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While blood vessels clearly have a fundamental role in supplying oxygen and nutrients, and transporting inflammatory cells throughout the body, they are also involved in organogenesis and maintenance. Blood vessels provide a niche that supports self‐renewal of stem cell populations in normal organs. This role unfortunately also extends to the field of cancer biology; it has been suggested that cancer stem cells are located in perivascular regions supporting their proliferation. Through cell‐to‐cell interactions, arteries also have the important function of guiding appropriate migration of neurites. Therefore, analysis of the molecular mechanisms responsible for blood vessel formation and maintenance is important for developing strategies to regulate tissue regeneration. According to the usual concept of angiogenesis, it is widely accepted that homogeneous endothelial cells from preexisting vessels sprout and proliferate during angiogenesis. Recently, however, at least three different endothelial cell types designated tip, stalk and phalanx cells have been suggested to be involved in new blood vessel formation in sprouting angiogenesis. Given this endothelial cell heterogeneity, the involvement of a stem cell system in preexisting blood vessels is proposed. In addition, endothelial cells possess the capacity to differentiate into mesenchymal stem cells upon stimulation with growth factors, and pericytes show stem cell behaviour in their ability to differentiate into a variety of different histotypes. Moreover, under normal physiological conditions, haematopoietic stem cells differentiate into mural cells to provide blood vessel stability. These findings make it necessary to reconsider issues concerning the regulation of blood vessels by accessory cells situated around those vessels.

Streptococcal preparation OK-432 is a bacterial immunopotentiator extensively used in Japan for adjuvant cancer therapy. Using C3H/He mice bearing MH-134 tumour cells, cytokine inductions of tumour necrosis factor-α, interleukin 1β interleukin 6 and interferon-γ were determined in spleen and tumour tissues by reverse transcriptase-polymerase chain reaction analysis. No significant induction of cytokine mRNA was observed after subcutaneous administration of OK-432 (OK-432, sc) or after intratumoural injection of IFN-γ (IFN-γ, it), compared with controls, either in spleen or tumour tissues. In contrast, subcutaneous administration of OK-432 followed by intratumoural OK-432 injection (OK-432, sc+it) was found to induce some cytokine mRNAs significantly. The mRNA levels of tumour necrosis factor α and interferon-γ in spleen tissue and those of interleukin 1β and interferon-γ in tumour tissues were significantly elevated in mice with OK-432, sc+it treatment compared with controls. These results suggest that treatment with OK-432, sc+it effectively induced splenic antitumour immunity as well as local immunity against tumour cells.

MDR1 gene expression was examined in acute leukemia cells from 75 Japanese patients at diagnosis (50 with acute myeloblastic leukemia [AML]: 10 M1, 18 M2, 5 M3, 8 M4, 9 M5; 25 with acute lymphoblastic leukemia [ALL]: 13 B-precursor, 12 T-lineage). The results of MDR1 mRNA expression by reverse transcriptase polymerase chain reaction were confirmed by immunostaining using the anti-P-glycoprotein monoclonal antibody UIC2 and by a functional study using the rhodamine efflux test. Morphologically, AML M1 cases had the highest incidence of MDR1 gene expression (6 of 10 patients). Phenotypically, CD7 and CD34 were the only surface markers that were significantly associated with MDR1 gene expression (P < .01). In CD7+CD4-CD8- ALL, which is thought to originate from the lymphohematopoietic stem cell, expressed the MDR1 gene with a high incidence (six of eight patients), whereas three surface CD3+ and one CD4+CD8+ T-cell ALL (T-ALL) did not have detectable MDR1 transcripts. Only two cases of 13 B-precursor ALL had MDR1 mRNA, one of which had the Philadelphia (Ph1) chromosome. No association was observed between MDR1 gene expression and CD34 positivity in ALL. Our results that MDR1 mRNA was frequently expressed in CD7+ AML and CD7+CD4-CD8- ALL, together with the previous reports indicating clinical similarities between these leukemias, provides a clue to clarify a relationship between CD7+ AML and CD7+CD4-CD8- ALL. In addition, MDR1 expression in CD7+ AML/ALL might be responsible for the poor response to conventional chemotherapies of these types of leukemia.

Twenty-three acute myelocytic leukemia (AML) patients with t(8;21) chromosomal abnormality, all classified as M2 (French-American-British [FAB] classification), were investigated. Blastic cells from all patients were positive for the stem cell-associated antigens, CD34 and HLA-DR, and the immature myeloid antigens, CD13 and CD33. The nonblastic leukemic cells expressed the more mature myeloid antigens, CD11b and CD15, with loss of the immature phenotype. The incidence of positivities for the stem cell-associated antigens, CD34 and HLA-DR, in t(8;21) AML cells was significantly higher in comparison with those in other AML showing granulocytic differentiation (M2 or M3). AML cells with t(8;21) also showed some phenotypic abnormalities. Frequent expression of CD19 was found in the blastic population of t(8;21) AML (18 of 23 cases) without other B-cell antigens and Ig gene rearrangements. CD19 expression was confirmed by immunocytochemistry and Northern blotting. The CD19+ blastic cells coexpressed both CD34 and HLA-DR. In addition, CD33+ cells among the blastic fraction in t(8;21) AML cells were fewer in number than in those of M2 or M3 AML without t(8;21). Our findings indicate that leukemic blasts of t(8;21) AML commonly express CD19 while preserving the stem cell-associated antigens, and differentiate into the granulocytic pathway with discordant maturation such as low CD33 expression.

