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Biomedical subjects

C J Lin

Publications and source records attributed to C J Lin.

At least 19 recordsLinked to original sources

Stereospecific blocking effects of naloxone against hemodynamic compromise and ventricular dysfunction due to myocardial ischemia and reperfusion.

Endogenous opioid peptides subserve regulatory roles in cardiovascular function and are released upon myocardial ischemia contributing to the development of ischemic arrhythmias and cardiogenic shock, which are reversed by the opioid antagonist naloxone. Since the hallmark of myocardial infarction is the impairment of hemodynamics and ventricular function, we evaluated further if blockade of opioids reverses the ischemia induced hemodynamic compromise, and if the effects are mediated by opioid receptors. Thirty-two mongrel dogs were anesthetized and artificially ventilated. Median thoracotomy was performed, the heart exposed, and the left anterior descending coronary artery isolated for subsequent occlusion and reperfusion. All cardiac parameters were recorded on an Electronics for Medicine recorder through the intracardiac catheters advanced from femoral vessels. Results indicate that naloxone significantly reversed the ischemic and reperfusion induced reduction in aortic, left ventricular and pulmonary arterial pressures, and left ventricular dp/dt. The inactive (+) stereoisomer of naloxone was without effect. These data demonstrate that opioids may have a role in the pathophysiology of myocardial infarction, mediated by opioid receptors, and provide new insight and strategies for the understanding and treatment of ischemic heart disease.

Animals

Differential cytotoxicity of cadmium to rat embryonic fibroblasts and human skin fibroblasts.

In order to identify why cadmium is differentially toxic to humans and rats, we compared cadmium-induced cytotoxic responses in rat embryonic fibroblasts (REF) and human skin fibroblasts (HFW). According to the values of the lethal concentration 50% for cadmium, REF were about 13-fold more sensitive than HFW to cadmium acetate (1.5 vs 25 microM). Furthermore, progression of S phase cells was more severely delayed by cadmium in REF than in HFW. At doses that killed 90% of REF or HFW (5 or 50 microM, respectively), 50% of DNA synthesis was inhibited in REF, whereas DNA synthesis was not apparently inhibited in HFW. The differential sensitivity to cadmium could not be simply due to different basal levels of metallothionein, since the cellular metallothionein content in HFW was only 1.6 times that in REF, and metallothionein was apparently induced by cadmium in both cells with similar synthesis rates. Furthermore, elevation of cellular metallothionein levels by zinc sulfate pretreatment decreased cadmium toxicity in both cell types, but did not alter their relative sensitivity to cadmium. The differential sensitivity was also not due to differences in cadmium accumulation, since HFW accumulated more cadmium than REF after a 24-hr exposure to 1 or 5 microM cadmium acetate. Although most of the cadmium remained in the cytoplasm, the nuclei of REF contained 12-fold more cadmium than nuclei of HFW (1.31 vs 0.11 micrograms Cd/mg nuclear protein). Therefore, our results indicate that a high level of cadmium accumulation in nuclei of REF may be responsible for cell killing through breakdown of nuclear functions.

Animals

Plasma levels of endogenous opioid peptides in patients with acute myocardial infarction.

There is substantial evidence that cardiac opioid receptors are activated during arrhythmias induced by administration of opioid peptides or myocardial ischemia, supporting the hypothesis that endogenous opioid peptides (EOP) are involved in myocardial infarction. This prospective clinical trial is designed to determine whether the ischemia-induced arrhythmias and extent of the infarct are related to the release of the EOP beta-endorphin in patients with acute myocardial infarction. Two groups were included in the study, patients with acute myocardial infarction, and healthy volunteers who served as controls. The results indicate that, compared to the controls, there was augmentation of ischemic arrhythmias and ischemic damage as assessed by serum creatine kinase activity, accompanied by an elevated level of beta-endorphin, in patients with acute myocardial infarction. The above data strongly indicate that EOP are indeed involved in the pathophysiology of myocardial infarction, and suggest these peptides have an important role in ischemic heart disease.

Aged

[Cytochrome P450-dependent monooxygenase system and anesthetics].

The cytochrome P450-dependent monooxygenases constitute the primary enzyme system responsible for the oxidative metabolism of a variety of xenobiotics and endogenous compounds including drugs, carcinogens, fatty acids and hormones. The monooxygenase system consists of multiple forms of P450 enzymes, NADPH-cytochrome reductase and phospholipids. The level sof P450s and associated monooxygenase activities are subject to be regulated by many environmental, physiological, and pathological factors. Inhalation and intravenous anesthetics are all metabolized through these biotransformation enzymes. The pharmacokinetic properties as well as the toxicity of the anesthetics are closely related to the inducing or inhibitory status of the monooxygenase isozymes. To understand the role of cytochrome P450-monooxygenases in drug metabolism is essential for us to handle the drug-to-drug interactions and adverse effects.

