Locality information. Kind Herts and coronaries.
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Acute Disease↗
Biomedical subjects
G Jones
Publications and source records attributed to G Jones.
In vitro metabolism of the vitamin D analog, 22-oxacalcitriol, using cultured osteosarcoma, hepatoma, and keratinocyte cell lines.
Using four cultured cell models representing liver, keratinocyte, and osteoblast, we have demonstrated that the vitamin D analog, 22-oxacalcitriol is degraded into a variety of hydroxylated and side chain truncated metabolites. Four of these metabolic products have been rigorously identified by high pressure liquid chromatography, diode array spectrophotometry, and gas chromatography-mass spectrometry analysis as 24-hydroxylated and 26-hydroxylated derivatives as well as the cleaved molecules, hexanor-1alpha,20-dihydroxyvitamin D3 and hexanor-20-oxo-1alpha-hydroxyvitamin D3. Comparison with chemically synthesized standards has revealed the stereochemistry of the biological products. Although differences exist in the amounts of products formed with the different cell types, it is apparent that 22-oxacalcitriol is subject to metabolism by both vitamin D-inducible and noninducible enzymes. Time course studies suggest that the truncated 20-alcohol is derived from a side chain hydroxylated molecule via a hemiacetal intermediate and the 20-oxo derivative is likely formed from the 20-alcohol. Biological activity measurements of the metabolites identified in our studies are consistent with the view that these are catabolites and that the biological activity of 22-oxacalcitriol is due to the parent compound. These results are also consistent with recent findings of others that the biliary excretory form of 22-oxacalcitriol is a glucuronide ester of the truncated 20-alcohol.
Animals↗
Multiple transcription start sites for the GnRH gene in rhesus and cynomolgus monkeys: a non-human primate model for studying GnRH gene regulation.
In humans, transcription of the gonadotropin-releasing hormone (GnRH) gene can be initiated at two transcription start sites to produce different GnRH mRNAs. The upstream transcription start site is used only in reproductive tissues and tumors. To determine if a similar pattern of GnRH gene expression exists in non-human primates, we cloned GnRH cDNA from rhesus monkey hypothalamic RNA using reverse transcriptase-polymerase chain reaction (RT-PCR) and the 5' flanking region of the monkey GnRH gene by PCR. A 96% similarity between monkey and human GnRH cDNA was found with 94% similarity in the upstream promoter region. An upstream transcriptional start site, was identified in cynomolgus monkey testicular mRNA, 504 base pairs upstream from the hypothalamic site, which was different from that identified in the human GnRH gene. Various cynomolgus monkey reproductive tissues were found to utilize this upstream transcriptional start site. In contrast, no evidence was found for the use of upstream transcriptional start sites in rat testis or placenta, suggesting that the reproductive tissue specificity of the upstream transcription start site may be a primate specific feature.
Amino Acid Sequence↗
Application of the bootstrap to calibration experiments.
In calibration experiments, a number of samples of known concentration are used to establish the relationship between a measured response and sample concentration; this relationship is then used to estimate the unknown concentration of further samples from their measured responses. In addition to the estimates themselves, it is useful to have available some measure of their precision, usually given in the form of confidence limits. The standard method of inverting prediction limits is found to work well in simple situations, but in nonlinear multivariate calibration it becomes intractable. The bootstrap offers an alternative methodology, but in the calibration framework its application is not obvious. We describe some considerations in bootstrapping calibration data and compare our methods with a previous attempt and with the standard method in linear, nonlinear, and multivariate situations. The bootstrap is found to be a useful tool in those situations where the standard method is difficult to implement.
Calibration↗
Glucuronidation associated with intrinsic resistance to mycophenolic acid in human colorectal carcinoma cells.
