Gastric acid level of humans must decrease in the future

Proton pump inhibitors strongly inhibit gastric acid production, but digestion problems do not generally arise. We can intake almost ordinary food even after total gastrectomy. Small intestine itself can digest and absorb food using various digestive enzymes without digestion in the stomach. The pH level of gastric acid in humans is much lower than that of most animals, and very close to that of carrion-eating animals called scavengers. It is assumed that ancient humans became bipedal approximately 4 million years ago. It was difficult for humans, who just started unstable bipedal locomotion, to catch quadrupedal-walking animals that can move faster, without special hunting tools. They may have eaten remaining carcasses, which is mainly the leftovers of carnivora species, as animal-derived food. The benefit to produce a volume of gastric acid for humans is carrion eating, in which disinfection by gastric acid is important. Humans produce a high concentration of gastric acid to enable consumption of a diet containing some bacteria and support this lifestyle by consuming significant energy to protect themselves from gastric acid. Now, the opportunity for strong deleterious bacteria to enter the gastrointestinal tract has decreased because of the organized clean environment. If this hygienic environment is maintained for a long time, our gastric acid level must be decreased gradually.     

Contralateral glissonian pedicle occlusion in a case of portal vein tumor thrombosis

To dissect portal vein branches directly and encircle them separately is a common procedure that is performed to control back flow bleeding during operations for hepatocellular carcinoma with portal vein tumor thrombosis. However, this technique has an increased risk of injuring contralateral portal branches and disseminating thrombosis fragments to the remnant liver. We present an alternative technique using right-sided glissonian pedicle occlusion for hepatocellular carcinoma with left portal vein tumor thrombosis due to complex anatomical vasculatures of the hepatic pedicle. This technique would be very useful for liver resection of hepatocellular carcinoma with the major type of portal vein tumor thrombosis.     

Survey on examinations for diagnosis of bone marrow failure in Japan: a report from the Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes

Using a registration sheet of a prospective registration system for aplastic anemia (AA)/myelodysplastic syndromes (MDS), by the National Research Group on Idiopathic Bone Marrow Failure Syndromes, Japan, we carried out a survey on examinations for diagnosis of bone marrow failure. Bone marrow trephine biopsy was performed in 66 of 105 cases (63%) [Original diagnosis: AA 51 cases (80%), MDS 12 (32%), undiagnosable 3 (75%)]. Bone marrow aspiration was performed in all cases, and aspiration was performed at least twice in 36 cases (34%). The first-line anatomic site for bone marrow aspiration was the posterior iliac crest (62%). Cytogenetic examination was performed in 93%. The concordance rate between the original and the central review diagnosis was 93% among the studied cases: AA, Idiopathic cytopenia of undetermined significance (ICUS) and MDS in total. Flow cytometry analysis to detect paroxysmal nocturnal hemoglobinuria (PNH)-type blood cells was performed in 32%.     

Dynamic live imaging of bone: opening a new era with ‘bone histodynametry’

Recent advances in optical imaging with two-photon excitation microscopy have enabled visualization of the inside of intact bone tissues in living animals. Using these advanced techniques, the dynamic behaviors of live bone cells and static histological information on bone tissue structures can be elucidated. The migration and positioning of osteoclast precursor monocytes, the bone-resorbing function of mature osteoclasts, and its functional coupling with bone-replenishing osteoblasts have been evaluated, including their dynamic properties in intact live bones. This novel ‘bone histodynametric’ methodology, combined with conventional histomorphometric analyses, will surely contribute to opening of a new era in bone and mineral research.     

An R132H Mutation in Isocitrate Dehydrogenase 1 Enhances p21 Expression and Inhibits Phosphorylation of Retinoblastoma Protein in Glioma Cells

Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to α-ketoglutarate (α-KG) and acquires new activity whereby it converts α-KG to 2-hydroxyglutarate. The IDH1 mutation induces down-regulation of tricarboxylic acid cycle intermediates and up-regulation of lipid metabolism. Sterol regulatory element-binding proteins (SREBPs) regulate not only the synthesis of cholesterol and fatty acids but also acyclin-dependent kinase inhibitor p21 that halts the cell cycle at G1. Here we show that SREBPs were up-regulated in U87 human glioblastoma cells transfected with an IDH1^R132H-expression plasmid. Small interfering ribonucleic acid (siRNA) for SREBP1 specifically decreased p21 messenger RNA (mRNA) levels independent of the p53 pathway. In IDH1^R132H-expressing U87 cells, phosphorylation of Retinoblastoma (Rb) protein also decreased. We propose that metabolic changes induced by the IDH1 mutation enhance p21 expression via SREBP1 and inhibit phosphorylation of Rb, which slows progressionof the cell cycle and may be associated with non-aggressive features of gliomas with an IDH1 mutation.     

