Search PubMed⌕ Search

Biomedical subjects

H S Sun

Publications and source records attributed to H S Sun.

At least 73 records · Page 4Linked to original sources

Clinicopathologic significance of the K-ras gene codon 12 point mutation in stomach cancer. An analysis of 140 cases.

BACKGROUND: The frequency and clinicopathologic significance of the K-ras gene point mutation in stomach cancer remain to be defined. METHODS: The authors investigated the frequency of K-ras codon 12 point mutations in stomach cancer using a sensitive polymerase chain reaction (PCR)-based method in 140 samples and correlated the findings with various clinicopathologic characteristics of the patients. RESULTS: The overall frequency of K-ras codon 12 point mutations in stomach cancer was 7.9% (11/140). DNA sequencing of nine cases with K-ras codon 12 point mutations identified seven cases with a single-base substitution of GGT to AGT (glycine to serine) and two with single-base substitution of GGT to AGT (aspartic acid). Tumors located in the upper third of the stomach had a significantly higher frequency of K-ras codon 12 mutations (3/8, 37.5%) compared with tumors located in the middle (4/29, 13.8%) or lower (3/99, 3.0%) thirds of the stomach (P = 0.001). No significant difference was observed in the frequency of K-ras codon 12 mutations in terms of other various clinicopathologic characteristics including tumor DNA ploidy and S-phase fraction. After a median follow-up of 26 months, disease free and overall survival were not significantly different between patients with stomach cancer with or without K-ras codon 12 mutation. Among eight patients with stomach cancer located in the upper part of the stomach, none of the three patients with K-ras gene-mutated tumors died versus four of five with tumors without K-ras gene mutations (P = 0.064). CONCLUSIONS: K-ras codon 12 point mutations are uncommon in stomach cancer (7.9%). There was significant correlation between K-ras mutations and vertical tumor location in the stomach, suggesting that different mechanisms may play a role in the pathogenesis of stomach cancer according to the location of tumors in the stomach.

Adult↗

Predictive factors for beneficial response to interferon-alfa therapy in chronic hepatitis C.

OBJECTIVES: Interferon is the only established treatment for chronic hepatitis C but the host-dependent or virus-related factors affecting the response rate to interferon therapy are not yet clear. The purpose of this study was to investigate the factors predictive of response to interferon-alfa therapy in chronic hepatitis C. METHODS: Twenty-five consecutive patients with chronic hepatitis C were randomized to three regimens of interferon-alfa: group A (n = 7, 3 MU every day for 3 months), group B (n = 8, 3 MU every other day for 3 months) and group C (n = 10, 3 MU every other day for 6 months). We quantified serum HC RNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR) and performed HCV genotyping using type-specific primers deduced form the NS5 region of the HCV genome. We also attempted to identify which demographic, biochemical and histologic factors in addition to virus-related factors would significantly predict beneficial response to interferon by multivariate analysis. RESULTS: Sustained responders were 8 (36.4%), nonsustained responders were 2 (9.1%) and nonresponders were 12 (54.5%) of 22 patients who had received complete therapy. The initial HCV RNA level (logarithmic transformed copy numbers per ml of serum) in sustained responders (5.75 +/- 0.39) was significantly lower than that of nonsustained responders (6.80 +/- 0.71) and nonresponders (6.70 +/- 0.52) (p < 0.05). In multivariate multiple logistic regression analysis, the serum HCV RNA level before therapy was only the independent predictor of a sustained response to interferon-alfa therapy (p = 0.001). CONCLUSIONS: Serum HCV RNA level before therapy was the most useful predictor of a sustained response to interferon-alfa therapy for chronic hepatitis C.

Adult↗

p53 protein overexpression and allele loss of p53 gene in gastric adenocarcinoma.

