For the oncogenesis of many malignancies, it is crucial to prevent the shortening of the telomeres by the action of telomerase. In this study, clinical data and disease outcomes were analyzed in conjunction with the telomerase activity (TA) and telomere length (TL) of peripheral blood mononuclear cells. The study was carried out in 22 patients with adult T-cell leukemia (ATL) (7 chronic and 15 acute types) and in 13 asymptomatic human T-lymphotropic virus type 1 (HTLV-1) carriers. The mean values of TA in acute and chronic type patients were 13.8 and 1.6 total product generated (TPG) units, respectively, as determined by telomeric repeat amplification assays. The mean TA values in HTLV-1 carriers and healthy volunteers were 1.8 and 0.7 TPG, respectively. The mean TA value in acute type patients was significantly higher than in the three other subject groups. The mean TL values in patients with acute and chronic types were 5.39 and 4.38 Kb, respectively, while the mean TL values in HTLV-1 carriers and healthy volunteers were 7.69 and 7.06 Kb, respectively. The mean TL values in all ATL patients and in non-ATL subjects were 5.2 and 7.3 Kb, respectively. The former value is significantly shorter than the latter (p < 0.01). Neither TA nor TL of ATL cells showed any significant association with the number of ATL cells, serum soluble interleukin-2 receptor, or serum lactate dehydrogenase in the peripheral blood of acute type patients. This suggests that the levels of TA and TL did not reflect the ATL tumor load. The median survival period of acute ATL patients with high TA and shortened TL was 0.47 years, however, which was significantly shorter than that of acute ATL patients with low TA and normal TL (4.21 years) (p < 0.002). These data suggest that high TA and shortened TL were associated with poorer prognosis, and that TA and TL may be novel markers for the prognosis of ATL patients.

These results suggest that HGF/SF is a possible regulatory factor for TPO gene expression and that HGF/SF increases platelet production through an enhancement of TPO mRNA expression in the livers of cirrhotic rats.

Most foraminifera, simple unicellular protists, create calcareous shells with precisely controlled architectures. We investigated the crystal fabric of porous shells of a hyaline radial foraminifer, Ammonia beccarii.The complex structures of the calcitic shell include micrometric single-crystalline domains around a straight pore ∼2 μm in diameter which are divided by strained intermediate regions. The c axes of calcite in the domains were almost perpendicular to the shell surface. The mesoscopic textures, such as periodic lateral lines with a ∼200-450 nm interval and vertical cracks with a ∼150 nm interval, were observed throughout the single-crystalline domains in the shell wall. Specific mechanical properties, such as a lower Young's modulus and a higher hardness of the shells than those of Iceland spar, are ascribed to the presence of the specific mesoscopic textures.

We produced bunched aragonite nanorods through crystal growth controlled by an acidic polysaccharide, alginate, in a supersaturated solution. The highly ordered arrays of c-axis-elongated aragonite nanorods ∼100 nm in diameter were grown on the (001) surface of a singlecrystalline aragonite substrate with specific adsorption of the soluble polysaccharide. Freestanding films consisting of ordered aragonite nanorods were obtained by using an insoluble polysaccharide, anhydrous chitosan, as a template for nucleation of the metastable phase. The orientation of the ordered rods in the films was improved by repetition of the crystal growth. Parallel control of the polymorphism, orientation, and morphology by molecular controlled crystal growth provides biomimetic hierarchical architectures of the metastable calcium carbonate crystals. ■ INTRODUCTIONA number of calcium carbonate (CaCO 3 )-based biominerals combine a macroscale single-crystalline body and a unique microstructure expressing excellent features, such as high mechanical strength, 1−6 specific optical properties, 7 and structural colors. 8 In the microstructure of seashells, thermodynamically stable calcite-type CaCO 3 is used for the prismatic layers and foliated structures, and metastable aragonite-type CaCO 3 mainly composes the nacreous layers and cross-lamellar structures. 9−11 In particular, the nacres and cross-lamellae composed of aragonite have received attention as an excellent model for lightweight and tough structural materials because of their superior mechanical properties. 4 The nacreous layers in bivalves are composed of polygonal aragonite platelets 200−800 nm thick and with an edge length of 2−8 μm, which consist of nanocrystals several tens of nanometers in size. 12−14 Interestingly, elongated acicular crystallites were observed in the nacreous tablet after various etching processes. 15 Bunched aragonite rods ∼100 nm in diameter are alternately stacked in the cross-lamellae of gastropods, bivalves, and scaphopods. 16−19 Especially, the bundled aragonitic fibers elongated in the c axis are clearly found as the third-order unit in the cross-lamellae of several bivalves. 18,19 The coral skeletons are also composed of bundled aragonite rods. 20−22 The particular bunched structures consisting of aragonite nanorods would provide a clue for development of new types of lightweight and tough structural materials. On the other hand, the synthesis of the biomimetic microstructures has not been achieved in artificial systems.In ambient conditions, thermodynamically stable calcite is produced preferentially. Thus, formation of thermodynamically metastable aragonite has been attained by changing the growth conditions, such as temperature, concentration, impurities, and coexisting substrates, in supersaturated calcium carbonate solutions. 23 A nacre-like aragonite film was directly fabricated on a natural aragonitic nacre substrate at room temperature. 24 The presence of a magnesium ion promoted the aragonite formation through inhibition of the growth of ...

