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Biomedical subjects

G Jones

Publications and source records attributed to G Jones.

At least 361 records · Page 20Linked to original sources
PubMed1991

Bone mass is related to creatinine clearance in normal elderly women.

We determined the relationship between bone mass and age, anthropometric variables, creatinine clearance (Ccr), and serum and urine biochemical variables in 77 normal white women (aged 41-86, mean = 67) living in their own homes. A total of 74 women were postmenopausal. Skeletal status was assessed in all subjects by x-rays of the hand with measurement of the mean combined cortical thickness (CCT) of the second metacarpal bones. In 53 women, bone mineral content of the radial shaft (RMBC) was also measured by single-photon absorptiometry (SPA) and lumbar bone mineral density (LBMD) was measured by dual-photon absorptiometry (DPA). Serum and urine biochemical variables were measured under standardized conditions on the sixth and seventh days of a controlled diet. There was a strong positive correlation between Ccr and bone mass. Although our subjects showed the expected linear decline in Ccr with age, we found that the relationship between Ccr and bone mass in the radius and lumbar spine was independent of age. On the other hand, the relationship between Ccr and CCT was not independent of age. We concluded that the relationship between Ccr and lumbar and radial bone mass is probably indicative of a relationship between glomerular filtration rate and bone mass, although this requires validation with a noncreatinine method for measurement of glomerular filtration rate. Age per se does not appear to be a cause of declining lumbar bone mass after the menopause.

Absorptiometry, Photon↗
PubMed1991

Identification of a common Plasmodium epitope (CPE) recognised by a pan-specific inhibitory monoclonal antibody.

A Plasmodium falciparum genomic expression library was screened with a monoclonal antibody produced from mice infected with Plasmodium yoelii. Eleven unique clones were isolated all of which contained the sequence NKND, IKND or KKND. This sequence was confirmed as the epitope of M26-32 by testing a series of overlapping peptides and the allowable substitutions determined by testing the binding of M26-32 to peptides containing all possible single amino acid replacements of NKND. Potential epitopes of M26-32 occur in many plasmodial proteins and this is consistent with the large number of proteins recognised in these parasites by Western blotting. Since this monoclonal antibody shows marked in vitro inhibition of P. falciparum growth, these data suggest that an anti-malarial vaccine may be produced by targeting such common plasmodial epitopes without necessarily identifying the corresponding antigens.

Amino Acid Sequence↗
PubMed1991

Flow cytometric evaluation of hypoxic cells in solid experimental tumours using fluorescence immunodetection.

Numerous methods have been proposed for the detection of hypoxic cells using nitroimidazoles labelled with both radioactive and stable isotopes where the isotopic label becomes bound as a result of reductive metabolism of the nitro group. A new probe for hypoxia, 7-(4'-(2-nitroimidazol-l-yl)-butyl)-theophylline, is described where an immunologically recognisable hapten (theophylline) is covalently linked to a 2-nitroimidazole. Bioreduction of the nitroimidazole leads to binding of bioreductive metabolites, and hence the theophylline side-chain, to intracellular molecules. Immunochemical procedures are then used to stain cells containing the bound theophylline using an FITC-conjugated anti-serum. Flow cytometric analysis of stained cells is facilitated by co-staining cellular DNA, which allows discrimination of single cells in the sample and rejection of cell clumps and debris. The alternative use of an immunoperoxidase-conjugated anti-serum has been used to demonstrate the localisation of hypoxic cells in frozen tumour sections.

Animals↗
PubMed1991

Dietary phosphate deprivation increases renal synthesis and decreases renal catabolism of 1,25-dihydroxycholecalciferol in guinea pigs.

In guinea pigs, dietary phosphate deprivation decreases plasma phosphate concentration, increases plasma 1.25-dihydroxycholecalciferol [1,25-(OH)2D3] concentration and causes hypercalcemia concurrent with the maximal increase in plasma 1,25-(OH)2D3 levels. Our objective was to determine whether increased synthesis or decreased catabolism contributed to the elevation in plasma 1,25-(OH)2D3. Preliminary experiments using renal mitochondria from guinea pigs fed a control diet revealed that 23,25-dihydroxycholecalciferol [23,25-(OH)2D3], not 24,25-dihydroxycholecalciferol [24,25-(OH)2D3], was the reciprocal side-chain metabolite to 1,25-(OH)2D3 in this species. An assay employing guinea pig renal mitochondria was used to measure the renal synthesis of 1,25-(OH)2D3 and 23,25-(OH)2D3 from [3H]25-OH-D3. These metabolites were unequivocally identified by combinations of HPLC, ultraviolet spectrophotometry and mass spectrometry. This renal mitochondrial assay was subsequently used to investigate the effect of dietary phosphate deprivation on guinea pig vitamin D metabolism. Within 1 wk the rate of synthesis of 1,25-(OH)2D3 was maximal in phosphate-deprived guinea pigs. This rate was significantly (P less than 0.005) higher than that achieved in same-day control guinea pigs. Conversely, within 1 d the synthesis of 23,25-(OH)2D3 was significantly (P less than 0.005) decreased in phosphate-deprived guinea pigs. Similarly, the rate of 1,25-(OH)2D3 metabolism was decreased within 1 d of dietary phosphate deprivation and was at a minimum within 1 wk. This rate was significantly (P less than 0.005) less than that attained in same-day control guinea pigs. These results suggest that both increased synthesis and decreased metabolism of 1,25-(OH)2D3 contribute to the plasma 1,25-(OH)2D3 elevation that occurs in response to dietary phosphate deprivation.

