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J Wu

Publications and source records attributed to J Wu.

At least 1,063 records · Page 59Linked to original sources
PubMed1996

The role of programmed cell death as an emerging new concept for the pathogenesis of autoimmune diseases.

Activation-induced apoptosis is a primary mechanism for downmodulation of an immune response leading to immune homeostasis and deletion of T cells with specificities which may be harmful. These include deletion of T cells with self-specificities (autospecific) and excessively high affinity for foreign antigen which may lead to an excessively heightened immune response and septic shock. Surface molecules involved in activation-induced apoptosis involve Fas and Fas ligand (FasL), as well as the T-cell receptor (TCR) which modulates the expression and function of these molecules. Fas signaling mechanisms include the hematopoietic cell phosphatase (HCP) and sphingomyelinase, while TCR-signaling mechanisms include Nur77 and fyn kinase and unknown molecules that modulate expression of FasL. Apoptosis signals are further modulated by inhibitors or inducers of apoptosis including Bcl-2, p53, and interleukin-1 beta converting enzyme (ICE). Further understanding of the interaction of these molecules in autoimmune disease may lead to more specific therapies for immunosuppression tailored to the genetic or environmentally induced, activation-induced apoptosis defect in patients.

Animals↗
PubMed1996

Mechanism of Safening Action of Dymuron and Its Two Monomethyl Analogues against Bensulfuron-methyl Injury to Rice (Oryza sativa)

The comparative efficacy and mechanism of action of the herbicide dymuron and its two optically active monomethyl analogues, (R)-1-(alpha-methylbenzyl)-3-(p-tolylurea) (R-MBTU) and S-MBTU, as safeners of rice against injury from bensulfuron-methyl were investigated. Bioassays using etiolated seedlings of rice (Oryza sativa L., cv. Lemont), grown either in agar or in liquid media containing bensulfuron-methyl, showed that this sulfonylurea herbicide is a potent inhibitor of rice root growth (I50 = 120 nM). Similar studies with the herbicide dymuron and its two optically active monomethyl analogues (R-MTBU and S-MTBU) showed that at 10 μM, dymuron and R-MBTU reduced rice root length by 25 and 17%, respectively, whereas S-MBTU had no effect on root growth of Lemont rice. Combined treatments with bensulfuron-methyl and dymuron or each of its two analogues confirmed that S-MTBU is an excellent safener of rice against bensulfuron-methyl, far more effective than either dymuron or R-MTBU. The protective action of S-MTBU appeared to result mainly from a drastic reduction in the uptake of bensulfuron-methyl by safened rice seedlings. Dymuron and R-MTBU reduced also the uptake of bensulfuron-methyl by rice seedlings, but to a lesser extent than S-MTBU. Quantitative changes in the metabolism of bensulfuron-methyl by safened rice seedlings were also observed, but did not appear to support the involvement of enhanced herbicide metabolism in the safening action of S-MBTU, R-MBTU, and dymuron. The major metabolites of bensulfuron-methyl detected in both safened and unsafened rice seedlings were tentatively identified as methyl-(4-hydroxy-6-methoxypyrimidin-2-yl-carbamoylsulfamoyl)-o-toluate; methyl-(aminosulfonyl)-o-toluate; and 1H-2,3-benzothiazin-4-(3H)-one-2,2-dioxide.

Journal Article↗
PubMed1996

Site-directed mutagenesis of the CP 47 protein of photosystem II: 167W in the lumenally exposed loop C is required for photosystem II assembly and stability.

The intrinsic chlorophyll-protein CP 47 is a component of photosystem II which functions in both light-harvesting and oxygen evolution. Using site-directed mutagenesis we have produced the mutant W167S which lies in loop C of CP 47. This strain exhibited a 75% loss in oxygen evolution activity and grew extremely slowly in the absence of glucose. Examination of normalized oxygen evolution traces indicated that the mutant was susceptible to photoinactivation. Analysis of the variable fluorescence yield indicated that the mutant accumulated very few functional PS II reaction centers. This was confirmed by immunoblotting experiments. Interestingly, when W167S was grown in the presence of 20 microM DCMU, the mutant continued to exhibit these defects. These results indicate that tryptophan 167 in loop C of CP 47 is important for the assembly and stability of the PS II reaction center.

Cyanobacteria↗
PubMed1996

Site-directed mutagenesis of the CP 47 protein of photosystem II: alteration of conserved charged residues which lie within lethal deletions of the large extrinsic loop E.

