Beta F1 Research Articles

A Rare Case of Primary Cardiac T-cell Lymphoma in Immunocompetent Adult

Abstract Introduction/Objective Primary cardiac lymphoma (PCL) is an extranodal lymphoma involving only the heart and/or the pericardium. It is exceedingly rare, accounting for <2% of primary cardiac neoplasms in a surgical series and 0.05% of a >12,000 autopsies’ series, and is often associated with an immunocompromised state. Most PCL are of B- cell lineage with T-cell lymphoma constituting < 10%. Methods/Case Report We report a case of unexpected sudden death due to primary cardiac T-cell lymphoma in a 48-year-old immunocompetent man without significant medical history who presented in cardiopulmonary arrest following a two-week history of cold-like symptoms. Autopsy revealed an irregular, discontinuous tan plaque on the epicardial surface that extended over the right and left ventricles, and sectioning revealed that extension of the lesion throughout the subvalvular myocardium of the left ventricular wall, interventricular septum, and medial aspects of the right ventricle. The lesion had irregular areas of necrosis and hemorrhage. No lymphadenopathy or other visceral lesions were identified. Histologically, the myocardium had a regionally necrotic, angiocentric infiltrate of atypical, large, pleomorphic lymphoid cells with large, irregular nuclei, vesicular chromatin, and conspicuous nucleoli. Initial immunohistochemical work-up showed a profile of CD45+/CD20-/CD3+ suggesting a T-cell origin with CD8 predominance (CD4-/CD8+). Further work-up demonstrated a profile as CD2+/CD7+/CD25+/CD30+/EBV(EBER- ISH)+/Ki67(70-80%)/ and ALK-1-/BCL6-/CD5-/CD10-/CD56-, supporting extranodal NK/T-cell lymphoma, extranasal type with a cytotoxic T-cell subtype (perforin+/granzyme B+/TIA-1+/TCR Beta F1+). Results (if a Case Study enter NA) NA. Conclusion Primary cardiac lymphoma with cytotoxic T-cell subtype is extremely rare and fatal. This case is the third report over the past two decades, to our knowledge, of a primary cardiac T-cell lymphoma leading to acute heart failure and sudden death in an immunocompetent adult.

CLOSED-FORM SOLUTION TO AN ECONOMIC GROWTH LOGISTIC MODEL WITH CONSTANT MIGRATION

This paper considers a Solow-Swan economic growth model with the labor force ruled by the logistic equation added by a constant migration rate, I. We prove the global asymptotic stability of the capital and production per capita. Considering a Cobb-Douglas production function, we show this model to have a closed-form solution, which is expressed in terms of the Beta and Appell F1 special functions. We also show, through simulations, that if I>0, it implies in a smaller capital and product per capita in the short term, but in a higher capital and product per capita in the middle and long terms. In both cases, these per capita variables converge to the same steady-state given by the model without migration. If I<0 the transient behavior is the opposite. Finally, if I=0, we recover the solution for the pure logistic case, involving Gauss' Hypergeometric Function 2F1.

Poikilodermatous mycosis fungoides with a CD8+ CD56+ immunophenotype: a case report and literature review

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. MF shows varieties in both its clinical presentation and immunophenotype. We herein report one case of poikilodermatous MF with a CD8+ CD56+ immunophenotype and present a literature review. A 20-year-old Japanese woman presented with a 10-year history of multiple poikilodermatous and reddish or brownish patches with mild pruritus on the chest, abdomen, back, buttock and thighs. Histopathologically, small- to medium-sized atypical lymphocytes infiltrated into the epidermis, indicating epidermotropism, along the basal layer, and distributed in band-like appearance in the papillary dermis. Immunohistochemically, atypical lymphocytes expressed CD3, CD8, CD56, T-cell intracellular antigen (TIA)-1, granzyme B and beta F1 but lacked expression of CD4, CD20, CD30 and Epstein-Barr virus (EBV) latent membrane protein 1. An EBV-encoded small non-polyadenylated RNA-1 (EBER-1) signal was not detected. On the basis of these findings, the diagnosis of CD8+ CD56+ MF was established. Poikilodermatous MF with a CD8+ CD56+ immunophenotype, as presented herein, is extremely rare. Although further investigation is needed to fully clarify the nature of this aberrant phenotype of MF, we stress that it is important to recognize this rare immunophenotype of MF to distinguish it from aggressive cytotoxic cutaneous lymphomas.

