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Biomedical subjects

C H Chien

Publications and source records attributed to C H Chien.

At least 37 records · Page 2Linked to original sources

Clinical application of gastric histology to monitor treatment of dual therapy in H. pylori eradication.

This preliminary study attempted to test whether pretreatment gastric histology of H. pylori infection may affect the success of dual therapy and to identify which parameter of gastric histology could be improved after dual therapy. One hundred forty-five dyspeptic patients with H. pylori infection received a two-week course of dual therapy (Amoxicillin 500 mg every 6 hr plus omeprazole 20 mg twice a day). In each patient, three pairs of gastric biopsies, sampled from the antrum, lower body, and upper body near the cardia, were collected before treatment and four weeks after completion of dual therapy. The density of H. pylori (score 1-5) and parameters of the modified Sydney system were applied to test the severity of H. pylori-related gastric histology in each specimen. The total bacterial load (score 1-15) was a sum of the density of H. pylori sampled from three biopsies. The overall rate of H. pylori eradication rate by dual therapy is 73.1% (106/145). Univariate analysis of parameters in pretreatment histology disclosed that the presence of mucosal atrophy (P < 0.01), lymphoid follicles (P < 0.005), and higher-density H. pylori (P < 0.001) predisposed to dual therapy failure. Multivariate analysis by stepwise logistic regression further confirmed that both the density of bacteria and the presence of lymphoid follicles are the two major factors related to the outcome of dual therapy (P < 0.001). Four weeks after dual therapy was completed, only patients with successful eradication significantly improved in these gastric histology parameters: acute activity, chronic inflammation, eosinophil infiltration, and mucosal atrophy. However, the lymphoid follicle and intestinal metaplasia were not significantly improved during the study period. The eradication rates among three subgroups with different total bacterial loads (group I: 1-5; II: 6-10; III: 11-15) disclosed a downward trend (I: 89.1%; II: 73%; III: 52.7%). It is concluded that dual therapy could improve gastric histology especially among patients with successful eradication of H. pylori. Evaluating pretreatment histologic parameters, including the density of H. pylori and the presence of lymphoid follicles, is valuable in predicting the success of dual therapy.

Amoxicillin↗

Lactate and the effects of exercise on testosterone secretion: evidence for the involvement of a cAMP-mediated mechanism.

The effects of swimming and lactate on the release of testosterone were examined in male rats. During in vivo experiments, male rats were catheterized via the right jugular vein and blood was collected at 0, 10, 15, 30, and 60 min following the exercise, or they were catheterized via the right jugular vein and the left femoral vein and blood was collected at 0, 2, 5, 10, 15, 30, 60, and 120 min after a 10-min infusion at lactate (13 mg.kg-1.min-1). Trunk blood and blood from the testicular vein were also collected after 10 min of swimming or water immersion. In an in vitro experiment, testicular fragments were challenged with lactate (0.01-10 mM) and/or human chorionic gonadotropin (hCG; 0.5 IU.mL-1), and the mediobasal hypothalamus (MBH) was challenged with lactate (8 mM). The post-exercise levels of plasma lactate and testosterone at 10, 15, and 30 min were higher than resting levels. Plasma luteinizing hormone (LH) was increased following 30 min of swimming. Administration of lactate or hCG increased in a dose dependent manner testicular cyclic adenosine 3':5' monophosphate (cAMP) and testosterone release. Plasma testosterone increased after swimming and lactate infusion. Incubation of MBH with lactate increased the gonadotropin-releasing hormone (GnRH) level in the medium. These results suggest that the increased plasma testosterone levels in male rats during exercise is at least partially a result of a direct and LH-independent stimulatory effect of lactate on the secretion of testosterone by increasing testicular cAMP production. Swim-elevated plasma LH may be a result of a rise of GnRH caused by lactate.

Animals↗

Early postnatal dexamethasone therapy for the prevention of chronic lung disease in preterm infants with respiratory distress syndrome: a multicenter clinical trial.

