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Biomedical subjects

L Zhang

Publications and source records attributed to L Zhang.

At least 145 records · Page 8Linked to original sources
PubMed2004

Receptor mechanisms mediating cyanide generation in PC12 cells and rat brain.

Cyanide is generated in neurons and this report examines the two different receptors which mediate cyanide formation in neuronal tissue. An opiate receptor blocked by naloxone increases cyanide production both in rat brain and in rat pheochromocytoma (PC12) cells. A muscarinic receptor in PC12 cells releases cyanide and the effect is blocked by atropine. In rat brain, in vivo, a muscarinic agonist inhibits cyanide generation, possibly by acting on receptor subtypes different from those in PC12 cells. Cyanide generation by a muscarinic agonist in PC12 cells is blocked by pertussis toxin but that caused by an opiate is not. Thus, two different receptors and two different second messenger systems can mediate cyanide generation in PC12 cells. In parallel with the in vivo data, cultured primary rat cortical cells also show decreased cyanide release following muscarinic stimulation. Both blockade of cyanide generation by muscarinic receptor activation and cyanide release by opiate agonists from cortical cells are pertussis toxin insensitive. Similarly, little cyanide generation was seen following cholera toxin treatment. These data indicate that opiate receptors increase and muscarinic receptors decrease cyanide production in rat brain tissue by G-protein independent mechanisms. This work supports the suggestion that the powerful actions of cyanide may be important for neuromodulation in the CNS.

Analysis of Variance↗
PubMed2004

Effect of ligustrazine on ischemia-reperfusion injury in murine kidney.

INTRODUCTION: Ischemia-reperfusion (I/R) injury is unavoidable in cadaveric renal transplantation. It contributes to acute rejection and chronic allograft dysfunction. Studies have shown that Ligustrazine, a purified and chemically identified component of a Chinese herbal remedy, is a potent blocker of vasoconstriction and has strong effects to scavenge oxygen free radicals. Since warm I/R is potentially more damaging than cold storage, we investigated the possible protective effect of Ligustrazine on warm I/R in mice. METHODS: Unilaterally nephrectomized C57BL/6 male mice were subjected to 50 minutes of left renal ischemia. Group I were sham-operated animals; group II, nontreated animals (saline, iP 30 minutes before I/R); and group III, Ligustrazine-treated animals (80 mg/kg, iP 30 minutes before I/R). Mice were sacrificed 24 hours postreperfusion. Serum creatinine, blood urea nitrogen, kidney malondialdehyde (MDA)level, and superoxide dismutase (SOD) were determined as well as examining the kidneys histologically with immunohistochemistry for Bcl-2, and ICAM-1. RESULTS: I/R produced a six fold increase in creatinine and urea nitrogen levels in group II. Ligustrazine halved the increase, as well as attenuated the necrosis and apoptosis in the tubules (P < .01). Ligustrazine decreased MDA levels and ameliorated the down-regulation of SOD activity. Bcl-2 was up-regulated following I/R, especially in the Ligustrazine-treated group (P < .01). The up-regulation of ICAM-1 was greatly diminished by Ligustrazine (P < .01). CONCLUSION: These findings suggest that Ligustrazine reduces the renal dysfunction associated with warm I/R of the kidney.

Animals↗
PubMed2004

Screening and analysis of porcine endogenous retrovirus in Chinese Banna minipig inbred line.

Pigs have been the most likely animal as the source of cells, tissues, and organs for xenotransplantation. But the use of pigs in xenotransplantation is associated with the risk of porcine endogenous retrovirus (PERV) transmission. Previous studies have identified that the proviruses are integrated into the genome of normal pigs and that virus particles released from the porcine cells can infect human cells in vitro. As a unique inbred pig, Banna minipig inbred (BMI) has a huge potential value for xenotransplantation and medical research. It has been the focal experimental animal for pig-to-human xenotransplantation in China, due to its clear genetic background and tiny individual differences. To evaluate whether the potential risk of PERV exists in inbred pigs, a series of screening experiments were performed herein. The results of PCR with primers specific for gag, pol, and env showed that proviruses existed in the genome of BMI, and the PERV subtypes were PERV-A and PERV-B. PERV mRNA was expressed functionally in BMI. Positive results of an RT assay identified that PERV in BMI had potential infectivity, but the concentration of PERV reverse transcriptase in BMI was almost 20 times lower than that of HIV. These results suggested that gag, pol and env genes of PERV were not lost during inbreeding, which created favorable conditions to produce viral particles that could possibly infect human cells in xenotransplantation.

