bluuebunny/crossref_metadata_2025 huggingface dataset:
NBK/BIK antagonizes MCL-1 and BCL-XL and activates BAK-mediated apoptosis in response to protein synthesis inhibition
Authors: Shimazu Tsutomu , Degenhardt Kurt , Nur-E-Kamal Alam , Zhang Junjie , Yoshida Takeshi , Zhang Yonglong , Mathew Robin , White Eileen , Inouye Masayori
Published: April 2007

Ribonucleases, antibiotics, bacterial toxins, and viruses inhibit protein synthesis, which results in apoptosis in mammalian cells. How the BCL-2 family of proteins regulates apoptosis in response to the shutoff of protein synthesis is not known. Here we demonstrate that an Escherichia coli toxin, MazF, inhibited protein synthesis by cleavage of cellular mRNA and induced apoptosis in mammalian cells. MazF-induced apoptosis required proapoptotic BAK and its upstream regulator, the proapoptotic BH3-only protein NBK/BIK, but not BIM, PUMA, or NOXA. Interestingly, in response to MazF induction, NBK/BIK activated BAK by displacing it from anti-apoptotic proteins MCL-1 and BCL-XL that sequester BAK. Furthermore, NBK/BIK- or BAK-deficient cells were resistant to cell death induced by pharmacologic inhibition of translation and by virus-mediated shutoff of protein synthesis. Thus, the BH3-only protein NBK/BIK is the apical regulator of a BAK-dependent apoptotic pathway in response to shutoff of protein synthesis that functions to displace BAK from sequestration by MCL1 and BCL-XL. Although NBK/BIK is dispensable for development, it is the BH3-only protein targeted for inactivation by viruses, suggesting that it plays a role in pathogen/toxin response through apoptosis activation.
MILTON IN THE CLASSROOM: SOME EXPERIENCES AND PERSPECTIVES: Teaching Milton to Undergraduates
Authors: Miller George
Published: April 2007

As a teacher of Milton to both undergraduate and graduate students, I was surprised by Professor Gallagher's recent article1 in response to the MLA seminar on teaching Milton‐surprised not by the argument or its assumptions but rather by the nature of the problem itself. I find that it is a problem to teach Milton to undergraduates. It is not because they are unsympathetic to Milton's ideas or beliefs or because they find them to be irrelevant, but more obviously because of the difficulties posed by a poetry and a prose as sophisticated and complicated as Milton's. My students range from the evangelical to the incredulous (you mean someone really believed in a fall?); however, they do not seem to find Milton any more irrelevant than they find Camus or Hemingway. I found Professor Gallagher's response thoughtful and provocative, but it did not address the problems that I encounter.
The Cromwell Association
Authors: Miller Leo
Published: April 2007

Poets, like the proverbial prophets, are often late in being honored in their own countries, and so now at long last, and in response to trans‐oceanic initiative from the United States, there is in Britain a new Association of Friends of Milton's Cottage. However, there has been active for some forty years an organization called The Cromwell Association.
The Quest of the Mysterious Engine
Authors: Turner W. Arthur
Published: April 2007

More than a quarter of a century ago I published an article with the not very imaginative title “Milton's Two‐Handed Engine.“1 I began with the now standard statement of the importance of the image and a list of several earlier interpretations, and set down nine conditions which it seemed to me the “engine” must meet in order to satisfy the demands of the poem itself as to meaning and propriety. I ended with my own suggestion that the engine was the lock on the door to Heaven, to which St. Peter carries the keys. Professor Merritt Hughes gave me credit for having turned attention from earthly instruments (such as the two houses of Parliament, etc.) “to the now prevailing tendency to interpret it theologically.” But (unintentionally I am sure) he misrepresented my interpretation by saying that the lock represented “the two sanctions of death and damnation.“2 Of course it should have been “salvation and damnation.“
The Mortalist Heresy in ‘Paradise Lost'
Authors: Campbell Gordon
Published: April 2007

In Book III of Paradise Lost Christ accepts his mission to redeem mankind with the words

Though now to Death I yield, and am his due All that of me can die, yet that debt paid, Thou wilt not leave me in the loathsom grave His prey, nor suffer my unspotted Soule For ever with corruption there to dwell.1
REVIEWS
Authors: Thomas Robert
Published: April 2007

On Reading Christopher Hill: A Review Essay
ABSTRACTS
Authors: Miller Leo
Published: April 2007

“Another Milton State Paper Recovered and a Mystery Demystified.”
On the Interpretation of Pd
Authors: Jeffreys Harold
Published: April 2007

Lehmann's observations of a large phase about 21°, lying a few seconds after the first arrival Pr, are discussed on two extreme hypotheses. On the first the distance varies as a quadratic function of sin e, so that dΔ/de vanishes at 21°, where there is a cusp in the time curve. The values of dt/dΔ for Pr and Pd are found to be such that there is no possible position for the nearer cusp. On the second, a cubic form for t is assumed up to 21° for Pd. Pr must enter between 17° and 18°. The Pd ray emerging at 21° must reach about 0.03 R below the Mohorovičić discontinuity. The times of Pr imply that at the transition there must be a considerable discontinuity of velocity gradient but only a small one of velocity. The nearer cusp would be near 15°, but as it lies less than a second after the first arrival it is probably undetectable.
A Magnetic Survey off the West Coast of the United States between Latitudes 32° and 36° N, Longitudes 121° and 128°W
Authors: Mason R. G.
Published: April 2007

A total magnetic intensity map covering the area between latitudes 32° and 36° N and longitudes 121° and 128° W is presented. It shows a series of narrow anomalies of about 400 γ amplitude trending northsouth for 300 miles over a substantially flat abyssal plain. Some possible interpretations are discussed. The anomalies arise at shallow depths beneath the ocean bottom and are consistent with the presence of relatively thin layers of magnetized material overlying a less magnetic crust; they could equally well arise from topography of the upper surface of a continuous magnetic basement for the most part concealed by an overlying blanket of sediments.