Anesthetics

A computer system for skeletal growth measurement.

In this paper, we have presented a new image-processing system for the measurement of skeletal growth in pediatric radiology. From a standard posterior and anterior view radiograph, taken from a left hand, the proposed system first automatically locates the phalangeal region of interest, and then measures the geometrical parameters associated with skeletal maturity. Finally, the bone age is estimated by using the standard phalangeal length table. Clinical studies reveal that the computer processing has resulted in an objective and accurate assessment of skeletal age. It greatly improves the shortcomings, including inter- and intraobserver variations and inaccuracy, reported in other research by manual methods. In conclusion, it is an inexpensive and useful tool for the evaluation of short-term abnormalities in the skeletal growth of children.

Adolescent

Delay of the excision of UV light-induced DNA adducts is involved in the coclastogenicity of UV light plus arsenite.

Chromatid exchanges and chromatid breaks were synergistically increased by a 2-h post-treatment with arsenite (VS treatment) but not with arabinofuranosyl cytosine (VA treatment) of UV-irradiated late-G1 Chinese hamster ovary cells. In order to determine the mechanism of this UV-arsenite coclastogenicity, we have compared the effects of arsenite and arabinofuranosyl cytosine on the generation of DNA strand breaks in UV-irradiated cells by alkaline elution and alkaline sucrose sedimentation. Only very small numbers of DNA breaks were detected immediately after VS treatment, however the breaks in parental strands increased as the cells reached mitosis in drug-free medium, whereas a large number of breaks were detected immediately after VA treatment but the breaks decreased thereafter. By labelling the newly synthesized DNA, we have also shown that the VS-treated cells had more breaks in daughter strands than the VA-treated cells at the time of reaching mitosis. The effect of a 2-h post-treatment with arsenite on the excision of UV-induced DNA adducts was further investigated by using the exponentially growing cells. The results confirmed that very low amount of breaks was detectable immediately after VS treatment, however the amount of breaks increased upon the removal of arsenite. Therefore, the breaks in the daughter strands of VS-treated cells may come from DNA replication using templates containing unexcised adducts, or using broken templates. It is conceivable that gaps in the overlapping regions of parental and daughter strands may result in chromatid breaks and that misreplication, because of unexcised adducts or gaps in the parental strands, may result in chromatid exchanges.

Animals

Musculoskeletal changes in children prenatally exposed to polychlorinated biphenyls and related compounds (Yu-Cheng children).

Fifty-five Yu-Cheng (oil-disease) children born between 1978 and 1985 to mothers who ate PCB-contaminated rice oil in 1978-1979 were studied and compared to age- and sex-matched control subjects in 1991. The children's growth profiles, bone mineral density and soft tissue composition, joint laxity, and serum parathyroid hormone, vitamin D, calcium, alkaline phosphatase, and phosphate were compared. The Yu-Cheng children were 3.1 cm (p < .05) smaller and had less total lean mass and soft tissue mass as compared to the matched control subjects. All other parameters studied were similar in both groups. The shorter height and decreased total lean mass and soft tissue content were only seen in the Yu-Cheng children who were the first born after the ingestion, but not in subsequent children. This was most likely due to decreased body burdens of the PCBs and related contaminants over time in the mothers.

Birth Order

Sick sinus syndrome with normal atropine response--a case report.

A 76-year-old woman was admitted due to recurrent syncope. Sinus bradycardia and intermittent sinus pauses (up to 2.24 sec) were documented by 24 hour Holter electrocardiogram. Although intravenous atropine can increase the sinus rate up to 100 bpm, electrophysiologic study showed marked prolongation of sinus node recovery time both at the control state and after autonomic blockades. Sick sinus syndrome was diagnosed, even with a normal atropine test, and a permanent pacemaker resulted in resolution of the syncope.

Aged

The morbidity and mortality associated with childhood onset systemic lupus erythematosus.

From 1977 till 1991, the diagnosis of systemic lupus erythematosus was made on 137 children aged 18 years or under in Chang Gung Memorial Hospital. The medical records were reviewed and the clinical data were analysed with emphasis on the morbidity and mortality of this disease. The clinical and laboratory characteristics were similar to the findings from most other reports. Renal failure accounted for 8% of the initial presentation. The non-infectious complications were, in the order of frequencies, hypertension, avascular necrosis of femoral head, cataract, encephalopathy, and venous thrombosis. Sepsis, cutaneous infection and urinary tract infection were the frequently encountered infectious complications. The major causes of death in childhood onset systemic lupus erythematosus were sepsis (42%) and renal failure (30.7%). Forty patients were lost to follow-up. The 5-year survival rate, calculated by life-table, was 76.3%.

