Takahiko Horiuchi

Nonsense mutations at Arg-1947 in two cases of familial neurofibromatosis type 1 in Japanese

We report two familial cases of NF1 presenting as C to T transitions changing an Arg-1947 codon to a stop codon. In one of the two families, cosegregation of the mutation with NF1 was demonstrated, indicating this mutation causes the disease in this family. As the same mutation at Arg-1947 has been reported previously in three cases of unrelated Caucasians (two are sporadic; the origin of the other is not reported), the codon at Arg-1947 (CGA) in the NF1 gene is considered to be a hotspot common among different ethnic groups and also among familial and sporadic cases.

Immunological Analysis of T Cells Bearing T Cell Receptor α/β or γ/δ in Patients with Granular Lymphocyte Proliferative Disorder

Immunological analysis of 2 cases of granular lymphocyte proliferative disorder with clonal expansion of CD3+4”8+ T cells bearing either T cell receptor α/β (patient 1) or T cell receptor γ/δ (patient 2) is reported. Significant cyto-toxic activity against K562 was observed in peripheral blood mononuclear cells (PBMC) isolated from patient 2, but not in PBMC from patient 1, although the cytotoxic activity of patient 1 could be augmented following incubation with anti-CD3 monoclonal antibody (MoAb). Northern blot analysis revealed that perforin mRNA was expressed in both patients. Proliferative response to phy-tohemagglutinin, anti-CD3 MoAb and 12-0-tetradecanoylphorbol-13-acetate was low in PBMC from both patients compared to that from healthy controls. Cytoplasmic free calcium of PBMC from the 2 patients increased similarly to that of healthy controls after treatment with anti-CD3 MoAb.

Monoclonal proliferation of double‐negative (CD4−CD8−) T‐cells bearing T‐Cell receptor‐αβ followed by subsequent development of Hodgkin's disease

Expression of CD4 or CD8 on the cell surface is an important guide for discriminating the immunologic functions of T‐cells. However, a minor T‐cell subset lacking both CD4 and CD8 molecules but bearing the usual form of T‐cell receptor (TCR)‐αβ (CD4−CD8−TCR‐αβ+ T‐cells) has recently been found not only in mice but also in humans, and the clinical relevance of this newly defined subpopulation to human diseases is now of considerable interest. The authors present a patient in whom CD4−CD8−TCR‐αβ+ T‐cells showed monoclonal proliferation in the peripheral blood for more than 3 years, then disappeared spontaneously, followed by subsequent development of Hodgkins disease. The pathologic roles of double‐negative T‐cell proliferation in this case are discussed from the viewpoint of premalignancy in lymphoproliferative diseases. Cancer 1994; 73:2818–23.

Interleukin-4 in chronic myelomonocytic leukemia. Growth suppression of hematopoietic precursors in the chronic phase and stimulation in the acute phase.

We examined the effects of interleukin-4 (IL-4) on the growth of hematopoietic precursors from a patient with chronic myelomonocytic leukemia (CMMoL). In the chronic phase of the disease, IL-4 inhibited spontaneous colony formation by CMMoL cells in semi-solid culture. However, in the acute phase, IL-4 promoted colony formation. These effects of IL-4 were abolished completely by the addition of anti-IL-4 neutralizing antibodies. The spontaneous colony formation by CMMoL cells in both the chronic and acute phases was inhibited by the addition of anti-IL-6 antibodies. On the other hand, neither anti-IL-6, anti-granulocyte macrophage colony-stimulating factor (GM-CSF), anti-IL-1 beta nor anti-tumor necrosis factor alpha (TNF alpha) antibodies inhibited IL-4-induced colony formation by CMMoL cells in the acute phase. IL-4 suppressed the production of IL-6 by CMMoL cells in both the chronic and acute phases. These results suggest that in the present patient, IL-4 suppressed the IL-6-mediated autocrine growth of CMMoL cells in both the chronic and acute phases, but directly stimulated their growth in the acute phase.