Visual event-related potentials in progressive supranuclear palsy, corticobasal degeneration, striatonigral degeneration, and Parkinson's disease

To determine whether there are characteristic changes in event-related potentials (ERPs) in parkinsonian syndromes we studied 8 patients with progressive supranuclear palsy (PSP), 10 patients with corticobasal degeneration (CBD), 9 patients with striatonigral degeneration (SND), and 16 patients with idiopathic Parkinson's disease (PD) with a mean duration of illness shorter than 5 years in each group. A visual oddball paradigm was employed to elicit P300. P300 to the rare target and rare nontarget stimuli and reaction time (RT) to rare target stimuli in each group were compared with those in the corresponding age-matched normal control group and to each other after age correction. The correlation of P300 and RT to motor disability score was also studied. In PSP P300 amplitude was markedly reduced while in CBD P300 latency was prolonged. P300 amplitude to rare nontargets in SND and PD was attenuated. The mean RT in the PSP and the CBD group was significantly longer than in the other two groups. The mean RT in PD and P300 amplitude to rare nontargets in both CBD and PD showed significant correlation with the severity of motor disability. Simultaneous measurement of P300 and RT may yield useful supplementary information in facilitating diagnosis of parkinsonian syndromes in addition to clinical criteria. Received: 6 April 1999, Received in revised form: 5 August 1999, Accepted: 12 January 2000     

No Improvement of Adult Height in Non-growth Hormone (GH) Deficient Short Children with GH Treatment

It is still in doubt whether the standard-dose growth hormone (GH) used in Japan (0.5 IU/kg/week, 0.167 mg/kg/week) for growth hormone deficiency is effective for achieving significant adult height improvement in non-growth hormone deficient (non-GHD) short children. We compared the growth of GH-treated non-GHD short children with that of untreated short children to examine the effect of standard-dose GH treatment on non-GHD short children. GH treatment with recombinant human growth hormone (rhGH) was started before the age of 11 yr in 64 boys and 76 girls with non-GHD short stature registered at the Foundation for Growth Science who have now reached their adult height. In 119 untreated boys and 127 untreated girls whose height standard deviation score (SDS) was below –2 SD at the age of 6 yr, height growth was followed until 17 yr. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, in both sexes. Adult height and adult height SDS were significantly greater in the untreated group than in the GH-treated group, in both sexes, although the change in height SDS did not differ significantly. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, so 57 boys and 57 girls whose height SDS at the age of 6 yr in the untreated group closely matched the height SDS before GH treatment in the GH-treated group were chosen for comparison. Height SDS did not differ significantly between the GH-treated group before GH treatment and the untreated group at the age of 6 yr, nor were there differences between these subgroups in adult height, adult height SDS, or height SDS change, in either sex. The effect of GH treatment is reported to be dose-dependent and doses over 0.23 mg/kg/week are reported to be necessary to improve adult height in non-GHD short children. Currently, the GH dose is fixed at 0.175 mg/kg/week in Japan, and we expected to find, and indeed concluded, that ordinary GH treatment in Japanese, non-GHD short children does not improve adult height.     

Vaccination of dendritic cells loaded with interleukin-12-secreting cancer cells augments in vivo antitumor immunity: characteristics of syngeneic and allogeneic antigen-presenting cell cancer hybrid cells.

Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-gamma production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy.     

Carbonic anhydrase II is a tumor vessel endothelium-associated antigen targeted by dendritic cell therapy.

Tumor-associated antigens are promising candidates as target molecules for immunotherapy and a wide variety of tumor-associated antigens have been discovered through the presence of serum antibodies in cancer patients. We previously conducted dendritic cell therapy on 10 malignant melanoma patients and shrinkage or disappearance of metastatic tumors with massive necrosis occurred in two patients. In this study, we found a 29-kDa protein against which antibody was elicited by dendritic cell therapy in one of the two patients. Matrix-assisted laser desorption ionization-time of flight/mass spectrometry analysis of the protein isolated by two-dimensional electrophoresis combined with Western blots revealed that the 29-kDa protein was carbonic anhydrase II (CA-II). Immunohistochemistry of the tumors and normal tissues showed that CA-II was expressed in the tumor vessel but not in normal vessel endothelium. CA-II expression in tumor endothelium was observed as well in other cancers including esophageal, renal, and lung cancers. In an in vitro angiogenesis model, CA-II expression of normal human vein endothelial cells was significantly up-regulated when cells were cultured in the acidic and hypoxic conditions indicative of a tumor environment. These findings suggest that CA-II is a tumor vessel endothelium-associated antigen in melanoma and other cancers, and elicitation of serum anti-CA-II antibody by dendritic cell therapy may be associated with good clinical outcome including tumor reduction.     

