bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth fractions in human prostatic carcinoma determined by Ki‐67 immunostaining
Authors: Raymond Wendy A. , Leong Anthony S‐Y. , Bolt John W. , Milios Jim , Jose John S.
Published: June 2005

Until recently, [3H]‐thymidine incorporation, DNA analysis by flow cytometry, and cell doubling times have been the main methods of studying tumour cell kinetics. All these techniques are laborious, expensive, and difficult to perform in a routine diagnostic laboratory. This study examined fresh frozen sections from 31 prostatic biopsy specimens with the hybridoma antibody Ki‐67, a marker of proliferating cells, using a modified avidin—biotin—peroxidase complex technique. The percentage of glandular cells decorated by this antibody, representing the growth fraction, was determined for both benign and malignant samples. Benign prostatic glands showed an average Ki‐67 score of 4 per cent, significantly less than the 16·3 per cent mean growth fraction found in prostatic carcinomas. There was a significant correlation between the tumour growth fraction as assessed by Ki‐67 staining, and the histological grade. A positive correlation was also found between the Ki‐67 score and the intensity of staining, and a definite trend was noted between the Ki‐67 score and the tumour clinical stage. Ki‐67 promises to be a useful marker in determining the prognosis of prostatic cancer.
Control of differentiation in human colorectal carcinoma cell lines: Epithelial—mesenchymal interactions
Authors: Richman Paul I. , Bodmer Walter F.
Published: June 2005

Mesenchymal elements have been investigated for their effects on the growth and differentiation of seven human colorectal carcinoma‐derived cell lines. Epithelial cells were cultured as monolayers on plastic; they were also grown on fibroblast lawns and in collagen matrices, with and without fibroblasts. In each case, differentiation was assessed morphologically with monoclonal antibodies directed against components of normal goblet and columnar cells. The results were compared with those obtained when the cell lines were grown in vivo as xenografts in athymic mice.

The xenografts allowed the greatest potential for differentiation, although two cell lines showed little or no response to mesenchyme either in vivo or in vitro. The presence of fibroblasts induced branched structures in all the remaining lines when these were cultured in collagen matrices. The collage matrix alone induced the formation of well‐defined glandular structures in SW 1222 cells, reminiscent of those seen in SW 1222 xenografts and normal colonic crypts.

Epithelial response to mesenchymal factors may require specific receptors, the expression of which dictates phenotype. Isolation and analysis of such receptors and factors could lead to clarification of the mechanisms underlying normal tissue morphogenesis and the growth and spread of neoplastic cells.
Silver‐stained nucleoli and nucleolar organizer region counts are of no prognostic value in thick cutaneous malignant melanoma
Authors: Howat Alec J. , Giri Dilip D. , Wright Andrew L. , Underwood James C. E.
Published: June 2005

Nucleolar organizer regions (NORs) can be stained by a simple one‐step silver technique; the black dots formed are termed AgNORs. Often AgNORs are tightly clustered, appearing as one silver‐stained nucleolus (AgNu). We have assessed this technique as a possible prognostic indicator for thick (> 3·0 mm) primary cutaneous malignant melanoma (CMM). Three groups were studied: (A) seven thick CMM that had not metastasized 8–20 years after excision; (B) three thick CMM that developed metastases 6–9 years after excision; and (C) twelve CMM that presented with metastases or developed them within 4 years of excision. Two methods of counting silver‐stained black dots in nuclei were employed: one method counted easily discernible black dots consisting of AgNus and dispersed AgNORs; the other attempted to count actual AgNORs both dispersed and clustered within AgNus. Scores per nucleus by the first method were 1·5–6·7 in group A, 1·1–2·6 in group B, and 1·4–5·4 in group C. AgNOR counts by the second method were 6·2–13·0 in group A, 5·4–8·9 in group B, and 5·3–10·5 in group C. No significant difference was present between groups for scores by either method. Due to the subjectively, technical difficulty, non‐reproducibility, and tedium associated with the second method of attempting to count individuals AgNORs, the first method is recommended. It is concluded that this technique is of no value in predicting prognosis for CMM.
Distinction between hepatocellular carcinoma, cholangiocarcinoma, and metastatic carcinoma based on immunohistochemical staining for carcinoembryonic antigen and for cytokeratin 19 on paraffin sections
Authors: Balaton A. J. , Nehama‐Sibony M. , Gotheil C. , Callard P. , Baviera E. E.
Published: June 2005

An antiserum to carcinoembryonic antigen (CEA) and a monoclonal antibody to cytokeratin 19 (CK 19) were studied for their suitability as diagnostic reagents for the differential diagnosis of primary and secondary malignant epithelial tumours of the liver, on paraffin sections. With the antiserum to CEA, positive bile canalicular structures were found in 60 per cent of the hepatocellular carcinomas. All the cholangiocarcinomas and 66·6 per cent of the metastatic carcinomas were positive for CEA, without displaying a canalicular staining pattern. All the hepatocellular carcinomas were negative for CK 19. All the cholangiocellular carcinomas and the metastatic carcinomas were positive for CK 19. This staining profile may prove helpful in difficult diagnostic cases.
Flow cytometric DNA analysis of 199 histologically favourable or unfavourable non‐Hodgkin lymphomas
Authors: Lehtinen Tuula , Aine Risto , Lehtinen Matti , Kallioniemi Olli‐Pekka , Leino Timo , Hakala Tapani , Leinikki Pauli , Alavaikko Martti
Published: June 2005

