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Biomedical subjects

R Mitchell

Publications and source records attributed to R Mitchell.

At least 199 records · Page 11Linked to original sources
PubMed1992

An evaluation of bone healing in cavities in the jaws implanted with a collagen matrix.

Bony defects in the jaws after surgery may show poor healing especially in the maxilla and the area may never completely be replaced by bone. 50 patients with pathological bony cavities in the jaws were used to assess the efficacy of a collagen matrix implanted into the treated bony defect and 50 patients in whom no material was implanted were used as controls. The results were assessed radiographically at 3, 6 and 12 months. At 3 months, bone deposition in the control group was in advance of the implanted group, but after 6 and 12 months healing appeared to be similar in both groups. No adverse effects were found due to the presence of the collagen implant. Collagen delayed the early osteogenic healing period, indicating that only when it has been resorbed can the area heal with osteogenic granulation tissue. As some radiolucent areas still remained in the healed implant group after 12 months it must be assumed that the collagen implant has only been replaced by host fibrous tissue and therefore does not possess osteoinductive properties.

Collagen↗
PubMed1992

The priming effect of luteinizing hormone-releasing hormone (LHRH) but not LHRH-induced gonadotropin release, can be prevented by certain protein kinase C inhibitors.

The priming effect of LHRH in vitro (which results in increased responsiveness of gonadotropes to both LHRH receptor-mediated and receptor-independent stimuli) is brought about by an unknown mechanism. The present results indicate that induction of the LHRH priming effect is inhibited in a concentration-dependent manner by the protein kinase C (PKC) inhibitors staurosporine, K252a, H7 and by the novel highly-selective PKC inhibitor, Ro 31-8220. In contrast, a range of other compounds that are relatively selective inhibitors of other kinases such as tyrosine kinases and Ca2+/calmodulin-dependent kinases were unable to prevent priming. The PKC inhibitors prevented priming without affecting initial LHRH-induced gonadotropin secretion. Thus, the priming-elicited increment in secretion was selectively removed, restoring hormone release to the level measured during an initial response to LHRH. Similar results were obtained on different days of the estrous cycle where the magnitude of the priming effect varies. Experiments on the time course of PKC inhibitor action revealed that the critical period was in the induction of the priming effect, not its expression. The PKC inhibitors had neither acute nor delayed effects on gonadotropin secretion induced by ionomycin. Staurosporine, K252a and Ro 31-8220 inhibited LHRH priming with identical potencies to their inhibition of phorbol ester-induced gonadotropin secretion. The reduced potency of H7 seen on LHRH priming compared to phorbol ester-induced gonadotropin release parallels results seen with this inhibitor on phorbol ester-induced secretion of growth hormone (Johnson and Mitchell (1989) Biochem. Soc. Trans. 17, 751-752) and on the pharmacological characteristics of PKCs partially purified from anterior pituitary tissue. In all aspects of this study, effects on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion appeared to be entirely similar.

Alkaloids↗
PubMed1992

Pyrolysis-gas chromatography-mass spectrometry of a series of bile acid sequestrants.

Pyrolysis of a series of polymers based on polystyrene and used as bile acid sequestrants produced characteristic mixtures of compounds which were analysed by gas chromatography-mass spectrometry. The nature of the substituent groups was clearly apparent while the polymer backbone gave rise to representative styrenes. The reproducibility of the results was examined by experimenting with the temperature of pyrolysis. It was found that at low temperatures very little fragmentation of the polystyrene backbone occurred but the substituents were still released in high yield. The orientation of the various substituted styrenes generated by pyrolysis was confirmed by the use of gas chromatography with infrared and mass spectrometric detection.

Bile Acids and Salts↗
PubMed1992

Human chorionic gonadotrophin contributes to the bioactivity of Pergonal.

