Age- and sex-stratified normal values for circulatory and ventilatory power during ramp exercise derived from a healthy Japanese population.

Circulatory power (CP) and ventilatory power (VP), obtained by cardiopulmonary exercise testing (CPX), have been suggested to be excellent prognostic markers for heart failure. However, the normal values of these parameters in healthy Japanese populations remain unknown; thus, we aimed to investigate these values in such a population. A total of 391 healthy Japanese participants, 20-78 years of age, underwent CPX with a cycle ergometer with ramp protocols. Systolic blood pressure (SBP), heart rate, oxygen uptake ([Formula: see text]O2) at peak exercise, and the slope of minute ventilation ([Formula: see text]E) versus carbon dioxide ([Formula: see text]CO2) ([Formula: see text]E vs. [Formula: see text]CO2 slope) were measured. CP was calculated by multiplying the peak [Formula: see text]O2 and SBP values, and VP was calculated by dividing the peak SBP value by the [Formula: see text]E versus [Formula: see text]CO2 slope. For males and females, the average CP values were 6119 ± 1280 (mean ± standard deviation) and 4775 ± 914 mmHg·mL/min/kg, respectively (p < 0.001). The average VP values for males and females were 8.0 ± 1.3 and 6.9 ± 1.3 mmHg (p < 0.001). CP decreased with age in both sexes. VP increased with age in females, with no significant change in males. We calculated the normal values for CP and VP in a healthy Japanese population. The results can contribute to the evaluation of patients' CPX results as a reference.

Usefulness of the predicted percentage ventilatory efficiency for carbon dioxide output during exercise in patients with chronic heart failure.

The ventilatory efficiency for carbon dioxide output ([Formula: see text]CO2) during exercise, as measured by the minute ventilation vs. [Formula: see text]CO2 slope ([Formula: see text]E vs. [Formula: see text]CO2 slope), is a powerful prognostic index in patients with chronic heart failure (CHF). This measurement is higher in women than in men, and it increases with age. This study aimed to investigate the usefulness of the predicted value of the percentage [Formula: see text]E vs. [Formula: see text]CO2 slope (%[Formula: see text]E vs. [Formula: see text]CO2 slope) as a prognostic index in patients with CHF. A total of 320 patients with CHF and a left ventricular ejection fraction (LVEF) < 45% (male, 85.6%; mean age, 64.6 years) who underwent symptom-limited cardiopulmonary exercise tests using a cycle ergometer were included in the study. The %[Formula: see text]E vs. [Formula: see text]CO2 was calculated using predictive formulae based on age and sex. Cardiovascular-related death was defined as the primary endpoint. The mean follow-up duration was 7.5 ± 3.3 years. Of 101 patients who died during the study period, 75 experienced cardiovascular-related deaths. The average [Formula: see text]E vs. [Formula: see text]CO2 slope was 32.8 ± 8.0, and the average %[Formula: see text]E vs. [Formula: see text]CO2 slope was 119.6 ± 28.2%. The cumulative incidence of cardiovascular-related death after 10 years of follow-up were 44.7% (95% CI 34.4-54.6%) in patients with %[Formula: see text]E vs. [Formula: see text]CO2 slope > 120 and 15.0% (95% CI 9.4-21.8%) in patients with %[Formula: see text]E vs. [Formula: see text]CO2 slope ≤ 120. The multivariate Cox regression analysis indicated that a %[Formula: see text]E vs. [Formula: see text]CO2 slope > 120 was an independent predictor of cardiovascular-related death (adjusted hazard ratio, 3.24; 95% confidence interval 1.65-6.67; p < 0.01). The %[Formula: see text]E vs. [Formula: see text]CO2 slope can be used for risk stratification in patients with CHF and an LVEF < 45%.

A novel surgical treatment for labial adhesion - The combination of Z- and Y-V-plasty: A case report.

Labial adhesion is characterised by complete or partial fusion of the labia minora. It occurs rarely in postmenopausal women. Although various methods have been proposed, there is no established treatment for postmenopausal patients with labial adhesions due to its low prevalence in this age group. Severe cases require surgical intervention, and the postoperative recurrence rate is relatively high at 14-20%. In this study, a novel therapeutic method was designed to treat labial adhesions: a combination of Z- and Y-V-plasty. An 82-year-old woman was diagnosed with severe long labial adhesion during an episode of urinary tract infection. The labia could not be separated manually; hence, Z-plasty was performed on the ventral side and Y-V-plasty on the anal side under general anaesthesia. No recurrence was noted eight months postoperatively. This method is relatively easy and produced the desired therapeutic effect with decreased risk of recurrence. This is a novel approach for postmenopausal patients with severe labial adhesion.

