Hitoshi Ohto

Transmission of Hepatitis C Virus from Mothers to Infants

Background Although there are case reports of vertical transmission of hepatitis C virus (HCV), it remains uncertain to what extent infected mothers transmit this virus to their infants. Methods We investigated the transmission of HCV from infected mothers to their babies by analyzing HCV RNA in the blood. Three independent studies were performed. First, 7698 parturient women were tested for anti-HCV antibodies; 53 were positive. Their 54 infants (including one set of twins) were followed prospectively for at least six months and tested for HCV infection. Second, the babies of six women with known HCV disease were prospectively studied. Third, the families of three HCV-infected infants were examined retrospectively. Results Of the 53 antibody-positive mothers, 31 were also positive for serum HCV RNA. Three of the 54 babies born to these mothers (5.6 percent) became positive for HCV RNA during the follow-up period. None of the babies of the 22 women who were antibody-positive but HCV RNA-negative became po...

Kinetics of fetal cellular and cell‐free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis

BACKGROUND: Fetal genetic material is detectable in the maternal circulation and has been used for noninvasive prenatal diagnosis. However, few data are available concerning its quantity and natural history during gestation.

Transplacental leakage ofHBeAg-positive maternal blood as the most likely route in causing intrauterine infection with hepatitis B virus

Thirty-two HBeAg-positive carrier mothers and their 32 babies were investigatedto elucidate the mechanism involved in intrauterine infection with HBV. Five mothers had symptoms and signs of threatened abortion and/or threatened preterm labor. Three mothers gave birth more than 6 weeks after the episodes, and their babies were those infected in utero. The other two gave birth within 1 week after the episodes, and the two babies were treated with HBIG immediately after birth; HBV infection was successfully prevented. Therefore we suggest that transplacental leakage of HBeAg-positive maternal blood, which is induced by uterine contractions during pregnancy and the disruption of placental barriers, is the most likely route to cause HBV intrauterine infection.

Survey of Transfusion-Associated Graft-Versus-Host Disease in Immunocompetent Recipients

premature newborns, neonates treated with exchange transfusions, patients with hematologic malignancies, and patients with solid tumors treated with chemotherapy or radiotherapy. Patients with solid tumors treated with only surgery were included.

Secondary anti‐D immunization by Del red blood cells

BACKGROUND:  Recent molecular studies of the RHD gene have revealed that Del individuals retain a grossly intact RHD gene or have a portion of RHD in their genomes. No Del phenotype has yet been shown to induce a primary or secondary alloanti‐D immunization, however.

Overview on platelet preservation: Better controls over storage lesion

Platelet storage lesion (PSL), correlating with reduced in vivo recovery/survival and hemostatic capacity after transfusion, is characterized essentially by morphological and molecular evidence of platelet activation and energy consumption in the medium. Processes that limit shelf-life are multifactorial, and include both necrosis and apoptosis. PSL is greatly influenced by factors including duration of storage, temperature, ratio of platelet number to media volume, solution composition with respect to energy content and buffering capacity, and gas permeability of the container. Recent progress for slowing PSL has been made with storage media that more effectively fuel ATP production and buffer the inevitable effects of metabolism. Improved oxygen-permeability of containers also helps to maintain aerobic-dominant glycolysis. Patients stand to benefit from platelet products of higher intrinsic quality that store well until the moment of transfusion.

Circulating myeloid-derived suppressor cells are increased and correlate to immune suppression, inflammation and hypoproteinemia in patients with cancer

Recent studies have identified myeloid-derived suppressor cells (MDSCs) that are potent suppressors of tumor immunity and therefore a significant impediment to cancer immunotherapy. It has been reported that MDSCs are generated by malignant diseases or inflammation. However, no systematic studies in patients have been described. In order to clinically characterize MDSCs, we tested PBMCs from patients with various types of cancer including cholangiocellular, hepatocellular and pancreatic carcinoma, esophageal, gastric and colorectal cancer, breast cancer and thyroid cancer, and GIST, and those from normal volunteers using flow cytometry analysis. A significant increase was seen in the percentages of MDSCs in PBMCs from patients compared with normal volunteers. Among these patients, MDSC level was higher in patients with cancer of the digestive system and patients with breast cancer compared with normal volunteers. MDSC level was significantly and inversely correlated to stimulation indices (SI) of PHA-blastogenesis of lymphocytes and serum concentration of total protein, and positively correlated to neutrophil count. MDSC percentage in patients with gastric and colorectal cancer was also significantly correlated to neutrophil count and inversely correlated with lymphocyte count, and showed highly significant correlation to neutrophil/lymphocyte rate (NLR). In patients with breast cancer, MDSC levels in preoperative patients was significantly increased compared to normal volunteers and significantly decreased in postoperative patients. Thus, it is clear that MDSCs are increased in patients with cancer and closely related to suppression of cell-mediated immune responses. These data also suggest that they are related to chronic inflammation and that their levels are increased further in the terminal stages of patients whose nutritional status is impaired as observed in hypoproteinemia. MDSC levels have also been shown to decrease after removal of tumors in patients with breast cancer.

