bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of parathyroid hormone, 1,25‐dihydroxycholecalciferol and prostaglandins on the cytoplasmic activity of isolated osteoclastsxs
Authors: Chambers T. J. , Dunn C. J.
Published: June 2005

Osteoclasts were isolated on glass or plastic substrates and the effect of bone‐active hormones and prostaglandins on their behaviour was observed. Untreated osteoclasts migrate across the substratum, actively extending pseudopodia which show intense “rippling” activity. Addition of parathyroid hormone (PTH), 1,25‐dihydroxycholecalciferol (1,25‐(OH)2D3), prostaglandins (PG) F2α, E2 and thromboxane B2 caused no change in the behaviour or morphology of these osteoclasts. Prostacyclin, however, caused rapid cessation of cytoplasmic rippling activity followed by gradual pseudopodial retraction in a manner indistinguishable from that previously observed in the presence of calcitonin. The cytoplasmic quiescence induced by prostacyclin was seen at concentrations of 10−9M and above. Quiescence was reversible and its duration depended upon the dose of the compound administered (prostacyclin decays rapidly). No such effect was observed on the behaviour of the other cell types contaminating the osteoclast cultures, nor on purified populations of osteoblasts or peritoneal macrophages.

We also tested the ability of PTH, 1,25‐(OH)2D3 and PGs to reverse calcitonin‐induced osteoclast quiescence. We found that even high doses showed no detectable stimulation of quiescent isolated osteoclasts. This suggests that the undoubted ability of these hormones to stimulate osteoclastic activity in vivo is mediated indirectly, following a primary hormonal interaction with another cell type.

We propose a model for the control of osteoclasis based on these observations. Prostacyclin may play the role of a local‐acting hormone, produced by osteoblasts, which terminates osteoclasis when the requirements of local bone morphogenesis are fulfilled. Calcitonin exerts a direct inhibitory action on isolated osteoclasts and we suggest that this is opposed in vivo by an osteoclastic stimulator, released by osteoblasts. The hormones PTH, 1.25‐(OH)2,D3, and PGE2, stimulate osteoclastic activity indirectly following a primary interaction with osteoblasts, and may do so either by reducing the release of prostacyclin by osteoblasts or increasing formation of the unknown stimulator, or both.
Reduced resorption of cortical bone in mice with induced osteopetrosis
Authors: Loutit J. F. , Howells G. R. , Green D.
Published: June 2005

Two groups of syngeneic radiation chimaeras were established, the reconstitution being with spleen from osteopetrotic mice on the one hand and normal bone marrow on the other. Induced osteopetrosis in the former was evident radiologically not only as metaphyseal opacity but as unduly dense cortices compared with the latter, particularly terminally after 16‐18 months. The radiological impressions were confirmed by measurement of cortical thickness in both longitudinal and transverse sections of undecalcified femoral shafts. Measurements were made with a Quantimet‐720 System‐30 Image Analyser. Terminally the differences were highly significant.

One concludes that defective osteoclasts of osteopetrotic mice derived from haematopoietic stem cells fail to resorb not only primitive woven bone but also cortical laminar bone.
Renal ultrastructure in acute tubular necrosis following Russell's viper envenomation
Authors: Date Anand , Shastry J. C. M.
Published: June 2005

Electron microscopic examination of renal biopsies from nine patients who developed renal failure after Russell's viper bite showed glomerular mesangial hypercellularity, vascular endothelial swelling, tubular epithelial necrosis and shedding, acellular segments of tubular basement membrane and an interstitial infiltrate composed of mast cells, eosinophils, lymphocytes and plasma cells. These cells showed many close contacts with each other and with fibroblasts. Severe vascular and tubular lesions were also present in the medulla. These abnormalities and other reported clinical and laboratory investigations in this condition, suggest that the primary lesion is a reversible intravascular coagulation with secondary ischaemic tubular damage. The inflammatory response in the interstitium is probably initiated by a release of antigens from damaged tubules.
The effects of various anti‐calcific, anti‐rheumatic and anti‐inflammatory drugs on local (simple) calcergy induced by lead acetate in the mouse
Authors: McClure J.
Published: June 2005

The diphosphonate compound ethane‐hydroxy‐1, 1‐diphosphonate (EHDP) is an effective inhibitor of the calcification reaction induced by the subcutaneous injection of lead acetate in the mouse. Dichloromethylene. diphosphonate (CI2MDP) has no such effect and prednisolone and sodium aurothiomalate are also ineffective in inhibiting the reaction. The rate of resorption of the calcified plaque is decreased by CI2MDP when this is administered on an extended basis. This effect disappears after prolonged treatment so that EHDP, calcitonin and CI2MDP have no effect after 7 weeks of daily treatment.
Slow cirrhosis—or no cirrhosis? A lesion causing benign intrahepatic portal hypertension
Authors: Levison D. A. , Kingham J. G. C. , Dawson A. M. , Stansfeld A. G.
Published: June 2005

We report the histological findings in livers from a group of 60 patients with benign intrahepatic portal hypertension. The lesion is benign in comparison with true cirrhosis in the sense that most of the patients survive many years from the time of diagnosis. The histological changes, in our view, differ from those of any variant of cirrhosis and generally do not progress even after many years. The essential features are: (1) irregular capsular thickening; (2) thickening of some portal tracts with fine fibrous septa radiating out from some of them; and (3) distortion of lobular architecture with hyperplastic expansion of some areas and compression of others and irregularly distributed central veins. We suggest that this is the lesion responsible for at least some cases of so‐called idiopathic non‐cirrhotic portal hypertension.
Delayed infarction of spinal cord white matter following X‐irradiation
Authors: Blakemore W. F. , Palmer A. C.
Published: June 2005

