Kobe Journal of Medical Sciences最新文献

Biliary atresia (BA) is a progressive obstruction and fibro-obliteration of the extrahepatic and intrahepatic biliary tract that causes cholestatic jaundice in infants, resulting in biliary cirrhosis and even death in the first year of life if the Kasai procedure is not performed at an earlier age. There are many prognostic factors that could affect the survival of patients with BA after Kasai surgery, however results still show some conflicting findings. A retrospective study was conducted using medical records of patients with BA who underwent Kasai surgery at Dr. Sardjito Hospital, Yogyakarta, Indonesia from June 2012 to April 2018. Twenty-nine BA patients were involved in our study, with 16 males and 13 females. Log-rank analysis showed a significant association between survival rate of BA patients with albumin level 1 month and 3 months after Kasai surgery, with p-values of 0.043 and 0.016, respectively. Interestingly, multivariate analysis revealed that cholangitis tended to have an association with BA patients' survival (p=0.09). In conclusion, the BA patients' survival might be affected by the presence of cholangitis after Kasai surgery. Further multicenter studies with a larger sample size are important to verify our results.

Sepsis and sepsis-related multiple organ failure are major causes of mortality in intensive care unit (ICU) settings. This study aimed to determine the effect of intravenous immunoglobulin G (IVIgG) on different types of immunoglobulin and anti-coagulant factor types in sepsis patients. A single-center observational study of patients with sepsis, severe sepsis, or septic shock was conducted from August 2008 to March 2013. Patients were divided into the IVIgG (immunoglobulin G [IgG] <870 mg/dL; lower normal range) and non-IVIgG (IgG ≥870 mg/dL) groups. The IVIgG group received IVIgG for three days, and other standard medications. Serial measurements were taken of serum IgG, immunoglobulin A (IgA), immunoglobulin M (IgM), total plasminogen activator inhibitor 1 (tPAI-1), and protein C. Patients in the IVIgG treatment group had significantly higher serum IgM level on Days 4 and 7 than on Day 1, but no significant changes in IgM levels were observed in patients in the non-IVIgG group. Patients in the IVIgG treatment had lower tPAI-1 levels on Days 4 and 7 than on Day 1 and increased protein C levels on Day 7 compared to those on Days 1 and 4. There were no significant differences in tPAI-1 levels or protein C levels in the non-IVIgG group, although a similar trend was observed. IVIgG administration increased patients' serum IgM and protein C levels and decreased their serum tPAI-1 levels. IVIgG has potential application for preventing sepsis-induced coagulopathy and disseminated intravascular coagulation.

Cytotoxin-associated gene A (CagA) is generally accepted to be the most important virulence factor of Helicobacter pylori and increases the risk of developing gastric cancer. East Asian CagA, which includes the EPIYA-D segment at the C-terminal region, has a significantly higher gastric carcinogenic rate than Western CagA including the EPIYA-C segment. Although the amino acid polymorphism surrounding the EPIYA motif in the C-terminal region has been examined in detail, limited information is currently available on the amino acid polymorphism of the N-terminal region of East Asian CagA. In the present study, we analyzed the sequencing data of East Asian CagA that we obtained previously to detect amino acid changes (AACs) in the N-terminal region of East Asian CagA. Four highly frequent AACs in the N-terminal region of East Asian CagA were detected in our datasets, two of which (V356A, Y677F) exhibited reproducible specificity using a validation dataset from the NCBI database, which are candidate AACs related to the pathogenic function of CagA. We examined whether these AACs affect the functions of CagA in silico model. The computational docking simulation model showed that binding affinity between CagA and phosphatidylserine remained unchanged in the model of mutant CagA reflecting both AAC, whereas that between CagA and α5β1 integrin significantly increased. Based on whole genome sequencing data we herein identified novel specific AACs in the N-terminal regions of EPIYA-D that have the potential to change the function of CagA.

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration or loss of lower motor neurons. The survival of motor neuron (SMN) 1 gene, which produces the SMN protein, has been identified as a responsible gene for the disease. SMN is ubiquitously expressed in any tissue and may play an important role on the metabolism in the human body. However, no appropriate biomarkers reflecting the alteration in the metabolism in SMA have been identified.

Methods: Low-molecular-weight metabolites were extracted from plasma of 20 human infants (9 SMA type 1 patients and 11 controls) and 9 infant mice (5 SMA-model mice, 4 control mice), and derivatized with N-methyl-N-trimethylsilyltrifluoroacetamide. Finally, the derivatized products were applied to Gas Chromatography/Mass Spectrometry apparatus. To confirm the metabolite abnormality in SMA type 1 patients, we performed SMN-silencing experiment using a hepatocyte-derived cell line (HepG2).

