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Biomedical subjects

B Jasani

Publications and source records attributed to B Jasani.

At least 127 records · Page 7Linked to original sources

Hyalinizing trabecular adenoma of the thyroid. A report of three cases with immunohistochemical and ultrastructural studies.

We have studied three examples of benign thyroid tumours which conform to the lesion recently described as hyalinizing trabecular adenoma. The prominent feature of this trabecular epithelial lesion is the extracellular deposition of an eosinophilic material that does not show the features of amyloid; the epithelial cells may be elongated, sometimes radially arranged around the eosinophilic material. All three tumours showed positive immunocytochemical staining for thyroglobulin, keratin, chromogranin and neuron-specific enolase. One tumour showed isolated cells with immunoreactivity for somatostatin, argyrophil cytoplasmic granularity with the Grimelius technique, and ultrastructurally demonstrable cytoplasmic electron-dense endocrine granules. The hyaline extracellular material in all three tumours showed strong immunoreactivity for both type IV collagen and laminin. Previous radiation may be important in the causation of this tumour, and it shows a frequent association with severe thyroiditis. We conclude that the main histological feature of this lesion, the hyaline material, is due to the overproduction of a basement membrane-like material by the neoplastic follicular cells. The presence in one tumour of evidence of endocrine differentiation may reflect the potential for follicular cells to show biphasic differentiation, a feature which may be more frequent than has been previously recognized. Several of the other features of this tumour--for example the frequent intranuclear cytoplasmic inclusions--may lead to diagnostic problems, and the entity deserves wider recognition.

Adenoma↗

Non-deleterious inhibition of endogenous peroxidase activity (EPA) by cyclopropanone hydrate: a definitive approach.

Endogenous peroxidase activity (EPA) poses a serious problem in immunoperoxidase localization of antigens unable to withstand deleterious effects of aldehyde fixatives, alcohols, and various oxidative reagents. This has forced the development of more selective inhibition methods. Of these, phenylhydrazine or azide combined with small amounts of H2O2 have proved quite effective. However, the precise mechanism of the action of these compounds on EPA generating proteins is not understood. Cyclopropanone hydrate is a compound whose inhibitory action on the heme moiety of horseradish peroxidase is well understood. The aim of this study was to investigate the effect of this compound on EPA and to compare its efficiency with that of optimal phenylhydrazine and sodium azide regimens. In addition, any gross deleteriousness of cyclopropanone hydrate towards immunoperoxidase immunolocalization of three of the most delicate lymphocyte surface antigens was investigated. Cyclopropanone hydrate was found to inhibit EPA with progressing strength between 0.15-15 mM. Over this range, H2O2 was found necessary for inhibition only for cyclopropanone hydrate concentrations up to 0.15 mM. Beyond this amount, the compound inhibited EPA equally strongly in the presence or absence of H2O2, reaching near-maximum inhibition at 15 mM. This and the H2O2-requiring regimens were found to cause no gross diminution in immunoperoxidase staining of CD4, CD6, and CD8 antigens in snap-frozen, acetone-fixed human tonsil sections. Cyclopropanone hydrate therefore provides a definitive non-deleterious mode of inhibiting EPA for immunoperoxidase staining of delicate antigens.

Animals↗

Multiple hormone storage by cells of the human pituitary.

While immunostaining serial semi-thin sections of acrylic resin-embedded normal human pituitary using antisera to human pituitary hormones, it became clear that several cells were stained by more than one antiserum. The tissue had been surgically excised from a patient with a prolactinoma. The tumor, which was immunoreactive only with antiprolactin antiserum, was distinctly different from the pieces of tissue under study which had normal pituitary architecture and demonstrated immunoreactivity with antisera against all six of the common pituitary hormones. A major immunoelectron microscopic investigation, using immunocolloidal gold and immunoperoxidase methods, revealed cells in which follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) were co-localized to the same electron-dense granules. Some similar cells also possessed electron-lucent granules immunoreactive only for anti-PRL antiserum. Adrenocorticotrophic hormone (ACTH) and PRL were also found in the same cell but were very largely localized to separate, morphologically different populations of electron-dense and -lucent storage granules. By employing double immunolabeling, a few granules in the ACTH/PRL cells were shown to be immunoreactive to both anti-ACTH and anti-PRL antisera. The possibility that the multipotential stem cells is discussed.

