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Biomedical subjects

I Downie

Publications and source records attributed to I Downie.

14 recordsLinked to original sources
PubMed2006

Positive immunostaining for thyroid transcription factor-1 in primary and metastatic colonic adenocarcinoma: a note of caution.

Immunohistochemistry for thyroid transcription factor-1 (TTF-1) is considered an important ancillary technique for distinguishing primary pulmonary adenocarcinomas from metastases. A case of metastatic colonic adenocarcinoma in a bronchial biopsy specimen that showed focal positive nuclear staining for TTF-1 is reported here. The primary colonic adenocarcinoma was retrieved from the file and immunostaining also showed focal nuclear positivity for TTF-1. This confirmed the morphological and clinical impression of colonic metastases in the bronchial biopsy specimen. To investigate this apparent aberrant TTF-1 expression, further sections from primary colonic adenocarcinoma were immunostained for TTF-1 using the SPT24 antibody clone. Three of the six cases studied showed focal nuclear positivity with the SPT24 clone. All six cases were subsequently shown to be negative with the 8G7G1 clone. It is concluded that the SPT24 antibody to TTF-1 may show focal nuclear positivity in adenocarcinomas of colorectal origin such that focal staining in small biopsy specimens should be interpreted with caution.

Adenocarcinoma↗
PubMed2001

Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies.

To identify the most accurate and useful panel to diagnose mesothelioma, we immunostained sections from 112 mesotheliomas, 18 adenocarcinomas, and 11 reactive pleural specimens with 13 antibodies. Positive results for mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were CAM5.2, 111, 18, and 11; vimentin, 30, 3, and 3; HBME-1, 75, 10, and 8; thrombomodulin, 31, 2, and 2; calretinin, 43, 6, and 11; and CD44H, 68, 10, and 4. Positive results for adenocarcinoma markers in mesotheliomas and adenocarcinomas, respectively, were carcinoembryonic antigen, 1 and 15; LeuM1, 7 and 9; and Ber-EP4, 5 and 12. All reactive pleura were negative. Positive results for markers to help distinguish mesothelioma from reactive pleura in mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were epithelial membrane antigen, 76, 17, and 6; p53, 78, 16, and 9; P-170 glycoprotein, 37, 4, and 2; and platelet-derived growth factor receptor beta, 31, 1, and 2. The differential diagnosis of mesothelioma from adenocarcinoma is based on negative markers. Individual mesothelial markers are of low sensitivity and specificity for mesothelioma. However, diagnostic accuracy is improved by the use of antibody panels. To date there are no antibodies that help distinguish mesothelioma from reactive pleura.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1997

Differential expression of CD32 isoforms following alloactivation of human T cells.

Receptors for the Fc region of immunoglobulin G (IgG) (Fc gamma Rs) exist in three main forms: membrane bound, soluble and cytoplasmic. The function of cytoplasmic Fc gamma Rs is poorly understood. We have previously demonstrated cytoplasmic Fc gamma RII (cCD32) within most normal human peripheral blood lymphocytes (PBL), including T cells. In this study we have investigated the hypothesis that following lymphocyte activation, up-regulation of cCD32 occurs, resulting in increased expression at the cell surface. Normal PBL were activated in vitro using a two-way mixed lymphocyte reaction (MLR) and expression of CD32 monitored by flow cytometry and by immunoperoxidase staining using specific monoclonal antibodies and aggregated mouse IgG subclasses. Furthermore, we designed oligonucleotide probes specific for the three main isoforms of CD32 and looked for changes in mRNA expression throughout the MLR using an in situ hybridization technique. Increased surface expression of CD32 was found on both activated human T and B lymphocytes, but this was found only in the early stages of the MLR, on days 3 and 4, and was virtually absent by day 7. An inverse relationship between cell surface expression of CD32 and mRNA for the IIb isoforms was noted with strong mRNA expression for IIb isoforms occurring in the later stages of the MLR (days 6-7) when interleukin-2R (IL-2R)-positive T cells were predominant. A soluble IgG binding factor (soluble CD32?) was also detected in the MLR culture supernatant. These observations provide support for the hypothesis that synthesis of IIb isoforms of CD32 occurs following alloantigen activation of human T lymphocytes.

