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Biomedical subjects

M Li

Publications and source records attributed to M Li.

At least 631 records · Page 35Linked to original sources
PubMed1998

Hemodynamic profile of corticotropin-induced hypertension in the rat.

OBJECTIVES: To examine hemodynamic variables in corticotropin-induced hypertension in rats and the effects of reversal of the hypertension by L-arginine on the hemodynamic profile. METHODS: Sixty male Sprague-Dawley rats were randomly divided into four groups: sham treatment (0.9% NaCl, injected subcutaneously); 0.5 mg/kg corticotropin per day, subcutaneously; 0.6% L-arginine in food plus sham; and L-arginine plus corticotropin. Systolic blood pressure, water and food intakes, urine volume, and body weight were measured every second day. After 10 days mean arterial blood pressure was measured by intra-arterial cannulation, and cardiac output, and renal, mesenteric, and hindquarter blood flows were determined using transonic small animal flowmeters. RESULTS: Injection of corticotropin increased blood pressure, water intake, urine volume, and plasma sodium concentration, and decreased body weight and plasma potassium concentration. It increased cardiac output (P < 0.01), mesenteric blood flow (P < 0.05), and renal vascular resistance (P < 0.05), and decreased renal blood flow (P < 0.05), but did not change calculated total peripheral resistance, hindquarter blood flow, mesenteric or hindquarter vascular resistance. L-arginine prevented corticotropin-induced rises in blood pressure (P < 0.001) and renal vascular resistance (P < 0.05), and a fall in renal blood flow (P < 0.05), but did not affect other hemodynamic variables. CONCLUSION: The hemodynamic profile of corticotropin-induced hypertension in the rat is characterized by a rise in cardiac output and renal vascular resistance, a fall in renal blood flow, but no change in total peripheral resistance, hindquarter blood flow, mesenteric vascular resistance, or hindquarter vascular resistance. L-arginine prevented corticotropin-induced rises both in blood pressure and in renal vascular resistance in the rat. These data suggest that the increase in renal vascular resistance might play a role in corticotropin-induced hypertension in the rat.

Adrenocorticotropic Hormone↗
PubMed1998

Adrenocorticotrophin dose-response relationships in the rat: haemodynamic, metabolic and hormonal effects.

OBJECTIVE: To determine adrenocorticotrophin dose-response relationships for increase of blood pressure and metabolic parameters of the Sprague-Dawley rat. METHODS: We injected 120 male Sprague-Dawley rats twice daily subcutaneously for 10 days with 0.5, 1, 5, 50, 100, 200 or 500 microg/kg synthetic adrenocorticotrophin per day (all n = 10) or subjected them to sham injection (0.9% NaCl; n = 50). Systolic blood pressure, 24 h food intake, water intake, urine volume and body weight were measured. Data from a further 45 rats treated with 500 microg/kg per day adrenocorticotrophin in previous studies were included in the blood pressure analyses. After we had killed these rats, their organ weights (kidney, heart, adrenal) and plasma electrolyte, adrenocorticotrophin and serum corticosterone concentrations were measured. RESULTS: On the final day of treatment systolic blood pressure of sham-injection control rats was 123 +/- 1 mmHg (n = 50). Compared with sham treatment, a low dose of adrenocorticotrophin (1 microg/kg per day) increased systolic blood pressure from 122 +/- 1 to 130 +/- 2 mmHg (P < 0.001) without any metabolic effects, whereas a high dose of adrenocorticotrophin (500 microg/kg per day) increased systolic blood pressure from 121 +/- 1 to 150 +/- 2 mmHg (P < 0.001, n = 55) with increases in intake of water and urine volume (P < 0.001, n = 10) and a decrease in body weight (P < 0.001, n = 10). Plasma adrenocorticotrophin and serum corticosterone concentrations for the sham-injection control group were 162 +/- 12 pg/ml (36 +/- 3 pmol/l) and 376 +/- 18 ng/ml (1038 +/- 50 nmol/l), respectively. Plasma adrenocorticotrophin concentration was elevated by injections of 100 (P < 0.05), 200 (P < 0.01) and 500 microg/kg adrenocorticotrophin per day (P = 0.001). Serum corticosterone concentration was not significantly different from that of sham-injection rats with 0.5-5 microg/kg adrenocorticotrophin per day but was increased by injection of 50-500 microg/kg adrenocorticotrophin per day (P < 0.001). CONCLUSIONS: These results define 1 microg/kg adrenocorticotrophin per day, administered subcutaneously, as the threshold dose for causing a rise in blood pressure in the rat Thus administration of adrenocorticotrophin increases systolic blood pressure at doses that induce minimal adrenocorticotrophin metabolic effects. Administration of a low dose of adrenocorticotrophin to the rat is a suitable model for stress-induced hypertension.

