PubMed HealthSearch

Biomedical subjects

I Lauder

Publications and source records attributed to I Lauder.

16 recordsLinked to original sources

Vimentin expression by Reed-Sternberg cells in Hodgkin's disease.

The expression of vimentin in Reed-Sternberg cells in 61 samples of Hodgkin's disease (HD) was examined using an avidin-biotin-peroxidase complex technique. Forty biopsies (66%) expressed vimentin, and expression was seen in all subtypes of HD. No immunophenotypic differences between vimentin-positive and vimentin-negative cases were noted. The significance of such expression is unclear, but may be related to the alterations in growth and differentiation that are typical of neoplastic cells.

Hodgkin Disease

Simultaneous in situ hybridisation of native mRNA and immunoglobulin detection by conventional immunofluorescence in paraffin wax embedded sections.

AIMS: The development of a technique for simultaneous in situ hybridisation for native mRNA and conventional immunofluorescence for cytoplasmic antigens in routine pathology specimens. METHODS: Cocktails of synthetic deoxyoligonucleotides coding for immunoglobulin J chain and kappa light chain were 3' end labelled enzymatically with digoxigenin using terminal deoxynucleotidyl transferase. Native mRNA sequences were "unmasked" using proteolytic digestion with proteinase K and hybrid detection was achieved with an alkaline phosphatase labelled anti-digoxigenin antibody. Alkaline phosphatase was visualised with Fast red/naphthol AS-MX phosphate. Fluorescein isothiocyanate (FITC) conjugated anti-isotype antibodies were used simultaneously at the detection stage to identify the isotype production by individual plasma cells in endoscopic duodenal biopsy specimens. RESULTS: The IgA plasma cells of the lamina propria were identified by immunofluorescence and hybrids were detected in the anticipated plasma cell population by Fast red visualisation. The reaction product was visible in bright field or ultraviolet illumination which allowed FITC and Fast red labels to be visualised together under ultraviolet light at 490 nm. Dual labelled cells were clearly visible. Morphology was well preserved throughout. CONCLUSIONS: This technique permits the demonstration of specific mRNA species in cells expressing immunoglobulin. It combines all the advantages of non-radioactive synthetic oligonucleotide probes and conventional immunofluorescence techniques in routine formol-saline fixed and paraffin wax embedded sections with good retention of morphology.

Antigens

Oncogene expression in primary myelodysplasia: correlation with haematological, karyotypic, and clinical progression.

AIMS: To see if the relative expressions of proto-oncogenes that are increased in acute myeloid leukaemia are raised in patients with myelodysplastic syndromes (MDS), and to see if they increase with progression to leukaemia. To note if there is a correlation between morphology, karyotype, and these proto-oncogene expressions and if any one proto-oncogene can predict prognosis. METHOD: Bone marrow from 130 patients was analysed at six monthly intervals over two years for relative mRNA expression of seven oncogenes, karyotype, and morphology. The technique used slot blot hybridisation and densitometric analysis. The results were compared with 14 surgical controls and 30 people with vitamin deficiency anaemia. RESULTS: Six of seven oncogenes showed increased expression which progressed with time, but did not correlate with morphological or karyotypic changes. Expression of four of the seven oncogenes was increased in megaloblastic and iron deficiency anaemia. C-mos showed differences among the five morphological subgroups; it correlated with abnormal location (p = 0.025) and seemed to influence prognosis. CONCLUSION: Increased proto-oncogenes reflect the overall marrow perturbation in MDS. C-mos may reflect persistence of monocyte pathway which confirms marrow stability.

Aged

[Nodular paragranuloma and Epstein-Barr virus: frequency of EBV DNA and clinical relevance].

Studies demonstrating Epstein-Barr virus (EBV) DNA in Hodgkin's disease (HD) provide little information about the EBV-status in the lymphocyte predominant subtype (nodular paragranuloma) which is due to the small number of cases investigated. Therefore we studied 99 typical cases of nodular paragranuloma for the presence of EBV-DNA using the polymerase chain reaction (PCR) technique. Genomic DNA was amplifiable in 71 cases; 29 cases (= 40%) were positive for EBV-DNA (EBNA-1). In situ hybridization revealed EBV-RNA (EBER-1) in L&H cells and in a few lymphocytes. PCR results were correlated to clinical follow-up data and did not show any statistically significant relationship between EBV positivity and survival of the patients.

Adult

Epstein-Barr viral DNA in Hodgkin's disease: amplification and detection using the polymerase chain reaction.

The presence of Epstein-Barr virus (EBV) DNA in biopsy tissues from patients with Hodgkin's disease (HD) was investigated by the polymerase chain reaction (PCR) using primers specific to a sequence within the EBV Bam H1W region. EBV genome was detected in 33 of 57 (58 per cent) cases of HD. Viral DNA was, however, also demonstrated in nine of 24 non-Hodgkin's lymphomas, in three of nine non-neoplastic lymph nodes and in seven of 12 normal peripheral blood samples used as controls. In all cases, the band obtained following PCR was verified using Southern blotting and hybridization with highly specific Bam H1W probes. The results suggest that the technique is sufficiently sensitive to detect EBV in persistent latent infection in B-lymphocytes. Distinction between virus present as a possible aetiological agent of malignancy or as a latent infection is not possible when PCR is used under these conditions. The possible role of EBV as an aetiological agent of HD remains unresolved.

Adolescent

Demonstration of insulin and glucagon mRNA in routinely fixed and processed pancreatic tissue by in-situ hybridization.