The thoraco‐lumbar spinal cord of 4 cats were subjected to 4000 RADS of X‐irradiation. Between 3 and 5 mth afterwards the animals developed weakness of the hind‐legs and became incoordinated. Small infarcts were found in the white matter of the irradiated area of spinal cord, accompanied by neuronal death and oedema of the grey matter close to the central canal. Ultrastructurally the infarcts were shown to stem from necrosis and thrombosis of small blood vessels. Comparison is made with the pathogenesis of spinal cord infarction that occurs in decompression sickness.
Benign schwannomas: A histopathological and morphometric study
Authors: Vilanova J. R. , Burgos‐Bretones J. J. , Alvarez J. A. , Rivera‐Pomar J. M.
Published: June 2005

A conventional histopathological and quantitative morphometric study of 28 capsulated peripheral and spinal nerve benign schwannomas demonstrated linear and parabolic correlation between Antoni B tissue, vascularity and tumour size. The results support the endoneural connective tissue origin of Antoni B, and suggest a model of tumour growth that is partially limited by the growth potential of the Antoni B and/or the vascular component.
The effect of cortisol on porcine articular tissues in organ culture
Authors: Tyler Jenny A. , Fell Honor B. , Lawrence C. E.
Published: June 2005

(1) The effects of hydrocortisone succinate (1.0.–0.01 μ HC/ml of medium) on porcine articular tissues in organ culture have been studied by histological and biochemical methods.

(2) 1.0 and 0.1 μg HC/ml considerably inhibited the severe breakdown of matrix that occurs in living and dead cartilage explanted in contact with synovial tissue.

(3) The depletion of matrix in living cartilage cultivated in the same dish as but not in contact with synovial tissue, is much diminished when the medium contains 1.0 or 0.1 μg HC/ml.

(4) Cartilage grown in the used medium of synovial tissue loses both proteoglycan and hydroxyproline; the addition of HC to the used medium has little (1.0 μg HC/ml) or (0.1 μg HC/ml) no inhibitory effect. If, however, the used medium is from synovial tissue that has been cultured in the presence of 1.0 or 0.1 μg HC/ml, loss of proteoglycan and collagen from the cartilage is much reduced.

(5) In isolated cartilage in normal medium there is outgrowth of cells from the cut surface and some loss of proteoglycan and collagen; outgrowth is completely, and loss of matrix components partially suppressed by 1.0 μg HC/ml.

(6) Isolated synovial tissue cultured in normal medium shrinks to about one‐third of its original size, loses much of its collagen and secretes neutral metallo‐proteinases into the medium; in the presence of 1.0 μg HC/ml these changes are largely prevented. The explants also secrete an inhibitor of metallo‐proteinases the production of which is not reduced by HC.
Necrosis of the pars recta (S3 segment) of the rat kidney produced by hexachloro 1:3 butadiene
Authors: Ishmael J. , Pratt Iona , Lock E. A.
Published: June 2005

Administration of hexachloro 1 : 3 butadiene (HCBD) intraperitoneally at a dose of 200 mg/kg body weight caused necrosis of the pars recta of the proximal tubules situated in the outer stripe of the outer medulla of the rat kidney. The earliest morphological changes detectable by light microscopy were observed after eight hours, with several proximal tubules showing necrosis. By sixteen hours a distinct band of tubular necrosis was seen in the outer stripe of the outer medulla. One and two days after dosing proximal tubular necrosis was still evident whereas distal tubules were unaffected. By three days, vacuolation was observed in the pars convoluta of some proximal tubules. Active tubular regeneration was apparent by day five, which was accompanied by a marked increase in renal water and nonprotein sulphydryl content (NP‐SH). By day fourteen substantial recovery had occurred. Ultrastructural changes were seen as early as one hour after HCBD (300 mg/kg, ip) although necrosis was not marked until 8 hr. Mitochondrial swelling was seen 1–4 hr after dosing in the S1 and S2 segments of the proximal tubule. By 8 hr the major pathological changes were largely confined to the S3 segment and consisted of loss of brush border, mitochondrial swelling and cellular necrosis. In conclusion HCBD produces a site‐specific nephrotoxic effect on the proximal tubule in the rat. The pattern of injury was similar to that associated with some other nephrotoxic and ischaemic models of acute renal failure.
Phagocytosis of the a band following Z line, and I band loss. Its significance in skeletal muscle breakdown
Authors: Cullen M. J. , Fulthorpe J. J.
Published: June 2005

A band phagocytosis, following Z line and I band loss. is described in polymyositis, in epsilon amino caproic acid induced myopathy and in an experimental myositis of guinea pigs. It is far less prominent in Duchenne muscular dystrophy.

