Search PubMed⌕ Search

Biomedical subjects

H Stein

Publications and source records attributed to H Stein.

At least 415 records · Page 23Linked to original sources

Increased serum levels of soluble IL-2 receptor, CD30 and CD8 molecules, and gamma-interferon in angioimmunoblastic lymphadenopathy: possible pathogenetic role of immunoactivation mechanisms.

Abnormal immunoreaction associated with increased cell activation phenomena might play a role in the pathogenetic events leading to the development of angioimmunoblastic lymphadenopathy (AILD). In the present study we investigated the serum levels of some soluble molecules related to cell activation in 24 patients with AILD at presentation. In particular, we measured by immunoenzymatic or immunoradiometric techniques the levels of the Tac peptide (sIL-2R), soluble CD30 (sCD30) and CD8 (sCD8) antigens, and gamma-IFN (gIFN). The results show that all the above molecules are increased as compared to normal controls, with a different pattern of increase for the different molecules. The sIL-2R levels were very high in all cases with no overlap between AILD and control samples (mean 6315 +/- 3374 U/ml, controls 271 +/- 112 U/ml, P less than 0.001). Very high values of the sCD30 antigen (722 +/- 895 U/ml) were detected in all cases but five, as opposed to the lack of detectable levels in controls. A significant increase of sCD8 (978 +/- 646 U/ml, controls 334 +/- 95 U/ml, P less than 0.01) and gIFN (329 +/- 236 U/ml, controls 97 +/- 43 U/ml, P less than 0.01) was also observed with some overlap between AILD samples and controls. The above findings further support the view that a condition of abnormally enhanced cell activation is likely to play a central role in the pathogenetic events leading to the composite clinicopathological picture of AILD.

Antigens, CD↗

LF61: a new monoclonal antibody directed against a trimeric molecule (150 kDa, 125 kDa, 105 kDa) associated with hairy cell leukaemia.

The newly produced monoclonal antibody (mAb) LF61 detects a molecule restricted to hairy cell leukaemia (HCL) among B-cell non-Hodgkin's lymphomas. In particular, the percentage of LF61 + HCL cells in different cases ranges from 10% to 100%. In normal lympho-haemopoietic tissues LF61 reacts with only about 2% of T-cells, mostly of the CD8 subset in the peripheral blood, extrafollicular areas of the tonsil, red pulp of the spleen and thymic medulla. Expression of the LF61 molecule is observed following stimulation of peripheral blood lymphocytes with phytohaemagglutinin (PHA) or pokeweed mitogen (PWM), suggesting that it represents an activation antigen. Due to its restricted reactivity with a small subset of normal CD8 + T-cells, LF61 in combination with a CD22 mAb is highly suitable for monitoring residual disease in interferon or deoxycoformicin-treated HCL patients. Polyacrylamide gel gradient electrophoresis shows that LF61 precipitates a 150 kDa, 125 kDa, 105 kDa trimeric molecule from the surface of HCL cells. Immunohistological and immunobiochemical results show that this molecule is the same as the one recognized by the still unclustered anti-HCL mAb B-ly7.

Antibodies, Monoclonal↗

Selection of a panel of monoclonal antibodies for monitoring residual disease in peripheral blood and bone marrow of interferon-treated hairy cell leukaemia patients.

A panel of monoclonal antibodies (mAbs) directed against B-cell and hairy cell leukaemia (HCL)-associated antigens was used to identify residual hairy cells in the peripheral blood and/or bone marrow samples from 20 patients with HCL, following treatment with interferon-alpha (IFN-alpha) or interferon-beta (IFN-beta). In all cases, hairy cells retained their characteristic phenotype, e.g. positivity for CD22, CD11c, CD25, CD32, and the HCL-associated trimeric protein (t-GP) recognized by the mAbs HML-1, B-ly7, LF61 and Ber-Act8. The most specific marker for identifying a small percentage of hairy cells in peripheral blood cytospins, was t-GP. In alkaline phosphatase/anti alkaline phosphatase (APAAP) stained preparations, t-GP+ hairy cells (provided with large cytoplasm and hairy surface) could be usually distinguished from t-GP+ normal lymphocytes (small-sized cells with smooth surface). In doubtful cases the percentage of residual hairy cells could exactly be estimated by double immunofluorescence staining for CD22 (B-cell marker) and t-GP. The rationale of the test is based on the finding that the small percentage (about 1%) of t-GP+ lymphocytes circulating in the peripheral blood of normal individuals are T-cells of the CD8 subset and not B-cells. The best markers for identifying residual hairy cells in routine bone marrow biopsies were CD45RA (mAb 4KB5) and CD20 (mAb L26). Immunohistological labelling was superior to morphological examination in picking up scattered hairy cells in bone marrow biopsies showing either severe hypoplasia or exuberant hyperplasia of normal haemopoietic series.

