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Biomedical subjects

H Cheng

Publications and source records attributed to H Cheng.

At least 343 records · Page 19Linked to original sources

Rapid antenatal diagnosis of beta-thalassemia in Chinese caused by the common 4-bp deletion in codons 41/42 using high-resolution agarose gel electrophoresis and heteroduplex detection.

The 4-bp deletion in codons 41/42 (-TTCT) in the beta-globin gene is a common mutation that causes beta-thalassemia in Chinese. A simple method, which involved PCR amplification of the relevant region, was used for the antenatal diagnosis of a fetus at risk for this mutation. The fetal PCR product showed a single fragment of normal size on MetaPhor gel. The homozygous normal status was further confirmed by the generation of heteroduplexes only after addition of homozygous mutant DNA.

Base Sequence↗

Transfer characteristics of lateral geniculate nucleus X-neurons in the cat: effects of temporal frequency.

The dependency of intrageniculate signal transfer on stimulus temporal frequency was investigated by comparing responses of individual X-relay cells with their direct retinal inputs in anesthetized and paralyzed cats. Temporal frequency response functions of lateral geniculate nucleus (LGN) X-cells were more narrowly tuned than those of their retinal inputs. The efficiency of signal transfer was consistently highest at or around the geniculate cells' optimal temporal frequency, and the degree of signal transfer, which was more closely related to the LGN cells' firing rate than to the firing rate of their retinal input, decreased for both lower and higher temporal frequencies. The high temporal frequency cut-offs were significantly lower in geniculate cell responses than those of their direct retinal inputs. This reduction in temporal resolution was exaggerated for relatively low stimulus spatial frequencies. The present results provide clear evidence for the notion that LGN cells function as nonlinear temporal filters and that this stimulus-dependent signal transmission appears to be regulated by complex local mechanisms.

Action Potentials↗

Propagation of excitation-contraction coupling into ventricular myocytes.

This paper examines the [Ca2+]i transient in isolated rat heart cells using a laser scanning confocal microscope and the calcium indicator fluo-3. We find that the depolarization-evoked [Ca2+]i transient is activated synchronously near the surface and in the middle of the heart cell with similar kinetics of activation. The time of rise of the transient did not depend on whether the sarcoplasmic reticulum (SR) Ca-release was abolished (by thapsigargin and ryanodine). The synchrony of activation and the similarity of levels of [Ca2+]i at the peripheral and deeper myoplasm (regardless of the availability of SR Ca-release) shows that sarcolemmal Ca channels and SR Ca-release channels are distributed throughout the rat heart cell and that the propagation of the action potential into the interior of the cell is rapid. In addition, the activation of calcium release from the SR by CICR is rapid (<< 2 ms) when compared to the time-course of calcium influx via the sarcolemmal Ca channel.

Aniline Compounds↗

Structure-function studies of [2Fe-2S] ferredoxins.

The ability to overexpress [2Fe-2S] ferredoxins in Escherichia coli has opened up exciting research opportunities. High-resolution x-ray structures have been determined for the wild-type ferredoxins produced by the vegatative and heterocyst forms of Anabaena strain 7120 (in their oxidized states), and these have been compared to structural information derived from multidimensional, multinuclear NMR spectroscopy. The electron delocalization in in these proteins in their oxidized and reduced states has been studied by 1H, 2H, 13C, and 15N NMR spectroscopy. Site-directed mutagenesis has been used to prepare variants of these ferredoxins. Mutants (over 50) of the vegetative ferredoxin have been designed to explore questions about cluster assembly and stabilization and to determine which residues are important for recognition and electron transfer to the redox partner Anabaena ferredoxin reductase. The results have shown that serine can replace cysteine at each of the four cluster attachment sites and still support cluster assembly. Electron transfer has been demonstrated with three of the four mutants. Although these mutants are less stable than the wild-type ferredoxin, it has been possible to determine the x-ray structure of one (C49S) and to characterize all four by EPR and NMR. Mutagenesis has identified residues 65 and 94 of the vegetative ferredoxin as crucial to interaction with the reductase. Three-dimensional models have been obtained by x-ray diffraction analysis for several additional mutants: T48S, A50V, E94K (four orders of magnitude less active than wild type in functional assays), and A43S/A45S/T48S/A50N (quadruple mutant).

Amino Acid Sequence↗

Spatial non-uniformities in [Ca2+]i during excitation-contraction coupling in cardiac myocytes.

