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We developed a 300,000-pixel ultrahigh-speed CCD with a maximum frame rate of 2,000,000 frames per second. The shooting speed of the CCD was possible by directly connecting CCD memories, which record video images, to the photodiodes of individual pixels. The simultaneous parallel recording operation of all pixels results in the ultimate frame rate. We analyzed a voltage wave pattern in the equivalent circuit model of the ultrahigh-speed CCD by using a SPICE simulator to estimate the maximum frame rate. The pixel area was consisted of 410 and 720 pixels in the vertical and horizontal and divided into 8 blocks for parallel driving. An equivalent circuit of one block was constructed from an RC circuit with 410 × 90 pixels. The voltage wave pattern at the final stage of an equivalent circuit was calculated when a square wave pulse was input. Results showed that the square wave pulse became blunt when the driving speed was increased. After estimation, we designed the layout of the new ultrahigh-speed CCD V6 and fabricated the device. Results of an image capturing experiment indicated a saturation signal level of 100% that was maintained up to 300,000 frames per second. A saturation signal level of 50% was observed in 1,000,000 frames per second and of 13% in 2,000,000 frames per second. We showed that the maximum frame rate is dependent on a drop of the saturation signal level resulting from the driving voltage wave pattern becoming blunt.

Background: The dodecapeptide HHLGGAKQAGDV (H12), corresponding to the fibrinogen γ‐chain carboxy‐terminal sequence (γ400‐411), is a specific binding site of the ligand for platelet GPIIb/IIIa complex. We have evaluated H12‐coated nanoparticles (polymerized albumin or liposome) as platelet function‐supporting synthetic products. Objectives: To strengthen the hemostatic ability of H12‐coated particles as a platelet substitute, we exploited installation of a drug delivery function by encapsulating adenosine diphosphate (ADP) into liposomes [H12‐(ADP)‐liposomes]. Methods and results: Via selective interaction with activated platelets through GPIIb/IIIa, H12‐(ADP)‐liposomes were capable of augmenting agonist‐induced platelet aggregation by releasing ADP in an aggregation‐dependent manner. When intravenously injected into rats, liposomes were readily targeted to sites of vascular injury as analyzed on computed tomography. In fact, comparable to fresh platelets, liposomes exhibited considerable hemostatic ability for correcting prolonged bleeding time in a busulphan‐induced thrombocytopenic rabbit model. In addition, the liposomes showed no activating or aggregating effects on circulating platelets in normal rabbits. Conclusion: H12‐(ADP)‐liposome may thus offer a promising platelet substitute, being made with only synthetic materials and exerting hemostatic functions in vivovia reinforcement of primary thrombus formation by residual platelets in thrombocytopenia at sites of vascular injury, but not in circulation.

Infective larvae of an intestinal nematode, Strongyloides venezuelensis, enter rodent hosts percutaneously, and migrate through connective tissues and lungs. Then they arrive at the small intestine, where they reach maturity. It is not known how S. venezuelensis larvae develop during tissue migration. Here we demonstrate that tissue invasion ability of S. venezuelensis larvae changes drastically during tissue migration, and that the changes are associated with stage-specific protein expression. Infective larvae, connective tissue larvae, lung larvae, and mucosal larvae were used to infect mice by various infection methods, including percutaneous, subcutaneous, oral, and intraduodenal inoculation. Among different migration stages, only infective larvae penetrated mouse skin. Larvae, once inside the host, quickly lost skin penetration ability, which was associated with the disappearance of an infective larva-specific metalloprotease. Migrating larvae had connective tissue migration ability until in the lungs, where larvae became able to settle down in the intestinal mucosa. Lung larvae and mucosal larvae were capable of producing and secreting adhesion molecules.

A newly developed high-speed color video camera, which can record 103 frames at rates of up to 1 million frames per second, has been used to obtain time-resolved color schlieren visualizations of shock wave phenomena. These trials constitute the first successful time-resolved application of the direction-indicating color schlieren method with frame rates up to 125 kHz. The instabilities of a supersonic flow over a double cone were made visible in unprecedented clarity, and the potential of the camera for schlieren visualizations was further demonstrated in experiments showing the explosion of a small firecracker and the bursting of a helium-filled toy balloon.

