The declining insulinogenic index correlates with inflammation and metabolic dysregulation in non-obese individuals assessed by blood gene expression.

AIMS: Diabetes onset is difficult to predict. Since decreased insulinogenic index (IGI) is observed in prediabetes, and blood gene expression correlates with insulin secretion, candidate biomarkers can be identified. METHODS: We collected blood from 96 participants (54 males, 42 females) in 2008 (age: 52.5 years) and 2016 for clinical and gene expression analyses. IGI was derived from values of insulin and glucose at fasting and at 30 min post-OGTT. Two subgroups were identified based on IGI variation: "Minor change in IGI" group with absolute value variation between -0.05 and +0.05, and "Decrease in IGI" group with a variation between -20 and -0.05. RESULTS: Following the comparison of "Minor change in IGI" and "Decrease in IGI" groups at time 0 (2008), we identified 77 genes correlating with declining IGI, related to response to lipid, carbohydrate, and hormone metabolism, response to stress and DNA metabolic processes. Over the eight years, genes correlating to declining IGI were related to inflammation, metabolic and hormonal dysregulation. Individuals with minor change in IGI, instead, featured homeostatic and regenerative responses. CONCLUSIONS: By blood gene expression analysis of non-obese individuals, we identified potential gene biomarkers correlating to declining IGI, associated to a pathophysiology of inflammation and metabolic dysregulation.

Eight-year longitudinal study of whole blood gene expression profiles in individuals undergoing long-term medical follow-up.

Blood circulates throughout the body via the peripheral tissues, contributes to host homeostasis and maintains normal physiological functions, in addition to responding to lesions. Previously, we revealed that gene expression analysis of peripheral blood cells is a useful approach for assessing diseases such as diabetes mellitus and cancer because the altered gene expression profiles of peripheral blood cells can reflect the presence and state of diseases. However, no chronological assessment of whole gene expression profiles has been conducted. In the present study, we collected whole blood RNA from 61 individuals (average age at registration, 50 years) every 4 years for 8 years and analyzed gene expression profiles using a complementary DNA microarray to examine whether these profiles were stable or changed over time. We found that the genes with very stable expression were related mostly to immune system pathways, including antigen cell presentation and interferon-related signaling. Genes whose expression was altered over the 8-year study period were principally involved in cellular machinery pathways, including development, signal transduction, cell cycle, apoptosis, and survival. Thus, this chronological examination study showed that the gene expression profiles of whole blood can reveal unmanifested physiological changes.

Correction to: A simple method for the automatic classification of body parts and detection of implanted metal using postmortem computed tomography scout view.

In the original publication of the article, the authors affiliations were incorrectly published. The corrected affiliations are given in this correction.

A simple method for the automatic classification of body parts and detection of implanted metal using postmortem computed tomography scout view.

Information on medical devices embedded in the body is important in the identification of an unidentified body. Computed tomography (CT) is a powerful imaging modality; however, metallic artifacts deteriorate the image quality because of the reconstruction method. On the contrary, CT scout view is less affected by metallic artifacts compared to CT. It is a simple method to classify the body into three rough parts for postmortem CT (PMCT) scout view, and an algorithm used to detect the location of the implanted metal has been developed for personal identification in forensic pathology. Of the test images, 97% were correctly classified into the three body parts. The true-positive rate for detection of the implanted metal in the scout view was 96.5%. Therefore, our simple methods are applicable in PMCT scout views and would be particularly useful for forensic pathology.

A Multi-Hemagglutinin-Based Enzyme-Linked Immunosorbent Assay to Serologically Detect Influenza A Virus Infection in Animals.

Mammals can play a role as an intermediate host in the emergence of mammalian-adapted reassortants or mutants of avian influenza A viruses, with pandemic potential. Therefore, detecting viral infection in animals followed by assessment of the hemagglutinin (HA) subtype of the agent is an indispensable process for risk assessment in pandemic preparedness. In this study, we tested the potential of an enzyme-linked immunosorbent assay as a rapid diagnosis method, using a panel of HA subtype antigens. By analyzing reference immune sera, we found that this novel assay could detect HA subtype-specific antibodies without considerable inter-subtypic cross-reactivities, contributing to diagnosis of influenza virus infection.