The in vivo efficacy of the antitumor, immunosuppressive antibiotic mycophenolic acid is known to be limited by its rapid conversion to the biologically inactive 7-0-glucuronide, catalyzed by UDP-glucuronosyl transferase activity, which is widely distributed among normal tissues, including intestinal epithelium. We have found that mycophenolic acid is also converted to its glucuronide by several lines of human colorectal carcinoma cells, including HT29, Lovo, and Colo-205. In contrast, malignant cell lines not of colorectal origin, including EMT6, HeLa, and SKOV3, showed no ability to metabolize mycophenolic acid. The 7-amino derivative of mycophenolic acid was not metabolized by HT29 cells. This compound was less potent than mycophenolic acid versus EMT6 and HeLa cells but showed inhibitory activity against HT29 cells comparable with the parent antibiotic. The rapid metabolism of mycophenolic acid by HT29 cells was associated with a markedly lower sensitivity to both the antiproliferative activity of the drug and to its ability to inhibit GTP synthesis, compared with cells lacking the capacity for significant glucuronidation. After an initial decline in cellular GTP in HT29 cells induced by mycophenolic acid, there was a progressive recovery in GTP over 48 h, accompanying the metabolism of the antibiotic. This recovery process was not observed in EMT6 cells. It is suggested that glucuronosyl transferase activity may occur widely in colorectal cancer cells and could contribute to resistance to drugs that are susceptible to inactivation by glucuronide conjugation.
Animals↗
Heterochronic quantitative microevolution: dental divergence in aboriginal Americans.
Studies of tooth crown morphology alone have proven valuable in defining human population differentiation. We test the hypothesis that quantitative comparisons of more complex whole tooth structure may prove informative in understanding human diversity. Three disparate populations in Native American genetic history were compared: Kodiak Island Western Eskimos, Peruvian Inca Amerindians, and Southeast Asians. Enamel depth (an increasing gradient extended from Southeast Asians to the Inca) and root parameters were the most discriminating variables. The observed microevolution appears to result from variation in timing of known X-linked, Y-linked, and autosomal genes that affect either ameloblast or odontoblast differentiation. The dental traits were sexually dimorphic, the effect being more pronounced in aboriginal Americans, with male teeth having robust roots and thin enamel compared to female. Southeast Asians were isometrically related. The prominence of sexual dimorphism and the importance of sex-linked genes in the determination of the dental phenotypes suggest that sexual selection was one evolutionary force acting on early Asian populations. Subsequently, the selection appears to have been relaxed in Southeast Asians. Observed divergence of tooth shape among the populations, i.e., differences in the appropriation process of tooth primordia, was mainly the consequence of genetic drift modulating heterochronic regulators of homeotic genes.
Analysis of Variance↗
Overview of the regulation of metamorphosis-associated genes in Trichoplusia ni.
A review is presented of our ongoing research program on the regulation of metamorphosis-associated proteins in Trichoplusia ni. Toward the identification of mechanisms by which juvenile hormone (JH) regulates expression of metamorphosis-associated proteins, we have identified a protein that is induced by JH (juvenile hormone esterase) and a related esterase that is not JH-inducible. We have also identified three hexamerins that are suppressible by JH, and one hexamerin that is not JH-suppressible. Expression of the hexamerins is regulated at the transcriptional, translational, and posttranslational levels in T. ni. The rate of transcription of the JH esterase gene increases at the time of the prepupal peak in JH, and exogenous application of JH can cause, within 3 h, the rate of transcription to be the markedly elevated above normal. Using in vitro functional transcription assay, cell line transfection functional assay, and preliminary DNase I hypersensitive site mapping we were able to identify the functional TATA box and transcription start sites of JH-sensitive genes. These methods were also observed to be powerful in the detection of regulatory DNA motifs involved in the modulation of transcriptional activity constitutively imparted by a core promoter. The experimental systems described here will also be effective in identifying those components through which JH regulatory effects are mediated. Should JH act on the genes in a primary manner, then the transcription factor mediating that action may be the (a) JH receptor. Should the JH action be in a secondary manner, then the transcription factor(s) whose activity at the JHE gene is regulated by JH will provide the tool to track back to the location and nature of the primary JH action.
Animals↗
Prevalent vertebral deformities: relationship to bone mineral density and spinal osteophytosis in elderly men and women.
