S-100 beta positive human T lymphocytes: their characteristics and behavior under normal and pathologic conditions

The characteristics of human S-100 beta-positive T lymphocytes (S-100 beta+ T cells) and their fluctuation in peripheral blood under normal and various pathologic conditions were investigated. S-100 beta+ T cells were small lymphocytes with no particular subcellular structures and showed a proliferative response to mitogens. They were present mainly in peripheral blood under normal conditions but accumulated in T zones of lymph nodes with nonspecific T-zone hyperplasia, where numerous interdigitating reticulum cells existed. In healthy adults approximately 1% to 4% (mean 3.4%) of peripheral blood mononuclear cells were S-100 beta+ T cells. The proportion of S-100 beta+ T cells in peripheral blood tended to significantly decrease (less than 0.5%) in patients with neoplastic diseases; this tendency was apparently related to tumor progression.     

Immunohistochemical studies on S-100 beta positive structures in the human hippocampus in regard to age and morphological change of dementia]

The histological localization of S-100 beta protein in the hippocampus of human autopsy brains of 47 males (71-103 years old) and 90 females (56-104 years old) was studied immunohistochemically. Astrocytes and their processes were positively stained, but neuronal cells were not stained. However, Alzheimer's neurofibrillary tangle-like, senile plaque-like and fibrillary spindle figures were stained positively. S-100 beta positive structures increased in grade with age, but not always equally on Alzheimer's neurofibrillary tangles or senile plaques stained by Bodian method. Astrocytes decreased in number with age, and showed marked compensatory hypertrophy of their processes. S-100 beta positive structures seemed to be related to astroglial changes in terms of degeneration or loss of synapses.     

Perfusion temperature during cardiopulmonary bypass does not affect serum S-100beta release

BACKGROUND: The potentially harmful effects of normothermia on neurological outcome during cardiopulmonary bypass (CPB) are controversial. METHODS: In this study, we compared the early and late release patterns of S-100beta, a marker of cerebral injury, after normothermic and moderately hypothermic CPB. Forty-eight patients undergoing coronary artery bypass grafting were randomly assigned to either the normothermia (37 degrees C) or the hypothermia (32 degrees C) group. Serum S-100beta levels were measured until 24 h after CPB. Neurological examination was performed before and after surgery. RESULTS: With the exception of intraoperative blood glucose levels, there were no differences between groups. This also applied to peak S-100beta values (Gr-N: 3.5 +/- 1.9 microg/l; Gr-H: 3.5 +/- 3.4 microg/l) and values after 24 h (Gr-N: 0.32 +/- 0.16 microg/l; Gr-H: 0.35 +/- 0.28 microg/l). CONCLUSIONS: The similar pattern of S-100beta release without evident neurological complications in the normothermia group does not suggest an increase in cerebral injury during normothermic CPB.     

Terminal deoxynucleotidyl transferase expression can precede T cell receptor beta chain and gamma chain rearrangement in T cell acute lymphoblastic leukemia

The nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is thought to contribute to the diversity of certain immunoglobulin and T cell receptor gene rearrangements through the addition of random nucleotides at their variable (V)-joining (J) region junctions. An acute lymphoblastic leukemia (ALL) with an immature T cell phenotype (CD7+, CD5+, CD1+/-, CD2+/-, CD3-, CD4-, CD8-) was found to be TdT+ with germline immunoglobulin heavy chain, T cell receptor beta chain, and T cell gamma chain genes. The data indicate that TdT expression can precede T gamma and T beta rearrangement during T lymphoid ontogeny consistent with its proposed association with the T cell receptor rearrangement process. Southern analysis of certain cases of T-ALL may not result in the detection of a monoclonal population of cells.     

