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H J Wolfe

Publications and source records attributed to H J Wolfe.

At least 73 records · Page 4Linked to original sources
PubMed1987

Contributions of immunohistochemical and molecular biological techniques to endocrine pathology.

Histochemistry has played a major role in the development and implementation of new methods for analysis of gene expression at the cellular level. With the techniques of immunocytochemistry and in situ hybridization, the products of RNA translation as well as specific messenger RNAs and genomic DNAs can be demonstrated and can provide highly dynamic analyses of gene transcription and translation in individual cells. In endocrine pathology, these approaches have been particularly effective for correlation of functional abnormalities with the varying manifestations of disease at the cellular level. In addition, these methods have been valuable in the formulation of novel clinical and pathological concepts, and will continue to provide important tools for diagnostic and prognostic assessment of neoplastic and non-neoplastic disorders of the endocrine system.

DNA↗
PubMed1987

Localization of thyrotropin-releasing hormone prohormone messenger ribonucleic acid in rat brain in situ hybridization.

We studied the distribution of pro- TRH mRNA in rat brain by in situ hybridization histochemistry using radiolabeled single stranded cRNA probes to confirm the hypothesis that the TRH precursor is distributed beyond regions that contain immunoreactive TRH. All regions of the central nervous system previously recognized to contain TRH showed hybridization. Hypophysiotropic neurons in the medial parvocellular division of the paraventricular nucleus showed more intense hybridization than anterior parvocellular division cells, suggesting regional differences in expression. In addition, regions not previously recognized to contain TRH in neuronal perikarya by immunocytochemistry showed specific hybridization for pro-TRH mRNA. These include cells in the olfactory bulbs, dorsal motor nucleus of the vagus, ventrolateral periaqueductal gray, reticular nucleus of the thalamus, and anterior commissural nucleus. Only a single hybridizing band was observed on Northern blots of RNA extracts of the periaqueductal gray and reticular nucleus, identical to that seen in extracts of the paraventricular nucleus. The appearance of pro-TRH mRNA in neurons not previously recognized to contain TRH but which contain the prohormone suggests that non-TRH peptides within the TRH precursor may be preferentially expressed in certain regions of the brain.

Animals↗
PubMed1987

Localization of somatostatin mRNA in the gut, pancreas and thyroid gland of the rat using antisense RNA probes for in situ hybridization.

A method for the localization of rat pre-prosomatostatin mRNA by in situ hybridization with 32P- and 3H-labeled antisense RNA probes is reported. Somatostatin mRNA was detected in endocrine cells of the rat gut mucosa, pancreas and thyroid in a distribution identical to immunoreactive somatostatin. In addition, in situ hybridization allowed localization of reactive neurons in the submucous and myenteric plexus of the gut, sites which are variably positive or negative for immunoreactive somatostatin even after colchicine treatment. These studies indicate that in situ hybridization is more sensitive than immunohistochemistry in some instances for demonstration of somatostatin in gene expression.

Animals↗
PubMed1987

New techniques in gene product analysis.

Many of the new technologies that have developed as a result of advances in cellular and molecular biology, genetics, and immunology have had a major impact in clinical medicine and will continue to provide important diagnostic and investigative tools in the future. The ability to localize a wide variety of gene products in tissues has been accomplished largely through the use of immunohistochemistry. Characterization of gene expression at the levels of specific messenger RNAs and genomic DNAs is now possible through the use of both blot and in situ hybridization techniques. These molecular biological technologies provide important new approaches for understanding the pathobiology of disease and for providing more objective and rational diagnostic and prognostic criteria in biopsy specimens. The pathologist is in a unique position to coordinate, implement, and lead efforts utilizing these new methods for the study of human disease. In addition, the pathologist must assume a leadership role in the assessment of the efficacies of the new technologies in resolving specific clinical problems and in providing novel approaches for clinical and basic research.

Genetic Techniques↗
PubMed1986

A prospective trial of colchicine for primary biliary cirrhosis.

