bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of p53 protein in infiltrating and in‐situ breast carcinomas
Authors: Walker Rosemary A. , Dearing Sheila J. , Lane David P. , Varley Jennifer M.
Published: June 2005

Five antibodies directed against the whole or part of p53 protein have been used to detect the protein immunohistochemically in 70 infiltrating breast carcinomas and 10 ductal carcinomas in situ. Mutations are known to occur in different conserved domains, and the antibodies employed spanned the expected sites.

P53 protein was identified in 53 per cent of infiltrating carcinomas using the antibodies PAb 240, PAb 1801, C19, and JG8. The antibody PAb 421 detected the protein in 31·5 per cent; all positive with the other antibodies. Well‐differentiated oestrogen receptor‐positive tumours had a low incidence of p53 detection. Variation in the percentage of reactivity was seen between carcinomas and in some cases between different antibodies in the same cancer. Those carcinomas with a high percentage of positive cells with all antibodies were more likely to have metastasized to nodes, be at an advanced stage, and be oestrogen receptor‐negative/epidermal growth factor receptor‐positive. There was no significant correlation with c‐erbB‐2 protein expression or retinoblastoma protein loss. p53 protein was detected in a high proportion of cells in three of the six comedo ductal carcinomas in situ studied but either not at all or at a lower level in tumours of the cribriform type.

P53 mutations are common in breast carcinomas, but heterogeneity within individual tumours in frequent. Marked expression of p53 appears to relate to tumour progression.
Co‐ordinate expression of the alpha‐6 integrin laminin receptor sub‐unit and laminin in breast cancer
Authors: D'Ardenne A. J. , Richman P. I. , Horton M. A. , McAulay A. E. , Jordan S.
Published: June 2005

Interactions between cells and extracellular matrices are mediated in part by a family of heterodimeric molecules known as integrins. We have investigated, using immunohistology, the distribution of six integrin alpha sub‐units in normal breast tissue and 26 breast carcinomas. Alpha‐1 integrin (collagen/laminin receptor sub‐unit) was detected in myoepithelium, but not in luminal epithelium nor in most (20/26) carcinomas. Its expression on fibroblasts was enhanced in demoeplastic stroma. Both benign and malignant epithelium showed uniform positive staining for alpha‐2 (collagen receptor sub‐unit) and for alpha‐3 (collagen/fibronectin/laminin receptor sub‐unit). All epithelium was negative for alpha‐4 (sub‐unit of a fibronectin receptor). Epithelial staining for alpha‐5 (fibronectin receptor sub‐unit) was weak in all samples. Alpha‐6 (sub‐unit of two integrin laminin receptors) showed conspicuous changes in all invasive carcinomas. In normal tissues, there was weak staining of epithelial cytoplasm with alpha‐6 antibody and moderate cell membrane staining. Strongest staining was present in a basement membrane distribution. In carcinomas, loss of cytoplasmic and cell membrane staining was variable, but basal membrane staining was diminished or absent in all tumours. Loss of basal membrane staining for alpha‐6 integrin corresponded closely to loss of immunoreactivity for its ligand laminin in invasive breast cancer.
Occult regional lymph node metastases from breast carcinoma: Immunohistological detection with antibodies CAM 5.2 and NCRC‐11
Authors: Galea M. H. , Athanassiou E. , Bell Jane , Dilks Beverly , Robertson J. F. R. , Elston C. W. , Blamey R. W. , Ellis I. O.
Published: June 2005

Ninety‐eight consecutive patients with primary operable breast cancer and an initial diagnosis of no regional lymph node metastases as assessed by conventional light microscopy were studied. Immunohistological staining of routine lymph node sections was assessed using two monoclonal antibodies: CAM 5.2 (Becton Dickinson) with specificity for low molecular weight cytokeratian, and NCRC‐11 (CRC Laboratories, Nottingham) with specificity for epithelial mucin antigen. Positive staining for occult metastases was seen in nine patients with CAM 5.2 and in eight of these nine with NCRC‐11. At a follow‐up out to 14 years, there was no difference in overall survival, in recurrence‐free survival, or in frequency of or time to presentation of local or regional recurrences between occult metastasis‐positive and occult metastasis‐negative patients.

This study concludes that while immunohistological staining of routine lymph node sections increases the diagnostic yield of metastases, it is not to be recommended as this increase is of no useful clinical value.
The significance of cerebrovascular amyloid in the aetiology of superficial (lobar) cerebral haemorrhage and its incidence in the elderly population
Authors: Ishihara Tokuhiro , Takahashi Mutsuo , Yokota Tadaaki , Yamashita Yoshimi , Gondo Toshikazu , Uchino Fumiya , Iwamoto Naoki
Published: June 2005

Cerebrovascular amyloid deposition (CVAD), caused by deposition of the β/A4 protein, has been previously identified as a cause of cerebral haemorrhage, yet its prevalence is uncertain. The presence of vascular amyloid was studied in brains of 169 patients by immunohistochemical and Congo red staining. Fifty patients had cerebral haemorrhage (CH), 56 had cerebral infarction (CI), and 63 had neither haemorrhage nor infarction (control group). CVAD was found in 38 per cent of the CH group, 25 per cent of the CI group, and 32 per cent of the control group. The incidence of CVAD increased with age in each group. Immunohistocemical staining with an antibody to β/A4 protein was more sensitive than Congo red staining in demonstrating the extent of vascular amyloid.

Within the CH group, CVAD was present in the vessels at the site of haemorrhage in 6/8 (75 per cent) of pure superficial (lobar) cerebral haemorrhages. While amyloid was detected in vessels in the brain of 10/37 (27 per cent) of pure deep cerebral haemorrhages, none was present in vessels at the site of haemorrhage.

