Biomedical subjects

L Wang

Publications and source records attributed to L Wang.

At least 361 records · Page 20Linked to original sources

PubMed2001

Presence of gonadotropin-releasing hormone (GnRH) and its mRNA in rat pancreas.

Gonadotropin-releasing hormone (GnRH) has been reported to exist in many non-hypothalamic tissues, such as the placenta, gonads, and mammary glands, while there still have been no reports concerning the existence and expression of GnRH in the mammalian digestive system. Immunocytochemistry and in situ hybridization results show that GnRH molecule and GnRH mRNA are both exclusively distributed in exocrine pancreas, and RT-PCR result further proves that GnRH transcription units do exist in the pancreas, which possess the same sequence as the hypothalamus GnRH mRNA. Quantitative analysis indicates that mRNA levels in rat pancreas remain at a low level (less than 10% of that in hypothalamus) without sexual or developmental difference. This is the first report suggesting the existence and gene expression of GnRH in rat pancreas.

Animals↗

PubMed2001

Delineation of functional regions within the subunits of the Saccharomyces cerevisiae cell adhesion molecule a-agglutinin.

a-Agglutinin from Saccharomyces cerevisiae is a cell adhesion glycoprotein expressed on the surface of cells of a mating type and consists of an anchorage subunit Aga1p and a receptor binding subunit Aga2p. Cell wall attachment of Aga2p is mediated through two disulfide bonds to Aga1p (Cappellaro, C., Baldermann, C., Rachel, R., and Tanner, W. (1994) EMBO J. 13, 4737-4744). We report here that purified Aga2p was unstable and had low molar specific activity relative to its receptor alpha-agglutinin. Aga2p co-expressed with a 149-residue fragment of Aga1p formed a disulfide-linked complex with specific activity 43-fold higher than Aga2p expressed alone. Circular dichroism of the complex revealed a mixed alpha/beta structure, whereas Aga2p alone had no periodic secondary structure. A 30-residue Cys-rich Aga1p fragment was partially active in stabilization of Aga2p activity. Mutation of either or both Aga2p cysteine residues eliminated stabilization of Aga2p. Thus the roles of Aga1p include both cell wall anchorage and cysteine-dependent conformational restriction of the binding subunit Aga2p. Mutagenesis of AGA2 identified only C-terminal residues of Aga2p as being essential for binding activity. Aga2p residues 45-72 are similar to sequences in soybean Nod genes, and include residues implicated in interactions with both Aga1p (including Cys(68)) and alpha-agglutinin.

Agglutinins↗

PubMed2001

beta-Adrenergic agonists increase phosphorylation of elongation factor 2 in cardiomyocytes without eliciting calcium-independent eEF2 kinase activity.

The beta-adrenergic agonist isoproterenol increased the phosphorylation of elongation factor eEF2 in ventricular cardiomyocytes from adult rats (ARVC). Phosphorylation of eEF2 inhibits its activity, and protein synthesis was inhibited in ARVC concomitantly with increased eEF2 phosphorylation. eEF2 kinase activity in ARVC extracts was completely dependent upon Ca(2+)/calmodulin. In contrast to other cell types, however, treatments designed to raise intracellular cAMP failed to induce Ca(2+)/calmodulin-independent activity. Instead, they increased maximal eEF2 kinase activity. Similar data were obtained when partially purified ARVC eEF2 kinase was treated with cAMP-dependent protein kinase in vitro. These data suggest that ARVC possess a distinct isoform of eEF2 kinase.

Adrenergic beta-Agonists↗

PubMed2001

Hypermethylation at 9q32-33 tumour suppressor region is age-related in normal urothelium and an early and frequent alteration in bladder cancer.

