Motivation: Structural characterization of protein interactions is necessary for understanding and modulating biological processes. On one hand, X-ray crystallography or NMR spectroscopy provide atomic resolution structures but the data collection process is typically long and the success rate is low. On the other hand, computational methods for modeling assembly structures from individual components frequently suffer from high false-positive rate, rarely resulting in a unique solution.
Results: Here, we present a combined approach that computationally integrates data from a variety of fast and accessible experimental techniques for rapid and accurate structure determination of protein–protein complexes. The integrative method uses atomistic models of two interacting proteins and one or more datasets from five accessible experimental techniques: a small-angle X-ray scattering (SAXS) profile, 2D class average images from negative-stain electron microscopy micrographs (EM), a 3D density map from single-particle negative-stain EM, residue type content of the protein–protein interface from NMR spectroscopy and chemical cross-linking detected by mass spectrometry. The method is tested on a docking benchmark consisting of 176 known complex structures and simulated experimental data. The near-native model is the top scoring one for up to 61% of benchmark cases depending on the included experimental datasets; in comparison to 10% for standard computational docking. We also collected SAXS, 2D class average images and 3D density map from negative-stain EM to model the PCSK9 antigen–J16 Fab antibody complex, followed by validation of the model by a subsequently available X-ray crystallographic structure.
firstname.lastname@example.org or email@example.com
Supplementary data are available at Bioinformatics online.
The structure activity relationships of N-(3-acyloxy-2-benzylpropyl)-N′-4-[(methylsulfonylamino)benzyl] thioureas, which represent simplified RTX-based vanilloids, were investigated by varying the distances between the four principal pharmacophores and assessing binding and antagonistic activity on rTRPV1. The analysis indicated that a 3-pivaloyloxy-2-benzylpropyl C-region conferred the best potency in binding affinity and antagonism. The molecular modeling of this best template with the tetrameric homology model of rTRPV1 was performed to identify its binding interactions with the receptor.
Vanilloid Receptor 1; TRPV1; antagonist; resiniferatoxin; molecular modeling; capsaicin
A series of TRPV1 agonists with amide, reverse amide, and thiourea groups in the B-region and their corresponding α-methylated analogues were investigated. Whereas the α–methylation of the amide B-region enhanced the binding affinities and potencies as agonists, that of the reverse amide and thiourea led to a reduction in receptor affinity. The analysis indicated that proper hydrogen bonding as well as steric effects in the B-region are critical for receptor binding.
Vanilloid Receptor 1; TRPV1; agonist; capsaicin
A series of N-(2-amino-6-trifluoromethyl-pyridin-3-ylmethyl) 2-(3-fluoro-4-methylsulfonylaminophenyl) propanamides were designed combining previously identified pharmacophoric elements and evaluated as hTRPV1 antagonists. The SAR analysis indicated that specific hydrophobic interactions of the 2-amino substituents in the C-region of the ligand were critical for high hTRPV1binding potency. In particular, compound 49S was an excellent TRPV1 antagonist (Ki(CAP) = 0.2 nM; IC50(pH) = 6.3 nM) and was thus ca. 100- and 20-fold more potent, respectively, than the parent compounds 2 and 3 for capsaicin antagonism. Furthermore, it demonstrated strong analgesic activity in the rat neuropathic model superior to 2 with almost no side effects. Compound 49S antagonized capsaicin induced hypothermia in mice, but showed TRPV1-related hyperthermia. The basis for the high potency of 49S compared to 2 is suggested by docking analysis with our hTRPV1 homology model in which the 4-methylpiperidinyl group in the C-region of 49S made additional hydrophobic interactions with the hydrophobic region.
