British journal of experimental pathology最新文献

Female New Zealand White rabbits, following sham laparotomy, total splenectomy and splenectomy with 50% splenic autotransplantation, have been injected intravenously with 99Tc-labelled type 2 Streptococcus pneumoniae. The blood clearance of isotope has been measured and the numbers of circulating bacteria quantitated by blood culture. On sacrifice of the animals the tissue uptake of the isotope has been measured. The results indicate 98% bacterial clearance from the blood within 7 min. The liver is the principal organ for reticuloendothelial uptake of the bacteria accounting for 60% of the total injected dose; 15% of the isotope clearance occurred in the lungs, and the spleen contributed only 3% of the total bacterial clearance. There was no difference in the observed pattern of clearance following splenectomy and following splenic reimplantation. Following the uptake of the bacteria in the tissues, the isotope dissociated from the bacterium and was excreted in the urine. The secondary rise in blood isotope level consequent upon this release was not accompanied by a secondary bacteraemia.

We have addressed the problem of distinguishing angiogenesis induced in the chick chorioallantoic membrane by injury and inflammation from angiogenesis induced by primary stimulation. Focal, slow-release application of trypsin stimulated a localized spoke-wheel pattern of vascularity. In comparison, a range of doses up to a sublethal amount of trypsin applied generally, in liquid form, resulted in no change in DNA synthesis or vessel content, despite a transient influx of inflammatory cells. This contrasts with previous work with fibrin degradation products, histamine and heparin which each produce characteristic patterns of increased DNA synthesis leading to angiogenesis in the entire 'dropped' area of the chorioallantoic membrane. Such general application, therefore, avoids the danger of misinterpretation of focal, toxic effects.

A polyclonal anti-cytokeratin antibody has been used to examine the expression of this intermediate filament both during normal development in the rat and in a variety of pathological states in the rat and mouse. Bile duct proliferation induced by the administration of alpha-naphthylisothiocyanate (ANIT) as well as the oval cell proliferation induced by 3'-methyl-4-dimethylaminoazobenzene (3-MeDAB) have been used to examine the expression of the rodent cytokeratins in the proliferating cells regarded as being of bile duct origin. Examples of cholangiofibrosis and cholangiocarcinomas were also examined for evidence of cytokeratin expression using this antibody, as well as proliferations of a morphological intermediate type between epithelial and mesenchymal. In all cases we have been able to demonstrate continuity of phenotypic expression of the cytokeratins recognized by this antibody in cells which are recognized as bile duct in origin, even where their morphological appearance does not resemble an epithelial cell type. Because this antibody can be used on formalin-fixed, paraffin-processed tissues, after trypsin treatment, it is proposed that it can be used routinely in the toxicological evaluation (even retrospectively) of bile duct related proliferations and tumours.

An assessment of mitochondrial bioenergetics in protein-malnourished rats indicates that there is a reduction of brain mitochondrial metabolism in protein malnutrition. Specifically, mitochondria of protein-malnourished offspring of malnourished rats exhibit (i) an enhancement of state 4 respiration, (ii) a reduction of ADP-stimulated state 3 respiration, (iii) a decrease in ADP:O ratios, (iv) reductions of FCCP-induced ATPase action and in the rates of proton and calcium ion translocation, and (v) diminished activities of redox enzymes. In general, these changes are less pronounced in malnourished weanling rats born of healthy dams. Although the exact molecular mechanism of these defects is not yet known, the alterations are definitely caused by diet-induced changes in the structure and integrity of inner mitochondrial membrane components.

We pursued previous studies on acute and later effects of different forms of humidification on rabbits' lungs during respiratory support. Arterial wall thickening and alveolar membrane damage was confirmed in the presence of water in the inspired gas. Interstitial collagen was significantly increased 2 weeks later. Though independent of the kind of respiratory support the findings were more pronounced with positive pressure ventilation than with a low continuous pressure with spontaneous breathing. These effects did not occur after humidification with precautions against condensation, and were thus attributable to particulate water. They were interpreted as evidence for lung injury and subsequent repair from this cause. Increased width of small artery walls, possibly from vasoconstriction, was similarly related.

