The Kobe Journal Of Medical Sciences[JOURNAL]
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200 papers
Association between Intra-Circuit Activated Clotting Time and Incidence of Bleeding Complications during Continuous Renal Replacement Therapy using Nafamostat Mesilate: a Retrospective Pilot Observational Study.
Miyatake Y, Makino S, Kubota K … +2 more , Egi M, Mizobuchi S
Kobe J Med Sci · 2017 Aug · PMID 29434171
It has been proposed that anticoagulant activity during continuous renal replacement therapy with nafamostat mesilate can be monitored by using intra-circuit activated clotting time. However, it is still unclear whether...
It has been proposed that anticoagulant activity during continuous renal replacement therapy with nafamostat mesilate can be monitored by using intra-circuit activated clotting time. However, it is still unclear whether activated clotting time would be useful for this purpose. We conducted a retrospective study and included 76 patients who required continuous renal replacement therapy using nafamostat mesilate. We obtained information for pre- and post-filter activated clotting times and bleeding complications. We calculated time-weighted average activated clotting time. We divided the patients into three activated clotting time groups (low, middle, high) according to the tertiles of pre- and post-filter activated clotting times. Regarding post-filter time-weighted average activated clotting time, the incidence of bleeding complications in the high activated clotting time group was significantly higher than those in the low and middle activated clotting time groups (p=0.04). The incidences of bleeding complications were not significantly different among the three groups according to pre-filter time-weighted average activated clotting time (p=0.35). In sensitive analysis, the duration on continuous renal replacement therapy without bleeding complications was significantly longer for filters with post-tw ACT<262 than for those with post-tw ACT≥262 (p=0.03). This result suggested that post-filter time-weighted average activated clotting time might be a good predictor of bleeding complications during continuous renal replacement therapy with nafamostat mesilate. Further study is required to refute or confirm our findings.
Role of SIRPα in Homeostatic Regulation of T Cells and Fibroblastic Reticular Cells in the Spleen.
Respatika D, Saito Y, Washio K … +5 more , Komori S, Kotani T, Okazawa H, Murata Y, Matozaki T
Kobe J Med Sci · 2017 Aug · PMID 29434170
Signal regulatory protein α (SIRPα), is an immunoglobulin superfamily protein that is predominantly expressed in macrophages and dendritic cells (DCs), especially CD4+ conventional DCs (cDCs). In this study, we demonstra...
Signal regulatory protein α (SIRPα), is an immunoglobulin superfamily protein that is predominantly expressed in macrophages and dendritic cells (DCs), especially CD4+ conventional DCs (cDCs). In this study, we demonstrated that, in addition to the reduced number of CD4+ cDCs, the number of T cells was significantly decreased in the spleen of Sirpa-/- mice, in which full-length of SIRPα protein was systemically ablated. The size of the T cell zone was markedly reduced in the spleen of Sirpa-/- mice. In addition, Sirpa-/- mice revealed a marked reduction of CCL19, CCL21, and IL-7 expression, which are thought to be important for homeostasis of T cells in the spleen. Consistently, the abundance of fibroblastic reticular cells (FRCs), a subset of stromal cells in the T cell zone, was markedly reduced in the spleen of Sirpa-/- mice compared with Sirpaf/f mice. Moreover, we demonstrated that the mRNA expression of Lymphotoxin (LT) α, LTβ, and LIGHT was significantly reduced in the spleen of Sirpa-/- mice. These data thus suggest that SIRPα is essential for steady-state homeostasis of T cells and FRCs in the spleen.
Different Patterns in Abdominal Stab Wound in the Self-Inflicted and Assaulted Patients: An Observational Analysis of Single Center Experience.
Nishimura T, Sakata H, Yamada T … +4 more , Terashima M, Shirai K, Yamada I, Kotani J
Kobe J Med Sci · 2017 Jul · PMID 29434169
Patterns of penetrating abdominal stab wounds (ASW) may be different according to the mechanism of injury. The purpose of this study was to review and characterize penetrating abdominal stab wounds in self-inflicted woun...
