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Biomedical subjects

Y Gu

Publications and source records attributed to Y Gu.

At least 127 records · Page 7Linked to original sources
PubMed2000

Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice.

Motor incoordination, immune deficiencies, and an increased risk of cancer are the characteristic features of the hereditary disease ataxia-telangiectasia (A-T), which is caused by mutations in the ATM gene. Through gene targeting, we have generated a line of Atm mutant mice, Atm(y/y) mice. In contrast to other Atm mutant mice, Atm(y/y) mice show a lower incidence of thymic lymphoma and survive beyond a few months of age. Atm(y/y) mice exhibit deficits in motor learning indicative of cerebellar dysfunction. Even though we found no gross cerebellar degeneration in older Atm(y/y) animals, ectopic and abnormally differentiated Purkinje cells were apparent in mutant mice of all ages. These findings establish that some neuropathological abnormalities seen in A-T patients also are present in Atm mutant mice. In addition, we report a previously unrecognized effect of Atm deficiency on development or maintenance of CD4(+)8(+) thymocytes. We discuss these findings in the context of the hypothesis that abnormal development of Purkinje cells and lymphocytes contributes to the pathogenesis of A-T.

Animals↗
PubMed2000

Defective embryonic neurogenesis in Ku-deficient but not DNA-dependent protein kinase catalytic subunit-deficient mice.

Mammalian nonhomologous DNA end joining employs Ku70, Ku80, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4, and DNA ligase IV (Lig4). Herein, we show that Ku70 and Ku80 deficiency but not DNA-PKcs deficiency results in dramatically increased death of developing embryonic neurons in mice. The Ku-deficient phenotype is qualitatively similar to, but less severe than, that associated with XRCC4 and Lig4 deficiency. The lack of a neuronal death phenotype in DNA-PKcs-deficient embryos and the milder phenotype of Ku-deficient versus XRCC4- or Lig4-deficient embryos correlate with relative leakiness of residual end joining in these mutant backgrounds as assayed by a V(D)J recombination end joining assay. We conclude that normal development of the nervous system depends on the four evolutionarily conserved nonhomologous DNA end joining factors.

Animals↗
PubMed2000

Feature detection of visual neurons in the nucleus of the basal optic root in pigeons.

Previous studies have shown that the nucleus of the basal optic root in birds is involved in optokinetic nystagmus, and its neurons respond not only to large-field stimuli but also to a single object moving through their excitatory receptive fields. The present study provides electrophysiological evidence that basal optic neurons in pigeons respond vigorously to motion of a black leading edge. The orientation of the edge is also an essential factor affecting visual responses of these cells, showing that any deviation of the edge from the direction perpendicular to the preferred direction decreases visual responses in most cases. Furthermore, visual responses increase as the edge is lengthened within the excitatory receptive field. However, a square, semicircle and isosceles with an area ratio of 1.00: 0.39: 0.50 but with an identical leading edge elicit almost the same responses, which are not dependent on the shape and area of visual stimuli. It suggests that these feature extraction properties, similar to those of neurons in the nucleus lentiformis mesencephali, may be specialized for detecting optokinetic stimuli rich in luminance contrasts, but not for realizing pattern recognition.

Animals↗
PubMed2000

The first alpha-fluoroallenylphosphonate, the synthesis of conjugated fluoroenynes, and the stereoselective synthesis of vinylfluorophosphonates using a new multifunctional fluorine-containing building block

Limitations on current methodologies for the introduction of CF(2) and CFH in complex alpha-fluorophosphonates led to the synthesis of a fluorine-containing building block TIPS-C&tbd1;CCFXP(O)(OEt)(2), where X = H or F. This multifunctional fluorine synthon reacts with carbonyl compounds under WHE conditions to give high yields of fluorinated conjugated enynes and enediyne. When X = F, trapping of the desilylated anion with an electrophile after TIPS removal provided exclusive access to gamma-substituted derivatives of alpha-fluorophosphonates. When X = H, TBAF deprotection of the silyl group yields H(2)C=C=CFP(O)(OEt)(2) through an allenyl-propargyl resonance stabilized anion. The allene moiety has been used as template in the stereoselective synthesis of alpha-fluoro-beta, gamma-diiodopropenyl phosphonate, via electrophilic iodination, and alpha-fluoro-gamma-amino-alpha,beta-unsaturated phosphonates, including unsaturated phosphononucleosides, by nucleophilic displacement of an allylic iodide. Hydroamination of H(2)C=C=CFP(O)(OEt)(2) using secondary amines produced (Z)-alpha-fluoroenaminophosphonates, whereas Diels-Alder cycloaddition with cyclopentadiene provides the corresponding exocyclic vinylfluorophosphonate.

