Endothelium-dependent contraction of canine coronary artery is enhanced after 24 hours of preservation with University of Wisconsin solution.
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Biomedical subjects
Publications and source records attributed to C H Chang.
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The Emergency Medical Services (EMS) aims to improve the survival rate of patients who are dead on arrival (DOA) at hospital, particularly those whose coronary artery disease (CAD) has induced sudden death. Based on the low prevalence of CAD-induced sudden death in Taipei city, as well as the differences between urban and rural communities in Taiwan, an understanding of the characteristics of rural areas is necessary in order to establish a well-organized and cost-effective EMS policy in this country. The data were drawn from a computer database which stored prehospitalization information from Ilan County from 1992 through 1994, including age, sex, response time, time spent on the scene, transportation time, service unit, reasons for emergency call and trauma mechanism. In 1096 study days, 20058 cases (18/day) were collected, of which 16560 (15/day; 83.6%) were transported to hospital. Trauma was responsible for the majority (77%) of these cases, followed by chronic diseases (4.0%), trivial matters (2.6%), drunkenness (2.3%), altered mental status (2.3%), suicide attempt (2.2%), and cardiac arrest (1.8%). Among the trauma cases, traffic accidents were the most common cause (84%); motorcycle accidents comprised 65% of trauma cases. The average response time was 6.6 minutes, time spent on the scene was 3.6 minutes, and transportation time was 17.7 minutes. Trauma and non-trauma accounted for half of the DOA cases, with each making up 0.9% of the total cases transported. In conclusion, it is important that the EMS needs of each community are known for a proper system appropriate to that particular area to be developed.
A 22-year-old woman was referred to our hospital because of severe anemia in the 20th week of gestation. Acute myelogenous leukemia was diagnosed and she was treated with multiple-agent chemotherapy in the second and third trimesters. Although the patient tolerated the intensive treatment, an intermittent sinusoidal fetal heart rate pattern was detected during chemotherapy. Complete remission was achieved at the 35th week of gestation. An underweight baby boy, suffering from pancytopenia, was delivered by cesarean section at 36 weeks' gestation. The baby recovered well and had adequate growth. No abnormalities where found at examination two months after birth. The fetal sinusoidal heart rate pattern may have been induced by severe anemia due to myelosuppression caused by the transplacental receipt of chemotherapeutic agents.
University of Wisconsin (UW) solution has been used almost routinely in the preservation of the hepatic, pancreatic, renal, and cardiac allografts. However, its effect on vascular endothelium is unknown. Experiments were designed to evaluate its effect on canine coronary endothelium. Canine coronary arteries (n = 8 in each group) were preserved in cold (4 degrees C) UW solution (group 1) and physiological solution (group 2) for 6 hr immediately after harvesting. Segments of preserved and control (group 3) coronary arteries with or without endothelium were then suspended in organ chambers to measure isometric force. Perfusate hypoxia (pO2 30 +/- 5 mmHg) caused endothelium-dependent contraction in the arteries of all 3 groups. However, vascular segments with endothelium of group 1 exhibited hypoxic contractions (107 +/- 26% of the initial tension contracted by prostaglandin F2 alpha 2 x 10(-6) mol/L, P < 0.05) that were significantly greater than those of the group 2 and group 3 segments with endothelium (25 +/- 5% and 20 +/- 4%). The hypoxic contraction in arteries of group 1 could be attenuated by NG-monomethyl-L-arginine (L-NMMA), the blocker of endothelial cell synthesis of the nitric oxide from L-arginine. The action of L-NMMA could be reversed by L-arginine but not D-arginine. Endothelium-dependent relaxation of coronary endothelium to acetylcholine and adenosine diphosphate and endothelium-independent relaxation and contraction of coronary smooth muscle were not altered by the UW solution. After preservation with the UW solution, endothelium-dependent contraction of the canine coronary arteries, occurs by L-arginine-dependent pathway, is enhanced. This augmentation by the UW solution would favor vasospasm after transplantation.
