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Biomedical subjects

K Zhang

Publications and source records attributed to K Zhang.

At least 415 records · Page 23Linked to original sources
PubMed1992

An EPROM-based heart-rate meter with wide range and multifunctions.

A digital heart-rate meter has been developed to display instantaneous as well as average heart-rate of 4 or 8 beats. The display resolution is 1 beat min-1 (BPM) in the range of 13-362 BPM, and 8 BPM in the range of up to 999 BPM. The whole circuit consists of 10 general-purpose integrated circuits (including LCDs). Two EPROM 2716 chips are preprogrammed with heart-rate data. A 12-bit binary counter, which sums the clock pulses between beat-to-beat intervals, is used to address the EPROMs to send appropriate data to the LCD display. We conclude that, with the resolution of 1 BPM, the relationship between the counting clock frequency f and upper display limit f' and lower display limit f" are: f' approximately square root 60f; f" = 60f/Nmax Where Nmax is the capacity of the EPROMs. To extend the dislay range, two clock frequencies, i.e. 256 Hz and 2048 Hz, are generated and switched automatically according to the heart-rate measured. The former is for the heart-rate less than 120 BPM, and the latter is for that higher than 120BPM.

Diagnosis, Computer-Assisted↗
PubMed1992

The Drosophila spitz gene encodes a putative EGF-like growth factor involved in dorsal-ventral axis formation and neurogenesis.

We describe the molecular characterization of the Drosophila gene spitz (spi), which encodes a putative 26-kD, EGF-like transmembrane protein that is structurally similar to TGF-alpha. Temporal and spatial expression patterns of spi transcripts indicate that spi is expressed throughout the embryo. Examination of mutant embryos reveals that spi is involved in a number of unrelated developmental choices, for example, dorsal-ventral axis formation, glial migration, sensory organ determination, and muscle development. We propose that spi may act as a ligand for cell-specific receptors, possibly rhomboid and/or the Drosophila EGF receptor homolog.

Amino Acid Sequence↗
PubMed1992

Integrin receptors and RGD sequences in human keratinocyte migration: unique anti-migratory function of alpha 3 beta 1 epiligrin receptor.

The migration of keratinocytes over the wound bed plays an important role in the re-epithelialization of cutaneous wounds. However, the mechanisms by which keratinocytes migrate over extracellular matrix components are unknown. In this study, we sought to determine if the RGD sequences in matrix molecules and recognition of these sequences by keratinocytes played a role in the locomotion of keratinocytes. After allowing the cells to attach to the matrix, RGD-containing peptides or control peptides were added to a keratinocyte migration assay. The addition of RGD-containing peptide dramatically inhibited keratinocyte locomotion on a matrix of fibronectin but not on collagen matrices. Therefore, RGD recognition is a critical step for fibronectin-mediated migration but not for collagen-mediated migration. Because the RGD sequences are recognized by cell-surface integrin receptors in a number of cell types, we next examined the roles of integrin receptors in human keratinocyte migration. Using monospecific antibodies that recognize integrin subunits, we found that blocking the beta 1 subunit inhibited the migration of keratinocytes on matrices of fibronectin, interstitial collagen, and basement membrane collagen. Blocking the alpha 5 beta 1 receptor significantly inhibited migration on fibronectin but not on collagen matrices. Conversely, blocking the alpha 2 beta 1 receptor inhibited migration on collagen matrices but not on fibronectin. Blocking the alpha 3 beta 1 receptor uniquely enhanced migration on fibronectin and collagen matrices. In contrast to cells apposed to matrices without the receptor blocked, the enhanced migration in the presence of anti-alpha 3 beta 1 antibody occurred at the later time points of the migration assay. The enhancement of migration by blocking the alpha 3 beta 1 integrin receptor suggests that the interaction of the alpha 3 beta 1 receptor with matrices is associated with immobility.

Amino Acid Sequence↗
PubMed1992

Biochemistry of the renal V-ATPase.

In most eukaryotic cells, vacuolar H(+)-ATPases (V-ATPases) are present primarily or exclusively in intracellular membrane compartments, functioning in the acidification of the endocytic and secretory vacuolar apparatus necessary for constitutive cell function. V-ATPases also participate in renal hydrogen ion secretion in both the proximal and distal nephron, residing at high concentrations on the plasma membrane, where they are regulated physiologically to maintain the acid-base balance of the organism. Recent experiments have begun to reveal how the kidney controls transcellular proton transport while still maintaining acidification of intracellular compartments. Control may occur by recruitment of proton pumps to or away from the plasma membrane. The proton-transporting plasma membrane of intercalated cells is a specialized apparatus that translocates the enzyme between an intracellular membrane pool and the plasma membrane in response to physiological stimuli. Regulation may also occur by changes in the kinetics of the V-ATPase. V-ATPases are a family of structurally similar enzymes which differ in the composition of specific subunits. Cytosolic regulatory enzymes present in renal cells may preferentially affect V-ATPases in selective membrane compartments.

