Association of an Increased Abnormal Mitochondria Ratio in Cardiomyocytes with a Prolonged Oxygen Uptake Time Constant during Cardiopulmonary Exercise Testing of Patients with Non-ischemic Cardiomyopathy.

Objective The cardiac function, blood distribution, and oxygen extraction in the muscles as well as the pulmonary function determine the oxygen uptake (VO2) kinetics at the onset of exercise. This factor is called the VO2 time constant, and its prolongation is associated with an unfavorable prognosis for heart failure (HF). The mitochondrial function of skeletal muscle is known to reflect exercise tolerance. Morphological changes and dysfunction in cardiac mitochondria are closely related to HF severity and its prognosis. Although mitochondria play an important role in generating energy in cardiomyocytes, the relationship between cardiac mitochondria and the VO2 time constant has not been elucidated. Methods We calculated the ratio of abnormal cardiac mitochondria in human myocardial biopsy samples using an electron microscope and measured the VO2 time constant during cardiopulmonary exercise testing. The VO2 time constant was normalized by the fat-free mass index (FFMI). Patients Fifteen patients with non-ischemic cardiomyopathy (NICM) were included. Patients were divided into two groups according to their median VO2 time constant/FFMI value. Results Patients with a low VO2 time constant/FFMI value had a lower abnormal mitochondria ratio than those with a high VO2 time constant/FFMI value. A multiple linear regression analysis revealed that the ratio of abnormal cardiac mitochondria was independently associated with a high VO2 time constant/FFMI. Conclusion An increased abnormal cardiac mitochondria ratio might be associated with a high VO2 time constant/FFMI value in patients with NICM.

Validity of anaerobic threshold measured in resistance exercise.

[Purpose] Intensity for resistance exercise is estimated based on the maximum muscle strength. Exercise prescription without evaluating the biological response has a challenge. This study aimed to confirm whether anaerobic threshold measured using cardiopulmonary exercise test in resistance exercise is appropriate or not. [Participants and Methods] Resistance exercise adopted for the study was right-leg knee extension. The participants were 10 healthy young males. We investigated whether the oxygen uptake kinetics achieved a steady state within 3 min during the constant-load test with knee extension at 80% anaerobic threshold using cardiopulmonary exercise test with knee extension. If oxygen uptake kinetics achieved a steady state within 3 min, the exercise intensity measured using cardiopulmonary exercise test was considered appropriate. [Results] Anaerobic threshold was measured using the conventional approach in all participants. The steady state of oxygen uptake kinetics could be achieved within 3 min. In the constant-load test with knee extension at 80% anaerobic threshold, the oxygen uptake kinetics achieved a steady state within 3 min. [Conclusion] Based on the findings, the anaerobic threshold obtained using cardiopulmonary exercise test with resistance exercise was judged as appropriate. The results of this study contribute to the accurate setting of exercise load for resistance exercise and condition setting for the evaluation of skeletal muscle function.

Use of Direct Hemoperfusion with Polymyxin B-Immobilized Fiber for the Treatment of Septic Shock Complicated with Lemierre Syndrome Caused by Fusobacterium necrophorum.

We report a case of septic shock treated with PMX-DHP that was complicated with Lemierre syndrome caused by Fusobacterium necrophorum. The patient was a 31-year-old man who was initially diagnosed with influenza. He received treatment; however, because his symptoms gradually worsened, he was transported to our hospital 10 days following his diagnosis. His initial examination revealed symptoms of respiratory distress and an altered level of consciousness. Based on laboratory and imaging results, it became clear that he suffered from septic shock of unknown etiology, disseminated intravascular coagulation, and acute renal and respiratory failure. We initiated treatment with vasopressors, an antibacterial agent, immunoglobulins as well as an appropriate ventilator management; however, his unstable circulatory condition continued. As soon as PMX-DHP was initiated, 2 days following admission to the ICU, his circulatory instability normalized. F. necrophorum was ultimately detected after a culture examination, and contrast-enhanced computed tomography revealed a jugular vein thrombus, which led to the diagnosis of Lemierre syndrome. The patient's condition gradually improved, and he was discharged from the ICU after 19 days.