Transcriptional silencing by CpG island hypermethylation of gene regulatory regions is one mechanism for inactivation of tumour suppressor genes. Chromosome 9q deletion is frequently found in transitional cell carcinoma (TCC) of the bladder and upper urinary tract and one of the putative tumour suppressor loci has been mapped to 9q32-33. A gene designated as DBCCR1 was identified in the candidate region and its mRNA expression is thought to be suppressed by hypermethylation. To understand the role of hypermethylation in TCC, we evaluated the methylation status of 20 CpG sites of the DBCCR1 5'-CpG island region in a total of 69 tumours from 45 patients, 21 normal urothelial specimens, and six bladder cancer cell lines. Aberrant hypermethylation levels were found in 36 (52%) of 69 tumours without any association with tumour grade or stage. Methylation was weakly detected in the normal urothelium in association with ageing. Although recurrent tumours tended to have higher methylation levels than the initial tumours, the methylation pattern was mostly maintained between multifocal TCCs in individual patients. The results suggest that hypermethylation of the DBCCR1 region is one of the earliest alterations in the development of TCCs and there may be an age-related hypermethylation-based field defect in normal urothelium. Methylator or methylation-resistant phenotype seems to be maintained during multifocal development or recurrence of most TCCs.

Adolescent↗

PubMed2001

Graft function and survival depend primarily on host factors in compromised recipient models of orthotopic liver transplantation in the rat.

BACKGROUND: Experimental models of liver transplantation use normal recipients, although most patients undergoing liver transplantation suffer from acute or chronic liver failure. This study was designed to analyze the outcome of orthotopic liver transplantation in compromised rat hosts. METHODS: Recipient animals were either rats with D-galactosamine-induced acute or rats with chronic liver failure secondary to common bile duct ligation. Liver damage was evaluated by monitoring enzymes, bilirubin, ammonia levels, prothrombin, thrombin time, and cytokines. In vivo function of hepatocytes and sinusoidal endothelial cells were evaluated by indocyanine green and hyaluronic acid uptake. Transplantation was performed in normal, acute, and chronic liver failure rats at different time points using either freshly harvested or cold-preserved syngeneic livers. RESULTS: Survival with fresh grafts decreased significantly when transplants were performed 48 hr after the induction of acute liver failure. No rats with acute liver failure survived transplantation with grafts stored for 12 or 24 hr although in chronic failure survival was more 80%. Survival of acute liver failure rats receiving 6 hr preserved grafts was 16.6% compared with 83.3% observed with fresh grafts transplanted at the same time point after D-galactosamine injection. Elevated tumor necrosis factor-alpha and interleukin-1beta levels as well as impaired sinusoidal endothelial cell function were detected in acute liver failure rats with 6 h preserved grafts. CONCLUSION: These results suggest that preoperative status and different host factors have a significant effect on outcome and graft function after liver transplantation in rats.

Animals↗

PubMed2001

CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B.

The caspase recruitment domain (CARD) is a protein-binding module that mediates the assembly of CARD-containing proteins into apoptosis and NF-kappaB signaling complexes. We report here that CARD protein 11 (CARD11) and CARD protein 14 (CARD14) are novel CARD-containing proteins that belong to the membrane-associated guanylate kinase (MAGUK) family, a class of proteins that functions as molecular scaffolds for the assembly of multiprotein complexes at specialized regions of the plasma membrane. CARD11 and CARD14 have homologous structures consisting of an N-terminal CARD domain, a central coiled-coil domain, and a C-terminal tripartite domain comprised of a PDZ domain, an Src homology 3 domain, and a GUK domain with homology to guanylate kinase. The CARD domains of both CARD11 and CARD14 associate specifically with the CARD domain of BCL10, a signaling protein that activates NF-kappaB through the IkappaB kinase complex in response to upstream stimuli. When expressed in cells, CARD11 and CARD14 activate NF-kappaB and induce the phosphorylation of BCL10. These findings suggest that CARD11 and CARD14 are novel MAGUK family members that function as upstream activators of BCL10 and NF-kappaB signaling.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Three distinct types of GnRH receptor characterized in the bullfrog.

