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Biomedical subjects

C F Chen

Publications and source records attributed to C F Chen.

At least 289 records · Page 16Linked to original sources

Synthesis of cyclic peptide homologs of glutathione as potential antitumor agents.

Two cyclic tripeptide homologs, cyclo(Glu[Cys-beta-Ala-]-OH) 8a, and cyclo(Glu[Cys-Gaba-]-OH) 8b, were synthesized by the pentafluorophenyl ester method in solution. These cyclic peptides are cyclo homologs of glutathione and are designed as potential antitumor agents. The 1H- and 13C-n.m.r. spectral parameters of cyclo(Glu[Cys(Bzl)-beta-Ala-]-OH) 7a were measured in DMSO-d6 and a possible conformation has been proposed. The cyclic peptide 8a showed low cytotoxic activities against three human tumor cell lines: KB, HeLa, and Colo 205.

Antineoplastic Agents↗

Synthesis of a cyclic hexapeptide with sequence corresponding to murine tumor necrosis factor-(127-132) as a novel potential antitumor agent.

A cyclic hexapeptide cyclo(Lys-Gly-Asp-Gln-Leu-Ser-) 10 was synthesized stepwise in solution by acylation of peptide ester trifluoroacetates directly with preactivated Boc-amino acids using the DCC/HOBt method; the final cyclization reaction was performed using the pentafluorophenyl ester method in solution (1-4). This peptide is a cyclic derivative of murine tumor necrosis factor-(127-132) and is designed as a potential antitumor agent. The cyclic peptide 10 displayed weak cytotoxic activity on three of the four human tumor cell lines tested.

Amino Acid Sequence↗

Molecular analysis of 25 Chinese families with Duchenne/Becker muscular dystrophy.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic X-linked progressive neuromuscular diseases. We have collected 25 Chinese families each with at least one DMD/BMD patient for DNA analysis in the Xp21 region. Eight genomic probes, 6 within and 2 flanking the DMD gene, and 7 restriction enzymes were used to detect 9 restriction fragment length polymorphisms (RFLPs): C7-EcoRV, J-Bir-BamHI, pERT87-30-BglII, pERT87-15-BamHI, pERT87-15-XmnI, pERT87-1-XmnI, XJ1.1-TaqI, XJ5.1-SphI, and 754-PstI. From analysis of unrelated subjects, we found that the 4 most informative RFLPs in the linkage study were pERT87-15-XmnI, pERT87-1-XmnI, XJ5.1-SphI and J-Bir-BamHI. Two flanking markers, C7 and 754, were noninformative in most families. Three families (12%) had gene deletion: family M-25 at pERT87-1 to 87-30; M-105 at XJ 5.1, 1.1, pERT87-1, and 87-15; and M-110 at XJ5.1, 1.1, and pERT87-1 to 87-30. Two recombinations were detected: M-10 between C7 and pERT87-15; and M-39 between J-Bir and pERT87-15. In the 25 mothers with affected sons, 2 had gene deletion, 1 was homozygous at all 9 polymorphic loci and the other 22 were heterozygous at more than one locus. Twenty-four at-risk female siblings were studied for carriership. Nine were classified as at high risk of carriership, 13 at low risk of carriership by haplotyping, and the remaining two were uncertain, with one due to recombination and the other to maternal homozygous haplotypes. Gene deletion and RFLP analysis are very useful in genetic counseling of Chinese DMD/BMD.

Chromosome Deletion↗

Flumazenil as an antagonist for midazolam anesthesia in outpatient surgery.

Rapid recovery is an essential component in the anesthesia of OPD surgery. In this study midazolam, the short-duration benzodiazepine, was used as an intravenous anesthetic in OPD surgery. At the end of the operation flumazenil, the specific antagonist of benzodiazepines, was given to reverse the effect of midazolam. Recovery of these patients was compared with those in the control group who received saline instead of flumazenil. In a randomized, placebo-controlled clinical study the antagonistic effect of flumazenil on midazolam was investigated in fifty ASA class I-II gynecologic outpatients subjected to D & C procedure under anesthesia induced with midazolam (0.3 mg/kg). They were divided into group A (flumazenil group) and group B (placebo group) with 25 patients in each. At the end of operation patients in group A were given 0.2 mg flumazenil intravenously to antagonize the residual effect of midazolam while patients in group B were given 2 ml normal saline intravenously as control. Our results showed that patients in group A exhibited a rapid and steady return of consciousness scaled by alertness, orientation of time and place and activity collaboration at 5, 30 and 60 min intervals following administration of flumazenil (p less than 0.005). There were no significant changes found in the hemodynamic or respiratory aspect between groups (p greater than 0.05). All the patients tolerated midazolam and flumazenil well. It is concluded that the use of flumazenil to antagonize the residual effect of midazolam is safe and effective as far as outpatient procedure is concerned.

