PubMed Health⌕ Search

Biomedical subjects

S J Jones

Publications and source records attributed to S J Jones.

At least 19 recordsLinked to original sources
PubMed1995

Characterization of the let-653 gene in Caenorhabditis elegans.

A mutation in the let-653 gene of Caenorhabditis elegans results in larval death. The lethal arrest is concurrent with the appearance of a vacuole anterior to the lower pharyngeal bulb. The position of the vacuole is consistent with a dysfunction of the secretory/excretory apparatus. Germline transformation rescue experiments were able to position the let-653 gene to two overlapping cosmid subclones. Sequence data generated from both cDNA and genomic DNA subclones indicated that let-653 encodes a mucin-like protein. Our characterization suggests that a mucin-like protein is essential for effective functioning of the secretory/excretory apparatus within C. elegans.

Amino Acid Sequence↗
PubMed1995

The rate of osteoclastic destruction of calcified tissues is inversely proportional to mineral density.

This study examined the relative ease with which three dissimilar mineralized tissues from one individual organ were resorbed by osteoclasts in vitro. Cells released from the long bones of prehatch chicks by agitating fragments of the chopped bones in medium were cultured for 24 hours on slices cut from an Elephas maximus molar so that enamel, dentine, and coronal cementum were present in bands on the surface of the slice. The resultant pits were measured using a video-rate, line-confocal reflection light microscope system. Variations in tissue mineralization were characterized by analysis of digital backscattered electron images. The enamel pits were smaller than the dentine and the cementum pits, but the dentine and cementum pits were not significantly different from each other. The sizes of the pits correlated with the relative mineral densities of the three tissues, showing that the rate of osteoclastic destruction of calcified tissues is inversely proportional to mineral density. This indicates that the initial step in osteoclasis, the removal of the mineral phase, determines the volume removed and is the rate-limiting step.

Animals↗
PubMed1995

Volumes of chick and rat osteoclasts cultured on glass.

We have examined the relationship between the number of nuclei of an osteoclast and its volume. Chick and rat cells were released from long bones by chopping the shafts and flushing the fragments in Eagle's Minimum Essential Medium with added 10% fetal calf serum. The bone cell suspension was seeded onto glass coverslips. In Experiment 1, rat and chick cells were allowed to settle for 15 minutes, more medium was then added, and the cells were cultured in 5% CO2 at 37 degrees C for 4 hours. In Experiment 2, only rat cells were used, and the cells were cultured in the presence or absence of 10(-6) M 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) in the medium for 4 or 6 hours. The coverslips were washed in 37 degrees C phosphate-buffered saline and fixed for 24 hours in 2.5% glutaraldehyde in isotonic cacodylate buffer (initially 37 degrees C). The chick cells were critical point dried (CPD) or freeze dried (FD); all rat cells were FD. After drying, cells were coated with gold by vacuum evaporation. The volumes and areas of osteoclasts were measured using a video-rate, line-confocal reflection laser scanning microscope and the number of nuclei in each cell was counted. The volumes and volumes per nucleus of the FD cells were larger than those of the CPD cells but there was no significant difference in plan-areas. Rat osteoclasts were larger than chick cells in all the measured parameters except the mean number of nuclei/cell. The correlation coefficients for the areas, volumes, and the numbers of nuclei for rat and chick cells were all high (r > 0.725). The volumes and volumes per nucleus, but not the areas or areas per nucleus, of the osteoclasts cultured with APD were significantly smaller than control cells. We conclude that FD causes less shrinkage than CPD; chick osteoclasts are about two-thirds the size of rat osteoclasts; and 10(-6) M APD caused a reduction of rat osteoclast volume and volume per nucleus of 21%.

Animals↗
PubMed1995

Clinical evaluation of VEPs to interleaved checkerboard reversal stimulation of central, hemi- and peripheral fields.