Closed-Form Solutions to an Economic Growth Logistic Model with Migration

This paper presents a Solow Growth Model with the labor force ruled by the logistic equation added by a constant migration rate, I. We prove the global asymptotic stability of the capital and production per capita. Considering a Cobb-Douglas production function, we show this model to have a closed-form solution. This transient behavior is expressed in terms of the Beta and Appell F1 functions. We also show that if I > 0, it implies in a higher (minor) output of the economy, and in a minor (greater) capital and production per capita in the short term (middle and long term); furthermore, these ratios converge to the same steady-state value of the no-migration model; if I

Subcutaneous panniculitis-like T-cell lymphoma

A 36-year-old woman was referred to our department, in June 2002, because she had a subcutaneous, painful inflammatory large mass located on the right gluteal region, which thereafter extended to the sacral area, accompanied by fever, malaise, myalgias, and enlargement of right inguinal lymph nodes. Laboratory investigations revealed a haemoglobin between 10.5 and 12.8 g/dl; ESR of 18 mm/h; C-reactive protein from 47.0 to 78.5 mg/l; ALT between 26 and 59 U/l; AST from 26 to 52 U/l; alkaline phosphatase 62–127 U/l; gamma GT 70–140 U/l; LDH 539–737 U/l; beta 2 microglobulin 5.2 mg/l. In peripheral blood, lymphocyte subsets were: CD3+ 91.6% (1222 cells/μl), CD4+ 73.3% (978.8 cell/μl), CD8+ 17.8% (237 cells/μl), CD19+ 6.8% (90 cells/μl), CD3-CD56+ 1.7% (22 cells/μl). The CT scan of the thorax, abdomen and pelvis showed a densification of the subcutaneous adipose tissue of the right lumbar region extending to the homolateral gluteal area. There were slightly enlarged inguinal lymph nodes on the right side. Skin biopsies revealed a subcutaneous panniculitic T cell lymphoma: CD8+ and TIA-1+, albeit CD4-negative. There was focal positivity for the beta F1 antibody (beta receptor of the TCR). PCR results on the possible clonal rearrangement of the TCR gene and EBV were negative. Bone marrow and liver biopsies were normal. In August 2002 there was a spontaneous clinical remission. New CT scan was performed which showed a diffuse densification of the subcutaneous tissue of the right lumbar region. Aspirative cytology didn’t reveal neoplastic cells. Therapy with subcutaneous IFN N/A in the dosage of 9, 000, 000 units, 3 times a week, was administered for 36 weeks. Sequential routine blood tests, beta 2 microglobulin and lymphocyte subsets were unremarkable. CT scan of the lumbar region performed every 12 weeks, showed regression of the subcutaneous tissue densification. Presently the patient is in clinical remission.

Testicular natural killer/t-cell lymphoma, nasal type, of true natural killer-cell origin.

The majority of primary testicular lymphomas are of B-cell type. Other primary lymphomas are rarely encountered in the testes. Natural killer (NK)/T-cell lymphomas of nasal type are aggressive extranodal lymphomas associated with Epstein-Barr virus infection that are usually encountered in the upper aerodigestive tract. They also occur in the skin, soft tissue, and colon. Primary testicular NK/T-cell lymphomas are rarely reported. We describe the case of a 66-year-old Korean man who presented with right-sided painless testicular enlargement and underwent radical orchiectomy. Histologic examination revealed an angiocentric and angioinvasive infiltrate of medium to large tumor cells with moderately abundant pale pink cytoplasm and folded and indented pleomorphic nuclei. Paraffin immunohistochemical studies showed positivity of the tumor cells for CD45, TIA-1, granzyme B, CD56, and CD3 epsilon. In situ hybridization showed diffuse positivity for Epstein-Barr virus-encoding RNA. The results of gene rearrangement studies for the gamma chain of the T-cell receptor were negative. The results of paraffin immunohistochemical studies for CD20, CD8, CD45RO, beta f1, and ALK-1 were negative. An extensive workup showed no evidence of lymphoma outside the testes. We report a rare case of primary testicular NK/T-cell lymphoma of the nasal type of true NK-cell origin.

