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N Yu

Publications and source records attributed to N Yu.

At least 55 records · Page 3Linked to original sources
PubMed1998

Inflammatory cytokines: putative regulators of neuronal and neuro-endocrine function.

The cytokines are a large and diverse family of polypeptide regulators with multiple regulatory functions that have been comprehensively evaluated in the immune system under strictly controlled experimental conditions. These peptide signals exhibit often unpredictable interactions when evaluated for their pathophysiological involvement in specific inflammatory conditions in vivo. In our joint efforts to understand the basis for early pathophysiological changes in the brains of HIV-infected subjects, we have developed animal models for lentivirus infections, and assessed the actions of various cytokines acutely on transmitter release properties in vitro, and in an in vivo transgenic mouse model. IL1beta, IL2, IL6, and IFNalpha will each enhance the release of AVP in slices of rat hypothalamus and amygdala. TGFbeta selectively blocks the ability of ACh to release AVP from hypothalamus or amygdala, but has no effects on the release stimulated by other cytokines. IFNalpha, but not TGFbeta will also activate CRH release; as with AVP, TGF selectively blocks the ACh-stimulated CRH release in both amygdala and hypothalamus. The IFNalpha-stimulated release of AVP and CRH appears to be mediated by cyclic GMP production, and this release by IFNalpha and IL-2 may be mediated in part by activation of constitutive nitric oxide synthase. These combined in vitro actions would suggest that cns cytokine actions should upregulate the hypothalamic pituitary adrenal axis. In a transgenic mouse model with increased astrocytic expression and release of the cytokine IL6, the HPA axis is upregulated, but the effect seems attributable to adrenocortical hypersensitization to ACTH. Lastly, in studies of cytokine mediated effects on astrocytic uptake of the excitatory transmitter glutamate, the reactive oxygen species hydrogen peroxide and peroxynitrite, but not nitric oxide, inhibited glutamate uptake in a concentration-dependent manner. Although superoxide and nitric oxide had no effect by themselves on the rate of glutamate uptake by astrocytes, the same cultures did respond to nitric oxide with a sustained increase in cytoplasmic free calcium. Thus while reactive oxygen species do provide a potential path to neurotoxicity but one apparently not involving nitric oxide. These various data provide important opportunities for early therapeutic interventions in neuro-inflammatory states such as Neuro-AIDS.

Animals↗
PubMed1998

Typing of HLA-B*15 alleles using sequence-specific primers.

We have developed a DNA based typing method to detect 38 known B*15 alleles using sequence-specific primers (PCR-SSP). This method involves 38 primers and 39 PCR-SSP reactions with results that can be obtained in 3 hours. The method is easy, fast and suitable for clinical typing for bone marrow and organ transplantation. We have typed 106 HLA-B15 samples using this method. For homozygous HLA-B15 samples, some B*15 allele combinations need to be resolved by additional PCR reactions not included in this article. The method allows the detection of potential new alleles requiring sequencing for confirmation, and it is useful to resolve unusual serological reaction patterns for different HLA-B15 serological specificities. In addition, it could be used to resolve ambiguous PCR-SSOP typing results and for recognition of mismatches in serologically matched unrelated individuals.

Alleles↗
PubMed1998

Neurotoxic effects of feline immunodeficiency virus, FIV-PPR.

FIV is a lentivirus of domestic cats that causes neurologic disorders which are remarkably similar to those found in HIV-1 infected people. Using feline neuron cultures, we investigated the potential of both FIV virus and FIV-Env protein to cause neuronal damage through the excitotoxicity mechanism. The neuron swelling and lactate dehydrogenase (LDH) release assays were used as measures of cellular damage. The effects of FIV Env protein on glutamate receptor mediated increases in intracellular calcium were also examined. We found that FIV virus and FIV-Env protein significantly increased LDH release from the neuron cultures. Additionally, an increase in neuron size was detected in the cultures exposed to the virus, while swelling did not occur with exposure to either saline, denatured virus, or FIV-Env by itself. However, when both 20 microM glutamate and the FIV-PPR Env protein were added to the culture, a significant increase in neuron cell size was observed. The NMDA calcium signals were similar in general form between the control and FIV-PPR Env exposed cultures. However, the FIV - PPR Env protein treated cultures resulted in significant enhancement of the NMDA induced calcium signal. Our results indicate that FIV Env protein (either within the virion or baculovirus expressed) induced neurotoxicity as measured by neuron swelling and LDH release assays and that exposure of feline neurons to FIV Env protein alters the handling of intracellular calcium. These findings help to validate the FIV/cat system as a potential animal model for evaluating therapeutic approaches that target the excitotoxicity mechanisms of lentivirus induced CNS disease.

