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Biomedical subjects

L Zhao

Publications and source records attributed to L Zhao.

At least 217 records · Page 12Linked to original sources

Genetic determination of cardiac mass in normotensive rats: results from an F344xWKY cross.

Genetic determinants affect adult cardiac mass and the predisposition to develop cardiac hypertrophy. The aim of this study was to identify quantitative trait loci (QTL) that control heart and left ventricular (LV) weight by use of normotensive inbred rat strains that differ in their adult cardiac mass phenotype. We studied 126 male F2 rats derived from a cross of normotensive Wistar-Kyoto and Fischer 344 rats. At 12 weeks of age, total heart weight and LV weight were measured. Genomic DNA from these animals was screened by use of polymorphic microsatellite markers across the whole genome (excluding the sex chromosomes). In this cross, the genetic contribution to total heart weight variation was 56%, and the genetic contribution for LV weight was 55%. Using the Mapmaker/QTL computer package, we identified a significant QTL on chromosome 3 with a log10 likelihood (LOD) score of 4.8, which accounted for 16.5% of the total variance of LV weight. This QTL was centered close to the marker D3Rat29. The QTL was also found to be significantly linked with total heart weight (LOD=4.4). These data provide the first demonstration of a QTL on chromosome 3 that plays a role in determining the difference in LV mass between normotensive Fischer 344 and Wistar- Kyoto inbred rat strains. The prostaglandin synthase 1 gene is located within the QTL.

Animals↗

Elements of a paracrine tubular renin-angiotensin system along the entire nephron.

The renin-angiotensin system is a major regulator of body sodium, predominantly through the actions of intrarenal angiotensin II of unclear origin. We show that polarized epithelium of the proximal tubule synthesizes and secretes angiotensinogen at its apical side and that the protein can be detected in urine as a function of dietary sodium. Furthermore, we demonstrate that renin is expressed and secreted in a restricted nephron segment, the connecting tubule, also in a sodium-dependent fashion. A paracrine renin-angiotensin system operating along the entire nephron may contribute to long-term arterial pressure regulation by integrating distant tubular sodium-reabsorbing functions.

Angiotensinogen↗

Mice without a functional relaxin gene are unable to deliver milk to their pups.

We have used gene targeting to generate relaxin (rlx)-deficient mice. The majority (15 of 17) of homozygous (rlx-/-) mice are fertile and produce normal litters. However their mammary development is deficient; pups are unable to suckle and die within 24 h of birth unless cross-fostered to a wild-type (rlx+/+) foster mother. The nipples of rlx-/- animals do not enlarge significantly during pregnancy, and their histology retains the appearance of the virgin state. Breast parenchyma is somewhat underdeveloped at term even though milk is produced. Mammary ducts become grossly dilated in these animals. Heterozygous (rlx+/-) mice lactate normally. The interpubic ligament does not relax during pregnancy in rlx-/- mice. Plasma osmolality during late gestation was significantly higher (P < 0.001) in rlx-/- mice than in wild-type controls.

Alleles↗

Urocortin messenger ribonucleic acid: tissue distribution in the rat and regulation in thymus by lipopolysaccharide and glucocorticoids.

Urocortin (Ucn), a new mammalian member of the CRF family, is a candidate endogenous ligand for type 2 CRF receptors. In a survey of peripheral tissues from adult male rats, we found that Ucn messenger RNA (mRNA) was abundant in the gastrointestinal tract and immune tissues such as thymus and spleen. We next tested the hypothesis that levels of Ucn mRNA levels in thymus and spleen would be altered after immune activation. As measured by ribonculease protection assay, lipopolysaccharide (LPS) induced a 2-fold time-dependent increase in thymic Ucn mRNA levels within 6 h. By contrast, splenic Ucn mRNA levels decreased after LPS. Because LPS activates the hypothalamus-pituitary-adrenal (HPA) axis, we examined whether the effects of LPS on Ucn mRNA might be mediated through changes in HPA axis hormones. Ucn mRNA in thymus, but not spleen, was significantly increased after ACTH injection; however, LPS did not increase Ucn expression in the thymus of adrenalectomized rats with corticosterone replacement, despite substantial increases in ACTH. Finally, sc injection of corticosterone stimulated Ucn mRNA comparably to that of LPS. Together, these results suggest that Ucn mRNA expression can increase after immune activation in a corticosterone-dependent manner, and that such changes in Ucn mRNA may be an additional consequence of HPA axis activation.

