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Biomedical subjects

M Dai

Publications and source records attributed to M Dai.

At least 37 records · Page 2Linked to original sources

A genetic investigation of E2A function in lymphocyte development.

Lymphocytes are derived from hematopoietic stem cells (HSC) following a series of regulated differentiation events. Multipotent HSCs become committed to the B cell lineage in bone marrow and the T cell lineage in the thymus after receiving appropriate signals from the corresponding microenvironment. These committed lymphoid cells must then undergo V(D)J recombination at the immunoglobulin gene or T cell receptor gene locus resulting in clonal production of functional B or T lymphocytes, respectively. Lymphocyte commitment and differentiation are accompanied by programmed gene expression or repression events which are driven by lineage and stage specific transcription factors. The basic-helix-loop-helix (bHLH) transcription factors encoded by the E2A gene are involved in several differentiation events during B and T cell development, including lineage commitment, initiation of V(D)J recombination, and antigen receptor mediated proliferation and differentiation. Several recent reviews have provided a comprehensive discussion of biochemical, cellular, and genetic research on E2A function in lymphocyte development (1,2). Here, we only discuss some of the genetic approaches our laboratory (except where it is noted) has undertaken to investigate the molecular pathways mediated by E2A transcription factors in lymphocyte development.

Animals↗

Promethazine affects optokinetic but not vestibular responses in monkeys.

BACKGROUND: Promethazine is used to treat motion sickness including Space Adaptation Syndrome, but there is incomplete information about how it affects vestibular and optokinetic responses. METHODS: Vestibular and optokinetic nystagmus, recorded with eye coils, were characterized in monkeys after administration of promethazine at dosages approximately equivalent to those used by humans in space. RESULTS: The initial increase of horizontal eye velocity during optokinetic nystagmus (OKN) was reduced after receiving the drug. Consequently, it took a longer time for eye velocity to rise to 60% of steady state value, the normal initial jump in eye velocity. Steady state OKN, maximum gains of optokinetic after-nystagmus (OKAN) and OKAN falling time constants were unaffected. The gains and time constants of the horizontal, vertical and roll angular vestibulo-ocular reflex (aVOR), the amplitude and velocity of saccades, and ocular counter-rolling (OCR), induced by off-vertical axis rotation (OVAR) were unaffected by promethazine. A two-component optokinetic model simulated the data simply by reducing the gain of the initial (rapid) component of OKN. A reduction in coupling between a non-linear element and the velocity storage integrator was required to simulate some vertical OKN data. CONCLUSIONS: Promethazine reduces the gain of the direct visual-oculomotor pathway in monkeys. It has little effect on saccades, the gain and time constant of the aVOR and the low frequency linear vestibulo-ocular reflex (IVOR), which orients the eyes during ocular counterrolling. The optokinetic deficit is consistent with reported reduction in ocular pursuit and VOR suppression after promethazine in humans.

Animals↗

[Inhibitory effect of paeonol on lipid peroxidational reaction and oxidational decorate of low density lipoprotein].

OBJECTIVE: To observe the effects of paeonol(Pae) on lipid peroxidational reaction and oxidational decorate of low density lipoprotein(LDL). METHOD: The rat model of hyperlipidaemia was established by feeding high lipid diet with cholesterol for 6 weeks. The contents of malondialdehyde(MDA) and oxidized low density lipoprotein(OX-LDL) were measured by thiobarbituric acid reactive substance(TBA) method and sandwich method of enzyme-linked immunosorbent assay for detection of polyclone antibody. LDL of serum in healthy person was separated by improve precipitate method. RESULTS: Pae(300, 150 mg.kg-1) could reduce significantly the levels of MDA of serum, aorta and liver; Pae(300 mg.kg-1) decreased obviously the content of OX-LDL of plasma; Pae(1,000, 200, 40 micrograms.ml-1) refrained markedly the course of oxidational decorate of LDL of serum in healthy person. CONCLUSION: Pae could reduce the levels of MDA and OX-LDL in hyperlipidaemia rats, and refrain the oxidational decorates of LDL of serum in healthy person.

Acetophenones↗

Canal and otolith afferent activity underlying eye velocity responses to pitching while rotating.

