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Biomedical subjects

X Du

Publications and source records attributed to X Du.

At least 127 records · Page 7Linked to original sources
PubMed1998

Effects of deleting A19 tyrosine from insulin.

A mutant proinsulin gene was constructed through PCR mediated mutagenesis. The code of A19Tyr was deleted. The mutant proinsulin, (deltaY)19-lys-proinsulin [(deltaY)19KPI], was expressed in E. coli and purified. After treatment with trypsin and carboxypeptidase B, and Resource Q separation, (deltaY)19-human insulin [(deltaY)19HI] was obtained. It retains 63.6% of receptor binding activity but only 2.2% of immune activity, and shows a longer retaining time on reverse-phase FPLC and a slower mobility by native PAGE analysis. These results suggest that the deletion of A19Tyr causes some conformational changes on insulin, which plays a minor role on the affinity of insulin to its receptor, and a major role on immunogenicity of the hormone.

Chromatography, Ion Exchange↗
PubMed1998

Role of oxygen derived radicals for vascular dysfunction in the diabetic heart: prevention by alpha-tocopherol?

The evidence that the generation of reactive oxygen intermediates (ROI) plays an important role for the increased cardiovascular risk in diabetes is summarised. In addition to the well known parameters of oxidative stress as lipid hydroperoxides and thiobarbituric acid substances (TBARS), recent observations indicate that isoprostanes which can be taken as a more specific parameter of oxidative stress, are generated in higher amounts by diabetic patients. This increased formation of isoprostanes can be inhibited by an installment of a close metabolic control or the supplementation with tocopherol. The cause for the elevated oxidative stress is not yet fully understood, however the autoxidation of glucose, the formation of advanced glycation endproducts and the activation of NADPH-oxidase seem to be relevant processes. Since ROI are able to quench nitric oxide and to inhibit the synthesis of prostacyclin, the antithrombotic, vasodilating and antiatherosclerotic properties of endothelium are impaired in diabetes. Additionally, the balance of endothelial mediators released by endothelium is shifted to angiotensin II and endothelin, compounds which enhance the proliferation of smooth muscle cells and may limit the coronary reserve of myocardium. The activation of the transcription factor NF-kappa B by glucose and its autoxidative products is regarded as a key event in the transformation of the vasculature in diabetes. Epidemiological observations and very recent clinical studies underlie the impact of ROI for the development of cardiovascular complications in diabetes and suggest that an antioxidative treatment might be helpful to reduce the cardiac risk in diabetes.

Animals↗
PubMed1997

Multiple signaling pathways direct the initiation of tyrosine hydroxylase gene expression in cultured brain neurons.

Previous studies have demonstrated that the synergistic interaction of acidic fibroblast growth factor (aFGF) and a second co-activator molecule can novelly induce expression of the CA biosynthetic enzyme tyrosine hydroxylase (TH) in non-TH expressing neurons of the striatum. Several co-activators have been identified, including substances present in L6 muscle cell extract (X. Du et al., J. Neurosci. 14 (1994) 7688-7694) catecholamines, such as dopamine (DA) (X. Du and L. Iacovitti, J. Neurosci. 15 (1995) 5420-5427; X. Du et al., Brain Res. 680 (1995) 229-233) and activators of protein kinase C (PKC) such as TPA (X. Du and L. Iacovitti, J. Neurochem. 68 (1997) 564-569). In the present study, we investigated whether activators of the protein kinase A (PKA) pathway also serve as effective co-activators of aFGF in the induction of TH gene expression. In addition, the combinatorial effects of the various TH-inducing agents were also evaluated. We found that, as with other co-activating molecules, the PKA stimulants IBMX and forskolin had no TH-inducing capacity when administered alone. However, co-treatment of 10 ng/ml aFGF with either (250 microM) IBMX or (10 microM) forskolin resulted in the novel expression of TH in 25% of plated neurons. The number of TH-expressing neurons was increased to 55% in aFGF-treated cultures co-incubated with aFGF and both (250 microM) IBMX and (10 microM) forskolin. Time course studies indicated that TH induction was rapid (peaking within 24 h) and enduring (lasting 4 days in culture). Induction of TH by aFGF and IBMX/forskolin was partially blocked by inhibitors of protein kinase, such as H7, H8 and H89, as well as pretreatment with protein (cyclohexamide) or RNA synthesis (amanitin and actinomycin D) inhibitors. The concomitant addition of combinations of co-activator molecules (DA, TPA and IBMX/forskolin) and aFGF resulted in the additive induction of TH. Maximal expression of TH (80% of striatal neurons) was accomplished when cultures were treated with aFGF and all co-activator molecules simultaneously. Our results suggest that there are multiple ways to signal the initiation of the TH gene, each of which requires the synergy of specific growth factors and either DA, PKA or PKC pathway activators. Since only the combination of growth factor and all co-activators together produces maximum TH induction, each molecule may signal a unique intracellular pathway which converges at targets on the TH gene.

