Biomedical subjects

Hitoshi Ohto

Publications and source records attributed to Hitoshi Ohto.

28 records · Page 2Linked to original sources

PubMed2004

[Case report on intra-tumor injection therapy of dendritic cells in advanced gastric cancer].

Dendritic cells (DC) are powerful antigen-presenting cells, and have attracted attention in recent years from the viewpoint of DC vaccine therapy against cancer. However, the existence of an immunosuppressive state in cancer individuals leads to anergy and failure in cytotoxic T cell (CTL) induction and DC migration to the target organ. It has been reported that injected intra-tumor DCs are expected to work phagocytosis of the tumor as a localized effect. Consequently CTL induction in the tumor and the regional lymphnodes results in a systemic effect. In this study, intra-tumor DC injection therapy was performed by means of endoscopic ultrasonography (EUS) in 2 gastric cancer cases. As a result, tumor markers and ascites of one case were on the decrease. The results indicate this method can be useful in advanced cancer patients.

Dendritic Cells↗

PubMed2003

Low frequency of observed anti-HLA among transfused preterm infants.

BACKGROUND: Although low-birth-weight infants (LBWI) often receive multiple transfusions, there is controversial information on their development of antibodies against WBCs or platelets. STUDY DESIGN AND METHODS: A total of 52 LBWI with birth weights less than 1500 g were randomly assigned to receive either RBCs that had been WBC- reduced (n = 25) or nonfiltered blood (n = 27). Serum samples collected from 37 infants at 3 months of age and from 30 children when they were 5 to 11 years old were tested. Anti-HLA was assayed with an anti-human globulin-augmented lymphocytotoxicity test against a panel consisting of 13 lymphocytes and against parental cells. RESULTS: None of 52 transfused LBWI of either group developed anti-HLA (95% CI, 0%-6.8% for overall, 0%-13.7% for the WBC-reduced group, and 0%-12.7% for the nonfiltered group). CONCLUSION: Multiply transfused LBWI rarely produced antibodies to HLA of blood donors and to noninherited maternal antigens. The benefits of WBC reduction to prevent HLA alloimmunization during infancy were not supported by this study and need further investigation.

Blood Transfusion↗

PubMed2003

Collection of MNCs and progenitor cells by two separators for PBPC transplantation: a randomized crossover trial.

BACKGROUND: Efficient collection of progenitor cells is essential for PBPC transplantation. Two apheresis machines (Amicus, Baxter Healthcare; and Spectra, Gambro BCT, software version 4.7) were compared prospectively by a crossover trial. STUDY DESIGN AND METHODS: Apheresis collections were performed for two consecutive days on patients for autologous and donors for allogeneic PBPC transplantation. The patients and donors, receiving a G-CSF, were randomized into two groups. In Group I, PBPCs were collected by the Amicus on the 1st day and the Spectra on the 2nd day, and the reverse order was used with Group II. A total of 60 apheresis procedures of 30 (16 in Group I and 14 in Group II) among 40 patients and donors enrolled were performed and evaluated. RESULTS: The nucleated cell counts, MNC counts, CD34+ PBPC counts, and amounts of CFU-GM collected per procedure were similar with the Amicus and the Spectra. On the other hand, the decrease of peripheral blood platelet counts of patients and donors was more prominent from using Spectra than Amicus (p < 0.0001). Components collected by the Amicus had fewer platelets than those collected by the Spectra (p < 0.0001). The efficiencies of collecting nucleated cells, MNCs, and CD34+ PBPCs were not different between the machines (p > 0.05). However, the efficiency of collecting platelets was significantly higher with Spectra than with Amicus (p < 0.0001). The Amicus took longer than the Spectra to process the same volume (p < 0.05). CONCLUSION: Amicus is superior to Spectra in avoiding apheresis-induced thrombocytopenia caused by platelets contaminating the collected samples. Therefore, the Amicus is useful for patients with thrombocytopenia or with a less-than-normal platelet count.

Adolescent↗

PubMed2003

HLA alloimmunization of surgical patients by transfusion with bedside leukoreduced blood components.

