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Biomedical subjects

J Zhong

Publications and source records attributed to J Zhong.

At least 127 records · Page 7Linked to original sources
PubMed1994

Molecular characterization of CD30+ anaplastic large-cell lymphoma: high frequency of c-myc proto-oncogene activation.

Anaplastic large-cell lymphoma (ALCL) represents a morphologically distinct type of non-Hodgkin's lymphoma (NHL) characterized phenotypically by the expression of the CD30 antigen, a new member of the nerve growth factor gene family. The lymphoid origin of ALCL has been documented using immunohistochemical and molecular genetic analyses. However, very little is known so far regarding the precise pathogenetic mechanisms involved in its development and progression. Therefore, we investigated bcl-2, p53, and retinoblastoma gene (Rb) expression immunohistochemically; the occurrence of bcl-2, c-myc, and Rb gene rearrangements using Southern blotting; and the presence of ras and p53 gene somatic mutations by single-strand conformation polymorphism assay in a panel of 18 well-characterized ALCLs. In addition, the presence of Epstein-Barr (EBV) and human T-cell lymphotropic virus type I (HTLV-I) genomes were investigated using polymerase chain reaction. We identified abnormal c-myc gene products in 6 of 18 cases (33%) of ALCL. On the other hand, the bcl-2 and Rb genes were not rearranged and K-, N-, and H-ras gene somatic mutations were not found. Significant levels of p53 protein expression were found in more than 60% of ALCLs, but only a single ALCL carried a p53 gene mutation (exon 5). Only 3 ALCL cases, all occurring in human immunodeficiency virus-infected patients, were positive for EBV genomes. On the other hand, contrary to previous findings, no HTLV-I products could be identified. Despite the fact that the c-myc proto-oncogene appears to be frequently altered in ALCL, no pathognomonic abnormality could be identified and therefore additional studies and new strategies should be designed to identify the pathogenetic mechanisms involved in the development of ALCL.

Adolescent↗
PubMed1994

A novel granulocyte-derived peptide with lipopolysaccharide-neutralizing activity.

Rabbit CAP18 (cationic antimicrobial protein, 18 kDa) is a leukocyte protein identified and purified using as an assay its capacity to bind and inhibit various activities of LPS. Oligonucleotide probes designed from the putative N-terminal protein sequence were used to obtain the corresponding cDNA from a rabbit bone marrow cDNA library. Examination of the cDNA sequence revealed that the protein fragment of the putative N-terminus was actually a 37-amino-acid C-terminal fragment. This fragment, designated CAP18(106-142), inhibits many activities of LPS. In the present studies, synthetic CAP18(106-142) is shown to: 1) bind to erythrocytes coated with diverse strains of LPS; 2) inhibit LPS-induced release of cytokines (TNF, IL-1, IL-6) and nitric oxide from macrophages; 3) inhibit LPS-induced LAL coagulation and 4) protect mice from LPS lethality. CAP18(106-142) may have therapeutic utility for conditions associated with elevated concentrations of LPS.

Amino Acid Sequence↗
PubMed1994

Intravascular susceptibility contrast mechanisms in tissues.

The factors affecting the rate of loss of transverse magnetization in gradient echo and spin-echo pulse sequences have been quantified using computer modeling for media containing arrays of susceptibility variations. The results are particularly relevant for describing the signal losses that occur in tissues containing capillaries of altered intrinsic susceptibility from the administration of exogenous contrast agents or arising from changes in blood oxygenation. The precise magnitudes and relationship of gradient echo and spin-echo decay rates depend on geometrical factors such as the sizes and spacings of the inhomogeneities, the rate of water diffusion, field strength, and echo times. The conventional separation of contributions to transverse decay rates arising from so-called static field effects and diffusion is shown to be inappropriate for many situations of practical interest because diffusion introduces a motional averaging of the static field even in gradient echo sequences. The result of diffusion in some regimes is to reduce the decay rate from field inhomogeneities in gradient echo sequences, so that T2* is longer in media such as tissue where water diffuses reasonably rapidly, than would be the case for stationary nuclei. The effects of different types of contrast agent and the implications for functional imaging based on the effects of deoxyhemoglobin in brain tissue are considered.

Capillaries↗
PubMed1994

BOLD MRI monitoring of changes in cerebral perfusion induced by acetazolamide and hypercarbia in the rat.