The anomalies are intersected by the Murray fracture zone, which interrupts their pattern in such a way as to suggest a right lateral displacement of about 84 nautical miles.
Lattice Dynamics of MgO, Al2MgO4 and Mg2SiO4 Spinel
Authors: Sammis Charles
Published: April 2007

The method of long waves is used to compute the volume dependence of the elastic properties of MgO, γ-Al2MgO4 (spinel), and γ-Mg2SiO4 (spinel structure) from a rigid-ion, central force model. A comparison of theoretical and experimental elastic constants for the first two compounds shows that the neglect of non-central forces and ionic polarization severely limits the application of the model for oxides and silicates. The Coulombic contributions to the elastic constants for both the 3-2 spinel (γ-Al2MgO4) and the 2–4 spinel (γ-Mg2SiO4) are expressed as dimensionless Madelunglike constants and are computed as a function of the oxygen parameter. The distortion of the two spinels from c.c.p. is shown to be primarily an electrostatic effect. The elastic properties of γ-Mg2SiO4 are predicted using the bond parameters for Mg-O found from data on periclase and for Si-O found from stishovite. Although the rigid-ion model is too restrictive to give geophysically useful predictions, it shows how lattice dynamics may be used as a framework through which laboratory data may be used to interpret seismic velocity and density profiles.
On the Calculation of Changes in the Earth's Inertia Tensor due to Faulting
Authors: Rice J. R. , Chinnery M. A.
Published: April 2007

Recent interest has arisen in the possibility that changes in the Earth's inertia tensor accompanying earthquakes may provide the excitation for the ‘Chandler’ wobble of the rotation axis. We present a simple procedure for calculating these changes based on the elastic reciprocal theorem and Volterra's formula. In particular, if t is the shear stress created in the slip direction on a prospective fault surface when a perfect, unfaulted sphere is steadily rotated at unit angular velocity about some axis, then the change in moment of inertia about that same axis is shown to be twice the work of τ when carried through the actual slip displacement which occurs in faulting. It is shown that changes of products of inertia may be computed in a similarly simple way. The method is applied to two homogeneous Earth models, the relation to previous treatments is discussed, and it is noted that inertia changes accompanying less-catastrophic mass movements may be calculated in a similar way. The development in the body of the paper is in the context of classical linear elasticity. An Appendix extends the reciprocal theorem and Volterra's formula, and hence the basis for similar inertia change calculations, to the linearized incremental deformation of self-gravitating, initially stressed elastic systems, such as real-Earth models.
Inversion of geophysical data using an approximate inverse mapping
Authors: Oldenburg D. W. , Ellis R. G.
Published: April 2007

Realistic geologic features are 3-D and inverse techniques which rely upon linearization and computation of a sensitivity matrix to show how a change in the model affects a particular datum, can require prohibitive amounts of computation. Even 104 data collected over an earth parametrized into 102× 102× 102 elements has a sensitivity matrix which is 104× 106. The generation of that matrix requires the solution of many 3-D forward problems and its solution is also computationally intensive. In this paper we formulate a general technique for solving large-scale inverse problems which does not involve full linearization and which can obviate the need to solve a large system of equations. The method uses accurate forward modelling to compute responses, but only uses an approximate inverse mapping to map data back to model space. The approximate inverse mapping is chosen with emphasis on the physics of the problem and on computational expediency. There are two ways to implement the AIM (Approximate Inverse Mapping) inversion. At any iteration step, AIM-MS applies the approximate inverse mapping to forward modelled data and also applies the same mapping to the observations; the model perturbation is taken as the difference between the resulting functions. In AIM-DS, an alteration to the data is sought, such that the approximate inverse mapping applied to the altered data yields a model which adequately satisfies the observations. The approximate mapping inversion is illustrated with a simple parametric inverse problem and with the inversion of magnetotelluric (MT) data to recover a 1-D conductivity model. To illustrate the technique in a realistically complicated problem we invert MT data acquired from a line of stations over a 2-D conductivity structure. TE and TM mode data are inverted individually and as determinant averages. As a final example we invert 900 data, with and without noise, to recover a model that is parametrized by 1500 cells of unknown conductivity. The inversion is found to be computationally efficient and robust.
Chronic hepatitis: a problem for the pathologist
Authors: SCHEUER P. J.
Published: April 2007