Acquired Immunodeficiency Syndrome↗
PubMed1998

[Abnormal augmentation of the evoked potential and morphological changes of guinea pig cochlea induced by cisplatin].

OBJECTIVE: To investigate the characteristic of cochlear microphone(CM), summating potential(SP), compound action potential(CAP) and the morphological changes of hair cells after selective damage to the inner ear by acute cochlear perfusion of cisplatin. METHODS: Dynamic changes of CM, -SP and CAP were recorded by glass electrode from the third turn of the scala media guinea pig's cochlea before and during cisplatin perfusion of the whole cochlea for 2 hours. RESULTS: It indicated that after one hour of the perfusion, the amplitude of CM, -SP and CAP decreased at stimulation intensity < or = 60 dB SPL, while the amplitude increased at stimulation intensity > or = 70 dB SPL, as compared with those before perfusion (the average of CM increased by 3.6 mV at 90 dB SPL, average of -SP increased by 1.6 mV at 120 dB SPL, average of CAP increased by 0.23 mV at 90 dB SPL). After two hours of perfusion, the amplitude of CM, -SP and CAP decreased in all the stimulation intensity. The succinic dehydrgenase (SDH) staining was decreased in OHCs, while that of IHC's remained normal. Transmission electron microscopic examination of organ of Corti showed morphological changes in OHCs, such as disappearance of nuclear chromosome, denature and reduction number, mitochondria while the structure of IHCs remained normal. CONCLUSION: The abnormal augmentation phenomenon of CM and -SP may be due to the abnormal modulation of Ca2+ in IHCs and OHCs. The abnormal augmentation of CAP suggests that the suppression effects of OHCs and efferent neurotransmitter on IHCs and afferent neurotransmitter may be reduced after OHCs damage.

Action Potentials↗
PubMed1997

Mutation in the mismatch repair gene Msh6 causes cancer susceptibility.

Mice carrying a null mutation in the mismatch repair gene Msh6 were generated by gene targeting. Cells that were homozygous for the mutation did not produce any detectable MSH6 protein, and extracts prepared from these cells were defective for repair of single nucleotide mismatches. Repair of 1, 2, and 4 nucleotide insertion/deletion mismatches was unaffected. Mice that were homozygous for the mutation had a reduced life span. The mice developed a spectrum of tumors, the most predominant of which were gastrointestinal tumors and B- as well as T-cell lymphomas. The tumors did not show any microsatellite instability. We conclude that MSH6 mutations, like those in some other members of the family of mismatch repair genes, lead to cancer susceptibility, and germline mutations in this gene may be associated with a cancer predisposition syndrome that does not show microsatellite instability.

Adenomatous Polyposis Coli Protein↗
PubMed1997

Paul-Straubel-Kingdon trap for true zero-point confinement of an individual ion and reservoir.

A modification of the Paul-Straubel trap previously described by us may profitably be operated in a Paul-Straubel-Kingdon (PSK) mode during the initial loading of an individual ion into the trap. Thereby the coating of the trap ring electrode by the atomic beam directed upon it in earlier experiments is eliminated, as is the ionization of an already trapped ion. Coating created serious problems as it spot-wise changed the work function of the ring electrode, which caused large, uncontrolled dc fields in the trap center that prevented zero-point confinement. Operating the Paul-Straubel trap with a small negative bias on the ring electrode wire is all that is required to realize the PSK mode. In this mode the tiny ring trap in the center of the long, straight wire section is surrounded by a second trapping well shaped like a long, thin-walled cylindrical shell and extending to the end-caps. There, ions may be conveniently created in this well without danger of coating the ring with barium. In addition, the long second well is useful as a multi-ion reservoir.

Journal Article↗
PubMed1997

Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases.