Animals↗
PubMed2004

Phylogenetic analysis of porcine endogenous retrovirus variation in three Chinese pigs.

PCR amplification was performed on genomic DNA extracted from peripheral blood lymphocytes of three species of Chinese pigs (Banna minipig inbreed [BMI], Wu-Zhi-Shan pig [WZSP], and Nei jiang pig [NJP]), using primers corresponding to the highly conserved regions of polymerase (pol) gene. Extracted PCR products were then cloned in a pGEM-T vector. Phylogenetic analysis of the nucleotide sequences of BMI-PERV, NJJP-PERV, and WZSP-PERV revealed them to be a novel category of PERV. In comparison to other type C retrovirus and lentivirus, their amino acid sequenced show about 30% to 57.7% identities. Our previous research demonstrated that PERV in the three pigs was highly expressed. It appears likely that functional loci encoding these novel PERV sequences exist, but this remains to be established. The novel sequences described in this report will allow such investigations to be actively pursued.

Animals↗
PubMed2004

Study of renal function matching between Banna Minipig Inbred line and human.

Pigs have been thought to be ideal candidates for xenotransplant donors. However besides the immunological barrier, physiological and pharmacokinetic comparabilities of kidney function between donor animals and humans are important factors for successful xenotransplantation. As a unique large inbred animal, Banna Minipig Inbred (BMI) has been reported to be a potential large animal suitable for xenotransplantation. However, its physical and pharmacokinetic compatibilities with humans have not been documented. The purpose of this investigation was to measure renal routine function, glomerular filtration rate (GFR), renal blood flow (ERPF), and drug metabolism to evaluate comparability to humans. The results suggested that the renal function of BMI was similar to that of humans to eliminate nonprotein nitrogenous end products of metabolism. Pharmacokinetics of p-aminohippurate (PAH) and inulin--the most widely used methods to assess ERPF and GFR--showed that BMI showed lower values than humans for GFR, but similar function to humans in ERPF. The pharmacokinetics of cefazolin; a widely used model drug to study kidney drug metabolizing capacity, showed greater overall renal drug elimination of BMI than of humans. These results suggested that BMI did show comparable data to human renal function.

Adult↗
PubMed2004

Activation of human coagulation system by liver-derived clotting factors of Banna minipig inbred line.

The liver synthesizes most of the coagulation factors that play a major role in arresting hemorrhage. Matching hepatic coagulation factors is an important premise in successful xenotransplantation. As a unique inbred pig, the Banna minipig inbred (BMI) animals have a huge potential value for pig-to-human xenotransplantation, due to its clear genetic background and tiny interindividual differences. Whether the coagulation factors synthesized by porcine liver can trigger human clotting pathways has not been reported. This study focused on the activities of BMI coagulant factors synthesized exclusively by the liver to activate human clotting pathways. In these experiments we prepared coagulant factors II, V, VII, X, and XII synthesized exclusively by liver from BMI and humans. The factors were used in common correction tests, added to the corresponding factor-deficient human plasma to determine prothrombin times or activated partial thromboplastin time, thereby calculating BMI and human coagulant factor activities. BMI clotting factors XII, VII, and X triggered human intrinsic, extrinsic, and common pathways, respectively. BMI clotting factors II, V, VII, X, and XII activities were 3.2-, 3.7-, 4.7-, 2.9-, and 4.5-fold as potent as those from humans.

Adult↗
PubMed2004

Study of hepatic function matching between Banna minipig inbred and humans.

