bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructural localisation of fibronectin in mouse kidney
Authors: Dixon A. Jane , Burns J.
Published: June 2005

The ultrastructural localisation of fibronectin in mouse kidney was investigated by indirect immunoperoxidase cytochemistry. In glomeruli, fibronectin was found predominantly in matrix between endothelial and mesangial cells. Smaller quantities were demonstrable in peripheral capillary walls both subendothelially and around visceral epithelial cell foot processes. It was present between parietal epithelial cells and Bowman's capsule and at the base of tubular epithelial cells outlining the inner aspect of tubular basement membranes.
Chondro‐osseous changes in cerebro‐oculo‐facial‐skeletal (COFS) syndrome
Authors: Hwang W. S. , Trevenen C. L. , Greenberg C. , Reed M. H.
Published: June 2005

Radiological and pathological findings were described in three cases of COFS syndrome. Early diagnosis of this syndrome is possible by the recognition radiologically of the characteristic proximal displacement of second metatarsals and pathologically by the extensive cell necrosis in the iliac crest biopsy. Pathological findings, including the presence of nuclear bodies in chondrocytes and amianthoid fibres surrounding necrotic cartilage cells, are compatible with a primary degenerative/ deformative disorder. The aetiology of this syndrome is unknown.
X‐ray microanalysis of the michaelis‐gutmann bodies of malakoplakia
Authors: Underwood J. C. E. , Durrant T. E. , Coup A. J.
Published: June 2005

The Michaelis‐Gutmann (MG) inclusion bodies of three cases of malakoplakia (prostate, testis, colon) were studied by X‐ray microanalysis to determine their elemental composition. Calcium and phosphorus were consistently found. Iron was detected in a few bodies. No other elements were detected. The electrondense laminations were of similar composition to the core material. Small aggregates of electron‐dense material containing calcium and phosphorus were also occasionally seen in phagolysosomes. These observations are consistent with view that MG bodies arise by a process of phagolysosomal coalescence and mineralisation.
Hyperplasia of the carotid body
Authors: Heath Donald , Smith Paul , Jago Ross
Published: June 2005

The histopathology of hyperplasia of the carotid bodies was studied in 6 cases of hypoxaemia and right ventricular hypertrophy secondary to pan‐acinar emphysema, and in five cases of systemic hypertension with left ventricular hypertrophy. The features of the hyperplasia were the same in the two groups. There was proliferation of sustentacular (type II) cells and compression of central cores of chief (type I) cells. It is speculated that the hyperplasia of sustentacular cells is associated in some way with the prevention of retention of sodium ions and water which characterises hypoxic cor pulmonale in “blue bloaters”, systemic hypertension, and ascent to high altitude with the complications of acute mountain sickness, and pulmonary and cerebral oedema.
Morpho‐functional patterns of kidney injury in the experimental leptospirosis of the guinea‐pig (L. icterohaemorrhagiae)
Authors: de Arriaga Ana J. Dávila , Rocha A. S. , Yasuda P. H. , de Brito T.
Published: June 2005

Thirty‐seven guinea‐pigs experimentally infected with a virulent strain of L. icterohaemorrhagiae, were submitted to a renal function study as evaluated through the maximal urinary concentration (MUC) test, blood urea nitrogen (BUN) and afterwards had their kidneys examined by light and electron microscopy. Vascular changes were also studied after the administration of colloidal carbon as a marker.

Though the MUC test and BUN determination, two groups of tubulo‐interstitial lesions can be visualised, one in animals without renal insufficiency, manifested chiefly by cell edema with RE dilation and another, in animals with renal insufficiency, characterised not only by marked cell edema and mitochondrial changes, but also by proximal tubule regenerative aspects without overt tubular necrosis. Interstitial edema and focal nephritis was prominent in both groups, a finding which minimises their role in the pathogenesis of renal failure in experimental leptospirosis.

Vascular injury, affecting the vessels of the renal micro‐circulation chiefly at the cortico‐medular junction, was observed in both groups. Its severity and extension ran parallel to the intensity of the tubular injury. This suggests a simultaneous action of a noxious agent liberated by the leptospires over both structures, tubular damage being accentuated by the local circulatory changes.
Structure of the glomic arteries
Authors: Jago Ross , Heath Donald , Smith Paul
Published: June 2005

The structure of the arteries which supply blood to the carotid bodies was examined in five cases in which the weights of the cardiac ventricles were normal and in which hypoxaemia due to emphysema or systemic hypertension were absent. The right glomic arteries were studied by light microscopy, and the left by electron microscopy. A sixth case, also free from myocardial hypertrophy, was used solely for an examination of the common carotid artery, the carotid sinus and the internal carotid artery by light and electron microscopy. The glomic arteries resembled the carotid sinus in being highly elastic with a rich supply of non‐myelinated nerve fibres and thus had a structure consistent with having a baroreceptor function.
Tissue reactions to implanted dental amalgam, including assessment by energy dispersive X‐ray micro‐analysis
Authors: Eley B. M.
Published: June 2005

