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R Cox

Publications and source records attributed to R Cox.

At least 127 records · Page 7Linked to original sources
PubMed1991

Murine radiation myeloid leukaemogenesis: a possible role for radiation-sensitive sites on chromosome 2.

There is a paucity of informative data on the potentially important role of specific sites of chromosomal instability in oncogenic processes. Chromosome 2 deletions and rearrangements are known to characterise radiation-induced acute myeloid leukaemia in the mouse. Here we statistically establish a concordance between chromosome 2 breakpoint clusters in these leukaemias and chromosome 2 rearrangements carried at a high in vivo frequency by progeny of irradiated haemopoietic cells. Mechanisms of radiation myeloid leukaemogenesis are discussed with respect to multiple radiation-sensitive sites encoded on chromosome 2 and the possible influence of genomic imprinting on inductive processes.

Alpha Particles↗
PubMed1991

DNA methylation changes in the IL-1 (2F) chromosomal region of some radiation-induced acute myeloid leukaemias carrying chromosome 2 rearrangements.

Acute myeloid leukaemias (AML) arising in irradiated CBA/H mice frequently have breakpoints in the F region of chromosome 2. The closely linked cytokine genes interleukin (IL)-1 alpha and beta map to this region, and the beta gene is deregulated in some AMLs. Using pulsed-field gel electrophoresis techniques, we show here that an 800 kb 2F region encoding IL-1 alpha and beta is not obviously rearranged in six leukaemias carrying chromosome 2 abnormalities. However, changes in IL-1 region DNA methylation in three leukaemias may be consistent with loss of hypermethylated sequences from one chromosome copy. These possible 2F region losses are discussed in relation to genomic imprinting and its potential role in murine myeloid leukaemogenesis.

Acute Disease↗
PubMed1990

The IL-1 alpha and beta genes are closely linked (less than 70 kb) on mouse chromosome 2.

The murine IL-1 alpha and IL-1 beta genes encode structurally and evolutionarily related cytokines that exert a regulatory role in numerous physiological processes including hemopoiesis. Previous studies have shown these genes to be closely linked in the F region of mouse chromosome 2. Here we show, using pulsed-field gel electrophoresis, that the IL-1 alpha and beta genes of the CBA/H mouse are very closely linked and contained within a SmaI genomic fragment of approximately 70 kb. From conventional and PFGE analyses we suggest that IL-1 beta lies 5' to IL-1 alpha and that the two genes are in the same orientation and separated by approximately 50 kb. The apparent clustering of such hemopoietic genes is discussed in relation to evolutionary tandem gene duplication and possible associations with chromosomal fragile sites and leukemogenesis.

Animals↗
PubMed1990

The molecular biology of radiation-induced carcinogenesis: thymic lymphoma, myeloid leukaemia and osteosarcoma.

In mice, external X- or gamma-irradiation may induce thymic lymphomas or myeloid leukaemias, while bone-seeking alpha-emitters may induce osteosarcomas and, to a lesser extent, acute myeloid leukaemia. The present paper aims to review briefly some of the experimental data with respect to the molecular mechanisms underlying these radiation-induced carcinogenic processes. Thymic lymphomagenesis proceeds through an indirect mechanism. Recombinant proviruses often occur in the tumour cell DNA, favouring the idea that they might be involved. However, there are indications that they might mediate tumour growth rather than induction. It is plausible that activation of ras oncogenes by somatic point mutations might play a role in the carcinogenic process, although at a yet undetermined stage. Myeloid leukaemogenesis is characterized by a very early, putative initiating event, consisting of non-random rearrangements and/or deletions of chromosome 2. These may be related to deletions in the developmentally important homeobox gene clusters and to rearrangements of the sequences flanking the IL-1 beta gene. Either a gene of the homeobox family or IL-1 beta might be considered as potentially involved in the induction process. Osteosarcomagenesis in mice is often associated with the expression of proviruses, and the tumours often contain somatically acquired proviruses. These viruses may contribute to tumour development by affecting various growth-suppressor genes. Viruses isolated from bone tumours, although non-sarcomagenic, induce osteopetrosis, osteomas and lymphomas upon infection of newborn mice. Osteogenic tumours frequently display amplification of a region on mouse chromosome 15, which encompasses c-myc and Mlvi-1 sequences. Enhanced transcription of various oncogenes is found in individual tumours, but no specificity for osteosarcomas has been identified. In vitro systems of skeletoblast differentiation are being developed to study tumour induction in vitro.