The promoter of the operon encoding the F0F1 ATPase of Streptococcus pneumoniae is inducible by pH

The genes encoding the subunits of the F0F1 membrane ATPase of Streptococcus pneumoniae were cloned and sequenced. The eight genes, transcribed to one mRNA, are organized in an operon encoding the c, a, b, delta, alpha, gamma, beta and epsilon subunits of 66, 238, 165, 178, 501, 292, 471 and 139 amino acid residues, respectively, that were expressed in an Escherichia coli system. To investigate the role of the ATPase in the regulation of the intracellular pH, the expression of the operon between pH 5.7 and 7.5 was studied. An increase in both the ATPase activity and the amount of the alpha and beta F1 subunits as shown by Western blot analysis was observed as the pH decreased. These increases were accompanied by an increase in the atp-specific mRNA, as shown by Northern blot and slot-blot analysis. Primer extension experiments and transcriptional fusions between the atp promoter and the reporter cat gene demonstrated that this pH-dependent increase in the mRNA was regulated at the level of initiation of transcription. Transcription of the operon occurs from a promoter with a consensus -35 box (TTGACA) and a -10 box (TACACT) that differs from the consensus (TATAAT). A point mutation at the -10 box of the promoter (change to TGCACT) avoided this increase, suggesting a role for this sequence in the pH-inducible regulation.

Immunophenotyping of acute lymphoblastic leukaemia in routinely processed bone marrow biopsy specimens.

AIMS: To assess the value of immunophenotyping of acute lymphoblastic leukaemia (ALL) in routinely processed bone marrow trephine biopsy specimens and to establish a minimum panel of antibodies to assess...

Clinical, immunohistochemical and phenotypic features of aggressive nodal cytotoxic lymphomas, including alpha/beta, gamma/delta T-cell and natural killer cell types.

Cytotoxic cells include natural killer (NK) cells and cytotoxic alpha beta and gamma delta T lymphocytes (CTLs). These cells express cytotoxic molecules of T-cell restricted intracellular antigen (TIA-1), and activated cytotoxic molecules of perforin, granzyme B, and FasL. Recent studies suggest that most extranodal T-cell lymphomas are derived from CTLs, and that NK cell lymphomas are extranodal. However, only a few nodal NK and cytotoxic lymphomas have been described so far. We present here the clinicopathological features of seven cases of nodal cytotoxic T and NK cell lymphomas. The study excluded anaplastic large-cell lymphomas expressing cytotoxic molecules. The neoplastic cells of all cases contained activated cytotoxic molecules of TIA-1, granzyme B, Fas ligand, and/or perforin. Phenotypically and genotypically, four cases showed alpha beta T cell type [CD2+, CD3+, T-cell receptor (TCR)-delta-1-, beta F1+, and TCR gene rearrangement], two cases showed gamma delta cell type [CD2+, CD3+, T-cell receptor (TCR) delta-1+, beta F1-, and TCR gene rearrangement], and one case showed NK cell type [CD2+, CD3-, CD56+, T-cell receptor (TCR) delta-1-, beta F1-, and TCR gene germline]. Using Southern blot analysis, Epstein-Barr virus (EBV) sequences were detected in six cases, and monoclonal terminal repeat proliferation was confirmed. In addition, in situ hybridization (ISH) studies for EBV showed EBV infection in almost all neoplastic cells. Clinically, all patients presented with peripheral lymphadenopathy in high clinical stages and showed an aggressive course. Hepatosplenomegaly was detected in six cases. During the course of the disease, bone marrow and extranodal invasion were noted in five cases. The nodal type showed an aggressive clinical course in all cases but one, as did the extranodal type. The nodal type varied in phenotype, but was closely associated with EBV infection.