The sequence and structure of a second human kappa 1 immunoglobulin light-chain variable domain, Wat, has been determined. The R-factor is 15.7% for 1.9-A data. One hundred and ninety-five water molecules were identified; 30 water molecules were located in identical positions in each of the monomers. Some of the water molecules are integral parts of the domains. This light chain is encoded by the same variable domain gene that encoded the previously characterized kappa I variable domain, Rei. Due to limited somatic mutation, the two highly homologous proteins differ in only 20 of the 108 residues. Wat crystallized in space group P6(4) while Rei crystallized in space group P6(1); in both crystals, the asymmetric unit was the noncovalent dimer. Although the basic domain structure is the same for both proteins, the relative positions of the domains within the two dimers differ. This difference is most likely accounted for by the replacement of Tyr36 in Rei by Phe in the Wat protein. Residue Tyr36 is part of the hydrogen-bonding network in the interface between the domains in Rei. Losing the hydrogen-bonding capability of residue 36 by replacement of Tyr by Phe alters the network of hydrogen bonds between the domains, resulting in a different domain-domain contact. The details of lattice contacts in the two crystals were compared. One type of contact that extends the beta-sheet of the individual domains was conserved, but because it involved different symmetry elements within the crystal, different crystal packing resulted. In the Wat crystal, one of the contacts shows an example of how a symmetrical binding site can "bind" an asymmetrical object. Further, the examination of the Wat crystal also illustrates how the different crystalline environments of the domains of the dimer results in different distributions of temperature factors for the residues within the domains.
The effects of diacytosis and intracellular transport rate on cytotoxicity of hybrid toxins were studied with conjugates of diphtheria toxin fragment A (DTA) to asialoorosomucoid (ASOR) and its reduced and carboxymethylated cyanogen bromide fragment I (RC-ASCNBr-I) in cultured rat hepatocytes. In the hepatocytes the kinetics of uptake of the conjugate of asialoorosomucoid (DTA-ASOR) and that of the conjugate of the cyanogen bromide fragment (DTA-RC-ASCNBr-I) were quite similar, but the rate of accumulation of DTA moiety into the lysosomes, as determined by Percoll density gradient centrifugation, was found to be greater for the latter than the former. However, after internalization, DTA-RC-ASCNBr-I was diacytosed to a lesser extent than that of DTA-ASOR, particularly when colchicine was present during internalization. Analysis of the subunits of DTA-ASOR internalized by the hepatocytes indicated that they were accumulated disproportionately in a time-dependent manner so that the glycoprotein moiety was accumulated progressively more than the toxin moiety. Cytotoxicity of DTA-ASOR toward the hepatocytes was 2-times as much as that of DTA-RC-ASCNBr-I. Colchicine enhanced the toxicity of DTA-RC-ASCNBr-I (33-fold) to a greater extent than that of DTA-ASOR (12-fold). The difference in enhancement by colchicine was also observed in the rate of cell intoxication by the conjugates. Both conjugates were more toxic to the hepatocytes after incubation with the cells at 18 degrees C than at 37 degrees C. In the presence of vanadate (0.2 mM), which enhanced diacytosis, toxicity of DTA-ASOR decreased by 5-fold. After incubation with the hepatocytes, a partial dissociation of DTA-ASOR was found to occur independently of the receptor-mediated endocytosis. Taken together, these results indicate that diacytosis, subunit dissociation and rapid transport of conjugate toward lysosomes affect kinetically the rate of accumulation of the conjugate into a yet unidentified compartment of toxin translocation.
The class II transactivator (CIITA) has been shown to be required for major histocompatibility complex (MHC) class II gene expression in B cells and its deficiency is responsible for a hereditary MHC class II deficiency. Here we show that CIITA is also involved in the inducible expression of class II genes upon interferon gamma (IFN-gamma) treatment. The expression of CIITA is also inducible with IFN-gamma before the induction of MHC class II mRNA. In addition, CIITA mRNA expression does not require new protein synthesis, although new protein synthesis is necessary for the transcription of class II. This suggests that synthesis of new CIITA protein may be essential to induce class II gene expression. We also showed that the JAK1 protein tyrosine kinase activity is required to induce the expression of CIITA upon IFN-gamma stimulation. This finding indicates that CIITA is part of the signaling cascade from the IFN-gamma receptor to the activation of class II genes. In addition, the expression of CIITA is sufficient to activate class II genes in the absence of IFN-gamma stimulation suggesting that CIITA is the major regulatory factor for the inducible expression of class II genes. Together, these data suggest that CIITA is the IFN-inducible cycloheximide sensitive factor previously shown to be required for the induction of MHC class II gene expression.