Prognostic significances of tumor-infiltrating S-100 positive dendritic cells and lymphocytes in patients with hepatocellular carcinoma

BACKGROUND/AIMS: To investigate the prognostic significances of dendritic cells and lymphocytes infiltration in hepatocellular carcinoma. METHODOLOGY: The clinicopathological and follow-up data of 44 patients with hepatocellular carcinoma, who underwent curative resection of tumor in our hospital from January 1995 to July 1996, were collected. Immunohistochemical staining was employed to detect the S-100 positive dendritic cells in the tumor tissue, and lymphocytes infiltration was evaluated simultaneously. The relationship of the tumor-infiltrating dendritic cells and lymphocytes to the postoperative recurrence-free time and survival rate was analyzed. RESULTS: Either the tumor-infiltrating dendritic cells or the tumor-infiltrating lymphocytes alone had no significant relationship to the postoperative recurrence-free time and survival rate. By taking into consideration both tumor-infiltrating dendritic cells and lymphocytes simultaneously, the patients were classified into two groups. Group A included patients having dendritic cell counts > or = 20 cells/10 high power fields together with positive lymphocytes infiltration (n = 17), and group B consisted of patients having dendritic cell count > or = 20 cells/10 high power fields but with negative lymphocytes infiltration or dendritic cell count < 20 cells/10 high power fields with either positive or negative lymphocytes infiltration (n = 27). There were no significant differences in clinicopathological features between two groups. The recurrence-free time was markedly longer in group A as compared with group B, with a median time of 21.6 months for group A and 4.1 months for group B (P < 0.05). The 1-, 3-, 4-year survival rates were significantly greater in group A than those in group B, being 83.5% vs. 42.2%, 61.8% vs. 28.4% and 48.7% vs. 23.0%, respectively (P < 0.01). CONCLUSIONS: Marked infiltration of dendritic cells together with lymphocytes in tumor tissue was closely related to the improved clinical prognosis in patients with hepatocellular carcinoma, and represented as an independent prognostic factor.     

Allogeneic CAR T cell therapies for leukemia

Allogeneic chimeric antigen receptor T (CAR T) cells can offer advantages over autologous T cell therapies, including the availability of “fit” cells for production, and elimination of risks associated with inadvertent transduction of leukemic blasts. However, allogeneic T cell therapies must address HLA barriers and conventionally rely on the availability of a suitable HLA-matched donor if graft-vs-host-disease and rejection effects are to be avoided. More recently, the incorporation of additional genome editing manipulations, to disrupt T cell receptor expression and address other critical pathways have been explored. Clinical trials are underway investigating non-HLA matched T cells expressing anti-CD19 CARs for the treatment of B cell acute lymphoblastic leukemia (B-ALL) and anti-CD123 CAR for acute myeloid leukemia (AML). Such approaches continue to be refined and improved to widen accessibility and reduce the cost of T cell therapies for a wider range of conditions.     

Neurotrophic protein S100 beta stimulates glial cell proliferation.

Nervous system development involves a coordinated series of events, including regulation of cell proliferation and differentiation by specific extracellular factors. S100 beta is a neurotrophic protein that has been implicated in regulation of cellular proliferation, but direct evidence was lacking. In this report, nanomolar concentrations of S100 beta are shown to stimulate proliferation of rat C6 glioma cells and primary astrocytes. An S100 mutant with a single amino acid change was inactive. S100 beta also stimulated increases in the steady-state levels of c-myc and c-fos protooncogene mRNAs and complemented the effects of platelet-derived growth factor. Two neuroblastoma cell lines did not proliferate in response to S100 beta, suggesting that the mitogenic activity of S100 beta is selective for astroglial cells. These results suggest that S100 beta may be involved in the coordinate development and maintenance of the central nervous system by synchronously stimulating the differentiation of neurons and the proliferation of astroglia.     

T cell leukemia presenting as chronic polyarthritis

T cell leukemia was detected in a woman who suffered from chronic polyarthritis. The peripheral blood leukocytes were increased in number and consisted of lymphocytes, 95% of which could be identified as T lymphocytes. T cell infiltration was found in the bone marrow, the synovial fluid, and tissue, and in nodules macroscopically resembling rheumatoid skin lesions. Further investigation of these cells by enzyme chemistry, immunohistochemistry, electron microscopy, and cytochemistry revealed that they had irregularly indented nuclei, no alpha-naphthyl acetate esterase activity, and only faint granular acid-phosphatase activity. The cells were negative for Ia-like antigen and surface immunoglobulin. Analysis of the cell surface glycopeptides showed the presence of abnormally enlarged carbohydrate structures. These data suggest that these leukemic T cells are a malignant equivalent of immature T cells.     

