Biomedical subjects
Publications and source records attributed to H Guo.
Make mice to take the decoction of Radix Achyranthes Bidentatae for 30 days. The result was that the SOD vigour in the senile model mice had been raised and the plasma LPO reduced.
Group II introns use intron-encoded reverse transcriptase, maturase and DNA endonuclease activities for site-specific insertion into DNA. Remarkably, the endonucleases are ribonucleoprotein complexes in which the excised intron RNA cleaves the sense strand of the recipient DNA by reverse splicing, while the intron-encoded protein cleaves the antisense strand. Here, studies with the yeast group II intron aI2 indicate that both the RNA and protein components of the endonuclease contribute to recognition of an approximately 30 bp DNA target site. Our results lead to a model in which the protein component first recognizes specific nucleotides in the most distal 5' exon region of the DNA target site (E2-21 to -11). Binding of the protein then leads to DNA unwinding, enabling the intron RNA to base pair to a 13 nucleotide DNA sequence (E2-12 to E3+1) for reverse splicing. Antisense-strand cleavage requires additional interactions of the protein with the 3' exon DNA (E3+1 to +10). Our results show how enzymes can use RNA and protein subunits cooperatively to recognize specific sequences in double-stranded DNA.
To investigate the effects of autonomic nerve activation on electrophysiological properties of ischemic atrial myocardium, experiments were performed in 10 open chest adult dogs anesthetized with xylazine and alpha-chloralose. Ischemia was created in the right atrial free wall by ligation of one or more branches of the right coronary artery. Bipolar electrograms were recorded from multiple sites in the ischemic and non-ischemic zones. The atria were paced at 400 ms and 180 ms to assess conduction properties. One hour after ligation, delayed activation, electrogram fractionation, and electrogram alternans were observed in the ischemic zone. All local conduction abnormalities were heart rate dependent in that they were only observed at a pacing cycle length of 180 ms. The average duration of ischemic zone electrograms was significantly prolonged from 17.7+/-1.6 ms to 26.4+/-1.6 ms (P<0.001). Right and left vagal stimulation significantly shortened the electrogram duration in the ischemic zone from 26.4+/-1.6 ms to 19.7+/-1.1 ms (P<0.01) and 20.0+/-1.1 ms (P<0.01), respectively. Ischemia-induced electrogram alternans was eliminated completely. During right and left stellate stimulation, electrogram duration was not altered and alternans was still present. In conclusion, vagal stimulation in this canine model improves local conduction in ischemic myocardium in the right atrium. This effect may be mediated by a reversal of the ischemia-induced membrane depolarization and a shortening of refractoriness in the atrium during vagal activation.
IL-8 is expressed by activated and neoplastic astrocytes and enhances the survival of hippocampal neurons in vitro. Since mRNA encoding chemokine receptors have been demonstrated in brain, the expression of chemokine receptors by specific cell types in anatomic regions of the central nervous system (CNS) was investigated. Archival tissues from various regions of the CNS were stained with specific mAbs to the Duffy Ag/receptor for chemokines, a promiscuous receptor that binds selected chemokines; the specific receptor for IL-8 (CXCR1); and the receptor (CXCR2) shared by IL-8 and melanoma growth stimulatory activity. The Duffy Ag/receptor for chemokines was expressed exclusively by Purkinje cells in the cerebellum. Chemokine binding and radioligand cross-linking confirmed the presence of a high affinity, promiscuous chemokine receptor in the cerebellum. Although CXCR1 was not expressed in the CNS, CXCR2 was expressed at high levels by subsets of projection neurons in diverse regions of the brain and spinal cord, including the hippocampus, dentate nucleus, pontine nuclei, locus coeruleus, and paraventricular nucleus, and in the anterior horn, interomediolateral cell column, and Clarke's column of the spinal cord. Fibers that express CXCR2 included those in the superior cerebellar peduncle and the substantia gelatinosa. Immunohistochemical analysis of the involved brain tissues from patients with Alzheimer's disease revealed expression of CXCR2 in the neuritic portion of plaques surrounding deposits of amyloid. These data suggest that chemokines may play a role in reactive processes in normal neuronal function and neurodegenerative disorders.
