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Biomedical subjects

B Jasani

Publications and source records attributed to B Jasani.

At least 91 records · Page 5Linked to original sources
PubMed1994

Possible role of tissue-bound calcium ions in citrate-mediated high-temperature antigen retrieval.

High-temperature preheating of sections in the presence of a salt (e.g., citrate) or a protein denaturant (e.g., urea) solution has been shown recently to provide a reliable alternative to tissue proteolysis for antigen retrieval from formaldehyde-fixed, paraffin-embedded tissues. However, the underlying mechanism of action of this form of pretreatment remains highly speculative. In this study, we show that calcium chelating agents such EDTA and EGTA are more effective than citrate in the retrieval of a citrate-sensitive nuclear antigen, Ki-67. Also, sodium carbonate and another calcium precipitating agent are both able to effect antigen retrieval at high temperatures. The overall data therefore suggest that either the chelation or the precipitation of tissue-bound calcium ions, and perhaps also other divalent metal cations, is a critical step in salt-mediated antigen retrieval. As a corollary, it is suggested that tight complexing of calcium ions or other divalent metal cations with proteins during formaldehyde tissue fixation is responsible for the masking of certain antigens.

Antigens↗
PubMed1994

The localization of mercury and metallothionein in the cerebellum of rats experimentally exposed to methylmercury.

Rats were dosed with methylmercuric chloride, either by gastric gavage (5 x 10 mg kg-1 body weight over a 15-day period), or in their drinking water (20 mg methylmercuric chloride l-1 for 14 or 42 days). Localization of mercury within the cerebellum was performed with a silver physical development technique, and metallothionein with dinitrophenyl hapten-sandwich immunohistochemistry. Mercury was detected in structurally undamaged Purkinje neurones and adjacent Bergmann glial cells; no mercury was detected in granule cells even though these small cells nearest the Purkinje layer had a high incidence of pyknotic nuclei. In general, metallothionein was detected mainly in Bergmann glial cells, Purkinje cells, astrocytes and glial cells of white matter; no metallothionein was detected in granule cells. We hypothesized that the resistance of Purkinje cells to methylmercuric chloride reflects their ability to transform organic mercurials to inorganic mercury that, in turn, induces the synthesis of radical-scavenging metallothionein molecules.

Administration, Oral↗
PubMed1994

Immunohistochemical metallothionein expression in colorectal adenocarcinoma: correlation with tumour stage and patient survival.

Metallothioneins (MTs), a set of ubiquitous low-molecular-weight proteins essential for the protection of cells against heavy metal ion toxicity, were demonstrated immunohistochemically using a monoclonal antibody (E9) against a conserved epitope of I and II isoforms in a series of 109 colorectal adenocarcinomas. In a semiquantitative analysis strong MT expression in the majority of tumour cells was observed in 34 (31%) cases, 24 (22%) tumours showed a focal MT positivity, and 51 (47%) almost completely lacked MT expression. These differences in MT expression were statistically significantly (P < 0.05) associated with the tumour stage (Dukes classification) and the lymph node involvement at the time of operation (pN stages). However, in contrast to previous findings obtained on a variety of tumours, MT positivity was associated with a favourable clinical outcome in colonic carcinoma, which may indicate their different biological behaviour. Survival curves of cases with MT-positive and MT-negative status differed from each other in a univariate analysis (Mantel-Haenszel: 8.9, P < 0.05) but lost significance when a multivariate analysis was carried out by means of the Cox proportional regression model with Dukes' stages as a stratification factor. It is concluded that immunohistochemically demonstrated MT expression is significantly associated with tumour stages but does not represent an independent prognostic variable in colorectal cancer. However, it may provide important information about some of the biological mechanisms underlying progression in colorectal cancer.

Adenocarcinoma↗
PubMed1994

Immunohistochemical demonstration of metallothionein in normal human breast tissue and benign and malignant breast lesions.