We have studied the nuclear DNA content of histologically favourable (n = 82) or unfavourable (n = 117) non‐Hodgkin lymphomas (NHLs) diagnosed between 1957 and 1978 in the Tampere University Central Hospital. The DNA analysis was done by applying a trypsin digestion method to archival tumour samples. DNA aneuploidy was seen in 40 per cent of the unfavourable cases and in 10 per cent of the favourable cases, but varied considerably between different histological subtypes. The unfavourable cases showed high proliferative activity (S‐phase fraction, SPF), while considerable variation in the SPF among the favourable NHLs was noted. Among the unfavourable NHLs, cases with DNA‐aneuploid tumours had significantly (P < 0.01) worse prognosis than stage and treatment matched cases with DNA‐diploid tumours. In general, survival of the patients who had high SPF tumours was significantly lower compared with patients with low SPF tumours (P < 0.01). However, SPF was not related to the prognosis in the unfavourable NHLs. We conclude that the flow cytometric DNA analysis revealed characteristic features in the favourable and unfavourable NHLs and may be useful in predicting the clinical outcome of patients.
Antigenic specificity of human alveolar macrophages and blood monocytes studied by an immunofluorescence technique
Authors: Nakstad Britt , Lyberg Torstein , Baklien Kåre , Boye Nils P.
Published: June 2005

Lung alveolar macrophages (AM) and blood monocytes (BM) are part of the mononuclear phagocyte system (MPS) and have been shown to be composed of several functionally and biochemically distinct subsets. AM and BM were each fractionated into four subfractions by centrifugation over Percoll, 95 per cent of the monocytes having a higher buoyant density than the high‐density AM fraction. Antigen distribution within the cell subfractions was studied by an immunofluorescence technique using a panel of ten monoclonal antibodies (MoAbs) reacting with separate antigenic determinants previously found on mononuclear phagocytes. Several antigens were present on both types of cells (Ki‐M1, Ki‐M6, Leu‐M3, Leu‐M5, 1D5, Dako‐Ma, and HLA‐DR), while other antigens were expressed exclusively on BM (MAS 072 and MAS 081) or on AM (Ki‐M8). Ki‐M1, Leu‐M3, Leu‐M5, and HLA‐DR were expressed to a greater degree on the surface of AM (95–96 per cent of cells) than on BM (5668 per cent), while an inverse relationship was noted for 1D5 antigen (present on 41 per cent of BM and 11 per cent of AM). Ki‐M6 and Dako‐Ma MoAbs recognized an intracellularly restricted antigen present in both AM and BM. Ki‐M1, Ki‐M8, MAS072, MAS081, Leu‐M3, Leu‐M5, 1D5, and HLA‐DR were expressed both in the cytoplasm and at the cell surface. Some antigens (1D5, Leu‐M3, MAS 072, MAS 081, and Dako‐Ma) showed an uneven distribution among subsets of both AM and BM. The variability found in the expression of both membrane and intracellular antigens underlines the remarkable heterogeneity among mononuclear phagocytes and emphasizes the potential value of MoAbs to study the sequential stages of maturation/differentiation within the monocyte/macrophage lineage.
Measurement of the S‐phase duration in normal and abnormal human endometrium by in vitro double labelling with bromodeoxyuridine and tritiated thymidine
Authors: Thornton James G. , Wells Michael , Hume William J.
Published: June 2005

The duration of the S phase of the cell cycle (ts) in the glands and stroma of normal, hyperplastic, and malignant endometrium was measured in vitro using a double labelling technique. Endometrial organ cultures were incubated sequentially in tritiated thymidine (3HTdR) and bromodeoxyuridine (BrdU) each for 1 h. Labelled cells were visualized in tissue sections using 3HTdR autoradiography and immunohistochemistry with an anti‐(BrdU) antibody. Three populations of cells, single labelled with either 3HTdR or BrdU, and double labelled cells, were easily identified and ts was calculated from both the rate of influx into, and efflux out of S. There were no significant differences in ts in the different tissue types or between influx and efflux in the glands. However, in the stroma ts calculated from the rate of efflux was significantly shorter than that calculated from the rate of influx, suggesting that during the cell culture period the rate of cell efflux from S was greater than influx. This is the opposite to what would be expected in an exponentially growing cell population and suggests that there may be an effect from the culturing conditions.
Changes in the cancer spectrum at autopsy: 1975–1984
Authors: Karwinski B. , Svendsen E. , Hartveit F.
Published: June 2005

In an autopsy series of 8571 cases from 1975 to 1984, cancer deaths increased significantly, particularly in those cases over 60 years of age. A similar trend was seen in the mortality statistics from the district. Study of the degree of correlation between the frequency for the different types of cancer and the total deaths from that cancer at autopsy in the population supplies guidelines for use in assessing the relevance of autopsy findings to epidemiological research. It is stressed that without autopsy control monitoring of cancer in a population is incomplete and unreliable. An autopsy frequency of 40 per cent or more for the cancer in question in the population as a whole is required combined with series of 5–600 cases if satisfactory studies are to be initiated. Such conditions are difficult to fulfil for the less common types, but offer a valid approach to the monitoring of those types of cancer that are numerous enough to merit such attention.
Histological evidence of natural killer cell aggregation against malignant melanoma induced by adoptive immunotherapy with lymphokine‐activated killer cells
Authors: Yamamura T. , Fujitani Y. , Kawauchi T. , Wada E. , Kobayashi Y. , Yoshikawa K. , Ogawa H. , Sugiyama H. , Ohsawa M. , Aozasa K.
Published: June 2005

