Biomedical subjects

H Jiang

Publications and source records attributed to H Jiang.

At least 379 records · Page 21Linked to original sources

PubMed1998

Cytochrome P450 2E1 DraI polymorphisms in lung cancer in minority populations.

Cytochrome P4502E1 (CYP2E1) is involved in the metabolic activation of carcinogenic N-nitrosamines. This study was performed to examine whether CYP2E1 DraI polymorphisms in intron 6 are related to susceptibility to lung cancer and are associated with carcinogenetic exposure. We therefore genotyped CYP2E1 by PCR amplification of peripheral WBC DNA from 126 patients with previously untreated lung cancer (85 African Americans and 41 Mexican Americans) and 193 controls (104 African Americans and 89 Mexican Americans). Mutagen sensitivity was measured with an in vitro assay quantitating bleomycin-induced chromatid breaks in peripheral blood lymphocyte cultures. The CYP2E1 DraI DD genotype was found in 86.5% of all cases and in 74.6% of all controls (P = 0.03), in 78.1% of 41 Mexican-American cases and in 69.6% of their controls (P = 0.70), and in 90.6% of African American cases and in 78.8% of their controls (P = 0.05). The DD genotype was found to be associated with a significantly higher risk of lung cancer overall with an odds ratio (OR) of 2.4 [95% confidence interval (CI), 1.1-5.3]. This risk was significantly elevated for men and for those who had ever smoked [ORs of 3.4 (95% CI, 1.3-8.7) and 2.6 (95% CI, 1.1-6.0), respectively], but not for women and nonsmokers [ORs of 0.7 (95% CI, 0.1-3.8) and 0.9 (95% CI, 0.1-10.6), respectively]. Stratified analysis showed an interaction that seemed greater than multiplicative between cigarette smoking and the CYP2E1 DraI DD genotype. The ORs for the CYP2E1 DraI DD genotype, cigarette smoking, and both risk factors combined were 1.5, 8.5, and 22.7, respectively. The CYP2E1 DraI polymorphism and the CYP2E1 PstI polymorphism in the upstream flanking regions were significantly associated in Mexican Americans but not in African Americans. We therefore conclude that the CYP2E1 DraI polymorphism seems to be associated with lung carcinogenesis. However, a larger study is warranted to evaluate the interactions among CYP2E1 DraI DD genotype, mutagen sensitivity, and cigarette smoking.

Aged↗

PubMed1998

Reduced expression of hMLH1 and hGTBP/hMSH6: a risk factor for head and neck cancer.

Head and neck cancer, like lung cancer, is considered a paradigm of an environmentally induced disease. Genetically determined variation in DNA repair capacity is thought to contribute to susceptibility to tobacco-related cancers. In this molecular epidemiology study, we investigated the association between DNA mismatch-repair (MMR) gene expression and the risk of head and neck cancer. Using our newly developed multiplex reverse transcription-PCR assay, we simultaneously evaluated the relative expression levels of five MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and hGTBP/hMSH6) in the peripheral blood lymphocytes of 78 patients (mean age = 59.6 +/- 12.4 years) with newly diagnosed head and neck cancer and 86 healthy controls (mean age = 58.2 +/- 12.9 years). The relative MMR gene expression was not correlated with disease stage or tumor site in the cases or with smoking and alcohol use in the controls. The expression levels increased with age in both cases and controls, but the mean expression of hMLH1, hPMS1, and hGTBP/hMSH6 was significantly lower in the cases than in the controls (P < 0.05). Using the median expression level in controls as the cutoff value, significantly increased odds ratios (ORs) were associated only with low expression of hMLH1 (OR = 4.4; 95% confidence interval = 2.1-9.1) and hGTBP/hMSH6 (OR = 2.1; 95% confidence interval = 1.1-4.1) after adjustment for age, sex, ethnicity, smoking status, and alcohol use. The results suggest that low hMLH1 and hGTBP/hMSH6 expression is associated with an increased risk of head and neck cancer. Additional studies with a larger number of subjects are warranted to confirm these findings.