This form of necrosis is always associated with lesions in the plasma membrane. It is argued that the ensuing ionic equilibration with the extracellular fluid allows activation of a calcium activated proteinase (CAP) which digests the Z line. Breakdown of the myofibrils into individual A bands promotes rapid phagocytosis of the myofibre contents and facilitates regeneration of the muscle.
Towards economy of effort in quantitative ultrastructural pathology: Efficient sampling schemes for studying experimental carcinogenesis
Authors: Mayhew T. M. , White F. H. , Gohari K.
Published: June 2005

Hamster cheek pouch mucosa was painted with DMBA in order to compare samples of epithelium at different pathological stages of carcinogenesis. Stereological methods were applied to ultrathin sections of tissue to estimate one ultra‐structural index of change, the surface ratio of lamina densa compared with the overlying plasma membrane of cells in stratum basale. Analysis of variance techniques were then employed to isolate and quantify the contributions which different levels of sampling (animals, tissue blocks, microscopic fields) made to the total observed variation in this surface ratio. Economical sampling schemes for future use were calculated from these sampling variances by taking into account the relative costs at each sampling level. Though illustrated by means of the hamster cheek pouch‐DMBA model, our results are pertinent to many other experimental models for quantitative histopathology.
Proctitis cystica profunda and radiation fibrosis in the rectum of the female wistar rat after X irradiation: A histopathological study
Authors: Hubmann F.‐H.
Published: June 2005

Part of the rectum of the female Wistar rat was X‐irradiated (1500 rad–3000 rad) without surgery. In the early phase (second week after irradiation) radiation damage of the rectum was haemorrhagic radiation proctitis and in the late phase a rectal obstruction. The dose‐effect relationship using rectal obstruction as the end point is a sigmoid curve with a LD50 of 2150 rad. Latency time decreases with increasing dose and is 150 days at the LD50. Histopathologic findings revealed excessive submucosal radiation fibrosis and numerous mucosal glands and cysts within the fibrotic submucosa. As the time after irradiation increased the extension of submucosal mucinous glands increased and sometimes the entire submucosa was replaced completely by mucosal glands and cysts. It is suggested that invasion of mucosal epithelium into the submucosa was allowed by manifold fragmentation of the muscularis mucosae due to lymphocysts having developed immediately after irradiation. The small arteries showed proliferation of the endothelium and adventitia, thickening and hyalinization of the wall, resulting in severe narrowing and even occlusion of the lumen.
Malignant histiocytosis presenting as lethal midline granuloma: Immunohistological study
Authors: Aozasa K. , Inoue A.
Published: June 2005

Recent advances in immunology have revealed that the “histiocytic” lymphoma of Rappaport is a proliferation of transformed lymphocytes rather than true histiocytes, and that the malignant cells in malignant histiocytosis (MH) are truly transformed histiocytes. We previously reported cases of MH presenting as lethal midline granuloma (MH‐LMG) utilising fresh tissue specimens for the detection of cytological markers in a small number of cases. The results showed the true histiocytic nature of the proliferating cells. In this study, paraffin‐embedded specimens from 16 cases with MH‐LMG were processed for immunoperoxidase procedures to confirm the true histiocytic nature of the proliferating cells. Five cases with nasal and paranasal lymphomas (ML) were also stained to test the usefulness of immunoperoxidase procedures for distinguishing the MH‐LMG from ML. Results were as follows; proliferating cells in MH‐LMG were histiocytic in nature, staining positive for lysozyme in MH‐LMG in contrast to the negative staining in ML.
The response of the murine lymphoid system to a chronic infection with Trypanosoma congolense. II. The lymph nodes, thymus and liver
Authors: Morrison W. I. , Murray Max , Hinson C. A.
Published: June 2005

The cellular responses in the lymph nodes, thymus and liver of mice infected with Trypanosoma congolense were examined and considered in relation to changes in the level of Ig in the serum. A significant proliferative response occurred in the lymph nodes only after 3 weeks of infection and involved mainly the B‐dependent folliçular areas in which there was marked germinal centre formation. This was associated with the appearance in the medullary cords of large numbers of plasma cells. Only a minor increase in the number of macrophages was observed in the lymph node sinuses and there was no obvious lymphoid depletion. A partial depletion of the cortical areas of the thymus in the later stages of the infection was the only remarkable feature in that organ. An abrupt but transient increase in the levels of the 4 classes of Ig which were monitored was observed about the time of the first peak of parasitaemia and was considered to result from the proliferative response in the spleen. A second and more pronounced increase occurred later coinciding with the onset of proliferative activity in the lymph nodes. There was marked cellular infiltration into the liver; this commenced about the time of the first peak of parasitaemia when it involved mainly lymphocytes and plasma cells and became progressively more severe involving a mixture of cell types including lymphocytes, plasma cells and erythropoietic and granulopoietic cells. In addition, there was an increase in the number of Kupffer cells lining hepatic sinusoids. Throughout most of the infection, focal hepatic necrosis and increased mitotic activity of hepatocytes were prominent features. The differences in timing and character of the cellular responses between the different lymphoid organs were considered to be due in part to the restriction of T. congolense to the intravascular spaces.
Histological features of skin reactions to human lymphoid cell line lymphokine in patients with advanced cancer
Authors: Dumonde D. C. , Pulley Melanie S. , Paradinas F. J. , Southcott Barbara M. , O'Connell D. , Robinson M. R. G. , den Hollander F. , Schuurs A. H.
Published: June 2005

Lymphokines (LCL‐LK) prepared from the human lymphoid cell line RPMI 1788 were injected intradermally into tumour‐bearing patients. Biopsies of skin reactions were obtained for histological study from 30 min. to 72 hr, and for comparison, biopsies were taken at similar times of tuberculin reactions in tuberculin‐positive patients. The early response to LCL‐LK consisted of polymorph adherence to vascular endothelium (at 30 min.) followed by poiymorph exudation, oedema and haemorrhage (1–2 hr); mononuclear and eosinophilic leucocyte emigration began at 4 hr; and by 12 hr, when the reaction was maximal clinically, there was widespread pleomorphic leucocytic infiltration of the dermis. At later times (48–72 hr) skin reactions to LCL‐LK showed predominantly mononuclear cell infiltration and hypertrophy of vascular endothelium. Electron microscopy at 48 hr revealed perivascular lymphocytes and macrophages.

