Biomedical subjects

H Stein

Publications and source records attributed to H Stein.

At least 181 records · Page 10Linked to original sources

PubMed1997

Strict lymphotropism of Epstein-Barr virus during acute infectious mononucleosis in nonimmunocompromised individuals.

Previous investigations of exfoliated oropharyngeal cells from individuals suffering from infectious mononucleosis (IM) suggested that the oropharyngeal epithelia are the primary target and also the site of life-long persistence of the Epstein-Barr virus (EBV). This concept was widely accepted. However, the investigation of histological sections with more sensitive EBV detection techniques has drawn this concept into doubt since EBV proved to be constantly absent in normal epithelial cells. To elucidate the discrepancy, throat washings and peripheral mononuclear blood cells from 16 patients suffering from IM were investigated for EBV-DNA and EBV gene products employing highly sensitive in situ hybridization, immunocytochemistry, and polymerase chain reaction. Although all patients exhibited latently infected B lymphocytes in peripheral blood, samples of exfoliated oropharyngeal cells were constantly EBV-negative with the exception of three cases. In these cases, the patients additionally suffered from purulent ulcerating tonsillitis, EBV-infected B cells, but no EBV-infected epithelial cells were detectable. These findings support the view that recirculating lymphocytes of B-cell origin, but not epithelial cells are the initial target of EBV during primary infection and that B cells also represent the site of life-long viral persistence.

Adolescent↗

PubMed1997

Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection.

We report here a series of 16 highly malignant diffuse large B-cell lymphomas of the oral cavity with unique immunohistologic features. Fifteen of these developed in human immunodeficiency virus-positive patients. All cases displayed morphologic features of diffuse large-cell lymphomas but strikingly differed from them in that they showed a minimal or absent expression of the leukocyte common antigen as well as of the B-cell antigen CD20. Instead, the tumor cells showed a constant reaction with the plasma cell characteristic antibody VS38c and a frequent reaction with the CD79a antibody. This, in conjunction with a variable expression of cytoplasmic Ig and a monoclonal rearrangement of the Ig heavy chain gene in all of the three tested cases confirmed the B-cell nature, the clonal origin, and the plasmacellular differentiation of these neoplasms. The majority of these tumors were negative for the BCL-6 protein, with the remaining cases showing only a partial and weak expression of this antigen. An association with the Epstein-Barr virus (EBV) was found in 9 of 15 tested cases showing abundant EBV-encoded nuclear RNA transcripts in the absence of EBNA-2. Five of the EBV-positive cases variably expressed LMP-1. We propose to name these tumors plasmablastic lymphomas, in accordance with their morphologic and immunohistologic features. Knowledge of this lymphoma entity is important to avoid confusion with nonlymphoid malignancies due to the lack of commonly used lymphoid markers.

Adult↗

PubMed1997

Human papillomavirus infection is not associated with bronchial carcinoma: evaluation by in situ hybridization and the polymerase chain reaction.

While a strong association between human papillomaviruses (HPVs) and squamous cell cancers of the female genital tract is known to exist, there is substantial controversy regarding the relationship of HPV with other non-genital carcinomas. Recently there have been some reports focusing on a possible association of HPVs with bronchial carcinomas. These studies mostly used either in situ hybridization (ISH) or the polymerase chain reaction (PCR). In view of these reports, 32 squamous cell carcinomas (SCCs) and six small cell carcinomas of the bronchus were examined for the presence of HPV DNA by both techniques: ISH using 35S-labelled, type-specific probes (HPV 6, 11, 16, 18), and PCR with consensus primers coding for more than 25 different HPV subtypes performed on formalin-fixed, paraffin-embedded material. None of the 38 bronchial carcinomas analysed was positive for HPV DNA, either by ISH or by PCR. On the other hand, additionally examined specimens of 15 cervical carcinomas were positive for HPV 16 DNA in at least three cases by ISH (20 per cent) and in 12 cases by PCR (80 per cent). We conclude that common HPV types do not play an important role in the pathogenesis of bronchial carcinoma.

Female↗

PubMed1997

Expression of cytotoxic molecules in intestinal T-cell lymphomas. The German Study Group on Intestinal Non-Hodgkin Lymphoma.

