Satoshi Shimizu

Granulocyte-macrophage colony-stimulating factor enhances macrophage accessory function in Con A-stimulated T-cell proliferation

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to augment various macrophage (M phi) functions, including antigen presentation in the antibody-producing response. We investigated the augmentative effect of GM-CSF on M phi A-cell activity in concanavalin A-stimulated T-cell proliferation. Pretreatment with GM-CSF of peritoneal M phi enhanced the T-cell proliferative response. This effect of GM-CSF was dose dependent and GM-CSF supplementation was needed at the beginning of M phi culture. We observed that GM-CSF induced M phi spreading and firm attachment accompanied with enlargement of the cytoplasm, but could not induce de novo expression of Ia antigen. GM-CSF treatment enabled M phi to produce more interleukin (IL)-1 and IL-6 upon stimulation with lipopolysaccharides or polyinosinic-polycytidylic acid, but was unable to stimulate M phi directly. This was confirmed by Northern blot analysis. These results indicate that GM-CSF augments M phi A-cell activity through the enhancement of the capacity of M phi to produce IL-1 and IL-6.

Intraoperative oliguria predicts acute kidney injury after major abdominal surgery

BackgroundnThe threshold of intraoperative urine output below which the risk of acute kidney injury (AKI) increases is unclear. The aim of this retrospective cohort study was to investigate the relationship between intraoperative urine output during major abdominal surgery and the development of postoperative AKI and to identify an optimal threshold for predicting the differential risk of AKI.nnnMethodsnPerioperative data were collected retrospectively on 3560 patients undergoing major abdominal surgery (liver, colorectal, gastric, pancreatic, or oesophageal resection) at Kyoto University Hospital. We evaluated the relationship between intraoperative urine output and the development of postoperative AKI as defined by recent guidelines. Logistic regression analysis was performed to adjust for patient and operative variables, and the minimum P -value approach was used to determine the threshold of intraoperative urine output that independently altered the risk of AKI.nnnResultsnThe overall incidence of AKI in the study population was 6.3%. Using the minimum P -value approach, a threshold of 0.3u2009ml kg -1 h -1 was identified, below which there was an increased risk of AKI (adjusted odds ratio, 2.65; 95% confidence interval, 1.77-3.97; P <0.001). The addition of oliguria <0.3u2009ml kg -1 h -1 to a model with conventional risk factors significantly improved risk stratification for AKI (net reclassification improvement, 0.159; 95% confidence interval, 0.049-0.270; P =0.005).nnnConclusionsnAmong patients undergoing major abdominal surgery, intraoperative oliguria <0.3u2009ml kg -1 h -1 was significantly associated with increased risk of postoperative AKI.

Differential Involvement of the Npl4 Zinc Finger Domains of SHARPIN and HOIL-1L in Linear Ubiquitin Chain Assembly Complex-Mediated Cell Death Protection.

ABSTRACT The linear ubiquitin chain assembly complex (LUBAC) participates in NF-κB activation and cell death protection. Loss of any of the three LUBAC subunits (catalytic HOIP, accessory HOIL-1L, or accessory SHARPIN subunit) leads to distinct phenotypes in mice and human. cpdm mice (chronic proliferative dermatitis in mice [cpdm]) that lack SHARPIN exhibit chronic inflammatory phenotypes, whereas HOIL-1L knockout mice exhibit no overt phenotypes, despite sharing highly homologous ubiquitin-like (UBL) and Npl4 zinc finger (NZF) domains. Here, we intercrossed mice lacking HOIL-1L and SHARPIN and found that reduction of HOIL-1L in cpdm mice exacerbated inflammatory phenotypes without affecting characteristic features of cpdm disease, whereas reduction of SHARPIN in HOIL-1L knockout mice provoked no overt phenotypes. Hence, loss of SHARPIN and reduction of LUBAC triggers cpdm phenotypes. We found that the NZF domain of SHARPIN, but not that of HOIL-1L, is critical for effective protection from programmed cell death by enhancing the recruitment of LUBAC to the activated TNFR complex. The binding activity to K63-linked ubiquitin chains that the NZF domain of SHARPIN, but not that of HOIL-1L, possesses appears to be involved in the recruitment. Thus, selective recognition of ubiquitin chains by NZFs in LUBAC underlies the regulation of LUBAC function.

Studies on various ageing phenomena in Japanese twins and siblings.