Administration, Cutaneous↗
PubMed1998

Insulin receptor exon 11+/- isoform mRNA in spontaneously hypertensive and adrenocorticotropin-hypertensive rats.

OBJECTIVE: To test the hypothesis that insulin resistance of the spontaneously hypertensive rat (SHR) and adrenocorticotropin-hypertensive rat is related to a difference in the proportion of the functionally different, alternatively spliced exon 11 isoforms of the insulin receptor. DESIGN: We determined the proportions of mRNA for the exon 11+ and exon 11- isoforms in various tissues of SHR and Wistar-Kyoto rats aged 3, 6, 9 and 12 weeks, which span the pre-hypertensive phase through to established hypertension, as well as in Sprague-Dawley rats with adrenocorticotropin-induced hypertension and Sprague-Dawley controls. METHODS: Detection of mRNA involved a reverse-transcriptase polymerase chain reaction technique specific for each isoform and quantification was by slot and dot blot hybridization. RESULTS: Mean proportions of exon 11+ mRNA in SHR, Wistar-Kyoto rats, adrenocorticotropin-hypertensive rats and Sprague-Dawley control rats at each age were 95% for liver, 82% for adipose tissue, 77% for kidney, 66% for adrenal, 53% for heart, 26% for cerebral cortex, 23% for hypothalamus, and 3% for skeletal muscle. There was also no difference in concentration of total insulin receptor mRNA. CONCLUSIONS: The absence of any difference in proportions of insulin receptor mRNA isoforms argues against the hypothesis that an alteration of differential splicing plays a role in the models of hypertension studied.

Adrenocorticotropic Hormone↗
PubMed1998

Immunoreactive endothelin-1 and its receptors in human adrenal tissues.

To elucidate the pathophysiologic significance of endothelin-1 (ET-1) in adrenal and the mechanism for reduced responsiveness to exogenous ET-1 in aldosterone-producing adenoma (APA), we have investigated ET-1 receptors by radioligand binding assay (RBA) in human normal adrenal (NA), APA, idiopathic hyperaldosteronism (IHA), and pheochromocytoma (PHEO), immunoreactive (ir-) ET-1 content in NA, APA and PHEO by radioimmunoassay (RIA), and immunohistochemical staining of ET-1 with the peroxidase-anti-peroxidase (PAP) method in NA, APA, and PHEO. A single class of high-affinity binding sites for ET-1 was found in human NA and tumor tissues. Dissociation constant (Kd) values of ET-1 receptors were similar in NA, APA, and IHA, but maximal binding capacity (Bmax) of ET-1 receptors was lower in APA than in NA and IHA. Both Kd and Bmax in PHEO were higher than those in NA, APA, and IHA. Ir-ET-1 content in tumors of APA and PHEO were higher than in NA. Immunohistochemical staining was more intense in the tumor cells of APA and PHEO than in NA. These results suggest that the reduced response to exogenous ET-1 in APA could be related to downregulation of ET-1 receptors in the tumor. Increased ET-1 content and receptors may lead to hypersecretion of catecholamine in PHEO. ET-1 produced in normal and tumor adrenal tissues may regulate aldosterone and catecholamine secretion from adrenals in a paracrine/autocrine fashion.

Adrenal Gland Neoplasms↗
PubMed1998

Effects of drugs on concurrent variable-interval variable-interval schedule performance.

