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D Jiang

Publications and source records attributed to D Jiang.

At least 19 recordsLinked to original sources
PubMed1996

p53 prevents maturation to the CD4+CD8+ stage of thymocyte differentiation in the absence of T cell receptor rearrangement.

Rearrangement of the immunoglobulin (Ig) and T cell receptor (TCR) gene loci allows for the generation of B and T lymphocytes with antigen-specific receptors. Complete rearrangement and expression of the TCR-beta chain enables immature thymocytes to differentiate from the CD4-CD8- to the CD4+CD8+ stage mice in which rearrangement is impaired, such as severe combined immunodeficient (SCID) mice or recombinase activating gene-deficient (RAG-/-) mice, lack mature B and T lymphocytes. Thymocytes from these mice are arrested at the CD4-CD8- stage of T cell development. We previously observed that thymocytes from RAG-2-/- mice exposed to gamma radiation differentiate from CD4-CD8- into CD4+CD8+ without TCR-beta chain rearrangement. We now report that irradiated RAG-2-/- thymocytes undergo direct somatic mutations at the p53 gene locus, and that p53 inactivation is associated with maturation of RAG2-/- thymocytes to the CD4+CD8+ stage. Generation of RAG2-/- and p53-/- double-deficient mice revealed that, in the absence of TCR-beta chain rearrangement, loss of p53 function is sufficient for CD4-CD8- thymocytes to differentiate into the CD4+CD8+ stage of T cell development. Our data provide evidence for a novel p53 mediated checkpoint in early thymocyte development that regulates the transition of CD4-CD8- into CD4+CD8+ thymocytes.

Animals↗
PubMed1996

Binaural masking level differences in the inferior colliculus of the guinea pig.

The binaural masking level difference (BMLD) is a striking and well-documented psychophysical effect which relates to the ability to use the phase of low-frequency sounds to dissociate them from masking noise. When identical tones and noise are presented to both ears, detectability is improved by up to 15 dB simply by inverting the phase of either the tone or noise in one ear. Measurements of BMLDs were made in single delay-sensitive neurones in the inferior colliculus of the guinea pig. These have confirmed and extended an earlier report [D. M. Caird, A. R. Palmer, and A. Rees, Hear. Res. 57, 91-106 (1991)] by demonstrating that when signals are optimized for the frequency, level, and interaural delay sensitivities of each neurone, BMLDs can be measured which are in a direction, and of a magnitude, consistent with appropriate psychophysical observations in human subjects. In addition, BMLDs were found to be consistent with the delay sensitivities of the neurones to the signal and masker, the major determinant of the masked threshold for optimized signals being the activity evoked in the neurone by the masking noise. Within-channel signal-to-noise (S/N) ratios at masked threshold for single neurones varied from +20 to -7 dB, depending on the binaural configuration and the units' delay sensitivities. In single neurones, the size of the BMLD for optimized signals increased with the level of the noise. The BMLD increased by 5 dB over a 40-dB range of noise, consistent with psychophysical observations. This came about because as noise level increased, masked threshold for optimized tones increased more slowly in Npi noise than in N0 noise. For all binaural comparisons, both positive (pi signals more detectable, as in the psychophysics) and negative BMLDs were observed, often in the same neurone, a result entirely consistent with the sensitivity to the interaural delay of the noise and tone signals. For 500-Hz signals in zero and pi phase masked by identical noise the majority of BMLDs determined with the PEST procedure was negative, a result which is taken to indicate that increases in spike rate may not be an appropriate cue for masked threshold under these conditions.

Animals↗
PubMed1996

Frequency extent of two-tone facilitation in onset units in the ventral cochlear nucleus.

