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Biomedical subjects

Z Zhou

Publications and source records attributed to Z Zhou.

At least 451 records · Page 25Linked to original sources

Functional analysis of T-cell antigen 4-1BB in activated intestinal intra-epithelial T lymphocytes.

The 4-1BB antigen has been recently demonstrated to be a 30 kDa inducible T-cell antigen and is expressed on the cell surface of activated splenic T cells and thymocytes. This novel T-cell antigen also associates physically with the T cell-specific protein tyrosine kinase, p56lck. We show here that the inducible T-cell antigen 4-1BB is expressed on activated intestinal intra-epithelial T lymphocytes (IEL). After activation, or in the presence of IL-2, the activated IELs showed higher levels of 4-1BB. Functional studies revealed that the activated IELs triggered with anti-4-1BB monoclonal antibody could enhance the level of IEL cytotoxicity against anti-CD3-secreting hybridoma cells. Cross-linking of anti-4-1BB antibody also enhanced the proliferation of IELs. These results suggest that the inducible antigen 4-1BB has broad biological functions which not only play a role in activated splenic T cells and thymocytes but also in the mucosal immune system.

Animals↗

Expression of the neurotensin gene in fetal human liver and fibrolamellar carcinoma.

OBJECTIVE: This study determined whether the neurotensin gene (NT/N) is expressed in the normal adult liver and focal nodular hyperplasia (FNH) and confirmed NT/N expression in fibrolamellar carcinoma; whether NT/N or the neurotensin receptor is expressed in the fetal liver; and whether hepatic resection leads to expression of NT/N. SUMMARY BACKGROUND DATA: Neurotensin (NT), a gut tridecapeptide localized in the gastrointestinal tract of the adult to the small bowel, is an important hormone-regulating gut motility, secretion, and mucosal growth. Expression of the NT/N gene has been identified in fibrolamellar carcinomas, but NT/N is not known to be expressed in the normal liver. METHODS: Sensitive ribonuclease (RNase) protection assays were used to determine whether NT/N is expressed in fibrolamellar carcinoma, FNH, or healthy fetal and adult livers. The authors also determined whether the receptor for NT was present in the fetal liver and whether liver resection and subsequent regeneration could lead to re-expression of NT/N in the rat. RESULTS: Neurotensin is expressed in fibrolamellar carcinoma and in the fetal human liver, but not in the adult liver or the samples of FNH. In addition, the authors were not able to detect expression of the NT receptor in the fetal liver and did not identify NT/N gene activation in the regenerating liver of the rat. CONCLUSIONS: The NT/N gene will be a useful molecular marker to differentiate fibrolamellar carcinoma from other liver tumors. The finding of NT/N expression in the fetal liver suggests a stem cell descendant that is common to both the liver and gut. The absence of NT/N expression in the regenerating liver suggests that NT does not play a role in this rapid growth process.

Animals↗

Metabolically based treatment of stunned myocardium.

Reversible myocardial ischemia is associated with a rapid decrease in contractility and prolonged postischemic ventricular dysfunction, due in part to altered intracellular calcium handling and/or contractile protein dysfunction. The maintenance of intracellular calcium homeostasis and force development by the contractile apparatus are dependent upon the free energy derived from ATP hydrolysis. This energy of hydrolysis is determined by the myocardial phosphorylation potential, an estimate of which can be made from the ratio (CrP)/(Cr) x (P(i)). Results from in vitro and in vivo studies suggest that pyruvate enhances contractility in both normal and stunned myocardium by enhancing myocardial phosphorylation potential. In regionally stunned porcine myocardium, pyruvate infusion increased recovery of regional ventricular function from 33% +/- 4% of preischemic systolic wall thickening to 81% +/- 4% and increased the (CrP)/(Cr) x (P(i)) ratio fivefold from 0.21 +/- 0.04 to 1.05 +/- 0.08. Thus, metabolic substrates that enhance myocardial energetics and ventricular function may be effective agents for attenuating postischemic ventricular function.

Animals↗

Distribution of red cell blood group systems in Achang and De'ang ethnic groups in China.

A survey on the distribution of red cell group systems, including ABO, MNSs, Rhesus and P, was carried out in the Achang and De'ang ethnic groups in Yunnan Province, South-West China. The Achangs are characterized by the highest frequency of IA in China, while the De'angs show a high frequency of IO and CDe. The distribution of these blood group systems in Achang and De'ang exhibits the same characteristics observed in other ethnic groups of South China.

ABO Blood-Group System↗

Condition judgement of dry eye in sicca syndrome.