CVAD is a common pathological finding in the elderly and has a significant association with pure superficial (lobar) cerebral haemorrhages.
Atrial amyloid deposits in the failing human heart display both atrial and brain natriuretic peptide‐like immunoreactivity
Authors: Pucci Angela , Wharton John , Arbustini Eloisa , Grasso Maurizia , Diegoli Marta , Needleman Philip , Viganò Mario , Polak Julia M.
Published: June 2005

Atrial amyloid deposits are common in the ageing human heart and contain α‐atrial natriuretic peptide (proANP99–126) immunoreactivity. However, atrial myocytes secrete both amino and carboxy terminal fragments of the ANP prohormone (proANP1–126) and also express an homologous, but separate brain natriuretic peptide (BNP). Characteristic amyloid deposits were identified in the atria of 9/22 patients (26–63 years of age) with end‐stage heart failure. Amyloid fibrils displayed immunoreactivity for both amino and carboxy terminal fragments of proANP1–126 and for the distinct BNP sequence. As in other endocrine organs, both mature and precursor peptide sequences appear to be constituents of amyloid fibrils. Whilst immunoreactivity for cardiac peptide hormones is co‐localized in atrial amyloid deposits, it is uncertain whether the increase in natriuretic peptide expression which accompanies cardiac failure contributes to the incidence of isolated atrial amyloidosis.
Interphase cytogenetics in paraffin sections of routinely processed hydatidiform moles and hydropic abortions
Authors: Van De Kaa Christina A. , Nelson Karin A. M. , Ramaekers Frans C. S. , Vooijs Peter G. , Hopman Anton H. N.
Published: June 2005

The differential diagnosis of complete (CM) and partial (PM) hydatidiform moles and hydropic abortions (HA) can be difficult when based on histology alone. Therefore, a more objective approach of chromosome ploidy analysis as detected by in situ hybridization (ISH) was performed on 6 μm paraffin sections of seven cases, originally classified as three CM, two PM, and two HA with a histologic pattern suggestive of triploidy. Probes for repetitive DNA targets in the (peri)centromeric region of chromosomes 1 and X and in the q arm of chromosome Y were used to determine chromosome ploidy and sex chromosome composition. The findings in the three CM were consistent with diploidy: two copies of chromosomes 1 and X and none of chromosome Y. In the two HA with a histologic pattern suggestive of triploidy, three copies of chromosomes 1 and X and none of chromosome Y confirmed triploidy. Two cases originally classified as PM both appeared to have two copies of chromosome 1 with an XX pattern in one case and an XY pattern in the other case, which is consistent with diploidy instead of triploidy. After reviewing, both cases most likely represented CM. We conclude that interphase cytogenetics by ISH on paraffin sections of hydatidiform moles and hydropic abortions enables chromosome ploidy analysis with preservation of histological context. The important advantages of this procedure are (1) precise discrimination between maternal and trophoblast cells, (2) no risk of selecting certain cell types as a result of the isolation procedure, (3) detection and localization of cell subpopulations with heterogeneous DNA content, (4) determination of the contribution of a single chromosome (e.g., sex chromosome), and (5) access to archival material.
Expression of Epstein–Barr virus replicative proteins in aids‐related non‐Hodgkin's lymphoma cells
Authors: Pallesen Gorm , Hamilton‐Dutoit Stephen J. , Rowe Martin , Lisse Ida , Ralfkiaer Elisabeth , Sandvej Kristian , Young Lawrence S.
Published: June 2005

Epstein‐Barr virus (EBV) infection in lymphoproliferative lesions has been assumed to be strictly latent. In order to investigate the possible occurrence of EBV replication in AIDS‐related lymphoma (ARL) cells, we studied 13 cases by immunohistology using monoclonal antibodies to the EBV‐encoded switch‐protein BZLF1, early antigens (EAs), late replicative proteins [virus capsid antigens (VCAs) and membrane antigens (MAs)], and to the latent proteins EB nuclear antigen 2 (EBNA 2) and latent membrane protein (LMP). EBV genomes were detected by in situ hybridization. EBV genomes and/or gene products were demonstrated in ten cases, including all immunoblast‐rich lymphomas, two Burkitts lymphomas, and a T‐cell anaplastic large‐cell lymphoma. The BZLF1 protein, which disrupts latency in B cells, was identified in six (60 per cent), and EAs in four (40 per cent) of the EBV‐positive ARL. Only one lymphoma (10 per cent) expressed VCAs and MAs. EBNA 2 and LMP were detected in three (30 per cent) and eight (80 per cent) of EBV‐positive cases, respectively. EBV DNA was detected in lymphoma cells in 7 of 12 (58 per cent) cases. The most important finding of this study was frequent spontaneous activation of latent EBV in ARL. Production of complete virus, however, was either aborted, or tumour cells expressing late productive cycle proteins (VCA, MA) were rapidly cleared from tissues. It is suggested that host factors that normally inhibit replication of EBV are deficient in AIDS patients.
HPV in full thickness cervical biopsies: High prevalence in CIN 2 and CIN 3 detected by a sensitive PCR method
Authors: Arends Mark J. , Donaldson Yvonne K. , Duvall Edward , Wyllie Andrew H. , Bird Colin C.
Published: June 2005

A new type‐specific, sensitive, non‐radioactive assay is described for the detection of human papillomavirus (HPV) DNA in tissues. Sequences within the E6 gene were amplified by the polymerase chain reaction (PCR), using primer pairs which clearly distinguish HPV types, including those with close sequency homology such as 6b and 11. The amplified DNA products were identified by non‐radioactive oligonucleotide hybridization and restriction endo‐nuclease mapping, and the method was sufficiently sensitive to detect between 3 and 5 SiHa cells (each containing 1–2) copies of (HPV 16 DNA) amongst 10 000 non‐HPV‐ containing cells. Frozen and archival paraffin sections were equally acceptable substrates for the reaction.