Leukopenic chronic T cell leukemia mimicking hairy cell leukemia: association with human retroviruses

We report two cases of a T cell lymphoproliferative disease not previously described, with cytologic and clinical features similar to those associated with Galton's "prolymphocytic" leukemia (PL). Our patients, like those with Galton's PL, had massive splenomegaly and minimal or absent hepatomegaly and lymphadenopathy. In contrast, however, our patients had leukopenia, as well as low percentages of leukemic cells in the peripheral blood and in the bone marrow. In splenic imprints, the nuclear chromatin pattern of most of the leukemic cells was intermediate between those of mature lymphocytes and those of lymphoblasts, and the nuclei contained single, centrally located, conspicuous nucleoli. In sections of the spleen, the leukemic cells diffusely infiltrated the red pulp in a pattern strikingly similar to that of hairy cell leukemia; however, when the leukemic cells were studied cytochemically, the cytoplasmic acid phosphatase positivity was punctate and tartrate-sensitive. The leukemic cells were sheep erythrocyte rosette-positive and expressed T cell-associated antigens. Initially, both patients responded well to therapeutic splenectomy. One patient received combination chemotherapy after splenectomy and is alive and well 24 months after diagnosis. The other patient was in complete clinical remission for one year after splenectomy and received chemotherapy at relapse. He died, however, 23 months after splenectomy, with disseminated disease. IgG antibody titers against human T lymphotropic virus type I (HTLV-I) were detected in one patient and against HTLV-II in the other. The leukemia in these patients represents a distinct clinicopathologic entity within the spectrum of peripheral T cell lymphoproliferative diseases that includes Galton's PL of T cell derivation, T cell chronic lymphocytic leukemia, T cell hairy cell leukemia, and adult T cell leukemia/lymphoma.     

Early T cell differentiated chronic myeloid leukemia blast crisis with rearrangement of the breakpoint cluster region but not of the T cell receptor beta chain genes

Early T cell differentiation is described in a case of Philadelphia chromosome-positive chronic myeloid leukemia (CML) in blast crisis, supporting multi-lineage differentiation potential of CML precursor cells. In the absence of myeloid markers, strong positivity for terminal deoxynucleotidyl transferase (TdT) and reactivity with T cell antibody 3A1, but lack of more mature T cell antigens, provided evidence for immature T cell differentiation. Molecular analysis of the breakpoint cluster region (bcr) in chromosome 22 revealed a rearrangement and thus confirmed the CML origin of the early T cell blasts. T cell receptor beta chain sequences were found in germline configuration and therefore suggest a very immature stage of T cell differentiation in the CML blasts.     

A case report of T cell prolymphocytic leukemia and Kaposi sarcoma and a review of T cell prolymphocytic leukemia

T cell prolymphocytic leukemia (T-PLL) is a rare mature T cell lymphoproliferative disease. It has been associated with an aggressive course, a poor response to conventional chemotherapy and a short median survival. Here we present a rare case of concurrent T-PLL and Kaposi sarcoma who achieved a complete hematologic and cytogenetic remission after a very short course of treatment with alemtuzumab. A review of T-PLL was done. In this review, clinical features, laboratory features and current therapeutic strategies of T-PLL are presented.     

Serum S-100beta protein release in coronary artery bypass grafting: laminar versus pulsatile flow.