Intestinal T-cell lymphoma (ITCL) represents a subgroup of peripheral T-cell lymphomas which is thought to arise from alpha beta intraepithelial T-lymphocytes. Since these lymphocytes may contain cytotoxic molecules, the question of whether this also holds true for ITCL arises. Twenty ITCL cases were examined for the presence of granzyme B, perforin, and T-cell-restricted intracellular antigen (TIA-1)/granule membrane protein of 17 kD (GMP-17). Two molecules with restricted expression in cytotoxic cells, granzyme B and perforin, were detected by immunocytochemistry and by in situ hybridization with an isotopically labelled RNA probe, respectively. Immunocytochemistry was also performed with the antibody 2G9, which recognizes two molecules, one expressed by cytotoxic cells (TIA-1) and the other found in granulocytes and cytotoxic cells (GMP-17). Granzyme B, TIA-1/GMP-17, and perforin were found in the neoplastic cells of 16/19 cases, 19/20 cases, and 16/17 cases, respectively, of ITCL, but not in the tumour cells of the control group, which consisted of intestinal B-cell lymphomas (five cases) and CD8-negative peripheral nodal T-cell lymphomas (six cases). At least one of these molecules was expressed in the tumour cells of all ITCL cases. 2G9 proved to be the most sensitive immunohistological marker, since reactivity with this antibody was not only observed in the highest number of cases, but also found in high numbers of neoplastic cells in positive cases. In conclusion, ITCL appears to show cytotoxic differentiation in all cases. In conjunction with immunophenotypic and genotypic data, our results support a uniform derivation of this tumour from intraepithelial alpha beta cytotoxic T-lymphocytes.

Adult↗

PubMed1997

Overexpression or ectopic expression of MUC2 is the common property of mucinous carcinomas of the colon, pancreas, breast, and ovary.

Mucinous carcinomas of the colorectum have been reported to overexpress the intestinal mucin MUC2. The purpose of this study was to determine whether this alteration is shared by mucinous tumours of the ovary, breast, and pancreas. A total of 40 breast carcinomas (22 of mucinous and 18 of ductal invasive type), 39 ovarian adenocarcinomas (16 mucinous, 23 serous), 47 colorectal carcinomas (25 mucinous and 22 non-mucinous), and 41 pancreatic adenocarcinomas (14 mucinous, 27 non-mucinous) were investigated by immunohistochemistry with the anti-MUC2 monoclonal antibody 4F1 and the expression pattern was ranked. MUC2 mucin is expressed in the normal colonic epithelium; in the normal epithelium of the breast, ovary, and pancreas, it was not detectable by immunohistochemistry or by reverse transcriptase-polymerase chain reaction (RT-PCR). In agreement with previous reports, the colonic mucinous carcinomas differed significantly from the non-mucinous carcinomas by strong MUC2 expression. In all mucinous carcinomas of the ovary, breast, and pancreas, de novo expression of the MUC2 gene was observed, which differentiated mucinous and non-mucinous carcinomas of these tissues (P < 0.001). The overexpression or ectopic expression of the MUC2 gene exhibited by mucinous carcinomas of four organs indicates a common genetic lesion associated with the mucinous tumour phenotype.

Adenocarcinoma, Mucinous↗

PubMed1997

Disappearance of the Epstein-Barr virus in a relapse of Hodgkin's disease.

Hodgkin's disease (HD) is associated with the Epstein-Barr virus (EBV) in approximately half of cases. This is a report of a case of nodular sclerosing HD of the B-cell type that was associated with EBV in the initial manifestation, but was found to be EBV-negative in the relapse of the tumour. Both tumours displayed similar clinical, pathological, and immunohistochemical features. This finding implies that in a given individual EBV can be lost from malignant tumours and therefore shows that the EBV infection is not required to maintain neoplastic growth of HD tumour cells.

Antigens, Viral↗

PubMed1997

Expression of vascular endothelial growth factor in lymphomas and Castleman's disease.