The VEPs of 195 patients referred for supportive evidence of multiple sclerosis or optic neuritis were studied by a new method of interleaved checkerboard reversal stimulation of different areas of the visual field. In the first group of 95 patients checks of 40' subtense reversed in the whole field (28 degrees x 20 degrees), alternatively in the left and right hemifields and alternately in the central (5 degrees radius) and peripheral fields. In the second group of 100 patients checks reversed in the whole field and in interleaved mode in 3 visual field areas, comprising the central (4 degrees radius) and left and right hemisurround fields. In the first group abnormal responses were recorded from 52 eyes and there was partial disagreement among the stimulus conditions in 10 of the 52. Abnormalities were seen uniquely to central field stimulation in 3 eyes but never to whole field stimulation alone. In the second group abnormal responses were recorded in 58 eyes, again never uniquely to whole field stimulation, while abnormalities confined to one or two areas of the visual field were seen in 24, providing evidence of peripheral field involvement alone in 8 eyes. In the first group, waveforms created from the sum of the left and right hemifield and central and peripheral field responses showed quite close conformity to the whole field VEP, although amplitudes were significantly lower and latencies significantly shorter. In 7 eyes responses would have been differently classified (normal or abnormal) using the sum as compared with the whole fields.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

An update and lessons from whole-genome sequencing projects.

A number of prokaryotic and eukaryotic genomes are currently being sequenced. Already, the nucleotide sequences of four yeast chromosomes and of 2.2 Mb from Caenorhabditis elegans have been reported. Human genomic sequences have also been used in comparative studies with both mouse and Fugu rubripes.

Animals↗
PubMed1995

Mineral density quantitation of the human cortical iliac crest by backscattered electron image analysis: variations with age, sex, and degree of osteoarthritis.

Bone samples from the rim of the iliac crest were obtained at autopsy from 59 patients aged 23 to 75 years, of whom 10 men and 10 women aged 50-75 years had osteoarthritis diagnosed by hand X-rays. An equal number in the same age group and 10 men and 9 women aged less than 50 years were without osteoarthritis. After embedding the bone in PMMA, the blocks were cut, polished, and coated with carbon. The fractions of bone falling within four consecutive bands of signal level were derived from digital backscattered electron imaging. Normal males had more low and medium density bone and normal females more very high density phase tissue proportionately. In both male and female osteoarthritis cases, low and medium fractions were low. The very high density fraction was mainly calcified fibrocartilage; when it was excluded from the calculations, the low, medium, and high phases occurred equally in normal males but increased stepwise in normal females and in osteoarthritis cases of both sexes. The results suggest a lower rate of bone renewal in females than males, and in male osteoarthritis subjects than normal males. An increased proportion of bone of high density would reduce the quality of the bone by increasing its stiffness.

Adult↗
PubMed1995

Bactericidal/permeability-increasing protein (BPI) is an important antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in vasculitis.

Indirect immunofluorescence (IIF) techniques have shown that ANCA are useful serological markers for some small vessel vasculitides, and ELISA assays, using purified molecules as solid-phase ligand, have helped to identify proteinase 3 (PR3) and myeloperoxidase (MPO) as two of the major ANCA antigens. There remain a substantial number of serum samples, which are positive by IIF, yet recognize neither PR3 nor MPO (double-negative samples). We found, by Western blot analysis of soluble neutrophil granule proteins, that certain of these double-negative samples recognized a 55-kD doublet of which the first eight residues shared N-terminal amino acid sequence homology with BPI, a potent antibiotic towards Gram-negative bacteria. We developed a simple, quick and robust two-step immunobiochemical method to purify BPI. This was then employed to detect anti-BPI autoantibodies by ELISA and Western blot analysis. We tested 100 double-negative samples and 400 consecutive new samples sent for routine ANCA testing in the anti-BPI ELISA. We found that 45 of the 100 double-negative and 44 of the 400 new routine samples recognized BPI. By Western blot analysis 20/20 positive anti-BPI samples blotted the 55-kD protein. Inhibition assays confirmed the specificity of binding. Review of the 89 anti-BPI-positive patients showed a male dominance (M:F ratio 55:34), a mean age of 60.4 years and clinical diagnoses ranging from organ limited vasculitis to widespread systemic vasculitis.

Adolescent↗
PubMed1995

Visual evoked potentials in phenylketonuria: association with brain MRI, dietary state, and IQ.

