Search PubMed⌕ Search

Biomedical subjects

L Gu

Publications and source records attributed to L Gu.

At least 91 records · Page 5Linked to original sources
PubMed1996

Genetic-dietary regulation of serum paraoxonase expression and its role in atherogenesis in a mouse model.

In an effort to identify genetic factors contributing to atherogenesis, we have studied inbred strains of mice that are susceptible (C57BL/6J) and resistant (C3H/HeJ) to diet-induced aortic fatty streak lesions. When maintained on a low-fat diet, HDL isolated from both strain C57BL/6J (B6) and C3H/HeJ (C3H) mice protect against LDL oxidation in a coculture model of the artery wall. However, when maintained on an atherogenic diet high in fat and cholesterol, the HDL isolated from B6 mice lose the capacity to protect, whereas HDL from C3H mice protect equally well. Associated with the loss in the ability of HDL to protect is a decrease in the activity of serum paraoxonase, a serum esterase carried on HDL that has previously been shown to protect against LDL oxidation in vitro. The levels of paraoxonase mRNA decreased in B6 mice upon challenge with the atherogenic diet but increased in C3H, indicating that paraoxonase production is under genetic control. In a set of recombinant inbred strains derived from the B6 and C3H parental strains, low paraoxonase mRNA levels segregated with aortic lesion development, supporting a role for paraoxonase in atherogenesis.

Amino Acid Sequence↗
PubMed1996

Genetic mapping of two blood pressure quantitative trait loci on rat chromosome 1.

A genetic map for rat chromosome 1 was constructed using 66 microsatellite markers typed on either or both of two populations derived from inbred Dahl salt-sensitive (S) rats: F2(LEW x S) n = 151, and F2(WKY x S) n = 159. These populations had been raised on a high salt (8% NaCl) diet. Systolic blood pressure and heart weight were found to be genetically linked to two separate regions on rat chromosome 1 in the F2(LEW x S) population. One region was centered around the anonymous SA locus and accounted for 24 mmHg of blood pressure. The other region was 55 cM from the SA locus centered around a cluster of cytochromes P450 loci, and accounted for 30 mmHg of blood pressure. Since blood pressure and heart weight were highly correlated these same regions were also linked to heart weight. These results were cross-specific as linkage of these chromosome 1 regions to blood pressure and heart weight was not observed in several other F2 populations derived by crossing S and other normotensive control strains. This is presumably due to different alleles and/or different genetic backgrounds in the various populations. The SA region of chromosome 1 was found to influence body weight in F2(LEW x S) rats. Combining the present data with our previously published data on the F2(LEW x S) population showed that four separate quantitative trait loci with additive effects accounted for 106 mmHg and 38% of the total variance of blood pressure and for 506 mg and 34% of the total variance of heart wt.

Animals↗
PubMed1996

Long-term follow-up of minimal residual disease in childhood acute lymphoblastic leukemia patients by polymerase chain reaction analysis of multiple clone-specific or malignancy-specific gene markers.

Two types of markers, namely the clone-specific markers including T-cell receptor (TCR) gamma, TCR delta, and Ig heavy-chain (IgH) gene rearrangements, and malignancy-specific fusion gene mRNA such as SIL-TAL-1, BCR-ABL, and HRX-partner genes, were investigated by molecular biology techniques in 65 Chinese patients with acute lymphoblastic leukemia (ALL). In combination, these markers were informative among 96% of patients. Minimal residual disease (MRD) was followed up in 23 of these patients with available materials over a period varying from 8 to 54 months with at least one leukemia-specific probe. In most children, MRD was decreased continuously to an ultimately undetectable level within 6 to 12 months after remission induction therapy. One patient exhibited low-level residual leukemic cells for 4 years before the MRD turned negative. Another patient remained in complete remission for 45 months, although a positive signal was detected at 34 months using TCR delta probe, but was negative with a TCR gamma marker which was positive at presentation. In three patients who relapsed, MRD either persisted through the clinical course or became positive and eventually increased 3-11 months before clinical relapse. These data suggested that the combined use of multiple gene markers is a valuable tool for the PCR-based MRD detection, since it can cover most ALL patients. Furthermore, long-term follow-up of MRD is helpful for determining the dosage as well as the period of maintenance chemotherapy and for predicting impending relapse.

