The criteria by Camitta for diagnosis in severe aplastic anemia (SAA) has been used since 1976. However, there has been no attempt to verify the Camitta's criteria, that the survival in patients with SAA may differ by absolute neutrophil count (ANC), platelet count (PLT), and corrected reticulocyte count (CRC), which are components of the Camitta's criteria.
117 SAA patients diagnosed by the Camitta's criteria were analyzed, retrospectively. Univariate and multivariate analyses were used to evaluate the factors affecting overall survival (OS).
Response by immunosuppressive therapy (IST) or stem cell transplantation (SCT) significantly affected OS (P=0.001). Therefore, we excluded treatment responders for analysis. Finally, 92 SAA patients including treatment non-responders by IST or SCT and conservative care group were analyzed by using univariate and multivariate analyses. The median age of analyzed patients was 54.5 years. Male to female ratio was 1:1. The median follow-up duration was 74.23 months (range, 54.71-93.74 months). The median ANC, PLT, and CRC were 394/µL, 12,000/µL, and 0.39%, respectively. In multivariate analyses, ANC <500/µL or ≥500/µL (P=0.015, HR 2.694, 95% CI: 1.20-6.01) and age (P=0.015, HR 1.022, 95% CI: 1.00-1.04) were the significant factors for OS.
ANC could be an essential, not an optional criterion for diagnosing SAA. This study suggests the possibility that the Camitta's criteria be modified. Studies in large cohorts are needed to transform the Camitta's criteria.
Camitta's criteria; Severe aplastic anemia; Absolute neutrophil count
AIM: To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis (LMC) of gastric cancer.
METHODS: We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to 2007.
RESULTS: The male-to-female ratio was 32:22, and the patients ranged in age from 28 to 78 years (median, 48.5 years). The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clinical or pathologic tumor, node and metastasis stage of the primary gastric cancer was IV in 38 patients (70%). The median interval from diagnosis of the primary malignancy to the diagnosis of LMC was 6.3 mo, ranging between 0 and 73.1 mo. Of the initial endoscopic findings for the 45 available patients, 23 (51%) of the patients were Bormann type III and 15 (33%) patients were Bormann type IV. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache (85%) and nausea/vomiting (58%) were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases (82%). Intrathecal (IT) chemotherapy was administered to 36 patients-primarily methotrexate alone (61%), but also in combination with hydrocortisone/± Ara-C (39%). The median number of IT treatments was 7 (range, 1-18). Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Seventeen patients (46%) achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk (95% CI: 4.3-9.1 wk). In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration (P = 0.038, P = 0.010, and P = 0.002, respectively). However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer survival duration (3.6, 6.7 and 14.6 wk, P = 0.030, RR: 0.415, 95% CI: 0.188-0.918).
CONCLUSION: Although these patients had a fatal clinical course, cytologic negative conversion by IT chemotherapy may improve survival.
Carcinomatosis; Gastric cancer; Intrathecal chemotherapy; Leptomeningeal
AIM: To assess the prognostic significance of nuclear factor-κB (NF-κB) and its target genes in gastric cancer.
METHODS: The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-κB RelA. Preoperative serum levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) were assessed via enzyme-linked immuno-sorbent assay. C-reactive protein (CRP) and serum amyloid A (SAA) were measured via immunotrubidimetry.
RESULTS: Positive rate of NF-κB RelA was 42.6%. NF-κB RelA expression in tumor tissues was also related to serum levels of IL-6 (P = 0.044) and CRP (P = 0.010). IL-6, SAA, CRP were related to depth of invasion, VEGF and SAA were correlated with lymph node metastasis. IL-6, VEGF, SAA and CRP were related to the stage. Univariate analysis demonstrated that immunostaining of NF-κB RelA, levels of IL-6, VEGF, SAA were significantly related with both disease free survival and overall survival (OS). Multivariate analysis verified that NF-κB RelA [hazard ratio (HR): 3.40, P = 0.024] and SAA (HR: 3.39, P = 0.045) were independently associated with OS.
CONCLUSION: Increased expression of NF-κB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients.