Animals↗

Developmental and hormonal regulation of murine scavenger receptor, class B, type 1.

The scavenger receptor, class B, type I (SR-BI), is the predominant receptor that supplies plasma cholesterol to steroidogenic tissues in rodents. We showed previously that steroidogenic factor-1 (SF-1) binds a sequence in the human SR-BI promoter whose integrity is required for high-level SR-BI expression in cultured adrenocortical tumor cells. We now provide in vivo evidence that SF-1 regulates SR-BI. During mouse embryogenesis, SR-BI mRNA was initially expressed in the genital ridge of both sexes and persisted in the developing testes but not ovary. This sexually dimorphic expression profile of SR-BI expression in the gonads mirrors that of SF-1. No SR-BI mRNA was detected in the gonadal ridge of day 11.5 SF-1 knockout embryos. Both SR-BI and SF-1 mRNA were expressed in the cortical cells of the nascent adrenal glands. These studies directly support SF-1 participating in the regulation of SR-BI in vivo. We examined the effect of cAMP on SR-BI mRNA and protein in mouse adrenocortical (Y1-BS1) and testicular carcinoma Leydig (MA-10) cells. The time courses of induction were strikingly similar to those described for other cAMP- and SF-1-regulated genes. Addition of lipoproteins reduced SR-BI expression in Y1-BS1 cells, an effect that was reversed by administration of cAMP analogs. SR-BI mRNA and protein were expressed at high levels in the adrenal glands of knockout mice lacking the steroidogenic acute regulatory protein; these mice have extensive lipid deposits in the adrenocortical cells and high circulating levels of ACTH. Taken together, these studies suggest that trophic hormones can override the suppressive effect of cholesterol on SR-BI expression, thus ensuring that steroidogenesis is maintained during stress.

Adrenal Glands↗

The treatment of congenital club foot by operation to correct deformity and achieve dynamic muscle balance.

We operated on 111 patients with 159 congenital club feet with the aim of correcting the deformity and achieving dynamic muscle balance. Clinical and biomechanical assessment was undertaken at least six years after operation when the patient was more than 13 years of age. The mean follow-up was for 11 years 10 months (6 to 36 years). Good and excellent results were obtained in 91.8%. Patients with normal function of the calf had a better outcome than those with weak calf muscles. The radiological changes were assessed in relation to the clinical outcome. The distribution of pressure under the foot was measured for biomechanical assessment. Our results support the view that muscle imbalance is an aetiological factor in club foot. Early surgery seems to be preferable. It is suggested that operation should be undertaken as soon as possible after the age of six months, although it may be carried out up to the age of five years. The establishment of dynamic muscle balance appears to be an effective method of maintaining correction. Satisfactory long-term results can be achieved with adequate appearance and function.

Biomechanical Phenomena↗

The effect of peers' alcohol consumption on parental influence: a cognitive mediational model.

OBJECTIVE: The current study was designed to elucidate familial and social influences on adolescent alcohol consumption by testing three hypotheses derived from the prototype/willingness model of adolescent risk behavior: (1) parents' prototypes of adolescent drinkers affect adolescent consumption through their impact on adolescents' prototypes, (2) strong parent-child relationships are associated with acceptance of parental influence regarding drinking and thus with less adolescent drinking and (3) association with peers who drink dilutes parental influence over adolescents' alcohol consumption. METHOD: Two hundred sixty-six rural adolescents, ages 15 through 17 at Time 1, and their parents and siblings completed questionnaires about drinking behavior and drinking-related cognitions at 1-year intervals for 3 years. RESULTS: Structural equation models provided evidence of transmission of prototypes of adolescent drinkers from parents to adolescents and evidence that these prototypes mediate adolescent alcohol consumption. They also provide evidence that although parents' prototypes and parent-adolescent relationships are important in shaping the adolescents' drinking, association with peers who drink significantly attenuates this influence. CONCLUSIONS: These data suggest that parents can influence their children's drinking, but that this influence has more of an impact if the adolescent is not involved in a drinking-conducive peer environment. The current analyses also suggest that the process of becoming an adolescent drinker involves an active rejection of parents' influence rather than a passive movement away from parents' attitudes and beliefs-a process that is accelerated by association with peers who drink.