To evaluate MRI methods for estimating cerebrovascular reserve, we computed changes in the R2* and R2 transverse relaxation rate and apparent diffusion coefficient (ADC) at 2.0 Tesla in five rats after administration of 30 mg of acetazolamide and in four rats during inhalation of 20% carbon dioxide gas. Significant decreases in R2*, corresponding to increases in gradient echo MRI signals, occurred in both the acetazolamide (average change -8.3%, P = 0.005) and the carbon dioxide (-2.7%, P = 0.009) treated animals. The computed values for R2 and ADC were unchanged. The magnitude of the gradient echo MRI changes observed should permit anatomic mapping of blood flow reactivity patterns in normal human subjects and in patients at risk for cerebrovascular disease.

Acetazolamide↗
PubMed1994

Localized in vivo 31P NMR spectroscopy of skin flap metabolism.

We have used a rectangular surface coil and chemical shift imaging to conduct in vivo localized 31P NMR metabolic studies in a rat dorsal skin flap model. This approach permits regional comparisons without manipulation of either coil position or subject within the magnet bore. Both the PCr:Pi ratio (reflecting ischemia insult) and the PCr:ATP ratio (reflecting phosphagen reserves) decreased as functions of time and distance from the vascular pedicle. The maximum change was nearly 6-fold for the PCr:Pi ratio, and 3-fold for the PCr:ATP ratio. Signal contamination from subjacent muscle is constant and does not interfere with the metabolic evaluations of skin flaps. This technique may facilitate a better understanding of cutaneous metabolic derangements, such as burns and skin flaps used in reconstructive surgery, as well as studies of pharmacologic regimens developed for their treatment. It also holds potential for application in the study of congenital and neoplastic metabolic disorders of skin.

Adenosine Triphosphate↗
PubMed1994

Measurements of transient contrast enhancement by localized water NMR spectroscopy.

It is shown that a localized spectroscopic method can be used to detect transient contrast enhancement of transverse relaxation and to measure cerebral blood volume. High-resolution spectra of the water resonance were recorded from small-volume elements of the brain following bolus administration of contrast agents. The integrated signal corresponds to the intensity that would be portrayed in a single voxel in an MR image. The spectral data can be analyzed to more precisely describe the alterations in tissue NMR signal incurred by the agent than is possible by simple image intensity measurement. In particular, the contributions to relaxation by diffusion of water molecules and static line broadening in the field inhomogeneities generated by intravascular contrast agents can be separately evaluated from the spectral analysis. The method has been used to study rat brain before and during bolus injections of contrast agents, and used to compare the differential effects of two different agents, viz., Gd-DTPA, and Dy-DTPA. While the integrated intensity change produced by Dy-DTPA was approximately 35% greater than that for Gd-DTPA, the corresponding linewidths differed by over 300%. This method may also provide measurements of changes in tissue oxygenation with high signal-to-noise ratios in brain activation studies.

Animals↗
PubMed1994

Inhibition of apoptosis as a mechanism of tumor promotion.

Recent evidence supports the concept that tumor growth in vivo depends on evasion of normal homeostatic control mechanisms that operate through induction of cell death by apoptosis. This study tested the hypothesis that a common property shared by known or suspected tumor promoters is the ability to block the process of apoptosis. A total of 10 tumor promoters were tested and all were found to inhibit DNA fragmentation and cell death of 7 different cell lines triggered into apoptosis by diverse agents. Resistance to apoptosis could be induced rapidly (within 1 h) by treating with relatively high concentrations of promoters. However, low physiological concentrations of promoters could also induce complete resistance to apoptosis after prolonged exposure (5-15 days of culture). Like tumor promotion in vivo, promoter-induced resistance to apoptosis was reversible after culturing in the absence of promoter. These findings provide new insight into the mechanism of tumor promotion and suggest a novel in vitro screening assay to detect new tumor-promoting agents in the environment.

Animals↗
PubMed1994

Cardiodynamic response to Escherichia coli endotoxemia: effects of fluid resuscitation.

We tested the influence of in vivo volume resuscitation on intrinsic contractile properties of left ventricular (LV) preparations of endotoxemic guinea pigs. Escherichia coli endotoxin (LPS)-injected animals were divided into nonresuscitated and resuscitated groups. Volume resuscitation improved cardiac output and stroke volume, increased arterial pH and body temperature, and decreased mortality. In isovolumetric LV preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) of LPS with (42 +/- 3) and without (42 +/- 2) fluid resuscitation were consistently less than control values (70 +/- 3). LV end-diastolic pressure-volume (compliance) decreased in LPS-nonresuscitated hearts, while LV compliance of LPS-resuscitated hearts was similar to control. Thus, intravascular volume expansion selectively improved LV diastolic compliance of LPS hearts without affecting LV systolic function. These findings suggest that LV systolic and diastolic dysfunctions associated with endotoxemia and Gram-negative sepsis may involve separate pathogenic mechanisms.