Clinicopathological features of gastric adenocarcinoma of the fundic gland (chief cell predominant type) by retrospective and prospective analyses of endoscopic findings.

BACKGROUND AND AIM: Gastric adenocarcinoma of the fundic gland type (chief cell predominant type) (GA-FG-CCP) is a variant of gastric adenocarcinoma with chief cell differentiation. GA-FG-CCP is rare and not well understood. The present study aimed to investigate the clinicopathological features of GA-FG-CCP using retrospective and prospective analyses of endoscopic findings. METHODS: A total of 20 patients including nine cases treated with endoscopic submucosal dissection (ESD) were diagnosed with GA-FG-CCP. Morphological changes were analyzed by retrospectively retracing past endoscopic records and following up after definitive diagnoses, including the status of Helicobacter pylori (H. pylori) infection. RESULTS: GA-FG-CCP were small and whitish lesions accompanied by atypical vascular growth and their macroscopic types were classified as 0-IIa (60%), 0-IIb (25%), and 0-IIc (15%), respectively. The lesions were found in the non-atrophic gastric mucosa of the upper (70%) or middle portion (30%), although gastric mucosal atrophy associated with current or past H. pylori infection was identified in 75% of cases. In the nine cases treated with ESD, submucosal invasion was identified in 80% of the resected lesions, but no lymphovenous infiltration was detected. Ki-67 labeling index of GA-FG-CCP was low at 3.2% and visible morphological changes were rarely detected during long-term endoscopic observation for 58.9 ± 13.1 months. CONCLUSIONS: These data indicate that GA-FG-CCP, even when submucosal invasion occurs easily, might be of low-grade malignancy as long as it is the chief cell predominant type without other epithelial abnormalities. In addition, GA-FG-CCP might develop despite H. pylori infection or gastric mucosal atrophy.

Fabrication of all-ceramic crowns by a new method.

A new method of all-ceramic production using alumina coping has been developed. The present study investigates the influence of secondary firing (glass infiltration firing) conditions. Samples of porcelain build-up without secondary firing were also assessed. The suitability of coping that included secondary firing was found to be affected by the rate of temperature increase during the secondary firing. However, cracking developed in the fired porcelain if porcelain was built up onto secondarily-fired coping. In contrast, cracking did not occur with coping that was not secondarily fired. The bending strength after porcelain build-up was 70 MPa or higher, suggesting the possibility of clinical applications as an anterior crown. These findings establish that this is method of producing all-ceramic crowns that allows for low-cost manufacture in a short period of about 1 h.

Development of flocculent Saccharomyces cerevisiae strain GYK-10 for the selective fermentation of glucose/fructose in sugar mills.

Advances in glucose/fructose-selective ethanol production have successfully enhanced raw sugar extraction from sugarcane juice by converting inhibitory substances (i.e., glucose/fructose) into ethanol, which is removed by subsequent operations in cane sugar mills. However, the commercial implementation of this breakthrough process in existing cane sugar mills requires a yeast strain that (i) can be used in food production processes, (ii) exhibits stable saccharometabolic selectivity, and (iii) can be easily separated from the saccharide solution. In this study, we developed a suitable saccharometabolism-selective and flocculent strain, Saccharomyces cerevisiae GYK-10. We obtained a suitable yeast strain for selective fermentation in cane sugar mills using a yeast mating system. First, we crossed a haploid strain defective in sucrose utilization with a flocculent haploid strain. Next, we performed tetrad dissection of the resultant hybrid diploid strain and selected GYK-10 from various segregants by investigating the sucrose assimilation and flocculation capacity phenotypes. Ten consecutive fermentation tests of the GYK-10 strain using a bench-scale fermentor confirmed its suitability for the implementation of practical selective fermentation in a commercial sugar mill. The strain exhibited complete saccharometabolic selectivity and sustained flocculation, where it maintained a high ethanol yield and conversion rate throughout the test.