The assay was applied to frozen sections full thickness cervical epithelium from 60 cases of cervical intraepithelial neoplasia (CIN) and 24 normal cervical controls. Prevalence of HPV 16 was similar (approximately 50 per cent) in both CIN 2 and CIN 3, and in the whole series HPV 16 was almost five‐fold more common than HPV 18. Low‐risk HPV types were present in 5 per cent of CIN 1, but 0 per cent of CIN2 and CIN3 biopsies. The data emphasize the biological similarity of CIN 2 and CIN 3 lesions, and their divergence from CIN 1.
Fibrinolysis and angiogenesis in wound healing
Authors: Thompson W. Douglas , Harvey John A. , Kazmi Majid A. , Stout Alistair J.
Published: June 2005

The healing wound offers a clear example of the sequence of events in chronic inflammation leading to repair. Although angiogenesis has an obvious and essential role in this process, it has been little studied. For an angiogenic factor to seem relevant, it would have to be shown to precede the peak of increased vascularity. To define this peak, the vessel content of simple, incised mouse wounds was estimated using morphometry of histological sections, and found to rise to a maximum at days 5 and 6. Total angiogenic activity of aqueous extracts was found to reach a peak at day 3. The detection of such activity on the chick chorioallantoic membrane is very dependent on the preparation technique and the choice of proteinase inhibitors. Previous in vitro work by us using purified material has shown fibrin degradation products to be effective in stimulating angiogenesis. Fibrin degradation products are prominent on immunoblotting from day 3, when macrophages are plentiful, with a similar band pattern to human granulation tissue.
Immunohistochemical positivity for neuron‐specific enolase and Leu‐7 in malignant mesotheliomas
Authors: Mayall Frederick G. , Jasant Bharat , Gibbs Allen R.
Published: June 2005

The discovery of immunostaining for neuron‐specific enolase (NSE) and Leu‐7 in a small cell mesothelioma prompted us to study some putative immunohistochemical markers of neuroendocrine differentiation in malignant mesotheliomas and to examine any diagnostically important immunohistochemical distinctions or similarities between malignant mesothelioma and other histologically similar lung tumours. Most mesotheliomas were positive for NSE (96 per cent) and Leu‐7 (70 per cent) and positivity for these two markers was also found in small cell carcinomas (NSE 25 per cent, Leu‐7 81 per cent) and adenocarcinomas (NSE 28 per cent, Leu‐7 28 per cent) but carcinosarcomas were positive for only NSE (44 per cent). Chromogranin A positivity was found only in occasional small cell carcinomas (6 per cent) and adenocarcinomas (6 per cent). No tumour was positive for bombesin. The high incidence of NSE and Leu‐7 positivity in mesotheliomas is an important original observation because it guards against the unjustified exclusion of mesothelioma from a differential diagnosis on the basis of positivity for these two markers.
Morphometric analysis of the glomerular capillary area—a comparison of minimal change nephrotic syndrome, focal glomerular sclerosis, and pre‐eclampsia
Authors: Ishitobi Fumio , Sagiya Atushi , Ueda Yoshihiko , Oka Kazuo , Kanaya Hiroaki , Iidaka Kazunari
Published: June 2005

A morphometric analysis was performed to compare the capillary area in non‐sclerotic glomeruli in focal glomerular sclerosis (FGS), pre‐eclampsia with focal sclerotic change of the glomeruli, and minimal change nephrotic syndrome (MCNS). The mean and standard deviation of the capillary area was greater in FGS than in pre‐eclampsia and MCNS. Tubulo‐interstitial lesions, such as tubular atrophy, interstitial fibrosis, and lymphocytic infiltration, were more severe in FGS than in pre‐eclampsia. The presence of tubulo‐interstitial changes including tubular atrophy and interstitial fibrosis with lymphocytic infiltration is thought to be an important prognostic factor in pre‐eclampsia as well as in FGS. Unequal dilatation of the glomerular capillaries in non‐sclerotic glomeruli may be harmful to the glomeruli and may lead to the development of glomerular sclerosis.
Standardization of interphase Ag‐NOR measurement by means of an automated image analysis system using lymphocytes as an internal control
Authors: Derenzini Massimo , Trerè Davide
Published: June 2005

Using an automated image analysis system, we have developed a procedure for standardizing the measurement of silver‐stained proteins of the nucleolar organizer regions (NORs) in cancer cells, irrespective of the fixative employed and the time of the staining reaction. We observed that the area of Ag‐NOR proteins from the same tumour was smaller in samples fixed with formalin‐containing solutions, buffered formalin, and Bouin liquid, compared with those fixed with absolute ethanol and ‘methcarn’ solution (1·77 ± 0·26 μm2 and 2·36 ± 0·35 μm2 versus 3·34 ± 0·54 μm2 and 3·72 ± 0·61 μm2).

Increased values of the Ag‐NOR area were also observed after lengthening the silver staining reaction. However, in both cases no difference was observed in the ratio between Ag‐NOR area of cancer cells and that of the lymphocytes infiltrating the stroma. The value of the ratio, which is called the ‘Ag‐NOR index’, was in fact very similar, for the same cancer, after employing different fixatives or staining times.