Adolescent

Beneficial effects of the opiate antagonist naloxone on hemodynamics and ventricular function following coronary artery occlusion and reperfusion in the dog.

It has been shown that endogenous opioid peptides (EOP) subserve important roles in cardiovascular regulation and are involved in the pathophysiology of myocardial ischemia, contributing to the deleterious effects. The aim of this study was to evaluate the effects of the opiate antagonist naloxone on the hemodynamics and ventricular function following coronary artery occlusion and reperfusion in the dog, utilizing the technique of cardiac catheterization. During myocardial ischemia and reperfusion, it was found that in the control group, there was reduction in the aortic, left ventricular, right atrial, pulmonary arterial and wedge pressures, and in the left ventricular dP/dt. The reduction in the aortic, left ventricular and pulmonary arterial pressures, and left ventricular dP/dt were significantly attenuated by pretreatment with naloxone. The results indicate a regulatory role of EOP in the cardiovascular function and suggest a possible involvement of EOP in myocardial ischemia and reperfusion causing detrimental effects such as arrhythmias, bradycardia, hypotension and, as shown in this study, impaired hemodynamics and ventricular function. The beneficial effects of naloxone on circulatory dynamics may have clinical implications in the prevention and treatment of ischemic heart disease.

Animals

The Taiwanese hepatitis C virus genome: sequence determination and mapping the 5' termini of viral genomic and antigenomic RNA.

The complete nucleotide sequence of hepatitis C virus (HCV) cloned from the liver tissue of a Taiwanese patient with post-transfusion type C hepatitis was determined. The 5' end of HCV genomic RNA was located 341 nucleotides upstream from the initiation codon for the viral polyprotein open reading frame. The 5' end of the viral antigenomic RNA was shown to have 13 consecutive As. Thus the 3' terminus of the viral genome is a stretch of U which ends about 50 nucleotides downstream from the stop codon of the large open reading frame. The nucleotide sequence homology between this HCV strain and two Japanese isolates was 90.5 and 90.7%, respectively. Homology with the United States strain, however, was only 77.8%. Accordingly, the indigenous Taiwanese HCV strain is of the same subtype as the Japanese isolates. Novel features of the viral genome termini are possibly relevant to HCV genome replication.

Amino Acid Sequence

Transesophageal echocardiography in adults with a continuous precordial murmur.

In order to assess the ability of echocardiography in the detection of intracardiac and extracardiac shunts, we studied 11 patients (aged 22-64 yr) with a continuous precordial murmur using transthoracic and transesophageal echocardiography, and correlated the results with the subsequent angiographic and surgical findings. We found that only in 5 of 6 patients with a patent arterial duct could the continuous flow pattern be detected in pulmonary artery using transthoracic echocardiography, whereas it could be readily and accurately identified by transesophageal echocardiography in all patients. The diameters of the patent arterial duct were also measured and found to be in good correlation with subsequent surgical findings (r = 0.98, p less than 0.05). In 2 patients with a ruptured aneurysm of sinus of Valsalva which originated from the right coronary sinus and perforated into the right ventricle, transesophageal echocardiography gave a better image than transthoracic echocardiography. In 2 patients with coronary artery fistula, the origin and site of drainage of the coronary artery could be imaged using transesophageal echocardiography, but the course of coronary artery fistula was more easily detected by transthoracic echocardiography. In one patient with aortopulmonary window, the defect between ascending aorta and main pulmonary artery could readily be imaged by transesophageal echocardiography. We therefore recommend transesophageal echocardiography when evaluating patients with precordial continuous murmur in whom intracardiac and extracardiac shunts or defects are suspected.

Adult

Functional study of hepatitis delta virus large antigen in packaging and replication inhibition: role of the amino-terminal leucine zipper.

The large hepatitis delta antigen (HDAg) has been found to be essential for the assembly of the hepatitis delta virion. Furthermore, in a cotransfection experiment, the large HDAg itself, without the hepatitis delta virus (HDV) genome and small HDAg, could be packaged into hepatitis B surface antigen (HBsAg) particles. By deletion analysis, it was shown that the amino-terminal leucine zipper domain was dispensable for packaging. The large HDAg could also help in copackaging of the small HDAg into HBsAg particles without the need for HDV RNA. This process was probably mediated through direct interaction of the two HDAgs as a mutated large HDAg whose leucine zipper domain was deleted such that it could not help in copackaging of the small HDAg. This mutated large HDAg did not suppress HDV replication, suggesting that this effect is probably also via protein interaction. These results indicated that functional domains of the large HDAg responsible for packaging with HBsAg particles and for the trans-negative effect on HDV replication can be separated.

