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Biomedical subjects

H Lin

Publications and source records attributed to H Lin.

At least 343 records · Page 19Linked to original sources

Roles of prostaglandins and nitric oxide in the effect of endothelin-1 on renal hemodynamics.

It is known that endothelin-1 stimulates the release of nitric oxide and prostaglandins in various vascular beds. We designed the present study to analyze the roles of prostaglandins and nitric oxide in the effect of endothelin-1 on the regulation of renal hemodynamics and renin release. We used N omega-nitro-L-arginine methyl ester (L-NAME) and meclofenamic acid to inhibit the production of nitric oxide and prostaglandins, respectively. With a nonfiltering kidney model, renal blood flow was reduced 21% in dogs treated with L-NAME and 18% in dogs treated with meclofenamic acid. Inhibition of nitric oxide and prostaglandins, however, produced opposite effects on estimated glomerular hydraulic pressure: L-NAME increased glomerular hydraulic pressure from 63.1 +/- 0.9 to 64.6 +/- 1.3 mm Hg (P < .01), and meclofenamic acid reduced glomerular hydraulic pressure from 63.3 +/- 1.4 to 59.8 +/- 1.6 mm Hg (P < .01). Endothelin-1 infusion produced a dose-dependent reduction in renal blood flow after blockade of nitric oxide and prostaglandins. The responses of glomerular hydraulic pressure were different in the two groups during endothelin-1 infusion. Endothelin-1 progressively reduced glomerular hydraulic pressure in a dose-dependent fashion in the meclofenamic acid group. However, endothelin-1 slightly increased glomerular hydraulic pressure until the infusion rate reached 5.0 ng/kg per minute. At that rate, endothelin-1 reduced glomerular hydraulic pressure from 63.3 +/- 1.4 to 47.0 +/- 1.4 mm Hg in the meclofenamic acid group (P < .01), a more than 25% reduction, whereas at the same dose, endothelin-1 reduced glomerular hydraulic pressure only less than 2% in the L-NAME group. In addition, blockade of nitric oxide and prostaglandins did not alter the inhibitory effect of endothelin-1 on renin release in the non-filtering kidney. Therefore, the present study demonstrates that the release of nitric oxide and prostaglandins might modulate the effects of endothelin-1 on the renal circulation. The present findings suggest that the differential vasoconstrictive effects of endothelin-1 on preglomerular and postglomerular vessels are associated with its stimulation of nitric oxide and prostaglandin production.

Animals↗

The role of segment polarity genes during early oogenesis in Drosophila.

In the Drosophila ovary, hedgehog (hh) signaling from cells near the apical tip of the germarium stimulates the proliferation and specification of somatic cells in region 2 of the germarium, 2-5 cells away from the hh-expressing cells (A. J. Forbes, H. Lin, P. Ingham and A. Spradling (1996) Development 122, 1125-1135). This report examines the role during early oogenesis of several genes that are known to function in hh-mediated signaling during embryonic and larval development (P. Ingham (1995) Current Opin. Genetics Dev. 5, 528-534). As in imaginal discs, engrailed (en) is co-expressed with hh in the germarium, while patched (ptc) and cubitus interruptus (ci) are expressed in somatic cells throughout the germarium and in developing egg chambers, with ptc expression being elevated within 10 cell diameters of the source of the hh signal. Moreover, the somatic cell overproliferation caused by ectopic hh expression is accompanied by elevated levels of ptc and is phenocopied in ptc- somatic clones. These analyses suggest that ptc and ci are components of the hh signaling pathway in the germarium. However, unlike embryos and imaginal discs, neither wingless (wg) nor decapentaplegic (dpp) appear to mediate the ovarian hh signal. wg is expressed in 'cap cells,' a subset of hh-expressing cells located adjacent to germ-line stem cells, but is unaffected by ectopic hh expression. Nor does the ectopic expression of wg or dpp mimic the effect of ectopic hh expression. We propose that Hh diffuses from apical cells, including cap cells, and regulates the proliferation of nearby ovarian somatic cells by antagonizing the negative effects of ptc on ci activity in these cells, thereby allowing the transcription of ci-dependent genes, including ptc itself.