Gene alterations of p53 tumor suppressor gene such as point mutations, deletions or insertions occur in various human cancers. p53 protein overexpression was studied immunohistochemically in 80 gastric adenocarcinomas using an anti-human p53 antibody (Pab 1801) and the avidin-biotin-peroxidase technique. We have also analyzed allele loss of the human p53 gene in 54 cases of gastric adenocarcinoma using polymerase chain reaction and restriction fragment length polymorphism. p53 immunostaining was also demonstrated in 48 of 80 carcinomas (60%). Normal mucosa was always negative. No relation could be found between p53 immunostaining and the degree of differentiation. 21 of the 54 patients(39%) were informative for the p53 exon 4. In ten of these informative cases(47.6%), tumor DNAs showed allele loss when compared with nonmetastatic lymph node DNAs. Seven of the ten(70%) showed p53 immunoreactivity. These findings suggest that mutations of the p53 gene may play a role in the development of gastric adenocarcinoma and that allele loss of p53 frequently occurs in p53 immunoreactive gastric adenocarcinoma.

Adenocarcinoma↗

Change in recruitment order of motor units in human parasternal intercostal muscles with sleep state.

Recruitment order of individual motor units in the early part of inspiration in parasternal intercostal muscles was observed in normal human subjects during wakefulness and non-rapid-eye-movement sleep. Electromyograms from bipolar fine wire intramuscular electrodes were recorded while the subjects lay supine in a sleep laboratory, and sleep stage was determined by polysomnography. From wakefulness to sleep there were numerous examples of shifts in order of recruitment among the low threshold units of early inspiration. There were corresponding shifts in the order of derecruitment of these units. Analysis of frequency of firing of units also suggested that the levels of excitatory input to one unit of a pair could be altered relative to the level of input of the other one. The data imply that there are at least minor differences in distribution of excitatory inputs from various sources among motoneurons of this muscle pool.

Electromyography↗

Effect of ursodeoxycholic acid on experimental hepatic porphyria induced by griseofulvin.

Griseofulvin(GF) has become the drug of choice as an antifungal agent for patients who suffer from many kinds of fungal infection. In order to clarify hepatic injury by griseofulvin(GF) overload and the effect of UDCA on GF-induced hepatic injury, the authors carried out biochemical, histologic, and ultrastructural studies of liver following treatment with griseofulvin and ursodeoxycholic acid(UDCA) in mice. Urine porphobilinogen excretion in the group treated with GF alone was significantly increased and reached the highest level in the 4th week and declined thereafter. Biochemical studies of the liver function showed no remarkable changes of serum bilirubin levels throughout the experimental period in all groups, except for SGPT and alkaline phosphatase activities which were significantly elevated and reached the highest level in the second week. Then they slightly decreased in GF treated groups(GF alone and GF plus UDCA) in comparison with the control group. Pathologic findings in the group treated with GF alone include focal liver cell necrosis(esp, zone 3), Mallory bodies in hepatocytes(esp, zone 1), Kupffer cell activation, and brown protoporphyrin pigments in the hepatocytes, bile canaliculi and interlobular bile ducts with a marked inflammatory cell infiltration in the portal tracts. Under the polarizing light microscope, bile ductular and canalicular thrombi showed a "Maltese cross" birefringence in mice treated with GF alone. There is no definite finding of fatty change in hepatocyte. Under the microscope, the liver appeared normal with an intact lobular architecture in the GF plus UDCA treated group. Electron microscopically, GF-induced changes include swelling of mitochondria, globular protoporphyrin crystals in the hepatocyte cytoplasm, markedly dilated bile cannaliculi and bile ducts and the formation of a Mallory hyaline bodies in the hepatocytes. There were no noticeable structural changes in the GF plus UDCA-treated group. Therefore the results suggest that GF causes hepatic injury, namely porphyria and cholestasis, and the treatment of UDCA may have cytoprotective and choleretic effects on GF-induced hepatic injuries.

Alanine Transaminase↗

Evaluation of omeprazole as a treatment for gastric and prepyloric ulcer in Korean patients.

