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J Hardy

Publications and source records attributed to J Hardy.

At least 199 records · Page 11Linked to original sources
PubMed1998

Vascular and transsynovial forces of the isolated stationary equine joint.

OBJECTIVE: To provide quantitative assessment of forces affecting filtration of synovial fluid in response to incremental changes in arterial and venous hemodynamics. ANIMALS: 7 clinically normal adult horses. PROCEDURE: Using a stationary, isolated metacarpophalangeal joint preparation, blood flow (Qa[cir]), tissue perfusion, arterial pressure (Pa[cir]), venous pressure (Pv[cir]), transsynovial fluid flow, total vascular resistance, vascular compliance, and tissue compliance were evaluated before and after arterial and venous pressure manipulations. At isogravimetric conditions, pre- and postcapillary resistance and ratios, osmotic reflection coefficient (sigma[d]), capillary pressure, net filtration pressure, and transitional microvascular pressure were determined. RESULTS: Synovial tissue blood flow was similar before, immediately after, and 3.5 hours after joint isolation. The sigma(d) for the joint was low, owing to the high oncotic pressure of synovial fluid at filtration-independent states. Transsynovial flow occurred in preference to lymph flow because of the high permeability of synovial tissue (low sigma[d]). Synovial fluid production and transfluid flow (synovium weight gain) increased at Pa(cir) > 200 mm of Hg, indicating a threshold phenomenon for synovial filtration. Net filtration pressure > 6 mm of Hg is needed to effect an increase in synovial fluid flow, and pressure of approximately 11 mm of Hg is necessary to increase lymphatic flow. Vascular compliance in the joint was low, but increased markedly with Pv(cir). Vascular and tissue compliance increased with increased Pa(cir). Vascular compliance changes caused by increased arterial pressure were minimal, compared with those caused by increased venous pressure owing to the greater elastance of arteries and the larger muscular arterial wall. CONCLUSION: This isolated joint preparation permitted evaluation of codependent hemodynamic, microvascular, and transsynovial flow responses to hemodynamic manipulations. Synovial tissue permeability was markedly affected by increased vascular forces altering filtration pressures toward synovial fluid production.

Animals↗
PubMed1998

Local hemodynamics, permeability, and oxygen metabolism during acute inflammation of innervated or denervated isolated equine joints.

OBJECTIVES: To determine oxygen metabolism, permeability, and blood flow in isolated joints in response to interleukin 1beta (IL-1beta) and contribution of innervation. SAMPLE POPULATION: One metacarpophalangeal (MCP) joint of 24 adult horses. PROCEDURE: The MCP joint was isolated for 6 hours in a pump-perfused, auto-oxygenated, innervated or denervated preparation. Isolated joints were assigned to the following 4 groups: control, control-denervated, inflamed, and inflamed-denervated, and inflammation was induced by intra-articular injection of IL-1beta. Circuit arterial and venous pressures, flows, and blood gas tensions, synovial fluid production, and intra-articular pressure were measured. Total vascular resistance; oxygen delivery, consumption, and extraction ratio (ER); and permeability surface area product were calculated. Synovial membrane blood flow was determined at 0, 60, and 330 minutes. Synovial membrane wet-to-dry ratio was obtained, and permeability to macromolecules was determined by intra-articular injection of Evans blue albumin and fluorescein isothiocyanate-conjugated dextran. RESULTS: Oxygen delivery and synovial membrane blood flow progressively increased but were not different among groups. Oxygen consumption and ER significantly increased in inflamed joints, as did intraarticular pressure and synovial fluid production. Inflamed joints had greater wet-to-dry ratio. Albumin permeability significantly increased in the villous synovial membrane of the inflamed groups, and dextran permeability was increased in the innervated groups, with a trend toward increased permeability in inflamed groups. CONCLUSION: Inflammation significantly increased oxygen demand, which was initially met by increased ER. Permeability to small molecules was increased with inflammation; innervation increased permeability to large molecules. Use of an isolated joint model enabled documentation of the physiologic responses of the joint to acute inflammation.

Albumins↗
PubMed1997

Association between the low density lipoprotein receptor-related protein (LRP) and Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting elderly people. It usually occurs after 65 years old (late-onset AD). The epsilon4 allele of apolipoprotein E (APOE) gene is a risk factor which contributes about 50% of the genetic risk for this form of the disease. The low density lipoprotein receptor-related protein (LRP) is a major receptor for APOE which is found in the senile plaques of AD brains. This makes it a good candidate gene for the disease. There is a polymorphism in the region upstream of the LRP gene that has been associated with AD in an American population. We examined this polymorphism by restriction fragment length polymorphism analysis in a French population with sporadic late-onset AD. In the previous report, a significant increase of the 87 bp allele was found in the AD cases; however, in our population, we observed a significant decrease with this same allele of the LRP gene. The possible reasons for this discrepancy, linkage disequilibrium or statistical anomaly, are discussed.

Age of Onset↗
PubMed1997

Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype.