Adaptor Proteins, Signal Transducing↗

PubMed1998

CT findings in splenic tuberculosis.

Splenic tuberculosis is rare and delay in diagnosis is common. We present two cases of splenic tuberculosis with their appearance on CT. The CT findings were multiple, round or ovoid, low-density lesions without calcification. Except for non-specific lymphadenopathy no abnormality nor history suggestive of tuberculosis was revealed prior to laparotomy. Although CT does not confirm a diagnosis of splenic tuberculosis, it would be a valuable examination to define the extent of disease and guide aspiration biopsy.

Abscess↗

PubMed1998

The use of a retinoid receptor antagonist in a new model to study vitamin A-dependent developmental events.

Multiple fetal anomalies occur in vitamin A deficient animals as well as in retinoic acid receptor gene 'knockout' mice, indicating that retinoic acid (an active metabolite of vitamin A) performs some essential functions in normal development. Additional approaches are needed to probe directly the stages and sites in the embryo where a presence of endogenous retinoic acid is indispensable. We have employed a new strategy for this purpose which involved an intervention in retinoic acid receptor (RAR)-dependent functions at specific developmental stages by means of a highly effective RAR antagonist, AGN 193109. We report that in an in vitro cell differentiation bioassay, AGN 193109 completely reversed the inhibitory action of a potent RAR agonist, AGN 190121. In pregnant mice, a single oral 1 mg/kg dose of the antagonist given on 8 day post coitum (dpc) produced a severe craniofacial anomaly (median cleft face or frontonasal dysplasia) and eye malformations in virtually all exposed fetuses. On the other hand, treatment on 11 dpc, a time in development when RARs are strategically expressed in the limb bud primordium, no limb anomalies could be induced by the antagonist. Even after a high dose of 100 mg/kg, limb development progressed normally in spite of the fact that measurable concentrations of the antagonist were present. Because retinoids are long known to influence skin morphology, we next monitored the effects of the antagonist on skin development. When given late in gestation, on 14 dpc, we found that the antagonist delayed differentiation and maturation of the fetal skin and hair follicles. We conclude that this model provides a convenient and pertinent system which enables us to seek and clarify true functions of retinoic acid and its cognate receptors in embryogenesis and in adult animals.

Animals↗

PubMed1998

Glucose does not stimulate apoprotein B secretion from HepG2 cells because of insufficient stimulation of triglyceride synthesis.

We have previously demonstrated a close relationship between oleic acid (OA)-stimulated triglyceride (TG) synthesis and apolipoprotein B (apoB) secretion in HepG2 cells. However, other investigators studying the association between glucose-stimulated TG synthesis and apoB secretion have reported variable results. The present study was carried out to answer the question: does TG derived from glucose have different effects on apoB secretion from HepG2 cells compared to TG derived from oleate? We observed that incubations of HepG2 cells for as long as 48 h in 30 mm glucose did not increase apoB secretion. We then demonstrated that the failure of glucose to stimulate apoB secretion from HepG2 cells results from insufficient stimulation of TG synthesis by glucose. Thus, incorporation of [3H]glycerol into [3H]TG in the presence of 30 mm glucose for up till 48 h was not increased compared to basal conditions. The inability of glucose to stimulate TG synthesis was also evidenced by the inability of both 8 -h and 24 -h incubations with 30 mm glucose to increase cell TG mass; similar incubations with OA increased TG mass 50-100%. Additional studies demonstrated that glucose conversion to either glycerol or fatty acids was minimal; this accounted for the lack of stimulation of TG synthesis. We conclude that in HepG2 cells, availability of high glucose levels in the media for as long as 48 h does not stimulate triglyceride synthesis, and that this is the basis for the failure of glucose to stimulate apoB secretion.

Apolipoproteins B↗

PubMed1998

Primary ureteral carcinoma. Report of 15 cases and comparison of the effectiveness of diagnostic methods.