Animals↗

hedgehog is required for the proliferation and specification of ovarian somatic cells prior to egg chamber formation in Drosophila.

The hedgehog (hh) gene plays a role in regulating cell proliferation and specifying cell identity in diverse systems. We show that hh is expressed at the extreme apical end of Drosophila ovarioles in terminal filament cells and a newly identified group of associated somatic cells. Reducing or ectopically expressing hh affects somatic cells in region 2 of the germarium, 2-5 cells away from the cells in which Hh protein is detected. hh activity stimulates the proliferation of pre-follicle somatic cells, and promotes the specification of polar follicle cells. hh signaling during egg chamber assembly appears to be closely related to, or part of pathways involving the neurogenic genes.

Animals↗

Allograft vascular disease: comparison of heart and other grafted organs.

A striking resemblance exists between the vasculopathy in several different allografts. The arteriopathy of epicardial coronary arteries is diffuse, involving proximal, distal, and small branch segments in a generally concentric pattern of intimal thickening. Smooth muscle cells in a lipid- and glycosaminoglycan-rich matrix are the predominant components of this expanded intima. Varying amounts of collagen are present, more being present late posttransplant. A superficial and, to a lesser degree, deep, bandlike infiltrate of T cells and macrophages is uniformly present, although it is somewhat more prominent in early lesions as compared to more severely narrowed arteries from longer-term, susceptible grafts. The media is likewise altered by areas of lipid and glycosaminoglycan deposition associated with smooth muscle cell loss and phenotypic modulation. The media is altered in an outside-to-inside direction, with percolation of adventitial leukocytes into the outer media. Virtually all of the coronary features are seen in the medium to large arteries of liver, pancreas, and kidney allografts. Chronic rejection in lung allografts is manifest by obliterative bronchiolitis; vascular changes, although architecturally similar, are somewhat less common and result in less-severe luminal narrowing. The role of allograft vasculopathy in chronic lung rejection is thus less certain. A finding perhaps unique to epicardial coronary arteries of heart allografts is the presence of eccentric lesions more typical of native atherosclerosis. Many of the latter grafts probably have preexistent, undetected donor disease. Sequential evaluation of vascular changes is limited in human biopsy material by their general absence in endomyocardial or core liver needle specimens. Fortunately, vascular changes can be detected in some renal and pancreas core needle biopsies, and these findings may provide an avenue for monitoring the effectiveness of immunosuppressive therapy, antiviral or lipid-altering therapies, or modifications of smooth muscle cell proliferation and glycosaminoglycan deposition yet to be developed.

Heart Transplantation↗

Preventing allograft rejection with CTLA4IG: effect of donor-specific transfusion route or timing.

BACKGROUND: Tolerance to alloantigen in transplant recipients could remove life-long dependence on immunosuppression. Evidence suggests that T-cell responses to alloantigen are dependent not only on T-cell receptor activation but also on costimulation by means of the CD28 receptor. The natural ligands for CD28, expressed on antigen-presenting cells, are B7 family members. CTLA4Ig (a soluble CD28 receptor analog) preferentially binds B7-1 and B7-2 and inhibits CD28 activation. Theoretically, T-cell receptor activation in the presence of alloantigen during CTLA4Ig blockade of CD28-B7 costimulation could render T cells tolerant to that specific alloantigen. In vivo CTLA4Ig significantly increases allograft survival times and can lead to transplantation tolerance. In the rat cardiac allograft model, donor-specific transfusion must be combined with CTLA4Ig to induce tolerance. Previously our laboratory has shown that timing is crucial in the induction of tolerance. METHODS: We examined the effect of differing routes (intravenous, portal vein, or intrathymic), as well as timing (before, at, and after transplantation), of donor-specific transfusion on its ability to synergize with CTLA4Ig using a rat heterotopic major histocompatibility complex-mismatch heart transplant model. RESULTS: We found that tolerance induced by CTLA4Ig and donor-specific transfusion was antigen specific and that timing, but not route of donor-specific antigen administration, had an impact on tolerance induction. Intravenous donor-specific transfusion had a beneficial effect on allograft survival equal to portal vein and intrathymic routes, which have been believed to be more tolerogenic. CONCLUSIONS: Almost universal engraftment can be induced with a combination of intravenous donor-specific transfusion at transplantation plus inhibition of CD28 activation by CTLA4Ig 48 hours after transplantation-a regimen which could have clinical application.