The intracellular calcium ([Ca2+]i) transient in adult rat heart cells was examined using the fluorescent calcium indicator fluo-3 and a laser scanning confocal microscope. We find that the electrically evoked [Ca2+]i transient does not rise at a uniform rate at all points within the cell during the [Ca2+]i transient. These spatial non-uniformities in [Ca2+]i are observed immediately upon depolarization and largely disappear by the time the peak of the [Ca2+]i transient occurs. Importantly, some of the spatial non-uniformity in [Ca2+]i varies randomly in location from beat to beat. Analysis of the spatial character of the non-uniformities suggests that they arise from the stochastic nature of the activation of SR calcium-release channels. The non-uniformities in [Ca2+]i are markedly enhanced by low concentrations of Cd2+, suggesting that activation of L-type calcium channels is the primary source of activator calcium for the calcium transient. In addition, the pattern of calcium release in these conditions was very similar to the spontaneous calcium sparks that are observed under resting conditions and which are due to spontaneous calcium release from the SR. The spatial non-uniformity in the evoked [Ca2+]i transient under normal conditions can be explained by the temporal and spatial summation of a large number of calcium sparks whose activation is a stochastic process. The results are discussed with respect to a stochastic local control model for excitation-contraction (E-C) coupling, and it is proposed that the fundamental unit of E-C coupling consists of one dihydropyridine receptor activating a small group of ryanodine receptors (possibly four) in a square packing model.

Animals↗

Pharmacokinetics and bioinversion of ibuprofen enantiomers in humans.

An open, randomized, six-way crossover study was conducted in 12 healthy males to assess pharmacokinetics and bioinversion of ibuprofen enantiomers. The mean plasma terminal half-life (t1/2) of R(-)ibuprofen was 1.74 hr when intravenously infused as a racemic mixture and was 1.84 hr when intravenously infused alone. The mean t1/2 of S(+)ibuprofen was 1.77 hr when dosed as S(+)ibuprofen. Examination of values of both the absorption and disposition parameters of R(-)ibuprofen revealed that the kinetics of R(-)ibuprofen were not altered by concurrent administration of S(+)ibuprofen. In this study, there was little or no presystemic inversion of R(-)ibuprofen to its S(+)isomer. Also, 69% of the intravenous dose of R(-)ibuprofen was systemically inverted and 57.6% of the oral dose of R(-)ibuprofen lysinate was bioavailable as S(+)ibuprofen. These results indicate that the bioinversion of R(-)ibuprofen administered orally is mainly systemic. Because bioinversion of R(-)ibuprofen is not complete, S(+)ibuprofen produced higher bioavailability of S(+)ibuprofen (92.0%) than either racemic ibuprofen (70.7%) or R(-)ibuprofen (57.6%). However, bioavailability of R(-)ibuprofen (83.6%) when dosed alone was not significantly different from when dosed as racemic mixture (80.7%).

Administration, Oral↗

Effect of liposome-muramyl tripeptide combined with recombinant canine granulocyte colony-stimulating factor on canine monocyte activity.

Liposome-muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) has been shown to activate monocytes in vivo to become tumoricidal resulting in reduction in metastasis as well as prolongation of survival time in murine and canine tumor models. Granulocyte colony-stimulating factor (G-CSF) is a cytokine which will stimulate the proliferation of granulocytes as well as monocytes. Recombinant canine G-CSF (rcG-CSF) was administered to normal dogs as a method of increasing the monocyte population prior to in vivo monocyte activation using L-MTP-PE. rcG-CSF administration resulted in a 3.5-fold increase in absolute monocyte counts and when combined with L-MTP-PE, resulted in an enhanced level of serum tumor necrosis factor-alpha activity compared to dogs treated with L-MTP-PE alone. G-CSF alone did not affect monocyte cytostatic activity, however, dogs receiving G-CSF had a significant increase in monocyte cytostatic activity following L-MTP-PE. The combined use of CSFs and effector cell activators deserves further evaluation in clinical trials.

Acetylmuramyl-Alanyl-Isoglutamine↗

Injecting drug use and HIV infection in southwest China.

OBJECTIVES: To determine the prevalence of drug injection among drug users, the seroprevalence of HIV and risk factors for HIV infection among injecting drug users (IDU), and to determine heterosexual transmission of HIV among IDU and their spouses in southwest China. METHODS: Using a cross-sectional design, we conducted an HIV seroprevalence and behavioral survey in three rural counties of Yunnan province, Ruili, Longchuan and Luxi in southwest China, bordering Myanmar (Burma). A total of 860 drug users were recruited in randomly selected communities at the three study sites (response rate, 97%). In addition, a random sample of 62 wives of HIV-infected IDU were assembled from 460 known HIV-positive IDU in Ruili and Longchuan (response rate, 81%). RESULTS: In the sample of 860 drug users, 33% reported injecting drugs. Among the 282 subjects who injected drugs, 82% began intravenous drug use after 1988; 64% injected drugs at least once every day. All subjects shared needles but none cleaned the injection equipment with alcohol or bleach. Overall, 49% tested HIV-positive. HIV seropositivity was independently correlated with a longer history of drug injecting, daily injecting, frequent needle-sharing, being younger, and living in Ruili county. Among the 62 wives of HIV-positive IDU, none used condoms during sex and 10% tested HIV-positive. CONCLUSIONS: We conclude that the introduction of HIV into drug-using communities and the rapid increase in heroin injecting in this population appear to have triggered an explosive HIV epidemic among IDU in southwest China. We recommend that AIDS prevention efforts should begin immediately and focus on discouraging the shift from opium smoking to heroin injecting, needle-sharing, and unprotected sex among drug users and their partners.

