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Biomedical subjects

K J Chang

Publications and source records attributed to K J Chang.

At least 127 records · Page 7Linked to original sources

Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo.

OBJECTIVE: To study the effect of E2 and P on the epithelial cell cycle of normal human breast in vivo. DESIGN: Double-blind, randomized study. Topical application to the breast of a gel containing either a placebo, E2, P, or a combination of E2 and P, daily, during the 10 to 13 days preceding breast surgery. PATIENTS: Forty premenopausal women undergoing breast surgery for the removal of a lump. MAIN OUTCOME MEASURES. Plasma and breast tissue concentrations of E2 and P. Epithelial cell cycle evaluated in normal breast tissue areas by counting mitoses and proliferating cell nuclear antigen immunostaining quantitative analyses. RESULTS: Increased E2 concentration increases the number of cycling epithelial cells. Increased P concentration significantly decreases the number of cycling epithelial cells. CONCLUSION: Exposure to P for 10 to 13 days reduces E2-induced proliferation of normal breast epithelial cells in vivo.

Administration, Topical↗

HER-2/neu overexpression in Chinese breast cancers: correlation with other prognostic factors.

HER-2/neu oncogene amplification or overexpression has generated considerable interest in predicting the outcome of breast cancer in Caucasians. In the present study, Northern blot analysis was used to investigate 44 primary breast cancers of different stages in Chinese patients. Nineteen tumors (43.2%) demonstrated more than two-fold expression of HER-2/neu mRNA over adjacent non-tumor breast tissue. The incidence of HER-2/neu overexpression in this series is higher than those reported in Caucasian studies. Ethnic variation is perhaps the only contributing factor. In node-negative patients, the incidence of HER-2/neu overexpression was also higher (33.3%), which could imply a worse prognosis in node-negative Chinese patients than in their Caucasian counterparts. A significant correlation between HER-2/neu overexpression and cancer stage was demonstrated. There were also trend relationships between HER-2/neu overexpression and other prognostic factors, including the number of positive axillary lymph nodes, tumor size, hormone receptor status and age at diagnosis, but none of these correlations were statistically significant. In axillary lymph node-negative patients, HER-2/neu overexpression was associated with estrogen receptor-negative status, a factor predicting worse outcome. These findings imply that HER-2/neu overexpression may identify a subgroup of node-negative patients with a poor prognosis who would otherwise have a favorable prognosis.

Blotting, Northern↗

Endoscopic ultrasound-guided fine needle aspiration in the diagnosis and staging of pancreatic tumors.

Endoscopic ultrasound (EUS) is useful in the detection of pancreatic carcinoma. One of its major limitations is the lack of specificity for malignancy, both for the primary tumor and for associated lymph nodes due to its inability to distinguish malignant infiltration from benign inflammation. EUS-guided fine needle aspiration (FNA) has now been developed, which allows for a tissue diagnosis of the primary tumor as well as lymph nodes, liver metastasis, and peritoneal/pleural fluid. The addition of EUS-guided FNA, with the specificity of a tissue diagnosis, to the high sensitivity and vascular assessment of EUS alone makes this the modality of choice for the diagnosis and staging of pancreatic carcinoma. The results of preliminary studies along with discussion regarding the technique, safety, cytologic adequacy, diagnostic accuracy, clinical utility, and future trends of EUS-guided FNA in pancreatic tumors are presented.

Biopsy, Needle↗

Cloning and expression of a cDNA encoding bovine muscarinic acetylcholine m3 receptor.

A cDNA clone encoding bovine muscarinic acetylcholine m3 receptor has been isolated from a bovine brain library. Sequencing of this clone has revealed a single open reading frame encoding a protein of 590 amino acids. Comparison with known muscarinic m3 receptor sequences from other species shows a high degree of conservation (92-98% homology) in the protein sequence. COS cells transfected with this cDNA expressed a single high-affinity (Kd = 43.9 pM) binding site for muscarinic receptor ligand N-[3H]methylscopolamine.

Amino Acid Sequence↗

Selective depression of T-lymphocyte subsets in gastric cancer patients: an implication of immunotherapy.

The lymphocytes and their subsets were determined in the peripheral blood of 62 gastric cancer patients and 68 controls using fluorescent conjugated monoclonal antibodies and flow cytometry (FACScan method). A significant increase in the total number of white blood cells from gastric cancer patients was noted in comparison to controls, but the percentage of lymphocytes was the same. The percentage of suppressor (cytotoxic) T cells (CD8) showed no difference in all stages of gastric cancer patients evaluated, but the percentage of helper (inducer) T cells (CD4) and the CD4/CD8 ratio decreased significantly in the advanced stages III and IV. Depression of the CD4/CD8 ratio was well correlated with tumor invasion, lymph node metastasis, and tumor size but not with sex, age, tumor location, gross type, or histologic differentiation. It appeared that the immune defect of gastric cancer patients was associated with the afferent arm (CD4) and worsened as the disease advanced. These results suggest that immunotherapy to stimulate the deficient immune system may play an important part in the multimodality treatment of patients with advanced gastric cancer.

