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Biomedical subjects

P M Close

Publications and source records attributed to P M Close.

12 recordsLinked to original sources

Detection of the T(14;18) translocation in follicle centre cell lymphomas in South African ethnic groups using PCR.

PCR was used to detect the t(14;18) translocation in 64 South African cases with follicle centre cell lymphoma. DNA was purified from paraffin-embedded tissue collected from different ethnic groups namely white, black and "mixed" race patients, and primers used to detect both mbr and mcr. The overall incidence of the translocation was 45%, which is similar to that of Caucasian and Chinese patients. The ratio of rearrangements occurring at the mbr and mcr was 7:1 which may be an overestimation. The ratio was three times higher for the "mixed" race group compared to whites, and this suggests that there may be ethnic variation in breakpoints in South African patients.

Chromosomes, Human, Pair 14

Analysis of low and high grade B-cell lymphoma subtypes using semi-nested PCR and two primer sets.

Immunoglobulin gene rearrangements in B-cell lymphoma subtypes may not always be detected by PCR if only one primer set is applied. We therefore analysed a range of low and high grade B-cell lymphoma subtypes for monoclonality using PCR, to determine appropriate primer selection strategies for routine diagnostic use. Semi-nested PCR was performed on 70 unequivocal B-cell lymphoma cases using paraffin-embedded tissue (PET). Consensus primers directed at the framework 3 (Fr3) and framework 2 (Fr2) regions of the immunoglobulin heavy chain (IgH) gene were used to detect monoclonality. Monoclonality was found in 77% of cases using primer Fr3, 58% using Fr2, and in 93% of cases when data were combined for both primers. In 89% of the 38 low grade and 97% of the 31 high grade B-cell lymphomas monoclonality could be detected when combining both primers. Fr3 gave superior results in most of the lymphoma subtypes analysed. We conclude that both Fr3 and Fr2 are useful, in a routine histopathology laboratory, for detecting monoclonality in most B-cell lymphoma subtypes. Certain subtypes, however, are sometimes not targeted by these primers and therefore require additional analyses.

Clone Cells

Reproducibility of a histogenetic classification of thymic epithelial tumours.

A histogenetic classification of thymic epithelial neoplasms proposed by Müller-Hermelink and co-workers has been shown by a number of recent studies to be of clinical and prognostic value. Reproducibility is an important criterion for the acceptance of any new classification for general diagnostic use. The reproducibility of this classification was tested on 51 cases of thymic epithelial neoplasia, by comparing results obtained by pathologists working from published criteria only with those results obtained by the pathologists who developed the classification. In 78% of cases there was complete concordance of results. Analysis of the 22% discordant cases showed that this discordance was due to a degree of subjectivity in determining cut-off points between categories adjacent to each other in the morphological spectrum of thymic epithelial neoplasia (medullary v. mixed, cortical v. well-differentiated thymic carcinoma). In terms of the important clinical distinction between benign (medullary and mixed) thymomas and those with more aggressive biological behaviour (cortical types and well-differentiated thymic carcinoma), the degree of reproducibility was 96%. The high degree of reproducibility of this histogenetic classification of thymic epithelial neoplasms should facilitate its acceptance and use in routine diagnostic pathology.

Adolescent

Massive thymic hyperplasia.

Massive thymic hyperplasia is an extremely rare form of true thymic hyperplasia most often described in infants and children. Hyperplasia of this order is not known to occur in any other organ, and its etiology and prognostic significance remain unknown. As there is no accurate way of preoperatively differentiating massive thymic hyperplasia from other tumors of the thymus and anterior mediastinum, we advise excision in all cases for histological analysis and relief of mediastinal compression. This description of 4 cases updates the 30 previously reported cases, and includes a literature review.

Child, Preschool

Anaplastic large-cell Ki-1 lymphoma. Pulmonary presentation mimicking miliary tuberculosis.

An unusual presentation of anaplastic large-cell (ALC) Ki-1 lymphoma is described, in which pulmonary involvement mimicked miliary tuberculosis. Lung involvement is uncommon in this type of lymphoma, and it is not clear from previous reports whether this was a presenting feature. Bone marrow involvement, rare in Ki-1 lymphoma, also was present in this case. Despite therapy skin involvement subsequently developed, and the patient died 3 months after presentation. Postmortem examination revealed lymphomatous involvement of the heart, liver, kidneys, stomach, and lymph nodes. This case highlights the need for awareness of ALC Ki-1 lymphoma particularly when it presents at uncommon extranodal sites.

Adult

Primary biphasic lymphoplasmacytic lymphoma of the lung. A mucosa-associated lymphoid tissue lymphoma with compartmentalization of plasma cells in the lung and lymph nodes.

A primary mucosa-associated lymphoid tissue lymphoma of the lung in a 27-year-old man was found. The tumor was composed mainly of centrocyte-like cells and plasma cells. These two components were demarcated sharply from each other, resulting in a zoning or biphasic pattern. This characteristic pattern also was present in the involved regional lymph nodes. Monoclonality of tumor cells was shown immunohistochemically and by in situ hybridization techniques. This article also highlights the use of in situ hybridization in detecting light chain mRNA in paraffin sections.

Adult

Zonal distribution of immunoglobulin-synthesizing cells within the germinal centre: an in situ hybridization and immunohistochemical study.