Human insulin and glucagon mRNA were identified in routinely processed pancreatic tissue by non-radioactive in-situ hybridization using digoxigenin-labelled oligonucleotide probes. Cocktails of synthetic oligonucleotides complementary to human insulin and glucagon mRNA were labelled with digoxigenin using terminal deoxynucleotidyl transferase (Tdt). Specific hybrids were detected with alkaline phosphatase-labelled anti-digoxigenin antibody and visualized by BCIP-nitroblue tetrazolium indicator substrate. The results showed highly sensitive and specific staining of islet cells on a range of routinely formalin-fixed and paraffin-embedded tissues. Post-mortem pancreatic tissue from adults and stillborn neonates yielded acceptable signals as long as tissue morphology was well preserved. Preliminary investigations using pancreatic endocrine cell tumours gave clear easily interpretable signals which were comparable to conventional immunostaining. The application of this technique promises to be of value in the investigation of pancreatic disease.

Adult

The expression of parathyroid hormone messenger RNA in normal and abnormal parathyroid tissue.

The distribution and expression of preproparathyroid hormone (PTH) mRNA were investigated in parathyroid tissue from 57 parathyroidectomy specimens. PTH mRNA was detected by in situ hybridization using digoxigenin-labelled oligonucleotide probes. Cell morphology was seen to correlate with PTH mRNA expression. Strong expression of PTH mRNA was confined to cells which on haematoxylin and eosin staining had large vesicular nuclei. These included both vacuolated and non-vacuolated cells. Chief cells with small dark nuclei and scanty cytoplasm had little or no expression. In both adenoma and chief cell hyperplasia, the striking difference from normal was the greatly increased proportion of cells expressing PTH mRNA. In adenomas, the rim of uninvolved parathyroid tissue showed PTH mRNA expression similar to that of normal parathyroid. In hyperplasia, there was frequently concordance of staining within individual nodules. The findings establish morphological criteria for activity of parathyroid tissue and support current concepts of the different pathogenesis of hyperplasia and adenoma. The expression of PTH mRNA in oxyphil change and parathyroid carcinoma was also investigated.

Humans

The effects of dexamethasone on the cell kinetics of a murine malignant lymphoma.

The effects of dexamethasone on the cell kinetics of a rapidly growing syngeneic B cell malignant lymphoma in Balb/c mice have been studied. Growth curves, stathmokinetic studies and frequency of labelled mitoses (FLM) experiments were performed in groups of dexamethasone treated and control animals. These studies showed that tumour growth was arrested after 8 days treatment at which time the tumour weights were approximately half those of control animals. Dexamethasone increased the duration of the cell cycle with a particular increase in the duration of DNA synthesis. The results indicated that the effect on tumour growth could be attributed to a reduction in the growth fraction.

Animals

Cell population kinetic profile of the mouse thymus, and the changes induced by prednisolone.

The cell population kinetic parameters of the thymus in BALB/c mice have been estimated using stathmokinetic and [3H]TdR techniques in both control animals and animals treated with prednisolone. FLM data were analysed by computer using the Gilbert program. The study showed that prednisolone had an inhibitory effect mainly in the DNA synthesis phase and in G1. Stathmokinetic data also showed a decrease in the cell birth rate and an increase in the apparent cell cycle time (or potential doubling time) after treatment. The labelling index, the mitotic index and the growth fraction were also decreased. The study also shows a good agreement between the data obtained by stathmokinetic and [3H]TdR techniques.

Animals

Spontaneous maturation of stage IV--S neuroblastoma.

A case of stage IV--S neuroblastoma is presented in which treatment has deliberately been kept to a minimum. Gradual maturation to ganglioneuroma has been documented and the patient's generally good progress has justified this approach.

Age Factors

Macrophage infiltration of breast tumours: a prospective study.

In 50 cases of infiltrating breast cancer investigated in a prospective study the number of macrophages within each tumour was assessed. The macrophages were identified by their cytoplasmic acid phosphatase activity. The number of lymphocytes and plasma cells within the tumours were graded by a scoring technique. Significantly fewer cases with metastases were found among those with high macrophage and plasma cell scores. There was no correlation between lymphoreticular infiltration and the degree of tumour differentiation, but in cases without metastases the lymphoreticular infiltration between tumour cells was nearly always only slight when the macrophage score was low.

Breast Neoplasms

Achondrogenesis type I. A familial subvariant?

The clinical, pathological, and radiological features of 2 male sibs with a severe and lethal form of micromelic dwarfism are desribed. The family also includes 2 normal sibs. The histological and radiological appearances suggested a diagnosis of achondrogenesis type I, but the markedly deficient ossification of the skull and the presence of intrauterine rib fractures were atypical. These changes have been observed in two other families with 2 or more infants with suspected achondrogenesis, raising the possibility that these familial cases may be a subvariant of achondrogesis or even a distinct disease entity. The disease appears to be inherited as an autosomal recessive and death occurs shortly after birth because of severe pulmonary hypoplasia.

Achondroplasia

A nephropathy occuring in rats treated with dinitrochlorobenzene and N-methyl-N-nitroso guanidine.

Chronic administration of a potent oral carcinogen N-Methyl-N-Nitroso guanidine (M.N.N.G.) failed to produce gastric carcinoma in CFHB Wistar rats sensitised to 2.4 dinitrochlorobenzene (D.N.C.B.). In addition animals receiving both D.N.C.B. alone and D.N.C.B. and M.N.N.G. developed a severe nephropathy characterised by heavy proteinuria and extensive renal cortical damage. The histological features include proliferation of parietal epithelial cells and mesangial sclerosis. An association between the nephropathy and long term D.N.C.B. administration is suggested and on the basis of investigation to date direct toxicity rather than immune complex disease seems more likely.

Animals