Results: We performed a comprehensive metabolomics analysis of plasma from the patients with SMA type 1 and controls, and found that phosphoethanolamine (PEA) was significantly higher in the patients than in the controls. HepG2 experiment also showed that SMN-silencing increased PEA levels. However, comprehensive metabolomics analysis of plasma from SMA-model mice and control mice showed different profile compared to human plasma; there was no increase of PEA even in the SMA-model mice plasma.

Conclusion: Our data suggested that PEA was one of the possible biomarkers of human SMA reflecting metabolic abnormalities due to the SMN protein deficiency.

Hemodialysis patients often become constipated. We analyzed the effect of prebiotics on the defecation status due to the intestinal environment in hemodialysis patients. Fifteen patients received prebiotics as partially hydrolyzed guar gum for four weeks. The defecation status was assessed using both the Bristol Stool Form Scale and the Japanese version of the Constipation Assessment Scale. The fecal status, microbiota measured by a terminal restriction fragment length polymorphism analysis, and fecal short-chain fatty acid concentrations by gas chromatography were compared before and after prebiotics ingestion. Prebiotics ingestion improved the individual stool form and decreased the constipation score from 5.1 to 3.0. The ratio of short-chain fatty acid-producing microbiota, such as Bifidobacterium and Bacteroides, increased after ingestion (2.35- and 3.17-fold, respectively). Furthermore, the concentration of short-chain fatty acids significantly increased (1.58-fold). The individual dendrogram distribution after ingestion was changed in 8 participants (53.3% of the subjects). In 5 participants (33.3% of the subjects), the clusters were even more noticeably different. Prebiotics improved the defecation status in hemodialysis patients due in part to the composition of intestinal microbiota and short-chain fatty acid concentrations.

Total management of chronic kidney disease has been well established, and the screening using dipstick urine test has already been widespread in Japan. Nevertheless, the number of dialysis patients is still rising. While clinical cooperation between general physicians and nephrologists is expected to improve prognoses of chronic kidney disease patients, real situation of the management in general practice has not been obvious. We conducted a questionnaire survey for the doctors of Hyogo Prefecture Medical Association excluding nephrologists to clarify the situation and the issue about chronic kidney disease management in general practice. Total 169 doctors replied to the questionnaire. In 74.0% of medical facilities, estimated glomerular filtration rate was automatically calculated and indicated in the result report with the measurement of serum creatinine. The compliance rates of the chronic kidney disease clinical guideline for Japanese regarding referral to nephrologists were 33.7% in cases of urine abnormality and 57.4% in cases of decreased kidney function. For the patients of diabetes without previous diagnosis of nephropathy, only 30.8% of doctors examined urine albumin at least every 6 months. In general practice, there is still much possibility to improve chronic kidney disease management. We have to continue to advocate the significance of clinical cooperation between general physicians and nephrologists, with high level of evidence.

Chronic kidney diseases (CKDs) lead to end-stage renal diseases (ESRD) which are characterized by glomerulosclerosis, tubular injury, anemia, inflammation, and interstitial fibrosis. Vitamin D is known to have renal protective effects. However, its effects relate to low and high doses of Vitamin D in CKD model is still unknown. CKD was performed using 5/6 subtotal nephrectomy procedure in male Sprague Dawley rats (3 months old, 200-300 grams, SN group; n=6), then rats were sacrificed on day 14 after operation. Sham operation was used for control (SO group; n=6). Calcitriol was administered in two doses : 0.01 µg/mL/100 gramsBW/day (SND1 group; n=6) and 0.05 µg/mL/100 gramsBW/day (SND2 group; n=6) intraperitoneally for 14 days. Glomerulosclerosis and tubular injury score were examined using PAS staining, meanwhile, interstitial fibrosis area fraction was assessed with Sirius Red staining. RT-PCR was performed for assessing nephrin, podocin, IL-6, CD68, Collagen-1, and TGF-β1 mRNA expressions. Immunostaining (IHC) was carried out to observe macrophage (CD68) and myofibroblast (α-SMA). SN demonstrated CKD condition with higher tubular injury, glomerulosclerosis, interstitial fibrosis, and inflammation compared to SO. Calcitriol-treated group (especially SND2) demonstrated significant lower tubular injury, glomerulosclerosis, and interstitial fibrosis compared to SN. SND2 group showed not only significantly lower CD68, IL-6, Collagen-1, and TGF-β1 mRNA expressions, but also higher mRNA expressions of nephrin and podocin. SND2 group also demonstrated reduction of macrophages infiltration and myofibroblasts expansion based on its histopathological appearance. Vitamin D may have a renoprotective effect on 5/6 subtotal nephrectomy model by attenuating podocytopathy, tubular injury, inflammation and interstitial fibrosis.

