Modeling of light propagation in the human neck for diagnoses of thyroid cancers by diffuse optical tomography.

Diffuse optical tomography using near-infrared light in a wavelength range from 700 to 1000 nm has the potential to enable non-invasive diagnoses of thyroid cancers; some of which are difficult to detect by conventional methods such as ultrasound tomography. Diffuse optical tomography needs to be based on a physically accurate model of light propagation in the neck, because it reconstructs tomographic images of the optical properties in the human neck by inverse analysis. Our objective here was to investigate the effects of three factors on light propagation in the neck using the 2D time-dependent radiative transfer equation: (1) the presence of the trachea, (2) the refractive-index mismatch at the trachea-tissue interface, and (3) the effect of neck organs other than the trachea (spine, spinal cord, and blood vessels). There was a significant influence of reflection and refraction at the trachea-tissue interface on the light intensities in the region between the trachea and the front of the neck surface. Organs other than the trachea showed little effect on the light intensities measured at the front of the neck surface although these organs affected the light intensities locally. These results indicated the necessity of modeling the refractive-index mismatch at the trachea-tissue interface and the possibility of modeling other neck organs simply as a homogeneous medium when the source and detectors were far from large blood vessels.

Effect of highly lipolyzed goat cheese on HL-60 human leukemia cells: antiproliferative activity and induction of apoptotic DNA damage.

To establish cheese as a dairy product with health benefits, we embarked on examining the multifunctional role of cheeses, especially in the field of cancer prevention. The current study was designed to investigate whether different types of commercial goat cheeses may possess antiproliferative activity, using an HL-60 human promyelocytic leukemia cell line as a cancer cell model. Among 11 cheese extracts tested at 500µg/mL, 6 (Crottin de Chavignol, Pouligny Saint-Pierre, Chabichou du Poitou, Valencay, Kavli, and Sainte-Maure de Touraine) resulted in a significant decrease of cell viability, which is consistent with a decrease in viable cell number. Compared with the half-maximal inhibitory concentration (IC(50)) value of individual cheeses in cellular proliferation assays, the Pouligny Saint-Pierre extract showed strong inhibition. Incubation of cells in the presence of Pouligny Saint-Pierre extract resulted in induction of cellular morphological changes and apoptotic DNA fragmentation as well as expression of the active form of caspase-3 protein. Based on the quantification of the ratio of free fatty acids to triglycerides in different cheese samples, a significant correlation was detected between lipolytic ripeness and IC(50) values for antiproliferative capacity tested in HL-60 cells. Collectively, these results support a potential role of highly lipolyzed goat cheeses in the prevention of leukemic cell proliferation.

Reduction of Poisson noise in measured time-resolved data for time-domain diffuse optical tomography.

A method to reduce noise for time-domain diffuse optical tomography (DOT) is proposed. Poisson noise which contaminates time-resolved photon counting data is reduced by use of maximum a posteriori estimation. The noise-free data are modeled as a Markov random process, and the measured time-resolved data are assumed as Poisson distributed random variables. The posterior probability of the occurrence of the noise-free data is formulated. By maximizing the probability, the noise-free data are estimated, and the Poisson noise is reduced as a result. The performances of the Poisson noise reduction are demonstrated in some experiments of the image reconstruction of time-domain DOT. In simulations, the proposed method reduces the relative error between the noise-free and noisy data to about one thirtieth, and the reconstructed DOT image was smoothed by the proposed noise reduction. The variance of the reconstructed absorption coefficients decreased by 22% in a phantom experiment. The quality of DOT, which can be applied to breast cancer screening etc., is improved by the proposed noise reduction.

Identification of molecular markers for pre-engraftment immune reactions after cord blood transplantation by SELDI-TOF MS.

Cord blood transplantation (CBT) is frequently associated with pre-engraftment immune reaction (PIR), which is characterized by high-grade fever that peaks around day 9 of transplantation. PIR mimics hyperacute GVHD or engraftment syndrome; however, it is considered to be of different etiology as it occurs before engraftment. Proteomic patterns have been studied in the fields of transplantation, but no specific marker has been identified. As there are no data to confirm the mechanism of PIR, we used a surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF MS) system to identify a specific marker for PIR. The protein expression profile of serum samples from CBT patients was analyzed with a SELDI-TOF MS system. A protein peak that commonly predominated in PIR was purified by an anion exchange column, isolated by SDS-PAGE, and identified by in-gel trypsin digestion, and mass fingerprinting. A 8.6-kDa protein and 11-kDa protein that increased by 10- to 100-fold in the serum of patients during PIR was identified as anaphylatoxin C4a and serum amyloid A. SELDI-TOF MS system in combination with other proteomic methods could serve as a potential diagnostic tool in discovering biomarkers for PIR after CBT.