We studied prototypes of platelet substitutes that bear on their surface a dodecapeptide, HHLGGAKQAGDV (H12). The peptide is a fibrinogen γ chain carboxy-terminal sequence (γ400−411) and recognizes specifically the active form of glycoprotein (GP) IIb/IIIa on the surface of activated platelets. We conjugated H12 to the end of poly(ethylene glycol) chains on the surface of a phospholipid vesicle with an average diameter of 220 nm to prepare H12−PEG−vesicles. The half-life of the H12−PEG−vesicles was significantly prolonged by PEG modification, and the ability of H12 on the surface of the vesicle to recognize GPIIb/IIIa was maintained even though the surface was modified with PEG chains. The H12−PEG−veiscles enhanced the in vitro thrombus formation of platelets that were adhering to a collagen-immobilized plate, when thrombocytopenia-imitation blood was passed over the plate. Based on the flow cytometric analyses of PAC-1 binding and P-selectin expression, the H12−PEG−vesicles were shown not to cause platelet activation. Furthermore, the H12−PEG−vesicles dose-dependently shortened the tail bleeding time of thrombocytopenic rats. It was confirmed that the H12−PEG−vesicles had a hemostatic effect and may be a suitable candidate for an alternative to human platelet concentrates transfused into thrombocytopenic patients.

The Japanese quarantine system monitors incoming passengers to detect imported pathogens at international airports. At one airport, we found that 74% of 13315 travellers returning with diarrhoea had visited only one country before entering Japan. On the basis of our results, we hypothesized that the international distribution and potential source of bacterial strains could be inferred by analysing strains isolated from travellers returning to Japan. In order to demonstrate the potential for this system, we randomly selected five Shigella sonnei strains and examined their restriction fragment length polymorphism patterns. One set of strains appeared to be closely related, while three sets, isolated from travellers who visited different countries were possibly related. These results suggest that international distributions and potential sources of S. sonnei may be inferred by monitoring isolates from passengers arriving at a Japanese quarantine station.

AbstractBackground/Aim: Today, two kinds of 1-84PTH assays are available in clinical practice. Few studies have directly compared the results of these assays in the same plasma. Methods: Plasma samples were collected from 235 dialysis patients and analyzed by the 1-84PTH-IRMA, intact PTH-IRMA, 1-84PTH-CLIA, and intact PTH-CLIA assays simultaneously. Results: The results obtained by the 1-84PTH-IRMA and 1-84PTH-CLIA were highly correlated to each other (r2 = 0.971, p < 0.0001). In 90.2–92.3% of patients, the assays agreed when classifying them into three categories based on the K/DOQI guidelines. However, the 1-84PTH assays agreed in only 41.3–83.4% of patients when classifying them into two categories by calculating 1-84PTH/(intact PTH – 1-84PTH). Conclusion: The results obtained by the two assays could be regarded as comparable in clinical practice. However, the 1-84PTH/(intact PTH-1-84PTH) ratio has to be carefully applied since it amplified the error of these assays.Copyright © 2005 S. Karger AG, Basel

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Hashimoto’s thyroiditis (HT) is an autoimmune disease of the thyroid gland, and like many other autoimmune diseases, it is associated with the HLA and CTLA-4 gene. We have examined the distribution of the HLA DRB4*0101 allele and a CTLA-4 exon 1 A/G polymorphism in Japanese HT patients and controls and investigated possible interactions of these genes with thyroid function. Seventy Japanese HT patients and 105 controls were included in this study. HT was diagnosed on the basis of positivity for thyroid peroxidase (TPO) autoantibodies and the presence of a palpable diffuse goiter. Genotyping was performed by polymerase chain reaction (PCR)-based methods. CTLA-4-GG or -AG was more prevalent in the patients, and the odds ratio for the G allele was 4.95. The frequency of DRB4*0101-positive individuals was significantly higher in HT (odds ratio=2.17). The TSH values of HT patients at the time of diagnosis were compared to CTLA-4 genotype and HLA-DRB4*0101 positivity. They were slightly higher in the CTLA-4-AG group than in the -GG group and significantly higher in the HLA-DRB4*0101-positive group than in the -negative group (p<0.01). When the TSH values were compared in 4 groups based on positivity or negativity for HLA-DRB4*0101 and CTLA-4 GG or AG, they were found to be significantly higher in the CTLA-4-AG and HLADRB4* 0101-positive group than in the 3 other groups (F=5.75, 3 degrees of freedom, p<0.01). These findings suggest that the interaction between the HLA-DRB4 and CTLA-4 genes determines the thyroid function of TPO-positive goitrous Japanese HT patients.