1. The frequency threshold curves (FTCs) of 91 single units in the cochlear nucleus of the anesthetized guinea pig were measured using a conventional single-tone paradigm and a two-tone paradigm designed to elucidate the frequency extent of two-tone facilitation in onset units (On). Units were classified according to existing classification schemes into primary-like (n = 3), chopper (n = 23), and three onset groups: OnI (n = 12), OnC (n = 29), and OnL (n = 24). Histological reconstructions show onset units to be widely distributed within the ventral cochlear nucleus in a manner generally consistent with its tonotopic organization. 2. The FTCs of onset units differed in their minimum thresholds, the steepness of their high- and low-frequency cutoffs, and their sharpness of tuning as quantified by the quality factor at 10 dB (Q10dB) above best frequency (BF) threshold values. There was considerable overlap in the sharpness of tuning between onset units and auditory nerve fibers, as indicated by the distribution of Q10dB values in the octave around 10 kHz: onset units had Q10dB values of 3.56 +/- 1.38 (SD), compared with 6.3 +/- 2.48 for auditory nerve fibers. The tuning of chopper units was similar to that of auditory nerve fibers (5.52 +/- 1.46). 3. Seventy-five percent of onset units showed some degree of facilitation (a threshold reduction) when their FTCs were measured in the presence of BF tones 4 dB below BF threshold. The frequency extent of such facilitation was variable, with a maximum of 6 octaves around the BF. In extreme cases facilitation could be measured when the BF tone was as low as 30 dB below BF threshold. 4. In 17% of onset units, suppressive effects were evident, as shown by noncontiguous frequency regions of facilitation. These suppressive effects might be a reflection either of suppression in the auditory nerve input or of a direct inhibitory input to the onset units. The strength of this effect suggests that inhibition is a likely explanation, consistent with the finding in previous morphological studies of profuse synapses with pleomorphic vesicles on multipolar cells. 5. FTCs of chopper and primary-like units measured in the presence of BF tones showed little facilitation. The facilitation that was observed in chopper units was confined to a narrow region around BF and disappeared when the facilitatory tone was lowered to 4 dB below BF threshold. 6. These data support the hypothesis that onset units, but not chopper or primary-like units, receive excitatory inputs from auditory nerve fibers with a wide range of BFs. However, the frequency range of facilitation and the magnitude of the threshold facilitation varied from unit to unit, suggesting that the off-BF inputs from auditory nerve fibers are not evenly distributed or equally effective in all units.

Acoustic Stimulation↗
PubMed1996

Responses of ventral cochlear nucleus onset and chopper units as a function of signal bandwidth.

1. The responses of units in the ventral cochlear nucleus in anesthetized guinea pigs have been measured to best-frequency tones, noise bands geometrically centered around the unit best frequency, and noise bands asymmetrically positioned around the best frequency. 2. Each unit isolated was characterized using peristimulus time histograms (PSTHs) to best-frequency tones at 20 and 50 dB suprathreshold, frequency-intensity response areas and rate-versus-level functions in response to best-frequency tones and wideband noise. The data reported here are derived from full analyses of 5 chopper units and 17 onset units. The onsets were divided into onset-I (OnI), onset-L (OnL), and onset-C (OnC) by the criteria described by Winter and Palmer: the PSTHs of OnI units show only an onset response, OnL units respond with a single spike at onset followed by a low level of sustained activity, and OnC units have PSTHs with one to four onset peaks and low levels of sustained discharge. 3. In response to geometrically centered noise bands of constant spectral density, the discharge of chopper units and one OnI unit increased over a relatively narrow range of bandwidths, corresponding to the equivalent rectangular bandwidth calculated from their response area, and then became constant. In contrast, OnL and OnC units showed increases in discharge rate with noise bandwidth over very wide ranges of bandwidth. The growth of the discharge rate with noise bandwidth was approximately linear on double logarithmic axes and therefore could be described by a power function with an exponent of 0.37. This relation held even for noise levels near threshold. 4. When noise bands with constant spectral density (at the input to the earphone) were presented with one edge fixed at the unit's best frequency, the discharge rate of most chopper units and the one OnI unit increased over a narrow range of bandwidths and then became constant. This pattern was observed irrespective of whether the second edge of the noise was progressively increased above, or decreased below, the best frequency. For two of the chopper units, in which lateral inhibitory sidebands could be demonstrated, increasing the noise bandwidth led first to increases and then to decreases in the discharge rate as the noise energy impinged upon the sideband. The chopper units act like energy detectors with a filter corresponding to their single tone response area, but, for some units, with the addition of inhibitory sidebands. 5. For the OnL and OnC units, increasing the noise bandwidth above or below best frequency caused progressive increases in the discharge rate over wide ranges of bandwidth. These increases occurred even for low noise spectral densities. The growth in discharge rate for these onset units was well fitted at all spectral density levels by power functions: one above best frequency and one below. At levels of the noise 40 dB above the unit threshold, the point at which the discharge rate reached 90% of its maximum was, on average, about 2 octaves below best frequency and 1 octave above. For some onset units, changes in the discharge rate were seen as the noise bandwidth was varied over about 14 kHz, which is about one-third of the total frequency hearing range of the guinea pig. 6. The data for onset units is consistent with the hypothesis that onset units in the ventral cochlear nucleus achieve their precision in the temporal domain by integration of the inputs from auditory nerve fibers with a wide range of best frequencies. The range of frequency over which onset units integrate frequency matches that of the inhibitory input to dorsal cochlear nucleus neurons, suggesting a possible role as an inhibitory interneuron.