The intrinsic chlorophyll-protein CP 47 is a component of photosystem II which functions in both light-harvesting and oxygen evolution. The large extrinsic loop E of this protein has been shown to interact with the oxygen-evolving site. Previously, Vermaas and coworkers have produced a number of deletions within loop E which yielded mutants which were unable to grow photoautotrophically and which could not evolve oxygen at normal rates. During the course of our site-directed mutagenesis program in Synechocystis 6803, we have altered all of the conserved charged residues which were present within six of these deletions. All ten of these mutants were photoautotrophic and evolved oxygen at normal rates. We speculate that the severe phenotypes of the deletion mutants observed by Vermaas and coworkers is due to large structural perturbations in the extrinsic loop E of CP 47.

Cyanobacteria↗
PubMed1996

The A alpha mating-type locus of Schizophyllum commune: structure and function of gene X.

Gene X maps immediately right of gene Y at the A alpha mating-type locus in Schizophyllum commune. Alleles X1, X3 and X4 were isolated, subcloned, and sequenced. The structure of the alleles and their relationship to the A alpha locus is described. The deduced X isoforms possess no recognized motifs common to other polypeptides and no significant similarity to any sequences in the protein data-bases. X alleles do not activate A-regulated development when transformed into recipient strains possessing different A alpha mating types or when these transformants are mated with tester strains. An X1-disrupted construction yielded a high frequency (33%) of homologous gene replacements. X-disrupted mutants have wild-type phenotypes and mate normally. Both the functional analyses and sequence data for X1, X3, and X4 suggest that the right boundary of the A alpha mating-type locus falls between A alpha Y and X. We propose that the Z and Y genes constitute the A alpha locus in its entirety.

Alleles↗
PubMed1996

Morin hydrate inhibits azo-initiator induced oxidation of human low density lipoprotein.

We demonstrated that the flavonoid morin hydrate at 75-100 microM protects against the oxidation of low density lipoprotein (LDL) by free radicals produced by 2,2'-azo-bis(2-amidinopropane) dihydrochloride. Morin hydrate reduces the relative electrophoretic mobility, malondialdehyde equivalents and lipid peroxide level of oxidized LDL. On the other hand, Trolox (an analogue of vitamin E) showed less protective effect in the present system. Since free radical mediated oxidation of LDL is implicated to be a cause of atherogenesis, morin hydrate may be a candidate chemotherapeutic agent herein.

Amidines↗
PubMed1996

Bradykinin and nitric oxide in infectious disease and cancer.

Vascular pathophysiology at the sites of bacterial infection and cancerous tissues share numerous common events similar to inflammatory tissue. Among them enhanced vascular permeability is the universal and hallmark event mediated by bradykinin. All 16 or more bacterial or fungal proteases we have examined activated one or more steps of the kinin generating Hageman-factor-kallikrein cascade. In the meantime, most of the microbial proteases rapidly inactivated various plasma inhibitors such as alpha 1-protease inhibitor and alpha 2-macroglobulin. In addition to the extracellular proteases, bacterial cell wall components (negatively charged LPS) of gram-negative bacteria and teichoic acid moieties of gram-positive bacteria activate the Hageman-factor-kallikrein system and exert hypotensive effects via kinin generation. Endotoxin (LPS) also induces nitric oxide synthase (NOS) which appears to exhibit a rather slow, but significant, effect in relaxing the vascular tone of the infected animal (thus hypotension). Furthermore, bacterial proteases can activate the matrix metalloproteinase (collagenase) resulting in exacerbation of tissue injury in the diseased animal. Many tumor cells or tissues excrete plasminogen activator, and hence activate plasminogen. The plasmin thus generated activates procollagenases, as well as the Hageman-factor-kallikrein system, resulting in pronounced extravasation. Fluid accumulation in pleural and ascitic carcinomatoses is largely due to the activated bradykinin-generating system. We can also demonstrate and control enhanced vascular permeability using kallikrein inhibitors, especially the polymer-conjugated soybean trypsin inhibitor which exhibits a prolonged plasma t1/2, kinin antagonists, NOS inhibitors, NO scavengers, inhibitors of prostaglandins and others. Bacterial proteases induce shock in mice which can be prevented by the soybean trypsin inhibitor by blocking the kallikrein-kinin cascade. Therapeutic use of kinin antagonists and a kallikrein inhibitor has been made for infectious diseases such as septicemia and in tumor pathology.