Vascular endothelial growth factor (VEGF) is one of the main angiogenic cytokines in human solid tumours and inhibition of VEGF-induced angiogenesis suppresses tumour growth. Some groups of malignant lymphoma, including peripheral T-cell lymphomas and Hodgkin's disease, are characterized by a conspicuous proliferation of small vessels. To test the hypothesis that VEGF may also be involved in the angiogenesis in lymphomas and other lesions of the lymphoid system, VEGF expression was analysed in tissues, employing in situ hybridization with a 35S-labelled RNA probe specific for this cytokine. Significant expression of VEGF transcripts was observed in Hodgkin's disease and peripheral T-cell lymphomas, particularly of the angioimmunoblastic type. In contrast, expression of this cytokine was minimal or absent in follicle centre lymphoma and chronic lymphocytic leukemia of B-cell type. VEGF was mainly observed in reactive non-lymphoid CD68-negative cells, which probably represent fibroblasts or myofibroblasts. In normal and ulcerated tonsils, VEGF was expressed in the squamous epithelium but only rarely found in the lymphoid tissue. Although infectious mononucleosis tonsils contained high numbers of VEGF-positive cells in the interfollicular zone, expression of this cytokine was not found in Epstein-Barr virus (EBV)-infected cells, as determined by simultaneous in situ hybridization for VEGF and EBV-encoded small nuclear RNAs (EBER). In 5/8 cases of Castleman's disease, germinal centres containing small vessels also showed expression of VEGF, in contrast to normal tonsillar germinal centres which are devoid of both vessels and VEGF transcripts. It is concluded that VEGF may be involved in the induction of the angiogenesis of both peripheral T-cell lymphomas and Hodgkin's disease, but not in low-grade B-cell lymphomas. In contradistinction to solid tumours, in which this cytokine is commonly secreted by the tumour cells themselves, in malignant lymphoma VEGF is not a product of neoplastic cells. Vascularization of germinal centres in Castleman's disease may also be a consequence of abnormal local expression of VEGF.

Castleman Disease↗

PubMed1997

Radical transhiatal esophagectomy with two-field lymphadenectomy and endodissection for distal esophageal adenocarcinoma.

Distal adenocarcinoma of the esophagus is defined as a tumor originating from an endobrachyesophagus or a tumor with its main tumor mass (more than two-thirds) located in the distal tubular esophagus. Controversy exists about the optimal mode of surgical resection. Some favor transthoracic esophagectomy, whereas others prefer transhiatal (blunt) esophagectomy. A radical transhiatal esophagectomy (RTE) combined with two-field lymphadenectomy and mediastinoscopic dissection of the upper thoracic esophagus (endodissection) is described herein. We assessed the short- and long-term results of this technique and compared them to a historical group of patients undergoing conventional transhiatal esophagectomy (THE) for adenocarcinoma of the distal esophagus. Altogether 124 patients underwent transmediastinal esophagectomy because of adenocarcinoma of the distal esophagus in our department between January 1986 and May 1995. Thirteen of these patients were excluded from this analysis because of preoperative chemotherapy. The remaining 109 patients were divided into two groups: 62 patients who underwent THE between January 1986 and March 1991 (51 men, 11 women; mean age 65.3 years, range 31-83 years) and 47 patients who had RTE between April 1991 and May 1995 (44 men, 3 women; mean age 63.4 years, range 41-84 years). To compare the long-term results of RTE and THE, we used a matched-pairs analysis considering tumor stage and age. The hospital (30-day) mortality was marginally lower in the RTE group (4.3% versus 6.4%), resulting in an overall mortality of 5.5%. The rate of pulmonary complications was insignificantly lower in the RTE group [19.1% RTE versus 25.8% THE; not significant (NS), and the rate of postoperative cardiac abnormalities significantly decreased after RTE (2.6% RTE versus 19.3% THE; p < 0.05). The overall rate of R0 resections was 87.2% (82.2% RTE, 87.1% THE). Overall survival was similar within the two study groups. Complete tumor removal, T and N stages, and the lymph node ratio were identified as prognostic factors for long-term survival. Overall survival was better after RTE than after conventional THE in patients with involved lymph nodes. The mean number of resected lymph nodes per patient in the RTE group was 26.7. Positive lymph nodes were most common in the paracardial region and at the lesser curvature (72%/10.8% of all invaded abdominal nodes). In the mediastinum positive nodes were most common in the paraesophageal and paraaortal region (48%/27% of all mediastinal nodes). Patients with positive abdominal and mediastinal lymph nodes had a poor long-term prognosis. Distal adenocarcinoma of the esophagus can be safely resected by RTE with two-field lymphadenectomy and endodissection. This technique allows radical "enbloc" resection of the tumor-bearing distal third of the esophagus, which includes the primary area of lymph node metastasis of adenocarcinoma of the distal esophagus: the lower mediastinum and paracardial region. The analysis showed that RTE incurred fewer cardiac complications and a better overall survival in N1-positive patients when compared retrospectively to THE. Intraoperative mediastinoscopy allows controlled dissection of the upper mediastinum and biopsy of several mediastinal lymph nodes, with the advantage of providing additional staging information.

