Mature adipocyte-derived dedifferentiated fat (DFAT) cells have a high proliferative activity and multi-lineage differentiation potential, similar to mesenchymal stem cells (MSCs). We hypothesized that DFAT cells isolated from different organ-derived adipose tissues would exhibit different properties. In the present study, we isolated DFAT cells from epicardial fat tissue (EC-DFAT) and subcutaneous fat tissue (SC-DFAT) from pigs and examined their differentiation capacity into cardiomyocytes. In vitro differentiation analysis revealed that both EC-DFAT and SC-DFAT cells exhibited adipogenic, osteogenic, chondrogenic and smooth muscle cell differentiation potential. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that expression of GATA binding protein 4 (GATA4), a marker for early differentiation of cardiomyocytes, was significantly higher in EC-DFAT cells compared with SC-DFAT cells under culture conditions for cardiomyocyte differentiation. Immunohistochemical analysis revealed that expression of the cardiomyocyte-specific transcription factor Nkx2.5, the gap junction protein connexin43 and the cardiac muscle-specific protein troponin I was frequently observed in EC-DFAT cells but not in SC-DFAT cells when the cells were cocultured with rat neonatal cardiomyocytes. These findings suggest that EC-DFAT cells can effectively differentiate into functional cardiomyocytes. EC-DFAT cells may be an attractive cell source for cardiomyocyte regeneration.
Graft-versus-host disease (GVHD) is known to be one of the lethal complications of hematopoietic cell transplantation (HCT). Recently, cell therapy using mesenchymal stem cells (MSC) has been applied clinically for steroid-resistant acute GVHD. Since it has been confirmed that dedifferentiated fat cells (DFAT) possess immunomodulatory effects that are similar to MSC, these cells have the potential to be applied to the treatment of GVHD. In this study, we evaluated the effect of intravenous administration of DFAT cells in a mouse model of acute GVHD. We found that the administration of DFAT cells tended to improve survival, suppressed weight loss and improved the clinical score of the GVHD mice. These findings suggest that DFAT cells could become a new cell source for the treatment of acute GVHD.
Purpose: Increasing evidence indicates that the neutrophil:lymphocyte ratio (NLR) broadly reflects systemic inflammatory and immune responses and may be a useful biomarker to predict outcomes for some solid cancers. However, the association between NLR and breast cancer prognosis remains unclear. We investigated the relationship between NLR and disease outcomes, i.e., metastatic capacity, recurrence free survival (RFS) and overall survival (OS), in patients with triple negative breast cancer (TNBC). Methods: We reviewed the medical records of patients with stage I-III TNBC who underwent surgery at our institution between 2005 and 2015. The NLR cut-off value of 2.2 was selected according to receiver operating characteristic (ROC) curves. Lymph node metastasis status, RFS and OS were evaluated. Differences were considered significant for p < 0.05. Results: Of 36 patients, 14 were assigned to the high NLR group (NLR ≥ 2.2) and 22 to the low NLR group (NLR < 2.2). The values for lymph node involvement and NLR revealed significant positive correlations. A median follow-up of 5.3 years revealed that the high NLR group had a significantly poorer RFS (66% vs 90% at 5 years, p = 0.02). The high NLR group had a worse tendency for OS at 5 years (82% vs 95% for the low NLR group, p = 0.23). Conclusion: High NLR reflects extensive lymph node metastasis and poor prognosis in patients with TNBC.
Myocardial ischemia induces an increase in extracellular K+ ([K+]e) and a decrease in extracellular pH (pHe). To clarify the role of mechanical and electrical activities in these changes, we investigated the effect of 2, 3-butanedione (BDM), a specific inhibitor of actin-myosin coupling, and pinacidil, an ATP-sensitive K+ channel opener, on [K+]e, pHe, action potential duration (APD) and regional contractility during 8 minutes of ischemia in porcine hearts. We inserted K+- and pH-sensitive electrodes and a pair of ultrasonic crystals into the mid-myocardium. We also placed a floating microelectrode in the subepicardium of the ischemic zone. The carotid artery was shunted to the LAD through a roller pump, and BDM (10 mM, n = 7) or pinacidil (50 νM, n = 8) was infused to the LAD shunt in advance of no-flow ischemia. Regional systolic shortening became dyskinetic with the BDM infusion and decreased from 20.1 ± 1.6% to 4.9 ± 1.6% with pinacidil. APD was not affected by BDM, but it decreased from 348 ± 14 ms to 206 ± 14 ms (P < 0.001) with the infusion of pinacidil prior to ischemia. Both pinacidil and BDM attenuated the rise in [K+]e, but the effect of pinacidil was greater. Both agents reduced the fall in pHe, but this effect was greater with BDM. Pinacidil-induced APD shortening was maintained during ischemia; BDM did not affect APD shortening during ischemia. The fall in pHe during ischemia appears to be related mainly to mechanical activity but the corresponding increase in [K+]e is more attributable to APD.
