Biomedical subjects

M Zhang

Publications and source records attributed to M Zhang.

At least 595 records · Page 33Linked to original sources

PubMed1998

Cervicothalamic tract termination: a reexamination and comparison with the distribution of monoclonal antibody Cat-301 immunoreactivity in the cat.

The distribution of cervicothalamic tract (CTT) terminations, labeled with anterogradely transported tracers (WGA-HRP or biotinylated dextran amine) injected into the lateral cervical nucleus of cats, was compared with the distribution of immunoreactivity for a cell-surface antigen detected with the monoclonal antibody Cat-301. The most abundant CTT termination is present in the ventrobasal complex (VB), mainly in its lateral part (VPL) and only sparsely in its medial part (VPM). In the VPL, the CTT preferentially terminates in a Cat-301-sparse peripheral rim of the nucleus and in between its lateral and medial subdivisions (VPLI and VPLm). CTT terminations are sparse in the central Cat-301-dense parts of the VPL. In the ventral periphery of VB (VBvp), situated in between the VPL/VPM and the external medullary lamina, thin CTT fibers with spaced varicosities is seen among the large fibers of passage. The VBvp is essentially devoid of Cat-301 immunoreactivity. Scattered clusters of CTT termination are also seen caudal and dorsal to the VB in the medial division of the posterior complex (POm), which is virtually devoid of Cat-301 immunoreactivity. In the caudal thalamus, dense and focused CTT termination is present in the medial extension of the magnocellular medial geniculate nucleus (MGmc) but absent from its main lateral part. The termination in the MGmc is centered upon clusters of cells displaying dense Cat-301 immunoreactivity. The present study demonstrates previously unrecognized or unconfirmed CTT terminations in the VPM and in the VBvp, and confirm previously described projections to the VPL, POm and MGmc. The preferential termination of the CTT in the Cat-301-sparse peripheral region of the VPL demonstrates that the CTT is related to a chemically defined VPL compartment. In the light of previous data, this observation suggests that the CTT is related to one or more thalamocortical channels that are partly or completely separate from that (those) activated through the dorsal column-medial lemniscal pathway. The organization of the thalamocortical channel(s) activated through the CTT remains to be elucidated. In contrast to the termination in the VPL, CTT termination in the medial MGmc is focused to clusters of Cat-301 immunolabeled cells. The significance of this difference between CTT recipient cells in the VPL and in the MGmc is unclear.

Animals↗

PubMed1998

Shine-Dalgarno-like sequences are not required for translation of chloroplast mRNAs in Chlamydomonas reinhardtii chloroplasts or in Escherichia coli.

Initiation of translation in Escherichia coli and related eubacteria involves well-defined interactions between a conserved Shine-Dalgarno (SD) sequence immediately upstream of the initiation codon in the mRNA leader and an equally conserved anti-SD sequence at the 3' end of the 16S rRNA. SD-like sequences found in the leaders of many, but not all, mRNAs from cyanobacteria and chloroplasts are hypervariable in location, size, and base composition compared to those in E. coli, while anti-SD sequences in the respective 16S rRNAs remain highly conserved. We have examined the function of the SD-like sequences found in the leaders of four chloroplast genes of the green alga Chlamydomonas reinhardtii using replacement mutagenesis to eliminate complementarity with the anti-SD sequences and insertion of canonical SD sequences (GGAGG) at positions -9 to -5 relative to the initiation codon. Promoter-leader regions of the atpB, atpE, rps4, and rps7 genes representing the diversity of chloroplast SD-like sequences were fused to aadA and uidA reporter genes encoding spectinomycin resistance and GUS activity respectively. Analysis of chloroplast transformants of C. reinhardtii and transformants of E. coli carrying the wild-type and mutant reporter constructs revealed that mutagenic replacement of the putative SD sequences had no effect on the expression of either the aadA or uidA reporter genes. Chloroplast transformants with the canonical SD sequence also showed no differences in reporter gene expression, whereas expression of the reporter genes was increased by 10 to 30% in the E. coli transformants. Collectively our results suggest that even though SD-dependent initiation predominates in E. coli, this bacterium also has the capacity to initiate translation by an SD-independent mechanism. In contrast, plant chloroplasts, and very probably their cyanobacterial ancestors, appear to have adopted the SD-independent mechanism for translational initiation of most mRNAs.

Animals↗

PubMed1998

Use of proliferating cell nuclear antigen as a marker of liver regeneration after partial hepatectomy in rats.

