Biomedical subjects

H Cheng

Publications and source records attributed to H Cheng.

At least 109 records · Page 6Linked to original sources

PubMed2000

Culture and adenoviral infection of adult mouse cardiac myocytes: methods for cellular genetic physiology.

Rapid development of transgenic and gene-targeted mice and acute genetic manipulation via gene transfer vector systems have provided powerful tools for cardiovascular research. To facilitate the phenotyping of genetically engineered murine models at the cellular and subcellular levels and to implement acute gene transfer techniques in single mouse cardiomyocytes, we have modified and improved current enzymatic methods to isolate a high yield of high-quality adult mouse myocytes (5.3 +/- 0.5 x 10(5) cells/left ventricle, 83.8 +/- 2.5% rod shaped). We have also developed a technique to culture these isolated myocytes while maintaining their morphological integrity for 2-3 days. The high percentage of viable myocytes after 1 day in culture (72.5 +/- 2.3%) permitted both physiological and biochemical characterization. The major functional aspects of these cells, including excitation-contraction coupling and receptor-mediated signaling, remained intact, but the contraction kinetics were significantly slowed. Furthermore, gene delivery via recombinant adenoviral infection was highly efficient and reproducible. In adult beta(1)/beta(2)-adrenergic receptor (AR) double-knockout mouse myocytes, adenovirus-directed expression of either beta(1)- or beta(2)-AR, which occurred in 100% of cells, rescued the functional response to beta-AR agonist stimulation. These techniques will permit novel experimental settings for cellular genetic physiology.

Adenoviridae↗

PubMed2000

Cementum-forming cells are phenotypically distinct from bone-forming cells.

Normal human cementum-derived cells (HCDCs), expanded in vitro, formed mineralized matrix when attached to a ceramic carrier and transplanted subcutaneously into immunodeficient mice. The mineralized matrix elaborated by transplanted HCDC exhibited several features identical to cementum in situ and was significantly different from bone deposited by similarly transplanted human bone marrow stromal cells (BMSCs). No bone marrow formation and very few or no tartrate-resistant acid phosphatase (TRAP)-positive cells (osteoclasts and osteoclastic precursors) were found in HCDC transplants. In contrast, in BMSC transplants both hematopoiesis and TRAP-positive cells were routinely observed. Furthermore, compared with BMSC-derived matrix, HCDC-derived matrix was less cellular, numerous empty lacunae were present, and fewer cells were found on the cementum matrix/ceramic carrier interface. The organization of collagen fibers in HCDC-derived matrix, as visualized by using the Picrosirus red staining method, was similar to cementum, with typical unorganized bundles of collagen fibers. In contrast, bone matrix elaborated by transplanted BMSC had lamellar structure, identical to mature bone in situ. Finally, cementocytes embedded in the cementum-like matrix were immunopositive for fibromodulin and lumican, whereas osteocytes within the bonelike matrix were negative. This pattern is consistent with the cementum and bone in situ, respectively. These results indicate that human cementum cells are phenotypically distinct from bone cells and provide further validation of the combined in vitro/in vivo model of human cementogenesis recently developed in our laboratory.

Adolescent↗

PubMed2000

Performance status of health care facilities changes with risk adjustment of HbA1c.

OBJECTIVE: To develop a risk adjustment method for HbA1c, based solely on administrative data and to determine the extent to which risk-adjusted HbA1c changes the identification of high- or low-performing medical facilities. RESEARCH DESIGN AND METHODS: Through use of pharmacy records, 204,472 diabetic patients were identified for federal fiscal year 1996 (FY96). Complete information (HbA1c levels, demographic data, inpatient records, outpatient pharmacy utilization records) was available on 38,173 predominantly male patients from 48 Veterans Health Administration (VHA) medical facilities. Hierarchical mixed-effects models were used to estimate risk-adjusted unique facility-level HbA1c. RESULTS: Predicted HbA1c demonstrated expected patterns for major factors known to influence glycemic control. Poorer glycemic control was seen in minorities and patients with greater disease severity, longer duration of disease (using treatment type or presence of amputation as surrogates), and more extensive comorbidity (measured by an adapted Charlson index). Better glycemic control was seen in Caucasians, older diabetic patients, and patients with higher outpatient utilization. The number of performance outliers was reduced as a result of risk adjustment. For mean HbA1c levels, 7 facilities that were initially identified as statistically significant outliers were no longer outliers after risk adjustment. For high-risk HbA1c (>9.5%) rates, 12 facilities that were initially identified as statistically significant outliers were no longer outliers after risk adjustment. CONCLUSIONS: Risk adjustment using only administrative data resulted in substantial changes in identification of high or low performers compared with non-risk-adjusted HbA1c. Although our findings are exploratory, risk adjustment using administrative data may be a necessary and achievable step in quality assessment of diabetes care measured by rates of high-risk HbA1c (>9.5%).

