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Biomedical subjects

K M Robinson

Publications and source records attributed to K M Robinson.

At least 73 records · Page 4Linked to original sources

Ultrastructural features of carcinomas induced in nude mice by the inoculation of human oesophageal carcinoma cell lines.

Thirty tumours induced in athymic mice by the inoculation of cells of human oesophageal carcinoma lines were examined by light and transmission electron microscopy, as were 24 cell strains derived from the mouse tumours. All tumours were carcinomas and displayed varying numbers of desmosomes and tonofilaments. Cytoplasmic organelles resembled those in human oesophageal carcinomas in vivo and marker structures such as intranuclear particles persisted in cells grown in nude mice and in vitro. As the nude mouse carcinomas displayed similarities both to one another and to human carcinomas in situ, the nude mouse xenograft system may become a useful model for further studies on tumour biology.

Animals↗

Tumorigenicity and other properties of cells from ten continuous human esophageal carcinoma cell lines in nude mice.

A total of 239 6-week-old nude mice of BALB/c origin were inoculated sc with human esophageal carcinoma cells of lines Hcu 10, Hcu 18, Hcu 37, and B5 (derived from poorly differentiated tumors), of lines Hcu 39, Hcu 57, and B17 (derived from moderately differentiated tumors), and of lines Hcu 13, Hcu 33, and Hcu 35 (derived from well-differentiated tumors), as well as with esophageal carcinoma lines 13.M1, 13.M5, 13.M7, 13M9, and 13.M1.M11 passaged through the mouse. Tumor take rates varied from 5 to 90% with an overall take rate of 21.9% (56 tumors). Latent periods ranged from 4 weeks to 9 months, and cells of each line gave rise to tumors of varying histologic differentiation. Cells of the poorly differentiated and well-differentiated lines gave rise to 23 infiltrating tumors, with metastasis being observed in a single mouse. All other tumors (33) were encapsulated and mobile. Thirty mice were observed for 6 months following removal of the primary tumor, and a single instance of recurrent carcinoma was noted. Cells from the nude mouse tumor xenografts adapted well to in vitro conditions and developed into continuous lines. The investigations confirmed the tumorigenic potential of 10 human esophageal carcinoma cell lines and provided information about properties of esophageal carcinoma cells in vivo and in vitro.

Animals↗

Surface features of three human cell lines established from diagnostic biopsies of esophageal carcinomas.

Cells from three human esophageal carcinoma cell lines recently established from diagnostic biopsy specimens were examined by scanning electron microscopy using a standardised technique. Each line was morphologically distinct, but displayed some features common to the other lines. Line B17, derived from a tumor classified histopathologically as being a moderately to well differentiated squamous carcinoma was characterised by cells of fairly uniform size and appearance with numerous well developed intercellular processes and abundant microvilli. Cell contacts were multiple and complex. Line B5, derived from a poorly differentiated tumor, comprised pleomorphic cells with fewer surface projections. Microvilli were most abundant in elevated nuclear regions and lateral processes were short and not as complex as those between B17 cells. Cells of line B29, derived from a squamous carcinoma classified histologically as moderately differentiated, typically displayed few surface projections though peripheral cytoplasmic ridges were frequently present.

Adult↗

Some effects of gamma-linolenic acid on cultured human oesophageal carcinoma cells.

Cells of two continuous human oesophageal carcinoma lines were treated by the addition of gamma-linolenic acid (GLA) at concentrations of 10-60 micrograms/ml culture medium. After 7 days of exposure to GLA, pronounced morphological changes became evident and culminated in cell death. GLA-mediated effects were time- and dose-dependent and varied slightly with the degree of histological differentiation of the lines tested. These findings may have clinical implications.

Antineoplastic Agents↗

Inhibition of mitogen-induced lymphocyte proliferation by autologous serum in oesophageal carcinoma.