Acoustic Stimulation↗
PubMed1996

Interaural delay sensitivity and the classification of low best-frequency binaural responses in the inferior colliculus of the guinea pig.

Monaural and binaural response properties of single units in the inferior colliculus (IC) of the guinea pig were investigated. Neurones were classified according to the effect of monaural stimulation of either ear alone and the effect of binaural stimulation. The majority (309/334) of IC units were excited (E) by stimulation of the contralateral ear, of which 41% (127/309) were also excited by monaural ipsilateral stimulation (EE), and the remainder (182/309) were unresponsive to monaural ipsilateral stimulation (EO). For units with best frequencies (BF) up to 3 kHz, similar proportions of EE and EO units were observed. Above 3 kHz, however, significantly more EO than EE units were observed. Units were also classified as either facilitated (F), suppressed (S), or unaffected (O) by binaural stimulation. More EO than EE units were suppressed or unaffected by binaural stimulation, and more EE than EO units were facilitated. There were more EO/S units above 1.5 kHz than below. Binaural beats were used to examine the interaural delay sensitivity of low-BF (BF < 1.5 kHz) units. The distributions of preferred interaural phases and, by extension, interaural delays, resembled those seen in other species, and those obtained using static interaural delays in the IC of the guinea pig. Units with best phase (BP) angles closer to zero generally showed binaural facilitation, whilst those with larger BPs generally showed binaural suppression. The classification of units based upon binaural stimulation with BF tones was consistent with their interaural-delay sensitivity. Characteristic delays (CD) were examined for 96 low-BF units. A clear relationship between BF and CD was observed. CDs of units with very low BFs (< 200 Hz) were long and positive, becoming progressively shorter as BF increased until, for units with BFs between 400 and 800 Hz, the majority of CDs were negative. Above 800 Hz, both positive and negative CDs were observed. A relationship between CD and characteristic phase (CP) was also observed, with CPs increasing in value as CDs became more negative. These results demonstrate that binaural processing in the guinea pig at low frequencies is similar to that reported in all other species studied. However, the dependence of CD on BF would suggest that the delay line system that sets up the interaural-delay sensitivity in the lower brainstem varies across frequency as well as within each frequency band.

Acoustic Stimulation↗
PubMed1995

Requirement for TNF-alpha and IL-1 alpha in fetal thymocyte commitment and differentiation.

CD25 expression occurs early in thymocyte differentiation. The mechanism of induction of CD25 before T cell receptor rearrangement and the importance of this mechanism for T cell development are unknown. In a thymus reconstitution assay, tumor necrosis factor alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha), two cytokines produced within the thymic microenvironment, induced CD25 expression on early immature thymocytes. Either TNF-alpha or IL-1 alpha was necessary for further thymocyte maturation and CD4+CD8+ differentiation. In irradiated mice reconstituted with CD117+CD25+ thymocytes, commitment to the T cell lineage was marked by the loss of precursor multipotency.

Animals↗
PubMed1995

Caloric restriction: conservation of cellular replicative capacity in vitro accompanies life-span extension in mice.

