Improvement in the Treatment of Childhood Cancer: Analysis of Survival Data from the National Children's Hospital (1965-1987)

Developments in the treatment of childhood cancer have beenevaluated in patients who had been treated in the National Children'sHospital from 1965 to 1987. The total number of patients was867, of which leukemia accounted for 376, malignant lymphoma61, neuroblastoma 174, Wilms' tumor 55, yolk sac tumor 29, rhabdomyosarcoma36 and hepatoblastoma 30. Patients were divided into three timeintervals: the 1960s, 1970s and 1980s. A marked improvementin five-year survival was recognized in Wilms' tumor and yolksac tumor, amounting to 80%, followed by rhabdomyosarcoma, acutelymphoblastic leukemia and malignant lymphoma. There was noimprovement in patients with acute non-lymphoblastic leukemia,neuroblastoma and hepatoblastoma. Prognostic factors for neuroblastomawere further analyzed, and the age of onset and stage of diseasewere found to have remained constant for 23 years. Factors relatingto the improvement of survival were discussed.     

Radioallergosorbent test (RAST) for specific IgE antibody to lidocaine,procaine and methylparaben

Although anaphylactoid reactions to local anesthetics are well known, a radioallergosorbent test (RAST) to detect specific drug reagin (IgE) anti-body has not been developed. We established RAST for local anesthetics by using carboxylic acid derivatives of lidocaine, procaine and methylparaben. Serum samples were taken from 100 volunteers who were regarded to be nonallergic to the drugs used. Negative RAST values obtained from these volunteers were 1653 ± 254(SD) cpm (lidocaine), 2750 ± 264cpm (procaine), and 2805 ± 336cpm (methyl paraben).(Kokubu M, Oda K, Shinya N: Radioallergosorbent test (RAST) for specific IgE antibody to lidocaine, procaine and methylparaben. J Anesth 3: 74–79, 1989)     

Transient induction of single GST-P positive hepatocytes by DEN

The single cells positive for placental glutathione S-transferase(GST-P), detectable in livers of rats soon after treatment withhepatocarcinogens, are possible ‘initiated cells’,the hypothesis tested in the present series of experiments.No low dose threshold was observed in male Sprague-Dawley ratsat different single doses of diethylnitrosamine (DEM) althougha plateau was reached between 160 and 200 mg/kg body weight.At the latter single dose 12 400 positive cells/cm³ were observedimmunohistochemically in rat livers after one week, the numbersthen decreasing to week 8 and thereafter rising again. In thenumbers then decreasing to week 8 and thereafter rising again.In the early stages single cells predominated but with timea gradual increase in mini-foci and larger lesions became evident.Application of selection pressure (feeding of diet containing0.02% 2-AAF plus partial hepatectomy) to rats 2–24 weeksafter single DEN-treatment resulted in the formation of largefoci positive for GST-P, especially in the early stages, thegrowth response being less pronounced with time. The numberof foci, on the other hand. was correlated with the number offoci, on the other hand, was correlated with the number ofsingle cells/mini-foci detected inhepatectomy tissue of thesame individuals. These results suggest that the early GST-Ppositive populations could be the precursor for preneoplasticfoci and nodules.     

Central distribution of efferent and afferent components of the pudendal nerve in rat