Immunohistologic studies have shown that synthesis of cytoplasmic immunoglobulin (cIg) is a normal function of some follicle centre cells (FCCs). The mechanisms regulating this synthesis of immunoglobulin and its function within the germinal centre are still poorly understood. In this study we applied a recently developed in situ hybridization method for the detection of kappa and lambda light chain mRNA to reactive lymph nodes and tonsils in order to investigate further the immunoglobulin-synthesizing cells of the germinal centre. FCCs containing detectable levels of light chain mRNA corresponded closely to cells containing cIg. The detection of light chain mRNA rather than its immunoglobulin product was found to be an advantage in that problems associated with the detection of extracellular immunoglobulin were eliminated. This was most apparent in germinal centres where the absence of 'network' immunoglobulin led to the observations that immunoglobulin-synthesizing FCCs are predominantly small centrocytes and that in a proportion of germinal centres they localize in that part of the light zone closest to the dark zone. This zonal distribution of immunoglobulin-synthesizing FCCs raises the possibility of further functional and micro-environmental subcompartments within the light zone.

Antibody-Producing Cells

Preliminary studies on toxic effects of cyclopiazonic acid alone and in combination with aflatoxin B1 in non-human primates.

Results of experimental studies on toxicity of cyclopiazonic acid (CPA), a mycotoxin isolated from Aspergillus flavus, and toxicity of this toxin in combination with aflatoxin B1 (AFB1) are reported. Experiments were conducted in 16 vervet monkeys of both sexes. One male monkey was given 1 mg/kg per day of CPA intragastrically and the dose was doubled every third day to eventually achieve 60 mg/kg per day. Two males and 3 female monkeys were fed 20 mg/kg per day of CPA and terminated after 60 and 120 days, respectively. Two monkeys received AFB1 0.1 mg/kg per day, 2 received the same dose of AFB1 and 20 mg/kg per day of CPA. Four monkeys of both sexes served as controls. Results of experiments showed low toxicity of CPA in non-human primates with mild pathological changes in hepatocyte rough endoplasmic reticulum, small vessels and myocardium. Combined treatment with CPA and AFB1 indicated lack of a synergistic cumulative effect of both toxins. Animals treated with AFB1 only developed more advanced liver lesions and died earlier than those which also received high doses of CPA.

Aflatoxin B1

The effect of chemotherapy on the morphology of human breast carcinoma.

Between biopsy diagnosis and mastectomy 16 patients with carcinoma of the breast received at least three courses of chemotherapy. When the biopsies and the tumour in the mastectomy specimens were compared, an increase in nuclear size, pleomorphism, vacuolation/chromatin clumping and nucleolar prominence were seen in 14 cases. Cytoplasmic changes included accumulation of lipid. There was no correlation between these morphological changes and the disease-free survival period and they could not be used to predict response to chemotherapy.

Adult

Case for conservative management of selected fibro-adenomas of the breast.

To assess the safety of a conservative approach to fibro-adenoma of the breast we prospectively studied 321 women with this clinical diagnosis, and performed aspiration cytology and excision biopsy. There was histological confirmation of fibro-adenoma in 217 (68 per cent), the remainder having various benign conditions and 4 (1.3 per cent) had carcinoma. Aspiration cytology had a sensitivity of 87 per cent and a specificity of 76 per cent for fibro-adenoma. Three cases of carcinoma were identified cytologically and the fourth was regarded as suspicious. To estimate the risk of missing carcinoma we compared the annual frequency of carcinoma with fibro-adenoma in young women and found a ratio of 1:470 between 15 and 19 years, 1:133 between 20 and 24 years and 1:9 in the 25-29 age group. To assess patients' views on non-operative treatment of benign breast masses we asked 124 women, 10 days postoperatively, whether they preferred a conservative approach for a cytologically benign lump: 26 (21 per cent) opted for conservative management in the future and 8 (7 per cent) would have preferred conservatism rather than their recent excision. A conservative approach is safe for clinically and cytologically benign breast lumps in women under 25 years, but very few will accept it.

Adenofibroma

Plasma concentrations and urinary excretion of nandrolone and/or its metabolites after intramuscular injection of nandrolone phenylpropionate to horses.

A radioimmunological method was used as a screening procedure to determine the period of detection or "clearance time", for the horse, of therapeutic doses of the synthetic anabolic steroid nandrolone phenylpropionate. Seven horses, either at rest or being exercised, were given a course of weekly intramuscular injections of the steroid. On the separate occasion, some of the horses were given a single intramuscular injection of the same compound. The weekly injections maintained a high plasma concentration of nandrolone and/or metabolites. The mean (+/- sd) period of detection in plasma of these compounds was 23 (+/- 2) days (range 21 to 25) in resting horses and 20 (+/- 6) days (range 14 to 27) in exercised animals. The mean period of detection in urine was 25 (+/- 7) days (range 16 to 32) and 25 (+/- 12) days (range 9 to 38) for resting and exercised horses, respectively. After a single intramuscular injection to resting horses, the mean periods of detection were 12(+/- 2) days (range 9 to 15) and 13 (+/- 2) days (range 11 to 16) in plasma and urine, respectively. In all experiments there was considerable individual variation in the time taken for the plasma and urine concentrations to return to pre-dose values. This variation was particularly marked in the urine of exercised horses given a course of injections. With horses in training, this period may be over 5 weeks, a period approaching the minimum of 42 days advocated by the Royal College of Veterinary Surgeons that the therapeutic use of anabolic steroids should be discontinued before racing.

Anabolic Agents

Diagnosis of an anemone cell tumor as a B-cell lymphoma by molecular analysis.

An 83-year-old man presented with mediastinal and axillary lymphadenopathy. Immunophenotyping and electron microscopy performed on an excision biopsy were inconclusive. On a repeat biopsy a year later the ultrastructural features typical of an anemone cell tumor were seen. A panel of monoclonal antibodies showed positivity for vimentin only. The diagnosis of a high-grade B-cell lymphoma could be made only after detection of immunoglobulin gene rearrangement by polymerase chain reaction gene amplification.

Aged