Animals↗
PubMed1997

A model for binding of structurally diverse natural product inhibitors of protein phosphatases PP1 and PP2A.

Protein phosphatases play significant roles in signal transduction pathways pertaining to cell proliferation, gene expression, and neurotransmission. Serine/threonine phosphatases PP1 and PP2A, which are closely related in primary structure (approximately 50%), are inhibited by a structurally diverse group of natural toxins. As part of our study toward understanding the mechanism of inhibition displayed by these toxins, we have developed research in two directions: (1) The standardization of an assay to be used in acquisition of the structure--activity relationship of inhibition data is reported. This nonradioactive assay affords detection levels of molecular phosphate released from a phosphorylated hexapeptide in subnanomolar quantities. The comparison of our IC50 values of these inhibitors against corresponding literature data provided validation for our method. (2) Computational analysis provided a global model for binding of these inhibitors to PP1. The natural toxins were shown to possess remarkably similar three-dimensional motifs upon superimposition and van der Waals minimization within the PP1 active site.

Antifungal Agents↗
PubMed1997

Case-control study of stroke and the quality of hypertension control in north west England.

OBJECTIVE: To examine the risk of stroke in relation to quality of hypertension control in routine general practice across an entire health district. DESIGN: Population based matched case-control study. SETTING: East Lancashire Health District with a participating population of 388,821 aged < or = 80. SUBJECTS: Cases were patients under 80 with their first stroke identified from a population based stroke register between 1 July 1994 and 30 June 1995. For each case two controls matched with the case for age and sex were selected from the same practice register. Hypertension was defined as systolic blood pressure > or = 160 mm Hg or diastolic blood pressure > or = 95 mm Hg, or both, on at least two occasions within any three month period or any history of treatment with antihypertensive drugs. MAIN OUTCOME MEASURES: Prevalence of hypertension and quality of control of hypertension assessed by using the mean blood pressure recorded before stroke) and odds ratios of stroke (derived from conditional logistic regression). RESULTS: Records of 267 cases and 534 controls were examined; 61% and 42% of these subjects respectively were hypertensive. Compared with non-hypertensive subjects hypertensive patients receiving treatment whose average pre-event systolic blood pressure was controlled to < 140 mm Hg had an adjusted odds ratio for stroke of 1.3 (95% confidence interval 0.6 to 2.7). Those fairly well controlled (140-149 mm Hg), moderately controlled (150-159 mm Hg), or poorly controlled (> or = 160 mm Hg) or untreated had progressively raised odds ratios of 1.6, 2.2, 3.2, and 3.5 respectively. Results for diastolic pressure were similar; both were independent of initial pressures before treatment. Around 21% of strokes were thus attributable to inadequate control with treatment, or 46 first events yearly per 100,000 population aged 40-79. CONCLUSIONS: Risk of stroke was clearly related to quality of control of blood pressure with treatment. In routine practice consistent control of blood pressure to below 150/90 mm Hg seems to be required for optimal stroke prevention.

Adult↗
PubMed1997

Characterization of host range factor 1 (hrf-1) expression in Lymantria dispar M nucleopolyhedrovirus- and recombinant Autographa californica M nucleopolyhedrovirus-infected IPLB-Ld652Y cells.