Accumulating evidence suggests that HtrA1 (high-temperature requirement A1) is involved in modulating crucial cellular processes and implicated in life-threatening diseases, such as cancer and neuropathological disorders; however, the exact functions of this protease in vivo remain unknown. Here, we show that loss of HtrA1 function increases fibroblast growth factor 8 (FGF8) mRNA levels and triggers activation of FGF signaling, resulting in dorsalization in zebrafish embryos. Notably, HtrA1 directly cleaves FGF8 in the extracellular region, and this cleavage results in decreased activation of FGF signaling, which is essential for many physiological processes. Therefore, HtrA1 is indispensable for dorsoventral patterning in early zebrafish embryogenesis and serves as a key upstream regulator of FGF signaling through the control of FGF levels. Furthermore, this study offers insight into new strategies to control human diseases associated with HtrA1 and FGF signaling.
Air pollution’s mortality effects may differ by subpopulation; however, few studies have investigated this issue in Asia. We investigated susceptibility to air pollutants on total, cardiovascular, and respiratory mortality in Seoul, Korea for the period 2000 – 2007. We applied time-stratified case-crossover analysis, which allows direct modeling of interaction terms, to estimate susceptibility based on sex, age, education, marital status, and occupation. An interquartile range increase in pollution was associated with odds ratios of 0.94 (95% confidence interval, 0.25 – 1.62), 2.27 (1.03–3.53), 1.94 (0.80 – 3.09), and 2.21 (1.00 – 3.43) for total mortality and 1.95 (0.64 – 3.27), 4.82 (2.18 – 7.54), 3.64 (1.46 – 5.87), and 4.32 (1.77 – 6.92) for cardiovascular mortality for PM10, nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), respectively. Ozone effect estimates were positive, but not statistically significant. Results indicate that some populations are more susceptible than others. For total or cardiovascular mortality, associations were higher for males, those 65 – 74 years, and those with no education or manual occupation for some pollutants. For example, the odds ratio for SO2 and cardiovascular mortality was 1.19 (1.03 – 1.37) times higher for those with manual occupations than professional occupations. Our findings provide evidence that some populations are more susceptible to the effects of air pollution than others, which has implications for public policy and risk assessment for susceptible subpopulations.
air pollution; effect modifiers; mortality; time-stratified case–crossover analysis; susceptible subpopulations
The objective of this study was to evaluate a monoclonal antibody-based test to detect Helicobacter pylori-specific antigen in gastric aspirates from humans.
Sixty-one volunteers were enrolled in the study. All of the subjects underwent a 13C-urea breath test (UBT) before esophagogastroduodenoscopy. Gastric aspirates were analyzed for pH and ammonia and used for polymerase chain reaction (PCR), culture, and monoclonal antibody-based detection of H. pylori. Multiple biopsies of the gastric antrum and body were obtained for a rapid urease test (RUT) and histological evaluation.
Thirty-six subjects were H. pylori-positive and 25 were H. pylori-negative according to the UBT results. Compared with the H. pylori-negative subjects, H. pylori-positive subjects had a higher pH (4.77±1.77 vs 3.49±1.30, p<0.05) and ammonia level (1,130.9±767.4 vs 184.2±126.3, p<0.0001). The sensitivities and specificities of the PCR test, RUT, culture test, and monoclonal antibody-based test were 100% and 72%, 89% and 100%, 47% and 100%, and 78% and 100%, respectively.
The monoclonal antibody-based test for diagnosing H. pylori infection in gastric aspirates has increased sensitivity compared with the culture test and specificity as high as that of the RUT. The test may be useful as an additive test for examining gastric aspirates.
Helicobacter pylori; Gastric aspirate; Monoclonal antibody-based test
Chronic autoimmune inflammation, which is commonly observed in rheumatoid arthritis (RA), disrupts the delicate balance between bone resorption and formation causing thedestruction of the bone and joints. We undertook this study to verify the effects of natural grape-seed proanthocyanidin extract (GSPE), an antioxidant, on chronic inflammation and bone destruction. GSPE administration ameliorated the arthritic symptoms of collagen-induced arthritis (CIA), which are representative of cartilage and bone destruction. GSPE treatment reduced the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and osteoclast activity and increased differentiation of mature osteoblasts. Receptor activator of NFκB ligand expression in fibroblasts from RA patients was abrogated with GSPE treatment. GSPE blocked human peripheral blood mononuclear cell-derived osteoclastogenesis and acted as an antioxidant. GSPE improved the arthritic manifestations of CIA mice by simultaneously suppressing osteoclast differentiation and promoting osteoblast differentiation. Our results suggest that GSPE may be beneficial for the treatment of inflammation-associated bone destruction.