Adult↗

A confocal laser scanning microscope designed for indicators with ultraviolet excitation wavelengths.

In this paper we describe the modifications necessary to upgrade, at affordable cost, a commercially available confocal laser scanning microscope for use with ultraviolet (UV) excitation. The optical problems associated with these modifications are described in detail, and easy solutions to solve them are suggested. The optical resolution of the instrument was tested with fluorescent beads and was found to be close to diffraction limited. The light losses due to lateral chromatic aberration were assessed in a thick fluorescent specimen and were found to be comparable to those usually observed with visible light. For a more visual example of the resolution of this instrument, isolated ventricular heart muscle cells were loaded with the fluorescent Ca2+ indicator indo 1. This allowed us to visualize subcellular structural detail and to illustrate the optical sectioning capability of the UV confocal microscope when recording indo 1 emission. Dual-emission line scans were used to perform ratiometric time-resolved detection of Ca2+ transients in voltage-clamped heart muscle cells loaded with the salt form of indo 1. The system presented in this paper should significantly broaden the range of fluorescent indicators that can be used in confocal microscopy.

Animals↗

[Survey on the current situation of epidemic of HIV infection in Yunnan Province].

This paper summarized the results of routine surveillance, sentinel surveillance in Yunnan province during the period of 1986 to 1992. In 1992, HIV infection rates of intravenous drug users (IDUs) were 80.7% in Ruili city, 43.0% in Longchuan county, 17.4% in Yinjiang county, 3.7% in Luxi county and 0 in Kunming city respectively; the comparison of the change on the HIV infection rate of IDUs between 1990 and 1992 showed that the rate in Ruili city increased by 12.8%, the rate in Longchuan grew by 8.2%, but the rate in Luxi did not go up. On the sentinel surveillance, the rates in Longchuan drug treatment center went up. In Shimao, the HIV positive were detected in prostitutes and the HIV positive rate was 3.6%. In Xishuangbanna, the HIV positive percentage among sex clients was 9.1%.

China↗

[The effects of extracellular matrix on Sertoli cells of rats in vitro].

This study was performed to observe the effects of extracellular matrix (ECM) on Sertoli cells attachment, spreading and morphology in vitro. The ECM used were FN and LN and biomatrix isolated from the liver and lung. The results showed that FN and LN promoted Sertoli cell attachment and spreading. The Sertoli cells grown on the biomatrix isolated from the lung assumed a columnar shape like that seen in vivo. The cells grown on biomatrix from the liver did not.

Animals↗

[Determination of finger vibrotactile threshold and its significance in patients with hand-arm vibration syndrome].

Vibrotactile sense threshold (VST) of the end of the middle fingers in 97 patients with established or suspected hand-arm vibration syndrome and 60 healthy controls was determined, and finger VST contour and vibration damage curve were plotted. Results revealed the most sensitive frequencies of VST were 8 Hz for the patients and 125 Hz for the controls, respectively. VST in the patients with hand-arm vibration syndrome was higher than that in the controls, and the threshold shift was initially at high frequency with a "V" dip at 125 Hz and 250 Hz. So, the authors think determination of VST is an auxiliary method used for diagnosis of hand-arm vibration syndrome.

Adult↗

Intrarenal cytokine mRNA expression and location in normal and IgA nephropathy tissue: TGF alpha, TGF beta, IGF 1, IL-4 and IL-6.