Journal Article↗
PubMed2000

Diagnostic criteria for pseudo-Class III malocclusion.

The aim of this study is to identify the diagnostic criteria for pseudo-Class III malocclusion and compare it with Class I malocclusion in the southern Chinese population. Sixty-seven patients (mean age, 10.9 +/- 1.8 years) were included in this study; 36 patients represented pseudo-Class III malocclusion. Selection criteria included the following: (1) anterior crossbite (at least 2 incisors with negative overjet and overbite); (2) mandibular displacement; (3) all patients were southern Chinese who had been followed after the growth spurt, none had developed a skeletal Class III malocclusion; (4) the patients were treated for an average of 7 months to procline upper incisors and retrocline lower incisors. None of the cases received any treatment that might affect skeletal growth. Thirty-one patients with Class I malocclusion were included in the Class I malocclusion group for the comparison of dentoskeletal characteristics with the pseudo-Class III malocclusion group. Selection criteria included the following: (1) skeletal Class I malocclusion with normal overjet and overbite, (2) mild to moderate crowding with Class I molar relationship, (3) straight facial profile. The following were included in the assessment of pseudo-Class III malocclusion cases: (1) family history, (2) molar and canine relationships at habitual occlusion and centric relation, and (3) dentoskeletal morphology. The results were that 72% of the examined cases in the pseudo-Class III malocclusion group showed no family history and 75% showed Class I molar relationship at habitual occlusion. Compared with the Class I malocclusion group, subjects in the pseudo-Class III malocclusion group showed a significantly decreased midface length, increased maxillary-mandibular difference, more retroclined upper incisors, and a retrusive upper lip. In conclusion, a pseudo-Class III malocclusion is characterized by retroclined upper incisors, retrusive upper lip, decreased midface length, and increased maxillary-mandibular difference. Findings of this study showed that patients with a pseudo-Class III malocclusion exhibit certain morphologic, dental, and skeletal characteristics that should be of aid in the diagnosis of pseudo-Class III malocclusion.

Centric Relation↗
PubMed2000

Molecular modeling of the interactions of trichosanthin with four substrate analogs.

Trichosanthin (TCS) is a ribosome-inactivating protein (RIP) that possesses N-glycosidase activity. It inactivates ribosomes and arrests protein synthesis by removing a specific adenine from 28S rRNA. A molecular dynamics simulated annealing method was applied to study the binding modes of TCS with substrate analogs, three oligonucleotides GAG, GAGA, and CGAGAG, based on the crystal structures of the stable complexes of TCS with NADPH and with the reaction product adenine. A water molecule proposed to be responsible for hydrolyzing the N-glycosidic bond was included in the model. All the oligoribonucleotides can dock into the active cleft of TCS without unfavorable contacts. The interaction energies between TCS and the three oligonucleotides were calculated. The interactions of TCS with NADH were also studied by a molecular dynamics simulated annealing method. The interaction energy between NADH and TCS was compared with that between NADPH and TCS, showing that the lack of 2'-phosphate group leads to an energy rise of 20 kcal/mol.

Models, Molecular↗
PubMed2000

Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system.

Mouse embryos deficient in Gata3 die by 11 days post coitum (d.p.c.) from pathology of undetermined origin. We recently showed that Gata3-directed lacZ expression of a 625-kb Gata3 YAC transgene in mice mimics endogenous Gata3 expression, except in thymus and the sympathoadrenal system. As this transgene failed to overcome embryonic lethality (unpublished data and ref. 3) in Gata3-/- mice, we hypothesized that a neuroendocrine deficiency in the sympathetic nervous system (SNS) might cause embryonic lethality in these mutants. We find here that null mutation of Gata3 leads to reduced accumulation of Th (encoding tyrosine hydroxylase, Th) and Dbh (dopamine beta-hydroxylase, Dbh) mRNA, whereas several other SNS genes are unaffected. We show that Th and Dbh deficiencies lead to reduced noradrenaline in the SNS, and that noradrenaline deficiency is a proximal cause of death in mutants by feeding catechol intermediates to pregnant dams, thereby partially averting Gata3 mutation-induced lethality. These older, pharmacologically rescued mutants revealed abnormalities that previously could not be detected in untreated mutants. These late embryonic defects include renal hypoplasia and developmental defects in structures derived from cephalic neural crest cells. Thus we have shown that Gata3 has a role in the differentiation of multiple cell lineages during embryogenesis.