The healing efficacy of omeprazole was assessed in 57 Korean patients with endoscopically-proven gastric (GU) and/or prepyloric (PPU) ulcers of at least 5 mm diameter. Fifty-three patients presented with GU, two with PPU and two with both types of ulcer. The maximum ulcer diameter was 5-10 mm in 27 patients and greater than 10 mm in 30 patients. All patients received 20 mg of omeprazole each morning for 4-8 weeks depending on ulcer healing. Ulcer healing rates were comparable using both 'intention to treat' (IT) and 'per protocol' (PP) analyses. Following the IT approach 82% (47 of 57) of patients were healed at 4 weeks and 98% (56 of 57) at 8 weeks. Following the PP approach, the corresponding healing rates were 83% (44 of 53) and 98% (55 of 56), respectively. Smoking was found to have a significant effect on ulcer healing at 4 weeks (P = 0.03), with 96% (26 of 27) of non/occasional smokers healed versus only 69% (18 of 26) of daily/heavy smokers. Ulcer size did not have a significant effect on healing, however. Ulcer symptoms, reported by all patients at entry, disappeared rapidly after commencement of omeprazole therapy. Only four patients reported mild symptoms at 4 weeks and no symptoms were reported at 8 weeks. No clinically significant changes in haematology or clinical chemistry (other than a rise in leucocytes in one patient) and no serious adverse events were observed. In conclusion, omeprazole 20 mg each morning was found to be safe and highly effective for treatment of gastric and prepyloric ulcer in Korean patients, producing a 98% healing rate. Symptom relief was rapid and the drug was well tolerated.

Adult↗

Recent advances in the treatment of digestive diseases.

Significant advances in the treatment of peptic ulcers have occurred during the last 25 years. Two important problem areas remain: resistant ulcers and ulcer relapse. Ulcers that remain unhealed after 8 weeks of treatment with full doses of active anti-ulcer drugs are considered resistant. Risk factors for the development of resistance are known, the most important being non-compliance with recognized effective therapy. A correlation exists between healing of duodenal ulcers and degree of gastric acid suppression. A duodenal ulcer that fails to heal with mild suppression of gastric acidity may, therefore, respond to more potent and longer acting drugs, such as famotidine or omeprazole. Prescribing drugs that may improve the mucosal defence may also be useful. For gastric ulcers, prolonging treatment may be effective. Currently available drugs provide some protection from ulcer relapse, but the risk of an ulcer recurring remains. Most recurrences are asymptomatic and ulcers are most likely to recur within a relatively short period of time. Success in the treatment of resistant ulcers and maintenance therapy to prevent relapse may require greater understanding of the pathology of ulcers and application of drug therapy that specifically corrects these abnormalities.

Anti-Ulcer Agents↗

Modulation of cellular transglutaminase: protease-induced activation.

Multiple molecular forms of transglutaminase are found in cells and each form is widely distributed. We find a 95 K dalton enzyme associated with membrane fractions. A 50 K dalton enzyme occurs primarily in epidermis and hair follicles. Cells after treatment with proteases show greater transglutaminase activity. The activated enzyme in rat chondrosarcoma cells is one of 95 K daltons, whereas mouse epidermal cells and rabbit endometrium cells after protease activation display enzymes of both 95 K daltons and 50 K daltons. The 95 K dalton enzyme, but not that of 80 K daltons, can be activated by proteases or sulfhydryl compounds after cell lysis. In cells that undergo terminal differentiation, e.g., reticulocytes, megakaryocytes, monocytes, chondrocytes, and epidermal cells, the forms of transglutaminase are modulated. Our findings suggest that these modulations in differentiating cells are the results of transglutaminase post-translational modifications that cause pronounced changes in catalytic activity.

Animals↗

Safety and immunogenicity of a new heat-inactivated hepatitis B virus vaccine in adult recipients.

A new heat inactivated HBV vaccine has been evaluated for safety and immunogenicity in 203 adult recipients. The vaccine was found to be safe and highly immunogenic. Three doses of 3 micrograms given at 0, 1 and 6 months, resulted in 96% seroconversion. Three doses of 3 micrograms given at 0, 1 and 2 months produced, more rapidly, seroconversion in 92% of those immunized. Antibody to a pre-S determinant developed in four of six subjects tested.

Adult↗