Prognostic and diagnostic significance of tumor budding associated with ß-catenin expression in submucosal invasive colorectal carcinoma.

Endoscopic resection has become a major curative treatment for early colorectal carcinoma without lymph node metastasis. However, lymph node metastasis, a poor prognostic factor in colorectal carcinoma, occurs in about 10% of the patients with submucosal invasive colorectal carcinoma. Therefore, it is important to identify a high-risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma. This study was designed to identify the relationship between tumor budding with ß-catenin expression and lymph node metastasis in submucosal invasive colorectal carcinoma. We investigated the immunohistochemistry of tumor budding in the 142 patients who underwent surgical resection for submucosal invasive colorectal carcinomas between 1984 and 1999 and the expression pattern of ß-catenin in budding tumor cells. Accordingly, all the patients were followed up for at least 10 years or until death. Among the 142 patients, lymph node metastasis was detected in 14 patients (9.9%). Univariate analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of ß-catenin in the nucleus was significantly associated with lymph node metastasis (P = 0.005). In contrast, tumor budding detected by hematoxylin and eosin staining was not associated with lymph node metastasis. Multivariate logistic regression analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of ß-catenin in the nucleus was a significant risk factor for lymph node metastasis (odds ratio, 7.124; 95% confidence interval, 1.407-36.062). Thus, tumor budding associated with ß-catenin expression is a risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma.

Clinical significance of white gastric crypt openings observed via magnifying endoscopy.

AIM: To evaluate the relationship between Helicobacter pylori (H. pylori)-induced gastritis and white gastric mucosal crypt openings (COs) in the gastric corpus. METHODS: A total of 175 consecutive patients (including 69 patients with gastric cancer) were enrolled in this study. We used magnifying endoscopy (ME) to observe the mucosa microsurface of the lesser and greater curvature of the gastric corpus (350 areas in all). We focused on areas with a round pit microstructure (primarily observed in non-atrophied areas) and evaluated the white openings of these gastric pits. We classified the whiteness of the COs as the "white-edged dark spot" type (consisting of a dark spot bordered by white); the "white" type (pure white with no dark spot); and the "dense white pit (DWP)" type (dense white, resembling a snowball). Gastritis was also histologically evaluated according to the updated Sydney System. RESULTS: We detected round COs using ME in 246 of the 350 areas examined. The histological examination showed significantly more mononuclear cells and neutrophil infiltration in the "white" and "DWP" types than the "white-edged dark spot" type (P < 0.001). Furthermore, significantly high-grade inflammation and evidence of active H. pylori-induced gastritis was observed in the "DWP" type (P < 0.001). Significant differences were observed in the whiteness of COs between H. pylori-positive (n = 139) and negative (n = 36) patients (P < 0.001). The sensitivity and specificity of the "white" and "DWP" types for predicting H. pylori infection were 78.5% and 81.7%, respectively. Of the patients with gastric cancer, 22.5% (18/80) had "white-edged dark spots", 51.3% (41/80) had "white" COs, and 26.3% (21/80) had "DWP"-type COs. "DWPs" were frequently observed among patients with undifferentiated gastric cancer [45.7% (16/35)]. CONCLUSION: CO whiteness detected via ME was associated with histological evidence of gastritis and helps to predict the severity of inflammation and H. pylori-induced activity.

Sternoclavicular joint septic arthritis following paraspinal muscle abscess and septic lumbar spondylodiscitis with epidural abscess in a patient with diabetes: a case report.