Although immunosuppressant immunophilin ligands promote neurite outgrowth in vitro, their neurotrophic activities are clearly independent of their immunosuppressive activity. In the present report, a novel nonimmunosuppressive immunophilin ligand, GPI-1046 (3-(3-pyridyl)-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate+ ++) is described. In vitro, GPI-1046 bound to FK506 binding protein-12 and elicited neurite outgrowth from sensory neuronal cultures with picomolar potency with maximal effects comparable to nerve growth factor. In vivo, GPI-1046 stimulated the regeneration of lesioned sciatic nerve axons and myelin levels. In the central nervous system, GPI-1046 promoted protection and/or sprouting of serotonin-containing nerve fibers in somatosensory cortex following parachloroamphetamine treatment. GPI-1046 also induced regenerative sprouting from spared nigrostriatal dopaminergic neurons following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice or 6-hydroxydopamine (6-OHDA) toxicity in rats. The rotational abnormality in 6-OHDA treated rats was alleviated by GPI-1046. These neurotrophic actions in multiple models suggest therapeutic utility for GPI-1046 in neurodegenerative diseases.
A computer program, GelExplorer, which uses a new methodology for obtaining quantitative information about electrophoresis has been developed. It provides a straightforward, easy-to-use graphical interface, and includes a number of features which offer significant advantages over existing methods for quantitative gel analysis. The method uses curve fitting with a nonlinear least-squares optimization to deconvolute overlapping bands. Unlike most curve fitting approaches, the data is treated in two dimensions, fitting all the data across the entire width of the lane. This allows for accurate determination of the intensities of individual, overlapping bands, and in particular allows imperfectly shaped bands to be accurately modeled. Experiments described in this paper demonstrate empirically that the Lorentzian lineshape reproduces the contours of an individual gel band and provides a better model than the Gaussian function for curve fitting of electrophoresis bands. Results from several fitting applications are presented and a discussion of the sources and magnitudes of uncertainties in the results is included. Finally, the method is applied to the quantitative analysis of a hydroxyl radical footprint titration experiment to obtain the free energy of binding of the lambda repressor protein to the OR1 operator DNA sequence.
Many of the tumor-associated matrix metalloproteinases that are implicated in metastasis are produced by stromal fibroblasts within or surrounding the tumor in response to stimulation by factors produced by tumor cells. In this study we transfected Chinese hamster ovary cells with putative cDNA for human extracellular matrix metalloproteinase inducer (EMMPRIN), a transmembrane glycoprotein that is attached to the surface of many types of malignant human tumor cells and that has previously been implicated in stimulation of matrix metalloproteinase production in fibroblasts. We show that these transfected cells synthesize EMMPRIN that is extensively post-translationally processed; this recombinant EMMPRIN stimulates human fibroblast production of interstitial collagenase, stromelysin-1, and gelatinase A (72-kDa type IV collagenase). We propose that EMMPRIN regulates matrix metalloproteinase production during tumor invasion and other processes involving tissue remodeling.
The expression of intercellular adhesion molecule-1 (ICAM-1) on pulmonary endothelial cells after stimulus and subsequent binding of neutrophils is a first step leading to lung injury. A similar process may dictate the binding of tumor cells to the pulmonary endothelium during metastasis. We report the development of a new technique that allowed us to monitor the location and relative expression of ICAM-1 levels on the luminal surface of the pulmonary microvasculature in vivo. This technique uses intravital microscopy together with a two-step labeling procedure involving fluorescent microspheres. Constitutive expression of ICAM-1 was not detectable to a significant level by our model, but expression was observed after upregulation by the systemic administration of TNF alpha. Sprague-Dawley rats were injected with 0-5.0 micrograms/kg TNF alpha and ICAM-1 expression was monitored through 24 hr. ICAM-1 expression was related to both the dose of TNF alpha administered and the time elapsed between injection of TNF alpha and observation. Injection of 5 micrograms/kg TNF alpha caused upregulation of ICAM-1 protein expression from 0.30 +/- 2.76 binding events/175,000 microns2 to 62.6 +/- 5.48 through 4 hr observation, after which levels returned to near baseline within 24 hr. The delay required for maximal expression is likely related to the time required for the cell to respond to the stimulus and generate ICAM-1 protein. Reductions in the relative numbers of ICAM-1 protein expressed between 4 and 24 hr in vivo are likely a result of protein turnover after the initial stimulus.
Combined subjective and objective nutritional assessment was performed on admission in 127 patients with oral and maxillofacial malignancies. On the basis of the nutritional assessment result, three typical nutritional parameters-body weight (BW) (X1), mid-upper-arm circumference (MAC) (X2), and hand grip strength (HGS) (X3) were used to establish a new nutritional assessment method that was developed by a computer-based discriminant analysis. The established model was as follows: Y1 = -126 + 1.09X1 + 1.34X2 + 0.23X3; Y2 = -95.63 + 0.96X1 + 1.17X2 + 0.19X3. In the model Y1 was regarded as good nutrition and Y2 as malnutrition. The larger value of Y stood for the patient's nutritional status (i.e. Y1 > Y2, well nourished; Y1 < Y2 malnourished). The new nutritional assessment correlates well with the combined subjective and objective nutritional assessment with a total agreement rate of 88.2%. With its simplicity and accuracy, the new nutritional assessment deserves a wide application in clinical situation.
