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Biomedical subjects

Yuji Yamamoto

Publications and source records attributed to Yuji Yamamoto.

At least 19 recordsLinked to original sources

Multiancestry genome-wide association and multiomics analyses elucidate spatiocellular features of multiple sclerosis genetics.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination disseminated in space and time. Here we performed a genome-wide association study (GWAS) using 688 MS cases and 205,199 controls from the Japanese population and identified significant associations in the major histocompatibility complex region and a population-specific risk variant in 11q24. Through cross-population GWAS meta-analyses using a total of 29,374 cases and 1,843,563 controls from 4 ancestral populations, we identified 22 novel susceptibility loci. Integration of GWAS and single-cell and single-nucleus RNA sequencing of peripheral blood mononuclear cells and subcortical lesions from patients with MS revealed enrichment of genetic risk factors for MS in CD4+ T helper cell lineage and regulatory T cells, as well as in endothelial cells. Furthermore, spatial transcriptomics of subcortical lesions demonstrated spatial and temporal heterogeneity in associations with MS genetic risk. Our study demonstrates the value of investigation of spatiocellular features of disease genetics across diverse populations and omics modalities.

Humans↗

Long-term outcome after hernia repair with the prolene hernia system.

PURPOSE: We evaluated the long-term outcome and symptoms after inguinal hernia repair using the Prolene Hernia System (PHS). METHODS: We reviewed the medical records of all patients who underwent PHS surgery at our hospital to assess the postoperative complications and recurrence rates. Late symptoms were evaluated by a standardized interview using a questionnaire. RESULTS: A total of 395 hernias in 367 patients were studied. Postoperative complications developed after 20 repairs (5.1%), including a severe mesh infection in one patient. Seven (1.8%) patients suffered recurrence. Of 395 cases, 363 (91.9%) responded to the interview. After a median follow-up interval of 19.3 months (range 1.0-55.8), moderate pain and moderate discomfort were reported by only 1.9% and 0.8% of patients, respectively. CONCLUSIONS: Prolene Hernia System surgery is a safe and feasible procedure with low rates of complication, recurrence, and late symptoms.

Adolescent↗

The Group B Streptococcus NADH oxidase Nox-2 is involved in fatty acid biosynthesis during aerobic growth and contributes to virulence.

Numerous Streptococcaceae produce an H2O-forming NADH oxidase, Nox-2, which has been generally implicated in aerobic survival. We examined the roles of Nox-2 in Group B Streptococcus (GBS), a leading agent of neonatal infections. While nox2 inactivation caused an aerobic growth arrest, no improvement was seen by addition of antioxidants to cultures, suggesting that this defect was not due to accumulation of toxic oxygen species. Using several approaches, we show that the observed inability of the nox2 mutant to grow aerobically is mainly due to an underlying defect in fatty acid (FA) biosynthesis: (i) the nox2 aerobic growth defect is fully and rapidly complemented by adding oleic acid to culture medium, and (ii) direct assimilation of this unsaturated FA in both wild type (WT) and nox2 GBS membranes is demonstrated and correlated with mutant growth rescue. We propose that NAD+ depletion in the nox2 mutant results in reduced acetyl-CoA production, which perturbs FA biosynthesis and hence blocks growth in aerobiosis. The nox2 aerobic growth defect was also complemented when GBS respiration metabolism was activated by exogenous haem and menaquinone. The membrane NADH oxidase activity generated by the functional respiratory chain thus compensates the cytoplasmic NADH oxidase deficiency. The nox2 mutant was attenuated for virulence, as assessed in lung, intraperitoneal and intravenous murine infection models. As the nox2 defect seems only to affect aerobic growth of GBS, its reduced virulence supports the suggestion that aerobic conditions and NADH oxidase activities are relevant to the GBS infection process.

Acetates↗

Application of peptide probe for evaluating affinity properties of proteins using quartz crystal microbalance.