It has been proposed recently that two types of GnRH receptors (GnRHR) exist in a particular species. Here we present data demonstrating that at least three types of GnRHR are expressed in a single diploid species, the bullfrog. Three different cDNAs, encoding distinct types of bullfrog GnRHR (bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3), were isolated from pituitary and hindbrain of the bullfrog. BfGnRHR-1 mRNA was expressed predominantly in pituitary, whereas bfGnRHR-2 and -3 mRNAs were expressed in brain. The bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3 proteins have an amino acid identity of approximately 30% to approximately 35% with mammalian GnRHRs and approximately 40% to approximately 50% with nonmammalian GnRHRs. Interestingly, bfGnRHR-2 has an 85% amino acid homology with Xenopus GnRHR. Less than 53% amino acid identity was observed among the three bfGnRHRs. All isolated cDNAs encode functional receptors because their transient expression in COS-7 cells resulted in a ligand-dependent increase in inositol phosphate production. Notably, all three receptors exhibited a differential ligand selectivity. For all receptors, cGnRH-II has a higher potency than mGnRH. In addition, salmon GnRH also has a strikingly high potency to stimulate all three receptors. In conclusion, we demonstrated the presence of three GnRHRs in the bullfrog. Their expression in pituitary and brain suggests that bfGnRHRs play an important role in the regulation of reproductive functions in the bullfrog.

Amino Acid Sequence↗

PubMed2001

Combined effect of all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia cells in vitro and in vivo.

All-trans retinoic acid (tRA) and arsenic trioxide (As(2)O(3)) induce non-cross-resistant complete clinical remission in patients with acute promyelocytic leukemia with t(15;17) translocation and target PML-RARalpha, the leukemogenic protein, by different pathways suggesting a possible therapeutic synergism. To evaluate this possibility, this study examined the effect of As(2)O(3) on tRA-induced differentiation and, conversely, the effect of tRA on As(2)O(3)-induced apoptosis. As(2)O(3) at subapoptotic concentrations (0.5 microM) decreased tRA-induced differentiation in NB4 cells but synergized with atRA to induce differentiation in tRA-resistant NB4 subclones MR-2 and R4 cells as measured by nitroblue tetrazolium reduction and tRA-inducible genes (TTGII, RARbeta, RIG-E). tRA cleaved PML-RARalpha into distinct fragments in NB4 but not in tRA-resistant MR-2 or R4 cells, whereas As(2)O(3) completely degraded PML-RARalpha in all 3 cell lines. As(2)O(3)-induced apoptosis was decreased by tRA pretreatment of NB4 cells but not of R4 cells and was associated with a strong induction of Bfl-1/A1 expression, a Bcl-2 protein family member. Severe combined immunodeficient mice bearing NB4 cells showed an additive survival effect after sequential treatment, but a toxic effect was observed after simultaneous treatment with tRA and As(2)O(3). These data suggest that combined As(2)O(3) and tRA treatment may be more effective than single agents in tRA-resistant patients. Although in vitro data do not always translate to in vivo response, toxicity and potential drug antagonism may be diminished by decreasing the concentration of As(2)O(3) when given at the same time with therapeutic levels of tRA.

Animals↗

PubMed2001

Depth of penetration of scanning laser Doppler flowmetry in the primate optic nerve.

OBJECTIVES: To estimate the measuring depth of the blood flow and to establish the vascular contributions to these measurements with scanning laser Doppler flowmetry (SLDF) of the primate anterior optic nerve. METHODS: Optic nerve blood flow in each eye of 8 monkeys was measured using SLDF before and following surgical occlusion of the central retinal artery (n = 4) or posterior ciliary arteries (n = 4). The regional blood flow in both eyes was determined using a nonradioactive microsphere method. RESULTS: The blood flow in the nerve fiber layer (NFL), including the prelaminar region, was measured with microspheres after central retinal artery occlusion; it was significantly reduced (-83%) with no significant change in the combined laminar and retrolaminar regions. The blood flow measured with SLDF had a 51% reduction. After posterior ciliary artery occlusion, the blood flow in the NFL was measured with microspheres and was not significantly affected (+2%); neither was that measured with SLDF (-12%). However, there was a 51% reduction in the laminar and retrolaminar regions when microspheres were used. The mean +/- SD tissue thickness of the NFL was 359 +/- 16 microm and 353 +/- 54 microm in each group. CONCLUSIONS: Scanning laser Doppler flowmetry measures blood flow principally in the NFL of the anterior optic nerve, which is primarily supplied by the central retinal artery. Blood flow in the laminar and retrolaminar regions makes a small contribution to the SLDF measurement, with an NFL thickness between 300 and 400 microm. CLINICAL RELEVANCE: Scanning laser Doppler flowmetry is used for the noninvasive evaluation of ocular microcirculation in diseases such as glaucoma. Because of the dual blood flow supply in the optic nerve and the limited penetration power of the laser, the instrument primarily measures the microcirculation on the surface of the optic nerve, which is largely supplied by the central retinal artery rather than the ciliary arteries.