Pitching the head while rotating (PWR) combines periodic activation of the semicircular canals and the otoliths to generate pitch and roll eye deviations and continuous horizontal nystagmus. Monkeys were tested after individual pairs of semicircular canals were plugged and single units were recorded in the vestibular nerve while the animals were sinusoidally pitched 20-40 deg about a spatial horizontal axis with 5- and 16-s periods and simultaneously rotated about a spatial vertical axis at 30-120 deg/s. As previously shown, the steady-state horizontal response disappeared after plugging the vertical semicircular canals, but was maintained when the lateral canals were plugged. When the left anterior and right posterior canal (LARP) pair was left intact, the steady-state response depended on the axis about which the pitching took place. When the axis was normal to the LARP plane, there was no steady-state response. When the pitching axis was perpendicular to the LARP normal, the response was maximal. Firing rates of otolith units were approximately in phase with pitch position, and the addition of rotation about a vertical axis did not change the response. Lateral canal units did not have a steady-state modulation during pitch or constant velocity rotation. During PWR, they oscillated at twice the pitch frequency. This corresponded to the frequency at which the canal was maximally activated as it aligned with the plane of rotation. The amplitude of modulation increased proportionally to rotational velocity, but the phase remained the same. These characteristics were unchanged during roll while rotating (RWR), which induces little continuous nystagmus. Anterior and posterior canal units were maximally excited near pitch-velocity maxima and minima, respectively, during pure pitching. During PWR, however, the phases of both components simultaneously shifted toward each other and toward being in phase with otolith units. The peak excitation tended toward a forward-pitch position when the rotation was to the ipsilateral side, and toward a backward pitch position when the rotation was to the contralateral side. With 120-deg/s rotation during a 16-s pitch period, the phase difference between anterior and posterior canal units was as small as 17 deg. These data support the postulate that the correlation between vertical canal and otolith units is the critical factor in generating continuous unidirectional horizontal nystagmus during PWR.

Animals↗

Effects of Chain Length and Structure of Cationic Surfactants on the Adsorption onto Na-Kaolinite.

The adsorption of a series of alkylammonium bromides (RR1N(CH3)2Br) with different chain lengths R and R1 on a nonswelling clay surface (sodium kaolinite) has been studied by microelectrophoresis and adsorption isotherms. An increase in the number of CH2 groups in the shorter alkyl chain of the double-chain surfactant, or the introduction of another kind of alkyl group (phenyl group), was found to have much less effect on the adsorption behavior than changing the length of the alkyl chain in the single-chain surfactants. It is inferred that the effective hydrophobicity of the shorter chains in these double-chain surfactants is reduced by their intramolecular association with the longer chain. Comparison of adsorption and micellization leads to an empirical quantitative description of the effects of alkyl chain length and structure on adsorption. Copyright 1999 Academic Press.

Journal Article↗

Spatial orientation of the angular vestibulo-ocular reflex.

During vestibular nystagmus, optokinetic nystagmus (OKN), and optokinetic afternystagmus (OKAN), the axis of eye rotation tends to align with the vector sum of linear accelerations acting on the head. This includes gravitational acceleration and the linear accelerations generated by translation and centrifugation. We define the summed vector of gravitational and linear accelerations as gravito-inertial acceleration (GIA) and designate the phenomenon of alignment as spatial orientation of the angular vestibuloocular reflex (aVOR). On the basis of studies in the monkey, we postulated that the spatial orientation of the aVOR is dependent on the slow (velocity storage) component of the aVOR, not on the short latency, compensatory aVOR component, which is in head-fixed coordinates. Experiments in which velocity storage was abolished by midline medullary section support this postulate. The velocity storage component of the aVOR is likely to be generated in the vestibular nuclei, and its spatial orientation was shown to be controlled through the nodulus and uvula of the vestibulocerebellum. Separate regions of the nodulus/uvula appear to affect the horizontal and vertical/torsional components of the response differently. Velocity storage is weaker in humans than in monkeys, but responds in a similar fashion in both species. We postulate that spatial orientation of the aVOR plays an important role in aligning gaze with the GIA and in maintaining balance during angular locomotion.

Humans↗

Model-based study of the human cupular time constant.

The time constant of the angular vestibulo-ocular reflex (aVOR), measured from the response to steps of rotation about a yaw axis, has frequently been estimated as a single exponential. However, the slow phase velocity envelope during per- or post-rotatory nystagmus is more accurately represented by two exponential modes. One represents activity in the vestibular nerve induced by deflection of the cupula, the other by activation that the input from the canals produces in the central velocity storage integrator. The sum of the cupula and the integrator responses describes the overall response of slow phase eye velocity and can be approximated by a double exponential. Frequently, there is a plateau in the initial portion of eye velocity response, but this may be masked by habituation, making the cupula contribution unobservable and impossible to estimate. Using a model-based technique to analyze responses with a clear plateau, we estimated peripheral and central vestibular time constants by double exponential fits to slow phase eye velocity. Cupular time constants were varied from 1 to 10 s to identify values that gave optimal fits of the data according to a Chi-square criterion. The mean cupular time constant for 10 human subjects was 4.2 +/- 0.6 s. Fits of the data were also good for time constants between 3.5 to 7 s, but not for 1 to 3 or 7.5 to 10 s. The estimated cupular time constants also fit responses where there was no plateau. In 8 monkeys, cupular time constants were estimated as 3.9 +/- 0.5 s, which agreed with those derived from activity in the vestibular nerve. There was no difference between monkey and human cupular time constants from these estimates. It is likely that the human cupular time constant is similar to that of the monkey and shorter than previously thought.