OBJECTIVE: We examined batch variation in the LH-like bioactive content of Pergonal and determined whether hCG contributes to this. DESIGN: Random selection of three batches of Pergonal, consisting of three ampoules in each batch. MEASUREMENTS: The LH content in each ampoule was determined by radioimmunoassay (R-LH), immunoradiometric assay (I-LH) and in vitro Leydig cell bioassay (B-LH) using the urinary hMG International Standard 70/45. Human chorionic gonadotrophin was determined by immunoradiometric assay (I-hCG) using the hCG IRP 75/537. The isohormone content of each batch was examined by chromatofocussing over the range pH 4.5-7.0 and the fractions collected were assayed for LH and hCG content. The variability in potency between batches was assessed by single factor analysis of variance. RESULTS: The gonadotrophin content of each batch (IU/ampoule, mean +/- SEM, n = 3 ampoules) was R-LH (40.9 +/- 0.5, 40.8 +/- 0.2, 39.3 +/- 0.7, P > 0.15), I-LH (39.0 +/- 1.5, 28.3 +/- 0.8, 36.9 +/- 3.3, P < 0.001), B-LH (27.3 +/- 0.3, 12.0 +/- 0.9, 19.3 +/- 0.9, P < 0.001) and I-hCG (16.4 +/- 0.7, 11.7 +/- 0.2, 10.5 +/- 0.5, P < 0.001). The chromatofocussing recoveries below pH 5.5 expressed as a percentage of the total amount of analyte eluted from the column and collated for all three batches of Pergonal were (mean % +/- SD, n = 3 batches) R-LH (58.4 +/- 4.0), I-LH (41.3 +/- 7.5), B-LH (81.4 +/- 2.8) and I-hCG (87.8 +/- 3.7). CONCLUSIONS: There was significant batch variation in the I-LH, B-LH and I-hCG (P < 0.001) but not the R-LH (P > 0.15) content of Pergonal. More than 80% of the total B-LH recovery chromatofocussed below pH 5.5 and corresponded to the region of highest I-hCG (> 87%) and lowest I-LH (< 42%) recovery. This was highly suggestive of hCG contributing to the LH-like bioactivity of Pergonal.

Chorionic Gonadotropin↗
PubMed1992

An investigation of LH pulsatility in burned men by bioassay and radioimmunoassay.

LH pulsatility studies were performed in six burned patients by removing blood samples at 10 min intervals over a 6 h period. All samples were assayed for LH by bioassay (B-LH), LH by radioimmunoassay (I-LH) and testosterone. Mean serum testosterone concentrations of the burned patients were low (6.7 +/- 1.6 nmol/l). I-LH levels were lower than B-LH in all samples. Frequency of bioactive or immunoreactive pulses as well as mean B-LH and I-LH concentrations were similar to previously published data from normal men examined in the same laboratory. The mean biological activity of LH (expressed as the ratio of B-LH to I-LH, the B:I ratio) was lower in burned subjects (1.9 +/- 0.1) than previously reported in normal men. The B:I ratios of burned men were lower (p less than 0.01) at pulse peaks than at nadirs (1.8 +/- 0.1 vs 2.0 +/- 0.1) and an increase in serum testosterone concentration did not follow an LH peak. Serum testosterone concentrations did not cross-correlate with B-LH or I-LH. This contrasts with the findings in normal subjects where the B:I ratios have been found to be higher at pulse peaks than at nadirs and an increase in serum testosterone concentration follows a pulse peak and serum testosterone cross-correlates with B-LH and I-LH. LH secreted in a pulse peak in normal men may contain a particularly biologically potent form of the molecule but this may not be the case in burned men.

Adult↗
PubMed1992

Rectangles may appear to reverse like trapezia when they rotate at an uneven rate.

A 1983-1985 theory by Mitchell and Power predicts that, when rotating rectangles undergo certain kinds of speed fluctuation, they should appear to reverse just as trapezia do. The prediction is partially confirmed. One of two 'mimic' rectangles underwent apparent reversals more often than a control rectangle undergoing even rotation and in the same places as rotating trapezia. However, its reversal frequency was less than those of the trapezia, and a second 'mimic' slowed an inappropriate distribution of reversals round the cycle. These anomalies call for some modification to Mitchell and Power's theory, but minor qualifications may be sufficient.

Adult↗
PubMed1991

Calcium influx through 'L'-type channels into rat anterior pituitary cells can be modulated in two ways by protein kinase C (PKC-isoform selectivity of 1,2-dioctanoyl sn-glycerol?).

