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Biomedical subjects

S Haywood

Publications and source records attributed to S Haywood.

At least 19 recordsLinked to original sources
PubMed1992

Is clutch size in birds affected by environmental conditions during growth?

Only environmental conditions occurring at the time of breeding have been shown to affect clutch size in birds, even though conditions experienced during growth are known to affect body size or egg size. We show here that environmental conditions experienced during early life can affect clutch size in captive zebra finches (Taeniopygia guttata) and wild great tits (Parus major). Not only do factors outside the immediate breeding season affect clutch size, but clutch size control mechanism is permanently influenced by conditions experienced during ontogeny.

Animals↗
PubMed1991

A histochemical and immunocytochemical study of hepatic copper and metallothionein in the pre- and post-natal rat.

Histochemical and immunocytochemical methods to demonstrate copper, copper-associated protein, lipfuscin, and metallothionein were applied to the liver of fetal and neonatal rats (mid-term, pre-term, and 1, 3, and 7 days post-natal). Copper was detected only at 1 and 7 days post-natal. No copper-associated protein was found in any liver examined. Lipofuscin granules were present around term in small numbers but were most abundant at 7 days post-natal when the majority of them were also positive for copper. Metallothionein staining, both nuclear and cytoplasmic, was maximal at mid-term and became less intense with maturity. Although nuclear staining was always present, cytoplasmic staining varied between different areas of the liver. No marked difference in staining intensity was found between 3 and 7 days post-natal. There are marked differences in copper metabolism in the maturing liver between the rat and man.

Animals↗
PubMed1991

The protective role of metallothionein in copper overload: I. Differential distribution of immunoreactive metallothionein in copper-loaded rat liver and kidney.

The cytotoxicity of copper is probably determined by its molecular association and subcellular localisation rather than its concentration within tissues. Metallothionein (MT) is a copper binding protein distributed between the particulate and soluble cellular components. The role of MT in conferring protection to the copper-loaded rat has been investigated by comparing the distribution of the immunoreactive protein between the soluble and particulate fractions of liver and kidney during the development of copper tolerance. Young male Wistar rats were fed a high copper (1 g/kg) diet for 16 weeks and killed sequentially during this period; liver and kidneys were retained. Pellet and supernatant preparations from homogenised, pooled samples of liver and kidney were subjected to chromatographic separation. Copper and zinc were analysed in whole tissue, homogenates and eluant fractions and MT identified likewise using an enzyme-linked immunoassay. Copper accumulated for 5 weeks in the liver falling subsequently accompanied by similar changes in MT content. Kidney copper and MT rose to maximum concentrations at 8 weeks and were maintained thereafter. Substantial differences were apparent in the relative distribution of MT between the two organs. MT was the major, predominantly cytosolic, copper-binding protein in the kidney but in the liver immunoreactive MT was pelleted and present in lower concentration than the high molecular weight cuproproteins. It was concluded that whilst MT plays a role in the detoxification and adaptation of rats to copper-loading the regulatory functions of liver and kidney may differ significantly in this respect.

Animals↗
PubMed1991

The protective role of metallothionein in copper-overload: II. Transport and excretion of immunoreactive MT-1 in blood, bile and urine of copper-loaded rats.

The regulation of copper homeostasis in copper overloaded animals occurs by excretion of excess of the metal in bile and urine, which may be facilitated by metallothionein (MT) a copper binding protein. The role of MT in the mobilisation and excretion of copper excess has been studied in copper-loaded rats during the development of tolerance. Young male Wistar rats were fed a high copper (1 g/kg) diet for 16 weeks during which period they were killed after prior collection of bile, blood and urine for analysis for copper and immunoreactive MT-1. In addition bile was separated chromatographically and the eluant fractions were assessed likewise for copper and MT-1. Biliary excretion of copper and MT-1 rose to a maximum after 6 weeks, falling subsequently as the rats became copper tolerant. Early increases in circulating copper and MT-1 occurred likewise but whereas MT-1 fell subsequently during the recovery period, serum copper remained elevated. By contrast, urinary copper and MT-1 maintained an increased output throughout. Chromatographic separation of bile revealed the presence of a range of immunoreactive MT-1 degradation products. It was concluded that the close correspondence between bile and serum MT reflected their hepatic derivation and implicated liver MT as an export protein in the early stages of copper overload. By contrast, urine MT, maintained independently of circulating MT levels, established the active secretory participation of the kidney in promoting the continued depletion of excess copper.

Animals↗
PubMed1991

Differential regulation of murine Mesocestoides corti infection by bacterial lipopolysaccharide and interferon-gamma.