Adult↗

[Inhibitory effect of paeonol on experimental atherosclerosis in quails].

OBJECTIVE: To study the effect of paeonol on experimental atherosclerosis in quails caused by high lipid feeding. METHOD: The effects of oral administration of 300 and 600 mg/kg of paeonol on lipid levels in serum, hemorrheology and aortic intimal abnormalities were investigated. RESULT: Paeonol decreased TC, TG, LDL, vLDL, APOB100 levels in serum and TC levels in aorta and liver. The ratios of HDL/TC, HDL2/HDL3, apoA1/apoB100 were elevated. In addition, the drug reduced the whole blood viscosity, Plasma viscosity and plasma fibrinogen, and inhibited erythrocyte aggregation. CONCLUSION: Oral administration of paeonol can reduce the development of atherosclerosis.

Acetophenones↗

GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2.

The principal inhibitory neurotransmitter GABA (gamma-aminobutyric acid) exerts its effects through two ligand-gated channels, GABA(A) and GABA(C) receptors, and a third receptor, GABA(B) , which acts through G proteins to regulate potassium and calcium channels. Cells heterologously expressing the cloned DNA encoding the GABA(B)R1 protein exhibit high-affinity antagonist-binding sites, but they produce little of the functional activity expected from studies of endogenous GABA(B) receptors in the brain. Here we describe a new member of the GABA(B) polypeptide family, GABA(B)R2, that shows sequence homology to GABA(B)R1. Neither GABA(B)R1 nor GABA(B)R2, when expressed individually, activates GIRK-type potassium channels; however, the combination of GABA(B)R1 and GABA(B)R2 confers robust stimulation of channel activity. Both genes are co-expressed in individual neurons, and both proteins co-localize in transfected cells. Moreover, immunoprecipitation experiments indicate that the two polypeptides associate with each other, probably as heterodimers. Several G-protein-coupled receptors (GPCRs) exist as high-molecular-weight species, consistent with the formation of dimers by these receptors, but the relevance of these species for the functioning of GPCRs has not been established. We have now shown that co-expression of two GPCR structures, GABA(B)R1 and GABA(B)R2, belonging to the same subfamily is essential for signal transduction by GABA(B) receptors.

Amino Acid Sequence↗

Vestibular adaptation to space in monkeys.

Otolith-induced eye movements of rhesus monkeys were studied before and after the 1989 COSMOS 2044 and the 1992 to 1993 COSMOS 2229 flights. Two animals flew in each mission for approximately 2 weeks. After flight, spatial orientation of the angular vestibulo-ocular reflex was altered. In one animal the time constant of postrotatory nystagmus, which had been shortened by head tilts with regard to gravity before flight, was unaffected by the same head tilts after flight. In another animal, eye velocity, which tended to align with a gravitational axis before flight, moved toward a body axis after flight. This shift of orientation disappeared by 7 days after landing. After flight, the magnitude of compensatory ocular counter-rolling was reduced by about 70% in both dynamic and static tilts. Modulation in vergence in response to naso-occipital linear acceleration during off-vertical axis rotation was reduced by more than 50%. These changes persisted for 11 days after recovery. An up and down asymmetry of vertical nystagmus was diminished for 7 days. Gains of the semicircular canal-induced horizontal and vertical angular vestibulo-ocular reflexes were unaffected in both flights, but the gain of the roll angular vestibulo-ocular reflex was decreased. These data indicate that there are short- and long-term changes in otolith-induced eye movements after adaptation to microgravity. These experiments also demonstrate the unique value of the monkey as a model for studying effects of vestibular adaptation in space. Eye movements can be measured in three dimensions in response to controlled vestibular and visual stimulation, and the results are directly applicable to human beings. Studies in monkeys to determine how otolith afferent input and central processing is altered by adaptation to microgravity should be an essential component of future space-related research.

Adaptation, Physiological↗

Do silent dopaminergic neurons exist in rat substantia nigra in vivo?