The accepted histological categories of chronic hepatitis are chronic persistent hepatitis (CPH) and chronic active or aggressive hepatitis (CAH). A third form, chronic lobular hepatitis (CLH), encompasses those cases in which the lesion is predominantly within the lobules and in which portal and periportal inflammation are mild, CLH has many synonyms. International agreement on a reproducible and rational nomenclature of chronic hepatitis is still far from complete. CPH is characterized by portal inflammation. Histological definition is simple, but there are diagnostic pitfalls. The category may need subdivision on the basis of immunological studies. CAH should be regarded as a complex rather than a single disease, and it is important to specify the aetiology and pathological components in each instance. The concept of CAH must be altered to incorporate the lesion bridging hepatic necrosis (BHN). Piecemeal necrosis, accompanied by inflammatory infiltration, is considered to be the most important of the various pathogenetic factors in CAH, but BHN probably plays a significant part in accelerating the development of cirrhosis. An excessive portal and periportal inflammatory reaction with or without BHN, in a liver biopsy taken during the course of an acute hepatitis, helps to predict a possible chronic course.
Acute pulmonary toxicity of a commercial fluorocarbon‐lipid aerosol
Authors: FAGAN D. G. , FORREST J. B. , ENHÖRNING G. , LAMPREY M. , GUY J.
Published: April 2007

The death of an adolescent after deliberate inhalation of the domestic fluorocarbon‐li9pid spray, PAM, triggered an investigation of the effects of this product on mammalian lung. Some of its constituents are known to destroy the lung‐surfactant system, but death from its inhalation by earlier victims was usually attrubuted to the fluorocarbon's cardiac arrhythmogenic properties. In the present study, we applied methods and experimentl models not previously used to study the effects of this aerosol material on the lung surgactant. We found morphological and functiohal acute disintegration of normal alveolar surfactant, leading to extensive alveolar collapse, with sustained and elevated surface tensions in vitro. This could result in fatal hypoxaemia at inspired concentrations of fluorocarbons insufficient to cause cardiac arrhythmias, and may explain at least partly the large number of deaths associated with inhalation of such products.
Pacinian neurofibroma
Authors: MacDONALD D. M. , WILSON‐JONES E.
Published: April 2007

At rare intervals in the literature, reports have appeared of a skin tumour containing structures resembling Pacinian corpuscles. Four such tumours collected over the course of 20 years are described and the literature reviewed.
Primary carcinoma of the trachea
Authors: SWEENEY E. C. , HUGHES F.
Published: April 2007

Two cases of primary carcinoma of the trachea are described. Both patients were female and had smoked cigarettes for many years. One of the tumours was a squamous cell carcinoma and the other an oat cell carcinoma, the commonest and the rarest forms of tracheal cancer respectively. The diagnosis in the case of oat cell carcinoma was confirmed by electron‐microscopic demonstration of neurosecretory granules, a unique observation at this site. Oat cell carcinoma of the trachea does not appear to have been recorded previously in a female.
Quantitative study of the lymphatic tissue and germinal centres in the spleen in infants dying from expected and unexpected causes (cot deaths)
Authors: BARZANJI A. J. , EMERY J. L.
Published: April 2007

The amount of malpighian body lymphatic tissue and germinal centre tissue in the spleens of infants dying in hospital and dying unexpectedly at home have been examined in 471 cases. The total weight of the spleens in children dying at home unexpectedly do not differ significantly from children dying from expected causes. There is an increase in both the amount of lymphatic tissue and in the amount of germinal centre tissue in the children found unexpectedly dead. It is concluded that these children do not show any evidence of cellular immunological deficiency but that they have probably been subjected to recurrent or to a greater amount of antigenic stimulation during their brief post‐natal existence.
Pulmonary histological appearances in fatal paraquat poisoning
Authors: REBELLO GEMMA , MASON J. K.
Published: April 2007

The paper describes the histological appearances in the lungs from 11 fatal cases of paraquat poisoning. The study originated as an attempt to define the sequential changes in the condition and, from them, to assess the mode of action of the herbicide in the human. The main features of the ‘paraquat lung’ include haemorrhage, extrusion of macrophages, oedema, ‘honeycombing’, fibrosis and, rarely, epithelial hyperplasia. The indications are that the changes are progressive once a threshold tissue concentration has been reached. The appearances are compared to those in poisoning by hyperbaric oxygen and it is hypothesized that the toxic action of paraquat is to sensitize the lungs to oxygen at atmospheric pressure.
Ultrastructural findings supporting the angioblastic nature of the so‐called adamantinoma of the tibia
Authors: LLOMBART‐BOSCH A. , ORTUÑO‐PACHECO G.
Published: April 2007

Electron microscopy of a case of adamantinoma of the tibia shows features which support a mesenchymal angioblastic origin rather than epithelial. Comparison is made between tissue from this tumour and a squamous cell carcinoma of the femur arising in chronic osteomyelitis.

In adamantinoma no desmosomes are found between tumour cells and their cytoplasmic ultrastructure shows features of mesenchymal cell type including evidence of pinocytic activity and bundles of filaments resembling hyperplastic endothelial cells. The stroma shows features similar to fibrous dysplasia of bone with fibroblasts, histiocytes and fibrolipoblastic lipid‐laden mesenchymal cells.