Fifteen cases of primary urothelial carcinomas of the ureter are reported (14 transitional cell carcinoma and 1 mixed transitional cell carcinoma and squamous cell carcinoma). There was a clear male predominance (11/4); the peak incidence was in the sixth decade. Most tumors originated from the distal third of the ureter. Multicentricity and high recurrence rate after partial ureterectomy were noted. The clinical signs were hematuria and flank pain. Urine cytology and IVU were diagnostic in a limited number of cases. Retrograde pyelography was very helpful. CT showed to be the image modality of choice for diagnosis and preoperative staging.

Aged↗

PubMed1997

Characterization of the scoliosis that develops after pinealectomy in the chicken and comparison with adolescent idiopathic scoliosis in humans.

STUDY DESIGN: The characteristics of the scoliosis that develops after pinealectomy in young chickens were determined from weekly posteroanterior radiographs. These data were compared with similar data collected from human patients with adolescent idiopathic scoliosis. OBJECTIVES: To characterize the scoliosis produced in young chickens after pinealectomy and to compare these characteristics with those seen in human patients with adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Although it has been recognized that pinealectomy produces scoliosis in chickens, the characteristics of these curves have never been well described other than by simple visual descriptions. METHODS: The characteristics of the scoliosis produced in chickens after pinealectomy done 3 days after hatching were measured from radiographs taken at weekly intervals. These characteristics were compared with similar data collected from human patients with adolescent idiopathic scoliosis. RESULTS: Similarities included development of single and double curves, degree of curvature, stability of the curve, numbers of vertebrae involved, direction of rotation, and progression characteristics. Differences included wedged vertebrae in the chickens, in conjunction with curve development and increased variability in vertebrae involved. CONCLUSIONS: There are many similarities in the development of scoliosis in young chickens after pinealectomy and in children with adolescent idiopathic scoliosis. The few differences might be related to the different biomechanical properties associated with the spine in the two species.

Adolescent↗

PubMed1997

Actions of the neurotrophins on calcium uptake.

The neurotrophins are important for their long-term effects on the survival and differentiation of many types of neurons during development. They also appear to protect mature neurons from injury caused by nutrient or oxygen deprivation. More recently, the neurotrophins have been implicated in such short-term processes as synaptic plasticity. A great deal of evidence suggests that intracellular calcium levels play a key role in neuronal survival during normal development, in neuronal injury following nutrient or oxygen deprivation, and in synaptic plasticity as well. Maintaining appropriate intracellular levels of calcium is important for proper biological function and it has been shown that one of the actions of the neurotrophins is to modulate intracellular calcium levels in a number of in vivo and in vitro systems. Some information about the mechanism(s) by which this is accomplished is now available. Understanding the mechanisms of neurotrophin action should provide insights into the processes by which the brain functions and, further, provide therapeutic tools for the treatment of neuronal injury and neurodegenerative diseases.

Animals↗

PubMed1997

Both N-terminal myosin-binding and C-terminal actin-binding sites on smooth muscle caldesmon are required for caldesmon-mediated inhibition of actin filament velocity.

It has been suggested that the tethering caused by binding of the N-terminal region of smooth muscle caldesmon (CaD) to myosin and its C-terminal region to actin contributes to the inhibition of actin-filament movement over myosin heads in an in vitro motility assay. However, direct evidence for this assumption has been lacking. In this study, analysis of baculovirus-generated N-terminal and C-terminal deletion mutants of chicken-gizzard CaD revealed that the major myosin-binding site on the CaD molecule resides in a 30-amino acid stretch between residues 24 and 53, based on the very low level of binding of CaDDelta24-53 lacking the residues 24-53 to myosin compared with the level of binding of CaDDelta54-85 missing the adjacent residues 54-85 or of the full-length CaD. As expected, deletion of the region between residues 24 and 53 or between residues 54 and 85 had no effect on either actin-binding or inhibition of actomyosin ATPase activity. Deletion of residues 24-53 nearly abolished the ability of CaD to inhibit actin filament velocity in the in vitro motility experiments, whereas CaDDelta54-85 strongly inhibited actin filament velocity in a manner similar to that of full-length CaD. Moreover, CaD1-597, which lacks the major actin-binding site(s), did not inhibit actin-filament velocity despite the presence of the major myosin-binding site. These data provide direct evidence for the inhibition of actin filament velocity in the in vitro motility assay caused by the tethering of myosin to actin through binding of both the CaD N-terminal region to myosin and the C-terminal region to actin.