We have tested whether life-long caloric restriction (CR) slows or delays the age-related loss of cellular replicative potential that occurs during normal aging in ad libitum (AL) fed mice. Both mean and maximum life spans of the restricted animals (60% of AL intake) were significantly extended 30-40% by CR treatment. Proliferative potential, measured by determining the fraction of cells capable of forming large clones in vitro, was compared in five cell types from six tissue sites from two strains of mice (Male (C57BL/6 x DBA/2)F1("B6D2F1") and female (C57BL/6 x C3H)F1("B6C3F1")). This included four nonhematopoietic organ sites: fibroblast cells from ear skin, tail skin, and subdermal connective tissue and epithelial cells from the medullary part of the kidney and two cell types, myofibroblasts and endothelial-like cells, from spleen and bone marrow. The proliferative potential of cells from AL mice decreased progressively with age in all tissues sites of both mouse strains. CR delayed or decreased the loss of proliferative potential in all situations, but the timing of this was tissue specific. For cells from the four nonhematopoietic tissues sites from female B6C3F1 female mice, CR delayed the onset of proliferative loss, such that the fraction of large clones was significantly greater for the CR 18- to 24-month-old mice than in AL controls at three of four sites (as determined by the fraction of large clones after 1 week of clonal growth). The proliferative loss in CR tissues then accelerated from 24 to 30 months, so that both CR and AL mice had similar fractions of large clones after 30 months of age. CR was also seen to delay loss of proliferative potential in cells from skin and kidney of B6D2F1 male mice at 23-24 months of age when cloned for 2 weeks. For fibroblast and endothelial-like cells from bone marrow and spleen stromal sites from both strains of mice, CR also significantly decreased loss of proliferative potential; furthermore, in these tissues the proliferative advantages remained or increased from 24 to over 30 months of age. In companion studies (N.S. Wolf et al., 1995. Exp. Cell. Res. 217, 000-000), CR was seen to decrease age-related losses in the maximal rates of cell replication in vivo in a panel of tissues from B6D2F1 male mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Caloric restriction: conservation of in vivo cellular replicative capacity accompanies life-span extension in mice.

In male mice of a long-lived hybrid strain (B6D2F1), long-term 40% caloric restriction (CR) extended both mean and maximum life spans by 36 and 20%, respectively, over that of ad libitum fed (AL) controls. Measurements of entry into S-phase were made in vivo of six different cell types in five different organs using 2-week exposures to BrdU. The labeling index (L.I.) in all organs studied was lower in young CR mice than in young AL fed mice. In most cases, the L.I. in AL mice fell to the levels of that in the CR mice by 13 months of age, and the two groups then remained so through old age. However, when the L.I. was measured in old CR mice which had been placed on the AL diet for a period of 4 weeks (this was termed refeeding (RF), it was found to be above that of similar age AL or CR mice and almost at the level of young AL mice. This was still true, but to a lesser degree, in a repeat study using an 8-week period of RF. In a separate but parallel in vitro study (companion paper, this volume), the superiority of CR over AL for retention of cellular replication capacity was confirmed by clone size distribution measurements made in several cell types in mice of several age groups. These results indicate that: (1) the rate of cell replication in AL diet mice diminishes greatly by early middle age in all organ sites studied and then plateaus or declines much more slowly; (2) CR broadly preserves in vivo cellular replicative capacity but often requires the energy levels provided by a switch to AL feeding to demonstrate this late in life; (3) accordingly, the replicative deficit in AL fed mice appears to be cumulative and is significant only in old age. The mechanism(s) involved is yet to be discovered but may be related to, or even the same as, that which extends life spans in CR animals. Correspondingly, and with corroborative data from our in vitro companion study, (W. R. Pendergrass et al., 1995. Exp. Cell. Res. 217, 309-316), we suggest that cell populations sustain an accrual of biochemical damage or physiological alterations which increasingly limit their replicative capacity as the animal ages, and that CR reduces the accrual of this damage.

Aging↗
PubMed1995

China: epidemiology of pregnancy-induced hypertension.

The study of 67,813 pregnancies and their outcome confirmed the intrinsic negative impact of hypertension on pregnancy and childbirth. Measures to overcome the differences in hypertensive experience of rural as opposed to urban women lie in the expansion of the maternal and child health services in the rural areas. Maternity care services need to increase early detection of hypertension, improve monitoring of anticipated twin deliveries, enhance nutrition, reduce anaemia and other known risk factors and improve health education.