The skin reaction to LCL‐LK appeared to superimpose an early component of marked polymorph infiltration, oedema and haemorrhage upon a mononuclear cell exudation similar to that seen in the tuberculin reaction.

It was concluded that the later phase of the skin reaction to lymphoid cell line lymphokine in the human bore a close histological similarity to the established tuberculin reaction. The LCL‐LK reaction occurred in patients anergic to recall antigens. Its intensity was mainly related to dose and did not vary substantially between different batches of lymphokines.
Changes induced by local injection of human lymphoid cell lymphokine into dermal metastases of breast carcinoma: A light and electron microscopical study
Authors: Paradinas F. J. , Southcorr Barbara M. , O'Connell D. , den Hollander F. , Schuurs A. H. , Pulley Melanie S. , Dumonde D. C.
Published: June 2005

Lymphokines (LCL‐LK) prepared from the human lymphoid cell line RPMI 1788 were injected into dermal nodular metastases of three patients with advanced breast carcinoma anergic to recall antigen (tuberculin). Three different injection schedules were employed. Ten such nodules were examined by excision biopsy and their histological appearances were compared with biopsies of four further nodules not injected with the lymphokine. Intranodular injection of LCL‐LK resulted in clinical regression of tumour and histological evidence of tumour‐cell necrosis with pleomorphic leucocytic infiltration by polymorphs, macrophages and lymphocytes. Electron microscopy of two such nodules failed to show close cell contact between leucocytes and tumour cells prior to tumour‐cell necrosis.

This study extends evidence that injection of inflammatory lymphokines into accessible tumour can result in local tumour regression and it suggests that such tumour‐cell destruction may be the result of a variety of factors operating during local inflammatory response.
Severity of glomerulonephritis induced in different strains of suckling mice by infection with lymphocytic choriomeningitis virus: Correlation with amounts of endogenous interferon and circulating immune complexes
Authors: Woodrow D. , Ronco P. , Riviere Y. , Moss J. , Gresser I. , Guillon J. C. , Morel‐Maroger L. , Sloper J. C. , Verroust P.
Published: June 2005

Renal lesions due to neonatal infection with lymphocytic choriomeningitis virus were studied in three different strains of mice known to produce different amounts of viral interferon. Very severe ultrastructural lesions similar to those induced by exogenous interferon were found as early as day 8 in C3H mice which produced the highest amount of interferon. Further studies could not be performed in these mice since all died by day 14. Balb/c mice produced the lowest amount of interferon and had very mild ultrastructural lesions. An intermediate pattern was found in Swiss mice. After 30 days of infection, severe immune complex type glomerulonephritis detectable by light microscopy and immunofluorescence was observed in Swiss mice whereas mild lesions only were found in Balb/c mice. Circulating immune complexes were present in both strains but in greater amounts in Swiss than Balb/c mice. These results suggest that two factors at least are important in the development of glomerulonephritis: interferon produced early in life and the load of circulating immune complexes.
An ultrastructural study of the origin and function of basophilic degeneration in human cardiac muscle—cardiac colloid. Type 1
Authors: Gregory M. A. , Olmesdahl P. J. , Whitton I. D.
Published: June 2005

The myofibres in biopsies obtained from the left ventricle during cardiopulmonary bypass, in patients undergoing surgery for mitral and aortic valve replacement and the correction of atrial septal defect, contained inclusions thought to be type 1 cardiac colloid. Electron microscopy showed this material to be synthesised by and contained within a grossly dilated rough endoplasmic reticulum. The presence of membrane‐bound aggregates of non‐fibrillar sarcoplasmic organelles within colloid deposits, together with osmiophilic inclusions thought to be related to lipofuscin, both within and moving from this structure, suggest that type 1 cardiac colloid is an autophagic vacuole designed to degrade ageing or redundant sarcoplasmic organelles.
Comparative histology of the mouse bladder following initial infection and re‐infection with Escherichia coli
Authors: Sivan Yaacov , Griffel Benjamin , Medalia Ora , Aronson Moshe
Published: June 2005

The present study continues our investigation of the bladder antimicrobial mechanisms following bacterial infection.

