PURPOSE:The primary biliary carcinoma is usually unresectable at presentation, because of early lymphatic spread. To determine the incidence and the spread pattern of lymph node metastases according to the location of the primary tumor, we analyzed the CT scans of the patients with primary biliary adenocarcinome. MATERIALS AND METHODS: We reviewed the CT scans of 92 patients with pathologically proven primary biliary adenocarcinoma, including 45 peripheral cholangiocarcinomas, 22 hilar cholangiocarcinomas, 18 gallbladder carcinomas, and 7 common bile duct carcinomas. Positive adenopathy was diagnosed when the node exceeded 10 mm in short axis. RESULTS:The overall incidence of nodal metastases was 59.8 % (55/92); 66.7 % in peripheral cholangiocarcinoma, 54.5 % in hilar cholangiocarcinoma, 55.6 % in gallbladder carcinoma, and 42.9 % in common bile duct carcinoma. The most commonly involved nodal group was the lesser omentum, followed by the celiac, periaortic, and peripancreatic group. The phrenic node group was only involved in the cases with the peripheral or hilar cholangiocarci nome. CONCLUSION:The primary biliary carcinoma has a high incidence of lymph node metastases at the time of diagnosis, and shows different nodal spread pattern according to the location of the primary tumor. Involvement of the phrenic node was limited to the peripheral and hilar cholangiocarcinoma.
Adenocarcinoma ; Axis, Cervical Vertebra ; Biliary Tract* ; Cholangiocarcinoma ; Common Bile Duct ; Diagnosis ; Gallbladder ; Humans ; Incidence ; Lymph Nodes* ; Neoplasm Metastasis* ; Omentum ; Tomography, X-Ray Computed

Evaluation of postpneumonectomy space (PPS) by CT in patients with lung cancer for operation-related complication or tumor recurrence is critical, but often difficult. We retrospectively analysed CT scans of 38 patients who underwent pneumonectomy for lung cancer. CT scans were obtained on 7-10th post-operative day for baseline image and at varying intervals of 2 to 24 months thereafter. Usual postoperative findings in patients without complication included mediastinal shifting, changes in subpleural space, changes in parietal pleura, and herniation of contralateral lung. Four patients had postoperative complications including empyema(n=3) and bronchopleural fistula(n=2). Twelve patients showed findings of tumor recurrence such as lymph node metastasis, local recurrence, and pericardial and contralateral pleural effusion. By comparing follow-up CT with baseline CT, we were able to detect early cancer recurrence and postoperative complications. Our results indicate that serial chest CT play an important role in the evaluation of the patients who underwent pneumonectomy for lung cancer.
Follow-Up Studies ; Humans ; Lung Neoplasms* ; Lung* ; Lymph Nodes ; Neoplasm Metastasis ; Pleura ; Pleural Effusion ; Pneumonectomy* ; Postoperative Complications ; Recurrence ; Retrospective Studies ; Thorax* ; Tomography, X-Ray Computed*

Low molecular weight GTP-binding proteins are molecular switches that are believed to play pivotal roles in cell growth, differentiation, cytoskeletal organization, and vesicular trafficking. Rab proteins are key players in the regulation of vesicular transport, while Rho family members control actin-dependent cell functions, i.e. the regulation of cytoskeletal organization in response to extracelluar growth factors and in dendritic neuron development. In this study, we have examined the regulation of small GTP-binding proteins that are implicated in neurosecretion and differentiation of neuron during ageing processes. Comparison of small GTP-binding proteins from the synaptosome and crude synaptic vesicles (LP2 membranes) of 2 months and 20 months old rat brain respectively showed no difference in the level of Rab family proteins (Rab3A and Rab5A). However, Rho family proteins such as RhoA and Cdc42 were elevated in LP2 membranes of the aged brain. The dissociation of Rab3A by Ca2+/calmodulin (CaM) from SV membranes was not changed during aging. Ca2+/CaM stimulated phosphorylation of the 22 and 55-kDa proteins in SV membranes from the aged rat brain, and inhibited phosporylation of 30-kDa proteins. GTPgammaS inhibited phosphorylation of the 100-kDa proteins and stimulated phosphorylation of the 70 kDa in LP2 membranes from both the young and aged rat brains, whereas GDPbetaS caused just the opposite reaction. These results suggest that protein phosphorylation and regulation of Rho family GTPases in rat brain appears to be altered during ageing processes.
*Aging ; Animal ; Brain/metabolism ; Calcium/pharmacology ; Cattle ; Comparative Study ; GTP-Binding Proteins/*metabolism ; Guanosine 5'-O-(3-Thiotriphosphate)/metabolism ; Molecular Weight ; Phosphorylation/drug effects ; Rats ; Rats, Sprague-Dawley ; Synaptic Membranes/*metabolism ; Synaptosomes/*metabolism ; cdc42 GTP-Binding Protein/biosynthesis/metabolism ; rab3A GTP-Binding Protein/metabolism ; rab5 GTP-Binding Proteins/metabolism ; rhoA GTP-Binding Protein/biosynthesis/metabolism

