Biomedical subjects
Publications and source records attributed to J Crocker.
A case is described of a patient presenting with enlarged lymph nodes and in whom a diagnosis of acute toxoplasmosis was made. The patient later developed Hodgkin's disease for which chemotherapy was started. Reactivation of the quiescent toxoplasma infection took place with devastating results. Prophylactic treatment in such cases is discussed.
In two studies, we explored the effects of trait self-esteem and threats to the self-concept on evaluations of others. In Study 1, subjects high, moderate, and low in self-esteem received either success, failure, or no feedback on a test and later evaluated three pairs of targets: in-groups and out-groups based on a minimal intergroup manipulation, those who scored above average and those who scored below average on the test, and themselves and the average college student. Study 2 explored the effects of self-esteem and threat on in-group favoritism in a real-world setting, campus sororities. Together, the results of these studies indicate that individuals high in self-esteem, but not those low in self-esteem, respond to threats to the self-concept by derogating out-groups relative to the in-group when the group boundaries have evaluative implications.
With the increasing use of immunoperoxidase technics, it may be difficult to differentiate between the dark staining of 3,3'-diaminobenzidine (DAB) compound reaction product and melanin pigment. The latter may be particularly observed in skin. Samples of both normal skin and melanotic malignant melanoma were treated for the removal of melanin by standard technics both before and after a peroxidase-antiperoxidase (PAP) immunohistologic sequence. Many methods for the removal of melanin pigment resulted in diminished DAB staining intensity. Some also caused cellular disruption. However, the method of choice was found to be treatment with 0.25 g/dL potassium permanganate and 1 g/dL oxalic acid before the immunoperoxidase sequence.
We have measured skin mast cell numbers, circulating basophils and whole blood histamine in 13 patients with polycythaemia vera. Itching was present in nine cases and correlated well with the numbers of skin mast cells but not with circulating basophils or whole blood histamine. Immediate relief of pruritus was achieved with aspirin, and myelosuppressive therapy was useful for long-term control of symptoms. Neither histamine (H1 or H2) antagonists nor iron replacement therapy were effective forms of treatment. The findings suggest that mast cell prostaglandins are an important factor in the pathogenesis of pruritus and that local vascular responses may trigger mast cell degranulation.
Invasion of a bladder tumour involves the degradation and penetration of the subepithelial basement membrane. A retrospective study of 69 superficial and 15 invasive transitional cell carcinomas of bladder and a prospective study of 43 mucosal biopsies were performed in order to assess the usefulness of immunohistochemical staining of the basement membrane components, type IV collagen and laminin as prognostic indicators in superficial bladder cancer. There was a significant association between pT category and basement membrane staining. The incidence of progression of superficial tumours with patchy or absent basement membranes was significantly greater than those with complete basement membranes but there was no association with superficial recurrence. Biopsies of dysplastic epithelium had thickened and reduplicated basement membranes, possibly as a result of increased cell turnover. The results suggest that a balance exists between basement membrane production and degradation in early malignancy. This technique may be of value in the early identification of microinvasion and in the prediction of subsequent progression.
Necropsy specimens were obtained from the lungs of 10 subjects who had no history of lung disease, 10 who had died with chronic bronchitis, and 10 with bronchiectasis. Tissue sections were stained for IgA1 or IgA2 using the immunoperoxidase technique, and the number of cells in the bronchi stained for these proteins was counted. The total number of IgA positive cells was increased in bronchitic and bronchiectatic lungs compared with those from control subjects. The number of IgA2 positive cells was similar in those with bronchitis and bronchiectasis and significantly higher than in controls. Similarly, cells containing IgA1 were increased in the lungs of subjects with chest disease but were higher in those with bronchitis than in those with bronchiectasis. The proportion of IgA2:total IgA containing cells was similar in sections from controls (mean (SD) 25 (5.0)%) and those with bronchiectasis (mean (SD) 24 (4)%), but lower in those with bronchitis (mean (SD) 19 (5.0)%). The results show that cells containing IgA1 predominate in the major bronchi but that the proportion of cells containing IgA2 is higher than in non-mucosal lymphoid tissues. Bronchitis and bronchiectasis are associated with greater numbers of cells producing IgA in the bronchi, and this is consistent with increased local production of IgA in the lung secretions of bronchitic subjects.
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A series of 20 bone marrow trephines biopsy and necropsy specimens were strained for IgA1 and IgA2 activity, together with total IgA, by means of an indirect immunoperoxidase technique using murine monoclonal antibodies applied to paraffin sections. The specimens showed normal histology and had been taken from patients not known to be suffering from haematological or related systemic disease. The IgA1, IgA2, and total IgA containing cells were counted and expressed as a percentage of all nucleate cells in the marrow cavities. Remarkably constant percentages of and ratios between these cell types were found. The same was true for a further 10 trephines taken from patients undergoing staging procedures for epithelial malignancies, where the marrow histology was normal. The pooled mean percentage of IgA1 containing cells from both groups was 1.18% of all cells, that for IgA2 containing cells 0.18%, and for total IgA positive cells 1.41%. In addition, 12 trephines containing known IgA producing myeloma were examined. Of these, 11 contained IgA1, the remainder contained IgA2 subclass.
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Gastric, duodenal, and rectal biopsy specimens from 20 patients with chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL), not primarily of gastrointestinal origin, were examined using the immunogold-silver staining (IGSS) technique. In paraffin sections the presence of kappa and lambda surface immunoglobulin in lymphoid infiltrates was shown. Using this technique, nine patients were shown to have infiltration of the gastrointestinal mucosa by monoclonal B cells at one or more sites. In a further case a lymphoid aggregate was shown to express both kappa and lambda surface light chains, suggesting that it had a benign nature.