Antibodies, Monoclonal↗

Lymphohistiocytic T-cell lymphoma (anaplastic large cell lymphoma CD30+/Ki-1 + with a high content of reactive histiocytes).

We describe 13 cases of a peculiar lymphoid tumour containing very large numbers of reactive histiocytes. The tumours occurred in young patients (mean age 14.8 y) who presented with systemic symptoms and superficial lymphadenopathy. Microscopic examination revealed a diffuse effacement of lymph node structure due to the presence of histiocytes intermingled with a variable number of anaplastic large lymphoid cells. The latter, in some cases, were isolated, while in others they were arranged in clusters or were diffusely present in residual sinuses. The large anaplastic cells expressed the activation markers CD30 (Ki-1), CD25 (interleukin-2 receptor), CD70 (Ki-24) and Ki-27, as well as varying combinations of T-associated molecules. The histiocytes expressed lysozyme and the CD11b (C3bi-R), CD11c (p150, 95) CD14, CD68 (KPI) and Ber-Mac3 antigens. Double staining with the antibody Ki-67 demonstrated that the proliferating components were the CD30-positive cells and not the histiocytes. T-cell receptor beta gene rearrangements were shown in three cases tested. The patients responded well to aggressive chemotherapy and nine are still alive, eight in complete remission. It is suggested that the tumour represents a well-defined clinico-pathological entity originating from activated T-lymphocytes.

Adolescent↗

An immunomorphometric study on megakaryocyte precursor cells in bone marrow tissue from patients with chronic myeloid leukemia (CML).

An immunomorphometric study was performed on trephine biopsies of the bone marrow in 41 patients with chronic myeloid leukemia (CML) to determine number and size of megakaryocytic precursor cells (pro- and megakaryoblasts). For specific staining, a monoclonal antibody against platelet glycoprotein IIIa (Y2/51) was employed which is applicable on routinely fixed and paraffin embedded tissue. In comparison with control specimens from 15 patients, in CML morphometric analysis revealed an increase in the total amount of megakaryocytes per square and cubic millimeter marrow tissue, but particularly in patients with thrombocythemia. Moreover, a non-disorderly expansion of the megakaryocyte precursor pool was recognizable by showing a relative frequency of pro- and megakaryoblasts in congruence with the normal value. In this context a significant correlation between the counts for Y2/51-positive megakaryocytic elements and promegakaryoblasts with the corresponding platelet values was encountered. The more mature stages of megakaryopoiesis (pro- end megakaryocytes) disclosed a relevant shift to smaller cell forms with rounded cell perimeters and a more compact aspect of their nuclei. Additionally, in 6 patients with CML, evolution into a subacute and manifest (micro)-megakaryoblastic transformation accompanied by myelofibrosis could be demonstrated by a retrospective review of file material.

Antibodies, Monoclonal↗

Detection of human papillomavirus type 16 DNA in carcinomas of the palatine tonsil.

Twenty eight tonsillar carcinomas of various histological types were investigated for the presence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human papillomavirus (HPV) types 6, 11, and 16 by in situ hybridisation using highly stringent procedures. In six cases an autoradiographic signal was obtained in the tumour cell nuclei with the HPV type 16 specific probe. No signal was obtained with any of the other probes. Immunohistochemical investigations with mouse monoclonal antibodies directed against the L1 protein of HPV type and a rabbit antiserum that detects common protein determinants of HPV gave negative results, thus indicating latent infection. Furthermore, a series of tonsils from controls with comparable age distribution was negative by both in situ hybridisation and immunohistology. These results indicate a possible role for HPV 16 in the aetiology of a proportion of tonsillar carcinomas.

Adult↗

Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial.

A new monoclonal antibody, Ber-EP4, directed against a partially formol resistant epitope on the protein moiety of two 34 kilodalton and 39 kilodalton glycopolypeptides on human epithelial cells is described. Immunostaining of a wide range of normal and neoplastic human tissues and cell lines showed that all carcinomas and all non-neoplastic epithelial cells, except hepatocytes, parietal cells, and apical cell layers in squamous epithelia, homogeneously expressed Ber-EP4 antigen. As Ber-EP4 does not detect any normal or neoplastic non-epithelial cells, this antibody might prove valuable for the differentiation of the following (i) non-epithelial tumours from undifferentiated carcinomas; (ii) hepatocytes from bile duct cells in certain liver diseases; (iii) mesothelial cells from carcinoma cells in lung biopsy specimens; and (iv) reactive mesothelial cells from carcinoma cells in smears of serous effusions.