Paroxysmal sympathetic hyperactivity and the later development of epilepsy in a chemotherapy-associated brain damage.

BACKGROUND: Chemotherapy in childhood leukemia potentially induces brain lesions and neurological sequelae. Paroxysmal sympathetic hyperactivity (PSH) is known as a treatment-associated complication; however, the full clinical spectra of PSH remain to be elusive. CASE REPORT: A 5-year-old girl was diagnosed of acute myeloid leukemia (AML) M5. After the intensification therapy, she developed recurrent symptoms of episodic tachycardia, hypertension and perspiration lasting for several hours per day. The low-frequency-high-frequency ratio on Holter electrocardiography was rapidly increased from 0.84 to 2.24 at the onset of the paroxysmal event, whereas the video-monitoring electroencephalography (EEG) never identified ictal patterns of epileptiform discharges during the episodes. Thus, the diagnosis of PSH was given at 7 years of age. Myoclonic and generalized tonic-clonic seizures frequently appeared from 10 years of age, which poorly responded to anticonvulsants. EEG showed diffuse slow-wave bursts with multifocal spikes. Serial head magnetic resonance imaging (MRI) revealed diffuse cerebral and hippocampal atrophy, but not inflammatory lesions in the limbic system. CONCLUSION: We first demonstrate a pediatric case with PSH who developed drug-resistant epilepsy 3 years after the onset of PSH. Our data suggest the pathophysiological link of persistent PSH with chemotherapy-associated brain damage.

Ventilatory efficiency during ramp exercise in relation to age and sex in a healthy Japanese population.

BACKGROUND: The current understanding of ventilator efficiency variables during ramp exercise testing in the normal Japanese population is insufficient, and the responses of tidal volume (VT) and minute ventilation (V̇E) to the ramp exercise test in the normal Japanese population are not known. METHODS: A total of 529 healthy Japanese subjects aged 20-78 years underwent cardiopulmonary exercise testing using a cycle ergometer with ramp protocols. VT and V̇E at rest, at anaerobic threshold, and at peak exercise were determined. The slope of V̇E versus carbon dioxide (V̇CO2) (V̇E vs. V̇CO2 slope), minimum V̇E/V̇CO2, and oxygen uptake efficiency slope (OUES) were determined. RESULTS: For males and females in their 20 s, peak VT (VTpeak) was 2192 ± 376 and 1509 ± 260 mL (p < 0.001), peak V̇E (V̇Epeak) was 80.6 ± 18.7 and 57.7 ± 13.9 L/min (sex differences p < 0.001), the V̇E vs. V̇CO2 slope was 24.4 ± 3.2 and 25.7 ± 3.2 (p = 0.035), the minimum V̇E/V̇CO2 was 24.2 ± 2.3 and 27.0 ± 2.8 (p < 0.001), and the OUES was 2452 ± 519 and 1991 ± 315 (p < 0.001), respectively. VTpeak and V̇Epeak decreased with age and increased with weight and height. The V̇E vs. V̇CO2 slope and minimum V̇E/V̇CO2 increased with age, while conversely, the OUES decreased with age. CONCLUSIONS: We have established the normal range of VT and V̇E responses, the V̇E vs. V̇CO2 slope, the minimum V̇E/V̇CO2, and the OUES for a healthy Japanese population. Some of these parameters were influenced by weight, height, sex, and age. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing in cardiac patients.

Changes in oxygen uptake kinetics after exercise caused by differences in loading pattern and exercise intensity.

AIMS: The kinetics of recovery-period oxygen uptake (VO2 ) are affected by the O2 deficit generated during exercise. However, studies using ramp tests (RTs) and constant work rate tests (CT) have differently characterized VO2 responses to increased exercise intensity differently. We used these two types of loading patterns to investigate the effects of low-intensity, medium-intensity, and high-intensity exercises on the half time (T1/2 ) of recovery-period VO2 and the mechanism. METHODS AND RESULTS: Ten healthy men aged 21.2 ± 0.9 years underwent symptom-limited cardiopulmonary exercise tests with the ramp protocol to determine their anaerobic threshold. All subjects subsequently underwent three submaximal RT and CT at low, moderate, and high intensities. In all RTs, subjects began exercise by warming up (20 W). In CT, T1/2 was significantly lengthened as exercise intensity increased (CT-low: 34.0 ± 3.9 s, CT-moderate: 39.5 ± 3.5 s, CT-high:44.6 ± 4.2 s; P < 0.01, ANOVA), whereas no significant change was observed in RT, which began with the same work rate (RT-low: 46.0 ± 5.7 s, RT-moderate: 45.7 ± 4.8 s, RT-high: 44.6 ± 3.5 s, RT-max: 44.8 ± 3.2 s; P = 0.868, ANOVA). Only high-intensity exercise resulted in two components (the fast and slow components) of VO2 decay, reflecting the increased O2 deficit by anaerobic metabolism. CONCLUSIONS: The exercise intensity at the beginning of an exercise affects early recovery-period VO2 , which is a fast component. The T1/2 of recovery-period VO2 occurs during the fast component, and an increase in O2 deficit affects both the fast and slow components, lengthening the T1/2 . The T1/2 of recovery-period VO2 in CT at moderate or high intensities, even if not symptom limited, can be used to evaluate exercise intolerance and early occurrence of anaerobic metabolism. Submaximal exercise tests may be considered as convenient methods for evaluating exercise tolerance in patients with cardiac failure.