Abatacept↗

Comparison of laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy in taiwan.

In order to clarify the feasibility of laparoscopically assisted vaginal hysterectomy (LAVH) using a not-for-extra charge instrument and to determine its cost-effectiveness in the Taiwan national health care system, we designed a prospective comparison which recruited candidates with nonmalignant uterine tumors prepared for hysterectomy to assess treatment by the laparoscopic versus the laparotomic approach. There were 144 patients in the laparoscopic group and 157 patients in the laparotomic group. The two groups were similar in characteristics. A total of 138 LAVHs were completed with six conversions (4.2%) to abdominal hysterectomy. Intraoperatively, the mean operating time in the LAVH group was longer than in the laparotomic group (134 vs 112 minutes, p < 0.001). No statistically significant differences were found between the two groups in mean estimated blood loss (260 vs 259 mL) and complications (5.8 vs 4.5%). Postoperatively, mean flatulence-relief time (27.4 vs 31.3 hours) and intramuscular meperidine requirements (1.6 vs 2.5 ampoules, 1 ampoule = 50 mg) were significantly less with LAVH. There were no differences in mean hemoglobin levels (10.7 vs 10.9 g/dL), complications (9.4 vs 13.4%, p = 0.288), or hospital stay (4.9 vs 5.2 days, p = 0.058). The mean total hospital charges (NT$48,390 vs 41,649) and insurance-paid costs (NT$43,992 vs 38,389) were significantly greater in the LAVH group. In conclusion, LAVH when performed by an experienced laparoscopist and for adequately selected patients, permits a better short-term convalescence, but is more expensive compared with conventional abdominal hysterectomy.

Adult↗

Prominence of apolipoproteins B, (a), and E in the intimae of coronary arteries in transplanted human hearts: geographic relationship to vessel wall proteoglycans.

BACKGROUND: Transplant arteriopathy (TA) is characterized by vessel wall thickening with prominent glycosaminoglycan and lipid deposits. In this light, we have recently demonstrated the distribution of proteoglycans in allograft coronary arteries. The aim of this study is to examine the distribution of apolipoproteins within allograft coronary arteries and to investigate their localization in relation to proteoglycans. METHOD: Particular transverse sections of left and right epicardial coronary arteries from 46 human cardiac allografts, 11 normal hearts, and 11 hearts with native atherosclerosis were stained immunohistochemically for apolipoprotein B, apolipoprotein (a) (apo[a]), apolipoprotein E (apoE), biglycan, decorin, and versican by use of an automated immunostainer. RESULTS: Apo(a) and apoE immunopositivity in TA was much more intense than that in native atherosclerosis, whereas the reverse was true for apoB. Prominent apoE deposits were evident circumferentially in endothelia and extracellularly in superficial intima of mildly diseased TA, as well as in deeper intima of severely diseased TA. Apo(a) had a staining pattern very similar to apoE except for a patchy deposition also seen in TA media. The intimal areas staining prominently with apoE or apo(a) in TA arteries corresponded very closely to the areas with proteoglycan deposits, especially versican. CONCLUSION: The distinctive patterns of apolipoprotein accumulation in TA and native atherosclefosis appear to reflect different pathogenetic processes in the two conditions. The colocalization of proteoglycans and apolipoproteins in TA intima supports the hypothesis that interactions between proteoglycans and apolipoproteins influence lipid retention and overload in allograft coronary arteries.

Apolipoproteins↗

Biglycan, decorin, and versican protein expression patterns in coronary arteriopathy of human cardiac allograft: distinctness as compared to native atherosclerosis.