At separate institutions, pattern reversal visual evoked potentials (VEPs) were recorded in children and older patients with phenylketonuria and compared with MRI of the brain. In nine patients aged less than 14 years, who were still on a diet low in phenylalanine, VEPs were clearly abnormal in only one and the abnormalities seen on MRI were mild. In 27 patients aged 14-31 years VEPs were abnormal in more than 80%, with significant reduction of amplitude and prolongation of latency despite the general absence of visual symptoms and abnormalities on routine neuro-ophthalmological examination. Among the older patients there was no significant correlation between VEP measures and plasma phenylalanine or tyrosine concentrations; neither was the incidence of VEP abnormalities dependent on whether or not the patients were still on a low phenylalanine diet. Some VEP amplitude measures were inversely correlated with the MRI lesion score, perhaps reflecting the severity of white matter abnormalities in the parieto-occipital region. In the older patients the amplitude of VEPs to stimulation of the central 8 degrees of the visual field was significantly correlated with IQ. The study confirms the high incidence of subclinical visual pathway involvement in older children and adults with phenylketonuria, and suggests the possibility of a link between the abnormal appearance of subcortical white matter on MRI and a physiological index of function of the CNS. As there was no evidence of general intellectual decline, it is suggested that the correlation between central field VEP amplitude and IQ may reflect abnormal development during infancy. Abnormalities on MRI, on the other hand, seem to be more closely related to current dietary state and phenylalanine concentration.

Adolescent↗
PubMed1995

Effects of ethanol on bone cells in vitro resulting in increased resorption.

Abuse of alcohol has been found to be an important risk factor for fractures and osteoporosis, and tissue culture experiments have indicated that low concentrations of ethanol can affect bone formation and resorption. This study investigated direct effects of ethanol on bone cells using an in vitro resorption assay. Osteoclasts from long bones of 19-day prehatch chicks were seeded onto slices of dentine and cultured with control medium alone, or medium containing 0.001%, 0.01% or 0.1% ethanol, at 37 degrees C with 5% CO2 for 24 h before being removed. The volumes and areas of resorption pits made in the dentine were measured using confocal laser reflection microscopy (Lasertech 1LM21 system) and the pits counted. An increase in the pit numbers and mean pit areas, volumes and volume/area ratios was observed with 0.001% and 0.01% ethanol, with a dose-related, bell-shaped curve of resorption. Greatest mean volume resorbed per pit (p < 0.05), mean area resorbed per pit (p < 0.01) and number of pits was at 0.01% ethanol. Volume/area (mean depth) per pit was greatest at 0.001% ethanol (p < 0.05). This study has shown that ethanol, even at blood concentrations experienced by the social drinker, has an immediate direct effect on bone cells in vitro, resulting in increased resorption by osteoclasts.

Animals↗
PubMed1994

Inhibition of bone resorption by selective inactivators of cysteine proteinases.

Inactivators of cysteine proteinases (CPs) were tested as inhibitors of bone resorption in vitro and in vivo. The following four CP inactivators were tested: Ep475, a compound with low membrane permeability which inhibits cathepsins B, L, S, H, and calpain; Ep453, the membrane-permeant prodrug of Ep475; CA074, a compound with low membrane permeability which selectively inactivates cathepsin B; and CA074Me, the membrane-permeant prodrug of CA074. The test systems consisted of 1) monitoring the release of radioisotope from prelabelled mouse calvarial explants and 2) assessing the extent of bone resorption in an isolated osteoclast assay using confocal laser microscopy. Ep453, Ep475, and CA074Me inhibited both stimulated and basal bone resorption in vitro while CA074 was without effect; the inhibition was reversible and dose dependent. None of the inhibitors affected protein synthesis, DNA synthesis, the PTH-enhanced secretion of beta-glucuronidase, and N-acetyl-beta-glucosaminidase, or the spontaneous release of lactate dehydrogenase. Ep453, Ep475, and CA074Me dose-dependently inhibited the resorptive activity of isolated rat osteoclasts cultured on bone slices with a maximal effect at 50 microM. The number of resorption pits and their mean volume was reduced, whilst the mean surface area remained unaffected. Again, CA074 was without effect. Ep453, Ep475, and CA074Me, but not CA074, when administered subcutaneously at a dose of 60 micrograms/g body weight inhibited bone resorption in vivo as measured by an in vivo/in vitro assay, by about 20%. This study demonstrates that cathepsins B, L, and/or S are involved in bone resorption in vitro and in vivo. Whilst cathepsin L and/or S act extracellularly, and possibly intracellularly, cathepsin B mediates its effects intracellularly perhaps through the activation of other proteinases involved in subosteoclastic collagen degradation.