Actins↗

PubMed1997

Two basic amino acids in the second inner loop of the interleukin-8 receptor are essential for Galpha16 coupling.

The involvement of basic residues of interleukin(IL)-8 receptors in coupling to the Gi and G16 proteins was investigated by using a series of IL-8 receptor mutants. Substitution of the basic amino acids in the third inner loop of the receptor does not alter the abilities of the receptor mutants to activate recombinant Galpha16 or phosphoinositide-specific phospholipase C (PLC) beta2 expressed in COS-7 cells. However, an IL-8 receptor mutant with double mutations at residues Lys158 and Arg159 of the second inner loop loses its abilities to activate Galpha16 but retains its ability to activate PLC beta2. The activation of PLC beta2 by an IL-8 receptor that is sensitive to pertussis toxin has been previously demonstrated to be mediated through Gbetagamma. Surprisingly, the IL-8 receptor mutants with substitution of Ala for either residue Lys158 or Arg159 can still activate Galpha16, which suggests that either of the two basic residues in the second inner loop of the IL-8 receptor is sufficient for Galpha16 coupling.

Amino Acid Sequence↗

PubMed1997

Molecular modeling and 3D-QSAR studies on the interaction mechanism of tripeptidyl thrombin inhibitors with human alpha-thrombin.

The mechanism of inhibition of peptidyl inhibitors with thrombin was studied using molecular modeling, molecular mechanics, and CoMFA statistical analysis. A new procedure for the elucidation of binding conformations, BCSPL, is described and was employed to obtain the binding conformers of a series of 18 tripeptidyl thrombin inhibitors. Energetic studies and QSAR analysis of the BCSPL-derived conformers indicated a modest correlation between the calculated binding energies of the title compounds and their inhibitory activities to human alpha-thrombin. CoMFA analysis of the BCSPL alignment resulted in a satisfactory model of the thrombin active site.

Antithrombins↗

PubMed1997

Expression of human p140trk receptors in p140trk-deficient, PC12/endothelial cells results in nerve growth factor-induced signal transduction and DNA synthesis.

Nerve growth factor (NGF) regulates proliferation, differentiation, and survival of sympathetic and sensory neurons through the tyrosine kinase activity of its receptor, p140trk. These biological effects of NGF depend upon the signal-mediating function of p140trk substrates which are likely to differ from cell to cell. To define p140trk receptor substrates and the details of signalling by NGF in the hybrid cell PC12EN, we stably transfected cultures with a vector encoding a full-length human p140trk cDNA sequence. Two stably transfected clones, one expressing p140trk with higher affinity (PC12EN-trk3; Kd 57.4 pM, Bmax 9.7 pmole/mg) and one expressing p140trk with a lower affinity (PC12EN-trk1; Kd 392.4 pM, Bmax 5.7 pmole/mg) were generated. Radioreceptor assays indicate that transfected p140trk receptors show slow NGF-dissociation kinetics, are resistant to trypsin or Triton X-100 treatment, are specific for NGF compared to other neurotrophins, and are internalized or downregulated as are native PC12 p140trk receptors. NGF stimulates p140trk tyrosine phosphorylation in a dose- (0.01-10 ng/ml) and time- (5-120 min) dependent manner, and tyrosine phosphorylation was inhibited by 200-1,000 nM K-252a. NGF-induced Erk stimulation for 60 min was assessed using myelin basic protein as a substrate. NGF treatment also led to an increased phosphorylation of p70S6k, SNT, and phospholipase C gamma, demonstrating that the major NGF-stimulated signalling pathways found in other cells are activated in PC12EN-trk cells. Staurosporine (5-50 nM) rapidly and dBcAMP (1 mM) more slowly, but not NGF induced morphological differentiation in PC12EN-trk cells. Rather, NGF treatment in low-serum medium stimulated a 1.3- and 2.3-fold increase in DNA synthesis measured by [3H]thymidine incorporation in PC12EN-trk1 and PC12EN-trk3, respectively. These data highlight the functionality of the transfected p140trk receptors and indicate that these transfected cells may serve as a novel cellular model facilitating the study of the mitogenic properties of NGF signalling and the transducing role of the p140trk receptor substrates.