Photochromic diarylethene derivatives containing 2,4-diphenylphenyl substituents formed stable amorphous solids and showed reversible solid-state photochromism. Refractive indices of the amorphous films changed reversibly with the photochromic reactions as much as Δn = 0.028 at 817 nm. Changes in both absorption band and static polarizability contributed to the large refractive index modulation.

AbstractBackground: We previously demonstrated that erythropoietin (Epo) expression increases in five-sixths nephrectomized rats, after muscle-targeted gene transfer by in vivo electroporation, using plasmid DNA expressing rat Epo (pCAGGS-Epo). Here, we apply this method to a rat model with severe anemia associated with chronic renal failure; these rats have hematocrit levels in the 30–35% range, similar to those in humans with end-stage renal disease. Methods: Wistar rats were treated to produce adenine-induced uremia. The uremic rats were then treated with muscle-targeted gene transfer using pCAGGS-Epo. Some uremic rats died from chronic renal failure; one of these was dissected, and the kidneys were histologically examined. For the remaining rats, we measured body weight and blood pressure, and obtained blood samples regularly. Results: The uremic rats showed severe anemia, with hematocrit levels at 32.6 ± 3.3%. Epo-gene transfer increased Epo expression and serum Epo levels, and also increased the hematocrit levels to 64.5 ± 4.8%. The dose of pCAGGS-Epo used in this study did not induce severe hypertension. Conclusions: Continuous Epo-gene expression improves the anemia associated with chronic renal failure, and without severe side effects. Our results support the potential use of gene electrotransfer for human gene therapy applications.Copyright © 2003 S. Karger AG, Basel

The parasitic female of Strongyloides venezuelensis keeps invading the epithelial layer of the host intestinal mucosa. Upon invasion, it adheres to the surface of the intestinal epithelial cells with adhesion molecules secreted from the mouth. It has been demonstrated that S. venezuelensis are expelled from the intestine because mucosal mast cells inhibit the attachment of adult worms to the mucosal surface. In the present study, we generated specific antibodies against secreted adhesion molecules to investigate their function in vivo, because these molecules have been demonstrated only in vitro in spite of the importance in the infection processes. A mouse monoclonal antibody specific to S. venezuelensis adhesion molecules inhibited the attachment of adult worms to plastic dishes and the binding of adhesion molecules to rat intestinal epithelial cells. Immunohistochemical study revealed that adhesion molecules were produced by oesophageal glands and were continuously secreted in vivo to line the wall of the tunnels formed by adult worms in the intestinal mucosa. Our findings indicate that adhesion molecules play essential roles in the infection processes of S. venezuelensis in the host intestine.

A new and efficient synthesis of 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline dihydrochloride, a key intermediate for the CCR5 antagonist TAK-779, is described. Reductive alkylation of methylamine with tetrahydro-4H-pyran-4-one followed by alkylation of N-methyl-N-(tetrahydropyran-4-yl)amine with 4-nitrobenzylbromide and reduction of N-(4-nitrobenzyl)-N-(tetrahydropyran-4-yl)amine results in a 78% isolated yield from the starting materials by a scalable method, using only commercially available reagents.