Adult↗

PubMed2000

Elevated levels of urine angiostatin and plasminogen/plasmin in cancer patients.

Previously, a specific angiogenesis inhibitor, angiostatin, discovered in urine and serum of tumor-bearing mice, was reported to potently block tumor growth and metastasis in animal models. Detection of angiostatin and its precursor proteins in urine from cancer patients has not been reported. Now, we report the development of an antibody-based analysis system that allows us to detect angiostatin and plasminogen/plasmin (Pgn/plasmin) in the urine of cancer patients. The detection system is a combination of a novel lysine-ELISA assay and Western immunoblot analysis using a specific antibody to human angiostatin and Pgn/plasmin. High levels of Pgn/plasmin were detected in the urine from various cancer patients, whereas healthy individuals showed relatively low levels of urine Pgn/plasmin. Of interest, angiostatin is detectable in urine samples of patients with various cancers, including acute lymphoblastic leukemia, suggesting that angiogenesis may play an important role in the development and progression of leukemia. Our data for the first time show that angiostatin and Pgn/plasmin are present at relatively high levels in the urine of human cancer patients. Detection of urine angiostatin in cancer patients helps us not only to understand the role of this angiogenesis inhibitor in cancer development and progression but also allows us to develop tools of cancer diagnosis and prognosis. Thus angiostatin has both therapeutic and diagnostic implications in cancer disease.

Adolescent↗

PubMed2000

Disposition and pharmacokinetics of the antimigraine drug, rizatriptan, in humans.

The absorption and disposition of rizatriptan (MK-0462, Maxalt(TM)), a selective 5-HT(1B/1D) receptor agonist used in the treatment of migraine headaches, was investigated in humans. In a two-period, single i.v. (3 mg, 30-min infusion), and single oral (10 mg) dose study with [(14)C]rizatriptan in six healthy human males, total recovery of radioactivity was approximately 94%, with unchanged rizatriptan and its metabolites being excreted mainly in the urine (89% i.v. dose, 82% p.o. dose). Approximately 26 and 14% of i.v. and oral rizatriptan doses, respectively, were excreted in urine as intact parent drug. In a second, high-dose study (60 mg p.o.), five metabolites excreted into urine were identified using liquid chromatography-tandem mass spectrometry and NMR methods. They were triazolomethyl-indole-3-acetic acid, rizatriptan-N(10)-oxide, 6-hydroxy-rizatriptan, 6-hydroxy-rizatriptan sulfate, and N(10)-monodesmethyl-rizatriptan. Urinary excretion of triazolomethyl-indole-3-acetic acid after i.v. and oral administrations of rizatriptan accounted for 35 and 51% of the dose, respectively, whereas the corresponding values for rizatriptan-N(10)-oxide were 4 and 2% of the dose. Plasma clearance (CL) and renal clearance (CL(r)) were 1325 and 349 ml/min, respectively, after i.v. administration. A similar CL(r) value was obtained after oral administration (396 ml/min). The primary route of rizatriptan elimination occurred via nonrenal route(s) (i.e., metabolism) because the CL(r) of rizatriptan accounted for 25% of total CL. Furthermore, the CL(r) was higher than normal glomerular filtration rate ( approximately 130 ml/min), indicating that this compound was actively secreted by renal tubules. The absorption of rizatriptan was approximately 90%, but it experienced a moderate first-pass effect, resulting in a bioavailability estimate of 47%.

Administration, Oral↗

PubMed2000

Role of macrophages in restricting herpes simplex virus type 1 growth after ocular infection.