Dental amalgam, either in the form of a solid rod or as a fine powder was implanted subcutaneously into guinea‐pigs and the tissue reactions were examined after varying time periods. The solid rods were enclosed by fibrous capsules within which only extremely limited breakdown occurred. This appears to result from electrolytic corrosion of the γ2 (SnHg) phase of the rod's surface. Powdered amalgam induced granulomata and most of the particles of amalgam were actively digested by macrophages and giant cells. This resulted in the progressive loss of mercury and tin from the lesion and the formation of minute particles containing silver and sulphur which became widely distributed throughout the lesion, being associated with basal lamina, collagen and elastic tissue and giving rise to the formation of a tattoo. In contrast, some particles of amalgam, too large to be interiorised. were encapsulated by collagen and persisted almost unchanged. Intracellular small amalgam particles and aggregates of fine particles, resulting from their degradation, were seen within lymph node macrophages. It is extremely likely that the sequence of events leading to the formation of an amalgam tattoo of the oral mucosa in Man are the same.
Differing patterns of altered glucocorticoid secretion in experimental malignant and benign hypertension. Influences upon the lymphoid system and on arterial connective tissue metabolism
Authors: Chatelain R. E. , Bumpus F. M. , Chernicky C. L. , Ferrario C. M.
Published: June 2005

Alterations in plasma glucocorticoid levels and in the evolution of the thymus gland were studied in groups of malignant (MHY) and benign (BHY) hypertensive rats sacrificed at 6, 9, 12 and 24 days after aortic ligation between the renal arteries. Although the degree of blood pressure elevation was similar in MHY and BHY animals, MHYs were characterised by severe weight loss, increased plasma renin activity and elevated blood urea nitrogen. MHY animals sacrificed at day 6 showed markedly increased plasma corticosterone (PC) levels (PC: 604 ± 3·9 μg/dl) accompanied by severe thymus atrophy (123 ± 19 mg). In 6‐day BHY animals elevated plasma corticosterone and thymus atrophy were also present but were not as marked as in MHY (BHY: PC: 38·8 ± 4·6 μg/dl, thymus wt: 244 ± 33 mg). Values from BHYs were, however, significantly different from sham‐operated (Sham‐op) controls (Sham‐op: PC: 22·6 ± 1·4 μg/dl; thymus wt: 631 ± 32 mg). In BHY animals sacrificed at day 9, plasma corticosterone had returned to baseline levels. From this time period onward, in BHY animals normal plasma corticosterone was accompanied by a steady recovery of the thymus gland, generalised lymphoid proliferation, and by the proliferation of collagen and elastin (measured by the in‐vitro incorporation of 14C‐l‐proline into both proteins) in the intima‐media and adventitia of the thoracic aorta. Contrary to the normalisation of plasma corticosterone and thymus recovery observed in BHYs, corticosterone remained chronically elevated in MHYs and thymus atrophy was present throughout the entire evolution oif the disease. In MHYs, the arterial connective tissue proliferation was repressed and the synthesis of collagen and elastin was similar to normotensive controls. A. Statistically significant decrease in collagen concentration was present in both intima‐media and adventitia of MHYs when compared to either BHMs or normotensive controls. Impaired vascular hypertrophy in MHYs coexisted with marked alterations in the lymphoid system. In the thymus severe atrophy, thymocyte depletion and a reverse corticomedullary pattern were observed. When the thymocytes remaining in the organ were challenged with the T cell mitogen concanavalin A they showed an impaired proliferative response. In the blood a significant reduction in circulating lymphocytes and marked neutrophilia were observed. These findings suggest that increased glucocrticoid secretion marks important modifications in cells and tissues involved in the production of necrotising arterial lesions during the evolution of malignant hypertension.
The cellular response to human colonic neoplasms: Macrophage numbers
Authors: Skinner J. M. , Jarvis L. R. , Whitehead R.
Published: June 2005

Tumour cells and macrophages are thought to interact and the behaviour of tumours may be modified by macrophage activity. Using an immuno‐histochemical method for the demonstration of lysozyme and a computerised image analysis system, the number of macrophages was assessed in and around tubulovillous adenomas and the different Dukes grades of adenocarcinomas of the colon. No significant differences were demonstrated and it is concluded that the behaviour of these neoplasms is not related to the number of associated macrophages.
The ultrastructural localisation of de‐nol (colloidal tripotassium dicitrato‐bismuthate—TDB) in the upper gastrointestinal tract of man and rodents following oral and instrumental administration
Authors: Coghill S. B. , Hopwood D. , McPherson S. , Hislop S.
Published: June 2005

In the presence of hydrochloric acid, tripotassium dicitrato‐bismuthate forms a particulate precipitate which is electron dense. In upper gastrointestinal tract endoscopic biopsies, following a single oral dose, precipitate was detected between superficial oesophageal epithelial cells and also lining lipid droplets within oesophageal cells. The precipitate does not appear to penetrate the thick mucus barrier in the normal stomach but reaches the epithelial cell surface in the duodenum and proximal jejunum. Small particles of bismuth complex are endocytosed by the enterocyte and enter multivesicular bodies. A similar series of events was observed in rodents and an approximate time course for adsoprtion and endocytosis was estimated.
A morphometric, biochemical and histochemical comparison of puromycin aminonucleoside and hyperalbuminaemic induced proteinurias in the female Wistar rat
Authors: Lawrence Gillian M. , Brewer D. B.
Published: June 2005

Biochemical, immunological, histochemical and electron microscope morphometric techniques were used to monitor the changes in urinary protein composition, albumin clearance and glomerular ultrastructure induced in female Wistar rats following i.p. injection of puromycin aminonucleoside (PAN) or bovine albumin (BSA). BSA injected rats maintained a high degree of selectivity with albumin constituting 90 per cent. of the total protein excreted even when mean protein excretion was in the order of 500 mg/24 hr. A similar degree of selectivity was only evident in PAN nephrotic rats at low levels of proteinuria. Levels of 500 mg/24 hr only 57 per cent. of the total protein was albumin. These differences correlated well with the increased number of glomeruli from PAN nephrotics compared with hyperalbuminaemic rats which, at these high levels of proteinuria, had bare areas of glomerular basement membrane caused by epithelial cell detachment (88 and 7 per cent. respectively).