Herein, we report an autopsy case of sporadic Parkinson‘s disease (PD). An 80-year-old woman was noted to have right hemi-tremor when she was 63 years old, and was diagnosed with PD at 66 years of age. In the interim, she experienced visual hallucinations and bone fractures twice because of falls. Her general cognition was normal. She was admitted to our hospital because of dyspnea. Although she was treated with antimicrobial agents, death ensued. Upon autopsy, diffuse alveolar damage was evident and was considered to be the cause of death. Macroscopic examination of the brain revealed that the substantia nigra and locus coeruleus were pale. Upon histological examination, accumulation of alpha-synuclein was observed in the substantia nigra, locus coeruleus, the dorsal nuclei of the vagus, and other neuronal tissues.
Despite having undergone mandatory PCV7 vaccinations, three young children were hospitalized with invasive pneumococcal infections. Among them, two cases were diagnosed as having meningitis and one had bacteremia. Serotype ‘15A’ in one meningitis case was outside the range covered by PCV7 and PCV13 vaccinations, and that case was fatal. Voluntary PCV13 vaccination has been in place in Japan since autumn 2013; however, serotype replacement with uncovered serotypes is a possibility that physicians should consider.
Lack of a prenatal diagnosis by amniocentesis, amnion cytogenetic testing: report of 2 cases. Case 1: We were not able to make a prenatal diagnosis by amnion cytogenetic findings, and Chromosomal microarray analysis (CMA) was normal. Therefore, we were able to avoid artificial termination of pregnancy. Case 2: We were not able to make a prenatal diagnosis of 4p-minus syndrome by additional Chromosomal microarray analysis (CMA). We were able to provide greater support for pregnancy and labor management.
Case: A 74-year-old male who was bedridden and lived alone and was supported by remote medical service was brought to our emergency department. Outcome: The patient exhibited necrotizing soft tissue infection in a sacral pressure ulcer, which required early debridement, antibiotic administration, vasopressor, mechanical ventilation and blood purification therapy. Group A Streptococcus (GAS) was detected from the sacral ulcer and blood culture. He was diagnosed as having streptococcal toxic shock syndrome (STSS). Conclusion: Pressure ulcers infected with GAS quickly lead to STSS. In the aging society, many medical personnel including health care workers have the opportunity to contact patients with contagious bacterium, and infectious precautions are required.
We experienced a case of loop diuretic resistance showing worsening systemic congestion and complaining of palpitation and dyspnea following overdosing with furosemide (120 mg/day), prescribed by a previous doctor, who was delivered to our hospital by ambulance. A 93-year-old woman was admitted to our hospital. The clinical diagnosis was severe congestive heart failure, based on dilated cardiomyopathy (DCM) accompanying anasarca, jugular venous distension, bilateral pleural effusion and pulmonary congestion on chest X-ray film and computed tomography. Left ventricular systolic function was remarkably deteriorated (EF; 33%) showing diffuse LV hypokinesia and reduced diastolic function (è; 3.7 cm/sec, E/è; 34). Critical volume retention was suspected due to dilated IVCD diameter (21 mm) and loss of respiratory collapsibility (< 50%) during echocardiography upon admission. From the first day after admission, the patient was treated with intravenous carperitide (0.5 μg/kg/min), furosemide 20 mg/day and potassium canrenonate 400 mg/day. From the 2nd day, tolvaptan 7.5 mg/day was administered. After 7 days, the intravenous furosemide and potassium canrenonate was changed to oral furosemide (20 mg/day) and spironolactone 100 mg/day. Carvedilol 5 mg/day and candesartan 2 mg/day were also administered from the 1st day. The combination of reducing the dose of furosemide (120 mg to 20 mg) and tolvaptan (7.5 mg/day) was effective for diuresis and resolution of the systematic severe congestion.