Patterns of penetrating abdominal stab wounds (ASW) may be different according to the mechanism of injury. The purpose of this study was to review and characterize penetrating abdominal stab wounds in self-inflicted wound patients and assaulted patients. We retrospectively analyzed patients with ASW who were admitted to our emergency department from 2007 to 2015. The patients were divided into two groups: self-inflicted wound group and assaulted group. There were 46 stabbing cases in 45 different patients (25 males, 21 females; average age 47 y, range 21 to 85 y). Thirty-three patients were in the self-inflicted wound group and 13 patients were in the assaulted group. Although injury sites were concentrated around the periumbilical and epigastric regions in the self-inflicted wound group, the left lateral abdomen was a favorite site in the assaulted group. The peritoneum was violated in the 17 patients in the self-inflicted wound group and 11 patients in the assaulted group. Both the self-inflicted wound group and assaulted group included patients with previous psychological disorders (28 and 5 patients, respectively). The mean Revised Trauma Score, Probability of Survival, Injury Severity Score and the Acute Physiology and Chronic Health Evaluation II scores were not significantly different between the groups although the Injury Severity Score tended to be higher in the assaulted group. The rate of the peritoneal violation was significantly higher in the assaulted group than in the self-inflicted wound group. We also should be aware of more likelihood of patients with psychological disorders among those with assault wounds.
Compatibility and Stability of Nab-Paclitaxel in Combination with Other Drugs.
Mizuta N, Nakagawa T, Yamamoto K … +6 more , Nishioka T, Kume M, Makimoto H, Yano I, Minami H, Hirai M
Kobe J Med Sci · 2017 Jul · PMID 29434168
Albumin-bound paclitaxel (Abraxane®, nab-paclitaxel) is not recommended to be administered concurrently or sequentially with other drugs due to concern for instability. The need to administer drugs separately increases i...
Albumin-bound paclitaxel (Abraxane®, nab-paclitaxel) is not recommended to be administered concurrently or sequentially with other drugs due to concern for instability. The need to administer drugs separately increases infusion time. We evaluated the compatibility and stability of solutions containing nab-paclitaxel and other drugs, including gemcitabine hydrochloride, carboplatin, dexamethasone sodium phosphate, granisetron hydrochloride, and palonosetron hydrochloride. We visually examined changes in appearance, pH, and concentration of the mixed solutions of nab-paclitaxel and other drugs for up to 24 h. Concentration was measured using high-performance liquid chromatography (HPLC). The appearance and pH of the mixed solutions did not change for up to 24 h. The change in concentration up to 24 h was within 2%. The chromatogram did not change until 8 h. The results showed that the physical compatibility and chemical stability of nab-paclitaxel were not influenced when it was combined with other drugs until 8 h. This study suggests that nab-paclitaxel could be administered in a mixture or sequentially with other drugs to reduce administration time.
History of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis and Acute Pancreatitis as Risk Factors for Post-ERCP Pancreatitis.
Funatsu E, Masuda A, Takenaka M … +11 more , Nakagawa T, Shiomi H, Yoshinaka H, Kobayashi T, Sakai A, Yagi Y, Yoshida M, Arisaka Y, Okabe Y, Kutsumi H, Azuma T
Kobe J Med Sci · 2017 May · PMID 29434167
BACKGROUND: Previous pancreatitis is a definite patient-related risk factor for pancreatitis after endoscopic retrograde cholangiopancreatography (post-ERCP pancreatitis: PEP). However, the effects of differences in the...
BACKGROUND: Previous pancreatitis is a definite patient-related risk factor for pancreatitis after endoscopic retrograde cholangiopancreatography (post-ERCP pancreatitis: PEP). However, the effects of differences in the history of PEP and acute pancreatitis on the occurrence of PEP have not been fully investigated. We examined the relationship between previous PEP or previous acute pancreatitis and procedural factors associated with PEP. METHODS: Clinical data on 1,334 consecutive patients undergoing ERCP between April 2006 and June 2010 were collected. A multivariate logistic regression analysis was conducted to assess the relationship between PEP and the cannulation time (<15 min vs. ≥15 min) or total procedure time (<30 min vs. ≥30 min) according to previous pancreatitis (previous PEP: pPEP or previous acute pancreatitis: pAP), with adjustments for clinical characteristics. RESULTS: Longer cannulation times (≥15 min) correlated with the occurrence of PEP in the pPEP group (OR=2.97; 95% CI=1.10 to 8.43, P=0.03) and in patients without previous pancreatitis (non-preP group) (OR=2.43; 95% CI=1.41 to 4.14, P= 0.002), but not in the pAP group (OR=2.78; 95% CI=0.50 to 22.42, P= 0.25). In contrast, longer procedure times correlated with the occurrence of PEP in the pAP group (OR=3.93; 95% CI=1.11 to 16.5, P= 0.03), but not in the pPEP group (OR=2.79; 95% CI=0.92 to 9.18, P= 0.068) or non-preP group (OR=0.71; 95% CI=0.39 to 1.24, P= 0.23). CONCLUSIONS: A higher risk of PEP with previous PEP was associated with longer cannulation times, whereas a higher risk of PEP with previous acute pancreatitis was associated with longer procedure times.