BACKGROUND: Septic arthritis of the sternoclavicular joint (SCJ) is extremely rare, and usually appears to result from hematogenous spread. Predisposing factors include immunocompromising diseases such as diabetes. CASE PRESENTATION: A 61-year-old man with poorly controlled diabetes mellitus presented to our emergency department with low back pain, high fever, and a painful mass over his left SCJ. He had received two epidural blocks over the past 2 weeks for severe back and leg pain secondary to lumbar disc herniation. He did not complain of weakness or sensory changes of his lower limbs, and his bladder and bowel function were normal. He had no history of shoulder injection, subclavian vein catheterization, intravenous drug abuse, or focal infection including tooth decay. CT showed an abscess of the left SCJ, with extension into the mediastinum and sternocleidomastoid muscle, and left paraspinal muscle swelling at the level of L2. MRI showed spondylodiscitis of L3-L4 with a contiguous extradural abscess. Staphylococcus aureus was isolated from cultures of aspirated pus from his SCJ, and from his urine and blood. The SCJ abscess was incised and drained, and appropriate intravenous antibiotic therapy was administered. Two weeks after admission, the purulent discharge from the left SCJ had completely stopped, and the wound showed improvement. He was transferred to another ward for treatment of the ongoing back pain. CONCLUSION: Diabetic patients with S. aureus bacteremia may be at risk of severe musculoskeletal infections via hematogenous spread.

Topographic differences in gastric micromucosal patterns observed by magnifying endoscopy with narrow band imaging.

BACKGROUND AND AIM: The distributions and grades of Helicobacter pylori induced gastritis are known to vary among H. pylori-associated diseases. The aim of this study was to investigate the differences in distributions of gastric micromucosal structures observed by magnifying narrow band imaging (NBI) endoscopy among patients with different H. pylori-associated diseases. METHODS: Ninety-five patients with active duodenal ulcers (n = 24) and diffuse-type (n = 24) and intestinal-type (n = 47) early gastric cancers were enrolled. The magnified NBI findings were evaluated at the lesser and greater curvatures in the upper gastric corpus and were classified according to the modified A-B classification system. Biopsy specimens were also evaluated. RESULTS: In a total of 190 areas observed with magnifying NBI, histological grading (inflammation, activity, atrophy and intestinal metaplasia) showed significant differences among the classified micromucosal patterns (P < 0.001). Types B-1 and B-2, with mild atrophic changes and few areas of intestinal metaplasia, were seen mostly in the duodenal ulcers group. Types B-3 and A-1, with moderate atrophic changes, were seen in the diffuse-type early gastric cancers at the lesser curvature. Types A-1 and A-2, with severe atrophic change and a high frequency of intestinal metaplasia, were seen in the intestinal-type early gastric cancers at the lesser curvature. The prevalence of micromucosal structures differed significantly among the three groups both at the lesser and greater curvatures (P < 0.001). CONCLUSIONS: Magnifying NBI endoscopy clearly revealed detailed micromorphological differences corresponding to the histology and endoscopic findings among patients with different H. pylori-associated diseases.

AtObgC, a plant ortholog of bacterial Obg, is a chloroplast-targeting GTPase essential for early embryogenesis.

Obg is a ribosome-associated GTPase essential for bacterial viability and is conserved in most organisms, from bacteria to eukaryotes. Obg is also expressed in plants, which predicts an important role for this molecule in plant viability; however, the functions of the plant Obg homologs have not been reported. Here, we first identified Arabidopsis AtObgC as a plant chloroplast-targeting Obg and elucidated its molecular biological and physiological properties. AtObgC encodes a plant-specific Obg GTPase that contains an N-terminal region for chloroplast targeting and has intrinsic GTP hydrolysis activity. A targeting assay using a few AtObgC N-terminal truncation mutants revealed that AtObgC localizes to chloroplasts and its transit peptide consists of more than 50 amino acid residues. Interestingly, GFP-fused full-length AtObgC exhibited a punctate staining pattern in chloroplasts of Arabidopsis protoplasts, which suggests a dimerization or multimerization of AtObgC. Moreover, its Obg fold was indispensable for the generation of the punctate staining pattern, and thus, was supposed to be important for such oligomerization of AtObgC by mediating the protein-protein interaction. In addition, the T-DNA insertion AtObgC null mutant exhibited an embryonic lethal phenotype that disturbed the early stage of embryogenesis. Altogether, our results provide a significant implication that AtObgC as a chloroplast targeting GTPase plays an important role at the early embryogenesis by exerting its function in chloroplast protein synthesis.

