Biomedical subjects

H Zhao

Publications and source records attributed to H Zhao.

At least 109 records · Page 6Linked to original sources

PubMed2001

Pregnancy and steroid hormones enhance the systemic and regional hemodynamic effects of calcitonin gene-related peptide in rats.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide known to be involved in the regulation of vascular resistance. Several lines of evidence suggest that CGRP plays a role in the vascular adaptations that occur during normal pregnancy; however, the effects of exogenous CGRP on systemic and regional hemodynamics during pregnancy remain unknown. Therefore, the purpose of this study was to determine the hemodynamic effects of systemically administered CGRP in adult pregnant (Day 19) and ovariectomized (ovx) rats using the radioactive microsphere technique. In addition, we also used ovariectomized rats treated for 3 days with estradiol (E2), progesterone (P4), E2 + P4 in sesame oil, or oil only to assess if these hormones regulate the CGRP-induced hemodynamic changes. On the day of study, catheters were inserted into the left cardiac ventricle (through the right carotid artery), right jugular vein, and caudal tail artery. Hemodynamic studies using radioactive microspheres were then performed in conscious rats 3 h after recovery from anesthesia. Blood pressure and heart rate were continuously monitored, and left ventricular pressure was determined immediately prior to each microsphere injection. Microspheres labeled with either (141)Ce or (85)Sr were injected prior to and 2 min following the i.v. bolus injection of CGRP (270 pmol/kg body weight [BW]). Mean arterial pressure (MAP) and total vascular resistance in pregnant rats was lower than in ovx rats, and this was further decreased with an i.v. bolus injection of 270 pmol CGRP/kg BW. Cardiac output was elevated with further increases upon CGRP administration in pregnant but not in ovx rats. The CGRP-induced changes in MAP, total vascular resistance, and cardiac output in E2 + P4 -treated rats were similar to that observed in Day 19 pregnant rats, indicating that CGRP effects on these parameters during pregnancy may be modulated by steroid hormones. Both pregnancy and E2 + P4 treatment in ovx rats caused significant decreases in CGRP-induced resistance in mesenteric, coronary, and renal vasculature. Thus, the vasodilatory sensitivity to CGRP during pregnancy may be mediated through decreased total vascular resistance, particularly to coronary, mesenteric, and renal vascular beds. Thus, CGRP-induced vasodilatory effects may play a role in mediating vascular adaptations that occur during pregnancy and that steroid hormones may modulate these CGRP effects.

Animals↗

PubMed2001

Quantification of MUC5AC protein in human tears.

PURPOSE: MUC5AC has been identified as a major secretory mucin of conjunctival goblet cells and precorneal tear film. However, no method has been reported to quantify MUC5AC protein in human tears. The objective of this study was to establish a method to measure the amount of MUC5AC in human tears and to correlate the amount of MUC5AC with age, gender, and dry eye diseases. METHODS: A goat antibody was raised to synthetic peptides corresponding to nonglycosylated epitopes of human MUC5AC mucin. This antibody and a horseradish peroxidase-coupled second antibody were used to develop a quantitative immunoassay to measure the MUC5AC concentration of tear samples collected on Schirmer strips. Porcine stomach mucin was used as a standard for the assay. The chemiluminescent MUC5AC signal was digitized and quantified. Tear samples from 19 healthy volunteers and 31 clinically diagnosed dry eye patients were analyzed. RESULTS: MUC5AC concentration in human tears ranged from undetectable to more than 200 microg/mL porcine stomach mucin equivalent. In the healthy population, low, moderate, and high concentrations were found in the tear samples from younger and older persons and from both men and women. The mean MUC5AC content in tears was lower in the dry eye patients than in the age- and gender-matched healthy individuals. CONCLUSIONS: A method was established to quantify MUC5AC in human tear samples obtained on Schirmer strips. There was no correlation between the amount of MUC5AC and age or gender in the healthy population. Dry eye disease patients, however, typically showed reduced concentrations of soluble MUC5AC in the tear film.

Adult↗

PubMed2001

Progressive decrease in constrictor reactivity of the non-absorbing intestine during chronic sepsis.