We entered 60 patients with primary biliary cirrhosis in a double-blind randomized controlled trial to determine whether colchicine is therapeutically effective. Thirty patients had early disease (Stages 1 and 2), and 30 had advanced disease (Stages 3 and 4). Fifteen patients with early disease and 15 with advanced disease received colchicine (0.6 mg twice daily), and the remainder received placebo. Patients were studied about every two months; those remaining in the blind phase at two years underwent repeat liver biopsy and were then placed on open-label colchicine (0.6 mg twice daily). With a few exceptions, the results in patients with early disease were similar to those in patients with advanced disease; hence, data on patients in all stages were combined in the main analysis. During the two-year study period the colchicine-treated patients, as compared with the placebo-treated patients, had improvement in levels of serum albumin, serum bilirubin, alkaline phosphatase, cholesterol, and aminotransferases. However, there was no such improvement in the severity of symptoms or physical findings; moreover, there was no significant difference in the histologic changes noted at liver biopsy in the two treatment groups. At four years after entry, the cumulative mortality from liver disease was 21 percent in patients given colchicine and 47 percent in those given placebo (P = 0.05). The only side effect of colchicine was diarrhea, noted in three patients. The consistent and significant improvement in a number of markers of liver disease and the apparent decreased mortality from liver disease suggest that colchicine may provide some long-term clinical benefit in patients with primary biliary cirrhosis. However, the failure of colchicine to reduce hepatic inflammation and fibrosis leaves uncertain the effect of the drug on the longterm outcome of this disease.

Alkaline Phosphatase↗
PubMed1986

Lymphatic and blood vessel invasion in breast carcinoma: a useful prognostic indicator?

Recent studies have presented compelling evidence to support the prognostic importance of peritumoral lymphatic and blood vessel invasion in breast cancer. This parameter appears to be particularly valuable in the hands of pathologists who are experienced in diseases of the breast and who have developed standardized criteria and expertise in their recognition. However, its application is seriously hampered by various factors, especially interobserver and intraobserver differences in interpretation. A more uniform and objective approach, such as the use of immunohistochemical techniques, may be helpful in overcoming these obstacles. This may render lymphatic and blood vessel invasion a reliably reproducible indicator that a practicing pathologist can utilize to recognize high-risk patients and recommend appropriate therapy. The extension of this approach to evaluate neoplasms of other organs--such as malignant melanomas and thyroid, uterine, and cervical carcinomas--should also be explored.

Blood Vessels↗
PubMed1986

Immunocytochemical demonstration of growth hormone-releasing factor in gastrointestinal and pancreatic endocrine tumors.

Growth hormone-releasing factor (GRF), a linear peptide that exists in a number of different molecular forms (GRF-44, -40, -37, and-31) has been shown to be responsible for the acromegaly associated with certain endocrine tumors of the pancreas and other foregut-derived structures. With the use of two anti-sera (#1A850 and G59/901) directed against different segments of the GRF molecule, a series of 24 pancreatic and 35 gastrointestinal endocrine tumors, not associated with acromegaly, were surveyed systematically for immunocytochemical localization of GRF in the tumor cells. Strong immunoreactivity for GRF was encountered in 10 tumors (6 pancreatic and 4 gastrointestinal). While all ten tumors were immunoreactive against G59/901, which recognizes GRF-44, -40, and -37, two jejunal carcinoids showed additional immunostaining with 1A850 that is specific for GRF-44. Seven of these ten tumors were also immunoreactive for a variety of other regulatory peptides and neurotransmitters, including gastrin, insulin, glucagon, serotonin, substance P, somatostatin, pancreatic polypeptide, vasoactive intestinal peptide (VIP), and adrenocorticotropic hormone (ACTH). No consistent pattern of association between GRF and the other regulatory substances was evident. These findings indicate that, even in the absence of associated acromegaly, up to 17% of endocrine tumors of the gastro-entero-pancreatic (GEP) axis show immunoreactivity for GRF and that such reactivity is associated more frequently with pancreatic (25%) than with gastrointestinal (11%) endocrine tumors.

Amino Acid Sequence↗
PubMed1986

Duodenal carcinoids in patients with and without neurofibromatosis. A comparative study.