The use of lymphocyte Ag‐NOR area as an internal control for the standardization of Ag‐NOR evaluation in cancer tissues was made possible by the fact that lymphocyte Ag‐NOR area is almost constant in human tumours independent of sex and age.
Caffeine potentiation of mefenamic acid‐induced lesions in the rat renal medulla
Authors: Hewitson Tim D. , Champion De Crespigny Paul J. , Kincaid‐Smith Priscilla
Published: June 2005

The effect of caffeine given in combination with mefenamic acid on the renal medulla was examined. Sprague‐Dawley rats were divided into four groups and gavage fed either suspension (control), mefenamic acid. mefenamic acid + caffeine or caffeine onlu for 4 months. Renal tissue taken from the corticomedullary junction was processed for electron microscopy. Ultrathin sections were cut after identification of vast rectae on survey sections. On subsequent morphometric analysis. percentage interstitial tissue was calculated from the total area of vasa recta less the noninterstitial tissue. The median prcentage of interstitial tissue in the mefenamic acid and caffeine group was 41 (range 33–50; n = 15) compared with 34 (20–48); n = 20 in mefenamic acid (P < 0.01), 29 (15–42; n = 15) in caffeine only (P < 0.001) and 32 (20–46; n = 18) in vehicle‐treated animals (P < 0.001). There were no significant differences between mefenamic acid alone and vehicle or caffeine‐only gruops or between caffeins‐only and vehicle‐treated controls.

This suggests that caffeine potentiates the effect of the non‐steroidal anti‐inflammatory drug. mefenamic acid, on the rat renal medulla, resulting in a quantitative increase in the intersitial tissue between adjacent afferent and efferent vasa recta.
Immunohistochemical demonstration of the Epstein–Barr virus‐encoded latent membrane protein in paraffin sections of Hodgkin's disease
Authors: Murray Paul G. , Young Lawrence S. , Rowe Martin , Crocker John
Published: June 2005

Paraffin sections from 46 cases of Hodgkin's disease were examined for the presence of the Epstein‐Barr virus (EBV)‐encoded latent membrane protein (LMP) using a sensitive (double layer alkaline phosphatase–anti‐alkaline phosphatase) immunohistochemical method. LMP was detected in 22 cases, the majority of positive cases being of nodular sclerosis (12/24), mixed cellularity (6/7), and lymphocyte depletion (3/3) subtypes. Only one of 12 cases of lymphocyte predominant disease was positive. In all cases, reactivity was confined to Hodgkin's and Reed‐Sternberg cells. These results provide further evidence for an association between EBV and Hodgkin's disease and indicate that LMP may be readily detected in archival material.
Immunohistochemical demonstration of glutathione S‐transferases in primary human breast carcinomas
Authors: Cairns J. , Wright C. , Cattan A. R. , Hall A. G. , Cantwell B. J. , Harris A. L. , Horne C. H. W.
Published: June 2005

The expression of cytosolic glutathione S‐transferase (GST) isoenzymes has been assessed in a series of 74 primary human breast carcinomas using an immunohistochemical method. GST pi was detected in sections from all 74 tumours; it was expressed by non‐epithelial (stromal and inflammatory) cells in 62 tumours (84 per cent), but by tumour epithelium in only 35 (47 per cent). Non‐neoplastic mammary epithelium was uniformly positive for GST pi. Expression of GST alpha and mu was observed in 19 and 42 per cent of the tumours, respectively, and was largely confined to the neoplastic component. Lack of staining of tumour epithelium for GST pi was significantly associated with poorer tumour differentiation (higher grade). There was no association between expression of any of the three isoenzymes and either menopausal status or expression of c‐erbB‐2 oncogene protein product.

Immunohistochemistry is a useful method for the investigation of expression and cellular localization of GSTs within tumours; such data are needed to improve our understanding of the role of these enzymes in neoplasia and in resistance to cytotoxic drug therapy.
Prognostic factors in bladder carcinoma: Histologic parameters and expression of a cell cycle‐related nuclear antigen (Ki‐67)
Authors: Mulder A. H. , Van Hootegem J. C. S. P. , Sylvester R. , Kate F. J. W. Ten , Kurth K. H. , Ooms E. C. M. , Van Der Kwast TH. H.
Published: June 2005

A total of 316 biopsies from patients with bladder carcinoma who entered a trial of the genito‐urinary group of the European Organization for Research and Treatment of Cancer (EORTC) were reviewed. The histological data were subsequently correlated with the clinical course. A strong correlation between the number of mitoses and the time of first recurrence, muscle invasion, and death was noted. Next the expression of Ki‐67 in frozen sections from 49 transitional cell carcinomas (TCCs) and the DNA content of the tumour cells were determined. The frequency of Ki‐67‐positive tumour cells increased with tumour grade and stage. Grade II TCCs and superficially infiltrating TCCs showed a wide range of Ki‐67 scores. There was a significant difference in Ki‐67 score between non‐infiltrating (Ta) and superficially infiltrating (T1) grade II TCCs. All DNA‐aneuploid carcinomas but also 15 out of 36 DNA‐diploid tumours contained more than 10 per cent Ki‐67‐positive cells. Only some of these tumours were DNA‐aneuploid or ‐tetraploid. The results indicate that the number of Ki‐67‐positive cells in grade II tumours may be a useful aid in separating grade II TCCs with a favourable prognosis from those with a poor clinical outcome.
Detection of calbindin‐D immunoreactivity in human follicular dendritic cells
Authors: Chilosi Marco , Doglioni Claudio , Pelosio Paola , Mombello Aldo , Montagna Licia , Benedetti Alice , Lestani Maurizio , Giovanni Pizzolo , Menestrina Fabio
Published: June 2005