Since the process of spontaneous clearance of bacteria (E. coli) from the mouse bladder is greatly accelerated upon re‐infection, a histopathological comparison was made of initially infected (II) versus re‐infected (RI) mice. It was reconfirmed that the spontaneous clearance upon re‐infection is indeed much faster than after the initial infection. There were morphological differences between these two courses of infection, as well as in the localization and composition of the inflammatory response. Thus cellular infiltration was more evident in the epithelium of the II mice, whereas the RI animals displayed increased cellular exudation in the lamina propria. It was also found that the dominant cell in the II mouse is the granulocyte and in the RI mouse—lymphocytes, macrophages and plasma cells. This last finding is suggestive of a local immunological process. The overall results are consistent with the notion that a local immune response develops in the infected bladder and participates in the enhanced clearance in RI animals.
Studies on the relationship between proteinuria and glomerular ultrastructural change in hyperalbuminaemic female wistar rats
Authors: Lawrence Gillian M. , Brewer D. B.
Published: June 2005

Increased albumin filtration was shown to cause glomerular epithelial cell foot process loss in female Wistar rats made hyperalbuminaemic by means of a series of intraperitoneal bovine albumin injections. It appeared to act by stimulating glomerular epithelial cell endocytosis with the result that protein droplets and vacuoles accumulated within the epithelium causing marked cytoplasmic swelling which forced the foot processes to spread out and fuse. The severity of this glomerular ultra‐structural damage rose with increasing bovine albumin dose and correlated well with induced proteinuria.
A new reproducible experimental model of analgesic nephropathy
Authors: Henry M. A. , Sweet R. S. , Tange J. D.
Published: June 2005

The uninephrectomised homozygous Gunn rat is more sensitive than other experimental animals to the nephrotoxic effects of analgesics. Phenacetin derivatives produce severe necrosis of proximal convoluted tubules and aspirin and phenazone renal papillary necrosis. The observations suggest that the components of compound analgesic preparations have separate and complementary nephrotoxic effects, and this is a possible factor contributing to the association of analgesic nephropathy with abuse of such preparations.
Myeloid bodies in drug‐induced acute tubular necrosis
Authors: Jao Wellington , Manaligod Jose R. , Gerardo Leo T. , Castillo Manuel M.
Published: June 2005

A growing list of drugs, metals, and chemicals has been implicated as the cause of functional and structural damage specifically to the proximal tubular epithelium. Renal biopsies were obtained from three patients who had developed nephrotoxic agent‐related acute renal failure. Two of the patients had received gentamicin and viomycin; the third patient had heavy exposure to chromium. All three biopsies showed acute tubular necrosis (ATN) on light microscopy. Electron microscopy revealed that the proximal tubular cells and, to a lesser degree, the distal tubular cells, contained abundant, variably sized myeloid bodies. In our previous experimental study of viomycin‐induced ATN in rats, similar ultrastructural findings of a gradual increase in the number of myeloid bodies in the proximal tubular cells were also observed.

The constant presence of myeloid bodies in the tubular epithelial cells following drug‐induced tubular necrosis suggests that they may represent lysosomal isolation of drug‐bound cytoplasmic structures, as a cellular mechanism to degrade toxic substances and, therefore, may serve as an ultrastructural marker of cellular drug uptake and drug disposition.
Ultrastructural appearances of acute renal papillary lesions induced by aspirin
Authors: Henry M. A. , Tange J. D.
Published: June 2005

Renal papillary necrosis develops 16 hr after intravenous administration of aspirin to the uninephrectomised homozygous Gunn rat. Ultrastructural studies show the papillary interstitial cells to be most severely affected, the first changes being visible at 1 hr. Changes in capillaries are late in onset, and this suggests that the lesions are due to a direct toxic effect rather than to ischaemia.
The uptake of horseradish peroxidase and its subsequent redistribution by guinea pig gallbladder in vivo
Authors: Coghill S. B. , Hopwood D. , Milne G.
Published: June 2005

Horseradish peroxidase (HRP) was injected into the emptied gallbladder of guinea pigs at laparotomy. The fate of the HRP was observed by light and electron microscopy over the following 2 hr. Within 5 min. HRP appeared in pits and apical vesicles either as a rim of increased electron density or more evenly distributed throughout the pit or vesicle. The pits and vesicles were more frequently seen at the edge of the cell apex. From 15 min. HRP was identified in the basolateral cell space in increasing quantities with spill over through the basement membrane into the lamina propria: by 30 min. and 2 hr, little further change was observed. The quantity of nonspecific electron density in epithelial cell multivesicular bodies and residual bodies made the assessment of intracellular handling of the HRP impossible. Dilution of the HRP in the lamina propria made the identification of the eventual fate of the HRP difficult to determine.
Differential toxicity of methylglyoxal‐bis[guanylhydrazone]
Authors: Dewey D. L. , Gaugas J. M. , Stratford M. R. L. , Minchinton A. I.
Published: June 2005

The toxicity to cultured cells of the cancer chemotherapeutic agent methylglyoxal‐bis[guanylhydrazone] (MGBG) varies considerably between different cell lines and is always more toxic in the absence of exogenous polyamine. We have looked at the relative MGBG toxicity of two different murine melanoma tumour cell lines (Harding‐Passey and Cloudman) and normal murine fibroblasts, and found wide variation with no correlation in sensitivity to MGBG between tumour and normal cells. High sensitivity to MGBG may be associated with high transport across the cell membrane.
The lectin binding affinity of Reed‐Sternberg cells
Authors: Morris Christine S. , Stuart A. E.
Published: June 2005