Adoptive immunotherapy with lymphokine‐activated killer (LAK) cells and systemic administration of recombinant Interleukin‐2 (RIL‐2) was carried out in a case of malignant melanoma with lung metastases. Histological specimens from the lung showed a metastatic melanoma heavily invaded by atypical lymphoid cells with convoluted nuclei of varying size. Immunohistochemistry revealed that these cells had the characteristic exclusively of natural killer cell (Leu‐7+). Nodules of these cells mimicked the appearance of non‐Hodgkin's lymphoma of pleomorphic type. Molecular cytogenetic analysis, however, showed the absence of rearranged bands for the T‐cell receptor beta‐chain gene, indicating the absence of T‐cell clones. At autopsy, 1 month after the LAK therapy, the heavy invasion of convoluted cells had disappeared. These findings clearly indicate that the LAK cell plus RIL‐2 therapy induced Leu‐7+ lymphoid cells, phenotypically suggestive of natural killer cell aggregation in the tumours.
Paucity of fibronectin in invasive lobular carcinoma of breast
Authors: d'Ardenne A. J. , Barnard N. J.
Published: June 2005

Fifty‐four cases of invasive carcinoma of breast were immunostained for fibronectin and laminin. They included 36 cases of invasive ductal carcinoma and 18 cases of invasive lobular carcinoma. Although there was some heterogeneity within tumours, it was found that whilst the majority of ductal carcinomas (31/36) had abundant fibronectin at cell/stroma boundaries or diffusely throughout stroma, a substantial proportion of lobular carcinomas (12/18) had very little (P<0.001). This difference could not be related to differences in laminin immunoreactivity, which was most commonly scanty or absent in both tumour types. It is postulated that the characteristic infiltration pattern of lobular carcinoma may be attributed in part to paucity of stromal fibronectin.
T‐cell antigen receptor beta‐chain variable region families: A study of their distribution in normal and reactive tissues
Authors: Clark David M. , Boylston Arthur W.
Published: June 2005

The beta chain of the T‐cell antigen receptor is constructed using a variable region gene from one of approximately 20 variable gene families. Antibodies that react with the products of these gene families have been used to demonstrate clonal proliferation of T cells. Here, we describe the expression of two beta‐chain variable region families in normal and reactive lymphoid tissues. In all the tissues studied, expression was scattered throughout the T‐cell areas, without any clustering of expression.
Correlation of morphology, immunophenotype, and flow cytometry with remission induction and survival in high grade non‐Hodgkin's lymphoma
Authors: O'brien Ciaran J. , Holgate Clive , Quirke Philip , Stuart Nicholas S. A. , Ellis Ian O. , Elston Christopher W. , Jones E. Lynn , Bird Colin C.
Published: June 2005

A series of cases of high grade non‐Hodgkin's lymphomas has been studied by morphology (1l0 cases), immunocytochemistry (90 cases), using reagents reactive in fixed paraffin‐embedded tissue, and flowcytometry (77 cases). B‐cell tumours constituted 67.0 per cent of the total, T‐cell tumours 22.0 per cent, and unclassified cases 8.8 per cent. Immunocytochemistry revealed two anaplastic carcinomas. Of the 77 cases studied by flow cytometry, 67.5 percent were diploid and 32.5 per cent DNA aneuploid. T‐cell tumours were more likely to be diploid than B‐cell tumours, though the difference did not reach statistical significance, T‐cell tumours had a significantly lower proliferative index (%S + G2) than B‐cell tumours (P = 0.002).

The overall remission induction rate was 68 per cent and actuarial 3‐year survival 47 per cent. There was a trend for cases with %S + G less than 22 percent to survive longer (P=0.07). This trend became statistically significant when aneuploid cases were added to the high PI group (P = 0.04). No correlation was seen between morphological or immunophenotypic groups and remission induction rates or survival.
Plasmacytoid monocytes (so‐called plasmacytoid T cells) in Hodgkin's disease
Authors: Facchetti Fabio , De Wolf‐Peeters Chris , Van Den Oord Joost J. , Desmet Valeer J.
Published: June 2005

The occurrence and distribution of piasmacytoid monocytes (so‐called plasmacytoid T cells) were investigated irnmunohistochemically in 40 cases of Hodgkin's disease. Large numbers of plasmacytoid monocytes were found in all cases of lymphocyte predominance, nodular sclerosing, and mixed cellularity Hodgkin's disease, characterized by a minor degree of architectural effacement. They occurred at the periphery of lymphoid aggregates which mimic the composite nodule of the reactive lymph node and which contained Reed‐Sternberg cells and their variants. Despite some immunophenotypic similarities, no further arguments were found to support a relationship between plasmacytoid monocytes and Reed‐Sternberg cells.