BACKGROUND: Cerebral injury after Cardiopulmonary bypass (CPB) is still a serious and unpredictable complication. The S-100beta serum marker has been suggested as potentially useful in the detection of cerebral injury during and after CPB. Direct comparisons of whether laminar or pulsatile pump flow in CABG leads to higher S-100beta values and which type might be more neuroprotective have not been made so far. METHODS: All 21 patients of the study were undergoing CABG for the first time and had no history of cerebral disease in whatever form. They were divided into two groups: laminar (n = 10) versus pulsatile (n = 11) pump flow. In all cases, a St?ckert roller pump (Fa. St?ckert, Munich, Germany) with a laminar and pulsatile running mode was used for cardiopulmonary bypass. Serum S-100beta levels were detected using a monoclonal immunoradiometric assay (Sangtec Medical AB, Bromma, Sweden). In total, 5 different samples were drawn per patient, starting before intubation and ending 36 hours after surgery. RESULTS: S-100beta peak values were found at skin closure. Median levels were lower in the pulsatile group. Due to the small study group and wide range, results are non-significant. CONCLUSION: The results indicate that pulsatile flow might have a more neuroprotective effect than laminar flow as S-100beta values were lower.     

Myofibroblasts and S-100 protein positive cells in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial pneumonia.

The aim of this study was to investigate whether idiopathic pulmonary fibrosis (IPF) can be distinguished from rheumatoid arthritis (RA)-associated interstitial pneumonia (RA-IP) by means of quantitatively assessing myofibroblasts and S-100 protein positive dendritic cells. Seven patients with IPF and twelve with RA, in whom the pathological findings were consistent with usual interstitial pneumonia (UIP) were studied. Antibodies to vimentin, alpha-smooth muscle actin (alpha-SMA) and S-100 protein were used for immunohistochemical studies performed using the streptavidin/biotin/peroxidase complex method, applied to dewaxed sections from each case. In fibrosis of RA-IP, appearance of both vimentin- and alpha-SMA-positive cells, namely myofibroblasts, was widely observed, together with the pathological patterns of honeycombing, UIP and bronchiolitis obliterans-organizing pneumonia (BOOP). Fibrosis, in cases of chronic IPF, was found to be characterized mainly by vimentin-positive but alpha-SMA-negative fibroblasts. Pulmonary tissues from RA-IP patients especially when associated with a BOOP pattern, contained many cells positive for S-100 protein. However, such cells were generally hard to find in cases of IPF. These findings suggests that idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial pneumonia can be differentiated from each other, to some extent, based on the appearance of myofibroblasts and the presence of S-100-positive dendritic cells.     

Intrafamilial transmission of adult T cell leukemia virus

In an investigation of the mode of transmission of adult T cell leukemia virus (ATLV) in family settings, 275 male and 444 female subjects positive for antibody to ATLV-associated antigen (anti-ATLA) were studied. Their children were surveyed for anti-ATLA status. None of the 82 children of a positive father and a negative mother were positive for anti-ATLA. In contrast, the antibody prevalence among children with a positive mother and a positive or negative father was 27.9% and 19.9%, respectively. Of 39 parents who had one or more anti-ATLA-positive children less than 20 years old, 56.3% of the fathers and 97.1% of the mothers were anti-ATLA positive. Algorithm computation showed the possibility of ATLV transmission from husband to wife to be 60.8% and from wife to husband to be 0.4% over a 10-year period. These data suggest that ATLV is transmitted from mother to child and from husband to wife in family settings.     

T cell prolymphocytic leukemia with new chromosome rearrangements

A 77-year-old woman presented to the outpatient hematology clinic in August 2001 with leukocytosis, recurrent bacterial infections, sweating and weight loss. Bone marrow biopsy showed 80% infiltration with lymphoid cells having a prolymphocytic morphology. Flow-cytometric immunophenotype analysis showed that over 80% of the cells were positive for CD2, CD3, CD4, CD5 and CD7 antigens and negative for terminal deoxynucleotidyl transferase and CD1a antigens. T cell prolymphocytic leukemia (T-PLL) was diagnosed on the basis of these findings. The diagnosis was later confirmed by cytogenetic analysis and fluorescence in situ hibridization. The patient had the following karyotype: 46,X,der(X)t(X;3) (q28;p25) t(X;16)(p14;q12), der(3) t(X;3)(q28;p25), der(6) t (X;6) (p14;q25), (8) (q10), del(11) (q14q23), der(13) t (5;13) (q34;p11), der(13) t(13;14)(q22;q11), inv(14)(q11q32), der (16) t(X;16)(q28;q12), r(17)(p13q21), der(20) t(17;20) (q21; q13),22p+. The cytogenetic rearrangements der(6)t(X;6) (p14;q25), der(13)t(13;14)(q22;q11),t(5;13)(q34;p11), r(17) (p13q21) and t(17;20)(q21;q13) have not been described previously in the literature in patients with T-PLL.     