Reed‐Sternberg cells from ten cases of Hodgkin's disease were examined by the direct immunofluorescence technique, for their affinity for nine lectins. The surrounding lymphocytes and monocytes of HD tissue were also assessed for their ability to bind lectins. RS cells showed considerable heterogeneity of reaction. Overall, there was a marked decrease in the binding of most of the lectins studied in HD cases as compared to normal peripheral blood mononuclear cells. This was particularly evident for RCA, PHA and PNA binding. It is suggested that there is a defect in carbohydrate metabolism, with fewer lectin‐binding sites on both RS cells and on the mononuclear cell populations in Hodgkin's disease. Further quantitative work is required to verify this.
Application of in‐vitro techniques to determine proliferation in human sarcoid lymph nodes
Authors: van der Gaag R. D. , van Maarsseveen A. C. M. Th. , Broekhuizen‐Davies J. M. , Stam J.
Published: June 2005

Sarcoidosis is suggested to be a granulomatous disease with high‐turnover characteristics. In this paper the turnover of the inflammatory cells (the epithelioid cells) in lymph node granulomas from sarcoidosis patients is described. Uniform slices of granulomatous lymph nodes were incubated with 3H‐thymidine; autoradiographically the DNA‐synthesizing cells, parameter for local proliferation, were detected and the L.I. (labelling index) was determined.

We observed mostly low‐turnover reactions, incidentally granulomas with high‐turnover characteristics are found within the same lymph node.

The uptake of 3H‐TdR demonstrates that these granulomas could be in different stages of activation.
Cutaneous basophil associated resistance to ectoparasites (ticks). Electron microscopy of Rhipicephalus appendiculatus larval feeding sites in actively sensitised guinea pigs and recipients of immune serum
Authors: McLaren Diane J. , Worms M. J. , Askenase P. W.
Published: June 2005

Electron microscopy has been used to monitor cellular activity in dermal lesions elicited by larval Rhipicephalus appendiculatus feeding on actively sensitised guinea pigs and recipients of immune serum. The early primary response is characterised by mononuclear cells, many of which appear to be activated fibroblasts. Collagen deposition is enhanced as the reaction progresses. Granulocytes of all types appear in the lesion between 18 and 96 hr but they show no evidence of degranulation. Free, membrane‐bounded eosinophil and basophil secretion granules may, however, be identified in the dermis at day 5 or 6, but they seem to be liberated as a consequence of cellular disruption, rather than active degranulation. Some feeding sites resume a normal morphology by day 7. Lesions induced in actively sensitised hosts by a secondary feeding tick population are dominated by basophils. These cells begin to infiltrate the dermis within 6 hr and they show evidence of anaphylactic degranulation at 12 hr. Maximal release of membrane‐free secretion granules occurs at about 18 hr post‐attachment, at which time eosinophils become prominent. Degranulating basophils show a reduction in numbers from 24 to 96 hr, and phagocytic macrophages ingest residual granules and cellular debris. Guinea pigs sensitised with immune serum and subjected to challenge exhibit lesions similar to but less dramatic than those of actively sensitised and challenged animals. Anaphylactic degranulation of basophils occurs both in the dermis and within blood vessels. The immunological consequences of these events are discussed in relation to other models of cutaneous basophil hypersensitivity.
Collagen production by human mesothelial cells in vitro
Authors: Harvey W. , Amlot P. L.
Published: June 2005

Serous effusions from a variety of malignant and non‐malignant conditions were found to contain cells which had the morphological, histochemical and ultrastructural characteristics of mesothelial cells. In culture they were the predominant cell type and synthesised large quantities of the interstitial collagens type I and III, with the proportion of type III frequently approaching or exceeding 50 per cent. There was no evidence that they synthesised basement membrane collagen chains of type IV or type V. Since mesothelial cells are assumed to secrete the mesothelial basement membrane, the synthesis of interstitial collagens by desquamated mesothelial cells appears to reflect a change in the phenotype of collagen synthesis. We suggest that this change may be an important factor in the fibrosis of the serosal wall which frequently accompanies diseases with chronic serious effusion.
Histopathology of experimental Legionnaires' disease in guinea pigs, rhesus monkeys and marmosets
Authors: Baskerville A. , Fitzgeorge R. B. , Broster M. , Hambleton P.
Published: June 2005

Guinea pigs, rhesus monkeys and marmosets were infected with L. pneumophila in small particle aerosols. Fever and acute fibrinopurulent pneumonia resulted. The lesions involved distal lung tissue only, spreading from terminal and respiratory bronchioles and producing heavy infiltration of alveoli by polymorphs and macrophages and widespread exudation of oedema fluid and fibrin. Lesions were not found in extra‐pulmonary sites.
The potential aggressiveness of synovial tissue in rheumatoid arthritis
Authors: Fassbender H. G. , Simmling‐Annefeld Marliese
Published: June 2005

Operation specimens of articular tissue from about 8000 patients with clinically evident rheumatoid arthritis have been studied by light microscopy and in 583 cases by electron microscopy over a period of several years. We examined the tissue in closest contact with eroded cartilage. In approximately 70 per cent. of cases this was a fibrous pannus of compact collagenous connective tissue with few fibrocytes; in approximately 25 per cent. of cases a pannus, consisting of loose granulation tissue, moderately rich in collagen fibres, fibroblasts, and small blood vessels; in approximately 5 per cent. of cases, however, we found, that the zone in close contact consisted of uniform layers of immature‐looking synovial cells with large nuclei. These immature‐looking cells encroach on the cartilage from the junction of synovium with the articular cartilage. The development of these aggressive cell structures seemed to be preceded by a fibrinous inflammatory exudate. The cells contain lysosomal enzymes which are able to destroy prcteoglycans and collagen fibres and could therefore be the basis of erosion of cartilage. The cell structures seem to be short‐lived and they are avascular at least initially. Most of the cells seem to die within a few days. The remaining cells assume the appearance of fibroblasts and form the later pannus. The cell content decreases as the pannus gets older. It is suggested that the destruction of articular cartilage takes place only during the short time in which these aggressive cell structures are present. The erosive synovial cells may however reappear during the intermittent course of the disease, after episodes of quiescence and acute inflammation.
The reversible detachment and deposition of surfactant and of pulmonary macrophages during bronchopulmonary lavage in the rat
Authors: Phizackerley P. J. R. , Newman G. E. , Smith H. , Cooper J. R.
Published: June 2005