Effects of highly ripened cheeses on HL-60 human leukemia cells: antiproliferative activity and induction of apoptotic DNA damage.

To establish cheese as a dairy product with health benefits, we examined the multifunctional role of cheeses. In this report, we clarify whether different types of commercial cheeses may possess antiproliferative activity using HL-60 human promyelocytic leukemia cell lines as a cancer model. Among 12 cheese extracts tested, 6 (Montagnard, Pont-l'Eveque, Brie, Camembert, Danablue, and Blue) revealed strong growth inhibition activity and induction of DNA fragmentation in HL-60 cells. Based on the quantification of nitrogen contents in different cheese samples, a positive correlation between the ripeness of various cheeses and their antiproliferative activity tested in HL-60 cells was displayed. Four varieties of Blue cheese ripened for 0, 1, 2, or 3 mo demonstrated that the Blue cheese ripened for a long term was capable of causing the strong suppression of the cell growth and the induction of apoptotic DNA damage as well as nucleic morphological change in HL-60 cells. Collectively, these results obtained suggest a potential role of highly ripened cheeses in the prevention of leukemic cell proliferation.

Consecutive national surveys of ABO-incompatible blood transfusion in Japan.

BACKGROUND AND OBJECTIVES: Morbidity and mortality from ABO-incompatible transfusion persist as consequences of human error. Even so, insufficient attention has been given to improving transfusion safety within the hospital. MATERIALS AND METHODS: National surveys of ABO-incompatible blood transfusions were conducted by the Japanese Society of Blood Transfusion, with support from the Ministry of Health, Labor and Welfare. Surveys concluded in 2000 and 2005 analysed ABO-incompatible transfusion data from the previous 5 years (January 1995 to December 1999 and January 2000 to December 2004, respectively). The first survey targeted 777 hospitals and the second, 1355 hospitals. Data were collected through anonymous questionnaires. RESULTS: The first survey achieved a 77.4% response rate (578 of 777 hospitals). The second survey collected data from 251 more hospitals, but with a lower response rate (61.2%, or 829 of 1355 hospitals). The first survey analysed 166 incidents from 578 hospitals, vs. 60 incidents from 829 hospitals in the second survey. The main cause of ABO-incompatible transfusion was identification error between patient and blood product: 55% (91 of 166) in the first survey and 45% (27 of 60) in the second. Patient outcomes included nine preventable deaths from 1995 to 1999, and eight preventable deaths from 2000 to 2004. CONCLUSION: Misidentification at the bedside persists as the main cause of ABO-incompatible transfusion.

Significance of pre-storage leucoreduction for autologous blood.

BACKGROUND AND OBJECTIVES: To reveal the associations between cytokines in blood and transfusion-related adverse events, we studied whether pre-storage leucoreduction of autologous blood could reduce the degree of inflammatory responses, infection rates, or the duration of hospitalizations. MATERIALS AND METHODS: Patients scheduled to donate autologous blood for elective orthopaedic surgery were assigned to receive either leucoreduced (LR) or non-leucoreduced (N-LR) autologous blood based on their date of birth. Levels of cytokines in the autologous blood, values for C-reactive protein, complete blood count and body temperature of the patients, as well as adverse clinical events, were evaluated periodically. RESULTS: Four hundred patients entered this study (LR group: 196, N-LR group: 204). The production of cytokines, excluding interleukin 1beta (IL-1beta), was suppressed for the LR group. However, for unknown reasons, IL-1beta actually increased during storage for the LR group. There were no differences between the two groups in the length of hospital stay, postoperative C-reactive protein changes, leucocyte count, or body temperature, and no clinical problems associated with blood transfusion were observed in either group. CONCLUSION: Pre-storage leucoreduction for autologous blood may be effective to suppress cytokine accumulation. However, clinical benefits such as prevention of febrile non-haemolytic reactions could not be demonstrated.

Observation of a near-threshold enhancement in the e+e- -->Lambda+_(c)Lambda-_(c) cross section using initial-state radiation.