Animals↗
PubMed1991

Newly synthesized glycoconjugates from two cell lines derived from rat osteogenic sarcoma: effects of Matrigenin activity from bone.

An activity isolated from bovine bone was previously shown to stimulate proteoglycan synthesis by several connective tissue cell lines from normal tissues (Matrigenin activity). The effect of this activity on glycoconjugate synthesis by two osteoblastic cell lines, ROS 17/2 and UMR-106, derived from rat osteogenic sarcoma, was examined after labelling of the cells with [3H]glucosamine and [35S]sulfate. The glycoconjugates from the cell layers and the media were separated by DEAE-Sephacel chromatography and the anionic glycoconjugates of the media were further analyzed by chromatography on Sepharose CL-2B and enzymatic digestion of the papain-released glycosaminoglycans. The ROS 17/2 cells secreted at least two distinct species of proteoglycan (one heparan sulfate rich and the other chondroitin sulfate rich), whereas the UMR-106 secreted primarily an anionic glycoprotein. The addition of Matrigenin activity to the ROS 17/2 cells resulted in stimulation of incorporation of radioactivity into the proteoglycan and hyaluronic acid, but in UMR-106 cultures it resulted in decreased incorporation into the anionic glycoprotein. The decrease in incorporation into the anionic glycoprotein from the medium was shown, by alkaline beta-elimination, to have occurred mainly in the oligosaccharide fraction, relative to control cultures.

Animals↗
PubMed1991

Further purification and characterization of newly synthesized anionic glycoconjugates secreted by cultured UMR-106 cells: evidence that the major anionic glycoconjugate secreted by these cells is similar to bone sialoprotein II.

Following incubation of UMR-106 cells for 48 h in the presence of [3H]glucosamine and [35S]sulfate, the newly synthesized anionic glycoconjugates were isolated from the culture medium by cetylpyridinium chloride/ethanol precipitation and further separated by DEAE-Sephacel chromatography into two radiolabelled fractions, a major component, UM I, and a minor component, UM II. UM I appeared to be homogeneous as shown by Sepharose CL-4B chromatography under dissociative conditions, and SDS-polyacrylamide gel electrophoresis. It showed a molecular mass of approximately 93 kDa on 4-15% gels. UM I was partially degraded by brief treatment with trypsin, releasing a small, terminal peptide that contained 47.6% of 35S but no 3H. Treatment of UM I with neuraminidase and 0.1 N H2SO4 (1 h at 80 degrees C), respectively, released 27% 3H and 38.4% 3H plus 41% 35S, suggesting the presence of a significant number of sialic acid residues, as shown by Sephadex G-50 chromatography of the digests. Amino acid analysis showed that the UM I glycoconjugate was rich in acidic amino acids (12.6% aspartic acid and 21.2% glutamic acid residues) and its N-terminal sequence was Phe-Ser-Met-Lys-Asn-Phe-, which is identical to the published N-terminal amino acid sequence of rat bone sialoprotein II. Keratanase treatment of UM I released 26% of the incorporated radioactivity, suggesting the presence of keratan sulfate chains. UM II contained a chondroitinase ABC-sensitive proteoglycan.

Amino Acid Sequence↗
PubMed1991

Methotrexate-induced asthma.

A patient with rheumatoid arthritis developed pulmonary symptoms and function test abnormalities consistent with asthma during methotrexate therapy. Assessments of airway responsiveness to methacholine during therapy revealed airway hyperreactivity that reverted to normal when the methotrexate was stopped. An extension of the methotrexate dosage interval from 7 to 10 days resulted in an abolition of the asthma, which remained in remission despite a return to a weekly cycle after a 3-month period of 10-day cycles.

Asthma↗
PubMed1990

Delayed detection of congenital hearing loss in high risk infants.

