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Biomedical subjects

D Hu

Publications and source records attributed to D Hu.

At least 73 records · Page 4Linked to original sources
PubMed2000

Genetic and teratogenic approaches to craniofacial development.

Craniofacial malformations are the most common birth defects that occur in humans, with facial clefting representing the majority of these defects. Facial clefts can arise at any stage of development due to perturbations that alter the extracellular matrix as well as affect the patterning, migration, proliferation, and differentiation of cells. In this review, we focus on recent advances in the understanding of the developmental basis for facial clefting through the analysis of the effects of gene disruption experiments and treatments with teratogens in both chickens and mice. Specifically, we analyze the results of disruptions to genes such as Sonic hedgehog (Shh), epidermal growth factor receptor (EGFR), Distal-less (Dlx), and transforming growth factor beta 3 (TGFbeta3). We also describe the effects that teratogens such as retinoic acid, jervine, and cyclopamine have on facial clefting and discuss mechanisms for their action. In addition to providing insight into the bases for abnormal craniofacial growth, genetic and teratogenic techniques are powerful tools for understanding the normal developmental processes that generate and pattern the face.

Animals↗
PubMed2000

[TBX5 mutation in Chinese patients with Holt-Oram syndrome].

OBJECTIVE: To analyse TBX5 mutation in Chinese patients with Holt-Oram syndrome(HOS). METHODS: Seven HOS families were analysed with single strand conformation polymorphism(SSCP) and sequencing. RESULTS: Three SSCP changes were detected and identified as the TBX5 gene mutation at three new sites. One of the changes is a frameshift mutation caused by a base cytidine deletion at the cDNA sequence of 416, which altered all the codons after the point, thus it can not encode the protein of normal amino acid sequence; another is a missense mutation induced by a base substitution(C-->A) at the cDNA sequence of 145, which made the codon of that point change from CAG-->AAG, and encoded amino acid changed from glutamine(Gln) to lysine(Lys), consequently the change weakened the function of TBX5 protein; the third is also a missense mutation which resulted from a base substitution (T-->C) at the cDNA sequence of 161, this change made the codon of that point change from ATC-->ACC, it changed the encoded amino acid from isoleucine(Ile) to threonine(Thr), which reduced the function of TBX5 protein. CONCLUSION: HOS in Chinese is caused by mutation in TBX5.

Abnormalities, Multiple↗
PubMed2000

[Effect of domestic glutathione on the alcoholic liver disease].

OBJECTIVE: To evaluate the effect and safety of domestic glutathione (GSH) on serum ALT, AST, SB levels in alcoholic liver disease (ALD) by multicenter, randomized and TAD controlled trial. METHODS: All the 110 patients with ALD enrolled had a history of drinking over 80g-120g daily for 5 years, and were randomized either into GSH (continuous infusion of 600g daily for 30d) or TAD (with the same dosage, course and route as GSH) group. The efficacy and safery were evaluated with clinical and biochemical (ALT, AST and GGT) parameters. RESULTS: After 8 weeks of treatment, the clinical signs were improved at a different degree in both groups. ALT, AST and SB showed no significant difference in the two groups (the efficacy rate of 93% vs 96%, P>0.05). CONCLUSION: The domestic GSH, with a good tolerance and safety, has a sound efficacy in the improvement of clinical signs and hepatic functions.

Adolescent↗
PubMed2000

[Study of hepatitis C virus specific immune responses in anti-HCV positive patients without hepatitis C viremia].

OBJECTIVE: To study the hepatitis C virus specific immune responses in anti - HCV positive patients without hepatitis C viremia. METHODS: 15 anti-HCV positive patients without hepatitis C viremia, 15 patients with chronic HCV infection and 15 normal controls were selected for this study. The T cell responses, NK cell (natural killer cells) activity, cytokine production and HCV specific antibodies were detected by MTT, LDH release and ELISA. RESULTS: Our study showed that the T cell proliferative reaction of patients without hepatitis C viremia was significantly higher than that of patients with chronic HCV infection and normal controls and the T cell response for HCV core antigen were higher than NS3 and N54, but there was no significant proliferative response to NS5 antigen. We also found that there were no differences in anti-HCV antibody production and NK cell activity between the two groups and the level of IFN-gamma in patients without hepatitis C viremia was higher than that in patients with persistent HCV infection. CONCLUSIONS: There are a lot of advantageous changes of HCV specific humoral and cellular immune response in anti-HCV positive patients without hepatitis C viremia, these immune responses may play a role in clearance of HCV.