The reactivity of lymphocytes from patients with oesophageal carcinoma in response to mitogenic stimulation with phytohaemagglutinin was assessed in four culture systems in an attempt to demonstrate an inhibitory effect of cancer serum on lymphocyte transformation. The metaphase index (number of cells at metaphase/1000 live cells) was used to determine lymphocyte reactivity of patients and controls in the presence of: (a) autologous plasma; (b) pooled AB serum; (c) pooled plasma from patients with oesophageal cancer, and (d) fetal calf serum. The division of lymphocytes from cancer patients was significantly depressed in the presence of autologous plasma (p<0,001) when compared with division of lymphocytes of control subjects. No significant difference was evident in pooled AB serum, homologous cancer plasma or fetal calf serum. The depressed lymphocyte reactivity in cancer patients appears to be related to a serum inhibitory factor.

Cells, Cultured↗

Transmission electron microscopy of human oesophageal carcinomas.

Twelve human oesophageal carcinoma samples were examined by both light and electron microscopy in order to characterise the ultrastructural features of this neoplasm. Those samples from well differentiated tumours contained abundant tonofilaments, mainly in a paranuclear position, while cells from poorly differentiated tumours displayed few such filaments but had more prominent cytoplasmic organelles. Desmosomes were well developed in all samples, some of which displayed numerous clearly defined intracellular desmosomes not necessarily associated with cell membrane material. Myelinoid figures were abundant and the bizarre forms which were present in some samples may be related either to abnormal metabolism or to viral activity. Glycogen, lipid droplets and intermediate filaments, possibly related to basement membrane material were observed in several samples. No single feature diagnostic for carcinoma of the oesophagus emerged from this study, but several structural similarities between oesophageal and other carcinomas were noted.

Cell Nucleus↗

Free fatty acid turnover and oxidation after burn shock in guinea pigs.

We have previously shown a rapid decrease in plasma free fatty acid (FFA) concentration and turnover rate immediately after extensive full-skin-thickness burn in a guinea pig model. In the present study the relationship between plasma FFA turnover rate and oxidation after burn was investigated, since the amount of plasma FFA oxidized is determined by the turnover rate and the percent of turnover that is oxidized. Using the constant infusion of 14C-palmitate, we examined the plasma FFA concentration and turnover rate, plasma FFA contribution to carbon dioxide production, percent of plasma FFA turnover that is rapidly oxidized to carbon dioxide, oxygen consumption, carbon dioxide production, and respiratory quotient. We found that in some cases, but not all, plasma FFA concentration and turnover rate were decreased 1-6 hours postburn. Both in the presence or absence of decreased FFA turnover rate, the percent of FFA turnover that was immediately oxidized to carbon dioxide was unchanged. After burn shock, the rate of oxidation of FFA appears to be controlled by the rate of FFA delivery to the tissues.

Adipose Tissue↗

Free fatty acid kinetics after burn shock in guinea pigs.

Extensive full-skin-thickness burn results in a change in the flux and utilization of the major metabolic fuels. Considerable work has been done on glucose metabolism after severe burn, but much less is known about free fatty acid (FFA) metabolism. Therefore, we studied the rate of appearance (Ra), the rate of disappearance (Rd), the metabolic clearance rate (MCR), and the plasma FFA concentration 0--6 hours after a 50% body surface area full-skin-thickness burn using a constant infusion of 14C-palmitate. We found that the plasma FFA concentration decreased from a control value of 0.60 +/- 0.05 microns/ml to 0.26 +/- 0.04 microns/ml of plasma at 2 hours postburn (P less than 0.05). This change appears to be due to a greater decrease in Ra than Rd. The MCR was unchanged during this period (26.7 ml/kg . min). In a second series of experiments, the plasma FFA concentration, Ra and Rd at 5.5--6 hours postburn did not differ from the preburn values. The rapid decline of plasma FFA 0--30 minutes postburn may relate to decreased blood flow to adipose tissue, which in the same guinea pig model had decreased about 80% at 15 minutes postburn, or to a shift toward esterification in the fat depots, decreasing FFA mobilization.

Animals↗

Contribution of altered lipolysis and reesterification in perturbations of free fatty acid kinetics during burn shock.