It is concluded that adamantinoma of the tibia should be considered to be an angioblastic tumour of bone.
Multiple vascular malformation in the ‘blue rubber bleb naevus’ syndrome: a case with aneurysm of vein of Galen and vascular lesions suggesting a link to the Weber–Osler–Rendu syndrome
Authors: ROSENBLUM W. I. , NAKONECZNA IRENE , KONERDING HAZLE S. , NOCHLIN D. , GHATAK NITYA R.
Published: April 2007

A case of Bean's syndrome is reported in which a wide variety of vascular malformations are illustrated. Among these were multiple arterio‐venous malformations including a so‐called vein of Galen aneurysm. A comparison of this case with those in the literature suggests that the pathology in patients with Bean's syndrome may be more varied than heretofore recognized, and that an overlap between this syndrome and the Osler–Weber–Rendu syndrome may exist.
Correlation of carcinoembryonic antigen in tissue sections with spread of mammary carcinoma
Authors: SHOUSHA S. , LYSSIOTIS T.
Published: April 2007

An immunoperoxidase technique for the histological demonstration of Carcinoembryonic Antigen (CEA) was applied to paraffin sections from 74 breast carcinomas and 43 benign breast lesions. Sixty‐six per cent of the carcinomas and the only case of granular cell myoblastoma examined were CEA positive. Two examples of mammary dysplasia (7%) showed foci of CEA positive acini. All tumour tissue found in lymphatics and in metastases in lymph nodes was CEA positive, including two cases where the primary tumour was CEA negative, and all the metastases examined from CEA positive tumours. A significant relationship was found between CEA positivity of the primary tumour and the presence of lymph node metastases.
Pure Sertoli cell tumour of the ovary: report of a case with ultrastructural observations
Authors: HARRIS M. , BALGOBIN B.
Published: April 2007

A case of pure Sertoli cell tumour of the ovary is described. Unusual features were its great size, lack of clinical hormonal activity and the presence of granulomas in its interstitium. Mitochondria with tubular christae are described for the first time in such a tumour. These, together with lipid droplets and plentiful smooth endoplasmic reticulum, suggest a potential for steroid hormone synthesis which was not expressed clinically. Dense membrane‐bound granules of undetermined type were present in large numbers. The presence of cilia and microvilli, and the absence of annulate lamellae and Charcot‐Böttcher crystalloids, suggests that the tumour cells may not be truly of Sertoli type.
Malignant schwannoma of the stomach in a patient with von Recklinghausen's disease
Authors: CROKER J. R. , GREENSTEIN R. J.
Published: April 2007

A patient with von Recklinghausen's disease died with a malignant schwannoma of the stomach and was found at autopsy to have neurofibromatosis of the gastrointestinal tract, a plexiform neurofibroma of the myocardium and a phaechromocytoma. Malignancy of the gastrointestinal tract in von Recklinghausen's disease is rare, and this case highlights the difficulties in histological diagnosis of malignant nerve sheath tumours.
Mucosal hyperplasia in colonic diverticula
Authors: RHATIGAN R. M. , SAFFOS ROSILIE O.
Published: April 2007

Benign, nonpolypoid mucosal hyperplasia has been consistently observed adjacent to colonic carcinomas. In order to determine the specificity of this association we looked for this type of mucosa in diverticulosis with or without diverticulitis, a disease thought not to be causally related to carcinoma. Nonpolypoid mucosal hyperplasia was frequently found within diverticula suggesting that this mucosal abnormality is, in some instances, unrelated specifically to malignancy.
The pathology of a cricopharyngeal dysphagia
Authors: CRUSE J. P. , EDWARDS D. A. W. , SMITH J. F. , WYLLIE J. H.
Published: April 2007

The paper describes the changes in the cricopharyngeal muscle in seven cases of dysphagia resulting from obstruction at this level which was relieved by myotomy. Histological features included degeneration and regeneration in the muscle fibres with interstitial fibrosis which was severe in some of the cases. It is considered that this restrictive fibrosis is the cause of the dysphagia and that it is secondary to muscle fibre damage, the cause of which is at present obscure. Minor degrees of muscle damage and regeneration were seen rarely in controls and fibrosis was never present. There was no evidence of underlying vascular or neurological disease in six cases; the seventh had a previous history of scleroderma but this was not thought to be the cause of the cricopharyngeal lesion. The age incidence ranged from 1 to 5 years at the onset of dysphagia; in six of the seven it was 50 years or more.
Sudden unexpected cardiac death—a practical approach to the forensic problem
Authors: DAVIES M. J. , POPPLE A.
Published: April 2007

Sudden cardiac death can usually be resolved by the pathologist into ischaemic heart disease, non‐vascular cardiac disease such as aortic stenosis or hypertrophic obstructive cardiomyopathy and infrequently a morphologically normal heart on naked eye examination. When ischaemic heart disease is present one third of cases have a recent occlusive coronary artery thrombosis. Two thirds of patients have coronary stenosis only; the minimum degree of disease reasonably associated with sudden death is one area of 85% stenosis. The majority of patients, however, have multiple areas of stenosis. The predominant causes of non‐ischaemic sudden death are severe LV hypertrophy, hypertrophic obstructive cardiomyopathy and the prolapsing mitral valve syndrome. Where the heart and coronary arteries are morphologically normal, review of any previous ECG's, a family history and histological examination of the myocardium and conduction system may reveal a cause or at least allow a reasonable assumption of cardiac arrhythmia to be made. Sudden unexpected death where the circumstances strongly suggest a cardiac cause may pose problems for the pathologist. Ischaemic heart disease (coronary atherosclerosis) is undoubtedly the most frequent cause but even when this is so the detailed pathology is controversial. It is when coronary artery disease is conspicuously absent, often in young individuals previously in good health, that a problem exists. Sudden death in infancy (cot death) is a different entity with its own problems and is not here discussed further.
Liver cell injury (bodies similar to Lafora's) in alcoholics treated with disulfiram (Antabuse)
Authors: VÁZQUEZ J. J. , PARDO‐MINDAN J.
Published: April 2007