Adult↗

Evaluation of a rapid tetrazolium-based colorimetric assay for selecting anticancer drugs.

A rapid colorimetric microtiter assay was used in this study to analysis drug cytotoxicity. Through the reduction of tetrazolium salt, MTT [3-(4, 5-dimethyl-thiazol-2-yl) 2,5-diphenyl tetrazolium bromide], by living cells to form a blue formazan product. The level of MTT cleavage by viable cells of various origins was found to be in direct proportion to the number of cells (between 500-10,000 cells/well). By MTT methods, the growth profile and chemosensitivity of 4 human tumor cell lines (KB, Hep-2, HA22T, and CoLo205) to 4 anticancer drugs (adriamycin, 5-fluorouracil, 6-mercaptopurine and cyclophosphamide) were assessed. Results from this assay were compared with data assimilated simultaneously by dye exclusion and clonogenic assay. In general, good correlation was observed among the clonogenic, dye exclusion and MTT assays for continuous drug exposures, yet the MTT assay was more rapid in testing in vitro chemosensitivity against human tumor cell lines. The dye exclusion assay was the most sensitive, followed by the clonogenic and then the MTT assays. The ID50 values obtained from the MTT assay were approximately 3 to 5 times lower than those from the other two methods. Based on these studies, MTT assay appears to be a rapid, convenient, economical and reasonable tool in the initial-stage screening of large number of the in vitro anticancer drugs.

Antineoplastic Agents↗

The renal functions following a profound hypothermia in rats.

The aftereffects of renal function were studied in rats exposed to profound hypothermia and 5 min of cardiac arrest. All experimental rats were reanimated and survived at least 1 week. It was observed that the water intake and the basal renal excretion of urine, potassium and urea were decreased 24 hr after cooling, but did return to normal within 1 week. The renal handling of a large volume of infused saline was retarded 4 hr but recovered by the end of 24 hr after hypothermia. At both 4 and 24 hr after deep cooling, clearance of inulin and p-aminohippuric acid showed there were no change in glomerular filtration rate and effective renal plasma flow. It was concluded that the renal function was altered shortly after deep cooling and 5 min of cardiac arrest, however, this alteration could be completely recovered thereafter.

Animals↗

Antiplatelet action of dehydrokawain derivatives isolated from Alpinia speciosa rhizoma.

5,6-Dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK) inhibited the aggregation and ATP release of rabbit platelets induced by arachidonic acid and collagen, without affecting those induced by ADP, PAF and thrombin. This inhibition was reversible and in a concentration-dependent manner. The IC50 of DK and DDK on arachidonate-induced platelet aggregation were calculated to be about 10 and 60 micrograms/ml, respectively. Thromboxane B2 formation caused by arachidonic acid was also suppressed by both antiplatelet agents. DK inhibited the intracellular calcium concentration rised by arachidonic acid, but not that by collagen or thrombin. DK also inhibited the secondary, but not the primary aggregation of human platelet-rich plasma induced by ADP and epinephrine. It is concluded that the antiplatelet effect of both DK and DDK is due to the inhibition of thromboxane A2 formation.

Adenosine Triphosphate↗

High energy laser irradiation and electric surgery for obstructive gastrointestinal cancer.

A total of 35 patients with advanced obstructive gastrointestinal cancer received monopolar electrosurgery and Nd: YAG laser therapy from January 1985 to June 1988. These included 13 cases of esophageal cancer (U/3 6, M/3 2, L/3 5), 14 case of gastric cancer (cardia 7, corpus 3, antrum 4), and 8 cases of rectal cancer. Twenty (esophageal 9, stomach 8, rectal 3) of 35 patients had much improved results, with the size of the lesion reduced over 90%, and the endoscope could smoothly pass through the stenotic area after electrosurgery or laser therapy. The other 12 patients had partially improved results with the tumor size being reduced 50-90% and the patients could take semiliquid food easily. Both groups of much improved or partial improved had a statistically significant difference (P less than 0.01) compared to the group of failures to treatment. Two patients developed bleeding after treatment. Twenty-one patients died of causes other than complications of electrosurgery or laser therapy. The average survival was 6.8 months. Nd: YAG laser and electrosurgery can provide good palliative results and contribute to a good quality of life in advanced obstructive gastrointestinal cancer.

Adult↗

A clinical controlled trial of endoscopic sclerotherapy for repeated esophageal variceal bleeding.