Adenocarcinoma↗

PubMed1997

[Cardiac sarcoidosis: diagnostic validation by endomyocardial biopsy and therapy with corticosteroids].

A 66-year-old woman with pulmonary sarcoidosis had a 1.5-year history of congestive heart failure presenting as dilated cardiomyopathy. Transvenous endomyocardial biopsy specimens initially revealed lymphocytic myocarditis but subsequently showed a non-cesating giant-cell granuloma typical of Boeck's sarcoid. In addition to standard therapy the patient was given corticosteroids. This case illustrates the difficulties and importance of diagnosing cardiac sarcoidosis as a potentially treatable form of dilated cardiomyopathy.

Aged↗

PubMed1997

S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

We evaluated S-100 levels in paired cerebrospinal fluid (CSF) and serum samples in a group of 135 patients referred to the German Creutzfeldt-Jakob disease (CJD) surveillance unit from June 1993 to May 1995. The patients were seen in a prospective case control study. The diagnosis of probable CJD during life was made in any patient presenting with rapidly progressive dementia of less than 2 years' duration, typical periodic sharp wave complexes (PSWCs) in the EEG and at least two of the following findings: myoclonus, visual/or cerebellar symptoms, pyramidal and/or extrapyramidal signs and/or akinetic mutism. Patients presenting with the above clinical signs and symptoms but without PSWCs were classified as possible, while those with a dementia of a duration exceeding 2 years and without PSWCs were classified as other. S-100 was determined in paired CSF and serum samples by a commercially available enzyme-linked immunosorbent assay. In a group of 76 patients with definite and probable CJD, S-100 concentration (median 25 ng/ml, range 2-117) in CSF was significantly higher (P < 0.0001) than in 32 patients diagnosed as other (median 4 ng/ml, range 1-19). Serum levels of S-100 were below 0.5 ng/ml in all groups. At a cut-off of 8 ng/ml an optimum sensitivity of 84.2% with a specificity of 90.6% for the diagnosis of CJD by the determination of S-100 in CSF is obtained. S-100 levels exceeding 8 ng/ml in CSF support the diagnosis of CJD in any patient presenting with rapidly progressive dementia.

Adult↗

PubMed1997

Cutaneous involvement in prelymphomatous angioimmunoblastic lymphadenopathy.

We describe prelymphomatous angioimmunoblastic lymphadenopathy with cutaneous involvement in a 73-year-old female patient. A maculopapular skin eruption was the first sign of the disease. Skin histology showed extensive perivascular and periadnexal mixed lymphoid infiltrates including centroblasts and immunoblasts with a high proliferative index and with focal erythrocyte extravasation. Lymph node histology confirmed the diagnosis, showing nearly complete effacement of the follicular architecture, a mixed lymphoid infiltrate, and numberous high endothelial venules in an expanded T-cell zone. Immunohistochemistry, however, demonstrated preservation of at least some follicular structures. T-cell receptor gene rearrangement analysis revealed oligoclonal patterns in both lymph node and skin specimens. In contrast, immunoglobulin heavy-chain gene rearrangement analysis revealed a polyclonal pattern. Accordingly, the disease was classified as a prelymphomatous stage of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) with specific involvement of both lymph node and skin. The patient was treated with high-dose corticosteroids, and long-lasting remission was induced. In contrast to our case, most reported cases of AILD show a monoclonal T-cell pattern indicating AILD-type lymphoma. Therefore we discuss the concept of prelymphomatous AILD developing into AILD-type lymphoma. Persistence of some antigenic stimulus may induce the proliferation of a monoclonal population of lymphoid cells from a polyclonal background in a multistep fashion. Proper treatment of AILD at an early, prelymphomatous stage may protract or inhibit development of full-blown, fatal AILD-type lymphoma.

Aged↗

PubMed1997

The hybrid ring tubular external fixator: a biomechanical study.