Adult↗
PubMed2000

The relationship between Th1/Th2-type cells and disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the imbalance of Th1/Th2-type cytokines in patients with systemic lupus erythematosus (SLE) and its relation to disease activity. METHODS: Intracellular cytokines were determined by flow-cytometry following whole-blood culture. RESULTS: Patients with systemic lupus erythematosus disease activity index (SLEDAI) > 10 had statistically significantly fewer CD4+ or CD8+ T cells producing IFN-gamma than patients with SLEDAI = 0, SLEDAI 1-10 or healthy controls (P < 0.01, P < 0.01 or P < 0.05, respectively). Patients with SLEDAI > 10 also had decreased ratio of IFN-gamma/IL-4 positive CD4+ or CD8+ T cells, compared with patients with SLEDAI = 0, SLEDAI 1-10 or healthy controls (P < 0.05). The decreased Th1 or Tc1 cells and the ratios of IFN-gamma: IL-4 positive CD4+ T-cells were significantly correlated with disease activity (P < 0.05). CONCLUSION: SLE is characterized by an imbalance of Th1/Th2 and Tc1/Tc2 cytokines. The decreased Th1 or Tc1 cells and the Th1/Th2 ratio are related to disease activity.

Adult↗
PubMed2000

[A preliminary study on body level of nitric oxide in workers exposed to carbon disulfide].

OBJECTIVE: To study changes in body plasma level of nitric oxide (NO) in workers exposed to carbon disulfide (CS(2)) and its possible mechanism. METHODS: Plasma levels of NO and lipid peroxide (LPO) and activity of erythrocyte superoxide dismutase (Ery-SOD) were determined in the workers exposed and unexposed to CS(2) in a chemical synthetic fiber works. RESULTS: Level of NO was (43.28 +/- 19.83) and (50.07 +/- 21.01) micromol/L in high- and low-dose exposed groups, respectively, significantly lower than that in the control group, which was (70.66 +/- 26.83) micromol/L (P < 0.05). Activity of Ery-SOD was 4 832.21 u/g Hb and 3,520.80 u/g Hb in high- and low-dose exposed groups, respectively, significantly higher than that in the control group, which was 2,425.34 u/g Hb (P < 0.05). Level of LPO was 19.38 and 17.09 micromol/L in high- and low-dose exposed groups, respectively, significantly higher than that in the control group, which was 4.37 micromol/L (P < 0.05). CONCLUSION: Occupational long-term exposure to CS(2) could induce reduction of NO level in the body with its mechanism related to increase of super-oxygen cation O(2)(*-) induced by CS(2).

Adolescent↗
PubMed2000

[The changing trends of demography and oral diseases for Chinese dentistry].

OBJECTIVE: The purpose of this paper is to discuss the changed trends of population, oral diseases and their effects on Chinese dentistry. METHODS: The demographic and epidemiologic data published in recent books and journals were reviewed and analyzed. RESULTS: As the 21st century approached, dentistry in China would face many changing trends and challenges. 1. a growing population and an aging population: The two sub-populations with the greatest need for prevention and treatment were children and old patients who were outpacing the supply of dental manpower. 2. The changed dental disease patterns: The prevalence of caries was increasing and more than two thirds of Chinese suffered from periodontal disease. The traditional dental approaches have not been able to satisfy the needs of Chinese. CONCLUSION: The challenge created by these demographic, economic and advances in dental technology is changing Chinese dentistry.

Adolescent↗
PubMed2000

[Ocular axial length and refractive changes in pediatric pseudophakia].