According to the generalized matching law the ratio of responses between two alternatives matches the ratio of reinforcers produced by these responses. In these experiments using concurrent variable-interval variable-interval schedules in pigeons, responding occurred more frequently on the key associated with the lower reinforcement density (undermatching) than would be predicted by perfect matching. Under control conditions, there was no bias toward responding on either key. Pentobarbital, methamphetamine, morphine and phencylidine all increased bias toward responding on the left key with the exception of one 10 mg/kg dose of pentobarbital that increased bias toward responding on the right key. Higher doses of methamphetamine and morphine, and most doses of phencyclidine increased matching, but high doses of pentobarbital further decreased matching. Morphine increased bias toward responding on the left key at much lower doses than those that affected matching, while phencyclidine increased matching at lower doses than those that increased bias. Pentobarbital produced small increases in response rates that were sometimes accompanied by small increases in key switching. All other drugs only decreased response rate and decreased the number of key switches. These data suggest that drugs disrupt responding under concurrent schedules both by increasing bias and by changing baseline matching functions.

Animals↗
PubMed1998

Effect of chinonin on acute hypoxic pulmonary vasoconstriction in Sprague-Dawley rats.

The objective of this study was to determine the influence of chinonin on acute hypoxic pulmonary vasoconstriction (HPV) in Sprague-Dawley (SD) rats and investigate its mechanism. Sixty-five SD rats were divided into five groups at random: six in the control group; six in the hypoxia group; 13 in the group of hypoxia with chinonin; 20 in the group of endothelin-1 (ET-1) with chinonin and 20 in the group of platelet activating factor (PAF) with chinonin. Their mean pulmonary arterial pressures (mPAP) were measured and the concentration of molondialdehyde (MDA) in plasma and the activity of phospholipase A2 (PLA2) of the lung tissues were detected. The PAF and ET-1 levels of plasma and lung homogenates were detected in the control and hypoxia groups. There was evidence of an increase in mPAP, MDA, PAF and ET-1 in the plasma, and activity of PLA2, PAF and ET-1 of the lung tissues when the rats inhaled a 10% mixture of oxygen in nitrogen. It appeared that chinonin may have been inhibiting the action of ET-1 and PAF. Chinonin could have prevented an increase in MPAP caused by hypoxia and inhibited the action of ET-1 and PAF. But chinonin had no influence on the increase in MDA in the plasma and the PLA2 activity of the lungs when hypoxia occurred. Chinonin can reduce HPV, but does not influence normal mPAP. It may do this by blocking the action of ET-1 and/or PAF or others. The definite mechanism needs to be studied further.

Animals↗
PubMed1998

Lyme disease Borrelia species in northeastern China resemble those isolated from far eastern Russia and Japan.

Fifty-nine Borrelia burgdorferi sensu lato culture isolates collected from northeastern China were characterized by 5S-23S rRNA intergenic spacer restriction fragment length polymorphism (RFLP) analysis and reactivity with monoclonal antibodies (MAbs). Among 59 culture isolates, 30 (50.8%) were Borrelia garinii and 17 (28.8%) were Borrelia afzelii, 2 were mixtures composed of B. garinii with RFLP pattern B and B. garinii with pattern C, and 9 were mixtures composed of B. garinii and B. afzelii. One isolate, ChY13p, produced a unique pattern and was identified as B. garinii based on analyses of 16S rRNA gene sequence, flagellin PCR-RFLP typing, and MAb reactivities. No Borrelia burgdorferi sensu stricto or Borrelia japonica isolates were detected. The results indicate that Lyme disease Borrelia species in northeastern China resemble those of Borrelia isolates from far eastern Russia and Japan.

Base Sequence↗
PubMed1998

Intercapsomeric disulfide bonds in papillomavirus assembly and disassembly.

