Biomedical subjects
M Cheng
Publications and source records attributed to M Cheng.
Effects of carbon monoxide on cardiac muscle cells in culture.
Embryonic rat cardiac muscle cells grown in the presence of various tensions of CO (5-95%) without the presence of O2 survived and exhibited reduced cell growth, which was concentration dependent. When cardiac muscle cells were grown in the presence of a mixture of CO (10-20%) and O2 (10-20%), the growth rate of these cells was comparable to that of the control cells. Cardiac myocytes continued to beat when exposed to varying tensions of CO, except in the case of 95% CO. The cells exposed to different concentrations of CO contained fewer myofibrils of different stages of differentiation compared with the control and the culture exposed to a mixture of 20% O2 and 20% CO, with cells that contained abundant, highly differentiated myofibrils. There was no significant difference in the structural organization of mitochondria between the control and the surviving experimental cells. It is evident from the present studies that O2 is required for the optimum in vitro cellular growth of cardiac muscle. Furthermore, CO in combination with O2 at a concentration of 10 or 20% can produce optimal growth of cardiac muscle cells in culture.
Methotrexate: assessment of in vivo clastogenicity and carcinogenicity.
The genotoxic and oncogenic potentials of methotrexate were studied in Sprague-Dawley rats. The rats received 0.1, 0.2, or 0.4 mg/kg of methotrexate as dietary admixtures on a 5 days on, 9 days off, regimen for 23 months. In the females of the high-dose group, there was a significant increase in mortality starting at 18 months. Significant increases in the number of rats with focal pulmonary interstitial fibrosis were seen in both sexes at the high-dose level. At the mid- and high-dose levels of both sexes, there was a significantly increased number of rats with myeloid and erythroid bone marrow hypoplasia. There was no evidence of either early onset or increased incidence of any tumor type in the treatment groups. Therefore, it is concluded that methotrexate does not have oncogenic potential. Also, at terminal sacrifice, bone marrow cells were harvested from selected animals on the last day of the 5-day dosing cycle and cytogenetic evaluation was performed. No significant increase in chromosomal aberrations was seen in any dose group relative to the control group. This observation further substantiates the absence of oncogenic potential due to methotrexate in rats.
[History of radix Phytolaccae processing].
Explore the source record for details and available documents.
Effect of total-body irradiation with bone marrow transplantation on toxicity of cisplatin.
In defined-flora, barrier-maintained rats (WAG/RijMCW males), radiation nephritis is the principal late toxicity seen after high-dose-rate, total-body irradiation (TBI) when hematologic toxicity is prevented by bone marrow transplantation. Pneumonitis develops only if rats are exposed to a conventional environment during and after bone marrow transplantation. Low-dose-rate TBI gives similar toxicity at doses twice as large. Rats surviving for 9 months after TBI show decreased tolerance for cisplatin. This decreased tolerance is related to dose and dose rate and is seen for radiation doses that show little or no renal toxicity. Evidence suggests that the decrease in renal tolerance is due to decreased renal platinum clearance in the irradiated kidneys.
Trace element status of children with PKU and normal children.
The trace mineral (chromium, copper, iron, selenium, and zinc) status of 10 children (4 to 13.8 years) with phenylketonuria (PKU) and 9 normal children (6.5 to 15.9 years) was assessed. The children with PKU were treated with a phenylalanine-free L-amino acid mix that supplied the following percentages (mean +/- standard deviation) of total daily intake: energy, 45 +/- 13; protein, 75 +/- 11; copper (Cu), 62 +/- 10; iron (Fe), 82 +/- 7; selenium (Se), 40 +/- 20; and zinc (Zn) 87 +/- 8. Diet records and blood samples were collected from each subject. Children with PKU had significantly greater mean intakes of Cu, Fe, and Zn than normal children. Mean serum Cu, Fe, and Zn concentrations of the children with PKU and normal children were not different despite significantly greater intakes by the children with PKU. Normal children had a significantly greater mean serum Se concentration and a mean blood chromium concentration 1.6 times that of children with PKU. Individuals whose primary source of protein is an elemental diet are especially at risk for multiple trace mineral deficiencies. Manufacturers of chemically defined medical foods should evaluate composition, specifically molar ratios between minerals, as a basis for product formulation.
Electron-diffraction study of free-standing liquid-crystal films.
Explore the source record for details and available documents.
Effects of extinction, pimozide, SCH 23390, and metoclopramide on food-rewarded operant responding of rats.