Low molecular weight GTP-binding proteins are molecular switches that are believed to play pivotal roles in cell growth, differentiation, cytoskeletal organization, and vesicular trafficking. Rab proteins are key players in the regulation of vesicular transport, while Rho family members control actin-dependent cell functions, i.e. the regulation of cytoskeletal organization in response to extracelluar growth factors and in dendritic neuron development. In this study, we have examined the regulation of small GTP-binding proteins that are implicated in neurosecretion and differentiation of neuron during ageing processes. Comparison of small GTP-binding proteins from the synaptosome and crude synaptic vesicles (LP2 membranes) of 2 months and 20 months old rat brain respectively showed no difference in the level of Rab family proteins (Rab3A and Rab5A). However, Rho family proteins such as RhoA and Cdc42 were elevated in LP2 membranes of the aged brain. The dissociation of Rab3A by Ca2+/calmodulin (CaM) from SV membranes was not changed during aging. Ca2+/CaM stimulated phosphorylation of the 22 and 55-kDa proteins in SV membranes from the aged rat brain, and inhibited phosporylation of 30-kDa proteins. GTPgammaS inhibited phosphorylation of the 100-kDa proteins and stimulated phosphorylation of the 70 kDa in LP2 membranes from both the young and aged rat brains, whereas GDPbetaS caused just the opposite reaction. These results suggest that protein phosphorylation and regulation of Rho family GTPases in rat brain appears to be altered during ageing processes.
*Aging ; Animal ; Brain/metabolism ; Calcium/pharmacology ; Cattle ; Comparative Study ; GTP-Binding Proteins/*metabolism ; Guanosine 5'-O-(3-Thiotriphosphate)/metabolism ; Molecular Weight ; Phosphorylation/drug effects ; Rats ; Rats, Sprague-Dawley ; Synaptic Membranes/*metabolism ; Synaptosomes/*metabolism ; cdc42 GTP-Binding Protein/biosynthesis/metabolism ; rab3A GTP-Binding Protein/metabolism ; rab5 GTP-Binding Proteins/metabolism ; rhoA GTP-Binding Protein/biosynthesis/metabolism

BACKGROUND: Angiogenesis plays a key role in the growth and metastasis of solid tumor. But it is not known whether the hematopoietic tumor depends on angiogenesis. To evaluate the prognostic roles of vascular endothelial growth factor (VEGF) expression and angiogenesis in patients with acute myelogenous leukemia, we analyzed the relationships between the level of VEGF expression, microvessel counts (MVC) in the bone marrow specimen of acute myelogenous leukemia patient and remission, relapse, and overall survival. METHODS: We evaluated bone marrow biopsy from 32 adult patients with newly diagnosed acute myelogenous leukemia and 16 controls with normal bone marrow. VEGF expression and MVC were assessed by immunohistochemical stain with monoclonal antibody to VEGF and polyclonal antibody to factor VIIIRAg, respectively. RESULTS: VEGF expression was higher in acute myelogenous leukemia than that of control (56.4+/-32.8% vs 19.0+/-25.9%, P=0.004). MVC was also higher in acute myelogenousleukemia than that of control (14.7+/-10.3 vs 6.2+/-3.8, P<0.001). Between high VEGF expression group and low VEGF expression group, there were no significant differences in the complete remission (CR), relapse and overall survival. There was no significant difference of MVC between CR group and non- CR group. Relapse group tends to have higher MVC than non-relapse group without statistical significance (P=0.06). There were no significant differences of MVC between hypervascular group and hypovascular group in remission, relapse and overall survival. CONCLUSION: In patients with acute myelogenous leukemia, VEGF expression and MVC were significantly higher than those of control. These findings suggest angiogenesis may play an important role in the pathogenesis of acute myelogenous leukemia. But there was no clinical correlation between the level of VEGF expression, MVC and remission, relapse and overall survival in this study. Further study willbe necessary for the establishment of prognostic role of VEGF expression and angioge-nesis and clinical efficacy of angiogenic inhibitors in acute myelogenous leukemia.
Adult ; Angiogenesis Inhibitors ; Biopsy ; Bone Marrow ; Humans ; Leukemia, Myeloid, Acute* ; Microvessels ; Neoplasm Metastasis ; Recurrence ; Vascular Endothelial Growth Factor A*

