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Biomedical subjects

F Law

Publications and source records attributed to F Law.

15 recordsLinked to original sources
PubMed1995

[Peak bone mass: facts and uncertainties].

Peak bone mass, which can be defined as the amount of bony tissue present at the end of the skeletal maturation, is an important determinant of osteoporotic fracture risk in adulthood. The techniques of single or dual energy absorptiometry measure the so-called "areal" or "surface" bone mineral density (BMD), a variable which has been shown to be directly related to bone strength. During puberty the gender difference in bone mass becomes expressed. This difference appears to be essentially due to a more prolonged bone maturation period in males than in females, with a larger increase in bone size and cortical thickness, as there is no significant sex difference in the volumetric trabecular density at the end of pubertal maturation. At the beginning of the 3rd decade, there is a large variability in the normal values of areal BMD in axial and appendicular skeleton. This large variance, which is observed at sites particularly susceptible to osteoporotic fractures in adulthood, such as lumbar spine and femoral neck, is barely reduced after correction for statural height, and does not appear to substantially increase during adult life. It is generally accepted that peak bone mass at any skeletal site is attained in both sexes during the mid-thirties. However, recent studies indicate that in healthy caucasian females, bone mass accumulation can virtually be completed before the end of the second decade, for both lumbar spine and femoral neck. Several variables are supposed to influence bone mass accumulation during growth: heredity, sex, diet components, endocrine factors, mechanical forces, and exposure to risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Peak bone mass.

Peak bone mass, which can be defined as the amount of bony tissue present at the end of the skeletal maturation, is an important determinant of osteoporotic fracture risk. Measurement of bone mass development. The bone mass of a given part of the skeleton is directly dependent upon both its volume or size and the density of the mineralized tissue contained within the periosteal envelope. The techniques of single-1 and dural-energy photon or X-ray absorptiometry measure the so-called 'areal' or 'surface' bone mineral density (BMD), a variable which has been shown to be directly related to bone strength. Bone mass gain during puberty. During puberty the gender difference in bone mass becomes expressed. This difference appears to be essentially due to a more prolonged bone maturation period in males than in females, with a larger increase in bone size and cortical thickness. Puberty affects bone size much more than the volumetric mineral density. There is no significant sex difference in the volumetric trabecular density at the end of pubertal maturation. During puberty, the accumulation rate in areal BMD at both the lumbar spine and femoral neck levels increases to four- to sixfold over a 3- and 4-year period in females and males, respectively. Change in bone mass accumulation rate is less marked in long bone diaphyses. There is an asynchrony between the gain in statural height and bone mass growth. This phenomenon may be responsible for the occurrence of a transient period of a relative increase in bone fragility that may account for the pattern of fracture incidence during adolescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

The effects of diamond-like carbon coatings on macrophages, fibroblasts and osteoblast-like cells in vitro.

The elaboration of metallic and polymeric particles from the wear of joint replacement components is widely implicated in the pathogensis of aseptic loosening of these implants. Diamond-like carbon (DLC) coatings show great potential as wear-retardant coatings and may offer a possible solution to this problem. We have studied the effects of DLC coatings on cells derived from the tissues that surround a total joint replacement (macrophages, fibroblasts and osteoblast-like cells). There was no evidence that DLC coatings, deposited on a variety of different substrates, caused cytotoxicity in vitro. Cells grown on the coated substrates exhibited normal cellular growth and morphology. DLC coatings are biocompatible in vitro and should now be tested in animal models to determine their behaviour in vivo.

Animals↗
PubMed1994

Transforming growth factor-beta: a down-regulator of the parathyroid hormone-related protein receptor in renal epithelial cells.