This study proved a possibility of a peptide probe for evaluating affinity properties of proteins. We have designed and synthesized three different peptide probes, H-Ala3-(Gly-Pro5)3-Gly-OH (peptide A), H-Ala3-(Gly-Pro5)-Gly-OH (peptide B) and H-Ala3-Gly-OH (peptide C) for testing their affinities to profilin. Each peptide probe was immobilized on a quartz crystal microbalance (QCM) sensor. The QCM sensor with the peptide A showed a 93 Hz decrease of resonant frequency which indicated profilin bound to the QCM sensor in a single layer. In a successive reaction with actin, the QCM analysis resulted in a 123 Hz decrease of resonant frequency which showed actin bound to the QCM sensor. A fluorescence microscope image of the sensor surface exhibited clear fluorescence after binding a rhodamine labeled actin on the sensor surface. These results supported stepwise reactions of profilin binding to the peptide A and actin binding to profilin. In the three peptide probes, the peptide A showed the highest affinity to profilin, i.e., sequence dependent affinity was confirmed.

Actins↗

New luminescent europium(III) chelates for DNA labeling.

The new europium(III) chelate [2,2',2'',2'''-[[4'-(aminobiphenyl-4-yl)-2,2':6',2''-terpyridine- 6,6''-diyl]bis(methylenenitrilo)]tetrakis(acetato)] europium(III) (ATBTA-Eu3+) and its 4,6-dichloro-1,3,5-triazinyl and succinimidyl derivatives (DTBTA and NHS-ATBTA, respectively) were synthesized and characterized. Both labeling complexes DTBTA-Eu3+ and NHS-ATBTA-Eu3+ are luminescent. Especially DTBTA-Eu3+ is strongly luminescent, with a luminescence quantum yield of 9.1%, molar extinction coefficient of 3.1 x 10(4) cm(-1) M(-1) (335 nm), and luminescence lifetime of 1.02 ms. The excitation and emission maximum wavelengths of DTBTA-Eu3+ are 335 and 616 nm, respectively. The complex is very stable in aqueous buffers, with a conditional formation constant log K(DTBTA-Eu) of 25.0 at pH 8, and can be conjugated to DNA and proteins. The chelates are also highly resistant to thermal decomposition, photodegradation, and ozone oxidation. These properties prove that DTBTA-Eu3+ is suitable as a luminescence label in DNA assays.

Chelating Agents↗

Evidence for a role of developmental genes in the origin of obesity and body fat distribution.

Obesity, especially central obesity, is a hereditable trait associated with a high risk for development of diabetes and metabolic disorders. Combined gene expression analysis of adipocyte- and preadipocyte-containing fractions from intraabdominal and subcutaneous adipose tissue of mice revealed coordinated depot-specific differences in expression of multiple genes involved in embryonic development and pattern specification. These differences were intrinsic and persisted during in vitro culture and differentiation. Similar depot-specific differences in expression of developmental genes were observed in human subcutaneous versus visceral adipose tissue. Furthermore, in humans, several genes exhibited changes in expression that correlated closely with body mass index and/or waist/hip ratio. Together, these data suggest that genetically programmed developmental differences in adipocytes and their precursors in different regions of the body play an important role in obesity, body fat distribution, and potential functional differences between internal and subcutaneous adipose tissue.

Adipocytes↗

Differences in torsional joint stiffness of the knee between genders: a human cadaveric study.

BACKGROUND: In many sports, female athletes have a higher incidence of anterior cruciate ligament injury than do male athletes. Among many risk factors, the lower rotatory joint stiffness of female knees has been suggested for the increased rate of anterior cruciate ligament injuries. HYPOTHESIS: In response to combined rotatory loads, female knees have significantly lower torsional joint stiffness and higher rotatory joint laxity than do male knees at low flexion angles, despite the fact that no such gender differences would be found in response to an anterior tibial load. STUDY DESIGN: Comparative laboratory study. METHODS: Joint kinematics of 82 human cadaveric knees (38 female, 44 male) in response to (1) combined rotatory loads of 10 N x m valgus and +/- 5 N x m internal tibial torques and (2) a 134-N anterior-posterior tibial load were measured using a robotic/universal force-moment sensor testing system. RESULTS: In response to combined rotatory loads, female knees had as much as 25% lower torsional joint stiffness (female: 0.79 N x m/deg; 95% confidence interval, 0.67-0.91; male: 1.06 N x m/deg; 95% confidence interval, 0.95-1.17) and up to 35% higher rotatory joint laxity (female: 26.2 degrees; 95% confidence interval, 24.5 degrees-27.9 degrees; male: 20.5 degrees; 95% confidence interval, 18.8 degrees-22.2 degrees) than did male knees (P < .05), whereas there were no gender differences in response to the anterior tibial load (P > .05). CONCLUSION: Female knees had lower torsional joint stiffness and higher rotatory joint laxity than did male knees in response to combined rotatory loads. CLINICAL RELEVANCE: Larger axial rotations of female knees in response to rotatory loads may affect the distribution of forces in soft tissues and the function of muscles that provide knee stability. Control algorithms used during the biomechanical testing of cadaveric knees and computational knee models might need to be gender specific.