Chronic sepsis leads to an impaired intestinal microcirculation, which might reflect altered microvascular control. We hypothesized that intestinal microvascular sensitivity to norepinephrine (NE) is decreased during chronic sepsis. Chronic sepsis was induced by a polymicrobial inoculation of implanted subcutaneous sponges in rats. Septic rats were studied either 24 or 72 h after a single inoculation (1-hit) of bacteria. Other rats received a second inoculation (2-hit) of bacteria 48 h later and were studied at 24 h after the second inoculation. NE (0.01-1.0 microM) responses in the non-absorbing terminal ileal arterioles (inflow A1, proximal-p and distal-d premucosal A3) were measured by video microscopy. NE threshold sensitivity (pD(T20) = -log of 20% response dose) was analyzed. pD(T20) was significantly decreased in A1, pA3, and dA3 of 1-hit 24-h septic rats (P < 0.05), and was further decreased in all vessels of 2-hit 72-h septic rats (P < 0.05). In contrast, the pDT(T20) of all three vessels significantly returned toward normal values after 72 h in rats that had only 1 bacteria inoculation. We conclude that an initial bacterial challenge decreases vasoconstrictor reactivity of the intestinal microcirculation and that subsequent repeated bacterial challenge exacerbates this defect in vasoconstrictor control in the non-absorbing intestine.

Animals↗

PubMed2001

Abundance of apoptotic neoplastic cells in diagnostic biopsy samples is not a prognostic factor in childhood primitive neuroectodermal tumors of the central nervous system.

PURPOSE: To assess if the abundance of apoptotic tumor cells is an independent prognostic factor in primitive neuroectodermal tumors (PNET) of the central nervous system. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tumor tissue sections from 78 clinically well-characterized children with PNET were evaluated by terminal deoxytransferase-mediated deoxyuridinie-5'-triphosphate (dUTP) nick-end labeling (TUNEL). Apoptotic indices (AI) were determined by counting TUNEL-positive tumor cells either in the highest staining region (AI hot spot) or in at least 15 randomly chosen fields (AI random). The AI hot spot and AI random were then correlated with clinical variables and survival outcome. RESULTS: AI hot spot (median 0.56%; range 0%-6.54%) and AI random (median 0.30%; range 0%-3.21%) showed considerable intertumor variability. Moreover, 53% of the evaluated PNET showed a more than two-fold difference between AI hot spot and AI random, showing important intratumoral variability of the abundance of apoptotic cells in a subset of the evaluated PNET. No significant associations were found between AI hot spot and AI random with clinical variables or survival outcome. CONCLUSION: The apoptotic index does not predict survival outcome and is not specifically associated with clinical variables of prognostic significance in childhood PNET.

Apoptosis↗

PubMed2001

Light control of Arabidopsis development entails coordinated regulation of genome expression and cellular pathways.

An expressed sequence tag-based microarray was used to profile genome expression underlying light control of Arabidopsis development. Qualitatively similar gene expression profiles were observed among seedlings grown in different light qualities, including far-red, red, and blue light, which are mediated primarily by phytochrome A, phytochrome B, and the cryptochromes, respectively. Furthermore, light/dark transitions also triggered similar differential genome expression profiles. Most light treatments also resulted in distinct expression profiles in small fractions of the expressed sequence tags examined. The similarly regulated genes in all light conditions were estimated to account for approximately one-third of the genome, with three-fifths upregulated and two-fifths downregulated by light. Analysis of those light-regulated genes revealed more than 26 cellular pathways that are regulated coordinately by light. Thus, light controls Arabidopsis development through coordinately regulating metabolic and regulatory pathways.

Arabidopsis↗

PubMed2001

Environmentally induced reversible conformational switching in the yeast cell adhesion protein alpha-agglutinin.