Inclusions, structurally similar to Lafora's bodies, are described in the liver cells of three chronic alcoholic patients who stopped drinking after disulfiram treatment. The inclusions were strongly positive with PAS and methenamine silver stains. Shikata stain for HBsAg was negative. On electron microscopy the inclusions are not membrane‐bound and contain glycogen beta‐granules, secondary lysosomes containing lamellar structures, lipid droplets and filaments; the SER was almost completely lost. In the patient least affected, the cells bearing inclusions were predominantly periportal in location, as is usual in Lafora's disease. In the two other patients the change involved the whole lobule. The possibility of an induced carbohydrate metabolic disorder, which could be due to the disulfiram, a drug that interferes with the activity of several hepatic enzymes is discussed. The presence of appearances suggestive of SER breakdown could also be interpreted as a manifestation of ‘disuse atrophy’ due to alcohol withdrawal.
The identification of ‘casein’ in human breast cancer
Authors: FORTT R. W. , GIBBS A. R. , WILLIAMS D. , HANSEN JANE , WILLIAMS I.
Published: April 2007

A retrospective study of ninety‐six cases of breast cancer was carried out to determine the prognostic values of a casein immunolocalization technique. This was performed using an indirect immunofluorescence method with antisera raised in rabbits to pooled human casein. Fluorescence positivity was graded according to its intensity and distribution. The pathology of each tumour was studied and the tumour type, histological grade and tissue response assessed. The relationship between these observations and the casein content of the tumour was studied. In addition the correlation between casein content and age, menopausal state, clinical staging and survival was investigated. The incidence of casein positivity in our series was 50% with approximately half of the positive cases showing strong fluorescence. There was a relationship between casein content and the age of the patients, with casein being more frequently found in tumours from younger patients. Tumours with a high casein content, in general, show a poorer survival than the group as a whole. This difference in survival was most marked in the first eight years after operation and restricted to those tumours in clinical stage I and histological grade I. The presence of casein in the tumours did not appear to be related to the other factors examined.
Paraganglion cells mimicking metastatic clear cell carcinoma
Authors: MÄKINEN JUDIT , NICKELS JUHA
Published: April 2007

Four patients are presented in whom normal paraganglion cells simulated metastases of clear cell carcinomas of the urogenital tract. The cells, located within and near the lumbar sympathetic ganglia, were initially interpreted by the pathologist as metastatic, but a later examination showed them to be normal paraganglion cells. One ganglion was also examined electron microscopically. Normal ganglion cells were seen, as were cells with intracytoplasmic osmophilic neurosecretory granules, confirming their paraganglionic origin. Awareness of the appearance of paraganglion cells in some instances is essential to avoid their misinterpretation as metastases of clear cell carcinomas.
Amyloid arthropathy in myelomatosis—intracytoplasmic synovial deposition
Authors: FRENCH B.T.
Published: April 2007

An unusual case is described of a West Indian man who presented with symptoms of an acute polyarthritis and who was found to have myelomatosis. At necropsy, generalized amyloidosis was found with particular involvement of synovial tissue. Myelomatosis presenting as an acute polyarthritis resembling rheumatoid arthritis is an uncommon, although well recognized entity, whereas an arthritic picture produced by amyloidosis is exceptional. The occurrence of joint pathology in myelomatosis and amyloidosis is discussed and the unique feature of intracytoplasmic amyloid deposition seen in this case is stressed.
Is malignant melanoma arising in a Hutchinson's melanotic freckle a separate disease entity?
Authors: McGOVERN V. J. , SHAW H. M. , MILTON G. W. , FARAGO G. A.
Published: April 2007

Several features which distinguish malignant melanoma arising in a Hutchinson's melanotic freckle (HMFM) from other types of malignant melanoma (MM) are described. Forty‐eight patients with HMFM of the head and neck region were compared with 98 patients with MM of the head and neck region. All patients were clinical stage I. There was a preponderance of women amongst HMFM patients but not MM patients and HMFM patients were significantly older than MM patients. Although HMFM patients had thicker tumours than MM patients, these thicker lesions had a lower degree of mitotic activity and a higher incidence of partial regression. Overall prognosis for HMFM patients was significantly better than for MM patients, this being particularly so for women, none of whom died of melanoma. There was no close correlation between prognosis of HMFM patients and the thickness of their tumours. Every one of the HMFM in this study displayed evidence of severe solar degeneration, but such degeneration per se did not appear to confer upon these lesions their benign biological behaviour.
Ultrastructure of transplant glomerulopathy
Authors: HSU H. ‐C. , SUZUKI Y. , CHURG J. , GRISHMAN E.
Published: April 2007

Thirty‐one specimens of tissue were obtained from 15 renal allografts 3–96 months after transplantation and studied by light, electron and in some cases also by immunofluorescence microscopy. All patients had a degree of renal insufficiency and almost all had proteinuria and moderate hypertension; nephrotic syndrome was present in one and hematuria in two. On histological examination one patient showed cellular proliferation suggestive of glomerulonephritis (recurrent or de novo) and another patient had numerous crescents. The most frequent glomerular lesion was widening of the lamina rara interna with subendothelial accumulation of finely granular material, formation of new subendothelial basement membrane and deposition of microfibrils and fine filaments. The mesangial changes were mainly those of mesangiolysis and mesangial sclerosis with deposition of mesangial matrix and microfibrils, but little cellular proliferation. Fragmented red blood cells were seen in nearly half of the patients. In another seven patients the lesion resembled focal segmental glomerulosclerosis. This combination of changes termed transplant glomerulopathy leads to diffuse glomerular sclerosis. Arterial intimal thickening and occasionally also thrombosis produced ischaemic changes in the kidney and in the glomeruli and contributed significantly to the process of transplant rejection.
Lobular endocrine neoplasia in fibroadenoma of the breast
Authors: EUSEBI V. , AZZOPARDI J. G.
Published: April 2007

