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Biomedical subjects

M Yin

Publications and source records attributed to M Yin.

At least 73 records · Page 4Linked to original sources
PubMed1997

Hemodynamic responses to endothelin-1 and endothelin antagonists microinjected into the nucleus tractus solitarius in rats.

The role of endothelin-1 (ET-1) within the nucleus tractus solitarius (NTS) in central cardiovascular control was investigated by local microinjections of ET-1 and ET-receptor antagonists. In urethane-anesthetized Sprague-Dawley rats, a unilateral microinjection of ET-1 (1.0, 3.3, and 10.0 pmol) into the NTS significantly increased arterial pressure, left ventricular systolic pressure, and dP/dt(max) in a dose-dependent manner, and slightly decreased heart rate in a dose-independent manner. The pressor effect lasted >90 min. In normotensive rats, neither PD147953, a selective ETA-receptor antagonist, nor PD142893, a mixed ETA- and ETB-receptor antagonist, microinjected into the NTS elicited any changes in arterial pressure or heart rate. The pressor and bradycardic effects evoked by microinjection of ET-1 into the NTS could be blocked by local pretreatment with PD147953 and completely eliminated by intravenous pretreatment with the ganglionic blocker hexamethonium. The arterial baroreflex sensitivity was almost totally suppressed by microinjection of ET-1 (3.3 pmol) in alpha-chloralose-anesthetized Sprague-Dawley rats. A similar pattern of changes in the hemodynamic variables was elicited by microinjection of ET-1 (3.3 pmol) into the NTS in spontaneously hypertensive rats (SHRs) compared with Wistar-Kyoto (WKY) rats. In SHRs, microinjection of PD142893 did not elicit any changes in arterial pressure or heart rate. These results suggest that ET-1 modulates reflex control of hemodynamics by activation of autonomic nerve via ETA receptors in the NTS, and that the responsiveness of SHRs to ET-1 or PD142893 is similar to that of WKY rats.

Animals↗
PubMed1997

[New method for preparing oridonin by column chromatography].

Compared with the traditional methods, the separation and preparation of oridonin by column chromatography have the advantages of fast speed, harmlessness and non-pollution of solvent, safety, economy and easily obtained, etc. After re-crystallizing the oridonin content is determined by TLC scanning to be as high as 97.03%.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Fatal excited delirium following cocaine use: epidemiologic findings provide new evidence for mechanisms of cocaine toxicity.

We describe an outbreak of deaths from cocaine-induced excited delirium (EDDs) in Dade County, Florida between 1979 and 1990. From a registry of all cocaine-related deaths in Dade County, Florida, from 1969-1990, 58 EDDs were compared with 125 victims of accidental cocaine overdose without excited delirium. Compared with controls, EDDs were more frequently black, male, and younger. They were less likely to have a low body mass index, and more likely to have died in police custody, to have received medical treatment immediately before death, to have survived for a longer period, to have developed hyperthermia, and to have died in summer months. EDDs had concentrations of cocaine and benzoylecgonine in autopsy blood that were similar to those for controls. The epidemiologic findings are most consistent with the hypothesis that chronic cocaine use disrupts dopaminergic function and, when coupled with recent cocaine use, may precipitate agitation, delirium, aberrant thermoregulation, rhabdomyolysis, and sudden death.

Adult↗
PubMed1996

Tumor necrosis factor alpha promotes nuclear localization of cytokine-inducible CCAAT/enhancer binding protein isoforms in hepatocytes.

Hepatocytes were cultured in the presence of recombinant tumor necrosis factor (TNF) alpha or mutated TNF alpha peptides that specifically activate either p55 or p75 TNF receptors to determine if TNF alpha can activate cytokine-inducible CCAAT/enhancer binding protein (C/EBP) isoforms by post-transcriptional mechanisms that are initiated by TNF receptors. Within 5-10 min after treatment with any of these agents, nuclear concentrations of C/EBP beta and C/EBP delta double and remain 2-4-fold greater than control cultures for 30 min (p < 0.01). Consistent with these results, gel mobility shift assays demonstrate 3-fold increased nuclear C/EBP beta- and C/EBP delta-DNA binding activity in TNF alpha-treated cells, and immunocytochemistry confirms rapid redistribution of these C/EBP isoforms into the nucleus. In contrast, mRNA and whole cell protein concentrations of C/EBP beta and delta are not altered by TNF alpha exposure, and nuclear concentrations of another C/EBP isoform, C/EBP alpha, are decreased by 80%. This novel evidence that TNF alpha initiates post-transcriptional activation of cytokine-inducible C/EBP isoforms identifies a mechanism that enables hepatocytes to respond immediately to inflammatory stress.

