A case of leg cellulitis caused by multidrug-resistant Streptococcus pseudoporcinus.

A 94-year-old woman was admitted to our hospital with a 5-day history of painful redness in the left lower leg. She was diagnosed with cellulitis and initiated antibiotic therapy with cefazolin. After two days, she presented with an extremely high fever (39.9°C), high C-reactive protein level (256 mg/L; normal, < 3), and signs of disseminated intravascular coagulation. In bacteriological examination, Streptococcus pseudoporcinus was detected from her lower leg wound purulence. An antibiogram revealed multidrug resistance except for cefepime, carbapenems, and vancomycin. We changed the antibiotics to cefepime and vancomycin according to the antibiogram and administered immunoglobulin concurrently. As the result of these therapies, her conditions gradually resolved over two weeks. S. pseudoporcinus, one of the ß-hemolytic Streptococcus species recently described, has been isolated from the genitourinary tract of women. To our knowledge, this is the first case of cellulitis caused by S. pseudoporcinus. Typically, most antibiotics indicate adequate drug susceptibilities of S. pseudoporcinus, but in our case, multidrug resistance contributed to the prolonged duration of treatment. Because the colonization of S. pseudoporcinus in healthy individuals is not rare, it could become an important pathogen in elderly people and in those who have underlying medical conditions, as with other ß-hemolytic Streptococci.

Matrin-3 is essential for fibroblast growth factor 2-dependent maintenance of neural stem cells.

To investigate the mechanisms underlying the maintenance of neural stem cells, we performed two-dimensional fluorescence-difference gel electrophoresis (2D-DIGE) targeting the nuclear phosphorylated proteins. Nuclear phosphorylated protein Matrin-3 was identified in neural stem cells (NSCs) after stimulation using fibroblast growth factor 2 (FGF2). Matrin-3 was expressed in the mouse embryonic subventricular and ventricular zones. Small interfering RNA (siRNA)-mediated knockdown of Matrin-3 caused neuronal differentiation of NSCs in vitro, and altered the cerebral layer structure of foetal brain in vivo. Transfection of Matrin-3 plasmids in which the serine 208 residue was point-mutated to alanine (Ser208Ala mutant Matrin3) and inhibition of Ataxia telangiectasia mutated kinase (ATM kinase), which phosphorylates Matrin-3 Ser208 residue, caused neuronal differentiation and decreased the proliferation of neurosphere-forming stem cells. Thus, our proteomic approach revealed that Matrin-3 phosphorylation was essential for FGF2-dependent maintenance of NSCs in vitro and in vivo.

Severe bacterial sepsis results in delayed diagnosis of tuberculous lymphadenitis in a rheumatoid arthritis patient treated with adalimumab.

Although tumor necrosis factor (TNF)-α inhibitors are effective in patients with rheumatoid arthritis (RA), an increased risk of infections often becomes a serious problem. It is well known that TNF-α inhibitors increase the risk of tuberculosis, but extrapulmonary tuberculosis often induced by them is difficult to diagnose using routine imaging examinations. We described a case of delayed diagnosis of a tuberculous lymphadenitis in a patient with RA treated with TNF-α inhibitor because of the complications of severe bacterial sepsis. In this case, rescreening with the interferon-γ release assay and excisional biopsy were useful in confirming the diagnosis of extrapulmonary tuberculosis. In the case we presented, she had other risk factors, that is, advanced age at the start of anti- TNF-α treatment or concomitant use of corticosteroid, might contribute to the development of complex infections. We should keep in mind that careful follow-up and appropriate examinations are necessary in caring for patients administering immunosuppressive treatments including anti- TNF-α drugs.

Healthy baby delivered vaginally from a brain-dead mother.

Case: A pregnant (20 gestational weeks) 32-year-old woman was found in cardiac arrest. Spontaneous circulation returned after 15 min. She became brain dead on the 13th hospital day. The patient was in stable circulatory condition under nasal desmopressin and 20-30 mg/day of hydrocortisone. On the 92nd hospital day at gestational week 33 + 3 days, natural labor began and a healthy 2,130-g girl (Apgar 6/8) was delivered vaginally with minimum assistance. Outcome: The baby was discharged 40 days after birth and followed up regularly. Conclusion: Brain death remains a hopeless condition for patients, but a brain-dead woman may still be able to naturally deliver a healthy baby.