PURPOSE: To evaluate the ocular axial length and refractive changes that occured in children who had cataract extraction with intraocular lens implantation and to investigate the factors that influenced the pseudophakic refraction. METHODS: A review of 12 eyes in 10 children (mean age 7.16 years, range 3.83 to 10.16 years) who had cataract extraction with intraocular lens implantation was undertaken. Patients were followed for an average of 35.8 months. The preoperative and the last postoperative axial length and corneal curvature (K readings) in both operated and unoperated eyes were measured. The distance from the vertex of the cornea to the anterior vertex of intraocular lens (AVpc) was measured in the final follw-up. The initial (in two weeks) and the last refractive status of pseudophakia were examined. Overall age at surgery averaged 7.16 years (range 3.83 to 10.16 years), with followed up of 35.8 months. RESULTS: In the 12 operated eyes, the mean axial growth was 0.39 mm, whereas in the other eight unoperated eyes it was 0.66 mm. Though the axial length of both eyes increased significantly after surgery (P < 0.05), there was no significant difference in the postoperative increase of axial length between the two groups(P > 0.05). In K readings, there was no significant difference between the operated and unoperated eyes before surgery and in the last follow-up respectively. There was no significant difference between the preoperation and the last follow-up in the operated and the unoperated eyes respectively. The average calculated AVpc (AVpc2) was 4.66 30 mm, but the average objective AVpc (AVpc1) measured with ultrasonic biometry was 3.83 mm. The average difference between them was 0.8320 mm and was significant (P < 0.01). According to SRK formula, using preoperative and the last postoperative axial length and corneal curvature to predict refractive changes, the myopic shift was -1.53 D, but the average objective refractive difference between the last and initial examination after surgery was -3.86 D. The average difference between the predicted and actual postoperative refractive changes was significant (P < 0.05). CONCLUSION: Our study suggests that there may be no effect on ocular growth in children (3 to 10 years) followed cataract extraction and intraocular lens implantation. Increasing of axial length and moving forward of intraocular lens induced by complication may result in myopic shift in pseudophakia of children. Slightly undercorrected eyes with intraocular lens in children after cataract extraction will gradually move to emmetropia or moderate myopia in adulthood.

Adolescent↗
PubMed1999

Mapping of a DNA binding region of the PI-sceI homing endonuclease by affinity cleavage and alanine-scanning mutagenesis.

The PI-SceI protein is a member of the LAGLIDADG family of homing endonucleases that is generated by a protein splicing reaction. PI-SceI has a bipartite domain structure, and the protein splicing and endonucleolytic reactions are catalyzed by residues in domains I and II, respectively. Structural and mutational evidence indicates that both domains mediate DNA binding. Treatment of the protein with trypsin breaks a peptide bond within a disordered region of the endonuclease domain situated between residues Val-270 and Leu-280 and interferes with the ability of this domain to bind DNA. To identify specific residues in this region that are involved in DNA binding and/or catalysis, alanine-scanning mutagenesis was used to create a set of PI-SceI mutant proteins that were assayed for activity. One of these mutants, N281A, was >300-fold less active than wild-type PI-SceI, and two other proteins, R277A and N284A, were completely inactive. These decreases in cleavage activity parallel similar decreases in substrate binding by the endonuclease domains of these mutant proteins. We mapped the approximate position of the disordered region to one of the ends of the 31 base pair PI-SceI recognition sequence using mutant proteins that were substituted with cysteine at residues Asn-274 and Glu-283 and tethered to the chemical nuclease FeBABE. These mutational and affinity cleavage data strongly support a model of PI-SceI docked to its DNA substrate that suggests that one or more residues identified here are responsible for contacting base pair A/T(-)(9), which is essential for substrate binding.

Alanine↗
PubMed1999

Reduction in mitochondrial membrane potential is an early event in Fas-independent CTL-mediated apoptosis.

Cytotoxic T lymphocytes (CTL) can destroy target cells via the Fas-mediated pathway or the granule-mediated pathway. We used Fas-negative target cells to examine for target-cell reduction in mitochondrial membrane potential (DeltaPsi(m)) induced by intact CTL via the granule-mediated pathway. We find that reduction in DeltaPsi(m) is an early step in Fas-independent CTL killing of target cells that precedes phosphatidyl serine translocation, cytosolic protein release, or loss of plasma membrane integrity. Target-cell reduction in DeltaPsi(m) and cytoplasmic protein release in Fas-independent CTL killing were inhibited by N-carbobenzoxy-Ala-Pro-Phe chloromethyl ketone, but not by caspase inhibitors N-carbobenzoxy-Val-Ala-Asp fluoromethyl ketone (z-VAD-fmk) or N-carbobenzoxy-Asp-Glu-Val-Asp fluoromethyl ketone (z-DEVD-fmk). This contrasts with Fas-mediated apoptosis, in which the reduction in DeltaPsi(m) can be inhibited by z-VAD-fmk or z-DEVD-fmk. Assessing the changes in target-cell DeltaPsi(m) can provide for a sensitive and rapid means with which to monitor CTL activity.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Prevention of experimental proliferative vitreoretinopathy with daunomycin and triamcinolone based on the time course of the disease.

