British journal of experimental pathology最新文献

The histopathological and electron microscopic features of experimental dermatophytosis due to Trichophyton quinckeanum in Balb/c mice have been studied in animals with primary, secondary and chronic infections. Infected animals all showed pathological changes with adherence of microconidia to keratinocytes within 4 h of infection. Other features were the early infiltration of neutrophils, the formation of a mycelial mass (scutulum) in the epidermis, and epidermal oedema. Increased thickness of the epidermis was measured within 3 days of infection, although this was mainly due to oedema. The main differences seen in secondary infections were the paucity of fungal elements, even after 24 h, a sustained increase in epidermal thickness, and the dense dermal infiltrate of mononuclear cells. Chronically infected animals showed similar changes to those at the peak of a primary infection, but in addition there were large numbers of mast cells in the dermis. Cells carrying Ia markers were identified in the epidermis (Langerhans cells) and the dermis (macrophages) in all infections and their distribution did not appear to change. Although recovery from infection has been correlated previously with T lymphocyte mediated responses an increase in the number of cell layers of the epidermis and a dense infiltrate of neutrophils at the zone of infection were both seen within 2 days of infection. It is suggested that neutrophil killing of fungi and increased epidermal proliferation, not dependent on T cell activation, may also be implicated in host defence against dermatophytes.

Acute cerebral infarction in gerbils, produced by unilateral carotid ligation, was used as a model to investigate secondary myocardial changes. The extent of the myocardial damage revealed by succinic dehydrogenase (SDH) histochemistry and by release of myocardial creatine phosphokinase (MB-CK) was measured in gerbils sacrificed from 3 to 48 h after either carotid ligation, carotid isolation only or skin incision only. For technical reasons dead animals were excluded from analysis. Of surviving ligated animals 74% developed neurological deficits related to brain ischaemia. A significant weight increase in the ipsilateral hemisphere was found at 6-10 h, and maximal histological damage at 16 h, both partially reversible thereafter. Non-ligated animals did not develop neurological changes, and showed neither brain swelling nor cerebral histopathology. Extensive cardiac damage was shown by the SDH method from 3 h postoperatively, and confirmed by the elevated serum levels of MB-CK in the carotid-ligated group. The SDH changes were identical with those described in the hearts of patients with acute intracranial lesions, and appeared to be reversible. The effect of beta-adrenergic blockade was assessed in this model. Metoprolol tartrate injected intraperitoneally 3 h before and 1 h after carotid ligation (10 mg/kg each dose) significantly decreased the extent of myocardial damage as estimated both with SDH histochemistry and MB-CK serum levels. It had no effect on the ischaemic brain changes. These results strongly support the concept of catecholamine mediation of myocardial injury resulting from acute brain lesions.

In rats with phosphoryl-creatine depletion (fed a standard Randoin-Causeret diet containing 1% beta-guanidine propionic acid) abnormal mitochondria were observed in slow skeletal muscles, often containing paracrystalline inclusions very like those induced by ischaemia or mitochondrial poisons and in human mitochondrial myopathy.

Bacteria-free filtrates of nine strains of Bacteroides ureolyticus, most of which had been isolated from the urethra of men with non-gonococcal urethritis, damaged the mucosal epithelium of human fallopian tube and bovine oviduct organ cultures. The damage, pronounced after three days, was manifested by loss of ciliary activity. Histological observations, supported by scanning electron microscopy, showed that this loss was due to disruption of the epithelia with sloughing of cells. It is likely that the inhibitory activity of the filtrates was due to endotoxin since lipopolysaccharides extracted from the bacteria had a similar deleterious effect on oviduct mucosal epithelia. It is speculated that B. ureolyticus has the potential for causing damage to the urethral mucosa by the same mechanism.

A post-embedding immunogold technique has been used for the ultrastructural localization of a lysosomal enzyme, beta-glucuronidase, in resting and activated T- and B-lymphocytes. The results presented here show that mitogen-induced stimulation of T- and B-cells was associated with an increase in the amount of enzyme in the Golgi complex and rough endoplasmic reticulum, organelles which were rarely present in the resting lymphocytes.

Major histocompatibility complex (MHC) antigen expression has been postulated to have an important role in host defences against tumour development. In this study the expression of MHC class I and class II antigens in vitro, both constitutive and in response to interferon gamma (IFN gamma), was examined in a series of cell lines established from a rat model of oral carcinogenesis. Constitutive expression of MHC class I and class II antigens was not related to the degree of malignancy of the cell lines, as reflected by their anchorage independence in agarose gels and their capacity to form tumours in athymic mice. MHC class I response to IFN gamma stimulation did not correlate with tumorigenicity, but the MHC class II response was significantly decreased in one of the four tumorigenic cell lines. The results show that the expression of MHC antigens in response to IFN gamma varied between different keratinocyte cell lines but did not consistently reflect the tumorigenic phenotype.