The murine neuroendocrine cell line, STC-1, was found to contain 296.8 +/- 1.8 fmol of cholecystokinin-like immunoreactivity (CCK-LI) per mg cell protein. Immunocytochemical stain of STC-1 cells maintained in monolayer culture indicated that CCK-LI activity was present in 93% of the cells. Analysis by reverse-phase high-performance liquid chromatography indicated that STC-1 cells contained CCK-8 and an unidentified form as the predominant storage form. form. However, only CCK-8 was released into the culture medium upon stimulation by various secretagogues. The release of CCK-LI from STC-1 cells was stimulated by dibutyryl cAMP, forskolin, KCl, A23187, 4 beta-phorbol 12-myristate 13-acetate and luminal stimulants, e.g., sodium oleate, L-tryptophan, camostat and plaunotol. The release of CCK-LI from STC-1 cells was also stimulated by a neuropeptide, bombesin. The stimulatory effects of most of these agents were dose dependent. The stimulatory effects of dibutyryl cAMP, forskolin, and plaunotol were potentiated by 3-isobutyl-1-methyl xanthine, while that of camostat was not. The results obtained in this study indicate that the release of CCK from STC-1 cells shares the same characteristics of CCK release as from the CCK-secreting cells of the intestinal mucosa observed both in the dog and the rat in vitro and in vivo. Thus, the cellular mechanism of CCK release which appears to be cAMP- and Ca(2+)-dependent may be modulated by cellular protein kinase C activity. The STC-1 cell appears to be a suitable model for studying the mechanism of CCK release.
Epidermal Langerhans cells (LC) are major histocompatibility complex (MHC) class II (Ia)-positive dendritic cells that act as potent antigen-presenting or accessory cells for primary and secondary T cell-dependent immune responses. Recent studies have disclosed that the morphological, functional, and phenotypic characteristics of LC are variably and drastically modulated by external stimuli both in vivo and in vitro. However, little is known of the biological significance of diverse cytokines in regulating the surface molecules of LC. To determine the regulatory properties of ICAM-1, Ia, and MHC class I (H-2K) molecules in LC, we have examined the effects of interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-10, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the expression of these molecules. Among the cytokines examined, IFN-gamma markedly and reproducibly up-regulates the expression of H-2K, but not ICAM-1, in Ia+ LC in a time- and dose-dependent manner. TNF-alpha consistently up-regulates the expression of ICAM-1, but not H-2K, in a time- and dose-dependent manner. IL-10 slightly but reproducibly inhibits the expression of ICAM-1, but not H-2K, in a time- and dose-dependent manner. IL-10 potently inhibits the TNF-alpha-induced ICAM-1 up-regulation, but not the IFN-gamma-induced H-2K up-regulation. Moreover, no cytokine consistently affects the Ia expression of LC. In addition, slight enhancing effects have been observed on H-2K expression by IL-4, and on ICAM-1 expression by IL-1 alpha, IL-1 beta, or GM-CSF. The present data suggest that the selective regulation is operative in a certain cell surface moiety of LC by various cytokines. These results further facilitate our understanding of immunobiology of LC.
Color Doppler ultrasonography and serum CA 125 were used to evaluate 114 adnexal tumors prior to surgery. Six patients were excluded from this study because of ovarian cancer, borderline ovarian malignancy, and tubal gestation. A total of 108 patients were eligible: 83 patients with benign and 25 patients with malignant ovarian tumors. Resistance index (RI) was used to determine the peripheral resistance of intratumoral vessels. The cutoff point for the RI was defined as 0.5. The blood flow was considered to be normal when the RI was greater than 0.5 and abnormal when it was less than 0.5. The blood flow was detected in 100% of malignant tumors and 59% of benign tumors. The initial cutoff value for CA 125 was 35 U/mL. Sensitivity, specificity, positive predictive value, and negative predictive value were compared in terms of RI, serum CA 125, and a combination of the two. Our conclusion is that the combination of RI and CA 125 gives a sensitivity of 100% and negative predictive value of 100%. If the cutoff point of CA 125 was raised from 35 to 65 U/mL, then a specificity of 100% and positive predictive value of 100% were also attained with the use of RI and CA 125 without changes in sensitivity or negative predictive value. We conclude that the combination of color Doppler ultrasonography and serum CA 125 is an effective method to differentiate benign from malignant ovarian tumors.
