Hiromichi Take

Role of breast milk in acquisition of cytomegalovirus infection.

The prevalence of IgG antibody against cytomegalovirus (CMV) was compared between the age‐matched (0 month to 2 years of age) groups of 212 breast‐fed children and 223 bottle‐fed children to examine the role of breast milk for acquisition of CMV. Mothers of both groups of children were also examined for CMV IgG antibodies. Both the breast‐fed and bottle‐fed children groups showed high seropositivity for CMV at 0 to 2 months of age, which gradually decreased and bottomed at 6 to 8 months of age. Thereafter, in the breast‐fed children group, the seropositivity rate increased up to 70% by 1 year of age. In contrast, in the bottle‐fed children group, the seropositivity rate remained at the bottom level of lower than 30%, without showing any apparent increases. The serological data of the children whose mothers were confirmed to be seropositive, revealed that mother‐to‐child transmission of CMV occurred in 11 of 17 (64.7%) of the breast‐fed children and in 24 of 87 (27.6%) of the bottle‐fed children. All the bottle‐fed children born to seronegative mothers remained seronegative for CMV up to 1 year of age. The bottle‐fed children showed significantly lower seropositivity than the breast‐fed children, although most of both groups of children were born to seropositive mothers. The results strongly suggested that about 40% of the breast‐fed children acquire CMV via breast milk and breast‐feeding has certain protective effects on congenital CMV disease in the offspring.

Restricted diversification of T-cells in chronic active Epstein-Barr virus infection: Potential inclination to T-lymphoproliferative disease

To assess the abnormal T‐cell expansion in chronic active Epstein‐Barr virus infection (CAEBV), T‐cell antigen receptor (TCR) repertoire was analyzed in four patients with the disease. All fulfilled the diagnostic criteria of CAEBV, presenting with fever, hepatosplenomegaly, cytopenia, abnormal high titers of anti EBV‐antibodies, and positive EBV genome of unknown cause. Southern blotting probed with EBV‐terminal repeats and TCR Cβ gene indicated clonal expansion of the infected cells in 3 and 2 patients, respectively. The number of CD4+ HLA‐DR+ cells appreciably increased in patients 1 (59%) and 2 (24%), who had a coronary aneurysm and central nervous system involvement, respectively. TCR gene expression examined by the inverse polymerase chain reaction methods revealed that Vβ gene usages were preferential in all patients (Vβ7 and Vβ12: patient 1, Vβ4: patient 2, Vβ13: patients 3 and 4), compared with those in healthy controls. Vα18 gene expression was remarkably high in patients 1 and 2. Moreover, Jβ gene expression was skewing in the reigning Vβ clones in all patients. Vβ4‐Jβ1.5 and Vβ13‐Jβ1.5 genes were clonally expressed in patients 2 and 4, respectively. These results suggest that CAEBV is associated with the restricted diversity of T‐cells, which may stem from the sustained expansion of oligoclonal T‐cells possibly driven by conventional viral antigens, but not, superantigens. Although the study is limited by the small number of patients, the unbalanced T‐cell repertoire might contribute to the evolution of T‐lymphoproliferative disease, otherwise, imply the innate defective immunity to EBV in CAEBV patients. Am. J. Hematol. 61:26–33, 1999.

Breast Milk Is Not a Significant Source for Early Epstein-Barr Virus or Human Herpesvirus 6 Infection in Infants: A Seroepidemiologic Study in 2 Endemic Areas of Human T-Cell Lymphotropic Virus Type I in Japan

In order to evaluate the possibility of Epstein‐Barr virus (EBV) and human herpesvirus 6 (HHV‐6) transmission via breast milk, a total of 331 serum specimens collected from bottle‐fed and breast‐fed children and their mothers, in 2 endemic areas of human T‐cell lymphotropic virus type I (HTLV‐I) in Japan, were assayed for antibodies to EBV and HHV‐6. The seroprevalences of EBV and HHV‐6 were over 95% both in the mothers of bottle‐fed children and in those of breast‐fed children. The seroprevalence of EBV at 12–23 months of age was 54.5% (36/66) and 55.8% (24/43) in breast‐fed children and bottle‐fed children, respectively. The seroprevalence of HHV‐6 at 12–23 months of age was 90.9% (60/66) and 93.0% (40/43) in breast‐fed children and bottle‐fed children, respectively. No difference was observed between the seroprevalences of EBV and HHV‐6 in breast‐fed and bottle‐fed children at 12–23 months of age. Our seroepidemiologic data indicate that breast milk is not a significant source of early EBV or HHV‐6 infection in infancy.

Long-term outcome of treatment with protocols AL841, AL851, and ALHR88 in children with acute lymphoblastic leukemia: results obtained by the Kyushu-Yamaguchi Children's Cancer Study Group.

We analyzed the long-term outcome and late effects of treatment in 187 patients with childhood acute lymphoblastic leukemia (ALL) diagnosed between 1984 and 1990. Overall survival and event-free survival rates were 68.2% +- 3.7% and 63.2% +- 3.6% at 15 years, respectively. Of 55 patients who relapsed after achieving the first complete remission (CR), only 17.4% were rescued by salvage therapy. The advantage of stem cell transplantation over chemotherapy was observed only in those patients with bone marrow relapse during therapy. The SD for score height in patients maintaining the first CR significantly decreased at the time of final follow-up compared with that at diagnosis: 0.059 to -0.800 (P < .0001). The decrease was remarkable in patients younger than 5 years at diagnosis. Other late effects included mild liver dysfunction in 18% and hepatitis C virus infection in 9%. Congestive heart failure was observed in only 2.9% of patients despite the high cumulative dose of daunorubicin (450 mg/m2). Although the survival rates of patients on our protocols were comparable to those of other study groups, some modification, including reduction in dose of cranial irradiation and/or anticancer drugs, should be considered to reduce late adverse effects in survivors of childhood ALL.