In order to document and compare proliferating cell nuclear antigen (PCNA) mRNA and protein levels with more traditional parameters of hepatic regenerative activity in a rat model, adult male Sprague-Dawley rats (4 to 6 per group) were killed at various times up to 96 hours after 70% partial hepatectomy. At each time interval, tissue PCNA mRNA abundance and protein levels were documented (by Northern and Western blot analysis, respectively) and compared with the results of PCNA immunostaining and 3H-thymidine incorporation into hepatic DNA. Tissue PCNA protein levels were also documented in additional groups of rats 12, 24, 36, and 48 hours after sham or 30% partial hepatectomy. PCNA mRNA expression after partial hepatectomy was variable: almost undetectable at 24 hours, levels returned to baseline at 36 hours, then fell again to low levels at 96 hours. PCNA protein levels remained stable for 36 hours, increased to fourfold above baseline (p < 0.01) at 48 hours, then remained elevated for the duration of the 96-hour study. Changes in PCNA by immunostaining were similar but tended to occur somewhat earlier (significant increases being detectable at 24 hours), whereas 3H-thymidine incorporation detected the earliest increases in DNA synthesis at 12 hours and peaked at 36 hours. Peak PCNA protein levels correlated with the extent (0%, 30%, or 70%) of hepatic resection. The results indicate that PCNA protein level as determined by Western blot analysis, but not PCNA mRNA expression, correlates with PCNA immunostaining and 3H-thymidine incorporation in the regenerating liver. These findings support the use of PCNA protein determinations as an additional quantitative measure of hepatic regenerative activity after partial hepatectomy in rats.

Animals↗

PubMed1998

Endoscopic vein harvest for coronary artery bypass grafting: technique and outcomes.

BACKGROUND: The greater saphenous vein is a common conduit for coronary revascularizations. Traditional vein harvesting uses long incision(s) that can lead to significant morbidities. A minimally invasive technique has been developed that allows the harvest of much of the saphenous vein with one incision and fewer morbidities. METHODS: Our technique and outcomes on 110 patients with minimally invasive harvest (endoscopic vein harvesting) is presented. Comparisons are made with an equivalent retrospective group within the same hospital and to a smaller (n = 28) prospective group at other hospitals. RESULTS: Endoscopic vein harvesting has evolved to one above-knee incision of 3 cm length that allows for the harvest of 35 cm of vein. Harvest times were longer for endoscopic vein harvesting, showed a learning curve, and appeared to reach a baseline of 35 minutes. Incision closure times were less for the endoscopic vein harvesting group. Total skin to skin operating times for the entire cardiovascular procedure did not differ between the groups. In relatively homogeneous populations, leg infection rates did not differ, but other leg morbidities were less for the patients who underwent endoscopic vein harvesting. Hospital readmissions for leg wound care were low in both groups although the number of office visits required for leg care was higher for patients undergoing traditional vein harvesting. Pain perception by the patients was much less for the endoscopic vein harvesting and remained lower for up to 4 weeks. CONCLUSIONS: Although endoscopic vein harvesting is a relatively new procedure, it is safe, effective, and less painful for the patient and carries fewer morbidities.

Coronary Artery Bypass↗

PubMed1998

Characterization of ethyl (3-quinuclidinyl) acetate (EQA) as a ligand for acetylcholine receptors.

Recent studies suggest that neuronal nicotinic acetylcholine receptors (nAChRs) may play a role in several CNS disorders and that subtype selective nicotinic ligands may be useful in the treatment of these disorders. Ethyl (3-quinuclidinyl)acetate (EQA) is a bulky, reverse-ester analog of ACh, that produces signs of cholinergic stimulation that may be nicotinic in origin The objective of the present study was to further evaluate EQA as a potential cholinergic ligand. Behavioral studies, smooth muscle assays, and radioligand binding assays were performed on this novel ligand. The effects of EQA on blood pressure and acetylcholinesterase activity were also evaluated. The results of the study suggest that EQA is an agonist at peripheral nicotinic acetylcholine receptors and may have antagonist properties at central nicotinic receptors.

Acetylcholine↗

PubMed1998

Metabolism of cystathionine, N-monoacetylcystathionine, perhydro-1,4-thiazepine-3,5-dicarboxylic acid, and cystathionine ketimine in the liver and kidney of D,L-propargylglycine-treated rats.