Base Sequence↗
PubMed1996

[Capsaicin-sensitive afferent neurons and endogenous nitric oxide (NO) mediate the gastric acid secretion and hyperemic responses to intragastric peptone].

Using hydrogen gas clearance technique to measure gastric mucosal blood flow (GMBF) and a high dose of capsaicin to ablate the capsaicin-sensitive afferent neurons, the role of capsaicin-sensitive neurons in the gastric acid secretion and hyperemic response to intragastric peptone was investigated. The results were as follows: (1) there was an increase in acid secretion associated with the hyperemic response to intragastric peptone; (2) pretreatment with a high dose of capsaicin to ablate afferent neurons completely abolished the gastric hyperemic response to intragastric peptone and partially inhibited the acid secretion; (3) the gastric hyperemic response to intragastric peptone was completely blocked by pretreatment with L-nitro-arginine methyl ester (L-NAME), whereas the acid secretion was significantly attenuated; (4) inhibited effects of L-NAME on acid secretion and GMBF could be reversed by pretreatment with L-arginine (L-ARG); (5) pretreatment with atropine inhibited gastric acid output (GAO) and partially attenuated GMBF. These results suggested that capsaicin-sensitive afferent neurons and endogenous NO were involved in the gastric acid secretion and hyperemic response to intragastric peptone and the hyperemic response was mediated by both cholinergic and noncholinergic neurons.

Animals↗
PubMed1996

[A prospective study on causal factors of female infertility with laparoscopy and transvaginal B-ultrasound].

OBJECTIVE: To study the casual factors of female infertility with laparoscopy and B-ultrasound. METHODS: Eighty-five infertile women were evaluated by serial transvaginal B-ultrasound scans for follicular development and ovulation and by laparoscopic examinations 2 to 6 days after ovulation. RESULTS: The patterns of follicular development and ovulation detected by B-ultrasound were: (1) ovulation from normal follicle (ONF) (56.47%); (2) ovulation from two follicles at the same time (O2F) (5.88%); (3) ovulation from small follicle (OSF) (16.47%); (4) ovulation from polycystic ovaries (PCO) (3.53%); (5) luteinized unruptured follicle syndrome (LUFS) (7.06%); (6) anovulation (10.90%). Laparoscopic examinations showed that the incidence of partial and complete tubal obstruction was 32.94% and pelvic adhesions 35.29%. Pelvic tuberculosis was found in 20.00%, which was the main disease leading to pelvic adhesions (46.67%), and tubal obstruction (60.71%). Endometriosis (EMS) was discovered in 36 cases (42.35%), among them, 30 (83.33%) had patent tubes. The stigmas or/and corpus hemorrhagica were seen in 60 out of 70 patients in whom ovulation had been diagnosed by B-ultrasound. 6 cases were defined as "mechanically unruptured follicle syndrome". CONCLUSIONS: Abnormal follicular development may result in female infertility. Pelvic tuberculosis is another main causal factor of infertility. Endometriosis related infertility may rather result from other factors than tubal obstruction. Laparoscopic examinations combined with transvaginal B-ultrasound scans are very useful approaches in the etiological study of female infertility.

Adult↗
PubMed1996

[Histologic examination and immunohistochemical analysis of estrogen and progesterone receptors of eutopic and ectopic endometrium in patients with endometriosis].