The yeast cell adhesion protein alpha-agglutinin is expressed on the surface of a free-living organism and is subjected to a variety of environmental conditions. Circular dichroism (CD) spectroscopy shows that the binding region of alpha-agglutinin has a beta-sheet-rich structure, with only approximately 2% alpha-helix under native conditions (15-40 degrees C at pH 5.5). This region is predicted to fold into three immunoglobulin-like domains, and models are consistent with the CD spectra as well as with peptide mapping and site-specific mutagenesis. However, secondary structure prediction algorithms show that segments comprising approximately 17% of the residues have high alpha-helical and low beta-sheet potential. Two model peptides of such segments had helical tendencies, and one of these peptides showed pH-dependent conformational switching. Similarly, CD spectroscopy of the binding region of alpha-agglutinin showed reversible conversion from beta-rich to mixed alpha/beta structure at elevated temperatures or when the pH was changed. The reversibility of these changes implied that there is a small energy difference between the all-beta and the alpha/beta states. Similar changes followed cleavage of peptide or disulfide bonds. Together, these observations imply that short sequences of high helical propensity are constrained to a beta-rich state by covalent and local charge interactions under native conditions, but form helices under non-native conditions.

Algorithms↗

PubMed2001

Testing equality of survival functions of quality-adjusted lifetime.

We present a method for comparing the survival functions of quality-adjusted lifetime from two treatments. This test statistic becomes the ordinary log-rank test when quality-adjusted lifetime is the same as the survival time. Simulation experiments are conducted to examine the behavior of our proposed test statistic under both null and alternative hypotheses. In addition, we apply our method to a breast cancer trial for comparing the distribution of quality-adjusted lifetime between two treatment regimes.

Biometry↗

PubMed2001

On estimating medical cost and incremental cost-effectiveness ratios with censored data.

Medical cost estimation is very important to health care organizations and health policy makers. We consider cost-effectiveness analysis for competing treatments in a staggered-entry, survival-analysis-based clinical trial. We propose a method for estimating mean medical cost over patients in such settings. The proposed estimator is shown to be consistent and asymptotically normal, and its asymptotic variance can be obtained. In addition, we propose a method for estimating the incremental cost-effectiveness ratio and for obtaining a confidence interval for it. Simulation experiments are conducted to evaluate our proposed methods. Finally, we apply our methods to a clinical trial comparing the cost effectiveness of implanted cardiac defibrillators with conventional therapy for individuals at high risk for ventricular arrhythmias.

Arrhythmias, Cardiac↗

PubMed2001

Statistical analysis of uniparental disomy data using hidden Markov models.

Genetic studies of uniparental disomy (UPD) employing many markers have helped geneticists to gain a better understanding of the molecular mechanisms underlying nondisjunction. However, most existing methods cannot simultaneously analyze all genetic markers and consistently incorporate crossover interference; they thus fail to make the most use of genetic information in the data. In the present article, we describe a hidden Markov model for multilocus uniparental disomy data. This method is based on the chi-square model for the crossover process and can simultaneously incorporate all marker information including untyped and uninformative markers. We then apply this novel method to analyze a set of UPD15 data.

Biometry↗

PubMed2001

Kinetic measurements of cell surface E-selectin/carbohydrate ligand interactions.

Selectin/ligand interactions initiate the multistep adhesion and signaling cascades in the recruitment of leukocytes from circulation to inflamed tissues and may also play a role in tumor metastasis. Kinetic properties of these interactions are essential determinants governing blood-borne cells' tethering to and rolling on the vessel wall. Extending our recently developed micropipette method, we have measured the kinetic rates of E-selectin/ligand interactions. Red cells coated with an E-selectin construct were allowed to bind HL-60 or Colo-205 cells bearing carbohydrate ligands. Specific adhesions were observed to occur at isolated points, the frequency of which followed a Poisson distribution. These point attachments were formed at the same rate with both the HL-60 and Colo-205 cells (0.14 +/- 0.04 and 0.13 +/- 0.03 microm2 s(-2) per unit density of E-selectin, respectively) but dissociated from the former at a rate twice as fast as did from the latter (0.92 +/- 0.23 and 0.44 +/- 0.10 s(-1), respectively). The reverse rates agree well with those measured by the flow chamber. The forward rates are orders of magnitude higher than those of Fcgamma receptors interacting with IgG measured under similar conditions, consistent with the rapid kinetics requirement for the function of E-selectin/ligand binding, which is to capture leukocytes on endothelial surfaces from flow.