OBJECTIVE: To measure and compare the mechanical properties in bending of the four-ring, and three-ring/one-tube hybrid external fixation frames. DESIGN. IN VITRO: measurements of the mechanical behaviour of ring and ring-tubular external fixation frames. In the latter, one ring of the full circular frame was replaced by one tube and Schanz screws. BACKGROUND: The mechanical properties of the classical Ilizarov four-ring external fixation frames has been compared to those of other external fixation frames by various authors. However, in clinical practice the hybrid fixation frame is being used with increasing frequency. Therefore the mechanical properties of the latter are of immediate interest and clinical value. METHODS: On explanted sheep tibiae with single and double osteotomies, frame stiffness in the four-point bending mode was measured at different K-wire tensions, comparing the values obtained from four-ring frames, to those of three-ring-tubular hybrid frames. These measurements were made under conditions of (a) bone distraction (BD), and (b) segment transport (ST), both at the initial and final stages of this procedure. RESULTS: In circular frames, frame stiffness in bending for increasing K-wire tension showed a Gaussian distribution both in distraction and post-ST with an optimum at 1000 N. In ring tubular hybrid frames, however, frame stiffness showed a more linear relationship to K-wire tension. CONCLUSIONS: In the four-ring Ilizarov external fixation frame, the exchange of one ring with one tube and one Schanz screw both reduced frame stiffness in bending and converted to linear its relationship to K-wire tension. RELEVANCE: Under clinical conditions, the use of a similar ring tubular hybrid external fixator allows the adjustment of frame stiffness in a simple and practical way. This is not the case with the original ring fixation frame.

Journal Article↗

PubMed1997

A 19-week-old fetus with craniosynostosis, renal agenesis and gastroschisis: case report and differential diagnosis.

A case of a fetus affected with craniosynostosis, unilateral renal agenesis and gastroschisis is reported. The propositus was delivered on the 19th week of gestation for premature rupture of the membranes. Macroscopy showed turricephaly, shallow orbits, exophthalmos, hypertelorism, hypoplastic maxilla with relative mandibular prognathism and gastroschisis. Additional autopsy findings included a premature bilateral closure of the lambdoid suture and a unilateral renal agenesis. The nosological aspects of this fetus and the differential diagnosis of well-described craniosynostosis syndromes with characteristic craniofacial growth patterns (Crouzon syndrome, Jackson-Weiss syndrome, Apert syndrome, Saethre-Chotzen syndrome, Pfeiffer syndrome) are discussed.

Abdominal Muscles↗

PubMed1997

Podocytes are the major source of IL-1 alpha and IL-1 beta in human glomerulonephritides.

To address the question of in situ production of IL-1 alpha and IL-1 beta in proliferative and non-proliferative forms of human glomerulonephritis (GN), we performed immunocytochemical and in situ hybridization studies on renal biopsies from patients with mesangial IgA-GN (N = 38), idiopathic membranous GN (MGN; N = 12), minimal change disease (MCD; N = 9), focal segmental glomerulosclerosis (FSGS; N = 5) and acute endocapillary GN (AGN; N = 3). Normal kidneys (N = 10) served as controls. Concomitantly, the expression of IL-1 receptor type I (IL-1 RI), IL-1 receptor type II (IL-1 RII) and of IL-1 receptor antagonist (IL-1 RA) was analyzed. Antibodies against antigens expressed on podocytes (PP-44), endothelial cells (CD31) and monocytes/macrophages (CD11b, CD14, CD68) were applied to attribute the expression of IL-1/IL-1 related peptides to intrinsic glomerular and/or blood-derived infiltrating cells. Our results demonstrate that IL-1 RII is constitutively expressed on endothelial cells, and its expression can be induced in proximal tubular cells and in the interstitium. In diseased glomeruli podocytes are capable of producing IL-1 alpha/beta. In MGN and MCD/FSGS, the expression of both IL-1 forms is particularly noted in early stages of the disease and is not only accompanied by a marked reactivity for IL-1 RI, but also for IL-1 RA. In segmental sclerosing lesions in FSGS and in IgA-GN with marked glomerular proliferation and/or sclerosis, a reduced expression of the PP-44 antigen and a diminished ability of podocytes to produce IL-1/IL-1 related peptides are noted. These results suggest that intrinsic glomerular production of IL-1 may be of relevance for the protection of glomeruli from continuing injury.

Acute Disease↗

PubMed1997

Neurological deficit in a consecutive series of vertebral fracture patients with bony fragments within spinal canal.