Adenosine Triphosphatases↗
PubMed1992

Effects of thymosin and insulin on suppressor T cell in type 1 diabetes.

In most studies the activity of suppressor T cells and the percentage of suppressor/cytotoxic T-lymphocyte subsets in type 1 diabetes have been found to be altered. To determine whether thymosin and insulin in vitro have a role in improving or normalizing these abnormalities, PBMC from 28 patients with type 1 diabetes of various durations were treated with thymosin or insulin and the activity and the percentage of suppressor T cells were detected by using the method of ConA-induced suppressor T cells and WuT8 (suppressor/cytotoxic) monoclonal antibody respectively. Both thymosin and insulin were found to have ability to improve and normalize the ConA-induced suppressor cell activity and the percentage of WuT8 cells in diabetic patients. Data have shown that the lower the activity and the percentage of suppressor T cells, the more intense the effects of both compounds. The strongest effects were found at the concentrations of 10 micrograms/ml thymosin and 10 ng/ml insulin. Thymosin was more effective than insulin. This experiment also suggested that the activated lymphocytes stimulated by mitogens (PHA or ConA) were required when insulin exerted a significant effect on suppressor T cells. We conclude that thymosin and insulin in vitro can exert immuno-regulatory or immunostimulating effects on suppressor T cells.

Adult↗
PubMed1992

[Clinical outcome of silent myocardial ischemia detected by bicycle ergometry study].

Seventeen patients with positive maximal or submaximal bicycle-exercise test accompanied by painlessness and 14 patients with susceptible coronary heart disease with negative exercise test were studied and traced for 36 months. The patients underwent repeated bicycle-exercise test of the same stress and compared with those before 36 months. The results showed that 7/17 patients (41.2%) had an increase in the depressed level of ischemic type ST segment induced by exercise test. 3 of them developed effort angina pectoris: 1 suffered from myocardial infarction, 1 had recurrent atrial flutter and left heart failure, and 1 suddenly died from cardiac disease. The cardiac event rate was 3/17 (17.6%) in this group. While 14 patients with negative exercise test had no cardiac events. It seems to mean that silent myocardial ischemia detected by exercise test might have potential danger of cardiac events.

Adult↗
PubMed1991

Heterogeneous amino acids in Ras and Rap1A specifying sensitivity to GAP proteins.

Guanosine triphosphatase (GTPase) activity of Ras is increased by interaction with Ras-GAP (GTPase-activating protein) or with the GAP-related domain of the type 1 neurofibromatosis protein (NF1-GRD), but Ras is not affected by interaction with cytoplasmic and membrane forms of Rap-GAP; Rap1A, whose effector function can suppress transformation by Ras, is sensitive to both forms of Rap-GAP and resistant to Ras-GAP and NF1-GRD. A series of chimeric proteins composed of portions of Ras and Rap were constructed; some were sensitive to Ras-GAP but resistant to NF1-GRD, and others were sensitive to cytoplasmic Rap-GAP but resistant to membrane Rap-GAP. Sensitivity of chimeras to Ras-GAP and cytoplasmic Rap-GAP was mediated by amino acids that are carboxyl-terminal to the effector region. Residues 61 to 65 of Ras conferred Ras-GAP sensitivity, but a larger number of Rap1A residues were required for sensitivity to cytoplasmic Rap-GAP. Chimeras carrying the Ras effector region that were sensitive only to Ras-GAP or only to cytoplasmic Rap-GAP transformed NIH 3T3 cells poorly. Thus, distinct amino acids of Ras and Rap1A mediate sensitivity to each of the proteins with GAP activity, and transforming potential of Ras and sensitivity of Ras to Ras-GAP are at least partially independent properties.

Cell Membrane↗
PubMed1991

Inhibition of human IgE production via Fc epsilon R-II stimulation results from a decrease in the mRNA for secreted but not membrane epsilon H chains.