Primary malignant lymphoma localized in the uterine cervix is a rare condition for which radiation therapy, surgery, or chemotherapy either alone or in combination have been the mainstay of treatment. The effectiveness of neoadjuvant chemotherapy for this condition, however, has not been evaluated. We experienced one case of primary malignant lymphoma of the uterine cervix, stage IIa according to FIGO, and IEA according to the Ann Arbor staging system for extranodal lymphomas, which was treated with neoadjuvant chemotherapy and surgery. The patient first underwent neoadjuvant chemotherapy consisting of cyclophosphamide, vinblastine, epirubicin, bleomycin, procarbazin, and oncovin (COP-BLAM) to reduce the size of the tumor. This was followed by an extended total hysterectomy, left salpingo-oophorectomy, and bilateral pelvic lymph node dissection. Neoadjuvant chemotherapy given before surgery resulted in a remarkable reduction in the tumor size which made the subsequent surgery technically easy. In addition, it is possible that intraoperative micrometastasis of the tumor cells could be better prevented. The patient received additional chemotherapy with COP-BLAM schedules postoperatively. No evidence of recurrent lymphoma has been observed in 2 years after the treatment. Neoadjuvant chemotherapy may be an effective treatment modality for primary malignant lymphoma of the uterine cervix.
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Sutureless intraluminal aortic graft has been used for substitution of aorta, with the advantages of decreasing the aortic cross-clamp time and decreased blood loss. From January 1991 to December 1992, 10 consecutive patients underwent emergency operations to repair acute type A aortic dissection in which sutureless intraluminal grafts were used for replacement of ascending aorta. There were 5 men and 5 women, with ages that ranged from 40 to 74 years (mean, 51 years). The inclusion method was used in all patients. Modified Cabrol shunts were created in 7 patients. Dacron graft (Meadox Medicals, Inc, Oakland, NJ) was used to wrap the ascending aorta in 7 patients. The circulatory arrest time was 33 +/- 13 (mean +/- standard deviation) minutes, and the cardiac ischemic time was 64 +/- 17 minutes. Retrograde superior vena cava cerebral perfusion during circulatory arrest was performed on 4 patients. All patients survived. One patient had a minor stroke and pneumonia with complete recovery. There was no evidence of pseudoaneurysm formation, graft erosion, graft migration, or aortic bleeding in the postoperative period. No patients had permanent renal deficit. Follow-up (1 to 22 months; mean, 9.6 months) of all patients revealed satisfactory graft function, with no device-related deaths and no known complications attributable to the prosthesis, such as thrombosis, erosion, pseudoaneurysm formation, or hemorrhage. Our experience suggests that grafting of the ascending aorta is less hazardous with the sutureless grafts than with the conventional sutured anastomosis technique. We are now using this method whenever possible in all substitutions of the aorta.
Prosthetic rings are customarily used for mitral annuloplasty to plicate and reinforce the annulus and keep the annulus from further dilating. From July 1984 to March 1992, mitral annular plication using polytetrafluoroethylene (PTFE) graft material was performed on 73 patients (age range, 15 to 69 years; mean, 35.7 years) with mitral regurgitation. The cause of the mitral regurgitation was rheumatic in 50.7% and degenerative in 36.9% of the patients. After other repair procedures on the mitral valve apparatus had been performed, a PTFE graft (3 mm) was tailored to the length of the free edge of the anterior leaflet and then inserted at the posterior part of the mitral annulus between the commissures. The operative mortality was 2.7%. Follow-up ranged from 0.7 to 8.5 years (mean, 5.6 years). Postoperative echocardiography confirmed that 94.2% of the survivors had either no or only mild mitral regurgitation with a large mitral valve area (2.7 +/- 0.3 cm2) and almost no pressure gradient across the mitral valve or left ventricular outflow tract. Two patients successfully underwent redo PTFE mitral annuloplasty. Two patients died, one 15 and the other 20 months later, due to myocardial failure, with no mitral regurgitation. The event-free survival rate was 90% +/- 4% at 8 years. We conclude that PTFE mitral annuloplasty is an effective procedure that yields good long-term results.
Coronary artery endothelium exhibits functional impairment after ischemia and reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia (60 minutes) followed by reperfusion (60 minutes) through a left internal mammary artery graft. In organ chamber experiments, control (left circumflex coronary artery) and reperfused (left anterior descending coronary artery) arterial segments were contracted with prostaglandin F2 alpha and exposed to hypoxia (oxygen tension = 35 +/- 5 mm Hg). Reperfused coronary rings with endothelium exhibited contractions to hypoxia that were significantly greater than contractions in control rings with endothelium (+78% +/- 8% and +14% +/- 5%, respectively; p < 0.05). This phenomenon could be blocked by NG-monomethyl-L-arginine. Electron microscopic studies showed platelet adhesion and aggregation, denudation of the endothelium and disruption of the intercellular junctions, edematous subendothelial matrix, and vesiculation of the smooth muscle cells in reperfused LAD. Swelling, vacuole formation, and loss of neurofilament occurred in the nerve fibers accompanying the vessels. These phenomena were not observed in control vessels. This study demonstrates that early after coronary artery bypass grafting, hypoxia can induce coronary vasospasm mediated by an L-arginine-dependent metabolic pathway in the endothelium. The ultrastructural changes in the coronary endothelium include platelet adhesion, aggregation, and platelet-induced contraction of coronary smooth muscle. The endothelium-dependent hypoxic coronary vasospasm and ultrastructural changes in the coronary endothelium may play an important role in the pathogenesis of myocardial ischemia and infarction after coronary artery bypass grafting.