Experimental cystathioninuria was induced by injection of D,L-propargylglycine in rats. The novel cystathionine metabolites, N-monoacetylcystathionine (NAc-cysta), perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), and cystathionine ketimine (CK), were identified previously in the urine of patients with cystathioninuria and D,L-propargylglycine-treated rats. In this study, we identified these compounds in the liver and kidney of D,L-propargylglycine-treated rats using liquid chromatography-mass spectrometry with an atmospheric pressure chemical ionization interface system (LC/APCI-MS) and an amino acid analyzer. The metabolism of these compounds in the liver and kidney of D,L-propargylglycine-treated rats was also studied. PHTZDC, NAc-cysta, and CK were accumulated in the rat tissues in proportion to the content of cystathionine after D,L-propargylglycine administration. The concentrations of these compounds in the liver were higher than those in the kidney, and these compounds reached maxima earlier in the liver than in the kidney.

Alkynes↗

PubMed1998

Proteins and cells on PEG immobilized silicon surfaces.

Silicon surfaces were modified by covalent attachment of a self-assembled (SA) polyethylene glycol (PEG) film. Adsorption of albumin, fibrinogen, and IgG to PEG immobilized silicon surfaces was studied by ellipsometry to evaluate the non-fouling and non-immunogenic properties of the surfaces. The adhesion and proliferation of human fibroblast and Hela cells onto the modified surfaces were investigated to examine their tissue biocompatibility. Coated PEG chains showed the effective depression of both plasma protein adsorption and cell attachment to the modified surfaces. The mechanisms accounting for the reduction of protein adsorption and cell adhesion on modified surfaces were discussed.

Animals↗

PubMed1998

The correlation of telomerase and IL-10 with leukemia transformation in a mouse model of chronic lymphocytic leukemia (CLL).

Telomerase activity is upregulated in activated and malignant lymphocytes. We studied the correlation of telomerase and IL-10 to leukemia transformation in the NZB mouse model of human chronic lymphocytic leukemia (CLL). Telomerase levels increased from early to late leukemic stages, likewise IL-10 gene expression levels increased with the leukemic progression. The inverse relationship of telomerase and IL-10 levels to the survival of NZB mice was also established. Our data suggested that telomerase and IL-10 were involved in transformation in the murine model of CLL and the detection of telomerase activities might be of value in the prediction of CLL progression.

Age Factors↗

PubMed1998

Persistently poor outcomes of undetected major depression in primary care.

Despite its relevance for quality care initiatives, the field of psychiatry has little scientific knowledge regarding the course of current major depression when primary care patients with the disorder remain undetected. Using statewide telephone screening, we identified and followed 98 adults with current major depression who made one or more visits to a primary care physician during the 6 months following baseline. Thirty-two percent of primary care patients with current major depression remained undetected for up to 1 year. Almost half of undetected patients developed suicidal ideation. Less than one-third of undetected patients made a visit during the month they reported their worst symptoms. Fifty-three percent of undetected patients reported five or more current symptoms at 1 year follow-up. Primary care patients with undetected major depression report persistently poor outcomes. Comparison of outcomes with detected patients suggests that quality improvement efforts directed at improving detection without improving management of detected patients may not improve outcomes.

Adult↗

PubMed1998

Expression genetics: a different approach to cancer diagnosis and prognosis.

Expression genetics is a new approach to the identification of cancer-related genes. Instead of studying gene mutations at the genome level, it focuses on the investigation of heredity at the RNA level. By isolating genes whose expression is up or down regulated in cancers, expression geneticists study their function in the context of gene regulation. A major goal of expression genetics in cancer is to correct gene expression in tumors by the application of potential therapeutic agents.

Gene Expression Regulation, Neoplastic↗

PubMed1998

The effects of ethanol and gamma aminobutyric acid alone and in combination on hepatic regenerative activity in the rat.

BACKGROUND/AIMS: Both ethanol and gamma aminobutyric acid (GABA) have been reported to inhibit hepatic regenerative activity in the rat. Because alcoholic beverages contain appreciable amounts of GABA, we documented whether the inhibitory effects of alcohol on the liver are derived from ethanol alone or the combination of ethanol plus GABA. METHODS: Adult male Sprague-Dawley rats (n=6/group) were treated with either ethanol (3 g/kg), GABA (500 mg/kg) or ethanol plus GABA (3 kg and 500 mg/kg, respectively), beginning 1 h prior to a 70% partial hepatectomy and continued every 4 h thereafter for a total of 24 h. Rats were then sacrificed and hepatic regenerative activity was documented by 3H-thymidine incorporation into hepatic DNA. RESULTS: DNA synthesis was significantly inhibited by ethanol (-37%, p<0.005) and GABA (-19%, p<0.05). Maximum inhibition was achieved with the combination of ethanol plus GABA (-52%, p<0.001). To determine whether the additive effects of ethanol plus GABA were mediated by ethanol-induced enhancement of hepatic GABA(A) receptor activity, additional rats (n=6/group) receiving the combination of ethanol plus GABA were pre-treated with a single injection of either ciprofloxacin (50 mg/kg), a GABA(A) receptor antagonist, or an equal volume of saline. In these experiments, ciprofloxacin pre-treatment prevented the inhibitory effects of the ethanol plus GABA combination. CONCLUSIONS: The results of this study indicate that the combination of ethanol plus GABA has a greater inhibitory effect on hepatic DNA synthesis following partial hepatectomy than ethanol alone. The clinical implication of this finding is that, when standardized for ethanol content, not all alcoholic beverages would be expected to have the same inhibitory effect on hepatic regeneration.