The calcium‐binding protein calbindin‐D (28 kD) has been analysed immunohistochemically in different human lymphoid tissues. Combined immunohistochemical staining showed that calbindin‐D (28 kD) is expressed by only a proportion of dendritic cells within the light zone of germinal centres, where antigens in the form of immune complexes are trapped and presented to B lymphocytes. All other cell types including macrophages, interdigitating cells, and various lymphocyte populations were negative. The expression of calbindin‐D in this functionally relevant subset of follicular dendritic cells could have a role in the regulation of proliferation and selection of memory B‐cells by modulating the concentration of calcium ions. Calbindin‐D may be a useful marker for analysing in situ the phases of follicular development in different physiological and pathological conditions.
Cytogenetic and molecular studies of t(14;18) and t(14;19) in nodal and extranodal B‐cell lymphoma
Authors: Clark Helen M. , Jones David B. , Wright Dennis H.
Published: June 2005

We have examined 107 cases of B‐cell lymphoma for the t(14;18) translocation, characteristically described in follicular lymphoma. B‐Cell lymphomas of extranodal origin, and in particular malignancies derived from mucosa associated lymphoid tissue (MALT), were compared with node‐based lymphomas of follicular and diffuse morphology. Cytogenetic techniques were supplemented by molecular analysis using probes which recognize both the major and the minor breakpoint regions of the bcl‐2 gene located on chromosome 18 (q21).

t(14;18) was detected in 55 per cent of follicular and 27 per cent of diffuse B‐cell lymphomas thought to be of follicle centre cell origin. Cytogenetics and molecular analysis proved equally effective in demonstrating the translocation.

t(14;18) was not observed in the 36 extranodal lymphomas examined, of which 20 were characterized histologically as lymphomas of MALT, using either technique. In addition, 30 cases demonstrated only a germline band when probed with a bcl‐3 probe specific for t(14;19), a translocation observed in chronic lymphocytic leukaemia (CLL). Cytogenetic abnormalities were detected in all cases of extranodal lymphoma, although no consistent abnormality was observed. Numerical abnormalities of chromosomes 3, 6, 16, and 18; structural abnormalities of chromosomes 2, 6, 8, and 9; and small marker chromosomes were frequently seen.

This study provides data which suggest that different genetic events are involved in the development of lymphoma of MALT from those giving rise to follicle centre cell lymphomas.
A comparison of proliferating cell nuclear antigen (PCNA) immunostaining, nucleolar organizer region (AGNOR) staining, and histological grading in gastrointestinal stromal tumours
Authors: Yu Carmen C.‐W. , Fletcher Christopher D. M. , Newman Paul L. , Goodlad John R. , Burton Julia C. , Levison David A.
Published: June 2005

Gastrointestinal stromal tumours are lesions in which it is difficult to predict clinical outcome from the histological appearances. Sixty cases were studied using three different methods of assessing aspects of cellular proliferation; these were (i) immunostaining for proliferating cell nuclear antigen (PCNA), (ii) interphase nucleolar organizer region staining (AgNORs). and (iii) a histological grading system based on mitotic counts. Both PCNA immunostaining and AgNOR counts were found to correlate well with histological grading and all three methods independently showed good correlations with survival. This suggests that these proliferation‐associated markers may be used as additional features to support histological grading in this relatively uncommon group of tumours.
Calcium dependence of A‐CAM function in human renal epithelium
Authors: Biddlestone L. R. , Fleming S.
Published: June 2005

Previously we have used immunocytochemistry to identify A‐CAM as a major cell adhesion molecule in human renal tubular epithelium. In this study, we demonstrate the calcium dependence of cell‐cell adhesion and A‐CAM function in cultured human renal epithelial cells. Separation of adjacent cells was seen within 1 min following sequestration of calcium from the culture medium with EDTA. This loss of intercellular adhesion in low calcium conditions was accompanied by the disappearance of A‐CAM immunoreactivity. The changes were reversible and on return to normal calcium concentrations, A‐CAM immunoreactivity reappeared and cell adhesion was re‐established. The time course of this recovery was slow, taking 2–3 h. These results demonstrate the calcium dependence of cell adhesion in cultured human renal epithelial cells and confirm the adhesive function of the immunoreactive A‐CAM molecule.
A search for Pneumocystis carinii in post‐mortem lungs by DNA amplification
Authors: Peters Sarah E. , Wakefield Ann F. , Sinclair Kathryn , Millard Peter R. , Hopkin Julian M.
Published: June 2005

DNA amplification of specific sequences and subsequent oligonucleotide hybridization were used to search for Pneumocystis carinii in post‐mortem lung samplings from non‐immunosuppressed individuals ranging from 15 to 70 years of age. No P. carinii‐specific DNA was detected in 45 DNA amplification reactions from 15 lungs.
Cyclosporin reduces proteinuria in rats with aminonucleoside nephrosis
Authors: Kokui Koh , Yoshikawa Norishige , Nakamura Hajime , Itoh Hiroshi
Published: June 2005

The effect of cyclosporin (CS) was assessed in Sprague–Dawley rats with puromycin aminonucleoside (PA) nephrosis induced by a single intraperitoneal injection of PA. Three groups of rats were injected intraperitoneally with CS (10 mg/kg body weight) daily, beginning 1 day before PA administration, or 5 or 10 days after PA administration, for 10 days. CS significantly reduced proteinuria in rats with PA nephrosis in comparison with untreated nephrotic controls. After discontinuation of the CS treatment, proteinuria gradually increased, reaching values similar to those in control nephrotic rats. CS pretreatment did not prevent the induction of PA‐induced nephrotic syndrome. Light microscopy and assessment of anionic sites in the glomerular basement membrane revealed no differences between normal rats, nephrotic controls, and CS‐treated rats. These results show that CS can reduce proteinuria in PA nephrosis, but cannot ameliorate the glomerular changes.
Myoendothelial contacts in the thoracic aorta of rat fetuses
Authors: Sosa‐Melgarejo Jorge A. , Berry Colin L.
Published: June 2005

