Histological characteristics of the human femoral head in patients with femoral neck fracture

The reparative reaction including angiogenesis and osteogenesis in human bone after an ischemic event remains unknown. To investigate the reparative reaction in human bone, the distribution of tartrate resistant acid phosphatase (TRAP)-positive cells and the expressions of hypoxia inducible factor-1?? (HIF-1??), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and CD31 were observed around the fracture site in 101 hips in 100 patients with femoral neck fracture. These 17 men and 83 women had a mean age of 80?years (range, 58?C97?years). Of the hips, 17 were Garden stage 3, and 84 were Garden stage 4. The mean duration from fracture to surgery was 6.3?days (range, 1?C14?days). Hematoxylin?Ceosin staining, TRAP staining, and immunohistochemistry using anti-HIF-1??, anti-VEGF anti-FGF-2, and anti-CD31 antibodies were performed for the coronal section of the retrieved whole femoral heads. TRAP-positive cells were detected near the trabecular bone around the fracture site in ten hips (10?%). HIF-1?? expression was detected in 41 hips (41?%), mainly in the endothelial cells of the vessels. VEGF showed diffuse cytoplasmic staining of the mononuclear cells in the edematous area in 39 hips (39?%) while FGF-2 was detected in the cytoplasm of mononuclear cells in the bone marrow in 82 hips (82?%). CD31 was expressed in the bone marrow vessels in 35 hips (35?%). There were significant differences in HIF-1?? expression relative to the duration between the fracture and the surgery, and in CD31 expression relative to Garden stage. HIF-1?? expression was detected around the fracture site in the early period after fracture and CD31 expression was detected more frequently in Garden 3 hips while VEGF and FGF-2 expressions were detected regardless of Garden classification.     

Biological effects of anhydrobiosis in an African chironomid, Polypedilum vanderplanki on radiation tolerance

PURPOSE: Anhydrobiotic organisms are known to have an extremely high tolerance against a range of stresses. However, the functional role of anhydrobiosis in radiation tolerance is poorly understood, especially in development following irradiation. The present study aims to evaluate effects of anhydrobiosis on radiation tolerance in an anhydrobiotic insect, Polypedilum vanderplanki. MATERIALS AND METHODS: Larval survival (48 h), anhydrobiotic ability, metamorphosis and reproduction after exposure to 1-9000 Gy of gamma-rays at the larval stage were compared between anhydrobiotic (dry) and normal (wet) phases. RESULTS: Wet larvae were killed in a dose-dependent manner at doses higher than 2000 Gy, and all died within 8 h after 4000 Gy exposure. In contrast, dry larvae survived even 5000 Gy, and some of them still tolerated 7000 Gy and were alive at 48 h after rehydration. Moreover, greater radiotolerance of dry larva, compared to wet ones, was demonstrated in terms of metamorphoses. However, anhydrobiosis did not protect against radiation damage in terms of producing viable offspring. CONCLUSION: These results indicate that anhydrobiosis enhances radiotolerance, resulting in increases of successful metamorphoses.     

Estimation of radiation tolerance to high LET heavy ions in an anhydrobiotic insect, Polypedilum vanderplanki