In order to analyze bonding contacts that stabilize the virion or promote capsid assembly, bovine papillomavirus (BPV) virions were subjected to buffer conditions known to disrupt polyomavirus virions. At physiologic ionic strength, incubation with dithiothreitol (DTT), EGTA, or DTT plus EGTA did not disrupt BPV virions as determined by electron microscopy. However, incubation of virions with DTT rendered the BPV L1 protein susceptible to trypsin cleavage at its carboxy terminus and rendered the genome susceptible to digestion with DNase I. When DTT-treated BPV virions were analyzed by analytical ultracentrifugation, they sedimented at 230S compared with 273S for untreated virions, suggesting a capsid shell expansion. Incubation with EGTA had no effect on trypsin or DNase I sensitivity and only a small effect upon the virion S value. A single cysteine residue conserved among BPV and human papillomavirus (HPV) L1 proteins resides within the trypsin-sensitive carboxy terminus of L1, which is required for capsid assembly. A recombinant HPV type 11 L1 protein, which was purified after expression in Escherichia coli and which has a Cys-to-Gly change at this position (Cys424), formed pentamers; however, unlike the wild-type protein, these mutant pentamers could no longer assemble in vitro into capsid-like structures. These results indicate an important role for interpentamer disulfide bonds in papillomavirus capsid assembly and disassembly and suggest a mechanism of virus uncoating in the reducing environment of the cytoplasm.

Animals↗
PubMed1998

Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor.

Interferons (IFNs) are a family of multifunctional cytokines with antiviral activities. The K9 open reading frame of Kaposi's sarcoma-associated herpesvirus (KSHV) exhibits significant homology with cellular IFN regulatory factors (IRFs). We have investigated the functional consequence of K9 expression in IFN-mediated signal transduction. Expression of K9 dramatically repressed transcriptional activation induced by IFN-alpha, -beta, and -gamma. Further, it induced transformation of NIH 3T3 cells, resulting in morphologic changes, focus formation, and growth in reduced-serum conditions. The expression of antisense K9 in KSHV-infected BCBL-1 cells consistently increased IFN-mediated transcriptional activation but drastically decreased the expression of certain KSHV genes. Thus, the K9 gene of KSHV encodes the first virus-encoded IRF (v-IRF) which functions as a repressor for cellular IFN-mediated signal transduction. In addition, v-IRF likely plays an important role in regulating KSHV gene expression. These results suggest that KSHV employs an unique mechanism to antagonize IFN-mediated antiviral activity by harboring a functional v-IRF.

3T3 Cells↗
PubMed1998

Human papillomavirus type 11 recombinant L1 capsomeres induce virus-neutralizing antibodies.

The human papillomavirus type 11 (HPV-11) L1 major capsid protein can be trypsinized to generate recombinant capsomeres that retain HPV genotype-restricted capsid antigenicity (M. Li, T. P. Cripe, P. A. Estes, M. K. Lyon, R. C. Rose, and R. L. Garcea, J. Virol. 71:2988-2995, 1997). In the present study, HPV-11 virion-neutralizing monoclonal antibodies H11.F1 and H11.H3, previously characterized as recognizing two distinct HPV-11 capsid-neutralizing antigenic domains (S. W. Ludmerer, D. Benincasa, and G. E. Mark III, J. Virol. 70:4791-4794, 1996), were each found to be highly immunoreactive with trypsin-generated capsomeres in an enzyme-linked immunosorbent assay (ELISA). Capsomeres were used to generate high-titer polyclonal immune sera that demonstrated HPV genotype-restricted reactivity by ELISA. The capsomere antisera were then tested in an in vitro infectivity assay and found to neutralize HPV-11 virions. In this assay, HPV-11 capsomere polyclonal antisera exhibited neutralization titers (10(-5) to 10(-6)) comparable to those obtained with a virion-neutralizing antiserum raised previously against intact HPV-11 VLPs (R. C. Rose, R. C. Reichman, and W. Bonnez, J. Gen. Virol. 75:2075-2079, 1994). These results indicate that highly immunogenic, genotype-restricted HPV capsid-neutralizing antigenic domains are contained entirely within capsomeres. Thus, capsomeres may be viable vaccine candidates for the prevention of HPV disease.

