Crystallization of the ribosome inactivating protein ML1 from Viscum album (mistletoe) complexed with beta-D-galactose.

A ribosome inactivating protein (ML1) from the mistletoe plant (Viscum album) has been crystallized. The crystals, grown in the presence of beta-D-galactose, are hexagonal, space group P6(1)22 or P6(5)22, a = b = 111.0 A, c = 309.3 A with 24 molecules per unit cell (assuming 33% solvent by weight). The protein of molecular mass 63 kDa is a heterodimer consisting of two chains, A and B, joined by a disulfide bond. The A-chain, 29 kDa, inhibits protein synthesis by depurinating an adenine residue (A4324) in a highly conserved RNA loop of the 28 S ribosomal subunit. The toxicity of the protein is mediated by the B-chain, 34 kDa, which has lectin activity, interacting with sugar residues of glycoproteins and glycolipids on the surface of target cells.

Mistletoe lectin I forms a double trefoil structure.

The quaternary structure of mistletoe lectin I (MLI), a type II ribosome inactivating protein, has been determined by X-ray crystallography. A definitive molecular replacement solution was determined for MLI using the co-ordinates of the homologue ricin as a search model. MLI exists as an [AB]2 dimer with internal crystallographic two-fold symmetry. Domain I of the B chains is non-covalently associated through interactions involving three looped chains (alpha, beta, gamma) in each molecule of the dimer, forming a double trefoil structure. The ricin molecule which shares 52% sequence homology with MLI has a disulphide bridge between Cys20 and Cys39 in the alpha loop. An evolutionary mutation has replaced Cys39 with serine in MLI. This mutation appears to allow the alpha loop the flexibility required to take up its place at the dimer interface, and also suggests a rationale for why ricin does not form dimers. Measurement of retention times using FPLC gel filtration confirms that dimerisation also occurs in solution between MLI B chains with an association constant Ka = 10(6) M.

Adult alpha1-antitrypsin deficiency.

Three adults with alpha 1-antitrypsin deficiency are described. In two of the cases the deficiency was genetically determined (cases 1 and 2), and each demonstrated unusual features of the disease. The liver in case 1 (homozygous) showed cholangiolar hyperplasia which has been recorded only once before. Case 2 (heterozygous) had emphysema and cirrhosis, a combination not previously documented in a heterozygote, in addition to malabsorption. Case 3 represents a case of spurious alpha 1-antitrypsin deficiency with cirrhosis included to emphasize the diagnostic improtance of phenotyping in such cases.

Tumour related cutaneous elastophagocytosis.

Dermal granulomatous inflammation was identified immediately adjacent to seven (77%) of nine atypical fibroxanthomas arising in sun damaged skin. Concomitant elastophagocytosis was observed in five (56%) of these seven patients. Similar inflammation with elastophagocytosis was found in association with only two (6%) of 36 epithelial tumours arising on the same background (10 basal and 10 squamous cell carcinomas, 10 nodular malignant melanomas, and six keratocanthomas). Granulomatous inflammation is an unusual dermal reaction to tumour and elastophagocytosis is rare. The fact that both of these features occur with inordinate frequency in association with atypical fibroxanthomas, when compared with other, more common skin tumours, suggests that atypical fibroxanthomas might modulate the inflammatory response, either passively, by its dermal location, or actively, by secreting locally effective cytokines.

Pleomorphic adenoma of the bronchus.

An example of pleomorphic adenoma of the bronchus is described in a 27 year old male student who was referred for evaluation of a coin lesion identified incidentally on chest x ray. The tumour exhibited the classic histological, immunohistochemical and ultrastructural features of this rare entity but, in addition, contained mature and immature adipose tissue in the stroma and showed transition, in its superficial portion, between ostensibly normal bronchial mucus glands and tumour tubules. Neither of these features has been commented upon previously.

Paraganglioneuroma of the duodenum: an evolutionary hybrid?

