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A Tang

Publications and source records attributed to A Tang.

At least 91 records · Page 5Linked to original sources
PubMed1996

Two S-phase checkpoint systems, one involving the function of both BIME and Tyr15 phosphorylation of p34cdc2, inhibit NIMA and prevent premature mitosis.

We demonstrate that there are at least two S-phase checkpoint mechanisms controlling mitosis in Aspergillus. The first responds to the rate of DNA replication and inhibits mitosis via tyrosine phosphorylation of p34cdc2. Cells unable to tyrosine phosphorylate p34cdc2 are therefore viable but are unable to tolerate low levels of hydroxyurea and prematurely enter lethal mitosis when S-phase is slowed. However, if the NIMA mitosis-promoting kinase is inactivated then non-tyrosine-phosphorylated p34cdc2 cannot promote cells prematurely into mitosis. Lack of tyrosine-phosphorylated p34cdc2 also cannot promote mitosis, or lethality, if DNA replication is arrested, demonstrating the presence of a second S-phase checkpoint mechanism over mitotic initiation which we show involves the function of BIME. In order to overcome the S-phase arrest checkpoint over mitosis it is necessary both to prevent tyrosine phosphorylation of p34cdc2 and also to inactivate BIME. Lack of tyrosine phosphorylation of p34cdc2 allows precocious expression of NIMA during S-phase arrest, and lack of BIME then allows activation of this prematurely expressed NIMA by phosphorylation. The mitosis-promoting NIMA kinase is thus a target for S-phase checkpoint controls.

Aspergillus nidulans↗
PubMed1996

Suppression of murine allergic contact dermatitis by CTLA4Ig. Tolerance induction of Th2 responses requires additional blockade of CD40-ligand.

Blockade of costimulation through the B7-CD28 pathway by CTLA4Ig can lead to Ag-specific T cell tolerance. Most models studied to date involve a Th1-dependent response. To investigate whether the tolerizing effects of CTLA4Ig might vary depending upon the cytokine nature of the immune response, we studied its effects on contact hypersensitivity (CHS) in response to two allergens. In BALB/c mice, both 2,4-dinitrofluorobenzene (DNFB) and FITC induce CHS. However, the DNFB response is Th1-predominant, while the FITC response is Th2 predominant. CTLA4Ig treatment during primary sensitization induced long-lasting unresponsiveness to DNFB, with 88% and 76% inhibition of primary (first challenge) and secondary (re-sensitization and re-challenge) CHS, respectively. In contrast, CTLA4Ig inhibited primary CHS to FITC by over 82% but had little effect on secondary CHS. Consistent with its effects on CHS, the suppressive effect of CTLA4Ig on Th2 cells was short-lived in FITC-sensitized mice, while Th1-like cytokine-secreting cells remained reduced in DNFB-sensitized mice, even when the animals were rechallenged with DNFB. The addition of anti-CD40L Ab to CTLA4Ig was able to induce long-lasting unresponsiveness to FITC, indicating the ability of cells mounting this Th2 response to receive costimulatory signals through either pathway. In conclusion, CHS can be mediated by both Th1 and Th2 cells, and the ability of CTLA4Ig to lead to long-standing nonresponsiveness in this model depends on the nature (i.e., cytokine profile) of the immune response.

Abatacept↗
PubMed1996

The in vivo mechanism of action of CTLA4Ig.

A single dose of CTLA4Ig, an inhibitor of CD28-mediated T cell costimulation, given 2 days after transplantation induces specific unresponsiveness to alloantigens in vivo. However, the mechanisms responsible are unknown. Using pigeon cytochrome c as a model Ag, we monitored the effect of CTLA4Ig on the fate of Ag-reactive T cells in normal mice and on pigeon cytochrome c-specific TCR transgenic cells adoptively transferred into congenic mice. CTLA4Ig significantly inhibits immunization with pigeon cytochrome c. In particular, ELISA and ELISPOT assays indicate an 80 to 90% reduction in Th1 (i.e, IL-2 and IFN-gamma) cytokine production and in the numbers of cytokine-producing cells. Interestingly, despite this profound reduction in cytokine-producing cells, Ag-reactive T cells expand in CTLA4Ig-treated animals, although the degree of expansion is reduced by 50% compared with that in control Ig-treated animals. Thus, loss of Th1 cytokine production in CTLA4Ig-treated animals is not fully explained by the decreased expansion of Ag-specific T cells. These results suggest two mechanisms of action for CTLA4Ig in vivo: inhibition of expansion of Ag-reactive cells and induction of anergy in the residual population.