Flow Cytometry↗
PubMed1997

Demonstration of cytoplasmic CD32 (Fc gamma RII) within human lymphocytes following microwave treatment.

We have recently described a cytoplasmic from of CD32 (Fc gamma RII) within the vast majority of normal human peripheral blood lymphocytes (PBL) including T cells. The function of cytoplasmic CD32 is not known. These flow cytometric studies were conducted using single cell suspensions of PBL that had been pre-fixed and permeabilized using methanol/triton-X-100. In this study we have attempted to visualize cytoplasmic CD32 by immunocytochemistry using normal PBL processed in various ways and have also looked for CD32 within tissue lymphocytes. Weak cytoplasmic CD32 staining was observed in paraffin sections of normal lymphocytes but only when sections were microwave treated. The intensity of staining for CD32 did however, appear to be much stronger within infiltrating lymphocytes found in autoimmune diseases or in rejecting allografts: an observation that suggests that up-regulation of cytoplasmic CD32 may occur when T cells become activated in vivo. Microwave treatment of PBL suspensions was shown to disrupt the outer cell membrane, thus effectively permeabilizing the cell and allowing for the detection of cytoplasmic components, like CD32, by flow cytometry. Microwave treatment may, therefore, afford an alternative method for cell permeabilization and may prove to be a useful method for the study of cytoplasmic molecules in cell suspensions and in paraffin-embedded tissues.

Antibodies, Monoclonal↗
PubMed1995

Cutaneous necrosis in pregnancy secondary to activated protein C resistance in hereditary angioedema.

A 26-year-old woman with hereditary angineurotic oedema (HAE) presented at 22 weeks gestation with severe cutaneous necrosis similar to that seen in coumarin skin necrosis. Protein S deficiency secondary to HAE and pregnancy was postulated. Treatment with heparin, C1-inhibitor concentrates, systemic steroids and surgical debridement resulted in a successful outcome for both mother and child. Subsequent investigations revealed normal levels of protein C, antithrombin III, total protein S, free protein S but reduced function protein S activity with evidence of activated protein C resistance. Cutaneous necrosis has not been reported in associated with activated protein C resistance previously and the possible mechanisms are discussed.

Adult↗
PubMed1994

A comparative study of the glomerular peripolar cell and the renin-secreting cell in twelve mammalian species.

The peripolar cell is a glomerular epithelial cell situated within Bowman's capsule at its vascular pole. It is believed to be a secretory cell which forms part of the juxtaglomerular apparatus. Scanning electron microscopy was used to perform a comparative study of the morphology and number of peripolar cells in twelve mammalian species. The number of renin-secreting cells in kidney sections stained by renin antibodies and immunocytochemistry was counted. There was a marked inter-species variation in the number, size and appearance of peripolar cells. They were largest and most abundant in sheep and goat and fewest in dog, cow and human. There was no correlation between the numbers of peripolar cells and renin-secreting cells. This does not support the view that the peripolar cell is part of the juxtaglomerular apparatus.

Animals↗
PubMed1993

Detection of lymphocyte Fc gamma receptor-blocking factors by the EA rosette inhibition assay. Refinement of the conventional method and development of a novel flow-cytometric assay.

Serum factors which interact with human peripheral blood lymphocyte Fc gamma receptors (Fc gamma Rs) may be detected in vitro by the EA rosette inhibition assay (EARIA). This assay has been used to detect circulating immune complexes and certain alloantibodies directed against cell surface antigens situated in close proximity to Fc gamma Rs. Three main types of FcR-blocking factor have been demonstrated by the EARIA in human serum following exposure to alloantigens. A strong correlation was observed between the presence of one of these FcR-blocking factors (FcBF1) and human renal allograft survival. This factor was previously shown to bind preferentially to CD32+ B cells and to inhibit antibody synthesis. In this study we have shown that detection of FcBF1 by the EARIA depends on the type of erythrocyte and on the amount of antibody used to sensitise the erythrocytes. Furthermore, we have developed a flow-cytometric version of the EARIA which is rapid, reproducible and, most importantly, objective. Inter-laboratory comparisons using this standardised EARIA should now be possible.