PURPOSE: Anhydrobiotic larvae of Polypedilum vanderplanki are known to show an extremely high tolerance against a range of stresses. We have recently reported that this insect withstands exposure to high doses of gamma-rays (linear energy transfer [LET] 0.2 keV/microm). However, its tolerance against high LET radiation remains unknown. The aim of this study is to characterize the tolerance to high-LET radiations of P. vanderplanki. MATERIALS AND METHODS: Larval survival and subsequent metamorphoses were compared between anhydrobiotic (dry) and non-anhydrobiotic (wet) samples after exposure to 1 - 7000 Gy of three types of heavy ions delivered from the azimuthally varying field (AVF) cyclotron with LET values ranging from 16.2 - 321 keV/microm. The tolerance against 4He ions was also compared among three chironomid species. RESULTS: At all LET values measured, dry larvae consistently showed greater radiation tolerance than hydrated larvae, perhaps due to the presence of high concentrations of the disaccharide trehalose in anhydrobiotic animals, and the radiation-induced damage became evident at lower doses as development progressed. Relative biological effectiveness (RBE) values based on the median inhibitory doses reached a maximum at 116 keV/microm (12C), and the maximum RBE clearly increased as development progressed. Lower D0 (dose to reduce survival from relative value 1.00 - 0.37 on the exponential part of the survival curve), and higher Dq (quasi-threshold dose) were found in individuals exposed to 4He ions, compared to gamma-rays, and in P. vanderplanki larvae compared to non-anhydrobiotic chironomids. CONCLUSION: Anhydrobiosis potentiates radiation tolerance in terms of larval survival, pupation and adult emergence of P. vanderplanki exposed to high-LET radiations as well as to low-LET radiation. P. vanderplanki larvae might have more efficient DNA damage repair after radiation than other chironomid species.     

Ghrelin after chemotherapy as a prognostic predictor of progression-free survival in patients with muscle-invasive bladder cancer

BackgroundAlthough the patients with muscle-invasive bladder cancer (MIBC) generally have poor prognosis, the utility of these biomarkers for the prediction of oncological outcomes in MIBC has not been completely explored. Ghrelin regulates processes associated with cancer, including cell proliferation, apoptosis, cell migration, cell invasion, and angiogenesis. Thus, we aimed to evaluate the impact of serum ghrelin levels on survival in MIBC.MethodsIn this study, we reviewed the clinical and pathological records of 56 patients who were diagnosed with MIBC between November 2015 and November 2019 at Gifu and Hirosaki University Hospitals. We focused on 27 patients who had received chemotherapy and collected blood samples before and after chemotherapy. Blood samples were collected before chemotherapy and after completing two cycles of chemotherapy. Serum acyl (AG) and desacyl ghrelin (DG) were measured using AG and DG enzyme-linked immunosorbent assay kits (SCETI, Tokyo, Japan), respectively.ResultsThe 3-year overall and progression-free survival (PFS) rates were 82.9% and 68.3%, respectively. According to the AG level after chemotherapy, the 3-year PFS rates were 77.5% and 53.0% in patients with AG levels ≥1.34 and <1.34 pg/mL, respectively (P=0.038). With regard to DG levels after chemotherapy, the 3-year PFS rates were 90.9% and 43.3% in patients with DG levels <92.3 and ≥92.3 pg/mL, respectively (P=0.039). On multivariate analysis, serum AG levels were significantly associated with PFS.ConclusionsThis study suggested the usefulness of the ghrelin as a prognostic predictor of PFS in patients with MIBC.     

Evaluation of paramalleolar and inframalleolar bypasses in dialysis- and nondialysis-dependent patients with critical limb ischemia

Objective

The aim of this study was to elucidate the efficacy of paramalleolar or inframalleolar bypass (PIMB) in hemodialysis-dependent (HD) patients with critical limb ischemia (CLI) and nonhemodialysis-dependent (NHD) patients in terms of clinical outcomes.

Left Ventricular Mass Regression After Implantation of St. Jude Medical Cardiac Valves in Small Aortic Roots

In this study, we analyzed the extent of regression of left ventricular hypertrophy in patients who received small St. Jude Medical (SJM) aortic valves and compared the results with those of another group receiving larger valves. Eighty-eight patients received either 19 or 21 mm valves (Group 1, 25 patients) or either 23 or 25 mm valves (Group 2, 53 patients). Echocardiographic studies were done before the operation and 5 years postoperatively. At follow-up a significant reduction in the left ventricular mass was found for both patient groups (p < 0.0001). Doppler echocardiography derived pressure gradients for both groups were obtained during the follow-up period. As expected, the patients in Group 1 had higher peak pressure gradients than did those in Group 2. However, there was no significant difference between the 2 groups or any significant correlations between peak pressure gradients and body surface area (BSA). Actuarial survival was 84.7% at 15 years for Group 1 and 85.9% at 17 years for Group 2. Actuarial freedom from valve related events was 91.4 % at 15 years for Group 1 and 82.7% at 17 years for Group 2. There was no significant difference in survival or valve related event free curves between the 2 groups. After implantations of SJM valves in small aortic roots, significant left ventricular mass regression was obtained, and the results were comparable to those for valves of other sizes. The long-term performance of aortic valve replacement with small valves was satisfactory as judged by improvement in the functional class of patients and survival statistics, the durability of the prosthesis, and valve related morbidity comparable to that of valves of other sizes.     