Metallothioneins (MTs) are a set of low molecular weight proteins with a high binding affinity to metal ions. MT over-expression has been recently demonstrated in invasive ductal carcinoma of the breast with poor clinical prognosis. In the present study, MTs have been immunohistochemically investigated in normal human breast tissue and a variety of benign, pre-invasive, and malignant breast lesions. In normal breast tissue, MTs were present in myoepithelial cells whereas the vast majority of luminal cells were MT negative. In lesions without increased cancer risk (adenosis and scleradenosis), MT was only immunolocalized in myoepithelial cells. In papillomas, MT was also found exclusively in myoepithelial cells. In most cases of epitheliosis, both the luminal and myoepithelial cells expressed MT. Atypical lobular hyperplasia, lobular carcinoma in situ, and 13/15 invasive lobular carcinomas showed no MT over-expression. The two invasive lobular carcinomas with MT over-expression were classified as pleomorphic lobular carcinomas with apocrine differentiation. In contrast to lobular cancerization, 12/24 ductal in situ carcinomas and 9/20 invasive ductal carcinomas showed MT over-expression. In situ components found within invasive ductal carcinomas usually reflected the MT status of their invasive counterpart. It is concluded from our immunohistochemical results that breast carcinoma cases with MT overexpression arise from lesions which also show MT overexpression. Thus MT expression in carcinomas may be regarded as a genuine feature of the tumour cells and seems not to be related to endogenous or exogenous factors known to induce MT synthesis.

Breast↗
PubMed1994

[Moist autoclaving. A simplified method for antigen unmasking].

Wet autoclaving is a simple, reliable and time-effective method for antigen retrieval in routinely processed archival material. Both routine diagnostic (e.g., oestrogen and progesterone receptors, cytoskeletal proteins) and research antibodies (e.g. various p53 antibodies, mdm-2, bcl-2, MIB-1) are reported to demonstrate its application. We autoclaving may allow successful application of antibodies in paraffin-embedded tissues designed for use on frozen sections. The technique has the potential to reliably handle up to 200 sections at a time, without evidence of any significant damage to the sections or nuclear morphology.

Antigens, Neoplasm↗
PubMed1994

Deep penetrating dermatofibroma versus dermatofibrosarcoma protuberans. A clinicopathologic comparison.

A study of the clinical, histological, and immunohistochemical features of 20 cases of deep penetrating dermatofibroma (DPDF) and eight cases with 14 specimens (eight primary, one reexcision, five secondary tumors) of dermatofibrosarcoma protuberans (DFSP) showed distinct entities. Clinically, DPDF usually appeared as a nodule (approximately 2 cm) of the (lower) limbs, whereas DFSP affected the trunk (shoulder) with irregularly arranged plaques or nodules (> 5 cm). Histologically, DPDF showed a regular silhouette with a smooth, nodular (four of 20) or scalloped (16 of 20) lower margin and variable sclerosis (nine of 20); DFSP, irregularly infiltrated fatty tissue in a lacelike/honeycomb (eight of 14), multilayered (three of 14), or mixed pattern (three of 14), but without sclerosis. Immunohistochemically, DPDF was mostly negative with QBEnd 10 (CD34; 18 of 20) but positive for factor XIIIa (17 of 20), actin (HHF35; 10 of 20), and metallothionein (MT; 12 of 20). DFSP was positive for CD34 (13 of 14), yet with some sparing of central tumor parts, highly cellular tumor nodules, and myxoid areas; factor XIIIa and MT were consistently negative, as was HHF35 in 11 of 14 cases. In a multivariate analysis of histologic and immunohistochemical criteria, the combination of sclerosis and labeling with MT was most valid (p = 0.0001) for diagnosis: all DPDF showed either labeling with MT in "early" (metabolically active) lesions or sclerosis in "late" lesions, not present in DFSP.

Adult↗
PubMed1993

In situ correlation of synthesis and storage of parathormone in parathyroid gland disease.