As a unique inbred pig Banna minipig inbred (BMI) is potentially suitable for pig-to-human xenotransplantation due to its clear genetic background and minor interindividual differences. Previous studies of BMI have focused on immunological barriers between BMI and humans. However, a comparison of liver function between donor animals and humans is an essential premise for successful xenotransplantation. In this study, we investigated routine hepatic functions, protein electrophoresis, and drug metabolism to compare capacity of liver synthesis, metabolism, and drainage between BMI and humans. The results showed no significant differences in the concentrations of albumin and globulin synthesized in the liver (alpha1, alpha2, and beta-globulin). Serum enzyme activities in BMI were higher than those in humans, and levels of total bilirubin and direct-reacting bilirubin of BMI were lower than those of humans. In BMI, the clearance of antipyrine, a widely used model drug to study hepatic drug metabolism, was 16 times greater than that by humans, with a mean residual time of antipyrine in BMI, one-tenth of that in human. These findings suggested that BMI livers are similar to humans in albumin and alpha, beta-globulin synthesis, but stronger in bilirubin elimination, enzyme activity, and drug metabolism. BMI livers may have stronger functions compared with those of humans. No incompatibility was identified in hepatic function between BMI and humans.

Adult↗
PubMed2004

[Another look at the implications of the DCCT study].

The fundamental role of good metabolic control has been demonstrated in type 1 and type 2 diabetes. Nevertheless, clinicians often wonder why some patients under good metabolic control develop complications while others remain free of such complications, despite a poorly controlled disease. The present study revisited material from the DCCT database, by classifying the 1441 patients as being under good or poor metabolic control if their HbA1c mean level fell in the lower (HbA1c<=6.9%) or upper (HbA1c>/=9.5%) quintile of the overall distribution of mean HbA1c levels observed in the DCCT population. The impact of metabolic control and of other potential factors related to the patient and his/her disease on the development and/or deterioration of complications, in particular diabetic retinopathy and nephropathy, was assessed. Although metabolic control is the major determinant of the risk of developing diabetic retinopathy and nephropathy, the study also emphasizes the significant role of other risk factors, in particularly BMI, disease duration, micro-albuminuria, HbA1c at baseline, gender and age on such complications. It is concluded that early control of the metabolic and clinical status of diabetic patients has major consequences on the evolution of the disease. Nomograms have been proposed to help the clinician in this task.

Adolescent↗
PubMed2004

Design and performance testing of quantitative real time PCR assays for influenza A and B viral load measurement.

BACKGROUND: The antiviral effect of anti-influenza drugs such as zanamivir may be demonstrated in patients as an increased rate of decline in viral load over a time course of treatment as compared with placebo. Historically this was measured using plaque assays, or Culture Enhanced Enzyme Linked Immunosorbent Assay (CE-ELISA). OBJECTIVES: to develop and characterise real time quantitative PCR (qPCR) assays to measure influenza A and B viral load in clinical samples, that offer improvements over existing methods, in particular virus infectivity assays. STUDY DESIGN: The dynamic range and robustness were established for the real time qPCR assays along with stability of the assay components. Cross validation of the real time PCR assays with CE-ELISA was performed by parallel testing of both serial dilutions of three different subtypes of cultured virus and a panel of influenza positive throat swab specimens. RESULTS: the assays were specific for influenza A and B and the dynamic ranges were at least seven logs. The assay variability was within acceptable limits but increased towards the lower limit of quantification, which was 3.33 log(10) viral cDNA copies/ml of virus transport medium (ten viral RNA copies/PCR). The components of the assay were robust enough to withstand extended storage and several freeze-thaw cycles. For the real time PCR assays the limit of quantification was equivalent to the virus infectivity cut off, which equates to a 93-fold increase in sensitivity. CONCLUSION: Well characterised real time PCR assays offer significant improvements over the existing methods for measuring the viral load of strains of influenza A and B in clinical specimens.

DNA, Complementary↗
PubMed2004

Pre-emptive gene therapy using recombinant adeno-associated virus delivery of extracellular superoxide dismutase protects heart against ischemic reperfusion injury, improves ventricular function and prolongs survival.

In high-risk patients, the ideal cardiovascular gene therapy requires a strategy that provides long-term protection of myocardium against episodes of ischemic/reperfusion injury. We report the development of an efficient, long-lasting pre-emptive gene therapy strategy in a rat model of ischemic-reperfusion (I/R) injury of heart. At 6 weeks prior to myocardial injury, the human extracellular superoxide dismutase (Ec-SOD) gene was delivered by direct intramyocardial injections, using a recombinant adeno-associated virus vector. Significant myocardial protection was documented by the decrease in infarct size at 24 h post I/R, improved left ventricular function at 7 weeks postinjury, and enhanced long-term survival in the SOD treated group. This concept of preinjury delivery and 'pre-emptive' gene therapy via the expression of a secreted protein that renders paracrine therapeutic action can be an effective strategy for organ protection against future injury.