PURPOSE: To investigate the role macrophages play in controlling herpes simplex virus (HSV)-1 replication after infection of the murine cornea. METHODS: Macrophage depletion in selected tissues before or after virus infection was achieved by repeated subconjunctival (SCJ) and/or intravenous (IV) injection of liposomes containing dichloromethylene diphosphonate (L-Cl2MDP). Controls received liposomes containing phosphate-buffered saline (L-PBS). The efficiency of depletion was evaluated by histologic examination. Virus content in infected tissues was determined by standard plaque assay. Delayed-type hypersensitivity (DTH) responsiveness was assessed using the ear-swelling assay. Antibody isotype responses to virus antigens and cytokine production were monitored by enzyme-linked immunosorbent assay. RESULTS: Balb/c mice given SCJ injection of L-Cl2MDP 4 and 2 days before HSV-1 corneal infection were found to have ocular virus titers as much as 10(5)-fold higher than that seen in the L-PBS-treated controls 8 days after infection. When L-Cl2MDP treatment was delayed until 2 and 4 days after infection, virus titers in the eye were analogous to those in the control animals. Subconjunctival and submandibular lymph node macrophages in mice given local (SCJ) L-Cl2MDP pretreatment were profoundly reduced, whereas the number of corneal Langerhans' cells and lymph node dendritic cells remained unchanged. Local L-Cl2MDP pretreatment was associated with significantly reduced DTH responsiveness to HSV-1 antigen, and an alteration in selected antibody isotype production. Depletion of macrophages in the subconjunctival tissue before corneal infection was not accompanied by enhanced virus growth at early times (2 or 4 days) after infection. CONCLUSIONS: Macrophages play an important role in restricting HSV-1 growth after corneal infection. These cells appear to be required for the development of an acquired immune response, presumably by functioning in antigen processing and presentation. The hypothesis that macrophages are major participants in innate immunity to HSV-1 corneal infection was not supported.

Acid Phosphatase↗

PubMed2000

[Evaluation and comparison of the Helicobacter pylori stool antigen test and the gastric mucosal antigen test].

OBJECTIVE: To evaluate the reliability of an enzyme-linked immunosorbent assay by the Helicobacter pylori (H. pylori) stool antigen test for the detection of H. pylori infection. METHODS: Stool specimens were collected from 224 patients who received upper gastrointestinal endoscopic examination for gastrointestinal symptoms. H. pylori status was evaluated by five different tests: culture, histology, biopsy rapid urease test, H. pylori stool antigen test, and H. pylori gastric active mucosal antigen test (parts of the patients). A commercial kit using an enzyme-linked immunosorbent assay was used to examined H. pylori antigen in the stool or in the gastric active mucosa. H. pylori status was defined as positive when two of the three tests (culture, histology and biopsy rapid urease test) were positive. RESULTS: 137 patients were diagnosed as H. pylori-positive. The H. pylori stool antigen test was positive in 143 patients and negative in 81 patients. The sensitivity and specificity were 96.4% and 87.4%, respectively. The overall accuracy was 92.9%. 39 patients were examined H. pylori antigen in the gastric active mucosa, and 27/39 were diagnosed as H. pylori-positive. The H. pylori gastric active mucosal antigen test was positive in 28 patients and negative in 11 patients. The H. pylori stool antigen test was positive in 30 patients and negative in 9 patients. The corresponding rate between gastric active mucosa and stool was 94.9%. CONCLUSION: The H. pylori stool antigen test is a simple, non-invasive method for accurate diagnosis of H. pylori infection.

Adolescent↗

PubMed2000

[Effect of lanthanum on growth and biochemical property of Sclerotinia sclerotiorum].

The study shows that La2O3 at a concentration of 30-450 mg.L-1 could inhibit the growth of S. sclerotiorum in both solid and liquid media and the inhibition effect was increased with its increasing concentration. The activity of pectinase produced by S. sclerotiorum in liquid medium was also increased with increasing La2O3 concentration.

Ascomycota↗

PubMed2000

[Niche breadth of Gymnosporangium haraeanum].

The resistant difference among different main pear cultivars in Anhui Province to pear rust caused by Gymnosporangium haraeanum was significant. According to disease index and diseased leaves of susceptible cultivars, the niche breadths of hosts were 0.7555 and 0.7951, respectively. The niche breadths of horizontal and vertical space of each cultivar were approximate to 1. The result shows that the infection of G. haraeanum was a random distribution.

Basidiomycota↗

PubMed2000

Molecular cloning, sequencing and expression of obese gene in the Chinese.