Primary intestinal gamma‐delta T‐cell lymphoma with evidence of Epstein–Barr virus

Primary intestinal T-cell lymphomas account for about 5% of all primary gastrointestinal lymphomas and are mostly associated with coeliac disease. They usually express the CD3-associated T-cell receptor alpha/beta heterodimer and HML1, and some are related with Epstein-Barr virus (EBV). As far as we know, the present report describes the first case of primary gamma-delta (gamma delta) EBV-associated intestinal T-cell lymphoma without enteropathy. Only hepatosplenic, nasal and cutaneous gamma delta T-cell lymphomas have previously been described. Our case concerned a 43-year-old man with no history of coeliac disease, who presented with multifocal small bowel involvement showing high grade T-cell lymphoma with medium sized and large pleomorphic cells and a small pleomorphic T-cell component. Angioinvasion and angiocentricity were occasionally present. Immunohistochemical studies of lymphoma cells showed a T-cell gamma delta phenotype (CD3+, CD2+, TCR delta 1+, V delta 2+ and beta F1-) without expression of CD4, CD8, CD5, or HML1. Most tumour cells were positive for the cytotoxic granular proteins TiA1 and granzyme B. Rearrangement of the TCR gamma chain gene was demonstrated by polymerase chain reaction and in-situ hybridization with EBER probes revealed strong nuclear positivity in virtually all neoplastic cells. We described the first case of primary intestinal gamma delta T-cell lymphoma without enteropathy in which EBV might fulfil a pathogenic role.

Amino acid residues required for binding of vascular cell adhesion molecule-1 to integrin alpha 4 beta 7.

The homologous Ig-like domains 1 and 4 of vascular cell adhesion molecule (VCAM)-1 present binding sites to the leukocyte integrins alpha 4 beta 1 and alpha 4 beta 7 . In the present study, amino acid substitution mutants were used to identify sequence motifs mediating binding of integrin alpha 4 beta 7 to the first domain of VCAM-1. We demonstrate that binding of integrin alpha 4 beta 7 to VCAM-1 containing the D40A mutation located in the loop between beta strands C1 and D1 was completely abrogated and was not restored by activating integrin binding functions with Mn2+. Thus, the I(39)DSP motif functions as a central recognition site for integrin alpha 4 beta 7. Analysis of the E66A mutation demonstrated that the G(64)NEH sequence, which is exposed on the loop structure between beta strands E1 and F1, represents an additional recognition site for alpha 4 beta 7 integrin. However, the inhibitory effect of the E66A mutation on cell binding was not specific for alpha 4 beta 7 but was also observed for integrin alpha 4 beta 1. In contrast to the I(39)DSP and G(64)NEH sequences, the K(79)LEK motif present in beta strand G1 was involved in binding to alpha 4 beta 1 but not alpha 4 beta 7. The function of G(64)NEH and K(79)LEK motifs in alpha 4++-integrin interactions was confirmed by divalent cation titration assays and peptide inhibition studies. Integrin binding to E66A or E81A;K82A mutants was restored by activation with saturating concentrations of Mn2+. Binding of both alpha 4 beta 1 and alpha 4 beta 7 integrins was not affected by E29A, R36A, E50A or E87A mutations. Together, these results identify the I(39)DSP and G(64)NEH motifs as common recognition sites for both alpha 4 beta 1 and alpha 4 beta 7 integrins, whereas the K(79)LEK sequence appears to confer specificity for alpha 4 beta 1 binding.

Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin

We identified eight cases of T-cell lymphoma with evidence of a gamma delta phenotype over a 13-year period. Seven of these cases conformed to a distinct clinicopathologic entity of hepatosplenic gamma delta T- cell lymphoma. Nearly all of these patients were young adult males (five of seven), with a median age at presentation of 20 years. They presented with marked hepatosplenomegaly, without lymphadenopathy or significant peripheral blood lymphocytosis. Thrombocytopenia was seen in all patients, and five of seven were mildly anemic. The clinical course was aggressive, and despite multiagent chemotherapy, the median survival duration was less than 1 year. The morphologic findings were uniform; a monomorphic population of medium-sized lymphoid cells with moderately clumped chromatin and a rim of pale cytoplasm infiltrated the sinusoids of the spleen, liver, and bone marrow. The cells had a characteristic immunophenotype: CD2+, CD3+, CD4-, CD5-, CD7+, CD16+, CD57-, CD25-, T-cell receptor (TCR)delta +, beta F1-. CD8 was positive in four of seven cases tested, and CD56 was positive in five of six. All cases expressed the cytotoxic granule-associated protein, TIA1, but perforin was detected in only one case. All cases with assessable DNA had a TCR gamma gene rearrangement, and lacked Epstein-Barr virus sequences. Isochromosome 7q was identified in two cases with cytogenetic information. The one case of cutaneous gamma delta T-cell lymphoma differed in its clinical manifestations, histologic appearance, and immunophenotype. We conclude that hepatosplenic gamma delta T-cell lymphoma is a distinct clinicopathologic entity derived from cytotoxic gamma delta T cells, and should be distinguished from other lymphomas of T-cell and natural-killer cell (NK)-like T-cell derivation.