Relationship of coffee consumption with a decline in kidney function among patients with type 2 diabetes: The Fukuoka Diabetes Registry

Aims/IntroductionThe evidence regarding the effects of coffee consumption on incident chronic kidney disease is inconclusive, and no studies have investigated the relationship in patients with diabetes. We aimed to prospectively investigate the relationship between coffee consumption and the decline in estimated glomerular function rate (eGFR) in patients with type 2 diabetes.Materials and MethodsA total of 3,805 patients (2,112 men, 1,693 women) with type 2 diabetes (mean age 64.2 years) and eGFR ≥60 mL/min/1.73 m² were followed (completion of follow up, 97.6%; median 5.3 years). Coffee consumption was assessed at baseline. The end‐point was a decline in eGFR to <60 mL/min/1.73 m² during the follow‐up period.ResultsDuring follow up, 840 participants experienced a decline in eGFR to <60 mL/min/1.73 m². Higher coffee consumption reduced the risk of decline in eGFR. Compared with no coffee consumption, the multivariate‐adjusted hazard ratios (95% confidence intervals) were 0.77 (0.63–0.93) for less than one cup per day, 0.77 (0.62–0.95) for one cup per day and 0.75 (0.62–0.91) for two or more cups per day (P for trend 0.01). This trend was unaffected by further adjustment for baseline eGFR and albuminuria. The mean eGFR change per year was −2.16 mL/min/1.73 m² with no coffee consumption, −1.89 mL/min/1.73 m² with less than one cup per day, −1.80 mL/min/1.73 m² with one cup per day and −1.78 mL/min/1.73 m² with two or more cups per day (P for trend 0.03).ConclusionsCoffee consumption is significantly associated with a lower risk of decline in eGFR in patients with type 2 diabetes.     

The Glymphatic System: A Review of the Challenges in Visualizing its Structure and Function with MR Imaging

The central nervous system (CNS) was previously thought to be the only organ system lacking lymphatic vessels to remove waste products from the interstitial space. Recently, based on the results from animal experiments, the glymphatic system was hypothesized. In this hypothesis, cerebrospinal fluid (CSF) enters the periarterial spaces, enters the interstitial space of the brain parenchyma via aquaporin-4 (AQP4) channels in the astrocyte end feet, and then exits through the perivenous space, thereby clearing waste products. From the perivenous space, the interstitial fluid drains into the subarachnoid space and meningeal lymphatics of the parasagittal dura. It has been reported that the glymphatic system is particularly active during sleep. Impairment of glymphatic system function might be a cause of various neurodegenerative diseases such as Alzheimer’s disease, normal pressure hydrocephalus, glaucoma, and others. Meningeal lymphatics regulate immunity in the CNS. Many researchers have attempted to visualize the function and structure of the glymphatic system and meningeal lymphatics in vivo using MR imaging. In this review, we aim to summarize these in vivo MR imaging studies and discuss the significance, current limitations, and future directions. We also discuss the significance of the perivenous cyst formation along the superior sagittal sinus, which is recently discovered in the downstream of the glymphatic system.     

Dietary intake of seaweed and minerals and prevalence of allergic rhinitis in Japanese pregnant females: baseline data from the Osaka Maternal and Child Health Study