Biomechanical Phenomena↗

Effect of the iliotibial band on knee biomechanics during a simulated pivot shift test.

The purpose of this study was to evaluate the effect of the iliotibial band (ITB) on the kinematics of anterior cruciate ligament (ACL) intact and deficient knees and also on the in situ force in the ACL during a simulated pivot shift test. A combination of 10 N-m valgus and 5 N-m internal tibial torques was applied to 10 human cadaveric knees at 15 degrees, 30 degrees, 45 degrees, and 60 degrees of flexion using a robotic/universal force-moment sensor testing system. ITB forces of 0, 22, 44, and 88 N were also applied. An 88 N ITB force significantly decreased coupled anterior tibial translation of ACL deficient knees by 32%-45% at high flexion angles, but did not have a significant effect at low flexion angles. Further, an 88 N ITB force significantly decreased in situ forces in the ACL at all flexion angles by 23%-40%. These results indicate that during the pivot shift test, the ITB can improve tibial reduction at high flexion angles while not affecting subluxation at low flexion angles. Additionally, the action of the ITB as an ACL agonist suggests that its use as an ACL graft might hinder knee stability in response to rotatory load.

Adult↗

Roles of environmental heme, and menaquinone, in streptococcus agalactiae.

Most bacteria require iron for growth. However, as it may not be directly available under aerobic conditions, bacteria may use iron-sequestering molecules, such as bacterially encoded siderophores, or heme, which is the major iron source in the animal host. Bacteria may also assimilate heme for purposes other than as an iron source. Once internalised, heme can activate, for example, a heme-dependent catalase and a cytochrome oxidase. In bacterial pathogen Streptococcus agalactiae, heme, in association with exogenous menaquinone, activates a respiratory chain. Respiration has radical effects on carbon metabolism. GBS respiration-grown cells display improved survival in an aerobic environment and greater virulence in a murine septicemia model. GBS might benefit from its ecological niches to capture heme and menaquinone, i.e., from other bacteria when it colonizes host mucosa, or from blood-containing organs during septicemia.

Animals↗

Distribution of orally ingested hydrochloric acid in the thoracoabdominal cavity after death.

The authors encountered a case of hydrochloric acid (HCl) poisoning, thought to be caused by oral ingestion of concentrated HCl. Coagulation of the surface of the tongue and the mucosa of the pharynx, esophagus, and stomach were observed at forensic autopsy. An overabundance of Cl- was found in the gastric contents, corresponding to 8.19 mL of concentrated HCl. This was suggested to be a lethal oral dose of concentrated HCl, and the cause of death was determined to be HCl poisoning. Measuring the pH and concentrations of various ions in body fluids and contents of the alimentary tract enabled postmortem diffusion of HCl to be determined.

Abdominal Cavity↗

Long polymeric tips of atomic force microscopy for large biological samples.

We show a new atomic force microscopy technique for obtaining high-resolution topographic images of large bio-samples. To obtain high-resolution topographic images for the samples, we fabricated a long polymeric tip with a small protrusion using two-photon adsorbed photo-polymerization techniques. The obtained tip length was over 50 microm, and the tip was used directly to visualize COS-1 and 293 cells. Compared with commercial tips, the long tip made it easier to obtain topographic images of the large cells. In the magnified topographic images, the sub-100-nm resolution was confirmed with the long tips. This long probe tip is expected to broaden large sample-related studies and applications in the future.