TREATMENT OF STANDARD-RISK ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN: The Results of Protocol AL841 from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan

A total of 62 patients with standard-risk acute lymphoblastic leukemia received three-drug induction consisting of vincristine, prednisolone, and L-asparaginase (l-Asp) followed by consolidation therapy with intermediate-dose methotrexate (MTX), intrathecal MTX, and 18 Gy of cranial irradiation. Maintenance therapy consisting of 6 drugs including daunorubicin (DNR, 450 mg/m2 in total) was continued for 3 years. Patients were randomized and half of them received weekly l-Asp during maintenance therapy as a late intensification. Complete remission (CR) was achieved in 61/62 (98.4%), and 11 of 61 patients relapsed. At 10 years, the event-free survival (EFS) was 80.6 +/- 5.0% and overall survival was 88.7 +/- 4.0%; median follow-up time was 9.3 years. The 10-year EFS of patients with additional l-Asp (84.8 +/- 6.2%) was superior to that without l-Asp (75.9 +/- 7.9%), although it was not statistically significant. No patients who received a full dose of DNR and maintained CR developed heart failure, although the shortening fraction decreased from 41.0% at diagnosis to 35.2% (median). The protocol AL841 provided good long-term disease control without severe late cardiac dysfunction.

Prevalence of appendectomy in Japanese families

We investigated the prevalence of appendectomy in Japan to determine the tendency of familial aggregation on appendicitis using a large scale study. A total of 517 Japanese women (aged 20 to 45 years) served as the subjects and were questioned regarding their family history of appendectomy due to appendicitis. We compared the prevalence of appendectomy in children (subjects + their siblings) of three groups of families: (i) both parents affected; (ii) one parent affected; (iii) no parents affected. The differences between groups were statistically significant using contingency table and Chi‐squared test. Our results suggest that about 40% of children with both parents affected, and about 20% of children with one parent affected may develop the disorder during childhood. This study may provide useful information in the nature of the development of appendicitis.

Advanced atrioventricular block associated with atrial tachycardia caused by Mycoplasma pneumoniae infection

Atrial tachycardia with atrioventricular (AV) block has been recognized as a common manifestation of digitalis toxicity. We describe here an unusual case of transient advanced AV block associated with atrial tachycardia in a 6 year old boy with evidence of Mycoplasma pneumoniae infection.

Impact of serum antibodies to p40tax gene product in the intrafamilial transmission of human T cell leukemia virus type I

We examined the sera of family members of human T cell leukemia virus type I (HTLV‐I) seropositive pregnant women who had visited Kagoshima City Hospital since 1986, and studied the routes of transmssion of HTLV‐I. A new enzyme linked immunosorbent assay (ELISA) for detecting the antibody to an HTLV‐I tax gene product, p40tax, has recently been developed. By this ELISA method, the positive rate of anti‐p40tax among HTLV‐I seropositive subjects, including 96 pregnant women (index subjects), 26 mothers, 13 husbands and 13 children was investigated. The percentage positive for anti‐p40tax among pregnant women, mothers, husbands, and children was 41.6, 50, 53.8 and 53.8%, respectively. This means that the positive rate of anti‐p40tax remains almost constant with increasing age. The rate of mother‐to‐child transmission of HTLV‐I was significantly higher in p40tax seropositive (29.6%) than in seronegative mothers (8.1%). The positive rate of anti‐p40tax in transmission from husband to wife (29%) and through blood transfusion (17%) was lower than the overall prevalence (46%). Thus, these data suggest that p40tax antibodies are associated with the frequency of HTLV‐I transmission and with the differences in the transmission routes.

Risk of HTLV-I infection in Japanese women who are last in birth order.

The percentage of last-born women among pregnant women who were seropositive for human T-lymphotropic virus type I (HTLV-I) significantly exceeded that among HTLV-I seronegative women (119/258 (46.1%): 89/251 (35.4%); P < 0.05). The findings suggest that last-born women are susceptible to HTLV-I infection. At least two possible interpretations of this birth-order effect are: (i) these last-born women were born to mothers who, on the average, were older than those of early-born women and, as a consequence, were more likely to have been seropositive and to have passed on HTLV-I to their daughters; (ii) husband-to-wife transmission of HTLV-I requires time to occur, so last-born women are more likely than early-born women to become infected.

Marriage patterns among HTLV-I seropositive women in Japan

A significantly higher percentage of asymptomatic HTLV-I seropositive pregnant women in the Kagoshima prefecture were married to men who were also born in that prefecture compared with seronegative women [138/166(83.1%), 221/306 (72.2%); P < 0.01]. A significantly higher percentage of the fathers of the seropositive women were born in the Kagoshima prefecture compared with the fathers of the seronegative women [152/166 (91.6%), 235/306 (76.8%); P < 0.01]. Additionally, a significantly higher seropositivity was found among pregnant women born in the Kagoshima prefecture who were married to men born in that prefecture compared with men born in other prefectures [5.8% (138/2374), 3.4% (28/819); P < 0.01]. Women born in other prefectures had a significantly lower seropositivity irrespective of the birthplace of their spouse [2.9% (12/418); P < 0.05, 3.0% (7/234)]. These findings indicate that HTLV-I seropositive women and their mothers chose their husbands from a smaller geographic region than seronegative women. This marriage pattern within an HTLV-I seropositive group may be one of the factors sustaining the present seroprevalence of HTLV-I.