BACKGROUND: Our previous experiments showed a limited effect of treatment with daunomycin when given at the inflammatory phase of the development of proliferative vitreoretinopathy (PVR) induced by macrophages in rabbits. In the present study, we tested the efficacy of daunomycin when given at the proliferative phase and combined with triamcinolone given separately at the inflammatory phase in the same model. METHODS: Four groups of rabbits, 16 animals in each, respectively received 5 microg daunomycin on day 6; 1 mg triamcinolone immediately after macrophage injection; 1 mg triamcinolone immediately and 5 microg daunomycin on day 6 (combined drugs); and 0.1 ml saline (controls). Ophthalmoscopy and 3H-thymidine autoradiography were use to evaluate the effects of drugs on traction retinal detachments and cellular proliferation in the vitreous and on the retina. RESULTS: Retinal detachment occurred in 33.3%, 16.1%, 8.3% and 83.3% (P<0.01) of the eyes treated with daunomycin, triamcinolone, combined drugs, and the controls, respectively. Autoradiography revealed significantly decreased numbers of labelled nuclei on days 7 and 14 in daunomycin-treated eyes compared with controls. Significantly decreased numbers of inflammatory cells and labelled cells were noted in eyes treated with triamcinolone and combined drugs. CONCLUSION: Daunomycin given at the proliferative phase, and combined with triamcinolone given at the inflammatory phase of PVR, can be more effective in preventing PVR development than daunomycin given at the inflammatory phase.

Animals↗
PubMed1999

From head to toe: conservation of molecular signals regulating limb and craniofacial morphogenesis.

Recent evidence indicates that many molecules involved in generating and patterning the limbs also play a role during craniofacial morphogenesis. On the surface, this is an unexpected finding given that these regions of the body have separate evolutionary origins, are composed of different embryonic tissues, and are quite dissimilar in their anatomy. Results from several experiments involving Sonic hedgehog and retinoic acid point to a remarkable conservation of the signaling pathways mediated by these morphogens across multiple organ systems. Moreover, mutants such as the extra-toes and doublefoot mouse, and the talpid chicken also provide insights on common developmental processes that underlie the formation of the limbs and face. The identification of highly conserved aspects of morphogenesis is important for understanding fundamental mechanisms of development, as well as for revealing the common denominator of countless birth defects and providing new strategies for their prevention and cure.

Animals↗
PubMed1999

Liver disease in Navajo neuropathy.

OBJECTIVE: To describe clinical and histologic features of liver disease in infants and children with Navajo neuropathy (NN). METHODS: Physicians at Navajo Area Indian Health Service facilities and neurologists and gastroenterologists at regional referral hospitals were surveyed for identification of patients born between 1980 and 1994 with known or suspected NN. Clinical records and liver histologic findings were reviewed. RESULTS: Liver disease was present in all children with NN. Three clinical phenotypes of NN were observed, based on age at presentation and course: infantile NN presented in 5 infants before 6 months of age with jaundice and failure to thrive and progressed to liver failure before 2 years of age; childhood NN presented in 6 children between 1 and 5 years of age with liver dysfunction, which progressed to liver failure and death within 6 months; and classical NN presented in 9 children with variable onset of liver disease but progressive neurologic deterioration. Liver histologic findings were characterized by multinucleate giant cells, macrovesicular and microvesicular steatosis, pseudo-acini, inflammation, cholestasis, and bridging fibrosis and cirrhosis. Cases of all 3 phenotypes occurred within the same kindred. CONCLUSIONS: Liver disease is an important component of NN and may be the predominant feature in infants and young children. We propose changing the name of this disease to Navajo neurohepatopathy.

Age of Onset↗
PubMed1999

A cluster of microvillous inclusion disease in the Navajo population.