Adult↗
PubMed1995

Perinatal transmission and maternal risks of human papillomavirus infection.

We conducted a prospective study to investigate whether human papillomavirus (HPV) could be vertically transmitted to neonates. Pregnant women (N = 203) were tested for HPV DNA infection during the third trimester and again during labor prior to delivery. Their newborns (N = 203) were tested 1 to 3 days after delivery. Among the mothers, 12.3% (N = 25/203) typed HPV positive at either or both maternal specimen collection periods, whereas only 1.0% of the neonates (N = 2/203) typed positive. This low transmission rate may be due in part to the fact that 65% of mothers who were HPV positive during the third trimester tested HPV negative by labor/delivery. The higher frequency of risks associated with maternal HPV infection were similar to those found in studies of cervical dysplasia and cancer: younger age at first intercourse and first pregnancy, number of sexual partners, and longer duration in use of oral contraceptives. In addition, those who were past smokers and had a shorter recency and latency period in smoking were more likely to be detected with HPV.

Adolescent↗
PubMed1995

Developmental hematopoiesis from prenatal to young-adult life in the mouse model.

Five measurements of hematopoietic function were made in the mouse from midfetal life to young adulthood. These included two in vivo (day-8 colony-forming unit-spleen [CFU-S8] and day-12 CFU-S [CFU-S12]) and two in vitro clonal measurements of hematopoietic stem and progenitor cells (high proliferative potential colony-forming cell [HPP-CFC] and CFC of low proliferative potential [LPP-CFC]) as well as an in vitro clonal measurement of colony-forming unit-fibroblast (CFU-F). The appearance, increase, subsequent decrease, and later emergence and increase of each of these parameters in the fetal-liver, newborn, growing-infant, and young-adult bone marrow were correlated and found to be in parallel. Exceptions to this included the earlier appearance in the fetal liver of CFU-F and the relatively differentiated hematopoietic LPP-CFC. The pattern of emergence of these progenitor cell subpopulations in the fetal liver may be related, in part to the timing of the hematopoietic microenvironment development and the relative frequencies of progenitor cell types in the circulation. This developmental study in the mouse model describes additional correlations between in vivo and in vitro colony-forming stem cells and fibroblastic stromal colony-forming cells, and it suggests the dependence of hematopoietic stem cells upon the stromal microenvironment for the necessary conditions for hematopoietic stem cell lodgment, growth, and maturation.

Aging↗
PubMed1995

[The significance of high-density lipoprotein subfractions and triglycerides in predicting coronary artery disease].

Serum Lipid profiles, including high-density lipoprotein (HDL) and its subfractions HDL2 and HDL3 were obtained in 78 cases undergoing coronary angiography. Coronary artery disease (CAD) was present in 51 patients and absent in 27. We used a scoring methold of CAD to reflect the extent or narrowing of coronary artery. The largest difference between the two groups was observed in HDL2 Cholesterol with a mean of 0.37 mmol/L in patients with CAD as compared with 0.49 mmol/L in normal subjects (P < 0.001) and in TG (1.85 mmol/L vs 1.16 mmol/L) as well. Smaller difference was found in TC (5.9 mmol/L vs 4.87 mmol/L, P < 0.05). No singnificant difference was found in serum HDL (P > 0.05). Multivariate regression analysis revealed that the most powerful indenpendent variable associated with the extent of CAD was HDL2 cholesterol and triglyceride. The score of CAD was significantly correlated with HDL2-c (r = 0.32 P < 0.01) and TG (r = 0.34 P < 0.01). It is shown that high serum level of TG (> 1.6 mmol/L) and low serum level of HDLC2 (< 0.37 mmol/L) were the strengest predictors of presence and extent of CAD.

Adult↗
PubMed1995

[Clinical observation and therapeutic mechanism of blocking agent of substance P nerves in the treatment of perennial allergic rhinitis].