Animals↗
PubMed1996

The effects of hormone replacement therapy on plasma vitamin E levels in post-menopausal women.

OBJECTIVE: To measure vitamin E levels in post-menopausal women before and after HRT, compared with levels in premenopausal women. DESIGN: Post-menopausal women (n = 21) had plasma vitamin E levels measured before treatment and after 6 and 12 months treatment with HRT (2 mg 17-beta-oestradiol and 1 mg norethisterone acetate). The pre-menopausal group (n = 20) had plasma vitamin E levels measured at day 15-18 of the menstrual cycle. RESULTS: There was no significant difference in vitamin E levels between the pre-menopausal group and the post-menopausal group. Plasma vitamin E levels were not significantly altered by 12 months HRT. CONCLUSION: Post-menopausal women did not have altered levels of vitamin E compared with pre-menopausal women. Similarly HRT has no effect on plasma vitamin E levels. We conclude therefore that HRT does not reduce vitamin E levels in a similar manner to oral contraceptives and consequently post-menopausal women are unlikely to need a vitamin E supplement.

Adult↗
PubMed1996

Prolongation of survival of alloskin grafts with no concurrent general suppression of the burned patient's immune system: a preliminary clinical investigation.

The adequate management of burns is the requisite to save the patient's life, to prevent the onset of secondary infections and to obtain healing with acceptable cosmetic results. Previous data have shown that the use of alloskin grafts in the acute phase of burns yields the best clinical results. Unfortunately, this approach is curbed by the patient's immune response which induces the rejection of the allografts. In this report we endeavoured to solve this problem by ways that would not imply the general suppression of the patient's immune system. Thus, we can now report that a longer survival of alloskin grafts can be induced in situ by pretreating the alloskin samples to be grafted with both an anti-beta 2-microglobulin monoclonal antibody (beta 2mAb) and irradiation with ultraviolet-C light (UVC). The advantage of our novel approach is that it does not need any concomitant administration of immunosuppressive agent(s) to the burned patients. In this study, we followed five severely burned patients grafted with alloskin samples pretreated with either beta 2mAb or beta 2mAb plus UVC irradiation. In comparison with untreated alloskin samples from the same source grafted in parallel, the mean survival time (MST) of the beta 2mAb-pretreated alloskin specimens increased by 35 per cent (i.e. from 18.3 +/- 3.2 days to 24.7 +/- 5.5 days) in three patients. Moreover, the MST of the alloskin grafts pretreated with both beta 2mAb and UVC irradiation was lengthened by 100 per cent (i.e. from 18.5 +/- 4.5 days to 37.0 +/- 8.0 days) in the remaining two patients. These preliminary results lend credence to the view that local immune suppression could be achieved in situ by our approach via: (1) the impairment of the proper functions of the HLA-class I antigen by the bound beta 2mAb; and (2) the inhibition of immune reactions taking place inside the alloskin grafts by some immunosuppressive signal(s) generated by the UVC-pretreated alloepidermal cells. Hence, our approach stands as an exciting and useful alternative to the otherwise well-known, deleterious general suppression of the burned patient's immune system.

Adolescent↗
PubMed1996

Effects of zolpidem on local cerebral glucose metabolism during non-REM sleep in normal volunteers: a positron emission tomography study.

Using positron emission tomography with fluorodeoxyglucose (18FDG or FDG), we compared the effects of zolpidem (10 mg), an imidazopyridine hypnotic, which is relatively selective for the BZ1 or omega receptor and placebo on cerebral glucose metabolism during the first non-REM sleep period of 12 young normal volunteers. Plasma zolpidem pharmacokinetics varied considerably among subjects, and plasma concentrations were lower than usually reported. In general, the effects of zolpidem on local cerebral glucose metabolism varied directly with plasma concentrations of zolpidem. Zolpidem induced changes in local cerebral glucose metabolism were unevenly distributed throughout the brain and were greater in subcortical areas than lateral cortical areas. Significant negative correlations were found between change in local absolute glucose metabolic rate (calculated by subtracting individual data on placebo nights from that on zolpidem nights) and plasma concentration of zolpidem for the following areas: medial frontal cortex, cingulate gyrus, putamen, thalamus, and hippocampus. The effects of zolpidem on local cerebral glucose metabolism were partially but not closely related to the reported density of BZ1 receptors.