Purpose: This study aimed to better understand the nursing care time spent with healthy term newborns from birth to discharge, giving insight into neonatal nursing staff management.

Method: In total, 30 healthy term newborns in a mixed hospital ward with an Obstetrics Department participated in this study. To measure care time, they had a wireless beacon attached to their cots. This measured how much time the nurses stayed in front of the cot from the time of birth until discharge, 24 hours/day. Collected data were tabulated every 24 hours after birth.

Results: Seventeen newborns had their data analyzed. The average length of hospital stay for the newborns was 8231.3 minutes. The average nursing care time for the newborns was 533.8 minutes. Nurses provided the highest care time during the first 24 hours after birth (157.6 minutes/24hr). After the first 24, the average nursing care time gradually decreased. The average nursing care time during the first 24 hours after birth was longer than the nursing care time for any other 24-hour periods, with a significant difference (p = 0.001 to 0.046).

Conclusion: The nursing care time for healthy newborns gradually decreased with the passage of time after birth. Healthy newborns should be treated as individuals, and the number of nursing staff should be adjusted according to the number of newborns in the ward to ensure nursing care quality and to prevent life-threatening events during the first 24 hours after birth.

The incidence rate of Acute Kidney Injury (AKI) gets escalated each year. Kidney ischemia/reperfusion injury (IR injury) is the main cause of AKI after major cardiovascular surgery, trauma, or kidney transplantation. Reperfusion is considered essential for ischemic tissue. However, the evidence revealed that reperfusion itself has impact in cellular destruction. Vitamin D is not only known as calcium regulating hormone, but also as renoprotective agent. This study aimed to investigate the effect of vitamin D treatment on kidney IR injury in mice. Kidney IR injury was performed using 30 minutes of bilateral clamping of renal pedicles, then released in male Swiss Webster mice (3 months, 30-40 grams, n=20), which were divided into three groups: sham operation (SO) group, IR injury (IRI) group, and IR injury with 0.25 µg/ kg body weight of vitamin D treatment (IR7+VD). Mice were terminated at day 7 post operation, kidneys were harvested and used for paraffin making, immunostaining and RNA extraction. Tubular injury was quantified based on Periodic Acid-Schiff's (PAS) staining. Immunostaining was done for quantification of macrophage (CD68) and myofibroblast (α-SMA). Reverse Transcriptase PCR (RT-PCR) was done to examine Monocyte Chemoattractant Protein-1 (MCP-1) and Toll-like Receptor 4 (TLR4) mRNA expression. Kidney IR injury induced significant increase of tubular injury, which was associated with higher myofibroblast and macrophage number. Meanwhile, Vitamin D treatment significantly reduced tubular, myofibroblast and macrophage number. RTPCR revealed reduction of TLR4 and MCP-1 mRNA expressions after Vitamin D treatment (p<0.05 vs IR group). Vitamin D ameliorates kidney IR injury through reducing inflammation and myofibroblast formation.

Introduction: This research aimed to evaluate the effect of lifestyle factors such as nutrient intake and physical activity on bone mineral density (BMD) and bone turnover in young women.

Materials and methods: BMD was assessed using Quantitative Ultrasound; lifestyle-related factors such as dietary habits, and physical activity were examined using questionnaires in 194 female college students. The biochemical markers of bone turnover were measured in the Osteopenia (BMD below the Young Adult Mean [YAM] -1.0SD, 16 subjects) and Normal (above the YAM-1.0SD, 31 subjects) groups.

Results: The percentage of osteopenia was 11.9%. Calcium and magnesium intake (p<0.05), and physical activity (p<0.1) were found to be factors influencing BMD. The level of osteocalcin and type 1 procollagen N-terminal propeptide (P1NP) were higher in the Osteopenia group than in the Normal group (p<0.05). There was tendency that showed relationship between the level of undercarboxylated osteocalcin (ucOC) and BMD (p<0.1). The level of bone-specific alkaline phosphatase was significantly higher in the 25OH vitamin D insufficiency group compared to sufficiency group (p<0.05). The levels of OC, tartrate-resistant acid phosphatase-5b and P1NP were lower in the ucOC <4.5 ng/ml group compared to ≥4.5 ng/ml group (p<0.01, p<0.05, p<0.1), respectively.

Conclusion: This study showed that BMD in young women is affected by calcium and magnesium intake, physical activity, and vitamin D and K levels. It was suggested that the insufficiency of vitamin D and K might be contributable to low BMD through the change of bone turnover.