Animals↗

PubMed1998

Cloning and characterization of glial cell line-derived neurotrophic factor receptor-B: a novel receptor for members of glial cell line-derived neurotrophic factor family of neurotrophic factors.

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with diverse biological functions. Signal transduction of GDNF is mediated by binding to a glycosyl-phosphatidylinositol (GPI)-linked receptor GDNFR-alpha and activation of c-RET tyrosine kinase. The recent discovery of a new GDNF homolog neurturin raises the possibility that multiple receptors exist for the members in the GDNF family. Here we report isolation of the gene encoding a new receptor called GDNFR-beta. Sequence analysis indicated that GDNFR-beta is also a GPI-linked protein, with 47% identity to GDNFR-alpha. The GDNFR-beta transcript was preferentially expressed in the brain, spleen and lung, but moderate levels of GDNFR-beta mRNA were also found in kidney and the entire gastrointestinal track. In situ hybridization revealed high expression levels in the entorhinal cortex and olfactory bulb, followed by cortex, septum, inferior and superior colliculus, and zona inserta. A laminar pattern of expression was detected in layer III of the cortex. Treatment with GDNF of PC12 cells transfected with the GDNFR-beta gene activated mitogen-activated protein kinase (MAPK) and elicited neurite outgrowth. GDNFR-alpha and GDNFR-beta together form a new family of GPI-linked receptors for GDNF-like molecules.

Amino Acid Sequence↗

PubMed1998

The non-synaptic expression of transforming growth factor-beta 2 is neurally regulated and varies between skeletal muscle fibre types.

In adult skeletal muscles, transforming growth factor-beta 2 is restricted to the postsynaptic domain of the neuromuscular junction. The various putative functions of this transforming growth factor-beta 2 predict different patterns of transforming growth factor-beta 2 expression in denervated muscles. We therefore denervated rat tibialis anterior, extensor digitorum longus and soleus muscles and examined the expression of transforming growth factor-beta 2 using semi-quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. Denervation up-regulated transforming growth factor-beta 2 expression extrasynaptically with little or no effect on synaptic expression. The up-regulation was detectable by one day, had become significant by three days and remained elevated for at least two weeks. This proves that the transforming growth factor-beta 2 associated with the neuromuscular junction is not under neural control and is consistent with transforming growth factor-beta 2 being a trophic factor for motoneurons. This pattern of transforming growth factor-beta 2 expression is similar to that described for other proteins associated with the neuromuscular junction, notably the acetylcholine receptor subunit genes. However, in contrast to the acetylcholine receptor subunit genes, the extent of up-regulation of transforming growth factor-beta 2 varied between fibre types, with the glycolytic IIB fibres being less affected than other fibre types.

Animals↗

PubMed1998

Three-step tumor imaging with biotinylated monoclonal antibody, streptavidin and 111In-DTPA-biotin.

The purpose of this study was to test the three-step targeting of tumors in mice using biotinylated antibody, streptavidin and radiolabeled biotin. Nude mice bearing subcutaneous LS180 human colon cancer xenografts were intravenously administered with 200 microg of the biotinylated anti-Tn monoclonal antibody MLS128, and 2 days later they got intravenous injection of 50 microg of streptavidin. They were intravenously injected 1, 4 or 7 days later with 0.5 microg of 111In-diethylenetriamine pentaacetic acid (DTPA)-biotin. The tumor uptake, determined 2 h later, was 1.4, 0.5 and 0.6% injected dose/gram of tissue (ID/g), respectively, and the blood radioactivity was 1.0, 0.2 and 0.2% ID/g, respectively. When the interval between the streptavidin and radiolabeled biotin injections was prolonged from 1 day to 7 days, the tumor-to-blood ratio 2 h after injection of 111In-labeled biotin increased from 1.5 to 4.0. Clear tumor images were obtained as early as 2 h after injection of radiolabeled biotin. In conclusion, these preliminary data suggested that the three-step method using the streptavidin-biotin system would be applicable in an experimental mouse tumor model and provides images of tumors rapidly and clearly after injection of radiolabeled biotin.