We report a measurement of the exclusive e+ e- -->Lambda+_(c)Lambda-_(c) cross section as a function of center-of-mass energy near the Lambda+_(c)Lambda-_(c) threshold. A clear peak with a significance of 8.2sigma is observed in the Lambda+_(c)Lambda-_(c) invariant mass distribution just above threshold. With an assumption of a resonance origin for the observed peak, a mass and width of M=[4634 (+8)_(-7)(stat)(+5)_(-8)(syst)] MeV/c(2) and Gamma_(tot)=[92 (+40)_(-24)(stat)(+10)_(-21)(syst)] MeV are determined. The analysis is based on a study of events with initial-state-radiation photons in a data sample collected with the Belle detector at the Upsilon(4S) resonance and nearby continuum with an integrated luminosity of 695 fb(-1) at the KEKB asymmetric-energy e+ e- collider.

Observation of the psi(4415)-->DD2*(2460) decay using initial-state radiation.

We report measurements of the exclusive cross section for e(+)e(-)-->D(0)D(-)pi(+) over the center-of-mass energy range 4.0 GeV to 5.0 GeV with initial-state radiation and the first observation of the decay psi(4415)-->D(0)D(-)pi(+). From a study of the resonant substructure in psi(4415) decay we conclude that the psi(4415)-->D(0)D(-)pi(+) decay is dominated by psi(4415)-->DD(2)(*)(2460). We obtain B(psi(4415)-->D(0)D(-)pi(nonresonant)(+))/B(psi(4415)-->DD(2)(*)(2460)-->D(0)D(-)pi(+))<0.22 at 90% C.L. The analysis is based on a data sample collected with the Belle detector with an integrated luminosity of 673 fb(-1).

Functional analysis of cytomegalovirus-specific T lymphocytes compared to tetramer assay in patients undergoing hematopoietic stem cell transplantation.

In order to evaluate whether we could predict reactivation of CMV by monitoring the number of CMV-specific cytotoxic T-lymphocytes (CTL), tetramer analysis was performed in 37 patients who underwent hematopoietic stem cell transplantation (HSCT). The results disclosed that the mean number of CMV-specific CTL at day 30 did not differ among patients who developed CMV antigenemia (22/microl) and those who did not (12/microl). Serial tetramer analysis showed that 21% of the patients had >10/microl CMV-specific CTL at the first detection of CMV antigenemia and 67% of the patients had more than 10/microl CMV-specific CTL at the onset of CMV disease. Intracellular staining upon stimulation by CMV lysates and peptide in patients with CMV colitis revealed that both IFN-gamma producing CD4+ and CD8+ lymphocytes were suppressed at the onset of CMV colitis (1.6 and 8/microl), which increased with recovery of the disease (19 and 47/microl). These data suggest that it is difficult to predict CMV reactivation solely by the number of CMV-specific CTL. We suggest that additional functional analysis by intracellular cytokine assay may be useful for immunomonitoring against CMV.

Measurement of the e+e- -->pi+pi- J/psi cross section via initial-state radiation at Belle.

The cross section for e(+)e(-)-->pi(+)pi(-)J/psi between 3.8 and 5.5 GeV/c(2) is measured using a 548 fb(-1) data sample collected on or near the Upsilon(4S) resonance with the Belle detector at KEKB. A peak near 4.25 GeV/c(2), corresponding to the so called Y(4260), is observed. In addition, there is another cluster of events at around 4.05 GeV/c(2). A fit using two interfering Breit-Wigner shapes describes the data better than one that uses only the Y(4260), especially for the lower-mass side of the 4.25 GeV enhancement.

Observation of two resonant structures in e+ e- -->pi+ pi- psi(2S) via initial-state radiation at Belle.

The cross section for e+ e- --> pi+ pi- psi(2S) between threshold and sqrt[s]=5.5 GeV is measured using 673 fb(-1) of data on and off the Upsilon(4S) resonance collected with the Belle detector at KEKB. Two resonant structures are observed in the pi+ pi- psi(2S) invariant-mass distribution, one at 4361 +/- 9 +/- 9 MeV/c2 with a width of 74 +/- 15 +/- 10 MeV/c2, and another at 4664 +/- 11 +/- 5 MeV/c2 with a width of 48 +/- 15 +/- 3 MeV/c2, if the mass spectrum is parametrized with the coherent sum of two Breit-Wigner functions. These values do not match those of any of the known charmonium states.

Measurement of the near-threshold e+e- --> D(*)+/-D(*)-/+ cross section using initial-state radiation.

We report a measurement of the exclusive e+e- -->D(*)+/-D*-/+ cross section as a function of center-of-mass energy near the D(*)+/-D*-/+ threshold with initial-state radiation. A partial reconstruction technique is used to increase the efficiency and to suppress background. The analysis is based on a data sample collected with the Belle detector with an integrated luminosity of 547.8 fb(-1).