Dialysis-related amyloidosis (DRA) is a common complication associated with long-term haemodialysis therapy. The elimination of β2-microglobulin (β2m), the major constituent of the amyloid fibrils in DRA, from circulation has been expected to bring some clinical benefit. Recently, a direct haemoperfusion method using selective β2m absorption column to eliminate circulating β2m has been introduced into clinical practice. According to a recently performed, prospective, multicentre study, joint pain, stiffness and daily activities were significantly improved in patients with established DRA after the introduction of selective β2m absorption therapy. Meanwhile, although osteoarticular lesions progressed in the control group, there was no significant progression in the selective β2m absorption therapy group. The absorptive affinity of the column for β2m is not quite specific and therefore some other unknown uraemic toxins might be removed also. However, the improvement of joint pain and the ability to undertake daily activities showed reversed correlations against plasma β2m clearance. Symptoms associated with the increased amount of extracorporeal circulation and increased economical burden are areas of concern for this therapy. In conclusion, selective β2m absorption therapy was suggested to have the potential to ameliorate established DRA symptoms and simultaneously prevent its local development. The mechanism by which DRA symptoms are ameliorated remains obscure.

A new helicity‐modulation technique has been applied for recording X‐ray magnetic circular dichroism (XMCD) at the K‐absorption edge in transition‐metal magnetic materials. This technique enables the measurement of the XMCD spectrum with high precision and under extreme conditions. The refined spectrum is presented at the Fe Kedge for pure Fe, Fe4N and Co‐ferrite. The method is very promising for site‐assignment of magnetic cations and for detailed investigation of the magnetic states in a local environment. In Mn3MC perovskites, the dependence of the Mn K‐edge XMCD spectrum on temperature and magnetic field demonstrates that the orbital moments are closely associated with the magnetic phase transition. New information obtained from the refined spectrum and novel phenomena observed in temperature and field variations is presented.

In this study, a specimen preparation technique for obtaining a plane view section of a specific layer in a specific area is reported, which combines two techniques: tripod polishing for thinning the specified area and chemical etching for extracting a specific layer. A plane view section of a specific layer in a semiconductor device can be prepared by this technique with a spatial resolution of less than 1 µm. This method uses mechanical polishing with a tripod-polisher in conjunction with chemical etching. First, the top side of the specimen is polished down to the layer of interest, and then the silicon substrate on the bottom side is polished by using a tripod polisher to form a tapered wedge-shape with the region of interest positioned at the edge. It is then subjected to chemical etching by potassium hydroxide to remove the leftover silicon. By using this method, a 400 nm thick titanium silicide layer can be extracted from a multi-layered semiconductor device for plane view TEM observation, and the microstructures of the silicide layer, which affect the electrical properties of the device, can be investigated.

Background: Recurrence of varices is still common after endoscopic treatment of esophageal varices. In this study, predictive signs of variceal recurrence were investigated by ultrasonic (US) miniature probe in patients treated by combined endoscopic ligation and sclerotherapy. Methods: Detectability of vessels by US miniature probe was evaluated first in rats. In 41 patients treated by combined therapy, the esophagus and the cardia region were examined by US miniature probe. In 25 patients examined by percutaneous transhepatic portography, the relationship between US miniature probe and percutaneous transhepatic portography findings was evaluated. Results: The smallest vessel detected by US miniature probe was 0.3 mm in diameter in the study using intra-abdominal vessels of rat. After variceal eradication, US miniature probe showed intramural vessels in the cardia that were classified as follows: grade I, a few vessels (19 patients, 46%); grade II, uniformly scattered vessels (11, 27%); grade III, abundant vessels resembling a honeycomb (11, 27%). As the sonographic grade increased, the rate of variceal recurrence increased. As the venographic grade of staining in the distal esophagus increased, the esophageal wall became thicker and the sonographic grade at the cardia increased. Conclusions: Endosonographic evaluation of the distal esophagus and cardia is predictive of variceal recurrence. (Gastrointest Endosc 2000;52:611-7.)