Antigens, Viral

Antiarrhythmic action of naloxone. Suppression of picrotoxin-induced cardiac arrhythmias in the rat.

The antiarrhythmic properties of the opiate antagonist naloxone have been reported in a variety of models of arrhythmia. To determine the generality and the possible central involvement of its antiarrhythmic activity, the effects of naloxone were assessed against cardiac arrhythmias induced by intravenous bolus injections of picrotoxin. Naloxone at doses of 0.33 and 1 mg/kg significantly reduced the incidence and severity of picrotoxin-induced arrhythmias in a dose-related manner, without alteration of blood pressure and heart rate. The results demonstrate the antiarrhythmic efficacy of naloxone in an additional animal model. They further suggest that the antiarrhythmic actions of naloxone may be mediated by the central nervous system via both the autonomic and GABAergic pathways.

Animals

Conservative treatment of neonatal hydronephrosis.

From February 1990 to January 1991, 19 cases of hydronephrosis in children of less than one year of age were managed at Mackay Memorial Hospital. In the majority of these patients, there were evident causes such as ureteropelvic junction stenosis, ureterovesical reflux or a posterior urethral valve for which definite therapeutic measures were performed. However, some cases had no obvious origins and the hydronephrosis was speculated to be from nonobstructive or physiologic dilatation of the kidneys. The conventional tools, such as intravenous pyelogram or renal ultrasound, which comprise the mainstay of diagnosis, provide limited information on renal functional status. Recent introduction of the Tc-99m diethylene triamine penta-acetic acid (DTPA) diuretic renal scan has enabled us to distinguish between obstructive and nonobstructive hydronephrosis and helps us to determine whether or not surgery is necessary. In the past year, eight patients with hydronephrosis of less than one year of age were diagnosed as nonobstructive after a series of evaluations using renal ultrasound, voiding cystourethrography (VCUG) and Tc-99m DTPA diuretic renal scan. Follow-up studies by echography or DTPA renal scan revealed spontaneous resolution of the dilated collecting systems in these cases and confirms our belief that some hydronephrosis in neonates and infants may resolve spontaneously and may just be a manifestation of physiologic change during development. The value of the Tc-99m DTPA diuretic renal scan in the diagnosis of obstructive uropathy is discussed.

Female

Surgical treatment for Perthes disease at risk.

The treatment of Perthes disease has remained controversial ever since the disorder was first described in 1910. It is generally accepted that surgical treatment is favorable if the patients are at risk clinically or radiologically. From March 1983 to March 1988, 13 patients suffering from severe Perthes disease were treated surgically at the National Taiwan University Hospital. There were 12 boys and one girl with an average age of eight years and eight months (ranging from five years and 10 months to 12 years and one month). They were all at risk either clinically or radiologically. All patients suffered from hip pain, limping and limited range of motion, except one who was pain-free. All femoral heads were classified as Catterall group III or IV, and had at least two radiologic risk signs. After nonsurgical treatment for an average duration of 13 months, including bed rest, traction and bracing as inpatients or outpatients, operations, including varus derotational osteotomy of the femur in three, Salter innominate osteotomy in one, combined surgery in three and triple innominate osteotomy in six patients, were performed. After following up for 36 months, we determined that surgical containment for Perthes disease can achieve satisfactory results. In our preliminary report, triple innominate osteotomy was one of the relatively simple and effective procedures.

Child

A single 3.7-kilobase messenger RNA hybridizes to immediate-early promoter enhancer of human cytomegalovirus in HL-60 and acute myeloid leukemia cells.

Expression of a mRNA cross-hybridized to human cytomegalovirus immediate-early gene promoter-enhancer was detected in the human promyelocytic leukemia cell line HL-60. The 0.6 kilobase of NruI/SacI DNA fragment of eukaryotic expression vector pCDM8 representing human cytomegalovirus immediate-early gene promoter-enhancer was used as the probe to hybridize with polyadenylated RNA by the Northern blot analysis. A 3.7-kilobase strand of polyadenylated RNA was visualized in the cytoplasmic fraction of HL-60 promyelocytes. In contrast, other human hematopoietic cell lines, hepatoma cells, and normal human fibroblasts did not show such a transcript by cross-hybridization. This transcript was called CMVE RNA. The expression of CMVE mRNA was also detectable in the fresh blast cells from patients with acute myeloid leukemia, and particularly from a patient with acute myeloid leukemia of the M3 type. Taken together, these findings suggest that the CMVE RNA-encoded gene plays an important role in the pathogenesis of acute promyelocytic leukemia.

Acute Disease