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Biomedical subjects

X He

Publications and source records attributed to X He.

At least 379 records · Page 21Linked to original sources

Electrophysiological evidence for a spinal antinociceptive action of dipyrone.

Electrophysiological experiments in anesthetized cats and rats were performed in order to study the effects of dipyrone on single afferent fibers from the knee joint and on spinal cord neurons with knee joint input. The neurons were activated and/or rendered hyperexcitable by an acute inflammation in the knee joint. In the joint nerve in cats, intravenous dipyrone (25-100 mg/kg) reduced ongoing activity in 10/12 thinly myelinated afferents but only in 1/10 unmyelinated afferents; the responses to movements of the inflamed knee were reduced in 8/10 thinly myelinated but only in 3/10 unmyelinated units. The reduction of activity was significant 20-30 min after application and was maximal at 60-180 min. In the spinal cord of spinalized cats, intravenous dipyrone (25-100 mg/kg) reduced ongoing activity and/or responses to pressure onto the inflamed knee in 14/16 neurons and in non-spinalized rats similar effects were seen in 10/11 neurons. Effects on spinal cord neurons started 5-10 min after application and were maximal after 20-40 min. These data show pronounced suppression of inflammation-induced nociception by dipyrone and they suggest that the spinal cord is a major site of action of this compound.

Analgesics↗

Epidemiology of oral candidiasis in HIV-infected patients: colonization, infection, treatment, and emergence of fluconazole resistance.

PURPOSE: To study the epidemiology of oral candidiasis and the effect of treatment of thrush in human immunodeficiency virus (HIV)-infected patients. PATIENTS AND METHODS: We conducted a prospective observational study of 92 patients over 1 year, including a nonblinded, randomized treatment trial of thrush with clotrimazole troches or oral fluconazole. Oral sites were cultured monthly and when thrush occurred. Candida albicans strains were typed by contour-clamped homogeneous electric field (CHEF) electrophoresis. Changes in strains were evaluated over time and in regard to their associations with particular sites, episodes of thrush, relapse after treatment, and colonization of sexual partners. Susceptibility to fluconazole was tested and CHEF analysis was done on these strains to determine the epidemiology of fluconazole resistance. RESULTS: Yeasts colonized 84% of patients. C albicans accounted for 81% of all isolates and was separated into 34 distinct strains. Most patients had persistent carriage of 1 or 2 dominant strains of C albicans. Three couples shared strains. Nineteen different C albicans strains caused 82 episodes of thrush in 45 patients. CD4 < 200/microL was associated with development of thrush. Clinical cure rates were similar with fluconazole (96%) and clotrimazole (91%), but mycologic cure was better with fluconazole (49%) than clotrimazole (27%). Following mycologic cure, colonization recurred with the same strain 74% of the time. Colonization with Torulopsis glabrata and Saccharomyces cerevisiae increased after treatment with either drug, but these organisms were never a sole cause of thrush. In a subset of 35 patients followed for over 3 months in whom fluconazole susceptibilities were performed, minimum inhibitory concentrations (MICs) to fluconazole increased only in those on fluconazole prophylaxis. Clinical failure of fluconazole was associated with an MIC > or = 64 micrograms/mL in 3 patients, and with an MIC of 8 micrograms/mL in 1 patient. In 2 of these 4 patients, the prior colonizing strain developed fluconazole resistance. In the other 2, new resistant strains were acquired. CONCLUSIONS: Many different strains of C albicans colonize and cause thrush in patients infected with HIV. Patients are usually persistently colonized with a single strain, and recurrences following treatment are usually due to the same strain. Transmission of strains may occur between couples. Fluconazole and clotrimazole are equally effective in treating thrush, but mycologic cure occurs more often with fluconazole. Fluconazole resistance in C albicans occurs most often in patients who have low CD4 counts and are taking fluconazole prophylactically for recurrent thrush. Fluconazole resistance may occur through acquisition of a new resistant strain or by development of resistance in a previously susceptible strain.

AIDS-Related Opportunistic Infections↗

Generation and characterization of a mouse/human chimeric antibody directed against extracellular matrix protein tenascin.