High efficiency leukocyte reducing filters can remove more than 99.9-99.99% of white cells from cellular blood components and are considered to be effective in decreasing HLA alloimmunization of patients with haematological malignancies. A multi-institution study was performed to determine whether white cell filtration would also be effective in preventing alloimmunization in surgical transfusion recipients. Patients who were to receive red cell blood transfusions during and/or within 48 hours after surgery were randomly assigned to receive red cells/ fresh frozen plasma that had been leukoreduced using a high efficiency filter at the bedside or buffycoat-depleted red cells transfused through an aggregate filter. Of 87 patients with no alloantibodies at entry, 17% (8/47) of those in the leukoreduction group, who received a mean of 0.3 x 10(6) leukocytes as a result of their transfusions, produced lymphocytotoxic antibodies at day 14 after transfusion, compared to 5% (2/40) in the buffycoat-depleted group, who had received a mean of 1,234.2 x 10(6) leukocytes. This difference in the alloimmunization rate between the two arms was not statistically significant. Reduction of leukocytes by bedside filtration does not appear to be effective in preventing HLA alloimmunization in surgical transfusion recipients. The alloimmunized cases suggest that an indirect allorecognition pathway may be involved in the formation of anti-HLA. Further measures are needed to reduce alloimmunization of immunocompetent patients.

Adult↗

PubMed2003

[Effect of DC therapy combined with chemotherapy in advanced cancer cases].

Dendritic cells (DC) are powerful antigen-presenting cells, and have attracted attention in recent years from the viewpoint of DC vaccine therapy against cancer. However, the existence of an immunosuppressive state in cancer individuals leads to anergy and immunotolerance, which has been reported to be caused by T cell and DC immunosuppressive subsets or cytokines such as Th2, Tc2, CD4+CD25+, DC2 and IL-10 against Th1, Tc1, DC1 and IL-12. Therefore, DC therapy could be incompatible with severe chemotherapy. Conversely, there are some reports that indicate tumor specific cytotoxicity in DC therapy could be augmentedly un exposure to tumor antigen caused by apoptosis in combination radiation or chemotherapy. In this study we examined the usefulness of DC therapy combined with chemotherapy and BRM (PSK) administration by analyzing the immunocyte subsets and cytokines as well as the combination effect. The results indicate this method can be useful in advanced cancer patients.

Adjuvants, Immunologic↗

PubMed2002

TT virus infection during childhood.

BACKGROUND: TT virus (TTV) is widespread in the general population, however, the mode of its transmission and the mechanism of maintaining it in the general population are unclear. STUDY DESIGN AND METHODS: To determine the possible mother-to-infant route of transmission, 54 infants bom to 50 anti-HCV-positive mothers were assessed longitudinally. Nucleotide sequences amplified by seminested PCR with primers targeting the N22 variable coding region of genotypes 1 through 6 were compared in mothers and their infants. RESULTS: The prevalence of TTV DNA was 30 percent (15/50; 95% CI, 18-45) in mothers and 44 percent (24/54; 95% CI, 31-59) in their infants. TTV DNA was detected during a follow-up period in 13 (87%; 95% CI, 60-98) of 15 infants born to infected mothers and in 11 (28%; 95% CI, 15-45) of 39 infants bom to DNA-negative mothers. None of 38 cord blood samples, but one of 14 blood samples, obtained at 1 month of age had detectable TTV DNA. The lowest infection rate at the earliest ages and the subsequent increasing prevalence of infection (22% at 6 months and 33% [43% cumulative rate] at 2 years) is consistent with an age-dependent acquisition of TTV by nonparenteral routes. In 13-mother-infant pairs positive for TTV DNA, six showed a high degree of nucleotide sequence similarity (99.1-100%), whereas the remaining seven pairs differed more than 10 percent from each other (46.8-89.2%). The viral load of matemal blood was not a plausible risk factor for transmission. Genotype 1, of which pathogenicity failed to be shown by measurement of hepatic enzymes, was more rapidly cleared (88 vs. 8% other genotypes, p < 0.001) among infants. CONCLUSIONS: These observations strongly suggest that the main factor for TTV acquisition in children involves their age-associated increase in environmental interactions with infectious materials. Genotype 1 might be involved in a weak or a limited pathologic role, which can possibly be diluted by other harmless genotypes.

Adult↗

PubMed2002

Treatment for the decline of ionized calcium levels during peripheral blood progenitor cell harvesting.

BACKGROUND: ACD-A solution containing sodium citrate and citric acid is used as an anticoagulant agent during peripheral blood progenitor cell (PBPC) harvesting, and in rare cases can cause fatal citrate intoxication. The aim of this study was to establish effective methods for stabilizing ionized calcium (ICa) levels during PBPC harvesting. STUDY DESIGN AND METHODS: ICa was measured during 46 apheresis procedures conducted in 26 patients. Four patients in four procedures were infused with calcium gluconate solution before PBPC harvesting; three patients in six procedures were infused with calcium gluconate when symptoms of citrate intoxication appeared; and four patients in five procedures received a continuous infusion. Five patients in five procedures took an isotonic sports drink containing calcium when hypocalcemic symptoms appeared. The ICa level, blood pressure, and pulse rate were measured. RESULTS: ICa declined rapidly from the preapheresis level of 1.081(+/-0.092) mM to 0.937(+/-0.081) mM (13.3%, p < 0.0001) 10 minutes after the start of apheresis and continued to decline until the completion of the procedure. When patients received a continuous infusion of calcium during apheresis, ICa was relatively stabilized. ICa significantly rose (6.1 +/- 3.6%, p < 0.02) within 2 to 5 minutes after oral intake of an isotonic sports drink containing calcium and was maintained within normal range for 31 to 55 minutes. CONCLUSION: An isotonic sports drink containing calcium has a quick stabilizing and a longer maintenance effect on ICa. Thus, we recommend the intake of an isotonic sports drink containing calcium as the easiest and best method for preventing hypocalcemia during apheresis.