Animals↗

[A resected case of stage IV gastric cancer successfully treated with TS-1/CDDP as neoadjuvant chemotherapy].

A resected case of gastric cancer is described. The patient was a 60-year-old woman who presented a type 3 gastric tumor complicated by invasion of the head of the pancreas and liver. Radical resection was not indicated, and we administered the following combination chemotherapy with TS-1 and CDDP. 120 mg/day of TS-1 was orally administered for 3 weeks followed by 2 drug-free weeks as 1 course and 9 5 mg (60 mg/m(2)) of CDDP was administered intravenously on day 8. After two courses, total gastrectomy and D2 lymph node dissection were performed. Radical surgery for cure was conducted. Microscopically, the histological effect was judged to be grade 1a. One year after the operation, the patient is still alive without recurrence and metastasis. TS-1/CDDP therapy is useful for advanced gastric cancer.

Adenocarcinoma↗

[A case of stage IVA intrahepatic biliary tract cancer successfully treated with gemcitabine].

We reported a case of non-resectable intrahepatic biliary tract cancer, treated with Gemcitabine and oral anticancer drugs. A 45-year-old man was admitted to the hospital due to abdominal distension and fatigue. CT scan revealed intrahepatic biliary tract cancer in the left lobe, which had metastasized to both lobes. Based on the diagnosis of non-resectable intrahepatic biliary tract cancer, systemic chemotherapy using gemcitabine (GEM) was employed. One course of the treatment consisted of 4 weeks. GEM 1,000 mg was administered once a week for 3 weeks followed by a week of no treatment. At the same time, the oral anti-cancer drug (5'-DFUR 600 mg/day) was administered every day. After 4 courses of chemotherapy, both the primary tumor and the hepatic metastasis were diminished, and the serum level of CA19-9 was reduced to the normal value. Relief from the abdominal distension allowed the patient to return to work. The chemotherapy was continued by outpatient-clinic treatment, preserving the quality of life for 13 months. The present case shows that gemcitabine/5'-DFUR combination is well supported in advanced unresectable biliary tract cancer.

Administration, Oral↗

Osteochondral autograft transplantation for osteochondritis dissecans of the elbow in juvenile baseball players: minimum 2-year follow-up.

BACKGROUND: Osteochondral autografts have recently become popular to treat articular cartilage defects, and they are used for unstable osteochondritis dissecans lesions as a means of biological fixation. PURPOSE: To evaluate the clinical results of osteochondral autograft transfer for osteochondritis dissecans of the elbow. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Osteochondral autograft transfer was performed on 18 baseball players (mean age, 13.6 years) with osteochondritis dissecans of the elbow. These included 9 lesions that were grade 3 (separated but in situ) and 9 lesions that were grade 4 (displaced fragment with osteochondral defect) based on magnetic resonance imaging. All patients were evaluated with a scoring system, radiographs, and magnetic resonance imaging, with the mean follow-up at 3.5 years. RESULTS: In patients with grade 3 lesions, the subjective score was increased, but the objective score did not change. Six of 9 patients returned to their previous sports performance levels. One quit baseball because of academic reasons, 1 changed his position, and 1 changed to softball. In patients with grade 4 lesions, both subjective and objective scores were increased significantly. All but 1 patient returned to their previous sports performance levels. In the 3 grade 4 lesions with a wide osteochondral defect, the irregularity of the articular surface remained on magnetic resonance imaging. CONCLUSION: Osteochondral autograft transplantation is a useful treatment for reattachment of the lesion as well as osteochondral resurfacing of elbow osteochondritis dissecans.