Pathogenic Potential of Eomesodermin-Expressing T-Helper Cells in Neurodegenerative Diseases

Eomesodermin-expressing (Eomes⁺) T-helper (Th) cells show cytotoxic characteristics in secondary progressive multiple sclerosis. We found that Eomes⁺ Th cell frequency was increased in the peripheral blood of amyotrophic lateral sclerosis and Alzheimer's disease patients. Furthermore, granzyme B production by Th cells from such patients was high compared with controls. A high frequency of Eomes⁺ Th cells was observed in the initial (acutely progressive) stage of amyotrophic lateral sclerosis, and a positive correlation between Eomes⁺ Th cell frequency and cognitive decline was observed in Alzheimer's disease patients. Therefore, Eomes⁺ Th cells may be involved in the pathology of amyotrophic lateral sclerosis and Alzheimer's disease. ANN NEUROL 2024;95:1093–1098     

Therapeutic effect of alpha-galactosylceramide-loaded dendritic cells genetically engineered to express SLC/CCL21 along with tumor antigen against peritoneally disseminated tumor cells

The close cooperation of both innate and acquired immunity is essential for the induction of truly effective antitumor immunity. We tested a strategy to enhance the cross-talk between NKT cells and conventional antigen-specific T cells with the use of alpha GalCer-loaded dendritic cells genetically engineered to express antigen plus chemokine, attracting both conventional T cells and NKT cells. DC genetically engineered to express a model antigen, OVA, along with SLC/CCL21 or monokine induced by IFN-gamma/CXCL9, had been generated using a method based on in vitro differentiation of DC from mouse ES cells. The ES-DC were loaded with alpha-GalCer and transferred to mice bearing MO4, an OVA-expressing melanoma, and their capacity to evoke antitumor immunity was evaluated. In vivo transfer of either OVA-expressing ES-DC, stimulating OVA-reactive T cells, or alpha-GalCer-loaded non-transfectant ES-DC, stimulating NKT cells, elicited a significant but limited degree of protection against the i.p. disseminated MO4. A more potent antitumor effect was observed when alpha-GalCer was loaded to ES-DC expressing OVA before in vivo transfer, and the effect was abrogated by the administration of anti-CD8, anti-NK1.1 or anti-asialo GM1 antibody. alpha-GalCer-loaded double transfectant ES-DC expressing SLC along with OVA induced the most potent antitumor immunity. Thus, alpha-GalCer-loaded ES-DC expressing tumor-associated antigen along with SLC can stimulate multiple subsets of effector cells to induce a potent therapeutic effect against peritoneally disseminated tumor cells. The present study suggests a novel way to use alpha-GalCer in immunotherapy for peritoneally     

A case of diffuse hepatic angiosarcoma diagnosed by FDG-PET

A 76-year-old woman was admitted to our hospital with a 2-month history of increasing abdominal distension, leg edema, and dyspnea. The serum transaminase level was about twice the upper limit of normal. The CT showed no tumor. Fluorine-18 2-deoxy-2-fluoro-D-glucose (FDG)-positron emission tomography (PET) showed diffuse abnormal accumulation throughout the entire liver. She was diagnosed by histopathological examination as having hepatic angiosarcoma causing veno-occlusive disease (VOD). This is the first report of hepatic angiosarcoma with FDG-PET.