We have recently provided evidence for the ability of transforming growth factor-beta 1 (TGF beta) to modulate PTH-related protein (PTHrP)-mediated responses in opossum kidney (OK) cells through reducing the number of PTHrP receptor-binding sites. In the present studies, we investigated the possible mechanisms by which TGF beta might regulate PTHrP receptor density in OK cells, an area that has remained largely unexplored. The steady state level of PTHrP receptor mRNA was time dependently reduced by TGF beta treatment, with the nadir (approximately 3-fold decrease) between 6-10 h, preceding the maximal inhibition on PTHrP receptor binding at 18 h. We then assessed whether the 41% reduction in binding consequent to 18-h TGF beta exposure was reversible. PTHrP-binding activity recovered considerably after 24 h (23% decrease compared with controls) and almost completely by 48 h. However, the addition of monensin or cycloheximide, but not actinomycin (at a dose effective in preventing TGF beta action in this system) during the 24-h recovery period prevented restoration of PTHrP binding. Upon removal of TGF beta, the PTHrP receptor message showed a trend toward recovery in the ensuing 24 h. Therefore, TGF beta provides an example of heterologous desensitization of the PTHrP receptor in OK epithelial cells by decreasing the expression of the receptor message. The desensitization was reversible, and the first 24-h recovery phase was dependent on synthesis and processing of new receptor proteins.

Animals↗
PubMed1993

Parathyroid hormone-related protein and calcium phosphate metabolism.

There is marked homology between the parathyroid hormone (PTH) and PTH-related protein (PTHrP) molecules at the amino terminal but the rest of the molecules are quite different, providing immunologically distinct peptides. However, they interact with the same receptor. Thus, PTHrP mediates biological actions reminiscent of PTH. PTHrP gene is a single copy gene, producing one to three mRNA transcripts through alternative splicing of the carboxy terminal, encoding peptides of 139, 141 or 173 amino acids. Having been recently isolated from malignant tumours, PTHrP is now considered to be the major mediator of humoral hypercalcaemia of malignancy (HHM). The PTH-like effects of PTHrP on the kidney and bone have been well characterized. The increase in renal tubular calcium reabsorption and the reduction in tubular phosphate reabsorption with a concomitant rise in nephrogenous cyclic AMP constitute the pathophysiological changes in the renal handling of calcium and phosphate in HHM. The osteotropic contribution to the malignant hypercalcaemia has been validated by enhanced osteoclastic bone resorption--an indirect effect of the amino terminal portion of the PTHrP molecule on osteoblasts. However, PTHrP has also been detected in a large number of normal adult tissues/organs as well as in human and animal fetuses. Fetal plasma calcium is higher than maternal and this is achieved by active transport of calcium across the placenta. Using ovine placental perfusion models, PTHrP, which is believed to originate from fetal parathyroid glands and the placenta itself, has been demonstrated to sustain this calcium gradient. Active placental transport of magnesium, but not phosphate, was also shown to be enhanced by PTHrP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Transforming growth factor-beta inhibits phosphate transport in renal epithelial cells.

The effect(s) of transforming growth factor-beta (TGF-beta) on Pi transport was investigated in confluent opossum kidney (OK) epithelial cells. TGF-beta induced a time- and concentration-dependent decrease in the initial rate of sodium-dependent Pi, but not alanine, transport. This selective inhibitory effect on Pi transport was largely reversible and was not associated with a rise in adenosine 3',5'-cyclic monophosphate production. The reduction in Pi uptake was also independent of changes in extracellular calcium concentrations and prostaglandin synthesis. TGF-beta-mediated Pi transport inhibition appeared to involve neither pertussis toxin-sensitive G protein(s) nor augmented protein kinase C activity. However, the probable role of a serine/threonine protein kinase in signal transduction was supported by the considerable attenuation of TGF-beta effect by H-7. Furthermore, the TGF-beta-induced Pi transport reduction was blunted by cycloheximide and abolished by actinomycin D. In conclusion, TGF-beta selectively inhibits the activity of the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. This action appears to be exerted via an unprecedented inhibitory pathway that might involve a serine/threonine protein kinase and alterations in the transcriptional and translational processes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Screening and psychological debriefing of adolescent survivors of life-threatening events.

There is a perceived need for schools and casualty departments to receive appropriate information and guidelines in order to minimise the effect of PTSD. A recommended screening battery for PTSD was administered at the start of a two-session debriefing group and again three months later to a group of seven young survivors of a minibus accident. No studies using this screen other than those of shipping disasters have been reported to date. Screen scores were compared with those of survivors of the cruise ship Jupiter. No significant differences were found between minibus survivors when assessed at six months (before intervention), and Jupiter survivors, who when assessed at five months had already undergone debriefing. Post-debriefing assessment of minibus survivors demonstrated significant reductions on all measures.