Animals↗

PubMed2001

Secondary sexual characteristics in boys: estimates from the national health and nutrition examination survey III, 1988-1994.

BACKGROUND: Descriptive data on pubertal stages for a representative population of racially and ethnically diverse boys in the United States have not been published to our knowledge. OBJECTIVE: To determine at what ages boys in the United States reach each of the 5 sexual maturity stages for genital and pubic hair growth. DESIGN AND SETTING: Cross-sectional survey from the National Health and Nutrition Examination Survey III (NHANES III), 1988-1994. PARTICIPANTS: A population-based sample of 2114 boys aged 8 to 19 years representing 16 575 753 boys according to NHANES III sampling strategies. The sample included white, African American, and Mexican American boys. MAIN OUTCOME MEASURES: Sexual maturity stages for genital maturation and pubic hair growth. RESULTS: The median (equivalent mean) ages at stage 2 for pubic hair development of white, African American, and Mexican American boys were 12.0 (95% confidence interval [CI], 11.7-12.3), 11.2 (95% CI, 10.9-11.4), and 12.3 (95% CI, 12.1-12.6) years, respectively, and at stage 2 for genital growth were 10.1 (95% CI, 9.6-10.6), 9.5 (95% CI, 8.9-10.0), and 10.4 (95% CI, 9.6-11.1) years, respectively. All 3 groups were significantly taller and heavier than boys in previous NHANES reports and showed earlier genital maturation and pubic hair growth than previous studies based on Tanner staging. Statistically significant differences among the 3 racial/ethnic groups were found in the median ages of onset of pubic hair growth and genital development at stage 5 with and without controlling for height and weight, indicating an earlier age of attainment for the African American boys. CONCLUSIONS: The median (mean) ages at the onset of genital and pubic hair growth were younger than in past studies. Additional studies are required to further evaluate these findings and to explore the public health implications.

Adolescent↗

PubMed2001

Synthesis and biological investigations of 5-substituted pyrimidine nucleosides coupled to a dihydropyridine/pyridinium salt redox chemical delivery system.

The syntheses, antiviral activities, and partition coefficients (P) of 3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-coupled nucleosides are described. These novel compounds were designed in an effort to enhance the lipophilicity, and thereby the delivery to the CNS, without compromising the anti-HSV-1 activity of the parental nucleosides. We have previously reported the synthesis of 3'-O-(1-methyl-1,4-dihydropyridyl-3- carbonyl) analogs of 5-iodo-(5), 5-vinyl-(6), and (E)-5-(2-iodovinyl)-2'-deoxyuridines (7). We now report the synthesis of 5-iodo-3'-O-(1-methyl-1,4-dihydropyridyl-3- carbonyl)-5'-O-acetyl-2'-deoxyuridine (15) and 3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2'-deoxyuridine (17). Quarternization of the 3'-O-(3-pyridylcarbonyl) compounds (10,12) using iodomethane afforded the corresponding 1-methyl pyridinium salts (13,14) which were reduced with sodium dithionite to yield the corresponding 3'-O-1-methyl-1,4-dihydropyridyl-3-carbonyl compounds (15,16). The deprotection of 3'-O-(1-methyl-1,4-dihydropyridyl- 3-carbonyl)-5'-O-t-butyldimethylsilyl-2'-deoxyuridine (16) with Bu4N+F- afforded 3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2'-deoxyuridine (17). Compounds 5-7 and 15 were evaluated for their antiviral activity in vitro against HSV-1, HSV-2, HCMV, and VZV, and were found to retain anti-HSV-1, HSV-2 and VZV activity as compared to their parental nucleosides (1-3). In addition, the cellular toxicity of 3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-coupled compounds (5-7 and 15) was found to be lower than the parent nucleosides. The lipophilicity of compounds (5-7,15,17) are enhanced substantially, compared to the parent nucleosides, as indicated by an increase in corresponding P values (1-octanol-water) upon replacement of the C-3' hydroxyl by 1-methyl-1,4-dihydropyridyl-3-carbonyl moiety.