Video-assisted thoracoscopic technique was evaluated in 28 patients who underwent operation for massive pericardial effusion. Excellent results were obtained using this newly developed approach for inspection of all pericardial surfaces as well as pleural and pulmonary disorders. No perioperative or postoperative complications ensued. Videothoracoscopy revealed positive lung malignancies in 11 patients, and these would not have been promptly diagnosed without thoracoscopy. Thoracoscopy also confirmed metastatic deposits on the pleura and diaphragm in 4 other patients. The visible nodules were proved to be metastatic adenocarcinoma. In 13 patients, thoracoscopy did not reveal malignancy, although 2 of these patients had a clinically suspected malignant lung tumor. Other indications for thoracoscopic drainage included 2 patients with impending pericardial tamponade after heart procedures and 6 patients with recurrent/loculated pericardial effusion. All of the patients showed promising and favorable postoperative courses after thoracoscopy. From our experience, video-assisted thoracoscopy was a safe and effective procedure, especially for those patients with combined pericardial effusion and abnormal pulmonary or pleural pathology in whom subxiphoid pericardial window was not clearly diagnostic at the time of operation. It was effective also in the situation with recurrent or loculated pericardial effusion which allowed localization and drainage of it. We believe that the use of videothoracoscopy to visualize the whole pericardial and pleural cavity will continue to be of great benefit to patients with combined pericardial and pleural/lung diseases.
From the root bark of Cudrania cochinchinensis (Lour.) Kudo et Masamune var. gerontogea (Sieb. et Zucc.) Kudo et Masamune, 3 xanthones, cudraxanthone I, 1,3,7-trihydroxy-2-(3-methylbut-2- enyl)-xanthone, and lancerin, were further isolated and characterized. It was found that pretreatment with 600 mg/kg oral dose of the EtOH root extract of Cudrania cochinchinensis var. gerontogea in mice inhibited the lipid peroxidation stimulated by FeCl2-ascorbic acid-adenosine 5'-diphosphate (ADP) mixture. For searching bioactive constituents, the isolated xanthones from this folk medicine were investigated in anti-lipid peroxidative activities in the rat liver homogenate. The results showed that most of the tested xanthones effectively exhibited anti-lipid peroxidation stimulated by (a) FeCl2-ascorbic acid mixture or (b) CCl4-nicotinamide adenine dinucleotide phosphate (NADPH) mixture. As shown by the result, gerontoxanthone C and I were more active than vitamin E.
OBJECTIVES: The purpose of this study was to examine the epidemiology of transurethral resection of the prostate (TURP) and associated risks among Medicare beneficiaries during the period of 1984 to 1990. METHODS: Medicare hospital claims for a 20% national sample of Medicare beneficiaries were used to identify TURPs performed during the study period. All reported rates were adjusted to the composition of the 1990 Medicare population. Risks of mortality and reoperation were evaluated using life-table methods. RESULTS: The age-adjusted rate of TURP reached a peak in 1987 and declined thereafter. Similar trends were observed for all age groups. In 1990, the rates of TURP (including all indications) were approximately 25, 19, and 13 per 1000 for men over the age of 75, 70 to 74, and 65 to 69, respectively. The 30-day mortality following TURP for the treatment of benign prostatic hyperplasia (BPH) decreased from 1.20% in 1984 to 0.77% in 1990 (linear trend, p = 0.0001). The cumulative incidence of a second TURP among men with BPH has likewise decreased steadily over time; in this study, the average was 7.2% over 7 years (5.5% when the indication for the second TURP was restricted to BPH only). CONCLUSIONS: The rate of TURP has been declining since 1987, conceivably due to increasing availability of alternative treatments or changes in treatment preferences of patients and physicians. Over the same period, the outcomes following TURPs have improved, perhaps due to improved surgical care and changes in patient selection.