Administration, Oral↗

PubMed2002

[Successful treatment with combined anti-thymocyte globulin and methylprednisolone for bronchiolitis obliterans after allogeneic bone marrow transplantation in a child with chronic myelogenous leukemia].

A 9-year-old boy with secondary chronic myelogenous leukemia after treatment of acute lymphoblastic leukemia underwent allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling in December 1998. Grade II acute GVHD developed on day 24 and chronic GVHD developed 5 months after BMT. Cough and dyspnea appeared 9 months after BMT. Despite administration of tacrolimus and methylprednisolone (m-PSL) pulse therapy, the dyspnea gradually increased in severity. Bronchiolitis obliterans was diagnosed on the basis of lung biopsy in January 1999. Because renal dysfunction made it difficult to continue the use of tacrolimus, we attempted antithymocyte globulin (ATG) + m-PSL therapy. Major BCR/ABL mRNA was transiently positive on RT-PCR after the ATG + m-PSL therapy, but no severe complications were observed. A decreasing V50/V25 level and increasing peak flow value were observed in respiratory function tests after ATG + m-PSL therapy, and the patient is currently free of dyspnea. Our findings suggest that ATG + m-PSL therapy is beneficIal for patients with drug-resistant bronchiolitis obliterans after BMT.

Anti-Inflammatory Agents↗

PubMedDate not supplied

Effects of PSK on T and dendritic cells differentiation in gastric or colorectal cancer patients.

BACKGROUND: Vaccine therapy targeting tumor antigens recognized by cytotoxic T cells (CTL) has been tried extensively. However, in a cancer-bearing state, the Th1/Th2 balance shifts to Th2 dominance, and this has been the obstacle to vaccine therapy to induce the CTL. DC1/DC2 subsets have also been reported to control the differentiation of Th subsets. The key to tumor immunotherapy is how to activate the DC1-Th1 lineage. PATIENTS AND METHODS: Six normal adults and 14 patients with gastric or colorectal cancers, who gave informed consent, were studied. The Th1/Th2 and DC1/DC2 ratios were determined by FACS. IL-12 and IL-10 production from PBMC were measured by ELISA. RESULTS: The Th1/Th2 and DC1/DC2 ratios were all significantly lower in the patients with gastric or colorectal cancers compared to normal adults. After protein-bound polysaccharide K (PSK) therapy in cancer patients, the Th1/Th2 balance shifted to Th1 dominance and the DC1/DC2 balance to DC1 dominance. IL-10 production was significantly decreased by PSK therapy. CONCLUSION: In the cancer-bearing state, the Th1/Th2 and DC/1/DC2 balance becomes Th2- and DC2-dominant. PSK therapy results in a shift of the Th1/Th2 and DC1/DC2 balance towards Th1 and DC1 dominance. We plan to examine whether combining dendritic cells (DC) vaccination therapy with oral PSK enhances the induction of T cell and DC differentiation in cancer patients.

Adult↗

PubMedDate not supplied

Understanding the response of dendritic cells to activation by streptococcal preparation OK-432.

BACKGROUND: The streptococcal preparation OK-432 induces maturation of T cells and dendritic cells (DCs). However, the mechanisms by which OK-432 induces DC maturation are not well understood. MATERIALS AND METHODS: The effects of OK-432 and TNF-alpha on peripheral blood mononuclear cells (PBMCs) were compared. Antibody-based approaches were used to detect proteins characteristic of antigen-presenting cells and cytokines. Cytotoxicity was evaluated by measuring the release of LDH after incubation of effector and target cells. The TLR-4 levels were measured by real-time quantitative PCR. RESULTS: Changes in cell surface marker levels were detected in both treatment groups but OK-432 had a greater effect on induction of Th-1-type cytokines. Furthermore, TLR-4 mRNA was up-regulated in cells from two out of five patients in response to OK-432, but not in response to TNF-alpha. CONCLUSION: OK-432 has a more profound effect on human DCs than TNF-alpha and may act through multiple signaling pathways.

Adult↗