Erythrocytes↗
PubMed1992

Non-granulated peripolar cells exist in the rat glomerulus.

The peripolar cell is a unique cell type in the mammalian glomerulus. Peripolar cells are said to be identifiable during light microscopy by their cytoplasmic granules and by their position at the vascular pole; and during scanning electron microscopy by their distinctive surface morphology. We used both techniques to count peripolar cells in 6 normal rat kidneys. Scanning microscopy revealed that 55(+/- 5)% of glomeruli contained at least one peripolar cell whereas light microscopy revealed granulated peripolar cells in only 4(+/- 2)% of glomeruli. Vascular poles which contained peripolar cells previously identified by scanning were then examined by light and by transmission electron microscopy. Serial sections through these peripolar cells demonstrated the absence of cytoplasmic granules. Our observations suggest that the majority of peripolar cells in the rat contain no granules.

Animals↗
PubMed1991

The glomerular peripolar cell: a review.

There is now morphological evidence from several species that the peripolar cell is a distinctive glomerular cell which may have a secretory function, although a secretory product has not been identified. Peripolar cells, like other glomerular epithelial cells, probably absorb plasma proteins from the glomerular filtrate. Peripolar cells may participate in regulation of sodium balance and the changes in renal function which occur at the time of birth. They are ideally situated to monitor the composition of the glomerular filtrate and/or the calibre of the glomerular arterioles. The relationship between peripolar cells and other granulated glomerular epithelial cells must be clarified, however their morphology and unique anatomical site is suggestive of a specialised function.

Animals↗
PubMed1990

The distribution of renin-containing cells in kidneys with renal artery stenosis--an immunocytochemical study.

In 10 kidneys removed for hypertension due to renal artery stenosis, the histological appearances varied from negligible ischaemic damage to end-stage ischaemic atrophy. We stained the renin-containing cells in tissue sections using an antiserum to pure human renin and an immunoperoxidase technique. In all kidneys there was hyperplasia of the renin-containing cells both in juxtaglomerular apparatuses (JGAs) and in arteries outside the JGA, where these cells extended proximally as far as the interlobular arteries. We mapped the distribution of renin-containing cells and found them in all zones of the renal cortex; in three kidneys they were predominantly in the superficial cortex; in four they were distributed more evenly throughout the width of the cortex; but in three kidneys the normal gradient was reversed, with most of the cells being in the juxtamedullary cortex and, in two of the cases, little or no stainable renin in the superficial cortical JGAs. We suggest that these abnormalities in the distribution of renin-containing cells could affect both the pattern of intrarenal blood flow and the site in the kidney at which secreted renin enters the blood.

Humans↗
PubMed1990

The peripolar cell: a distinctive cell type in the mammalian glomerulus. Morphological evidence from a study of sheep.

We used scanning electron microscopy to study the glomerular peripolar cell in the kidneys of seven sheep. Peripolar cells were present in a variable proportion (3.6-100%) of glomeruli. Although on average two peripolar cells were present at each vascular pole, up to ten were seen on occasion. They were more often related to the afferent than to the efferent arteriole. Mapping the relative position of each cell failed to reveal any zonal distribution in the renal cortex. Scanning electron microscopy showed that they were globular in shape and had a bossellated surface. We showed by examination of cells which had been broken open that this appearance was due to the presence of cytoplasmic granules that produced bulging of the cell membrane. We suggest that scanning electron microscopy is a suitable method for studying this cell in the mammalian kidney.

Animals↗