Expression of interleukin-6 receptor, leukemia inhibitory factor receptor and glycoprotein 130 in the murine cerebellum and neuropathological effect of leukemia inhibitory factor on cerebellar Purkinje cells

Expression of glycoprotein 130 and the related receptors, including interleukin-6 receptor and leukemia inhibitory factor receptor, was examined in the murine cerebellum at the protein level. Western blot analysis revealed that interleukin-6 receptor, leukemia inhibitory factor receptor and glycoprotein 130 were expressed in the murine cerebellum. Immunoreactivities for interleukin-6 receptor, leukemia inhibitory factor receptor and glycoprotein 130 were strongly localized on the cell body of Purkinje cells, indicating that both interleukin-6 and leukemia inhibitory factor could act directly on Purkinje cells in murine adult mice. The expressions of interleukin-6 receptor, leukemia inhibitory factor receptor and glycoprotein 130 were observed on the cell membranes of Purkinje cells by immunoelectron microscopy. Immunoreactivity for the interleukin-6 receptor was also detected in the cytoplasm of Purkinje cells. Injection of a murine hemopoietic cell line, FDC-P1 cells, transfected with the complementary DNA encoding the leukemia inhibitory factor led to a reduction in calbindin-positive dendrites of the Purkinje cells.

The present results suggest that the leukemia inhibitory factor affects cerebellar functions through Purkinje cells.     

Studies of monoamine oxidase and semicarbazide-sensitive amine oxidase. I. Inhibition by a selective monoamine oxidase-B inhibitor, MD 780236

In vitro studies of the effect of MD 780236, a selective monoamine oxidase (MAO)-B inhibitor, on a semicarbazide-sensitive amine oxidase (SSAO) in rat testis and lung showed that this compound dose-dependently inhibited SSAO activity. The extents of inhibition of MAO-A, -B and SSAO in these two rat tissues by this compound after 30 min of preincubation were found to be MAO-B greater than MAO-A greater than SSAO. This selectivity was also evident in preparations without preincubation. Degree of inhibition of SSAO was not significantly influenced by pretreatment with either 10(-3) M clorgyline, I-deprenyl or 10(-4) M SKF 525A. Inhibition of SSAO was not enhanced by varying the time of preincubation of the enzyme and the compound, indicating direct action on and reversible inhibition of SSAO. The inhibition of SSAO by MD 780236 was non-competitive with or without preincubation, with a K1 value of 110 muM. Although MD 780236 is a selective and "suicide substrate" inhibitor of MAO-B, these present results indicate that this compound may also inhibit SSAO activity, but by a mechanism different from that for MAO-B. These findings confirm an earlier hypothesis that compounds that inhibit both MAO and SSAO have totally different modes of action on these two different amine oxidases.     

Validation and reliability of a Japanese version of the Shoulder Pain and Disability Index: A cross-sectional study

BackgroundThe Shoulder Pain and Disability Index (SPADI) is a simple disease specific questionnaire that is used to evaluate the impact of shoulder disorders. The purpose of this study was to translate the SPADI into Japanese (SPADI-Jp) and evaluate its reliability and validity in Japanese patients with shoulder disorders.MethodsCross-cultural adaptation of the SPADI was performed according to international guidelines. A total of 100 patients with shoulder disorders participated in this study. Each participant was asked to finish the SPADI-Jp, Disability of Arm, Shoulder and Hand (DASH), and the Short-Form 36 (SF-36) at the initial visit. Thirty-four patients repeated the SPADI-Jp to assess the test–retest reliability. The test–retest reliability was quantified using the interclass correlation coefficient (ICC), while Cronbach's alpha was calculated to assess the internal consistency. The construct validity was assessed using Spearman's rank correlation coefficients.ResultsInternal consistency in the SPADI-Jp was very high (0.969), as measured by the Cronbach's alpha. The ICC of the SPADI-Jp was 0.930. There was a strong, positive correlation between the DASH and the SPADI-Jp (r = 0.837, p < 0.001). The SPADI-Jp was significantly correlated with most of the SF-36 subscales. The correlations of the SPADI-Jp with physical subscales of the SF-36 were stronger than those with the other subscales.ConclusionsWe demonstrated that the SPADI-Jp is a reliable and valid self-assessment tool. Because cross-cultural adaptation, validation, and reliability of the disease-specific questionnaire for shoulder pain and disability have not been evaluated in Japan, the SPADI-Jp can be useful for evaluating such patients in the Japanese population.     