[A case of gastrointestinal stromal tumor of the stomach arising from the muscularis mucosae].

A 75-year-old man, in whom upper gastrointestinal endoscopy revealed a submucosal tumor in the greater curvature of the gastric angle, was hospitalized for further investigations. Since the tumor was shown to be located in the submucosal layer by endoscopic ultrasonography, we performed endoscopic mucosal resection. Pathological studies of the resected specimen revealed a gastrointestinal stromal tumor of the stomach. It was also formed that the tumor was connected not to muscularis propria, but to the muscularis mucosae. There has been no previous report about a case of gastrointestinal stromal tumor of the stomach arising from the muscularis mucosae in Japan.

Lipocalin-type prostaglandin D synthase as a melanocyte marker regulated by MITF.

Microphthalmia-associated transcription factor (MITF) is responsible for differentiation of melanocytes. A recessive MITF mutant, black-eyed white Mitf(mi-bw) mouse, is characterized by white coat color and deafness, due to the lack of melanocytes in the skin and inner ears. By cDNA microarray analysis, we have identified lipocalin-type prostaglandin D synthase (L-PGDS), whose mRNA is undetectable in the homozygous Mitf(mi-bw) skin. Immunohistochemical analysis of wild-type mice identified the specific expression of L-PGDS in follicular melanocytes. L-PGDS mRNA is expressed in B16 mouse melanoma cells, but undetectable in human melanoma cell lines. RNA interference analysis against MITF suggests that L-PGDS expression is dependent on MITF in B16 melanoma cells. Furthermore, we have provided evidence that MITF is involved in the melanocyte lineage-specific transcription of the mouse L-PGDS gene. Thus, L-PGDS represents a newly identified melanocyte marker. MITF may modulate the production of prostaglandin D(2) by activating the L-PGDS gene in melanocytes.

Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2.

Heme oxygenase (HO) catalyzes physiological heme degradation and consists of two structurally related isozymes, HO-1 and HO-2. Here we show that HO-2-deficient (HO-2(-/-)) mice exhibit hypoxemia and hypertrophy of the pulmonary venous myocardium associated with increased expression of HO-1. The hypertrophied venous myocardium may reflect adaptation to persistent hypoxemia. HO-2(-/-) mice also show attenuated ventilatory responses to hypoxia (10% O2) with normal responses to hypercapnia (10% CO2), suggesting the impaired oxygen sensing. Importantly, HO-2(-/-) mice exhibit normal breathing patterns with normal arterial CO2 tension and retain the intact alveolar architecture, thereby excluding hypoventilation and shunting as causes of hypoxemia. Instead, ventilation-perfusion mismatch is a likely cause of hypoxemia, which may be due to partial impairment of the lung chemoreception probably at pulmonary artery smooth muscle cells. We therefore propose that HO-2 is involved in oxygen sensing and responsible for the ventilation-perfusion matching that optimizes oxygenation of pulmonary blood.

Gingival sulcus simulation model for evaluating the penetration characteristics of elastomeric impression materials.

PURPOSE: This study evaluated the ability of five elastomeric impression materials to penetrate the gingival sulcus beyond the preparation margin. MATERIALS AND METHODS: A model of brass and agar gel was made to simulate human sulci and clinical gingival conditions. Two addition-curing silicones, one condensation-curing silicone, one polyether, and one polysulfide were tested. Ninety impressions of the model were made, six impressions with each material with differing sulcular widths. The centers of sulcular extension of these impressions were found with a measuring microscope. RESULTS: Two-way ANOVA showed significant differences among impression materials, sulcular widths, and their interactions. The penetration ability of polyether showed greater extension than the other materials, regardless of sulcular width. Polysulfide penetrated less than the two silicones with 0.2- and 0.1-mm sulcular widths but more with the narrow 0.05-mm sulcular width. CONCLUSION: These results suggest that the viscoelastic behavior of elastomers depends on the width of sulci. Moreover, the sulcus simulation model effectively contributes to the investigation of their characteristics.