Detailed electron microscope morphometric and immunohistochemical studies showed that there were also important quantitative differences in a number of superficially similar glomerular structural alterations. In PAN nephrotic rats all glomeruli showed very marked epithelial cell foot process loss and reduced staining with colloidal iron. In glomeruli from hyperalbuminaemic rats there was a wide variation in the extent of epithelial ceil foot process loss and reduced colloidal iron staining was only demonstrable in those glomeruli which had swollen epithelia containing large numbers of vacuoles and protein droplets. Similarly, while protein droplets were smaller and less numerous in glomeruli from PAN‐injected rats, they were present in most glomeruli whereas their distribution was much more variable in glomeruli from BSA‐injected rats.

All the data collected therefore indicated that there were important differences in the types of proteinuria and glomerular ultrastructural damage present in PAN nephrotic and hyperalbuminaemic rats and suggested that their induction may have involved entirely different mechanisms. Evidence gathered from one experimental model should thus only be used with extreme caution to aid in interpretation of data obtained from the other.
Gallbladder epithelial acid hydrolases in human cholecystitis
Authors: Kouroumalis E. , Hopwood D. , Ross P. E. , Milne G. , Bouchier I. A. D.
Published: June 2005

The lysosomal enzymes β‐glucuronidase and acid phosphatase were studied in 112 patients with cholecystitis. Acid phosphatase activity was generally lower in patients with cholesterol stones compared with cases with pigment stones. β‐glucuronidase activity was higher in acalculous cholecystitis than in any other group, a fact compatible with the concept that in lithiasis the enzyme is secreted into the bile and therefore may participate in nidus formation. Histochemistry at light microscopical level clearly demonstrates the lysosomal distribution of these enzymes and their presence in the macrophages infiltrating lamina propria in cholesterolosis. Electron histochemistry in 45 patients showed acid phosphatase activity in lysosomes and some in mucous droplets. Thiamine pyrophosphatase activity, a marker for the Golgi system, showed a close association with these mucous droplets. The secretion of mucus will be accompanied by a secretion of acid phosphatase, and by implication other acid hydrolases, into the bile.
Pathological aspects of cholangiocarcinoma
Authors: Weinbren K. , Mutum S. S.
Published: June 2005

Tissue specimens resected from liver and bile‐ducts were examined in an attempt to distinguish features of cholangiocarcinoma from those of ether tumours and from reactions to duct obstruction and changes in the tumour‐bearing liver. Macroscopical and microscopical features were compared and certain changes were found only in cases of cholangiocarcinoma. The type of tumour correlated moderately well with the level of bile duct involved and some microscopical findings were noted only in patients suffering from cholangiocarcinoma. Mucin was demonstrable in all 33 cholangiocarcinomas. Other striking features included heterogeneity of epithelial cells within the same acinus and a tendency to spread between hepatocyte plates, along duct walls and in relation to nerves.

Reactive hyperplasia of ductal subepithelial mucous glands was found in association with duct obstruction with and without cholangiocarcinoma.

Sclerosis, a common accompaniment of cholangiocarcinoma was noted in other tumours.
The histopathology of tissues in “resistant” and “susceptible” strains of mice infected with a moderate dose of Mycobacterium lepraemurium
Authors: Adu Hannah O. , Turk J. L. , Curtis Jill
Published: June 2005

A systematic study by light and electron microscopy of tissues from BALB/c and C57BL/6 mice infected subcutaneously with 107 Mycobacterium lepraemurium organisms was carried out at various times throughout the infection. The relatively resistant C57BL/6 mice had an earlier inflammatory response at the site of the infection than did the susceptible BALB/c mice. The infiltration in the former strain contained fibroblast‐like cells and epithelioid cells early on in the infection. Few lymphocytes were observed in both strains throughout the infection. The spread of acid‐fast bacilli was slower in the resistant strain (C57BL/6). The findings indicated that the rate of cellular infiltration at the infection site and the nature of the cells in the infiltration may determine the outcome of this infection.
Functional abnormalities in the beige mouse eosinophil assessed using T. spiralis as a target
Authors: Jungery M. , McLaren D. J. , Ogilvie B. M.
Published: June 2005

These studies on eosinophils from beige mice have shown that such cells possess morphologically abnormal granules and that they also have an impaired capacity to interact in vitro with a non‐phagocytosable target such as the infective larva of Trichinella spiralis. However, beige mice with these functionally abnormal eosinophils are able to control a T. spiralis infection as well as the normal heterozygote mice.