Susceptibility to Plasmodium chabaudi depends on the relative dominance of T_h1/T_h2 responses in host mice. A T_h2-dominant response during the early phase of infection in susceptible A/J mice causes a fatal disease course due to severe malaria. Schistosoma mansoni is a potent inducer of a T_h2-dominant response not only to the parasite antigens, but also to other antigens concurrently existing in the host animals. In spite of S. mansoni infection, these A/J mice escape death from malaria and showed accompanied enhanced production of IFN-γ to malaria antigens. Treatment with anti-IFN-γ mAb in S. mansoni-infected A/J mice abolished the resistance to malaria, indicating that IFN-γ was responsible for the resistance to P. chabaudi in S. mansoni-infected A/J mice. Results in this study show that under certain circumstances, S. mansoni infection can promote type 1 immune responses in A/J mice that normally develop T_h2 responses.

Background:Features of enhanced color flow images in small hepatocellular carcinoma (HCC) are not fully elucidated. The purpose of this study was to clarify the characteristic vascular images in small HCC observed by enhanced color Doppler. Methods:Enhanced color Doppler using the contrast agent Levovist was performed on 13 patients with HCC smaller than 30 mm. Enhanced color flow appearance was compared with angiographic findings. Time-intensity changes after injection of the contrast agent were analyzed in HCC nodules. Results:Significant improvement in the detection of color flow signals was obtained in small HCC using Levovist, from 33% in precontrast to 92% in postcontrast (p < 0.005).Three patterns of enhanced color flow images, which were related to the angiographic findings, were observed. The time-intensity curve was classified into two types by “time to peak” and “time on plateau” and was associated with the patterns of enhanced images. Conclusion:Enhanced color flow imaging promises to be a useful method for evaluating tumor vascularity noninvasively and to contribute to the elucidation of the hemodynamics in small HCC.

Polarization tunability and analysis of X‐rays is one of the most advancing features of third‐generation synchrotron radiation sources. In order to apply such developments to the observation of magnetic effects, a diffractometer for X‐ray magnetic absorption and scattering experiments was constructed on BL39XU at SPring‐8. The efficiency of the apparatus is clearly demonstrated by several observations of the magnetic effects. In particular, a diamond phase plate plays an essential role in regulating both circular and linear polarization states.

The neurotoxin of strain 111 (111/NT) associated with type B infant botulism showed antigenic and biological properties different from that (Okra/NT) produced by a food-borne botulism-related strain, Okra. The specific toxicity of 111/NT was found to be about 10 times lower than that of Okra/NT. The monoclonal antibodies recognizing the light chain cross-reacted with both neurotoxins, whereas most of the antibodies recognizing the carboxyl-terminal half of the heavy chain of Okra/NT did not react to 111/NT. Binding experiments with rat brain synaptosomes revealed that 125I-labeled 111/NT bound to a single binding site with a dissociation constant (Kd) of 2.5 nM; the value was rather lower than that (0.42 nM) of 125I-Okra/NT for the high-affinity binding site. In the lipid vesicles reconstituted with ganglioside GT1b, 125I-Okra/NT interacted with the amino-terminal domain of synaptotagmin 1 (Stg1N) or synaptotagmin 2 (Stg2N), fused with the maltose-binding protein, in the same manner as the respective full-length synaptotagmins, and the Kd values accorded with those of the low- and high-affinity binding sites in synaptosomes. However, 125I-111/NT only exhibited a low capacity for binding to the lipid vesicles containing Stg2N, but not Stg1N, in the presence of ganglioside GT1b. Moreover, synaptobrevin-2, an intracellular target protein, was digested to the same extent by the light chains of both neurotoxins in a concentration-dependent manner. These findings indicate that the 111/NT molecule possesses the receptor-recognition site structurally different from Okra/NT, probably causing a decreased specific toxicity.

To examine metal flow behaviour experimentally in the spreading extrusion process, a round billet is spread by means of a spread ring and extruded through a die opening wider than the internal diameter of the container. In spreading extrusion, the extrusion load is reduced by about 30% in comparison with basic extrusion. However, the metal flow balance in spreading extrusion worsens, because of the high frictional force generated at the interface of the billet and spread ring during the filling process. When the profile is wide or when spread ring height is low, the geometry of the plastic deformation zone on the die face changes from an ellipse into a figure of eight at the wide zone at both ends of the die opening. As a result, the metal flow balance markedly worsens, due to an increase in the size of the plastic deformation zone and frictional resistance acting on the spread ring wall.