Background: Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS). Methods: We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed. Results: rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles. Conclusion The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

The release of neurotransmitter is regulated in the processes of membrane docking and membrane fusion between synaptic vesicles and presynaptic plasma membranes. Synaptic vesicles contain a diverse set of proteins that participate in these processes. Small GTP-binding proteins exist in the synaptic vesicles and are suggested to play roles for the regulation of neurotransmitter release. We have examined a possible role of GTP-binding proteins in the regulation of protein phosphorylation in the synaptic vesicles. GTPgammaS stimulated the phosphorylation of 46 kappa Da protein (p46) with pI value of 5.0-5.2, but GDPbetaS did not. The p46 was identified as protein interacting with C-kinase 1 (PICK-1) by MALDI-TOF mass spectroscopy analysis, and anti-PICK-1 antibody recognized the p46 spot on 2-dimensional gel electrophoresis. Rab guanine nucleotide dissociation inhibitor (RabGDI), which dissociates Rab proteins from SVs, did not affect phosphorylation of p46. Ca2+/ calmodulin (CaM), which causes the small GTP- binding proteins like Rab3A and RalA to dissociate from the membranes and stimulates CaM- dependnet protein kinase(s) and phosphatase, strongly stimulate the phosphorylation of p46 in the presence of cyclosporin A and cyclophylin. However, RhoGDI, which dissociates Rho proteins from membranes, reduced the phosphorylation of p46 to the extent of about 50%. These results support that p46 was PICK-1, and its phosphorylation was stimulated by GTP and Ca2+/CaM directly or indirectly through GTP-binding protein(s) and Ca2+/CaM effector protein(s). The phosphorylation of p46 (PICK-1) by GTP and Ca2+/CaM may be important for the regulation of transporters and neurosecretion.
Animals ; Calcium/*metabolism ; Calmodulin/*metabolism ; Carrier Proteins/*chemistry/*metabolism ; Guanine Nucleotide Dissociation Inhibitors/metabolism ; Guanosine Triphosphate/metabolism/*pharmacology ; Molecular Weight ; Monomeric GTP-Binding Proteins/metabolism ; Phosphorylation/drug effects ; Rats ; Recombinant Fusion Proteins/*chemistry/*metabolism ; Synaptic Membranes/chemistry/drug effects/*metabolism ; Synaptic Vesicles/chemistry/drug effects/*metabolism