Antiviral Agents↗

PubMed2001

Allelic loss and gain, but not genomic instability, as the major somatic mutation in primary hepatocellular carcinoma.

To identify genetic abnormalities in primary hepatocellular carcinoma (HCC), we performed microsatellite analysis (MSA) on 60 Chinese HCC specimens. Utilizing a semi-quantitative MSA and 292 highly polymorphic markers spanning all 22 autosomes, we found that somatic allelic imbalance (AI) occurred frequently in HCC. To evaluate the nature of the AI, comparative genomic hybridization was performed on 20 HCC specimens. The combined use of these two methods revealed frequent allelic loss on 17p, 9p21-p23, 4q, 16q21-q23.3, 13q, 8p21-p23, and 6q24-q27, whereas there was frequent allelic gain on 1q, 17q, and 8q24. The region with the highest incidence of genomic imbalance was 17p13 (65%), followed by 9p21-p23 (55%), 4q (35-51%), 16q21-q23.3 (52%), 17p12 (49%), 13q (39-46%), 8p21-p23 (41-45%), 8q24 (41%), and 1q32 (40%). In addition, aberrations of 19p13.3, 16p13.3, 13q33-q34, 9q13-31, and 7q were reported for the first time. The presence of a close correlation of 17p13 deletion with abnormalities of some other loci implies that 17p13 could play a crucial role in oncogenesis. Interestingly, microsatellite instability was rarely seen in our patients, in contrast to that observed in European HCC samples.

Adult↗

PubMed2001

Chitosan-alginate-CaCl(2) system for membrane coat application.

Water-based formulations are preferred for membrane coat application because they do not require the use of noxious solvents. A novel aqueous chitosan-alginate-CaCl(2) system was evaluated as a potential formulation to produce water-insoluble membranes of biodegradable polymers. Chitosan-alginate coacervates were prepared by controlled reaction of chitosan (0.25% w/v) and sodium alginate (0.25% w/v) solutions. Coherent membranes were obtained by casting and drying the coacervates suspended in aqueous CaCl(2) solutions (0.05-0.07% w/v). Increasing the calcium content did not modify membrane thickness (25-26 microm), but reduced the water vapor transmission rate from 658 to 566 g/m(2)/day, and improved the tensile strength of the membranes from 9.33 to 17.13 MPa. Differential scanning calorimetry, Fourier transform infrared spectroscopy, and elemental analyses of the chitosan-alginate coacervates indicated they were stable for up to 4 weeks of storage in distilled water at ambient temperature. Membranes of the stored coacervates required less calcium to attain maximum mechanical strength. They also had higher water vapor transmission rates than corresponding films prepared from fresh coacervates. On the basis of the properties of the cast film and its storage stability, the chitosan-alginate-CaCl(2) system can be considered for potential membrane coat application.

Alginates↗

PubMed2001

Antitumor effect of an HER2-specific antibody-toxin fusion protein on human prostate cancer cells.

