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Biomedical subjects

M Butler

Publications and source records attributed to M Butler.

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

Adaptation to non-ammoniagenic medium and selective substrate feeding lead to enhanced yields in animal cell cultures.

Methods for the adaptation of three animal cell lines to media in which glutamine is replaced with either glutamate or 2-oxoglutarate are described. The cell lines differ in their rate of adaptation. The consequences of the adaptation of the McCoy cell line to a glutamate-based medium was measured in terms of: cell yield (increased by 17%), ammonia accumulation (reduced by 70%), glucose consumption (decreased by greater than 70%) and lactate accumulation (decreased by greater than 75%). The value of such adaptation and concomitant changes in energy metabolism lies in the potential for increased cell yields. Batch feeding of adapted cells in a microcarrier culture with a cocktail of glucose and amino acids resulted in increases in cell yields of 80% compared to unfed controls.

Adaptation, Physiological↗
PubMed1990

A systems model of chronic musculo-skeletal pain.

A comprehensive systems model of chronic musculo-skeletal pain is presented. Physical and mechanical events may impinge directly upon the organism to produce pain. In addition life experience, as interpreted by each individual, may result in unpleasant affect which may lead through three psychosomatic pathways to musculo-skeletal pain. The suggested pathways are conversion, dysponesis and neurotransmitter disturbance. It is suggested that the construing of the self as being "ill", "an invalid" or a "pain person" is a crucial step in the development of the chronic pain syndrome and that therapies which fail to change this self-construct are unlikely to meet with long-term success.

Chronic Disease↗
PubMed1990

The effect of radiation and cytotoxic platinum compounds on the growth of normal and tumour bladder explant cultures.

Using an explant tissue culture model developed by this group for use with human surgical and biopsy specimens, data are presented showing the response of normal and tumor bladder urothelium to radiation in combination with cis- and carboplatin. Cellular response is measured after two weeks in culture as a reduction in the extent of outgrowth from the explant. The outgrowth has been shown to be growing and to be epithelial. Results showed that when either drug or radiation is used singly, the tumour is resistant to treatment while the normal cells are severely affected. However, appropriate combinations of either drug with radiation reverse the unfavourable therapeutic ratio and result in higher tumour cell kill. The model may be useful for investigating mechanisms of radiation/chemotherapy action at the cellular level and, if integrated into appropriate clinical trials, may serve as an easy-to-use in vitro test for optimising single agent or combination therapy regimens.

Carboplatin↗
PubMed1989

A beltless tocodynamometer--a preliminary report.

The clinical usefulness of a newly developed beltless external tocodynamometer system was evaluated in a group of 56 patients in active, early, premature, or false labor. The uterine activity records so obtained were compared with those made in the same patients using the tocodynamometer with belt (49 patients) and the intrauterine pressure catheter (seven patients). The records were classified as "usable" if the baseline was above zero and the peak of the recorded contraction was at least 15 mmHg above the baseline. Both systems were studied under similar clinical conditions. Overall, of the 7434 minutes of recordings in 49 patients using the beltless system, 7008 minutes (94%) were usable. In contrast, only 2515 out of 5667 minutes (45%) of recordings made with the belted system were usable (P less than .001). Seven additional patients were monitored simultaneously with the beltless tocodynamometer and the intrauterine pressure catheter systems. Of the 1367 minutes' total monitoring time, the recovery rates of usable data for the beltless and intrauterine pressure catheter systems were 85 and 87%, respectively (P = not significant). These preliminary results indicate that the beltless system is a convenient, simple-to-use external tocodynamometric system that assesses uterine activity more efficiently than the belted system.

Adult↗
PubMed1988

The superiority of continuous cold blood cardioplegia in the metabolic protection of the hypertrophied human heart.

The effects of sanguineous and asanguineous cardioplegia on the generation of myocardial acid in the hypertrophied human heart during aortic clamping and reflow were elucidated by continuous intraoperative monitoring of myocardial pH in 42 patients undergoing valve replacement, with or without coronary bypass. The patients were divided into three groups: Group I (n = 14) received intermittent crystalloid cardioplegia; group II (n = 14) received intermittent blood cardioplegia; and group III (n = 14) received continuous blood cardioplegia. The groups were matched according to six previously elucidated determinants of myocardial acidosis. Measurements were made of myocardial pH, hydrogen ion concentration ([H+]), and the difference in pH units between myocardial pH and the pH of neutrality of water at the corresponding temperature (delta pHn). Throughout aortic clamping, myocardial pH in groups I and II fell significantly by 0.46 +/- 0.08 and 0.15 +/- 0.07 units, respectively (p less than 0.001) between the groups). In contrast, myocardial pH remained statistically unchanged throughout aortic clamping in group III (p less than 0.001 compared to groups I and II). Similar relationships were observed in [H+] and delta pHn during aortic clamping. During the early reflow, myocardial acidosis was observed in all three groups and delta pHn in group III increased from -0.26 +/- 0.10 at the end of aortic clamping to -0.57 +/- 0.07 during reperfusion (p less than 0.03). Patients in groups II and III required significantly less inotropic and mechanical cardiac support than patients in group I (p = 0.017). Hence, although continuous blood cardioplegia does not completely prevent acid accumulation during reflow, it provides better metabolic protection of the hypertrophied human heart than either intermittent crystalloid or intermittent blood cardioplegia.