Clinical and hematological characteristics of hepatosplenic T gamma/delta lymphoma with isochromosome for long arm of chromosome 7.

Hepatosplenic T gamma/delta lymphoma is a rare entity of peripheral T cell lymphoma. Three of 386 patients with non-Hodgkin's lymphoma in our institute were found to have this subtype of lymphoma. All had chromosomal abnormalities of isochromosome 7q and trisomy 8. The clinical and hematological features of these three patients are reported. All were males with ages ranging from 23 to 29 years. Initial presentation comprised purpura and variable degree of hepatosplenomegaly. None had superficial lymphadenopathy. Hematologically, they showed pictures resembling immune related thrombocytopenia and/or hemolytic anemia. Examination of the bone marrows revealed hypercellularity with increased number of megakaryocytes and erythroid cells and various degrees of abnormal lymphoid cell infiltration. The histopathologic section of the spleen from one patient who underwent splenectomy revealed abnormal cell infiltration in the sinusoids of the red pulp. Lymphoma cells showed T gamma/delta lymphoid immunophenotype (CD3+ CD2+ CD4- CD8-, TCR delta-1+, and beta F1-). The platelet counts were elevated transiently after initial treatment with corticosteroids, but the condition soon deteriorated. All died of refractory lymphoma five to nine months after diagnosis. Review of the literature, showed that only four other cases have been reported until now and although no cytogenetic data were available for these patients, they had very similar clinical pictures as those in this series. It is suggested that hepatosplenic T gamma/delta lymphoma represents a rare, but distinct, clinicopathological and cytogenetic entity.

γ/δ T-Cell Lymphoma Involving the Subcutaneous Tissue and Associated with a Hemophagocytic Syndrome

A case of gamma/delta-positive T-cell lymphoma localized primarily in the subcutaneous adipose tissue and associated with an extensive hemophagocytic syndrome and a rapid, fatal outcome is presented. Previous reports of gamma/delta cutaneous and subcutaneous T-cell lymphomas are reviewed. To define the characteristics of a T-cell subset of neoplastic cells bearing the gamma/delta receptor in a subcutaneous lymphoma, we undertook clinical and laboratory examinations, morphological evaluation of biopsies, electron microscopy, and extensive immunohistochemical studies. Immunohistochemical studies showed that the neoplastic cells expressed the gamma/delta T-cell receptor (CD3+, C gamma M1+) and were CD2+, CD43+, CD45+, CD45RO+, PCNA+, but were beta F1-, CD1-, CD4-, CD8-, CD15-, CD20-, CD25-, CD30-, CD45R-, CD57-, CD68-, Mac 387-, and HLA Dr-. To the best of our knowledge, this is the first report of a subcutaneous T-cell lymphoma of gamma/delta type involving the subcutaneous tissue and associated with a hemophagocytic syndrome.

Functionally important amino acids in the TCR revealed by immunoselection of membrane TCR-negative T cells.

A spontaneous TCR cell surface variant (3P11) of the Jurkat T cell line is described and characterized. 3P11 was selected by incubation of Jurkat cells with anti-TCR mAb followed by passage through Ig anti-Ig columns and cloning. 3P11 contained mRNA for both Ti alpha and Ti beta and CD3 gamma, delta, epsilon and zeta. Biochemical analyses demonstrated that all of the TCR components were produced in 3P11 cells. The Ti alpha beta/CD3 gamma delta epsilon zeta complex was assembled in the endoplasmic reticulum but the zeta did not associate with this complex. Epitopes recognized by the Ti beta chain specific mAb beta F1 and JOVI as well as anti-V beta 8 were affected in the 3P11 Ti beta chain indicating that the 3P11 Ti beta chain was mutated. Transfection of a wild-type Ti beta cDNA into 3P11 cells reconstituted TCR expression. Sequence analyses of the 3P11 Ti beta chain demonstrated a guanine to adenine change in the second nucleotide of the triplet coding for cysteine191 resulting in a cysteine to tyrosine exchange. Cysteine191 is the C-terminal cysteine involved in the intrachain disulfide bond in the C domain of the Ti beta chain; thus, the 3P11 Ti beta chain did not contain this disulfide bond. Transfection of a site-directed Ti beta chain containing the 3P11 mutation into a Ti beta negative variant of the Jurkat cell line resulted in a TCR phenotype identical with 3P11 demonstrating that the mutation identified in the 3P11 Ti beta chain was the sole cause for the 3P11 defect.

