PubMed Health⌕ Search

Biomedical subjects

R Forrest

Publications and source records attributed to R Forrest.

At least 19 recordsLinked to original sources
PubMed1999

Human germ cell tumor cell lines express novel leukemia inhibitory factor transcripts encoding differentially localized proteins.

The polyfunctional cytokine leukemia inhibitory factor (LIF) has been implicated in the maintenance of many stem and progenitor cell populations and as an autocrine growth factor for many tumor cell populations, including germ cell tumors. Studies of LIF transcript expression in germ cell tumor cell lines identified two novel human LIF transcripts, hLIF-M and hLIF-T, containing noncoding alternate first exons that are conserved among all reported LIF genes. Embryonal carcinoma (EC) cell lines expressed these transcripts at consistent levels and hLIF-M was generally the predominant LIF transcript in these cells. This expression pattern was characteristic of EC cells since variable independently regulated expression of these transcripts was evident in other cell lines. Overexpression analysis demonstrated that each alternate hLIF transcript generated different levels of extracellular LIF activity as a consequence of the translation of distinct but partially overlapping sets of proteins. Secreted LIF proteins translated from alternate initiation codons were expressed from the hLIF-D and hLIF-M transcripts. Intracellular, potentially cell-autonomous, proteins were encoded by the hLIF-M and hLIF-T transcripts. Since EC cell lines also expressed LIF receptor transcripts, the novel LIF transcription profiles and proteins identified here suggest a role for autocrine and/or cell-autonomous LIF signaling during germ cell tumorigenesis.

Alternative Splicing↗
PubMed1999

Complex conserved organization of the mammalian leukemia inhibitory factor gene: regulated expression of intracellular and extracellular cytokines.

Leukemia inhibitory factor (LIF) is a member of the IL-6 family of pleiotropic cytokines, which are extensively involved in modulating hematopoiesis and immunity. We have undertaken a detailed analysis of LIF genomic organization and gene transcription and investigated the proteins expressed from alternate transcripts. Previously unidentified LIF transcripts, containing alternate first exons spliced onto common second and third exons, were cloned from murine embryonic stem cells, human embryonal carcinoma cells, and primary porcine fibroblasts. Based on sequence homology and position within the genomic sequence, this confirmed the existence of the LIF-M transcript in species other than the mouse and identified a new class of transcript, designated LIF-T. Thus, a complex genomic organization of the LIF gene, conserved among eutherian mammals, results in the expression of three LIF transcripts (LIF-D, LIF-M, and LIF-T) differentially expressed from alternate promoters. The first exon of the LIF-T transcript contained no in-frame AUG, causing translation to initiate downstream of the secretory signal sequence at the first AUG in exon two, producing a truncated LIF protein that was localized within the cell. Enforced secretion of this protein demonstrated that it could act as a LIF receptor agonist. Regulated expression of biologically active intracellular and extracellular LIF cytokine could thus provide alternate mechanisms for the modulation of hematopoiesis and immune system function.

Alternative Splicing↗
PubMed1998

Potent antimitotic and cell growth inhibitory properties of substituted chalcones.

A series of substituted chalcones was synthesised and screened for cytotoxic activity against the K562 human leukaemia cell line. (E)-3-(3"-Hydroxy-4"-methoxyphenyl)-2-methyl-1-(3',4',5'- trimethoxyphenyl)-prop-2-en-1-one [IC50 (K562) 0.21 nM] was found to be the most active. A relationship between the conformation and cytotoxicity of the chalcones is discussed.

Antineoplastic Agents↗
PubMed1997

A proposal for minimum detectable compartment in MIRD dosimetry modelling.

The accuracy of radiation dose estimates from radiopharmaceutical administrations has recently become more important for three main reasons: (i) clinical providers are demanding more information on diagnostic procedures; (ii) regulatory groups are scrutinizing dosimetry for research subjects; and (iii) accurate organ doses are crucial in therapeutic administrations. These dose estimates are a sensitive function of the residence times. Because most clinical data acquisition protocols are limited to the first 24 h after dose administration, the area under the remainder of the time-activity curve (TAC) must be estimated. Estimation methods range from assuming physical decay only (overly conservative) to extrapolating end point physiological kinetics (overly liberal). This study demonstrates how much the results from these two methods vary and develops an alternative method which more accurately estimates this remainder term. A method, called the minimum detectable compartment (MDC), is constructed so that an accurate dose estimate can be made with a realistic measure of the remainder term. The method for determining MDC uses standard hypothesis testing. Using an analogue of the traditional minimal detectable activity calculation, a model with and without constant compartments is fitted to the TAC. The size of the constant compartment is varied until the relative likelihood of the two models meets the desired measure of power and sensitivity. Computer simulations of a simple mono-exponential are used to demonstrate the MDC as a function of the model, the number of data points, the range of the data and the noise in the data. The MDC is a very sensitive function of the data range. It falls by more than 50% when the data range is increased from two to three half-lives. In addition, the MDC is moderately sensitive to the noise in the data and relatively insensitive to the number of data points. These findings suggest that the MDC method can also be uses a priori to indicate what type of data collection regimen is necessary to achieve a certain accuracy.

Humans↗
PubMed1996

A portable survey meter method for locating and quantifying removable contamination after 131I therapies.

Identifying 131I surface contamination and decontaminating the removable fraction from rooms where patients have received iodine therapies is a common task at many hospitals. The current regulatory preferred method for this task is wipe testing for removable contamination. The purpose of this paper is to evaluate the suitability of a sensitive survey meter for this task. Both methods and their detection systems are evaluated in the laboratory as well as in a clinical environment. The results indicate that the portable survey meter method is better at both locating and quantifying removable contamination. An additional benefit of the survey meter method is the ability to clean rooms promptly for reoccupancy.

Humans↗
PubMed1986

Polyglycolic acid mesh in experimental renal trauma.

We investigated the efficacy of kidney wrapping with polyglycolic acid (PGA) mesh for control of hemorrhage and preservation of renal function following extensive potentially lethal kidney lacerations in the dog. Wrapping of lacerated kidneys resulted in reapposition of the renal parenchyma and prompt, sustained hemostasis. At 21 days following injury the renal lacerations were well healed. Among five dogs with lacerations involving the entire surface of one kidney, the mean of the ratios of the creatinine clearance of the affected kidney divided by the creatinine clearance of the uninjured contralateral kidney was 0.83 +/- 0.14. Among ten dogs with lacerations confined to the lower pole of one kidney, five were treated by mesh wrapping and five by partial nephrectomy. The mean of the ratios of the creatinine clearance of the affected kidney divided by the creatinine clearance of the uninjured contralateral kidney was 0.93 +/- 0.17 for the former group and 0.58 +/- 0.06 for the latter group. Perirenal infection following kidney wrapping developed in only one dog who had an E. coli bacteriuria at the time of injury. Blood pressure was monitored in eight dogs treated with mesh wrapping. None became hypertensive. These data suggest that PGA mesh may have clinical utility in the management of selected renal injuries in humans.

Animals↗