We have previously shown, using IgE-anti-IgE immune complexes or mAb directed against CD23, that ongoing production of secreted IgE from the human plasma cell line AF-10 can be inhibited via the low affinity FcR for IgE (CD23). Changes occurring in the various forms of epsilon messenger RNA (epsilon mRNA) during this suppression were investigated. mRNA levels of lambda L chain were also assessed as well as beta-actin controls. Changes in membrane IgE and secreted IgE and lambda protein were simultaneously measured. Using a genomic probe corresponding to the human epsilon C region domains, three sets of epsilon-mRNA bands were identified (2.1, 3.0, and 3.8 kb). Only the largest of these (3.8 kb) contained the full epsilon membrane sequence and coded for true membrane epsilon protein. The 2.1-kb species of epsilon-mRNA contained no membrane sequence and coded for classical secreted epsilon protein. The intermediate epsilon-mRNA species (3.0 kb) was shown to contain membrane sequence but did not contain the full epsilon membrane sequence. The product of this mRNA would, in fact, function as a secreted protein. When IgE production by AF-10 cells was suppressed via Fc epsilon R-II, there was a 50% fall in the steady state levels of both forms of mRNA (2.1 and 3.0 kb) that code for secreted epsilon protein. Similarly, there was a fall in lambda-mRNA corresponding to the observed decrease in free lambda secretion. In marked contrast, levels of both membrane IgE protein and mRNA coding for membrane epsilon were unaltered on the suppressed AF-10 cells. These data suggest that inhibition of IgE production via Fc epsilon R-II is related to a fall in mRNA for secreted proteins (epsilon and lambda) and probably reflects a post-transcriptional mechanism effecting mRNA for secreted vs membrane protein mRNA.

Antigen-Antibody Complex↗
PubMed1991

Conversion of the E1A Cys4 zinc finger to a nonfunctional His2,Cys2 zinc finger by a single point mutation.

Trans-activation by the adenovirus E1A 289R protein requires a zinc finger defined by Cys-154, Cys-157, Cys-171, and Cys-174. Whereas individually replacing the four cysteine residues with serines resulted in a loss of transactivation, only three of the Cys----Ser mutants (C157S, C171S, and C174S) lost the ability to bind Zn(II). X-ray absorption fine structure analysis revealed that, in the wild-type protein, Zn(II) is coordinated by four cysteine residues whereas in the C154S mutant, Zn(II) is coordinated by two histidines and two cysteines. The mutant protein probably retains, as ligands, two cysteines on the right side of the zinc finger (Cys-171 and Cys-174) and recruits two of the four histidines on the left side (His-149, His-152, His-158, and His-160), despite the presence of Cys-157. This finding may shed light on the general structural requirements of zinc fingers.

Adenoviridae↗
PubMed1991

Structural differences in solution and crystalline forms of met-myoglobin.

For several decades X-ray diffraction studies have been the paragon of biological structure studies at atomic resolution. Diffraction provides three-dimensional structure information, which is essential to our fundamental understanding of protein function. However, since X-ray diffraction cannot be done to atomic resolution on proteins in their native solution or membrane-bound state, the possibility exists that the conformations of the protein in crystals are slightly different from the conformations in solution, and attempts to interpret details of the structure may be misleading and without physiological relevance. In this paper, we show that this concern is justified for a familiar protein, myoglobin. Performing X-ray absorption fine structure experiments on both solution and crystalline met-myoglobin (met-Mb), we find significant differences in the local environment of the iron between the two states. Specifically, the average iron-nearest neighbor atom distance in the crystalline form is 0.05 A shorter than that in the solution form, and the iron-nearest neighbor bond is more rigid in the crystalline met-Mb. Possible artifactual explanations for the differences have been ruled out.

Animals↗
PubMed1991

CD40 stimulation provides an IFN-gamma-independent and IL-4-dependent differentiation signal directly to human B cells for IgE production.