Thirty-seven patients with postnecrotic cirrhosis of the liver and 13 patients with primary hepatoma were proven to have repeated bleeding from ruptured esophageal varices. Clinically controlled trials were performed by assigning patients to either sclerotherapy or control arms (25 patients each). Combined intra-variceal and para-variceal injection before an upper endoscopic examination was performed in the sclerotherapy group. In all 25 sclerotherapy cases (100%) hemostasis was successful, which was a statistically significant success rate compared to the control group (52.0%) (p less than 0.01). In the sclerotherapy group 20% (5/25 cases) developed rebleeding, which was less than the 48.0% (7 cases of continuous bleeding and 5 cases of rebleeding) of the control group (p less than 0.05). Four cases (16.0%) in the sclerotherapy group died of erosive gastritis with massive bleeding, compared to 8 fatalities (32.0%) in the control group, because of uncontrolled esophageal variceal bleeding. Endoscopic sclerotherapy is a very effective method for arresting bleeding esophageal varices, and for decreasing the rebleeding rate.

Adult↗

The hypoglycemic effect of the crude drug prescription resources from Taiwan on experimental diabetic-mellitus (II)--the antihyperglycemic effect of tang-niao-tung no. 2 and no. 3.

The water extracts of crude drugs of Taiwan Tang-Niao-Tung (T.N.T.) No. 2 and No. 3 were administered to normal and diabetic rats for investigating the antihyperglycemic effect of these two prescriptions. It was found that the blood glucose level in normal rats was temporarily increased after T.N.T. No. 2 and No. 3 administration; this may be caused by the starch content of the drugs component. In contrast, the diabetic rats have shown a significant decrease (P less than 0.01) of blood glucose in 2, 4, 6 hours after T.N.T. No. 2 and No. 3 have been given. The blood glucose percentage at 6 hours was 78.1% of T.N.T. No. 2 and 79.2% of T.N.T. No. 3 as compared to the original level. The hypoglycemic effect of T.N.T. No. 2 and No. 3 on alloxan-induced diabetic rats have suggested that action mechanism might not mediate through the release of insulin or positive feedback of glucose to insulin, neither acted on insulin receptor. It might be possible by the indirect promoting of enzyme activity. However, the pharmacological effect of some drugs could elucidate the hypoglycemic action of these prescriptions. Temporary promotion of blood glucose in normal rats will decline to normal level by 12 hours after T.N.T. No. 2 and No. 3 administration. The pharmacological effect of these herb prescriptions for diabetic rats is valuable for further study.

Animals↗

Suppression of serum immunoreactive human epidermal growth factor by acute increase in prolactin in women.

Epidermal growth factor (EGF) is known to stimulate proliferation of various mammalian cells and secretion of prolactin (PRL) from rat anterior pituitary tumor cells. The effect of an acute increase in serum PRL induced by thyrotropin releasing hormone (TRH) or metoclopramide (MCP) on the serum immunoreactive EGF concentration was examined in nine hyperprolactinemic patients and eight normoprolactinemic women. The basal level of serum EGF in normoprolactinemic subjects was 472.8 +/- 51.1 pg/ml (Mean +/- SEM), which was not significantly different from that in hyperprolactinemic patients (487.8 +/- 22.5 pg/ml). The serum EGF concentration was decreased to 40-50% of the basal level after the abrupt increase in serum PRL induced by the injection of TRH or MCP in normoprolactinemic subjects, but no significant change in serum EGF occurred in hyperprolactinemic patients after MCP injection, in spite of a significant increase in PRL. These results suggest that an acute increase of serum PRL in normoprolactinemic women, but not in hyperprolactinemic patients, suppresses serum EGF.

Adenoma↗

Tumoricidal effect of controlled-release polymeric needle devices containing adriamycin HCl in tumor-bearing mice.

Controlled-release polymeric needle devices containing adriamycin HCL (ADH) were investigated by an in vitro dissolution study in normal saline solution and an in vivo antitumor activity in C3H mice bearing mammary carcinoma and nude mice bearing brain tumor. HPMC was used as a release rate regulator. The ADH released from needle devices was controlled by the types of polymer used and the addition of HPMC. EVA needle devices exhibit a zero order release behavior better than that of PLA needle devices. Tumor growth was markedly inhibited by treatment with needle devices after locally inserted into the solid tumor. The rank of antitumor activity of the needle devices is EVA greater than PLA greater than EVA-HPMC greater than PLA-HPMC. No significant changes in body weight of mice after treatment were found in treated groups as compared to controlled groups. The preliminary results of our study suggest that needle device dosage form shows a controlled release behavior and may be applicable as a drug carrier for delivery of antitumor drug in cancer chemotherapy.

Animals↗

Diagnostic value of adenosine deaminase and gamma-interferon in tuberculous and malignant pleural effusions.