Immunological characterizations of adult T cell leukemia cells

Profiles of antigens, associated with activation of normal T cells, on adult T cell leukemia (ATL) cells obtained from ATL patients with various clinical stages (acute, chronic, smoldering), were examined. The expressions of Ki 67, OKT 9 and CD 38 antigens were correlated with the spontaneous 3H-thymidine uptake and also with the severities of the disease. CD 25 and CD 28 antigens were expressed on ATL cells from all clinical stages. A loss of CD 7 antigen was observed in peripheral blood ATL cells. HLA-DR antigen was detected on smoldering and chronic ATL cells, but the antigen was not present on acute ATL cells. Surprisingly, both of these antigens were present on lymph-node ATL cells, which proliferate 15-50 fold more than peripheral blood ATL cells do. These findings confirmed that ATL cells preferentially proliferate in lymph nodes, and CD 7 and HLA-DR antigens might contribute to the proliferation. A cDNA named pLD 78 was isolated from a library constructed from the poly (A)+RNAs of tumor promoter and mitogen stimulated human tonsillar lymphocytes, using a differential hybridization technique. pLD 78 DNA sequence codes for a polypeptide consisting of 92 amino acid residues, including a putative signal sequence. A computer search with the National Biomedical Research Foundation library showed that this proteis had homologous sequences with several proteins, which are involved in inflammation and tumorigenesis. The highest homology was found with mouse macrophage inflammatory protein (MIP).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacologic marrow purging in murine T cell leukemia

Deoxycoformycin in combination with deoxyadenosine was used to purge 6C3HED malignant T cells from murine marrow in vitro. Adenosine deaminase activity of 6C3HED cells was ablated by incubation with 10(- 6) mol/L deoxycoformycin (dCF). During a 12-hour incubation with 10(-6) mol/L dCF and 10(-4) mol/L deoxyadenosine, tumor cells sequentially accumulated dATP, became depleted of NAD followed by ATP, then died. More than 5 logs of 6C3HED cells were killed as measured by survival of mice injected with treated tumor cells. Identical incubation of 5 x 10(6) marrow cells did not interfere with rescue of syngeneic lethally irradiated mice. Long-term survival was demonstrated in 12 of 14 mice that received marrow that had been contaminated with 5% 6C3HED cells, incubated with deoxycoformycin and deoxyadenosine, then used to rescue lethally irradiated mice. This murine model provides information not available from in vitro assays and may be useful in the development of strategies to purge malignant T cells from marrow.     

中枢神经系统转移癌患者脑脊液S-100 β蛋白含量测定

目的　测定中枢神经系统 (CNS)转移癌患者脑脊液 (CSF)S 10 0 β蛋白含量 ,并探讨其对CNS转移癌患者脑损伤的评估价值。方法　CNS转移癌患者重度组 7例 ,中度组 10例 ,轻度组 8例 ;2 0例作为正常对照。CSFS 10 0 β蛋白含量采用酶联免疫吸附试验双抗体夹心法检测 ,同时进行CSF细胞学检查。结果　CNS转移癌重度、中度和轻度三组患者CSFS 10 0 β蛋白含量均明显高于对照组(P均 <0 .0 1) ,其中重度组 >中度组 >轻度组 ;重度组患者CSF淋巴细胞比例最低 ,且与对照组和轻度组比较差异有显著性 (P <0 .0 1和P <0 .0 5 )。结论　CNS转移癌患者CSFS 10 0 β蛋白含量高低与脑组织损伤的严重程度呈正相关。