Expression of TCL1 in hematologic disorders.

OBJECTIVE: TCL1, MTCP1 and TCL1b are three members of a new family of oncogenes that are expressed in T cell leukemias of ataxia telangiectasia patients (T-PLL, T-CLL). TCL1 is located at 14q32.1 and activated by juxtaposition to the alpha/delta-locus at 14q11 or beta-locus at 7q35 of the T cell receptor during the reciprocal translocations t(14;14)(q11;q32), t(7;14)(q35;q32), or inversion inv(14)(q11;q32). TCL1 encodes a predominantly cytoplasmic protein of 114 aa (14 kD) of unknown function. Recent studies suggest that TCL1 promotes cell survival rather than stimulating cell proliferation, as previously proposed. METHODS: In an attempt to clarify the contexts in which TCL1 is expressed, we investigated TCL1 expression in 114 lymphoma and leukemia patients by Northern blot, RT-PCR and immunohistochemistry. RESULTS: TCL1 expression is restricted to lymphoid cells, and is found in neoplastic (T and B cell neoplasms, and Hodgkin's disease) and nonneoplastic proliferations (reactive lesions). Out of 114 cases, 18 neoplasms of myeloid and 4 cases of epithelial origin were TCL1-negative. In lesions of the lymphoid system, both low- and high-grade lymphomas were found to express TCL1. CONCLUSIONS: We propose that TCL1 expression especially in high-grade B cell non-Hodgkin's lymphomas might interfere with B cell differentiation and promote the transition from low- to high-grade lymphoma.

Expression of nitric oxide synthase III in human thyroid follicular cells: evidence for increased expression in hyperthyroidism.

Nitric oxide mediates a wide array of cellular functions in many tissues. It is generated by three known isoforms of nitric oxide synthases (NOS). Recently, the endothelial isoform, NOSIII, was shown to be abundantly expressed in the rat thyroid gland and its expression increased in goitrous glands. In this study, we analyzed whether NOSIII is expressed in human thyroid tissue and whether levels of expression vary in different states of thyroid gland function. Semiquantitative RT-PCR was used to assess variations in NOSIII gene expression in seven patients with Graves' disease, one with a TSH-receptor germline mutation and six hypothyroid patients (Hashimoto's thyroiditis). Protein expression and subcellular localization were determined by immunohistochemistry (two normal thyroids, five multinodular goiters, ten hyperthyroid patients and two hypothyroid patients). NOSIII mRNA was detected in all samples: the levels were significantly higher in tissues from hyperthyroid patients compared with euthyroid and hypothyroid patients. NOSIII immunoreactivity was detected in vascular endothelial cells, but was also found in thyroid follicular cells. In patients with Graves' disease, the immunostaining was diffusely enhanced in all follicular cells. A more intense signal was observed in toxic adenomas and in samples obtained from a patient with severe hyperthyroidism due to an activating mutation in the TSH receptor. In multinodular goiters, large follicles displayed a weak signal whereas small proliferative follicles showed intense immunoreactivity near the apical plasma membrane. In hypothyroid patients, NOSIII immunoreactivity was barely detectable. In summary, NOSIII is expressed both in endothelial cells and thyroid follicular cells. The endothelial localization of NOSIII is consistent with a role for nitric oxide in the vascular control of the thyroid. NOSIII expression in thyroid follicular cells and the variations in its immunoreactivity suggest a possible role for nitric oxide in thyrocyte function and/or growth.

Immunohistochemical demonstration of interleukin-1 beta induced changes in acute-phase proteins and albumin in rat liver.

Interleukin-1 beta is a potent mediator of the acute-phase response. However, the effects of interleukin-1 beta administration on the topic in vivo production of acute-phase proteins and albumin are so far not well understood. Overnight fasted rats were subcutaneously injected with 0.2 mL 0.9% NaCl (control group) or 6.25 micrograms recombinant human interleukin-1 beta, and rectal temperature was measured at intervals up to 48 h. Livers were perfused-fixed in vivo prior to injection (base-line), and at 9, 24, and 48 h following the interleukin-1 beta injection. Fibrinogen, orosomucoid (alpha 1-acid glycoprotein) and albumin were immunostained using a streptavidin-biotin-immunoperoxidase technique. Rectal temperature peaked 5 h after the single interleukin-1 beta injection, and fell gradually to base-line values by 24 h. Prior to injection only a few hepatocytes, randomly scattered throughout the liver lobule, stained positive for fibrinogen and orosomucoid. In contrast, all hepatocytes stained uniformly positive for fibrinogen and orosomucoid 9 h after interleukin-1 beta injection, whereas at 24 h a predominant centrilobular staining pattern occurred. Due to fasting, albumin positive hepatocytes were already reduced at base-line in both groups. Interleukin-1 beta induced a further significant loss of albumin positive cells in the periportal zone (35 +/- 21%) at 9 h when compared with controls (58 +/- 11%, p = 0.037). In conclusion, subcutaneous interleukin-1 beta (probably by stimulation of interleukin-6) strongly induces fibrinogen and orosomucoid expression in rat liver, and suppresses immunohistochemically stainable albumin in a heterogenous way, mainly in the periportal zone.