OBJECTIVE: To study the differences of histologic dating and steroid receptors between ectopic and eutopic endometrium in patients with endometriosis. METHODS: Histologic examinations were done on eutopic and ectopic endometrium in 28 patients with pelvic endometriosis, and estrogen and progestrone receptors concentrations were determined by immunochemical ABC method in 15 patients. All the ectopic tissues were biopsied from peritoneal lesions. RESULTS: In 67.9% patients, the ectopic endometrium development was retardated and 14.3% accelerated as compared with eutopic endometrium, and only 17.9% identical. The estrogen receptors (ER) and progesterone receptors (PR) contents of ectopic endometrium were significantly lower than those of eutopic endometrium in glandular cells (P < 0.01, P < 0.05 respectively), while differences were not significant in stroma cells. CONCLUSIONS: The advantage of the immunochemical technique is that it can definitely locate the site of receptors in the histologic section. The difference in histologic dating and ER and PR concentrations in the eutopic and ectopic endometrium may be accounted for by the different steroid environments and pathogenic theory of peritoneum metaplasia.

Endometriosis↗
PubMed1996

[Effects of gastric mucosal blood flow (GMBF) on the role of adaptive cytoprotection of rat gastric mucosa].

By the use of hydrogen gas clearance technique, we have investigated the role of GMBF in the adaptive cytoprotection induced by intragastric perfusion with low concentration prior to high concentration of HCl plus ethanol. The results were as follows: (1) intragastric perfusion with low concentration prior to high concentration of HCl plus ethanol led to an adaptive cytoprotection, i.e., the gross and the deep damage were decreased by 47.09% and 44.57% respectively, as compared with those caused by high concentration of HCl plus ethanol alone; correspondingly, GMBF also showed an adaptive hyperemic response, i.e., GMBF was increased by 28.02% as compared with that due to high concentration alone; (2) close arterial infusion of vasopressin blocked the adaptive hyperemic response and abolished the adaptive cytoprotection; (3) intravenous indomethacin reduced the basal GMBF, and abolished both the adaptive hyperemic response and cytoprotection; furthermore, the gross and deep damage were aggravated compared with that caused by high concentration alone. The results showed that the adaptive hyperemic response of gastric mucosa was involved in the adaptive cytoprotection and suggested that the adaptive cytoprotection of endogenous prostaglandin might be partially related to the increase of GMBF.

Adaptation, Physiological↗
PubMed1995

Relationship of DNA topoisomerase II alpha and beta expression to cytotoxicity of antineoplastic agents in human acute lymphoblastic leukemia cell lines.

The levels of expression of topoisomerase II alpha and topoisomerase II beta were investigated in six established cell lines of human childhood acute lymphoblastic leukemia (ALL) as a function of doubling time, cell cycle distribution, and of sensitivity to the antineoplastic agents Adriamycin and etoposide. The slowest growing cell line, ALL-G, was most sensitive to both drugs, whereas the fastest growing cell line, ALL-C, was 15.3- and 6.4-fold more resistant than ALL-G to Adriamycin and etoposide, respectively. Furthermore, ALL-W, the second most rapidly dividing cell line, was most resistant to both Adriamycin (22.8-fold) and etoposide (14.1-fold). Expression of topoisomerase II alpha varied inversely with doubling time, whereas no correlation was found between topoisomerase II beta levels and doubling time. Expression of topoisomerase II beta varied inversely with that of topoisomerase II alpha. The level of topoisomerase II alpha correlated directly with the percentage of cells in S and G2-M phases, whereas topoisomerase II beta expression varied directly with the number of cells in G1. An inverse correlation was found between the level of expression of topoisomerase II beta and resistance to Adriamycin, whereas a direct correlation was observed between the level of expression of topoisomerase II alpha and resistance to Adriamycin. Studies with etoposide, although not statistically significant, were consistent with the pattern observed with Adriamycin. These findings suggest that in ALL cells, cytocidal activity of Adriamycin and etoposide may be mediated, at least in part, by topoisomerase II beta.

