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Biomedical subjects

D Shen

Publications and source records attributed to D Shen.

140 records · Page 8Linked to original sources
PubMed1980

Establishment of three human liver carcinoma cell lines and some of their biological characteristics in vitro.

Three cell lines derived from liver carcinoma specimens of two male and one female operated patients have been successfully established in vitro and designated by the names of BEL-7402, BEL-7404 and BEL-7405. In the course of the establishment (from the 2nd transfer onwards) studies were made to characterize them. The doubling time of cell population was found to be 20--26 hr. They formed tumor nodules upon heterologous transplantation. They appeared as epithelial-like cells in morphology and showed, in addition to desmosomes, the presence of cytoplasmic tonofibrills which were typical of epithelial cells by electron microscopy. The ultrastructural features were different from normal human liver cells, but similar to clinical hepatoma cells. They had hypotriploid chromosone number with one abnormally long acrocentric chromosome present in all 3 cell lines and additional small acrocentric chromosome and chromosome fragment in BEL-7405 line of cells. AFP were detected intracellularly by the indirect immunofluorescent method. LDH isoenzyme showed a pattern different from that of human adult liver, but similar to those of embryonic liver and clinical hepatoma with the increase of the percentage of LDH-1 (H-type) at the expanse of LDH-5 (M-type), i.e. with a higher H/M ratio. The results suggest the 3 lines of liver carcinoma cells as rapidly growing and not well differentiated epithelial-like malignant cells.

Aged↗
PubMed1978

A microcomputer based portable hemodialysis system.

A microprocessor controlled portable hemodialysis system (The Suitcase Kidney) has been designed and 18 dialyses have been successfully completed. The microprocessor is shown to be an improvement and simplification over the conventional discrete control mechanisms presently used to monitor and control system functions. The microprocessor is shown to reduce development time, complexity and size of the system while improving patient safety. A description of the system is presented emphasizing the functioning of the microcomputer.

Computers↗
PubMed1976

Time-dependent change in renal clearance of bethanidine in humans.

Blood levels and urinary excretion rates of bethanidine were determined in three normal human subjects following oral administration of a single dose of the drug. The postabsorptive decline of blood concentration with time was noticeably slower than the corresponding decline in the urinary excretion rate. The discrepancy can be attributed to a continual decrease in the renal clearance of bethanidine throughout the study. Therefore, pharmacokinetic modeling of urinary excretion data alone would lead to erroneous conclusions concerning the persistence of drug in the blood.

Bethanidine↗
PubMed1975

Pharmacokinetics of bethanidine in hypertensive patients.

The pharmacolinetics of bethanidine-14C was studied in three hypertensive patients. A 25-MG DOSE OF BETHANIDINE-14 C hemisulfate was administered intravenously. Plasma levels of drug were measured over the first 6 hr. In 3 to 4 days, 89% to 94% of the dose was excreted in the urine. Thin-layer chromatography (TLC) and isotope dilution analysis of the urine samples indicated that only intact bethanidine was excreted. Plasma level and urinary excretion rate profiles had miltiphasic characteristics. Estimated half-lives of the terminal phase ranged from 7 to 11 hr. Average renal clearance over the initial 6 hr approached renal plasma flow. In 2 of the patients, renal clearance between 2 and 4 hr after administration was reduced to one-helf that observed during the initial 2-hr period. After single oral administration of a 25-mg dose of bethanidine-14C hemisulfate, 48% of 61% was excreted in urine and 15% to 48% in feces. Peak urinary excretion rates were reached 6 hr following administration. The urinary excretion kinetics of bethanidine during and after repetive oral dosing was also studied. A 25-mg dose was dividied into 12 to 16 equal doses and administered avery 6 hr. A larger fraction of the cumulative dose was recovered in the urine (72% to 74%) than after the single dose, suggesting higher availability at the lower dose. Steady-state urinary excretion rates were achieved in 4 to 7 doses. The steady-state urinary excretion levels were consistent with pharmacolinetic predictions based on single oral dose data. When 2 of the patients were given imipramine for 2 days prior to an oral 25-mg dose of bethanidine-14C hemisulfate, the terminal half-lives of the urinary excretion rate profiles were shorter than those in the same patients not given imipramine.

Administration, Oral↗
PubMed1975

Pharmacodynamics of minoxidil as a guide for individualizing dosage regimens in hypertension.