Animals↗

PubMed1997

Roles of phospholipase C beta2 in chemoattractant-elicited responses.

The physiological roles of phospholipase C (PLC) beta2 in hematopoiesis, leukocyte function, and host defense against infection were investigated using a mouse line that lacks PLC beta2. PLC beta2 deficiency did not affect hematopoiesis, but it blocked chemoattractant-induced Ca2+ release, superoxide production, and MAC-1 up-regulation in neutrophils. In view of these effects, it was surprising that the absence of PLC beta2 enhanced chemotaxis of different leukocyte populations and sensitized the in vivo response of the PLC beta2-deficient mice to bacteria, viruses, and immune complexes. These data raise questions about the roles that PLC beta2 may play in signal transduction induced by chemoattractants in leukocytes.

Animals↗

PubMed1997

Down-regulation of epidermal growth factor receptors by nerve growth factor in PC12 cells is p140(trk)-, Ras-, and Src-dependent.

Nerve growth factor (NGF) treatment causes a profound down-regulation of epidermal growth factor receptors during the differentiation of PC12 cells. This process is characterized by a progressive decrease in epidermal growth factor (EGF) receptor level measured by 125I-EGF binding, tyrosine phosphorylation, and Western blotting. Treatment of the cells with NGF for 5 days produces a 95% reduction in the amount of [35S]methionine-labeled EGF receptors. This down-regulation does not occur in PC12nnr5 cells, which lack the p140(trk) NGF receptor. However, in PC12nnr5 cells stably transfected with p140(trk), the NGF-induced heterologous down-regulation of EGF receptors is reconstituted in part. NGF-induced heterologous down-regulation, but not EGF-induced homologous down-regulation of EGF receptors, is blocked in Ras- and Src-dominant-negative PC12 cells. Treatment with either pituitary adenylate cyclase-activating peptide (PACAP) or staurosporine stimulates neurite outgrowth in PC12 cell variants, but neither induces down-regulation of EGF receptors. NGF treatment of PC12 cells in suspension induces down-regulation of EGF receptors in the absence of neurite outgrowth. These results strongly suggest a p140(trk)-, Ras- and Src-dependent mechanism of NGF-induced down-regulation of EGF receptors and separate this process from NGF-induced neurite outgrowth in PC12 cells.

Animals↗

PubMed1997

A two-site model for ApoB degradation in HepG2 cells.

Newly synthesized apolipoprotein B (apoB) undergoes rapid degradation in a pre-Golgi compartment in HepG2 cells. A major site of this early degradation seems to be on the cytosolic side of the endoplasmic reticulum (ER) membrane and is sensitive to N-acetyl-leucinyl-leucinyl-norleucinal (ALLN), which can inhibit neutral cysteine proteases and/or proteasome activity. Oleate (OA) treatment, which facilitates translocation of nascent apoB across the ER membrane, also reduces early degradation. In the present studies, we have used brefeldin A (BFA), which inhibits vesicular transport from the ER to the Golgi, to demonstrate that apoB can also be degraded by an ER luminal proteolytic activity that is distinct from the ALLN-sensitive proteases. Thus, when BFA-treated HepG2 cells were co-treated with ALLN, which protects apoB but does not facilitate its translocation into the ER lumen, degradation of newly synthesized apoB was significantly reduced compared with cells incubated with BFA alone. However, apoB degradation was rapid and complete when OA was added to media containing either BFA or ALLN/BFA. These results suggested that OA, by increasing translocation of nascent apoB into the ER lumen, exposed apoB to an ALLN-resistant proteolytic pathway. When we incubated HepG2 cells with dithiothreitol (DTT)/OA/BFA or DTT/OA/ALLN/BFA, degradation of apoB was inhibited. Furthermore, addition of DTT resulted in the accumulation of a 70-kDa amino-terminal fragment of apoB. Both full-length and amino-terminal apoB were degraded if DTT was removed from the incubation media; both were secreted if only BFA was removed. Thus, even after apoB is translocated into the ER lumen (thereby avoiding the initial proteolytic pathway), it can potentially be degraded by a lumenal proteolytic process that is ALLN-resistant but DTT-sensitive. The present results, together with previous studies, suggest that at least two distinct steps may be involved in the posttranslational degradation of apoB: 1) the first occurs while apoB is partially translocated and is ALLN-sensitive; and 2) the second occurs in the ER lumen and is DTT-sensitive. Finally, our results support the hypothesis that degradation of partially translocated apoB generates a 70-kDa amino-terminal fragment that is mainly degraded in the ER lumen by a DTT-sensitive pathway.