Phospholipase D is Dispensable for Epidermal Growth Factor-Induced Chemotaxis.
Hirai C, Badawy SMM, Zhang L … +3 more , Okada T, Kajimoto T, Nakamura S
Kobe J Med Sci · 2017 May · PMID 28490713
α-Synuclein (α-Syn) is implicated in several neurodegenerative disorders, including Parkinson's disease, known collectively as the synucleinopathies. α-Syn is known to be secreted from the cells and may contribute to the...
α-Synuclein (α-Syn) is implicated in several neurodegenerative disorders, including Parkinson's disease, known collectively as the synucleinopathies. α-Syn is known to be secreted from the cells and may contribute to the progression of the disease. Although extracellular α-Syn is shown to impair platelet-derived growth factor-induced chemotaxis, molecular mechanism of α-Syn-induced motility failure remains elusive. Here we have aimed at phospholipase D (PLD) as a potential target for α-Syn and examined the involvement of this enzyme in α-Syn action. Indeed, extracellular α-Syn caused inhibition of agonist-induced PLD activation. However, inhibition of hydrolytic activity of PLD by 1-butanol treatment showed little or no effect on agonist-induced chemotaxis. These results suggest that some signaling pathways other than PLD may be involved in α-Syn-induced inhibition of chemotaxis.
Application of Physiologically-Based Pharmacokinetic Modeling for the Prediction of Tofacitinib Exposure in Japanese.
Suzuki M, Tse S, Hirai M … +1 more , Kurebayashi Y
Kobe J Med Sci · 2017 May · PMID 28490712
Tofacitinib (3-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3 -oxopropanenitrile) is an oral Janus kinase inhibitor that is approved in countries including Japan and the United States...
Tofacitinib (3-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3 -oxopropanenitrile) is an oral Janus kinase inhibitor that is approved in countries including Japan and the United States for the treatment of rheumatoid arthritis, and is being developed across the globe for the treatment of inflammatory diseases. In the present study, a physiologically-based pharmacokinetic model was applied to compare the pharmacokinetics of tofacitinib in Japanese and Caucasians to assess the potential impact of ethnicity on the dosing regimen in the two populations. Simulated plasma concentration profiles and pharmacokinetic parameters, i.e. maximum concentration and area under plasma concentration-time curve, in Japanese and Caucasian populations after single or multiple doses of 1 to 30 mg tofacitinib were in agreement with clinically observed data. The similarity in simulated exposure between Japanese and Caucasian populations supports the currently approved dosing regimen in Japan and the United States, where there is no recommendation for dose adjustment according to race. Simulated results for single (1 to 100 mg) or multiple doses (5 mg twice daily) of tofacitinib in extensive and poor metabolizers of CYP2C19, an enzyme which has been shown to contribute in part to tofacitinib elimination and is known to exhibit higher frequency in Japanese compared to Caucasians, were also in support of no recommendation for dose adjustment in CYP2C19 poor metabolizers. This study demonstrated a successful application of physiologically-based pharmacokinetic modeling in evaluating ethnic sensitivity in pharmacokinetics at early stages of development, presenting its potential value as an efficient and scientific method for optimal dose setting in the Japanese population.
Purification, Crystallization and X-ray Diffraction Study of the C-terminal Domain of Human Herpesvirus 6A Immediate Early Protein 2.
Wang J, Nishimura M, Wakata A … +1 more , Mori Y
Kobe J Med Sci · 2017 Apr · PMID 28490711
Human herpesvirus 6A (HHV-6A) starts its replication cycle following the action of immediate early proteins that transactivate viral promoters. Immediate early protein 2 (IE2) of HHV-6A is a 1500 amino acid polypeptide w...