Neuromyelitis optica (NMO) is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON) and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD), and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced.
Muscle wasting in sepsis is associated with increased proteolysis. Interleukin-15 (IL-15) has been characterized as an anabolic factor for skeletal muscles. Our study aims to investigate the role of IL-15 in sepsis-induced muscle atrophy and proteolysis.
Mice were rendered septic either by cecal ligation and puncture or by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg i.p.). Expression of IL-15 mRNA and protein was determined by reverse transcriptase polymerase chain reaction and Western blot analysis in the control and septic limb muscles. C2C12 skeletal muscle cells were stimulated in vitro with either LPS or dexamethasone in the presence and absence of IL-15 and sampled at different time intervals (24, 48, or 72 hours). IL-15 (10µg/kg) was intraperitoneally administered 6 hours before sepsis induction and limb muscles were sampled after 24 hours of sepsis. Cathepsin L activity was determined to measure muscle proteolysis. Atrogin-1 and muscle-specific ring finger protein 1 (MuRF1) expressions in limb muscle protein lysates was analyzed.
IL-15 mRNA expression was significantly lower in the limb muscles of septic mice compared to that of controls. Cathepsin L activity in C2C12 cells was significantly lower in presence of IL-15, when compared to that observed with individual treatments of LPS or dexamethasone or tumor necrosis factor α. Further, the limb muscles of mice pre-treated with IL-15 prior to sepsis induction showed a lower expression of atrogin-1 and MuRF1 than those not pre-treated.
IL-15 may play a role in protection against sepsis-induced muscle wasting; thereby, serving as a potential therapeutic target for sepsis-induced skeletal muscle wasting and proteolysis.
Interleukin-15; Muscular Atrophy; Proteolysis; Muscle Retardation; Sepsis
We report a rare case of the concurrent manifestation of central diabetes insipidus (CDI) and type 2 diabetes mellitus (DM). A 56 year-old man was diagnosed as a type 2 DM on the basis of hyperglycemia with polyuria and polydipsia at a local clinic two months ago and started an oral hypoglycemic medication, but resulted in no symptomatic improvement at all. Upon admission to the university hospital, the patient's initial fasting blood sugar level was 140 mg/dL, and he showed polydipsic and polyuric conditions more than 8 L urine/day. Despite the hyperglycemia controlled with metformin and diet, his symptoms persisted. Further investigations including water deprivation test confirmed the coexisting CDI of unknown origin, and the patient's symptoms including an intense thirst were markedly improved by desmopressin nasal spray (10 µg/day). The possibility of a common origin of CDI and type 2 DM is raised in a review of the few relevant adult cases in the literature.
Polyuria; Central diabetes insipidus; Type 2 diabetes mellitus; Water deprivation test
IL-17-producing CD4+ T cells (Th17) play important functions in autoimmune diseases and allograft rejection of solid organs. We examined the effects of IL 17 and its mechanism of action on arthritis in a murine collagen-induced arthritis (CIA) model using bone marrow transplantation (BMT) system. DBA/1J mice were administered a lethal radiation dose and then rescued with bone marrow derived from either wild-type (WT) or IL-17-/- mice on C57BL/6 background mice. CIA was induced after the bone marrow transplant, and disease progression was characterized. DBA/1J mice with CIA that received IL-17-/- donor bone marrow showed potently inhibited development and severity of clinical arthritis as compared with CIA mice that received WT bone marrow. Reduced secretion of the pro-inflammatory cytokines tumor necrosis factor-α, IL-1β, and IL-6, and collagen-specific T cell responses were observed in mice that received IL-17-/- bone marrow. IL-17 blockade also inhibited effector T cell proliferation by reciprocally regulating the Treg/Th17 ratio. IL-17 blockade prevented joint destruction in mice with CIA. These findings suggest that CIA with BMT is a viable method of immunological manipulation and that IL-17 deficiency suppresses severe joint destruction and inflammation in CIA mice. There may be clinical benefits in blocking IL-17 and BMT in the treatment of rheumatoid arthritis.