Postmortem interval estimation using the animal model of postmortem gas volume changes.

It is important to estimate the postmortem interval in forensic autopsy. Many methods to estimate the postmortem interval have been reported, and are typically associated with internal examination. However, there are issues such as rejection of autopsy by the family and a lack of forensic doctor in internal examination. Therefore, it is necessary to develop new methods, such as autopsy imaging, that can substitute for internal examination. Here, we first evaluated whether gas volume in the body increased with postmortem interval. Time-dependent X-ray CT imaging of euthanized Crl:CD (SD) rats (n = 3) was performed immediately after euthanasia and at seven subsequent time points up to 168 h (7 days) at 24-hour intervals. The data revealed that gas volume in the body increased in a time-dependent manner. Next, we reconstructed 3D images of isolated gas and calculated the gas volume using Amira software. In all cases, the volume of both portal venous gas and intestinal gas increased in a time-dependent manner. The volume of portal venous gas increased exponentially, while the volume of intestinal gas increased in a linearly with time. These data might be suggested that the postmortem gas volume change is one of indicators for estimating the postmortem interval. In addition, it would be possible to estimate more accurate postmortem interval by combining not only gas volume changes at the above two sites but also gas volume changes of the other sites such as heart cavities, kidney parenchyma, or abdominal aorta.

Bone comparison identification method based on chest computed tomography imaging.

The aim of this study is to examine the usefulness of bone structure extracted data from chest computed tomography (CT) images for personal identification. Eighteen autopsied cases (12 male and 6 female) that had ante- and post-mortem (AM and PM) CT images were used in this study. The two-dimensional (2D) and three-dimensional (3D) bone images were extracted from the chest CT images via thresholding technique. The similarity between two thoracic bone images (consisting of vertebrae, ribs, and sternum) acquired from AMCT and PMCT images was calculated in terms of the normalized cross-correlation value (NCCV) in both 2D and 3D matchings. An AM case with the highest NCCV corresponding to a given PM case among all of the AM cases studied was regarded as same person. The accuracy of identification of the same person using our method was 100% (18/18) in both 2D and 3D matchings. The NCCVs for the same person tended to be significantly higher than the average of NCCVs for different people in both 2D and 3D matchings. The computation times of image similarity between the two images were less than one second and approximately 10min in 2D and 3D matching, respectively. Therefore, 2D matching especially for thoracic bones seems more advantageous than 3D matching with regard to computation time. We conclude that our proposed personal identification method using bone structure would be useful in forensic cases.

Sex determination based on a thoracic vertebra and ribs evaluation using clinical chest radiography.

Our aim was to investigate whether sex can be determined from a combination of geometric features obtained from the 10th thoracic vertebra, 6th rib, and 7th rib. Six hundred chest radiographs (300 males and 300 females) were randomly selected to include patients of six age groups (20s, 30s, 40s, 50s, 60s, and 70s). Each group included 100 images (50 males and 50 females). A total of 14 features, including 7 lengths, 5 indices for the vertebra, and 2 types of widths for ribs, were utilized and analyzed for sex determination. Dominant features contributing to sex determination were selected by stepwise discriminant analysis after checking the variance inflation factors for multicollinearity. The accuracy of sex determination using a combination of the vertebra and ribs was evaluated from the selected features by the stepwise discriminant analysis. The accuracies in each age group were also evaluated in this study. The accuracy of sex determination based on a combination of features of the vertebra and ribs was 88.8% (533/600). This performance was superior to that of the vertebra or ribs only. Moreover, sex determination of subjects in their 20s demonstrated the highest accuracy (96.0%, 96/100). The features selected in the stepwise discriminant analysis included some features in both the vertebra and ribs. These results indicate the usefulness of combined information obtained from the vertebra and ribs for sex determination. We conclude that a combination of geometric characteristics obtained from the vertebra and ribs could be useful for determining sex.