Adolescent↗

Growth index, assessed with Ki-67 and ssDNA labeling; a significant prognosticator for patients undergoing curative resection for hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: The aggressiveness and greater malignant potential of cancers are characterized by several biological phenomena such as accelerated growth invasiveness, and the ability to form distant metastasis. Thus, knowledge of such biological difference may be a more accurate prognosticator for cancer patients. Tumor growth depends on the degree of imbalance between cell production and loss. This study aimed to clarify a possible role for the modified prognosticator, growth index (GI); defined as the difference between Ki-67 (%) and single-stranded DNA (ssDNA) (%) labeling indices, in patients undergoing curative resection for hepatocellular carcinoma (HCC). METHODS: Tissue specimens were obtained from 40 HCC patients who underwent curative surgery. Immunohistochemical staining was performed using the avidin-biotin-peroxidase-complex method. RESULTS: The GI in HCC ranged from -1.90% to 28.65%, median 3.73. GI was related to histologic grade, intrahepatic metastasis, and pathologic T stage. Cumulative survival was poorer in patients with higher GI (> or = median value). Multivariate analysis demonstrated that GI is an independent prognosticator along with vascular invasion and intrahepatic metastasis. CONCLUSIONS: The higher GI values were significantly associated with histologic aggressive features of HCCs, and GI was a significant independent prognosticator in HCC patients after curative resection.

Aged↗

Ghrelin improves renal function in mice with ischemic acute renal failure.

Growth hormone and IGF-1 have been suggested to have tissue-protective effects. Ghrelin is a stomach-derived growth hormone secretagogue. The effects of ghrelin on ischemia/reperfusion-induced renal failure in mice were examined. Ischemic acute renal failure was induced by bilateral renal artery clamping for 45 min and reperfusion for 24 h. Ghrelin (100 microg/kg mouse) or vehicle was injected subcutaneously six times before surgery and three times after surgery every 8 h. Twenty-four hours after reperfusion, the right kidney was isolated and perfused. Acetylcholine (ACh)- and adrenomedullin-induced endothelium-dependent vasorelaxation of renal vessels significantly improved in ghrelin-pretreated mice (%Delta renal perfusion pressure by 10(-7) M ACh -63.5 +/- 3.7 versus -41.2 +/- 5.5%; P < 0.05). This change was associated with significant increases of nitric oxide release in the kidneys of ghrelin-treated mice (10(-7) M ACh 35.5 +/- 5.8 versus 16.9 +/- 3.5 fmol/g kidney per min; P < 0.05). Serum concentration of urea nitrogen (53 +/- 7 versus 87 +/- 15 mg/dl; P < 0.05) and renal injury score were significantly lower in the ghrelin group (2.5 +/- 0.8 versus 5.3 +/- 1.5; P < 0.01). Tubular apoptotic index was significantly lower in the ghrelin group (5 +/- 5 versus 28 +/- 4; P < 0.05). Furthermore, the survival rate after the 60-min ischemic period was higher in the ghrelin group (80 versus 20%; P < 0.05). Ghrelin treatment significantly increased the serum level of IGF-1. However, such renal protective effects of ghrelin on ischemia/reperfusion injury were not observed in insulin receptor substrate-2 knockout mice. These results suggest that ghrelin may protect the kidneys from ischemia/reperfusion injury and that this effect is related to an improvement of endothelial function through an IGF-1-mediated pathway.

Acute Kidney Injury↗

Synthesis of morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) by dipeptidyl aminopeptidase IV derived from Aspergillus oryzae.

Morphiceptin (Tyr-Pro-Phe-Pro-NH(2)), tetrapeptide, was synthesized using dipeptidyl aminopeptidase IV (DP IV, EC 3.4.14.5) derived from Aspergillus oryzae RIB 915 as a catalyst. Tyr-Pro-OEt was incubated with Phe-Pro-NH(2) in the presence of DP IV under various conditions of temperature, concentrations of ethylene glycol, pH, reaction time, and others. Morphiceptin was obtained at 40% yield under the optimal reaction conditions: substrate, 4 mM Tyr-Pro-OEt.HCl and 20 mM Phe-Pro-NH(2).HCl; enzyme, DP IV, 0.275 nkat; solvent, 60% ethylene glycol containing 20 mM phosphate buffer at pH 7.0; amine, 4.2 mM diisopropylamine at 4 degrees C for 24 h. Amino group protection was unnecessary for synthesis of morphiceptin by DP IV.

Aspergillus oryzae↗