Aged↗
PubMed1988

Light and electron microscope localization of the microtubule-associated tau protein in rat brain.

We have studied the distribution of microtubule-associated tau proteins in rat brain using monoclonal and affinity-purified polyclonal antibodies. Tau staining is prominent in axons in white matter areas of brain, as reported by Binder et al. (1985). In addition, we also find tau protein in neuron cell bodies, especially in the brain stem and basal ganglia and in the cell bodies of interfascicular oligodendroglia. Using electron microscopy, tau antibodies and colloidal gold-labeled second antibodies, gold particles are found associated with microtubules in axons and in the cytoplasm of cell bodies, while the nuclei, mitochondria, and myelin remain unlabeled. In double-staining experiments, tau staining co-localizes with that of tubulin. Our studies indicate that tau proteins are more widely distributed in brain than previously reported and cannot be used as an exclusive marker for axons.

Animals↗
PubMed1987

Ureteral meatotomy by Sachse urethrotome in the management of lower ureteral stones.

From January 1981 to June 1985 inclusive 170 patients were hospitalized for transurethral ureteral stone manipulation. A meatotomy with the Sachse urethrotome was done in 46 of these patients because the stone was impacted in the intramural ureter or the basket containing the stone became impacted. This method resulted in successful endoscopic removal of the stones in 43 patients.

Adult↗
PubMed1987

Comparability of old and new World Health Organization criteria for definite myocardial infarction.

New epidemiological criteria for definite myocardial infarction are now in use as part of the international study of trends and determinants of cardiovascular disease coordinated by the World Health Organization (MONICA Project). In this paper we use data from a myocardial infarction register to assess the comparability of the old and new World Health Organization criteria for definite myocardial infarction. The new criteria were applied to 905 cases who had been categorized as definite myocardial infarction on the old criteria. 739 (82%) of these cases met the new criteria for definite myocardial infarction; a further 157 cases (17%) met the new criteria for possible myocardial infarction. This study indicates that the two sets of criteria produce results that are too dissimilar for reliable comparisons to be made between studies using different criteria for definite myocardial infarction.

Adult↗
PubMed1987

Alzheimer's neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule associated proteins tau and MAP2.

Ten monoclonal antibodies raised against Alzheimer's neurofibrillary tangles (ANTs) were characterized for reactivity with heat-stable microtubule fractions from bovine and human brain. Five of the antibodies showed very little reaction, but the other five reacted strongly with heat-stable microtubule associated proteins (MAPs). The proteins recognized by these antibodies have estimated molecular weights similar to those of known heat-stable MAPs, tau (52-68 kd) and MAP2 (200-250 kd). That the proteins are indeed tau and MAP2 is demonstrated by reaction of electroblotted proteins with antibodies raised in mouse and guinea pig against bovine brain tau and MAP2. One anti-ANT antibody reacts only with tau, two bind strongly to tau and weakly to MAP2, one recognizes both tau and MAP2 equally well, and one primarily stains MAP2. Extraction of ANT with 2% SDS does not remove tau or MAP2 epitopes from ANT, indicating that epitopes shared with heat-stable MAPs are integral components of ANT. The existence of tau epitopes in ANT is also demonstrated by immunoblotting of ANT-enriched fractions with anti-tau antibodies. Most of the material recognized by anti-tau antibodies in ANT-enriched fractions is present in large molecules excluded by 3% polyacrylamide gel upon electrophoresis. Anti-tau antibodies immunostain ANT in immunofluorescence and immunoperoxidase studies. The immunostaining can be blocked by absorption of anti-tau antibodies with purified tau proteins from bovine brain. Not all ANTs in any given tissue section or isolated Alzheimer perikarial preparations, however, are stained by anti-tau antibodies. These results are consistent with previous studies that have demonstrated heterogeneity of ANTs. Whether this heterogeneity is due to biochemical modification of MAPs or absence of MAPs in some ANTs is unknown. The significance of what appear to be shared epitopes recognized by monoclonal antibodies in tau and MAP2, and the implications this may have on the pathogenesis of ANT formation, requires further investigation.

Alzheimer Disease↗
PubMed1986

Microheterogeneity of microtubule-associated tau proteins is due to differences in phosphorylation.

