Search PubMed⌕ Search

Biomedical subjects

R Ball

Publications and source records attributed to R Ball.

At least 91 records · Page 5Linked to original sources
PubMed1990

Transforming growth factor-beta inhibits lactogenic hormone induction of beta-casein expression in HC11 mouse mammary epithelial cells.

HC11 mouse mammary epithelial cells can undergo a limited functional differentiation in terms of beta-casein synthesis in response to the combined action of dexamethasone and prolactin. Transforming growth factor-beta (TGF-beta) can inhibit beta-casein expression in HC11 cells in a dose-dependent manner. This effect is reversible and specific as shown by comparison with the effect of other growth factors. TGF-beta also inhibits DNA synthesis of HC11 cells. These findings suggest a possible role of TGF-beta as an inhibitor of functional differentiation in the mammary gland.

Animals↗
PubMed1989

Identification and characterisation of an antithrombin III mutant (AT Dublin 2) with marginally decreased heparin reactivity.

The antithrombin III (ATIII) isoform patterns of plasma and serum samples from cancer patients and controls were analysed by isoelectric focusing and immunoblotting. A novel ATIII banding pattern was identified in two individuals: a patient with breast carcinoma who developed deep venous thrombosis and a blood donor. Family studies in the patient showed the abnormal pattern to be due to a mutant form of ATIII (AT Dublin 2). The coagulation properties of AT Dublin 2 heterozygotes were normal. Immunologic and activity levels of ATIII, measured by standard techniques, were normal. Mutant plasma ATIII showed reduced thrombin reactivity at low concentrations of thrombin and demonstrated decreased reactivity with heparin over a range of heparin concentrations. This was confirmed using a modified ATIII heparin cofactor activity assay with varying heparin concentrations. The abnormal ATIII was also found to elute from heparin agarose at a lower ionic strength than normal ATIII. Two dimensional gel electrophoresis showed the abnormal ATIII to have similar molecular size distribution to normal ATIII. Neuraminidase treatment of normal and mutant plasma reduced the ATIII isoforms to one in both samples. The possible role of AT Dublin 2 in predisposing to hypercoagulation is discussed.

Adult↗
PubMed1989

New mammary epithelial and fibroblastic cell clones in coculture form structures competent to differentiate functionally.

We have established and characterized a spontaneously immortalized, nontumorigenic mouse mammary cell line, designated IM-2. IM-2 cells synthesize large amounts of the milk protein beta-casein upon addition of lactogenic hormones. The induction of beta-casein occurs rapidly and does not require any exogenous extracellular matrix components. The IM-2 cell line is morphologically heterogeneous and could be separated into cell clones with epithelial and fibroblastic characteristics. In monoculture, none of the epithelial clones could be induced to synthesize caseins. Coculture of epithelial and fibroblastic clones, however, rendered the epithelial cells competent to differentiate functionally; the addition of lactogenic hormones to these cocultures resulted in the synthesis of beta-casein in amounts comparable to that seen with the original IM-2 line. Using this unique cell system, we have investigated the interrelationships between different steps in differentiation leading to hormone-induced casein production. Independent of hormones, epithelial-fibroblastic cell contacts led to the formation of characteristic structures showing the deposition of laminin. We found that the epithelial cells located in these structures also exhibited significantly increased levels of cytokeratin intermediate filament polypeptides. Double immunofluorescence revealed that the cells inducible by hormones to synthesize casein, colocalized exactly with the areas of laminin deposition and with the cells showing greatly intensified cytokeratin expression. These results suggest that hormone-independent differentiation events take place in response to intercellular epithelial-mesenchymal contacts. These events in turn bring about a state of competence for functional differentiation after lactogenic hormonal stimulation.

Animals↗
PubMed1989

Low-normal concentrations of free thyroxin in serum in late pregnancy: physiological fact, not technical artefact.

Free thyroxin (FT4) concentrations, total thyroxin/thyroxin-binding globulin (T4/TBG) ratios, and thyrotropin (TSH) and albumin concentrations were measured in serum in a longitudinal study in each of the three trimesters of 25 normal pregnancies. In late pregnancy, FT4 estimates by assays reputedly either affected or unaffected by albumin were in the lower half of the reference range for nonpregnant subjects. T4/TBG ratios and albumin concentrations were similarly lower. FT4 overall was significantly (P less than 0.001) correlated with these latter two values. Serum TSH concentrations increased as FT4 declined in late pregnancy. Nonesterified fatty acid (NEFA) concentrations were too low to displace T4 from its binding proteins and were not correlated with other measurements. Within any one of the trimesters, FT4 and T4/TBG were independent of variations in TBG or albumin concentrations. This implies that lower FT4 concentrations in late pregnancy are real, merely coinciding with parallel decreases in albumin. They are not artefacts of albumin-affected assays.