The murine anti-tenascin monoclonal antibody 81C6, following iodination, has been shown to be an efficient localizing and therapeutic agent in both subcutaneous and intracranial human glioma xenograft models in athymic mice and rats. Similarly, effective monoclonal antibody 81C6 localization has been demonstrated in glioma patients, and Phase I trials with the intact murine IgG2b kappa molecule are currently in progress. In order to maximize the potential for repeated administration by minimizing murine Fc-mediated immunogenicity and reducing Fc-mediated immune effects, we created murine 81C6 variable region/human IgG2 chimeric monoclonal antibodies by the molecular cloning of the variable region genes of mouse 81C6 and their genetic linkage to human constant region exons. The resulting chimeric constructs were introduced into SP2/0 cells, and stable transfectomas were selected by G418 and mycophenolic acid resistance. The resistant clones were screened for anti-tenascin activity on tenascin-coated plates by enzyme-linked immunosorbent assay. The N-terminal amino acid sequence of both heavy and light chains of the purified chimeric 81C6 antibody matched exactly with that of the native mouse 81C6 as well as with that deduced from the nucleotide sequence. The production level of chimeric 81C6 (13.9 mg/ml) from ascites in the highest expressing transfectoma was much higher than that of native mouse 81C6 (2.5 mg/ml). The chimeric antibody showed the same specificity and equivalent affinity for human intact tenascin or tenascin-expressing cells as the native mouse 81C6 antibody. Direct comparison of radioiodinated chimeric and radioiodinated mouse 81C6 biodistribution in subcutaneous and intracranial xenograft-bearing mice showed higher tumor-to-normal tissue ratios for chimeric 81C6 as compared with native mouse 81C6. The improved localizing and clearance characteristics of chimeric 81C6 in xenograft model systems suggests that chimeric 81C6 would be an improved reagent for intracompartmental therapy of tenascin-expressing tumors in the human central nervous system.

Animals↗

Evidence for cholecystokinin receptor subtype in endocrine pancreas.

Cholecystokinin (CCK) is a gut hormone that regulates pancreatic endocrine functions via CCKA receptors. CCK4 (Trp-Met-Asp-Phe-NH2) has an insulinotropic effect, but is 1000-fold less potent than CCK8. The in vitro potencies and selectivity of newly synthesized CCK4 analogs were investigated. Exchanging various a amino acids, for example Met by Nle and modifying Phe and/or Trp, led to compounds that were much more effective than CCK4 itself and show insulinotropic effects comparable with those of CCK8. Compounds that possess electron withdrawing groups on the C-terminal phenylalanine were especially effective; compounds with electron-donating groups had no effect. In contrast to CCK8 the synthetic CCK4 compounds were selective for the endocrine pancreas: they had no agonistic or antagonistic effect on the contraction of the guinea pig ileum, amylase release from isolated acini, and no major effect on the feeding behavior of mice being supplied with either compound by an implantable AlzetR pump for 8 days. The data indicate that some of the synthetic tetrapeptides exhibit a high affinity for the CCK receptor of the endocrine pancreas and that they are highly selective for this (peripheral) CCKA receptor subtype. The beta-cell CCKA receptors are different from those in exocrine pancreas, smooth muscle, and those for regulating appetite; these peripheral receptor subtypes can be discriminated for the first time.

Amylases↗

Unsteady entrance flow development in a straight tube.

The entrance conditions for pulsatile flow are important in the understanding blood flow out of the heart and in developing regions at branches. The pulsatile entrance flow was solved using a spectral element simulation of the full unsteady Navier-Stokes equations. A mean Reynolds number of 200 and a range of Womersley parameters from 1.8 to 12.5 was used for a sinusoidal inlet flow waveform 1 + sin (omega t). Variations in the entrance length were observed during the pulsatile cycle. The amplitude of the entrance length variation decreased with an increase in the Womersley parameter. The phase lag between the entrance length and the inlet flow waveform increased for Womersley parameter alpha up to 5.0 and decreased for alpha larger than 5.0. For low alpha, the maximum entrance length during pulsatile flow was approximately the same as the steady entrance length for the peak flow. For high varies; is directly proportional to, the pulsatile entrance length was more uniform during the cycle and tended to the entrance length for the mean flow. The wall shear rate reached its far downstream value after only about half of the entrance length and also exhibited a dependence on alpha. The results quantify the entrance conditions typically encountered in studies of the arterial system.

Evaluation Studies as Topic↗

Azole resistance in oropharyngeal Candida albicans strains isolated from patients infected with human immunodeficiency virus.

For 212 oropharyngeal isolates of Candida albicans, the fluconazole MICs for 50 and 90% of strains tested were 0.5 and 16 micrograms/ml, respectively, and those of itraconazole were 0.05 and 0.2 micrograms/ml, respectively. Of 16 isolates for which fluconazole MICs were > 64 micrograms/ml, itraconazole MICs for 14 were < or = 0.8 micrograms/ml and for 2 were > 6.4 micrograms/ml. Most fluconazole-resistant strains remained susceptible to itraconazole; whether itraconazole will prove effective for refractory thrush remains to be shown.

AIDS-Related Opportunistic Infections↗

Studies of the biosynthesis of 3,6-dideoxyhexoses: molecular cloning and characterization of the asc (ascarylose) region from Yersinia pseudotuberculosis serogroup VA.