In this paper, we presented 32 dry eyes of 16 random patients with primary Sicca Syndrome graded with rose bengal (rb), Break up time of tear film (BUT) and Schirmer 1 test (S1T). Of them, the lip biopsy and tear beta 2-M level were examined and overall studied. The results showed that the grade of dry eye was closely related with both the degree of lymphocyte infiltration of lip glands and level of tear beta 2-M, and indicated that our grading method for dry eye based on rb, BUT and S1T is depandable, and the lymphocyte infiltration of both lip and lacrymal gland may be the same qualitatively and quantitatively. so, how many lymphocytes appeared in the lip gland, how much concentration would be the tear beta 2-M Therefore judging the condition of dry eye by these 5 tests is dependable and simple too, as they need no complicated equipment.

Adult↗

[Introduction and cultivation of Cinnamomum cassia Presl].

Based on the study of biological characteristics, growth determination, quality examination, harvest and processing features, it has been proved that the introduction and cultivation of Cinnamomum cassial are feasible in such southern subtropics as the valleys along the Yangtze River in the southern part of Sichuan province. Specific cultivating techniques to adapt to the local climate are reviewed in the paper.

China↗

[Clinicopathologic and immunohistochemical studies of midline malignant reticulosis in palate].

Fourteen patients (10 males and 4 females) with midline malignant reticulosis (MMR) in palate were studied. The symptoms were most commonly swelling and ulceration. In some cases, the lesion involved nasal, maxillary sinus and facial skin, but no regional lymph nodes were involved. A necrotizing infiltration of atypical lymphoid cells (ALCs) mixed with inflammatory cells was confirmed as the histopathologic feature of MMR. In 2 of 14 cases, ALCs formed a continuous sheet in several high-power fields with a few inflammatory cells. This overlapping feature may be a transitional form between MMR and malignant lymphoma. Immunohistochemical staining results indicated that in 10 of 14 cases, ALCs were CD3 positive; in 7 of 14 cases, ALCs were UCHL1 positive; and in all 14 cases, ALCs were L26 negative. We deem MMR a T-cell lymphoma in substance, but it should be treated as a histopathologic entity distinct from malignant lymphoma.

Adult↗

DUN1 encodes a protein kinase that controls the DNA damage response in yeast.

DNA damage induces the expression of many genes proposed to enhance DNA repair capacities. We investigated the mechanism by which DNA damage induces transcription of RNR3, a subunit of ribonucleotide reductase. Five complementation groups of DNA-damage uninducible (dun) mutants were identified. Each is sensitive to DNA damage. dun1 mutants are also defective for RNR1 and RNR2 induction but are proficient for induction of other genes, defining the existence of at least two distinct DNA damage induction pathways. DUN1 encodes a nuclear protein kinase that is also a phosphoprotein. Phosphorylation of Dun1 increases in response to DNA damage in a Dun1-dependent manner, suggesting an increase in autophosphorylation activity. These results establish the existence of a eukaryotic SOS response regulated by protein phosphorylation.

Amino Acid Sequence↗

Macrophage inflammatory protein-1 alpha rapidly modulates its receptors and inhibits the anti-CD3 mAb-mediated proliferation of T lymphocytes.

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is a member of the intercrine/chemokine family which consists of basic, heparin-binding, small molecular weight proteins. We have previously shown that a T cell line, CTLL-R8, carried high-affinity receptors for MIP-1 alpha and the proliferation of CTLL-R8 cells was inhibited by murine recombinant (mr) MIP-1 alpha. We extended our previous studies to murine resting splenic T lymphocytes to determine whether the inhibition of T cell proliferation is a general property of MIP-1 alpha. The resting splenic T cells carried approximately 680 high-affinity binding sites for mrMIP-1 alpha; more than 90% of the primary T cells carried MIP-1 alpha receptors. When the T cells were stimulated with immobilized anti-CD3 mAb in the presence of accessory cells, the MIP-1 alpha binding was reduced. The lowest binding was obtained 2 h after anti-CD3 mAb stimulation due to the internalization of MIP-1 alpha receptors. mrMIP-1 alpha inhibited the anti-CD3 mAb-mediated proliferation of murine splenic T lymphocytes. The maximum inhibition was obtained when mrMIP-1 alpha was added 30 min before anti-CD3 mAb stimulation. Slight inhibition of T cell proliferation was observed when mrMIP-1 alpha was added at the same time as anti-CD3 mAb stimulation. These results indicate that T lymphocytes are regulated negatively by MIP-1 alpha, which occurs when the T cells are exposed to MIP-1 alpha before activation. The negative effect of MIP-1 alpha seems to be mediated in part by the inhibition of IL-2 production, for there was a reduction in both the IL-2 mRNA levels and the IL-2 activity in supernatants from T cells preincubated with MIP-1 alpha before anti-CD3 mAb stimulation.

Animals↗

Novel T cell antigen 4-1BB associates with the protein tyrosine kinase p56lck1.