Tsukushi is involved in the wound healing by regulating the expression of cytokines and growth factors.

During the wound-healing process, macrophages, fibroblasts, and myofibroblasts play a leading role in shifting from the inflammation phase to the proliferation phase, although little is known about the cell differentiation and molecular control mechanisms underlying these processes. Previously, we reported that Tsukushi (TSK), a member of the small leucine-rich repeat proteoglycan family, functions as a key extracellular coordinator of multiple signalling networks. In this study, we investigated the contribution of TSK to wound healing. Analysis of wound tissue in heterozygous TSK-lacZ knock-in mice revealed a pattern of sequential TSK expression from macrophages to myofibroblasts. Quantitative PCR and in vitro cell induction experiments showed that TSK controls macrophage function and myofibroblast differentiation by inhibiting TGF-ß1 secreted from macrophages. Our results suggest TSK facilitates wound healing by maintaining inflammatory cell quiescence.

A validation of presepsin levels in kidney dysfunction patients: four case reports.

Here, we measured presepsins (PSPs) in four patients with acute kidney injury (AKI) or chronic kidney disease (CKD) and discuss the relationship between PSP and kidney dysfunction. Case 1: an 83-year-old man was admitted to the ICU to manage postoperative respiratory failure with AKI. He had undergone resection for rectal cancer and ileal conduit replacement. On day 1 in the ICU, Escherichia coli (E. coli) was isolated by urine culture. PSP level (pg/ml) on day 2 was 2,745 without elevation of other conventional biomarkers. On day 6, the patient was diagnosed with severe sepsis, and E. coli was isolated by blood culture. By then, PSP had risen to 3,977, along with elevation of other conventional biomarkers. His kidney function recovered gradually after continuous administration of hemodiafiltration; however, PSP continued to rise up to 6,051, along with high systemic inflammatory response syndrome (SIRS) and Acute Physiology and Chronic Health Evaluation (APACHE) II values. The patient expired on day 13 due to multiple organ failure. Case 2: a 78-year-old woman with CKD on hemodialysis (HD) was admitted to the ICU after cardiovascular surgery. Continuous HD was administered postoperatively, and PSP ranged from 1,473-1,870 without signs of sepsis. Temporary elevation of other conventional biomarkers was observed postoperatively. Case 3: a 74-year-old woman with CKD on HD was admitted to the ICU after neurosurgery. She underwent intermittent HD postoperatively, and PSP ranged from 1,240-1,935 without sepsis symptoms. Temporary elevation of other conventional biomarkers was observed postoperatively. Case 4: a 62-year-old man with CKD was admitted to the ICU to control gastrointestinal bleeding. PSP was 606 without signs of infection or elevation of other conventional biomarkers. In cases 2, 3, and 4, bacteria were not isolated in blood cultures. Patients' clinical prognoses were good, with low or moderate SIRS and APACHE II scores. PSP in kidney dysfunction patients will be high despite non-infectious conditions. Therefore, evaluation of PSP in kidney dysfunction patients will be difficult. Further investigation is needed to clarify the relationship between PSP and kidney dysfunction.

Tsukushi controls the hair cycle by regulating TGF-ß1 signaling.

The hair follicle contains stem/progenitor cells that supply progeny for skin development and the hair cycle. Several signaling molecules belonging to the Wnt, BMP, shh, and transforming growth factor ß (TGF-ß) signaling cascades are involved in the normal hair follicle cycle. However, the systemic mechanism of how these humoral factors are controlled remains largely unknown. Previously, we reported that Tsukushi (TSK), a member of the small leucine-rich repeat proteoglycan family, functions extracellularly as a key coordinator of multiple signaling networks. Here, we show that TSK is expressed at the restricted areas of hair follicle during the morphogenesis and the hair cycle. Targeted disruption of the TSK gene causes the hair cycle to be delayed with low levels of TGF-ß1 and phosphorylated Smad2/3 (pSmad2/3) expression. Biochemical analysis indicates that TSK directly binds to TGF-ß1. Our data suggest that TSK controls the hair cycle by regulating TGF-ß1 signaling.