We report 4 unrelated patients with characteristic microscopic findings of microvillous inclusion disease (MID) with early-onset phenotype. All 4 patients came from the Navajo reservation in northern Arizona. A literature search revealed a fifth unrelated Navajo child with MID. The unusually high incidence in this population indicates that a founder effect might be responsible for an increased frequency of this rare genetic disorder in the Navajo. It is recommended that all Navajo infants presenting with severe diarrhea during early infancy undergo investigation for MID.

Arizona↗
PubMed1999

Hyperalgesia due to nerve damage: role of nerve growth factor.

The hypothesis that nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) contribute to hyperalgesia resulting from nerve damage was tested in rats in which the sciatic nerve was partially transected on one side. Administration of antisera raised against NGF and BDNF relieved mechanical and thermal hyperalgesia in these animals. It has been suggested that NGF may elicit hyperalgesia by inducing mast cells to release algesic agents such as serotonin (5-HT). We found that degranulation of mast cells with compound 48/80 relieved mechanical and thermal hyperalgesia produced by nerve damage. We also found that local injection of the 5-HT2A and 5-HT3 receptor antagonists ketanserin and ICS 205-930 into the affected hind paw relieved mechanical hyperalgesia in a dose-dependent fashion. These findings support the idea that in this rat model of hyperalgesia due to peripheral nerve damage, NGF acts on mast cells to induce release of 5-HT, which sensitizes nociceptors. Hyperalgesia due to nerve injury and hyperalgesia due to inflammation may share some common features.

Animals↗
PubMed1999

Hyperalgesia due to nerve injury: role of prostaglandins.

The hypothesis that prostaglandins contribute to hyperalgesia resulting from nerve injury was tested in rats in which the sciatic nerve was partially transected on one side. Subcutaneous injection of indomethacin (a classic inhibitor of cyclo-oxygenase) into the affected hindpaw relieved mechanical hyperalgesia for up to 10 days after injection. Subcutaneous injection of meloxicam or SC-58125 (selective inhibitors of cyclo-oxygenase-2) into the affected hindpaw also relieved mechanical hyperalgesia, but with a shorter time-course. Subcutaneous injection of SC-19220 (an EP1 prostaglandin receptor blocker) into the affected hindpaw produced significant relief of mechanical and thermal hyperalgesia. Comparable injections into the contralateral paw or abdomen had no effect on mechanical or thermal hyperalgesia, suggesting that the effects we observed were local rather than systemic. We conclude that prostaglandins, probably prostaglandin E1 or E2, contribute to the peripheral mechanisms underlying hyperalgesia following nerve injury. These data provide further evidence that inflammatory mediators contribute to neuropathic pain, and may warrant further study of peripherally administered non-steroidal anti-inflammatory drugs as a possible treatment for such pain in patients.

Animals↗
PubMed1999

The role of sonic hedgehog in normal and abnormal craniofacial morphogenesis.

There is growing evidence that implicates a role for Sonic hedgehog (SHH) in morphogenesis of the craniofacial complex. Mutations in human and murine SHH cause midline patterning defects that are manifested in the head as holoprosencephaly and cyclopia. In addition, teratogens such as jervine, which inhibit the response of tissues to SHH, also produce cyclopia. Thus, the loss of SHH signaling during early stages of neural plate patterning has a profound influence of craniofacial morphogenesis. However, the severity of these defects precludes analyses of SHH function during later stages of craniofacial development. We have used an embryonic chick system to study the role of SHH during these later stages of craniofacial development. Using a combination of surgical and molecular experiments, we show here that SHH is essential for morphogenesis of the frontonasal and maxillary processes (FNP and MXPs), which give rise to the mid- and upper face. Transient loss of SHH signaling in the embryonic face inhibits growth of the primordia and results in defects analogous to hypotelorism and cleft lip/palate, characteristics of the mild forms of holoprosencephaly. In contrast, excess SHH leads to a mediolateral widening of the FNP and a widening between the eyes, a condition known as hypertelorism. In severe cases, this widening is accompanied by facial duplications. Collectively, these experiments demonstrate that SHH has multiple and profound effects on the entire spectrum of craniofacial development, and perturbations in SHH signaling are likely to underlie a number of human craniofacial anomalies.

Animals↗