We conclude that plasmacytoid monocytes represent one of the monocyte‐derived cells that contribute to the cellular reaction in Hodgkin's disease.
Diagnostic fine needle core biopsy of deep lymph nodes for the diagnosis of lymphoma in patients unfit for surgery
Authors: Wothfrspoon Andrew C. , Norton Andrew J. , Lees William R. , Shaw Penny , Isaacson Peter G.
Published: June 2005

The use of a technique for safe percutaneous fine needle biopsy of inaccessible lymph nodes is described. In a prospective study of 24 patterns, including five cases positive for the human immunodeficiency virus (HIV), this technique was used to provide diagnostic material. A firm diagnosis was made in 21 cases; four cases of Hodgkin's disease, 14 non‐Hodgkin's lymphomas, one case of Kaposi's sarcoma, one case of mycobacterial infection, and one which showed the features of persistent generalized lymphadenopathy (PGL). In the cases of lymphoma, available serial sections allowed characterization of the tumour with immunocytochemistry. In three cases, no diagnosis could be made, with one of these requiring a subsequent open biopsy. Percutaneous fine needle biospy is ideal for patients unfit or unsuitable for general anaesthesia or surgery. The biopsy obtained gives the pathologist sufficient tissue for an accurate diagnosis in the majority of cases. The preservation of architecture and multiple sections available are advantages over fine needle aspiration.
Null cell adenomas of the pituitary gland. An immunohistochemical study
Authors: Holm Ruth , Nesland Jahn M. , Attramadal Arne , Halse Johan , Johannessen Jan V.
Published: June 2005

Fourteen null cell adenomas of the pituitary gland were examined immunohistochemically with antisera against three general neuroendocrine markers and 22 hormones. All cases showed positive immunostaining for neuron‐specific enolase, ten cases for synaptophysin, and six cases expressed chromogranin immunoreactivity. Hormone immunoreactivity was detected in a few cells in ten of the 14 cases studied and the number of hormones demonstrated in each case was one or two, Thyroid‐stimuating hormone was detected in five of the 14 cases, gastrin in four, β‐endorphin in two, calcitonin gene related peptide in one, prolactin in one, and follicle‐stimulating hormone in one.
Immunoreactivity for laminin and type IV collagen in malignant and benign fibrous histocytoma
Authors: Soini Ylermi , Autio‐Harmainen Helena , Miettinen Markku
Published: June 2005

Sixteen malignant fibrous histiocytomas (MFH) and ten benign fibrous histiocytomas of the skin were studied immunohistochemically for the distribution of two basement membrane (BM) proteins, laminin and type IV collagen, in order to evaluate their cellular nature. Linear staining for both proteins was present in the vascular BMs. Intracytoplasmic laminin was observed in the neoplastic fibroblast‐like and pleomorphic giant cells in 11 MFHs. Two MFHs also showed similar staining for type IV collagen. In the giant cell subtype of MFH, the reactive giant cells were totally negative whereas the neoplastic cells were strongly positive for laminin. Extracellular fibres staining positively for both BM proteins were seen in two MFHs.

Except for the capillary network, the benign fibrous histiocytomas were negative for laminin and type IV collagen.

On the basis of the present results, we favour the concept that MFHs are primitive mesenchymal tumours, some of which may show histogenetic relationships with tumours of BM forming mesenchymal cells.
Vascular changes in irradiated lungs: A morphometric study
Authors: Wilkinson M. J. , Maclennan K. A.
Published: June 2005

The lungs from eight patients who had received thoracic irradiation for the treatment of malignant disease have been studied and a morphometric analysis of the vascular changes present has been made. We found a marked difference between the changes we observed in the pulmonary vessels and those described in systemic vessels after exposure to irradiation. In the former the changes are more pronounced in the venous circulation, and in the latter they are described as being almost confined to the arteries. This difference is a reflection of the difference in oxygen saturation of the blood in the two types of vessels. We suggest that this difference can be explained by the possible role of super‐oxide free radicals in the generation of these effects.
In situ hybridization demonstration of poly‐adenylated RNA sequences in formalin‐fixed paraffin sections using a biotinylated oligonucleotide poly d(T) probe
Authors: Pringle James H. , Primrose Lindsay , Kind Clive N. , Talbot Ian C. , Lauder Ian
Published: June 2005

An in situ hybridization technique has been developed for assessing poly(A)+ RNA preservation in routine pathology specimens. The method detects poly‐adenylated RNA sequences in tissue sections using a biotinylated polydeoxythymidine poly d(T)) probe. The probe was prepared from single‐stranded 25–30 base oligo d(T) and was biotinylated using the enzyme terminal deoxynucleotide (ransferase with biotin‐11‐dUTP and dTTP in the ratio 1:4. The hybridization protocol uses varying concentrations of proteinase K to unmask mRNA sequences and the biotin labelled hybrids are demonstrated after hybridization under standard conditions by the application of streptavidin and biotinylated alkaline phosphatase. Alkaline phosphatase was visualized using a Fast Red naphthol‐capture method and the sections were counterstained with haematoxylin.

The results have confirmed that the method is specific for poly(A)+ RNA and shows that poly(A)+ RNA can be demonstrated in routine formalin‐fixed sections using non‐radioactive techniques with retention of morphology. It also provides a means of optimizing the hybritdization conditions for specific mRNA probes and produces a staining pattern demonstrating the relative level of poly(A)+ RNA per cell which may reveal new information about cell activity and tissue function.
A non‐parametric grading system for intestinal metaplasia: Correlations with gastric tissue enzymes
Authors: Finch P. J. , Fallowfield M. E.
Published: June 2005

A novel method for grading intestinal metaplasia, with general applicability, is described. Highly significant agreement was found by kappa analysis both for intra‐observer (k=0.90) and for inter‐observer (k=0.85) variation, confirming the reproducibility of the method. The ranks derived by this method were correlated with gastric tissue levels of the enzymes beta‐glucuronidase, lactic dehydrogenase (LDH), and %m‐LDH. A significant (P<0.05) positive correlation was found between intestinal metaplasia and %m‐LDH, but there was no correlation between intestinal metaplasia and beta‐glucuronidase or LDH.
Cytoskeletal features of immature pulmonary vascular smooth muscle cells: The influence of pulmonary hypertension on normal development
Authors: Allen Kim M. , Haworth Sheila G.
Published: June 2005