Animals↗

PubMed2001

Interaction of alpha-agglutinin and a-agglutinin, Saccharomyces cerevisiae sexual cell adhesion molecules.

alpha-Agglutinin and a-agglutinin are complementary cell adhesion glycoproteins active during mating in the yeast Saccharomyces cerevisiae. They bind with high affinity and high specificity: cells of opposite mating types are irreversibly bound by a few pairs of agglutinins. Equilibrium and surface plasmon resonance kinetic analyses showed that the purified binding region of alpha-agglutinin interacted similarly with purified a-agglutinin and with a-agglutinin expressed on cell surfaces. At 20 degrees C, the K(D) for the interaction was 2 x 10(-9) to 5 x 10(-9) M. This high affinity was a result of a very low dissociation rate ( approximately 2.6 x 10(-4) s(-1)) coupled with a low association rate (= 5 x 10(4) M(-1) s(-1)). Circular-dichroism spectroscopy showed that binding of the proteins was accompanied by measurable changes in secondary structure. Furthermore, when binding was assessed at 10 degrees C, the association kinetics were sigmoidal, with a very low initial rate. An induced-fit model of binding with substantial apposition of hydrophobic surfaces on the two ligands can explain the observed affinity, kinetics, and specificity and the conformational effects of the binding reaction.

Agglutinins↗

PubMed2001

ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1.

Chk1 is an evolutionarily conserved protein kinase that regulates cell cycle progression in response to checkpoint activation. In this study, we demonstrated that agents that block DNA replication or cause certain forms of DNA damage induce the phosphorylation of human Chk1. The phosphorylated form of Chk1 possessed higher intrinsic protein kinase activity and eluted more quickly on gel filtration columns. Serines 317 and 345 were identified as sites of phosphorylation in vivo, and ATR (the ATM- and Rad3-related protein kinase) phosphorylated both of these sites in vitro. Furthermore, phosphorylation of Chk1 on serines 317 and 345 in vivo was ATR dependent. Mutants of Chk1 containing alanine in place of serines 317 and 345 were poorly activated in response to replication blocks or genotoxic stress in vivo, were poorly phosphorylated by ATR in vitro, and were not found in faster-eluting fractions by gel filtration. These findings demonstrate that the activation of Chk1 in response to replication blocks and certain forms of genotoxic stress involves phosphorylation of serines 317 and 345. In addition, this study implicates ATR as a direct upstream activator of Chk1 in human cells.

Adenoviridae↗

PubMed2001

Urea signaling to ERK phosphorylation in renal medullary cells requires extracellular calcium but not calcium entry.

The renal cell line mIMCD3 exhibits markedly upregulated phosphorylation of the extracellular signal-regulated kinase (ERK) 1 and 2 in response to urea treatment (200 mM for 5 min). Previous data have suggested the involvement of a classical protein kinase C (cPKC)-dependent pathway in downstream events related to urea signaling. We now show that urea-inducible ERK activation requires extracellular calcium; unexpectedly, it occurs independently of activation of cPKC isoforms. Pharmacological inhibitors of known intracellular calcium release pathways and extracellular calcium entry pathways fail to inhibit ERK activation by urea. Fura 2 ratiometry was used to assess the effect of urea treatment on intracellular calcium mobilization. In single-cell analyses using subconfluent monolayers and in population-wide analyses using both confluent monolayers and cells in suspension, urea failed to increase intracellular calcium concentration. Taken together, these data indicate that urea-inducible ERK activation requires calcium action but not calcium entry. Although direct evidence is lacking, one possible explanation could include involvement of a calcium-dependent extracellular moiety of a cell surface-associated protein.

Animals↗

PubMed2001

Nerve growth factor enhances calcitonin gene-related peptide expression in the spontaneously hypertensive rat.