The depolarisation-induced influx of 45Ca2+ into anterior pituitary tissue and GH3 cells through 'L'-type, nimodipine-sensitive channels was investigated. In anterior pituitary prisms, phorbol esters, activators of protein kinase C, caused an enhancement of K(+)-induced 45Ca2+ influx. However, in the GH3 anterior pituitary cell line, phorbol esters inhibited K(+)-induced 45Ca2+ influx. The modulation by phorbol esters in both tissues was stereo-specific and time- and concentration-dependent. The diacylglycerol analogue, 1,2-dioctanoyl sn-glycerol was able to mimic the phorbol ester-induced enhancement of calcium influx into anterior pituitary pieces, but was ineffective in GH3 cells. 1,2-Dioctanoyl sn-glycerol may selectively activate an isoform of protein kinase C which is responsible for enhanced 'L'-type Ca(2+)-channel activity.

Animals↗
PubMed1991

Inhibition of depolarisation-induced calcium influx into GH3 cells by arachidonic acid: the involvement of protein kinase C.

The influx of 45Ca2+ induced in GH3 cells by exposure to 60 mM K+ medium was inhibited by arachidonic acid (AA) in a concentration-dependent manner. This action of AA was not prevented by inhibitors of its metabolism but was reversed by the inhibitors of protein kinase C (PKC), H7 and staurosporine but not their less active congeners HA 1004 and K252a, respectively. Presumed down-regulation of PKC by pretreatment with phorbol 12,13-dibutyrate (PDBu) also greatly diminished the effect of AA. Experiments to assess effects of AA on 45Ca2+ efflux and on cytosolic Ca2+ concentrations indicated that an additional PKC-independent action of AA involving the release of intracellularly stored calcium was present. Both direct activation of certain PKC isoform(s) by AA and the synergistic influence on PKC activity by its concomitant raising of intracellular Ca2+ concentrations, may be physiologically important in the regulation of depolarisation-induced Ca2+ entry.

Animals↗
PubMed1991

Establishment in culture and characterization of a strain with mast cell and monocytic properties from the bone marrow of a child with diffuse cutaneous mastocytosis.

Bone marrow was isolated from a child with congenital mastocytosis. Upon prolonged in vitro culture, initially in the presence of interleukin-3 (IL-3), a population of relatively large fusiform, strongly adherent cells grew out plus a subpopulation of smaller nonadherent cells. The morphology of the adherent cells was not typical of fibroblasts, epithelial cells, nor of standard hematopoietic cell types, whereas the morphology of the nonadherent cells resembled mast cells. Neither cell type required the presence of IL-3 nor a feeder layer of fibroblasts for continued growth. Attempts to isolate the two populations were unsuccessful. This cell strain comprised of both cell populations has been termed human bone marrow-derived mastocytosis cells (HBM-M). These cells were found to possess some of the cytochemical, ultrastructural, and surface phenotypic features of degranulated mast cells. They reacted with the mast cell marker, monoclonal antibody YB5.B8, but not with the basophil specific monoclonal antibody Bsp-1 and released the inflammatory mediators histamine, leukotriene C4, prostaglandin D2, and platelet-activating factor constitutively. This release was not potentiated by immunologic- or nonimmunologic-activating stimuli. In addition, they exhibited cytochemical and surface phenotypic features of monocytes. Our results indicate that a population of abnormal proliferative cells exist in the marrow of this patient; that these cells may be responsible for the patient's pronounced systemic proliferation of mast cells and the associated symptoms; and that the cell's mast cell, monocyte properties may be indicative of a common bone marrow-derived mast cell/monocyte precursor.

Antibodies, Monoclonal↗
PubMed1991

The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing.

Vascular endothelial growth factor (VEGF) is an apparently endothelial cell-specific mitogen that is structurally related to platelet-derived growth factor. By Northern blot and protein analyses, we show that VEGF is produced by cultured vascular smooth muscle cells. Analysis of VEGF transcripts in these cells by polymerase chain reaction and cDNA cloning revealed three different forms of the VEGF coding region, as had been reported in HL60 cells. The three forms of the human VEGF protein chain predicted from these coding regions are 189, 165, and 121 amino acids in length. Comparison of cDNA nucleotide sequences with sequences derived from human VEGF genomic clones indicates that the VEGF gene is split among eight exons and that the various VEGF coding region forms arise from this gene by alternative splicing: the 165-amino-acid form of the protein is missing the residues encoded by exon 6, whereas the 121-amino-acid form is missing the residues encoded by exons 6 and 7. Analysis of the VEGF gene promoter region revealed a single major transcription start, which lies near a cluster of potential Sp1 factor binding sites. The promoter region also contains several potential binding sites for the transcription factors AP-1 and AP-2; consistent with the presence of these sites, Northern blot analysis demonstrated that the level of VEGF transcripts is elevated in cultured vascular smooth muscle cells after treatment with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate.