Adolescent↗

Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis.

By virtue of its potential effects on rates of energy expenditure, uncoupling protein 3 (UCP3) is an obesity candidate gene. We identified nine sequence variants in UCP3, including Val9Met, Val102Ile, Arg282Cys, and a splice site mutation in the intron between exons 6 and 7. The splice mutation results in an inability to synthesize mRNA for the long isoform (UCP3L) of UCP3. Linkage (sib pair), association, and transmission disequilibrium testing studies on 942 African-Americans did not suggest a significant effect of UCP3 on body composition in this group. In vastus lateralis skeletal muscle of individuals homozygous for the splice mutation, no UCP3L mRNA was detectable; the short isoform (UCP3S) was present in an increased amount. In this muscle, we detected no alterations of in vitro mitochondrial coupling activity, mitochondrial respiratory enzyme activity, or systemic oxygen consumption or respiratory quotient at rest or during exercise. These genetic and physiologic data suggest the following possibilities: UCP3S has uncoupling capabilities equivalent to UCP3L; other UCPs may compensate for a deficiency of bioactive UCP3L; UCP3L does not function primarily as a mitochondrial uncoupling protein.

Alternative Splicing↗

Absence of habituation to repeated exposures to a rotating optokinetic drum with brief intersession intervals.

The purpose of this study was to investigate whether participants would habituate to repeated exposures to a rotating drum with brief intersession intervals. Participants were 41 college students, divided into a High Susceptibility group and a Low Susceptibility group based on their subjective symptoms of motion sickness during the first exposure to the rotating drum. The study consisted of three 16-min. exposures to a rotating drum with intersession intervals of 30 min. Contrary to expectation, for the High Susceptibility group, the symptom score mean of the first session was significantly less than that of the second and third sessions; and the drum viewing time of the first session was longer than that of the second and third sessions. In the Low Susceptibility group, the symptom score and drum viewing time were not significantly different among the three sessions. In conclusion, participants did not habituate to three repeated exposures to a rotating drum with intersession intervals of 30 min. Instead, a sensitization response occurred for the participants high in susceptibility.

Adult↗

[Detection of NV-HB/s DNA and c-myc mRNA in mice inoculated with hepatitis B nucleic acid vaccine--NV-HB/s].

OBJECTIVE: To explore the persistence period of plasmid in mice muscles injected with NV-HB/s and the possible influence on oncogene C-myc. METHODS: Anti-HBs was detected by ELISA; NV-HB/s was detected by In-situ and Southern-blot hybridization separately; C-myc mRNA was detected by In-situ hybridization. RESULTS: All mice injected with NV-HB/s were positive of anti-HBs after 1 month of immunization; NV-HB/s was negative when detected by In-situ hybridization; By Southern-blot hybridization, the positive rates of NV-HB/s were decreasing from 100% in 2 months to 25% after 6 months of inoculation. CONCLUSIONS: NV-HB/s would be disintegrated little by little after injected into mouse muscles; no C-myc activation was observed in 6 months after NV-HB/s inoculation.

Animals↗

Ultrastructure of stomatal development in Arabidopsis (Brassicaceae) leaves.

Stomatal development was studied in wild-type Arabidopsis leaves using light and electron microscopy. Development involves three successive types of stomatal precursor cells: meristemoid mother cells, meristemoids, and guard mother cells (GMCs). The first two types divide asymmetrically, whereas GMCs divide symmetrically. Analysis of cell wall patterns indicates that meristemoids can divide asymmetrically a variable number of times. Before meristemoid division, the nucleus and a preprophase band of microtubules become located on one side of the cell, and the vacuole on the other. Meristemoids are often triangular in shape and have evenly thickened walls. GMCs can be detected by their roughly oval shape, increased starch accumulation, and wall thickenings on opposite ends of the cells. Because these features are also found in developing stomata, stomatal differentiation begins in GMCs. The wall thickenings mark the division site in the GMC since they overlie a preprophase band of microtubules and occur where the cell plate fuses with the parent cell wall. Stomatal differentiation in Arabidopsis resembles that of other genera with kidney-shaped guard cells. This identification of stages in stomatal development in wild-type Arabidopsis provides a foundation for the analysis of relevant genes and of mutants defective in stomatal patterning, cell specification, and differentiation.