We have previously shown that free fatty acid (FFA) mobilization is severely decreased during burn shock in the guinea pig. Glycerol mobilization was also decreased, indicating that decreased lipolysis was a major contributing factor to the impairment of FFA mobilization. In order to assess the contribution, if any, of increased FFA reesterification to the perturbations of FFA kinetics, we used the constant infusion technique, simultaneously infusing 14C-palmitate and 3H-glycerol. By this method we measured the rate of triglyceride hydrolysis (glycerol turnover) and the mobilization of FFA from adipose tissue (palmitate turnover). It was found that FFA turnover was decreased by 65% (39.4 +/- 4.1 to 16.7 +/- 1.4 mumole/kg . min, P less than 0.001), and glycerol turnover was decreased by 48% (23.6 +/- 2.5 to 12.3 +/- 1.1 mumole/kg . min, P less than 0.001) at 2 hr postburn. The FFA:glycerol ratio decreased from 1.87 +/- 0.20 to 1.43 +/- 0.15 (P less than 0.02), suggesting that increased FFA reesterification contributed to the decrease of FFA mobilization from adipose tissue during burn shock.

Animals↗

Surface features of normal and neoplastic human esophageal cells in vivo and in vitro.

Normal and neoplastic human esophageal cells were studied in vivo and in vitro by scanning electron microscopy in an attempt to elucidate surface differences between them as the cell surface may play an important role in the malignant process. Superficial biopsy specimens of normal and malignant esophageal mucosa were examined and compared. Polygonal normal esophageal surface cells were covered by a complex arrangement of microridges and bordered by well developed intercellular ridges. Malignant esophageal cells were more rounded, possessed reduced numbers of microridges and cell borders were indistinct. Cultured cells growing from explants of normal and malignant esophageal mucosa were studied. Normal esophageal cells in vitro were tightly adherent, flattened, lacked microridges and displayed few surface projections. Cultured malignant cells were not as tightly adherent and possessed abundant surface projections such as microvilli and lateral processes. Thus, distinct surface differences were recognised between normal and malignant esophageal mucosal cells both in vivo and in vitro.

Cell Division↗

Growth patterns, ultrastructure, and chromosomal constitution of normal kidney and nephroblastoma cells in short-term culture.

Nephrectomies were performed on four children with nephroblastomas (Wilms' tumor). Tumor tissue and normal kidney tissue were taken from each patient and were cultured. The in vitro characteristics of the cultured cells were then compared with their known in vivo characteristics. The normal kidney cells showed uniform cell morphology, had a relatively slow and orderly growth pattern and had the usual diploid chromosomal constitution. The tumor cells on the other hand were irregular in morphology and had a rapid and disorderly growth pattern. Electron microscopic examination confirmed the variation in the tumor cell morphology. In addition, microfilaments were seen to be abnormally abundant in many of the cells and some cells contained membrane-bound granules. Desmosomes were absent. Chromosome analyses showed cells from three of the nephroblastoma samples to maintain a constant hyperdiploid karyotype during the first few passages in vitro, whereas the normal kidney cells continued to have the normal diploid karyotype. Our study suggests that nephroblastoma and normal kidney cells are stable in culture, that is they retain most of their cellular characteristics in vitro and do not undergo rapid dedifferentitation in short-term culture.

Cell Division↗

Liver protein synthesis and catabolism in mirex-pretreated rats with enlarging livers.

Incorporation and retention of [14C]amino acids in protein were studied in rats with enlarging livers. Rats were injected (i.v.) with 20 mg of mirex per kg b. wt. to stimulate liver enlargement with a concomitant and proportional increase in liver total protein. Eighteen hours later, mirex-pretreated and control rats received an i.p. dose of a L-[14C]amino acid mixture and were killed at predetermination intervals up to 48 hr. Mirex-pretreated rats incorporated [14C]amino acids into liver protein at the same rate as controls, but retained more of the radiolabeled amino acids in liver protein for a longer time. In a second experiment, (14C]bicarbonate was substituted for the amino acid mixture to determine whether differences in [14C]amino acid retention were due to reutilization or mobilization. The change in protein metabolism, which leads to an almost 2-fold increase in liver total protein within 66 hr, appears to be due to a decrease in the quantity of protein catabolized per unit time rather than an increase in the rate of protein synthesized.

Animals↗