Human herpesvirus 6A (HHV-6A) starts its replication cycle following the action of immediate early proteins that transactivate viral promoters. Immediate early protein 2 (IE2) of HHV-6A is a 1500 amino acid polypeptide with a C-terminal region that is conserved among beta-herpesvirus subfamily members. In this study, a structural domain in the homologous C-terminal region was subjected to secondary structure prediction, and residues 1324-1500 were subsequently designated as the C-terminal domain of IE2 (IE2-CTD). The gene fragment encoding IE2-CTD was inserted into an E. coli expression vector and expressed as a fusion protein with maltose binding protein (MBP) at the N-terminus. IE2-CTD has a theoretical isoelectric point (pI) of 9.29, and strong cation exchange column chromatography was effective for purification. Needle-shaped crystals of IE2-CTD were obtained using the sitting-drop vapour diffusion method, and larger selenomethionine-labelled crystals of space group P2₁ diffracted X-rays to 2.5 Å resolution using synchrotron radiation. Data were collected at the selenium absorption peak wavelength for experimental phasing by the single anomalous dispersion method. The resulting electron density map clearly shows the protein backbone, and full structural determination and refinement are in progress.
Increased Pittsburgh Compound-B Accumulation in the Subcortical White Matter of Alzheimer's Disease Brain.
Wakabayashi Y, Ishii K, Hosokawa C … +8 more , Hyodo T, Kaida H, Yamada M, Yagyu Y, Tsurusaki M, Kozuka T, Sugimura K, Murakami T
Kobe J Med Sci · 2017 Mar · PMID 28289271
Using 11C-Pittsburgh compound B (PiB)-PET and MRI volume data, we investigated whether white matter (WM) PiB uptake in Alzheimer's disease (AD) brain is larger than that of cortical PiB uptake-negative (PiB-negative) bra...
Using 11C-Pittsburgh compound B (PiB)-PET and MRI volume data, we investigated whether white matter (WM) PiB uptake in Alzheimer's disease (AD) brain is larger than that of cortical PiB uptake-negative (PiB-negative) brain. Forty-five subjects who underwent both PiB-PET and MRI were included in the study (32 AD patients with cortical PiB-positive and 13 cortical amyloid -negative patients). Individual areas of gray matter (GM) and WM were segmented, then regional GM and WM standard uptake value ratio (SUVR) normalized to cerebellar GM with partial volume effects correction was calculated. Three regional SUVRs except WM in the centrum semiovale in the AD group were significantly larger than those in the PiB-negative groups. Frontal WM SUVR in the AD group vs frontal WM SUVR in the PiB-negative group was 2.57 ± 0.55 vs 1.64 ± 0.22; parietal, 2.50 ± 0.52 vs 1.74 ± 0.22; posterior cingulate, 2.84 ± 0.59 vs 1.73 ± 0.22; and WM in the centrum semiovale, 2.21 ± 0.53 vs 2.42 ± 0.36, respectively. We found that PiB uptake in AD brain is significantly larger than that in PiB-negative brain in the frontal, parietal and posterior cingulate subcortical WM, except in the centrum semiovale.
Changes in Heart Rate and Autonomic Nervous Activity after Orthopedic Surgery in Elderly Japanese Patients.
Tan C, Saito N, Miyawaki I
Kobe J Med Sci · 2017 Feb · PMID 28289270
Evidence regarding nursing support for delirium prevention is currently insufficient. An evaluation of changes in autonomic nervous activity over time after surgery would elucidate the features of autonomic nervous activ...
Evidence regarding nursing support for delirium prevention is currently insufficient. An evaluation of changes in autonomic nervous activity over time after surgery would elucidate the features of autonomic nervous activity in patients with delirium. These results could provide a basis for effective nursing intervention and timing for preventing the onset of delirium. Here, we aimed to obtain basic data on effective nursing interventions for preventing the onset of postoperative delirium. Heart rate variability was recorded during the morning and nighttime on the day before surgery until 3 days postoperatively in elderly patients who underwent orthopedic surgery to investigate the manner in which heart rate and autonomic nervous activity changed over time. Data were collected over 11 months from July 2013 to November 2014. Surgical stress led to the maintenance of heart rate at a significantly higher value from the day of the surgery until postoperative day 3 compared to that before surgery. Moreover, the autonomic nervous activity remained unchanged during the morning, and it was significantly lower during the night from postoperative day 1 until postoperative day 3 than before the surgery. These results suggest that there is a decrease in parasympathetic nervous activity during the nighttime postoperatively.