The aims of this study were to ascertain vertebral deformity prevalence in elderly men and women and to describe the association between bone mineral density (BMD) at the lumbar spine and femoral neck, severity of spinal degenerative disease and vertebral deformity prevalence. We performed standardized spinal radiographs in a random sample of 300 elderly men and women participating in the Dubbo Osteoporosis Epidemiology Study, a population-based study of fracture risk factors. Radiographs were read independently by masked observers for the prevalence of vertebral deformity and severity of osteophytosis. BMD was measured by dual-energy X-ray absorptiometry. The prevalence of vertebral deformities was critically dependent on the criterion used. The less strict criteria seemed to overestimate deformities at either end of the spine region analysed. However, irrespective of the criterion used, prevalence of deformity was higher in men than in women (25% vs 20% for the 3 SD criterion, 17% vs 12% for the 4 SD criterion and 27% vs 25% for the 25% criterion). Femoral neck BMD was more strongly associated with vertebral deformities than spinal BMD for the 25% criterion (OR/SD change in BMD 1.39 (p = 0.02) vs 1.20 (p = 0.19)), 3 SD criterion (OR/SD change in BMD 1.45 (p = 0.01) vs 1.10 (p = 0.34)) and 4 SD criterion (OR/SD change in BMD 1.98 (p = 0.0002) vs 1.68 (p = 0.008)). BMD was also more strongly associated with biconcave deformities than either wedge or crush deformities and more so in men than in women. Severity of spinal osteophytosis was not associated with vertebral deformity. In conclusion, femoral neck BMD is at least equivalent to the lumbar spine BMD in strength of association with prevalent vertebral fractures. Spinal osteophytosis falsely elevates BMD without a concomitant decrease in fracture risk, indicating that any interpretation of spinal BMD needs to be adjusted for osteophytosis. These findings support the use of femoral neck bone densitometry in older men and women. Moreover, these data indicate that current criteria for radiological assessment of vertebral deformity are sufficiently loose to include a substantial proportion of non-fractures in the elderly, with important implications for the design of clinical trials. However, irrespective of the criterion used, vertebral deformities in men are at least as common, if not more so, than in women, suggesting that vertebral osteoporotic fractures are overlooked in men.
Absorptiometry, Photon↗
Does the composition of propane-1,2-diol alter over time?
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Cryopreservation↗
Resistant starch lowers fecal concentrations of ammonia and phenols in humans.
We investigated the effect of resistant starch (RS) on markers of colonic protein metabolism. Eleven subjects participated in a randomized crossover study in which they consumed either high-RS (39 +/- 3 g/d, -chi +/- SEM) or low-RS (5 +/- 0.4 g/d) diets for 3 wk. All other macronutrients were kept constant. During the high-RS diet daily excretion of fecal nitrogen increased from 1.84 +/- 0.15 to 2.86 +/- 0.42 g/d (P < 0.01) and excretion of fecal phenols fell from 9.2 +/- 1.4 to 5.3 +/- 0.8 mg/d (P < 0.01). Fecal concentrations of ammonia decreased from 397 +/- 33 to 278 +/- 49 microgram/g (P < 0.01) and phenols decreased from 69 +/- 8 to 39 +/- 10 microgram/g (P < 0.001). Daily output of urinary ammonia, urea, phenols, and total nitrogen did not change significantly, but pH decreased from 6.4 +/- 0.1 to 6.2 +/- 0.1 (P < 0.05) during the high-RS period. These results suggest that RS significantly attenuates the accumulation of potentially harmful byproducts of protein fermentation in the human colon.
Adult↗
Injectable gold compounds: an overview.
Injectable gold compounds have enjoyed widespread, but occasionally controversial, use in rheumatoid arthritis since the 1920s. This overview examines the data from controlled trials and longer-term observational studies. We conclude that gold is equivalent to other widely used second-line agents in terms of efficacy. Toxicity profiles are similar, apart from methotrexate. It is most efficacious and toxic in the first 2 yr of treatment. There appears to be a dose-response relationship for both efficacy and toxicity. Gold is one of the few agents that decreases the rate of progression of erosions (RR 0.38, 95% CI 0.23-064). Gold compounds, therefore, have a definite place in the rheumatologist's armamentarium, but further research is required to determine optimal monitoring regimes as well as the role of maintenance therapy and combination therapy.
Antirheumatic Agents↗
Role of quasideuteron absorption in the 6Li( pi +, pp) reaction at T pi +=100, 165 MeV.
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Journal Article↗
Striking the balance: a grounded theory analysis of staff perspectives.
Staff from four units for adults with profound learning disabilities described their relationship with a particular client during individual discussions. Issues arising from discussion were elaborated in subsequent individual and group meetings, evolving into an account of interactional aspects of professional care based on a core typology of relationships (Provider, Meaning-maker, Mutual and Companion). The process of this grounded theory analysis is exemplified. The analysis concludes with four propositions about staff-client relationships, and discussion of their implications for clinical services.
Adult↗
Knowledge and conscious control of motor actions under stress.
