptor, which reaches a steady state of approximately 50% internalized in 15 min. The low level rate of TM and HA internalization observed is comparable to the rate of normal plasma membrane turnover. Furthermore, this uptake of TM does not require a signal in its extracellular domain.

Amino Acid Sequence↗
PubMed1997

Sch 54445: a new polycyclic xanthone with highly potent antifungal activity produced by Actinoplanes sp.

A novel antifungal agent, Sch 54445, was isolated from the fermentation broth of an Actinoplanes species. Sch 54445 was identified as a polycyclic xanthone related to the albofungin family of compounds on the basis of analyses of spectroscopic data. As a broad-spectrum antifungal agent, Sch 54445 exhibits highly potent activities against various yeasts and dermatophytes with MIC values approximately 0.00038 microgram/mL.

Actinomycetales↗
PubMed1997

Chronic endogenous hypercholecystokininemia promotes pancreatic carcinogenesis in the hamster.

In order to examine the effect of cholecystokinin on spontaneous and induced pancreatic carcinogenesis in the hamster, two sets of experiments were carried out, one involving long-term hypercholecystokininemia and one involving cancer induction during hypercholecystokininemia. The effect of hypercholecystokininemia, induced by pancreaticobiliary diversion (PBD), was studied for 8 months. Neither PBD animals nor sham-operated controls developed premalignant or malignant pancreatic lesions. However, in the PBD group the mean pancreatic weight, total protein content and DNA content were increased by 30, 29 and 27% respectively. No such increases were found in PBD animals receiving a cholecystokinin-A receptor antagonist during the last 24 days of the experiment. In the cancer induction study, the effect of PBD on N-nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis was studied for 3 months. Putative premalignant pancreatic lesions were diagnosed in all PBD hamsters and in four of 15 sham-operated controls. Pancreatic ductular carcinoma in situ was only found in PBD animals. The [3H]thymidine labeling index of the pancreatic lesions was significantly higher in the PBD group than in the controls. No such increase was observed in PBD animals receiving a cholecystokinin-A receptor antagonist during the last 5 days of the experiment. It is concluded that chronic endogenous hypercholecystokininemia promotes early phase pancreatic carcinogenesis, but does not per se cause development of premalignant or malignant pancreatic lesions in the hamster.

Animals↗
PubMed1997

Two separate regions in the genome of the tobacco etch virus contain determinants of the wilting response of Tabasco pepper.

Infection of Tabasco pepper by the tobacco etch virus (TEV) typically causes wilting associated with root necrosis. However, a strain of TEV, designated TEV nonwilting (TEV NW), is able to infect Tabasco pepper plants but does not cause wilting. In order to locate the genetic determinants responsible for the wilting response, a full-length cDNA clone of TEV NW from which infectious transcripts can be derived was made. A number of chimeric constructs were prepared by substituting cDNA fragments between TEV HAT (which causes wilting) and TEV NW clones. This approach was used to identify two wilting determinants in TEV HAT: one encompasses the 3' one-third of the P3 encoding region; the other spans the 3' end of the CI, the 6-kDa protein, and the 5' end of the VPg-NIa coding regions. Substitutions of both these TEV NW fragments into TEV HAT resulted in infection but not wilting of Tabasco pepper, while the replacement of either of the fragments alone did not alter the wilting response. This indicates that both TEV NW regions contain determinants necessary but not sufficient to alter the wilting response and that both must be present in order to avoid the wilting response. There was no difference between the in vitro transcription-translation products derived from constructs containing these regions from TEV HAT and TEV NW.

Amino Acid Sequence↗
PubMed1997

Effect of chronic endogenous hypergastrinaemia on pancreatic growth and carcinogenesis in the hamster.

BACKGROUND: To examine the effect of gastrin on spontaneous and induced pancreatic carcinogenesis in the hamster. METHODS AND RESULTS: Two sets of experiments were carried out, one involving long term hypergastrinaemia and one involving cancer induction during hypergastrinaemia. The effect of hypergastrinaemia accomplished by gastric fundectomy was studied for eight months. Neither fundectomised hamsters nor sham operated controls developed premalignant or malignant pancreatic lesions. In the fundectomy group, the mean pancreatic weight, total protein content, and DNA content was increased by 28%, 25%, and 25% respectively. No such increases were found in fundectomised animals receiving a cholecystokinin-B receptor antagonist during the last 24 days of the experiment. In the cancer induction study, the effect of fundectomy on N-nitrosobis(2-oxopropyl) amine induced pancreatic carcinogenesis was studied for three months. There were no significant differences in the incidence or [3H]-thymidine labelling index of focal pancreatic lesions between fundectomised and sham operated control animals. CONCLUSIONS: Fundectomy with chronic hypergastrinaemia induces pancreatic hypertrophy, but does not enhance N-nitrosobis (2-oxopropyl)amine induced pancreatic carcinogenesis in the hamster. The increases in growth were inhibited by a cholecystokinin-B receptor antagonist, indicating that the trophic effect of fundectomy is mediated by gastrin.

Animals↗
PubMed1997

Neurokinin receptor inhibitors: fermentation, isolation, physico-chemical properties, structure and biological activity.

Seven neurokinin (NK) receptor inhibitors SCH 60059 (1), SCH 60065 (2), SCH 64879 (3), SCH 60061 (4), SCH 60063 (5), SCH 60057 (7), and SCH 64878 (9) and two uncharacterized components 6 and 8, were isolated from the fermentation broth of a fungus taxonomically classified as an Acremonium sp. These compounds were isolated from the fermentation broth by ethyl acetate extraction. Purification and separation of the individual compounds were achieved by NK1 and NK2 assay-guided fractionation using gel filtration, reverse phase chromatography and HPLC. The NK active compounds were identified to be a family of polyhydroxy isoprenoid derivatives, including glycosylated members, by spectroscopic and degradation studies. Compounds 1 approximately 5 and 7 contain nine isoprene units connected in head to tail fashion and compound 9 contains fifteen isoprene units connected in a similar manner. All these compounds showed dual inhibition in NK1 and NK2 assays with IC50 values ranging from 2.5 approximately 11 microM in the NK1 assay and 6.8 approximately 16 microM in the NK2 assay.

Acremonium↗
PubMed1997

Relationship of short-term verbal memory to the need for hyperbaric oxygen treatment after carbon monoxide poisoning.

It has long been known that carbon monoxide (CO) poisoning has a spectrum of effects on cognitive functioning, including memory, perception, and attention. The current study reports the investigation of the effects of CO poisoning on short-term verbal memory, both rote and context aided. Impairment was measured before and after hyperbaric oxygen (HBO) treatment. Twenty-six patients who had been admitted for emergency treatment after exposure to significant CO poisoning were tested using a measure of short-term recall for word lists with no or varying degrees of internal context-aided structure. Impairment of context-aided memory (but not rote memory) has been previously reported to be associated with low relative frontal volume in psychiatric patients. Carbon monoxide poisoning was significantly associated with impairment of context-aided memory, with the degree of pretreatment impairment predicting the number HBO treatments judged to be necessary on the basis of clinical monitoring of the patient. In patients with poisoning of moderate severity, pretreatment performance in context-aided memory improved after the first HBO treatment. The implications of these findings for the effects of CO poisoning on frontal area function are discussed. The memory measure used in this study appears to have considerable potential usefulness in the clinical assessment of the severity of CO poisoning in patients treated in an emergency setting.

Adolescent↗