OBJECTIVE: To examine the methods used to investigate children at high risk of congenital hearing impairment, and to see whether the introduction of evoked response audiometry has reduced the mean age at which hearing loss is identified. DESIGN: Clinicians who notified children to the national congenital rubella surveillance programme were asked retrospectively to complete a questionnaire examining the methods used to identify hearing impairment and the age at testing in two consecutive five year cohorts. The presence or absence of hearing loss was confirmed by obtaining the results of audiometric evaluations and, whenever possible, a recent pure tone audiogram. SETTING: The United Kingdom. PATIENTS: Children notified to the national congenital rubella surveillance programme and born in 1978-87 in whom IgM specific for rubella was detected shortly after birth. MAIN OUTCOME MEASURES: The age at which hearing loss was identified and the degree of loss in decibels at 250, 500, 1000, 2000, and 4000 Hz measured by pure tone audiometry. RESULTS: 61 (52%) Of 117 children born in 1978-82 had a hearing impairment of 40 dB or greater in both ears. The mean loss was 93 dB. In the following five years 75 (47%) of 159 children had impaired hearing, their mean loss being 96 dB. The age at which the hearing loss was confirmed decreased from 11.6 to 9.8 months as a result of earlier auditory evoked response testing. Nevertheless, only eight (13%) of the children with hearing impairment born in 1978-82 and 16 (21%) of those born in 1983-7 had these tests performed in the first six months of life. CONCLUSIONS: Unacceptable delays in identifying hearing loss occurred in this high risk group because of failure to arrange auditory evoked response testing in early infancy. Evoked response audiometry is sensitive and specific and should be undertaken within the first few months of life for all infants known to be at risk of sensorineural hearing loss.

Age Factors↗
PubMed1990

Metabolism of a cyclopropane-ring-containing analog of 1 alpha-hydroxyvitamin D3 in a hepatocyte cell model. Identification of 24-oxidized metabolites.

MC969 is an analog of the calcemic drug 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) in which carbons 25,26, and 27 in the side chain are incorporated into a cyclopropane ring. Metabolites of MC 969 were generated in an in vitro human hepatocyte cell model, Hep 3B. The identity of the metabolites was established by comigration on HPLC with authentic standards, and by mass spectrometry of native and chemically modified metabolites. Unequivocal identification of the 24-keto- and the two epimeric 24-alcohol metabolites is provided. No 25-hydroxylated metabolites were detected. In competition studies, MC 969 was able to inhibit 25-hydroxylation of tritiated vitamin D3 more effectively than 1 alpha-OH-D3 itself, indicating that the vitamin D3-25-hydroxylase may be responsible for generation of one or more of the metabolites observed.

Cell Line↗
PubMed1990

Molecular cloning, regulation, and complete sequence of a hemocyanin-related, juvenile hormone-suppressible protein from insect hemolymph.

A cDNA library was prepared from mRNA isolated from the lepidopteran Trichoplusia ni during larval-pupal metamorphosis. Differential probing was used to identify clones for mRNAs which are suppressible by exogenous juvenile hormone treatment. In vitro transcribed cRNAs from these clones were translated in vitro and challenged with antiserum specific for a known acidic, juvenile hormone-suppressible hemolymph protein (AJSP-1) that is associated with larval metamorphosis. Three clones were found which encoded immunoreactive translation products; their identity was confirmed by comparison of the N-terminal sequence of the mature AJSP-1 protein with the cDNA sequence. As inferred from the cDNA sequence, the protein encompasses 704 amino acid residues, including a N-terminal signal peptide; widely distributed as well as more localized stronger sequence similarities indicate that the protein is distantly related to hemocyanins and hemocyanin-like insect proteins. However, on the basis of amino acid sequence and composition, immunological reactivity, and hormonal sensitivity, the protein is distinct from previously described insect proteins. Its juvenile hormone suppressibility can be ascribed to suppression of the mRNA. RNA blot analysis using the cloned cDNA as a probe demonstrated that the transcript (approximately 2.8 kilobases) is of very low abundance during the penultimate stadium but becomes very abundant during the last larval stadium, when juvenile hormone rapidly declines. Furthermore, treatment of larvae with a juvenile hormone analog strongly suppresses the abundance of the message.

Amino Acid Sequence↗
PubMed1990

Glycosylation and isoform variation of juvenile hormone esterase in the fat body and hemolymph during metamorphosis of Trichoplusia ni (Lepidoptera).

Two major isoforms of juvenile hormone esterase (JH esterase) from metamorphosing larvae of Trichoplusia ni were characterized with respect to isoform variation, glycosylation (lectin reactivity) and hormonal induction. Both forms are similarly inducible by juvenile hormone, and both become similarly glycosylated, as measured by concanavalin A binding. In prepupae, synthesis of new JH esterase from a low baseline and glycosylation within fat body are limiting steps in modulation of the level of JH esterase in the hemolymph. In contrast, during the pupal stage regulation of hemolymph JH esterase activity changes to a level other than synthesis of new enzyme or its glycosylation.

Animals↗