The neuregulins (NRGs) are a family of multipotent epidermal-growth-factor-like (EGF-like) factors that arise from splice variants of a single gene. They influence the growth, differentiation, survival and fate of several cell types. We have now discovered a set of new neuregulin-like growth factors, which we call neuregulin-2 (NRG-2): these are encoded by their own gene and exhibit a distinct expression pattern in adult brain and developing heart. Like NRG-1, the EGF-like domain of the new ligands binds to both the ErbB3- and ErbB4-receptor tyrosine kinases. However, NRG-2 stimulates different ErbB-receptor tyrosine-phosphorylation profiles from NRG-1. Our results indicate that NRG-1 and NRG-2 mediate distinct biological processes by acting at different sites in tissues and eliciting different biochemical responses in cells.

Amino Acid Sequence↗
PubMed1997

SecE-depleted membranes of Escherichia coli are active. SecE is not obligatorily required for the in vitro translocation of certain protein precursors.

Membrane vesicles were prepared from Escherichia coli cells in which SecE was depleted to 2% of wild-type membranes. SecE depletion had pleiotropic effects; SecD, SecF, SecG, and SecY were decreased 4-6-fold, whereas SecA was increased about 16-fold over that of wild-type membranes. These membranes were substantially active in the in vitro translocation of proOmpA, which was mediated by the SecA pathway since it was inhibited by azide. Similar substantial translocation activities were observed for proLamB and proLpp in the SecE-depleted membranes. However, the translocation of proPhoA was more severely impaired. These data indicate that SecE may enhance but is not obligatorily required for the translocation of at least certain precursors, and suggest that the effects of the SecE depletion on protein translocation may be precursor-dependent.

Adenosine Triphosphatases↗
PubMed1997

Accurate typing of HLA-A antigens and analysis of serological deficiencies.

We are reporting the results of HLA-A typing by PCR-SSOP complemented by PCR-SSP of samples obtained from the National Marrow Donor Program (NMDP). These samples were a representative group from 2486 tested in duplicate by serology. A total of 390 samples gave HLA-A discrepant results. Comparing the molecular typing results of 238 samples (samples with available DNA) with the serological typing results, 54 homozygotes and 184 heterozygotes produced a total of 422 assignments by molecular methods. We found assignment discrepancies in 147/422 (35%) in laboratory 1 and 144/422 (34%) in laboratory 2 (a combined group of 4 NMDP laboratories; laboratory 1 is not included). The serological discrepancies found were of 3 categories: a) false negatives, b) incomplete typing (discrepancies due to the level of resolution within a cross-reactive or CREG group) and c) false positives. Major problems were identified using serology for typing HLA-A antigens: a) inability to identify all WHO-recognized specificities, more frequently in non-Caucasians or in HLA-A specificities known to be found more frequently in non-Caucasians for laboratory 1 and incorrect assignments of A19 specificities in laboratory 2, b) incorrect assignments in cells with poor viability and c) false-positive assignments in homozygotes. We propose a possible strategy to type HLA-A specificities with two steps: a) a minimum of serology for typing specificities for common CREG groups: A1, A2, A3, A11, A9, A10, A28, A19. However, a given laboratory can determine the level of serological assignments needed as a first step. And b) molecular methods to identify splits: A23, A24, A29, A30, A31, A32, A33, A34, A36, A66, A74 and A80. The technique described is useful for large-scale bone marrow donor typings for cells with poor viability, and for resolving ambiguous results including false-positive assignments of homozygous cells.

DNA↗
PubMed1997

Error rate for HLA-B antigen assignment by serology: implications for proficiency testing and utilization of DNA-based typing methods.