We previously identified a gene, host range factor 1 (hrf-1), in Lymantria dispar M nucleopolyhedrovirus (LdMNPV) which promoted Autographa californica M nucleopolyhedrovirus (AcMNPV) replication in a nonpermissive cell line IPLB-Ld652Y (Ld652Y). A recombinant AcMNPV, vAcLdPS, that bore hrf-1 controlled by two synthetic baculovirus late promoters and that replicated in Ld652Y cells was constructed. In this study, we constructed a new recombinant AcMNPV, vAcLdPD, bearing only hrf-1 controlled by its own promoter. vAcLdPD replicated in Ld652Y cells in the same manner as vAcLdPS, confirming that hrf-1 alone was sufficient to promote AcMNPV replication in Ld652Y cells. hrf-1 was transcribed as a delayed early gene in LdMNPV but as an immediate early gene in both recombinant AcMNPVs. Primer extension analysis showed that the initiator sequence TCAGT was used as the transcription start site in both LdMNPV and recombinant AcMNPVs. Additional sequencing revealed several regulatory motifs in the hrf-1 upstream region. hrf-1 transcripts in LdMNPV- and vAcLdPS-infected Ld652Y cells terminated near the polyadenylation signal at the end of hrf-1 ORF while in vAcLdPD, the hrf-1 transcripts terminated at a downstream polyadenylation signal at the end of ORF 603. Using Western blot analysis, we detected HRF-1 expression in both recombinant AcMNPV-infected Ld652Y cells but not in LdMNPV-infected Ld652Y cells.

Animals↗
PubMed1997

Experimental study on the effects of aprotinin on myocardial ischemia and reperfusion.

Direct effects of a high-dose aprotinin on the normally perfused hearts and the myocardial protection after ischemia and reperfusion were investigated in an isolated working rat heart model. In trial I, hearts had no ischemia and were perfused with either K-H solution or the K-H solution containing aprotinin (200 KIU/ml) for 55 min. No statistically significant difference was observed in hemodynamics between the two groups. In trial II, hearts were exposed to 150 min period of global ischemia at 15 degrees C with 4 degrees C multidose St. Thomas' II solution (STS). The control group I received normal K-H solution; the group II was treated with the solution with aprotinin added. The group III was similar to the group I and received the STS enriched with aprotinin. On reperfusion, the recovery of hearts in group III was significantly better than those of the group I and II, as reflected by better hemodynamics and myocardial ATP levels and milder myocardial ultrastructural injury. There was no difference between the group I and II. These results suggest that the aprotinin a dose of 200 KIU/ml has no harmful effects on normally perfused hearts and has a marked myocardial protective effect on the prolonged myocardial ischemia when used in cold crystalloid cardioplegia.

Animals↗
PubMed1997

Protein kinase C activators work in synergy with specific growth factors to initiate tyrosine hydroxylase expression in striatal neurons in culture.

Our previous studies indicate that, in the noncatecholamine (non-CA) neurons of the striatum, expression of the gene for the CA biosynthetic enzyme tyrosine hydroxylase (TH) can be initiated by the synergistic interaction of acidic fibroblast growth factor (aFGF) and a second partner molecule. In this study, we sought to determine whether the activators of protein kinase C (PKC) signaling pathways, either alone or in conjunction with various growth factors, is sufficient to induce TH in striatal neurons. We found that when the active beta from of 4 beta-12-O-tetradecanoylphorbol 13-acetate (TPA), but not the inactive alpha analogue, was incubated in the presence of aFGF, basic FGF, or brain-derived neurotrophic factor, TH expression was initiated. Activation of the PKC pathways alone (in the absence of growth factors) did not mimic these effects, suggesting that multiple pathway activation is required for novel TH expression. Although other specific activators of PKC were effective growth factor partners, TPA was the most potent with an ED50 of 0.008 muM. Conversely, inhibitors of protein kinases, such as H7, H8, or H89, prevented the expression of TH by aFGF and TPA. Because pretreatment with protein (cycloheximide) or RNA synthesis (amanitin and actinomycin D) inhibitors eliminated the inductive effect of aFGF and TPA, we conclude that de novo transcription and translation are necessary for the expression of TH after convergence of both PKC and growth factor pathways.

Animals↗
PubMed1997

Responses of insect cells to baculovirus infection: protein synthesis shutdown and apoptosis.