Adult↗
PubMed1989

Umbilical artery velocimetry as a predictor of adverse outcome in pregnancies complicated by oligohydramnios.

Oligohydramnios is associated with increased perinatal mortality and morbidity. Traditional methods of in utero fetal evaluation have been unsuccessful in reliably distinguishing oligohydramnios with normal outcome from that associated with increased perinatal morbidity. A prospective study was undertaken to establish the predictive value of Doppler velocimetry in identifying the fetus with oligohydramnios at increased risk of adverse perinatal outcome. Twenty-two gravid women with subjective oligohydramnios on ultrasound had continuous-wave umbilical artery velocimetry. Subjects were divided into two groups based on the results of Doppler analysis. Group 1 (N = 13) had normal umbilical Doppler waveforms. In this group, 12 of 13 patients had normal perinatal outcome, defined by the absence of intrapartum fetal distress or evidence of intrauterine growth retardation. Group 2 consisted of nine subjects with abnormal waveforms. Perinatal morbidity occurred in 100% in this group. We conclude that an abnormal umbilical artery waveform may provide confirmatory evidence of impending fetal compromise when the antenatal sonographic diagnosis of oligohydramnios is made.

Amniotic Fluid↗
PubMed1987

Positron emission tomography assessment of effects of benzodiazepines on regional glucose metabolic rate in patients with anxiety disorder.

Patients with generalized anxiety disorder (n = 18) entered a 21-day, double-blind, placebo-controlled random assignment trial of clorazepate. Positron emission tomography with 18F-deoxyglucose was carried out before and after treatment. Decreases in glucose metabolic rate in visual cortex and relative increases in the basal ganglia and thalamus were found. A correlation between regional changes in metabolic rate and regional benzodiazepine receptor binding density from other human autopsy studies was observed; brain regions highest in receptor density showed the greatest decrease in rate.

Adult↗
PubMed1987

[Long latency auditory evoked potentials: value of multichannel analysis and of high-resolution graphic mapping].

Auditory Evoked Potentials maps (AEP) were computed from 32 simultaneously recorded channels over both hemispheres using a linear interpolation algorithm. Reference electrode was extracephalic. Stimulus was a 781 Hz tone (intensity 70 dB HL, duration 256 msec). Average AEP were from 128 responses to randomly delivered stimuli. Direct current and frequencies over 50 Hz were removed by means of a digital filter (FFT). Results from 15 subjects showed before 120 msec a symmetrical response of AEP at vertex with left ear, right ear or binaural stimulation. Between 120 and 170 msec, maps of evoked responses were asymmetrical showing greater potentials over temporal areas contralateral to the stimulated ear.

Cerebral Cortex↗
PubMed1987

The interrelationship of beta endorphin, ACTH and cortisol in depressive illness: a controlled study.

Plasma cortisol, ACTH and beta endorphin were measured before and after dexamethasone in 8 severely depressed patients and 8 age- and sex-matched controls to examine the relationship of ACTH and endogenous opioids to cortisol in depression. Despite having significantly higher plasma levels of cortisol than the controls, the depressed patients did not have correspondingly elevated plasma levels of ACTH. Beta-endorphin levels were also similar in the two groups. All three hormones suppressed to some degree after dexamethasone, but cortisol suppressed less in patients than controls. Our findings suggest that in severe depressive illness abnormalities exist in the hypothalamic-pituitary-adrenal axis peripherally as well as centrally.

Adrenocorticotropic Hormone↗
PubMed1987

Opioid peptides and psychiatric illness.

In the 10 years since Hughes et al (1975) identified from porcine brain two related pentapeptides with potent opiate activity, abnormalities of endorphin and enkephalin production or metabolism have been postulated in many disease states. The possibility of an advance in our understanding of the aetiology of functional psychiatric illness has led to a considerable body of research, which is discussed in this paper.

Animals↗
PubMed1986

Changes in the extent of microtubule assembly can regulate initiation of DNA synthesis.