When forming a sheet metal, the free surface of the sheet becomes rough with increasing plastic strain. This is well known as orange peel phenomena and has a great effect not only on the surface quality of a product but also on the forming limit. In an attempt to increase the forming limit of thin sheet metals, in the present paper, a new forming technique is proposed in which surface asperities generated during the forming process are polished to eliminate the weak portions of the sheet which lead to the onset of a localized necking. Balanced biaxial stretching of aluminium sheets and foils is carried out in this manner, and how the forming limit can be increased is examined. It is shown that the forming limit of sheet metal can be appreciably improved by a simple method of polishing the surface roughness during the stretching process. The polishing of surface roughness at the strain somewhat before the onset of localized necking is recommended to efficiently increase the forming limit. The effect of polishing surface roughness on the forming limit becomes large as the thickness of sheet decreases. For aluminium sheets with 0.1 and 0.2 mm in thickness, for example, the forming limit strains achieved have been about 1.4 times as large as those for the ordinary balanced biaxial stretching without the interstage polishing. When such processes of stretching and subsequent polishing are repeated in turn 2 or 3 times, further increase in the forming limit can be achieved.

TEK, or TIE-2, is a receptor tyrosine kinase (RTK) that is known as a functioning molecule of vascular endothelial cells. TEK comprises a subfamily of RTK with TIE, and these two receptors play critical roles in vascular maturation, maintenance of integrity and remodelling. We generated mAb against the extracellular domain of human TEK protein to elucidate its expression pattern in human hematopoietic cells. Flow cytometric analysis of bone marrow cells revealed that TEK was expressed in 27% of CD34⁺, 20% of c-KIT⁺ cells and 26% of CD34⁺CD38^- cells, indicating that TEK is expressed in a subset of primitive hematopoietic stem cells (HSC). TEK was also expressed in 20% of CD19⁺ B lymphocytes but not in other lineage-committed cells. Progenitor assays in methylcellulose culture showed that CD34⁺TEK⁺ cells formed significantly less BFU-E and CFU-Mix than CD34⁺TEK^- cells, but there was no difference in the number of CFU-GM between these two populations. Two recently identified TEK ligands, termed Angiopoietin-1 and -2, bound to TEK with similar affinities, and Angiopoietin-1 effectively induced TEK phosphorylation in hematopoietic cells. Angiopoietin-2 also induced a low level of TEK phosphorylation and weakened the phosphorylation induced by Angiopoietin-1, suggestive of an elaborate regulator of the TEK-TEK ligand signaling pathway. Although neither ligand affected the proliferation of TEK-transfected hematopoietic cells or the colony formation of CD34⁺TEK⁺ bone marrow cells, both promoted the adhesion of TEK-transfected hematopoietic cells to a collagen matrix or a layer of bone marrow stromal cells. These findings indicate that the TEK-TEK ligand signaling pathway is regulated in a refined manner and is involved in hematopoietic cell-microenvironment interaction.

TEK, or TIE-2, is a receptor tyrosine kinase (RTK) that is known as a functioning molecule of vascular endothelial cells. TEK comprises a subfamily of RTK with TIE, and these two receptors play critical roles in vascular maturation, maintenance of integrity and remodeling. We generated mAb against the extracellular domain of human TEK protein to elucidate its expression pattern in human hematopoietic cells. Flow cytometric analysis of bone marrow cells revealed that TEK was expressed in 27% of CD34+ cells, 20% of c-KIT+ cells and 26% of CD34+CD38- cells, indicating that TEK is expressed in a subset of primitive hematopoietic stem cells (HSC). TEK was also expressed in 20% of CD19+ B lymphocytes but not in other lineage-committed cells. Progenitor assays in methylcellulose culture showed that CD34+TEK+ cells formed significantly less BFU-E and CFU-Mix than CD34+TEK- cells, but there was no difference in the number of CFU-GM between these two populations. Two recently identified TEK ligands, termed Angiopoietin-1 and -2, bound to TEK with similar affinities, and Angiopoietin-1 effectively induced TEK phosphorylation in hematopoietic cells. Angiopoietin-2 also induced a low level of TEK phosphorylation and weakened the phosphorylation induced by Angiopoietin-1, suggestive of an elaborate regulator of the TEK-TEK ligand signaling pathway. Although neither ligands affected the proliferation of TEK-transfected hematopoietic cells or the colony formation of CD34+TEK+ bone marrow cells, both promoted the adhesion of TEK-transfected hematopoietic cells to a collagen matrix or a layer of bone marrow stromal cells. These findings indicate that the TEK-TEK ligand signaling pathway is regulated in a refined manner and is involved in hematopoietic cell-microenvironment interaction.

A new deep drawing process of sheet metals is developed to facilitate small-lot production of deep cups with large drawing ratio. In this process, unlike the conventional deep drawing method, a few drawn cups are always stacked on the punch and used as a part of punch for the subsequent deep drawing of a given blank. Before drawing a new blank, a drawn cup which is in contact with the punch is stripped off. The repetition of such stripping and drawing operations makes it possible to carry out both the first-stage drawing and the subsequent slight redrawings in one drawing operation using only one pair of punch and die. In this paper, this new deep drawing process is applied to the production of tapered cups and the main feature of the process is shown.

Placebo needles that can fool acupuncture practitioners as to the type of needle used have been considered almost impossible to develop until now.