Neonatal lupus erythematosus in Japan

BACKGROUND Although more than 200 cases of neonatal lupus erythematosus (NLE) have been reported, the prognosis, clinical characteristics, and genetic background of the patients are still obscure. Their symptoms seem to vary in different races. OBJECTIVE We had an opportunity to see two clinically different types of NLE. It is important to define the clinical characteristics in Japanese cases and to compare them to caucasian NLE cases reported earlier. METHODS Sixty Japanese infants with NLE and their mothers reported in Japan were investigated and compared with cases reported from other countries. RESULTS Japanese cases were highly associated with anti-SS-A/Ro, anti-SS-B/La, anti-ribonuclear protein, and anti-DNA antibodies. A low frequency of congenital heart block was noted but 8.3% of the cases progressed to systemic lupus erythematosus. HLA-DRw12 was a significantly relative risk in NLE. CONCLUSION The clinical characteristics of Japanese NLE patients were different from those of caucasian patients reported in the literature.

The natural history of maternal immunization against foetal platelet alloantigens

Summary.  Foetomaternal alloimmune thrombocytopenia (FMAIT) occurs when maternal antibodies of an antigen‐negative mother cause destruction of sensitized foetal platelets. In Caucasian populations, 6–12% of human platelet antigen (HPA)‐1a‐negative women develop anti‐HPA‐1a, and the incidence of clinically affected cases is estimated to be 10–20% of immunized women. This study was performed in order to elucidate the rate of maternal immunization, incidence of FMAIT and the likely outcome of the condition in Asians. Excluding two or more pregnancies during the period, serum samples from 24 630 pregnant women, mainly Japanese, were screened for antibodies against platelet alloantigens by means of mixed passive haemagglutination (MPHA) (Anti‐HPA‐MPHA, Olympus, Tokyo). Antibodies were detected in 0·91% (223/24 630) of the womens samples and the immunization rate was correlated with the number of pregnancies. Antibody specificity included anti‐HPA‐4b (49), anti‐HPA‐5a (three), anti‐HPA‐5b (168), anti‐HPA‐4b + 5b (one) and anti‐Naka (CD36) (two). No alloimmunization was observed within the HPA‐1, HPA‐2, HPA‐3 or HPA‐6 systems. Among HPA‐4b‐ or HPA‐5b‐negative women, 24% or 14% estimated, respectively, had antibodies and 26% (10/38) or 10% (12/125) of neonates, respectively, born to these mothers developed thrombocytopenia. Two neonates born to mothers having anti‐HPA‐4b developed generalized purpura. No cases of intracranial bleeding or death due to FMAIT were recorded. Generalized purpura due to FMAIT occurs in one in 9359 (95% CI: 1 in 77 519–1 in 2591) pregnancies solely because of HPA‐4b incompatibility.

Nuclear disasters and health: lessons learned, challenges, and proposals

Past nuclear disasters, such as the atomic bombings in 1945 and major accidents at nuclear power plants, have highlighted similarities in potential public health effects of radiation in both circumstances, including health issues unrelated to radiation exposure. Although the rarity of nuclear disasters limits opportunities to undertake rigorous research of evidence-based interventions and strategies, identification of lessons learned and development of an effective plan to protect the public, minimise negative effects, and protect emergency workers from exposure to high-dose radiation is important. Additionally, research is needed to help decision makers to avoid premature deaths among patients already in hospitals and other vulnerable groups during evacuation. Since nuclear disasters can affect hundreds of thousands of people, a substantial number of people are at risk of physical and mental harm in each disaster. During the recovery period after a nuclear disaster, physicians might need to screen for psychological burdens and provide general physical and mental health care for many affected residents who might experience long-term displacement. Reliable communication of personalised risks has emerged as a challenge for health-care professionals beyond the need to explain radiation protection. To overcome difficulties of risk communication and provide decision aids to protect workers, vulnerable people, and residents after a nuclear disaster, physicians should receive training in nuclear disaster response. This training should include evidence-based interventions, support decisions to balance potential harms and benefits, and take account of scientific uncertainty in provision of community health care. An open and joint learning process is essential to prepare for, and minimise the effects of, future nuclear disasters.