Oxidative stress may be involved in monocrotaline (MCT)-induced endothelial cell injury and upregulation of extracellular matrix proteins in the pulmonary vasculature. To test this hypothesis, cytotoxicity, expression and distribution of tenascin (TN) as well as cellular oxidation were determined in porcine pulmonary artery endothelial cells (PAECs) exposed to MCT and/or to an oxygen radical scavenger, dimethylthiourea (DMTU). Relative to controls, treatment with 2.5 mM MCT for 24 hr produced cytotoxicity as evidenced by changes in cellular morphology, cell detachment, hypertrophy, reduction in cellular proliferation and severe cytoplasmic vacuolization. Parallel studies showed that MCT markedly altered the expression and distribution of TN in PAEC as determined by immunocytochemistry. Western analysis showed that MCT increased cellular TN content and promoted the appearance of an additional, smaller TN isoform. Northern analysis demonstrated an increase in the steady-state level of TN-specific mRNA in response to MCT treatment. Exposure to MCT also increased the synthesis of cell-associated and media-associated TN as determined by immunoprecipitation. In addition, MCT increased the intensity of cellular oxidative stress as measured by 2,7-dichlorofluorescein fluorescence. Co-treatment with DMTU prevented MCT-induced cytotoxicity, alterations in TN distribution and content, and reduced the increase in DCF fluorescence. These results suggest that MCT-induced cytotoxicity and upregulation of TN are mediated, at least in part, by induction of cellular oxidative stress.
While a number of factors may initiate structural alterations within the cardiovascular system in response to hypertension, there are obligate cellular signaling mechanisms, such as the polyamines, through which they must operate. This study examined the effects of polyamine synthesis inhibition using eflornithine, a suicide inhibitor of ornithine decarboxylase on blood pressure, compensatory remodeling of the cardiovascular system, and cardiac and aortic polyamine contents using an aortic coarctation model in rats. Eflornithine treatment failed to reduce carotid arterial blood pressure and actually significantly elevated vascular pressure above and below the coarctation site by 14 days of hypertension. Eflornithine only transiently reduced aortic polyamine content of hypertensive rats while this agent reduced coarctation-induced aortic medial wall thickening and the synthesis/deposition of fibronectin and laminin in the hypertensive aorta. Increases in left ventricular mass and polyamine content were concomitantly reduced in hypertensive rats administered eflornithine. These results suggest that multiple polyamine regulatory pathways may maintain vascular polyamine content in response to aortic coarctation; however de novo polyamine synthesis is essential for select aspects of vascular remodeling, including matrix synthesis. Cardiac tissue, in contrast, may rely principally on de novo polyamine synthesis.
We studied the systemic manifestations of myasthenia gravis and its putative pathogenesis. 644 clinically, pharmacologically and electrophysiologically diagnosed patients with myasthenia gravis (MG) were studied. 33 patients had Graves disease, 5 periodic paralysis, 4 Hashimoto disease, and 4 epilepsy, polymyositis, rheumatoid arthritis and Guillain-Barre syndrome each. 45 patients had positive anti-skeletal-muscle antibodies, 9 positive anti-thyroid antibody, and 3 positive SSA and SSB. 11 MG patients with positive pyramidal signs (MG+PS) had no evidence of multiple sclerosis (MS) or other neurologic diseases. Compared with 12 MG patients without pyramidal signs (MG-PS) and 23 normal controls (NCs), they had not only high levels of IgGcsf and IgG syn, but also increased ratio of AChRAbcsf/AChRAbs (P < 0.05). Four MG patients had epilepsy. Four MG patients had severe memory disorders. Three MG patients had diseases of the peripheral nerves without diabetes mellitus and toxin. SGPT was significantly increased in 22 MG patients than in 9 normal controls (P < 0.05). These systemic manifestations were improved while MG was improved by immunological therapy. MG is a systemic autoimmune disease predominantly involving AChR on the postsynaptic membrane of N-M conjunction.