Protein synthesis is globally shut down at late times postinfection in the baculovirus Autographa californica M nuclear polyhedrosis virus (AcMNPV)-infected gypsy moth cell line Ld652Y. A single gene, hrf-1, from another baculovirus, Lymantria dispar M nucleopolyhedrovirus, is able to preclude protein synthesis shutdown and ensure production of AcMNPV progeny in Ld652Y cells (S. M. Thiem, X. Du, M. E. Quentin, and M. M. Berner, J. Virol. 70:2221-2229, 1996; X. Du and S. M. Thiem, Virology 227:420-430, 1997). AcMNPV contains a potent antiapoptotic gene, p35, and protein synthesis arrest was reported in apoptotic insect cells induced by infection with AcMNPV lacking p35. In exploring the function of host range factor 1 (HRF-1) and the possible connection between protein synthesis shutdown and apoptosis, a series of recombinant AcMNPVs with different complements of p35 and hrf-1 were employed in apoptosis and protein synthesis assays. We found that the apoptotic suppressor AcMNPV P35 was translated prior to protein synthesis shutdown and functioned to prevent apoptosis. HRF-1 prevented protein synthesis shutdown even when the cells were undergoing apoptosis, but HRF-1 could not functionally substitute for P35. The DNA synthesis inhibitor aphidicolin could block both apoptosis and protein synthesis shutdown in Ld652Y cells infected with p35 mutant AcMNPVs but not the protein synthesis shutdown in wild-type AcMNPV-infected Ld652Y cells. These data suggest that protein synthesis shutdown and apoptosis are separate responses of Ld652Y cells to AcMNPV infection and that P35 is involved in inducing a protein synthesis shutdown response in the absence of late viral gene expression in Ld652Y cells. A model was developed for these responses of Ld652Y cells to AcMNPV infection.

Animals↗
PubMed1997

A community based stroke register in a high risk area for stroke in north west England.

STUDY OBJECTIVE: To develop a community based stroke register to assess the magnitude of the problem of stroke in an entire health district in a high risk area for stroke. DESIGN: Community based stroke register from general practice data. SETTING: East Lancashire Health Authority with a 1995 population of 534,287. PATIENTS: The stroke register was developed and maintained for one calendar year in East Lancashire between 1 July 1994 and 30 June 1995. Efforts were made to include all patients who had a stroke during this period from participating general practices, using several sources of referral. MAIN RESULTS: Of the district's 118 general practices, 93 (79%) participated fully, covering a population of 405,272. A total of 932 strokes, including 642 first ever cases, were cross checked and confirmed, with only 50% from any single source, mainly the practices. The total stroke incidence rate was 1.60 per 1000 per year, adjusted for the England and Wales 1991 census population. The rate increased considerably with age from 0.88/1000 for ages 50-54 to 20.56/1000 for ages 85-89 years. From 50-74 years, the age specific incidence was higher in men, but overall it was higher in women (1.87; 95% confidence interval 1.67, 2.04 per 1000) than in men (1.31; 1.15, 1.47 per 1000), and slightly lower than in Oxford a decade earlier. The rate also varied in different localities, with higher rates in the central towns of Hyndburn (2.05/ 1000), Blackburn (1.63/1000), and Burnley (1.80/1000) and lowest values in rural areas (1.18/1000 in Pendle). Case fatality from stroke at 28 days was 34% and the hospital admission rate was high at 70%. CONCLUSIONS: The multiple source registration method is required for a stroke register. Stroke incidence in this area was still high and there was considerable variation across the district. Case fatality rates were similar to those in previous studies.

Adult↗
PubMed1997

Protective effects of interleukin-11 in a murine model of ischemic bowel necrosis.

The present study examined the effect of interleukin-11 (IL-11) in a murine model of bowel ischemia (BI). Prophylactic IL-11 administration in BI mice (induced by occluding the superior mesenteric artery for 90 min) was associated with significantly decreased morbidity and mortality. IL-11-treated mice demonstrated rapid recovery of intestinal mucosa as evidenced by an increase in mitotic activity and suppression of apoptosis in intestinal crypt cells as well as increased peripheral platelet and leukocyte counts primarily due to an increase in peripheral lymphocyte number in BI mice. In contrast to vehicle-treated mice, which uniformly developed thrombocytopenia after ischemic injury, no IL-11-treated BI mice developed thrombocytopenia during the experimental period. These data suggest a role for IL-11 in the treatment of gastrointestinal mucosal diseases due to a wide variety of causative injuries.

Animals↗
PubMed1997

[R wave relative oscillometric blood pressure measurement].