A subpopulation of inactive or "silent" dopaminergic neurons has been reported to exist in vivo in rat substantia nigra, comprising up to 50% of nigral dopaminergic neurons. The existence of this large proportion of silent neurons has been inferred from various experimental manipulations, but never demonstrated directly. In the present study, striatal or medial forebrain bundle stimulation was used to activate antidromically substantia nigra dopaminergic neurons in vivo. Antidromic spikes of dopaminergic neurons observed by extracellular single-unit recordings in the absence of spontaneous activity were employed as indicators of the presence of a silent cell. A total of 312 dopamine neurons were recorded, including 190 neurons that could be antidromically activated from the striatum and/or the medial forebrain bundle. All neurons exhibited spontaneous activity. The firing rates were unimodally distributed about the mean of 4 spikes/s, and very few cells were observed to fire at less than 0.5 spikes/s. The numbers of spontaneously active and antidromically activated dopaminergic neurons per track were recorded and compared with the number of antidromically responding silent dopaminergic neurons per track after systemic apomorphine administration. Under control conditions, 0.80 +/- 0.10 or 1.36 +/- 0.13 spontaneously active neurons per track could be antidromically activated at 1.0 mA by striatal or medial forebrain bundle stimulation, respectively. After apomorphine completely suppressed spontaneous activity, 0.69 +/- 0.08 and 1.39 +/- 0.14 antidromic neurons per track were detected by stimulating the striatum or medial forebrain bundle respectively at 1.0 mA, demonstrating that silent dopaminergic neurons can be reliably identified through antidromic activation. In sharp contrast to previous reports, these data suggest that silent neurons do not comprise a substantial proportion of the total number of dopaminergic neurons in the substantia nigra. Reverse chi2 analysis revealed that, if they exist at all, silent dopaminergic neurons make up less than 2% of the dopaminergic cells in the substantia nigra. These findings are related to current theories of the mechanisms of action of antipsychotic drugs and the maintenance of near-normal levels of dopamine in the striatum following large-scale loss of nigral dopaminergic neurons.

Animals↗

A case-control study of hepatitis B and C virus infection as risk factors for hepatocellular carcinoma in Henan, China.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and is particularly prevalent in China. China is also a hyperendemic area for hepatitis B virus (HBV) infection. Although a strong association between HBV infection and HCC has been established previously, the role of hepatitis C virus (HCV) infection and the interaction between HBV and HCV in the development of HCC has not been adequately explored. The major objective of this study is to determine the relationship between HBV or HCV infection and HCC by use of case-control study in Henan, China. METHOD: In all, 152 HCC patients and 115 control patients were collected from four hospitals in Henan, China between January 1994 and October 1995. The demographic characteristics of the two groups were comparable. In further analysis, a 1:1 pair-matched case-control study was performed. Of 152 HCC patients, 113 were randomly selected to be pair-matched by sex and age (+/-5 years) to controls with non-hepatic disease. All the cases and controls were interviewed during hospitalization by two specially trained interviewers using a standard questionnaire. All sera were tested for HBV and HCV markers. Odds ratios (OR) and 95% CI for HCC risk factors were calculated by logistic regression model controlling for possible confounding factors such as sex and age. The multivariate analysis was done on the basis of the univariate analysis. RESULTS: The results of this study indicated that the prevalence of hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) were much higher in HCC patients (63.2% and 11.2% respectively) than in the control patients (5.2%, 3.5%). The difference between two groups was significant (P < 0.05). Risk factor analysis revealed that both HBV and HCV infection were important factors for HCC in Henan, China and HBV appeared to have a key role in the development of HCC. Odds ratios of HBsAg and HBV infection were 28.82 (95% CI: 11.18-78.78) and 31.22 (95% CI: 13.86-72.15), respectively. Moreover, the risk of developing HCC increased significantly and showed an additive effect when both viral markers of HBV and HCV infection were considered (OR = 42.85). Results from the 1:1 pair-matched case-control study also showed that HBV infection was an important risk factor for HCC, which was consistent with the results from the group-matched case-control study. CONCLUSION: This is the first reported case-control study of HCC in Henan, China. This study provides further evidence that chronic HBV infection is strongly associated with the development of HCC among this population. Our results have demonstrated that HCV and HBV infection are independent and probably additive risk factors for HCC.

Adult↗

Functional replacement of the mouse E2A gene with a human HEB cDNA.