CD4-CD8 Ratio↗

Factors related to tumor size of breast cancer at treatment in Taiwan.

METHODS. Personal information and clinical and pathological records were collected for 178 of 310 new cases of breast cancer in 1991 Cancer Registry of Taiwan. RESULTS. Among the subjects studied, 89.3% of the breast cancers were found incidentally. Delayed treatment, doctor shopping, and taking traditional medicine were common. Only 19.7% of the tumors were not more than 2 cm in diameter when the patients received treatment. The most important factors related to tumor size at treatment were occupation, family economic status, and action after detection. Those who were employed, had higher family economic status, and saw a doctor immediately after the tumor was detected were likely to have smaller (< or = 2 cm) tumors at treatment. The application of screening methods, however, did not show any significant relationship. The authors suggested implementing a breast self-examination health education program, evaluating cost-benefits of different screening methods, and setting up a breast cancer screening model that can meet the needs of Taiwanese women.

Adult↗

Acute myocardial infarction in the young adults.

A review was done on 631 patients with acute myocardial infarction who underwent coronary angiography within 30 days after onset of myocardial infarction at Yonsei University Severance Hospital from January, 1985, to August, 1993. The incidence of acute myocardial infarction in patients under 40 years of age was 10.3% (65/631). Acute myocardial infarction below the fourth decades was the predominant disease of men. Risk factor analysis revealed a history of cigarette smoking and hypercholesterolemia were more frequently found in the young patients, but a history of hypertension and diabetes were more frequently found in the elderly patients. Angiographically, the incidence of one vessel disease and normal or minimal lesion coronary anatomy were more frequent in the young patients and incidence of multi-vessel disease were more frequent in the elderly patients. Of the 65 patients under 40 with acute myocardial infarction, the patients with multi-vessel disease tended to have a history of diabetes mellitus in comparison with those with normal coronary anatomy or one vessel disease.

Adult↗

Five-drug combination chemotherapy (FAPEL) for advanced gastric cancer: a pilot study.

To test if the incorporation of 5-fluorouracil (5-FU) and leucovorin in a modified etoposide, doxorubicin, cisplatin (EAP) regimen could diminish its toxicity and improve its efficacy, 18 patients with far-advanced, unresectable gastric cancer, diagnosed at National Taiwan University Hospital between January 1991 and December 1992, were treated with a FAPEL combination chemotherapy. The regimen consisted of doxorubicin 25 mg/m2 i.v. on day 1, cisplatin 60 mg/m2 i.v. infusion on day 1, etoposide 60 mg/m2/day i.v. infusion on days 1-3, 5-fluorouracil 500 mg/m2/day i.v. on days 1-3, and leucovorin 50 mg/day i.v. on days 1-3; repeated every three to four weeks. The patients included nine metastatic, six locally advanced and inoperable, and three post-gastrectomy recurrent cancer patients with median Karnofsky performance status of 60%. There were 11 men and seven women with a median age of 52.5 years. The patients tolerated the treatment toxicity relatively well and received an average of 4.3 courses of chemotherapy. Most patients completed the protocol therapy except one who refused and another who died of leucopenic sepsis. Myelosuppression was the limiting toxicity, with Eastern Cooperative Oncology Group (ECOG) grade 3-4 leucopenia developing in 35.9% and grade 3-4 thrombocytopenia developing in 11.5% of a total of 78 courses given. The overall objective response rate was 44.4% with 5.5% complete responses and 38.9% partial responses. The overall median survival was seven months (0.5-21 months). The median survival of responders and non-responders was 13 months (5-21 months) and three months (0.5-7 months), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Can cecal diverticulitis be differentiated from acute appendicitis?

Cecal diverticulitis is a rare disease entity, the diagnosis of which remains a difficult problem. The clinical picture of cecal diverticulitis is almost indistinguishable from acute appendicitis. We reviewed 11 cases of pathologically documented cecal diverticulitis who underwent treatment from May 1981 to April 1992. They were diagnosed incorrectly as acute appendicitis, ruptured appendicitis or appendiceal abscess prior to operative intervention. Thirty patients diagnosed correctly with acute appendicitis from March 1992 to April 1992 were included for a comparative study. We found that cecal diverticulitis presented with a longer duration of symptoms, initial pain over the right lower quadrant of the abdomen, older age, less migration of pain, nausea, vomiting, fever and leukocytosis, and an incidence of Alvarado's score > or = 7 than acute appendicitis.