The distribution and expression of parathyroid hormone (PTH) were investigated in normal and abnormal parathyroid tissue. PTH was detected using a monoclonal antibody with specificity for the 44-68 region of the PTH molecule. Prominent reactivity for PTH was seen in normal parathyroid with a granular pattern of staining. Active parathyroid tissue (adenoma and hyperplasia) showed much less reactivity for PTH, although there was prominent reactivity in the normal tissue around adenomas. Comparison of expression of PTH with that of parathormone mRNA showed a reciprocal pattern in normal tissue and, to a less marked extent, in abnormal tissue. Parathyroid carcinoma in particular had coinciding areas of PTH and PTH mRNA expression. Oxyphil cells had little or no PTH expression, except in the associated 'colloid' in some cases. The findings indicate an inverse relationship between storage and cellular synthesis of PTH, this being more marked in physiological than in pathological conditions of the parathyroid.

Adenoma↗
PubMed1993

Ultimobranchial body nests in human fetal thyroid: an autopsy, histological, and immunohistochemical study in relation to solid cell nests and mucoepidermoid carcinoma of the thyroid.

The mid portion of the lateral thyroid lobes from 64 fetuses was systematically analysed for the presence of ultimobranchial body nests. The nests showed a prevalence of 1/24 (4.2 per cent) or 13/40 (32.5 per cent) depending on whether a single- or a multi-step sectioning method was employed, respectively, and showed anatomical, morphological, and histochemical features similar to those of ultimobranchial postnatal thyroid solid cell nests. Histochemical studies revealed the presence of mucosubstances in 73 per cent of the cases, calcitonin-immunoreactive cells in 36 per cent, and both carcinoembryonic antigen and high-molecular-weight cytokeratin-immunoreactive epidermoid cells in 85.7 per cent, respectively. These findings indicate that these markers, which are also expressed by solid cell nests of the thyroid, are of value for the detection and tracing of ultimobranchial tissue to earlier stages of development. The findings of this study support the hypothesis that mucoepidermoid carcinomas of the thyroid are of ultimobranchial tissue origin.

Animals↗
PubMed1993

Mechanisms of tolerance in the copper-loaded rat liver.

The aim of this study was to contribute to the understanding of the pathogenesis of copper-induced damage and subsequent recovery and tolerance to copper in the copper-loaded rat liver. Male Wistar rats were allocated randomly into groups of four, fed a pelleted diet containing 1500 mg/g copper, and killed at 1, 5, 6, 10, and 15 weeks. Two additional groups were treated as follows: (a) 5 weeks copper loading followed by 5 weeks with normal rodent diet (group 5-0), (b) 5 weeks copper loading followed by 5 weeks normal diet and 5 weeks of copper reloading (group 5-0-5). Control rats were fed a normal rodent diet that contained 18 mg/kg of copper. Tissues were collected for histology, histochemistry, immunocytochemistry, and copper analysis by atomic absorption spectrophotometry and X-ray microanalysis. In the rats continuously fed the high copper diet, copper concentration rose to 444 +/- 32 micrograms/g of liver (wet weight) by Week 1 and to 726 +/- 170 micrograms/g at Week 5, decreasing to 417 +/- 9 micrograms/g at Week 15. X-ray microanalysis and dot mapping microanalysis demonstrated copper within the nucleus, nucleolus, and lysosomes of these continuously loaded rats. Recovery with unloading of liver copper was demonstrated by both qualitative and quantitative methods in group 5-0 (41.32 +/- 19 micrograms/g). Recovery and tolerance were associated with a reduction in nucleolar copper. Copper tolerance was demonstrated in group 5-0-5 and in continuously copper-loaded rats by Weeks 10 and 15. Copper tolerance was reflected by a change in intracellular levels and distribution of copper and an efficient copper unloading mechanism.