The wide spread availability of computerized tomography has added a new dimension to the anatomical evaluation of vertebral fractures. This diagnostic modality has shown that in these fractures, the protrusion of bone spicules into the spinal canal is often encountered. The clinical significance of this finding and its relation to the need of establishing indications for surgery in these patients is controversial. The neurological outcome of patients with postraumatic bony encroachment of the spinal canal is not well documented in the literature, and therefore the adequate therapeutic approach is neither clear nor is it unanimous. Whether treatment should be aggressively surgical with decompression and/or segmental fusion, or conservative, the goal has to be prevention of secondary injury to the spinal cord. This presentation is a mean 4 year follow up study of 38 consecutive patients with spinal fractures and spinal canal narrowing, who were treated conservatively. The results demonstrate that the initial neurological findings have a very significant prognostic value for the neurological outcome, regardless of the spinal segment involved, the type of injury and spinal canal narrowing as demonstrated by computerized tomograms. We conclude that in trauma patients with vertebral fractures and spicules in the spinal canal without evidence of an initial neurological deficit, a favorable neurological prognosis can be predicted, following conservative management.

Adolescent↗

PubMed1997

Expression of several members of the TNF-ligand and receptor family on tonsillar lymphoid B cells.

Although the expression patterns of the members of the tumour necrosis factor receptor and ligand families have extensively been studied by flow-cytometry on stimulated peripheral blood mononuclear cells (PBMNC), little or no flow-cytometric or immunohistological data exist about their expression in lymphoid tissue. According to the data obtained from stimulated PBMNC, several members of these molecule families (e.g. CD40 ligand [CD40L], CD30, CD27, hOX40) have been considered to be either T-cell restricted or strongly T-cell associated. The present study on samples from palatine tonsils revealed that most of these molecules are also expressed by tonsillar B cells. The additional analysis of the co-expression of these molecules also disclosed the existence of CD40+/CD40L+ and CD27+/CD70+ (CD27L+) lymphoid cells in tonsillar tissue.

Antigens, CD↗

PubMed1997

Carbohydrate recognition on MUC1-expressing targets enhances cytotoxicity of a T cell subpopulation.

The influence of the epithelial mucin MUC1 on T cell-mediated lysis was analysed using lymph node lymphocytes (LNL) from patients with colorectal carcinoma. LNL were stimulated with allogeneic, MUC1-transfected B cells and the bulk cultures were cloned. Alloreactive cytotoxic T cell clones were obtained which preferentially lysed MUC1-expressing targets. The majority was CD4+ and MHC-class II-restricted, and a minor group was CD8+ and MHC-class I-restricted. All the clones expressed CD3 and TCR alpha beta, and were CD56-. The capacity to preferentially kill MUC1-expressing targets was stable in several clones for up to 6 months in culture. The enhancing effect of MUC1 on the lysis was investigated in more detail. It was only seen after inhibition of O-linked glycosylation in the targets. Furthermore, this effect was completely abrogated by the monoclonal antibody 3C9, directed against the Thomsen-Friedenreich antigen (T-antigen, Gal beta 1-3GalNAc bound alpha 1-3 to Ser/Thr) as well as by the soluble disaccharide Gal beta 1-3GalNAc, but not by other similar disaccharides. The authors conclude that in their system the preferential killing of MUC1-expressing targets is due to the recognition of an internal carbohydrate epitope accessible on under-glycosylated MUC1, possibly T-antigen, by an auxiliary receptor molecule on T cells.

Antibodies, Neoplasm↗

PubMed1997

Differential expression of apoptosis, Bcl-x and c-Myc in normal and malignant lymphoid tissues.

Bcl-x and c-Myc have an important role for the immune response by regulating the programmed cell death (apoptosis) of lymphocytes. Dysfunction of these selection processes can lead to the development of malignant lymphoma. The present study aimed at defining the differential expression of apoptosis, Bcl-x and c-Myc in normal and in malignant lymphoid tissues. Follicular centre lymphoma (FCL-F) and mantle cell lymphoma (MCL) contained the lowest apoptotic indices (AIs), whereas Burkitt's lymphoma (BL) had the highest AIs. The AIs correlated significantly with the growth rates of the tumours and with the extent of Bcl-x expression. Bcl-x was expressed in almost all BL cells, but in few tumour cells in FCL-F and in MCL. c-Myc, in contrast, was found in the majority of the tumour cells in FCL-F and in MCL, but not in BL. Whereas the extent of Bcl-x expression correlated positively with the growth rates, an inverse correlation was observed between the percentages of c-Myc-positive tumour cells and the growth rates of the tumours. We conclude that normal and malignant lymphoid tissues have a distinct pattern of apoptosis and that expression of Bcl-x and c-Myc in B cell lymphoma is differentially regulated.

Apoptosis↗