Extramedullary hemopoiesis recognized as hemopoietic foci increased in the liver ofSchistosoma japonicum-infected mice in parallel with kinetic changes in periovular granuloma formation. At the peak of the response, about 65% of the hepatic hemopoietic foci were of eosinophil lineage. WhenS. japonicum-infected mice were irradiated, hepatic hemopoietic foci rapidly disappeared within 3 days, whereas inflammatory cells in the periovular granulomas slowly reduced in number. When the number of hemopoietic stem cells in the liver were examined by spleen-colony assay, kinetic changes in the number of hemopoietic stem cells in hepatic nonparenchymal cells paralleled those of hepatic hemopoietic foci. Hemopoietic stem cells were rare in the granuloma cells. These results indicate that in response to the increased demand for eosinophils and other inflammatory cells, the liver acts as an extramedullary hemopoietic organ in which inflammatory cells are generated from hemopoietic stem cells.

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Careful measurements of the dielectric dispersion and spontaneous polarization of thiourea reconfirmed the existence of the ferroelectric commensurate (δ = 1/8) phase between 177.5K (T81) and 178.1K (T8u) under zero bias field. The kinetic process of the field-induced C(δ = 1/8)-IC phase transition was studied by observing the time evolutions of polarization and dielectric constant. The time evolutions of both quantities were similar to those observed for the C-IC transition in Rb2ZnCl4 studied previously, and can be explained by our theory of time evolution of DC lattice for a first-order C-IC transition.

A complementarity-determining region (CDR) of the mouse monoclonal antibody (mAb) F58 was constructed with specificity to a neutralization-inducing region of human immunodeficiency virus type 1 (HIV-1). The mAb has its major reactivity to the amino acid sequence I--GPGRA in the V3 viral envelope region. All CDRs including several framework amino acids were synthesized from the sequence deduced by cloning and sequencing mAb F58 heavy- and light-chain variable domains. Peptides derived from the third heavy-chain domain (CDR-H3) alone or in combination with the other CDR sequences competed with F58 mAb for the V3 region. The CDR-H3 peptide was chemically modified by cyclization and then inhibited HIV-1 replication as well as syncytium formation by infected cells. Both the homologous IIIB viral strain to which the F58 mAb was induced and the heterologous SF2 strain were inhibited. This synthetic peptide had unexpectedly potent antiviral activity and may be a potential tool for treatment of HIV-infected persons.

Objective: To evaluate the effects of minimal-dose aprotinin in patients undergoing coronary artery bypass grafting, we conducted a prospective randomized study. Methods: A total of 167 patients were randomized to receive no aprotinin treatment (control, n = 57), minimal-dose aprotinin (1.0 x 10^6 KIU; n = 55), or low-dose aprotinin (2.7 +/- 0.5 x 10^6 KIU; n = 55). Blood loss and transfusion requirements, parameters of clotting and fibrinolysis, renal function, and early graft patency rates were assessed. Results: Postoperative blood loss and transfusion requirements were significantly (p = 0.01) lower in both the minimal-dose and low-dose groups than in the control group. The increase in D-dimer level after cardiopulmonary bypass was significantly (p < 0.05) less marked in the low-dose group than in the control group. The @a"2-plasmin inhibitor and plasminogen activator inhibitor-1 levels were significantly (p < 0.05) greater in the minimal-dose and low-dose groups than in the control group after bypass, suggesting the prevention of fibrinolysis by both aprotinin doses. No statistically significant differences in postoperative renal function and early vein graft patency rates were noted (control group, 93.8%; minimal-dose group, 98.5%; low-dose group, 92.3%; p = 0.25). Conclusions: Aprotinin was not associated with a significant increase in the prevalence of renal dysfunction or early vein graft occlusion. Minimal-dose aprotinin inhibited enhanced fibrinolytic activity and reduced blood loss and transfusion requirements after bypass equivalently to low-dose aprotinin. The dose of 1 x 10^6 KIU added to the pump prime may be acceptably effective in reducing blood loss in patients undergoing primary coronary operations. J Thorac Cardiovasc Surg 1997;114:261-9