Nuclear factor-κB; Vascular endothelial growth factor; Interleukin-6; C-reactive protein; Serum amyloid A; Stomach; Carcinoma
Myelodysplastic syndrome (MDS) is a preleukemic condition that transforms into acute myeloid leukemia. However, the genetic events underlying this transformation remain poorly understood. Aberrant DNA methylation may play a causative role in the disease and its prognosis. Thus, we compared the DNA methylation profiles in refractory anemia with excess blast (RAEB) to those in refractory cytopenia with multilineage dysplasia (RCMD).
Bone marrow samples were collected from 20 patients with primary MDS (9 with RAEB and 11 with RCMD), and peripheral blood samples were collected from 4 healthy controls. These samples were assessed using a commercial whole genome-wide methylation assay. Methylation-specific polymerase chain reaction (PCR) was used to detect the methylation of candidate gene promoters in RAEB and RCMD.
Microarray data revealed significant hypermethylation in 69 genes within RAEB but not RCMD. Candidate genes were mapped to 5 different networks, and network 1 had the highest score due to its involvement in gene expression, cancer, and cell cycle. Five genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with malignant disease progression. Among them, the methylated promoter pairs of GSTM5 (55.5% and 20%), BIK (20% and 0%), and ANGPTL2 (44.4% and 10%) were observed more frequently in RAEB.
DNA methylation of GSTM5, BIK, and ANGPTL2 may induce epigenetic silencing and contribute to the increasing blasts and resulting MDS progression; however, the functions of these genes were not determined. Further study focusing on epigenetic silencing using various detection modalities is required.
Myelodysplastic syndrome; DNA methylation; GSTM5; ANGPTL2; BIK
Numerous studies have shown both the detrimental and beneficial effects of reactive oxygen species (ROS) in animals, plants, and fungi. These organisms utilize controlled generation of ROS for signaling, pathogenicity, and development. Here, we show that ROS are essential for the pathogenic development of Sclerotinia sclerotiorum, an economically important fungal pathogen with a broad host range. Based on the organism's completed genome sequence, we identified two S. sclerotiorum NADPH oxidases (SsNox1 and SsNox2), which presumably are involved in ROS generation. RNA interference (RNAi) was used to examine the function of SsNox1 and SsNox2. Silencing of SsNox1 expression indicated a central role for this enzyme in both virulence and pathogenic (sclerotial) development, while inactivation of the SsNox2 gene resulted in limited sclerotial development, but the organism remained fully pathogenic. ΔSsnox1 strains had reduced ROS levels, were unable to develop sclerotia, and unexpectedly correlated with significantly reduced oxalate production. These results are in accordance with previous observations indicating that fungal NADPH oxidases are required for pathogenic development and are consistent with the importance of ROS regulation in the successful pathogenesis of S. sclerotiorum.
Nucleotide excision repair (NER) modulates platinum-based chemotherapeutic efficacy by removing drug-produced DNA damage. To summarize published data on the association between polymorphisms of NER genes (ERCC1 and ERCC2) and responses to oxaliplatin-based chemotherapies, we performed a meta-analysis of gastric and colorectal cancer for commonly studied polymorphisms ERCC1 rs11615C>T and ERCC2 rs13181T>G.
Patients and methods
In 17 previous published studies, 1787 cancer patients were treated with the oxaliplatin-based regimen. Primary outcomes included therapeutic response (TR) (i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS) and overall survival (OS). We calculated odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) to estimate the risk or hazard.
We found consistent and clinically substantial risk or hazard for TR, PFS and OS in the oxaliplatin-treated gastric and colorectal cancer patients with an ethnic discrepancy. For ERCC1 rs11615C>T, the T allele was associated with reduced response, PFS and OS in Asians (TR: OR, 0.53 and 95% CI, 0.35–0.81; PFS: HR, 1.69 and 95% CI, 1.05–2.70; and OS: HR, 2.03 and 95% CI, 1.60–2.59). For ERCC2 rs13181T>G, the G allele was associated with reduced response, PFS and OS in Caucasians (TR: OR, 0.56 and 95% CI, 0.35–0.88; PFS: HR, 1.41 and 95% CI, 1.02–1.95; and OS: HR, 1.42 and 95% CI, 1.11–1.81).