It has been found that both adenosine deaminase (ADA) and gamma-interferon (r-IFN) are higher in tuberculous pleural effusions than in other types of pleural effusion. Both mechanisms may be related to the T-lymphocytes in effusions. We studied 39 pleural effusions: 19 tuberculous and 20 malignant [The ADA was determined according to the Giusti method and r-IFN by ELISA]. We compared the ADA and r-IFN levels in both groups of effusions and tried to determine if there was any correlation between them. The results showed: (1) The ADA enzyme level was significantly higher in tuberculous effusions than in malignant effusions as was expected (133.0 +/- 50.4 vs 32.0 +/- 17.7 U/L). (2) The r-IFN was also significantly higher in tuberculous effusions than in malignant effusions (30.4 +/- 17.4 vs 2.9 +/- 2.8 U/ml). (3) The coefficients of regression for the ADA and r-IFN levels were poor. In conclusion, both tests for measuring ADA and r-IFN levels are excellent methods for differentiating tuberculous and malignant effusions, and especially measurement of the r-IFN level could serve as a more specific test for differentiating malignant pleural effusions with high ADA levels. However, no strong correlation was found between the ADA and r-IFN levels.

Adenosine Deaminase↗

[Influence of microinjection of bicuculline into ventrolateral medulla on the suppression of cardiac function induced by diazepam in rabbits].

Experiments were carried out on 48 rabbits anaesthetized with urethane (1 g/kg). The animals were immobilized with gallamine triethiodide and ventilated artificially. Both intravenous injection of diazepam (0.5 mg/kg) and intracerebroventricular injection of flurazepam (2 mg in 50 microliters) or gamma-aminobutyric acid (GABA) (300 micrograms in 50 microliters) decreased the peak value of left ventricular pressure area of cardiac force loop and dp/dtmax. These suppressive effects of diazepam and flurazepam were prevented by intracerebroventricular injection of picrotoxin (15 micrograms in 50 microliters) or microinjection of bicuculline (3 micrograms in 0.5 microliter) into bilateral rostral ventrolateral medulla (gamma VLM). The results suggest that the inhibitory effects of diazepam on cardiac function may be mediated by activation of GABA receptor in gamma VLM.

Animals↗

Evaluation of rapid colon preparation with Golytely.

The traditional cleansing method of the large bowel usually involves dietary restrictions, purgatives and enema. They are time consuming and uncomfortable, and may result in dehydration. Though Golytely, an oral lavage solution, has been developed since 1980 as an alternative for cleansing the colon and much literature has favored it, it has not been widely used in Taiwan. In this study, we used Golytely without enema for rapid colon cleansing in a consecutive series of 48 patients. The efficacy, change of vital signs, body weights, electrolytes, and urine specific gravity were evaluated. Patient's acceptance of this method was compared with that of 32 patients who received castor oil as cleansing method. The average amount of Golytely used in this preparation was 3.16 liters, and the average time was 8 hours and 43 minutes. About 87% of patients receiving Golytely achieved a good to excellent preparation. There were no significant changes in vital signs, body weights, electrolytes and urine specific gravity. The patient's acceptance of Golytely was better than that of castor oil.

Colon↗

Voltage-sensitive calcium channels in normal and transformed 3T3 fibroblasts.

Patch clamp recordings of whole-cell and single channel currents revealed the presence of two voltage-sensitive calcium channel types in the membrane of 3T3 fibroblasts. The two calcium channel types were identified by their unitary properties and pharmacological sensitivities. Both calcium channel types were present in all control 3T3 cells, but one type was selectively suppressed in 3T3 cells that had been transformed by activated c-H-ras, EJ-ras, v-fms, or polyoma middle T oncogenes. The presence of voltage-sensitive calcium channels in these nonexcitable cells and the control of their functional expression by transforming oncogenes raises questions about their role in the control of calcium-sensitive processes such as cell motility, cytoskeletal organization, and cell growth.

Animals↗

Mass screening for hyperprolactinemia and prolactinoma in men.

To determine the incidence of hyperprolactinemia and prolactinoma without symptoms in men, the serum levels of prolactin were measured in 4803 men. Of these, 14 had hyperprolactinemia with prolactin level of over 50 ng/ml, and 3 had prolactin levels of more than 500 ng/ml. Of these 3 subjects, 2 were found to have pituitary prolactinoma by computed tomograph scanning and surgery, the other subject, who was highly suspected to have prolactinoma, refused further examinations. The serum prolactin levels of 51-100 ng/ml in 11 subjects may have been induced by drugs (sulpiride) or unknown factors. The present survey suggests that the incidence of prolactinoma in men in the general population might be estimated to be 1:1600, and that mass screening is useful for early diagnosis of asymptomatic prolactinoma.

Adult↗