Higher postictal parasympathetic activity following greater ictal heart rate increase in right- than left-sided seizures.

OBJECTIVES: The objectives of this study were to determine how hemispheric laterality of seizure activity influences periictal heart rate variability (HRV) and investigate the ability of HRV parameters to discriminate right- and left-sided seizures. METHODS: Long-term video electroencephalogram-electrocardiogram recordings of 54 focal seizures in 25 patients with focal epilepsy were reviewed. Using linear mixed models, we examined the effect of seizure laterality on linear (standard deviation of R-R intervals [SDNN], root mean square of successive differences [RMSSD], low frequency [LF] and high frequency [HF] power of HRV, and LF/HF) and nonlinear (standard deviation [SD]1, SD2, and SD2/SD1 derived from Poincaré plots) periictal HRV parameters, the magnitude of heart rate (HR) changes, and the onset time of increased HR. Receiver operating characteristics (ROC) were used to determine the ability of these parameters to discriminate between right- and left-sided seizures. RESULTS: Postictal SDNN, RMSSD, LF, HF, SD1, and SD2 were higher in right- than left-sided seizures. Root mean square of successive difference and HF were decreased after left- but not right-sided seizures. Standard deviation of R-R intervals, LF, and SD1 were increased after right- but not left-sided seizures. Increased ictal HR was earlier and larger in right- than left-sided seizures. Postictal HF showed the greatest area under the ROC curve (AUC) (0.87) for discriminating right- and left-sided seizures. CONCLUSIONS: Our data suggest that postictal parasympathetic activity is higher, whereas ictal HR increase is greater, in right- than left-sided seizures. Involvement of the right hemisphere may be associated with postictal autonomic instability. Postictal HRV parameters may provide useful information on hemispheric laterality of seizure activity.

Quantitation of Rotundone in Grapefruit (Citrus paradisi) Peel and Juice by Stable Isotope Dilution Assay.

Aroma extract dilution analyses of the aromas of peels and juices of white and pink grapefruits revealed that rotundone, responsible for peppery, spicy, and woody odors, was detected for the first time at high flavor dilution factors of 256-1024. In both juices, rotundone was detected at the highest flavor dilution factor of 1024. Rotundone in grapefruits was quantitated by a stable isotope dilution assay with a newly synthesized deuterium-labeled internal standard, rotundone-d2,3: its levels were 2180 and 1920 ng/kg in white and pink grapefruit peels and 29.6 and 49.8 ng/kg in white and pink grapefruit juices, respectively. On the basis of these results, sensory analysis was performed to assess the effects of rotundone on a white grapefruit juice aroma reconstitute. This sensory analysis revealed that rotundone does not impart a woody odor or affect any of the existing attributes, but increases various attributes, thus confirming that rotundone is indispensable for the aroma of grapefruit juice.

Identification and Characterization of 3-epi-Rotundone, a Novel Stereoisomer of Rotundone, in Several Kinds of Fruits.

A novel stereoisomer of rotundone, 3-epi-rotundone, was identified in the aroma of grapefruit, orange, apple, and mango. 3-epi-Rotundone was prepared by the isomerization of rotundone, and its structural elucidation was confirmed by comparing the 1D and 2D nuclear magnetic resonance and nuclear Overhauser effect spectroscopy spectra with those of rotundone. The odor thresholds of rotundone and 3-epi-rotundone in water were determined by a triangle test as 5 and 19100 ng/kg, respectively. The odor of 3-epi-rotundone was evaluated as woody, spicy, peppery, citrus, grapefruit-like, powdery, and celery-like, which was a greater range of odor characteristics than that for rotundone. Results of odor evaluation of 3-epi-rotundone revealed that its unique organoleptic properties, which were odor description (woody, spicy, and peppery), anosmic properties in neat form, and strong adaptation, were similar to those of rotundone. 3-epi-Rotundone might be a valuable substance to apply new types of woody, peppery, and spicy notes.