Calcitonin gene-related peptide (CGRP) expression is markedly reduced in dorsal root ganglia neurons in the spontaneously hypertensive rat (SHR). This decrease in such a potent vasodilator may contribute to the elevated blood pressure. Therefore, the purpose of this study was to determine whether stimulation of neuronal CGRP expression in SHR, by means of the administration of nerve growth factor, would lower the blood pressure. Nerve growth factor (10 nmol/L per kg/d, IP) was given to 12-week SHR (n=8 to 11/group) once a day for 1, 3, and 7 days. Control SHR received vehicle only. All rats were instrumented for CGRP receptor antagonist (CGRP(8-37)) administration (intravenous) and mean arterial pressure recording. Both the 1- and 3-day NGF treatments lowered the mean arterial pressure to 147+/-5 and 147+/-3 mm Hg, respectively, compared with controls (166+/-3 mm Hg). However, by day 7, the mean arterial pressure had returned to control levels (169+/-5 mm Hg). CGRP(8-37) administration produced a significant mean arterial pressure increase in all 3 nerve growth factor-treated groups (14+/-2, 10+/-2, and 13+/-2 mm Hg). CGRP mRNA levels in dorsal root ganglia were increased in the 3 neurotrophin-treated groups, whereas CGRP peptide content was higher at days 3 and 7. Therefore, nerve growth factor treatment of SHR can enhance neuronal CGRP expression. At days 1 and 3, nerve growth factor produces a depressor response that is primarily mediated by CGRP as evidenced by the pressor effect of CGRP(8-37.) At day 7, CGRP also plays a counterregulatory role, even though the mean arterial pressure has returned to control levels. This finding may result from a nerve growth factor-mediated upregulation of a pressor system that counteracts the hypotensive actions of CGRP. Thus, these data suggest that the decreased production of CGRP in SHR could contribute to the hypertension.

Animals↗

PubMed2001

Omapatrilat in subtotal nephrectomy-salt hypertension: role of calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide, plays a counterregulatory role in subtotal nephrectomy-salt (SN-salt)-induced hypertension, reflecting a stimulation of the efferent vasodilator function of perivascular sensory nerves. To determine the effect of omapatrilat, a dual ACE and neutral endopeptidase inhibitor, on blood pressure and the potential antihypertensive role for CGRP, 24 male Sprague-Dawley rats were separated into 4 groups: (1) SN-salt, (2) SN-salt plus omapatrilat (80 mg. kg(-1). d(-1) in the drinking water), (3) sham-operated plus salt, (4) sham-operated plus salt and omapatrilat. After 11 days the mean arterial pressure was higher in the SN-salt group (174+/-10 mm Hg) versus the sham-operated-salt (109+/-4 mm Hg) and sham-operated-salt plus omapatrilat (105+/-3 mm Hg) groups. Omapatrilat treatment of the SN-salt rats significantly decreased the mean arterial pressure to 123+/-7 mm Hg and significantly reduced the heart-to-body weight ratio. Intravenous administration of a specific CGRP receptor antagonist produced a significant 10+/-2 mm Hg mean arterial pressure increase in the untreated SN-salt hypertensive rats but was without effect in the other groups. This indicates that CGRP does not contribute to the antihypertensive actions of omapatrilat. In addition, CGRP mRNA and protein content in dorsal root ganglia were decreased approximately 25% in the SN-salt plus omapatrilat rats. Thus, omapatrilat not only markedly reduces the blood pressure in this model of renal failure-induced hypertension but may also prevent the abnormal compensatory stimulation of the vasodilator activity of the peripheral sensory nervous system.

Animals↗

PubMed2001

Magnetic resonance imaging of the upper airway in children with Down syndrome.