The 3,6-dideoxyhexoses are found in the lipopolysaccharides of gram-negative bacteria, where they have been shown to be the dominant antigenic determinants. Of the five 3,6-dideoxyhexoses known to occur naturally, four have been found in various strains of Salmonella enterica (abequose, tyvelose, paratose, and colitose) and all five, including ascarylose, are present among the serotypes of Yersinia pseudotuberculosis. Although there exists one report of the cloning of the rfb region harboring the abequose biosynthetic genes from Y. pseudotuberculosis serogroup HA, the detailed genetic principles underlying a 3,6-dideoxyhexose polymorphism in Y. pseudotuberculosis have not been addressed. To extend the available information on the genes responsible for 3,6-dideoxyhexose formation in Yersinia spp. and facilitate a comparison with the established rfb (O antigen) cluster of Salmonella spp., we report the production of three overlapping clones containing the entire gene cluster required for CDP-ascarylose biosynthesis. On the basis of a detailed sequence analysis, the implications regarding 3,6-dideoxyhexose polymorphism among Salmonella and Yersinia spp. are discussed. In addition, the functional cloning of this region has allowed the expression of Ep (alpha-D-glucose cytidylyltransferase), Eod (CDP-D-glucose 4,6-dehydratase), E1 (CDP-6-deoxy-L-threo-D-glycero-4- hexulose-3-dehydrase), E3 (CDP-6-deoxy-delta 3,4-glucoseen reductase), Eep (CDP-3,6-dideoxy-D-glycero-D- glycero-4-hexulose-5-epimerase), and Ered (CDP-3,6-dideoxy-L-glycero-D-glycero-4-hexulose-4-reductase), facilitating future mechanistic studies of this intriguing biosynthetic pathway.

Amino Acid Sequence↗

Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C.

Resistance to activated protein C (APC) is the most prevalent inherited cause of venous thrombosis. The APC resistance phenotype is associated with a single point mutation in the factor V gene, changing Arg506 in the APC cleavage site to a Gln. We have investigated 50 Swedish families with inherited APC resistance for this mutation and found it to be present in 47 of them. Perfect cosegregation between a low APC ratio and the presence of mutation was seen in 40 families. In seven families, the co-segregation was not perfect as 12 out of 57 APC-resistant family members were found to lack the mutation. Moreover, in three families with APC resistance, the factor V gene mutation was not found, suggesting another still unidentified cause of inherited APC resistance. Of 308 investigated families members, 146 were normal, 144 heterozygotes, and 18 homozygotes for the factor V gene mutation and there were significant differences in thrombosis-free survival curves between these groups. By age 33 yr, 8% of normals, 20% of heterozygotes, and 40% of homozygotes had had manifestation of venous thrombosis.

Arginine↗

Inhibition of macrophage-induced, antigen-specific T-cell proliferation by poly I:C role of suppressor macrophages.

Poly I:C treatment can inhibit the ability of macrophages (M phi) to induce antigen-specific T-cell proliferation. This study investigated whether this inhibition is the result of suppressor or cytotoxic activity. Pretreatment of M phi with indomethacin in vivo, in vitro or both failed to reverse the inhibition of T-cell proliferation induced by poly I:C-treated, keyhole limpet haemocyanin (KLH)-pulsed M phi, suggesting that prostaglandin production does not mediate the inhibition of T-cell proliferation. The transfer of supernatants from cultures containing poly I:C-treated, KLH-pulsed M phi to cultures containing saline-treated, KLH-pulsed M phi and T cells did not inhibit T-cell proliferation, suggesting that the inhibition of T-cell proliferation by poly I:C is not mediated by the production of soluble suppressor factors. As addition of poly I:C-treated, KLH-pulsed M phi to cultures containing saline-treated, KLH-pulsed M phi did not significantly inhibit KLH-specific T-cell proliferation, the inhibition of T-cell proliferation is also not mediated by direct cell contact or short-range soluble suppressor factors. In addition, poly I:C-treated, KLH-pulsed M phi did not induce cytolysis of syngeneic T cells. These results indicate that cytotoxic or suppressor effector functions of M phi are not involved in the mechanism by which poly I:C inhibits M phi-induced, antigen-specific T-cell proliferation.

Animals↗

[Effect of indirect fluorescent antibody test for the diagnosis of amoebiasis].

Indirect fluorescent antibody test (IFAT) was performed by the method of [symbol: see text] (1971) with some slight modifications for the diagnosis of amoebiasis. The antigen used was prepared from 48-hour culture of Entamoeba histolytica (strains G2, G3, and G5) in LAS diphasic medium and only those amoebae clinging the culture were collected. The serum samples or blood drops on filter paper were positive by the improved IFAT in all of the 54 cases of amoebic liver abscess and the positive reactions of most cases were very marked. Of 23 cases of acute amoebic dysentery, 19 were positive, the positive rate being 82.6%. The results also show that 42 cases of other diseases and 40 healthy persons were all negative.