On light microscopy the neural component of a hybrid neural and endocrine duodenal tumour was characterised by ganglion cells and the endocrine component by epithelioid cells which were both argentaffin and argyrophil. Spindle-shaped cells of indeterminant lineage were also present. Electron microscopy revealed 'pale' and 'dark' cells, the former corresponding to the epithelioid cells and containing many membrane-bound neurosecretory granules, the latter probably corresponding to the spindle cells and containing large numbers of neurofilaments. Occasional cells contained both neurofilaments and secretory granules arranged in a consistent pattern in the cytoplasm. These composite cells may have represented an incompletely differentiated precursor of both the neural and endocrine elements of the tumour.

Mucin-producing atypical bronchial carcinoid.

In a case of atypical mucin-producing bronchial carcinoid in a 40-year-old man covert metastases were present at the time of lobectomy and were revealed at necropsy--a feature highlighting the malignant potential of the atypical carcinoid.

Hepatic lesions in patients treated with synthetic anabolic steriods.

Hepatic abnormalities are described in three patients who received synthetic anabolic steroids. A child with Franconi's anaemia was treated for four years and at necropsy the liver showed generalized hyperplasia, hyperplastic nodules, and a benign hepatoma. Two adults received only three months' therapy with synthetic androgens; in one there was generalized hepatic hyperplasia and in the other widespread nodular hyperplasia. It is suggested that anabolic steroids may induce tumours through intermediate hyperplastic lesions, a sequence similar to that seen during tumour induction by carcinogens in experimental animals.

Pulmonary carcinoid tumours: a comparative regional study.

Twenty-two pulmonary carcinoid tumours (18 central, 4 peripheral) were seen in this department over an 11-year period. The majority of the tumours displayed a mixed pattern on microscopic examination, and cell-nest formation was a prominent feature in sixteen. The findings are at variance with the results of a similar series reported from Japan and suggest that there is regional variation in the tumour pattern of pulmonary carcinoids. Various aspects of the histopathology are discussed, and a causal relationship between ossification of bronchial cartilage in these tumours and locally produced calcitonin is postulated.

Chronic Brucella infection of the supra-patellar bursa with sinus formation.

A case of supra-patellar bursitis with the formation of discharging sinus is described. B abortus was isolated from resected bursal tissue. While osteoarticular complications of brucellosis are common and a number of different clinical syndromes are now recognised, disease of the bursae is rare and as far as is known sinus formation has not been described before in this setting.

'Pseudocirrhosis' in hereditary haemorrhagic telangiectasia.

Telangiectasia-associated hepatic fibrosis (TAHF) in a 68-year-old woman with hereditary haemorrhagic telangiectasia (HHT) is described. The patient died of oat-cell carcinoma of the lung. In addition to the structural alterations which have been described previously in HHT, the liver exhibited focal midlobular hepatocytic necrosis and tumour metastases. The possibility that treatment of HHT was causally related to some of the hepatic abnormalities found in our patient and the differentiation of TAHF from true cirrhosis are discussed.

Apoptotic and mitotic indices in malignant melanoma and basal cell carcinoma.

AIMS: To assess the relative frequency of mitotic and apoptotic cells in malignant melanoma and basal cell carcinoma. METHODS: Retrospective evaluation of haematoxylin and eosin stained slides from 10 basal cell carcinomas, 10 nodular melanomas, and 10 superficial spreading melanomas, with counting of apoptotic and mitotic cells per 1000 cells. Selected cases were studied with in situ end-labelling. RESULTS: The ratio of apoptotic to mitotic cells was higher in basal cell carcinoma than in either form of melanoma because of the presence of a greater number of apoptotic cells in basal cell carcinoma. CONCLUSION: The differing growth rates and biological behaviour of these two tumours is reflected in the apoptotic:mitotic ratio. Further assessment of this ratio is warranted, both between tumour types and between individual tumours of one type, to determine its value as an indicator of biological potential.

The role of small bowel follow-through examination in the diagnosis of coeliac disease.