Adaptation, Psychological↗
PubMed1993

Transforming growth factor-beta modulates the parathyroid hormone-related protein-induced responses in renal epithelial cells.

PTH-related protein (PTHrP), the major mediator of hypercalcemia of malignancy, reduces tubular phosphate (Pi) reabsorption through its PTH-like renotropic actions. Another peptide detected in tumoral cells, transforming growth factor-beta (TGF beta), has been shown to considerably suppress the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. The unexplored interactions between TGF beta and PTHrP were examined in opossum kidney (OK) cells. Using confluent OK cells, we showed that TGF beta attenuated the inhibition of Pi transport mediated by PTHrP. Similarly, 18 h TGF beta incubation resulted in a substantial reduction of the cAMP response elicited by PTHrP without apparent involvement of pertussis toxin-sensitive guanine nucleotide binding protein(s). The number of PTHrP(1-34) binding sites in TGF beta-treated cells was decreased with the affinity unchanged. Forskolin- and prostaglandin E2-stimulated cAMP productions were not significantly altered by TGF beta treatment. Therefore, TGF beta reduced Pi transport in OK cells, modulated the actions of PTHrP, and decreased its receptor number. Whether this happens in vivo is as yet unknown.

Animals↗
PubMed1988

Failure of intraventricular gammaglobulin and alpha interferon for persistent encephalitis in congenital hypogammaglobulinaemia.

A boy with congenital hypogammaglobulinaemia died at the age of 12 years after a viral meningoencephalitis of two and a half years duration due to an untypable picornavirus. He had received intravenous immunoglobulin every four weeks from the time of the start of immunoglobulin replacement treatment at the age of 3 years. The encephalitis did not respond to high dose intravenous gammaglobulin (2500 g during 22 months). The virus could not be isolated during the administration of intraventricular immunoglobulin (38.15 g) and intraventricular recombinant alpha interferon (121 X 10(6) units), but recurred rapidly each time intraventricular treatment was stopped. Further modes of treatment are still required for prevention and treatment of this disorder.

Agammaglobulinemia↗
PubMed1988

Toxicokinetics and bioavailability of paraquat in rats following different routes of administration.

The toxicokinetics and bioavailability of [14C]paraquat were examined in rats which had received a single dose (11.6 micrograms/kg) of the herbicide by the iv, intragastric, dermal or pulmonary route. In the pulmonary route studies, rats were exposed to an aqueous solution or liquid aerosols of [14C]paraquat through a tracheal cannula or [14C]paraquat aerosols in a nose-only inhalation chamber. After intratracheal, intragastric, and dermal administration of [14C]paraquat to the rat, the average bioavailabilities were 0.45 +/- 0.22, 0.12 +/- 0.03, and 0.038 +/- 0.027, which corresponded to 20.3 nmol, 5.4 nmol and 1.7 nmol of [14C]paraquat, respectively. Since the dose administered to the rat in the [14C]paraquat aerosol studies was unknown, the bioavailability for this exposure route could not be determined. However, about 27.5 nmol of [14C]paraquat was observed into the systemic circulation of the rat after inhaling [14C]paraquat aerosols through a tracheal cannula. [14C]paraquat administered to the rat iv was eliminated from the blood with a half-life of about 68 min. Urine and feces were the major excretion routes. The radioactivity absorbed into the systemic circulation of the rat was approximately equal to that excreted in the urine; about 23.8 nmol, 8.5 nmol and 1.5 nmol of [14C]paraquat were recovered from the urine of the rat after inhalation of [14C]paraquat aerosols in a nose-only exposure chamber, intragastric injection and dermal absorption of [14C]paraquat, respectively. Tissue distribution studies showed that the bulk of the [14C]paraquat administered to the rat by the inhalation and dermal routes remained at the sites of administration.

Administration, Cutaneous↗