Amino Acid Sequence↗
PubMed1996

The PAF antagonist TCV-309 reduces graft PMN infiltration and enhances early function of 24-hour-preserved rat kidneys with long warm ischemia.

The purpose of this study was to investigate whether treatment with TCV-309, a PAF antagonist, improves life-sustaining function of renal grafts that have suffered warm ischemia (WI) prior to cold storage (CS) and whether TCV-309 influences leukocyte sequestration in tissues. Syngeneic kidneys with 20 min of WI and 24 hr of CS were transplanted into bilateral nephrectomized rats. In the treated group, TCV-309 was administered (i.v. 1 mg/kg) 5 min before reperfusion. Rats in the control group received saline. On day 14, 80% rats survived in the treated group, which was higher than the controls (0%). At 24 hr of reperfusion, myeloperoxidase (MPO) activity, a marker enzyme for PMNs, in the treated kidney was significantly lower than the controls, but did not differ from the normal values. The MPO activity in the controls was higher than the normal values. In conclusion, the PAF antagonist improves posttransplant function of rat kidneys subjected to a period of WI and CS. PMNs are involved in postischemic renal injury, which is, at least partially, mediated by PAF. The effectiveness of PAF antagonist in treatment of recipients may lead to its clinical application in transplantation of ischemically injured kidneys.

Animals↗
PubMed1996

Adenovirus-mediated transfer of CCAAT/enhancer-binding protein-alpha identifies a dominant antiproliferative role for this isoform in hepatocytes.

CCAAT/enhancer-binding protein (C/EBP) isoforms are thought to be important regulators of the hepatocyte phenotype. However, the specific physiological roles of different isoforms are poorly understood because hepatocytes express multiple C/EBPs, and various isoforms have overlapping functions. To identify the functions of C/EBPalpha in mature hepatocytes, replication-defective adenovirus vectors were used to efficiently and homogeneously overexpress the mouse C/EBPalpha gene in a SV40 virus-conditionally transformed rat hepatocyte line that can be induced to express C/EBPbeta and C/EBPdelta but that has little endogenous C/EBPalpha expression. Hepatocytes were infected with a recombinant adenovirus vector carrying the cDNA for C/EBPalpha driven by Rous sarcoma virus promoter elements (AdCEBPalpha) or a similar vector carrying the Escherichia coli lacZ gene (Adbetagal). Staining for beta-galactosidase demonstrated an infection efficiency of 100% at a multiplicity of infection of 25 plaque-forming units/cell and persistence of foreign gene expression for at least 9 days. Cultures infected with AdCEBPalpha had 50-fold higher levels of C/EBPalpha mRNA and protein than those infected with Ad-beta-gal, but similar expression of C/EBP-beta. Infection with AdCEBPalpha inhibited proliferation in cells expressing little C/EBPbeta, even when proliferation was driven by the SV40 transforming antigen, and also blunted mitogenic induction of the c-myc proto-oncogene in nontransformed cells with high levels of C/EBPbeta. Although overexpression of C/EBPalpha consistently increased C/EBPalpha DNA binding activity, it was not sufficient for albumin expression. Infection with AdCEBPalpha only increased albumin mRNA levels in nontransformed cells that also expressed relatively high levels of C/EBPbeta. Thus, in hepatocytes, C/EBPalpha has a dominant antiproliferative function, but must interact with other factors to regulate hepatocyte-specific gene expression.

Adenoviridae↗
PubMed1996

Short-term outcome of kidney transplants from non-heart-beating donors after preservation by machine perfusion.