Using a silver staining technique, nucleolar organiser regions were identified in routinely processed paraffin sections of a range of dermal melanotic lesions. The technique shows argyrophilic NOR associated proteins (AgNORs), which are seen in nuclei as black dots. Although the nuclei of melanocarcinoma in situ, melanocarcinoma per se, and lentigo maligna contained similar numbers of AgNORs, in melanocarcinomas a mean of 7.9 AgNORs per nucleus was found, while in naevocellular naevi, this figure was 1.2. The AgNOR method, which is unknown to most histopathologists, could perhaps be used quantitatively or semiquantitatively to assist in the diagnosis of melanotic lesions in the skin (and elsewhere).
An argyrophil technique for the demonstration of nucleolar organiser regions has been applied to routinely processed paraffin sections of 15 specimens of small cell carcinoma and 15 biopsy specimens infiltrated by lymphocytes. To avoid tautological problems, the nature of the specimens was confirmed by means of immunohistochemical staining for neurone specific enolase and leucocyte common antigen. The specimens of small cell carcinoma were readily differentiated from those containing lymphocytes by the argyrophil method, the range of mean number of nucleolar organiser regions per nucleus being 4.2-7.3 for small cell carcinoma cells and 0.9-1.7 for lymphocytes. This method separates malignant epithelial cells from benign lymphocytic cells and has potential in both clinical and research investigation of respiratory tumours.
Ectopic production and secretion of hormones by a wide variety of tumours has been known for many years. Recently human chorionic gonadotropin (HCG) production and/or secretion have been noted in 15 cases with prostatic adenocarcinoma (Fukutani et al. 1983; Papapetrou et al. 1980: Broder et al. 1977; Menon & Stefani 1980; McManus et al. 1976) and in two with upper urinary tract transitional cell carcinoma (Fukutani et al. 1983; McManus et al. 1976). In this study we utilised the indirect immunoperoxidate technique to demonstrate beta-HCG production in prostatic adenocarcinoma and upper urinary tract urothelial tumours. Of 100 cases of prostatic adenocarcinoma beta-HCG production was demonstrated in nine cases, eight of which were poorly differentiated, and of 14 urothelial tumours of the upper urinary tract beta-HCG production was present in two high grade transitional cell carcinomas.
A peroxidase--antiperoxidase technique for S100 protein has been applied to 122 breast lesions from 122 patients. These included 35 cases of fibrocystic disease, 16 cases of sclerosing adenosis, 24 cases of papilloma and papillomatosis, 43 intraduct carcinomas, and four intralobular carcinomas. In fibrocystic disease, S100 protein was demonstrable in large amounts in cells between the duct lining cells and the basement membrane of the ducts, being most pronounced in those exhibiting adenosis. Areas of epitheliosis showed scattered positive cells within the ducts with more strongly positive cells around these ducts. Apocrine metaplasia was moderately positive. No S100 protein was demonstrable in the epithelial lining cells of cysts or within the stroma. In sclerosing adenosis individual cells and groups of cells in the fibrous tissue were strongly positive. In papillomatosis and papilloma, the vascular core and epithelium failed to stain, but a discontinuous layer of cells between the epithelium and basement membrane was positive. In intraduct and intralobular carcinoma the tumor cells were uniformly negative, and wherever fibrocystic disease was also present, S100 protein was variably demonstrable. The study corroborated the view that fibrocystic disease and benign proliferative processes of the breast appear to contain cells that correspond to myoepithelial cells, and suggests that S100 protein may serve as a useful marker in the separation of benign proliferative breast lesions from in situ carcinoma.
Cathepsin B synthesis by the human HL60 promyelocyte cell line was investigated by immunohistochemistry and by the assay of the enzyme in cell lysates using a fluorimetric substrate. HL60 cells were shown to produce cathepsin B in response to treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). Intracellular levels of cathepsin B and immunohistochemical staining of the enzyme were related to time in culture with increasing concentrations of TPA from 1 nmol/1 to 8.0 nmol/1. Synthesis of cathepsin B was associated with TPA-induced phagocytic activity of cells in culture, expression of alpha-naphthyl acetate esterase and reduced cell division. Cathepsin B production was, therefore, related to differentiation of the HL60 promyelocytes into mature macrophage-like cells. Cathepsin B activity in HL60 cell lysates was significantly increased by incubation of the cells with 10 micrograms/ml endotoxin (lipopolysaccharide) from Escherichia coli, but not carrageenan. The production of cathepsin B by TPA-induced HL60 cells was significantly reduced by 0.25 mumol/1 dexamethasone and the non-steroidal anti-inflammatory compound 4-(6-methoxy-2-naphthyl)-butan-2-one but not by indomethacin. The HL60 promyelocytic cell line is a useful model for the study of factors affecting proteinase synthesis by human mononuclear phagocytes.
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A series of 36 iliac crest trephines, previously shown to contain follicular lymphoid aggregates, were examined using the immunogold-silver staining technique. This showed the presence of kappa and lambda surface immunoglobulin in paraffin sections of the specimens. In those trephines from patients known to be suffering from chronic lymphocytic leukaemia there was distinct monoclonality for expression of either kappa or lambda surface light chains on the lymphocyte cell surfaces in and usually between the lymphoid nodules. In specimens containing aggregates, which had previously been diagnosed as benign on morphological and clinical criteria, both kappa and lambda chains were expressed. A small number of trephines containing aggregates of uncertain nature were also examined; these all showed monoclonal expression of either kappa or lambda chains and subsequently proved to be clinically malignant. Dendritic reticulum cells, shown by staining for surface immunoglobulin, were observed only in benign aggregates.