Adult↗

Detection of a mucin marker for the adenoma-carcinoma sequence inhuman colonic mucosa by monoclonal antibody AM-3.

The monoclonal antibody AM-3 was raised against mucins extracted from human colorectal carcinomas. It reacted strongly with sections of paraffin wax embedded colorectal carcinoma. In colonic adenoma tissue the percentage of cells expressing the epitope detected by AM-3 correlated with the degree of dysplasia. In contrast to immunohistochemical staining, which did not show the presence of the antigen in histologically normal mucosa, the more sensitive enzyme linked immunosorbent assay (ELISA) and immunoblot assays showed that it was weakly expressed in this tissue. AM-3 reacted with variable frequency with several normal and malignant human tissues, indicating that the detected epitope is not restricted to colonic tissue. In colonic carcinomas it is present on a sialomucin of apparent relative molecular mass of more than 440,000. These data suggest that the antigen detectable with AM-3 may be useful in the assessment of premalignant changes in colonic adenomas.

Adenoma↗

Testicular sex cord stromal tumour with granulosa cell differentiation: detection of steroid hormone receptors as a possible basis for tumour development and therapeutic management.

A testicular sex cord stromal tumour with granulosa cell differentiation, typical of granulosa cell tumours of the adult type, was investigated immunohistologically on snap frozen and paraffin wax embedded material. The predominance of vimentin and the additional expression of cytokeratin subtypes 8 and 18, as well as the negative staining for epithelial membrane antigen, accorded with results previously reported, for ovarian granulosa cell tumours; the lack of expression of desmoplakin, however, was a distinctive feature. Together with negative staining for leucocyte common antigen, the antigen pattern facilitates the differential diagnosis between granulosa cell tumour and undifferentiated carcinoma or gonadal lymphoma, although its suitability for differentiating within the group of gonadal stromal tumours seems to be limited. The small growth fraction, shown by the monoclonal antibody Ki-67, is typical of the clinical behaviour of granulosa cell tumours. The expression of oestrogen and progesterone receptors, also recently found in testicular Leydig cell tumours, may provoke new approaches to the management of testicular granulosa cell tumours, as well as a new hypothesis on the development of these tumours.

Aged↗

Further characterization of the mucin antigen associated with malignant transformation of human colonic mucosa, detectable with the monoclonal antibody AM-3.

The recently obtained monoclonal antibody AM-3 reacts with an antigenic determinant present in several normal and neoplastic human tissues. In the large intestine the expression of the antigen is very low, but it increases dramatically after malignant transformation. In colonic adenomas the antigen expression correlates with the grade of dysplasia. The detected epitope is membrane-bound in the epithelial membranes of the liver, kidney and esophagus, while the membrane-bound and secretory forms are detectable in the salivary gland and in transformed colonic mucosa. However, the epitope is located on different molecules in all the investigated tissues. Its resistance to denaturing agents and its sensitivity to neuraminidase treatment in preparations from every investigated tissue suggest that it is a common carbohydrate-containing epitope.

Antibodies, Monoclonal↗

Degenerative arthritis after intra-articular fractures of the knee. Long-term results.

We reviewed 31 of 33 consecutive patients with intra-articular fractures of the knee at 6 to 22 years (average 14). Of these, 77% had excellent or good results; the others had various degrees of degenerative osteoarthritis. There was no significant difference between the results after surgical or conservative treatment. Secondary degeneration was not related to cause or type of fracture, but its incidence increased with the patient's age at the time of injury, though not with the length of follow-up. Early mobilisation appeared to be beneficial in preventing later degenerative changes.

Adult↗

Cast or external fixation for fracture of the distal radius. A prospective study of 126 cases.

In a prospective 4-year study, 126 consecutive patients with a fracture of the distal radius were followed. Functional, anatomic, and radiographic final results of fixation with above-the-elbow cast immobilization were compared with the results obtained with external fixation. The results following external fixation of comminuted intraarticular fractures were better than those of similar fractures treated in a cast. Aged osteoporotic patients tolerated better residual deformities, and the clinical results had a relatively low correlation with the final anatomic alignment. We suggest that extraarticular fractures of the distal radius should be treated with cast immobilization. Comminuted intraarticular fractures of the distal radius should be treated with external fixation, which maintains accurate anatomic position until solid fracture healing is achieved.

Adult↗

[Fine structure of megakaryocyte precursor cells (promegakaryoblasts) derived from smears and sections of bone marrow tissue in patients with chronic myeloid leukemia and so-called primary osteomyelofibrosis with accompanying thrombocythemia].