Four cases of endocrine neoplasia within fibroadenomas of the breast are described. The tumours are identifiable by light microscopic, silver impregnation and ultrastructural studies. Argyrophilia and the presence of dense‐core granules establish the identity of this tumour type. The differential diagnosis from, and possible relation to, lobular carcinoma in situ are discussed.
The pathology of the liver in porphyria cutanea tarda
Authors: CORTÉS J. M. , OLIVA H. , PARADINAS F. J. , HERNANDEZ‐GUÍO C.
Published: April 2007

We report the findings in 53 biopsies from 45 patients with porphyria cutanea tarda (PCT). Red autofluorescence and birefringent acicular cytoplasmic inclusions were constant findings in all untreated cases. Autofluorescence occurs in other hepatic porphyrias, but acicular inclusions appear to be specific for PCT; we have seen them in subclinical porphyria and before development of cutaneous symptoms. They are probably uroporphyrins and they tend to disappear during rinsing by water during most staining procedures. We recommend unstained paraffin sections for their demonstration. Liver damage in PCT has features distinct from other liver diseases, including alcoholic liver disease. These include constant but mild periportal siderosis, focal lipofuscin deposition, focal lobular hepatocyte necrosis associated with groups of pigment‐laden macrophages, focal steatosis, marked hepatocyte hyperplasia and the presence of periductal lymphocyte aggregates. The latter have not been previously described in PCT and were present in 43 % of our cases. There is a direct relationship between increasing age and progressive distortion of liver architecture, with fibrosis present at a mean age of 48 years, cirrhosis at 57 and hepatocellular carcinoma at 66. The characteristic liver histology and the natural history of PCT are against this being the result of any non‐specific liver damage and favour instead a specific liver disease whose pathogenesis may be mainly the result of the metabolic defect of PCT.
The relation of different inflammatory cell types to the various parenchymal components of rejecting kidney allografts
Authors: REITAMO S. , KONTTINEN Y. T. , RANKI ANNAMARI , HÄYRY P.
Published: April 2007

Histochemical and immunoperoxidase techniques were used to characterize the spatial relationships of various inflammatory cell types to the different transplant structures in human renal allograft rejection. T lymphocytes were identified by acid α‐naphthyl acetate esterase (ANAE) staining, plasma cells by intracyto‐plasmic immunoglobulin, mononuclear phagocytes by intracytoplasmic ‘dispersed’ ANAE reaction and/or lysozyme staining and granulocytes by intra‐cellular lactoferrin. In the two cases of acute rejection the infiltrate around the blood vessels consisted mainly of lymphocytes, whereas the infiltrate around the tubules and within the glomerular tufts consisted mainly of mononuclear phagocytes. In acute rejection only a few plasma cells and granulocytes were seen. In the single case of chronic rejection studied, the lymphocytes were no longer concentrated exclusively around the blood vessels, but diffusely distributed throughout the kidney parenchyma. The different distribution of various inflammatory cells may reflect differences in the functions of these cell types in graft destruction.
Follicular adenoacanthoma of the thyroid gland
Authors: MAHONEY J. P. , SAFFOS ROSILIE O. , RHATIGAN R. M.
Published: April 2007

A 67‐year‐old euthyroid black woman presented with a painful palpable thyroid nodule. Microscopic examination revealed an extensively infarcted follicular carcinoma with minimal capsular and vascular invasion and advanced squamous metaplasia. From the regions of squamous metaplasia, ultrastructural analysis demonstrated both squamous and adenomatous features within the same individual cells. We stress the prognostic importance of histologic distinction between adenoacanthomas and adenosquamous or squamous cell carcinomas. The literature is reviewed and the aetiology, pathology, classification and prognosis of primary thyroid cancers with squamous epithelium are discussed.
Pulmonary calcification and elastic tissue damage in pseudoxanthoma elasticum
Authors: JACKSON A. , LOH CHI‐LOONG
Published: April 2007

A case of pseudoxanthoma elasticum with extensive calcification and elastic tissue damage in the lung is described. This patient had classical skin changes, peripheral arterial calcification, and heart block, but no retinal changes. Hypercalcemia was excluded. Pulmonary involvement is in keeping with the concept of the basic abnormality being in the elastic fibres, and such involvement should be considered as a cause of respiratory symptoms in patients with this condition.
Benign papillary mesothelioma of peritoneum: a histological, histochemical and ultrastructural study of six cases
Authors: GOEPEL J. R.
Published: April 2007

Six cases of localized benign papillary mesothelioma of peritoneum were retrieved from laboratory files over a 20‐year period. One presented because of pain following torsion and the remaining five were incidental findings at operation. Light microscopy showed a delicate papillary stroma covered by a single layer of mesothelial cells. The mesothelial cells often showed punctate periodic acid‐Schiff staining of cytoplasm. The brush border and stroma showed alcian blue positive staining which was abrogated by prior incubation with hyaluronidase. Electron microscopy revealed typical features of mesothelial cells with long microvilli, rough endoplasmic reticulum in relation to mitochondria, bundles of microfilaments, and tight junctions. Between cells there was a series of intercommunicating channels containing occasional lymphocytes and debris. These features are compared with nodular mesothelial hyperplasia, malignant mesothelioma and adenomatoid tumours of the genital tract. The necessity to distinguish benign papillary mesothelioma from metastatic carcinoma is stressed and relies on the recognition of their mesothelial origin.
Histological differential diagnosis between lymph node toxoplasmosis and other benign lymph node hyperplasias
Authors: MIETTINEN M.
Published: April 2007

