Fatal case of Capnocytophaga sepsis from a dog bite in a patient with splenic hypoplasia.

Background: Capnocytophaga canimorsus is an oral commensal bacteria in dogs and may cause severe infection following a dog bite. This is a case of fatal C. canimorsus sepsis with acute infectious purpura fulminans (AIPF) in a healthy patient with splenic hypoplasia. Case Presentation: A healthy 49-year-old man was admitted to the intensive care unit (ICU) for septic shock and AIPF 4 days after a dog bite to his mouth. Computed tomography revealed a small spleen measuring 53 cm3 but no other source of infection. Despite intensive care, the patient died of multiple organ failure and progressive shock on the fifth ICU day. Polymerase chain reaction of blood samples identified the C. canimorsus gene on a later day. Conclusion: Capnocytophaga canimorsus from dog bites may cause fatal AIPF. Splenic hypoplasia and bite wounds in well-perfused areas such as the oral cavity are possible risk factors for sepsis. All dog bites should warrant medical attention.

Increase in glycemic set point, alongside a decrease in waist circumference, in the non-diabetic population during the Japanese National Intervention Program for metabolic syndrome: A single-center, large-scale, matched-pair analysis.

BACKGROUND: In 2008, the Japanese government implemented a National Intervention Program for metabolic syndrome. Low-risk individuals were not direct targets of this intervention. Nevertheless, they were indirectly enlightened by this massive campaign. Documentation of the metabolic shifts in low-risk individuals following the program launch may inform public health policy regarding approaches to metabolic risks in the general population. METHODS: We conducted a cross-sectional analysis of data from non-diabetic participants who underwent general health check-ups at the Physical Check-up Center of Sumitomo Hospital. Participants during 2007-2008 were pair-matched with those during 2015-2016 with respect to sex, age, smoking status, hemoglobin level, and red blood cell (RBC) count. Each participant was included only once in the study. RESULTS: Totals of 3,140 men and 2,048 women were pair-matched. The non-diabetic participants showed lower waist circumference, blood pressure, heart rate, and serum lipid concentrations during the second study period. In contrast, the entire distributions of fasting plasma glucose (FPG) concentration in both sexes and glycated hemoglobin (HbA1c) in women were shifted upwards. In men, Δ FPG was +1.6 mg/dL (P < 0.001) and Δ HbA1c was ±0% (P = 0.6). In women, Δ FPG was +3.0 mg/dL (P < 0.001), and Δ HbA1c was +0.1% (P < 0.001). Δ Homeostasis model assessment of ß-cell function was -6.6 in men (P < 0.001) and -10.3 in women (P < 0.001). The homeostasis model assessment of insulin resistance did not change significantly. CONCLUSIONS: The "glycemic set point" has increased in non-diabetic people in Japan during recent years. Lifestyle or environmental changes may have caused this metabolic shift through obesity-independent pathways, possibly through effects on pancreatic ß-cell function. The underlying mechanism awaits further investigation.

Resuscitation from Cardiac Arrest with Tension Gastrothorax Due to Acquired Diaphragmatic Hernia.

Tension gastrothorax is a rare cause of obstructive shock induced by a distended stomach herniating into the thorax through a diaphragmatic defect. We report the process of diagnosis and emergency treatment for tension gastrothorax during cardiopulmonary resuscitation (CPR). A 71-year-old woman with multiple surgical histories had nausea and vomiting for two days. She was transferred to our hospital with circulatory failure and loss of consciousness. She presented pulseless electric activity and received CPR immediately after arrival. The right atrium and right ventricle were collapsed in the echocardiography. A chest X-ray demonstrated a dilated intestine extending from the peritoneal cavity to the mediastinum. The nasogastric tube (NGT) drained 1000 mL of stomach content and alleviated the abdominal distension, and spontaneous circulation returned immediately after the drainage. Thoracoabdominal CT showed the stomach and the transverse colon had escaped from the peritoneal cavity to the mediastinum. We diagnosed the situation as tension gastrothorax due to an acquired diaphragmatic hernia. History of multiple surgery and multiple operative scars was the first step of the diagnostic process, and the chest X-ray during CPR was the key to the diagnosis. Tension gastrothorax can be misdiagnosed as other conditions. A chest X-ray should be preceded in non-trauma settings, unlike the setting of a tension pneumothorax in trauma patients. Gastrointestinal decompression with NGT placement could be attempted quickly to improve the hemodynamic condition.

The use of veno-venous extracorporeal membrane oxygenation for massive hemoptysis following a traumatic lung injury: a case report.

BACKGROUND: Published reports regarding the use of veno-venous extracorporeal membrane oxygenation (V-V ECMO) for massive hemoptysis following a thoracic injury are still scarce. CASE PRESENTATION: A 34-year-old man developed massive hemoptysis from the right lung after a 2 m fall and being compressed with an iron pipe weighing 500 kg. He was immediately intubated using a double-lumen tube, and one-lung ventilation was started. Endotracheal hemorrhage was controlled by sealing the right lumen. V-V ECMO was initiated to endure the lethal hypoxemia while waiting for the right lung to heal. He came off of V-V ECMO after 17 days and was discharged on foot on day 46. CONCLUSION: The strategy of using V-V ECMO in combination with one-lung ventilation is useful and should be strongly considered to save lethal massive hemoptysis cases following traumatic lung injury.