Animals↗
PubMed2004

Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer.

BACKGROUND: The type IV collagenases/gelatinases matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) play an important role in cancer invasion and metastasis. In the present study, we measured the expression of mRNAs and enzymatic activities of MMP-9 and -2 in prostate tissues and serum samples from men with or without prostate cancer. METHODS: A total of 44 tissue samples (three from healthy volunteers, 21 from patients with benign prostate hyperplasia, 10 from patients with localized prostate cancer and 10 from patients with metastatic disease) and 71 serum samples were collected (20 from healthy volunteers, 26 from patients with benign prostatic hyperplasia, 10 from patients with localized cancer, 15 from patients with metastatic cancer). The level of mRNA for MMP-2 and -9 was determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The enzymatic activity of MMPs was determined by zymography. RESULTS: Expression of MMP-9 mRNA was significantly higher in malignant than in nonmalignant prostate tissues (P < 0.001), while no significant difference of MMP-2 expression was detected in different prostate tissues. Results of zymography showed that there was significant difference in the enzymatic activity of MMP-9, but not MMP-2, among normal prostate, BPH, localized and metastatic prostate cancer tissues, serum samples (P < 0.05). The active form of MMP-2, with a molecular mass of 62 kDa, was detected in normal prostate, BPH and prostate cancer tissues, but not in the serum samples. Moreover, there was a significant difference in the ratio of the active form (62 kDa) and proform (72 kDa) of MMP-2 among normal, BPH and prostate cancer tissues. This ratio was further increased in metastatic prostate cancer tissues. CONCLUSION: The activity of MMP-9 and the ratio of active form/proform of MMP-2 are associated with the progression and metastasis of prostate cancer.

Adult↗
PubMed2004

Cooperation between Drosophila flies in searching behavior.

In Drosophila melanogaster food search behaviour, groups of flies swarm around and aggregate on patches of food. We wondered whether flies explore their environment in a cooperative way as interactions between individual flies within a population might influence the flies' ability to locate food sources. We have shown that the food search behavior in the fruit fly Drosophila is a two-step process. Firstly, 'primer' flies search the environment and randomly land on different food patches. Secondly, the remaining group of flies move to the most favorable food source and aggregate there. We call this a 'search-aggregation' cycle. Our data demonstrate that flies do not individually assess all available food resources. Rather, social interactions between flies appear to affect their choice of a specific food patch. A genetic analysis of this 'search-aggregation' behavior shows that flies carrying mutations in specific genes (for example, the dunce (dnc) gene which codes for a phosphodiesterase) were defective in this search-aggregation behavior when compared to normal flies. Future investigations of the neuronal signaling involved in this behavior will help us to understand the complexities of this aspect of Drosophila social behaviour.

Animals↗
PubMed2004

Evaluation of sICAM-1, sVCAM-1, and sE-Selectin levels in patients with metastatic breast cancer receiving high-dose chemotherapy.

Soluble forms of some cell adhesion molecules (CAM), sICAM-1, sVCAM-1, and sE-selectin, are elevated in the sera and plasma of patients with inflammation, arthritis, diabetes, and cancer. Increased levels of these soluble molecules in patients with cancer have been shown to correlate with disease progression and survival. This suggests that increased expression of the soluble forms of CAMs may play an important role in cancer cell growth and metastasis and may be prognostic and/or predictive of malignant disease. In this retrospective study, we assessed the clinical significance of sICAM-1, sVCAM-1, and sE-selectin in 95 patients with metastatic breast cancer enrolled in clinical trials of high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). The significance of soluble HER-2 (sHER-2) and sFAS status, determined in previous studies for this group of patients, was also included in this analysis. Univariate analysis showed that sICAM-1, sVCAM-1, sFas, sHER-2 positive status, and the presence of liver metastases were significant prognostic factors for both progression-free survival (PFS) and overall survival (OS) in the total patient group. In multivariable analysis, HER-2 and sFAS were shown to be independent prognostic factors for PFS and OS. Within the various treatment groups examined, sICAM-1 was a prognostic factor for clinical outcome for patients with metastatic breast cancer enrolled in trials with cyclophosphamide- and carboplatin-based or vinblastine-based HDC, but not in trials with paclitaxeland cyclophosphamide-based HDC.