BACKGROUND: HER2/neu has been implicated in the oncogenesis of human prostate cancer. Clinical studies have suggested that overexpression of HER2 may be one of the indicators of poor prognosis in prostate cancer patients. METHODS: We used Western blot analysis to examine the expression of HER2 in a panel of established human prostate cancer cell lines and used an MTT assay to evaluate the cytotoxicity on these cells of a recombinant fusion protein consisting of an HER2-specific single-chain antibody and the Pseudomonas exotoxin A, scFv(FRP5)-ETA. RESULTS: LNCaP cells express high levels of HER2 protein. Exposure of LNCaP cells to scFv(FRP5)-ETA caused remarkable cell death. In contrast, PC3M cells, which express an undetectable level of HER2 protein, were resistant to scFv(FRP5)-ETA-induced cytotoxicity. MDA PCa 2a, MDA PCa 2b, and DU145 cells express low-to-medium levels of HER2 protein and showed an HER2 level-dependent response to scFv(FRP5)-ETA-induced cytotoxicity. The scFv(FRP5)-ETA-induced cytotoxicity of LNCaP cells could be inhibited by an anti-HER2 monoclonal antibody (mAb), which downregulated the levels of HER2 protein, indicating the specificity of scFv(FRP5)-ETA in inducing cytotoxicity in LNCaP cells. Using an apoptosis ELISA, we demonstrated that scFv(FRP5)-ETA induced apoptosis in LNCaP cells. The apoptosis was inhibited by the presence of dihydrotestosterone (DHT) in culture medium. Exposure of LNCaP cells to scFv(FRP5)-ETA caused reduction in the level of the prostate-specific antigen (PSA). CONCLUSIONS: Our data suggest that scFv(FRP5)-ETA might be a useful agent for the treatment of human prostate cancer cells with high levels of HER2 expression.

ADP Ribose Transferases↗

PubMed2001

The Acute toxicity of alpha-branched phenylsulfonyl acetates in Photobacterium phosphoreum test.

The acute toxicity (15-min EC(50)) of 20 alpha-substituted phenylsulfonyl acetates was measured using the Microtox test with Photobacterium phosphoreum. On the basis of TLSER, quantitative structure-activity relationships (QSARs) were calculated for the inhibition of bioluminescence. With the parameters molecular volume (V(mc)), dipolarity/polarizability (pi*), and the covalent contribution to Lewis basicity (epsilon(b)), a squared correlation coefficient (r(2)(adj)) of 0.868 and standard error of 0.094 for log EC(50) were obtained. By introducing a structural indicator variable (I), the regressive quality was improved (correlation coefficient of 0.948 and standard error of 0.059); the descriptors V(mc), pi*, and the electrostatic basicity contribution (q(-)) were significant. -NO(2)-- and -SO(2)--groups are active centers of these compounds. The strong hydrogen bonding effects between the compound active centers and FMNH(2) play an important role in the greater toxicity of these chemicals.

Luminescent Measurements↗

PubMed2001

"Piecemeal" necrosis: renamed troxis necrosis.

Piecemeal necrosis, currently called interface hepatitis, is a feature of viral hepatitis as well as autoimmune hepatitis and steatohepatitis. The mechanism of liver cell loss and piecemeal necrosis needs to be determined. We hypothesize that piecemeal necrosis in hepatitis is due to a piecemeal removal of hepatocyte cytoplasm by lymphocytic ingestion. To test this hypothesis, 61 consecutive liver biopsies were examined by light microscopy, by immunohistochemistry and by electron microscopy, and the lymphocytic-hepatocytic interaction was morphologically assessed. In cases of hepatitis C, hepatitis B, autoimmune hepatitis, primary biliary cirrhosis, and steatohepatitis, piecemeal necrosis was found. Using cytokeratin stains, it was apparent that the lymphocyte-hepatocyte interaction and piecemeal necrosis leads first to binding of the lymphocyte to hepatocyte plasma membrane and then blebbing or indentation of the hepatocyte by the lymphocyte, followed by endocytosis of liver cell cellular components and digestion in the lymphocyte lysosomes. This process is repeated while the cytoplasm and the nucleus of the hepatocyte disappear bite by bite, and only nubbins of residual hepatocytic cytoplasm remain, either attached to intact hepatocytes or surrounded and sequestered within scar tissue and lymphocytes. We conclude that piecemeal necrosis is a gradual disappearance of hepatocytes as a result of lymphocyte-hepatocyte binding and ligand internalization of liver surface molecules by the lymphocyte. This gradual process leads to a slow reduction of hepatocyte size and eventual disappearance at the interface between the lobule and portal tracts. To term this new kind of necrosis, we propose the name troxis necrosis, after the Greek noun meaning "nibbling."