Analysis of Variance↗
PubMed1994

A general model of microcirculatory blood flow effects in gradient sensitized MRI.

A general expression is derived for the NMR signal from a fluid undergoing random directional flow such as encountered within the microcirculation. The dependence of the echo amplitude on flow velocity, sample morphology, and experimental parameters are described in terms of a temporal velocity autocorrelation function. The width of the correlation function determines whether the flow can properly be described as diffusive. Comparison is made between the velocity autocorrelation method outlined here and the IVIM model for tissue perfusion. Conditions for the validity of the latter approach for extracting physiologic information from apparent diffusion measurements are discussed. The approach outlined leads to a more robust measure of microcirculatory blood velocity from NMR measurements.

Biophysical Phenomena↗
PubMed1994

Rabbit CAP18 derived peptides inhibit gram negative and gram positive bacteria.

CAP18 (cationic antimicrobial protein of 18 kDa) was originally isolated from rabbit granulocytes using as an assay the agglutination of Re-lipopolysaccharide coated erythrocytes. The C-terminal 37 amino acids of CAP18 comprise the LPS-binding domain called RNIP, reactive nitrogen inhibitory peptide. Synthetic RNIP has broad antimicrobial activity versus both gram positive [IC50 = 130-200 nM] and gram negative bacteria [IC50 = 20-100 nM). Susceptible strains include Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes. Antimicrobial activity is highly dependent upon peptide structure. Although a 32 amino peptide resulting from truncation of five amino acids from the C terminus of RNIP is highly active, other fragments of RNIP including truncation of its N-terminus do not exhibit antimicrobial activity. Unlike previously characterized antimicrobial peptides derived from granulocyte proteins RNIP is active in serum. RNIP or a derivative peptide may have therapeutic potential for bacterial sepsis.

Amino Acid Sequence↗
PubMed1994

[Effects of "moist burn ointment--mei bao" on production of IL-2 in burn rats and its clinical problems].

Since "Mei Bao" has been used in clinical treatment of burn wounds, there is a diversity of opinions concerning its effect. We carried out a series of experiments to observe its therapeutic effect, bacteriostatic property, and its effect on production of IL-2 in thermally injured rats. These results indicate that obvious infection occurred after its use on burn wounds and healing is delayed. Hyperplastic scars accompanying with deformity appeared after healing. The cost of treatment is high. There is no improvement in immune reaction, and no bacteriostatic property is observed.

Adolescent↗
PubMed1994

Expression of mRNAs encoding subunits of the N-methyl-D-aspartate receptor in cultured cortical neurons.

The expression of mRNAs encoding subunits of the N-methyl-D-aspartate (NMDA) receptor was examined in cortical neurons maintained in primary culture. Cultures were prepared from embryonic day 17 rat neocortex. At this developmental age, levels of NR1, NR2A, NR2B, and NR2C mRNA were low or undetectable. Expression of NR1 mRNA increased progressively between days 1 and 21 in vitro. The amount of NR2A mRNA did not change between days 1 and 7 but increased between days 7 and 21. In contrast, levels of NR2B mRNA increased between days 1 and 7, with little further change after day 7. The level of NR2B mRNA was approximately 4-fold higher than that of NR2A mRNA in 21-day cultures. Using ligand binding assays, the proportion of NMDA receptors having a low affinity for ifenprodil was also found to increase over time in culture. The increase in the expression of receptors having a low affinity for ifenprodil and the increase in NR1 and NR2A mRNAs were reduced or prevented by maintaining cells in medium with a low concentration of serum. The results are consistent with the hypothesis that inclusion of the NR2A subunit in native NMDA receptors is responsible for their low affinity for ifenprodil. Splice variants of NR1 lacking the 5' (amino-terminal) insert were found to be the predominant forms of NR1 in cultured neurons. Variants containing the 5' insert represented only a small (< or = 5%) fraction of total NR1 mRNA, and their proportion was not altered as a function of time in culture. Time-dependent changes in the properties of NMDA receptors and in the expression of subunit mRNA occurring in cultured neurons are similar to changes observed in developing rat brain. Thus, the developmental sequence of NMDA receptor expression that occurs in vivo is partially retained in neurons maintained in vitro.