Adult↗
PubMed2004

A new genomic duplication syndrome complementary to the velocardiofacial (22q11 deletion) syndrome.

Fluorescence in situ hybridization (FISH) analysis can reveal undetected chromosomal rearrangements. We report a patient with cleft palate, hydronephrosis, and minor dysmorphic features, including low-set posteriorly rotated ears, down-slanting palpebral fissures, mandibular micrognathia, and brachymesophalangia. Routine chromosome analysis identified no abnormality of chromosome 22; FISH analysis with the TUPLE1 probe disclosed an interstitial duplication of 22q11.2. FISH analysis did not reveal the duplication on the initial testing of metaphase chromosomes, although, on review, the area was brighter on one chromosome in each metaphase spread. FISH analysis of interphase cells showed three TUPLE1-probe sites with two chromosome-specific identification probes in each cell. Family history showed two older full siblings, a brother with behavior problems, oppositional defiant disorder, and learning problems and a sister with hydronephrosis and mild delays. The father and both siblings had similar facial features, and all three had the same interstitial duplication of the TUPLE1 probe. This family illustrates the novel complementary duplication syndrome of the velocardiofacial syndrome, which adds it to the expanding list of genomic deletion/duplication syndromes. The laboratory results further show the utility and need for careful analysis of interphase cells even in samples where good quality metaphases are available.

Abnormalities, Multiple↗
PubMed2004

Additive effects of leflunomide and tacrolimus in prevention of islet xenograft rejection.

Leflunomide is a low molecular weight immunosuppressive drug which inhibits the enzymes dehydroorotate dehydrogenase and protein tyrosine kinase, both of which are important components in the immune response. As the mechanisms of action of leflunomide and tacrolimus are different, we postulated an additive or synergistic effect of the two drugs and investigated the effects of leflunomide alone, or in combination with a suboptimal dose of tacrolimus, on xenogeneic islet transplantation in a rat-to-mouse model. A total of 1200-1500 rat islets were transplanted under the left kidney capsule of streptozotocin-induced diabetic BALB/c mice. The median survival time (MST) of the untreated group was 6 days. Leflunomide at 5, 10 and 20 mg/kg/d administrated for 10 days significantly prolonged MST to 10, 16 and 20 days. A dose of tacrolimus (2 mg/kg/d) was associated with a graft survival of 9 (range 6-12) days; most grafts rejected during ongoing therapy. When tacrolimus (2 mg/kg/d) was combined with leflunomide (10 mg/kg/d), the survival time of the islet xenografts was increased further to 22 days, significantly longer than with leflunomide or tacrolimus alone. In summary, our findings demonstrate that leflunomide prolonged xenogeneic islet graft survival, and that its immunosuppressive effect was improved when combined with tacrolimus.

Animals↗
PubMed2004

Identification of mariner elements from house flies (Musca domestica) and German cockroaches (Blattella germanica).

Full-length mariner elements were isolated and sequenced from house flies (Musca domestica) and German cockroaches (Blattella germanica). The amino acid sequence of the house fly mariner element (accession number: AF373028) showed 99.5% identity with Mos1 and peach elements, whereas the German cockroach mariner element (accession number: AF355143) showed 98.8% and 99.8% identity, respectively. Sequence analysis revealed that the mariner elements in house flies and German cockroaches differed from the active Mos1 mariner element by seven and 15 nucleotides, respectively. Four essential nucleotide substitutions at positions 64, 154, 305, and 1203, which have been proposed to contribute to the loss of activity of the inactive elements, were detected in the German cockroach mariner element. In contrast, although the mariner element in house flies contained substitutions at positions 64, 154, and 305, it retained T at position 1203, identical to active mariner elements. Mariner is present in approximately eight copies in the German cockroach genome.

Amino Acid Sequence↗