Kinematics of the thoracic spine in trunk lateral bending: in vivo three-dimensional analysis

Background contextIn vivo three-dimensional kinematics of the thoracic spine in trunk lateral bending with an intact rib cage and soft tissues has not been well documented. There is no quantitative data in the literature for lateral bending in consecutive thoracic spinal segments, and there has not been consensus on the patterns of coupled motion with lateral bending.PurposeTo demonstrate segmental ranges of motion (ROMs) in lateral bending and coupled motions of the thoracic spine.Study designIn vivo three-dimensional biomechanics study of the thoracic spine.Patient sampleFifteen healthy male volunteers.Outcome measuresComputed analysis by using voxel-based registration.MethodsParticipants underwent computed tomography of the thoracic spine in three supine positions: neutral, right maximum lateral bending, and left maximum lateral bending. The relative motions of vertebrae were calculated by automatically superimposing an image of vertebrae in a neutral position over images in bending positions, using voxel-based registration. Mean values of lateral bending were compared among the upper (T1–T2 to T3–T4), the middle-upper (T4–T5 to T6–T7), the middle-lower (T7–T8 to T9–T10), and the lower (T10–T11 to T12–L1) parts of the spine.ResultsAt lateral bending, the mean ROM (±standard deviation) of T1 with respect to L1 was 15.6°±6.3° for lateral bending and 6.2°±4.8° for coupled axial rotation in the same direction as lateral bending. The mean lateral bending of each spinal segment with respect to the inferior adjacent vertebra was 1.4°±1.3° at T1–T2, 1.3°±1.2° at T2–T3, 1.4°±1.3° at T3–T4, 0.9°±0.9° at T4–T5, 0.8°±1.0° at T5–T6, 1.1°±1.1° at T6–T7, 1.7°±1.2° at T7–T8, 1.3°±1.2° at T8–T9, 1.6°±0.7° at T9–T10, 1.8°±0.8° at T10–T11, 2.3°±1.0° at T11–T12, and 2.2°±0.8° at T12–L1. The smallest and the largest amounts of lateral bending were observed in the middle-upper and the lower parts, respectively. There was no significant difference in lateral bending between the upper and the middle-lower parts. Coupled axial rotation of each segment was generally observed in the same direction as lateral bending. However, high variability was found at the T2–T3 to T5–T6 segments. Coupled flexion was observed at the upper and middle parts, and coupled extension was observed at the lower part.ConclusionsThis study revealed in vivo three-dimensional motions of consecutive thoracic spinal segments in trunk lateral bending. The thoracolumbar segments significantly contributed to lateral bending. Coupled axial rotation generally occurred in the same direction with lateral bending. However, more variability was observed in the direction of coupled axial rotation at T2–T3 to T5–T6 segments in the supine position. These results are useful for understanding normal kinematics of the thoracic spine.     

Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence

Despite their high degree of genomic similarity, reminiscent of their relatively recent separation from each other ( approximately 6 million years ago), the molecular basis of traits unique to humans vs. their closest relative, the chimpanzee, is largely unknown. This report describes a large-scale single-contig comparison between human and chimpanzee genomes via the sequence analysis of almost one-half of the immunologically critical MHC. This 1,750,601-bp stretch of DNA, which encompasses the entire class I along with the telomeric part of the MHC class III regions, corresponds to an orthologous 1,870,955 bp of the human HLA region. Sequence analysis confirms the existence of a high degree of sequence similarity between the two species. However, and importantly, this 98.6% sequence identity drops to only 86.7% taking into account the multiple insertions/deletions (indels) dispersed throughout the region. This is functionally exemplified by a large deletion of 95 kb between the virtual locations of human MICA and MICB genes, which results in a single hybrid chimpanzee MIC gene, in a segment of the MHC genetically linked to species-specific handling of several viral infections (HIV/SIV, hepatitis B and C) as well as susceptibility to various autoimmune diseases. Finally, if generalized, these data suggest that evolution may have used the mechanistically more drastic indels instead of the more subtle single-nucleotide substitutions for shaping the recently emerged primate species.     

Endothelial damage caused by cytomegalovirus and human herpesvirus-6

Infection with cytomegalovirus (CMV) or human herpesvirus-6 (HHV-6) may have a role in vascular endothelial damage after bone marrow transplantation (BMT). In total, 41 patients who underwent BMT were classified into four groups (12, 10, 7, and 12 patients who were infected with both CMV and HHV-6, CMV alone, HHV-6, and neither virus, respectively). Levels of thrombomodulin, plasminogen activator inhibitor-1, and cyclic GMP were 7.5+/-1.7 FU/ml, 76.4+/-24.1 ng/ml, and 9.51+/-1.1 pmol/ml, respectively, in the patients with both viruses, while the respective values were 2.9+/-0.67 FU/ml, 33.8+/-8.09 ng/ml, and 2.90+/-1.4 pmol/ml in patients infected with CMV alone, 4.8+/-0.96 FU/ml, 47.7+/-9.21 ng/ml, and 5.48+/-0.55 pmol/ml in patients with HHV-6 alone, and 1.6+/-0.39, 17.5+/-7.88 ng/ml, and 0.45+/-0.3 in those with neither virus. All three markers were significantly higher in the three groups with at least one virus than in the uninfected patients (P<0.05), and were also higher in patients with HHV-6 alone than in those with CMV alone (P<0.05). These results suggest that infection by CMV or HHV-6 causes vascular endothelial injury, with HHV-6 having a stronger effect than CMV, and combined infection having a stronger effect than either virus alone. Such viral infection may be a cause of thrombotic microangiopathy after BMT.