Adaptation, Physiological↗
PubMed1993

The distribution of amyloid plaques in the cerebellum and brain stem in Down's syndrome and Alzheimer's disease: a light microscopical analysis.

The distribution and severity of the neuropathological changes in 57 cases of Alzheimer's disease, and 11 patients with Down's syndrome were investigated with reference to the cerebellum. A modified silver stain and a monoclonal antibody raised against amyloid beta-protein were used to identify amyloid plaques. The highest incidence of amyloid plaques in the cerebellum (93%) was found in the group of patients who developed dementia before 65 years of age. This figure dropped to 56% in those patients with dementia beginning after 75 years. In 37 of these cases the distribution of the pathological changes of the disease were also examined in the brain stem. The severity of the pathological changes in the cerebellum corresponded to the involvement of the brain stem nuclei with connections to the cerebellar cortex. The possibility that the disease process spreads to the cerebellum by involving the fibres from the brain stem is discussed with reference to previous anatomical and neurochemical studies.

Adult↗
PubMed1993

Immunohistological evidence for second or somatic mutations as the underlying cause of dystrophin expression by isolated fibres in Xp21 muscular dystrophy of Duchenne-type severity.

Using five monoclonal antibodies against different parts of the dystrophin molecule, we have studied the dystrophin composition of 17 dystrophin-positive fibres in a muscle biopsy from a boy with Xp21 muscular dystrophy of Duchenne-type severity. The fibres showed five distinct, reproducible, immunoreactive dystrophin profiles. All the profiles included both the N-terminal and the C-terminal domains, but between these domains, different fibres were negative for different antibodies, suggesting the somatic loss of certain exons. We interpret this as the first in situ evidence of an individual having different patterns of missing exons leading to restoration of the reading frame in various ways in the original germline frame-shifting deletion of exons 35-43. It follows that various somatic mutations had taken place in different fibres.

Antibodies, Monoclonal↗
PubMed1993

Immunohistochemically demonstrated metallothionein expression in malignant melanoma.

Metallothioneins are ubiquitous proteins with a high affinity for heavy metal ions, e.g. zinc, copper and cadmium. Experimentally, metallothionein over-expression in cell lines derived from a variety of cancers has been associated with resistance to anticancer drugs and irradiation therapy. Using a monoclonal antibody (E9) to metallothionein we investigated immunoreactive expression in routinely fixed and paraffin-embedded tissue from 63 cases of malignant melanoma and 13 secondary deposits. Whereas a variety of cells in normal skin showed metallothionein expression, all forms of benign naevi studied were uniformly negative. In contrast 13/30 'thin' (< or = 1.5 mm; 0.7 +/- 0.4), 25/29 'thick' malignant melanoma (> 1.5 mm; 5.5 +/- 3.9) and 12/13 metastases were positive. Six patients with thin and 19 with thick melanoma with metallothionein expression died during a mean observation period of 6.4 +/- 1.8 and 3.6 +/- 2.5 years, respectively, their survival distribution function analyses giving statistically significant results for both the vertical tumour thickness (P < 0.0001) and metallothionein expression (P < 0.0001). These immunohistochemical results, based on routinely processed paraffin-embedded tissue, suggest that metallothionein expression in malignant melanoma is significantly associated with progressive disease and might therefore be a useful prognostic indicator.

Adult↗
PubMed1993

Quantitative immunohistochemical evaluation by image analysis of metallothionein in copper-loaded rat kidney.

Kidneys of copper-loaded rats were investigated immunohistochemically with a directly peroxidase-conjugated monoclonal antibody against metallothionein (MT). By means of an image analyzing system the area and the staining intensity of MT immunoreactivity in the proximal convoluted tubule (PCT) cells were determined. In the present study we compared the data obtained by image analysis with analytically determined tissue copper and MT concentrations of rats fed a high-copper diet (1 g/kg) for 16 weeks and sacrificed sequentially during this period. Our results provide evidence that the area of MT immunoreactivity correlates significantly with tissue copper and MT concentrations. Both the copper and MT concentrations in kidney rose to a maximum at 8 weeks and remained constant thereafter. The observed rise in the staining intensity of MT in PCT cells to a maximum at 6 weeks, which subsequently declined, suggests a continuing redistribution of copper and MT in the kidneys even after a maximum of concentration copper and MT is reached in the tissue.