NER ERCC1 rs11615C>T and ERCC2 rs13181T>G polymorphisms are useful prognostic factors in oxaliplatin treatment of gastric and colorectal cancer. Larger studies and further clinical trials are warranted to confirm these findings.
Chemotherapy; DNA repair; Meta-analysis; Pharmacogenetics; Platinum
The optical properties of In0.8Ga0.2As self-assembled quantum dots (SAQDs) grown on GaAs wire structures formed by utilizing SiO2-patterned exact and 5°-off (001) GaAs substrates have been studied with micro-photoluminescence (μ-PL). Single PL peak was occurred for In0.8Ga0.2As SAQDs grown on SiO2-patterned exact (001) GaAs, whereas double PL peaks were showed for SAQDs grown on 5°-off (001) GaAs substrates as the width of the opening windows increased. The power-dependent μ-PL spectra show that the first and second peaks of these double peaks were originated from the well-defined ground and excited state, respectively. These results demonstrated that In0.8Ga0.2As SAQDs selectively grown by utilizing SiO2-patterned 5°-off (001) GaAs substrates have well-defined zero-dimensional quantum states.
Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is common and is the second most common cause of death. Clinical studies regarding chemotherapy for CRC with PC have been classically rather limited in scope. We evaluated the efficacy of modified oxaliplatin, leucovorin, and fluorouracil (m-FOLFOX4) regimen for PC of CRC origin.
Materials and Methods
CRC patients with PC were treated with cycles of oxaliplatin at 85 mg/m2 on day 1, leucovorin 20 mg/m2 followed by 5-fluorouracil (5-FU) via a 400 mg/m2 bolus and a 22 hours continuous infusion of 600 mg/m2 5-FU on days 1-2 at 2-week intervals.
Forty patients participated in this study. Median age was 55 years. Thirty-two patients (80.0%) received previous operation, and 60.0% of PC occurred synchronously. Thirty-five patients (87.5%) were assessable and exhibited measurable lesions. Two patients (5.7%) demonstrated complete response and five patients (14.3%) showed partial response. The median time to progression was 4.4 months (95% confidence interval, 2.5 to 6.3 months), the median overall survival time was 21.5 months (95% confidence interval, 17.2 to 25.7 months). There was no treatment related death. Presence of liver metastasis (p=0.022), performance status (p=0.039), and carcinoembryonic antigen level (p=0.016) were related to the time to progression. Patients with low carcinoembryonic antigen level (37.2 months vs. 15.6 months, p=0.001) or good performance status (22.5 months vs. 6.8 months, p=0.040) showed better overall survival.
The m-FOLFOX4 regimen was determined to be effective for CRC patients with PC.
Colorectal neoplasms; Peritoneum; Carcinoma; Drug therapy
Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus with an extremely broad host range. This pathogen produces the non-specific phytotoxin and key pathogenicity factor, oxalic acid (OA). Our recent work indicated that this fungus and more specifically OA, can induce apoptotic-like programmed cell death (PCD) in plant hosts, this induction of PCD and disease requires generation of reactive oxygen species (ROS) in the host, a process triggered by fungal secreted OA. Conversely, during the initial stages of infection, OA also dampens the plant oxidative burst, an early host response generally associated with plant defense. This scenario presents a challenge regarding the mechanistic details of OA function; as OA both suppresses and induces host ROS during the compatible interaction. In the present study we generated transgenic plants expressing a redox-regulated GFP reporter. Results show that initially, Sclerotinia (via OA) generates a reducing environment in host cells that suppress host defense responses including the oxidative burst and callose deposition, akin to compatible biotrophic pathogens. Once infection is established however, this necrotroph induces the generation of plant ROS leading to PCD of host tissue, the result of which is of direct benefit to the pathogen. In contrast, a non-pathogenic OA-deficient mutant failed to alter host redox status. The mutant produced hypersensitive response-like features following host inoculation, including ROS induction, callose formation, restricted growth and cell death. These results indicate active recognition of the mutant and further point to suppression of defenses by the wild type necrotrophic fungus. Chemical reduction of host cells with dithiothreitol (DTT) or potassium oxalate (KOA) restored the ability of this mutant to cause disease. Thus, Sclerotinia uses a novel strategy involving regulation of host redox status to establish infection. These results address a long-standing issue involving the ability of OA to both inhibit and promote ROS to achieve pathogenic success.