A molecular signature for purified definitive endoderm guides differentiation and isolation of endoderm from mouse and human embryonic stem cells.

Embryonic definitive endoderm (DE) generates the epithelial compartment of vital organs such as liver, pancreas, and intestine. However, purification of DE in mammals has not been achieved, limiting the molecular "definition" of endoderm, and hindering our understanding of DE development and attempts to produce endoderm from sources such as embryonic stem (ES) cells. Here, we describe purification of mouse DE using fluorescence-activated cell sorting (FACS) and mice harboring a transgene encoding enhanced green fluorescent protein (eGFP) inserted into the Sox17 locus, which is expressed in the embryonic endoderm. Comparison of patterns of signaling pathway activation in native mouse DE and endoderm-like cells generated from ES cells produced novel culture modifications that generated Sox17-eGFP⁺ progeny whose gene expression resembled DE more closely than achieved with standard methods. These studies also produced new FACS methods for purifying DE from nontransgenic mice and mouse ES cell cultures. Parallel studies of a new human SOX17-eGFP ES cell line allowed analysis of endoderm differentiation in vitro, leading to culture modifications that enhanced expression of an endoderm-like signature. This work should accelerate our understanding of mechanisms regulating DE development in mice and humans, and guide further use of ES cells for tissue replacement.

Conserved markers of fetal pancreatic epithelium permit prospective isolation of islet progenitor cells by FACS.

Prospective isolation and characterization of progenitor cells is a paradigmatic strategy for studies of organ development. However, extraction of viable cells, fractionation of lineages, and in vitro analysis of progenitors from the fetal pancreas in experimental organisms like mice has proved challenging and has not yet been reported for human fetal pancreas. Here, we report isolation of pancreatic islet progenitor cells from fetal mice by FACS. Monoclonal antibodies that recognize cell-surface proteins on candidate stem cells in brain, skin, and other organs enabled separation of major pancreatic cell lineages and isolation of native pancreatic cells expressing neurogenin 3, an established marker of islet progenitors. New in vitro cell culture methods permitted isolated mouse islet progenitors to develop into hormone-expressing endocrine cells. Insulin-producing cells derived in vitro required or expressed factors that regulate fetal beta cell differentiation; thus, the genetic programs normally controlling in vivo mouse islet development are similarly required in our system. Moreover, antibodies that recognize conserved orthologous cell-surface epitopes in human fetal pancreas allowed FACS-based enrichment of candidate islet progenitor cells expressing neurogenin 3. Our studies reveal previously undescribed strategies for prospective purification and analysis of pancreatic endocrine progenitor cells that should accelerate studies of islet development and replacement.

Characterization of TROY-expressing cells in the developing and postnatal CNS: the possible role in neuronal and glial cell development.

A member of the tumor necrosis factor receptor superfamily, TROY, is expressed in the CNS of embryonic and adult mice. In the present study, we characterized TROY-expressing cells in the embryonic and postnatal forebrain. In the early embryonic forebrain, TROY was highly expressed in nestin-positive neuroepithelial cells and radial glial cells, but not in microtubule-associated protein 2-positive postmitotic neurons. During the late embryonic and postnatal development, expression of TROY was observed in radial glial cells and astrocytes, whereas its expression was not detected in neuronal lineage cells. In addition, TROY was exclusively expressed in Musashi-1-positive multipotent/glial progenitors in the postnatal subventricular zone. To investigate the functions of TROY in neural development, we overexpressed TROY in PC12 cells and established stably expressing cell clones. As expected, the signals from overexpressed TROY were constitutively transduced via the activation of the nuclear factor-kappaB and the c-Jun N-terminal kinase pathways in such clones. In addition, upregulation of negative basic helix-loop-helix transcription factors, HES-5 and Id2 proteins, was observed in the TROY-overexpressing clones. Interestingly, the overexpression of TROY in PC12 cells strongly inhibited nerve growth factor-induced neurite outgrowth with reduction of some markers of differentiated neurons, such as neurofilament 150 kDa and neuron-specific beta-tubulin. These findings suggest that the signaling from TROY regulates neuronal differentiation at least in part.

3alpha/beta,20beta-hydroxysteroid dehydrogenase (porcine testicular carbonyl reductase) also has a cysteine residue that is involved in binding of cofactor NADPH.

Besides residue of the catalytic triad that is conserved in the short-chain dehydrogenase/reductase (SDR) superfamily, a Cys side chain reportedly plays functional roles in NADP-dependent 15-hydroxyprostaglandin dehydrogenase and human carbonyl reductase (CR). The three-dimensional structure of porcine 3alpha/beta,20beta-hydroxysteroid dehydrogenase, also known as porcine testicular carbonyl reductase, demonstrates the proximity of the Cys 226 side chain to the bound NADP. However, no clear explanation with respect to the basis of the catalytic function of the Cys residue is yet available. By chemical modification, point mutation, and kinetic analysis, we determine that two Cys residues, Cys 149 and Cys 226, are involved in the enzyme activity. Furthermore, we found that pretreatment with NADP markedly protects the enzyme from inactivation by 4-(hydroxyl mercury) benzoic acid (4-HMB), thereby confirming that Cys 226 is involved in binding of the cofactor. On the basis of the tertiary structure of 3alpha/beta,20beta-HSD, the possible roles of Cys residues, especially that of Cys 226, in enzyme action and in the binding of cofactor NADPH are discussed.