Animals↗
PubMed1992

Elevated serum CA 19-9 levels in hepatobiliary cystadenoma with mesenchymal stroma. Two case reports with immunohistochemical confirmation.

Hepatobiliary cystadenomas with mesenchymal stroma (CMS) are rare tumors. Two cases are reported that illustrate many features of CMS, including polypoid involvement of the common hepatic duct in one case. Both tumors were associated with elevated serum levels of the tumor-associated antigen CA 19-9 but normal levels of carcinoembryonic antigen and alpha-fetoprotein. Immunohistochemical analysis confirmed the presence of CA 19-9 in the epithelial component of the tumor. The implications of these findings are discussed, both in relation to the histogenesis of CMS and its preoperative diagnosis. A minimally elevated level of CA 19-9 was found in only one of five patients with hydatid disease of the liver, an important differential diagnosis in clinical management.

Adult↗
PubMed1992

Regressing atypical histiocytosis, a regressing cutaneous phase of Ki-1-positive anaplastic large cell lymphoma. Immunocytochemical, nucleic acid, and cytogenetic studies of a new case in view of current opinion.

BACKGROUND: Regressing atypical histiocytosis is a rare multifocal cutaneous tumor characterized by large, spontaneously regressing, ulcerating skin nodules. Although initially self-remitting, the condition may progress to systemic lymphoma. METHODS: Using material from one patient, an attempt was made to clarify the nature of this condition with immunophenotyping, genotyping, and chromosome studies. RESULTS: Immunophenotyping studies indicated the condition was of T-cell lineage, although T-cell receptor gene studies showed polyclonal rearrangement. This case progressed to systemic lymphoma. CONCLUSIONS: The authors believe regressing atypical histiocytosis is a regressing phase of Ki-1-positive anaplastic large cell lymphoma of the skin.

Adult↗
PubMed1992

Dinitrophenyl (DNP) hapten sandwich staining (DHSS) procedure. A 10 year review of its principle reagents and applications.

Over the past 10 years an immunoperoxidase method using dinitrophenyl (DNP) hapten-labelled primary or secondary probes has been devised. Its widely successful application in research and diagnostic work has depended upon the development of certain key reagents. These include a novel non-deleterious DNP labelling compound, a unique multivalent monoclonal bridge antibody, and an efficient DNP hapten substituted or anti-DNP linked marker enzyme. In this article the development of these reagents and various modifications of the basic technique are reviewed in conjunction with the special applications accruing from their use.

Antibodies, Monoclonal↗
PubMed1992

Immunocytochemically detectable metallothionein in granulation tissue surrounding mucosal ulceration.

Metallothioneins (MTs) are low-molecular-weight heavy metal binding proteins which are effective free oxygen radical scavengers in vitro. Free oxygen radicals have been implicated in the pathogenesis of stress-induced acute gastric mucosal ulceration and ischaemic injury in rat and man. Experimentally, MTs can have a protective role in stress-induced ulceration in rats. The possible cytoprotective role of MTs in chronic mucosal ulceration in man has not been previously studied. Evidence for locally produced MTs in human chronic gastric and small bowel ulcers has been sought by immunocytochemical staining using a monoclonal antibody (E9) to MT. At the base of ulcers MT has been localized to spindle cells (fibroblasts) in granulation tissue. Labelling of macrophages with a pan-macrophage marker KP1, and double labelling with KP1 and E9 showed two distinct populations, and MT appeared to be localized primarily in fibroblast-like cells.

Antibodies, Monoclonal↗