Adult↗

Tamm-Horsfall protein is a marker of renal and extra-renal rhabdoid tumours.

A monoclonal antibody (MAb) to Tamm-Horsfall protein (THP) was used to stain 6 renal rhabdoid tumours (RRT) and 2 primary extra-renal rhabdoid tumours (E-RRT). One of the E-RRT was a tumour from the posterior fossa of a 3-year-old child and the other was a lump from the right side of the neck in an 18-month-old girl. Five of 6 RRT and both cases of E-RRT were positive for THP. Both cases of E-RRT also reacted with vimentin and cytokeratin MAbs. On electron microscopy, cells from both E-RRT were seen to contain concentric whorls of intermediate filaments characteristic of rhabdoid tumours. Viable tissues from one RRT and one E-RRT (the posterior fossa tumour) were available for tissue culture. Ninety-five percent of the cells growing out of both tumours were polygonal and approximately 5% of these cells were THP-positive.

Biomarkers, Tumor↗

Immunohistologically definable light chain restriction in autoimmune disease.

Analysis of serum immunoglobulins from patients suffering from autoimmune disease has shown that pathogenically relevant autoantibodies directed at organ specific antigens are light chain restricted, i.e., they are entirely lambda or kappa type in a given patient. Furthermore, plasma cells involved at tissue level in the production of such antibodies, for example in Graves' disease, have also been shown to express a marked light chain bias as judged immunohistologically. On the basis of these findings, a study was conducted to determine the light chain status of tissue plasma cell infiltrates associated with Sjögren's disease, a known autoimmune disease. Of the six cases examined, all six showed a marked lambda light chain bias, with two patients exhibiting a monotypic plasma cell infiltrate of IgA, lambda isotype. The significance of the overall observations is discussed in the context of other examples of light chain restricted B-cell responses and the generally increased incidence of benign and malignant B-cell neoplasia in autoimmune disease.

Cell Count↗

Antigen CA125 in tumor tissue and serum from patients with adenocarcinoma of the ovary.

The presence of cancer antigen CA125 has been assessed immunohistologically in formalin-fixed tumor tissue and immunoradiometrically in serum from 41 women with residual epithelial ovarian carcinoma after diagnostic laparotomy. CA125 was detected in tumor tissue from the majority of patients (34/41), including those with normal serum levels (15/18). The major determinant of serum CA125 concentration appears to be the size of the residual tumor. The results suggest that in the majority of patients with small residual tumor masses and normal postoperative serum antigen levels, progressive disease may well be associated with increasing serum CA125 levels.

Adenocarcinoma↗

Light microscopic immunocytochemical demonstration of thyroid-stimulating hormone (TSH) receptors on normal rat thyroid cells.

We present a method for immunohistochemical demonstration of surface-associated thyroid-stimulating hormone (TSH) receptors on direct imprints of rat thyroid follicular cells at the light microscopic level, by use of dinitrophenyl (DNP)-labeled bovine TSH as the primary probe in a DNP-hapten sandwich staining (DHSS) procedure. The light microscopically invisible diaminobenzidine (DAB) product of the enzyme reaction was amplified with a DAB enhancement technique (silver amplification), which yielded a reliable and distinct light microscopically visible cell surface staining. The consistently negative control results after inhibition with TSH receptor-specific reagents provide evidence in support of immunohistochemical localization of surface membrane-associated TSH receptors.

Animals↗

Immunological events leading to destructive thyroiditis in the AUG rat.

Single or infrequent observations in patients or animals with autoimmune thyroid disease (AITD) have failed to elucidate the exact sequence of pathogenetic events leading to thyroid cell destruction. A detailed serial morphological and functional study of experimental AITD (EAITD) in the female AUG rat was therefore undertaken. Following induction of EAITD with thyroglobulin (Tg) in adjuvant antibodies to Tg were detectable one week after the initial immunization, at which stage Ia positive vascular endothelium was observed within the thyroid. This was followed by large numbers of Ia positive dendritic-like cells. With time, in almost all the animals whose titre of Tg antibody rose above a critical level, lymphocytic infiltration was observed consisting mainly of Ia positive B cell aggregates with fewer scattered T cells. This was associated with raised levels of serum TSH and concomitant focal follicular hyperplasia and necrosis. Expression of Ia was mainly restricted to the outer epithelial wall of follicular thyrocytes in direct contact with invading lymphoid cells, although occasional staining on the internal apical membrane was observed as a late event in the destructive process. The Ia expression on thyroid epithelial cells was only observed in areas of thyroid lymphoid infiltration. The immune infiltration of the thyroid in the AUG rat appears to be very similar to that observed in Hashimoto's thyroiditis, with the exception that Ia was not regularly observed on the apical surfaces of thyrocytes. Whether or not the diminished or absent epithelial Ia expression contributes to the spontaneous recovery of the disease observed in this model remains to be resolved.

