Publications by authors named "Yuki Fukushima"

8 Publications

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Effects of Infection on Health Status and Productivity of Dairy Cows Reared inside Barns.

Pathogens 2021 May 24;10(6). Epub 2021 May 24.

Center for Animal Disease Control, University of Miyazaki, Miyazaki 889-2192, Japan.

The objective of the present study was to investigate the effects of on the severity of anemia, the prevalence of disease within 21 days after calving and productivity in cows raised inside barns. This longitudinal observational study, which was conducted on a commercial dairy farm in Japan, involved 627 Holstein cows subjected to PCR analysis for . In study 1, we collected blood samples from 156 sick cows within 21 days after calving, and we found the prevalence of infection to be 65.4%. In study 2, we randomly selected 471 cows during the dry period and collected blood samples to conduct PCR analysis for and determined the prevalence of infection to be 69.0%. Compared with the values for the -uninfected group, the -infected cows had significantly decreased hemoglobin concentrations and hematocrit, but there were no differences in the other complete blood count indexes between the two groups. In addition, there were no differences in productivity and the prevalence of major diseases between the -infected and uninfected cows. In summary, had few effects on anemia, productivity and the health of cows raised inside a barn.
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http://dx.doi.org/10.3390/pathogens10060650DOI Listing
May 2021

Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.

Med Mol Morphol 2021 May 8. Epub 2021 May 8.

Department of Radiology, Sapporo Medical University School of Medicine, S1 W16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer.
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http://dx.doi.org/10.1007/s00795-021-00290-wDOI Listing
May 2021

A large-scale survey of Theileria orientalis infection in grazing dairy heifers in Kyushu, Japan.

J Vet Med Sci 2021 Jan 12;83(1):36-41. Epub 2020 Nov 12.

Center for Animal Disease Control, University of Miyazaki, Miyazaki 889-2192, Japan.

The objective of the present study was to investigate the prevalence of Theileria orientalis infection and the influence of this disease on dairy grazing heifers in Kyushu by monitoring red blood cell (RBC) indexes, and to evaluate the efficacy of diminazene diaceturate treatment of T. orientalis-infected animals. A monthly epidemiological survey was conducted for Holstein heifers, which were reared from 10 to 16 months of age on a large commercial dairy farm and grazed on eight independent grasslands from April to November, 2009. During the survey, a total of 2,803 blood samples were collected from the 891 grazing heifers, in which the prevalence of T. orientalis infection was 52.4%. Compared with the heifers before infection, heifers with high parasitemia (more than 100 parasites per 10 RBC) had significantly decreased RBC indexes, such as RBC count, hemoglobin concentration, and hematocrit (P<0.05), whereas heifers with low parasitemia (less than 100 parasites per 10 RBC) had similar RBC indexes as those before infection. Treatment with diminazene diaceturate had lower efficacy in heifers with high parasitemia than those with low parasitemia (40.7% and 73.2% became negative, respectively, P<0.05). In summary, T. orientalis infection is a potentially serious problem in Kyushu, and it is important to routinely implement control programs for heifers that are grazed on grasslands in this region.
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http://dx.doi.org/10.1292/jvms.20-0567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870415PMC
January 2021

Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy.

Jpn J Clin Oncol 2020 Oct;50(11):1290-1297

Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Objective: To evaluate proteins related to tumor immune response and treatment outcome from radiotherapy for uterine cervical cancer patients.

Methods: We performed a retrospective immunohistochemical staining of 81 patients with uterine cervical cancer who underwent definitive radiotherapy. We examined the expression of programmed death ligand 1, human leukocyte antigen class I, tumor-infiltrating CD8+, and forkhead box P3+ (FoxP3+) T cells in tumor tissues.