IgE induction from human cells has generally been considered to be T cell dependent and to require at least two signals: IL-4 stimulation and T cell/B cell interaction. In the present study we report a human system of T cell-independent IgE production from highly purified B cells. When human cells were co-stimulated with a mAb directed against CD40 (mAb G28-5), there was induction of IgE secretion from purified blood and tonsil B cells as well as unfractionated lymphocytes. Anti-CD40 alone failed to induce IgE from blood mononuclear cells or purified B cells. The effect of the combination of anti-CD40 and IL-4 on IgE production was very IgE isotype specific as IgG, IgM, and IgA were not increased. Furthermore, anti-CD40 with IL-5 or PWM did not co-stimulate IgG, IgM, or IgA and in fact strongly inhibited PWM-stimulated IgG, IgM and IgA production from blood or tonsil cells. IgE synthesis induced by anti-CD40 plus IL-4 was IFN-gamma independent as is the in vivo production of IgE in humans; the doses of IFN-gamma that profoundly suppressed IgG synthesis induced by IL-4, or IL-4 plus IL-6, had no inhibitory effect on anti-CD40-induced IgE production. Anti-CD23 and anti-IL-6 also could not block anti-CD40 plus IL-4-induced IgE production, but anti-IL-4 totally blocked their effect. IgE production via CD40 was not due to IL-5, IL-6 or nerve growth factor as none of these synergized with IL-4 to induce IgE synthesis by purified B cells. Finally, we observed that CD40 stimulation alone could enhance IgE production from in vivo-driven IgE-producing cells from patients with very high IgE levels; cells that did not increase IgE production in response to IL-4. Taken together, our data suggest that the signals delivered for IgE production by IL-4 and CD40 stimulation may mimic the pathway for IgE production seen in vivo in human allergic disease.

Antigens, CD↗
PubMed1991

Active site conformation in myoglobin as determined by X-ray absorption spectroscopy.

X-ray absorption fine structure experiments were performed to study structural and dynamic aspects of the active site of various forms of myoglobin. The structures determined for deoxyMb, MbCO, and MbO2 are consistent with the structure established by X-ray absorption fine structure experiment and X-ray crystallography. The first shell of ferrous MbNO determined contains 5 nitrogens located at 2.02 A and a short NO bond length of 1.76 A. This study focuses on the change of the XAFS Debye-Waller factor with temperature, which is a measure of thermal and static disorder. It was found that the changes of Debye-Waller factor with temperature for the Mb proteins, except deoxyMb, are consistent with a simple Einstein model, in which a single frequency was assumed for the bond stretching modes. In contrast, the temperature dependence of deoxyMb cannot be fitted to the Einstein model and a large disorder was found at low temperatures, which indicates the existence of conformational substates of the active site.

Animals↗
PubMed1991

In vitro and in vivo investigations of dihydropyridine-based chemical delivery systems for anticonvulsants.

A dihydropyridine-based chemical delivery system (CDS), intended to improve drug delivery to the brain, was investigated with a series of analogues of the anticonvulsant striripentol. In vitro experiments demonstrated that the rates of hydrolysis of the corresponding pyridinium conjugates were influenced markedly by small changes in the structure of the drug moiety to be released. Thus, allylic esters were hydrolyzed rapidly to drug in all aqueous media, while the analogous saturated esters and an allylic amide derivative were almost totally stable. The mechanism of hydrolysis, which is particular to this series of CDS conjugates, appeared to occur via ionization to a resonance-stabilized carbocation intermediate. The same CDS compounds were investigated in vivo and compared to the corresponding drugs after intravenous administration. Only those CDS compounds that were found to hydrolyze in vitro released appreciable amounts of drug in vivo. Prolonged release of the drug from the CDS in the brain could be demonstrated for these compounds, but the gain in the ratio of brain-to-plasma AUC when the CDS was administered depended on the innate distribution characteristics of the drug. Thus, the drug D3, which had a high brain-to-plasma AUC ratio, did not show an improvement in this ratio when administered as CDS3. In contrast, stiripentol with a poor brain-to-plasma AUC ratio showed a two- to threefold increase in this ratio when administered as a CDS. These investigations highlight the need for a thorough understanding of the mechanism of drug release and the importance of the pharmacokinetic properties of the drug in designing a carrier system for delivery of drugs to the brain.

Animals↗
PubMed1991

The crooked neck gene of Drosophila contains a motif found in a family of yeast cell cycle genes.

The crooked neck (crn) gene of Drosophila encodes a protein of 702 amino acids and contains 16 tandemly arranged copies of a 34-amino-acid repeat that is similar to the tetratrico peptide repeat (TPR). Multiple copies of the TPR motif have also been found in a family of yeast genes, including several members that are necessary for cell division. TPR-containing proteins encoded by the yeast genes CDC16, CDC23, and nuc2+ are required for progression through the G2/M transition of the cell cycle. Loss of zygotic expression of crn causes defects in the proliferation of brain neuroblasts and results in the absence of identified neuronal lineages in the central and peripheral nervous systems. The sequence similarity and mutant phenotypes are consistent with a cell cycle requirement for the crn gene product.

Amino Acid Sequence↗