Abatacept↗
PubMed1996

Immunosuppression through blockade of CD28:B7-mediated costimulatory signals.

It is now well established that T cells require two signals for activation and effector function. The first signal is provided through the T cell receptor for antigen. The best-characterized pathway which provides the second, or costimulatory, signal is through the CD28 receptor on the surface of T cells. In vitro, ligation of the T cell receptor without a second signal induces a long-lived state of anergy in T cells. CD28 has two known ligands, B7-1 and B7-2, expressed on activated antigen-presenting cells. A soluble fusion protein called CTLA4Ig has been produced which binds B7-1 and B7-2 and acts as a competitive inhibitor of CD28. In vitro and in vivo studies with CTLA4Ig demonstrate that it is an extremely effective immunosuppressive agent in models of transplantation and autoimmunity. Mechanistic studies indicate that CTLA4Ig may work by partially inhibiting the expansion of antigen-reactive cells and inducing anergy in the residual population.

Animals↗
PubMed1996

Regulation of keratinocyte growth factor gene expression in human skin fibroblasts.

Human keratinocyte growth factor (KGF) is a recently identified mitogen for epithelial cells produced by normal stromal fibroblasts. KGF has been shown to stimulate keratinocyte migration and promote re-epithelialization of skin suggesting a critical role for KGF in wound healing. To understand how KGF might be regulated during wound healing, we examined the ability of the pro-inflammatory cytokines interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) transforming growth factor-beta 1 (TGF-beta 1) and interferon-gamma (IFN-gamma) to modulate KGF gene expression in cultured human fibroblasts, using northern blot analysis. Exposure to IL-1 alpha (20 units/ml) or IL-1 beta (100 units/ml) for 24 h increased KGF mRNA expression by 352% and 504%, respectively, with early induction seen at 2 h and maximal induction seen at 8 h. TNF-alpha (30 ng/ml) increased KGF mRNA expression by 535% at 24 h, with induction first seen at 8 h. The maximal induction of KGF mRNA was observed when IL-1 alpha, IL-1 beta and TNF-alpha were used at 100 units/ml, and 3 ng/ml, respectively, although concentrations 100-500-fold lower (IL-1 alpha, 0.02 units/ml; IL-beta, 0.02 units/ml; and TNF-alpha, 0.03 ng/ml) were nearly as stimulatory, increasing KGF mRNA expression by 175%, 254% and 322%, respectively. IL-6 (200 units/ml), TGF-beta 1 (5 ng/ml) and IFN-gamma (200 units/ml) did not change the level of KGF mRNA at 24 h in human fibroblasts under the same conditions. The protein synthesis inhibitor cycloheximide abrogated the effects of IL-1 alpha, IL-1 beta and TNF-alpha on KGF gene induction, indicating that new protein synthesis is required in the process. Dexamethasone (10(-7) M), known to inhibit inflammatory reactions and retard wound healing, also inhibited the induction of KGF mRNA expression by IL-1 alpha, IL-1 beta and TNF-alpha. Individual variation in KGF mRNA expression was see when fibroblasts from different aged donors were analysed, but no consistent age-associated change was observed. These results suggest that IL-1 alpha, IL-1 beta and TNF-alpha up-regulate KGF gene expression in fibroblasts and might be responsible for its induction following skin wounding or other injury.

Adult↗
PubMed1996

d-Sotalol decreases defibrillation energy requirements in humans: a novel indication for drug therapy.