OBJECTIVE: To construct the human obese (ob) cDNA clone in the Chinese, and analyze the expression of the ob gene in adipose tissue of obese, non-obese subjects and nooinsulin-dependent diabetes mellitus (NIDDM) Chinese patients. METHODS: A ob cDNA clone was isolated by reverse transcription polymerase chain reaction (RT-PCR). Four groups of Chinese subjects participated in the study: 1) 12 obese subjects [body mass index (BMI): 28.5 +/- 2.3 kg/m2]; 2) 11 non-obese subjects (BMI: 21.0 +/- 1.5 kg/m2); 3) 8 obese NIDDM patients (BMI: 27.0 +/- 1.4 kg/m2); 4) 11 non-obese NIDDM patients (BMI: 21.2 +/- 1.4 kg/m2). The expression of ob gene mRNA in abdominal subcutaneous adipose tissue was examined using RNA dot blot hybridization with a digoxigenin-labeled human ob cDNA probe. The hybridized signals were quantitated by densitometry. RESULTS: A full human ob cDNA fragment which included a glutamine codon at +49 was obtained. A base substitution (A to G) in the coding region at position 287 was found, resulting in a glutamine being replaced by an arginine. Expression of the ob gene was significantly higher in Chinese obese subjects compared to non-obese ones (P < 0.05), and positively correlated with the BMI. No significant difference in the amount of ob mRNA was detected between non-diabetic and diabetic groups at the same BMI level. CONCLUSIONS: We constructed a full length human ob cDNA clone. The expression of the ob gene was significantly higher in Chinese obese subjects than in non-obese ones. The metabolic and hormonal changes associated with NIDDM are not the main factors regulating the expression of the ob gene.

Adult↗

PubMed2000

[Primary study on characteristics of insulin secretion rate, metabolic clearance rate and sensitivity in non-insulin-dependent diabetic subjects from multiplex diabetic pedigrees].

OBJECTIVE: To investigate the characteristics of insulin secretion rate (ISR), metabolic clearance rate (MCR-I) and sensitivity and to explore their relationship with obesity in non-insulin-dependent diabetic subjects from multiplex diabetic pedigrees (MDP). METHODS: Fifteen subjects with normal glucose tolerance and 11 non-insulin-dependent diabetic patients from MDP were included in the study. Frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed. Glucose, insulin (INS) and connecting-peptide (C-P) concentrations were measured. A computer procedure devised by our laboratory was used to calculate the value of ISR at each time point, then MCR-I was acquired. Insulin sensitivity index (SI) was calculated according to minimal model technique about glucose in FSIVGTT. RESULTS: The ISR curve in control group was biphasic, while in non-insulin. In non-insulin-dependent diabetic group, areas under the curves of C-P (AUCC) and ISR level (AUCS) measured during 0 approximately 16 min were 7.9 nmol.min(-1).L(-1) +/- 2.8 nmol.min(-1).L(-1), and 6.1 nmol +/- 2.2 nmol, respectively, which were significantly lower than those in control group 17.7 nmol.min(-1).L(-1) +/- 4.92 nmol.min(-1).L(-1) and 12.3 nmol +/- 3.9 nmol (P < 0.01). The two parameters were slightly higher than those in control group 155 nmol.min(-1).L(-1) +/- 44 nmol.min(-1).L(-1) vs 101 nmol.min(-1).L(-1) +/- 30 nmol.min(-1).L(-1) and 76 nmol +/- 26 nmol vs 54 nmol +/- 20.0 nmol (P < 0.05)measured during 16 approximately 180 min. There was no significant difference, between the two groups about the amount of insulin secretion during 3 hours (82 nmol +/- 28nmol vs 68 nmol +/- 21 nmol, P = 0.2). In control group, there were significant positive correlation, between AUCS, waist-hip ratio (WHR), and body surface area, (BSA) and significant negative correlation between MCR-I, SI and WHR, BSA (P < 0.01), and also between MCR-I and SI. In non-insulin-dependent diabetic group, AUCS were significantly correlated with body mass index (BMI) (P < 0.01), and MCR-I had significant negative correlation with AUCC (P < 0.01). CONCLUSIONS: There are obvious impaired first phase insulin secretion after glucose challenge in non-insulin-dependent diabetic subjects from MDP. Decrease in endogenous MCR-I might be an important factor to hyperinsulinemia and insulin resistance. Increased insulin secretion, decreased MCR-I and insulin sensitivity can be observed in abdominal obese subjects of control group.