A morphological study of beige eosinophils revealed the presence of structurally distinct lysosomal secretion granules. Some resembled granules in normal eosinophils while others were grossly enlarged and contained multiple crystalloids. When these peritoneal eosinophils were allowed to interact with T. spiralis in vitro in the presence of specific antibody and/or complement, they behaved differently. Cells containing only large granules adhered loosely and temporarily; they were not observed to degranulate. In contrast, cells containing a mixture of granules, or only small granules were able to adhere and degranulate.

Despite the defects in the eosinophils of beige mice, the course of an infection with the nematode parasite T. spiralis in beige animals was similar to that in normal animals. Therefore, if eosinophils are crucial in the control of this infection as suggested from other studies, the defect in beige eosinophils is not sufficient to prevent an apparently normal response to the parasite.
An acth‐induced renal glomerular lesion in the mouse: Immunofluorescence microscopy
Authors: Feldman David L. , Gorfien Stephen F. , Christian John J.
Published: June 2005

Mice were injected with adrenocorticotropic hormone (ACTH) and the glomerular lesion that was induced was studied by light and immunofluorescence microscopy. By light microscopy, kidneys from ACTH‐treated mice showed typical ACTH‐induced glomerular lesions. Immunofluorescence of kidneys from ACTH‐treated mice revealed intense staining for IgG and IgM in the extraglomerular mesangium (EGM), in Bowman's space, and in the ascending thick limb of Henle near the macula densa. Staining for immunoglobulins was unchanged after treatment with acid buffer. Immunoreactivity for complement (C3) was confined largely to the EGM and Bowman's space. Staining for albumin was almost exclusively in Bowman's space or the peripheral glomerular tuft in discrete aggregates. The above patterns of IgG, IgM, C3 and albumin were seen in control mice, although much less frequently. The results show that in mice, treatment with ACTH results in the increased accumulation of plasma proteins in the juxtaglomerular apparatus (JGA). This effect may reflect a role for the JGA in the normal clearing of plasma proteins from the glomerulus and/or directly from the blood.
Prognosis in breast cancer patients with tumour cells in the efferent vessels of their axillary nodes
Authors: Hartveit F. , Skjærven R. , Mæhle B. O.
Published: June 2005

The presence of tumour cells in the efferent vessels of the axillary nodes of breast cancer patients is termed efferent vascular invasion (EVI). The EVI status had been recorded in 112 cases which have now been followed for a mean of 120 ± 8 months. At the start of the 10th year 17 per cent. of the EVI positives cases were alive, compared to 54 per cent. of the EVI negative. The EVI status has thus strong prognostic implications. It can be recorded in association with primary treatment on routine histological examination. No special equipment is required.
An autoradiographic study of the cell proliferation during involution of the rat pancreas
Authors: Walker N. I. , Pound A. W.
Published: June 2005

After ligation of the rat pancreas, DNA synthesis in centoacinar cells and cells of the intercalary ducts, proximal and distal to the ligature, was suppressed for about 18 hr. This preceded a large increase in thymidine labelling of the nuclei of these cells. The increase in the thymidine indices was much greater and more prolonged in the distal pancreas where duct‐like structures were formed that replaced the acini. DNA synthesis in acinar cells proximal to the ligature was suppressed for 36 hr preceding an increase in the thymidine indices much smaller than that in the duct cells. DNA synthesis in acinar cells distal to the ligature ceased and the acinar cells progressively died.

We propose that the pancreas is composed of proliferative units, each comprising acinar cells, centroacinar cells and intercalary ducts, which react as a whole when acinar cell loss occurs in pathological processes.
The effect of diphosphonates on heterotopic ossification in regenerating achilles tendon of the mouse
Authors: McClure J.
Published: June 2005

Midpoint tenotomy of the mouse Achilles tendon is followed by regeneration with heterotopic ossification at the junction of tendon stump and the regenerated segment. This heterotopic bone formation occurs through a process of endochondral ossification and the cartilage cells appear to arise by a process of fibroblast transformation. Five weeks after tenotomy 60 per cent. of specimens show cartilage and bone formation whilst the remaining 40 per cent. show chondrification only. After 10 weeks all specimens showed bone formation with trabecular bone and haemopoietic marrow. The treatment of tenotomised animals with either disodium ethane‐1,1‐diphosphonate (EHDP) or disodium dichloromethylene diphosphonate (Cl2 MDP) has no effect on the process of heterotopic ossification which can be detected at the radiological or light microscopical level.
The behaviour of human ameloblastoma tissue in cell culture
Authors: Prime S. S. , Sim F. R. P. , Toh B. H.
Published: June 2005

Human ameloblastoma tissue was investigated using cell culture techniques, transmission electron microscopy and fluorescent microscopy. Cultured cellular morphology was dependent on the type of substratum, with polygonal cells predominant on collagen substrata in contrast to an elongated cellular morphology on glass substrata. The presence of tonofilaments and desmosomes confirmed the epithelial origin of these cells. The distribution of Con A surface receptors and cytoplasmic actin in the same cell was studied using a double fluorochrome technique. Incubation with fluorescein isothiocyanate‐labelled Con A at 37°C for increasing time periods resulted in the Con A receptors showing progressive changes in staining patterns from clusters, to caps to perinuclear globules. Sequential changes in cytoplasmic actin, labelled by a specific anti‐actin auto‐antibody traced with rhodamine‐labelled goat anti‐human globulin, corresponded to the Con A staining patterns.
Histopathological diagnosis of hydatidiform mole
Authors: Ockleford C. D. , Reti L. L. , Calvert J. P. , Badley R. A.
Published: June 2005