Apolipoproteins B↗

PubMed1997

Lung carcinoma patients with a family history of cancer and lymphocyte primary chromosome 9 aberrations.

BACKGROUND: Deletion of chromosome 9p has been reported in numerous tumor types. The authors demonstrated in an earlier study that spontaneous chromosome aberrations on chromosome 9 in peripheral blood lymphocytes (PBLs) were a significant risk predictor for lung carcinoma. METHODS: The current study evaluated the relationship between self-reported family history of cancer and spontaneous chromosome aberrations in the PBLs of 97 previously untreated lung carcinoma patients. The authors' hypothesis was that individuals exhibiting specific chromosome aberrations might have inherited genetic instability and thus be more likely to report a family history of cancer. For each individual, a personal interview was conducted to construct a detailed family history, and 100 metaphases from PBLs were analyzed for spontaneous aberrations by G-banding. RESULTS: The patients reported having 829 first-degree relatives, including 74 (8.9%) with cancer. A significantly elevated odds ratio (OR) of 2.7 was noted in smokers for having chromosome 9 aberrations and a first-degree relative with cancer. When the family history of cancer was dichotomized into lung carcinoma or other cancers, the OR associated with chromosomal aberrations was 8.5 for lung carcinoma but only 2.3 for other cancers. In addition to chromosome 9 aberrations, other spontaneous chromosome aberrations and family history of cancer were also evaluated, but no associations were found. There were no associations between age, gender, ethnicity, or smoking status and the chromosome 9 aberration profile. CONCLUSIONS: The findings of this study suggest that chromosome 9 aberrations may be a marker of cancer susceptibility and may be associated with familial aggregation of cancer.

Black People↗

PubMed1997

Both p140(trk) and p75(NGFR) nerve growth factor receptors mediate nerve growth factor-stimulated calcium uptake.

Human p140(trk) and p75(NGFR) were transfected separately into 3T3 cells. Nerve growth factor stimulates calcium uptake into both transfectants but not into untransfected 3T3 cells. p140(trk) cells were stimulated maximally by 25 ng/ml; 100 ng/ml was submaximal for p75(NGFR) cells. K-252a inhibits the effect of NGF on p140(trk) cells but not on p75(NGFR) cells; brain-derived neurotrophic factor stimulates calcium uptake in p75(NGFR) cells but not in p140(trk) cells. The data suggest that both nerve growth factor receptors could be involved in the nerve growth factor-mediated actions of calcium on its target cells: neuronal survival, neuronal protection, and synaptic plasticity.

3T3 Cells↗

PubMed1997

cDNA sequence and expression of bovine prodynorphin.

Prodynorphin (ProDYN) in the anterior pituitary gland appears to be processed differently from the brain, and the ProDYN-derived peptides may function differently in the anterior pituitary than in the brain. To further investigate the roles of ProDYN-derived peptides in the anterior pituitary, we have determined the nucleotide (nt) sequence of the cDNA encoding bovine ProDYN. This is the first time a complete cDNA sequence for ProDYN has been reported. The nt and deduced amino acid (aa) sequences were compared to the known ProDYN of other species. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) combined with Southern blot analysis demonstrated that the expression of ProDYN in both the anterior and posterior pituitary glands was much lower than that in the neural tissues of the striatum and hypothalamus.

Amino Acid Sequence↗