[A case of gastric cancer with metastasis to cervical lymph nodes and pulmonary lymphangitis carcinomatosa responding to neoadjuvant chemotherapy with TS-1 and CDDP].

The patient was a 61-year-old man who had gastric cancer with metastasis to cervical lymph nodes and pulmonary lymphangitis carcinomatosa. He received daily oral administration of 120 mg of TS-1 (day 1-21) and systemic administration of 100 mg of CDDP (day 8) as one treatment course. As the metastatic lesions had disappeared after chemotherapy, he underwent total gastrectomy. Histopathological examination of resected regional lymph nodes revealed marked fibrosis and a small amount of scattered cancer cells. Although much peritoneal dissemination was observed macroscopically, histopathological examination of these tumors revealed only fibrosis with no cancer cells. These findings supported the effect of this neoadjuvant chemotherapy. He died of recurrence of the carcinoma 203 days after surgery, without any sign of recurrence of metastasis to cervical lymph nodes or pulmonary lymphangitis carcinomatosa.

Influence of environmental factors on tooth displacement.

An analysis of static occlusion including occlusal force and occlusal contact area in intercuspal position may be helpful but a dynamic analysis of occlusion should be regarded as more important for analyzing the stomatognathic system. Anthropological research has shown that the Japanese and the Mongolian populations share morphological and genetic similarities, although their dietary lives are not the same. The purpose of this study was to evaluate the relationship between environmental factors such as dietary life and stomatognathic function with a dynamic analysis of physiological tooth displacement. Ten clinically healthy subjects were recruited (mean age 24.8 +/- 1.0 years). The subjects were divided into two groups 1) Mongolian group: five Mongolians grown with a more or less natural texture diet and 2) Japanese group: five Japanese grown with a relatively soft diet. The displacement of the upper left first molar was measured during function using a three-dimensional tooth displacement transducer Type M-3. The tooth displacement in the Japanese group occurred mostly in an apicopalatal direction, but intruded basically parallel to the tooth axis in the Mongolian group. The stress-strain curve revealed that elastic socket deformation and viscous elements were more pronounced in the Japanese group. It was concluded that environmental factors such as dietary life could influence tooth displacement during function.

Three-dimensional reconstruction and fractal geometric analysis of serrated adenoma.

Serrated adenoma (SA) is a relatively newly defined entity of colorectal neoplasm first characterized by Longacre and Fenoglio-Preiser in 1990. This lesion is characterized by a complicated serrated edge of crypts. In this study, we performed three-dimensional (3-D) reconstruction, including 3-D distribution patterns of Ki-67-positive cells and fractal dimension of SA, in order to evaluate the nature of the complicated architecture, including its possible morphogenesis. We studied nine colonoscopic polypectomy specimens including three SAs, three tubular adenomas (TAs), and three hyperplastic polyps (HPs). Sixty serial tissue sections per case were stained alternately with hematoxylin and eosin (H&E) and Ki-67 immunostain. Each serial image was then digitized for 3-D computer analysis and the distribution pattern of Ki-67-positive cells was evaluated. Ki-67-immunostained sections were also subjected to 2-D quantitative morphometric study. In addition, the fractal dimensions of images from H&E-stained sections were examined using a box-counting method. Results of the 3-D reconstruction study demonstrated that glandular budding and branching were more frequent in SA than in TA or HP. These findings were confirmed quantitatively by the results of fractal geometric analysis of these polyps (fractal dimension:1.34 +/- 0.08 for SA, 1.23 +/- 0.07 for TA, and 1.28 +/- 0.12 for HP). Ki-67-positive cells in HP were localized mainly in the bottom of crypts and those in TA were diffusely distributed, while Ki-67-positive cells in SA were mainly aggregated in the depressed sites of serrated epithelia. These findings were also confirmed quantitatively using 2-D morphometry. These distribution patterns of the proliferative zone of SA are considered to contribute to the formation of the characteristic serrated epithelia and the complicated morphological appearance of SA.