Animals↗
PubMed1990

The expression of myosin genes in developing skeletal muscle in the mouse embryo.

Using in situ hybridization, we have investigated the temporal sequence of myosin gene expression in the developing skeletal muscle masses of mouse embryos. The probes used were isoform-specific, 35S-labeled antisense cRNAs to the known sarcomeric myosin heavy chain and myosin alkali light chain gene transcripts. Results showed that both cardiac and skeletal myosin heavy chain and myosin light chain mRNAs were first detected between 9 and 10 d post coitum (p.c.) in the myotomes of the most rostral somites. Myosin transcripts appeared in more caudal somites at later stages in a developmental gradient. The earliest myosin heavy chain transcripts detected code for the embryonic skeletal (MHCemb) and beta-cardiac (MHC beta) isoforms. Perinatal myosin heavy chain (MHCpn) transcripts begin to accumulate at 10.5 d p.c., which is much earlier than previously reported. At this stage, MHCemb is the major MHC transcript. By 12.5 d p.c., MHCpn and MHCemb mRNAs are present to an equal extent, and by 15.5 d p.c. the MHCpn transcript is the major MHC mRNA detected. Cardiac MHC beta transcripts are always present as a minor component. In contrast, the cardiac MLC1A mRNA is initially more abundant than that encoding the skeletal MLC1F isoform. By 12.5 d p.c. the two MLC mRNAs are present at similar levels, and by 15.5 d p.c., MLC1F is the predominant MLC transcript detected. Transcripts for the ventricular/slow (MLC1V) and another fast skeletal myosin light chain (MLC3F) are not detected in skeletal muscle before 15 d p.c., which marks the beginning of the fetal stage of muscle development. This is the first stage at which we can detect differences in expression of myosin genes between developing muscle fibers. We conclude that, during the development of the myotome and body wall muscles, different myosin genes follow independent patterns of activation and accumulation. The data presented are the first detailed study of myosin gene expression at these early stages of skeletal muscle development.

Animals↗
PubMed1990

2-Aminobenzamide, an inhibitor of ADP-ribosylation, antagonizes induced DNA hypomethylation during differentiation of murine Friend erythroleukemia cells by N'-methylnicotinamide.

The ADP-ribose synthesis inhibitor 2-aminobenzamide was found to reduce the induction of haemoglobin synthesis in murine Friend erythroleukemia cells, cultured continuously for 96 h with 5 mM N'-methylnicotinamide, with over 50% inhibition at equimolar doses. 2-Aminobenzamide was optimally effective as an inhibitor of differentiation if present only during the time period 24-48 h after initial N'-methylnicotinamide exposure. A transient, genome-wide DNA hypomethylation accompanies induction by N'-methylnicotinamide. Although 2-aminobenzamide does not seem to affect normal DNA methylation in cultured cells, the observed DNA hypomethylation in cells cultured for 24 h with 5 mM N'-methylnicotinamide was antagonized over 50% by equimolar 2-aminobenzamide. We suggest that ADP-ribosylation has a positive modulatory role in erythroid differentiation, and possibly in the process(es) leading to DNA hypomethylation following inducer exposure.

Adenosine Diphosphate Ribose↗
PubMed1990

Assessment of the poorly contractile or acontractile bladder in the older male in the absence of neuropathy.

Up to 30% of patients who undergo prostatectomy are left with residual symptoms. Most have persistent detrusor instability, but some have poorly contractile or acontractile bladders. Over a 2-year period, 42 neurologically normal patients were shown to have a hypocontractile or acontractile bladder on urodynamic testing; 27 had undergone outflow tract surgery. Four patients who were totally incontinent had undergone at least 2 transurethral resections. The remainder had severe frequency, urgency and nocturia. Urodynamically, all but 7 patients with poor compliance had normal filling cystometrograms, all but 8 had residual urine volumes less than 100 ml, and 26 had less than 5 ml. Thus their symptoms are difficult to explain. Apart from the insertion of an artificial sphincter in those with total incontinence, treatment did not improve any of these patients.

Adult↗
PubMed1990

Treatment of outflow tract obstruction due to benign prostatic hyperplasia with the pollen extract, cernilton. A double-blind, placebo-controlled study.