Results: In biopsy specimen, patients with a higher number of CD8+ T cells and FoxP3+ T cells had a better disease-specific survival than patients with a lower number of CD8+ T cells and FoxP3+ cells (P = 0.018 and P = 0.009). Multivariate analysis showed that equivalent dose in 2 Gy fractions (EQD2) of the minimum dose to 90% of the high-risk clinical target volume, FoxP3+ T cells and expression of human leukocyte antigen class I were significant prognostic factors. When the EQD2 is 70 Gy or more, a higher local control rate is obtained regardless of the number of CD8- or FoxP3-positive cells. When EQD2 is <70 Gy, the number of CD8-positive cells has a significant impact on treatment outcome: the recurrence rate (local recurrence rate + distant metastasis rate) was 46.2% in the group with a CD8 value of 230 or higher, whereas the recurrence rate was 75.7% in the group with a CD8 value of less than 230.

Conclusion: The combination of CD8 or FoxP3 with EQD2 can be potentially useful to predict the treatment results of radiotherapy for cervical cancer, leading to individualized optimal selection of treatment for cervical cancer.
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http://dx.doi.org/10.1093/jjco/hyaa149DOI Listing
October 2020

Epidemiological study to investigate the incidence and prevalence of clinical mastitis, peracute mastitis, metabolic disorders and peripartum disorders, on a dairy farm in a temperate zone in Japan.

BMC Vet Res 2020 Oct 14;16(1):389. Epub 2020 Oct 14.

Course of Animal and Grassland Sciences, Graduate School of Agriculture, University of Miyazaki, Miyazaki, Japan.

Background: Our aim was to investigate the incidence and prevalence of clinical mastitis, peracute mastitis, metabolic disorders, and peripartum disorders, and to examine factors affecting the prevalence of each disease in cows raised on a large dairy farm in a temperate climate in Japan. The present study was performed on a large commercial dairy farm with approximately 2500 Holstein cows. Data were collected from 2014 to 2018, and involved 9663 calving records for 4256 cows.

Results: The incidence rate on the farm was 21.9% for clinical mastitis, 10.4% for peracute mastitis, 2.9% for metabolic disorders, and 3.2% for peripartum disorders. The prevalence rates for clinical mastitis, peracute mastitis, metabolic disorders, and peripartum disorders were 28.0, 13.3, 3.7, and 4.0%, respectively. In all four diseases, the probability of time to occurrence for each disease was associated with parity and calving season (P < 0.05). Regarding metabolic disorders and peripartum disorders, the probability of occurrence decreased during the first 10 days after calving.

Conclusions: Our results showed that clinical mastitis occurred most often in this temperate zone, and that metabolic disorders and peripartum disorders occurred from calving to day 10 post-calving.
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http://dx.doi.org/10.1186/s12917-020-02613-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557088PMC
October 2020

Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy.

Strahlenther Onkol 2020 Aug 17;196(8):725-735. Epub 2020 Jan 17.

Department of Radiology, Sapporo Medical University School of Medicine, S1W16, Chuo-Ku, 060-8543, Sapporo, Hokkaido, Japan.

Purpose: To evaluate radiotherapy-induced changes in the expression of programmed death ligand 1 (PD-L1), programmed death 1 (PD-1), and human leukocyte antigen class I (HLA-1) in patients with uterine cervical cancer, as well as infiltration of CD8+ and Forkhead box P3+ (FoxP3+) T lymphocytes into tumor tissue and the prognostic value of these parameters.

Materials And Methods: We performed immunohistochemical analysis of pre-radiotherapy biopsies and corresponding post-radiotherapy resected tissues in 104 uterine cervical cancer patients undergoing preoperative chemoradiotherapy or radiotherapy alone. We scored the expression of various proteins to distinguish positive from negative samples.

Results: PD-L1-expressing tumor cells (PD-L1 TC) increased significantly after chemoradiotherapy (p = 0.043). CD8+ T cell infiltration (p = 0.002) and FoxP3+ T cell infiltration (p = 0.003) decreased significantly after chemoradiotherapy. Expression of PD‑1, PD-L1-expressing immune cells (PD-L1 IC), and HLA‑1 did not change after chemoradiotherapy. In biopsy specimens obtained before chemoradiotherapy or radiotherapy, greater infiltration of CD8+ T cells (p = 0.001) and FoxP3+ T cells (p = 0.003) were significant predictors of better overall survival (OS). In surgical specimens obtained after chemoradiotherapy or radiotherapy, greater infiltration of PD-L1 TC was the only significant predictor of better OS (p < 0.001) and was related to a significantly lower probability of out-of-field recurrence (p = 0.005).