Many liver-invasive parasites cause extensive liver damage which may result in an impaired ability to catabolize endotoxin. The influence of endogenous endotoxin on the progress of liver-invasive parasitic diseases has been investigated in murine Mesocestoides corti infection. Invasion of liver tissue by tetrathyridia resulted in extensive parenchymal destruction with fibrosis. In association with this, undetoxified endotoxin, in potentially biologically active concentration, was found on peritoneal macrophages, 5 months post-M, corti infection. Host susceptibility was influenced by the Lps gene for responsiveness to lipopolysaccharide (LPS). The parasite burden of LPS-responsive (C3H/HeN) mice was significantly increased in the livers of these mice when compared to LPS-resistant (C3H/HeJ) mice. LPS reduced the ability of normal peritoneal macrophages to kill tetrathyridia, when co-cultured in vitro. LPS also abrogated the ability of recombinant interferon-gamma (r.IFN-gamma) to enhance macrophage larvicidal activity. These in vitro findings were confirmed in vivo. Daily intraperitoneal administration of LPS, at low concentration, caused a 4-fold increase in parasite burden in the liver, while r.IFN-gamma at optimal concentration reduced parasite burden by 57%. Post-infection macrophages have previously been shown to be refractory to cytokine-activation for larval killing. In this report, we conclude that (1) this refractoriness may be due to the presence of undetoxified endotoxin on post-infection macrophages and (2) endotoxin may reduce host resistance by abrogating effector macrophage response to IFN-gamma.

Animals↗
PubMed1990

Histochemical and immunocytochemical evaluation of copper and metallothionein in the liver and kidney of copper-loaded rats.

Histochemical methods do not always show a good correlation with analytical measurement of copper content and consequently immunoreactive staining techniques for metallothionein (MT) have recently been employed for the differential diagnosis of copper-associated diseases. This study compares histochemical with immunocytochemical methods for the assessment of copper status. Male rats were fed a high copper (1 g/kg) diet for 16 weeks and killed sequentially during this period. The livers and kidneys were analysed for copper and zinc (atomic absorption spectrophotometry), and sections were stained with rubeanic acid and rhodanine for copper and for immunoreactive MT using the DNP localization system. Immunoreactive stains for MT corresponded better with copper content than histochemical stains and were more sensitive, albeit less selective, indicators of copper accumulation. Moreover, major differences in intracellular staining were apparent between the two methods, attributed to differences in copper binding and microcompartmentalization of metal.

Animals↗
PubMed1989

Cellular mechanisms of toxicity and tolerance in the copper-loaded rat. II. Pathogenesis of copper toxicity in the liver.

The distribution of copper has been studied in the liver of the copper-loaded rat at the ultrastructural level by X-ray electron probe microanalysis in order to clarify the pathogenesis of copper-induced damage. Male rats fed a high copper diet (1500 ppm) for 16 weeks were killed at intervals; their livers were removed and fixed in 4% paraformaldehyde and 2% glutaraldehyde for electron microscopy and were analyzed for copper by AA spectrophotometry. Three different forms of lysosomes were identified with respect to their morphology and X-ray emission profiles: Type I lysosomes appeared early and contained iron and zinc in addition to markedly elevated copper peaks, whereas later appearing Type II lysosomes included sulfur and phosphorus in addition to copper. Type III lysosomes were associated with the recovery period and contained much reduced elemental residue. Degenerative changes were not observed in any of the three types of lysosomes. Copper and other elemental residues, including sulfur, were also identified within the hepatic parenchymal cell nuclei and by contrast were associated with irreversible nuclear damage. Nuclear copper is directly injurious to this organelle and responsible for the subsequent cell death whereas copper contained within lysosomes is apparently innocuous.

Animals↗
PubMed1989

Variations in the intralobular distribution of copper in the livers of copper-loaded rats in relation to the pathogenesis of copper storage diseases.

There are differences in the hepatic intralobular distribution of copper in copper storage related diseases which may be of pathogenetic significance. Male rats fed a high copper diet (1500 ppm) for 16 weeks were killed at intervals in an attempt to compare copper distribution in their livers with those in human, canine and ovine copper toxicosis. Copper was found to accumulate almost exclusively in the periportal and mid-zones of the rat liver lobules and was associated with progressive pathological changes which included focal and periportal degeneration and necrosis. This pattern of copper distribution contrasts markedly with the centrilobular retention reported in familial canine copper toxicosis and chronic copper poisoning in sheep which suggests that, in these conditions, a secretory deficiency may be less important than a metabolic zonal defect of intracellular copper metabolism. The pathological changes observed in copper-loaded rats have a different micro-anatomical localization from those in dogs and sheep, but show similarities to the early changes reported in the latter species and indicate the possibility of a similar cellular lesion.