Acute Disease↗

Behavioral effects of the systemically active delta opioid agonist BW373U86 in rhesus monkeys.

The behavioral effects of (+-)-4-((alpha R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- hydroxybenzyl)-N,N-diethylbenzamide dihydrochloride (BW373U86), a nonpeptidic, systemically active, delta opioid agonist, were examined in rhesus monkeys. BW373U86, the mu agonist alfentanil and the kappa agonist U69,593 [(5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro- (4,5)dec-8-yl)benzeneacetamide] all produced a dose-dependent suppression of response rates maintained under a fixed ratio 30 schedule of food presentation. The rate-suppressing effects of BW373U86 lasted 1 to 2 hr and were no longer apparent after 4 hr. The selective delta antagonist naltrindole (NTI) antagonized the effects of BW373U86 with relatively high potency (pKB = 6.5) and the antagonist effects of NTI against BW373U86 lasted approximately 4 hr. NTI was less potent in antagonizing alfentanil (pKB = 5.1) and the highest dose of NTI examined (10.0 mg/kg) did not antagonize U69,593. BW373U86 did not generalize to the discriminative stimulus effects of the mu agonist alfentanil or the kappa agonist ethylketocyclazocine. BW373U86 also did not produce antinociceptive effects in the warm-water tail-withdrawal procedure, significant respiratory depressant effects in monkeys breathing either air or 5% CO2 or reinforcing effects in a self-administration procedure. The highest dose of BW373U86 examined (1.78 mg/kg) produced convulsions in one monkey. The high relative potency of NTI to antagonize the rate-suppressing effects of BW373U86 was consistent with the characterization of BW373U86 as a systemically active, delta-selective agonist in rhesus monkeys. Under the conditions evaluated in the present study, the delta receptors to which BW373U86 binds do not appear to mediate antinociceptive, respiratory depressant or reinforcing effects in monkeys.

Analgesics↗

Opioid agonist binding affinity is increased by magnesium in the presence of guanosine diphosphate but decreased by magnesium in the presence of guanyl-5'-yl imidodiphosphate.

Opioid receptors exist in multiple affinity states for agonists. Cations and guanine nucleotides affect mu-agonist affinity by modulating the interaction between receptor molecule and G-protein. In this study, we systematically examined the effects of cations and guanine nucleotides on the binding of mu-agonist [D-Ala2, N-Me-Phe4, Met-(O)5-ol]enkephalin in rat spinal cord and brain membranes. A homogeneous class of low-affinity receptors was obtained by conducting binding assays in the presence of Na+ (100 mM) + guanosine diphosphate (100 microM). The addition of Mg++ (5 mM) shifted a portion of the low-affinity receptors to the high-affinity state. In membranes preincubated with Na+ + guanosine diphosphate and with the binding assay performed in the presence of Mg++, a homogeneous class of high-affinity receptors was induced by the agonist. Further addition of Na+ + guanyl-5'-yl imidodiphosphate (30 microM) to the above Mg++-containing medium converted all receptors to a low-affinity state, whereas Na+ + guanyl-5'-yl imidodiphosphate produced a mixture of high- and low-affinity states. Our results suggest that, depending on which guanine nucleotide is bound with G-proteins, mg++induces opposite effects on the states of mu-receptor affinity: high affinity with GDP and low affinity with guanyl-5'-yl imidodiphosphate. Sodium ion promotes the low-affinity receptor conformation and increases total low-affinity binding sites. The affinity of the opiod antagonist naloxone is not sensitive to regulation by Mg++ and guanine nucleotides, except that the total receptor binding is increased by Na+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Endoscopic ultrasound-guided fine needle aspiration of pancreatic carcinoma.

Endoscopic ultrasound (EUS) is reported to be the single best modality for visualizing small pancreatic carcinomas. Whereas tissue diagnosis by fine needle aspiration (FNA) can be performed with computed tomography (CT) or transabdominal ultrasound guidance, the diagnostic accuracy is limited by the ability of these modalities to visualize the lesion. Real time EUS-guided fine needle aspiration has recently been reported as a new diagnostic modality. The application of EUS-guided FNA in the diagnosis of small pancreatic carcinoma has not been reported. We present a case in which transduodenal EUS-guided FNA was successful in establishing a definitive tissue diagnosis of pancreatic carcinoma in a 1.6-cm lesion in the head of the pancreas. This case along with a review of the literature highlights the great potential of this new modality in the diagnosis of pancreatic carcinoma.

Adenocarcinoma↗

Molecular cloning and sequence analysis of the cDNA for ancrod, a thrombin-like enzyme from the venom of Calloselasma rhodostoma.