OBJECTIVE: To study the inhibitory effect induced by combined treatment of TNF alpha and antisense oligodeoxynucleotide on the growth of human pancreatic adenocarcinoma cell line (PC-2) cells. METHOD: TNF alpha and synthesized antisense c-myc or Ki-ras phosphorothioate oligodeoxynucleotide (ASPODN) were added to the culture media of PC-2 cells, whereas the groups treated with TNF alpha or ASPODN alone were used as controls. The cell growth rate was estimated by cell count and MTT analysis, the endogenous target gene expression was studied by adopting RT-PCR-Southern blot technique, and cell apoptosis was detected in situ. RESULTS: The cell growth was inhibited much more obviously in the groups of combined treatment than in the groups treated with TNF alpha or ASPODN alone. Marked inhibition of endogenous Ki-ras and c-myc expression was observed in the groups treated with Ki-ras and c-myc ASPODN. The amounts of apoptotic cells were 8.0% and 8.4% in the groups of TNF alpha + Ki-ras ASPODN and TNF alpha + c-myc ASPODN, and were 5.2%, 4.8% and 5.4% for TNF alpha, Ki-ras ASPODN and c-myc ASPODN respectively. CONCLUSION: Our results demonstrate that the inhibitory effect induced by combined treatment of TNF alpha and ASPODN on cell growth was stronger than that induced by TNF alpha or ASPODN alone.
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Six flavonoids were isolated from the seed of Cuscuta australis and four of them were identified as kaempferol, quercetin, astragalin and hyperoside. Hyperoside was obtained from this plant for the first time. In comparison with the flavonoids in C. chinensis, it is found that quercetin and its glycoside are the main flavonoids in C. australis. This result suggests that the flavonoids can be used to distinguish these two medicinal materials.
Oxygen derived free radical system has been to be implicated in the pathogenesis of many diseases, such as cardiovascular disease, tumor, trauma and radiation injury. Many studies have suggested that oxygen free radical initiate a series of events that result in cell membrane alterations leading to the development of cell injury. The objective of the present study was to examine the circadian characteristics of some parameters of this system in the blood. One parameter was superoxide dismutase (SOD), a major oxygen free radical scavenger; the other was malondialdehyde (MDA), an important product of lipid peroxidation initiated by oxygen free radicals. Blood samples were collected at 6 h intervals beginning at 08:00 over a 24 h span in nine healthy volunteers (5 females, 4 males, average age 30 +/- 5 years). All participants were synchronized for one week with diurnal activity from 07:00 to 23:00 and nocturnal rest, with three meals served at 07:30, 12:00 and 19:00. Plasma SOD, MDA levels were measured by pyrogallol autoxidation assay, thiobarbituric acid spectrophotometry respectively, and the data were fitted with a 24 h cosine curve and analyzed further by a population-mean cosinor. The results showed that the plasma SOD levels exhibited a highly significant circadian rhythm (P < 0.001) in healthy subjects, with acrophase (phi) at 21:17, mesor (M) of 3975.3 +/- 680.5 u/g Hb, and amplitude (A) of 273.62 u/g Hb. A circadian rhythm of plasma MDA was also detected (P < 0.01), phi = 15:15, M = 4.23 +/- 0.86 mumol/L, A = 2.37 mumol/L). The evaluation of circadian natures of SOD and MDA may be important in the prevention, diagnosis and treatment of associated diseases.
The proliferation of vascular smooth muscle cells (VSMC) has been thought to play an important role in the development of hypertension and atherosclerosis. The aim of this study was to investigate the effect of Tianma Injection and its major component Gastrodin on the proliferation of cultured VSMC. VSMC were cultured and randomly divided into the control, Tianma and Gastrodin groups. The results showed that Tianma Injection significantly decreased cell numbers dose-dependently and time-dependently, and it inhibited 3H-TdR incorporation in VSMC. It also increased the content of PGI2 production in VSMC. However, no significant differences of the above measurements were observed between the Gastrodin and control groups. The suggest that Tianma Injection can inhibit VSMC proliferation and the effect possibly results from its increasing PGI2 production content, and that the inhibiting effect of Tianma is irrelated to Gastrodin.
In order to elucidate whether there are any features of HLA haplotype in perennial allergic rhinitis and the essentials of its genetic background, the antigen specificities of HLA-A, B loci in 31 non-kindred adult cases of southern Chinese of Han nationality were detected and calculated the antigen frequency, gene frequency and relative risk value of different alleles evaluated by serological methods. The results were compared with 78 healthy adult individuals of Guizhou Han (control group) and revealed that RR (relative risk) of HLA-B27 was as high as 8.25, RR of A31 (2.68), A28 (2.57), B12 (2.57) and A33 (2.27) were also higher than the control group. It is suggested that the presence of the above mentioned antigens are positively associated with the genetic liability of the patients. The RR of A9, B60, A24, B22, B51, B15, B16, B48, B46, B7, A11 and A2 were all lower than 1 representing the genetic stability to allergic rhinitis. The antigen frequency of B27 and A9 were significantly different from that of the control group.