Necrotrophic fungal pathogens need to kill plant cells to establish disease and obtain nutrition. While such pathogens are economically important, they are relatively understudied and mechanistic details important for pathogenic success are limited. Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus that infects virtually all dicotyledonous (>400 species) plants. Our data indicate that oxalic acid production and modulation of reactive oxygen species (ROS) are key components for the successful interaction of this fungus with the host plant. Here, we use a GFP regulated reporter system to analyze the host redox status during infections with wild type and a non-pathogenic oxalic acid (OA) deficient Sclerotinia mutant. Additionally, we show that secreted OA enables Sclerotinia to hijack the host cell redox machinery, initially creating reducing conditions followed by an oxidizing environment that is necessary for pathogenesis. We also provide evidence that the OA-deficient mutants are actively recognized by the plant resulting in the elicitation of a hypersensitive-like response and resistance. Our study provides insight into how Sclerotinia, and quite possibly other necrotrophic pathogens, co-opt host redox and cell death pathways for successful colonization of the host.
Cleidocranial dysplasia (CCD) is caused by haploinsufficiency in RUNX2 function. We have previously identified a series of RUNX2 mutations in Korean CCD patients, including a novel R131G missense mutation in the Runt-homology domain. Here, we examine the functional consequences of the RUNX2R131G mutation, which could potentially affect DNA binding, nuclear localization signal, and/or heterodimerization with core binding factor-β (CBF-β). Immunofluorescence microscopy and western blot analysis with subcellular fractions show that RUNX2R131G is localized in the nucleus. Immunoprecipitation analysis reveals that heterodimerization with CBF-β is retained. However, precipitation assays with biotinylated oligonucleotides and reporter gene assays with RUNX2 responsive promoters together reveal that DNA binding activity and consequently the trans-activation of potential of RUNX2R131G is abrogated. We conclude that loss of DNA binding, but not nuclear localization or CBF-β heterodimerization, causes RUNX2 haploinsufficiency in patients with the RUNX2R131G mutation. Retention of specific functions including nuclear localization and binding to CBF-β of the RUNX2R131G mutation may render the mutant protein an effective competitor that interferes with wild type function.
RUNX2; RUNX2R131G; Core binding factor-β (CBF-β); Cledocranial dysplasia (CCD); subcellular localization; heterodimerization; DNA binding activity; Trans-activation
The role of first-line trastuzumab-based therapy has been firmly established in patients with human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer. In this trial, we evaluated the efficacy and safety of a vinorelbine and trastuzumab combination chemotherapy in patients who were pretreated with anthracyclines and taxanes.
Thirty-three patients with HER2 overexpressing metastatic breast cancer, all of whom had previously been treated with anthracyclines and taxanes, were included in this study. The patients were treated with 25 mg/m2 of vinorelbine (over a 15-minute infusion) on days 1 and 8 every 3 weeks. Additionally, trastuzumab was administered at an initial dose of 4 mg/kg over 90 minutes, and was subsequently administered at weekly doses of 2 mg/kg (over 30 minutes).
The median age of the patients was 53 years (range, 39-72 years). The overall response rate was 30.3% (10 patients; 95% confidence interval [CI], 23-57%). The median time to progression was 6.8 months (95% CI, 5.3-8.2 months). The median overall survival was 12.4 months (95% CI, 10.3-14.6 months). In the 194 cycles of treatment, the incidence rates of grade ≥3 neutropenia and anemia were 7.2% and 1.0%, respectively. Neutropenic fever was detected in three cycles (1.5%). The non-hematological toxicities were not severe: grade 1 or 2 nausea or vomiting was detected in 15.2%, and grade 2 neuropathy was noted in 6.1% of patients. None of the patients experienced any serious cardiac toxicity, and no treatment-related deaths occurred.
These results show that a combination chemotherapy consisting of vinorelbine and trastuzumab is useful in patients with HER2-overexpressing metastatic breast cancer who were pretreated with anthracyclines and taxanes, with a favorable toxicity profile.