Journal Article↗

Molecular modeling on kappa opioid receptor and its interaction with nonpeptide kappa opioid agonists.

AIM: To study the interaction between kappa-opioid receptor and its nonpeptide agonists. METHODS: The "conservation patterns" for G-protein coupled receptors (GPCR) were used to determine 7 transmembrane (TM) regions. Taking the crystallographic coordinates of bacteriorhodopsin (BR) as the template, the 3D structural model was constructed for 7 TM of kappa-opioid subtype with molecular mechanics (MM) method. Five highly active nonpeptide kappa-opioid agonists were docked into the 7 helices of kappa-opioid receptor to study the ligand-receptor interaction. RESULTS: Four important interactions between U-50488-like agonists and kappa-opioid receptors were drawn according to our modeling study: (1) the protonated pyrrolidine nitrogen of the ligands formed a hydrogen-bond with the carboxyl of Asp138; (2) the carbonyl oxygen of ligands forms a hydrogen bond to the hydroxyl of Ser187; (3) the aryl groups connected to acylamide of the agonists inserted into a hydrophobic cavity enclosed by residues Val239, Val236, Phe235, Val232, Leu186, and Trp183; (4) the pyrrolidine of the ligands in the complexes was surrounded by Ile290, Asp138, Ile194, Ile135, and Cys131. CONCLUSION: The proposed interaction mechanism is helpful for further mutant experiments and designing novel potent kappa-opioid agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

[Determination of plasma serotonins level in patients with pregnancy induced hypertension].

OBJECTIVE: To determine whether levels of serotonin(5-HT) and 5-hydroxy-indolescetic acid (5-HIAA) play an important role in the pathogenesis of pregnancy induced hypertension (PIH). METHODS: Maternal venous blood were collected from 60 women with PIH and 40 normotensive pregnant women in third trimester as control, and umbilical venous blood were collected from 38 newborns in each groups. Plasma and platelet 5-HT and 5-HIAA levels were measured by spectrophotometry. RESULTS: The mean 5-HT level was (54.16 +/- 10.13) nmol/L and 5-HIAA was (43.62 +/- 6.37) nmol/L in maternal plasma, while they were (50.23 +/- 7.83) nmol/L and (41.73 +/- 8.61) nmol/L in umbilical plasma respectively in the normotensive group. The mean 5-HT was (86.24 +/- 14.37) nmol/L and 5-HIAA was (62.37 +/- 8.34) nmol/L in maternal plasma of patients with PIH. While the mean 5-HT was (71.56 +/- 10.13) nmol/L and 5-HIAA was (62.37 +/- 11.37) nmol/L in umbilical plasma in PIH group. 5-HT and 5-HIAA levels in maternal and umbilical blood of PIH groups were significantly higher than that in the control group (P < 0.01). CONCLUSIONS: The markedly elevated plasma 5-HT and 5-HIAA levels might be caused by the increased release of 5-HT by platelet. The result showed that elevated levels of 5-HT and 5-HIAA in patients with PIH might take part in the pathogenesis of PIH.

Adult↗

[GB virus-C infection in Chinese patients with hepatocellular carcinoma].

Hepatitis B and C viruses (HBV, HCV) are closely related with hepatocellular carcinoma(HCC). The association between the new discovered GB-virus C (GBV-C) and HCC has not yet been known. In this study, 124 HCC patients were detected for the prevalence of GBV-C RNA by the one-step nested reverse transcription polymerase chain reaction (RT-PCR) and followed by hybridization using GBV-C probes located at 3'-untranslated region (3'-UTR) from its reported genomes. The results showed that 33 of 124 (26.6%) HCC cases were GBV-C RNA positive, including 12 cases positive HBsAg and anti-HCV, and 3 for cases negative HBsAg and anti-HCV. The clinical background of the patients with HBsAg and/or anti-HCV who were also positive for GBV-C RNA did not differ from the background of those who were negative for GBV-C RNA except the ratio of blood transfusion history. In conclusion, GBV-C has a high prevalence in Chinese HCC patients. Even though no sufficient data supports the causality of GBV-C on hepatocarcinogenesis, further researches aimed at whether GBV-C infection aggravates the incidence of HCC are warranted.