BACKGROUND: Histochemical staining has demonstrated previously dramatic deposits of glycosaminoglycans associated with prominent lipid accumulations in thickened vessel walls of allograft coronary arteries. In this study, we characterized the amount, distribution, and types of proteoglycan in the walls of coronary arteries from human cardiac allografts and from native atherosclerotic (NA) controls as part of a strategy to understand the pathogenesis of transplant arteriopathy (TA). METHOD: We used polyclonal rabbit antibodies against human biglycan, decorin, and versican localize the proteoglycan molecules in standardized transverse sections of the proximal left anterior descending and right coronary arteries. Slides were scored in a blinded fashion for intensity of proteoglycan staining (0 to 6+) and for localization in the vessel walls. RESULTS: Unique patterns of proteoglycan distribution were present in TA and NA. Biglycan was particularly prominent in intima and evolving atheromata in severely diseased TA coronary arteries, but not in NA. Decorin was present mainly in adventitia of all vessels and in the intima of NA. Prominent versican accumulation occurred in intima and media of TA coronaries, associated with smooth muscle cells and foam cells. There was a reciprocal pattern of biglycan and decorin staining. Versican colocalized with biglycan. Intimal biglycan and versican deposits were positively correlated to the extent of luminal narrowing in TA. CONCLUSION: The distinctive staining patterns for biglycan, decorin and versican in both native and allograft disease indicate that the synthesis and distribution of these proteoglycans are regulated by different local mechanisms in different atheromatous diseases.

Biglycan↗

[Study on the mutagenicity of salted pork from high risk area of stomach cancer and its relation to pathological changes of gastric mucosa].

To investigate the relations between salted pork (SP) from Zhuanghe (a high risk area of stomach cancer in northeast China) and stomach cancer three studies had been done, including the mutagenicity of SP, the effect of SP on the gastric mucosa of residents in Zhuanghe area who had consumed SP for 10-30 years and the mucosal lesions of dogs taking SP. The results showed that the extract of SP was a strong mutagen in strain TA98 and led to increased micro-nuclei rate (MNR) and micro-nuclei cell rate (MNCR) of V79 cell at a dose range of 20-80 mumol/ml. There were dose-effect relations between SP and MNR, MNCR. The results also indicated that pathological changes of gastric mucosa of residents who consumed SP had remarkable difference from those of the control group. In people who had consumed SP for 10 years, mucosal lesions including necrosis and erosion were seen; for those consumed SP for 10+(-)20 years, there were hyperplasia and dysplasia and those for 20+(-)30 years different degrees of dysplasia and even malignant change could be observed. The research also found that SP had damaging effect on gastric mucosa in dogs taking SP. The mucosal lesions became more severe with time of feeding SP. The conclusion is that SP is a strong mutagen, long-term exposure to SP may result in repeated gastric mucosal damage and repair, and finally in severe dysplasia and malignancy.

Animals↗

[Effect of anisodamine in prevention and treatment of visceral complications in serious burns].

From January 1992 to December 1994, anisodamine was used in 156 cases of serious burns. The results showed that there was a significant lowering of incidence of visceral complications in the treatment group than in the control group. Also the cure rate of visceral complications was significantly elevated in the treatment group than control group. The result indicated that anisodamine had both prevention and treatment effects on visceral complications in serious burns.

Adult↗

[Mitral valve replacement under beating heart in 137 cases].

To avoid damage of myocardial ischemia, myocardial hypoxia and reperfusion injury, we designed mitral valve replacement in beating heart under extracorporeal circulation with low dose temperature of 31 degrees C to 35 degrees C in 137 cases of rheumatic heart disease, congenital heart disease mitral stenosis and mitral insufficiency, or concurrent aortic insufficiency. The patients were rept in unblocking aorta, unfilling cardiac arrest perfusion, idle pulse and dradycardia of 40-50 times/min, nose temperature of 32 +/- 1 degrees C. Patients with concurrent aortic insufficiency should first undergo replacement of aorta under cold cardiac arrest and then replacement mitral valve under beating heart to reduce the time of cold heart ischemia. Plastic surgery for tricuspid valve was done under beating heart. Good postoperative prognosis was nated: an average arterial pressure of 9.5-10.5 kPa (70 to 80 mmHg), dose of dopamine was obviously reduced. No low cardiac output syndrome, acute renal failure and severe arrythmia were observed in 137 cases, except 4 deaths due to infection and blood coagulation (2.9%). A left cardiac chamber no-level air removal device and aorta perfusioner leading flow device were designed for exsufflation of left pneumatocardia.