Animals↗
PubMed2000

Assessing number-specific error in the recall of onset of last menstrual period.

The goal of this investigation was to determine whether women who did not report preferred numbers for their last menstrual period (LMP) may be a group of women who are particularly careful in keeping track of their menstrual cycles and therefore have more accurate LMP dating--based on a comparison with ultrasound examinations. We also sought to estimate the frequency with which preferred numbers are reported in different sources of data and for different subgroups of women. First, we examined the 1987 California birth certificates in which LMP was collected at the time of birth (n = 504853). We also examined the records of 43880 women participating in the California Alpha-fetoprotein (AFP) Screening Program between 1986 and 1987, for whom gestational ages based on both early ultrasound examination and LMP were collected before 20 weeks of gestation. In the 1987 California birth certificates, seven numbers--1, 5, 10, 15, 20, 25 and 28--were recorded more frequently than expected. An estimated 12.9% of these records had preferred numbers. The most frequently recorded number was 15, occurring 2.5 times more often than expected (P < 0.01). In the data of the AFP Screening Program, the same seven numbers were preferred, and approximately 7.9% of records were affected by number preference. Comparisons with measurements of gestational age based on ultrasound demonstrated that LMP-based gestational ages in which non-preferred numbers are reported for the LMP are slightly more accurate than those in which preferred numbers are reported (P < 0.01). In most cases, number preference appears to introduce small errors into measurements of gestational age, probably as a result of rounding. Thus, the effect of number preference may be primarily of interest to research studies in which small errors in the measurement of gestational age will have a significant impact on findings.

Birth Certificates↗
PubMed2000

Development of antirotavirus agents in Asia.

Human rotaviruses are the major etiologic agents of diarrhea in infants and young children under 2 years of age worldwide. Rotavirus diarrhea is a life-threatening disease for children; many efforts are made to reduce the morbidity and mortality in Asia. To date many natural compounds and some Western medicines have exhibited their antirotavirus effects in clinical studies, in animal experiments and in vitro. Compared with antirotavirus agents in the USA and Europe, natural compounds have been identified as ideal candidates for antirotaviral drugs in Asia because they are cheaper and effective, have no side-effect and no toxicity. We have attempted to reveal the antirotavirus mechanism of some natural compounds. We found that cacao pigment, tea extract and pine seed shell extract inhibit rotavirus adsorption to cells while cacao pigment may also inhibit rotavirus reproduction in vitro. The usage of antirotavirus agents in Asia demonstrated that additional effective approaches to control rotavirus infection, such as antirotavirus agents, are necessary, in particular for the children with rotavirus diarrhea who have severe complications.

Antiviral Agents↗
PubMed2000

Different methods and results in the treatment of obstetrical brachial plexus palsy.

Mallet's test was used to evaluate shoulder and elbow functional results following conservative treatment, neurolysis, and nerve transfer and grafting in 31 patients with obstetrical brachial plexus palsy, who had no recovery of biceps contraction by 3 months of age. Twelve of them had been treated conservatively for 3 to 4 years. Nine patients with upper trunk conducting neuromas underwent neurolysis at the age of 4 to 6 months. Nerve transfer and grafting were performed in 10 patients at the age of 3 to 6 months. Upper trunk conducting neuromas were found in six of them. The follow-up period was, on average, 44.3 and 51.5 months in the nerve transfer and grafting group and in the neurolysis group, respectively. Excellent and good results in shoulder abduction, external rotation, and elbow flexion were found in 70 percent of patients in the nerve transfer and grafting group. However, none of the conservative treatment and neurolysis groups had a good result. The authors conclude that when there is no recovery of biceps contraction by 3 months of age, surgical intervention is indicated. Neuroma should be managed by nerve transfer and grafting, even though intraoperative electrophysiologic studies show that the neuroma is a conducting one.

Brachial Plexus Neuropathies↗
PubMed2000

AIDS vasculopathy.

Persons infected with HIV display a variety of vascular abnormalities and harbor particularly striking alterations in endothelial morphology and function. We review the effects of the virus and viral products on the endothelium and emphasize their effects on altering the clinical expression of HIV-associated diseases.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Delayed toe transplantation: experimental study and clinical application.