Epidemiological Investigation of Parasitic Infection of Schoolchildren from Six Elementary Schools in Sakon Nakhon Province, Thailand.
Doi R, Itoh M, Chakhatrakan S … +1 more , Uga S
Kobe J Med Sci · 2017 Feb · PMID 28289269
We conducted an epidemiological study of intestinal parasitic infection in 572 schoolchildren aged 4 to 12 years old from six elementary schools in Sakon Nakhon Province, Thailand from June 2013 to August 2014. We collec...
We conducted an epidemiological study of intestinal parasitic infection in 572 schoolchildren aged 4 to 12 years old from six elementary schools in Sakon Nakhon Province, Thailand from June 2013 to August 2014. We collected fecal, blood, and urine samples to investigate parasitic infection and conducted a questionnaire survey. Soil samples were examined for egg contamination. Fecal examination, using the formalin-ether sedimentation method, revealed that 39% of schoolchildren were infected with eight genera and eight species of parasites; three nematodes, two trematodes, one cestode, and two protozoa. Prevalence rates across the six schools (schools A through F) were: A (13%), B (15%), C (53%), D (11%), E (20%), and F (43%). Schools C and F showed significantly higher prevalence rates than the other schools (p<0.05). In school C, Necator americanus was detected in 49% of schoolchildren tested, while in school F a high prevalence of Opisthorchis viverrini and Heterophyes heterophyes, at a rate of 23% and 21%, respectively, was detected. The questionnaire survey revealed that health, hygiene practices and awareness were poor in school C. However, school F showed high levels of cognizance and practices relating to the prevention of infection. The schoolchildren ate a staple diet of undercooked river fish and the results revealed a high rate of fish-borne parasites. Soil samples showed Toxocara sp. contamination in and around the campus. Toxocara antibodies were detected in over 6% of schoolchildren. The use of urine samples, as opposed to serum samples, was found to be effective for antibody testing.
Meaning and Limitation of Cortical Bone Width Measurement with DentaScan in Medication-Related Osteonecrosis of the Jaws.
Iwata E, Akashi M, Kishimoto M … +4 more , Kusumoto J, Hasegawa T, Furudoi S, Komori T
Kobe J Med Sci · 2017 Feb · PMID 28289268
Mandibular cortical bone measurement with x-ray imaging is known to be a potentially useful tool in the detection of dimensional changes caused by bisphosphonate. The primary purpose of this study was to assess the meani...
Mandibular cortical bone measurement with x-ray imaging is known to be a potentially useful tool in the detection of dimensional changes caused by bisphosphonate. The primary purpose of this study was to assess the meaning and limitation of cortical bone measurement with computed tomography (CT) in patients with medication-related osteonecrosis of the jaw (MRONJ). The investigators obtained DentaScan images of the mandible from 15 patients with MRONJ, 15 patients with a history of antiresorptive agent administration without symptoms of MRONJ (non-MRONJ), and 15 control subjects. The cortical bone width measured on DentaScan images was compared between the three groups (ANOVA and Tukey's test). Interobserver reliability between two observers was also assessed. The values of interclass correlation coefficient were 0.48 in the MRONJ group, 0.29 in the Non-MRONJ group, and 0.34 in control group. The cortical bone widths calculated both by observer 1 and observer 2 were thicker in patients with MRONJ than in the non-MRONJ group and controls. There were significant differences in cortical bone width among the MRONJ, non-MRONJ, and control groups in observer 1 (P < 0.001) and observer 2 (P < 0.001), specifically comparing the MRONJ group with the non-MRONJ group and the control group. Cortical bone width measurement is useful for the distinction between medication-related osteonecrosis of the jaw and normal bone, in spite of the low interobserver reliability.
The Analysis of Polymorphism of Alcohol Dehydrogenase 3 (ADH3) Gene and Influence of Liver Function Status in Indonesia.
Suhartini, Mustofa, Nurhantari Y … +1 more , Rianto BU
Kobe J Med Sci · 2017 Jan · PMID 28239076
Indonesian culture actually has no historical record of behaviors in consuming alcohol, but there are many recent reports of alcohol abuse among Asian people involving their traditional drink. In genotype studies, the da...