PURPOSE: It may be worthwhile to assess the possible protective effect of the traditional Japanese diet on allergic disorders. This cross-sectional study investigated the relationship between dietary intake of seaweed, vegetables, fruit, antioxidants, fiber, and minerals and the prevalence of allergic rhinitis. METHODS: Study subjects were 1002 Japanese pregnant women. Allergic rhinitis (including cedar pollinosis) was defined as present if subjects had received drug treatment at some point during the previous 12 months. Information on dietary factors was collected by using a self-administered diet history questionnaire. RESULTS: Seaweed intake was associated independently with a decreased prevalence of allergic rhinitis. Significant inverse dose-response relationships were found between calcium and phosphorus intake and allergic rhinitis prevalence. There also was a tendency for an inverse association between magnesium consumption and allergic rhinitis. Additional adjustment for calcium or magnesium intake apparently did not influence the inverse association with seaweed consumption. Consumption of vegetables, fruit, vitamins C and E, fiber, and zinc showed no association with allergic rhinitis, whereas a significant positive relationship was observed between beta-carotene intake and allergic rhinitis. CONCLUSIONS: High dietary intake of seaweed, calcium, magnesium, and phosphorus may be associated with a decreased prevalence of allergic rhinitis.     

Significant accumulation of KRAS mutations in bronchiolar metaplasia-associated honeycomb lesions of interstitial pneumonia

Interstitial pneumonia (IP) is a major risk factor for lung adenocarcinoma (LADC). IP-related LADC predominantly develops in the bronchiolar metaplasia lining in honeycomb lesions. Kirsten rat sarcoma virus (KRAS) is the most common oncogene mutated in IP-related LADC. The present study examined the metaplastic epithelia in honeycomb lesions for KRAS mutations using digital droplet polymerase chain reaction (ddPCR), a sensitive method used to detect infrequent mutations. Significantly higher KRAS mutation variant allele frequencies (VAFs) were detected in the metaplastic lung epithelia from 13 patients with IP compared with those in 46 non-lesioned lung samples from patients without IP (G12V, P=0.0004, G12C, P=0.0181, and G12A, P=0.0234; Mann Whitney U test). Multivariate analyses revealed that higher KRAS G12V (logistic regression model; P=0.0133, odds ratio=7.11) and G12C (P=0.0191, odds ratio=5.81) VAFs in patients with IP were independent of confounding variables, such as smoking and age. In patients with IP, metaplastic epithelia exhibited significantly higher KRAS G12V and G12C VAFs compared with the non-lesioned counterparts (paired t-test; G12V, P=0.0158, G12C, P=0.0465). These results suggested that IP could increase KRAS mutations and supported the hypothesis that bronchiolar metaplasia could be a precursor for IP-related LADC.     

Influence of Altered Knee Angle on Electromyographic Activity of Hamstring Muscles Between Nordic Hamstring Exercise and Nordic Hamstring Exercise with Incline Slope Lower Leg Board

BackgroundPrevious studies have shown that performing the Nordic hamstring exercise (NHE) with different board slope angles can affect hamstring activation. However, changes in muscle length with different board slopes can alter joint angles leading to the moment arm (MA) at the knee changing during the NHE.PurposeThis study aimed to investigate the influence of changing muscle length on hamstring electromyographic activity during an isometric NHE, while maintaining an equal moment arm.Study DesignA crossover study designMethodsSixteen male volunteers performed two types of conventional NHE, one with knees on the floor (NHE) and one with the legs placed upon an incline slope of a lower leg board (NHEB). To compare between the conventional and inclined NHE, the moment arm at the knee was calculated to be equal by an examiner holding the lower legs at points marked at 77% and 94% of the length of the lower leg. The four sub-groups comprised of: 1) NHE-77%, 2) NHE-94%, 3) NHEB-77%, and 4) NHEB-94%. The hamstring EMG activity was measured at the biceps femoris long head (BFlh) and at the semitendinosus (ST) and related compensatory muscles. The RMS data were normalized as a percentage of the maximum isometric values (normalized EMG [nEMG]). Significant main effects findings were followed up with Tukey’s post-hoc test using SPSS software and statistical significance was set at the p < 0.05 level.ResultsThe BFlh EMG activity values for NHE-77% were significantly higher than those for NHE-94% (p= 0.036) and NHEB-77% (p < 0.001), respectively, while ST during NHE-77% was significantly higher only in NHEB-77% (p < 0.001). In addition, NHEB-94% was significantly greater than NHEB-77% for both BFlh (p < 0.001) and ST (p < 0.001).ConclusionThese results indicate that hamstring electromyographic activity is decreased when the hamstring muscle is lengthened during the Nordic hamstring exercise.Level of Evidence3