This paper reported the clinical effects and therapeutic mechanism of blocking agent of substance P(SP) nerves on prerennial allergic rhinitis. We applied capsaicin (CAP) in the treatment of 50 cases of perennial allergic rhinitis once a week and 4 times as a therapeutic course. By using highly specific and highly sensitive SP radioimmunoassay, the SP contents in nasal secretions were determined before and after CAP therapy. The results showed that clinical symptoms of allergic rhinitis were obviously relieved and SP content in the nasal secretions was remarkably reduced from 29.444 +/- 14.280pmol/L before CAP therapy to 16.848 +/- 10.622 pmol/L after therapy (P < 0.001). Of the 50 cases, 35 cases (70.0%) showed the best effects, 12 cases (24.0%) better effects and 3 cases (6.0%) no effects. The total effective rate was 94.0%. The study indicated that therapeutic mechanism of CAP on perennial allergic rhinitis is related to the reducing of SP and the blocking of axonal reflex of the SP nerves.

Administration, Intranasal↗
PubMed1994

Sublethal gamma-radiation induces differentiation of CD4-/CD8- into CD4+/CD8+ thymocytes without T cell receptor beta rearrangement in recombinase activation gene 2-/- mice.

DNA recombination of the immunoglobulin (Ig) or T cell receptor (TCR) gene loci is an essential step in the production of lymphocytes bearing antigen-specific receptors. Mice that lack the ability to rearrange their Ig and TCR gene loci are devoid of mature B and T cells. Complete rearrangement and expression of the TCR-beta chain has been suggested to allow immature thymocytes to switch from the CD4-/CD8- to the CD4+/CD8+ stage of thymic development. Thus, thymocytes from severe combined immune deficient (SCID) mice or mice deficient in recombinase activation genes (RAG), which do not undergo proper DNA rearrangement, are arrested at the early CD4-/CD8- stage of development. B cell precursors in SCID or RAG mice do not progress from the B220+/sIgM-/heat stable antigen (HSA)+/CD43+ to the B220+/sIgM-/HSA+/CD43- stage. In an attempt to reconstitute RAG-2-/- mice with bone marrow- or fetal liver-derived progenitor cells, we subjected these mice to sublethal doses of gamma-radiation. It is surprising that in the absence of donor cells, irradiated RAG-2-/- mice revealed a dramatic change in their lymphoid phenotype. 14 d after irradiation, the majority of thymocytes had advanced to the CD4+/CD8+ stage of T cell development and a small number of bone marrow precursors had progressed to the CD43-, HSAhi stage of B cell development. Analysis of the resulting CD4+/CD8+ thymocytes revealed no surface expression of the TCR/CD3 complex and no V-D-J rearrangement of the TCR-beta gene locus. Our findings provide evidence for a novel pathway that allows the transition of thymocytes from the CD4-/CD8- to the CD4+/CD8+ stage and that does not appear to require TCR-beta chain rearrangement.

Animals↗
PubMed1994

Identification of a p53 binding site in the human retinoblastoma susceptibility gene promoter.

p53 is a tumor suppressor gene found to be mutated in a wide variety of tumors. The encoded p53 protein has properties of a classical transcription factor, but the promoter targets for its regulation are largely unknown. We have investigated the ability of p53 to regulate activity of the human retinoblastoma susceptibility gene (Rb) promoter using a cotransfection assay in CCL-64 and Saos-2 cells. p53 was able to stimulate transcription from the Rb promoter at low input doses of p53 expression plasmid, whereas transcription was repressed at high input doses. The stimulatory effect of p53 on Rb promoter activity mapped to a region between 4 and 92 base pairs upstream from the start site of translation, whereas the region controlling repression by p53 mapped to the basal transcriptional control region of the promoter between -207 and -185. Moreover, an oligonucleotide containing Rb promoter sequences between -63 and -88 was sufficient to confer stimulation by p53 when inserted upstream from a minimal heterologous promoter. Gel mobility shift analysis was used to demonstrate that p53 can bind to a sequence within the -63 to -88 oligonucleotide with homology to a p53 binding site. The presence of a functional p53 binding site in the human retinoblastoma tumor suppressor gene promoter suggests that p53 can regulate Rb promoter activity.

Base Sequence↗