INTRODUCTION: We assessed the effect of d-sotalol on defibrillation voltage and energy requirements in patients undergoing automatic defibrillator implantation. Drugs that primarily prolong cardiac refractoriness generally decrease the energy requirements for defibrillation in animal models. Despite the widespread use of antiarrhythmic drugs in patients with implanted cardioverter defibrillators, the effect of such drugs on defibrillation energy requirements in humans has not been well studied. Sotalol (in the d,l racemic form) is an antiarrhythmic with beta-blocking and cardiac refractoriness prolonging effects. The d-isomer of sotalol is largely devoid of beta-blocking effects; both forms decrease defibrillation energy requirements in animals. We hypothesized that d-sotalol would decrease defibrillation voltage and energy requirements in humans. METHODS AND RESULTS: Fifteen patients undergoing implanted cardioverter defibrillator implantation were studied before and 20 minutes after d-sotalol infusion (2 mg/kg IV in 15 min, followed by 1 mg/kg per hour). The estimated energy (E50) and voltage (V50) for 50% success in defibrillation (estimated from two successive defibrillation "threshold" measurements), ventricular effective refractory period, monophasic action potential duration, and mean cycle length of ventricular fibrillation were measured, along with heart rate, blood pressure, and plasma concentration of d-sotalol. There was a significant decrease in defibrillation energy (E50 = 12.4 +/- 5.0 J before and 8.4 +/- 4.0 J after d-sotalol, P < 0.003) and voltage (V50 = 440 +/- 77 V before and 354 +/- 93 V after d-sotalol, P < 0.001). Consistent with the Class III effect of d-sotalol, ventricular effective refractory period increased from 284 +/- 21 to 330 +/- 24 msec (P < 0.001), and action potential duration was prolonged from 296 +/- 28 to 340 +/- 22 msec (P < 0.001). Following d-sotalol, there was a tendency for induced tachyarrhythmia to self-terminate (23/102 episodes before vs 74/150 after sotalol, P < 0.001), and ventricular fibrillation cycle length was increased from 216 +/- 20 msec before to 274 +/- 23 msec (P < 0.001) after d-sotalol, despite the persistence of a rapid, disorganized rhythm of the surface ECG. No patient suffered adverse effects. CONCLUSIONS: d-Sotalol lowers defibrillation energy by a mean 32% +/- 27% at concentrations producing a 16% +/- 7% increase in ventricular effective refractory period. Along with its other antiarrhythmic effects, d-sotalol may increase the safety margin for defibrillation or allow lower programmed energies in patients with implanted defibrillators.

Adrenergic beta-Antagonists↗
PubMed1996

[Cochlear ischemia and changes in compound action potentials in the guinea pig].

To determine the degree of decrease in cochlear blood flow (CoBF) which causes compound action potentials (CAPs) to disappear, a cochlear ischemic model was created by compressing the internal auditory artery in guinea pig. CoBF was measured with a laser Doppler flowmeter, and CAPs were recorded with an electrode placed on the round window membrane. The amplitude and latency of the N1 wave of CAPs changed as CoBF decreased. When CoBF diminished to as much as 70% below the original level, N1 disappeared. In this study, we also observed the N1 recovery process following CoBF reperfusion after 20 minutes of cochlear ischemia. N1 recovery in the group with an incomplete decrease in CoBF was better than in the group with a complete decrease in CoBF. These findings suggest that both the degree of compromise of CoBF and the duration of ischemia are important factors affecting the recovery of auditory function.

Animals↗
PubMed1996

[The changes in cochlear blood flow and auditory brainstem response in the pressure-induced animal model of acoustic neuroma].

Changes in cochlear blood flow (CoBF) and auditory brainstem response (ABR) in a pressure-induced animal model of acoustic neuroma were examined. A suboccipital approach was used to expose the right cerebello-pontine angle in guinea pigs. Under surgical microscope, the bundle of nerves and vessels at the entrance of the internal auditory meatus was exposed without retraction. The two pressure points, one anterior to and the other posterior to the center of the bundle were separately compressed by a pressure probe (1mm in diameter). CoBF from the basal turn or second turn of the right cochlea was measured with a laser Doppler flowmeter. ABR was recorded from the electrodes placed on the vertex and the right mastoid process. With compression, the changes in CoBF and ABR were found in a total of 19 animals. We classified these changes into three types based mainly on CoBF. In type I (n = 9), an increase rather than a decrease of CoBF was noted, and an increase in the I-II inter-peak latency with a decrease in the amplitudes of wave II-IV in ABR were observed. Those changes were mainly attributed to the blockage of cochlear nerve. In type II (n = 6), CoBF was completely stopped and all waves of ABR disappeared during compression. This suggested the presence of cochlear ischemia. After relaxation of compression both CoBF and ABR recovered, but I-II inter-peak latency remained delayed. CoBF in type III (n = 4) decreased and then slowly recovered. In type III, all waves transiently disappeared, and wave I reappeared with recovery of CoBF. The changes in type III were caused by damage to both the artery and the nerve. In addition, the changes in CoBF and ABR were closely related to the pressure points. The changes in type I were often found in compression of the anterior pressure point, whereas the changes in type II are associated with the posterior pressuring point (p < 0.05). The results indicate that the cochlear nerve or the internal auditory artery is more susceptible to damage by compression of an anterior or posterior pressure point, and that the compression position is an important determinant in the type of auditory dysfunction and the degree of hearing loss.