Animals↗

Lack of sampling site variation in chorion villus biopsy as assessed by DNA, enzymatic, morphological and cytogenetical analyses.

A study of villus samples from eight random sites on five electively aborted chorion sacs was performed to determine any significant differences in yield, quality and composition of DNA, iduronate sulphate sulphatase activity and karyotype status. The villi were also examined for their histological characteristics (e.g. stem, intermediate or terminal villi) and for HCG and BGP immuno-reactivities. The overall findings indicated no significant site to site variations in any of the parameters studied. It is therefore proposed that any villus should be equally suitable for prenatal diagnosis.

Chorion↗

Histological demonstration of immunoreactive metallothionein in rat and human tissues.

Antibody to rat liver metallothionein prepared by the method of Brady and Kafka (1979) was used to localise immunoreactive metallothionein using a sensitive DNP hapten sandwich technique applied to formalin fixed wax embedded tissues. Rat tissues examined were liver, kidney and small intestine, taken from normal animals, from animals fasted after receiving either an oral dose of water, or 1 ml zinc acetate solution either orally or by intraperitoneal injection, (3-4 mg Zn++/Kg body weight). Human tissues examined were 6 histologically normal liver biopsies and small intestine including histologically normal jejunal biopsies and samples of ileum obtained at operation. Pathological tissue including liver from cases of Indian childhood cirrhosis with copper retention and ileum from cases of inflammatory bowel disease were also examined. Immunoreactive metallothionein (IMT) was found in both rat and human liver localised in the hepatocyte cytoplasm, nucleus, sinusoids and canaliculi. In some livers IMT was found in the portal and hepatic veins. In the small intestine the IMT was localised consistently in the enterocyte cytoplasm and nucleus, and in the basement membrane region. The rat kidney IMT was localised in the cytoplasm of the distal convoluted tubules the collecting tubules and the ducts of Bellini. The distribution of IMT in rat tissues showed changes associated with fasting, stress and zinc administration. In man, inflammatory bowel disease appeared to decrease the intestinal IMT and no significant difference was seen when patients had received steroid therapy. The greatest amounts of IMT were seen in the control group of patients. The distribution of IMT in human liver in Indian childhood cirrhosis did not correspond with that of copper associated protein.

Animals↗

An improved method for the inhibition of endogenous peroxidase non-deleterious to lymphocyte surface markers. Application to immunoperoxidase studies on eosinophil-rich tissue preparations.

The inhibitory effect of phenylhydrazine and azide combined with either pre-formed or nascent hydrogen peroxide H2O2 upon endogenous peroxidatic activity, expressed by tissue eosinophils in different disease states, was investigated. It was found that whilst endogenous peroxidatic activity due to eosinophils in a Hodgkin's disease and a histiocytosis X case were adequately inhibited by phenylhydrazine combines with pre-formed or nascent H2O2, the eosinophils in the Onchocerca volvulus nodule were either not at all or only partly inhibited by the two regimens. On the other hand, a combination of azide with nascent H2O2 proved consistently effective against this resistant form of endogenous peroxidatic activity. Using human tonsil sections this protocol was shown to be non-deleterious to T4('CD4'), T6('CD1') and T8('CD8') lymphocyte surface antigens as evidenced by the application of a standard indirect immunoperoxidase technique and the relevant monoclonal antibodies.

Antigens, Surface↗

Presence and possible significance of immunohistochemically demonstrable prolactin in breast apocrine metaplasia.