Breast neoplasms; Metastasis; Trastuzumab; Vinorelbine
Relatively little has been studied on the AMA-1 vaccine against Plasmodium vivax and on the plasmid DNA vaccine encoding P. vivax AMA-1 (PvAMA-1). In the present study, a plasmid DNA vaccine encoding AMA-1 of the reemerging Korean P. vivax has been constructed and a preliminary study was done on its cellular immunogenicity to recipient BALB/c mice. The PvAMA-1 gene was cloned and expressed in the plasmid vector UBpcAMA-1, and a protein band of approximately 56.8 kDa was obtained from the transfected COS7 cells. BALB/c mice were immunized intramuscularly or using a gene gun 4 times with the vaccine, and the proportions of splenic T-cell subsets were examined by fluorocytometry at week 2 after the last injection. The spleen cells from intramuscularly injected mice revealed no significant changes in the proportions of CD8+ T-cells and CD4+ T-cells. However, in mice immunized using a gene gun, significantly higher (P<0.05) proportions of CD8+ cells were observed compared to UB vector-injected control mice. The results indicated that cellular immunogenicity of the plasmid DNA vaccine encoding AMA-1 of the reemerging Korean P. vivax was weak when it was injected intramuscularly; however, a promising effect was observed using the gene gun injection technique.
Plasmodium vivax; DNA vaccine; apical membrane antigen (AMA); CD8+ T-cell; gene gun
The essential osteoblast-related transcription factor Runx2 and the female steroid hormone estrogen are known to play pivotal roles in bone homeostasis; however, the functional interaction between Runx2- and estrogen-mediated signaling in skeletal tissues is minimally understood. Here we provide evidence that aromatase (CYP19), a rate-limiting enzyme responsible for estrogen biosynthesis in mammals, is transcriptionally regulated by Runx2. Consistent with the presence of multiple Runx2 binding sites, the binding of Runx2 to the aromatase promoter was demonstrated in vitro and confirmed in vivo by chromatin immunoprecipitation assays. The bone-specific aromatase promoter is activated by Runx2, and endogenous aromatase gene expression is upregulated by Runx2 overexpression, establishing the aromatase gene as a target of Runx2. The biological significance of the Runx2 transcriptional control of the aromatase gene is reflected by the enhanced estrogen biosynthesis in response to Runx2 in cultured cells. Reduced in vivo expression of skeletal aromatase gene and low bone mineral density are evident in Runx2 mutant mice. Collectively, these findings uncover a novel link between Runx2-mediated osteoblastogenic processes and the osteoblast-mediated biosynthesis of estrogen as an osteoprotective steroid hormone.
Coughing is a side effect of opioids that is rarely studied. Here, we evaluated the incidence of remifentanil induced coughing during anesthesia induction in an attempt to identify its risk factors and to examine the preventive effects of lidocaine and salbutamol.
A total of 237 patients scheduled to undergo general anesthesia were allocated randomly into three groups. Group C received no medication, while Group L received 2% lidocaine at 0.5 mg/kg intravenously 1 minute prior to remifentanil infusion and Group S inhaled one metered aerosol puff of salbutamol 15 minutes prior to entering the operating room. Remifentanil was infused at 5 ng/ml by target controlled infusion and coughing was measured for five minutes and graded as none, mild, moderate, or severe based on the number of coughs.
The incidences of coughing were 30.4%, 25.3%, and 35.4% in Groups C, L, and S, respectively. The incidences, onset times, and severity of coughing did not differ significantly among groups. In addition, multivariate analysis showed that non-smoking and a lower body weight were risk factors of remifentanil-induced coughing (odds ratio, 8.13; P = 0.024, 1.11, and 0.004, respectively).
The incidence of remifentanil-induced coughing was 30%. A total of 0.5 mg/kg lidocaine and 1 metered aerosol puff of salbutamol did not prevent coughing. Non-smoking and low body weight were found to be risk factors of remifentanil-induced coughing.
Cough; Lidocaine; Remifentanil; Salbutamol
We report a case of interruption in the supply of breathing gas during general anesthesia caused by malposition of the Drager Vapor 2000® vaporizer, which was accidentally tilted and lifted off the Selectatec manifold of the anesthesia machine. Because the patient was an 1-month-old infant, we couldn't check if he had experienced awareness with recall. We emphasize the importance of checking the anesthetic vaporizer after mounting it on the back bar of the anesthesia machine.