There is increasing documentation of the presence of endothelial–smooth muscle communication in both small and large arteries. We have found that morphological evidence of these contacts appears early in development. Intimate contacts between endothelial and muscle cells in the thoracic aorta of normal rat fetuses have been studied with transmission electron microscopy. These myoendothelial contacts were seen in the form of cytoplasmic projections passing through fenestrae in the elastic lamellae. Most of these cell processes seem to arise from the muscle cells and they usually have a club‐shaped configuration. The specific nature of the cell–cell contact was predominantly via simple appositions with an intercellular space of 6–15 nm. Myoendothelial contacts are potential sites for electrical and metabolic communication between elements of the intima and media, ensuring that the vessel wall works as a unit. The demonstrated necessity of intact endothelium for smooth muscle cell response to load may depend on this type of contact.
Lysosomes as key organelles in the pathogenesis of prion encephalopathies
Authors: Laszlo Lajos , Lowe James , Self Tim , Kenward Nigel , Landon Michael , McBride Trisha , Farquhar Christine , McConnell Irene , Brown John , Hope James , Mayer R. John
Published: June 2005

The causation, structural origin, and mechanism of formation of spongiform lesions in transmissible encephalopathies are unknown. We have used immunogold electron microscopy to locate ubiquitin conjugates, hsp 70, and β‐glucuronidase (markers of the lysosomal compartment) and prion protein(PrP) in both control and scrapie‐infected mouse brain.

In scrapie‐infected brain, lysosomes and lysosome‐related structures (multivesicular and tubulovesicular dense bodies) are present in abnormally high numbers in neuronal cell processes. These structures contain PrP, together with the lysosomal markers ubiquitin conjugates, hsp 70, and β‐glucuronidase, which could also be identified spilling from tubulovesicular dense bodies into areas of early rarefaction in neuronal processes; we suggest that these areas of rarefaction are the precursor lesions of spongiform change.

We advance the hypothesis that spongiform change is brought about by cytoskeletal disruption in neuronal processes caused by liberation of hydrolytic enzymes from lysosomes overloaded with the abnormal isoform of PrP (PrPsc). We suggest that the lysosomal system is probably acting as the bioreactor for processing of normal PrP to the abnormal isoform. The continuous production of increasing quantities of abnormal PrPsc in lysosome‐related bodies will eventually cause disruption of the lysosomal membrane with destruction of the neuronal cytoskeleton and the initiation of vacuolation. Later, death of the cell will be associated with release of the PrPsc isoform into the extracellular environment. Repeated rounds of phagocytosis, lysosomal biogenesis of PrPsc, lysosomal membrane rupture, hydrolytic enzyme release, and neuronal lysis will lead to an exponential increase in cell damage and cell death.

The recognition of the central role played by lysosmes in the pathogenesis of this group of diseases opens new avenues for potential therapeutic intervention.
Tumour suppressor gene products, proliferation, and differentiation markers in lung neuroendocrine neoplasms
Authors: Barbareschi Mattia , Girlando Salvatore , Mauri Francesco A. , Arrigoni Gianluigi , Laurino Licia , Palma Paolo Dalla , Doglioni Claudio
Published: June 2005

Typical carcinoid, atypical carcinoid, and small cell lung cancer (SCLC) fall within the spectrum of neuroendocrine lung neoplasms. This paper investigates the immunohistochemical expression of the products of tumour suppressor genes p53 and retinoblastoma (RB), together with proliferation (PCNA and Ki67) and neuroendocrine differentiation markers, in 14 typical carcinoids, ten atypical carcinoids, four borderline atypical carcinoid/SCLC, and 11 SCLC. We demonstrated that the phosphoprotein p53 and RB product can be immunolocalized on routine histological material. p53 protein was absent in all typical and atypical carcinoids, while it was abnormally expressed in eight SCLC and one borderline case. RB product was detected in all typical carcinoids and in two atypical carcinoids, while it was consistently absent in the other cases. PCNA‐labelled cells were less than 4 per cent in typical carcinoids, about 40 per cent in atypical carcinoids, and over 70 per cent in SCLC. PCNA labelling index discriminates between typical and atypical carcinoids. Neuroendocrine differentiation was evaluated by a semi‐quantitative method: a mean score value was obtained, which was high in typical carcinoids, intermediate in atypical carcinoids, and low in SCLC. Our data show that the decrease in neuroendocrine features from typical carcinoid to SCLC is paralleled by an increase in proliferative activity and by an altered expression of tumour suppressor gene products. The above findings have diagnostic relevance.
Immunolocalization of regenerating cells after submassive liver necrosis using PCNA staining
Authors: Koukoulis George , Rayner Anne , Tan Kai‐Chah , Williams Roger , Portmann Bernard
Published: June 2005