Two microscopical methods are described which are useful for the identification of hydatidiform molar trophoblast. The first is an application of Nomarski's differential interference contrast microscopy which allows whole‐mounted villi to be studied by optical sectioning. The second is an application of indirect immunofluorescence microscopy using a specific antiserum directed against the endothelial cell structural protein known as vimentin.
Ultrastructure of pulmonary alveoli and macrophages in experimental Legionnaires' disease
Authors: Baskerville A. , Dowsett A. B. , Fitzgeorge R. B. , Hambleton P. , Broster M.
Published: June 2005

Guinea pigs, rhesus monkeys and marmosets infected with Legionella pneumophila in small particle aerosols developed an acute fibrinopurulent bronchopneumonia. Changes from 24 hr included exudation into alveoli of protein‐rich, often fibrinous fluid and many polymorphonuclear leucocytes (PMN) and macrophages. Damage to alveolar capillary endothelium consisted of widespread cytoplasmic swelling and vesiculation, but necrosis of endothelium and the associated alveolar epithelium was focal and less common. Phagocytosis of L. pneumophila organisms was predominantly by macrophages, but the bacteria were also seen in PMN. Free organisms were present in alveoli and capillary lumina at all stages of the infection but were not observed in lung parenchymal cells. Some infected macrophages and PMN became necrotic and lysed to release intact bacteria. In all species of experimental animal, intracytoplasmic aggregations of granular material, believed to be glycogen, were seen frequently in macrophages and PMN which had phagocytosed L. pneumophila. These deposits of glycogen may reflect either an increased energy demand by the host cell or an interference with its carbohydrate metabolism.
An electron microscopic study of the effects of vinblastine sulphate on the ultrastructure of the kidney, trachea, liver, peripheral nerve and small intestine of the rat
Authors: Rollason T. P. , Brewer D. B. , Bliss D. J.
Published: June 2005

The effects of vinblastine in high doses on the kidney, liver, trachea, peripheral nerve and small intestine of rats have been studied by scanning and transmission electron microscopy. Dramatic structural changes were seen in glomerular visceral epithelial cells, hepatocytes and small intestinal epithelial cells which appear to be due to the effect of vinblastine on microtubules and possibly also on other proteins and cell membranes. Ciliary microtubules appeared resistant to vinblastine effects.
Ultrastructural features of carcinomas induced in nude mice by the inoculation of human oesophageal carcinoma cell lines
Authors: Robinson K. M. , Bux S.
Published: June 2005

Thirty tumours induced in athymic mice by the inoculation of cells of human oesophageal carcinoma lines were examined by light and transmission electron microscopy, as were 24 cell strains derived from the mouse tumours. All tumours were carcinomas and displayed varying numbers of desmosomes and tonofilaments. Cytoplasmic organelles resembled those in human oesophageal carcinomas in vivo and marker structures such as intranuclear particles persisted in cells grown in nude mice and in vitro. As the nude mouse carcinomas displayed similarities both to one another and to human carcinomas in situ, the nude mouse xenograft system may become a useful model for further studies on tumour biology.
Tissue culture of guinea‐pig gall‐bladder epithelium
Authors: Elhamady M. S. , Hopwood D. , Milne G. , Ross P. , Bouchier I. A. D.
Published: June 2005

Tissue culture of gall‐bladder was attempted in the following media: Dulbecco, Eagle's minimum essential medium, NCTC 135, medium 199 and Ham's F12. Growth occurred in all of them for up to 2 weeks assessed by light microscopy. No enhancement of growth was induced by collagenase trypsin insulin or hydrocortisone. Scanning electron microscopy confirmed that new cells colonised the free surface of the explant. Transmission electron microscopy showed good preservation of the original tall epithelial cells for the period of study. The new migrating cells were flatter, but retained the morphological features of the columnar cells. Secretory granules were absent after 1 day in culture but increased amounts of glycogen and lipid began to appear in the epithelium.
Membrane‐bound structures at the interface between tumour and dermis in basal cell carcinoma. An ultrastructural study
Authors: Morley Susan M. , Rennison A. , Macadam R. F.
Published: June 2005

During an ultrastructural study of the interface area between tumour and dermis in 23 basal cell carcinoma (BCC), membrane‐bound structures were noted in the dermis adjacent to the basal lamina in 12 tumours (52 per cent), but none of the controls.

Serial sectioning demonstrated cytoplasmic connections between these structures and tumour cells. Their formation and interaction with adjacent stromal cells is discussed.
The brain in experimental portal‐systemic encephalopathy. I. Morphological changes in three animal models
Authors: Pilbeam C. M. , Anderson R. McD. , Bhathal P. S.
Published: June 2005

Morphological features of three models of portalsystemic encephalopathy in the rat were studied and compared with plasma ammonia levels and clinical observations.

Carbon tetrachloride‐induced cirrhosis with terminal coma produced a wide variety of structural changes in the brain whose severity was related to plasma ammonia levels at the time of death. These changes included diffuse gliosis, Alzheimer cells and focal neuronal necrosis but did not include spongiform changes in cerebral or cerebellar cortex.