Indonesian culture actually has no historical record of behaviors in consuming alcohol, but there are many recent reports of alcohol abuse among Asian people involving their traditional drink. In genotype studies, the damage of the liver caused by consuming alcohol is influenced by the presence of the polymorphism enzyme gene. The lack of study regarding such topic is a signal to further investigate ADH3 gene distribution and its effect on liver function status. The total of 197 research subjects of Javanese descent received alcohol dehydrogenase 3 (ADH3) genetic polymorphism and liver status tests in the city of Yogyakarta, Indonesian. An analytical study with a cross-sectional design was then conducted on the subjects, with the resulting isolated DNAs amplified through polymerase chain reaction (PCR). The genotype of ADH3 was determined by means of restriction fragment length polymorphism (RFLP) using Ssp1 restricting enzyme. Liver function status was assessed by measuring serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT) and gamma glutamyl transferase (GGT) using a photometric system. Gene types of ADH3*1 (2.1%), ADH3*2 (82.7%) and ADH3*1/3*2 (15.2%) on the subjects were concluded, finding that there is no difference between the gender. In conclusion most of the ADH3 gene polymorphism of the subjects were ADH3*2 (82.7%). The influence of genetic polymorphisms on the status of liver function in the subjects showed significant difference according to GGT measurement, but the same cannot be said on the other two values measuring SGOT and SGPT.
Time-Dependent Changes in Psychosocial Distress in Japanese Patients with Implantable Cardioverter Defibrillators.
Saito N, Taru C, Miyawaki I
Kobe J Med Sci · 2016 Dec · PMID 28239075
This prospective study clarified changes in the mood states of Japanese patients with implantable cardioverter defibrillators as well as factors related to the mood states. Using a longitudinal repeated-measure design, 2...
This prospective study clarified changes in the mood states of Japanese patients with implantable cardioverter defibrillators as well as factors related to the mood states. Using a longitudinal repeated-measure design, 29 patients with implantable cardioverter defibrillators completed the Profile of Mood States-Short Form Japanese Version questionnaire before discharge and 1, 4, 7, and 13 months after implantation. One month after discharge, the mood states of the patients with implantable cardioverter defibrillators improved. From 7 to 13 months after discharge, moods deteriorated; 13 months after discharge, moods were equivalent to those at the time of discharge. No relationship with defibrillation experience was detected in this study, but employment, age, sex, and lack of experience of syncopal attack were factors related to poor mood states for patients with implantable cardioverter defibrillators. Therefore, Japanese patients with implantable cardioverter defibrillators with any factor deteriorating their mood state should be monitored so that their mood state does not deteriorate again between six months and one year after implantation.
Joint Attention Development in Low-risk Very Low Birth Weight Infants at Around 18 Months of Age.
Yamaoka N, Takada S
Kobe J Med Sci · 2016 Oct · PMID 28239074
The purpose of this study was to clarify the developmental characteristics of joint attention in very low birth weight (VLBW) infants with a low risk of complications. Section B of the Checklist for Autism in Toddlers (C...
The purpose of this study was to clarify the developmental characteristics of joint attention in very low birth weight (VLBW) infants with a low risk of complications. Section B of the Checklist for Autism in Toddlers (CHAT) was administered to 31 VLBW and 45 normal birth weight (NBW) infants aged 18-22 months, while the sessions were recorded with a video camera. A semi-structured observation scale was developed to assess infants' joint attention from the video footage, and was shown to be reliable. VLBW, compared to NBW, infants showed significantly poorer skills in 2 of 4 items on responding to joint attention, and in 6 of 10 items on initiating joint attention. VLBW infants need more clues in order to produce joint attention. The difficulty was attributed to insufficient verbal and fine motor function skills. Continuous follow-up evaluation is essential for both high-risk and low-risk VLBW infants and their parents.
Effects of Topical Application of Betamethasone on Imiquimod-induced Psoriasis-like Skin Inflammation in Mice.
Mori H, Arita K, Yamaguchi T … +2 more , Hirai M, Kurebayashi Y
Kobe J Med Sci · 2016 Sep · PMID 28239073
Psoriasis is a chronic inflammatory skin disease mediated by dysregulated auto-reactive immune system. In this study, in order to confirm and further extend the pharmacological basis of topical steroids in psoriasis ther...