The antihypertensive effect of minoxidil was studied in 6 patients with varying degrees of hypertension. Their baseline mean arterial pressure (MAP bi) ranged from 122 to 197 mm Hg. Single oral doses between 2.5 and 25 mg were administered in sequence and the time-course of hypotensive action was followed. We have reported previously that when the peak lowering of MAP is linearly regressed against log dose, both the dose-response slope (M) and threshold dose (Dt) are positively correlated with the MAP bi of individual patients. This investigation focuses on the temporal pattern of effect. It was found that the hypotensive effect of minoxidil declined linearly with time at a rate consistent with an average effective biologic half-life of about one day. The rate of decline of effect was apparently independent of dose but was dependent on MAP bi. Since both response to and duration of effect of minoxidil are functions of MAP bi, there is an abvious need to individualize dosage regimens based on the severity of disease. Using pharmacodynamic parameters, guidelines for loading dose, maintenance dose, and dosing frequency as a function of the degree of hypertension are suggested. Loading dose requirements were found to increase with MAP bi while maintenance doses were largely independent of the severity of the disease. Frequently of dosing was found to range from 3 times a day in very severe hypertension to once a day in moderate hypertension.

Administration, Oral↗
PubMed1975

Predictability of blood levels of gentamicin in man.

Data from 42 patients were analyzed to determine the predictability of the peak serum level and the t1/2 of gentamicin on the bases of age, sex, body weight, serum concentration of creatinine, and blood hematocrit. Renal function was normal in 21 patients and impaired in 21. The most striking finding was the relatively poor predictability of t1/2 of gentamicin from serum concentration of creatinine. The overall correlation coefficient was 0.749 (P less than 0.001) in contrast to values of greater than 0.9 reported by others. tthere was a significant correlation of the t1/2 of gentamicin with the reciprocal of hematocrit (r * 0.647, P less than 0.001). Linear regression equations taking account of sex, serum creatinine concentration, and reciprocal of hematocrit provided a somewhat higher correlation coefficient (0.821) with the t1/2 of gentamicin than did the equation including serum creatinine concentration alone but were still not fully satisfactory. Thus the pharmacokinetics of gentamicin may not be adequately predictable from standardized equations or nomograms.

Adolescent↗
PubMedDate not supplied

Missense alterations of BRCA1 gene detected in diverse cancer patients.

The mutations in the breast cancer susceptible gene BRCA1 are responsible for about 50% of inherited breast cancers and confer increased risk of breast and ovarian cancer to its carriers. BRCA1 gene mutations may also be related with other types of cancers such as prostate cancer and colorectal cancer. The goal of this study was to investigate if BRCA1 mutation could be detected in diverse types of cancers. We used PCR-NIRCA and PCR-SSCP methods for screening the BRCA1 mutation hot regions, exons 2, 5, 11, 16 and 20. The positive samples were sequenced to confirm the nature of the mutations. We have identified a rare sequence variant, A3537G (Ser 1140Gly) in a B cell lymphoma patient and two polymorphisms, A1186G (Gln356Arg) in a brain cancer patient and A3667G (Lys1183Arg) in a germline tumor patient. In conclusion, 3 missense alterations of BRCA1 gene have been identified in cancers other than breast cancer.

Adult↗
PubMedDate not supplied

Effect of selenium in combination with Adriamycin or Taxol on several different cancer cells.

The anti-neoplastic properties of an Selenium compound were studied in vitro on several tumor cell lines: Breast (MCF-7, MCF-10, SKBR-3, BCAP37), Lung (RH2), Prostate (LNCap and PC-3), Colon (T84, Caco-2), Small Intestine (HCF8), and Liver (HepG2). We also examined additive or synergistic effect of Selenium in combination with standard anti-cancer drugs, Adriamycin (Doxorubicin) and Taxol. The effect of Selenium was assessed by apoptosis; DNA synthesis; growth rate by MTT assay; uptake of amino acid MeAIB by System A; and morphological changes. Our results demonstrate that MCF-7 and SKBR-3 showed increase in apoptosis as measured by DNA fragmentation and increase in "rounded" cells and membrane "blebbing", decrease in MeAIB uptake, and decrease in DNA synthesis. These changes were Selenium dose dependent with optimal inhibition at Selenium concentration between 4 and 40 ng/ml after 72 hrs of treatment. Similar observations were made with RH2, HCF8, Caco-2, and HepG2 cells. In contrast, LNCap, PC-3, and T-84 were not significantly affected by Selenium. However, addition of Adriamycin or Taxol in combination with Selenium caused small but significant inhibition of prostate cancer cells LNCap and PC-3. Addition of chemotherapeutic agents either Taxol or Doxorubicin with Selenium caused further inhibition of MCF-7, SKBR-3, RH2, HCF8, and HepG2 cells. In conclusion, Selenium has a significant anti-neoplastic effect on breast, lung, liver, and small intestinal tumor cells. Supplementation of Selenium enhanced chemotherapeutic effect of Taxol and Doxorubicin in these cells beyond that seen with the chemotherapeutic drugs used alone. These in vitro studies on several cancer cell lines suggest a potential benefit of Selenium-enhancement of anticancer effects other systems, and therefore offer further relevance to clinical trials efforts.

Amino Acids↗