Conclusion: Chemoradiotherapy induced an immunologic shift that increased PD-L1 TC. Chemoradiotherapy has immunological effects that can influence the results of treatment for uterine cervical cancer.
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http://dx.doi.org/10.1007/s00066-019-01571-1DOI Listing
August 2020

Influence of PD-L1 expression in immune cells on the response to radiation therapy in patients with oropharyngeal squamous cell carcinoma.

Radiother Oncol 2018 11 21;129(2):409-414. Epub 2018 Sep 21.

Department of Radiology, Sapporo Medical University School of Medicine, Japan. Electronic address:

Background And Purpose: To investigate influences of proteins involved with tumor immunity on outcomes of radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC).

Material And Methods: We performed immunohistochemical staining to examine expressions of p16 and proteins involved with tumor immunity in 92 OPSCC patients treated with radiotherapy.

Results: Patients with abundant infiltrating CD8-positive cells had the significantly better overall survival (OS) rate than patients with fewer CD8-positive cells (p = 0.026). Patients with higher PD-L1 expression in tumor cells (TC 1-3) had a better outcome than those with low PD-L1 expression in tumor cells (TC 0) for both OS (p = 0.019) and progression-free survival (PFS) rate (p = 0.032). Patients with high PD-L1 expression in infiltrating immune cells (IC 3) showed significantly better OS (p = 0.009) and PFS (p = 0.011) than those with low PD-L1 expression (IC 0-2). Patients with p16-negative and IC 3 showed similar OS to patients with p16-positive and IC 0-2. P16-positive tumors had a significantly higher CD8-positive cell infiltration and PD-L1 expression in tumor cells than p16-negative tumors.

Conclusions: In addition to tumor p16 expression, PD-L1 expression in TC and IC can be useful for predicting the response of OPSCC to radiotherapy.
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http://dx.doi.org/10.1016/j.radonc.2018.08.023DOI Listing
November 2018

Influence of XRCC4 expression in esophageal cancer cells on the response to radiotherapy.

Med Mol Morphol 2017 Mar 23;50(1):25-33. Epub 2016 Jun 23.

Department of Radiology, Sapporo Medical University Schoolo of Medicine, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation and is mainly repaired by the non-homologous end joining (NHEJ) repair. Immunohistochemical analysis of proteins involved in NHEJ, such as XRCC4 (X-ray repair cross-complementing protein 4), Ku86 and DNA-PKcs (DNA-dependent protein kinase, catalytic subunits), may be useful for predicting tumor radiosensitivity. We examined 92 patients with esophageal squamous cell carcinoma (ECSS) who were treated by radiotherapy between 1999 and 2008. Immunohistochemical examination of tumor tissue for Ki-67 and DSB-related proteins, including XRCC4, Ku86, and DNA-PKcs, was performed using pretreatment biopsy specimens. Low expression of XRCC4 was detected in 31 of 92 examined samples (33.7 %). The 5-year overall survival (OS) rate was 67.7 % in the low expression group and 31.0 % in the high expression group (P = 0.00). Multivariate analysis confirmed that advanced T-stage (HR 3.24, P = 0.01), radiation dose less than 66 Gy (HR 2.23, P = 0.02), absence of systemic chemotherapy (HR 2.59, P = 0.05), and high expression of XRCC4 (HR 12.0, P = 0.02) were independent prognostic factors for predicting poor OS. Other DSB-related proteins and Ki-67 were not predictive factors. XRCC4 expression might have an influence on results of radiotherapy for patients with ESCC.
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http://dx.doi.org/10.1007/s00795-016-0144-5DOI Listing
March 2017