The material from 667 lymph nodes, originally suspected of toxoplasmosis, was histologically re‐examined, to evaluate criteria for diagnosis and differential diagnosis. The results showed that at least 80% of benign lymph node enlargements containing small groups of epithelioid cells were associated with high titres of Toxoplasma antibodies. Furthermore, 85–95% of the lymph nodes in association with high Toxoplasma antibodies showed the typical histological appearances of toxoplasmosis. The histological diagnosis of toxoplasmosis is thus both fairly specific and sensitive. Other lymph node lesions with small groups of epithelioid cells must be considered in the differential diagnosis. Sarcoidosis and tuberculosis usually have a predominance of distinct large epithelioid cell granulomata. Lymph nodes with sinus histiocytosis showing the formation of small groups of epithelioid cells, do not demonstrate prominent hyperplasia and include sparse germinal centres and were not associated with toxoplasmosis. Lymph nodes with disturbed general structure and small groups of epithelioid cells must be carefully assessed because of the significant possibility of malignancy.
‘Transitional’ and hyperplastic‐metaplastic mucosa occurring in solitary ulcer of the rectum
Authors: FRANZIN G. , SCARPA A. , DINA R. , NOVELLI P.
Published: April 2007

Non‐polypoid hyperplastic mucosa similar to that adjacent to colorectal carcinomas and adenomas, the so‐called ‘transitional mucosa’ (TM), was found in 16 out of 27 cases of solitary ulcer syndrome of the rectum. In 18 cases fully developed hyperplastic (metaplastic) mucosa was also found. It is suggested that chronic ischaemia which takes place in the solitary ulcer syndrome leads to TM as an exaggerated regenerative phenomenon. Later maturation of TM could lead to hyperplastic (metaplastic) changes.
Abnormalities of the colonic regulatory peptides in Hirschsprung's disease
Authors: BISHOP ANNE E. , POLAK JULIA M. , LAKE B. D. , BRYANT M. G. , BLOOM S. R.
Published: April 2007

We describe here a depletion of peptide containing nerves and cells in Hirschsprung's disease, in comparison with specimens of bowel taken from age‐matched neonates with no evidence of chronic constipation. VIP content in the diseased specimens was reduced by almost 80%, from 110 ± 10.6 (mean ± SEM) pmol VIP/g wet weight of tissue in controls to 23.8 ± 3.5 pmol/g in the mid‐portion of the diseased specimens. In addition, the numbers of enteroglucagon and somatostatin cells in the mucosa were significantly reduced in the aganglionic portions. Enteroglucagon cells were reduced from 55 ± 7 in controls to 27 ± 2 in proximal portions rising to 44 ± 3 and 49 ± 4 cells/mm2 in middle and distal areas. Somatostatin cell numbers also fell, from 5.5 ± 1.9 to 1.8 ± 0.8, 2.5 ± 0.7 and 3.8 ± 0.9 cells/mm2 in similar areas. Further investigation of the abnormalities of the diffuse neuroendocrine system in Hirschsprung's disease may help in understanding the nature of this condition and provide additional information on the role of these peptides in the control of gut function.
Scanning electron microscopy
Authors: CARR K. E. , TONER P. G. , SALEH K. M.
Published: April 2007

The technology of scanning electron microscopy (SEM) is described in brief. Its application to the study of cell and tissue structure is demonstrated and the evolution of the concept of ‘topographical histology’ is discussed. Some current literature on the applications of SEM is reviewed under the headings of experimental pathology and human pathology. While SEM has become an indispensable technique for the experimental morphologist, its application to diagnostic pathology and cytology is still at an early exploratory stage.
Pseudolymphomas of the stomach: a lesion characterized by progressively transformed germinal centres
Authors: HYJEK ELZBIETA , KELÉNYI G.
Published: April 2007

Pseudolymphomas of the stomach are frequently associated with chronic peptic ulcer. Out of the 11 cases studied, there were characteristic pathohistological signs of chronic ulceration in eight and suspicion of chronic ulcer in three. Thus it seems that pseudolymphomas frequently represent an exaggerated lymphocytic reaction to chronic ulcer. The pseudolymphomatous reaction is essentially a follicular hyperplasia with the gradual development of progressively transformed germinal centres. These large nodular structures are usually found in the submucosa and, at first inspection, the transformed follicle can easily be mistaken for a possibly malignant diffuse lymphomatous lesion. However, once the existence of the condition is realized, its recognition by the pathologist should be easy. A heavy plasma cell infiltration of polytypic immunoglobulin type associated with progressively transformed germinal centres might be a consequence of long‐standing antigenic stimulation.
Infiltrating lobular carcinoma of the breast
Authors: DIXON J. M. , ANDERSON T. J. , PAGE D. L. , LEE D. , DUFFY S. W.
Published: April 2007