In this study, the short-term outcome of renal transplants from non-heart-beating donors (NHBD) preserved by machine perfusion (MP) is evaluated and compared to preservation by cold storage (CS). Twenty-two NHBD kidneys were procured during 1993 and 1994 after in situ perfusion with histidine-tryptophan ketoglutarate and preserved by continuous perfusion using University of Wisconsin organ preservation solution for MP as a perfusate. Between 1980 and 1992, 57 NHBD kidneys were procured and preserved by CS. Donors in the MP group sustained increased first warm ischemia times (WIT1) (P < 0.1) and recipients in the MP group suffered longer anastomosis time, worse HLA-DR mismatch, and more initial use of cyclosporin as immunosuppressant; all these factors are known to be deleterious to short-term outcome. Despite these unfavorable conditions, delayed function (DF) rate was decreased in the MP group, although not significantly. However, when considering only kidneys with WIT1 > or = 45 min, short-term outcome was significantly better in the MP group (P < 0.05). We conclude that MP is superior for the preservation of NHBD kidneys, especially after prolonged warm ischemia.

Adult↗
PubMed1996

Correlation between the intensity of cytomegalovirus infection and the amount of perivasculitis in aortic allografts.

We previously demonstrated that cytomegalovirus (CMV) infection enhanced perivascular inflammation in rat aortic allografts. In this study, we investigated the relationship between the CMV infection load and the magnitude of perivasculitis (chronic rejection) in aortic transplants. Rats received orthotopic abdominal aortic grafts, different degrees of total body irradiation (TBI) for immunosuppression and CMV inoculation. The spleens of the rats receiving 5 Gy of TBI contained more infectious virus and viral antigens than those of rats receiving 3 Gy of TBI or no TBI. Although the number of inflammatory cells infiltrating the perivascular area was decreased after TBI, CMV infection resulted in increased perivasculitis in rats that received 5 Gy of TBI as compared to non-infected animals. This virus-induced effect was characterized predominantly by an increased T-cell infiltration, including CD4 and CD8 T-cells. It is concluded that an enhanced systemic CMV infection during severe immunosuppressive therapy can accelerate the development of chronic rejection, which seems to be mediated mainly by T-cells.

Animals↗
PubMed1996

Retrograde oxygen persufflation in combination with UW solution enhances adenine nucleotide contents in ischemically damaged rat kidney during cold storage.

Retrograde oxygen persufflation (ROP) has been reported to be beneficial to kidney preservation. The purpose of this study was to investigate whether use of ROP during cold storage (CS) with Universita of Wisconsin (UW) solution could ameliorate energy metabolism and functional recovery of ischemically injured rat kidneys and, moreover, to study the particular role of adenosine (ADO) in CS with ROP. Kidneys subjected to 30 min of warm ischemia (WI) were preserved for 24 h in 4 degrees C UW solution with or without ROP and with or without ADO. Measurements of tissue high-energy phosphate levels showed that reduced total adenine nucleotides (TAN) after 30 min of WI further declined during the subsequent CS. In ROP kidneys, however, TAN were less reduced, suggesting that even during CS, TAN can still be regenerated in the injured kidneys when ROP is combined with UW solution. When UW did not contain ADO, regeneration of TAN by ROP was slightly less than in the case of UW with ADO. This indicates that the supply of molecular oxygen is a significant factor in TAN resynthesis during CS. There was no statistically significant difference in survival rate between the ROP and CS groups, indicating that an improved energy status is not the sole determinant of functional recovery. We conclude that the gaseous oxygen supply provided by ROP during CS in UW solution ameliorates the energy state of ischemically injured rat kidneys and that exogenous ADO from the UW solution contributes to the improvement of energy metabolism to a limited extent.

Adenine Nucleotides↗
PubMed1996

Alcohol and cytokine-inducible transcription factors.

Cytokines, such as TNF alpha, modulate the behavior of many cells by regulating the expression of a wide array of genes. When a cytokine binds to its receptor on the cell surface, the receptor becomes activated and activates signal transduction cascades. These cascades typically involve a series of phosphorylation reactions that lead to sequential activation of various kinases. The targets of these kinases include DNA binding proteins that regulate the transcription of target genes. The activity of DNA binding proteins, such as c-Jun and NF-kappa B, titrates the transcriptional activity of cytokine-regulated genes. Both acute and chronic alcohol consumption of ethanol increase hepatic expression of TNF alpha. After acute ethanol consumption, this is associated with increased induction of several TNF-dependent regenerative events, including the activation of c-Jun and increased binding activity of NF-kappa B. However, chronic consumption of ethanol appears to impede TNF alpha signaling in the liver because it attenuates the increases in c-JUN activity and NF-kappa B binding, which normally follow partial hepatectomy. These results suggest that one mechanism by which ethanol influences liver cell behavior is by influencing local expression of TNF alpha and changing the activity of TNF-regulated transcription factors.