Biopsy↗

PubMed2001

Adrenergic blockade reduces skeletal muscle glycolysis and Na(+), K(+)-ATPase activity during hemorrhage.

BACKGROUND: Recent evidence suggests that hyperlactatemia in shock may reflect accelerated aerobic glycolysis linked to activity of the Na(+), K(+)-ATPase rather than hypoxia. Epinephrine stimulates glycolysis in resting muscle largely by stimulating Na(+), K(+)-ATPase activity. This study evaluates the effects of hemorrhagic shock, with and without combined alpha- and beta-adrenergic receptor blockade, on lactate production, glycogenolysis, Na(+)-K(+) pump activity, and high-energy phosphates in rat skeletal muscle. METHODS: Male Sprague-Dawley rats in four treatment groups were studied: unhemorrhaged control not receiving blockers (CN), controls receiving blockers (CB), shocked animals not receiving blockers (SN), and shocked rats receiving blockers (SB). Shocked rats (SN and SB) were bled to a MAP of 40 mm Hg, maintained for 60 min. Blocker groups (CB and SB) received propranolol and phenoxybenzamine. Arterial blood was drawn for plasma lactate, epinephrine, norepinephrine, and gas analysis. Lactate, glycogen, glucose 6-phosphate, ATP, phosphocreatine, and intracellular Na(+) and K(+) were determined in extensor digitorum longus and soleus muscles. For comparison, muscles were exposed to epinephrine and/or ouabain in vitro. RESULTS: With the exception of P(a)CO(2), HCO(3), and base excess in the SN group, no significant differences in arterial blood gas parameters were noted. Adrenergic blockade significantly reduced plasma lactate concentration. In shocked rats, adrenergic blockade significantly reduced muscle lactate and glucose 6-phosphate accumulation. Intracellular Na(+):K(+) ratio was decreased in SN rats, implying increased Na(+)-K(+) pump activity. Adrenergic blockade raised the intracellular Na(+):K(+) ratio in shocked animals, implying decreased pump activity. Epinephrine exposure in vitro stimulated muscle lactate production, raised glucose 6-phosphate content, and significantly reduced soleus phosphocreatine stores. CONCLUSIONS: Neither hypoxia nor defective oxidative metabolism appeared responsible for increased glycolysis during hemorrhagic shock. Adrenergic blockade concurrently reduced plasma lactate, muscle levels of lactate and glucose 6-phosphate, and muscle Na(+)-K(+) pump activity during shock. Rapid skeletal muscle aerobic glycolysis in response to increased plasma epinephrine levels may be an important contributor to increased glycolysis in muscle and increased plasma lactate during hemorrhagic shock.

Adenosine Triphosphate↗

PubMed2001

Statistical analysis of hippocampal asymmetry in schizophrenia.

The asymmetry of brain structures has been studied in schizophrenia to better understand its underlying neurobiology. Brain regions of interest have previously been characterized by volumes, cross-sectional and surface areas, and lengths. Using high-dimensional brain mapping, we have developed a statistical method for analyzing patterns of left-right asymmetry of the human hippocampus taken from high-resolution MR scans. We introduce asymmetry measures that capture differences in the patterns of high-dimensional vector fields between the left and right hippocampus surfaces. In 15 pairs of subjects previously studied (J. G. Csernansky et al., 1998, Proc. Natl. Acad. Sci. USA 95, 11406-11411). we define the difference in hippocampal asymmetry patterns between the groups. Volume analysis indicated a large normative asymmetry between left and right hippocampus (R > L), and shape analysis allowed us to visualize the normative asymmetry pattern of the hippocampal surfaces. We observed that the right hippocampus was wider along its lateral side in both schizophrenia and control subjects. Also, while patterns of hippocampal asymmetry were generally similar in the schizophrenia and control groups, a principal component analysis based on left-right asymmetry vector fields detected a statistically significant difference between the two groups, specifically related to the subiculum.

Brain Mapping↗