Antineoplastic Agents↗
PubMed1995

Acetylation of lysine 40 in alpha-tubulin is not essential in Tetrahymena thermophila.

In Tetrahymena, at least 17 distinct microtubule structures are assembled from a single primary sequence type of alpha- and beta-tubulin heterodimer, precluding distinctions among microtubular systems based on tubulin primary sequence isotypes. Tetrahymena tubulins also are modified by several types of posttranslational reactions including acetylation of alpha-tubulin at lysine 40, a modification found in most eukaryotes. In Tetrahymena, axonemal alpha-tubulin and numerous other microtubules are acetylated. We completely replaced the single type of alpha-tubulin gene in the macronucleus with a version encoding arginine instead of lysine 40 and therefore cannot be acetylated at this position. No acetylated tubulin was detectable in these transformants using a monoclonal antibody specific for acetylated lysine 40. Surprisingly, mutants lacking detectable acetylated tubulin are indistinguishable from wild-type cells. Thus, acetylation of alpha-tubulin at lysine 40 is non-essential in Tetrahymena. In addition, isoelectric focusing gel analysis of axonemal tubulin from cells unable to acetylate alpha-tubulin leads us to conclude that: (a) most or all ciliary alpha-tubulin is acetylated, (b) other lysines cannot be acetylated to compensate for loss of acetylation at lysine 40, and (c) acetylated alpha-tubulin molecules in wild-type cells contain one or more additional charge-altering modifications.

Acetylation↗
PubMed1995

Generation and characterization of monoclonal antibodies specific for members of the mammalian 70-kDa heat shock protein family.

The 70-kDa heat shock proteins (hsp70) are a highly conserved, abundant, and ubiquitous family of proteins expressed by all organisms from bacteria to humans. It is well established that hsp70 family members function as molecular chaperones and aid in the intracellular folding of newly synthesized or denatured proteins. Current evidence suggests an emerging role for hsp70 family members in immune responses and in clinically important responses to stress and tissue damage. Here we report the generation and characterization of several MAbs to hsp70 family members. Immune responses to this highly conserved family were induced in mice by immunization with synthetic peptides that contain regions of the mouse mitochondrial hsp70 coupled to a potent helper T cell epitope derived from tetanus toxoid. The resulting MAbs include ones specific for the human and mouse mitochondrial hsp70 and others that show cross-reactivity among the family members and recognize the mitochondrial hsp70, the endoplasmic reticulum resident hsp70, Bip/grp78, the constitutively expressed cytosolic hsp70, hsc70, and the heat-induced member, hsp70. Significantly, these MAbs are effective in Western blotting, in immunoprecipitation, and in immunofluorescence, and thus should find applications in the purification and detection of members of this important family.

Amino Acid Sequence↗
PubMed1995

Chlamydia trachomatis RNA polymerase alpha subunit: sequence and structural analysis.

We describe the cloning and sequence analysis of the region surrounding the gene for the alpha subunit of RNA polymerase from Chlamydia trachomatis. This region contains genes for proteins in the order SecY, S13, S11, alpha, and L17, which are equivalent to Escherichia coli and Bacillus subtilis r proteins. The incorporation of chlamydial alpha subunit protein into the E. coli RNA polymerase holoenzyme rather than its truncated variant lacking the amino terminus suggests the existence of structural conservation among alpha subunits from distantly related genera.

Amino Acid Sequence↗
PubMed1995

Gene-specific signal transduction between microtubules and tubulin genes in Tetrahymena thermophila.