Little data exist on the proliferative state of liver cells and its relationship with various morphological findings in acute liver failure (ALF) in man. In this study we used the monoclonal antibody NCL‐PCNA (clone PC‐10) against the proliferating cell nuclear antigen (PCNA) to detect cycling cells in paraffin sections of 3 normal livers, 14 post‐mortem needle‐specimens of submassive hepatic necrosis (SHN) due to paracetamol overdosage (POD), and 10 hepatectomy specimens obtained at transplantation in patients with acute or subacute liver failure of presumed viral aetiology. In normal livers, only occasional sinusoid‐lining cells were stained, whereas in SHN following POD or presumed viral hepatitis, hepatocytes of variable morphology showed significant immunoreactivity. Following POD, immuno‐reactivity was higher in samples taken within 5–6 days than in those obtained at 9–11 days, a pattern reminiscent of the decrease in the rate of regeneration, previously documented after partial hepatectomy in humans. Immunolabelled hepatocytes were aggregated in multiacinar ‘nodules’ in cases with a map‐like distribution of collapsed and non‐collapsed parenchyma. Ductules demonstrated comparatively less staining, but extensive labelling was exceptionally found in areas of complete hepatocellular dropout. In these areas, small elongated cells with strongly PCNA‐positive ovoid nuclei, forming periporal sprouting cords or incorporated into the lining of ductules, were most remarkable in that they closely resembled ‘oval cells’ described in animal studies.
Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value
Authors: Bryne Magne , Koppang Hanna S. , Lilleng Rune , Kjærheim Åsmund
Published: June 2005

Several recent studies have indicated that cells at the invasive tumour margins often are different from cells within other parts of various human cancers. In this work, we have studied all squamous cell carcinomas of the floor of the mouth registered in Norway during the years 1963–1972 (N= 96). Borderline cases and cases given no treatment were excluded. Of the remaining 79 cases, biopsy specimens acceptable for histological grading were obtained from 61 patients. Only the most invasive margins of the tumours were histologically graded independently by two pathologists according to a multifactorial grading system. The results confirmed our previous findings that grading of invasive tumour margins is an independent prognostic factor in Cox's multivariate survival analysis (P<0.01). Inter‐observer agreement was calculated by kappa statistics, and good agreement was obtained (kappa = 0.63). Neither agreement nor prognostic value was improved after calibration of the pathologists. Conventional Broders' grading of the whole biopsy had no prognostic value (P<0.38). We conclude that invasive cell grading may be of value for treatment planning of oral cancers, and that further studies of the deep, invasive parts of oral and other cancers are needed in order to obtain a better understanding of tumour cell invasion and metastasis.
Assessment of p53 protein expression in normal, benign, and malignant oral mucosa
Authors: Ogden Graham R. , Kiddie Roy A. , Lunny Declan P. , Lane David P.
Published: June 2005

Recent studies have shown the accumulation of high levels of p53 protein to be associated with malignant disease, within a range of tissues. This paper assesses p53 expression in oral mucosal disease. Biopsies were obtained from a range of oral disorders which included normal, benign, premalignant, and malignant oral tissue. In addition, oral smears were obtained from a limited number of patients with biopsy‐proven oral cancer. Expression of the p53 protein was assessed using the polyclonal antibody CM1, together with a standard immunoperoxidase technique. A total of 37 oral cancers were assessed, of which 20 were found to express the p53 protein (54 per cent of cases). The p53 protein was not identified in normal, benign, or premalignant oral mucosa (54 cases). The identification of p53 within biopsies of oral mucosal lesions would appear to correlate with oral malignancy.
Degranulation of cystic fibrosis nasal polyp mast cells
Authors: Henderson William R. , Chi Emil Y.
Published: June 2005

The ultrastructure of nasal polyps from cystic fibrosis (CF) patients was compared with non‐CF nasal polyps in this study. Morphometric analysis showed that CF nasal polyps contained greater numbers of mast cells, endothelial cells, lymphocytes, and plasma cells compared with the non‐CF specimens. Morphologic evidence of degranulation was seen in approximately 30 per cent of the CF mast cells but was not observed in the non‐CF mast cells. Increased numbers of small granules, vacuolated granules, and lipid bodies were noted in the CF compared with the non‐CF nasal polyp mast cells. Also observed was a decrease in collagen in the extracellular space of the CF nasal polyps compared with the non‐CF specimens. Although eosinophils were observed in the non‐CF nasal polyp tissue, these leukocytes were absent in the CF nasal polyps. These data indicate that striking morphologic differences exist between CF and non‐CF nasal polyps with mast cell degranulation, a salient feature of CF specimens.
Improve your hospital autopsy rate to 40–50 per cent, a tale of two towns
Authors: Champ Caroline , Tyler Xenia , Andrews Peter S. , Coghill Stuart B.
Published: June 2005

In the light of medical audit, all pathology departments are scrutinizing their hospital autopsy rate. In most countries, the rate has fallen over the last few decades to between 10 and 20 per cent. However, it is still possible to achieve a much higher rate.

We compare two neighbouring District General Hospital (DGHs): Northampton, with the more usual autopsy rate of 11 per cent, and Kettering, with a higher rate of 40–50 per cent. These hospitals are comparable in almost every way except for the system used to request permission for an autopsy. These differences were evaluated and the following factors were found to be of importance in achieving a high rate:

centralization of death certificates within the mortuary and personal contact between the certifying doctor and the relatives within the bereavement room;

mortuary pathology technicians are designated as bereavement officers and act as coordinators between relatives, clinicians, and pathologists; and

regular clinico‐pathological meetings and a positive attitude to autopsies by clinicians.
The fractal dimension may be a useful morphometric discriminant in histopathology
Authors: Cross Simon S. , Cotton Dennis W. K.
Published: June 2005