Using an immunohistochemical technique, the development of the cytoskeletal proteins desmin, vimentin, and actin (using alpha isotype and non‐isotype specific antibodies) was assessed using a semi‐quantitative grading system in the pulmonary vascular smooth muscle of nine normal pigs and 19 normal humans at different ages, and in 13 children with pulmonary hypertensive congenital heart disease. In the normal of both species, immunostaining for vimentin decreased after birth and then increased gradually while immunostaining for desmin and alpha actin increased steadily with age. In pulmonary hypertension, immunostaining for alpha actin and vimentin showed an accelerated increase at between 2 and 8 months. Also, the media showed regional differences in immunostaining which preceded the development of intimal proliferation. The inner media showed less immunoreactivity for all cytoskeletal proteins studied than did the outer media. Within areas of intimal proliferation many cells were immunonegative. These results suggest that the cytoskeletal features of medial smooth muscle cells are remodelled in the normal infant; that this process is altered from at least 2 months in the pulmonary hypertensive infant; and that the smooth muscle cells immediately beneath the internal elastic lamina are remodelled before migrating to form intimal proliferation. Changes in cytoskeletal composition can be related to the previously described postnatal maturation of pulmonary vascular smooth muscle cells.
Lectin binding and desmin expression during necrosis, regeneration, and neurogenic atrophy of human skeletal muscle
Authors: Helliwell Timothy R. , Gunhan Omer , Edwards Richard H. T.
Published: June 2005

Changes in the cytoplasm of skeletal muscle fibres during necrosis, regeneration, and neurogenic atrophy have been studied in a wide range of human neuromuscular diseases with a panel of eleven biotinylated lectins and by immunohistochemical staining for the cytoskeletal protein desmin. Increased binding of several lectins was observed in both necrotic and regenerating fibres, with Concanavalin A the most consistently positive lectin. Staining for desmin was strong in the cytoplasm of regenerating and partially damaged fibres and was lost in necrotic fibres, although there were differences in the staining reactions of the two antidesmin antibodies used. In fibres which had undergone neurogenic atrophy, cytoplasmic lectin binding was seen only with Griffonia simplicifolia I lectin, and desmin was expressed more strongly than in normal fibres. Lectin binding and immunohistochemical staining from desmin can supplement the information obtained from muscle biopsies by conventional histochemical methods and lead to a better understanding of the mechanisms of muscle damage.
Effect of pituitary gonadotrophins on proliferation of primary cultures of human ovarian stroma
Authors: Snowden J. A. , Bradbury K. , Thornton J. G. , Wells M.
Published: June 2005

Proliferation of ovarian stromal cells is a common phenomenon in peri‐and post‐menopausal ovaries. It is generally assumed to be secondary to the rise in circulating gonadotrophins at the menopause, though the process by which it occurs is poorly understood. This study aimed to examine the effect of menopausal levels of pituitary gonadotrophins on the growth of primary cultures of ovarian stroma. A culture system was developed using primary explants of ovarian stroma on a collagen substrate. The effect of follicle stimulating hormone (FSH; 10−5 g/l) and luteinizing hormone (LH; 10−5 g/l) on the proliferation of cultures derived from the cortices and medullae of ten ovaries was evaluated using a dual radiothymidine labelling technique. FSH was stimulatory to cortical cultures from 9/10 ovaries and medullary cultures from 7/10 ovaries, while LH was stimulatory to cortical cultures from 6/9 ovaries and medullary cultures from 5/10 ovaries. The responsiveness of the cultures did not correlate with the degree of hyperplasia in vivo. This study demonstrates that pituitary gonadotrophins may modulate the growth of stromal cells in culture, and thus may play a role in the process whereby stromal proliferation occurs in peri‐and post‐menopausal ovaries.
c‐erbB‐2 oncogene product staining in gastric adenocarcinoma. An immunohistochemical study
Authors: Falck Vincent G. , Gullick William J.
Published: June 2005

The c‐erbB‐2 oncogene has been shown to be amplified in a variety of human adenocarcinomas. Antibodies to the protein product, p185, have been used for immunostaining of paraffin‐embedded material, and have demonstrated that high levels of c‐erbB‐2 protein expression correlate with gene amplification under certain conditions. In studies by others, amplification has been demonstrated in 40 per cent of tubular type adenocarcinomas of the stomach, and an immunohistochemical study on frozen tissue has demonstrated staining in 3 out of 10 cases. Our study, using paraffin‐embedded material, demonstrates staining in 19 per cent of 126 cases using a polyclonal antibody. Of the positive cases, 75 per cent were tubular or papillary type (P<·025), and prominent staining was restricted to this group. Three cases showed well‐defined positive areas in keeping with clonal expression of p185. No specific staining of normal or dysplastic epithelium adjacent to the carcinomas was found.
An observation of DNA ploidy, histological grade, and immunoreactivity for tumour‐related antigens in primary and metastatic breast carcinoma
Authors: Hitchcock Andrew , Ellis Ian O. , Robertson John F. R. , Gilmour Alan , Bell Jane , Elston Christopher W. , Blamey Roger W.
Published: June 2005

A cohort of 36 cases of advanced breast carcinoma were included in the study. DNA ploidy, histological grade, and immunoreactivity for carcino‐embryonic antigen (CEA), carcino‐embryonic antigen with normal cross‐reacting antigen (CEA/NCA), and to NCRC‐11 were assessed in primary breast carcinomas and metastases from the ovary and axillary lymph nodes. Changes in these variables between primary tumours and their metastases were found in 44 per cent of cases for DNA ploidy, 44 per cent of cases for histological grade, 17 per cent of cases for immunoreactivity to NCRC‐11, 28 per cent of cases for CEA, and 56 per cent of cases for CEA/NCA immunoreactivity, respectively. Alteration of one factor appeared to be independent of changes in other factors.