Psoriasis is a chronic inflammatory skin disease mediated by dysregulated auto-reactive immune system. In this study, in order to confirm and further extend the pharmacological basis of topical steroids in psoriasis therapy, we investigated the effect of betamethasone ointment on imiquimod (IMQ)-induced skin inflammation in mice. In BALB/c mice, topical IMQ at the dose of 250 µg each on both sides of the ear induced marked psoriasis-like skin inflammation within 5 days. The same dose of IMQ produced only slight to moderate skin inflammation even on Day 7 in CB-17 scid mice. IMQ-induced skin inflammation was associated with increased levels of mRNA transcripts expression of signature cytokines of T helper (Th)1/Th17 cells, i.e., interferon-γ, interleukin (IL)-17 and IL-22 on Day 5. In addition, levels of mRNA expression of the markers of keratinocytes, i.e., IL-1β, S100A8, and S100A9, were dramatically elevated in IMQ-treated mice. The IMQ-induced changes in cytokine expression were significantly suppressed by topical treatment with betamethasone ointment. IMQ failed to produce significant changes in the mRNA levels of tumor necrosis factor-α as a marker of macrophages and NK1.2 as a marker of natural killer cells and natural killer T cells. In contrast, mRNA level of a Th2 cytokine IL-13 was significantly decreased by IMQ treatment and further suppressed by betamethasone. These findings provide the first pharmacological evidence that the topical application of betamethasone prevents IMQ-induced psoriasis-like skin inflammation in mice by inhibiting gene expressions of various cytokines related to Th1 cells, Th17 cells and keratinocytes.
Genetic Interactions among AMPK Catalytic Subunit Ssp2 and Glycogen Synthase Kinases Gsk3 and Gsk31 in Schizosaccharomyces Pombe.
Qingyun, Ma Y, Kato T … +1 more , Furuyashiki T
Kobe J Med Sci · 2016 Aug · PMID 27604537
In Schizosaccharomyces pombe, Ssp2, an ortholog of AMP-activated protein kinase (AMPK), is critical for cell growth at restrictive temperatures and under glucose depletion as well as sexual differentiation under nitrogen...
In Schizosaccharomyces pombe, Ssp2, an ortholog of AMP-activated protein kinase (AMPK), is critical for cell growth at restrictive temperatures and under glucose depletion as well as sexual differentiation under nitrogen depletion. To identify genes genetically related to Ssp2, we performed a genetic screening to search for the genes whose overexpression rescued the growth defects in Δssp2 cells at restrictive temperatures, and identified 35 cosmids as multicopy suppressor genes. In Southern blot analyses, 22 out of these cosmids were hybridized to an ssp2+ probe. Using nucleotide sequencing, we identified the gsk3+ gene in one of the cosmids, and the remaining 12 cosmids were hybridized to a gsk3+ probe. Overexpression of the gsk3+ gene or the gsk31+ gene, another GSK3 member, rescues defective growth of Δssp2 cells at restrictive temperatures and under glucose depletion as well as sexual differentiation under nitrogen depletion. Δgsk3Δgsk31 double knockout cells, but neither Δgsk3 nor Δgsk31 single knockout cells, phenocopy Δssp2 cells. The deletion of the gsk3+ or gsk31+ gene augments the phenotypes of Δssp2 cells. These findings suggest that Gsk3 and Gsk31 are critical and interact with Ssp2 in multiple cellular functions.
Expressions of Collagen I and III in Hypoxic Keloid Tissue.
Wulandari E, Jusman SW, Moenadjat Y … +2 more , Jusuf AA, Sadikin M
Kobe J Med Sci · 2016 Jul · PMID 27604536
BACKGROUND: Wound heals itself spontaneously as physiological process. However, in some individuals, small wounds such as parenteral injections or body piercings may cause increased expression of collagen synthesis. The...