Adult↗

[The effects of zinc on liver metallothionein in scalded rats].

OBJECTIVE: To investigate the changes in liver metallothionein (MT) in scalded rats. METHODS: The scalded rats in deficient zinc condition were fed with diets containing zinc 4 micrograms/g, 10 micrograms/g, and 80 micrograms/g respectively. The changes in serum zinc, liver zinc and liver MT were observed. RESULTS: The serum zinc decreased, liver zinc and MT increased. The higher diet zinc levels were, The higher serum zinc, liver zinc and MT became. The correlation analysis showed that the changes between liver zinc level and liver MT was positive relationship(r = 0.85, P < 0.01). CONCLUSION: Serum zinc decrease, liver zinc increase after burn. This is connect with increment of MT synthesis in liver, zinc is inducer to MT. It can improve synthesis of liver MT.

Animals↗

Congenital choledochal cyst with pancreatitis.

OBJECTIVE: To understand the relationship among congenital choledochal cyst, anomalous junction of pancreaticobiliary duct (AJPBD) and pancreatitis. METHODS: 25 children with choledochal cyst treated in our hospital were included in this study. Their ages ranged from 2 months to 14 years. Intraoperative cholangiography was performed in 24 children. Pancreatic samples obtained from the head and body of the pancreas at operation were observed under light and electron microscope. Serum amylase was analyzed one week before and after operation respectively. Bile amylase in the cyst and gallbladder was measured at operation. RESULTS: The incidence of AJPBD was 70%. Inflammatory cell infiltration and fibrous hyperplasia were seen in the pancreatic specimens of 5 children, of whom 4 had AJPBD. No ultrastructural changes were found in 2 children without AJPBD, while different changes were seen in 6 with AJPBD, including those showing no pathological changes under light microscope. All the changes became more severe as the age of the patient increased. The bile and serum amylase levels were higher in children with AJPBD than those without AJPBD (P < 0.05). CONCLUSION: Congenital choledochal cyst has a close relationship with AJPBD and pancreatitis. Pancreatic pathological changes have a long and chronic course from ultrastructural changes to macroscopic changes for the developing of pancreatitis.

Adolescent↗

[Effect of extremely low frequency magnetic field on brain response to selective mental arithmetic under simulated weightlessness].

Objective. To study effects of extremely low frequency magnetic field (ELMF) on brain function state during weightlessness. Method. The brain event-related potentials (ERPs) during a selective mental arithmetic task were compared in 40 normal subjects (20-25 yrs) before and after ELMF (5 Hz) stimulation during simulated weightlessness (head down tilt -10 degrees, HDT). Result. The amplitude of slow positive potentials which were supposed to be related to the mental arithmetic activity decreased significantly especially in 100 min after HDT, but it did not decrease significantly after ELMF stimulation. Conclusion. ELMF stimulation may improve the brain function state during simulated weightlessness.

Adult↗

[Clinical application of impulse oscillometry].

OBJECTIVE: To discuss the clinical significance of impulse oscillometry(IOS) to determine the resistance of large and small airways and the compliance of lung. METHODS: The IOS indices of 40 normal cases, 50 cases of chronic obstructive pulmonary diseases (COPD) and 60 cases of pleural effusion were determined at 5-35 Hz. Their FEV1/FVC and maximal expiratory flow-volume curve (MEFV curve) were measured in conventional method at the same time. RESULTS: Compared with normal cases, the peripheral resistance of the 50 patients with COPD rose obviously and the central airway resistance rose in some of them, the resonance frequency increased, but the peripheral reactance descended at the same time (P < 0.01). Resistance curve show markedly nonlinear decreasing course with increasing frequency. The resistance increased and the reactance descended in end-expiration. FEV1/FVC < 50%, MEFV curve showed severe obstructive shape. 60 patients with pleural effusion were found the resistance increasing and reactance descending to negative values in end-inpiration at low frequencies (inverse values relation at low frequencies). FEV1/FVC were nearly normal, MEFV curve showed restrictive dysfunction shape only in half of them. CONCLUSIONS: IOS can reflect variation of airway resistance and lung compliance. The future development of IOS could be prosperous.

Humans↗