arthritis, experimental; bone marrow transplantation; interleukin-17; Th17 cells; T-lymphocytes, regulatory; transplantation, homologous
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. There are few reports on the burden of disease of MS, worldwide. The authors aim to estimate burden of disease and estimate the epidemiologic indexes of MS in Korea using available epidemiologic data.
Epidemiologic indexes were computed using DISMOD II software based on prevalence from nationwide survey, incidence estimated from extrapolation, mortality from National Statistics Office, and duration of disease from literature as input indexes. We calculated disability-adjusted life year (DALY) as a measure of premature mortality and disability, equivalent to years of healthy life lost due to a given condition.
The incidence of MS in Korea was 0.1 per 100,000, higher in female than in male. The highest incidence was estimated in the age group between 35 and 44 years in male and age group between 25 and 29 years in female. Total burden of disease of MS was 1,394 DALY, comprised of 292 (21%) years of life lost and 1,101 (79%) years lived with disability. The mean age at onset of MS was 33 years old in men and 32 years old in female. Estimated duration of disease was 35 years in men and 40 years in female. Most of the DALY of MS occurred in the adult population between 25 and 54 years of age.
Although MS is a rare disease in Korea, most of the DALY arises from young people, which results in a major financial burden on the patient, family, health system and society.
Multiple sclerosis; Burden of disease; DISMOD II; Incidence; Prevalence; Quality of Life
Interleukin (IL)-32 and IL-17 play critical roles in pro-inflammatory responses and are highly expressed in the synovium of patients with rheumatoid arthritis (RA). We investigated the relations between these two cytokines (IL-17 and IL-32) for their ability to induce each other and to stimulate osteoclasts in RA fibroblast-like synoviocytes (FLSs) and T cells.
FLSs were isolated through surgical synovectomy obtained from patients with RA or osteoarthritis (OA). Real-time PCR were performed to evaluate the expression of IL-32, IL-17 and osteoclast-related genes. Immunohistochemical staining and tartrate-resistant acid phosphatase (TRAP) staining were performed to determine the distribution of inflammatory cytokines and the presence of osteoclastogenesis.
IL-17 induced the expression of IL-32 in the FLSs from RA patients, as assessed by microarray. IL-32 production was increased by IL-17. IL-32 in the FLSs from RA patients induced the production of IL-17 in CD4+ T cells. IL-32 and IL-17 were colocalized near TRAP-positive areas in joint specimens. IL-17 and IL-32 synergistically induced the differentiation of osteoclasts, as demonstrated by the expression of osteoclast-related genes. IL-32 and IL-17 also could induce resorption by osteoclasts in a RANKL-dependent manner.
IL-17 affected the expression of IL-32 in FLSs of RA patients and IL-32 induced the production of IL-17 in CD4+ T cells. Both IL-17 and IL-32 cytokines can reciprocally influence each other's production and amplify the function of osteoclastogenesis in the in RA synovium. Separately, IL-17 and IL-32 each stimulated osteoclastogenesis without RANKL. Together, the two cytokines synergistically amplified the differentiation of osteoclasts, independent of RANKL stimulation.
A 67-year-old woman presented with memory impairment and behavioral changes. Brain MRI indicated hepatic encephalopathy. Abdominal CT scans revealed an intrahepatic portosystemic venous shunt that consisted of two shunt tracts to the aneurysmal sac that communicated directly with the right hepatic vein. The large tract was successfully occluded by embolization using the newly available AMPLATZERTM Vascular Plug II and the small tract was occluded by using coils. The patient's symptoms disappeared after shunt closure and she remained free of recurrence at the 3-month follow-up evaluation.