Identification of Rotundone as a Potent Odor-Active Compound of Several Kinds of Fruits.

An investigation of the aromas of grapefruit, orange, apple, and mango revealed the presence of an odor-active compound that gave off a strong woody odor when assessed by gas chromatography-olfactometry. We isolated the compound from a high-boiling fraction of an orange essential oil, and subsequent nuclear magnetic resonance analyses of the isolated compound identified it as rotundone. Mass spectra and retention indices obtained from aroma concentrates of grapefruit, apple, and mango were identical to those of rotundone, which was therefore determined to be the common woody compound in these fruits. Sensory analyses were performed to assess the effects of rotundone on model beverages of the various fruits. It was revealed that rotundone added at even subthreshold levels to model beverages did not confer directly the woody odor, but had significant effects on the overall flavors of the beverages, helping them to better approximate the natural flavors of the fruits.

Optimization of Recovery and Analysis of RNA in Sorted Cells in mRNA Quantification After Fluorescence-activated Cell Sorting.

In our previous studies, we established a method to analyze cells collected by fluorescence-activated cell sorting (FACS), named mRNA quantification after FACS (FACS-mQ), in which cells are labeled with fluorescent dyes in a manner that minimizes RNA degradation, and then cells sorted by FACS are examined by analyzing their gene expression profile. In this study, we examined methods to maximize the yield of recovered RNA after in-tube immunocytochemistry in addition to RNA analysis using a small dose of extracted RNA. Paraformaldehyde fixation resulted in reduced RNA recovery, while preservation at 4 °C with 40 mM dithiothreitol was suitable for preventing RNA degradation in cells after immunocytochemistry. Using extracted RNA, four methods of analysis: quantitative reverse transcription - polymerase chain reaction (qRT-PCR), a combination of whole transcriptome amplification (WTA) or linear amplification and quantitative polymerase chain reaction (qPCR), and 2-step qRT-PCR, were compared. The combination of WTA and qPCR was less sensitive compared with the other methods. When RNAs from a small number of cells were used, qRT-PCR and 2-step qRT-PCR showed a greatly elevated relative expression level to ACTB mRNA in analyses of genes with a low expression level. These results suggested that among these methods, linear amplification was the most promising.

Improvement of nutritional composition and antioxidant capacity of high-amylose wheat during germination.

High-amylose wheat was subjected to various germination conditions and changes in its nutritional values and antioxidant capacity were investigated. Amounts of soluble dietary fiber, total protein and free lipid of germinated high-amylose wheat increased with increased germination times, whereas no significant changes were observed for insoluble dietary fiber and free fatty acids. Total free amino acid contents of high-amylose wheat gradually increased from 129.7 to 314.4 mg/100 g of grain (db) during 48 h of germination. As compared to ungerminated wheat, essential and functional amino acids including isoleucine, leucine, phenylanaline, valine and gamma-amino butyric acid in the 48 h-germinated wheat increased by 3-10 times. Total phenolic contents of both free and bound phenolics and their antioxidant capacities significantly increased after 24 h of germination and were further improved with prolonged germination times. It appears that nutritional values and bioactive compounds of high amylose wheat significantly improved for enhanced food applications.

An improved protocol for mRNA quantification after fluorescence-activated cell sorting with an increased signal to noise ratio in flow cytometry.

We established a method to analyze cells collected by fluorescence-activated cell sorting (FACS) named mRNA quantification after FACS (FACS-mQ), in which cells are labeled with a fluorescent dye in a manner that minimizes RNA degradation, and then cells sorted by FACS are examined by analyzing their gene expression profile. In this study, we established a modified protocol to analyze molecules with a low expression level, such as N-cadherin and thyroid transcription factor, by improving the signal to noise ratio in flow cytometry. Use of a fluorophore-conjugated second antibody and the appropriate choice of a fluorescence dye showed a marked increase in the signal to noise ratio. Use of the Can Get Signal Immunostain in diluting antibodies shortened the reaction time. In real-time reverse transcription-PCR, a significant decrease in the copy number of intracellular mRNAs was not observed after in-tube immunostaining. These results indicated that the present protocol is useful for separating and analyzing cells by FACS-mQ, targeting a molecule with a low expression level.

Identification of potential prognostic markers for knee osteoarthritis by serum proteomic analysis.