OBJECTIVES: To study whether early postnatal (<12 hours) dexamethasone therapy reduces the incidence of chronic lung disease in preterm infants with respiratory distress syndrome. MATERIALS AND METHODS: A multicenter randomized, double-blind clinical trial was undertaken on 262 (saline placebo, 130; dexamethasone, 132) preterm infants (<2000 g) who had respiratory distress syndrome and required mechanical ventilation shortly after birth. The sample size was calculated based on the 50% reduction in the incidence of chronic lung disease when early dexamethasone is used, allowing a 5% chance of a type I error and a 10% chance of a type II error. For infants who received dexamethasone, the dosing schedules were: 0.25 mg/kg/dose every 12 hours intravenously on days 1 through 7; 0.12 mg/kg/dose every 12 hours intravenously on days 8 through 14; 0.05 mg/kg/dose every 12 hours intravenously on days 15 through 21; and 0. 02 mg/kg/dose every 12 hours intravenously on days 22 through 28. A standard protocol for respiratory care was followed by the participating hospitals. The protocol emphasized the criteria of initiation and weaning from mechanical ventilation. The diagnosis of chronic lung disease based on oxygen dependence and abnormal chest roentgenogram was made at 28 days of age. To assess the effect of dexamethasone on pulmonary inflammatory response, serial tracheal aspirates were assayed for cell counts, protein, leukotriene B4, and 6-keto prostaglandin F1alpha. All infants were observed for possible side effects, including hypertension, hyperglycemia, sepsis, intraventricular hemorrhage, retinopathy of prematurity, cardiomyopathy, and alterations in calcium homeostasis, protein metabolism, and somatic growth. RESULTS: Infants in the dexamethasone group had a significantly lower incidence of chronic lung disease than infants in the placebo group either judged at 28 postnatal days (21/132 vs 40/130) or at 36 postconceptional weeks (20/132 vs 37/130). More infants in the dexamethasone group than in the placebo group were extubated during the study. There was no difference between the groups in mortality (39/130 vs 44/132); however, a higher proportion of infants in the dexamethasone group died in the late study period, probably attributable to infection or sepsis. There was no difference between the groups in duration of oxygen therapy and hospitalization. Early postnatal use of dexamethasone was associated with a significant decrease in tracheal aspirate cell counts, protein, leukotriene B4, and 6-keto prostaglandin F1alpha, suggesting a suppression of pulmonary inflammatory response. Significantly more infants in the dexamethasone group than in the placebo group had either bacteremia or clinical sepsis (43/132 vs 27/130). Other immediate, but transient, side effects observed in the dexamethasone group are: an increase in blood glucose and blood pressure, cardiac hypertrophy, hyperparathyroidism, and a transient delay in the rate of growth. CONCLUSIONS: In preterm infants with severe respiratory distress syndrome requiring assisted ventilation shortly after birth, early postnatal dexamethasone therapy reduces the incidence of chronic lung disease, probably on the basis of decreasing the pulmonary inflammatory process during the early neonatal period. Infection or sepsis is the major side effect that may affect the immediate outcome. Other observable side effects are transient. In view of the significant side effects and the lack of overall improvement in outcome and mortality, and the lack of long term follow-up data, the routine use of early dexamethasone therapy is not yet recommended.

Chronic Disease↗

Site-directed mutations of the catalytic and conserved amino acids of the neuraminidase gene, nanH, of Clostridium perfringens ATCC 10543.

The small nanH gene encoding the neuraminidase from Clostridium perfringens ATCC 10543 was cloned in JM109 using pUC19 as a vector. Sequence analysis revealed an ORF encoding 382 amino acids without a signal peptide sequence. Four regions of amino-acid sequence, 71-82, 140-151, 208-219, and 255-266 constituted four repeated and conserved sequence motifs-Ser-X-Asp-X-Gly-X-Thr-Trp-, the "Asp boxes." When compared, the nanH polypeptides of C. perfringens ATCC 10543 and Salmonella typhimurium LT12 shared 33% sequence identity and 60% similarity if conservative replacements were included. The homology-modeled structure of C. perfringens NanH showed the same folding topology as the x-ray three-dimensional structure of NanH in S. typhimurium LT12. Amino acid residues Arg37, Arg56, Asp62, His63, Asp100, Glu230, Asp247, Tyr347, and Glu362 located around the pocket of modeled C. perfringens small nanH were superimposed with the active-site pocket of S. typhimurium LT12, nanH. The catalytic amino-acid residues as well as the role of the "Asp boxes" have not been characterized for C. perfringens and S. typhimurium. In this study, Asp100, Glu230, and Asp62 were found to be involved in the catalytic activity of C. perfringens small nanH with immunoreactive properties and site-directed mutagenesis analysis. Four "Asp-box" motifs were found remote from the active-site pocket. Mutational and immunoreactive analysis of the highly conserved amino acids located in the "Asp boxes" suggest that these highly conserved residues are important in maintaining the tertiary structure of NanH. The results of this study provide some knowledge for the design of new inhibitors of small neuraminidase.

Amino Acid Sequence↗

Lactate stimulates progesterone secretion via an increase in cAMP production in exercised female rats.

The effect of exercise on the production of ovarian progesterone was examined in female rats. During in vivo experiments, diestrous rats were catheterized via the right jugular vein (RJV), and blood samples were collected before and after 10, 15, 30, and 60 min of swimming. In addition, blood samples were collected from the RJV before and 2, 5, 10, 15, 30, 60, and 120 min after 10 min of infusion of lactate (13 mg.kg-1.min-1) through the left femoral vein. To explore if lactate modulates progesterone secretion by acting directly on rat ovary or on anterior pituitary gland (AP), an in vitro experiment that mimicked the in vivo condition was performed. The ovarian tissue was challenged with lactate (0.01-10 mM) or porcine follicle-stimulating hormone (1 microgram/ml) and 3-isobutyl-1-methylxanthine (1 mM) for 60 min, and the AP was challenged with lactate ranging from 0.1 to 10 mM or 10 nM gonadotropin-releasing hormone for 30 min. The postexercise levels of plasma glucose, lactate, and progesterone at 10, 15, and 30 min were significantly higher than the corresponding basal levels. Plasma luteinizing hormone (LH) did not change after exercise. An elevation of plasma lactate and progesterone was found at 15 and 30 min subsequent to 10 min of infusion of lactate. Lactate ranging from 0.01 to 10 mM significantly increased ovarian adenosine 3',5'-cyclic monophosphate (cAMP) and progesterone production in a dose-dependent manner. LH concentration in plasma was not changed subsequent to lactate infusion. LH level in media samples was not altered after incubation of AP with lactate. These results suggest that the increase of plasma progesterone level in rats during exercise is independent of LH secretion and at least in part is due directly to a stimulatory effect of lactate on the production of ovarian cAMP.

1-Methyl-3-isobutylxanthine↗

Clinical characteristics of and response to combination chemotherapy and subsequent application of international prognostic index in non-Hodgkin's lymphoma--an experience from a medical center in Southern Taiwan.

A retrospective analysis was performed of 117 non-Hodgkin's lymphoma (NHL) patients (72 male and 45 female, mean age 55 years) treated at NCKUH between July 1988 and December 1993. Of the 115 patients who could be classified by Ann Arbor staging system, 26 patients (22.2%) were in stage 1; 23 (19.7%) in stage 2; 29 (24.8%) in stage 3; and 37 (31.6%) in stage 4. According to the International Working Formulation, three patients (2.6%) were low grade NHL, 90 (76.9%) were intermediate, and 8 (6.8%) were high grade NHL. Histologically, diffuse large cell NHL accounted for 52.1% of cases, followed by 16.2% of cases exhibiting diffuse mixed NHL. Immunophenotype analysis was available in 95 cases, which revealed 76 (80%) cases exhibiting B-cell origin, 17 (18%) cases exhibiting diffuse mixed NHL. Immunophenotype analysis was available in 95 cases, which revealed 76 (80%) cases exhibiting B-cell origin, 17 (18%) cases exhibiting T-cell origin and 2 (2%) cases were of null cell type. All patients underwent two groups of induction chemotherapy, either CHOP (Cyclophosphamide, Epirubicin, Oncovin, and Prednisolone), or "modified" COPBLAM (Cyclophosphamide, Epirubicin, Oncovin, and Prednisolone), or "modified" COPBLAM (Cyclophosphamide, Epirubicin, Oncovin, Vinblastine, Bleomycin, Procarbazine, and Prednisolone). Seventy-two cases treated through COPBLAM and 45 cases treated through CHOP were evaluated. The response rate (RR) to COPBLAM treatment was 72.2% and was 68.9% for the CHOP group (P = 0.51). The 5-year overall survival rate (OAS) was 44.1% for COPBLAM, versus 40% for CHOP (P = 0.15). The disease-free survival (DFS) was 72.6% at 63 months for COPBLAM and 58% at 51 months for CHOP (P = 0.16). Neither B cell nor T-cell lineages of NHL showed any statistical difference in RR (P = 0.53, DFS (P = 0.58) or OAS (P = 0.97) to the different treatments. Using multiple logistic analysis, two independent factors, high LDH and advanced stage, were found to adversely affect the rate of complete remission. The application of the International Prognostic Index to our patients needs modification, which suggests the necessity of more evaluation before it can accurately be applied to all international series of NHL.

Adult↗

The composition and central projections of the internal auricular nerves of the dog.

The cranial components and central terminations of the sensory nerves supplying the concave surface of the puppy's pinna, namely, the rostral, middle and caudal internal auricular nerves (RIAN, MIAN and CIAN) were investigated using horseradish peroxidase retrograde and transganglionic labelling techniques. All the 3 internal auricular nerves received contributions from the vagus. The RIAN received additional fibres from the trigeminal nerve while the MIAN and CIAN contained fibres derived from the facial nerves. In the brainstem, collaterals from the descending fibres of the afferents were given off at all levels to the medially located spinal trigeminal nucleus (SpV) which extended rostocaudally from the principal nucleus of the trigeminal nerve, subnuclei oralis, interpolaris and caudalis of the SpV to C1 or C2 cervical segment. The greatest density of central projections was observed in the subnucleus caudalis and C1. In the latter, the terminal field in the dorsal horn was roughly wedge-shaped, tapering off medially from lamina I towards lamina V. A somatotopic organisation was observed in the spinal trigeminal tract (SpVtr) and spinal trigeminal nucleus (SpV) in which the projection fibres and terminal fields of the RIAN were located lateral to those of the MIAN and CIAN. Some nontrigeminal nuclei, e.g. paratrigeminal and cuneate nuclei, nucleus X and the nucleus of the solitary tract were also labelled following HRP application to the internal auricular nerves. The localisation of the central projections of the internal auricular nerves as well as the 2nd order neurons in some specific nuclei to which the afferent fibres project is consistent with the concept of a brainstem somatovisceral link.

Animals↗

Calcitonin inhibits testosterone and luteinizing hormone secretion through a mechanism involving an increase in cAMP production in rats.

Effects of calcitonin peptides, including human calcitonin (hCT), salmon calcitonin (sCT), and calcitonin gene-related peptide (CGRP), on the secretion of testosterone and luteinizing hormone (LH) in male rats were studied. Male rats were injected intravenously with human chorionic gonadotropin (hCG), calcitonin peptides, or hCG plus calcitonin peptides. Blood samples were collected at several intervals following hormone challenge. In an in vitro experiment, testis blocks were incubated with hCG (0, 0.05, 0.5, or 5 IU/ml) or hCG (0.5 IU/ml) plus calcitonin peptides (0-10(-9) or 10(-6) M) at 34 degrees C for 30 minutes. Both medium and plasma samples were extracted by ether and analyzed for testosterone by radioimmunoassay (RIA). The concentration of calcium in each plasma sample was measured by an automatic calcium analyzer. The anterior pituitary gland (AP) was incubated with or without calcitonin peptides (0-10 nM) at 37 degrees C for 30 minutes. They were then incubated with gonadotropin releasing hormone (GnRH, 10 nM) for a further 30 minutes. The concentration of LH in AP medium was measured by RIA. The accumulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in both testicular tissues and APs were measured by RIA. A single intravenous injection of calcitonin peptides decreased the basal and hCG-stimulated levels of plasma testosterone gradually from 60 to 180 or 360 minutes after challenge. The plasma calcium was not altered by the injection of calcitonin peptides and/or hCG. Administration of calcitonin peptides in vitro resulted in a dose-dependent inhibition of both basal and hCG-stimulated release of testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Transcriptional activation of c-myc proto-oncogene by estrogen in human ovarian cancer cells.

NIH:OVCAR-3 is a human ovarian cancer cell line that expresses a moderate amount of estrogen receptors, 28 fmol/mg protein. We have found that estrogen at a concentration of 10(-7) M induced a 2.3-fold increase in the growth of NIH:OVCAR-3 cells after 48 h stimulation. A 4-fold increase in c-myc mRNA expression at 30 min and a 7.5-fold increase at 50 min post-induction with estradiol were observed. Nuclear run-on analysis indicated that c-myc transcripts increased 4-fold within 10 min of estrogen addition. The half-life of c-myc mRNA was 64 min +/- 5 min and was not affected by estrogen. Antisense oligonucleotide to c-myc specifically inhibited the estrogen stimulated c-myc protein expression as well as the growth of NIH:OVCAR-3 cells. A control ovarian cancer cell line OC-3-VGH that had few estrogen receptors (1 fmol/mg protein) did not respond to estrogen in growth; however, these cells respond to estrogen with a 1.5-fold increase in c-myc mRNA. The stability of c-myc mRNA of these cells was not affected by estrogen. Our results indicate that transcriptional induction of c-myc expression by estrogen plays a critical role in the proliferation of NIH:OVCAR-3 cells.

Cell Division↗

Interrelationship between thyroxine and estradiol on the secretion of thyrotropin-releasing hormone and dopamine into hypophysial portal blood in ovariectomized-thyroidectomized rats.

Effects of thyroxine (T4) on the secretion of thyrotropin-releasing hormone (TRH) and catecholamines into hypophysial portal blood and on the concentrations of arterial plasma thyroid-stimulating hormone (TSH) and prolactin (PRL) in ovariectomized and thyroidectomized (Ovx-Tx) rats were studied. Immediately after ovariectomy, rats were Tx or sham Tx. The Ovx-Tx rats were injected subcutaneously with estradiol benzoate (EB, 0.5 microgram/kg b.w.) or sesame oil, and T4 (20 micrograms/kg b.w.) or saline once daily for 2 weeks. The Ovx rats with intact thyroid gland were injected with saline and oil only. The hypophysial portal blood samples were collected and mixed with or without 2,3-dimercaptopropanol before extraction by methanol or perchloric acid, respectively. The femoral arterial blood was also collected. The concentrations of TRH in methanol-extracted portal plasma and that of TSH and PRL in arterial plasma were measured by radioimmunoassay. The concentrations of catecholamines in perchloric acid-extracted portal plasma samples were measured by radioenzymatic assay. Thyroidectomy in Ovx rats resulted in an increase in portal plasma TRH and arterial plasma TSH. Despite the presence or absence of estradiol, T4 replacement in Ovx-Tx rats decreased portal plasma TRH and arterial plasma TSH to euthyroid levels. Combination of the injection of T4 and EB in vivo caused significantly decreased levels of portal plasma dopamine and increased arterial plasma PRL compared with those in vehicle-injected Ovx-Tx animals. Concentrations of neither norepinephrine nor epinephrine in hypophysial portal plasma paralleled the altered concentrations of PRL or TSH in arterial plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Correlation between angiogenesis and basic fibroblast growth factor expression in experimental brain infarct.

BACKGROUND AND PURPOSE: Cerebral endothelial cells are quiescent under normal conditions; they are stimulated to proliferate around an infarct, although the mechanism is unclear. In the present study we explored the relation between angiogenesis and the expression of basic fibroblast growth factor (bFGF) by participating cells in brain infarct. METHODS: Brain infarct was created in rats by ligation of a branch of the left middle cerebral artery followed by permanent occlusion of the left common carotid artery and temporary occlusion of the right common carotid artery. The brains were removed after 1 to 14 days and studied with histological and immunohistochemical methods. Bromodeoxyuridine (BRdU) was used as an S-phase marker for the proliferative cells. RESULTS: Enhanced bFGF immunoreactivity was observed in neurons adjacent to the infarct after 1 day, and the change subsequently spread to distant neurons in the ipsilateral hemisphere. After 2 days blood vessels and glial cells around the infarct began to incorporate BRdU. During the first week new capillaries accompanied by macrophages extended into the infarct. The macrophages, endothelial cells, and reactive astrocytes expressed mild to moderate bFGF immunoreactivity. CONCLUSIONS: The spatial and temporal correlation between bFGF expression and angiogenesis in conjunction with the well-known biological properties of bFGF suggest that bFGF produced by neurons, macrophages, and glial cells may participate in angiogenesis in brain infarct.

Animals↗

Effect of human calcitonin on the secretion of luteinizing hormone in orchiectomized rats.

The effect of human calcitonin (hCT) on the secretion of luteinizing hormone (LH) was examined in castrated rats. Male rats were orchiectomized (Orch) 2 weeks before they were treated with a single bolus injection of gonadotropin-releasing hormone (GnRH, 1 microgram/kg of body weight), hCT (3.4 ng/kg), or the combination of GnRH and hCT through a right jugular vein catheter. Blood samples (0.5 ml each time) were collected immediately before (0-min) and then at 15, 30, 60, 120 and 180 min after hormone injection. Plasma LH concentration was measured with a radioimmunoassay technique. Plasma calcium concentration was determined in an automatic analyzer. hCT significantly diminished both the basal and GnRH-stimulated levels of plasma LH without any relation to the reduced plasma levels of calcium. These results clearly demonstrated a plasma calcium-unrelated inhibitory effect of hCT on LH secretion.

Animals↗

Successful resection of a minute icteric hepatocellular carcinoma--case report.

A 38-year-old male was admitted to our department with jaundice. Imaging studies including ultrasonography, ERCP, PTC and computed tomography (CT) revealed a hilar lesion. Right hepatic lobectomy, caudate lobectomy, excision of CBD and restoration of biloenteric continuity was performed. Pathological examination showed an icteric hepatoma (1.2 x 0.8 x 0.8 cm in size) originating in the caudate lobe. The tumor thrombus occupied the common hepatic duct and the right intrahepatic duct. The postoperative course was fairly unremarkable, and the patient has remained in good health for four years after surgery without any sign of recurrence.

Adult↗

An immobilized-enzyme system for the determination of sialic acid using cloned neuraminidase from Clostridium perfringens A.T.C.C. 10543.

Neuraminidase expressed by cloned nanH of Clostridium perfringens has been immobilized and employed to determine the concentration of sialic acid in human serum. Two enzyme pairs, cloned neuraminidase-N-acetylneuraminate (NANA) lyase and pyruvate oxidase-peroxidase, have been respectively co-immobilized on to 1,12-aminododecane-agarose with glutaraldehyde. The relative specific activities of the co-immobilized neuraminidase and NANA lyase were 61 and 77%, and those of pyruvate oxidase and peroxidase were 51 and 96% of the corresponding soluble enzymes respectively. The optimal reaction pH at 37% C for each of the co-immobilized enzymes was about 1 pH unit higher than that of the corresponding soluble enzyme. The optimal reaction temperature of peroxidase was increased as a result of immobilization. The thermostability of the immobilized cloned neuraminidase, NANA lyase, pyruvate oxidase and peroxidase were increased 80-, 83-, 115- and 147-fold at 45 degrees C over the soluble forms respectively. The results correlated satisfactorily with those obtained by using a soluble enzyme system. The system is thus a reliable assay method for sialic acid in serum.

Cloning, Molecular↗

Innervation of the ligament of the femoral head in the formosan rock monkey: a retrograde HRP tracing and ultrastructural study.

The innervation of the ligament attached to the femoral head of the Formosan rock monkey (Macaca cyclopis, Swinhoe) was investigated by means of the retrograde HRP tracing method and by electron microscopy. WGA/HRP was injected into the ligament of the left femoral head. Numerous neurons labelled with HRP were found in the ipsilateral lumbar sympathetic ganglia, from L1 to L7, with a peak in the L3 to L5 region. Labelled neurons were also found in the ipsilateral spinal dorsal root ganglia, from L1 to L7 and concentrated at L4. Ultrastructurally, the nerve fascicles to the ligament had an average diameter at 32.8 microns. They contained both myelinated and unmyelinated axons and accompanied the blood vessels. Sensory receptors were not found in the ligamentum proprium but free nerve endings were observed in the walls of the blood vessels. The present results indicate that the nerve fibres to the ligament of the femoral head may be involved in regulating blood vessel calibre in addition to having a sensory function.

Animals↗

Elevation of carcinoembryonic antigen related to biliary malignancy in hepatolithiasis.

Bile duct neoplasms occur relatively often in patients with hepatolithiasis in Taiwan. In this study, 49 patients with a positive immunoperoxidase stain for carcinoembryonic antigen (CEA) in the bile duct glands were examined in relation to the concentration of CEA in serum and bile. The bile concentrations of CEA in 15 control patients, 16 patients with hepatolithiasis only, 7 with hepatolithiasis and bile duct carcinoma, and 11 with bile duct carcinoma only were 4.09 +/- 4.12, 70.49 +/- 81.62, 137.73 +/- 66.15, and 144.3 +/- 117.31 ng/ml (mean +/- SD), respectively. A positive CEA stain from the bile duct was seen in 13.33%, 81.23%, 85.71%, and 90.91% of each group, respectively. No strongly positive staining, (2+ or 3+) was found in the control group, but it was found frequently in the hepatolithiasis and bile duct carcinoma groups. The findings of this study therefore suggest the probability of a combined neoplasm in patients with hepatolithiasis if the CEA value is unusually elevated in the serum or bile.

Bile↗

Point mutation of the ras oncogene in human ovarian cancer.

The ras oncogene exists in a variety of human cancers, including carcinomas of bladder, breast, colon, kidney, liver, lung, ovary, pancreas, and stomach. The ras genes acquire transforming activity either by enhanced expression or by a single point mutation. A single base-pair mutation at specific sites within ras genes endows them with the capacity to transform certain cell lines in vitro. In this study, we showed the patterns of point mutations in codons 12, 13, and 61 of ras genes in human ovarian cancer. The experimental procedures were isolation of genomic DNA from normal ovary and ovarian cancer tissue specimens, amplification of a genomic DNA segment (about 100 bp) using different 5' and 3' extension primers in the polymerase chain reaction (PCR), labeling and purification of synthetic mutation-specific oligonucleotide probes, slot-blot hybridization, and autoradiography. The three reaction steps for the PCR cycle were: 96 degrees C for 1 min in step 1, 56 degrees C for 1 min in step 2, and 74 degrees C for 1 min in step 3. The PCR reaction was repeated totally for 30 cycles. In 28 tissue specimens of human ovarian cancer examined, one specimen was found with a c-Ha-ras point mutation at codon 12, two had a c-Ki-ras mutation at codon 12, and one had a c-Ki-ras mutation at codon 13.

Autoradiography↗