The mammalian E2A, HEB, and E2-2 genes encode a unique class of basic helix-loop-helix (bHLH) transcription factors that are evolutionarily conserved and essential for embryonic and postnatal development. While the structural and functional similarities among the gene products are well demonstrated, it is not clear why deletion of E2A, but not HEB or E2-2, leads to a complete arrest in B-lymphocyte development. To understand the molecular basis of the functional specificity between E2A and HEB/E2-2 in mammalian development, we generated and tested a panel of E2A knockin mutations including subtle mutations in the E12 and E47 exons and substitution of both E12 and E47 exons with a human HEB cDNA. We find that the alternatively spliced E12 and E47 bHLH proteins of the E2A gene play similar and additive roles in supporting B lymphopoiesis. Further, we find that HEB driven by the endogenous E2A promoter can functionally replace E2A in supporting B-cell commitment and differentiation toward completion. Finally, the postnatal lethality associated with E2A disruption is fully rescued by the addition of HEB. This study suggests that the functional divergence among E12, E47, and HEB in different cell types is partially defined by the context of gene expression.

Alleles↗

[Epidemiological study on risk factors of Chlamydia trachomatis infection in pregnant women].

54 Pregnant women and 216 without were detected for anti-Chlamydial antibodies, using indirect hemagglutination test on a 1:4 matched Case-control study to look for risk factors of Chlamydia trachomatis infection. A total number of 26 independent variables were selected for analysis, in which 8 factors were confirmed as associated factors by single variable analysis. Of the above 8 factors, 4 were significantly correlated to the infection under the multifactorial conditional logistic regression model, which were: extramarital sex life, history of urogenital tract infection, age of sexual intercourse debut and the use of intrauterus contraception.

Adult↗

[Pharmacological studies on Chinese bone extract granules].

The Chinese Bone Extract Granules could enhance the immunity of mice with spleen-deficiency, increase the serum calcium content of rats with bone loose, inhibit the gastrointestinal movement of mice with spleen-deficiency and improve the absorption of D-xylose in small intestine of rats with spleen-deficiency. The maximal tolerance dose for mice to take orally twice a day was greater than 50 g/kg. The subacute toxicologic test for 6 weeks of continuous feeding to rats did not show any obvious toxicity.

Animals↗

[Fetal hemodynamic surveillance of twin transfusion syndrome].

OBJECTIVE: To evaluate the ratio of peak systolic to least diastolic flow velocity (S/D), pulsatile index (PI) and resistance index (RI) of the umbilical arterial doppler flow at 20-40 gestational weeks in twin pregnancy for the surveillance of twin transfusion syndrome. METHODS: The fetal hemodynamics in 36 cases of twin pregnancy were monitored by Combison A-ZIPE 4871 with spectral doppler ultrasound. RESULTS: The value of S/D ratio and PI in 4 patients with twin transfusion syndrome at 32-34 weeks were significantly higher than those of normal twin (P < 0.01). Two cases of twin reversed arterial pressure (TRAP), i.e. artery to artery transfusion in one of the twin with acardius, were found at 26 and 26 + 4 weeks respectively. CONCLUSION: The S/D ratio and PI of umbilical artery might be useful indices for the surveillance of twin transfusion syndrome.

Adult↗

Modulation of vergence by off-vertical yaw axis rotation in the monkey: normal characteristics and effects of space flight.

Horizontal movements of both eyes were recorded simultaneously using scleral search coils in 2 rhesus monkeys before and after the COSMOS 2229 space-flight of 1992-1993. Another 9 monkeys were tested at comparable time intervals and served as controls. Ocular vergence, defined as the difference in horizontal position between the left and right eyes, was measured during off-vertical yaw axis rotation (OVAR) in darkness. Vergence was modulated sinusoidally as a function of head position with regard to gravity during OVAR. The amplitude of peak-to-peak modulation increased with increments in tilt of the angle of the rotational axis (OVAR tilt angle) that ranged from 15 degrees to 90 degrees. Of the 11 monkeys tested, 1 had no measurable modulation in vergence. In the other 10, the mean amplitude of the peak to peak modulation was 5.5 degrees +/- 1.3 degrees at 90 degrees tilt. Each of these monkeys had maximal vergence when its nose was pointed close to upward (gravity back; mean phase: -0.9 degree +/- 26 degrees). After space flight, the modulation in vergence was reduced by over 50% for the two flight monkeys, but the phase of vergence modulation was not altered. The reduction in vergence modulation was sustained for the 11-day postflight testing period. We conclude that changes in vergence are induced in monkeys by the sinusoidal component of gravity acting along the naso-occipital axis during yaw axis OVAR, and that the modulation of the vergence reflex is significantly less sensitive to linear acceleration after space flight.

Animals↗