A procedure is described for carrying out repetitive bronchopulmonary lavage in the rat, in which a given volume of iavage fluid is introduced into the lungs from a reservoir and then withdrawn from the lungs back into the reservoir, the process being repeated a number of times. During this procedure there is a nett release of endogenous surfactant and macrophages from the lungs. [14C] pulmonary surfactant was prepared from rats previously injected intravenously with [1‐14C] palmitate, and pulmonary macrophages labelled with 85Sr were prepared from rats which had received by intratracheal injection a suspension of fused clay particles labelled with 85Sr. It was shown by carrying out repetitive bronchopulmonary lavage with 0.15M‐NaCl containing either exogenous [14C]‐surfactant or [85Sr]‐macrophages that the release of endogenous surfactant and macrophages from the lung into the lavage fluid occurred concomitantly with the retention within the lung of radioactive exogenous surfactant and macrophages from the lavage fluid. It is concluded that the process of surfactant and macrophage detachment during bronchopulmonary lavage is reversible and that the exchange processes are of substantial magnitude.
The role of plasma factors in the adherence of leucocytes to vascular endothelial cells
Authors: Sedgwick A. D. , Mackay A. R. , Bates M. B. , Willoughby D. A.
Published: June 2005

Studies have been undertaken to search for humoral factors present in the plasma from animals undergoing inflammation which may promote specific cell types to adhere to vascular endothelium. We have tested both plasma from animals with “acute” pleural inflammation and animals with “chronic” carrageenan air pouch granulomata for the presence of leucocyte pro‐adhesive activity. Plasma from animals with carrageenan pleurisy had augmented polymorph adhesive activity. This activity was absent in the plasma from animals with air pouch granulomata. No such pro‐adhesive activity for mononuclear cells was detected in this plasma. We conclude that the initial influx of polymorphs during the early stages of inflammation may in part be due to systemic pro‐adhesive factors. It is proposed that these factors in combination with chemotaxins released at the lesion site are responsible for the early dominance of polymorphs.
Immunopathology of experimental schistosome (S. Mansoni) egg granulomas in mice—possible defence mechanisms mediated by local immune complexes
Authors: de Brito T. , Hoshino‐Shimizu Sumie , da Silva L. C. , Kanamura Hermīnia , Costa Cecīlia M. , Pinto P. S.
Published: June 2005

A ten month experimental S. Mansoni infection was followed in mice by studying schistosome egg granulomatous inflammation, antigen and immunoglobulins deposits in the granulomata and the circulating antibodies. During the experimental infection it was demonstrated that while the granulomatous reaction matures there is a progressive restriction of the antigens to the miracidia. Furthermore, immunoglobulins, particularly IgG and C3 deposits were demonstrated in the granulomata.

Our data support the concept that schistosome egg granuloma is a hypersensitivity high turnover granuloma that is particularly efficient in walling off the antigen. Whereas the granuloma is built up largely by a cell mediated immune reaction, antibody deposits are also found, probably functioning as a local humoral antibody barrier which allows a slow and progressive neutralisation of the antigens. Viewed as a whole, experimental schistosome egg granuloma might be considered as a mixed, chiefly cell but also humoral antibody mediated immune reaction.
An ultrastructural study of the macrophages of the carrageenan‐induced granuloma in the rat lung
Authors: Bowers R. R. , Stapleton M. E. , Lew P. D.
Published: June 2005

The intralobular injection of 0.17 ml of 2 per cent. carrageenan into the rat lung induced an inflammatory granulomatous response. This inflammation was characterized in the early stages by immediate polymorphonuclear (PMN) leucocyte infiltration into the alveoli. Within 2 days the PMN's began to disappear and were replaced by carrageenan‐containing macrophages. Alveolar macrophages actively phagocytised the injected carrageenan and were the dominant cell type in the alveoli for the length of this study (365 days). These low‐turnover alveolar macrophages, which with light microscopy stained pinkish‐red metachromatically with toludine blue due to their carrageenan content, underwent changes in vacuole morphology as well as changes in size and shape. Throughout the course of this inflammation, these macrophages had carrageenan‐containing vacuoles which could be seen undergoing fusion to form larger vacuoles which at times constituted half the size of the entire macrophage cytoplasm. The carrageenan in the vacuoles was an amorphous flocculent appearing material for the initial 14 days but changed to a more fine filamentous form for the remainder of the study. This was probably due to its partial digestion by lysosomal enzymes. The general composition of the cytoplasm remained fairly constant during the 365 days. Pinocytotic vesicles and free ribosomes were abundant and the many mitochondria were small and rounded. Smooth endoplasmic reticulum lysosomes, and Golgi apparati, although not prominent, were present but the most striking feature of the cytoplasm was the presence of numerous lamellar bodies (phagocytosised surfactant). Some of the macrophages increased greatly in overall size (five to seven times) compared to their initial size. A few isolated macrophages could be seen degenerating but no general necrosis was seen. Except for one isolated case, no epithelioid cells were observed in this carrageenan inflammation. Fibrosis, if present at all, was very localised and was only evident at day 340 post‐injection. This fibrosis generally involved one or two carrageenan‐containing macrophages encapsulated by a few collagen fibres. No widespread fibrosis was ever observed in this study which confirmed earlier histological and biochemical investigations.
The kinetics of mononuclear phagocyte infiltration in neoplasms: Reactions to nonspecific stimuli in a rat fibrosarcoma
Authors: Woods A. E. , Papadimitriou J. M. , van Bruggen Ivonne
Published: June 2005