Animals↗
PubMed1996

High resolution sonographic detection of axillary lymph node metastases in breast cancer.

Axillary lymph node status is crucial in the evaluation of prognosis and in treatment planning of breast cancer. High-resolution real-time sonographic scans of the breast and both axillae were performed on 114 patients with breast carcinoma, all of whom had axillary lymph node dissection and histologic assessment. The sensitivity of high-resolution ultrasonography in the detection of axillary nodal metastases was 84.1%, with a specificity of 97.1%, accuracy of 92.1%, positive predictive value of 94.9%, and negative predictive value 90.7%. Ultrasonography of the axilla provides good information on anatomy and pathology and may have a potential role in the prognostic work-up of patients who are not surgical candidates.

Adult↗
PubMed1996

Role of high frequency ultrasonography in the evaluation of palpable breast masses in Chinese women: alternative to mammography?

We prospectively assessed the accuracy of high resolution breast ultrasonography in the diagnosis of palpable breast masses in comparison to clinical palpation and x-ray mammography. Four hundred and eight Chinese women with palpable breast lumps had clinical assessment followed by ultrasonography of the breast, mammography (for women over 35 years), and fine needle aspiration cytology. Excisional biopsy or surgery was performed for suggestive lesions. The clinical, mammographic and ultrasound diagnoses were compared with the final pathologic diagnosis. In the determination of whether a lesion was malignant, the sensitivity, specificity, and positive predictive values were 97%, 97%, and 85%, respectively, for ultrasonography; 92%, 94%, and 84%, respectively, for mammography; and 88%, 92%, and 67%, respectively, for clinical evaluation. The specificity for combined clinical palpation and ultrasonography was higher (99%) than that for combined clinical palpation and mammography (96%). Addition of ultrasonography to combined clinical palpation and mammography increased specificity. Mammography in addition to combined clinical palpation and ultrasonography did not significantly improve the sensitivity, specificity, or positive predictive value. This limited usefulness raises the question as to whether it should be eliminated in the workup of a palpable mass in the average Chinese patient. Its main advantage is the detection of extended foci of carcinoma in situ related to a palpable mass, which often is undetected by ultrasonography.

Adult↗
PubMed1996

[The evaluation of clinical staging by preoperative CT examination in patients with bladder cancer].

50 patients with bladder cancer, treated from september 1988 to September 1994 was analysed to compare preoperative CT examination with postoperative pathological diagnosis. The coincident staging of CT and pathological finding was found to be 86% (43/50). In the remaining 7 patients, 4 were of overstaging and 3 were of understaging respectively. The cause of incorrecting staging by preoperative CT was usualy due to the difficulty in determing if lymph node metastasis occurs. It is suggested that to improve the preoperative CT staging, the thin phase scanning to the area of lymph nodes around the iliac artery and obsturatorius should be carried out if the patient has been confirmed to have hydronephrosis.

Adult↗
PubMed1995

Bone marrow purging with dibutyl phthalate--experimental basis and a preliminary clinical application.

It has been found recently that di-n-butyl phthalate (DBP) possesses a new pharmacological activity in the selective elimination of tumor cells from marrow. In combination with long-term liquid culture of marrow cells in vitro, DBP purged autologous bone marrow transplantation has first been applied to a case of acute myeloid leukemia at the first complete remission with successful reconstitution of hematopoiesis.

Adult↗
PubMed1995

Pneumococcal vaccine and HIV infection: report of a vaccine failure and reappraisal of its value in clinical practice.