Hepatic encephalopathy; Portosystemic shunt; Surgical; Embolization; Therapeutic
A pancreatic hamartoma is a rare benign lesion that may be mistaken for malignancy. A pancreatic hamartoma can present with vague, non-specific symptoms, which can be difficult to diagnose despite modern diagnostic tools. We report here a pancreatic hamartoma diagnosed after surgical resection. A 52-year-old female presented with postprandial abdominal discomfort. Abdominal computed tomography and pancreatic magnetic resonance imaging revealed a 2.2 × 2.5-cm cystic mass in the pancreatic head. The patient underwent a pylorus-preserving pancreaticoduodenectomy. The histopathological and immunohistochemical studies helped make the diagnosis of pancreatic hamartoma. Here, we report a case of pancreatic hamartoma and review the relevant medical literature.
Hamartoma; Pancreas; Pancreaticoduodenectomy
Broncholiths are defined as calcified materials that occur in a tracheobronchial tree or in a cavity communicating with that. Broncholith has variable clinical features. The therapeutic options to remove broncholiths are so variable that clinicians need to select the most safe and effective methods by mass size, mobility, and location. As yet, there is no consistent guideline removing a broncholith. We report 2 successful cases of removing a fixed broncholith by flexible bronchoscopy guided cryoadhesion. With repeated technique of thawing and freezing with ryoprobe, we could extract the fixed broncholith safely. This method is promising as a way to remove broncholith in the future.
Bronchial Diseases; Calculi; Cryotherapy; Bronchoscopy
Soon after the first novel influenza A (H1N1) death was documented in Korea on August 15, 2009, prompt treatment with antiviral drugs was recommended when an infection was suspected. Free antiviral drugs were distributed to patients who met the case definition in the treatment guidelines, and patients prescribed the antiviral drugs were included in the Antiviral Drug Surveillance System (ADSS). A total of 2,825,821 patients were reported to the ADSS from September 1 to December 31, 2009. Odds ratios were calculated to compare the risks of severe diseases, as indicated by general hospital admissions or intensive care unit (ICU) admissions according to demographic characteristics, underlying medical conditions, and behavioral factors. Approximately 6% of the total population received antiviral drugs during the study period. Of these, 2,709,611 (95.9%) were outpatients, 114,840 (4.06%) were hospitalized, and 1,370 (0.05%) were admitted to the ICU. Children aged 0–9 yr accounted for 33.94% of all reported cases, whereas only 3.89% of the patients were ≥ 60 yr. The estimated incidence of novel influenza A (H1N1) during the pandemic was 5.68/100 of all reported cases. Mortality due to influenza A (H1N1) during the pandemic was 0.33/100,000, with the highest mortality of 1.31/100,000 for patients aged ≥ 60 years. Severe pandemic H1N1 influenza was associated with the presence of one or more underlying medical conditions in elderly aged ≥ 60 years and with lower economic status. Moreover, influenza A (H1N1) appeared to be age-specific in terms of mortality. Although the incidence and admission rates of influenza A (H1N1) were higher in younger age groups, fatal cases were much more likely to occur in the elderly (≥60 years). In contrast to earlier influenza A (H1N1) reports, the risks of a severe outcome were elevated among those who were underweight (body mass index < 18.5 kg/m2).
Ultrasound-guided cannulation of a large-bore catheter into the internal jugular vein was performed to provide temporary hemodialysis vascular access for uremia in a 65-yr-old woman with acute renal failure and sepsis superimposed on chronic renal failure. Despite the absence of any clinical evidence such as bleeding or hematoma during the procedure, a chest x-ray and computed tomographic angiogram of the neck showed that the catheter had inadvertently been inserted into the subclavian artery. Without immediately removing the catheter and applying manual external compression, the arterial misplacement of the hemodialysis catheter was successfully managed by open surgical repair. The present case suggests that attention needs to be paid to preventing iatrogenic arterial cannulation during central vein catheterization with a large-bore catheter and to the management of its potentially devastating complications, since central vein catheterization is frequently performed by nephrologists as a common clinical procedure to provide temporary hemodialysis vascular access.