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.     

CYTOMEGALOVIRUS OOPHORITIS WITH CORTICAL NECROSIS DURING REMISSION OF ACUTE LYMPHOCYTIC LEUKEMIA

Ovarian involvement of cytomegalovirus (CMV) is rarely observed in autopsy and biopsy materials. Cortical necrosis of the ovaries was found in an autopsy case with generalized CMV infection. The patient was an 11-year-old girl in a remission state of acute lymphocytic leukemia. Autopsy revealed several areas showing necrotic change up to 2 mm in size in the cortex of both ovaries. Many cytomegalic cells were found in both the necrotic and intact areas of the cortex. CMV had infected the granulosa, thecal and stromal cells as well as vascular endothelial cells. Oocytes of neither primary nor graafian follicles showed cytomegalic changes, although they were destroyed due to the necrosis. CMV antigen was immunohistologically detected in these cytomegalic cells. Ultrastructurally, herpesvirus-type particles were revealed in the nuclei and cytoplasm of the cytomegalic cells. This case demonstrated that ovarian infection with CMV can potentially induce cortical necrosis and decrease the number of oocytes. ACTA PATHOL JPN 38 : 1069 ∼ 1076, 1988.     

Urinaryα 1 as an index of proximal tubular function in early infancy

Urinary ₁-microglobulin (U-A₁M) was measured in healthy term infants on days 1, 4, 7, 14, 28, 90 and 180 of life. U-A₁M was high until day 14 and declined thereafter. It was significantly correlated with urinary ₂-microglobulin (U-B₂M) throughout the study, but not with serum A₁M on days 1 or 7. Similar to U-B₂M, U-A₁M in the clinically stable term infants with intrauterine growth retardation (n=4–7) was not elevated on days 1–7. In the sick infants who needed immediate resuscitatio at birth (n=4–8), U-A₁M as well as U-B₂M was high on days 1–7 and then decreased to normal levels, suggesting that U-A₁M can be used as a sensitive marker of acute proximal tubular damage and its recovery. These observations indicate that U-A₁M is a useful index of proximal tubular function in early infancy.     

Deuterium chemical shift imaging for the estimation of cerebral perfusion in rabbit infarction model

In order to develop a new technique for the measurement of local cerebral blood flow (CBF), the deuterium chemical shift imaging (²H-CSI) technique, an application of in vivo nuclear magnetic resonance (NMR), was used for the estimation of cerebral perfusion in rabbit infarction model. The ²H chemical shift images of rabbit brain were obtained every 30 seconds before and after intravenous injection of deuterated saline. The changes in ²H NMR signal intensity documented that the cerebral perfusion in the damaged area due to infarction decreased obviously compared to that in the intact area. These findings indicate that the ²H-CSI technique can be applied to the measurement of local CBF. The readily availability and limited toxicity of deuterated water may make possible to use this method in clinical cases.(Kito K, Arai T, Mori K, et al.: Deuterium chemical shift imaging for the estimation of cerebral perfusion in rabbit infarction model. J Anesth 7: 447–453, 1993)     

Molecular basis of carotid body tumor and associated clinical features in Japan identified by genomic,immunohistochemical, and clinical analyses

Carotid body tumor (CBT) is classified as a paraganglioma (PGL). Here, we report the genetic background, protein expression pattern, and clinical findings of 30 Japanese CBT cases. Germline pathogenic or likely pathogenic (P/LP) variants of genes encoding succinate dehydrogenase subunits (SDHs) were detected in 15 of 30 cases (50%). The SDHB variants were the most frequently detected, followed by SDHA and SDHD variants. One case with SDHAF2 variant was bilateral CBT, and other two multiple PGL cases were not detected P/LP variants. The three cases with germline variants that could be tested did not have somatic P/LP variants of the same genes. Immunohistochemical analysis showed negative SDHB signals in CBT tissues in five cases with germline P/LP variants of SDHB, SDHD, or SDHA. In addition, SDHB signals in CBT tissues were negative in four of nine cases without germline P/LP variants of SDHs. These findings suggest the involvement of unidentified molecular mechanisms affecting SDHs.