Eleven early-onset dementia families, all with affected individuals who have either presented clinical symptoms of early onset familial Alzheimer's disease (EOFAD) or have been confirmed to have EOFAD by autopsy, and two early onset cases with biopsy-confirmed AD pathology, were screened for missense mutations in the entire coding region of presenilin-1 (PS-1) and -2 (PS-2) genes. Missense mutations were detected by direct sequence analysis of PCR products amplified from genomic DNA templates of affected individuals. Three pedigrees were attributable to known mutations in the PS-1 gene: P264L, E280A and the splice acceptor site (G to T) mutation, which results in the deletion of residues 290-319 of PS-1 (PS-1 delta 290-319). In a fourth pedigree, a novel PS-1 mutation was identified in exon 7 (M233T), which is homologous to a pathogenic PS-2 mutation (M239V), and is characterized by a very early average age of onset (before the age of 35). In one early onset case, another novel PS-1 mutation was identified in exon 8 (R278T). Of the five remaining families and the other early onset case, none have missense mutations in the PS-1 or PS-2 genes, or in exon 16 and 17 of the APP gene. Moreover, two of the PS-1 mutations, PS-1 delta 290-319 and R278T, are associated with the co-presentation of familial spastic paraparesis (FSP) in some of the affected family members. Our data raise the possibility that the phenotypic spectrum associated with PS-1 mutations may extend beyond typical FAD to include FSP, a disease heretofore unsuspected to bear any relationship to FAD. In addition, our data suggest that other novel EOFAD loci, in addition to APP and the presenilin genes, are involved in the aetiology of up to 50% of EOFAD cases.

Adult↗
PubMed1997

Early-onset Alzheimer's disease with a presenilin-1 mutation at the site corresponding to the Volga German presenilin-2 mutation.

We describe a new mutation causing Alzheimer's disease (AD) in presenilin-1 (N135D) that is at the homologous site to the presenilin 2 mutation (N141I) in Volga German kindreds. The phenotype of PS1 N135D is an early-onset (34-38 years) disease. The mutation forms part of, and extends, the alpha-helical array of mutations in transmembrane 2 of the presenilins and leads to the suggestion that disruption of this helical face is the molecular insult that leads to disease.

Adult↗
PubMed1997

Localization of frontotemporal dementia with parkinsonism in an Australian kindred to chromosome 17q21-22.

An Australian family with autosomal dominant presenile nonspecific dementia was recently described. The disease results in behavioral changes, usually disinhibition, followed by the onset of dementia accompanied occasionally by parkinsonism. Twenty-eight affected individuals were identified with an age of onset of 39 to 66 years (mean, 53 +/- 8.9 years). We mapped the disease locus to an approximately 26-cM region of chromosome 17q21-22 with a maximum two-point LOD score of 2.87. Affected individuals share a common haplotype between markers D17S783 and D17S808. This region of chromosome 17 contains the loci for several neurodegenerative diseases that lack distinctive pathological features, suggesting that these dementias, collectively referred to as frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), are caused by mutations in the same gene. The entire coding region of five genes, mapped to the FTDP-17 candidate region, were also sequenced. This analysis included the microtubule-associated protein tau that is the major component of the paired helical filaments observed in Alzheimer's disease. No pathogenic mutations were identified in either the tau gene or in any of the other genes analyzed.

Adult↗
PubMed1997

Temporal changes in dynamic inter fragmentary motion and callus formation in fractures.

This study examined whether callus proliferation at long bone fractures is triggered by cyclical inter-fragmentary displacement which arises from routine activity. It also examined whether a growing callus increases the stability of a fracture, thereby reducing displacement amplitude during relative motion. Seven tibial fractures stabilised with external fixators were monitored up to and beyond fixator removal. An instrumented spatial linkage was developed which was attached to the bone screws to measure inter-fragmentary displacement at the fracture in all six degrees of freedom during routine walking. Callus index (final bone width/initial bone width) was measured at the posterior and lateral cortical surfaces from orthogonal radiographs. In all seven subjects, callus growth was initiated subsequent to a peak in displacement which occurred within the first 42 days; at nine of the 14 surfaces occurred callus initiation occurred within 14 days of the peak displacement. With the exception of two lateral surfaces, maximum callus size, subsequent to fixator removal (at up to 119 days after removal). Displacement reduced during callus growth in five out of six subjects. Since the reduction in displacement did not arise from reduced weight-bearing, increasing callus size must correlate with progressive mechanical union. This was confirmed by end point stiffness tests. Therefore, peak cyclical displacement appears to be the stimulus for callus growth, the effect of which is to reduce displacement and strain which allows the following stages of bone formation and remodelling to unite the fracture.

Adult↗
PubMed1997

Amyloid, the presenilins and Alzheimer's disease.