Nine duodenal carcinoids from patients with von Recklinghausen's neurofibromatosis (VRNF) were investigated for their morphologic, immunocytochemical, and ultrastructural characteristics, and were compared with seven similar tumors from patients without VRNF. Strong similarities were found between tumors in each group. Irrespective of their association with VRNF, duodenal carcinoids arose in adults and usually produced jaundice, upper intestinal bleeding, or obstruction. Tumors larger than 2.0 cm had already metastasized when first detected. All tumors showed a mixed architectural pattern; five tumors associated with VRNF were of the psammomatous type, as opposed to two of those without VRNF. While no tumors showed argentaffinity, stray argyrophil cells were present only in the three tumors not associated with VRNF. All of the tumors showed immunocytochemical evidence of somatostatinomas, and only one VRNF-associated tumor showed immunoreactivity for an additional regulatory substance, as opposed to three of those not associated with VRNF. Thus, while VRNF-associated duodenal carcinoids are not otherwise distinctive, they tend to be pure somatostatinomas (eight of nine cases), whereas similar tumors unassociated with VRNF are frequently multihormonal (three of seven cases). While many more duodenal carcinoids need to be investigated systematically for their immunocytochemical profile, detection of a pure somatostatinoma in the duodenum should alert one to the possibility of coexistent VRNF.

Adult↗
PubMed1986

Intramammary lymphatic invasion in breast carcinomas. Evaluation using ABH isoantigens as endothelial markers.

Recent studies indicate that intramammary lymphatic invasion represents an important prognostic parameter in breast carcinomas. However, the identification of intramammary lymphatic invasion in tissue sections is a subjective procedure, frequently hampered by factors such as fixation artefacts and interobserver variations. In this study, monoclonal antibodies to ABH isoantigens were applied on formalin-fixed, paraffin-embedded breast carcinoma tissue by using the avidin-biotin-peroxidase complex technique. In addition, the H antigen was localized using the Ulex europeus agglutinin I lectin binding technique. Isoantigen localization provided excellent delineation of lymphatics and blood vessels, in general unhampered by the retention of isoantigen expression in some breast carcinomas. In comparison, Factor VIII-related antigen localization required prior trypsin enhancement and was less sensitive and less consistent. The staining for isoantigens was more intense in vascular than in lymphatic endothelium. ABH isoantigen localization of lymphatic channels identified lymphatic tumor emboli peripheral to and within the carcinomas, and distinguished bona fide intramammary lymphatic invasion from tissue shrinkage artefacts. The applicability to routinely processed tissue permits retrospective studies and renders the identification of intramammary lymphatic invasion a more objective procedure. Further studies are needed to assess the role of this technique in evaluating the prognostic value of intramammary lymphatic invasion; the technique may be extended also to the study of other neoplasms.

ABO Blood-Group System↗
PubMed1986

Argyrophil cells in Brenner tumors: histochemical and immunohistochemical analysis.

Argyrophil cells were identified by the single-impregnation Grimelius technique in 11 of 28 (39%) Brenner tumors, accounting for less than 1% of the tumor cell population in all the cases. All tumors with argyrophil cells were stained to demonstrate calcitonin, somatostatin, gastrin, adrenocorticotropic hormone, neurotensin, insulin, glucagon, and serotonin; and four of them (three benign and one borderline) were also stained for chromogranins with the monoclonal antibody LK2H10. Serotonin was present in nine of the 11 cases with argyrophil cells. Neurotensin and somatostatin were found in one borderline tumor, which also contained serotonin. Chromogranin reactivity was demonstrated in all four cases in which it was examined. Ultrastructural examination of one tumor revealed that the argyrophil cells contained secretory granules, 80 nm in diameter, and had elongated cytoplasmic processes that extended between the more numerous nonargyrophil tumor cells. The argyrophil cells of Brenner tumors are similar to those of urothelium in the frequency with which they are immunoreactive for serotonin and the rarity with which they are reactive for peptide hormones. These cells differ from those of mucinous ovarian tumors, which often contain both serotonin and peptide hormones. The findings of this study lend additional support to the close similarity of the epithelial components of Brenner tumors and urothelium.

Brenner Tumor↗
PubMed1986

Anti-lymphocyte antibody Leu-7 (HNK-1) recognizes a constituent of neuroendocrine granule matrix.