The development of clones with metastatic potential does not appear to be related to consistent changes in any one of the factors examined and suggests that none of these factors would be of prognostic value in advanced breast carcinoma.
Endocytosis of horseradish peroxidase‐poly‐lysine conjugate by glomerular epithelial cells: An in vivo study
Authors: Wang Yiming , Bass Paul S. , Higgins Malcolm , Thomas J. Hywel , Davies David R.
Published: June 2005

Native horseradish peroxidase (HRP) is known to pass rapidly through glomeruli when injected into rats. We have found that a conjugate of HRP with poly‐lysine is readily endocytosed by glomerular epithelial cells (GEC). We have used this conjugate to study the GEC endocytotic process in male Wistar rats. The conjugate has an approximate molecular weight of 55–58000, a pI of > 10·0, and almost the same secondary conformation as HRP; it does not increase urinary protein excretion significantly or alter the morphology of the renal glomeruli. After intravenous injection of the conjugate, it could be found in the GBM from 1 min to 4 h. At 1 min, it was evenly distributed on GEC foot processes and plasma membrane. GEC start to take up the conjugate from 1 min post‐injection, by cellular membrane invagination. This reached a maximum at 4 h. Some of the endocytosed conjugate passed to lysosomes from the endosomal system. The amount of peroxidase demonstrable in the glomerular epithelial cells was considerably reduced by 24 h.
Endotoxaemia and hepatic injury in obstructive jaundice
Authors: Shibayama Yuro
Published: June 2005

To examine whether endotoxaemia contributes to the development of bile infarction and whether obstructive jaundice enhances endotoxin hepatotoxicity, the present study was undertaken in rats. The development of bile infarction and the elevation of serum transaminase activities in rats following ligation of the common bile duct were not prevented by administration of polymyxin B, neomycin, or lactulose, which have anti‐endotoxin properties. Moreover, the morphological and functional changes in obstructive jaundice were not enhanced by administration of endotoxin. These data indicate that endotoxaemia does not contribute to the development of bile infarction. On the other hand, the administration of a small dose of endotoxin to rats with biliary obstruction‐a dose which does not induce abnormalities of liver function tests or any morphological changes in the liver in non‐jaundiced rats‐led to focal hepatocellular coagulative necrosis and elevation of serum transaminase levels. These data indicate that endotoxin‐induced hepatic injury is potentiated in obstructive jaundice.
Malignant lymphomas of true histiocytic origin. A clinical, histological, immunophenotypic and genotypic study
Authors: Ralfkiaer Elisabeth , Delsol Georges , O'Connor Nigel T. J. , Brandtzaeg Per , Brousset Pierre , Vejlsgaard Gunhild L. , Mason David Y.
Published: June 2005

The clinical, histological, immunophenotypic and genotypic properties of four cases of lymphoma of true histiocytic origin are described. The cases were identified by typing 925 non‐Hodgkin's lymphomas by immunophenotypic and/or genotypic techniques, and they all presented with skin lesions. The histological and immunophenotypic examination showed dense, diffuse infiltrates of markedly pleomorphic mononuclear cells that were positive for macrophage‐associated markers, and negative for B‐cell, T‐cell and myeloid cell‐associated antigens. Staining for Ki‐l and epithelial membrane antigen was also negative. Gene rearrangements studies were performed in three cases, and all of these showed germline configuration of both T‐cell receptor and immunoglobulin genes. In all cases, the clinical course was aggressive with rapid and widespread dissemination to internal organs, poor response to conventional chemotherapy, and short survival times (0.5 to 14 months). This suggests that although true histiocytic tumours are very rare, their recognition may be important for clinical and/or prognostic reasons.
Calgranulin expression and association with the keratinocyte cytoskeleton
Authors: Clark B. R. , Kelly S. E. , Fleming S.
Published: June 2005

The molecules calgranulin A and B are two intracellular calcium‐binding proteins which are expressed by the lesional keratinocytes of inflammatory dermatoses. We have investigated the induction of the calgranulin proteins in an in vitro system and characterized the epidermal form of calgranulin. Using calgranulin‐specific monoclonal antibodies, we have shown that these proteins are expressed within the epidermis of skin explants after 12–24 h culture in vitro. The induction of Calgranulin‐specific staining on culture was prevented, however, by the inclusion of cycloheximide in the culture medium, in sufficient quantities to prevent de novo protein synthesis. Indirect immunofluorescence staining was used to analyse the subcellular localization of the calgranulin proteins. The specific staining pattern with antibodies which recognize the individual calgranulin proteins was retained in detergent insoluble cytoskeletal preparations of epidermis. In Western blotting experiments epidermal calgranulins could be solubilized only by using a urea‐based protein extraction buffer. After sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis of the epidermal extracts a single antigen, with a molecular weight of 13.0 kD was detected with the calgranulin‐specific antibody MAC 387. The expression of calgranulins, similar to other members of the same protein family, may regulate cytoskeletal changes in skin disease.
Epithelial–mesenchymal interactions can influence the phenotype of carcinoma metastases in the mucosa of the intestine
Authors: Shepherd N. A. , Hall P. A.
Published: June 2005