Gas leak; Selectatec; Vaporizer
Patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at risk for experiencing serious adverse effects following 5-fluorouracil (5-FU) based chemotherapy. Neurotoxicity is considered an extremely rare side effect of 5-FU. We report here on an unusual case of 5-FU induced encephalopathy. A 38-year-old woman with advanced gastric carcinoma was treated with adjuvant chemotherapy that consisted of infused 5-FU (1,000 mg/m2) for 5 days and cisplatin (60 mg/m2) on day 1 following total gastrectomy. Nineteen days after starting chemotherapy, the patient displayed a sudden onset of slurred speech, confusion, cognitive disturbances and paranoia. A magnetic resonance image (MRI) of the brain showed no structural abnormalities, and the other laboratory tests provided no explanations for her symptoms, other than a slightly elevated ammonia level. The patient was treated with a lactulose retention enema and thiamine infusion, the 5-FU was halted and her symptoms then recovered after 7 days.
5-FU; Neurotoxicity; Encephalopathy
A combination of busulfan (Bu) and cyclophosphamide (Cy) has been used as a standard myeloablative regimen for allogeneic hematopoietic stem cell transplantation (HSCT). Recent studies postulate that fludarabine (Flu) is a less toxic substitute for Cy.
Forty-two patients who were diagnosed with acute leukemia or myelodysplastic syndrome and received BuFlu (n=17) or BuCy (n=25) from August, 1999 to July, 2009 at Dong-A University Medical Center were retrospectively analyzed.
The median follow-up duration was 39.75 months. The BuFlu group showed a lower incidence of mucositis (P=0.005), but there was no significant intergroup difference in the time of engraftment, nausea/vomiting, acute/chronic graft-versus-host disease, hepatic veno-occlusive disease, or hemorrhagic cystitis. Moreover, the 2 groups showed no significant difference in the cumulative risk of relapse, event-free survival, or overall survival.
BuFlu administration can be employed as a preparative regimen for allogeneic HSCT and shows efficacy and transplant-adverse effects comparable to those of BuCy. However, randomized prospective studies in more patients are warranted.
Myeloablative regimen; Allogeneic hematopoietic stem cell transplantation; Fludarabine; Busulfan
A pathologic splenic rupture refers to a rupture without trauma. A splenic rupture as the initial manifestation of acute myeloid leukemia is extremely rare. In this study, we described a rare case of acute myeloid leukemia presenting principally as an acute abdomen due to a pathologic splenic rupture in a 35-year old male patient. We can assert that a pathologic splenic rupture in hematologic diseases is a potentially life-threatening complication, which necessitates immediate operative intervention. Any such patient complaining about left upper abdominal tenderness should be closely observed, and further diagnostic investigations (ultrasonograph of the abdomen, abdominal CT scan) should be initiated in order to rule out a splenic rupture. The oncologist should be aware of this rare initial presentation of acute myeloid leukemia (AML) M2, as the condition generally necessitates a prompt splenectomy.
Acute myeloid leukemia M2; pathologic; splenic rupture
4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is a major costimulatory receptor that is rapidly expressed on the surface of CD4+ and CD8+ T cells after antigen- or mitogen-induced activation. The interaction of 4-1BB with 4-1BBL regulates immunity and promotes the survival and expansion of activated T cells. In this study, the expression of 4-1BB and 4-1BBL was examined during regeneration of the murine thymus following acute cyclophosphamide-induced involution. Four-color flow cytometry showed that 4-1BB and 4-1BBL were present in the normal thymus and were preferentially expressed in the regenerating thymus, mainly in CD4+CD8+ double-positive (DP) thymocytes. Furthermore, the CD4loCD8lo, CD4+CD8lo and CD4loCD8+ thymocyte subsets, representing stages of thymocyte differentiation intermediate between DP and single-positive (SP) thymocytes, also expressed 4-1BB and 4-1BBL during thymus regeneration but to a lesser degree. Interestingly, the 4-1BB and 4-1BBL positive cells among the CD4+CD8+ DP thymocytes present during thymus regeneration were TCRhi and CD69+ unlike the corresponding controls. Moreover, the 4-1BB and 4-1BBL positive cells among the intermediate subsets present during thymus regeneration also exhibited TCRhi/int and CD69+/int phenotypes, indicating that 4-1BB and 4-1BBL are predominantly expressed by the positively selected population of the CD4+CD8+ DP and the intermediate thymocytes during thymus regeneration. RT-PCR and Western blot analyses confirmed the presence and elevated levels of 4-1BB and 4-1BBL mRNA and protein in thymocytes during thymus regeneration. We also found that the interaction of 4-1BB with 4-1BBL promoted thymocyte adhesion to thymic epithelial cells. Our results suggest that 4-1BB and 4-1BBL participate in T lymphopoiesis associated with positive selection during recovery from acute thymic involution.
