PDZD8-deficient mice accumulate cholesteryl esters in the brain as a result of impaired lipophagy.

Dyslipidemia including the accumulation of cholesteryl esters (CEs) in the brain is associated with neurological disorders, although the underlying mechanism has been unclear. PDZD8, a Rab7 effector protein, transfers lipids between endoplasmic reticulum (ER) and Rab7-positive organelles and thereby promotes endolysosome maturation and contributes to the maintenance of neuronal integrity. Here we show that CEs accumulate in the brain of PDZD8-deficient mice as a result of impaired lipophagy.

Protrudin and PDZD8 contribute to neuronal integrity by promoting lipid extraction required for endosome maturation.

Endosome maturation depends on membrane contact sites (MCSs) formed between endoplasmic reticulum (ER) and endolysosomes (LyLEs). The mechanism underlying lipid supply for this process and its pathophysiological relevance remains unclear, however. Here, we identify PDZD8-the mammalian ortholog of a yeast ERMES subunit-as a protein that interacts with protrudin, which is located at ER-LyLE MCSs.

[Anesthetic management of a patient with congenital myopathy complicated with severely impaired pulmonary function].

A 17-year-old man, who had received a diagnosis of congenital myopathy, was scheduled for superficial temporal artery to middle cerebral artery anastomosis procedure. Preoperative respiratory examinations showed the breathing capacity of 450 ml because of a scoilosis, deformity of a thorax and severe muscular atrophy. Anesthesia was maintained with propofol, fentanyl, remifentanil and vecuronium to avoid malignant hyperthermia (MH).

Pulse steroids as induction therapy for children with ulcerative colitis.

Background: Corticosteroids therapy, classically the first-line treatment for ulcerative colitis (UC), often causes serious side-effects. Theoretically, pulse steroid therapy where high doses are given for a shorter period may have maximal beneficial effects and minimal side-effects as induction therapy for UC. We have therefore retrospectively compared induction therapy using pulse steroids with conventional steroid treatment for children and adolescents with moderate-to-severe UC.

Well-controlled proinflammatory cytokine responses of Peyer's patch cells to probiotic Lactobacillus casei.

In order to clarify the probiotic features of immunomodulation, cytokine production by murine spleen and Peyer's patch (PP) cells was examined in response to probiotic and pathogenic bacteria. In spleen cells, probiotic Lactobacillus casei induced interleukin (IL)-12 production by CD11b(+) cells more strongly than pathogenic Gram-positive and Gram-negative bacteria and effectively promoted the development of T helper (Th) type 1 cells followed by high levels of secretion of interferon (IFN)-gamma. Although the levels of IL-12 secreted by PP cells in response to L.

Peroxisome proliferator-activated receptor γ 2 mutation may cause a subset of ulcerative colitis.

Aim: Previous studies suggest the homeostasis between acquisition of tolerance to the indigenous microflora and protective immune responses appears to be disrupted in inflammatory bowel disease (IBD). Some experimental studies indicate peroxisome proliferator-activated receptor γ (PPARγ) has been implicated as a regulator of intestinal inflammatory responses. In addition, the toll-like receptor (TLR)-4 can regulate expression of PPARγ in colonic epithelial cells.

Anti-infectious activity of synbiotics in a novel mouse model of methicillin-resistant Staphylococcus aureus infection.

The anti-infectious activity of synbiotics against methicillin-resistant Staphylococcus aureus (MRSA) infection was evaluated using a novel lethal mouse model. Groups of 12 mice treated with multiple antibiotics were infected orally with a clinical isolate of MRSA at an inoculum of 10(8) CFU on day 7 after starting the antibiotics. A dose of 400 mg/kg 5-fluorouracil (5-FU) was injected intraperitoneally on day 7 after the infection.

Bispectral index during epidural puncture predicts anterograde amnesia in patients given midazolam premedication.

Purpose: We hypothesized anterograde amnesia could be predicted by the bispectral index (BIS) during epidural puncture in patients premedicated with intramuscular midazolam.

Methods: We investigated 64 consecutive patients undergoing gynecological laparotomy under general anesthesia combined with epidural anesthesia. Midazolam (5 mg) was administered intramuscularly at 15 min before arrival at the operating room.

Effects of the enteral administration of Bifidobacterium breve on patients undergoing chemotherapy for pediatric malignancies.

Purpose: Probiotics are expected to be effective in prophylaxis of infection in cancer patient, since infections in neutropenics are mainly caused by endogenous flora through the intestinal mucosa. However, the experience with the use of probiotics in immunocompromised patients is limited, and precise fecal bacteria analysis has not been reported. The aim of the study was to evaluate the effects of the enteral administration of the probiotic, Bifidobacterium breve strain Yakult, on its ability to prevent infection, fecal micro flora, and intestinal environments in cancer patients on chemotherapy.