The similarity in the pattern of responding produced by extinction and dopamine (DA) receptor blockers has led to the suggestion that DA neurons may participate in the usual effects of reward on behaviour. The purpose of the present study was to evaluate the effect of receptor-subtype specific DA antagonists on food-rewarded operant responding. Rats were trained to lever press for food on a variable interval 30-s schedule. They then received one of the following treatments prior to testing on the next 5 days: saline, nonreinforcement, the DA receptor blocker pimozide (0.5 or 1.0 mg/kg), the D1 receptor blocker SCH 23390 (0.01, 0.05, 0.1 mg/kg), and the D2 receptor blocker metoclopramide (1.0, 5.0, 10.0 mg/kg). Nonreinforcement resulted in both intra- and intersession declines in responding. The drugs produced dose-dependent decreases in overall responding. Additionally, both doses of pimozide and the higher doses of SCH 23390 and metoclopramide altered intrasession patterns of responding when compared to saline, with their greatest effect being in the latter portion of the session. Intersession declines were seen with the highest doses of SCH 23390 and metoclopramide and control studies showed that these declines could not be attributed to a buildup of the drug with repeated dosing. It was concluded that both D1 and D2 receptors participate in the control of behaviour by reward.
Isolation, long-term culture, and ultrastructural characterization of adult cardiomyopathic cardiac muscle cells.
A long-term cell culture system for adult cardiomyopathic hamster cardiac muscle cells has been established. The diseased and control hearts were dissociated into single cell suspension with the modifications of our previous technique using collagenase and hyaluronidase as applied to the dissociation of the adult rat heart. The postperfusion of the diseased heart with Krebs-Ringer phosphate buffer and bovine serum albumin was very helpful in obtaining greater yield of viable diseased muscle cells; the cells were cultured for 4 wk. Approximately 60% of the myocytes from the diseased heart and 85% of the myocytes from the normal heart attached to the substrates and survived throughout the culture period. Approximately 60 to 70% of the cardiac myocytes from the diseased and control hearts were bi- or multinucleated; 30% of the diseased and 80% of the normal myocytes showed rhythmic contractility. Electron microscopy revealed the presence of two kinds of cardiac muscle cells in the diseased cell culture on the basis of their myofibril content: one with scanty myofibrils and another with abundant myofibrils. Myocytes with sparse myofibrils showed certain characteristic features that included autophagic vacuoles, amorphous matrix of fine filamentous texture, scattered strips of myofibrils, and abnormal organization of the Z-line. Cardiac muscle cells with abundant myofibrillar content contained unorganized myofibrils in certain sarcomeres. These studies demonstrate the feasibility of maintaining diseased cardiac muscle cells from adult cardiomyopathic hamsters for at least 4 wk in monolayer culture.
The clinical utility and evaluation of drug screening techniques.
A better understanding of the methods of drug detection, their sensitivities, and limitations increases the efficiency of medical decision making for better patient care. Many of the sociomedical and medicolegal questions are yet to be answered through court challenge. The physician must remember his or her role as a clinician, and practice the art in a fashion that best serves the interest of his or her teenage patient.
[Clinical application of carcinoembryonic antigen (CEA) monoclonal antibodies (McAbs)].
CEA McAbs, recognizing three different epitopes on CEA molecules, were used to measure serum CEA level in cancer patients by enzyme-immunoassay (EIA). The results, as compared with those using polyclonal antibodies, indicated that the positive rate was higher while the false positivity was lower. Immunohistochemistry of tumour sections showed that the CEA McAbs are bonded to 80-90% of gastrointestinal cancers. Although the normal colon epithelium occasionally reacted with CEA McAbs, other normal tissues did not. After in vivo administration of radio-labeled CEA McAbs to nude mice xenograft with human colon cancer, the radio-isotope was found to be concentrated preferentially in the tumour. The ratio of tumour and normal tissue was 3.6-11.8 after 48 hours following administration. Thus, the CEA McAbs can be used clinically not only for serum CEA determination but also for diagnostic imaging.
A clinical study of treating Hashimoto's thyroiditis by moxibustion.
Explore the source record for details and available documents.
Biochemical evidence for cellular dedifferentiation in adult rat cardiac muscle cells in culture: expression of myosin isozymes.
Myosin isozyme pattern in adult rat cardiac ventricular muscle cells in long-term culture was investigated. The myosin isozymes profile of cultured cardiac myocytes underwent a change in a serum-containing medium from two weeks onward, showing an embryonic rat ventricular myosin isozymes pattern that contained predominant isozyme V3. When adult cardiac myocytes were grown in a serum-containing medium supplemented with T4, these cells contained a predominant V1 band whose electrophoretic mobility and Ca2+-ATPase activity were comparable to those of the adult rat ventricle in vivo. This study has demonstrated that the adult cardiac ventricular muscle cells in long-term culture contain a predominant myosin isozyme V3 unlike their counterparts in vivo. Supplemented T4 modulated the embryonic type isozyme V3 to the adult type V1.
DNA synthesis of adult mammalian cardiac muscle cells in long-term culture.