Animals↗

[Effect of hemorheological factors on coronary flow during myocardial ischemia].

Intracoronary infusion of some drugs may induce superimposed coronary vasodilation upon endogenous vasodilation during myocardial ischemia, which was suggested as coronary vasodilator reserve. For an investigation of this phenomenon, 8 pigs were anesthetized, chest-opened, LAD (left anterior descending coronary artery)-dissected and instrumented. The LAD pressure was reduced to 4.67 kPa (35mmHg), and then intracoronary infusion of adenosine, saline, or anisodamine (at the same rate of 2ml/min) was started and maintained for 9 minutes. The three solutions all produced a significant increase in the coronary flow, including the saline (compared with the control, P < 0.05). The hemorheological examination of the distal coronary blood revealed a reduced hematocrit, plasma viscosity and whole blood viscosity during the saline and anisodamine infusion periods (P < 0.05), but in the adenosine infusion, the statistical analysis on hemorheological data revealed no significance compared with the control (P > 0.05). The results showed that the coronary vasodilator reserve induced by intracoronary drugs during myocardial ischemia might be partly accounted by regional hemodilution in the LAD bed. The study suggested that a decrease in blood viscosity might play an important role in the improvement of the narrowed coronary circulation, even more important than vasodilator drugs.

Adenosine↗

[The effects of extracellular matrix on Sertoli cells of rats in vitro].

This study was performed to observe the effects of extracellular matrix (ECM) on Sertoli cells attachment, spreading and morphology in vitro. The ECM used were FN and LN and biomatrix isolated from the liver and lung. The results showed that FN and LN promoted Sertoli cell attachment and spreading. The Sertoli cells grown on the biomatrix isolated from the lung assumed a columnar shape like that seen in vivo. The cells grown on biomatrix from the liver did not.

Animals↗

[Effect of nifedipine on T wave in ischemic myocardium].

Calcium antagonists are generally considered to have no substantial effect on repolarization of the myocardium, so they have no direct effect on T wave, either. But in a pig model of myocardial ischemia, intracoronary nifedipine was found to reverse the inverted T wave induced by ischemia to upright promptly. Ten pigs were anesthetized with the chest opened, anterior interrentricular branch of left coronary artery (LAD) was narrowed to 4.67 kPa of LAD pressure, and then adenosine or nifedipine was infused into the coronary respectively. During the 9-minute ischemia, intracoronary adenosine or intracoronary nifedipine got the similar HR, LVEDP, LVDP, CAP, CAQ, and the intracoronary adenosine even got higher CAQ than the intracoronary nifedipine did. However, the T wave was retained inverted during the adenosine infused, but during the intracoronary nifedipine, the inverted T wave was promptly turned upright. The relevant factors and mechanisms are discussed.

Adenosine↗

[Effects of endotoxin on coronary circulation].

To investigate the effects of endotoxin (ETX) on coronary circulation, we infused endotoxin (4ng/ml) intravenously in a small dose (0.3ng/kg.min-1) which did not reduce the blood pressure, nor did it disturb the coronary autoregulation, and the flow kept constant during the ETX infusion. But when the left coronary artery descending branch (LAD) was narrowed and the LAD pressure was reduced to 4.67kPa, the ETX showed a vasodilator effect on the LAD (pre-ETX 65.2 +/- 29.2 ml/min, post-ETX 89.5 +/- 32.7 ml/min, P < 0.05). This effect suggested that the ETX in a small dose had a vasodilator effect on a narrowed coronary artery, even when it did not disturb the hemodynamics. The possible mechanisms were surveyed preliminarily.

Animals↗

[Comparative study of ischemia-induced and reperfusion-induced ventricular fibrillation in pigs].

To have a better understanding of reperfusion-induced ventricular fibrillation (VF), we studied the relevant morbidity in pigs and compared it with that of the ischemia-induced VF. In 10 hearts of anesthetized chest-open pigs, a total of 127 cycles of various degrees and varied duration of ischemia and reperfusion were completed. VF occurred 13 times (10.2%). Of these, 11 were ischemia-induced VF, while only 2 were reperfusion-induced VF. In two cases of ischemia-induced VF, electric defibrillation failed before the reestablishment of left anterior interventricular branch of coronary artery flow, but after adequate reflowing, all VF turned out to be sinus-rhythm by electric defibrillation. The results suggest that ventricular fibrillation be mainly induced by ischemia but less induced by reperfusion.

Animals↗