Anti-lymphocyte monoclonal antibody HNK-1 (Leu-7) reacts with the cell surfaces of natural killer (NK) lymphocytes and with myelin-associated glycoprotein (MAG). This antibody reacts intensely with normal and neoplastic adrenal medullary cells. A small proportion of normal pancreatic islet cells, anterior pituitary, and gastroenteropancreatic endocrine cells also show Leu-7 immunoreactivity. In adrenal medulla, ultrastructural immunocytochemical studies and immunoblot analyses reveal that Leu-7 reacts with an intracellular protein of MW 75 KD which is localized within the matrices of the chromaffin granules. The MW of this protein differs from those of MAG and chromogranin A. The findings suggest that Leu-7 immunoreactivity might be a new marker for specific subsets of secretory granules.

Adrenal Gland Neoplasms↗
PubMed1986

Establishment of a continuous somatostatin-producing line of medullary thyroid carcinoma cells from BALB/c mice.

A continuous line of somatostatin-producing medullary thyroid carcinoma cells was established from a transplantable tumour in BALB/c mice. Virtually all of the somatostatin immunoreactivity co-chromatographed with somatostatin 14. The tumour cells replicated in spinner cultures with a doubling time of approximately 4 days, and the concentration of somatostatin released into the culture medium increased in proportion to the number of cells. Two- to threefold increases in amounts of stored and released somatostatin were observed after treatment of the cells with bromodeoxyuridine. This cell line might be valuable for studies of somatostatin regulation in normal and neoplastic C-cells, and for other studies of C-cell biology which require a mouse model.

Animals↗
PubMed1985

ABH blood group isoantigen expression in breast carcinomas--an immunohistochemical evaluation using monoclonal antibodies.

The ABH blood group isoantigen status of a retrospective series of 233 invasive breast carcinomas was examined, employing monoclonal antibodies (MCAB) against A, B, and H antigens with the avidin-biotin-peroxidase complex method. In addition, the H antigen was localized with Ulex Europeus Agglutinin I (UEAI) binding. The MCABs provided consistent and specific staining of erythrocytes and endothelium, as well as normal and neoplastic breast epithelium. The anti-H MCAB yielded cleaner background and less intense staining, but otherwise the staining distribution was comparable to the UEA I technique. Contrary to previous reports, deletion of isoantigen expression was not universal in all invasive carcinomas. Whereas 64%, 77%, and 73% of carcinomas from groups A, B, and AB patients, respectively, demonstrated total isoantigen loss, the remaining tumors exhibited variable degrees of isoantigen expression. Moreover, those carcinomas with complete loss of A and B determinants still displayed variable degrees of H immunoreactivity. Carcinomas from group O patients had different degrees of H antigen deletion, with only 12% showing total loss. Statistical analysis revealed that the isoantigen status bore no significant relationship to various epidemiologic, clinical, and pathologic parameters and did not serve as a useful prognostic determinant.

ABO Blood-Group System↗
PubMed1985

Tumor marker expression in breast carcinomas and relationship to prognosis. An immunohistochemical study.

A collaborative immunohistochemical study was carried out to examine the expression and prognostic significance of tumor markers in a retrospective series of 233 invasive breast carcinomas. The patterns of tumor marker expression in 94 patients with short remission duration (recurrence within five years) were compared with 50 patients with intermediate (at five to ten years) and 89 patients with long (no recurrence at ten years or longer) remission durations. The antigens examined were carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), placental lactogen, alpha-lactalbumin, and pregnancy-specific beta-1 glycoprotein. Carcino-embryonic antigen was the most frequently expressed antigen, whereas HCG was demonstrated least frequently. Also, the ABH isoantigen status was examined using monoclonal antibodies; isoantigen expression was observed in a subset of breast carcinomas, contrary to previous reports of total deletion in breast cancer. Two of the markers, CEA and HCG, were examined by both laboratories, each with two different antisera and also with both PAP and ABC immunohistochemical technics. Meticulous efforts were taken to provide quality control and ensure reproducibility of results. These included the use of serial sections of duplicate pathologic material by both institutions, standardization of experimental conditions and interpretation criteria, double-blind evaluation of exchanged slides, and use of standardized data sheets to record staining extent and intensity. No significant disagreements were observed between data obtained through the different approaches. The steps that were taken to minimize interobserver and interinstitutional differences in this study are presented as a model for collaborative immunohistochemical studies. The expression of tumor markers, alone or in combination, was not found to bear any significant relationship to prognostic indicators, such as the likelihood of recurrence, interval before recurrence, or presence of metastasis.