Summary Central distribution of efferent and afferent components of the pudendal nerve was examined in the rat by the horseradish peroxidase (HRP) method after HRP application to the central cut end of the pudendal nerve. The pudendal motoneurons were located in the dorsolateral, dorsomedial and lateral groups at L5 and L6. Each of the dorsolateral and dorsomedial groups constituted a slender longitudinal cell column. Pudendal motoneurons in the lateral group were scattered at L5, rostrodorsally to the dorsolateral group. The neurons in the dorsolateral and lateral groups were labelled with HRP applied to the nerve branch innervating the ischiocavernosus and sphincter urethrae muscles. The neurons in the dorsomedial group were labelled with HRP applied to the branch supplying the sphincter ani externus and bulbospongiosus muscles. Some dendrites of pudendal motoneurons in the dorsomedial group extended to the contralateral dorsomedial group. These crossing dendrites were observed not only in male rats but also in female. The average number of the pudendal motoneurons in the dorsolateral and dorsomedial groups were larger in male rats than in female. A few neurons of the intermediolateral nucleus at upper L6 were also labelled with HRP applied to the dorsalis penis (clitoridis) nerve. Axon terminals of the pudendal nerve were distributed, bilaterally with an ipsilateral predominance, to the gracile nucleus, as well as to the dorsal horn and dorsal commissural gray from L4 to S2. A few labelled axons were seen in the intermediolateral nucleus at L6 and S1. Axon terminals from the dorsalis penis nerve were distributed more medially in the dorsal horn than those from the perinealis nerve.     

Morphometric difference in the human maxillary nerve fibers between dentulous and edentulous jaw subjects

This study was conducted to quantify the change in the number and size of myelinated nerve fibers of the maxillary nerve with tooth loss in humans. We carried out a morphometric analysis to compare the number and size of myelinated nerve fibers in the human maxillary nerve between four dentulous and four edentulous jaw cases. Our results indicated that the number of axons decreased by approximately 13,000 with tooth loss. The average size of axons remained unchanged, but there was a change in the fiber size distribution, namely the loss of a large number of small-sized axons was accompanied by the total disappearance of small number of large-sized axons.     

Cellular localization of Babesia bovis merozoite rhoptry-associated protein 1 and its erythrocyte-binding activity

The cellular localization of Babesia bovis rhoptry-associated protein 1 (RAP-1) and its erythrocyte-binding affinity were examined with anti-RAP-1 antibodies. In an indirect immunofluorescent antibody test, RAP-1 was detectable in all developmental stages of merozoites and in extracellular merozoites. In the early stage of merozoite development, RAP-1 appears as a dense accumulation, which later thins out and blankets the host cell cytoplasm, but retains a denser mass around newly formed parasite nuclei. The preferential accumulations of RAP-1 on the inner surface of a host cell membrane and bordering the parasite's outer surface were demonstrable by immunoelectron microscopy. An erythrocyte-binding assay with the lysate of merozoites demonstrated RAP-1 binding to both bovine and equine erythrocytes. Anti-RAP-1 monoclonal antibody 1C1 prevented the interaction of RAP-1 with bovine erythrocytes and significantly inhibited parasite proliferation in vitro. With the recombinant RAP-1, the addition of increasing concentrations of Ca(2+) accentuated its binding affinity with bovine erythrocytes. The present findings lend support to an earlier proposition of an erythrocytic binding role for RAP-1 expressed in B. bovis merozoites and, possibly, its involvement in the escape of newly formed merozoites from host cells.     

FGF signaling segregates biliary cell-lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro.

Intrahepatic bile ducts (IHBDs) are indispensable for transporting bile secreted from hepatocytes to the hepatic duct. The biliary epithelial cells (BECs) of the IHBD arise from bipotent hepatoblasts around the portal vein, suggesting the portal mesenchyme is essential for their development. However, except for Notch or Activin/TGF-beta signaling molecules, it is not known which molecules regulate IHBD development. Here, we found that FGF receptors and BMP4 are specifically expressed in the developing IHBD and the hepatic mesenchyme, respectively. Using a mesenchyme-free culture of liver bud, we showed that bFGF and FGF7 induce the hepatoblasts to differentiate into BECs, and that BMP4 enhances bFGF-induced BEC differentiation. The extracellular matrix (ECM) components in the hepatic mesenchyme induced BEC differentiation. Forced expression of a constitutively active form of the FGF receptor partially induced BEC differentiation markers in vivo. These data strongly suggest that bFGF and FGF7 promote BEC differentiation cooperatively with BMP4 and ECMs in vivo.     