Animals↗
PubMed1989

Cellular mechanisms of toxicity and tolerance in the copper-loaded rat. III. Ultrastructural changes and copper localization in the kidney.

The distribution of copper and related changes have been studied in copper-loaded rat kidneys at the ultrastructural level by X-ray electron probe microanalysis, in order to clarify the pathogenesis of copper-induced damage and subsequent recovery in this organ. Male rats fed a high copper diet (1500 ppm) for 16 weeks were killed at intervals; their kidneys were removed and portions of kidney cortex fixed in 4% paraformaldehyde and 2% glutaraldehyde for electron microscopy: other samples were analysed for copper by AA spectrophotometry. Increasing copper accumulation was associated with progressive PCT cell disarray and characterized by irreversible nuclear damage coincident with the intranuclear accumulation of Cu, S, P, and Ca. Copper was also identified within structurally intact lysosomes associated with Zn and Fe (Type I lysosomes) or P and S (Type II lysosomes, putative Cu-MT). Subsequent copper decline and tubular recovery was associated with the facilitated lysosomal sequestration of copper and excretion of copper-containing cell products into the tubule lumina, Cu-MT and alpha-2 urinary protein-copper. The cytotoxicity of copper in the kidney, as well as the liver, is associated primarily with irreversible nuclear damage, whereas lysosomal copper sequestration protects the cell from injury.

Animals↗
PubMed1988

Cellular mechanisms of toxicity and tolerance in the copper-loaded rat. I. Ultrastructural changes in the liver.

Ultrastructural changes have been studied in the copper-loaded livers of rats in order to clarify the pathogenesis of damage induced by the metal and the subsequent recovery. Male rats fed a high copper diet (1500 ppm) for 16 weeks were killed at intervals. Their livers were removed and portions fixed in 4% paraformaldehyde and 2% glutaraldehyde for transmission electron microscopy and analysed for copper by AA spectrophotometry. Increasing copper concentrations were associated with an increase in the numbers and diversity of lysosomes, swelling of smooth endoplasmic reticulum, mitochondria and canalicular microvilli and fragmentation of rough endoplasmic reticulum. Nuclear degeneration occurred early, culminating in lysis. Subsequent changes included a decline in liver copper, extrusion of apoptotic bodies and the recovery of remaining hepatocytes with retention of inert remnants (Mallory body-like structures). Excess copper is associated primarily with irreversible nuclear damage and does not appear to cause disruption of lysosomes. The mechanism of cellular adaptation remains unclear.

Animals↗
PubMed1988

Hepatitis and copper accumulation in Skye terriers.

Livers of nine related Skye terriers with liver disease were evaluated for histological changes and copper content. Lesions ranged from hepatocellular degeneration and necrosis (zone 3) with intracanalicular cholestasis and mild inflammation, to chronic hepatitis with cholangioplasia and cirrhosis. Excess copper (801-2,257 micrograms/g) was related to the severity of cholestasis. Skye terrier hepatitis is a distinct disease entity and may be derived from a disorder of intracellular bile metabolism culminating in disturbed bile secretion and the accumulation of copper.

Animals↗
PubMed1987

Evaluation of histochemical methods for the detection of copper overload in rat liver.

Histochemical methods have invariably shown a good correlation with copper analysis by absorption spectrophotometry in the identification of canine copper storage diseases. But, in Wilson's disease (WD) in humans no such correlation exists and similar discrepancies have also been observed in copper-loaded rats. This study attempts to quantify stainable copper in the livers of copper-loaded rats and relate this to the hepatic copper concentrations. Male rats fed a high copper diet (1500 ppm) for 16 weeks were killed at intervals. The livers were analysed for copper and graded according to stainable copper present in paraffin sections stained with rhodanine and rubeanic acid. Initially there was a good correlation between histochemically demonstrable copper and its total concentration, but subsequently, when high liver levels of the metal were present, copper staining was very variable. This unrealiability has similarities with WD, in which the higher hepatic concentrations of presymptomatic patients are difficult to detect by conventional copper stains. The variation in the binding of copper and its intracellular localisation suggested by these results may have considerable significance in the pathogenesis of copper storage diseases.

Animals↗
PubMed1986

Clinical course of renal adenocarcinoma associated with hypercupraemia in a horse.

A four-year-old shire mare with haematuria, colic, terminal weight loss and an abdominal mass had a large unilateral renal adenocarcinoma. Clinical signs were monitored for 11 months. Increased serum copper concentrations were measured on two occasions. Hypercupraemia is discussed as a possible paraneoplastic change.

Adenocarcinoma↗