Hemodialysis; Complication; Central Venous Catheterization
Transpedicular screw fixation has some disadvantages such as postoperative back pain through wide muscle dissection, long operative time, and cephalad adjacent segmental degeneration (ASD). The purposes of this study are investigation and comparison of radiological and clinical results between interspinous fusion device (IFD) and pedicle screw.
From Jan. 2008 to Aug. 2009, 40 patients underwent spinal fusion with IFD combined with posterior lumbar interbody fusion (PLIF). In same study period, 36 patients underwent spinal fusion with pedicle screw fixation as control group. Dynamic lateral radiographs, visual analogue scale (VAS), and Korean version of the Oswestry disability index (K-ODI) scores were evaluated in both groups.
The lumbar spine diseases in the IFD group were as followings; spinal stenosis in 26, degenerative spondylolisthesis in 12, and intervertebral disc herniation in 2. The mean follow up period was 14.24 months (range; 12 to 22 months) in the IFD group and 18.3 months (range; 12 to 28 months) in pedicle screw group. The mean VAS scores was preoperatively 7.16±2.1 and 8.03±2.3 in the IFD and pedicle screw groups, respectively, and improved postoperatively to 1.3±2.9 and 1.2±3.2 in 1-year follow ups (p<0.05). The K-ODI was decreased significantly in an equal amount in both groups one year postoperatively (p<0.05). The statistics revealed a higher incidence of ASD in pedicle screw group than the IFD group (p=0.029).
Posterior IFD has several advantages over the pedicle screw fixation in terms of skin incision, muscle dissection and short operative time and less intraoperative estimated blood loss. The IFD with PLIF may be a favorable technique to replace the pedicle screw fixation in selective case.
Degenerative; Fusion device; Interspinous; Lumbar disease; Posterior; Adjacent segmental degeneration
To evaluate the effect of extracorporeal shock wave therapy (ESWT) in myofascial pain syndrome of upper trapezius with visual analogue scale (VAS) and pressure threshold by digital algometer.
Twenty-two patients diagnosed with myofascial pain syndrome in upper trapezius were selected. They were assigned to treatment and standard care (control) groups balanced by age and sex, with eleven subjects in each group. The treated group had done four sessions of ESWT (0.056 mJ/mm2, 1,000 impulses, semiweekly) while the control group was treated by the same protocol but with different energy levels applied, 0.001 mJ/mm2. The VAS and pressure threshold were measured twice: before and after last therapy. We evaluated VAS of patients and measured the pressure threshold by using algometer.
There were two withdrawals and the remaining 20 patients were three men and 17 women. Age was distributed with 11 patients in their twenties and 9 over 30 years old. There was no significant difference of age, sex, pre-VAS and pre-pressure threshold between 2 groups (p>0.05) found. The VAS significantly decreased from 4.91±1.76 to 2.27±1.27 in the treated group (p<0.01). The control group did not show any significant changes of VAS score. The pressure threshold significantly increased from 40.4±9.94 N to 61.2±12.16 N in the treated group (p<0.05), but there was no significant change in the control group.
ESWT in myofascial pain syndrome of upper trapezius is effective to relieve pain after four times therapies in two weeks. But further study will be required with more patients, a broader age range and more males.
Extracorporeal shock wave therapy; Myofascial pain syndrome; Upper trapezius; Visual analogue scale; Pressure threshold
International Digestive Endoscopy Network (IDEN) is an international meeting covering scientific subjects of diverse topics about upper gastrointestinal (GI) endoscopy, colonoscopy, endoscopic ultrasonography, and PB endoscopy. IDEN is organized by Korean Society of Gastrointestinal Endoscopy and the Korean Gastrointestinal Endoscopy Research Foundation, and took its first step in 2011 in Seoul, Korea. IDEN inaugurated a new era of diagnostic and therapeutic GI endoscopy. IDEN 2012 was designed to offer participants from all over the world with opportunities to share up-to-date knowledge about basic and clinical aspects of GI endoscopy and to engage in in-depth discussion with worldwide well-known experts. During the 2 days of meeting, there were 62 invited lectures, 28 case-based discussions, 20 video lectures, and 6 breakfast with the experts. There were a total of 598 participants registered from 12 countries, including Asian countries, Europe, and USA as well as Korea.