In this paper we report two cases in which morphological differentiation of gastric adenocarcinoma has occurred when metastatic tumour was present within the lamina propria of the intestinal mucosa. In one case, there were metastases in the small intestinal mucosa and in the second case, in the mucosa of the appendix. The morphology of the intramucosal tumour simulated that of an adenomatous neoplasm. The recognition of this occurrence may be important in the differential diagnosis of primary and secondary adenocarcinomas of the gastrointestinal tract. The phenomenon is not only of diagnostic interest: the data presented here provide in vivo evidence that gastrointestinal carcinomas may differentiate in response to epithelial–mesenchymal interactions in a similar way to that seen in experimental models.
The malignancy grading method is not a reliable assessment of malignancy in mesothelioma
Authors: Tierney G. , Wilkinson M. J. , Jones J. S. P.
Published: June 2005

The ploidy of a series of pleural lesions–reactive proliferations, malignant mesotheliomas and metastatic tumours– was measured on a Leitz Miamed DNA image analyser using Feulgen‐stained slides. The technique successfully recognized all the metastatic tumours as malignant; this corresponds to previous work. However, it was not successful in classifying mesothelial lesions as benign or malignant, resulting in a very high false‐negative rate and a moderately high false‐positive rate. Mesothelial lesions appear to have a wide range of ploidy values irrespective of their biological behaviour. Thus, for primary mesothelial tumours, the ploidy value cannot be used as a reliable diagnostic index.
Do AgNOR counts reflect cellular ploidy or cellular proliferation? A study of trophoblastic tissue
Authors: Suresh Uma R. , Chawner Linda , Buckley C. Hilary , Fox Harold
Published: June 2005

There is considerable debate as to whether AgNOR counts reflect cellular ploidy or cellular proliferation. Trophoblastic tissue from hydropic abortions and from hydatidiform moles offers an excellent model for analysing this problem. Thus, complete moles show considerable cell proliferation but are diploid, whilst partial moles show murkedly less cell proliferation but are triploid: hydropic abortuses are diploid and show no cellular proliferation, AgNOR counts in villous cytotrophoblastic cells from hydropic abortions and from complete hydatidiform moles are similar, but those in partial hydatidiform moles are 50 per cent higher than in either hydropic abortions or complete moles. Thus, in non‐neoplastic trophoblastic tissue AgNOR counts are clearly a reflection of ploidy rather than of cell proliferation.
Immunohistochemical determination of CD23 expression in Hodgkin's disease using paraffin section
Authors: Rowlands D. C. , Hansel T. T. , Crocker J.
Published: June 2005

The leukocyte antigen CD23 is expressed during B‐cell development, and functions as an IgE receptor and a lymphocyte growth factor. We studied the expression of CD23 in paraffin sections of lymphoid tissue using the monoclonal antibody BU38. Fifteen cases of Hodgkin's disease, ten reactive lymph nodes, eight B‐cell, and seven T‐cell non‐Hodgkin's lymphomas were analysed immunohistologically. CD23 positivity was seen on follicular dendritic cells and a small number of lymphocytes in reactive nodes. Thirteen of the 15 cases of Hodgkin's disease showed CD23 expression in both neoplastic cells and reactive lymphocytic infiltrate. The antigen was demonstrated in four of the B‐cell of the T‐cell tumours. CD23 may be important in mediating she mixed cellular infiltrate characteristic of Hodgkin's lymphoma.
Immunohistochemical demonstration of altered intracellular localization of the c‐Myc oncogene product in human colorectal neoplasms
Authors: Williams Alistair R. W. , Piris Juan , Wyllie Andrew H.
Published: June 2005

The distribution of the c‐myc oncogene product p62 was examined by immunohistochemistry using the monoclonal antibody Mycl‐9E10 in a series of 50 colorectal resections for carcinoma. The specimens were specially handled to ensure rapid fixation in formalin, and a significant improvement was shown in the quality and localization of staining compared with routinely handled specimens. Non‐neoplastic mucosa showed the presence of nuclear staining of epithelial ceiis in 93 per cent of the samples, whilst all carcinomas showed cytoplasmic staining and infrequent nuclear staining. Adenomas showed an intermediate pattern, with significantly more frequent cytoplasmic distribution than non‐neoplastic mucosa, but less than carcinomas. The results show that whilst fixation conditions are important in the immunolocalization of the C‐myc protein product, there may be a consistent difference between non‐neoplastic mucosa and carcinoma in the manner of association of p62 with the nucleus.
Androgen receptor heterogeneity in human prostatic carcinomas visualized by immunohistochemistry
Authors: De Winter Jacobus A. Ruizeveld , Trapman Jan , Brinkmann Albert O. , Boersma Wim J. A. , Mulder Eppo , Schroeder Fritz H. , Claassen Eric , Van Der Kwast Theodorus H.
Published: June 2005