Lymphocyte sub‐populations in the bladder wall in normal bladder, bacterial cystitis and interstitial cystitis

To identify lymphocyte sub-populations within the bladder wall in normal controls, in patients with bacterial cystitis (BC) or interstitial cystitis (IC). Bladder biopsies were taken from 21 patients with IC, four with BC and five normal controls. Immunofluorescent staining of biopsies was performed using monoclonal antibodies to the T cell markers CD3, CD4, CD8, TCR delta 1, delta TCS1, beta F1 and IML. Plasma cells were identified using monoclonal antibodies to IgA, IgG and IgM. The location and numbers of cells were determined. Peripheral blood lymphocyte counts were also performed in each case. T cells (CD4+ and CD8+) were significantly more abundant within the bladder biopsies from patients with interstitial cystitis than in those from the normal controls, and were present within the urothelium and submucosa but not the detrusor. There was no difference between the numbers of T cells present in the biopsies from patients with interstitial cystitis and in those with bacterial cystitis. However, the presence of gamma delta T cells was significantly associated with interstitial cystitis. IgA+ and IgM+ plasma cells were located within the urothelium and submucosa but not the detrusor in patients with IC and the numbers present in these patients were significantly greater than in those with BC or the normal controls. The peripheral blood lymphocyte counts were not altered in any of the study cases. The increased numbers of CD4+, CD8+ and gamma delta cells as well as IgA+, IgG+ and IgM+ plasma cells within the urothelium and submucosa in patients with IC suggest that these cells play an active role in the pathogenesis of the disorder. The previously described abnormal urothelial expression of HLA-DR and hyperexpression of Class I molecules in patients with IC may enable these cells to cause destruction of the urothelium--the end stage of IC.

Lack of restricted T-cell receptor beta-chain variable region (V beta) usage of reactive T-lymphocytes in Hodgkin's disease.

T-cell response against tumour-associated antigens is mediated by the TCR complex. To determine a possibly restricted TCR-V beta repertoire in reactive T-lymphocytes in Hodgkin's disease (HD), 20 cases (of which 10 were EBV-positive cases) were investigated using 14 monoclonal antibodies (MoAbs) recognizing 11 different TCR-V beta region family products and Northern blot analysis with cDNA probes specific for mRNA transcripts of 11 V beta families that were not detectable by MoAbs. Four V beta families (V beta 5, V beta 6, V beta 8, V beta 19) were investigated using both immunohistochemistry (IHC) with anti-V beta MoAbs and Northern blot analysis. Immunohistochemical and Northern blot findings were correlated with the detection of the Epstein-Barr virus (EBV) genome in Hodgkin's and Reed-Sternberg cells (H-RS). The non-neoplastic lymphocytes in HD were predominantly of T-phenotype (CD3+). Most of these cells were TCR-alpha beta+ (beta F1+) and only a few T-cells were reactive for TCR-delta 1 antibody (TCR-gamma delta+). In the majority of cases helper/inducer T-cells (CD4+) outnumbered suppressor/cytotoxic T-cells (CD8+). Labelling of these samples with the panel of 14 anti-V beta MoAbs showed that only a small percentage (0.2-5.5%) of beta F1+ lymphocytes were positive with each of these MoAbs. The proportion of these cells was comparable to that seen in normal tissues. Most TCR V beta+ cells were randomly distributed, but in virtually all cases occasional V beta+ cells pertaining to the various V beta families were seen in close contact to H-RS cells. Using total RNA extracted from malignant and normal tissues, no visible band was detected with the various V beta probes. As determined in the present study, the percentage of T-cells expressing a given V beta family must be > or = 10% to be detected with Northern blot. Thus, the percentage of V beta+ cells expressing V beta families which were explored only with Northern blot were within the same range as those of the 11 different TCR-V beta region families assessed with IHC, i.e. 1-10% of lymphoid cells. The results of the present study show that in HD there is no restricted T-cell V beta repertoire usage regardless of the detection of EBV. In addition, since the various V beta families are represented in T-cell subpopulations forming rosettes around H-RS cells, we conclude that the T-cells attracted by H-RS cells constitute a polyclonal population.