Various mutations in the amyloid protein precursor and presenilin genes can lead to early onset, autosomal Alzheimer's disease. A series of mis-sense mutations (with one exception) in each of these genes has been shown to cause disease in a fully penetrant fashion. It has recently been shown, both in vivo and in model systems, that tissues expressing these mutations have increased production of amyloid (A beta) ending at residue 42. It has also recently been shown that this form of A beta is deposited early and selectively in the disease process and is more fibrillogenic in vitro. It is argued that these genetic and molecular biological data provide strong support for the veracity of the 'amyloid cascade hypothesis' for disease pathogenesis, and that this hypothesis offers a coherent framework for drug discovery.

Alzheimer Disease↗
PubMed1997

Primary sellar haemorrhagic melanoma: case report and review of the literature.

Primary melanoma of the sella turcica is very unusual with only four previous cases reported in the medical literature. This report describes a 47-year-old man whose headaches, endocrine dysfunction and neuro-imaging suggested a haemorrhagic pituitary macroadenoma. The histological examination showed a haemorrhagic melanoma. An extensive search for a primary source proved negative. The patient underwent three neurosurgical interventions and radiotherapy and died two years after presentation. Previous cases of primary melanoma in the pituitary region, as well as various hypotheses for this unusual site of origin are reviewed, followed by a discussion of the particular characteristics of melanin pigments on MRI. This case report illustrates that primary sellar melanoma may present as a haemorrhagic adenoma of the pituitary gland and have an unfavourable outcome despite repeated neurosurgical interventions and radiation therapy.

Cerebral Hemorrhage↗
PubMed1997

Food materials adhesion: a review.

This article reviews the various theories of adhesion mechanism and, more specifically, studies concerning foodstuffs adhesion to industrial equipment and packaging surfaces. Adhesion is governed by mechanical interlocking, wetting, electrostatic and chemical forces, and diffusion. Direct conclusions about the validity of one of these theories were seldom made in the empirical studies reviewed. The different food adhesion determination methods were detailed: direct observations, evaluations (weighting, UV absorbance, and adhesive loss), adhesion strength measurements, and indirect measurements via the wetting theory (tilted plane method, contact angle, and surface tension). The importance of proteins, product rheological properties, solid surface rugosity, and wetting phenomena in many adhesion cases is highlighted. Conclusions were made that fundamental mechanisms of food-contact surfaces interactions still need to be investigated to improve understanding in the science of food materials.

Adhesiveness↗
PubMed1997

Clinicopathological features of familial Alzheimer's disease associated with the M139V mutation in the presenilin 1 gene. Pedigree but not mutation specific age at onset provides evidence for a further genetic factor.

Sixteen affected individuals are described from two families with early onset autosomal dominant familial Alzheimer's disease. A mutation at codon 139 in the presenilin 1 gene on chromosome 14 results in a methionine to valine substitution which cosegregates with the disease in these families. Onset of dementia was before the age of 50 years in all individuals. The ages at onset within each family were tightly clustered but were significantly different between the families; this difference could not be accounted for by apolipoprotein E status and suggests the existence of a further genetic factor that modifies age at disease onset. The pattern of cognitive decline was similar in both families: early memory loss (initially selective for verbal memory in some individuals) was followed soon after by loss of arithmetic skills while naming and object perception skills were relatively preserved. A speech production deficit was observed in three members of one family but not in the other. Seizures were common and usually predated by myoclonic jerks by a number of years. Serial MRIs showed progressive cortical atrophy with periventricular white matter change appearing 3-4 years into the disease. PET revealed parieto-temporal hypometabolism in all individuals scanned. The diagnosis of Alzheimer's disease was confirmed with typical histopathology in one individual from each family.

Adult↗
PubMed1997

The presenilins and Alzheimer's disease.

The presenilin 1 and presenilin 2 genes have been identified as pathogenic loci involved in the majority of early onset, autosomal dominant Alzheimer's disease. A series of (predominantly) missense mutations have been identified in the two genes which lead to disease. The presenilins are probably eight transmembrane domain proteins with both termini in the cytoplasmic compartment. They have a wide tissue distribution and are found in the endoplasmic reticulum and early Golgi. The mechanism of pathogenesis of the mutations is not clear although, both in patients and in in vitro systems, the effects of presenilin mutations are reminiscent of the effects of the pathogenic mutations in the amyloid precursor protein gene which lead to increases in the amount of amyloid-beta42(43) being produced from the metabolism of the amyloid protein precursor. Thus, the presenilin data provide independent support for the amyloid cascade hypothesis of Alzheimer's pathogenesis. Work on the Caenorhabditis elegans homologues of the presenilins, spe-4 and sel-12, suggests that the presenilins may have a more general and direct role in the processing and trafficking of membrane-bound proteins and that, in part, the pathogenic mutations may disrupt this role.

Alzheimer Disease↗
PubMed1997

A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43).

We report a novel mutation in the amyloid precursor protein gene (APP I716V) which probably leads to familial early onset Alzheimer's disease with an onset age in the mid 50s. Cells transfected with cDNAs bearing this mutation produce more A beta 1-42(43) than those transfected with wild-type APP and this effect is additive with that of the previously reported APP V717I mutation thus providing a novel approach for further increasing A beta 1-42(43) in model systems.

Age of Onset↗