A recent study by Masters (1992) investigated the effect of stress upon the performance of a well-learned motor skill, golf putting, acquired under implicit and explicit learning conditions. Masters found that stress had a detrimental effect on performance for the explicit learning group but not for the implicit learning group. However, the implicit learning group was required to perform articulatory suppression during the learning trials but not during the stress trials. As such, it is possible that the subjects in the implicit learning group continued to improve during the stress session simply because they were performing an easier task. This paper reports an experiment which re-examines Masters' (1992) conclusions by replicating and extending his method. An additional implicit learning group was included which was required to carry out articulatory suppression during both the learning trials and the stress trials. It was hypothesized that this 'new' implicit learning group would suffer the same disruption to performance as the explicit learning group, providing evidence which would contradict Masters' explanation. Thirty-two subjects were allocated to one of four groups. Performance measures were analysed using two-factor analysis of variance (4 x 5: groups x sessions) with repeated measures on the sessions factor. The main dependent variable was the number of putts successfully completed. The analysis revealed that both the implicit learning groups continued to improve their performance under stress whilst the explicit learning group did not. Despite limitations to both Masters' (1992) and the present study, these results add support to Masters' explicit knowledge hypothesis.
Adult↗
Concurrent validity of the MMPI-2 feminine gender role (GF) and masculine gender role (GM) scales.
Since the development of the revised Minnesota Multiphasic Personality Inventory (MMPI-2; Butcher, Dahlstrom, Graham, Tellege, & Kaemmer, 1989), no independent studies have been conducted to validate the new GF and GM scales, the only published study being based on the original standardization sample. To determine the concurrent validity of these scales, our study correlated GF and GM with scores obtained from the Bem Sex-Role Inventory, the Sex Role Behavior Scale, and the Sex Role Identity Scale. Because the sex-role literature has suggested numerous personality correlates of masculinity and femininity, the 16-PF was included to assess this dimension of the new scales, as well as measures of social desirability. Results revealed the GF and GM scales to have low internal consistency and low concurrent validity with established sex-role measures. Relative to construct validity, their patterns of correlation with personality measures suggest that GF and GM are more related to personality traits of interpersonal potency and sensitivity, respectively, than to masculinity and femininity. Overall, although the data yielded by these new scales provide additional information over Scale 5, they do not appear to hold as much promise as hoped for.
Adolescent↗
The peripheral auditory characteristics of noctuid moths: responses to the search-phase echolocation calls of bats
The noctuid moths Agrotis segetum and Noctua pronuba show peak auditory sensitivity between 15 and 25 kHz, and a maximum sensitivity of 35 dB SPL. A. segetum shows a temporal integration time of 69 ms. It is predicted that bats using high-frequency and short-duration calls will be acoustically less apparent to these moths. Short-duration frequency-modulated (FM) calls of Plecotus auritus are not significantly less acoustically apparent than those of other FM bats with slightly longer call durations, based on their combined frequency and temporal structure alone. Long-duration, high-frequency, constant-frequency (CF) calls of Rhinolophus hipposideros at 113 kHz are significantly less apparent than those of the FM bats tested. The predicted low call apparency of the 83 kHz CF calls of R. ferrumequinum appears to be counteracted by their long duration. It is proposed that two separate mechanisms are exploited by bats to reduce their call apparency, low intensity in FM bats and high frequency in CF bats. Within the FM bats tested, shorter-duration calls do not significantly reduce the apparency of the call at the peripheral level, though they may limit the amount of information available to the central nervous system.
Journal Article↗
Cigarette smoking and vertebral body deformity.
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Aged↗
Functional identification of the transcription start site and the core promoter of the juvenile hormone esterase gene in Trichoplusia ni.
The juvenile hormone (JH) esterase gene in T. ni encodes a protein that is responsible for the degradation of JH. The 5' structural characterization of this JH-sensitive gene was accomplished using reverse transcription PCR (RT-PCR) and northern analysis. The transcriptional start site of the JHE gene was biochemically determined by two methods: a 5' rapid amplification of cDNA ends (RACE) procedure which produced independent products with a sequence identical to the sequence of an exon encoded 5' to the putative first intron and by northern analysis with intronic and exonic probes. Both the transcription start site and the region containing the core promoter were also functionally identified by use of an in vitro transcription assay. The product of the in vitro transcription reaction, under the control of the putative core promoter region, initiated at the same base as identified by the RACE procedure, whether the reaction was driven by lepidopteran or by dipteran nuclear extracts. This result is the first functional identification of the core promoter region and transcription start site of any JH-sensitive gene.
Amino Acid Sequence↗