Animals↗
PubMed1994

Simulation of bone resorption-repair coupling in vitro.

In the normal adult human skeleton, new bone formation by osteoblasts restores the contours of bone surfaces following osteoclastic bone resorption, but the evidence for resorption-repair coupling remains circumstantial. To investigate whether sites of prior resorption, more than the surrounding unresorbed surface, attract osteoblasts or stimulate them to proliferate or make new matrix, we developed a simple in vitro system in which resorption-repair coupling occurs. Resorption pits were produced in mammalian dentine or bone slabs by culturing chick bone-derived cells on them for 2-3 days. The chick cells were swept off and the substrata reseeded with rat calvarial osteoblastic cells, which make bone nodules in vitro, for periods of up to 8 weeks. Cell positions and new bone formation were investigated by ordinary light microscopy, fluorescence and reflection confocal laser microscopy, and SEM, in stained and unstained samples. There was no evidence that the osteoblasts were especially attracted to, or influenced by, the sites of resorption in dentine or bone before cell confluence was reached. Bone formation was identified by light microscopy by the accumulation of matrix, staining with alizarin and calcein and by von Kossa's method, and confirmed by scanning electron microscopy (SEM) by using backscattered electron (BSE) and transmitted electron imaging of unembedded samples and BSE imaging of micro-milled embedded material. These new bone patches were located initially in the resorption pits. The model in vitro system may throw new light on the factors that control resorption-repair coupling in the mineralised tissues in vivo.

Animals↗
PubMed1994

Peptone, a low-cost growth-promoting nutrient for intensive animal cell culture.

The effect of addition of peptone to serum-free and serum supplemented media for the growth of hybridoma cells in various systems was studied. Supplementation of defined medium with either proteose peptone or meat peptone resulted in significant increases in cell number and specific monoclonal antibody production in batch culture system. Other peptones were either inactive or less effective. In continuous culture, using medium supplemented with new born calf serum, the addition of peptone resulted in 125% and 150% increases in cell and antibody concentrations respectively. Similar increase in cell number (128%) was also obtained in spin-filter perfusion culture when medium was supplemented with peptone. By comparison, the substitution of a defined 1 x MEM amino acids mixture resulted in only a 50% increase. At higher perfusion rates the cell number maintained in steady state using peptone supplement could be increased to 1.3 x 10(7) cells ml-1 while the serum concentration was reduced from 5% to 1% at a perfusion rate of 2.5 volumes per day.

Animals↗
PubMed1994

Effects of age on the ability to remember common and rare proper names.

Difficulties in remembering proper nouns increase with age. One factor is that names are arbitrary labels. Another is that because many people share the same names, mutual discriminability between names is less than than that between other words. Discriminability between names may reduce as the number of acquaintances increases. Also, most people have both a first and a second name. These have to be learned as a pair, but they may be of unequal distinctiveness and so be unequally well remembered. An experiment was designed to evaluate the relative effects of distinctiveness of first and second names on free and cued recall. Subjects (aged 60-69 or 70-79 years, matched on Mill-Hill vocabulary score) were asked to remember one of four lists of 16 names. Each was presented four times. The names were either common, rare, or a combination of the two--a common first name with a rare surname, or vice versa. Subjects first freely recalled the names. They were next cued by either first name or surname to recall the remaining half of name pairs. Interactions between effects on recall of subjects' ages and of the relative distinctiveness of first and second names provide partial support for a model incorporating "relative distinctiveness" as a factor in failures of name recall in old age.

Age Factors↗
PubMed1994

Erectile dysfunction in multiple sclerosis. Associated neurological and neurophysiological deficits, and treatment of the condition.