A retrospective study of 105 barium follow-through examinations on 102 patients suspected of having malabsorption syndrome has been carried out to assess the usefulness of this technique in the diagnosis of coeliac disease. Comparison with histological and biochemical data has been made. Of the 34 examinations on 31 patients with a proven diagnosis of coeliac disease, 30 examinations showed both abnormal X-ray and biopsy findings, two examinations showed normal X-ray appearance but abnormal jejunal biopsy and two showed normal jejunal histology but abnormal X-ray findings. There were two cases with sensitivity, non-invasive nature, ease and cheapness of the technique, barium follow-through examination is suggested as the initial investigation in patients suspected of coeliac disease.

Chronic myelomonocytic leukemia revealed by uncontrollable hematuria.

Nephrectomy was performed for uncontrollable unilateral hematuria in an apparently healthy 72-year-old man. The suburothelial connective tissue of the kidney was infiltrated by primitive myeloid cells with associated acute vasculitis and foci of extramedullary hematopoiesis. Subsequently, the patient was shown to have chronic myelomonocytic leukemia. Although renal involvement and vasculitis have been recorded previously in chronic myelomonocytic leukemia, this is the first occasion, to our knowledge, where their concurrence resulted in such a spectacular presentation.

Real-time quantitative analysis of E-cadherin expression in ret/PTC-1-activated thyroid neoplasms.

Papillary thyroid carcinoma (PTC), the most common variety of thyroid cancer, is found in a variety of morphologic variants, usually grows slowly, and is clinically indolent, although rare, aggressive forms, with local invasion or distant metastases, occur. Our group has previously demonstrated an association between Hashimoto thyroiditis and ret/PTC-1 activation, and have hypothesised that c-ret activation might be implicated in immune reaction to thyroid epithelium. The objective of this study was to examine expression of the cellular adhesion molecule, E-cadherin, in various thyroid tumor types and Hashimoto thyroiditis in the context of ret/PTC-1 positivity by using laser capture microdissection and TaqMan reverse transcription-polymerase chain reaction (RT-PCR). Variable down-regulation of E-cadherin among carcinomas was demonstrated, with anaplastic carcinomas showing little or no expression. Follicular thyroid carcinomas consistently had significantly decreased E-cadherin expression compared with papillary thyroid carcinomas. The ret/PTC-1-positive papillary thyroid carcinoma (PTCret+) and Hashimoto thyroiditis cases had consistently lower E-cadherin expression levels than the corresponding ret/PTC-1-negative papillary carcinomas (PTCret-), suggesting not only an association between ret activation and the loss of cellular adhesion but also, more significantly, an association between papillary thyroid carcinoma and Hashimoto thyroiditis.

Transbronchial brushing of peripheral lung lesions.

The use of transbronchial brushing in six patients with peripheral lung lesions is described. In all of the four cases of carcinoma the brushings contained diagnostic cells and in two of these cases previous bronchoscopy had failed to provide histological evidence of tumour. More widespread application of this simple and useful diagnostic technique is advocated.

Herpes simplex encephalitis and sarcoidosis.

Fatal herpes simplex encephalitis occurring in a patient with sarcoidosis is described. Ultrastructural study of brain tissue revealed the presence of herpesvirus particles. The association of these 2 diseases has not been recorded before. The encephalitis in this case probably represents an opportunistic viral infection in the face of depressed cellular immunity. Progressive multifocal leukoencephalopathy, a disease of putative viral aetiology, is known to occur in patients with sarcoidosis and it is suggested that this case represents a similar pathogenetic association.

Granulosa cell tumour of the ovary metastasising to the heart: A light and electron microscopic study.

A malignant granulosa cell tumour of the ovary, which pursued a slowly progressive course over 23 years, is described. The mode of spread of the tumour was unusual, and caused bizarre clinical manifestations terminally. The light and electron microscopic appearances of the tumour are described and discussed in relation to the findings of other authors.

Disseminated herpes zoster in the elderly.

We describe three cases of disseminated herpes zoster occurring in the elderly, and discuss the investigation and diagnosis of this condition. The presentation may be atypical with excoriated papular lesions. We suggest that disseminated herpes zoster does occur in the non-immunocompromised elderly patient, and is sometimes overlooked.