4-1BB is a 30-kDa inducible T cell Ag, and is expressed predominantly as a 55-kDa dimer on both CD4+ and CD8+ T lymphocytes. The cytoplasmic tail of 4-1BB contains the sequence Cys-Arg-Cys-Pro, which is similar to the sequence Cys-X-Cys-Pro, which mediates the binding of the CD4 and CD8 molecules to the protein tyrosine kinase p56lck. An anti-4-1BB mAb, 53A2, was used to determine whether 4-1BB may associate with p56lck. The 53A2 mAb specifically recognized 4-1BB on a CD8+ T cell line, CTLL-2, and coimmunoprecipitated a 56-kDa protein along with 4-1BB. Peptide mapping indicated that the 56-kDa phosphoprotein was identical to p56lck. The coimmunoprecipitation of p56lck with 4-1BB also occurred in nonlymphoid cells such as insect (Sf-21) and HeLa cells when the two recombinant proteins were coexpressed. Analysis of mutant p56lck recombinant proteins showed that two cysteine residues critical for p56lck-CD4 (or -CD8) complex formation are also required for the p56lck-4-1BB interaction. These studies establish that 4-1BB physically associates with p56lck.

Amino Acid Sequence↗

MAP kinase-related FUS3 from S. cerevisiae is activated by STE7 in vitro.

Pheromone-stimulated haploid yeast cells undergo a differentiation process that allows them to mate. Transmission of the intracellular signal involves threonine and tyrosine phosphorylation of the redundant FUS3 and KSS1 kinases, which are members of the MAP kinase family. FUS3/KSS1 phosphorylation depends on two additional kinases, STE11 and STE7 (refs 2, 5, 6). Genetic analyses predict an ordered pathway where STE11 acts before STE7 and FUS3/KSS1 (refs 2, 7). Here we report that STE7 is a dual-specificity kinase that modifies FUS3 at the appropriate sites and stimulates its catalytic activity in vitro. From these data and previous genetic results, we argue that STE7 is the physiological activator of FUS3. Recent indications that MAP kinase activators are related to STE7 suggest that signal transduction pathways in many, if not all, eukaryotic organisms use homologous kinase cascades.

Calcium-Calmodulin-Dependent Protein Kinases↗

Inducible T cell antigen 4-1BB. Analysis of expression and function.

4-1BB is an inducible receptor-like protein expressed in both cytolytic and Th cells. Optimal induction of 4-1BB mRNA in T cells required both PMA and ionomycin stimulation, indicating that protein kinase C activation and increases in intracellular Ca2+ were required for its expression. 4-1BB was categorized as an early activation gene since the protein synthesis inhibitor, cycloheximide, blocked the induction of 4-1BB mRNA. A rat mAb, 53A2, was generated against recombinant soluble 4-1BB and was used to characterize this molecule. 4-1BB is a 30-kDa glycoprotein and appears to exist as both a monomer and a 55-kDa dimer on the cell surface of a T cell clone. The 4-1BB protein may be post-translationally modified since its predicted backbone is 25 kDa. FACS analysis indicated that 4-1BB was inducible and expressed on the cell surface of activated splenic T cells and thymocytes. Cross-linking of 4-1BB on anti-CD3-stimulated T cells with 53A2 resulted in a dramatic enhancement of T cell proliferation. This suggests that 4-1BB may function as an accessory signaling molecule during T cell activation.

Amino Acid Sequence↗

DNA damage and cell cycle regulation of ribonucleotide reductase.

Ribonucleotide reductase (RNR) catalyzes the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis. In addition to the well documented allosteric regulation, the synthesis of the enzyme is also tightly regulated at the level of transcription. mRNAs for both subunits are cell cycle regulated and inducible by DNA damage in all organisms examined, including E. coli, S. cerevisiae and H. sapiens. This DNA damage regulation is thought to provide a metabolic state that facilitates DNA replicational repair processes. S. cerevisiae also encodes a second large subunit gene, RNR3, that is expressed only in the presence of DNA damage. Genetic analysis of the DNA damage response in S. cerevisiae has shown that RNR expression is under both positive and negative control. Among mutants constitutive for RNR expression are the general transcriptional repression genes, SSN6 and TUP1. Mutations in POL1 and POL3 also activate RNR expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis. A protein kinase, Dun1, has been identified that controls inducibility of RNR1, RNR2 and RNR3 in response to DNA damage and replication blocks. This result suggests that the RNR genes in S. cerevisiae form a regulon that is coordinately regulated by protein phosphorylation in response to DNA damage.

Allosteric Regulation↗

Calcium permeability of nicotinic acetylcholine receptor channels in bovine adrenal chromaffin cells.