The effect was studied of chronic alcohol intake in the rat during pregnancy and lactation on the brown adipose tissue (BAT) in pups. The idea was to find a possible relationship to cot death since in some cot death victims increased amounts of BAT have been observed. Exposure to ethanol increased the relative weight of the brown adipose tissue in pups and enhanced both its total protein content and the activities of the oxidative enzymes, succinate dehydrogenase and cytochrome oxidase. In the BAT of pups sympathetic activity, as demonstrated by noradrenaline, was also increased by long-term exposure to alcohol. In theory, an increased thermogenic capacity of the BAT in the newborn together with other factors such as emotional stress and infections could lead to death from hyperthermia, in which case only non-specific morphological signs would be found in the cadaver.

Epidermal keratinocytes and melanocytes have a close functional interrelationship. In order to study this relationship we used computer-assisted three-dimensional morphometry (CAM) to investigate the shape and size changes of the cutaneous melanocyte in healing guinea-pig skin. The combination of CAM with osmium iodide staining and resin embedding of tissue gave excellent results and allowed qualitative and quantitative morphometric assessment of melanocytes in vertical epidermal sections. The changes in melanocytes and keratinocytes during healing of a standard 1 cm full thickness wound in the guinea-pig were studied. After an initial decrease, more melanocytes per mm2 of epidermis were seen (from 36 days). These were smaller in volume with shorter, less branched dendrites compared to controls. An unexpected finding was a late phase of melanocyte proliferation, at the end of our study period (99 days). Clearly, the complex changes in the melanocyte-keratinocyte relationship during wound healing continue throughout and beyond the period of our study.

Cultured vascular endothelium secretes the enzyme lysyl oxidase which cross-links both collagen and elastin. The major reducible cross-link synthesized by cultured human umbilical arterial and venous endothelium is dihydroxylysinonorleucine (di-OH-LNL). Treatment of the cultures with the lathyrogen beta-aminopropionitrile (BAPN), which inhibits lysyl oxidase, inhibited synthesis of this cross-link. Cultured porcine aortic endothelium synthesized three major reducible lysine-derived cross-links: dihydroxylysinonorleucine (di-OH-LNL), hydroxylysinonorleucine (OH-LNL) and lysinonorleucine (LNL); BAPN also inhibited synthesis of these three cross-links. Earlier in-vivo observations on BAPN-treated chick embryos had shown a 20% increase in the hydration of cartilage and other tissues; the likeliest explanation was that cross-link disruption permitted the proteoglycans in cartilage to express their hydrophilic nature when freed of their collagenous network. Capillary basement membrane contains laminin, proteoglycan and type IV collagen. Following the finding of oedema in lathyritic cartilage, we would propose that agents which disrupt collagen cross-links in cultured vascular endothelium, damaging capillary basement membrane, be considered as one possible mechanism in the pathogenesis of oedema.

Experiments were undertaken to demonstrate and partially explain the protective effect of bovine lactoferrin (LB) when administered intravenously to mice 24 h before a challenge with a lethal dose of Escherichia coli. About 70% of mice pretreated with LB survived challenge. The survival rates in control mice treated with E. coli alone and pretreated with bovine serum albumin (BSA), were 4 and 8%, respectively. Human lactoferrin (LH) had almost the same protective effect as LB. Sufficient amounts of ferric ions were given to mice, in single and multiple doses, for full serum transferrin saturation 30 min before or after E. coli administration. The multiple dose of ferric ions did not change considerably the survival rate of mice pretreated with LB. In contrast, a single dose of ferric ions gradually decreased the survival rate of the mice after the first week of experiment. From day 14 this decrease was statistically significant in all groups of mice treated with a single dose of ferric ions when compared with mice pretreated only with LB, and the difference ranged from 25 to 35% on day 30. The possible mechanism(s) of protective effect of LB and role of iron ions are discussed.