Alcohol Drinking↗
PubMed1996

Differential regulation of hepatocyte DNA synthesis by cAMP in vitro in vivo.

Adenosine 3',5'-cyclic monophosphate (cAMP) prevents epidermal growth factor (EGF)-induced DNA synthesis in many types of cultured cells, including hepatocytes, but its effects on cellular proliferation in vivo are unknown. This study compares the effects of supplemental cAMP on hepatocyte proliferation induced in vivo by 70% partial hepatectomy (PH) and in vitro by EGF and determines the effects of cAMP on AP-1, a family of growth-regulatory transcription factors, and the kinase cascades that normally activate AP-1. Although injection of dibutyryladenosine 3',5'-cyclic monophosphate (30 mg/kgip) at the time of PH increased liver cAMP concentrations at least 100-fold for several hours, it did not inhibit hepatic incorporation of [3H]thymidine or proliferating cell nuclear antigen expression 24 h after PH. cAMP treatment led to a complete inhibition of extracellular signal-related kinase (ERK) activity and transiently reduced NH2-terminal Jun nuclear kinase (JNK) activity after PH but did not decrease the expression of c-jun mRNA or protein. Consistent with the known cAMP stimulation of jun-B in cultured cells, cAMP treatment increased jun-B mRNA, protein, and DNA binding activity post-PH. Surprisingly, cAMP treatment enhanced Raf kinase activity after PH in rats. In primary hepatocyte cultures, supplemental cAMP inhibited JNK and ERK activity, total AP-1 and c-Jun transcriptional activities, and DNA synthesis. Thus elevated cAMP inhibited ERK and JNK activity in culture and in vivo and inhibited hepatocyte proliferation in culture but not in vivo. This suggests that in vivo mechanisms compensate for cAMP inhibition of certain growth-related signaling cascades and emphasizes potential risks of extrapolating from simple cell culture systems to explain physiology in intact animals.

Animals↗
PubMed1996

Role of gamma-aminobutyric acid B receptors in baroreceptor reflexes in hypertensive rats.

Previous studies demonstrated that stimulation of gamma-aminobutyric acid B (GABA(B)) receptors in the nucleus tractus solitarius of spontaneously hypertensive rats (SHR) elicited a larger increase in arterial pressure compared with control Wistar-Kyoto rats. Since stimulation of GABA(B) receptors in the nucleus tractus solitarius attenuates cardiovascular responses evoked by electrical stimulation of the aortic depressor nerve in normotensive rats and there is evidence of a central neural attenuation of aortic depressor nerve-evoked responses in SHR, we conducted studies to test the hypothesis that enhanced stimulation of GABA(B) receptors in the nucleus tractus solitarius in SHR is responsible for the attenuation of the aortic depressor nerve-evoked responses. Electrical stimulation of the left aortic depressor nerve resulted in frequency-dependent decreases in arterial pressure, heart rate, and splanchnic sympathetic nerve activity in urethane-anesthetized control rats. These responses were not significantly altered by injection of the GABA(B) receptor antagonist CGP 35348 into the ipsilateral nucleus tractus solitarius. The responses evoked by aortic depressor nerve stimulation were attenuated in SHR. This attenuation was particularly apparent with more prolonged periods (>15 seconds) of high-frequency (25-Hz) stimulation, with the depressor and sympathetic nerve responses diminishing during the course of stimulation. This time- and frequency-dependent attenuation of baroreceptor-evoked depressor responses was reversed by injection of CGP 35348 into the ipsilateral nucleus tractus solitarius. Rats made hypertensive by treatment with deoxycorticosterone plus salt did not have attenuated aortic depressor nerve-evoked responses. These results suggest that alterations in GABA b-mediated neural transmission in the nucleus tractus solitarius contribute to the attenuation of the baroreceptor reflex observed in SHR.

Animals↗
PubMed1996

Ischemia-reperfusion injury of rat kidney relates more to tubular than to microcirculatory disturbances.