To improve the accuracy of oscillometric blood pressure measurement, an artifact rejection method for oscillations detection called R wave-relative method was developed. It was mainly based on the correlation between ECG R wave and oscillation. Combining with identification of oscillation characteristics this method can distinguish valid signals from interference. This algorithm has been implemented in 8098 microcontroller. Its program flowchart has also been presented in this paper.

Algorithms↗
PubMed1997

[Analysis of the causes of neonatal deaths at term in pregnancy induced hypertension patients].

OBJECTIVE: To study the neonatal developmental status, its causes of death and their possible correlation in women complicated with pregnancy induced hypertension (PIH). METHODS: 46 autopsies of neonatal death at term with PIH and their clinical data were collected. The developmental status was evaluated by body weight, body length, and the weights of lungs, kidneys, liver and brain. The causes of death were reviewed by the clinicopathologic findings. RESULTS: The neonatal development features for mild PIH in term pregnancy approached to the normal levels of 37 to 38 gestation weeks. In the infants with moderate and severe PIH, the body weights, the weights of lungs and liver were significantly decreased in comparison with those of the mild PIH, respectively (P < 0.05), while the weights of kidneys and brain were not significantly decreased. The causes of death showed that pulmonary hypoplasia accounted for 23.9%, primary pulmonary atelectasis 10.9%, pulmonary hyaline membrane disease 21.7%, massive pulmonary hemorrhage 13.0%, the meconium aspiration 19.6% and others 10.9%. There was no difference in sex among the dead infants. CONCLUSIONS: The PIH syndrome had retarded the process of fetal growth and development, and associated with the severity of PIH, mostly involving the lung and the liver. The pulmonary hypoplasia and immaturity were the primary causes for neonatal death in PIH women.

Cause of Death↗
PubMed1997

[The relationship between the pathologic features of the uninvolved endometrium and prognosis in postmenopausal endometrial carcinoma].

OBJECTIVE: To investigate the relationship between the pathologic features of the uninvolved endometrium and prognosis in postmenopausal endometrial carcinoma. METHOD: The clinicopathologic features of 204 cases of endometrial carcinoma were analyzed retrospectively, according to the proliferative and atrophic uninvolved endometrium, a long term follow-up was done. RESULTS: The patients with proliferative uninvolved endometrium (PUE) were more much related with the clinical risk factors than those of atrophic uninvolved endometrium (AUE) (P < 0.001). AUE cases had more virulent types of nonendometrial carcinoma than those of PUE (27% vs 5.5%, P < 0.001), and had much worse grade, much deeper myometrial invasion and much vascular invasion (P < 0.001). The overall 5-year survival rate was 96.7% in the PUE cases and 86.2% in the AUE cases (P < 0.001). CONCLUSION: The histopathologic types of the uninvolved endometrium were related to the prognosis of the patients with endometrial carcinoma. The patients with proliferative uninvolved endometrium had better prognosis than those with atrophic uninvolved endometrium.

Adenocarcinoma↗
PubMed1997

[The development of a fluid percussion device for brain injury of animals].

This paper discusses a fluid percussion device for brain injury. The injury is produced by striking the cork with a pendulum dropped from a known fall height to produce transient high pressure through a fluid transfer system. Experimental results show the device has the advantages of making a controllable, repeatable, and precise injury, and it can produce different levels of injury on different animals.

Animals↗
PubMed1996

Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ib alpha.

The zeta-form 14-3-3 protein (14-3-3zeta) regulates protein kinases and interacts with several signaling molecules. We reported previously that a platelet adhesion receptor, glycoprotein (GP) Ib-IX, was associated with a 29-kDa protein with partial sequences identical to 14-3-3zeta. In this study, the interaction between GPIb-IX and recombinant 14-3-3zeta is reconstituted. Further, we show that the 14-3-3zeta binding site in GPIb is within a 15 residue sequence at the C terminus of GPIb-alpha, as indicated by antibody inhibition and direct binding of 14-3-3zeta to synthetic GPIb-alpha cytoplasmic domain peptides. The 14-3-3zeta binds to recombinant wild type GPIb-IX but not to the GPIb-alpha mutants lacking C-terminal 5 or more residues, suggesting that the C-terminal 5 residues of GPIb-alpha are critical. Similarity between the GPIb-alpha C-terminal sequence and the serine-rich regions of Raf and Bcr kinases suggests a possible serine-rich recognition motif for the 14-3-3 protein.

14-3-3 Proteins↗