Effect of suplatast tosilate on antileukotriene non-responders with mild-to-moderate persistent asthma.

Background: Immunomodulatory therapy has been recently introduced for the management of asthma. Suplatast tosilate (ST), a new immune-modifying drug, is known to improve the airway function by inhibiting the release of Th-2 cytokines. However, its efficacy as a controller listed in the guideline, Global Initiative for Asthma 2005 has not been established.

Breast cancer resistance protein/ABCG2 is differentially regulated downstream of extracellular signal-regulated kinase.

Breast cancer resistance protein (BCRP)/ABCG2 is a drug efflux pump responsible for multidrug resistance in cancer cells. We report that dephosphorylation of extracellular signal-regulated kinase (ERK) by treatment with mitogen-activated protein kinase/ERK kinase (MEK) inhibitors causes two opposing effects, transcriptional upregulation and prompted protein degradation of endogenous BCRP in breast cancer MCF-7 cells. Endogenous BCRP was eventually found to be upregulated.

Innate immune therapy with a Bacillus Calmette-Guérin cell wall skeleton after radical surgery for non-small cell lung cancer: a case-control study.

Purpose: We investigated whether adjuvant immunotherapy with Bacillus Calmette-Guérin (BCG) cell wall skeleton (CWS) and surgical resection was better than resection, with or without other adjuvant therapy, for patients with non-small cell lung cancer (NSCLC).

Methods: The case group comprised 71 patients who underwent radical surgery for NSCLC, followed by BCG-CWS immunotherapy, with follow-up data available. The case-control study was designed with one control selected for each case-group patient.

Neonatal transient eosinophilic colitis causes lower gastrointestinal bleeding in early infancy.

Background: Lower gastrointestinal bleeding (LGB), particularly in newborns, is of serious concern and requires urgent investigation and hospital care. Whereas allergic proctocolitis caused by food protein is a significant cause of LGB in infants with eosinophilia, there are several cases of diseases with symptoms similar to those of allergic proctocolitis but without an apparent allergic reaction influence.

Patients And Methods: We examined 2 neonates using rectosigmoidoscopy who showed eosinophilia and experienced fresh LGB soon after birth and before their first feedings.

Brachial-ankle pulse wave velocity and metabolic syndrome in a Japanese population: the Minoh study.

To investigate the association between brachial-ankle pulse wave velocity (baPWV) and metabolic syndrome (MS), we examined 374 men and 622 women aged 40 to 69 years who did not have a past history of either coronary heart disease or stroke. We used a modified National Cholesterol Education Program definition of MS that utilizes body mass index instead of waist circumference. Age-adjusted mean values of baPWV were greater when obesity, high systolic and diastolic blood pressures, high triglyceride level, low high-density lipoprotein cholesterol, high fasting glucose level or MS itself were present.

Association between C-reactive protein and insulin resistance in a Japanese population: the Minoh Study.

Objective: To investigate the association between C-reactive protein (CRP) and insulin resistance.

Materials And Methods: This study included 1,624 Japanese participants (652 men and 972 women) aged 40 to 69 years who were non-diabetics or did not have medication for hypertension or dyslipidemia, a history of cardiovascular disease or CRP levels >10 mg/l. Serum CRP level, fasting glucose level, and fasting insulin level were measured, and the degree of insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR).

Association between fasting glucose and C-reactive protein in a Japanese population: the Minoh study.

To investigate the association between fasting glucose and C-reactive protein (CRP), we examined 1715 Japanese individuals (723 men and 992 women) aged 40-69 years who did not have medication for hypertension, diabetes, or dyslipidemia, a history of cardiovascular disease or CRP levels>10mg/l. There was a statistically significant unadjusted correlation between CRP and each component of the metabolic syndrome, including fasting glucose, fasting insulin, body mass index, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol (negative), and triglycerides in both men and women. With adjustment for age, cigarette smoking, alcohol intake, and other components of the metabolic syndrome, the CRP increments (as back-transformed) compared with the lowest tertile of normal fasting glucose were 0.

C-reactive protein concentration is more strongly related to metabolic syndrome in women than in men: the Minoh Study.

Background: The gender differences in the association between C-reactive protein (CRP) and features of the metabolic syndrome (MS) need to be elucidated among Japanese.

Methods And Results: The study population included 715 men and 988 women aged 40-69 years who were not taking anti-hypertensive, lipid-lowering, hypoglycemic, anti-thrombotic, or non-steroidal anti-inflammation medications, and did not have a past history of cardiovascular disease or CRP concentration >10 mg/L. Except for high-density lipoprotein cholesterol, the unadjusted correlation between CRP and each MS component, including body mass index (BMI), systolic and diastolic blood pressures, triglycerides, fasting glucose, fasting insulin, and uric acid, was greater in women than in men.