BACKGROUND: Wound heals itself spontaneously as physiological process. However, in some individuals, small wounds such as parenteral injections or body piercings may cause increased expression of collagen synthesis. The condition is known as keloid. Histopathology of keloid demonstrates extensive tissue proliferation that extends beyond the margin of primary wound. As a result, it develops uncontrolled or excessive fibrogenesis and tremendous source of collagen that still causes clinical problems until now. A wound, no matter how small the size is, will be followed by increased expression of collagen synthesis. Procollagen I and III is one of markers indicating the development of fibrosis. In fibrosis, there is hypoxia, which is characterized by stabilization of HIF-1α. Therefore, our study was aimed to obtain information about expression of collagen I and III in hypoxic keloid tissue. METHOD: The study design was observational descriptive. Keloid specimens were obtained from biopsy and preputium skins as the control specimens were obtained from circumcision. There were 10 tissue specimens for each specimen group. The analysis performed were evaluation of mRNA expression on collagen I, collagen III and HIF-1α using RT-PCR, the evaluation of HIF-1α protein level using ELISA and the expression of collagen I and collagen III protein using immunohistochemistry. Statistically, data was analyzed by unpaired t-test. RESULTS: In keloid with excessive cell proliferation, we found that the expression of procollagen I mRNA increased 35 times and the expression of procollagen III mRNA increased 27.1 times compared to preputium control group (p<0.05). The expression of procollagen I protein in the dermal layer of keloid was 61% and in the preputium was 37% (p<0.05). The expression of collagen III protein in the dermal layer of keloid was 39% and in the preputium was 16% (p<0.05). There was a 5-fold increase on expression of HIF-1α mRNA in keloid tissue compared to those in preputium (p<0.05). The levels of HIF-1α protein in keloid tissue was 0.201 ng/mg protein and the level in preputium was 0.122 ng/mg protein (p<0.05). There was a strong positive and extremely significant correlation between the expression of HIF-1α protein and procollagen III (R=0.744; p<0.05, Pearson), but HIF-1α with procollagen I are weak correlation (R=0.360; p>0.05, Pearson) Conclusion: Expression of collagen I and III have important role in hypoxic keloid tissue characterized by increased expressions. The expression of collagen I and III is associated with stable HIF-1α in keloid tissue.
Secondary Bilateral Orbital Involvement from Primary Non-Hodgkin Lymphoma of the Cheek.
Furudoi S, Yoshii T, Komori T
Kobe J Med Sci · 2016 Jul · PMID 27604535
We describe a patient with oculomotor nerve palsy due to secondary orbital infiltration from the primary malignant lymphoma of the cheek. The patient was a 78-year-old female who had non-Hodgkin lymphoma (diffuse large B...
We describe a patient with oculomotor nerve palsy due to secondary orbital infiltration from the primary malignant lymphoma of the cheek. The patient was a 78-year-old female who had non-Hodgkin lymphoma (diffuse large B cell lymphoma [DLBCL]) of the cheek. The patient received chemotherapy and local radiation therapy. The combined treatment brought about complete remission. About 6 months after the last treatment the patient began to have left blepharoptosis and impaired vision. Findings from ophthalmological and neurosurgical examinations suggested no intraorbital or intracranial lesions. Repeated MRI and CT scans also showed no such lesions. One month later, the patient suddenly had a left oculomotor disturbance, diplopia and exophthalmus, followed by right oculomotor nerve palsy. An MRI revealed bilateral intraorbital tumors. Recurrence at the orbital tissue of malignant lymphoma originated from the left cheek appeared to cause the ophthalmological symptoms. Salvage chemotherapy was performed and her ocular symptoms were recovered. However, the patient died approximately 10 months after recurrent orbital tumor onset.
Efficiency of Balloon Kyphoplasty in the Treatment of Osteoporotic Vertebral Compression Fractures.
Baz AB, Akalin S, Kiliçaslan ÖF … +3 more , Tokatman B, Arik H, Duygun F
Kobe J Med Sci · 2016 Jul · PMID 27604534
Eighty-seven osteoporotic vertebral fractures of 82 patients were treated with balloon kyphoplasty. Preoperative, postoperative and follow-up outcomes of functional impairment, pain scores and vertebral height restoratio...
Eighty-seven osteoporotic vertebral fractures of 82 patients were treated with balloon kyphoplasty. Preoperative, postoperative and follow-up outcomes of functional impairment, pain scores and vertebral height restorations of the patients were recorded and evaluated statistically. Seventy-two of the patients were female (87.8%) and 10 (12.2%) were male. Mean age of all patients were 66.4 years. Preoperative mean Anterior Vertebral Body Height of 48.20±13.94 % and Middle Vertebral Body Height of 59.40±14.26 % were recorded as 79.91±9.50 % and 86.90±8.38 % respectively postoperatively and noted to be 73.26±8.59 % and 84.65±8.19 % at last controls respectively. The mean Oswestry Disability Index and Visual Analog Pain Scale also improved significantly. Local Kyphosis of all the patients were also evaluated and a significant improvement was noted postoperatively. The long term results of this study suggest that balloon kyphoplasty is an effective and safe treatment option in osteoporotic vertebral fractures and should be considered for functional improvement, pain relief and height restoration.
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