As compared with control subjects, children with Down syndrome have different size and shape relationships among tissues composing the upper airway, which may predispose them to obstructive sleep apnea (OSA). We hypothesized that Down syndrome children without OSA have similar subclinical differences. We used magnetic resonance imaging to study the upper airway in 11 Down syndrome children without OSA (age, 3.2 +/- 1.4 yr) and in 14 control subjects (age, 3.3 +/- 1.1 yr). Sequential T1- and T2-weighted spin-echo axial and sagittal images were obtained. We found a smaller airway volume in subjects with Down syndrome (1.4 +/- 0.4 versus 2.3 +/- 0.8 cm(3) in controls, p < 0.005). Subjects with Down syndrome had a smaller mid- and lower face skeleton. They had a shorter mental spine-clivus distance (5.7 +/- 0.6 versus 6.2 +/- 0.4 cm, p < 0.05), hard palate length (3.2 +/- 0.4 versus 3.7 +/- 0.2 cm, p < 0.005), and mandible volume (11.5 +/- 3.7 versus 16.9 +/- 2.9 cm3, p < 0.0005). Adenoid and tonsil volume was significantly smaller in the subjects with Down syndrome. However, the tongue, soft-palate, pterygoid, and parapharyngeal fat pads were similar to those of control subjects. This study shows that Down syndrome children without OSA do not have increased adenoid or tonsillar volume; reduced upper airway size is caused by soft tissue crowding within a smaller mid- and lower face skeleton.

Child↗

PubMed2001

Contribution of nitric oxide to the apoptotic process in human B cell chronic lymphocytic leukaemia.

B cell chronic lymphocytic leukaemia (B-CLL) is characterised by defective apoptosis that cannot be explained solely on the basis of the known chromosomal abnormalities. We and other have now reported that the leukemic cells spontaneously display the inducible isoform of nitric oxide synthase, iNOS. Inhibition of the iNOS pathway leads to increased apoptosis of the tumoral cells in vitro, indicating that the endogenous release of NO contributes to their resistance to the normal apoptotic process. The factors that induce the expression of iNOS in vivo in the leukemic cells are not yet identified. Yet, as interaction of B-CLL leukemic cells with bone marrow stromal cells promotes their survival, the involvement of adhesion molecules and integrins may be suspected. The engagement of CD23 stimulates iNOS activation in the tumoral cells, suggesting that in vivo interaction of CD23 with one of its recognised ligands may contribute to iNOS induction. A role for CD40-CD40 ligand interaction may also be hypothesised. The mechanisms involved in the anti-apoptotic role of NO are not fully understood, but may implicate the inhibition of caspase activity, hence the impairment of the Fas pathway. In addition, the mitochondrial membrane potential disruption appears to be a NO-sensitive step in the apoptosis cascade. The presence of a NOS displaying anti-apoptotic properties has now been recognised in different cell types, including various leukaemia. A better knowledge of the mechanisms governing the ultimate fate of NO, anti- versus pro-apoptotic would allow the development of new therapeutic approaches for the treatment of these diseases.

Apoptosis↗

PubMed2001

Relationship between ABO blood groups and carcinoma of esophagus and cardia in Chaoshan inhabitants of China.

AIM: To study the relationship between ABO blood groups and carcinoma of esophagus and cardia in Chaoshan inhabitants of China, which is a unique Littoral high-risk area of esophageal carcinoma in China. The poor communication and transportation in the past has made Chaoshan a relatively closed area and kept its culture and custure of old China thousand years ago. METHODS: Data on age, sex, ABO blood type and X-ray or pathological diagnose of the patients with carcinoma of esophagus or cardia were collected from the Tumor Hospital. First Affiliated Hospital, Second Affiliated Hospital of Shantou University Medical College; and the Central Hospital of Shantou and the Central Hospital of Jieyang. A total of 6685 patients with esophageal carcinoma (EC) and 2955 patients with cardiac cancer (CC) in Chaoshan district were retrospectively assessed for their association with ABO blood groups. RESULTS: The distribution of ABO blood groups in patients with EC or CC was similar to the normal local population in Chaoshan. However, blood group B in male patients with CC and in the patients with carcinoma in the upper third esophagus was 2.3% and 4.7% higher than the corresponding controls. The relative risk B O was 1.1415 (P<0.05) and 1.2696 (P<0.05), respectively. No relationship was found between ABO blood groups and tumor differentiation. CONCLUSION: ABO blood group B is associated with the incidence of CC in male individuals and carcinoma in the upper third esophagus. The distribution of ABO blood groups varies in the different geographical and ethnic groups. As a result, proper controls are very important for such studies.

ABO Blood-Group System↗