Damage of the Mouse Testis by Tritiated Water and <137>^Cs-γ-Rays

Tritiated water at 23.2, 46.3 or 92.5 MBq/animal and ^Cs-γ-rays at 9.5 Gy (equivalent 370 MBq) or lower doses were administered to 6-week old male C3H/HeNCrj and C57BL/6NCrj mice, as well as FI Crj: B6C3F1 (C3H × C57BL) progeny. Each set of six to ten animals were autopsied 30 days after the first irradiation. Testis weights were decreased dose dependently, relative values being highest in the C3H and lowest in the C57BL case, with B6C3F1 intermediate. Vacuolization in seminiferous tubules appeared in the 23.2 MBq group and increased with the dose. Focal pyknosis and karyomegaly were found at 46.3 MBq, while primary and secondary spermatocytes and spermatids disappeared with 92.5 MBq. Only a few spermatogonia and Sertoli cells remained after exposure to 9.5 Gy ^Cs-γ-rays. Sizes of seminiferous tubules were decreased dose dependently, with no strain differences. When male B6C3F1 mice were irradiated with Cs-γ-rays at 0.119 (equivalent 4.63 MBq tritiated water) or 2.38 Gy (equivalent 92.5 MBq tritiated water), body weights and size of the seminiferous tubules were decreased at both doses, and the larger dose also caused reduction of testis weight and abnormal sperm. However, all changes except for the alteration in weights had disappeared 1 month after the final irradiation. It is considered that the size of seminiferous tubules may be a good parameter for radiation damage in the testis

Effects of Weaning by Surrogate Mothers (ACI) on Tumor Development in SD Rats Treatedwith Methylnitrosourea (MNU) and/or N-Methyl-N-nitro-N-nitrosoguanidine (MNNG)

In this experiment, MNU was administered, followed by MNNG, to assess effects ofsurrogate mothering on tumor. One or two day old male SD pups were treated with or without30mg/kg body weight of methylnitrosourea (MNU) and nursed by SD or ACI surrogate mothersfor 5 weeks. When 6-weeks-old they were then treated with 100ppmN-methyl-N-nitro-N-nitrosoguanidine (MNNG) or tap water for 16 weeks. The tumor incidencein the MNNG alone group was significantly lower than with MNU alone or MNU+MNNG (p<0.01).Kidney or nerve tumors mainly developed in the MNU group, gastric tumors in the MNNG group,and the two combined in the MNU+MNNG group. The incidence and mean number of tumors didnot significantly differ between the two weaning groups. However, mean survival time withthe ACI surrogate mothers after treatment with MNU was increased as compared with the SDmother group. Cumulative development of tumors in the ACI surrogate mother group was alsodelayed (p<0.05). Similar results were obtained with MNU+MNNG and MNNG alone. The presentexperiment suggested that tumor induction might be effected by components of the mother'smilk

Proton beam therapy for intrahepatic cholangiocarcinoma: A multicenter prospective registry study in Japan

Introduction: Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose concentration that may improve local control. Methods: Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6-76 Gy (RBE) in 20-22 fr, 13 received 74.0-76.0 Gy (RBE) in 37-38 fr, and 6 received 60-70.2 Gy (RBE) in 20-30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Results: The 59 patients (35 men, 24 women; median age 71 years; range 41-91 years) had PS of 0 (n=47), 1 (n=10) and 2 (n=2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A (n=46), B (n=7), and unknown (n=6); the median maximum tumor diameter was 5.0 cm (range 2.0-15.2 cm); and the clinical stage was I (n=12), II (n=19), III (n=10), and IV (n=18). At the last follow-up, 17 patients were alive (median follow-up 36.7 months; range 24.1-49.9 months) and 42 had died. The median OS was 21.7 months (95% CI 14.8-34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI 6.1-11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of Grade 3 or higher. Discussion/Conclusion. PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors

Changes in Variable Number of Tandem Repeats in 'Candidatus Liberibacter asiaticus' through Insect Transmission.

Citrus greening (huanglongbing) is the most destructive citrus disease worldwide. The disease is associated with three species of 'Candidatus Liberibacter' among which 'Ca. Liberibacter asiaticus' has the widest distribution. 'Ca. L. asiaticus' is commonly transmitted by a phloem-feeding insect vector, the Asian citrus psyllid Diaphorina citri. A previous study showed that isolates of 'Ca. L. asiaticus' were clearly differentiated by variable number of tandem repeat (VNTR) profiles at four loci in the genome. In this study, the VNTR analysis was further validated by assessing the stability of these repeats after multiplication of the pathogen upon host-to-host transmission using a 'Ca. L. asiaticus' strain from Japan. The results showed that some tandem repeats showed detectable changes after insect transmission. To our knowledge, this is the first report to demonstrate that the repeat numbers VNTR 002 and 077 of 'Ca. L. asiaticus' change through psyllid transmission. VNTRs in the recipient plant were apparently unrelated to the growing phase of the vector. In contrast, changes in the number of tandem repeats increased with longer acquisition and inoculation access periods, whereas changes were not observed through psyllid transmission after relatively short acquisition and inoculation access periods, up to 20 and 19 days, respectively

Schematic model of strategy of Table 2.

<p>The black circle indicates the area used for DNA extraction. Numbers at the lower right, which are x n, indicate the number of samples in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138699#pone.0138699.t002" target="_blank">Table 2</a>.</p

Primers for characterization of variable tandem repeats in four loci of the genome of '<i>Ca</i>. Liberibacter asiaticus' strains.

<p>Primers for characterization of variable tandem repeats in four loci of the genome of '<i>Ca</i>. Liberibacter asiaticus' strains.</p

Analysis of the stability of tandem repeats through adult acquisition–adult transmission experiments.

<p>^a‘<i>Ca</i>. L. asiaticus’-infected greenhouse grown rough lemon (Source-R1) used as an inoculum source for psyllid transmission of the pathogen.</p><p>^bAnterior part (including head and prothorax) of each psyllid individual after acquisition feeding on source-R1 plant and inoculation feeding on recipient yuzu seedling.</p><p>^cPosterior part (including mesothorax, metathorax, and abdomen) of each psyllid individual after acquisition feeding on source-R1 plant and inoculation feeding on recipient yuzu seedling.</p><p>^dRecipient plants that became infected upon psyllid transmission of the bacterium from the source plant 'Source-R1'.</p><p>^eLast number between the psyllid as vector and the recipient plant was one-to-one correspondence, respectively.</p><p>^fUnderline shows varied number of VNTR compared with that from source plant ‘Source-R1’.</p><p>^gPsyllid, <i>Diaphorina citri</i>; yuzu, <i>Citrus junos</i>.</p><p>Analysis of the stability of tandem repeats through adult acquisition–adult transmission experiments.</p