The 1.54 kb cDNA for ancrod, a thrombin-like enzyme, was cloned from a lambda ZAP cDNA library derived from the venom glands of Calloselasma (Agkistrodon) rhodostoma. The cDNA sequence reveals that ancrod is synthesized as a pre-zymogen of 258 amino acids, including a putative secretory peptide of 18 amino acids and a proposed zymogen peptide of 6 amino-acid residues. The amino-acid sequence of the predicted active form of the enzyme exhibits a high degree of sequence similarity to those of mammalian serine proteases (trypsin and pancreatic kallikrein) and other thrombin-like enzymes (batroxobin and flavoxobin). Key amino-acid residues (His43, Asp88, Ser182 and Asp176) that are thought to be involved in the substrate cleavage and in the substrate-binding reaction are conserved. Ancrod contains 13 cysteine residues. Based on alignment with the amino-acid sequences of trypsin and batroxobin, six disulphide bridges can be predicted to be present in the ancrod protein. The existence of a free cysteine, which changes the common sequence surrounding the Ser182 active site from Gly-Asp-Ser-Gly-Gly-Pro to Cys-Asp-Ser-Gly-Gly-Pro, is unusual for a serine protease.

Amino Acid Sequence↗

Binding of BW 373U86, a non-peptidic delta opioid receptor agonist, is not regulated by guanine nucleotides and sodium.

BW 373U86 is a novel, non-peptidic delta-opioid receptor ligand with agonist properties in mouse brain and in the mouse isolated vas deferens. The sensitivity of BW 373U86, and of the peptide delta-opioid agonists [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2,Glu4]deltorphin, to regulation by guanine nucleotides and sodium was evaluated in competition studies against the 5 selective radioligand [3H]naltrindole. The IC50 values for DPDPE and [D-Ala2,Glu4]deltorphin were significantly increased in brain and mouse vas deferens in the presence of Gpp(NH)p and NaCl. In contrast, the IC50 values for BW 373U86 were not altered in the presence of Gpp(NH)p and NaCl in either tissue. The data indicate that the agonist properties of BW 373U86 may not be affected by the supposed uncoupling of the alpha-subunit of the G-protein from a receptor thought to be G-protein linked.

Animals↗

DNA hypomethylation of proliferating cell nuclear antigen gene in human hepatocellular carcinoma is not due to cell proliferation.

Proliferating cell nuclear antigen (PCNA) gene expresses preferentially in proliferative cells or tissues. The levels of PCNA mRNA are very low in livers of adult mammals. Expression of PCNA gene in hepatocellular carcinoma tissues was, however, elevated; and 5'-CCGG-3' sequences of the gene in neoplastic tissue were less methylated. Such DNA hypomethylation was concluded, on the basis of two observations, not to be due to the cell proliferation in hepatoma tissues. First, while the expression of PCNA was increased during serum-stimulation of quiescent Hep G2 cells, the DNA methylation pattern of PCNA gene remained unchanged. Second, in rat liver regeneration, the PCNA mRNA level rose and declined, but the DNA methylation status of PCNA gene was unaltered. Therefore, the DNA hypomethylation of the PCNA gene found in hepatocellular carcinoma was not due to cell proliferation, but a possible consequence of cell transformation.

Animals↗

Nucleotide sequence of a full-length cDNA encoding a common precursor of platelet aggregation inhibitor and hemorrhagic protein from Calloselasma rhodostoma venom.

The nucleotide sequence of a full-length cDNA encoding the common precursor of a platelet aggregation inhibitor, rhodostomin and a hemorrhagic protein from Calloselasma rhodostoma snake venom is presented. The 1.98-kb cDNA contains an open reading frame encoding 478 amino acid residues. The complete structure of the precursor protein encoded by the cDNA is elucidated.

Amino Acid Sequence↗

Microinjection of Rap2B protein or RNA induces rearrangement of pigment granules in Xenopus oocytes.

Rap2B, a member of the ras superfamily of low-molecular-mass GTP-binding proteins, induced a characteristic rearrangement of the pigment granules in Xenopus oocytes following its microinjection, resulting in numerous unpigmented spots on the animal hemisphere. This phenomenon, termed 'mottling', was also induced by microinjection of in vitro-transcribed Rap2B RNA or of purified recombinant Rap2A. Following the microinjection of Rap2B, more than 90% of the oocytes showed signs of mottling within 10 h. The time course of mottling paralleled the association of the recombinant Rap2B with an oocyte membrane fraction. Like other members of the ras superfamily, Rap2B possesses a C-terminal CAAX motif that serves as a signal for post-translational processing. Mutation of the cysteine residue in the CAAX motif to serine prevents the association of Rap2B with oocyte membranes, and also prevents mottling. This result suggests that post-translational processing of Rap2B is required for the observed effect. Mottling was blocked by boiling Rap2B prior to its microinjection or by co-injection of the cytoskeletal reagent phalloidin.

Animals↗