Adolescent↗

Failure of B-cell differentiation in mice lacking the transcription factor EBF.

Early B-cell factor (EBF) is a cell type-specific transcription factor that is expressed at all antigen-independent stages of B-lymphocyte differentiation and participates in the regulation of the mb-1 gene. Here we show, by targeted gene disruption in mice, that EBF is necessary for the generation of immunoglobulin-expressing B cells. EBF-deficient mice lack B cells that have rearranged their immunoglobulin D and JH gene segments, but contain B220+CD43+ progenitor cells that express germline mu and IL-7 receptor transcripts. Various non-lymphoid tissues that express EBF are apparently normal in homozygous mutant mice, including olfactory neurons in which EBF was identified as Olf-1 (refs 5, 6). Together, these data suggest that EBF plays a specific and important role in the transcriptional control of B-cell differentiation at a stage before Ig (immunoglobulin) gene rearrangement but after commitment of cells to the B-lymphoid lineage.

Animals↗

EBF contains a novel zinc coordination motif and multiple dimerization and transcriptional activation domains.

Early B cell factor (EBF) was identified and cloned as a transcription factor expressed specifically in B lymphocytes and adipocytes. This protein was also identified as olfactory factor 1 (Olf-1) in olfactory neurons. In this study, we analyzed the structural requirements for DNA binding, homodimerization and transcriptional activation by EBF. A carboxyl-terminal region, containing a repeat of alpha-helices related to the helix-loop-helix motif, is important for dimerization of EBF in solution and can confer dimerization upon a heterologous DNA binding protein. The amino-terminal DNA binding domain by itself is monomeric, but can mediate assembly of dimers on optimized and correctly spaced half-sites. Mutational analysis of the DNA binding domain of EBF indicated that a novel zinc coordination motif consisting of H-X3-C-X2-C-X5-C is important for DNA recognition. Deletion analysis and transfer of regions of EBF onto a heterologous DNA binding domain identified a serine/threonine-rich transcriptional activation domain. Moreover, the DNA binding domain of EBF can mediate transcriptional activation from optimized binding sites. Thus, EBF contains both a complex DNA binding domain that allows for dimerization and transcriptional activation, and additional dimerization and activation domains.

Amino Acid Sequence↗

Loss of P16INK4 expression is frequent in high grade gliomas.

P16INK4 is a cell cycle regulator that specifically binds to and inactivates cyclin-dependent kinase 4 (CDK4). Its encoding gene (p16/CDKN2) maps to chromosome 9p21, a region that undergoes frequent loss of heterozygosity in a variety of human tumors. We have analyzed the p16/CDKN2 gene and its expression in a series of primary glioma samples. Although homozygous deletion or mutation of the p16/CDKN2 gene was uncommon in this series and P16INK4 protein was detectable in all grade II tumors, it was present in only 50% of grade III and grade IV samples. Conversely, in some grade IV tumors that level of P16INK4 protein was elevated; in these cases, its target, CDK4, was amplified and overexpressed. These results suggest: (a) the involvement of P16INK4 in glioma progression; (b) that mechanisms other than mutation or deletion can down-regulate expression of the p16/CDKN2 gene; and (c) that the balance between CDK4 and its cognate inhibitor, P16INK4, may confer a cell growth advantage and facilitate tumor progression.

Astrocytoma↗

Bacteriophage T4 gene 17 amplification mutants: evidence for initiation by the T4 terminase subunit gp16.