A patient with acute adult T-cell leukemia (ATL) in whom spontaneous remission was observed without any specific treatment having been given is described. The abnormal cell phenotype was CD4+, CD45RO+ and CD8-. As the number of abnormal cells decreased, CD4+ cell count decreased and CD8+ cells and CD45RA+ cells increased to normal levels (45 and 77%, respectively). Further, the number of cells with CD45RO antigen of intermediate fluorescence intensity increased. Five months after admission, we assessed the patient as being in a state of complete clinical remission; no abnormal cells were detected in peripheral blood, lymph node enlargement had disappeared and the serum chemistry was normal. When the abnormal cells in peripheral blood had disappeared, Southern blot analysis for HTLV-I proviral DNA still revealed a weak monoclonal band with EcoRl digestion, and HTLV-I proviral DNA was detected by polymerase chain reaction analysis. Thus, it appeared that very few abnormal cells persisted although the laboratory findings for ATL were normal. Our case could contribute to the understanding of the mechanism that underlies spontaneous remission in ATL.

To determine the mechanism of the purified protein derivative (PPD)-specific hyporesponsiveness in Mycobacterium bovisBCG-vaccinated human T-cell leukemia virus type 1 (HTLV-1)-infected individuals, we examined cytokine production in response to PPD in the following four groups of individuals: (i) HTLV-negative, PPD nonresponders (n = 11; NN); (ii) HTLV-negative, PPD responders (n = 18; NP); (iii) HTLV-positive, PPD nonresponders (n = 15; PN); and (iv) HTLV-positive, PPD responders (n = 15; PP). In vitro stimulation with PPD resulted in both proliferative responses and gamma interferon (IFN-γ) production in NP and PP (P < 0.02), with minimal proliferation and IFN-γ production in the NN and PN groups. Further, PPD-specific interleukin 10 (IL-10) production was significantly reduced in the PN group (P < 0.01), while the other groups had comparable levels. Cytokine reconstitution experiments demonstrated that while addition of recombinant IL-12 (rIL-12) plus anti-IL-4 restored PPD-specific responses in the NN group, it had no effect in the PN group. However, addition of rIL-12 resulted in the increased production of IFN-γ in both nonresponder groups (NN and PN), suggesting that the lack of IFN-γ production was not responsible for the PPD anergy. We conclude that PPD-specific anergy in HTLV-1-infected individuals appears to be due in part to their inability to respond to rIL-12.

We conducted a phase II clinical study to evaluate the therapeutic efficacy of cladribine (2-chlorodeoxyadenosine [2-CdA]) in the treatment of Japanese patients with hairy cell leukemia (HCL). Seven patients with classic HCL and 3 with a prolymphocytic HCL variant were administered 2-CdA (0.09 mg/kg per day) by continuous intravenous infusion for 7 days. Seven patients responded to this therapy, with 5 patients achieving a complete response (CR). After a median follow-up of 792 days (range, 599-1253 days), there were no cases of clinical relapse, and the median duration of the response in the responders was 670+ days (range, 470+ to 1121+ days). The median duration of the CR in the CR patients was 953+ days (range, 480+ to 1121+ days). At treatment initiation, most patients had hematologic impairment as a manifestation of HCL. During the early stage after administration, further hematologic impairment occurred, but subsequent peripheral blood counts gradually recovered as 2-CdA treatment showed antitumor activity. Infections occurred at a high incidence at this time, but all cases could be controlled with appropriate treatment. 2-CdA was surmised to represent a useful therapeutic approach for Japanese patients with HCL.

Aragonite helical fibers in the shell of a pteropod Cavolinia globulosa are shown to consist of single-crystalline rod-like building blocks ∼1 μm long and ∼100–200 nm wide. Although the building blocks of the orthorhombic crystal share similar c-axis orientations along the surface normal, their a and b directions rotate in a stepwise fashion. The crystallographic rotation of the unit rods and the twisted stacking of the fibers along the helical axis form the specific hierarchical architecture of the pteropod shell.