The kinetics of macrophage infiltration into a transplantable rat fibrosarcoma were investigated. Monocytes obtained from normal rats and labelled with 51Cr were injected into normal or fibrosarcoma‐bearing rats which had previously been implanted with cotton pellets impregnated with BCG, B. pertussis carrageenan or levan. The subcutaneous tissues of normal and fibrosarcoma‐bearing rats as well as the neoplasm itself were the sites for pellet implantation. The various additives induced an enhancement of macrophage infiltration into cotton pellets implanted for 1 week into subcutaneous tissues of normal rats. No significant effect was found in pellets implanted for 3 or 14 days. Macrophage infiltration into pellets in the neoplasm was consistently reduced when compared with controls. This occurred regardless of the length of time of implantation, the type of substance added to the pellet or (in the case of BCG or B. pertussis) whether the rats were pre‐sensitised to the pellet additive or not. Pellets removed from the subcutaneous tissues of fibrosarcoma‐bearing rats were either similar to or more often higher in radioactivity than those implanted into the neoplasm itself. The results indicate that the capacity of macrophages to respond to inflammatory stimuli is reduced in fibrosarcoma‐bearing rats, but especially in the stroma of the neoplasm.
Induction of renal tumours in rats by the administration of 1,2 dimethylhydrazine
Authors: Sunter J. P. , Senior P. V.
Published: June 2005

Administration of dimethylhydrazine (DMH) to adult rats by two subcutaneous injections each of 120 mg(base)/kg body weight and spaced 10 days apart resulted in the development of renal tumours in over 90 per cent. of treated animals at 30 weeks after injection. The tumours were frequently bilateral and multiple, and had the structure of the “mesenchymal” tumours which occur in a high incidence following treatment with nitrosamines.

The incidence of tumours both in the small intestine and in the colon was lower than that experienced using a weekly DMH treatment schedule.
The effects of maternal influenzal viraemia in late gestation on the conceptus of the pregnant ferret
Authors: Rushton D. I. , Collie M. H. , Sweet C. , Husseini R. H. , Smith H.
Published: June 2005

Pregnant ferrets were inoculated intra‐cardially on day 30 of gestation with influenza virus. The animals were sacrificed on days 5 to 11 after inoculation and the products of conception including the uterus were examined virologically and histopathologically. The results indicate that the initial site of infection of the conceptus is the haemophagous organ and that spread occurs from this site to the endometrium, placental labyrinth and fetus. Lesions in the fetus are confined to the liver and respiratory tract. In the liver they may represent either a viral hepatitis or a secondary response to placental damage resulting in the stimulation of erythropoiesis. In the respiratory tract they first occur in the nasal sinuses and upper airways suggesting that infection is via the amniotic fluid rather than via the blood stream. The relevance of these findings to human pregnancy is discussed.
The brain in experimental portal‐systemic encephalopathy. II. Water and electrolyte changes
Authors: Pilbeam C. M. , Anderson R. McD. , Bhathal P. S.
Published: June 2005

The water content and amounts of sodium, potassium and chloride were measured in the brains of normal rats, rats with PCA, normal rats fed ammoniated cationic exchange resin, and rats with PCA fed the resin. Plasma eletrolytes and ammonia levels were also measured, and sodium and Chloride spaces were calculated. Rats with PCA showed increased water content, sodium space and chloride space in the brainstem compared to controls. Rats with PCA fed ammoniated resin showed increased chloride content and Na+ : K+ ratio in the brainstem, and an increased chloride space in the brainstem. In these rats the chloride spaces in the cerebrum and cerebellum exceeded the sodium spaces. It is concluded that high circulating ammonia levels can in vivo produce ionic shifts which may interfere with nervous function. It is also concluded that increased cytoplasmic osmolarity produced by ammonium ion‐induced stimulation of (Na+ + Ka+) ATPase may result in the appearnce of swollen astrocytes in conventional electron micrographs.
The effect of treatment of the associated disease on the development of amyloidosis in the experimental animal
Authors: Kennedy J. S. , Anderson J. D.
Published: June 2005

Thirty‐five golden hamsters infected with Leishmania donovani were treated with Pentostam and followed up to determine the effect of treatment on the development of secondary amyloidosis.

Seventy untreated golden hamsters infected with L. donovani were followed up as controls to determine the pattern of development of secondary amyloidosis.

Amyloid developed in all animals‐treated and untreated. The treatment significantly prolonged the survival time, but did not inhibit the development of renal amyloid in animals shown by biopsy to be free from renal amyloid at the time of treatment. When amyloid was present in kidney at the time of treatment it progressed invariably to renal failure.