Adult↗
PubMed1996

Abnormality in the early signal transduction pathway is responsible for the impaired proliferative response and low K+ current in a T-cell clone by stimulation with anti-CD3 antibody.

Two T-cell clones were established from young and old C57BL/6 mice, respectively. The proliferative response to anti-CD3 stimulation was significantly greater in the young (YT5) than in the old (OT13) T cell clone. However, a similar high response was observed in both T-cell clones upon stimulation with phorbol myristate acetate (PMA) and ionomycin (INM). The calcium-dependent K+ current (IK(Ca)) was recorded with the patch-clamp method in these T-cell clones. With anti-CD3 stimulation, the amplitude of the outward K+ current was significantly lower in OT13 than in YT5 cells. With stimulation with PMA and INM, however, no significant difference in IK(Ca) was obtained between the two types of cells. The level of proliferative response of T-cells to mitogens was well reflected by the amplitude of IK(Ca). Some abnormality in the early pathway of signal transduction, which led to the intracellular Ca2+ influx, appears to be responsible for the impaired proliferation of the old T-cell clone.

Aging↗
PubMed1996

Cerebral metabolic activity correlates of subsyndromes in chronic schizophrenia.

Seventy-nine patients with schizophrenia and 47 healthy controls received positron-emission tomography (PET) with 18F-2-deoxyglucose uptake while executing the Continuous Performance Test (CPT). Patients had been off all psychoactive medication for at least four weeks. Patients' symptoms were assessed with the Brief Psychiatric Rating Scale and factor scale scores were obtained. These scores were used in cluster analysis to identify patients with predominantly delusional, negative, disorganized, and remitted symptoms. To address the interconnective nature of cerebral functioning, regions of interest were defined on the basis of the results of a factor analysis of metabolic rate in selected brain regions. This procedure identified six cortical and eight subcortical region of interest factors. Metabolic rate factor scale scores were compared between the patients' clusters and the healthy controls. The delusional cluster showed a significantly reduced hippocampal activity, while the negative symptoms cluster presented with a prominent hypofrontality and significantly increased left temporal cortex values. Concurrently, both clusters were associated with a decreased activity on the factor 'anterior cingulum and medial frontal gyrus'. The disorganized cluster was characterized by a significant overactivity in the parietal cortex and motor strip and a decreased activity in the corpus callosum. The subsyndromes of chronic schizophrenia are therefore characterized by deviant patterns of cerebral activity rather than deficits in a single location.

Adult↗
PubMed1996

A quasi-one-dimensional theory for anisotropic propagation of excitation in cardiac muscle.

It has been shown that propagation of excitation in cardiac muscle is anisotropic. Compared to propagation at right angles to the long axes of the fibers, propagation along the long axis is faster, the extracellular action potential (AP) is larger in amplitude, and the intracellular AP has a lower maximum rate of depolarization, a larger time constant of the foot, and a lower peak amplitude. These observations are contrary to the predictions of classical one-dimensional (1-D) cable theory and, thus far, no satisfactory theory for them has been reported. As an alternative description of propagation in cardiac muscle, this study provides a quasi-1-D theory that includes a simplified description of the effects of action currents in extracellular space as well as resistive coupling between surface and deeper fibers in cardiac muscle. In terms of classical 1-D theory, this quasi-1-D theory reveals that the anisotropies in the wave form of the AP arise from modifications in the effective membrane ionic current and capacitance. The theory also shows that it is propagation in the longitudinal, not in the transverse direction that deviates from classical 1-D cable theory.

Action Potentials↗
PubMed1996

Detection of dysplasia at colonoscopy using laser-induced fluorescence: a blinded study.

BACKGROUND: Laser-induced fluorescence spectroscopy has the potential to detect colonic dysplasia in vivo. However, previous studies have limited their analyses to multivariate regression techniques and unblinded retrospective evaluation. The purpose of this study was to develop a probability-based algorithm to detect colonic dysplasia using laser-induced fluorescence spectroscopy and to evaluate it in a blinded manner. METHODS: Fluorescence spectra were collected from normal mucosa and colonic polyps during colonoscopy using 370 nm excitation. Tissue was classified as normal, hyperplastic, or adenomatous by histologic examination. Preliminary data was used to devise an algorithm to differentiate tissue type based on probability distributions of the fluorescence intensity at 460 nm and the ratio of the intensity at 680 nm to that at 600 nm. The algorithm was then tested in a blinded fashion. RESULTS: The algorithm correctly determined the tissue type in 88% of cases, equal to the agreement of independent pathologists. Sensitivity, specificity, and positive predictive value for the detection of dysplasia was 90%, 95%, and 90%, respectively. CONCLUSIONS: Dysplasia was detected in vivo using fluorescence spectroscopy and a probability-based algorithm. This method may form the basis for a new surveillance technique for patients with increased risk for dysplastic transformation.