Porta‐caval anastomosis (PCA) did not appear to produce any significant neurological symptoms. Rats with PCA of durations 1–30 weeks were studied and over this time the structural changes included astrocytic nuclear swelling, swelling of perivascular astrocytic foot‐processes and spongiform change in the molecular layer of the cerebellum. No evidence of Alzheimer cells or gliosis was seen and plasma ammonia levels at no stage exceed twice the normal levels.

Porta‐caval anastomosis followed by gavage feeding with ammoniated cationic exchange resin produced severe neurological symptoms and marked hyperammonaemia. In these animals not only astrocytes but oligodendrocytes and neurons showed nuclear and cytoplasmic swelling and numerous Alzheimer type II cells were seen, together with a diffuse gliosis, but no evidence of spongiform change in the cerebral or cerebellar cortex was seen.

It is concluded that ammonium ions are important in the genesis of morphological changes in the brain in rat models of portal‐systemic encephalopathy, but the relevance of these changes to neurological dysfunction is uncertain.
Possible Stewart's nasal granuloma with dissemination to meninges, peripheral nerves and muscle and renal glomerular IgA deposition
Authors: Mirakhur Meenakshi , Allen Ingrid V. , Hill Claire M.
Published: June 2005

A case of Stewart type, non‐healing nasal granuloma complicated by dissemination to meninges, peripheral nerve and muscle is described. The deposition of IgA in renal glomeruli in this condition is documented and the significance of this finding is discussed.
The long‐term evolution of mycobacterial BCG and preformed immune complex BCG/anti‐BCG granulomas in rats
Authors: Ridley Marian J. , Heather C. J. , Ridley D. S. , Willoughby D. A.
Published: June 2005

In previous studies it was found that infections with BCG or complexed BCG/anti‐BCG in rat skin produced granulomas that appeared to resolve at 8 months. In this follow‐up study 1 year later, it appeared that while lesions due to preformed complexes had resolved, those due to BCG alone had undergone a massive reactivation. Nevertheless despite the loss of CMI the infection was restricted. The bacilli, present in enormously increased numbers, were dead; the host macrophages were large and activated. Epithelioid cells and dendritic cells were common. The granuloma was confluent, with patchy necrosis and inconspicuous polymorph infiltration.

Although preformed complexes with viable bacilli formed at equivalence had produced a resolving lesion, the outcome of the natural infection was complicated by an imponderable balance of immunological responses. CMI does not appear to have been a determinant during the crucial phases of the infection.
Experimental epithelioid cell granulomas tubercle formation and immunological competence: An ultrastructural analysis
Authors: Ridley Marian J. , Heather C. J. , Brown I. , Willoughby D. A.
Published: June 2005

An ultrastructural study of the cells comprising tubercles in experimental mycobacterial granulomas in rats is presented. Tubercle formation was compared in: (1) primary infections due to BCG at 49 days, (2) reinfection with BCG at 7 days, 8 months after primary infection and (3) lesions due to preformed BCG/anti‐BCG complexes in antibody excess in unprimed animals at 10 days. The most rapid elimination of antigen with resolution of the lesion in the reinfection lesions, was effected by the early recruitment of cells morphologically characteristic of activated macrophages and immature epithelioid cells. The next best performance was in the immune complex lesion which at its height was maintained by a roughly constant size due to promonocytes, monocytes, macrophages, activated macrophages and immature epithelioid cells accumulated at the site. True epithelioid cells were rare. The slowest rate of healing in the primary 49 day granulomas, was associated with the whole spectrum of mononuclear phagocyte series of cells. All granulomas were surrounded by a cuff of mixed lymphocytes, interdigitating cells and fibroblasts.

The rapid resolution of the reinfection lesions appeared as a loosely compacted infiltration of cells which allowed intimate contact of lymphocytes and macrophages. This was distinct from the tightly compared and compartmentalised zones of lymphocytes and macrophages which inhibited contact in the most slowly resolving lesions. An intermediate arrangement was seen in the immune complex granuloma. Another factor which predisposed to rapid resolution was the high vascularity of the central region of the granulomas. In the slow resolving group vascularity was diminished and peripherally situated.
Acute arterial fibrinoid deposition and ischaemic parenchymal damage of the kidney. Pathogenic factors in the development of malignant hypertension
Authors: Chatelain R. E. , Dardik Beatriz N. , Shainoff J. R.
Published: June 2005

The development and evolution of hypertensive vascular lesions affecting the arterial supply of (a) the kidney and (b) organs other than the kidney were studied in rats developing either malignant (MHY) or benign (BHY) hypertension 3, 6, 9 and 12 days after aortic ligation between the renal arteries. Vascular disease evolved into two distinct patterns which suggested acute renal damage to be the determinant for the development of either the malignant or benign form of hypertension. Three days after aortic ligation MHY and BHY animals showed widespread fibrinoid deposition in vascular territories above the aortic ligature. However, in MHYs these lesions were much more severe and, in the kidney, they were accompanied by the development of focal parenchymal atrophy, microinfarcts and hyalin droplet degeneration of cells of the Bowman capsule. The degree of renal damage correlated with elevations in blood urea nitrogen (BUN) and plasma creatinine; however, there was no correlation with rises in blood pressure, plasma renin activity (PRA), aldosterone or corticosterone which were similarly elevated in 3‐day MHY and 3‐day BHY animals.