Persistent nucleated red blood cells in peripheral blood is a poor prognostic factor in patients undergoing stem cell transplantation.

We compared detection rates and counts of nucleated red blood cell (NRBC) in the peripheral blood of survivors and nonsurvivors (total 44 patients) of stem cell transplantation. The rate of NRBC detection increased to 79.5% after transplantation. After engraftment, the detection rate of NRBC decreased to 17.0% in survivors, but increased to 100% in nonsurvivors. The NRBC count increased after transplantation in both groups. This increase was transient in survivors, but increased after engraftment in nonsurvivors. The mean NRBC count after engraftment was 872 vs. 40.3 for nonsurvivors vs. survivors, respectively. At postengraftment, all patients who were negative for NRBC survived, but 10 of the 15 patients who were positive for NRBC died (66.7%). The survival rates of patients with a NRBC count >200 x 10(6)/l were significantly lower than those of patients whose counts were <100 x 10(6)/l. These data indicated that persistent NRBC in peripheral blood is a poor prognostic factor, and suggested that monitoring NRBC after SCT might provide useful clinical information.

Heterologous expression of the flavonoid 3',5'-hydroxylase gene of Vinca major alters flower color in transgenic Petunia hybrida.

Flavonoid 3',5'-hydroxylase (F3'5'H) is the key enzyme for the expression of blue or purple flower color. A full-length cDNA for the F3'5'H gene was cloned from petals of Vinca major, and its genomic clone, designated VmFH1 (accession number AB078781 in the GenBank/EMBL/DDBJ databases), was isolated from leaves by a PCR-based strategy. Nucleotide sequence analysis revealed that VmFH1 contains one intron and an open reading frame encoding a polypeptide of 506 amino acid residues. The deduced amino acid sequence shows between 51% and 83% identity with those of previously reported F3'5'H genes. Southern blot analysis showed that there are 3-4 copies of the F3'5'H gene in the genome of V. major. Transcripts of the F3'5'H gene were detected in young flower petals but not in leaves as revealed by RT-PCR analysis. When VmFH1 was expressed in transgenic Petunia hybrida under the control of the cauliflower mosaic virus 35S promoter, some transgenic plants showed drastic flower color alteration from red to deep red with deep purple sectors. These transgenic plants accumulated 3',5'-hydroxylated anthocyanins in their petals, which were never detected in non-transgenic plants by high-performance liquid chromatography analysis. These results indicate that VmFH1 isolated from V. major encodes F3'5'H and is active in a heterologous plant species.

Repeated administration of cytokines improve the ex-vivo generation of human dendritic cells.

The in vitro generation of dendritic cells (DCs) enables us to practice antitumor immune therapy. Peripheral monocytes can differentiate to DCs in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) in vitro. To generate a large number of DCs, we compared the number of DCs generated from leukapheresis products to those from conventional blood samplings in healthy volunteers. The induction rates of the DCs were equal for these two blood samplings, and 10(7) DCs were obtainable from one leukapheresis product. In contrast, the number of DCs varied significantly depending on the individual (30-50% in good responders vs. less than 10% in poor responders). DCs appeared as aggregates of indented cells during culture in good responders, while large cells were floating sparsely in poor responders. Repeated administration of GM-CSF and IL-4 improved the yields of DCs and induced proliferation of autologous lymphocytes in poor responders. As a prototype of cell therapy, the generation of DCs will require a titration of differentiation processes, depending on each individual's responsiveness to cytokines.

Specific somatosensory processing in somatosensory area 3b for human thumb: a neuromagnetic study.

OBJECTIVES: We examined the relation between somatosensory N20m primary responses and high-frequency oscillations (HFOs) after thumb and middle finger stimulation. METHODS: Somatosensory evoked fields (SEFs) from 12 subjects were measured following electric stimulation of the thumb and middle finger. SEFs were recorded with a wide bandpass (3-2000 Hz) and then N20m and HFOs were separated by subsequent 3-300 and 300-900 Hz bandpass filtering. RESULTS: The N20m peak-to-peak amplitude did not differ significantly between thumb and middle finger SEFs. In contrast, HFOs had a significantly larger number of peaks and were higher in the maximum amplitude and the total amplitude after thumb stimulation than after middle finger stimulation. CONCLUSIONS: Our present data demonstrate a different relation between N20m and HFOs after thumb and middle finger stimulation. In view of the fact that the human thumb has uniquely evolved functionally and morphologically, the somatosensory information from the thumb will be processed differently for a fine motor control. We speculate that HFOs are generated by inhibitory interneurons in layer 4 in area 3b. Thus, enhanced activity of interneurons reflected by high amplitude HFOs exerts stronger inhibition on downstream pyramidal cells in area 3b for thumb stimulation.