Adult rat cardiac ventricular muscle cells were isolated and cultured in monolayer for 30-45 days. Most of the cardiac muscle cells undergo external and internal structural alterations, resembling embryonic/neonatal cardiac muscle cells in culture (Nag and Cheng, 1981; Nag et al., 1983). These cultured cells underwent DNA synthesis and mitosis as revealed by autoradiography studies that involved the exposure of the cells to [3H]-thymidine for 24 hr prior to the termination of the culture at selected intervals. During the first week of culture, cardiac muscle cells showed less than 5% labeled cells. The labeling index of myocytes attained a peak in the second week of culture, exhibiting approximately 23% labeled cells. The labeling indices of cardiac muscle cells declined over the period of 30 days of culture. During the end of the incubation period, approximately 4% of the myocytes were labeled. When the extent of the total cell population involved in DNA synthesis was examined by exposing the cells to [3H]-thymidine continuously for long periods of time, it was observed that approximately 26% of the cardiac muscle cells regained the capacity for DNA synthesis during 1-10 days of culture. From day 1 to day 14, approximately 29% of the total muscle cell population was labeled. When the cells were exposed to the radioactive isotope continuously for 30 days, approximately 31% of the cells incorporated radioactive isotope, showing their capacity for DNA synthesis. Approximately 90% of the cardiac muscle cells in long-term culture contained more than one nucleus. The nuclei were often observed in multiples of two. Labeled mitotic apparatus was observed in cardiac myocytes, indicating the replication of DNA, followed by karyokinesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal irradiation and the pharmacology and toxicity of methotrexate and cisplatinum.
We used a rat model to study the effects of renal irradiation on the pharmacology of methotrexate (MTX) and cisplatinum (cis-Pt). Unanesthetized rats were given bilateral kidney irradiation (20 Gy in 9 fractions). At 9 months after irradiation, 3% of the animals had died and survivors showed moderately impaired renal function. At 15 months, 30% of the animals had died and survivors showed severely impaired renal function. Some animals were given i.v. MTX 1 week to 15 months after irradiation. In irradiated rats, the area under the MTX plasma clearance curve equaled that of controls through 6 months, and was significantly above controls from 9 months on. Other animals were given i.p. cis-Pt 1 week to 9 months after irradiation. The acute toxicity of cis-Pt was the same in control and irradiated rats when cis-Pt was given immediately before or after irradiation. Beginning 3 months after irradiation there was a progressive increase in cis-Pt toxicity and a simultaneous decrease in urinary platinum excretion. Irradiated animals that survived cis-Pt treatment showed increased radiation nephritis; the greatest effect occurred when cis-Pt was given 3 months or more after irradiation. MTX and cis-Pt clearance decreased when renal dysfunction was first observed and changes in renal function preceded changes in drug clearance and toxicity.
Distributions of vimentin and desmin filaments in embryonic cardiac muscle cells in culture.
Immunofluorescence studies on the distributions of vimentin and desmin in embryonic rat cardiac muscle cells in culture were carried out, using antibodies against vimentin and desmin. The cell culture was continued for 5 days. Both vimentin and desmin increased in concentration as the cardiac myocytes matured in culture. Vimentin and desmin were mainly organized as filamentous structures and oriented in longitudinal and other directions within the cytoplasm of the cells. Cross-striated fluorescence of vimentin and desmin was rarely observed in cardiac myocytes, although cross-striated myofibrils were present during early and late periods of culture. Desmin did not show preferential adherence to the Z-line of the cultured myocytes. Vimentin was observed on the nuclei of cardiac myocytes in the form of complex network and beaded structures during culture period. Both vimentin and desmin were present in fibroblastic cells in culture. Our observations suggest that vimentin and desmin in cardiac myocytes in culture probably provide a skeletal framework, which facilitates the assembly of myofibrils. Also, these intermediate filaments are probably involved in the organization of cellular organelles in the cell cytoplasm. The role of the intermediate filaments found on the nucleus and its periphery is probably to maintain the position of the nucleus in the cytoplasm of the cell, providing an adherence between the nucleus and adjacent cytoplasmic sites.
Genetic toxicology evaluation of the novel semi-synthetic antibiotic piperacillin.
Piperacillin (T-1220, Pipracil) a semi-synthetic antibiotic was evaluated in a battery of genetic toxicology assays. The assays employed were: the microbial assay, the host mediated assay, the microbial assay incorporating urine samples from mice dosed with piperacillin, the in vivo cytogenetic assay, and the dominant lethal assay. In all assays, piperacillin produced consistent negative results indicating that piperacillin does not have mutagenic potential.
Effects of growth factors on the ultrastructure of cardiac muscle cells in culture.
Explore the source record for details and available documents.