The hypothesis is presented that fractal geometry, and the fractal dimension in particular, is likely to be a more useful method of image analysis in histopathology than the use of regular Euclidean geometry. The concept of the fractal dimension is described and it is suggested that many human tumours have a fractal structure over a wide range of scales. It is postulated that the fractal dimension will be useful in discriminating between different diagnostic categories and may also allow more precise prognostic stratification within single diagnostic groups.
Immunoreactivity for p‐170 glycoprotein in malignant mesothelioma and in non‐neoplastic mesothelium of the pleura using the murine monoclonal antibody JSB‐1
Authors: Ramael Marc , Bossche Jan Van Den , Buysse Corinne , Van Meerbeeck Jan , Segers Kurt , Vermeire Paul , Van Marck Eric
Published: June 2005

The results of an immunohistochemical study of P‐170 glycoprotein immunoreactivity in human non‐neoplastic mesothelium (35 cases) and in malignantmesothelioma (33 cases) using the murine monoclonal antibody JSB‐1 are reported. The majority of malignant mesothelioma cases exhibited cytoplasmic and membrane immunoreactivity in neoplastic cells. These findings are highly significant when compared with the absence of immunoreactivity in normal mesothelium.
Immunoelectron microscopy of cationized bovine serum albumininduced glomerulonephritis in the rabbit
Authors: Al‐nawab M. D. , Bass P. S. , Das A. K. , Davies D. R.
Published: June 2005

Chronic immune complex glomerulonephritis was induced in a group of New Zealand white rabbits by daily intravenous injections of cationized bovine serum albumin (cBSA). The animals were serially killed and renal tissue was embedded in the hydrophilic resin Lowicryl K4M for immunoelectron microscopy. The results demonstrate the progressive deposition of rabbit IgG in the glomerular basement membrane in this model, with aggregation of immunoglobulins occurring only in the subepithelial space. Proteinuria developed concurrently with this event. Glomerular visceral epithelial cell (GVEC) endocytosis of immune material was observed at various stages of the disease process, suggesting that GVECs may be part of a clearance mechanism acting within the glomerulus.
Peripolar cells, granulated glomerular epithelial cells, and their relationship to the juxtaglomerular apparatus in malignant hypertension
Authors: Gardiner D. Stuart , Lindop George B. M.
Published: June 2005

We have examined 12 autopsy kidneys from cases of malignant hypertension and compared them with normal controls. Peripolar cells and other granulated glomerular epithelial cells were counted in serial paraffin sections, and renin‐containing cells were quantified using an immunoperoxidase technique and a human renin antiserum. There were significantly more peripolar cells and other granulated glomerular epithelial cells in the cases of malignant hypertension. Most granulated glomerular epithelial cells were podocytes, situated at the periphery of the tuft. Peripolar cells correlated in number with other granulated glomerular epithelial cells and they had a similar distribution within the renal cortex, but there was no correlation between either of these cells and the number of renin‐containing cells. There was hyperplasia of renin‐containing cells in some juxtaglomerular apparatuses (JGAs), although the proportion of renin‐positive JGAs was unaltered. These results suggest that peripolar cells and other glomerular epithelial cells react in a similar way in malignant hypertension, but they do not support the hypothesis that peripolar cells are part of the JGA.
The ultrastructure of oesophageal carcinomas: Multidirectional differentiation. A transmission electron microscopic study of 43 cases
Authors: Newman Joseph , Antonakopoulos George N. , Darnton S. Jane , Matthews Hugoe R.
Published: June 2005

Forty‐three oesophageal carcinomas, comprising 15 squamous cell carcinomas, 22 adenocarcinomas, 5 small cell carcinomas, and 1 adenosquamous carcinoma, were examined by transmission electron microscopy. The ultra‐structural features of each tumour type are detailed. Multi‐directional differentiation (heterogeneity) was observed in 11 cases: 5 squamous cell carcinomas with focal glandular features; 4 adenocarcinomas with focal squamous features; and 2 small cell carcinomas, one with glandular and the other with squamous features. Abnormal distributions of desmosomes in squamous cell carcinomas and of polarity of tumour cells in adenocarcinomas are described.
Diagnosis of the acute ischaemic heart by ion elution from myocardium
Authors: Reid W. A. , Brown D. , Purves D. , Barnes I.
Published: June 2005

The post‐mortem diagnosis of acute myocardial ischaemia may be difficult to establish in the absence of morphological changes in the myocardium or recent coronary thrombosis. Ischaemic cell injury leads to potassium (K) efflux and sodium (Na) influx and, if the blood is still circulating, the K : Na ratio of the tissue falls. In this study, the K : Na ratio was measured by eluting the ions from samples of myocardium and assaying the eluate. The method yields similar results to those obtained by a previous method, in which myocardial samples were homogenized. The K : Na ratios on samples of horizontal slices through the heart were plotted on maps of the slices. A low K : Na ratio corresponded to, but extended beyond, areas where there was morphological evidence of ischaemia. The method is simple and may be of use in routine practice.
Renal cell carcinoma: Comparison of morphological and flow cytometric parameters of primary tumour and invasive tumour lying within the renal vein
Authors: Novelli M. R. , Maciver A. G.
Published: June 2005

Histological assessment and DNA flow cytometry have been performed on 15 kidneys containing primary adenocarcinomas which had invaded the renal vein. Comparison of morphological variables showed that samples of the intravenous tumour were more commonly composed of granular cells (53 per cent) than were samples from the main tumour mass (16 per cent), and were also of higher nuclear grade. In 7 of 14 kidneys, DNA studies showed either a higher S‐phase fraction (five cases) or DNA aneuploidy (two cases) in tumour cells lying within the renal vein. The mean S‐phase fraction was also shown to increase in higher nuclear grades. Thus, both morphological and biological differences exist between invasive tumour cells lying within the renal vein and those in the main tumour. This is a useful model for the investigation of venous invasion and may give a better prediction of the metastatic potential of renal cell carcinoma.