Blood Glucose↗

PubMed2000

[Application of indigo disulphonate spectrophotometry on the determination of ozone in indoor air].

Spectrophotometric determination of ozone in indoor air by using indigo disulphonate was investigated. The results showed that the average recovery of ozone was 99% and the relative standard deviation was 2.3% when the concentration of indoor ozone was in the range of 0.2-1.0 microgram/ml. The lowest detection concentration was 0.009 mg/m3 (sampling 20 L) when the range of determination was 0.18-10.0 mg/10 ml.

Air Pollutants↗

PubMed2000

[An experimental study on the effect of positional asphyxia on cardiac and pulmonary functions].

The purpose of the study is to explore the effect of positional asphyxia on cardiac and pulmonary functions and its role in causing death. respiration, pulmonary artery pressure and cardiac output were measured by inserting the swan-ganz into the pulmonary artery from the femoral vein. Results showed that: (1) the respiration was stable before hanging, getting faster during hanging, and becoming irregular at the terminal stage of hanging; (2) the pulmonary artery pressure increased significantly during and at the terminal stage of hanging as compared with that before hanging; (3) the cardiac output was stable before and during hanging, but decreased significantly at the terminal stage of hanging. It is concluded that hanging may cause respiratory imbalance and hypoxia, resulting in cardiac and pulmonary dysfunction. The death caused by hanging belongs to respiratory death, the characteristic of which is primary respiratory arrest followed by secondary cardiac arrest.

Airway Obstruction↗

PubMed2000

[The degradation performance of bioabsorbable acylchitin fiber reinforced PLA composite materials in vitro and in vivo].

The present authors have investigated the degradation performance of acylchitin fiber reinforced polylactide composite materials plates both in vitro and in vivo. The initial flexural strength and the initial flexural modulus of this plate are 114.72 MPa and 3980.05 MPa, respectively. The flexural strength of this plate decreases to 31.42 MPa after the plate has been submerged in injectio natrii lactatic ringeri tissue fluid for a period of 16 weeks at 37 degrees C. Both the in vitro degradation performance and the strength retention of this plate are better than those of the self-reinforced PGA/PLA and PGA, though the initial strength of the latter two being much higher than that of the former. The degradation products of the chitin/PLA composite materials can be absorbed by metabolic pathway.

Animals↗

PubMed1999

Constitutive beta2-adrenergic signalling enhances sarcoplasmic reticulum Ca2+ cycling to augment contraction in mouse heart.

1. Transgenic overexpression of the beta2-adrenergic receptor (beta2AR) in mouse heart augments baseline cardiac function in a ligand-independent manner, due to the presence of spontaneously active beta2AR (beta2AR*). This study aims to elucidate the mechanism of beta2AR*-mediated modulation of cardiac excitation-contraction (EC) coupling. 2. Confocal imaging was used to analyse Ca2+ sparks and spatially resolve Ca2+ transients in single ventricular myocytes from transgenic (TG4) and non-transgenic (NTG) littermates. Whole-cell voltage- and current-clamp techniques were used to record L-type Ca2+ currents (ICa) and action potentials, respectively. 3. In the absence of any beta2AR ligand, TG4 myocytes had greater contraction amplitudes, larger Ca2+ transients and faster relaxation times than did NTG cells. 4. The action potentials of TG4 and NTG myocytes were similar, except for a prolonged end-stage repolarization in TG4 cells; the ICa density and kinetics were nearly identical. The relationship between peak Ca2+ and contraction, which reflects myofilament Ca2+ sensitivity, was similar. 5. In TG4 cells, the frequency of Ca2+ sparks (spontaneous or evoked at -40 mV) was 2-7 times greater, despite the absence of change in the resting Ca2+, sarcoplasmic reticulum (SR) Ca2+ content, and ICa. Individual sparks were brighter, broader and lasted longer, leading to a 2.3-fold greater signal mass. Thus, changes in both spark frequency and size underlie the greater Ca2+ transient in TG4 cells. 6. The inverse agonist ICI 118,551 (ICI, 5 x 10-7 M), which blocks spontaneous beta2AR activation, reversed the aforementioned beta2AR* effects on cardiac EC coupling without affecting the sarcolemmal ICa. However, ICI failed to detect significant constitutive beta2AR activity in NTG cells. 7. We conclude that beta2AR*-mediated signalling enhances SR release channel activity and Ca2+-induced Ca2+ release in TG4 cardiac myocytes, and that beta2AR* enhances EC coupling by reinforcing SR Ca2+ cycling (release and reuptake), but bypassing the sarcolemmal ICa.