Mammalian cells regulate tubulin mRNA abundance by a posttranscriptional mechanism dependent on the concentration of tubulin monomer. Treatment of mammalian cells with microtubule-depolymerizing drugs and microtubule-polymerizing drugs causes decreases and increases in tubulin mRNA, respectively (D. W. Cleveland, Curr. Opin. Cell Biol. 1:10-14, 1989). In striking contrast to the case with mammalian cells, perturbation of microtubules in Tetrahymena thermophila by microtubule-depolymerizing or -polymerizing drugs increases the level of the single alpha-tubulin gene message by increasing transcription (L. A. Stargell, D. P. Heruth, J. Gaertig, and M. A. Gorovsky, Mol. Cell. Biol. 12:1443-1450, 1992). In this report we show that antimicrotubule drugs preferentially induce the expression of one of two beta-tubulin genes (BTU1) in T. thermophila. In contrast, deciliation induces expression of both beta-tubulin genes. Tubulin gene expression was examined in a mutant strain created by transformation with an in vitro-mutagenized beta-tubulin gene that conferred resistance to microtubule-depolymerizing drugs and sensitivity to the polymerizing drug taxol and in a strain containing a nitrosoguanidine-induced mutation in the single alpha-tubulin gene that conferred the same pattern of drug sensitivities. In both cases the levels of tubulin mRNA expression from the drug-inducible BTU1 gene in the mutant cells paralleled the altered growth sensitivities to microtubule drugs. These studies demonstrate that T. thermophila has distinct, gene-specific mechanisms for modulating tubulin gene expression depending on whether ciliary or cytoplasmic microtubules are involved. They also show that the cytoplasmic microtubule cytoskeleton itself participates in a signal transduction pathway that regulates specific tubulin gene transcription in T. thermophila.

Animals↗
PubMed1995

Transforming growth factor beta 1 messenger RNA in Reed-Sternberg cells in nodular sclerosing Hodgkin's disease.

AIMS: To determine the cellular origin of the most potent cytokine present in Hodgkin's disease, transforming growth factor (TGF) beta, the polycellular population of Hodgkin's tissue was studied using in situ hybridisation. METHODS: A biotin labelled oligo-complementary DNA (cDNA) was constructed according to the previously determined sequence for TGF beta 1 cDNA. Forty three frozen and paraffin wax embedded tissue samples replaced by Hodgkin's disease or non-Hodgkin's lymphoma, three Reed-Sternberg cell lines, one Ki1 positive lymphoma cell line, and an epithelial cell line were studied for expression of TGF beta 1 messenger RNA (mRNA) as well as secretion of the TGF beta 1 protein and expression of the CD30 epitope. RESULTS: The results obtained with the 24 frozen tissue samples confirmed that the TGF beta antigen is found predominantly in the nodular sclerosing Hodgkin's disease (NSHD) subtype. Nineteen paraffin wax embedded tissue samples were used to measure the simultaneous expression of CD30 and TGF beta 1 mRNA. The latter was found in eight of eight NSHD samples, two of six mixed cellularity samples, and two of five non-Hodgkin's lymphoma samples. No evidence of fibroblast expression of TGF beta 1 mRNA was noted. CONCLUSIONS: Activated lymphocytes in NSHD express TGF beta 1 mRNA, but binucleate Reed-Sternberg cells and mononuclear Hodgkin's cells are the primary sources of activated TGF beta in Hodgkin's disease.

Base Sequence↗
PubMed1995

Homozygous deletions of the CDKN2 (MTS1/p16ink4) gene in cell lines established from children with acute lymphoblastic leukemia.

Homozygous deletions of the CDKN2 (MTS1/p16ink4) gene have been found at high frequency in cell lines derived from a variety of adult solid tumors. In order to investigate the status of the CDKN2 gene in cell lines established from childhood acute lymphoblastic leukemia (ALL), we surveyed 25 lines representing the major pediatric ALL phenotypes for the presence of this gene by Southern blot analysis. Homozygous deletions of all or part of the CDKN2 gene were detected in 21 (84%) cell lines, including 11 of 14 (79%) early-pre-B-ALL, four of five (80%) pre-B-ALL, and six of six T-ALL lines. CDN2 mRNA was detected by Northern blotting in each of the four lines containing an intact CDKN2 gene. These data suggest an important role for CDKN2 deletion in the cause and/or progression of pediatric ALL.