Analysis of postmortem changes in internal organs and gases using computed tomography data.

Postmortem computed tomography (PMCT) is a useful method to identify various causes of death and measure the volume of internal organs and gases. The purpose of this study was to investigate postmortem changes as measured by PMCT, and the relationship between the volume of organs and gases and postmortem interval (PMI). Forty-six cadavers (22 men, 24 women) were examined by CT before autopsy. The volumes of the lungs, intrahepatic gas, and intrarectal gas were measured by CT using a workstation. A stepwise regression analysis was used to establish a predictive equation to ascertain the measured volume using factors including sex, age, height, body mass index (BMI), body surface area (BSA), and PMI. For estimation of PMI, stepwise regression analysis was used. In the equations for each measured volume, height, diaphragmatic height, and BSA were adopted for the left lung; height and diaphragmatic height were adopted for the right lung; PMI was adopted for intrahepatic gas; and sex and PMI were adopted for intrarectal gas. In the PMI equations, left lung volume, intrahepatic gas, and intrarectal gas were adopted together with sex, weight, and BMI. Values of intrahepatic gas decreased with postmortem changes, while intrarectal gas increased. This may be useful in investigation of postmortem changes. It will be necessary to include other parts of the intestine and to analyze volume changes in gases from these parts after death.

Interrelationship among Fe-His Bond Strengths, Oxygen Affinities, and Intersubunit Hydrogen Bonding Changes upon Ligand Binding in the ß Subunit of Human Hemoglobin: The Alkaline Bohr Effect.

Regulation of the oxygen affinity of human adult hemoglobin (Hb A) at high pH, known as the alkaline Bohr effect, is essential for its physiological function. In this study, structural mechanisms of the alkaline Bohr effect and pH-dependent O2 affinity changes were investigated via 1H nuclear magnetic resonance and visible and UV resonance Raman spectra of mutant Hbs, Hb M Iwate (αH87Y) and Hb M Boston (αH58Y). It was found that even though the binding of O2 to the α subunits is forbidden in the mutant Hbs, the O2 affinity was higher at alkaline pH than at neutral pH, and concomitantly, the Fe-His stretching frequency of the ß subunits was shifted to higher values. Thus, it was confirmed for the ß subunits that the stronger the Fe-His bond, the higher the O2 affinity. It was found in this study that the quaternary structure of α(Fe3+)ß(Fe2+-CO) of the mutant Hb is closer to T than to the ordinary R at neutral pH. The retained Aspß94-Hisß146 hydrogen bond makes the extent of proton release smaller upon ligand binding from Hisß146, known as one of residues contributing to the alkaline Bohr effect. For these T structures, the Aspα94-Trpß37 hydrogen bond in the hinge region and the Tyrα42-Aspß99 hydrogen bond in the switch region of the α1-ß2 interface are maintained but elongated at alkaline pH. Thus, a decrease in tension in the Fe-His bond of the ß subunits at alkaline pH causes a substantial increase in the change in global structure upon binding of CO to the ß subunit.

Slowly progressive insulin-dependent diabetes in a patient with primary biliary cirrhosis with portal hypertension-type progression.

A 73-year-old woman had previously been diagnosed with CREST syndrome, PBC and diabetes. Hepatic fibrosis was not evident, in spite of the transudative ascites and active esophageal varices. ACA were positive, whereas AMA and anti-gp210 antibodies were negative. She showed low urinary excretion of C-peptide and was weakly positive for anti-GAD antibody. She was diagnosed with a form of PBC that progresses via portal hypertension rather than liver failure and with SPIDDM. Her HLA type did not contain risk allele for IDDM or PBC. SPIDDM should be considered when patients with PBC with portal hypertension-type progression develop diabetes.