The fractional contribution of Ca to current flow through neuronal-type nicotinic acetylcholine receptor channels was determined by quantitative fluorescence microfluorimetry using fura-2. The method, which has been applied already to several types of cells and channels is described in detail here. At -70 mV and 2 mM external Ca concentration it was found that Ca contributes 2.5% to the net current. The fractional contribution was found to be voltage dependent, increasing at negative potentials e-fold for a 110 mV potential difference. Total non-specific cation current was found to have a bell-shaped dependence on external Ca concentration peaking at 2 mM.

Adrenal Glands↗

Effect of isoprenaline on I(f) current in latent pacemaker cells isolated from cat right atrium: ruptured vs. perforated patch whole-cell recording methods.

Whole-cell recording techniques were used to study the time-dependent inward current activated on hyperpolarization (I(f)) and its response to isoprenaline in latent atrial pacemaker cells isolated from cat right atrium. To determine whether the response to isoprenaline depended on the type of recording method, we analysed I(f) using either a standard ruptured-patch, or a nystatin-perforated-patch, whole-cell recording method. All cells beat rhythmically at 35 degrees C and exhibited normal pacemaker action potentials and I(f) current, regardless of the recording method. With the ruptured-patch method, pacemaker action potentials ceased activity within a few minutes and I(f) amplitude decreased "ran down" to 74% of control within 10 min of rupturing the patch. Isoprenaline (1 microM) elicited variable changes in I(f) amplitude among different latent pacemaker cells resulting in no net change in mean current amplitude (n = 6). In addition, isoprenaline failed to change the voltage dependence of the I(f) activation curve. On the other hand, using a nystatin-perforated-patch method, pacemaker action potentials and I(f) exhibited no significant changes over the same 10 min period. Under these conditions, isoprenaline consistently increased I(f) in all cells studied (+90%) at -80 mV; n = 8), and increased the spontaneous rate of pacemaker action potentials by 58 +/- 7% (n = 5). Moreover, isoprenaline elicited a significant positive shift (+11 mV) in the half-maximal activation voltage of the I(f) activation curve (n = 3). We conclude that latent atrial pacemakers consistently exhibit I(f) current, and that isoprenaline consistently elicits an increase in I(f) amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Long-term use of IgA-depleted intravenous immunoglobulin in immunodeficient subjects with anti-IgA antibodies.

The use of intravenous immunoglobulin is standard practice for antibody replacement in the humoral immunodeficiency diseases. Most infusions proceed uneventfully, but a proportion of infusions (5-8%) produces some degree of an infusion reaction. While the cause of most of these infusion reactions is unknown, an established, but rare cause of reactions is IgA antibodies in the serum of the patient, which apparently forms an immune complex with the traces of IgA in the infused immunoglobulin. This article describes our studies of five immunodeficient patients who had high-titered anti-IgA antibodies and a history of severe infusion reactions to intravenous immunoglobulin products not depleted of IgA (IgA content, 270-720 micrograms/ml). Over a 6-year period we gave these patients IgA-depleted intravenous immunoglobulin for a total of 170 infusions. These infusions were generally well tolerated; however, mild to moderate infusion reactions did occur in 9 of the 170 infusions (5.3%). These reactions were not related to the IgA content of the immunoglobulin solutions used--ascertained to vary between 0.4 and 2.9 micrograms/ml of IgA. Levels of plasma C3a and C4a increased after immunoglobulin infusions but the appearance of these components was not accompanied by any infusion reaction. We conclude that the long-term infusions of IgA-depleted intravenous immunoglobulin, within the range of IgA concentrations investigated, into patients with even very high-titered antibodies to IgA, is a safe practice.

Adolescent↗

Genotoxic effects of subacute treatments with wood dust extracts on the nasal epithelium of rats: assessment by the micronucleus and 32P-postlabelling.

Human exposure to wood dust has been epidemiologically linked to a number of enhanced incidences of various neoplasias, including those of the nose. Among different suspected woods, long-term exposure to the dust of beech (Fagus silvatica) is strongly associated with development of these tumors. Experimentally, it has been shown that a simple alcoholic extract of beech wood dust is mutagenic toward some bacteria and tumorigenic on mouse skin. For the present study, different groups of male Wistar rats were treated with aqueous, ethanol, or methanol extract of untreated beech wood dust via nasal drip at three concentrations for 48 h. Animals were killed 24 h after the last treatment and the nasal tissues were isolated to be examined for possible induction of micronuclei and DNA adducts. A clear dose-dependent increase in the number of micronuclei (P < 0.01) was observed after treatment of rats with each alcoholic extract of wood dust. In contrast, no DNA adducts could be detected with these extracts using the 32P-postlabelling technique. No increased number of micronucleated cells was found with solvents alone or with aqueous extract of dust. These data might support the early hypothesis that wood dust per se contains some in vivo genotoxic and thus possibly carcinogenic components extractable by an alcohol.

Animals↗