On review of the histology of 1050 primary breast carcinomas, 103 cases of infiltrating lobular carcinoma were identified and clinical and survival data collected in each case. The tumours were then separated into four groups on the basis of histological pattern and these groups shown to have significantly different survival times. Assessment of the presence of in situ carcinoma, elastosis and intracyto‐plasmic lumina was performed in each case and the effect of these features on survival investigated. In addition to stage of disease at presentation, the major significant factor in predicting survival of patients with this type of invasive carcinoma is histological type.
Immunoperoxidase staining of Legionella pneumophila
Authors: BOYD J. F. , McWILLIAMS E.
Published: April 2007

Immmunoperoxidase staining has been applied to sections of pneumonic lung from a previously published case of Legionnaires’ disease. Specific staining of Legionella pneumophila was accomplished with sub‐group 1 antiserum, which also revealed staining of phagosomes, and in some areas diffuse background staining of ‘soluble’ antigen. Some organisms remained unstained with the specific antiserum, and these were revealed by progressive haemalum staining. In other sections, some organisms stained specifically with rabbit anti‐μ chain serum but not with anti‐γ chain serum, this result suggesting that the organisms were coated with patient's IgM specific antibody.
Ulceration and prognosis in cutaneous malignant melanoma
Authors: McGOVERN V. J. , SHAW H. M. , MILTON G. W. , McCARTHY W. H.
Published: April 2007

A review of 1818 patients with cutaneous malignant melanoma revealed that for both patients with localized disease (clinical stage I) and those with regional lymph node metastases at first presentation (clinical stage II), ulceration of the primary lesion was a poor prognostic sign. Although ulcerated lesions tended to be considerably thicker than non‐ulcerated lesions, this factor did not entirely explain the poor prognosis recorded for patients with ulcerated lesions. In men and women matched by the thickness of their tumours, prognosis for those with ulcerated lesions was worse than for those with non‐ulcerated lesions. This effect was particularly marked in women. It was concluded that since this histological feature was an independent prognostic determinant, it should be reported by the pathologist as a guide to the clinician in assessing prognosis in patients with melanoma.
The endometrial hyperplasias and their relationship to endometrial neoplasia*
Authors: FOX H. , BUCKLEY C. H.
Published: April 2007

The various forms of endometrial hyperplasia are classified and a description given of their pathology and of their inter‐relationships. The nosological status of endometrial adenocarcinoma in situ and the histological differentiation between hyperplasia with severe cellular atypia and endometrial adenocarcinoma are discussed. The aetiology and pathogenesis of the various endometrial hyperplasias are considered and grounds are given for the belief that glandular hyperplasia with cellular atypia is a form of intraendometrial neoplasia. A new terminology, based on the biological nature of the various endometrial abnormalities, is proposed and a plea is made for the introduction of the term ‘intraendometrial neoplasia’ to encompass all forms of endometrial glandular hyperplasia with cellular atypia and intraendometrial adenocarcinoma.
Multiple bilateral breast adenomata in identical adolescent Negro twins
Authors: MORRIS J. A. , KELLY J. F.
Published: April 2007

Identical adolescent Negro twins presented with multiple bilateral breast adenomata. There were three pure tubular adenomata, one mixed tubular and fibroadenoma, four glandular fibroadenomata and one typical intracanalicular fibroadenoma. Tubular adenomata are exceedingly rare and this report adds a further three to the literature. Furthermore, the close similarity of the glandular fibroadenomata and tubular adenomata, the occurrence of tubular and fibroadenomatous areas in the same tumour, and the simultaneous occurrence of both tumour types in the same genetic setting, point to a close relationship between these types of neoplasm. The simultaneous occurrence of breast adenomata in identical twins suggests, but does not prove, an important genetic contribution to the aetiology of these tumours. The twins were both virgins, and, therefore, it is clear that pregnancy is not a pre‐requisite for the development of tubular adenomata, as has been suggested.
Histochemically demonstrable enzyme activities and their independence of the hormone receptor content in female breast carcinoma
Authors: PARTANEN S. , SYRJANEN K.
Published: April 2007

Acid phosphatase, leucine aminopeptidase, monoamine oxidase and non specific esterase activities were histochemically demonstrated in specimens derived from 15 infiltrating ductal carcinomas of female breast. The relative areas occupied by the enzyme‐positive carcinoma cells were visually estimated and, in the cases of leucine aminopeptidase, assessed morphometrically. All enzyme activities were found to be subject to major variations within a single carcinoma and between individual carcinomas, and the activity of any single enzyme was independent of that of three others. None of the enzyme activities correlated with the estrogen and progesterone receptor values, nor the histological grade of malignancy of the tumour. Thus, histochemically demonstrable enzyme activities seem to be of no use in predicting the hormone receptor content in infiltrating ductal carcinomas of the female breast.
Angiomyelolipoma of the liver
Authors: PETERS W.M. , DIXON M.F. , WILLIAMS N.S.
Published: April 2007

A case of angiomyelolipoma of the liver occurring in a 54–year‐old woman is described. The literature concerning lipomatous liver tumours is reviewed, and the possible histogenetic origin of this neoplasm is discussed.
Malakoplakia of middle ear: a case report
Authors: AZADEH B. , ARDEHALI S.
Published: April 2007

Malakoplakia of the mastoid cavity occurring in a 10‐year‐old boy is reported. Malakoplakia of the middle ear does not previously appear to have been recorded. The patient has had repeated ear infections and an episode of meningitis. Clinical and histological features are described. Possible pathogenesis is discussed.