International Digestive Endoscopy Network; Korean Society of Gastrointestinal Endoscopy; Endoscopy
Disease progression of ankylosing spondylitis has been considered irreversible. However, we report a case of spontaneous regression of syndesmophyte development following allogeneic peripheral blood stem cell transplantation in a patient with acute myeloid leukemia, who was also diagnosed as having ankylosing spondylitis. To the best of our knowledge, this is the first case report presenting the partial radiologic regression of syndesmophytes.
A 39-year-old man with active ankylosing spondylitis achieved clinical remission and partial radiological regression of cervical spine syndesmophytes following a peripheral blood stem cell transplantation for acute myeloid leukemia. Our patient received an allogeneic peripheral blood stem cell transplantation following a pre-transplantation conditioning regimen of total body irradiation and cyclophosphamide. The donor was a human leukocyte antigen-matched 29-year-old man. Our patient has remained asymptomatic and has received no medication for ankylosing spondylitis for nearly three years.
Several explanations are proposed for the regression of syndesmophytes and clinical improvement in active ankylosing spondylitis observed in our patient, including changes in bone remodeling and immune reconstitution following stem cell transplantation, the effect of immunosuppressive agents, or fluctuation in the natural course of ankylosing spondylitis although further studies are required. The regression of syndesmophytes in ankylosing spondylitis in this case raises the possibility that stem cell transplantation might contribute to the development of a novel therapeutic strategy for treatment of the disease.
The preoperative prediction of malignant potential in patients with gastric submucosal tumors (SMTs) plays an important role in decisions regarding their surgical management.
We evaluated the predictors of malignant gastric SMTs in 314 patients with gastric SMTs who underwent surgery in Chonnam National University Hospital.
The malignant SMTs were significantly associated with age (odds ratio [OR], 1.067; 95% confidence interval [CI], 1.042 to 1.091; P < 0.0001), presence of central ulceration (OR, 2.690; 95% CI, 1.224 to 5.909; P = 0.014), and tumor size (OR, 1.791; 95% CI, 1.483 to 2.164; P < 0.0001). Receiver operating characteristic curve analysis showed that tumor size was a good predictor of malignant potential. The most relevant predictor of malignant gastric SMT was tumor size with cut-offs of 4.05 and 6.40 cm.
Our findings indicated that age, central ulceration, and tumor size were significant preoperative predictors of malignant SMTs. We suggest that 4 cm be selected as a threshold value for malignant gastric SMTs. In patients with a gastric SMT larger than 4 cm with ulceration, wide resection of the full thickness of the gastric wall or gastrectomy with adequate margins should be performed because of its malignant potential.
Stomach neoplasms; Submucosal tumor; Malignant factor; Preoperative predictor
Little is known about the clinicopathological features of female gastric carcinoma (FGC) patients. We compared the clinicopathologic features and outcomes of FGC patients with curative resection with those of male gastric carcinoma (MGC) patients. We reviewed the hospital records of 940 FGC patients between 1986 and 2005 at Chonnam National University Hospital. Multivariate analysis showed that presence of serosal invasion, lymph node metastasis, and operative type were significant prognostic factors for survival of FGC patients with curative resection. Furthermore, the overall 5-year survival rate of FGC patients with curative resection (53.4%) was higher than that of MGC patients (47.6%, p<0.05). In advanced cases, no significant difference was observed in the overall 5-year survival rate between the FGC and MGC patients (41.6% vs 37.4%, p>0.05). Therefore, serosal invasion, lymph node metastasis, and type of operation were statistically significant parameters associated with survival. Early detection is more important for improving the prognosis of female patients with gastric cancer than for male patients.
Female gastric carcinoma; Prognosis; Early detection of cancer