Sciatic nerve glucose, sorbitol, fructose and myo-inositol levels were measured over a 24-week period in rats made diabetic using a single intraperitoneal injection of streptozotocin at 45 mg kg-1 body weight. In addition, the effect of the aldose reductase inhibitor Sorbinil (Pfizer Ltd) at 25 mg kg-1 day-1 in reversing the accumulation of nerve polyols following 8 weeks of diabetes was investigated. Following induction of diabetes 47, 471 and 456% increases and a 43% decrease in sciatic nerve glucose, sorbitol, fructose and myo-inositol concentrations (mumol g-1 wet weight) respectively, were observed by day 14. Over the remainder of the experimental course untreated diabetic control animals demonstrated relatively consistent elevations in sciatic nerve glucose, sorbitol and fructose. Although a significant, progressive reduction in sciatic nerve myo-inositol to 30% of onset values was observed over the first 84 days of the study, this was followed by a spontaneous partial recovery (31%) over the remainder of the experimental course. However, sciatic nerve myo-inositol levels at the end of the study were still significantly lower than onset values (P less than 0.01). Sorbinil treatment, initiated after 8 weeks of diabetes, and without effect on sciatic nerve glucose levels, normalized sorbitol concentrations following 4, 8, or 12 weeks of treatment but only partially reversed the accumulation of fructose by 368, 161 and 199%, compared to age-matched non-diabetic control values, at the above times, respectively. Mean myo-inositol levels were progressively increased following Sorbinil treatment over the experimental period, although the increase was only significant, compared to results from untreated diabetic animals, at weeks 4 and 16.(ABSTRACT TRUNCATED AT 250 WORDS)

Low ionic strength acidic buffer, Sephadex G-200 and Benzamidine-Sepharose (BZ) gel chromatography, have been used for the partial purification of alveolar hydatid cyst (AHC) induced amyloid enhancing factor (AEF). BZ-gel bound AEF (AEF-BZ) demonstrated AEF activity in the mouse bioassay, proteolytic activity against Hide powder azure showed two major and three minor peptides on SDS-PAGE. Pretreatment of AEF-BZ with 10 mM phenylmethylsulphonyl fluoride or 20 mM p-chloromercuribenzoic acid completely abolished its bioactivity in vivo and proteolytic activity in vitro. Polyclonal anti-AEF antibody (AAA) was generated which on passive transfer into mice completely abolished the bioactivity of both casein-induced, or AHC-induced AEF. The AAA absorbed on Sepharose gel conjugated to normal mouse serum developed one common precipitin band between AE and AEF-positive sera from AHC-infected and old retired mice and in immunostaining it bound to the cytoplasmic granular components of a majority of splenic and peritoneal leucocytes from AHC-infected mice. In contrast, only a few normal mouse leucocytes showed positive staining. We suggest that AEF, in all probability, is a serine/thiol protease of leucocyte origin whose intracellular and humoral concentrations increase significantly during amyloidosis. The role of lysosomal proteases and anti-AEF antibody which has been successfully generated for the first time is discussed with reference to the origin of AEF and its presumed biological function in amyloidogenesis.

Antigen-induced arthritis in the rabbit (AIAR) provides the closest experimental equivalent to human rheumatoid arthritis in terms of infiltration of synovial tissue by lymphoid cells. A method is described for quantitative histological analysis of AIAR. Measurements of total cell numbers, lymphocyte and polymorphonuclear leucocyte infiltration, and thickness of infiltrated synovium were obtained for ranges of antigen dosage and duration of arthritis. The method has been devised as part of a system for the analysis of joint swelling, synovial fluid biochemistry and cytology, cartilage proteoglycan chemistry and synovial histology on the same specimen.

Rat mesothelial cell cultures were shown to have considerable plasminogen dependent and independent fibrinolytic activity in vitro using an 125I fibrin degradation assay. At non-toxic doses of the mineral dusts titanium dioxide, quartz and crocidolite asbestos, as assessed by 51Cr release, the fibrinolytic activity of mesothelial cells was inhibited. Quartz had the greatest inhibitory effect and crocidolite asbestos had the least. These results suggests that inhibition of mesothelial cell fibrinolysis does not, on its own, explain pleural fibrosis due to toxic mineral dusts.