Bacteriophage T4 genes 16 and 19 containing the 24 bp homology regions that recombine to form Hp17 mutants were cloned into plasmids. When the two homology sequences were cloned either together into one or separately into two compatible plasmids, a polymerase chain reaction assay showed that recombination occurred in vivo. The recombinant sequence was identical with that found in T4 phage Hp17 mutants, and was produced in recombination-deficient Escherichia coli. Mutational analysis revealed a requirement for functional gene 16 but not gene 17 to recombine the sequences. Moreover, gp16, the terminase small subunit, was required, since an amber gene 16 produced the recombinant sequence only when suppressed. Mutations in the gene 16 recombination sequence (3GA and 15TG) that eliminated Hp17 formation in T4 phage increased the synthesis of the large terminase subunit, gp17 in T4 infections, suggesting gp16 interaction with this site. gp16 binding to gene 16 and gene 19 pac-like sites may synapse the homologous sequences to lead to Hp17 mutant formation, and this suggests a synapsis mechanism for control of T4 DNA maturation and concatemer processing in packaging.

Bacteriophage T4↗

Opposing effects of plasma epinephrine and norepinephrine on coronary thrombosis in vivo.

BACKGROUND: It is well known that plasma catecholamines and myocardial infarction have a close relation and that coronary artery thrombosis is a major cause of myocardial infarction. In addition, epinephrine is known to be a prothrombogenic agent in vivo. However, the role of the other major circulating catecholamine, norepinephrine, in the development of coronary thrombosis is somewhat uncertain, although the role of norepinephrine is often considered analogous to the role of epinephrine. Therefore, the present study was designed to investigate the effect of norepinephrine and its interaction with epinephrine on coronary thrombosis. METHODS AND RESULTS: To compare the effects of epinephrine and norepinephrine on coronary thrombosis, we analyzed the frequency of cyclic blood flow reductions (CFRs) in an anesthetized canine model of coronary thrombosis (n = 25). Three experiments were used in the present study. In the first experiment with epinephrine infusion, plasma epinephrine was elevated from 0.46 +/- 0.25 to 27.7 +/- 1.85 nmol/L. The frequency of CFRs increased by more than 60%, from 7.1 +/- 0.5 to 11.5 +/- 0.7 in 40 minutes (P < .01). The second experiment included three experimental periods: control, norepinephrine infusion, and norepinephrine infusion plus epinephrine infusion. Norepinephrine was infused to raise plasma norepinephrine from 1.3 +/- 0.2 to 32.4 +/- 4.3 nmol/L. The frequency of CFRs in the dogs was markedly reduced, from 7.89 +/- 0.42 to 2.41 +/- 1.08 in 40 minutes (P < .01), whereas arterial pressure was elevated from 88 +/- 3 to 118 +/- 5 mm Hg (P < .01). However, when epinephrine infusion was added to the norepinephrine infusion, the frequency of CFRs increased from 2.41 +/- 1.08 to 7.74 +/- 1.12 in 40 minutes (P < .01). In the third experiment, a servocontrol device was used during the norepinephrine infusion to prevent rises in coronary arterial pressure. As a result of the norepinephrine infusion, the frequency of CFRs was reduced from 7.47 +/- 0.71 to 0.83 +/- 0.65 in 40 minutes (P < .01), even though the coronary arterial pressure was not altered. CONCLUSIONS: The present study demonstrated that infusion of epinephrine stimulated coronary artery thrombosis, whereas infusion of norepinephrine inhibited coronary artery thrombosis. In addition, the inhibitory effect of norepinephrine on coronary thrombosis is independent of increases in coronary arterial pressure. Therefore, the present findings suggest that epinephrine and norepinephrine have opposing effects on coronary thrombosis in dogs.

Animals↗

Computer-assisted surgery planning for lower extremity deformity correction by the Ilizarov method.

Starting in 1952, Prof. Gavril Ilizarov, a Russian orthopedic surgeon, devised a complex method of long bone deformity correction using an external bone fixation system consisting of rings and wires. We have developed a computer-assisted surgery planning system to aid in correction using the Ilizarov method. The hardware for the system is composed of an ultrasonic digitizer as input device, an HI plotter as output device, a 386/486 personal computer with super VGA monitor, and a mouse interfacing between user and computer. The software includes two separate programs. The main program is a menu-driven two-dimensional graphics program, which divides the planning procedure into several major stages, including preoperative planning and postoperative verification. The second program uses the information generated from the first program to create an image of the ideal three-dimensional frame construction to give a general impression of the appearance of the constructed frame.

Computer Simulation↗