Delay of the operation in toe transplantation was performed with circulatory crisis, and 100 percent survival of the transplants was achieved. In 10 cases of toe transplantation in which circulatory crisis occurred, the operation was delayed. The vascular pedicle was divided, and the toe was transferred 17 to 21 hours after the donor toe was dissected. To investigate the mechanism of delayed toe transplantation, experiments in rabbits were carried out. In 36 rabbits, the hind limbs were severed except for the vascular pedicle. The endothelin content and nitric oxide content of the tissues in the hind limb and the arterial wall were tested in postoperative intervals of 4, 8, 16, 24, and 48 hours, respectively. The results showed that in 10 cases of delayed toe transplantation, all toes survived. As for the results of the experiment, there was significant increase of endothelin content and decrease of nitric oxide content in the local tissues and the arterial wall 4 to 8 hours after the operation. In postoperative 16 to 24 hours, endothelin content returned to normal level, and nitric oxide content increased remarkably. It is concluded that delayed pedicle division and toe transfer is an effective method in toe transplantation with vascular variations and circulatory crisis. The mechanism is related to the endothelin and nitric oxide content in the local tissue and the arterial wall. The indications for delayed toe transfer are also discussed.

Adolescent↗
PubMed2000

FHL2 (SLIM3) is not essential for cardiac development and function.

LIM domain-containing proteins play critical roles in vertebrate development and cellular differentiation. Recently, four members of the four and one-half LIM protein (FHL) family have been identified and cloned. One of these, FHL2, is expressed in a restricted manner in the cardiovascular system throughout development into adulthood, suggesting that FHL2 may play an important role in cardiovascular development and function. Here we describe the generation and analysis of mice carrying a null mutation of the FHL2 gene. FHL2-deficient mice are viable and maintain normal cardiac function both before and after acute mechanical stress induced by aortic constriction. These data suggest that FHL2 is not essential for cardiac development and function.

Animals↗
PubMed2000

Altered membrane proteins and permeability correlate with cardiac dysfunction in cardiomyopathic hamsters.

A mutation in the delta-sarcoglycan (SG) gene with absence of delta-SG protein in the heart has been identified in the BIO14.6 cardiomyopathic (CM) hamster, but how the defective gene leads to myocardial degeneration and dysfunction is unknown. We correlated left ventricular (LV) function with increased sarcolemmal membrane permeability and investigated the LV distribution of the dystrophin-dystroglycan complex in BIO14.6 CM hamsters. On echocardiography at 5 wk of age, the CM hamsters showed a mildly enlarged diastolic dimension (LVDD) with decreased LV percent fractional shortening (%FS), and at 9 wk further enlargement of LVDD with reduction of %FS was observed. The percent area of myocardium exhibiting increased membrane permeability or membrane rupture, assessed by Evans blue dye (EBD) staining and wheat germ agglutinin, was greater at 9 than at 5 wk. In areas not stained by EBD, immunostaining of dystrophin was detected in CM hamsters at sarcolemma and T tubules, as expected, but it was also abnormally expressed at the intercalated discs; in addition, the expression of beta-dystroglycan was significantly reduced compared with control hearts. As previously described, alpha-SG was completely deficient in CM hearts compared with control hearts. In myocardial areas showing increased sarcolemmal permeability, neither dystrophin nor beta-dystroglycan could be identified by immunolabeling. Thus, together with the known loss of delta-SG and other SGs, abnormal distribution of dystrophin and reduction of beta-dystroglycan are associated with increased sarcolemmal permeability followed by cell rupture, which correlates with early progressive cardiac dysfunction in the BIO14.6 CM hamster.

Animals↗
PubMed2000

Regional variation in receptive field properties of tectal neurons in pigeons.

The present study provides the first electrophysiological evidence for dorsoventral variation in the receptive field properties of tectal cells in pigeons. According to their receptive field organization, visual response properties and laminar locations, 95 tectal neurons recorded in the present study could be categorized into two groups: (1) Fifty-five DL-neurons were recorded in the dorsal, dorso-lateral, lateral and ventro-lateral tectum and characterized by an excitatory receptive field surrounded by an inhibitory receptive field. Most of them almost equally responded to white and black objects, but did not respond to switch-on and -off of a light spot. (2) Forty VC-neurons were recorded in the ventral tectum and characterized by an excitatory receptive field alone. Their responses to switch-on of a light spot and to a white object were significantly stronger than those to light-off and to a black object, respectively. DL-neurons preferred higher velocity, whereas VC-neurons preferred lower velocity. The recording sites of 53 of 95 cells (56%) examined were marked with pontamine sky blue, showing that DL-neurons were located in tectal layers I-IV, predominantly in layer II, whereas VC-neurons were mainly concentrated in sublayer IIc. The receptive fields of VC-neurons were located within the rostroventral visual field possibly corresponding to the red field of the pigeon retina, suggesting that they might be associated with visual food-foraging behaviors.

Animals↗