Amino Acid Sequence↗
PubMed1991

The assignment of the 655 nm spectral band of cytochrome oxidase.

The spectral characteristics of the '655 nm' band of cytochrome oxidase were found to be affected by ligands of the binuclear centre, including formate and chloride, and by the resting/pulsed transition. The band titrated with near n = 1 characteristics at a midpoint of about 400 mV, in contrast to haem a3, which exhibits strong redox interaction and a titration range at significantly lower potential. Thus, although the total reduced-oxidised difference spectrum of haem a3 shows a trough at about 655 nm, this characteristic is absent in the low potential region. The 655 nm feature may arise from a charge transfer band of ferric high-spin haem a3, which is modulated by the redox state of CuB, as suggested by Beinert et al. [(1976) Biochim. Biophys. Acta 423, 339-355].

Animals↗
PubMed1991

Electrocardiography and postextrasystolic potentiation: utilization of the two methods to predict postrevascularization segmental myocardial function.

We previously reported that postextrasystolic potentiation (PESP) is a useful predictor of changes in systolic wall function (SWF) following coronary revascularization. In the current study we analyzed ECG changes related to corresponding myocardial segments to determine their correlation with PESP and SWF. We found: (1) The PESP response in a jeopardized segment was a valid predictor of improved SWF even when Q waves, ST-segment changes, or T-wave changes were present. (2) However, when Q waves were present in two or more of the corresponding leads, positive PESP was less likely to be observed. (3) Thus Q waves in two leads predicted the least postrevascularization improvement. (4) Segments with no corresponding Q-wave postrevascularization usually improved SWF. (5) Furthermore, a continuum of responsiveness to PESP was found, ranging from T-wave changes, ST-segment changes to Q-wave changes, indicating dissociation between electrical and mechanical events. In conclusion, the ECG together with PESP provide good predictive information relative to the efficacy of revascularization. PESP is a more valuable predictive indicator. ECG alone may be of value in that the occurrence of Q waves in two or more corresponding leads predicts a low probability of improved SWF. Further studies are indicated to investigate the dissociation between electrical and mechanical events.

Blood Pressure↗
PubMed1991

Pulsatile immunoreactive and bioactive luteinizing hormone secretion in adolescents with chronic renal failure. The Cooperative Study Group on Pubertal Development in Chronic Renal Failure (CSPCRF).

Delayed or arrested pubertal development is common in children with chronic renal failure (CRF). Normal puberty is initiated by the onset of episodic nocturnal secretion of luteinizing hormone (LH) containing an increasing proportion of bioactive hormone. To test the functional integrity of the hypothalamo-pituitary axis in CRF we measured immunoreactive (i-LH) and bioactive (bio-LH) plasma LH concentrations at 15-min intervals from 2000 to 0700 hours in 65 pubertal patients aged 10-23 years [46 boys/19 girls; 20 on conservative treatment (CT), 13 on dialysis (D), 32 with transplants (TP)]. i-LH was determined by radio-immunoassay and bio-LH by a mouse Leydig cell assay. Peak detection was performed by the cluster analysis computer programme. The mean (+/- SD) number of i-LH (in both sexes) and bio-LH pulses (in boys) per profile, and the mean peak area of i-LH (in both sexes) and bio-LH (in girls) were higher in TP than in CT or D patients. The ratio of bio-LH to i-LH increased during puberty in CT (G1 vs G4/5, 0.3 +/- 0.5 vs 1.8 +/- 0.,4) and TP (0.6 +/- 0.7 vs 1.8 +/- 0.7) but remained low in male D patients (0.4 +/- 0.7 vs 1.1 +/- 0.8). The ratios were subnormal, however, even in mature TP patients compared with healthy adults. The bio-LH/i-LH ratio and the bio-LH peak area best predicted integrated nocturnal testosterone concentrations in TP but not in uraemic male patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