Animals↗
PubMed1998

Identification of an immunoreceptor tyrosine-based activation motif of K1 transforming protein of Kaposi's sarcoma-associated herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) is consistently identified in Kaposi's sarcoma and body cavity-based lymphoma. KSHV encodes a transforming protein called K1 which is structurally similar to lymphocyte receptors. We have found that a highly conserved region of the cytoplasmic domain of K1 resembles the sequence of immunoreceptor tyrosine-based activation motifs (ITAMs). To demonstrate the signal-transducing activity of K1, we constructed a chimeric protein in which the cytoplasmic tail of the human CD8alpha polypeptide was replaced with that of KSHV K1. Expression of the CD8-K1 chimera in B cells induced cellular tyrosine phosphorylation and intracellular calcium mobilization upon stimulation with an anti-CD8 antibody. Mutational analyses showed that the putative ITAM of K1 was required for its signal-transducing activity. Furthermore, tyrosine residues of the putative ITAM of K1 were phosphorylated upon stimulation, and this allowed subsequent binding of SH2-containing proteins. These results demonstrate that the KSHV transforming protein K1 contains a functional ITAM in its cytoplasmic domain and that it can transduce signals to induce cellular activation.

Amino Acid Sequence↗
PubMed1998

Downregulation of a human colonic sialyltransferase by a secondary bile acid and a phorbol ester.

Fecal constituents such as bile acids and increased sialylation of membrane glycoproteins by alpha-2,6-sialyltransferase (HST6N-1) may contribute to colorectal tumorigenesis. We hypothesized that bile acids and phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TPA)] would upregulate HST6N-1 in colonic cells. However, deoxycholate (DOC) (300 mumol/l), a secondary bile acid, and TPA (20 ng/ml) decreased expression of an approximately 100-kDa glycoprotein bearing alpha-2,6-linked sialic acid in a colon cancer cell line (T84) in vitro. HST6N-1 mRNA levels were reduced approximately 80% by treatment (< or = 24 h) with DOC or TPA but not by cholate, a primary bile acid. Treatment (24 h) with DOC or TPA decreased activity of this enzyme to 30% and 13% of control, respectively. These effects of DOC and TPA were transcriptional and were mediated by Ca2+ and protein kinase C, respectively. Thus DOC and TPA both downregulated, and did not upregulate, alpha-2,6-sialyltransferase expression in vitro, but by different transduction pathways. As colorectal tumors grow, their progressive removal from the fecal milieu that normally downregulates this enzyme may favor invasion and metastasis.

Calcium↗
PubMed1998

Store-operated calcium entry promotes shape change in pulmonary endothelial cells expressing Trp1.

Activation of Ca2+ entry is known to produce endothelial cell shape change, leading to increased permeability, leukocyte migration, and initiation of angiogenesis in conduit-vessel endothelial cells. The mode of Ca2+ entry regulating cell shape is unknown. We hypothesized that activation of store-operated Ca2+ channels (SOCs) is sufficient to promote cell shape change necessary for these processes. SOC activation in rat pulmonary arterial endothelial cells increased free cytosolic Ca2+ that was dependent on a membrane current having a net inward component of 5.45 +/- 0.90 pA/pF at -80 mV. Changes in endothelial cell shape accompanied SOC activation and were dependent on Ca2+ entry-induced reconfiguration of peripheral (cortical) filamentous actin (F-actin). Because the identity of pulmonary endothelial SOCs is unknown, but mammalian homologues of the Drosophila melanogaster transient receptor potential (trp) gene have been proposed to form Ca2+ entry channels in nonexcitable cells, we performed RT-PCR using Trp oligonucleotide primers in both rat and human pulmonary arterial endothelial cells. Both cell types were found to express Trp1, but neither expressed Trp3 nor Trp6. Our study indicates that 1) Ca2+ entry in pulmonary endothelial cells through SOCs produces cell shape change that is dependent on site-specific rearrangement of the microfilamentous cytoskeleton and 2) Trp1 may be a component of pulmonary endothelial SOCs.