A case of cutaneous T-cell lymphoma expressing γδ T-cell receptors

Cutaneous T-cell lymphoma expressing gamma delta T-cell receptors (TCRs) is rare; only a few cases have been reported. We report another case of the disease that had a fatal outcome and differs from two previously reported cases in its clinical, histologic, and immunohistochemical aspects. The patient had multiple skin tumors with central crusts; she showed no response to chemotherapy and died within 1 year. Histologic findings included perivascular infiltrates in the dermis and subcutaneous tissue with no epidermotropism; the large lymphoid cells had a phenotype of CD1-, CD3+, CD4-, CD8-, CD25-/+, CD30-, CD38-/+, HLA-DR+, and gamma delta TCR (beta F1-, TCR delta 1+, delta TCS1-, Ti gamma A+, BB3-). The differences in the phenotype of gamma delta T-cell malignancies may reflect the uniqueness of its clinical and histologic features. A study of gamma delta T-cell malignancies may disclose important biologic features of gamma delta TCR+ cells.

Investigation of bone marrow lymphocyte subsets in normal, reactive, and neoplastic states using paraffin-embedded biopsy specimens.

Bone marrow lymphocyte subsets in normal and reactive states and in neoplastic diseases involving the marrow were investigated with a select panel of monoclonal antibodies reactive on routinely processed, paraffin-embedded trephine biopsy material. In all cases, the antibodies beta F1 and UCHL1 (CD45RO) stained virtually equal numbers of T cells (reactive and neoplastic), whereas antibody OPD4 stained only about one half of this number of T cells. Antibody L26 (CD20) stained B cells (reactive and neoplastic) in all specimens. The T-cell to B-cell ratio in the normal marrow was between 4:1 and 5:1, and a significant increase in T-cell numbers was observed in reactive and myelodysplastic states. A significant increase in B-cell numbers, however, was seen only in marrow infiltrated by B-cell lymphoma. Bone marrow exhibiting infiltrates of B-cell lymphoma, acute leukemia, or myeloproliferative disorders showed normal or decreased numbers of T cells. These findings show that antibodies UCHL1, beta F1, and L26 can be used to determine the numbers of B and T lymphocytes in paraffin-embedded, formalin-fixed bone marrow specimens and thus may help to distinguish reactive T lymphocytosis from B-cell lymphoma.

Characterization of a strong positive cis-acting element of the human beta-myosin heavy chain gene in fetal rat heart cells.

A strong positive element within the proximal promoter region of the human beta-myosin heavy chain (beta-MHC) gene that is required for high level expression in primary cultures of fetal rat heart cells was localized by transient assays and DNase I footprinting to positions- 277/-298. Using gel shift studies, this sequence was found to bind specifically at high affinity (Kd approximately 4 x 10(-9) M) to a transcriptional factor (beta F1) found in nuclear extracts from rabbit heart. Dimethyl sulfate interference studies suggested that beta F1 may bind as a dimer to two hexameric imperfect direct repeats containing the consensus sequence 5'-(C/G)-T-G-(T/A)-G-G-3'. Gel shift analyses suggested that beta F1 is related to the M-CAT factor, which is known to control muscle-specific expression of the cardiac troponin T gene. A clustered mutation of the region between the putative binding half-sites and within the "M-CAT"-like domain abolished beta-MHC promoter activity. The sequence of the positive element also contains binding motifs for several transcriptional factors that regulate viral and cellular genes, including AP4, AP5, TEF-1, and MyoD-like proteins. When multiple copies of the beta-MHC element were inserted downstream from the transcriptional initiation site of the thymidine kinase gene, it did not act as a classical enhancer, showing some dependence upon orientation.