Expression of the human androgen receptor was examined in 26 primary prostatic carcinomas by immunohistochemical staining with a polyclonal antibody reactive with the N‐terminal domain of the human androgen receptor. Eighteen carcinomas showed homogeneous staining for the androgen receptor, whereas in seven cases a considerable heterogeneity in expression of the receptor was found. In one case, only a very limited number of immunoreactive tumour cells were detected. Comparison of androgen receptor expression with the tumour grading score, according to the MD Anderson grading system, revealed that the proportion of immunostained tumour cells and—to a lesser extent—the intensity of immunostaining were decreased in the more aggressive (grade III) tumours. The use of immunohistochemistry for detection of expression of androgen rereptor in prostatic carcinomas may become a new and sensitive method for predicting prostatic tumour behaviour under hormonal therapy and prognosis.
Natural killer cells in cutaneous malignant melanoma
Authors: Kernohan N. M. , Sewell H. F. , Walker F.
Published: June 2005

Using immunocytochemical techniques on fresh surgical samples, a series of 16 cases of cutaneous malignant melanoma (CMM) were examined to characterize further the host inflammatory response. Antibodies to the following cluster of differentiation (CD) antigens were used: CD‐3, CD‐4, CD‐8 (T‐cell markers), CD‐11b, CD‐14 (macrophage marker), CD‐16 [an antigen expressed by natural killer (NK) cells and granulocytes], and CD‐25. Also examined were a small number of other melanocytic lesions [two cases of lentigo maligna (Hutchinson's melanotic freckle) and five of intradermal naevi]. The results of the study document a population of cells with the morphological and immunophenotypic characteristics of NK cells in association with 10 of the 16 cases of CMM. These cells were consistently absent from the other melanocytic lesions studied. The presence of NK cells in association with some cases of CMM bears no clear relationship to the Breslow thickness, Clark level, tumour ulceration, or the presence of activated T cells as determined by expression of the CD‐25 antigen. Whilst an explanation for the significant numbers of NK cells in some CMM lesions is unclear, their presence in intimate association with tumour cells does prompt speculation regarding a possible role in determining the biological behaviour of the tumour. Additionally, the study has confirmed and extended previous findings with respect to the broad characterization of mononuclear cells present in the host infiltrate associated with CMM.
A quantitative analysis of the mesangium in children with IgA nephropathy: Sequential study
Authors: Suzuki Junko , Yoshikawa Norishige , Nakamura Hajime
Published: June 2005

Quantitative analysis of the mesangial matrix and cells was performed on serial renal biopsies from 41 children with IgA nephropathy. In the repeat renal biopsy, nine patients showed a significant increase of mesangial matrix, 29 showed no change and in three there was a significant decrease. Eight of the nine patients (89 per cent) with a matrix increase had persistent proteinuria at the second biopsy, whereas only 14 of the 32 (44 per cent) without a matrix increase had persistent proteinuria (P<0.05). Although the mesangial matrix increased in patients with persistent proteinuria, there was no decrease in patients with clinical remission. In contrast to the mesangial matrix, mesangial cells significantly decreased in 23 patients, did not change in 16, and significantly increased in only two in the second biopsy. These findings suggest that mesangial matrix increase is usually an irreversible change and that persistent proteinuria is associated with matrix increase with worsening in glomerular morphology and clinical outcome. This study indicates the importance of serial renal biopsy in children with IgA nephropathy with persistent proteinuria.
Ki‐ras oncogene mutations in non‐HPV‐associated anal carcinoma
Authors: Hiorns Lynne R. , Scholefield John H. , Palmer James G. , Shepherd Neil A. , Kerr Ian B.
Published: June 2005

Human papillomavirus 16 (HPV 16) DNA is found in a high proportion of anal squamous cell carcinomas in whose genesis it is thought to play an important role. In addition, it can be shown to cooperate in vitro with activated ras oncogenes in cellular transformation. We have therefore screened a series of such tumours for activating mutations of the ras oncogene family using DNA amplified in vitro by the polymerase chain reaction (PCR) and a series of synthetic oligonucleotide probes. Mutations were seen in only two cases (both Ki‐ras codon 12), neither of which was HPV‐associated. Our results suggest that ras activation is not a common event in the genesis of these tumours and, when it does occur, it does not appear to cooperate with HPV.
The histological changes in transbronchial biopsy after treatment of acute lung rejection in heart‐lung transplants
Authors: Clelland Colin A. , Higenbottam Timothy W. , Stewart Susan , Scott John P. , Wallwork John
Published: June 2005

Transbronchial lung biopsies taken during episodes of acute lung rejection in heart‐lung transplant patients were examined histologically. When the diagnosis was confirmed by microscopy, the patients were treated with augmented immunosuppression by high‐dose corticosteroids. A second biopsy was obtained an average of 23.5 days after commencement of treatment. These biopsies were examined to determine the histological changes caused by treatment.

In most cases, there were both quantitative and morphological differences between the infiltrates in acute rejection and in the remaining perivascular infiltrates after treatment. In acute rejection, 26 of 28 biopsies contained perivascular lymphocytic infiltrates, lymphocytes being large and blast‐like. Although 20 of 28 follow‐up biopsies still contained perivascular infiltrates, they were smaller and the lymphocytes smaller in size. Half the biopsies in rejection contained neutrophils, but less than half contained eosinophils in the perivascular infiltrates. After treatment, all these cells were less numerous. Another feature of treated rejection was the presence of haemosiderin around vessels suggesting earlier acute vascular injury. However, haemosiderin persists long after the cellular infiltrate has disappeared and cannot be considered a reliable feature of recently treated acute lung rejection. The bronchiolar infiltrates showed a similar pattern of responses to the perivascular infiltrates.