1. We collected 27 pairs of twins (MZ 21, DZ 6) ranging from 41 to 80 years, and 16 pairs of homosexual siblings (SL) ranging from 62 to 90 years, all of whom were Japanese in the western district of Honshū-Island. First, we measured the bodily constitution, certain body parts and certain bones, and investigated their life- histories. Next, we investigated various senescent phenomena. That is: — the approximate number of gray hairs on the head, the appearance and the size of alopecia senilis in the parietal region, the approximate number of wrinkles in the frontal region, the comparative number of sulci cutis on the nape of neck, the back of the right hand, and the anterior chest, the development of senile pigment spots on the face, the back of the right hand, the extensor surface of the right forearm, and the upper half of the back, the appearance of the senile wart, the development of pinguecula, the development of arcus senilis, the development of marginal protuberances on the lumbar vertebral bodies, and the upper end of the tibia, the existence of fabella in the right knee, and the calcification in the wall of the arch of the aorta. With regard to these items we calculated the middle percentage deviation, the coefficient of correlation, or the rate of concordance, and on the photographs or X-ray photographs the resemblance between both partners was examined. 2. We have concluded that the following items are mainly subject to the control of heredity. That is, the approximate number of gray hairs on the head, the existence, the localization and the shape of alopecia senilis on the parietal region in ♂, the localization and the shape of wrinkles on the frontal region, the localization and the development of senile pigment spots on the face, the development of pinguecula and of arcus senilis of the eye, the development and the shape of marginal protuberances on the lumbar vertebral body, and the development of marginal protuberances on condylus lateralis et medialis of the tibia. On the other hand, the following items were found to be fairly subject to influence of the environmental factors. That is, the appearance of alopecia senilis on the parietal region in ♀, the number of wrinkles on the frontal region, the comparative number of sulci cutis on the nape of neck, the back of the right hand, and the anterior chest, the number of senile pigment spots on the back of the right hand, the extensor surface of the right forearm, and the upper half of the back, the appearance of senile wart on the body, and the calcification in the arch of the aorta. 3. Concerning those senescent phenomena, which are strikingly subject to the control of heredity, a certain degree of difference between both partners of MZ was sometimes recognized. When the differences in the progression of various senescent phenomena between both partners of MZ were observed, it was often recognized that some senescent phenomena make more progress in one partner, while on the other hand the other ones do in another partner. 4. In order to decide certain environmental factors, which have influence upon the difference between both partners of MZ, we referred to the existence of heavy labor for long duration, the number of deliveries, the grade of the sunburn, the habit of alcoholic drinking, smoking, and history of various diseases. However, we could not decide that some of these factors had certain definite relationship with the progression of certain senescent phenomena. However, we might probably presume that the old-styled Japanese hair dressing worn for many years had a certain relationship with the appearance of the baldness in ♀.

Cooperative Domain Formation by Homologous Motifs in HOIL-1L and SHARPIN Plays A Crucial Role in LUBAC Stabilization

SUMMARY The linear ubiquitin chain assembly complex (LUBAC) participates in inflammatory and oncogenic signaling by conjugating linear ubiquitin chains to target proteins. LUBAC consists of the catalytic HOIP subunit and two accessory subunits, HOIL-1L and SHARPIN. Interactions between the ubiquitin-associated (UBA) domains of HOIP and the ubiquitin-like (UBL) domains of two accessory subunits are involved in LUBAC stabilization, but the precise molecular mechanisms underlying the formation of stable trimeric LUBAC remain elusive. We solved the co-crystal structure of the binding regions of the trimeric LUBAC complex and found that LUBAC-tethering motifs (LTMs) located N terminally to the UBL domains of HOIL-1L and SHARPIN heterodimerize and fold into a single globular domain. This interaction is resistant to dissociation and plays a critical role in stabilizing trimeric LUBAC. Inhibition of LTM-mediated HOIL-1L/SHARPIN dimerization profoundly attenuated the function of LUBAC, suggesting LTM as a superior target of LUBAC destabilization for anticancer therapeutics.

Immortalization of Murine Leukocytes by Oncogenes

In the course of study to obtain murine dendritic cell lines using oncogenic retroviruses, we have established several immortalized cell lines with characteristics different from those of dendritic cells. The transformants were mainly round nonadherent cells, capable of growing in soft agar, and negative for nonspecific esterase activity. Profiles of cell surface antigens were examined by indirect immunofluorescence technique. The cell lines were positive for Fc receptor (2.4G2), J11d (J11d.2), and B220 (RA3‐3A1/6.1) antigens and negative (or dull positive in small percentages) for Ia (M5/144.15.2), IL‐2 receptor (3C7), Thy‐1 (B5‐5), Mac‐1 (M1/70.‐15.11.5), and macrophage (F4/80) antigens. They were negative for both surface and cytoplasmic immunoglobulins. Several clones were established from these transformant cell lines and cell surface antigens were examined. Antigenic profiles of these clones were very similar to those of the parental cell lines. Some of these clones, however, seemed to increase their Ia antigen expression. The results suggest that the transformants originated from early B‐lineage cells.