Adenomatous Polyps↗
PubMed1996

Validation of a new computer program for Minnesota coding.

The Minnesota code (MC) is a classification system for electrocardiograms (ECGs) that is used for ECG coding in epidemiologic studies. As the MC measurement procedures and rules are complex, visual coding is time-consuming and error-prone. Automation should reduce measurement and coding errors. The authors developed an MC program, closely adhering to the MC regulations. To validate the program, a test set of 300 ECGs containing a wide variety of codable patterns was collected. The ECGs were coded independently by the program and by an experienced human reader. A reference code ("truth") was established by resolving disagreements through a consensus procedure. If the computer and human agreed, they were considered to be correct. Sensitivity and specificity were computed for each of the nine main code categories of the MC, both for the computer and for visual coding. The results show that the program is as good as or better than the human reader for sensitivity and specificity of all MC categories. Particularly noteworthy is the good program performance for arrhythmia coding. Most coding differences between the program and truth arise from small, borderline measurement differences in combination with the all-or-none character of the coding criteria. In conclusion, computerized Minnesota coding is a valuable alternative or supplement to visual coding.

Arrhythmias, Cardiac↗
PubMed1996

Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation.

T cell antigen receptor (TCR) stimulation induces tyrosine phosphorylation of many intracellular proteins, including the proto-oncogene Vav, which is expressed exclusively in hematopoietic and trophoblast cells. Vav is critical for lymphocyte development and activation. Overexpression of Vav in Jurkat T cells leads to potentiation of TCR-mediated IL-2 gene activation. However, the biochemical function of Vav is unknown. Here, we demonstrate that the major induced tyrosine phosphoprotein associated with Vav is the hematopoietic cell-specific SLP-76. The Vav SH2 domain is required for this interaction and for TCR-mediated Vav tyrosine phosphorylation. Similar to Vav, overexpression of SLP-76 markedly potentiates TCR-mediated NF-AT and IL-2 gene activation. Furthermore, overexpression of both Vav and SLP-76 synergistically induces basal and TCR-stimulated NF-AT activation. These results suggest that a signaling complex containing Vav and SLP-76 plays an important role in lymphocyte activation.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Regulation of L-DOPA biosynthesis by site-specific phosphorylation of tyrosine hydroxylase in AtT-20 cells expressing wild-type and serine 40-substituted enzyme.

De novo L-DOPA biosynthesis was studied in stably transfected AtT-20 cells expressing wild-type- or [Leu40]-recombinant tyrosine hydroxylase (rTH). Basal rates of DOPA accumulation were much higher by cells expressing rTH in which Leu was substituted for Ser4O (S40L-rTH) than by those expressing wild-type rTH (WT-rTH). Treatment of WT-rTH cells with forskolin produced an increase in DOPA accumulation and a concomitant increase in WT-rTH phospho-Ser40 content, whereas DOPA production by cells expressing S40L-rTH was entirely unaffected by forskolin. After forskolin treatment of 32Pi-prelabeled cells, WT-rTH was phosphorylated at Ser8, Ser19, Ser31, and Ser40, whereas 32P incorporation into S40L-rTH was restricted to Ser8, Ser19, and Ser31. Relatively prolonged treatment of AtT-20 cells expressing WT-rTH with either a depolarizing agent (elevated potassium) or a phosphatase inhibitor (okadaic acid) increased DOPA production and increased the phosphorylation state of Ser40; but, unlike forskolin, these treatments also increased DOPA production by cells expressing S40L-rTH. Thus, the present studies demonstrate that Ser40 phosphorylation mediates forskolin-induced increases in DOPA biosynthesis directly but that mechanisms other than Ser40 phosphorylation can mediate the increases in DOPA biosynthesis produced either by depolarization or by protein phosphatase inhibition.

Animals↗