An immunomorphometric study (antiglycoprotein III a - Y2/51) was performed on routinely processed trephine biopsies in 24 patients with chronic myeloid leukemia (CML) as well as so-called primary osteomyelofibrosis (OMF) to determine the frequency and fine structure of promegakaryoblasts (PMB). With respect to controls, there was a significant increase in megakaryocytes in both entities with an orderly expansion of the precursor subpopulation in CML, but a relative decrease in OMF. In comparison with smears of aspirates, sizes of PMB were reduced by about 25% (factor 1.4) in the corresponding bone marrow sections.

Bone Marrow↗

[Vertebral trabecular bone in various age groups and in osteoporosis-- morphometry and bone matrix biochemistry].

Vertebral trabecular bone was analysed by morphometry and bone matrix biochemistry. Trabecular bone volume (TBV) and mean trabecular plate thickness (MTPT) decreased with age. TBV was significantly correlated with MTPT and mean trabecular plate density (MTPD). The individual structure of trabecular bone could be described by both MTPT and MTPD together, but changes of these parameters, that were pathognomonic for osteopenia, were not found. By measuring TBV 3 cases of severe osteopenia were identified (TBV less than 2s of controls); 2 of them showed matrix abnormalities so far not described. In one case (a 67 year old woman without risk factors for osteoporosis) an abnormal high content of type III collagen was found, in the other case (a 44 year old woman with acromegaly) bone matrix analysis atypically revealed a significant fraction of type II collagen. Further studies will be needed to assess the pathogenetic or diagnostic importance of these new findings.

Adult↗

[Epstein-Barr virus and malignant lymphomas--studies on incidence and localization of viral DNA].

Tissue specimens from 198 cases of Hodgkin's disease and 151 non-Hodgkin lymphomas as well as 34 non-malignant lymph node biopsies were examined for the presence of Epstein-Barr virus (EBV) DNA by polymerase chain reaction. EBV-specific DNA sequences were detected in DNA extracts of 58% of Hodgkin's disease biopsies. Non-Hodgkin lymphomas and benign lymph node lesions were associated with EBV in far smaller proportions. In Hodgkin's disease biopsies, subsequent in situ hybridization revealed an exclusive localization of EBV DNA in the tumour cells, suggesting an involvement of EBV in the pathogenesis of Hodgkin's disease in a substantial proportion of cases.

Base Sequence↗

[Demonstration of DNA tumor viruses in carcinomas of the upper respiratory tract].

In situ hybridization (ISH) using 35S-labeled probes was applied to the detection of viral DNAs in 115 epithelial tumours from various sites. Epstein-Barr virus (EBV) DNA was detected in 83% of undifferentiated nasopharyngeal carcinomas (NPC) while none of seven squamous cell NPC displayed an EBV-specific autoradiographic signal. Also, all other tumours investigated, including thymomas, thymic carcinomas, tonsillar carcinomas and medullary breast carcinomas were negative upon ISH to EBV-specific probes. These results suggest a unique association of undifferentiated NPC with EBV. 28 tonsillar carcinomas were further analyzed for the presence of human papillomavirus (HPV) DNA. Six carcinomas showed an HPV16-specific signal while hybridization to HPV6- and HPV11-specific probes yielded negative results. No HPV-DNA was detected in any of 30 tonsils with chronic inflammation, thus excluding that the finding of HPV16 in a proportion of tonsillar carcinomas is merely circumstantial. These results point to a possible etiologic role of HPV16 in the pathogenesis of some tonsillar carcinomas.

DNA Tumor Viruses↗

Multiple myeloma in a patient at risk for AIDS.

An increased incidence of tumors and B-cell lymphomas development has been reported in persons with or at risk for acquired immunodeficiency syndrome (AIDS). This report focuses on a 50-year-old homosexual man with HIV antibodies who met the established criteria for the diagnosis of multiple myeloma: an IgG monoclonal spike greater than 2 g/dl and a plasma cell count greater than 20% in the bone marrow aspirate. Serum protein immunoelectrophoresis showed monoclonal IgG kappa, and in the urine no excess of kappa chains was found. Laboratory data revealed a total IgG of 38 g/l, IgA of 5.2 g/l, and IgM of 2.3 g/l; the calcium level was normal; ESR was 119/130, and no plasmocytoid cells were seen in the differential count. No lytic lesions were found in the skeletal survey. The helper/suppressor T-cell ratio was depleted with 0.1 and HLA-DR was highly elevated with 56% in the immunofluorescent analysis. The development of the most differentiated B-cell tumor broadens the spectrum of B-cell neoplasias in patients with a predominant helper T-cell defect and focuses on the role of disordered immunoregulation and chronic antigenic stimulation in predisposing to B-cell malignant transformation associated with AIDS.

Bone Marrow↗