Acute kidney injury after pediatric liver transplantation: incidence, risk factors, and association with outcome

PurposeData on the incidence of, risk factors for, and association with outcomes of acute kidney injury (AKI) after pediatric liver transplantation are scarce. We conducted a retrospective cohort study to determine the incidence of AKI after pediatric liver transplantation. In addition, we examined risk factors for AKI and association of AKI with outcomes.MethodsThis study included 156 children aged between 3xa0months and 18xa0years undergoing liver transplantation at Kyoto University Hospital. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines based on serum creatinine and urine output. We used multivariable logistic regression with stepwise variable selection to identify independent risk factors for AKI.ResultsAKI occurred in 72 patients (46.2%); 34 (21.8%) had stage 1, 32 (20.5%) had stage 2, and 6 (3.8%) had stage 3 AKI. Factors independently associated with the development of AKI were increased preoperative total bilirubin level (adjusted odds ratio, 1.04 per 1xa0mg/dl; 95% confidence interval, 1.01–1.09; Pxa0=xa00.026) and increased intraoperative blood loss (adjusted odds ratio, 1.03 per 10xa0ml/kg; 95% confidence interval, 1.00–1.06; Pxa0=xa00.022). AKI was significantly associated with prolonged hospitalization (median, 61 vs. 46xa0days; Pxa0=xa00.028). In-hospital mortality rate was 4.2% in patients with AKI and 3.6% in those without AKI (Pxa0=xa01.000).ConclusionThe incidence of AKI after pediatric liver transplantation was 46.2%. Increased preoperative total bilirubin level and increased intraoperative blood loss were independently associated with the development of AKI. AKI was associated with prolonged hospitalization.

Successful tracheal intubation with the GlideScope® in a patient with CHARGE syndrome

To the Editor: CHARGE syndrome is a rare heterogeneous disorder characterized by multiple congenital anomalies with an incidence of 0.1–1.2 per 10,000 births [1]. The acronym CHARGE stands for five characteristic features of the syndrome: coloboma, heart defect, choanal atresia, retarded growth, genital hypoplasia, and ear anomalies [1]. Because of congenital malformations, CHARGE patients are likely to undergo multiple surgical interventions. CHARGE patients usually present with upper airway malformations and swallowing impairment, making perioperative airway management challenging [2]. We describe a case of successful airway management using the GlideScope (Verathon, Bothell, WA, USA) in a patient with CHARGE syndrome. A 4-year-old boy (height 87 cm, weight 11 kg), admitted to our hospital for bilateral orchiopexy, had been diagnosed with CHARGE syndrome based on the presence of four major diagnostic criteria [1]. He had undergone several surgical procedures associated with his congenital anomalies, and the anesthetic records indicated that tracheal intubation had become increasingly difficult with growth (Table 1). General anesthesia was induced with inhalation of 5 % sevoflurane and 50 % nitrous oxide in oxygen. After confirming successful facemask ventilation, 10 mg rocuronium was administered. Direct laryngoscopy with a Macintosh 2 blade provided a Cormack–Lehane grade IV view. The tip of the epiglottis could be viewed with a Pentax airway scope (AWS), and we could not get the blade under the epiglottis. Using a GlideScope GLV2, tracheal intubation with a 4.5-mm uncuffed tube was achieved by directing the tube blindly above the arytenoids. Anesthesia was maintained with 2 % sevoflurane and fentanyl (30 lg total). Upon emergence from anesthesia, retractive breathing with excessive lower airway secretion became apparent and bronchospasm was suspected. Administration of 50 mg intravenous hydrocortisone, 0.05 mg intramuscular epinephrine, and 0.5 mg transdermal tulobuterol gradually improved the respiratory condition, and the trachea was extubated after 30 min. The patient recovered uneventfully and was discharged home next day. Preoperative assessment of CHARGE patients should include individual assessment for heterogeneous upper airway anomalies. Our patient presented with an asymmetrical and comparatively smaller face with micrognathia. Previous anesthetic records should be reviewed with consideration of possible anatomic changes of the upper airway with growth. Stack and Wyse reported more difficult tracheal intubation with growth in some CHARGE patients [3]. An appropriate strategy for difficult intubation in these patients is necessary. The laryngeal mask airway (LMA) and AWS are potential candidate devices commonly used for difficult intubations, but these were not effective in our case, likely because of the airway anomaly. Fiberoptic intubation is another option, but previous attempts proved difficult in this patient at age 3 during surgery for bilateral orchiopexy (Table 1). Our case indicates that the GlideScope may facilitate intubation in patients presenting with an upper airway anomaly for which neither the AWS or LMA is appropriate. S. Shimizu (&) T. Koyama T. Mizota K. Fukuda Department of Anesthesia, Kyoto University Hospital, 54 Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8507, Japan e-mail: satosyl@gmail.com

Acute Obstruction of Craniocervical Venous Drainage in a Lung-Transplant Patient

CENTRAL VENOUS CATHETER (CVC)-related thrombosis is a well-described complication. Although most patients with CVC-related thrombosis remain asymptomatic, acute obstruction of craniocervical drainage is potentially lifethreatening. This report describes a rare case of a patient with severe craniofacial congestion during staged chest closure 4 days after bilateral lung transplantation. Vascular studies revealed a massive thrombosis of the right internal jugular vein (IJV) and chronic obstruction of the innominate vein, possibly related to the CVC. The potential effect of acute obstruction of the IJV system on clinical outcome and the importance of confirming the patency of craniocervical venous drainage when selecting pulmonary artery catheter (PAC) and CVC insertion sites, especially in patients with a history of CVC placement, are discussed.