Delay of the diagnostic lumbar puncture and intrathecal chemotherapy in children with acute lymphoblastic leukemia who undergo routine corticosteroid testing: Tokyo Children's Cancer Study Group study L89-12.

PURPOSE: To determine the effects of eliminating initial lumbar punctures in 418 consecutively treated children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Patients were enrolled onto a trial conducted in central Japan between 1989 and 1992. Treatment consisted of standard four-drug induction therapy followed by a risk-based intensification phase, reinduction therapy, late intensification, and remission maintenance therapy (total of 104 weeks). The initial lumbar puncture, with an intrathecal injection of chemotherapy, was performed after 1 week of prednisolone sensitivity testing (day 8). End points included response to prednisolone, CNS status at the time of the day 8 lumbar puncture, subsequent adverse events in CNS and bone marrow, and event-free survival (EFS). RESULTS: The remission induction rate was 93.1% with a 6-year EFS rate (+/- SE) of 68.7% +/- 2.4%, which is similar to historical results for patients who received their diagnostic lumbar puncture and first instillation of intrathecal chemotherapy on day 0. Overall, 84.5% of the patients had good responses to prednisolone, whereas 15.5% had poor responses. Clinical outcome was strikingly better for the good responders (6-year EFS, 74.1% +/- 2.5% compared with 40.1% +/- 6.4% for patients with poor responses), suggesting that omission of intrathecal chemotherapy did not alter the predictive value of drug sensitivity testing. Eighteen patients experienced CNS relapse as their first adverse event (cumulative risk, 5.1%; 95% confidence interval, 2.7% to 7.4%), coincident with reports from groups using conventional strategies of CNS clinical management. Bleeding into the CSF at the time of the day 8 lumbar puncture was apparent in 29 cases (8.1%), but leukemic blasts were identified in only two. CONCLUSION: Delay of the initial lumbar puncture and intrathecal injection of chemotherapy seems to be feasible in children with ALL. Further controlled evaluations are needed to establish the validity of this conclusion.

Six months of maintenance chemotherapy after intensified treatment for acute lymphoblastic leukemia of childhood.

PURPOSE: We postulated that intensification of chemotherapy immediately after remission induction might reduce the leukemic cell burden sufficiently to allow an abbreviated period of antimetabolite therapy. PATIENTS AND METHODS: Three hundred forty-seven children (ages 1 to 15 years) with previously untreated acute lymphoblastic leukemia (ALL) were enrolled onto the Tokyo L92-13 study, which excluded patients with mature B-cell ALL and patients less than 1 year old. One hundred twenty-four patients were classified as standard risk, 122 as high risk, and 101 as extremely high risk, according to age, peripheral-blood leukocyte count, selected genetic abnormalities, and immunophenotype. All subjects received four drugs for remission induction, followed by a risk-directed multidrug intensification phase and therapy for presymptomatic leukemia in the CNS. Maintenance chemotherapy with oral mercaptopurine and methotrexate was administered for 6 months, with all treatment stopped by 1 year after diagnosis. RESULTS: The mean (+/- SD) event-free survival (EFS) and overall survival rates for all patients were 59.5% +/- 3.4% and 81.5% +/- 2.2%, respectively, at 5. 5 years after diagnosis. EFS rates by risk category were similar (60. 2% +/- 6.0% for standard risk, 57.7% +/- 5.6% for high risk, and 62. 5% +/- 5.7% for extremely high risk), whereas overall survival rates differed significantly (91.2% +/- 2.7%, 80.0% +/- 4.1%, and 72.1% +/- 4.5%, respectively, P <.0001 by the log-rank test). There were 107 relapses. Eighty-five (79.4%) of these 107 patients achieved second complete remissions, with subsequent EFS rates of 61.5% +/- 7. 9% (standard risk), 42.6% +/- 8.1% (high risk), and 9.6% +/- 6.4% (extremely high risk). Of the five risk factors analyzed, only the response to prednisolone monotherapy among extremely high-risk patients proved important. CONCLUSION: Early treatment intensification did not compensate for a truncated phase of maintenance chemotherapy in children with standard- or high-risk ALL. However, 6 months of antimetabolite treatment seemed adequate for extremely high-risk patients who were good responders to prednisolone and received intensified chemotherapy that included high-dose cytarabine early in the clinical course.