Between 6 and 12 days a marked clearance of fibrinoid took place in all organ beds of BHYs, but in the non‐renal vasculature of MHY animals fibrinoid remained prominent and served as the central core for necrotising arterial lesions. In the kidney of MHYs some reduction in the fibrinoid content was observed, but the parenchymal damage perpetuating from the earlier stages had exacerbated leading to collagen deposition and a marked increase in the collagen concentration of the renal cortex. These features were accompanied by further elevations in PRA and corticosteroids and a progressive deterioration of renal function. By contrast, in 12‐day BHY animals, despite sustained hypertension, PRA and corticosteroids were falling from their previously higher levels and normal renal function was maintained. These studies warrant inference that extensive parenchymal damage of the kidney due in part to severe arterial fibrinoid deposition is one of the initial events in the development of malignant hypertension.
Acute haematogenous osteomyelitis: An experimental model
Authors: Emslie Kerry R. , Ozanne N. R. , Nade S. M. L.
Published: June 2005

A simple and reproducible model of acute haematogenous staphylococcal osteomyelitis is described. Twenty‐nine day‐old chickens were inoculated intravenously with 104–108 viable organisms Staphylococcus aureus per kg body weight and were killed 1–8 days after inoculation. Macroscopic septic foci could be detected within 24 hr of inoculation and were most commonly situated in the metaphyseal region of the proximal tibia and distal femur. Lesions in other organs were not observed. The production of osteomyelitis was dependent on the bacterial inoculum size. It was estimated that 5.5 × 105 viable organisms per kg body weight of chicken were required to produce osteomyelitis in 50 per cent of injected chickens. Chicken weights were monitored throughout the experiment. A close negative correlation existed between the logarithm of the bacterial inoculum size and the chicken growth rate in the first 24 hr following inoculation (r = −0.968, P< 0.01). The chicken growth rate was therefore used as an accurate predictor of osteomyelitis in individual chickens.
Mucosal alkaline phosphatase and bile lipids in the gallbladder in cholecystitis
Authors: Kouroumalis E. , Hopwood D. , Ross P. E. , Bouchier I. A. D.
Published: June 2005

Histochemically, alkaline phosphatase was localised in epithelial brush‐border and capillary endothelium of the lamina propria in 41 gallbladders studied. Three distinct patterns of the brush‐border enzyme distribution were observed, namely, complete delineation, patchy localisation and a brush‐border totally devoid of enzyme activity.

Where no histochemical activity was found, biliary chenodeoxycholate was 50 per cent. higher than in cases of patchy distribution and twice as high as in cases with complete staining of the brush‐border. Conversely, biliary cholate levels were significantly higher in completely stained cases. Biliary cholesterol was higher in the cases with no histochemical activity and this was reflected in a significantly higher lithogenic index. Significant quantities of cholesterol esters were found in bile from the focal activity group only.

Total alkaline phosphatase activity assayed in gallbladders from 112 patients with cholecystitis and/or lithiasis showed that activity was significantly lower in patients with pigment stones than patients with cholecystitis and/or cholesterol stones. This activity was not related to biliary lipid composition in the 77 bile samples analysed.

This evidence indicates that biliary lipid composition is associated with the histochemical distribution of alkaline phosphatase in gallbladder mucosa.
Microgibbosities in hydatidiform mole
Authors: Ockleford C. D. , Clode A.
Published: June 2005

Ultrastructural analysis of the surface of the syncytial absorptive epithelium of the aberrant form of human placenta known as hydatidiform mole reveals modifications of the micro‐villous apical surface. We have described these features as microgibbosities. They are apparently groups or rings of microvilli greater than the usual length in the surrounding cytoplasm. The existence of such microvilli and the probable consequences for the control of the dynamics of microvillar cytoskeletal elements should be accommodated by future theories of microvillar biogenesis.
Methods to analyse the human genome
Authors: Williamson Robert , Darling Susan M.
Published: June 2005

There is much interest in the use of gene‐specific probes for the study of dysfunction in human pathology. For the haemoglobinopathies, globin gene recombinants (either prepared from DNA sequences complementary to messenger RNA, or from genomic DNA) are used to determine whether globin genes are present, whether they are expressed in the nucleus, and whether they are correctly processed to give functional mRNAs. This has not only allowed a fuller understanding of the molecular aetiology of the thalassaemias, but also permitted antenatal diagnosis both by direct analysis of the gene lesion, and by linkage analysis using adjacent genes. Similar approaches are being applied to many other single gene defects.