A clinical failure of pneumococcal vaccine is reported. A 22 year old African woman was given 23-valent pneumococcal vaccine at her initial presentation with HIV infection. She was asymptomatic and had a CD4+ lymphocyte count above 500 cells/mm3. Eighteen months later she died of meningitis and septicaemia due to Streptococcus pneumoniae type 9 (an antigen included in the 23-valent vaccine). Pneumococcal antibody levels performed on stored blood demonstrated no serological response to the vaccine. This is the first reported case of clinical failure of pneumococcal vaccine in an HIV infected patient who received vaccine whilst at the asymptomatic stage of HIV infection and with relatively intact immune function. The literature pertaining to pneumococcal vaccination in the context of HIV infection was reviewed. Pneumococcal vaccination is recommended for HIV positive patients in the UK by the Departments of Health. It is likely that many physicians are not aware of these recommendations or are concerned about the poor efficacy of the vaccine, and it may consequently be underused in clinical practice. But the potential gain to the HIV positive patient is such that the vaccine should be offered to all HIV positive patients as soon as they present for medical care, irrespective of the stage of HIV disease. Physicians and patients should be aware that the vaccine is not fully protective and that episodes of sepsis, pneumonia and meningitis could still be pneumococcal in origin and should be treated appropriately. Awareness of the substantial risks of pneumococcal disease in HIV infected patients with prompt diagnosis and effective treatment is the most important strategy to decrease morbidity and mortality.

Adult↗
PubMed1995

Ultrasonographic demonstration of normal axillary lymph nodes: a learning curve.

High frequency transducers with near field resolution allow visualization of superficial structures in the axilla, such as the lymph nodes, which could not be visualized with older equipment. We have been able to observe normal axillary nodes in 61.5% of 26 women who had histologic correlation of normal lymph nodes at axillary dissection. We studied 663 women with a clinically palpable breast lump using breast and axillary ultrasonography. They were divided into four groups. The first group consisted of all women who had undergone surgery and had histologic correlation of axillary nodes. The second, third, and fourth groups were made up of three consecutive series of 221 women examined. Women from group one were included in groups two, three, and four. A steep learning curve of 7.1 to 41.9 to 64.7% was observed in the detection of normal axillary nodes, suggesting that these appearances can be recognized easily.

Axilla↗
PubMed1994

Human dTMP kinase: gene expression and enzymatic activity coinciding with cell cycle progression and cell growth.

dTMP kinase (E.C.2.7.4.9.) catalyzes the phosphorylation of dTMP to the corresponding diphosphate. This enzyme is essential for DNA synthesis in vivo and is an important intermediate enzyme in the pathway of many pyrimidine analog drugs. In this report, we describe the isolation of the human dTMP kinase gene by functional complementation of a Saccharomyces cerevisiae cell cycle mutant, cdc8. The cDNA sequence revealed an open reading frame that encodes a protein with the molecular weight of 23,806. The deduced protein sequence was compared to known dTMP kinase sequences from different organisms. Although functionally complementary and structurally conserved, expressed human dTMP kinase in yeast shows little enzymatic activity. In contrast, active human dTMP kinase can be expressed from the gene cloned into the baculovirus expression system, as evidenced by increased enzymatic activity by four- to five-fold. Unlike yeast dTMP kinase, human dTMP kinase does not contain a cysteine residue after the conserved glycine-rich loop, but its enzymatic activity is still affected by the sulfhydryl inhibitor, 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB). The levels of dTMP kinase mRNA and its enzymatic activity fluctuate during the cell cycle, peaking at the S phase. Thus, like Saccharomyces cerevisiae CDC8 (encoding dTMP kinase), the human homolog mRNA and enzymatic activity are also cell cycle regulated. We have also examined four neuroblastoma cell lines for dTMP kinase mRNA levels and its kinase activities, which appear to vary according to cell growth rate. Our results suggest that the expression of the dTMP kinase gene and its activity coincide with various stages of cell growth. The identification of the human dTMP kinase gene and expression of its product in the baculovirus expression system should facilitate study of the mechanism of gene regulation and its role in pyrimidine metabolism.

Amino Acid Sequence↗