BACKGROUND: As osteoarthritis (OA) is a highly heterogeneous disease in terms of progression, establishment of prognostic biomarkers would be highly beneficial for treatment. The present study was performed to identify novel biomarkers capable of predicting the progression of knee OA. METHODS: A total of 69 plasma samples (OA patients undergoing radiographic progression, n = 25; nonprogression, n = 33; healthy donors, n = 11) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), and ion peaks of interest were identified by liquid chromatography and matrix-assisted laser desorption/ionization (MALDI)-TOF MS. The identities of these proteins were further validated by immunoprecipitation combined with SELDI-TOF MS analysis. RESULTS: SELDI-TOF MS analysis indicated that the intensities of 3 ion peaks differed significantly between progressors and nonprogressors. Subsequent analyses indicated that these peaks corresponded to apolipoprotein C-I, C-III, and an N-terminal truncated form of transthyretin, respectively. The identities of these proteins were confirmed by the loss of ion peaks in SELDI-TOF MS spectra by immunoprecipitation using specific antibodies for the respective proteins. CONCLUSIONS: Three potential biomarkers were identified whose serum levels differed significantly between OA progressors and nonprogressors. These biomarkers are expected to be prognostic biomarkers for knee OA and to facilitate the development of novel disease-modifying treatments for OA.

CIINE Reflects Collagenase-Specific CII Breakdown in Cartilage Explant and Whole Body of Canine.

To evaluate collagenase inhibitors for the treatment of osteoarthritis and to correlate them with clinical pathology, canine cartilage explant and anterior cruciate ligament transection (ACLT) models were examined by quantifying the CII neoepitope (CIINE). This peptide is a putative marker for collagenase-specific type II collagen (CII) degradation, which is a critical step in osteoarthritis pathology. The concentration of CIINE in supernatants of canine cartilage explants showed increase upon IL-1ß-stimulation and collagenase inhibitors suppressed this elevation of CIINE. In the canine ACLT model, levels of CIINE in urine (uCIINE) increased as lesions of knee joint cartilage developed and decreased in response to collagenase inhibitors. Our results suggest that CIINE reflects collagenase-specific CII degradation in canine explants and whole bodies. It is anticipated that these data will establish a tool for clarifying and bridging the efficacy and mechanism of collagenase inhibitors at the preclinical stage of drug discovery.

[A case of mucinous tubular and spindle cell carcinoma of the kidney].

Mucinous tubular and spindle cell carcinoma (MTSCC) is a distinct entity in the World Health Organization classification of kidney tumors since 2004. Herein, we report a case of a patient with MTSCC of the kidney. A 48-year-man visited our hospital with a chief complaint of occult blood in his urine, confirmed by urine occult blood reaction. Computed tomography revealed a solid tumor in the right kidney. The tumor was 40×38 mm in length and was slightly enhanced (cT1aN0M0). Therefore, we performed radical nephrectomy. On analysis of the resected specimen, we found that the number of comparatively small malignant cells had increased markedly, forming branched tubular cuboidal cells. Further more, positive results were obtained on staining the stroma with both PAS and alcian blue stains characteristic of papillary renal cell carcinoma ; however, extracellular mucinous material was found to be depleted. Therefore, we needed to differentiate between papillary renal cell carcinoma and MTSCC. Finally, on the basis of the immunohistochemical staining results-vimentin (＋), CK34ßE12 (-), and CD10 (-)-MTSCC was confirmed.

Heart rate and blood pressure response to ramp exercise and exercise capacity in relation to age, gender, and mode of exercise in a healthy population.

BACKGROUND: The responses of heart rate (HR) and blood pressure to the ramp exercise test are not known and the current understanding of peak oxygen uptake and anaerobic threshold (AT) values in the normal Japanese population is insufficient. METHODS AND RESULTS: A total of 749 healthy Japanese subjects aged 20-78 years underwent a cardiopulmonary exercise test using a cycle ergometer or treadmill ergometer with ramp protocols. HR, systolic blood pressure (SBP), and oxygen uptake VO2 at rest, at AT, and at peak exercise were determined. HR and SBP at peak exercise in a cycle ergometer and treadmill ergometer test decreased with age. Work rate at peak exercise in a cycle ergometer increased with body weight and decreased with age. VO2 at AT and at peak exercise were higher in treadmill ergometer testing than in cycle ergometer testing, and were not affected by exercise protocol. Both of these decreased with age. CONCLUSIONS: The normal responses of HR and SBP to ramp exercise testing are reported for the first time. AT, peak VO2, and VO2 at each stage are shown for a healthy population. Some of these parameters were influenced by weight, gender, and age, as well as mode of exercise and the protocol used. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing.