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Biomedical subjects

M R Griffiths

Publications and source records attributed to M R Griffiths.

28 records · Page 2Linked to original sources
PubMed1997

Correcting the magnification error of fan beam densitometers.

Dual-energy X-ray absorptiometry (DXA), using a narrow pencil-shaped X-ray beam coupled to a single detector, has been used extensively. More recently, DXA using a fan- shaped X-ray beam coupled to an array of detectors has been introduced. This new generation of scanners causes an inherent magnification of scanned structures as the distance from the X-ray source decreases. This magnification, which occurs in the medial-lateral direction but not in the craniocaudal direction, does not affect bone mineral density (BMD). There are, however, significant changes of bone mineral content (BMC), bone area, and parameters of hip geometry, with varying distance of the bone scanned from the X-ray source. Variability of soft tissue thickness in vivo, by altering the distance of the skeleton from the scanning table and X-ray source, may cause clinically significant errors of BMC, bone area, and proximal femur geometry when measured using fan-beam densitometers. We analyzed the geometry of Lunar and Hologic fan beam scanners to derive equations expressing the true width of scanned structures in terms of the apparent width and machine dimensions. We also showed mathematic ally that performing an additional scan, at a different distance from the X-ray source than the first scan, provides simultaneous equations that can be solved to derive the real width of a scanned bone. This hypothesis was tested on the Lunar Expert using aluminium phantoms scanned at different table heights. There was an excellent correlation, r = 0.99 (p < 0.001), between the predicted phantom width and the measured phantom width. In conclusion, this study shows that the magnification error of fan beam DXA can be corrected using a dual scanning technique. This has important implications in the clinical usefulness of BMC and geometrical measurements obtained from these scanners.

Absorptiometry, Photon↗
PubMed1992

Light microscopic and ultrastructural distribution of type VI collagen in human liver: alterations in chronic biliary disease.

We have investigated the distribution of type VI collagen in normal human liver obtained from cadaveric renal transplant donors, using a peroxidase-antiperoxidase method for light microscopic visualization, and an immunogold labelling method for ultrastructural localization. The distribution was compared with that of the more abundant interstitial collagen type III, using antibodies to amino terminal procollagen type III. Staining for type VI collagen was identified in Glisson's capsule, in portal tract stroma and within the space of Disse. Perisinusoidal staining showed intra-acinar heterogeneity with the intensity in acinar zones 2 and 3 being greater than in zone 1. Type III collagen was also found in the space of Disse although no significant intra-acinar variation in staining intensity was noted. Immuno-gold labelling for type VI collagen was demonstrated on amorphous or microfilamentous material lying between, and occasionally appearing to interconnect, cross-striated collagen fibrils, whereas labelling for amino terminal procollagen type III was exclusively on fibrils. Intracellular staining for type VI collagen was noted in perisinusoidal (lto) cells. These results confirm that type VI collagen is a ubiquitous constituent of the normal hepatic extracellular matrix and suggest that it may be synthesized by perisinusoidal (lto) cells. The distribution of type VI collagen was also studied in biopsy material from patients with different histological stages of primary biliary cirrhosis. Intense staining was noted around proliferating bile ductules within developing fibrous septa and in established septa of cirrhotic liver. These observations indicate that this 'minor' matrix component may play an important role in hepatic fibrogenesis.

Chronic Disease↗
PubMed1992

A comparison of morphoea and lichen sclerosus et atrophicus in vitro: the effects of para-aminobenzoate on skin fibroblasts.

To study the effects of para-aminobenzoate on the dermis, fibroblast cell lines derived from lesions of lichen sclerosus et atrophicus, from morphoea and from normal skin were incubated with Potaba in vitro. Monolayer cultures containing Potaba showed a dose-dependent inhibition of proliferation beginning at 1,000 micrograms/ml with total inhibition at 10,000 micrograms/ml. Mean ID50 values for the three groups were not significantly different. There was a similar dose dependent inhibition of glycosaminoglycan secretion in all 3 groups, except at 10,000 micrograms/ml where secretion by lichen sclerosus et atrophicus and morphoea fibroblasts was significantly more inhibited than normal lines. Inhibition of the glycosaminoglycan secretion at 10-1,000 micrograms/ml was a direct effect of the drug rather than an indirect effect of changes in cell density, and lichen sclerosus et atrophicus fibroblasts produced about 40% more GAG than the morphoea or normal lines growing at similar densities. Collagen synthesis was increased in both lichen sclerosus et atrophicus and morphoea cell lines, with increased non-collagenous protein in morphoea lines. These results confirm that there are differences between lichen sclerosus et atrophicus and morphoea, and suggest glycosaminoglycan secretion as a possible target for the therapeutic action of Potaba.

4-Aminobenzoic Acid↗
PubMed1991

Basement membrane proteins in the space of Disse: a reappraisal.

The distribution of two major basement membrane components, type IV collagen and laminin, was studied within the perisinusoidal space of Disse in normal human liver using (i) an immunoperoxidase method for light microscopy and (ii) immunogold labelling for ultrastructural localisation. Although immunoreactivity depended on the mode of tissue fixation, both proteins could be identified at this site using a panel of affinity purified antibodies. These findings indicate that these proteins are normal constituents of the perisinusoidal extracellular matrix, and refute the hypothesis that capillarization of the sinusoids in chronic liver disease results from neo-expression of laminin in the space of Disse.

Basement Membrane↗
PubMed1990

Ultrastructural localization of extracellular matrix proteins in liver biopsies using ultracryomicrotomy and immuno-gold labelling.

We describe a technique for the localization of extracellular matrix proteins in wedge and needle biopsy specimens of human liver. Using ultra-thin (50-70 nm) sections of puncture perfusion fixed tissue, extracellular matrix proteins were localized using a protein A-gold labelling procedure. We obtained good preservation of ultrastructural detail and specific labelling for collagen types I, III and IV and fibronectin. The method represents a sensitive means of identifying the extracellular distribution and the cellular origin of these proteins in normal and diseased human liver.

Biopsy↗
PubMed1990

Immunohistochemical localization of a plasma protein (glycoprotein 60) which inhibits complement-mediated prevention of immune precipitation.

Using various immunocytochemical techniques it has been shown that glycoprotein 60 (gp60), an IgG Fc-binding protein recently isolated from normal human plasma, is found localized in human hepatocytes, platelets and a subpopulation of normal peripheral blood lymphocytes (PBL). This protein, which appears to be identical to a 60,000 MW IgG-binding protein (60-IBF) previously isolated from normal human PBL culture supernatants, also appears to be distinct from the three well-defined leucocyte Fc gamma-receptors: Fc gamma RI, Fc gamma RII and Fc gamma RIII.

Antigens, CD↗
PubMed1989

Localization of adrenergic and neuropeptide tyrosine-containing nerves in the mammalian liver.

The distribution of adrenergic nerves in guinea pig and rat liver was studied by the immunolocalization of fibers containing tyrosine hydroxylase and dopamine beta-hydroxylase, enzymes involved in the synthesis of catecholamines. In both species, adrenergic fibers were identified within portal tracts, often in close proximity to hepatic artery branches. In guinea pig liver, but not rat liver, abundant intraacinar fibers were identified; fibers were also seen within the walls of terminal hepatic vein radicles and larger hepatic veins. The presence of peptidergic nerves containing the regulatory peptide neuropeptide tyrosine and the C-flanking peptide CPON was investigated by indirect immunofluorescence. The distribution of these nerves was similar to that of tyrosine hydroxylase- and dopamine beta-hydroxylase-positive nerves and showed the same species difference. The effector sympathetic nature of tyrosine hydroxylase- and neuropeptide tyrosine-positive fibers in rat liver was confirmed by chemical denervation studies using 6-hydroxydopamine.

Adrenergic Fibers↗
PubMed1989

Intrasplenic hepatocyte transplantation in rats with experimental liver injury: morphological and morphometric studies.

Isolated rat hepatocytes were transplanted into the splenic parenchyma of syngeneic animals. The effects on the degree of colonization by the transplanted cells of three forms of experimental liver injury in recipient animals were studied. Significant colonization was observed in animals with carbon tetrachloride (CCl4)-induced injury combined with portacaval shunt (PCS) and in animals with common bile duct (CBD) ligation but not in control animals or in animals with CCl4-induced injury alone. Transplanted cells in the CCl4/PCS group resembled normal hepatocytes. In contrast, in the CBD group, the intrasplenic hepatocytes exhibited a pattern of 'ductular metaplasia' similar to that observed in the obstructed liver of the recipients. Transplanted syngeneic hepatocytes can thus proliferate in the spleen in response to liver injury in the recipient. The morphological appearances of the transplanted cells can be modified depending on the nature of the liver injury.

Animals↗