Animals↗

PubMed1998

Effect of administration route and dose of streptavidin or biotin on the tumor uptake of radioactivity in intraperitoneal tumor with multistep targeting.

The effect of the administration route and dose of streptavidin or biotin on the biodistribution of radioactivity in multistep targeting was studied in nude mice bearing intraperitoneal (IP) colon cancer xenograft. The multistep targeting included a two-step method using biotinylated antibody and radiolabeled streptavidin and a three-step method with radiolabeled biotin based on the two-step method. A monoclonal antibody, MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected intravenously (i.v.) or i.p. in nude mice bearing human colon cancer LS180 IP xenografts for pretargeting. In the two-step method, i.p.-injected streptavidin showed a higher tumor uptake and tumor-to-nontumor ratios than i.v.-injected streptavidin regardless of administration route of pretargeting. The tumor uptake of radiolabeled streptavidin was increased with a high dose of biotinylated antibody pretargeting, but decreased with an increasing dose of streptavidin. In the three-step targeting, i.p. injection also gave a higher tumor uptake of radiolabeled biotin than i.v. injection. In conclusion, i.p. administration of radiolabeled streptavidin or biotin resulted in more efficient IP tumor targeting with the multistep methods.

Animals↗

PubMed1998

Increased streptavidin uptake in tumors pretargeted with biotinylated antibody using a conjugate of streptavidin-fab fragment.

Radiolabeled streptavidin accumulated in tumors pretargeted with biotinylated antibody. However, the absolute delivery of radioactivity was limited. To increase the tumor uptake of radioactivity further, we conjugated streptavidin with a mouse monoclonal antibody (MAb) fragment, OST6Fab, which recognizes antigen on human osteosarcoma. Another mouse MAb, OST7, which also reacts with the same tumor but recognizes an epitope different from the OST6 epitope, was biotinylated. The radioiodinated streptavidin-OST6Fab conjugate was administered to tumor-bearing mice after the biotinylated OST7 pretargeting. The uptake of the conjugate in tumors pretargeted with the biotinylated antibody was significantly higher than that of streptavidin and that of the conjugate of streptavidin and irrelevant Fab fragment. Renal uptake of radioactivity was decreased markedly, and the blood clearance was retarded by the conjugation with Fab fragment. In conclusion, the conjugate of streptavidin with specific Fab fragment increased the accumulation of radioactivity in tumors pretargeted with biotinylated antibody.

Animals↗

PubMed1998

Terminal differentiation of human breast cancer through PPAR gamma.

We have previously demonstrated that PPAR gamma stimulates the terminal differentiation of adipocyte precursors when activated by synthetic ligands, such as the antidiabetic thiazolidinedione (TZD) drugs. We show here that PPAR gamma is expressed at significant levels in human primary and metastatic breast adenocarcinomas. Ligand activation of this receptor in cultured breast cancer cells causes extensive lipid accumulation, changes in breast epithelial gene expression associated with a more differentiated, less malignant state, and a reduction in growth rate and clonogenic capacity of the cells. Inhibition of MAP kinase, shown previously to be a powerful negative regulator of PPAR gamma, improves the TZD ligand sensitivity of nonresponsive cells. These data suggest that the PPAR gamma transcriptional pathway can induce terminal differentiation of malignant breast epithelial cells and thus may provide a novel, nontoxic therapy for human breast cancer.

Breast Neoplasms↗

PubMed1998

Clinical investigation of the pressure and shear stress on the trans-tibial stump with a prosthesis.

A system for measuring pressures and bi-axial shear stresses at the body support interfaces has been developed. This system has been used, in five unilateral trans-tibial amputees, to investigate the stresses at multiple points on the residual limb and prosthetic socket interface during standing and walking. The subjects investigated regularly used a patellar-tendon-bearing socket. The maximum peak pressure at the measured points was 320 kPa over the popliteal area during walking. The maximum shear stress was 61 kPa over the medial tibia area. Variable wave-forms of stress during walking were observed at the different measured points. The influence of the angular alignment on the stresses was investigated on one subject. It was found that a miss-alignment of +/- 8 degrees produced a change in peak longitudinal shear stress of between 8% and 11.5%.

Adult↗