Until recently, the majority of HLA class I typing has been performed by serology. Expensive commercial typing trays are frequently used for testing non-Caucasian subjects and new strategies using DNA-based methods have been adopted for improving clinical histocompatibility testing results and adapted as supplements in proficiency testing. A double-blind comparison of the typing of HLA-B specificities in 40 samples was carried out between serology and two polymerase chain reaction (PCR) methods, PCR amplification with sequence-specific primers (PCR-SSP) and PCR amplification and subsequent hybridization with sequence-specific oligonucleotide probes (PCR-SSOP). The results demonstrated 22.5% misassignments of HLA-B antigens by serology. There was complete concordance between the results obtained with the two PCR based typing methods. A second panel of 20 donor samples with incomplete or ambiguous serologic results was analyzed by PCR-SSP and SSOP Both PCR methods identified correctly the HLA-B antigens. Our results suggest that more accurate typing results can be achieved by complementing serologic testing with DNA-based typing techniques. The level of resolution for HLA-B antigen assignment can be obtained by this combination of serology and limited DNA-based typing is equivalent to the HLA-B specificities defined by the WHO-HLA Committee. This level of resolution cannot routinely be achieved in clinical histocompatibility testing or in proficiency testing using serologic reagents only.

DNA↗
PubMed1997

Inhibition of astrocyte glutamate uptake by reactive oxygen species: role of antioxidant enzymes.

BACKGROUND: The recent literature suggests that free radicals and reactive oxygen species may account for many pathologies, including those of the nervous system. MATERIALS AND METHODS: The influence of various reactive oxygen species on the rate of glutamate uptake by astrocytes was investigated on monolayers of primary cultures of mouse cortical astrocytes. RESULTS: Hydrogen peroxide and peroxynitrite inhibited glutamate uptake in a concentration-dependent manner. Addition of copper ions and ascorbate increased the potency and the efficacy of the hydrogen peroxide effect, supporting the potential neurotoxicity of the hydroxyl radical. The free radical scavenger dimethylthiourea effectively eliminated the inhibitory potential of a mixture containing hydrogen peroxide, copper sulphate, and ascorbate on the rate of glutamate transport into astrocytes. The inhibitory effect of hydrogen peroxide on glutamate uptake was not altered by the inhibition of glutathione peroxidase, whereas the inhibition of catalase by sodium azide clearly potentiated this effect. Superoxide and nitric oxide had no effect by themselves on the rate of glutamate uptake by astrocytes. The absence of an effect of nitric oxide is not due to an inability of astrocytes to respond to this substance, since the same cultures did respond to nitric oxide with a sustained increase in cytoplasmic free calcium. CONCLUSION: These results confirm that reactive oxygen species have a potential neurotoxicity by means of impairing glutamate transport into astrocytes, and they suggest that preventing the accumulation of hydrogen peroxide in the extracellular space of the brain, especially during conditions that favor hydroxyl radical formation, could be therapeutic.

Animals↗
PubMed1997

[Total hip replacement in patients with steroid-induced femoral head necrosis].

In order to evaluate the long-term effect of total hip replacement (THR) in patients with steroid-induced femoral head necrosis, 40 cases of 50 hips received THR patients were followed up for an average of 8.5 years after operation. Evaluation was carried act according to Harris score system. In these cases, average score was seventy-five points. Revision rate among them was 2% after four years and 18% after five to eight and a half years, with as overall rate of 20%. It was found that the main reason for revision was looseness of the prosthesis. In this follow-up, it showed that besides foreigen body reaction, abnormal osseous remodelling was the main factor in long-term failure of this arthroplasty. It was also proved that it was a good selection to perform cemented total hip replacement in younger patients, which could improve living quality.

Adult↗
PubMed1996

Signaling through CD38 augments B cell antigen receptor (BCR) responses and is dependent on BCR expression.

mAbs directed against the ectoenzyme CD38 will induce B cell proliferation in normal resting B lymphocytes, but cannot induce proliferation in B cells that are unresponsive to B cell Ag receptor (BCR) cross-linking. Using the CD38- murine B cell line A20 we have examined the relationship between CD38- and BCR-mediated signaling after transfection of wild-type or mutant CD38 molecules. Although association between CD38 and the BCR was not detectable, co-cross-linking of CD38 and the BCR gave rise to a synergistic response, and expression of CD38 lowered the threshold for BCR-induced responses. Generation of Ig loss variant clones established that coexpression of the BCR was required for CD38-mediated signal transduction. The cytoplasmic tail of Ig alpha or Ig beta rescued CD 38 responsiveness in the CD38+Ig- cells provided that the chimeric molecules were coligated with CD38. Separate experiments indicated that the cytoplasmic tail of CD38 is not required for CD38 signaling. The anti-CD38-induced response was dependent on the influx of extracellular calcium but was not accompanied by detectable tyrosine phosphorylation of any cellular proteins. Together, these data demonstrate that the CD38 molecule can influence BCR-induced responses and that CD38 signaling is dependent on the BCR complex, perhaps to utilize a functional cytoplasmic tail(s) for intracellular signaling.