Existence of phenol oxidase in the argasid tick Ornithodoros moubata

Phenol oxidase (PO, EC 1.10.3.1) activity was detected in the hemolymph of the fourth instar nymphs of the argasid tick, Ornithodoros moubata, with peak levels corresponding to the days before the majority of the nymphs had molted, suggestive of a protective role of PO during the ecdysial phase. Higher PO activity was detected in plasma relative to the hemolymph and was negligible in hemocytes. The concentration of the hemolymph and plasma assayed clearly influenced the level of PO activity, and was significantly reduced ( P<0.005) after treatment with 1-phenyl-2 thiourea, a specific PO inhibitor. This is the first report of the existence of PO in the hemolymph and plasma of a soft tick species. The regulation of PO activity and its precise role in soft tick immunity, particularly during the ecdysial phase, are interesting and need to be examined further.     

Roles of the Maltese cross form in the development of parasitemia and protection against Babesia microti infection in mice

Babesia microti, a hemoprotozoan parasite of rodents, is also important as a zoonotic agent of human babesiosis. The Maltese cross form, which consists of four masses in an erythrocyte, is characteristic of the developmental stage of B. microti. Monoclonal antibody (MAb) 2-1E, which specifically recognizes the Maltese cross form of B. microti, has been described previously. In the present study, we examined the roles of the Maltese cross form during the infectious course of B. microti in mice. The number of the Maltese cross form increased in the peripheral blood of infected mice prior to the peak of parasitemia. With confocal laser scanning microscopy, MAb 2-1E was found to be reactive with the ring form, with the parasites undergoing transformation to the Maltese cross form and subsequent division, and also with extracellular merozoites. Furthermore, the Maltese cross form-related antigen (MRA) gene was isolated from a B. microti cDNA library by immunoscreening with MAb 2-1E, and the nucleotide sequence was determined. Genomic analyses indicated that the MRA gene exists as a single-copy gene in B. microti. Immunization of mice with recombinant MRA induced significant protective immunity against B. microti infection. These findings indicate that the Maltese cross form plays important roles in both the development of parasitemia and the protective response against the infection.     

Etiological Study of Diarrheal Patients in Vientiane, Lao People’s Democratic Republic

The etiological agents of diarrhea in Vientiane, Lao People’s Democratic Republic (Lao PDR), were studied in the period from October 1996 to August 1997. A total of 880 patients with diarrhea visiting medical facilities were examined for Shigella, Salmonella, diarrheagenic Escherichia coli, Vibrio, Aeromonas, Campylobacter, and rotavirus. Shigella spp., heat-stable enterotoxin (ST)-producing E. coli, and serogroup-based enteropathogenic E. coli were found to be the main organisms causing diarrhea in Vientiane, with frequencies of 16.8% (148 of 880), 17.2% (111 of 645), and 11.0% (97 of 880), respectively. Relatively low incidences were observed in the cases of Salmonella spp., (0.6%; 5 of 880), Campylobacter spp. (4.4%; 39 of 880), and rotavirus (6.1%; 9 of 148), and no isolates of V. cholerae O1 or O139 or Aeromonas were recovered. An analysis of the incidences of enteropathogens with respect to age and seasonal variations demonstrated that the frequencies of isolation of Shigella spp. and heat-labile enterotoxin-producing E. coli were significantly higher in those aged 1 to 5 years than in those younger than 1 year of age and those older than 5 years of age (P < 0.0001 and P < 0.05, respectively) and that the frequencies of isolation of Shigella spp. and ST-producing E. coli were significantly higher in the rainy season than in the dry season (P < 0.005 and P < 0.001, respectively). Almost all strains of Shigella spp. tested were resistant to ampicillin, tetracycline, and erythromycin and were susceptible to cefdinir and ofloxacin. This is the first intensive and longitudinal study to define the etiologic agents of diarrheal diseases in Lao PDR.