Peptide regulatory factors (PRFs) are critical components in the regulation of glomerular inflammatory response to immune injury and may also have a primary role in modulating intrinsic cell proliferation and matrix synthesis. Dysregulation of PRFs and glomerular infiltration with inflammatory, including mononuclear, cells occur in models of nephritis, but direct evidence for their role is not established in normal and diseased tissue in man. Using in situ hybridization techniques capable of detecting specific cellular messenger RNA we have evaluated normal human and IgA nephropathy diseased renal tissue for expression and location of PRF encoding mRNA. Permeabilized tissue was examined by autoradiography using 35S labelled-antisense, and -sense riboprobes for TGF alpha, TGF beta, IGF 1, IL-4, and IL-6 encoding mRNA. TGF beta was constitutively expressed in normal glomerular mesangium, capillary loop, Bowman's capsule, and vascular endothelial and tubular cells, but was downregulated in IgA nephropathy tissue. In contrasting and distinct patterns, TGF alpha encoding mRNA was found in neither tissue, whereas IGF 1 mRNA was expressed in normal and also in diseased tissue. IGF 1 mRNA activity was intense within tubular cell cytoplasm in normals, with similar characteristics in IgA nephropathy. Cytokines IL-4 and IL-6 mRNAs were absent in normals, with IL-4 detectable throughout renal substance in disease; IL-6 gene transcription was intense in glomerular and vascular endothelial sites in IgA nephropathy. These findings implicate selective gene induction and suppression in disease, suggesting functional downregulation of glomerular TGF beta, coincident with autocrine functions for IL-6 and IL-4 in the pathogenesis of IgA-related nephropathy.

Cytokines↗

[Long-term efficacy of hepatitis B vaccine in newborn and revaccination study].

Two-hundred and sixty-nine newborns were followed up for 4 and 5 years after completion of vaccination (10 micrograms x 3). The anti-HBs positive rates remained 82.54% and 72.03%, respectively. The low-level titer (> or = 10-99 mIU/ml) made up 44.61%, and the medium-level titer (> or = 100-99mIU/ml) 32.34%. The highest titer was 857 mIU/ml. A 10 micrograms dose of hepatitis B vaccine was given to these children. The anti-HBs level went up greatly in the first month after revaccination, but started to drop in the third month, decreased rapidly in the sixth month, and in the twelveth month the level trended to restore the level before revaccination. This paper indicated that the home-made hepatitis B vaccine was effective. Revaccination was not necessary within 5-7 years after initial vaccination. Revaccination to children whose anti-HBs level was < 10mIU/ml was beneficial but the anti-HBs persistence was short.

Child, Preschool↗

Binocular interactions in striate cortical neurons of cats reared with discordant visual inputs.

The postnatal development of cortical binocularity is known to be adversely affected by early abnormal visual experience. However, little information exists on how the signals from the two eyes are combined in individual cortical neurons of animals reared with early discordant binocular visual experience. Since this is a fundamental issue in understanding visual cortical development, we used extracellular single-unit recording methods to study binocular integration in striate cortical neurons of strabismic cats. Specifically, we measured the sensitivity of individual cells to the relative interocular spatial phase of dichoptically presented drifting sinusoidal gratings (i.e., to binocular retinal image disparity). Clear alterations in ocular dominance were observed in all strabismic subjects. Nevertheless, the majority of cortical neurons exhibited some form of binocular interactions when both eyes were stimulated together. The most prominent aspect of cortical physiology in the strabismic animals was the relatively high prevalence of suppressive binocular interactions. Suppression was most frequently found in kittens reared with 2 weeks of early optical dissociation and among adult cats that received 2 weeks of early optical dissociation and a prolonged recovery period. However, substantial excitatory binocular interactions were also maintained in these animals. With an extended period of interocular misalignment (3 or 8 months), all forms of binocular interactions, excitatory and suppressive, were drastically reduced and a greater number of neurons were truly monocular. Although the reduction in the strength of binocular interactions occurred in all units irrespective of their monocular spatial properties, the effect was more pronounced among those units tuned to higher spatial frequencies and this spatial-frequency-dependent effect was larger in the subjects receiving longer periods of binocular dissociation. The results suggest that the "breakdown" of cortical binocular properties in strabismic subjects is not an all-or-none process, and that suppressive binocular interactions may be closely associated with the abnormal binocular interactions exhibited by strabismic humans. Furthermore, our findings are consistent with the notion that cortical disparity-detecting mechanisms are spatial-frequency dependent and, thus, can be selectively altered depending on an animal's early visual experience.

Animals↗

The recognition of UV-irradiation melanocyte with HMB-45 monoclonal antibody.

Monoclonal antibody HMB-45 was previously thought to be melanoma specific antibody and was taken recently as a marker for melanocyte proliferation or activation. A single UV-irradiation system which may induce a functional activity change in melanocytes was used to test the irradiated epidermal melanocyte for expression of HMB-45. Melanocytes, in the epidermis of the biopsies taken 7 days after a single UV exposure, showed markedly stained HMB-45, accompanied by morphological changes such as enlarged size, rich cytoplasma and elongated dendrites. We conclude that since morphological changes in irradiated melanocytes may be interpreted as signs of functional activity changes, melanocytes are exposed to stimulatory factors induced by UV light and get into a functional activating state to produce melanosome and HMB-45 antigen. Besides, the presence of HMB-45 in a single UV exposed epidermal melanocyte may support the hypothesis that its expression is inducible and is closely related to the functional activity of melanocyte.

Adult↗