Animals↗
PubMed1993

Role of protein phosphorylation in TNF-induced apoptosis: phosphatase inhibitors synergize with TNF to activate DNA fragmentation in normal as well as TNF-resistant U937 variants.

This study examined the role of protein phosphorylation in TNF induction of apoptosis in several tumor cell lines by testing the effects of agents that either stimulate or inhibit protein phosphorylation. The serine-threonine phosphatase inhibitors, okadaic acid (OKA) and calyculin A (CLA), synergistically augmented TNF-induced apoptosis in several TNF-sensitive tumor cell lines including the U937 histiocytic lymphoma, the BT-20 mammary carcinoma, and the LNCap prostatic tumor cell line. Furthermore, the phosphatase inhibitors completely reversed the TNF resistance of a variant (U9-TR) derived from U937. CLA also inhibited phosphatase activity in cell-free extracts from both U937 and U9-TR at the same concentrations (0.4-2.0 nM) that it synergized with TNF. In contrast, TNF treatment of U937 cells did not result in inhibition of phosphatase activity mediated by protein phosphatase 1 (PP1) and PP2A in cell extracts. Since the phosphatase inhibitors are known to increase the overall levels of protein phosphorylation in cells, this suggested that TNF may act by stimulating protein kinase (PK) activity. This hypothesis was supported by the results of testing a panel of relatively specific protein kinase inhibitors. TNF activation of DNA fragmentation was blocked by a potent inhibitor of myosin light chain kinase (MLCK) but was unaffected by inhibitors of cAMP or cGMP-dependent PKs. We postulate that a defect in the activation of MLCK or possibly some other as yet unknown PK may be responsible for the TNF resistance of U9-TR. Furthermore, this resistance may be circumvented by promoting protein phosphorylation with the serine-threonine-dependent phosphatase inhibitors.

Alkaloids↗
PubMed1993

Changes in water diffusion and relaxation properties of rat cerebrum during status epilepticus.

Diffusion-weighted (DW) imaging has been used to record changes associated with status epilepticus (SE) in rat brain. It was found that the apparent diffusion coefficient (ADC) of water in brain decreased 14-18% during SE, and it fell a further 20-22% when the animals were sacrificed. The transverse decay time constant T2* showed corresponding reductions, but no significant changes were seen in relaxation times T1 or T2 values. Changes in ADC in status epilepticus are similar to those seen in stroke and ischemia but occur under very different conditions of blood flow and metabolism.

Animals↗
PubMed1993

On generalized photocurrent spectral moments and the recovery of speed distribution in laser Doppler flowmetry.

Laser Doppler flowmetry (LDF) is a noninvasive method to assess tissue blood flow. By calculating the first moment of the Doppler signal power spectral density, a real-time output is generated that scales linearly with the perfusion flux defined as the product of average speed and concentration of moving blood cells (MBC's) if multiple scattering is negligible. However, this first spectral moment alone is apparently deficient to provide further information about the MBC's under study and therefore unable to answer more intricate questions in LDF. Without assuming any specific MBC speed or scattering vector distribution, a generalized formula for photocurrent spectral moments is first derived in the case of low and moderate MBC concentration. Then as a direct and important use of the formula, the speed distribution of MBC's is obtained via Henyey-Greenstein phase function and a Fourier inversion. The important implications and applications of this formulation in extracting more MBC information are discussed together with some other related issues.

Fourier Analysis↗
PubMed1993

Antimicrobial activity of rabbit CAP18-derived peptides.

A cationic antimicrobial protein of 18 kDa (CAP18) was originally isolated from rabbit granulocytes by using as an assay the agglutination of Re-lipopolysaccharide-coated erythrocytes. The C-terminal 37 amino acids of CAP18 (CAP18(106-142)) make up the lipopolysaccharide-binding domain. Synthetic CAP18(106-142) has broad antimicrobial activity against both gram-positive (50% inhibitory concentration, 130 to 200 nM) and gram-negative (50% inhibitory concentration, 20 to 100 nM) bacteria. Susceptible strains include Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhimurium. Antimicrobial activity is highly dependent on peptide structure. Although a 32-amino-acid peptide resulting from the truncation of 5 amino acids from the C terminus of CAP18(106-142) is highly active, other fragments of CAP18(106-142), including CAP18(106-142) with a truncated N terminus, do not exhibit antimicrobial activity. Unlike previously characterized antimicrobial peptides derived from granulocyte proteins, CAP18(106-142) is active in serum. CAP18(106-142) or a derivative peptide may have therapeutic potential for bacterial sepsis.

Agglutination Tests↗