There are, however, other possible ways to study human hereditary disease using recombinants. It is now feasible to use random human chromosome‐specific sequences to establish a linkage map for the entire human genome. Such a map may then be used either to determine the chromosomal localisation of any “single gene” phenotype by linkage analysis, or to study the contribution of different genes to a complex phenotype determined by several genes, as in multifactorial disease.
Growth factors and their action in vivo and in vitro
Authors: Gospodarowicz D.
Published: June 2005

The molecular nature and mechanism of action of several of the growth factors including epidermal growth factor, fibroblast growth factor and platelet‐derived growth factor is reviewed. The ectopic production of growth factors may be important in the growth development of certain tumours. In addition, attention is directed to the importance of the extracellular matrix in controlling cell proliferation and differentiation.
The cell surface and its metabolism
Authors: Crumpton Michael J. , Owens Raymond J. , Gallagher Christopher J. , Davies Adelina A.
Published: June 2005

The cell surface structure is highly dynamic. In particular, binding of ligand induces the redistribution of receptors on the cell surface as well as the internalisation of ligand‐receptor complexes. Internalisation in turn leads to a recycling of the receptor or to a decrease in the cell'S responsiveness to the ligand. Modulation of the cell surface structure is apparently regulated intracellularly by components of the cell'S cytoskeleton. A crucial component in this respect is likely to be a sub‐membranous filamentous network that is linked directly to the cytoplasmic face of the surface membrane. In erythrocytes this network can be separated from purified preparations of the plasma membrane by virtue of its insolubility in nonionic detergents. Application of this procedure to the plasma membrane fraction of human B lymphoblastoid cells has yielded a detergent‐insoluble residue comprising actin and a 68,000‐Mr polypeptide as major components, together with polypeptides of 28,000‐, 33,000‐ and 120,000‐Mr as prominent but more minor components. The association of the 68,000‐Mr protein with the detergent‐insoluble residue and the original plasma membrane is Ca2+‐dependent. Burkitt lymphoma cells differ noticeably from lymphoblastoid cells in that the 68,000‐Mr protein is not associated with the inner face of the surface membrane. This difference may reflect the malignant phenotype of Burkitt lymphomas or the hypothetical sub‐population of normal B lymphocytes from which the lymphomas are derived.
Differentiation and neoplasia. Invasion and metastasis; experimental systems
Authors: Eccles Suzanne A.
Published: June 2005

In a series of six transplantable mammary carcinomas and 11 squamous cell carcinomas of mice, evidence of tumour “progression” was obtained in the majority.

Progression was evidenced by increased growth rates, transplantability and metastatic capacity, and decreased differentiation and immunogenicity (when present initially).

The degree of differentiation was inversely related to the metastatic capacity of a particular tumour, and the rate of change in both parameters during serial transplantation was comparable.

Treatment with retinoids in vivo and in vitro failed to stimulate differentiation of anaplastic cell lines, or to influence their growth and metastasis in the absence of host anti‐tumour immune reactivity.
Germ cell tumours of the testis
Authors: Risdon R. A.
Published: June 2005

The application of new techniques, particularly the identification of tumour markers, in the study of testicular germ cell tumours is presently leading to a reassessment of opinions regarding the origin and classification of these neoplasms. Some aspects of this controversy are examined.
Nuclear imaging techniques with radiolabelled antibodies
Authors: Fairweather D. S. , Bradwell A. R. , Dykes P. W.
Published: June 2005

The behaviour of radioimmunolocalisation with respect to neoplasia is reviewed. The present limitations are outlined and several new approaches to improve its clinical utility are discussed.
Dormant metastases—Studies in experimental animals
Authors: Alexander Peter
Published: June 2005

Several experimental systems related to tumour cell dormancy are outlined together with some of the possible mechanisms by which the host might maintain tumour foci in such a quiescent state.
Decreased numbers of pulmonary blood vessels: Reality or artifact?
Authors: Mooi Wolter , Wagenvoort C. A.
Published: June 2005

A decrease in numbers of pulmonary arteries has been implicated in various forms of both human and experimental pulmonary hypertension. However, data in support of this hypothesis have not been conclusive. Especially, intravascular fixation under pressure and the size of the areas of lung tissue subjected to quantitation, may have influenced the results. In order to investigate these factors, we fixed lungs of ten normal rats in three different ways, i. e. by perfusion of the pulmonary vasculature, by immersing collapsed lungs and by instilling the fixative through the trachea with intact thoracic cavity. Subsequently, blood vessels were counted in histological sections. Our study illustrates that perfusion of vessels under pressure decreases the number of recognizable arteries. Also the small areas, used in previous studies for counting vessels, produce unreliable results. Our conclusion is that a decreased number of lung vessels as a factor in pulmonary resistance has not been conclusively demonstrated.
An enzyme histochemical study of the sinuses of reactive lymph nodes
Authors: Crocker J. , Williams Mary
Published: June 2005

The enzyme histochemistry of the cells lining and within the marginal and medullary sinuses of twenty human reactive lymph nodes has been studied. The sinuses contain luminal (‘reticular’) cells which are strongly positive for certain hydrolytic enzymes, including acid‐α‐naphthyl acetate esterase, acid phosphatase and β‐glucuronidase. In addition, the lining (‘littoral’) cells on both sides of the medullary sinuses are positive for these enzymes. In contrast, enzyme‐containing lining (‘littoral’) cells of the marginal (subcapsular) sinuses are observed only on the inner aspect of the sinuses, the outer aspect being negative. Alkaline phosphatase is not present in the sinusoidal cells but 5′‐nucleotidase is seen in varying amounts. These findings are supported by an ultrastructural study of three of the nodes, using a staining method for esterase activity. The different enzyme histochemical properties of the littoral cells in the marginal and medullary sinuses closely mirrors that observed when, for example, these structures are stained immunohistochemically for IgA or J chain.