4-1BB ligand; antigens, CD137; cell differentiation; thymus gland; T-lymphocytes
The Tamjin River which flows from Jangheung-gun via Gangjin-gun to the South Sea was reported to be a highly endemic area of Metagonimus yokogawai infection in 1977 and 1985. However, there were no recent studies demonstrating how much change occurred in the endemicity, in terms of prevalence and worm burden, of metagonimiasis in this river basin. Thus, a small-scale epidemiological survey was carried out on some residents along the Tamjin River basin in order to determine the current status of M. yokogawai infection. A total of 48 fecal samples were collected and examined by the Kato-Katz thick smear and formalin-ether sedimentation techniques. The egg positive rate of all helminths was 50.0%, and that of M. yokogawai was 37.5%, followed by C. sinensis 22.9% and G. seoi 4.2%. To obtain the adult flukes of M. yokogawai, 6 egg positive cases were treated with praziquantel 10 mg/kg in a single dose and purged with magnesium sulfate. A total of 5,225 adult flukes (average 871 specimens per person) of M. yokogawai were collected from their diarrheic stools. Compared with the data reported in 1977 and 1985, the individual worm burdens appeared to have decreased remarkably, although the prevalence did not decrease at all. It is suggested that the endemicity of M. yokogawai infection along the Tamjin River has been reduced. To confirm this suggestion, the status of infection in snail and fish intermediate hosts should be investigated.
Metagonimus yokogawai; human infection; prevalence; endemicity; Tamjin River
To evaluate the usefulness of the Korean Isolate-1 (KI-1) antigen for serodiagnosis of toxoplasmosis, antigen profiles of KI-1 tachyzoites were analyzed in comparison with RH tachyzoites by SDS-PAGE and immunoblotting. ELISA was performed on latex agglutination (LA)-positive and negative serum samples using KI-1 and RH antigens. Immunoblotting of the KI-1 antigen showed multiple antigen bands with molecular sizes of 22-105 kDa. Among them, 1 and 6 common bands were noted against a KI-1-infected and a RH-infected human serum, respectively, which represented differences in antigenic profiles between KI-1 and RH tachyzoites. However, all 9 LA-positive human sera were found positive by ELISA, and all 12 LA-negative sera were negative by ELISA; the correlation between the ELISA titers and LA titers was high (r = 0.749). Our results suggest that tachyzoites of KI-1 may be useful for serodiagnosis of human toxoplasmosis.
Toxoplasma gondii; Toxoplasmosis; Korean isolate-1 (KI-1); RH strain; Serodiagnosis; Antigen
To evaluate mid-term imaging, clinical follow-up, and restenosis rates from patients that had undergone percutaneous transluminal renal artery angioplasty (PTRA) for symptomatic renal artery fibromuscular dysplasia (FMD).
Materials and Methods
Between March 1999 and July 2006, 16 consecutive renal artery FMD patients underwent PTRA for poorly controlled hypertension. The patients were enrolled into this retrospective study after receiving 19 primary and four secondary PTRAs in 19 renal artery segments. Follow-up monitoring of blood pressure, use of antihypertensive medication, and the serum creatinine level after PTRA were assessed at 1, 3, 6, 9, 12 months, and each following year. The degree of restenosis was evaluated with computed tomographic angiography (CTA) after PTRA at 6, 12 months, and every year if possible. Technical and clinical success rates for the treatment of FMD, and restenosis rates for the renal artery were evaluated.