Forty-eight men with multiple sclerosis and erectile dysfunction were evaluated. Emphasis was placed on the neurological features and the relationship between impotence and the bladder dysfunction in multiple sclerosis. Erectile failure was invariably associated with pyramidal signs in the lower limbs and with urinary symptoms. All of the men with impotence and marked pyramidal dysfunction in their legs were found by cystometric studies to have bladder hyperreflexia. The severity of the urinary symptoms was related to the degree of pyramidal impairment in the lower limbs. The posterior tibial and the pudendal cortical evoked potentials were abnormal in most of the men with multiple sclerosis and erectile failure. However, recording the pudendal cortical responses in patients with multiple sclerosis and impotence provided no more information than the tibial cortical evoked potentials. The neurological examination findings together with the results of the neurophysiological and cystometric tests suggest that erectile dysfunction in multiple sclerosis is due to spinal lesions situated proximal to the sacral cord. The feasability of papaverine intracorporeal injection therapy for men with multiple sclerosis and impotence was assessed. Papaverine intracorporeal injections produced satisfactory erections in the majority of the impotent men. Erectile failure in patients with multiple sclerosis was successfully managed for up to 2 years, by intracorporeal self-injection therapy.

Adult↗
PubMed1994

Temporal response of rabbits to beta-adrenergic agonist feeding: tissue weight, calpains and calpastatin activities, and nucleic acid and protein concentrations.

Forty-eight crossbred rabbits were used in three replications of a 2 x 4 factorial arrangement to investigate the short-term responses of tissue accretion, calpains and calpastatin activity, and nucleic acid and protein concentrations to beta-adrenergic agonist (BAA) feeding. Rabbits were fed a 17% CP diet with or without 7 ppm of L644,969 and slaughtered after 1, 4, 8, or 16 d of treatment. Empty body dressing percentage and biceps femoris weight (as a percentage of empty body weight [EBW]) were significantly higher in the treated rabbits than in the controls after 16 d of treatment. Heart and liver weights (as a percentage of EBW) were higher (P < .05) after 1 d and liver weight (as a percentage of EBW) was lower (P < .05) after 16 d in treated vs controls. Except for an elevation of skeletal muscle m-calpain after 16 d, BAA-supplementation did not affect the calpain-calpastatin system. Muscle RNA concentrations and RNA:DNA ratios were higher (P < .05) in treated rabbits after 1 d and remained higher thereafter. Protein:RNA ratios were lower (P < .01) in treated than in control rabbits after 4 d and remained lower throughout the trial. Muscle DNA content was lower after 4 d and higher after 16 d; RNA content was higher after 4, 8, and 16 d; and protein content was higher after 16 d in treated vs control rabbits. Liver nucleic acid and protein concentrations were not affected by BAA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1993

Effects over time of feeding a beta-adrenergic agonist to wether lambs on animal performance, muscle growth, endogenous muscle proteinase activities, and meat tenderness.

Forty wether lambs were used in a 2 x 4 factorial arrangement to determine the response of animal performance, muscle growth, proteinase activity, and meat tenderness to beta-adrenergic agonist (BAA) supplementation. Lambs were fed a finishing diet with or without 4 ppm of L644,969 and slaughtered after 0, 2, 4, and 6 wk of treatment. The ADG was higher (P < .05) in the treated than in the control lambs after 2 wk and returned to control levels thereafter. Semitendinosus weight and calpastatin activity were higher and mu-calpain activity was lower in the treated than in the control lambs after 2, 4, and 6 wk. Cathepsin B activity was higher (P < .01) and cystatin-like activity was lower (P < .05) after 2 wk in treated than in control lambs but returned to control levels thereafter. Longissimus protein:DNA was higher after 4 (P < .05) and 6 (P < .01) wk in the treated lambs than in the controls. The concentration of RNA and RNA:DNA ratio were higher (P < .01) in the longissimus and semitendinosus muscles in the treated lambs after 2 wk and remained higher throughout the study. Semitendinosus protein and RNA content were higher after 2, 4, and 6 wk and DNA content was higher after 2 and 6 wk in the treated than in the control lambs. Longissimus shear-force values were higher (P < .001) in the treated than in the control lambs at all slaughter end points. These data indicate a rapid alteration of muscle growth, activity of the calpain-calpastatin system, and meat tenderness during BAA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