Paraffin wax embedded formalin-fixed benign breast disease tissue taken from 17 patients (15 with microcystic disease and 2 with fibroadenoma) was studied for the presence of tissue bound prolactin using a rabbit antiserum against human prolactin applied in conjunction with a highly sensitive modified version of the dinitrophenyl (DNP)-hapten sandwich staining (DHSS) procedure. Sections taken from 14 of the 15 cases showing apocrine cystic changes exhibited strong prolactin staining restricted to the cytoplasm of metaplastic apocrine cells lining the cysts. Normal lobules and ducts and blunt duct proliferations were all negative, as were also the two cases of fibroadenoma. In contrast 6 out of 8 cases of breast cancer examined showed heterogenously distributed cytoplasmic staining in the cancer cells. Maximal prolactin staining in the apocrine cells was observed at antiserum dilutions as high as 1:60,000. This compared favourably with a 1:120,000 dilution that gave maximal levels of staining in the prolactotrophs present in serial sections taken from formalin fixed paraffin wax embedded post mortem human anterior pituitaries. In both types of tissues the specific staining was abolished by pre-absorption of the antiserum with human prolactin (10 micrograms ml-1). No staining was observed when the anti-prolactin serum was either omitted or substituted with DNP-labelled normal rabbit serum. Apocrine metaplasia in cystic disease of the breast has recently been found to be associated with an increased breast cancer risk. The strong and selective presence of immunohistochemically demonstrable prolactin in the metaplastic cells may be of significance in view of the hormone's known growth stimulating effect on the breast epithelium.

Adenofibroma↗

Chromogranin A and B and secretogranin II in medullary carcinomas of the thyroid.

We have studied the presence of chromogranins A and B and secretogranin II in medullary carcinomas of the thyroid using the methods of immunoblotting and immunohistochemistry. All three antigens were identified by immunoblotting. Chromogranin A and secretogranin II behaved identically to the adrenal antigens in electrophoresis, whereas the molecular size of chromogranin B in the thyroid tissue appeared slightly smaller, possibly due to a higher degree of proteolytic processing. In immunohistochemistry, positive staining was obtained with all three antigens throughout the tumor tissue. All three antigens, as well as the hormone calcitonin, were apparently present in the same cells. Our study suggests that in addition to chromogranin A, the other two antigens (chromogranin B and secretogranin II) may also be useful markers for tumors arising from endocrine tissues.

Carcinoma↗

Synchronous duodenal neuroendocrine tumours in von Recklinghausen's disease--a case report of co-existing gangliocytic paraganglioma and somatostatin-rich glandular carcinoid.

The co-existence of a gangliocytic paraganglioma and a glandular psammomatous carcinoid in the duodenum of a patient with von Recklinghausen's disease and bilateral phaeochromocytomas is reported. The two lesions were considered to be distinctive by light microscopy, electron microscopy and immunocytochemistry. The cells of the glandular carcinoid showed strong cytoplasmic immunoreactivity for somatostatin and contained only scanty intracytoplasmic microfilaments on electron microscopy. In contrast, the endocrine cells of the gangliocytic paraganglioma were positive for pancreatic polypeptide and serotonin, were negative for somatostatin, and contained conspicuous intracytoplasmic aggregates of filaments. The histogenic relationship between the two tumours is discussed. This case strengthens the known association of glandular duodenal somatostatinoma with von Recklinghausen's disease and phaeochromocytoma and, in the light of a previous case report, suggests that von Recklinghausen's disease and gangliocytic paraganglioma may co-exist more commonly than expected.

Carcinoid Tumor↗

Study of childhood renal tumours using a monoclonal antibody to Tamm-Horsfall protein.

A monoclonal antibody to Tamm-Horsfall glycoprotein was used for the immuno-localization of Tamm-Horsfall protein in formalin fixed, paraffin embedded tissue sections of childhood renal tumours, normal children's kidneys, and human fetal kidneys. The procedure was a dinitrophenyl hapten sandwich staining method. The antibody, diluted 1/100,000, gave a very strong and specific staining of the loop of Henle and distal tubules of normal and fetal kidneys. No staining was seen in Wilms' tumour, mesoblastic nephroma, and bone metastasizing renal tumour of childhood. In contrast, two of seven renal carcinomas and three of four rhabdoid renal tumours were positive for Tamm-Horsfall protein.

Antibodies, Monoclonal↗