We have shown that MT depolymerization by colchicine and other drugs is sufficient to initiate DNA synthesis in serum-free cultures of embryonic fibroblasts and that stabilization of MTs with taxol inhibits this initiation. Growth factors and oncogenic DNA viruses also initiate DNA synthesis by a taxol-sensitive mechanism that appears to require MT depolymerization or rearrangements. Because we have shown that microtubule heterogeneity exists within single fibroblastic cells, we have carried out a series of experiments to determine the extent of microtubule disruption necessary to initiate DNA synthesis. We have compared the effects of various concentrations of colchicine and taxol on initiation of DNA synthesis with their effects on cytoplasmic MT complexes as visualized by indirect immunofluorescence microscopy and quantitated by direct binding of radiolabeled monoclonal antibody to cytoskeletons. The opposing effects of these drugs on MTs shows that there is a correlation between the extent of MT depolymerization and initiation of DNA synthesis. Initiation of DNA synthesis by colchicine in the presence of taxol is half-maximal when taxol and colchicine are added to cultures at a ratio of about 13 to 1. At this drug ratio, taxol stabilizes MTs near the nucleus, but MTs near the cell periphery are depolymerized. Maximal inhibition of DNA synthesis by taxol occurs only at taxol to colchicine ratios where MTs extend throughout the cytoplasm to the cell periphery. Thus, depolymerization of a small fraction of total MTs, particularly those near the periphery, may be sufficient to initiate proliferative events.

Alkaloids↗
PubMed1986

Continuous ambulatory peritoneal dialysis as treatment of severe congestive heart failure in the face of chronic renal failure. Report of eight cases.

Eight patients with severe heart failure and renal insufficiency whose conditions were refractory to diuretics were treated by continuous ambulatory peritoneal dialysis. Seven of the eight patients died. Although the patients no longer had uncontrolled congestive heart failure, hospitalization rates failed to improve due to dialysis complications and underlying heart disease. The one long-term survivor was being treated with diuretics alone after peritoneal dialysis was used to control heart failure. Although survival was short after initiation of dialysis (median survival, 225 days), this therapy may merit further study in patients less ill.

Aged↗
PubMed1985

Hormonal regulation of cell surface expression of the major histocompatibility antigen H-2Ld in transfected cells.

The murine major histocompatibility antigens are cell surface glycoproteins which play an important role in the recognition of foreign antigens by cytotoxic T lymphocytes. Modulation of the level of expression of histocompatibility antigens could therefore be useful for the study of the interaction between the antigen presenting cells and T lymphocytes. The glucocorticoid hormone-inducible promoter, located in the long terminal repeat of mouse mammary tumor virus, was used to replace the promoter region of a cloned H-2Ld class I gene. The chimeric gene was introduced into cultured cells. Glucocorticoid induction of MMTV LTR H-2Ld mRNA could be shown by blot analysis. An S1 nuclease protection assay indicated that the transfected cells accurately initiate the chimeric mRNA. Immunoprecipitation of H-2Ld protein with a specific monoclonal antibody showed inducibility also at the cellular protein level. Fluorescence-activated cell sorter analysis monitored a 3-fold increase of H-2Ld on the cell surface when the transfected cells were grown in the presence of dexamethasone. This increase of H-2Ld expression was accompanied by a corresponding decrease on the cell surface of the endogenous H-2Kk.

Animals↗
PubMed1985

New acceptor cell for transfected genomic DNA: oncogene transfer into a mouse mammary epithelial cell line.

A line of mouse mammary epithelial cells (NMuMG) has been characterized for its ability to be stably transfected with exogenous DNA. A transfection frequency of at least 1 cell per 1,000 was obtained with the pSV2neo plasmid. Several thousand G418-resistant NMuMG cell clones can easily be generated in cotransfection of genomic DNA and pSV2neo. The NMuMG cells were isolated from normal mammary glands and do not form malignant lesions when injected into nude mice. We have cotransfected NMuMG cells with pSV2neo and genomic DNA from the human EJ bladder carcinoma line, a cell line which contains an activated c-rasH oncogene. When a pool of 4,700 G418-resistant colonies was injected into nude mice, tumors were obtained. These tumors contain a transfected human rasH gene. Genomic DNA transfection into a line of mouse epithelial cells, in combination with the selection of stable transfectants and tumor induction in nude mice, can be used to screen human tumor DNA for the presence of activated oncogenes.

Animals↗