Whilst prostatectomy remains the "gold standard" for the treatment of outflow tract obstruction due to benign prostatic hyperplasia, medical treatment--if only for symptomatic relief--appears to be an attractive alternative. Most of the pharmacological agents in use block the hormonal or the sympathetic neurological pathways that influence prostate growth and function. All of these drugs are known to have side effects. Sixty patients with outflow obstruction due to benign prostatic hyperplasia (BPH) were entered into a double-blind, placebo-controlled study to evaluate the effect of a 6-month course of the pollen extract, Cernilton. There was a statistically significant subjective improvement with Cernilton (69% of the patients) compared with placebo (30%). There was a significant decrease in residual urine in the patients treated with Cernilton and in the antero-posterior (A-P) diameter of the prostate on ultrasound. However, differences in respect of flow rate and voided volume were not statistically significant. It is concluded that Cernilton has a beneficial effect in BPH and may have a place in the treatment of patients with mild or moderate symptoms of outflow obstruction.

Aged↗
PubMed1990

Twenty-year follow-up of primary mega-ureter.

47 children diagnosed as having obstructed or non-refluxing, non-obstructed, primary mega-ureters were followed up by questionnaire. 2 patients had developed renal failure over 20 years, the remainder were free of urinary tract infection or hypertension. 21 of these patients were followed up with clearance and differential renal function studies. All but 4 kidneys associated with operated mega-ureters at long term follow-up had good function.

Child↗
PubMed1990

Prognostic factors for patients relapsing after radiotherapy for early-stage Hodgkin's disease.

Prognostic factors were analyzed retrospectively in 109 patients who relapsed after treatment with radiation only for Hodgkin's disease. Factors analyzed included initial stage, age, time to first relapse, histology, sex, extent of initial irradiation, sites of relapse, relapse stage (RS), average relative dose intensity (ARDI) of chemotherapy, and type of salvage therapy. Ninety-three percent of the patients received either standard or modified mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). With a median follow-up of 8.3 years, the actuarial survival and freedom from second relapse (FF2ndR) was 57% at 10 years. The extent of disease at the time of relapse, or so-called RS was found to be the single most important prognostic factor. Nearly 90% of patients with RS IA or IEA (favorable group) were disease free, and nearly 60% of patients with RS IIA, IIEA, or IIIA (intermediate group) were disease free compared with only 34% of patients with B symptoms or stage IV disease (unfavorable group). In a subset analysis, the use of combined modality therapy (CMT) was associated with an improved FF2ndR and survival in patients from the intermediate and unfavorable relapse groups. Age greater than 50 years was associated with an increased risk of second relapse and a lower survival. The other factors analyzed appeared to be of no independent prognostic value.

Adolescent↗
PubMed1989

Detection of 5-methylcytosine removal from DNA of Friend erythroleukemia cells following exposure to several differentiating agents.

The use of a 32P-labeling procedure has allowed us to monitor the stability of 5-methylcytosine (5-mC) in the existing fraction of DNA in differentiating Friend erythroleukemia cells (FELCs). The levels of 5-mC in existing DNA of control cells remained constant for 20 h, at nearly 3.95% of total labeled cytosine. Exposure of pre-labeled cells to 5 mM N'-methylnicotinamide (N'-MN), 4 mM hexamethylene bisacetamide (HMBA), or 270 mM dimethylsulfoxide (DMSO) over the same time-period resulted in the loss of 6.1, 4.8 and 1.8%, respectively, of the 5-mC from the pool of labeled cytosine present in the existing fraction of the DNA.

5-Methylcytosine↗
PubMed1989

Interleukin-1 beta gene deregulation associated with chromosomal rearrangement: a candidate initiating event for murine radiation-myeloid leukemogenesis?

The incidence of acute myeloid leukemia (AML) in CBA/H mice following exposure to single acute doses of ionizing radiation has previously been determined. A high proportion of these AMLs are characterized by rearrangement of murine chromosome 2 in the C2 and/or E5-F regions, and there is evidence that these events are a direct consequence of radiation damage to multipotential hemopoietic cells. Using a combination of in situ chromosome hybridization and mRNA analyses, we show that the cytokine gene interleukin-1 beta (IL-1 beta) is encoded in the chromosome 2 F region and is translocated in a chromosome 2---2 rearrangement in an x-ray-induced AML (N36). Also, IL-1 beta is specifically deregulated in N36 and in two other chromosome 2-rearranged AMLs but not in a fourth, which has two cytogenetically normal chromosome 2 copies. We suggest that radiation-induced specific chromosome 2 rearrangement associated with IL-1 beta deregulation may initiate murine leukemogenesis through the uncoupling of normal proliferative control mechanisms in multipotential hemopoietic cells.

Animals↗