Several pathophysiological mechanisms have been purported to be involved in the development of acute ischemic renal failure, such as impairment of tubular function and/or of the renal microcirculation. However, it has not been elucidated as yet which of these mechanisms relates to the extent of kidney damage. Besides, little is known about the time course relationship between tubular and microcirculatory disturbances during the development of ischemia-reperfusion injury. We therefore performed intravital videomicroscopy of the proximal tubules as well as the peritubular microcirculation of the rat renal cortex during the first 24 hr of reperfusion after varying lengths of warm ischemia (30 min, 30 WI group; 60 min, 60 WI group; 90 min, 90 WI group). In a separate group of animals subjected to the same protocol, the survival rate (SR) was determined. The SR in these groups were 100%, 20% and 0%, respectively. Initially, the tubular and microcirculatory changes (i.e., increased tubular diameter and reduced capillary blood flow) relate well to the length of warm ischemia as well as the SR. At a later stage of reperfusion, however, we observed that peritubular capillary blood flow and tubular diameter recovered more quickly in the 90 WI group than in the 30 WI and 60 WI groups. As a result, these parameters as obtained at 24 hr of reperfusion did not relate anymore to the survival rate. Besides, at this stage a severe loss of integrity of the tubular wall was noted in the 60 WI and 90 WI groups. These findings suggest that kidney viability is not determined by the extent of recovery of microcirculatory blood flow and/or tubular diameter during early reperfusion, but by the integrity of the tubular wall.

Analysis of Variance↗
PubMed1995

Early-onset multifocal inflammation in the transforming growth factor beta 1-null mouse is lymphocyte mediated.

Transforming growth factor beta 1 (TGF beta 1)-null mice die fro complications due to an early-onset multifocal inflammatory disorder. We show here that cardiac cells are hyperproliferative and that intercellular adhesion molecule 1 (ICAM-1) is elevated. To determine which phenotypes are primarily caused by a deficiency in TGF beta 1 from those that are secondary to inflammation, we applied immunosuppressive therapy and genetic combination with the severe combined immunodeficiency (SCID) mutation to inhibit the inflammatory response. Treatment with antibodies to the leukocyte function-associated antigen 1 doubled longevity, reduced inflammation, and delayed heart cell proliferation. TGF beta 1-null SCID mice displayed no inflammation or cardiac cell proliferation, survived to adulthood, and exhibited normal major histocompatibility complex II (MHC II) and ICAM-1 levels. TGF beta 1-null pups born to a TGF beta 1-null SCID mother presented no gross congenital heart defects, indicating that TGF beta 1 alone does not play an essential role in heart development. These results indicate that lymphocytes are essential for the inflammatory response, cardiac cell proliferation, and elevated MHC II and ICAM-1 expression, revealing a vital role for TGF beta 1 in regulating lymphocyte proliferation and activation, which contribute to the maintenance of self tolerance.

Animals↗
PubMed1995

Protection of canine renal grafts by renin-angiotensin inhibition through nucleoside transport blockade.

The aims of this study were (1) to investigate the effect of R 75231, a nucleoside transport inhibitor, on renin-angiotensin release after renal ischemia-reperfusion and (2) to establish a possible protective effect of this drug on renal function. We used a canine model for auto- transplantation of kidneys that had been subjected to 30 min of warm ischemia and subsequently to 24h of cold storage in HTK preservation solution, with immediate contralateral nephrectomy. R 75231 was injected intravenously into six dogs in two equal portions of 0.05 mg/kg both 30 min and 10 min before reanastomosis was established. Another six dogs were used as a control group. At 2 weeks post-transplantation, five out of six dogs in the R 75231 group and one out of six in the control group were still alive. Starting on day 4, serum creatinine was lower in the R 75231 group than in the control group (p < 0.005). In contrast to the control group, an inversion of the median preischemia adenosine/inosine ratio was observed in the R 75231 group after reperfusion (0.4 preischemia vs 4.0 after 60 min of reperfusion). Reperfusion of the graft resulted in an immediate increase in renin, angiotensin I, and angiotensin II venous blood levels in the control group. In the R 75231 group, renin, angiotension I, and angiotensin II levels were significantly lower. We conclude that administration of R 75231 before reperfusion has a protective effect on post-transplant function of kidneys that have been subjected to prolonged warm ischemia. This effect may, at least in part, be ascribed to inhibition of the breakdown and disposal of endogenous adenosine which, in turn, inhibits the excessive stimulation of the renin-angiotensin system in the early phase of reperfusion.

Animals↗