The technical success rate for primary PTRA was 79% (15/19) and the complication rate was 16% (3/19). Hypertension improved in 80% (12/15) of the patients after four weeks follow-up, and was finally cured or improved in 93% (14/15) during the mean follow-up period of 23.6 months. There was a cumulative 22% (4/18) restenosis rate during the follow-up period. All of the patients were treated with a second PTRA without complications and all of the patients were cured of hypertension after the second PTRA.
Percutaneous transluminal renal artery angioplasty for clinically symptomatic renal FMD is technically and clinically successful and safe to perform. For all patients with restenosis, there was a good response after undergoing a second PTRA.
Percutaneous transluminal renal artery angioplasty; Fibromuscular dysplasia; Renal artery stenosis, angioplasty; Renovascular hypertension
Extranodal presentation of diffuse large B cell lymphoma (DLBL) is frequently observed in the gastrointestinal tract, CNS, bone, testes and liver. However, the simultaneous detection of multiple extranodal involvement at presentation is quite an uncommon occurrence. In this study, we report on a patient with an uncommon presentation of DLBL, and he had symptoms of left knee joint pain and hematemesis, characterized by bone and stomach involvement. Computed tomography and fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning revealed a rapid, extensive spread to the bones and soft tissues. Subsequent histopathological examination verified the bony and gastric CD20-positive DLBL localization. We diagnosed this case as DLBL of stage IV with an international prognostic index of 3, and classified him into the high intermediate risk group. This patient was treated via chemotherapy with an R-CHOP regimen. After achieving a partial response, the patient received autologous peripheral blood stem cell transplantation. The patient attained partial remission, as shown on the FDG-PET scan, and he displayed improvement of his left femur pain.
Extranodal; Diffuse large B-cell lymphoma; Stomach; Bone
A case of Diphyllobothrium latum infection in a 49-year old man is described, and diphyllobothriasis latum in the Republic of Korea is briefly reviewed. An incomplete strobila of a tapeworm, 95 cm in length, without scolex and neck, was spontaneously discharged in the feces of a patient. On the basis of morphologic characteristics of the worm and eggs, the worm was identified as D. latum. The patient was successfully treated with a single dose (15 mg/kg) of praziquantel. The most probable source of infection was salmon flesh according to the past history of the patient. The first case of D. latum infection was documented in 1971, and this is the 43rd recorded case in the Republic of Korea. The 43 cases were briefly reviewed. The patients' main complaints were gastrointestinal troubles, such as mild abdominal pain, indigestion, and diarrhea, and discharge of tapeworm segments in the feces. The suspected infection sources included raw or improperly cooked flesh of fresh or brackish water fish, including the perch, mullet, salmon, and trout.
Diphyllobothrium latum; salmon; praziquantel; case report; review
Mesenchymal chondrosarcoma is a rare cartilaginous ne - oplasm of an extraskeletal origin, and this predominately occurs in the head and neck, and also in the lower extremities. Fewer than twenty cases of cardiac mesenchymal chondrosarcoma have so far been reported on. For the most part, the results of treatment for patients with this condition have been dismal. In this study, we describe a case of cardiac mesenchymal chondrosarcoma that responded to chemotherapy following surgical biopsy. A 46-year-old man was referred for evaluation of his pleural effusions in both lungs. Chest computed tomography revealed an ovoid-shaped mass in the posterior wall of the patient's left atrium. The echocardiogram revealed a large ovoid-shaped immobile mass (11×6 cm2) in the pericardiac space, which was attached to the posterior wall of the left atrium. Emergency pericardiostomy with closure thoracostomy was performed. Seven days later, a thoracotomy was performed for reduction and diagnosis of the cardiac mass. The pathological diagnosis was extraskeletal mesenchymal chondrosarcoma of the heart.. Postoperative chemotherapy was performed for the huge remaining mass with a combined regimen of etoposide, ifosfamide and cisplatin. After 6 cycles, the patient showed a partial response without symptoms. Although cardiac mesenchymal chondrosarcoma has been reported to be chemotherapy-resistant with a short survival duration, chemotherapy may prove to be an effective treatment modality.
Mesenchymal chondrosarcoma; Extraskeletal; Heart