We have studied the heterogeneity of the microtubule-associated tau proteins using tau-specific antibodies and two-dimensional electrophoresis. Both monoclonal and polyclonal antibodies to tau proteins recognize five bands in cow brain microtubule proteins run on sodium dodecyl sulfate (SDS)-polyacrylamide gels, with apparent molecular weights between 56,000 and 66,000. Immunoblots of cow brain microtubules separated on two-dimensional gels, using nonequilibrium pH gradient electrophoresis in the first dimension and SDS-gel electrophoresis in the second, reveal that greater than 30 isoforms of tau exist. The tau proteins vary in pI from 6.5 to 8.5, with the higher-molecular-weight forms being more acidic. The microheterogeneity of tau is not induced by cycling of microtubules, because two-dimensional immunoblots of tau from total brain are almost identical to those of tau from cycled tubules. Adult rat brain tau, which appears as three doublet bands on SDS gels, also exhibits considerable isoelectric heterogeneity, as does tau from 7-day-old rats, which appears as only one band on SDS gels. After dephosphorylation of cow brain tau with alkaline phosphatase, the highest-molecular-weight band disappears on SDS gels. On two-dimensional gels, the number of tau variants decreases by more than half after dephosphorylation, and the more basic species increase greatly in intensity. Preliminary experiments with tau labeled in vivo with 32PO4 also indicate that the more acidic tau proteins are the more highly phosphorylated forms. Thus, isoelectric heterogeneity of tau proteins exists at all ages and is due, at least in part to differences in the state of phosphorylation of tau isoforms.

Alkaline Phosphatase↗
PubMed1986

Immunoreactive calcitonin in amyloid fibrils of medullary carcinoma of the thyroid gland. An immunogold staining technique.

A lymph node containing metastatic medullary carcinoma of the thyroid gland was examined immunohistochemically for the presence of calcitonin by light and electron microscopy. Electron microscopy showed dense, selective labeling of the tumor-associated amyloid fibrils and labeling of the scanty intracytoplasmic neurosecretory granules. By light microscopy, a few tumor cells showed strong staining, whereas the amyloid fibrils showed equivocal staining.

Amyloid↗
PubMed1986

Presence of fibronectin in articular cartilage in two animal models of osteoarthritis.

Fibronectin content was determined in articular cartilage in a spontaneous dog model and in a meniscectomy rabbit model of osteoarthritis. Determination of the fibronectin content of urea extracts of articular cartilage by an enzyme linked immunosorbent assay (ELISA) disclosed that degenerated cartilage contained from 10- to 40-fold more fibronectin than normal cartilage. The finding that cartilage fibronectin content was increased in both animal models suggests that elevated cartilage fibronectin content is a general feature of the osteoarthritic process. Immunoperoxidase studies disclosed that fibronectin was distributed throughout the matrix in hyaluronidase treated normal and osteoarthritic cartilage from both animal models, but quantitative differences in fibronectin were not observed by these techniques.

Animals↗
PubMed1985

A comparison of bipolar and monopolar diathermy probes in experimental animals.

The effects of monopolar and bipolar diathermy were studied in laboratory animals. The power required to coagulate transected vessels in air was established and the effect of immersion in saline and water during electrocoagulation was investigated. Tissue heat conduction from each type of probe was measured and compared. Tissue damage was assessed by light microscopy of histochemically stained sections. The bipolar system operated at a lower power output (13 W) with less heat conduction, and was unaffected by the surrounding medium.

Animals↗
PubMed1985

Growth limitations in high density microcarrier cultures.

The growth of anchorage-dependent animal cells on microcarriers has enabled treatment of these cell lines as quasi-suspension cultures allowing the production of high cell densities. Analysis of the parameters affecting the final cell yield shows that if an optimal microcarrier/cell seeding ratio is provided, the surface area for cell growth is unlikely to be limiting. The culture medium could become limiting to cell growth by nutrient depletion or through the accumulation of growth inhibitors. In batch cultures of MDCK cells the analysis of amino acid utilization showed that some amino acids are nearly completely depleted from the medium during the growth period. Glutamine in particular was rapidly consumed reflecting its likely role as a major energy source. The use of a novel perfusion system for such cultures produces much higher cell densities. In 500 ml cultures perfused at 1 ml/min most of the amino acids maintained a steady concentration. The glutamine concentration was reduced not completely depleted. Under these conditions the ammonia concentration of the medium increased to a value of 2.3 mM when cell growth ceased. This level of ammonia accumulation occurred in both perfused and unperfused cultures. Investigations of the parameters affecting the growth of BHK cells in microcarrier cultures showed the rapid utilization of glutamine which was optimal at an initial concentration of 4 mM. Glucose showed rapid but not complete utilization in these experiments. The ammonia accumulation in the medium was shown to be directly related to the initial glutamine concentration and under optimal conditions rose to a level of 2.5 mM. This level of ammonia was shown to be growth inhibitory when added to cultures during inoculation. Growth experiments using culture medium diluted with isotonic salt solutions showed that the final cell yield was not directly related to the medium dilution in either perfused or unperfused cultures. This suggests that the accumulation of a growth inhibitor is responsible for growth limitation rather than nutrient depletion. The measurements of ammonia accumulation suggest that this could be the growth inhibitor which limits the final cell yield.

Amino Acids↗