Amino Acid Sequence↗
PubMed1998

Lack of effect of spaceflight on bone mass and bone formation in group-housed rats.

As part of an experiment to study the role of corticosteroids in bone changes during spaceflight, male Sprague-Dawley rats (6 wk old, 165 g body weight) were placed in orbit for 17 days, in groups of six, in animal-enclosure modules (AEMs) aboard the space shuttle Columbia (STS-78). Control rats were group housed in a similar manner in ground-based AEMs or standard vivarium cages. Adrenal hypertrophy occurred in flight rats, but bone histomorphometric analyses revealed a lack of significant changes in bone mass and bone formation in these animals. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were nearly the same in flight and ground-based rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral necks of flight rats. In the tibial diaphysis, periosteal bone formation rate was found to be identical in flight and ground-based rats. The results indicate that, under conditions of group housing in AEMs, spaceflight has minimal effects on bone mass and bone formation in rapidly growing rats. These findings emphasize the need to investigate the importance of rat age, strain, and especially housing conditions for studies of the skeletal effects of spaceflight.

Adrenal Cortex Hormones↗
PubMed1998

Expression of inhibitor of apoptosis proteins (IAPs) in rat granulosa cells during ovarian follicular development and atresia.

The inhibitor of apoptosis proteins (IAPs) constitute a family of highly conserved apoptosis suppressor proteins that was originally identified in baculoviruses. Although IAP homologs have been recently identified and demonstrated to suppress apoptosis in mammalian cells, their expression and role during follicular development and atresia are unknown. The present study was conducted to address these questions. Using established in vivo models for the induction of follicular development and atresia in immature rats, it was possible to compare the immunolocalization of X-link inhibitor of apoptosis protein (Xiap) and human inhibitor of apoptosis protein-2 (Hiap-2), two members of the IAP family, at defined stages of follicular maturation and to relate the differences observed with those of follicular cell proliferation and apoptosis [as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry and in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL), respectively]. In addition, granulosa cell DNA and proteins were assessed for apoptotic fragmentation by 3'-end labeling/agarose gel electrophoresis (DNA ladder) and Hiap-2 and Xiap protein content by Western blot analysis, respectively. Hiap-2 and Xiap expression in both granulosa and theca cells increased with follicular maturation, reaching maximal levels at the antral stage of development. The immunoreactivity for PCNA, Xiap, and Hiap-2 decreased markedly in atretic (TUNEL-positive) follicles at the small to medium sized antral stage of development, suggesting follicular atresia may be associated with decreased granulosa cell IAP protein content and decreased proliferation. Atresia was also associated with a change in the intracellular distribution of IAPs in granulosa cells. Biochemical analysis of DNA fragmentation (DNA ladder) in granulosa cells from preantral and early antral follicles indicates extensive apoptosis that was associated with minimal IAP protein content. Gonadotropin treatment increased Hiap-2 and Xiap protein content and suppressed apoptosis in granulosa cells, resulting in the development of follicles to the antral and preovulatory stages. In addition, gonadotropin withdrawal induced apoptotic DNA fragmentation in granulosa cells in early antral and antral follicles, which is accompanied by a marked decrease in Hiap-2 and Xiap expression. These data suggest that IAPs may be involved in the suppression of granulosa cell apoptosis by gonadotropin in small to medium-sized antral follicles and play an important role in determining the fate of the cells, and thus also the eventual follicular destiny (atresia vs. ovulation).

Animals↗
PubMed1998

Sarcolemmal defect and subsarcolemmal lesion in a patient with gamma-sarcoglycan deficiency.

We report a case of gamma-sarcoglycanopathy with sarcolemmal defects and subsarcolemmal lesions indistinguishable from those in Duchenne muscular dystrophy. Both disorders share certain ultrastructure features that suggest a common pathogenesis related to primary deficiency of transmembrane glycoproteins (e.g., sarcoglycans) or deficiency in dystrophin, which produces a secondary deficiency in sarcoglycans. The lack of transmembrane glycoproteins may contribute to membrane lesions and associated muscle fiber degeneration and necrosis.

Child↗