ADP-ribosyl Cyclase↗
PubMed1996

Excitation transfer spectroscopy with two metastable 138Ba+ ions in same trap.

In the absence of lasers approaching trapped ion clock transitions in sharpness we propose to replace the 12.49 m laser field exciting the D3/2-D5/2 transition of the single Ba+ ion A in D3/2 with the near-field of a close by identical ion B in the excited D5/2 state. We tune the frequency of the near-field by the differential Stark shift generated when the center of mass of the tuned ions is slightly moved out of the trap center by a small bias voltage. We demonstrate that the resultant resonant energy exchange can be made considerably faster than the natural lifetime of either metastable level and show how it might be detected.

Journal Article↗
PubMed1995

Tamoxifen with and without radiation after partial mastectomy in patients with involved nodes.

PURPOSE: To determine the effect of tamoxifen on local control after partial mastectomy with and without adjuvant breast irradiation. METHODS AND MATERIALS: A retrospective study of 97 node positive patients identified from the records of the London Regional Cancer Center included 44 patients who received tamoxifen and breast irradiation (40 or 50 Gy plus booster dose) after partial mastectomy, and 53 patients who received tamoxifen only after partial mastectomy. Base line characteristics of the two groups were similar. RESULTS: At 39 months actuarial follow-up there was a breast tumor recurrence (BTR) in 5% vs. 21% of patients when radiation was omitted (p = 0.0388), but there was no difference in the cause-specific mortality of the two treatment groups. Cox Regression analysis (on only 10 BTR) showed age and adjuvant radiation as significant predictors of BTR. In patients not receiving radiation, no BTR was seen in 22 patients > or = 70 years of age at diagnosis vs. 8 BTR in 31 patients < 70 years (p = 0.0130). All BTR occurred while patients were receiving tamoxifen. CONCLUSIONS: Tamoxifen alone with omission of radiation after partial mastectomy provides inferior breast tumor control in node positive patients. This is especially true for patients under 70 years of age. Patients aged 70 years or older at the time of diagnosis of breast cancer who receive tamoxifen have a low rate of breast tumor recurrence when radiation is omitted. These patients represent a group for whom radiation might not be necessary.

Adult↗
PubMed1995

Multiple protein kinase activities required for activation of sperm flagellar motility.

A specific peptide inhibitor of the cyclic AMP (cAMP)-dependent protein kinase (PKI-peptide) is a very effective inhibitor of the cAMP-dependent activation of motility of Ciona spermatozoa, when PKI-peptide is present at the beginning of incubation of demembranated spermatozoa with cAMP and ATP. Under conditions where approximately 120 sec is required for full activation of motility, the window of sensitivity to the PKI-peptide lasts for only 25-30 sec. Examination of sperm pellet proteins labeled with 32P ATP during activation reveals a major 25 kDa phosphoprotein and 2 minor phosphoproteins whose phosphorylation is highly sensitive to to inhibition by the PKI-peptide and essentially complete during this early phase. These sperm proteins appear to be immediate substrates for cAMP-dependent protein kinase, and phosphorylation of one or more of these appears to be requires, but not sufficient, for activation of motility. The phosphorylation of other proteins is reduced or eliminated when PKI-peptide is present at the beginning of incubation, but is unaffected by later addition of PKI-peptide. Some of these substrates appear to be likely candidates for axonemal proteins that must be phosphorylated during the later stages of incubation in order to complete the activation process. This selection is based upon a high degree of inhibition by inclusion of PKI-peptide or other inhibitors at the start of the incubation process, on near-completion of their phosphorylation by the end of the 2 min incubation period required for the activation of motility, and evidence that these proteins are phosphorylated during in vivo activation of motility. Although these observations suggest the presence of a second kinase activity that is upregulated by the initial activation of the cAMP-dependent protein kinase, assays using exogenous substrates have not yet been able to identify such a kinase activity.

Animals↗