Blotting, Northern↗
PubMed1995

V-J junctional sequences of T cell receptor gamma gene in acute lymphocytic leukemia.

T cell receptor TCR gamma gene rearrangement in a series of acute lymphocytic leukemia (ALL) patients was studied using PCR technique. 18 V-J junctional sequences (designated by N sequence) of TCR gamma gene were amplified with the V gamma and J gamma primers, using an unsymmetrical PCR and analysed by direct sequencing, demonstrating that in Chinese ALLs, the N sequences of TCR gamma gene are indeed clone-specific. Based on the known N sequences, several oligo-nucleotides were synthesized as probes, which were specific for the leukemic clone, and were used to detect the minimal residual disease (MRD) in 4 ALL cases. The sensitivity of this method was 0.1%-0.01%.

Adult↗
PubMed1995

[Junctional sequences of T cell receptor V delta 2-D delta 3 or D delta 2-D delta 3 rearrangements in acute lymphoblastic leukemia].

T-cell receptor (TCR) delta chain gene rearrangements were studied by polymerase chain reaction (PCR) analysis in 46 patients with acute lymphoblastic leukemia (ALL). Sixteen patients were found to have incomplete rearrangements of the TCR delta genes. Among them, 13 patients displayed V delta 2-D delta 3 rearrangement, while 3 had both V delta 2-D delta 3 and D delta 2-D delta 3 rearrangements. To determine the junctional sequence of TCR delta gene, PCR products from the 16 patients were sequenced directly or after M13 cloning. The results showed the junctional sequences of TCR delta gene are highly specific for each allele. This sequence diversity resulted from several factors including deletion of the 3' end of V delta 2 or D delta 2 segment and 5' end of D delta 3 segment, the presence of D delta 1 or D delta 2 sequences, insertion of N nucleotides and the association of P nucleotides with intact V delta 2 and D delta 3 segments. In addition, analysis of N-nucleotide contents revealed that the amount of GC was much larger than that of AT (70%: 30%), indicating the insertion of N nucleotide was not fully random. Our sequence data confirmed that the imcomplete rearrangement of TCR delta gene is an early event in the lymphoid cell ontogenesis, and its N sequences in V-(D)-J junctional region may be used as a specific marker of clonality to detect the minimal residual disease (MRD) in ALL.

Adolescent↗
PubMed1995

[Different patterns of follicular development and luteal function].

OBJECTIVE: To study the relationship between luteal function and different patterns of follicular development. METHODS: Different patterns of follicular development as observed under transvaginal B-ultrasound in 85 infertile patients included: (1) Ovulation from normal follicle (ONF). (2) Ovulation from two follicles at the same cycle (O2F). (3) Ovulation from small follicle (OSF). (4) Ovulation from polycystic ovaries (PCO). (5) Luteinized unruptured follicle syndrome (LUFS). (6) Anovulation with follicular atresia. The luteal function of the first 5 types was evaluated by serum and peritoneal fluid estrogen, progesterone levels, endometrial histology, estradiol receptor (ER) and progesterone receptor (PR) analyaes, and the length of luteal phase. RESULTS: The incidence of luteal phase deficiency (LPD): short luteal phase was 10.42%, retardation of endometrial development was 4.17% in ONF, no LPD in O2F, 21.42% in OSF, 2/3 in PCO, 3/6 in LUFS, respectively. The incidence of LPD was 14.58% in ONF, 56.52% in abnormal follicular development groups (OSF, O2F and LUFS) (P < 0.005). It was found that the retardation of endometrial development was associated either with lowered serum P level or normal serum P but lowered ER and PR concentrations. The latter condition was recognized as "pseudocorpus luteum deficiency". CONCLUSIONS: The different patterns of follicular development may exert a great influence over luteal function through the different production of steroid hormones and their receptors.

Corpus Luteum↗