Action Potentials↗

PubMed1999

Recent advances in cardiac beta(2)-adrenergic signal transduction.

Recent studies have added complexities to the conceptual framework of cardiac beta-adrenergic receptor (beta-AR) signal transduction. Whereas the classical linear G(s)-adenylyl cyclase-cAMP-protein kinase A (PKA) signaling cascade has been corroborated for beta(1)-AR stimulation, the beta(2)-AR signaling pathway bifurcates at the very first postreceptor step, the G protein level. In addition to G(s), beta(2)-AR couples to pertussis toxin-sensitive G(i) proteins, G(i2) and G(i3). The coupling of beta(2)-AR to G(i) proteins mediates, to a large extent, the differential actions of the beta-AR subtypes on cardiac Ca(2+) handling, contractility, cAMP accumulation, and PKA-mediated protein phosphorylation. The extent of G(i) coupling in ventricular myocytes appears to be the basis of the substantial species-to-species diversity in beta(2)-AR-mediated cardiac responses. There is an apparent dissociation of beta(2)-AR-induced augmentations of the intracellular Ca(2+) (Ca(i)) transient and contractility from cAMP production and PKA-dependent cytoplasmic protein phosphorylation. This can be largely explained by G(i)-dependent functional compartmentalization of the beta(2)-AR-directed cAMP/PKA signaling to the sarcolemmal microdomain. This compartmentalization allows the common second messenger, cAMP, to perform selective functions during beta-AR subtype stimulation. Emerging evidence also points to distinctly different roles of these beta-AR subtypes in modulating noncontractile cellular processes. These recent findings not only reveal the diversity and specificity of beta-AR and G protein interactions but also provide new insights for understanding the differential regulation and functionality of beta-AR subtypes in healthy and diseased hearts.

Adrenergic beta-Agonists↗

PubMed1999

The evolutionarily conserved Dim1 protein defines a novel branch of the thioredoxin fold superfamily.

Dim1 is a small evolutionarily conserved protein essential for G2/M transition that has recently been implicated as a component of the mRNA splicing machinery. To date, the mechanism of Dim1 function remains poorly defined, in part because of the absence of informative sequence homologies between Dim1 and other functionally defined proteins or protein domains. We have used a combination of molecular modeling and NMR structural analysis to demonstrate that approximately 125 of the 142 amino acids of human Dim1 (hDim1) define a novel branch of the thioredoxin fold superfamily. Mutational analysis of Dim1 based on the predicted fold indicates that alterations in the region corresponding to the thioredoxin active site do not affect Dim1 activity. However, removal of a very short carboxy-terminal extension generates a dominant negative form of the protein [hDim1-(1-128)] that when overproduced induces cell cycle arrest in G2, via a mechanism likely to involve alteration of Dim1 association with partner molecules. In sum, this study identifies the Dim1 proteins as a novel sixth branch of the thioredoxin superfamily involved in cell cycle.

Amino Acid Sequence↗

PubMed1999

The conserved core of human immunodeficiency virus type 1 Nef is essential for association with Lck and for enhanced viral replication in T-lymphocytes.

The Nef protein of the primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), is a myristylated protein associated with increased viral replication and enhanced pathogenicity. Both the potentiation of T-lymphocyte activation and the enhanced serine-phosphorylation of HIV-1 capsid by Nef correlate with increased viral replication. We report the functional interactions of the Nef proteins with Src kinases. The Nef proteins from HIV-1 and SIV bind to Lck as well as Hck, Lyn, and Fyn. The SH3 and SH2 domains of Lck are sufficient for coprecipitation with non-tyrosine-phosphorylated Nef proteins. The conserved core region of HIV-1 Nef is essential for the interaction with Lck and is also important for enhanced HIV-1 replication in T-lymphocytes. In addition, we show that SIV and HIV-1 Nef proteins are differentially tyrosine-phosphorylated. The kinase-active Lck tyrosine-phosphorylates SIVmac239 Nef but does not phosphorylate HIV-1 Nef. These data suggest that the association of Nef and Lck is central to the enhanced viral replication of HIV-1 and SIV in T-lymphocytes.

Base Sequence↗