ABO Blood-Group System↗
PubMed1985

Spontaneous proliferative lesions of the adrenal medulla in aging Long-Evans rats. Comparison to PC12 cells, small granule-containing cells, and human adrenal medullary hyperplasia.

Aging rats of the Long-Evans strain spontaneously develop diffuse and nodular hyperplasia of the adrenal medulla in association with other abnormalities commonly encountered in human multiple endocrine neoplasia syndromes. The cells which comprise the adrenal nodules resemble those in the parent tumor of the rat PC12 pheochromocytoma cell line in that they show varying degrees of spontaneous or nerve growth factor-induced neurite outgrowth in culture and they contain little or no epinephrine. In addition, cells from at least some of the nodules contain immunoreactive neurotensin and neuropeptide-Y, which are also found in PC12 cells. There are a number of striking resemblances between the cells in adrenal nodules and the small granule-containing cells in the normal rodent adrenal. The findings suggest that spontaneous rat adrenal medullary nodules and PC12 cells might be derived from small granule-containing cells, or that cells within the nodules might regain properties of immature chromaffin cells and acquire characteristics of small granule-containing cells and of PC12 cells in the course of neoplastic progression. They further suggest a possible relationship between proliferative capacity and neurotransmitter phenotype in the adult rat adrenal medulla. By virtue of their sparse epinephrine content and their small granules, the cells in adrenal medullary nodules of Long-Evans rats differ from those in adrenal medullary nodules of humans with multiple endocrine neoplasia syndromes.

Acetylcholinesterase↗
PubMed1984

Nerve growth factor may function as a survival factor for human neuroblastoma cells in culture.

Cells from two human neuroblastomas were found to exhibit a marked dependency on nerve growth factor (NGF) for survival in primary cultures. Cells from both tumors also responded to NGF by forming processes, but survival was not necessarily associated with process outgrowth. Lines of replicating cells could not be obtained from either tumor. NGF-dependent survival has not previously been reported as a characteristic of NGF-responsive human neuroblastoma cells in primary cultures or in cultures of established cell lines. Our findings suggest that tumors which require NGF for survival might constitute a biologically distinctive subset of neuroblastomas, or that NGF might function as a survival factor for some human neuroblastomas only in suboptimal or deleterious environments.

Cell Survival↗
PubMed1984

Endometrial carcinoma with argyrophil cells: a histochemical and immunohistochemical analysis.

Fourteen of fifty-three cases of endometrial carcinoma (26 per cent) contained varying, usually small numbers of argyrophil cells, as demonstrated by Grimelius silver nitrate staining of formalin-fixed paraffin-embedded sections. In eight cases the argyrophilia was present in the apical region of glandular cells (type 1 cells) or throughout the cytoplasm of glandular or squamous cells (type 2 cells). The distribution of argyrophilia in these cells closely paralleled that of mucin or glycogen, and pretreatment of the sections with disease resulted in a loss of argyrophilia in the glycogen-rich tumors. In six cases individual round, ovoid, and flask-shaped argyrophilic cells were present also within the glandular epithelium (type 3 cells). In all six cases, similarly distributed cells were positive immunohistochemically for serotonin. Immunohistochemical staining for a battery of polypeptide hormones (calcitonin, gastrin, somatostatin, adrenocorticotropin [ACTH], and neurotensin) revealed positive staining for ACTH in one of the six tumors that contained type 3 cells and positive staining for somatostatin in another. Ultrastructural examination of the ACTH- and serotonin-positive tumor disclosed cells with granules 80 nm in diameter. Types 1 and 2 argyrophil cells were found in small numbers in several specimens of normal proliferative and secretory endometrium, but type 3 argyrophil cells were not identified in these specimens. Although focal argyrophilia is a frequent feature of endometrial carcinomas (26 per cent), the presence of type 3 argyrophil cells containing hormones, as evidenced by the immunohistochemical demonstration of serotonin and occasionally polypeptide hormones, is much less common (11 per cent).

Adenocarcinoma↗