OBJECTIVES: Uterine sarcoma is a rare malignant tumor, which is usually diagnosed in postmenopausal women. These sarcomas are occasionally misdiagnosed as uterine fibroids, thereby leading to delayed diagnosis in the advanced stages. We analyzed the sonographic and clinical characteristics of unexpected uterine sarcomas detected after surgery in women in the late reproductive age.METHODS: The medical records of 61 patients preoperatively diagnosed with uterine leiomyomas through sonography but confirmed as uterine sarcomas after surgery from January 2005 to December 2018 at Asan Medical Center were retrospectively analyzed. We evaluated the clinical symptoms, sonographic findings, and Doppler indexes, and investigated whether there were any significant characteristics that could clearly differentiate uterine sarcoma from fibroids.RESULTS: The most common clinical finding was increased mass size (15 patients, 24.6%), while 9 patients (14.8%) showed no symptoms. Ultrasonography showed that the maximum diameter of most fibroids was > 5 cm (49 patients, 80.3%), and the average diameter was 75.6 ± 36.3 mm. All the patients showed heterogeneous echogenicity in sonographic imaging. Secondary degeneration of the myomas was reported in 36 patients (59%), and approximately 90% (32/36, 88.9%) showed cystic changes. Of the 40 patients who underwent the evaluation of vascularity, 35 showed increased vascularity of the mass.CONCLUSIONS: In this study, sarcomas misdiagnosed as leiomyomas were usually > 5 cm, and ultrasonography showed heterogeneous echogenicity and irregular cystic degeneration. No definite clinical symptoms were helpful; a thorough evaluation is necessary to rule out uterine sarcomas in women having uterine mass with these characteristics.
Chungcheongnam-do ; Delayed Diagnosis ; Diagnostic Errors ; Female ; Humans ; Leiomyoma ; Medical Records ; Myoma ; Retrospective Studies ; Sarcoma ; Ultrasonography

Acinetobacter baumannii is known for its multidrug antibiotic resistance. New approaches to treating drug-resistant bacterial infections are urgently required. Cathelicidin-related antimicrobial peptide (CRAMP) is a murine antimicrobial peptide that exerts diverse immune functions, including both direct bacterial cell killing and immunomodulatory effects. In this study, we sought to identify the role of CRAMP in the host immune response to multidrug-resistant Acinetobacter baumannii. Wild-type (WT) and CRAMP knockout mice were infected intranasally with the bacteria. CRAMP−/− mice exhibited increased bacterial colony-forming units (CFUs) in bronchoalveolar lavage (BAL) fluid after A. baumannii infection compared to WT mice. The loss of CRAMP expression resulted in a significant decrease in the recruitment of immune cells, primarily neutrophils. The levels of IL-6 and CXCL1 were lower, whereas the levels of IL-10 were significantly higher in the BAL fluid of CRAMP−/− mice compared to WT mice 1 day after infection. In an in vitro assay using thioglycollate-induced peritoneal neutrophils, the ability of bacterial phagocytosis and killing was impaired in CRAMP−/− neutrophils compared to the WT cells. CRAMP was also essential for the production of cytokines and chemokines in response to A. baumannii in neutrophils. In addition, the A. baumannii-induced inhibitor of κB-α degradation and phosphorylation of p38 MAPK were impaired in CRAMP−/− neutrophils, whereas ERK and JNK phosphorylation was upregulated. Our results indicate that CRAMP plays an important role in the host defense against pulmonary infection with A. baumannii by promoting the antibacterial activity of neutrophils and regulating the innate immune responses.

Background: We evaluated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific humoral and cellular responses for up to 6 months after the 3rd dose of ancestral coronavirus disease 2019 (COVID-19) vaccination in people living with HIV (PLWH) and healthy controls (HCs) who were not infected with COVID-19. Methods: Anti-spike receptor-binding domain IgG (anti-RBD IgG) concentrations using chemiluminescence immunoassay and neutralizing antibodies using focus reduction neutralization test (FRNT) were assessed at 1 week after each dose of vaccination, and 3 and 6 months after the 3rd dose in 62 PLWH and 25 HCs. T-cell responses using intracellular cytokine stain were evaluated at 1 week before, and 1 week and 6 months after the 3rd dose. Results: At 1 week after the 3rd dose, adequate anti-RBD IgG (> 300 binding antibody unit /mL) was elicited in all PLWH except for one patient with 36 CD4 T-cell count/mm3 . The geometric mean titers of 50% FRNT against wild type (WT) and omicron BA.5 strains of SARS-CoV-2 in PLWH with CD4 T-cell count ≥ 500 cells/mm3(high CD4 recovery, HCDR) were comparable to HC, but they were significantly decreased in PLWH with CD4 T-cell count < 500/mm3 (low CD4 recovery, LCDR). After adjusting for age, gender, viral suppression, and number of preexisting comorbidities, CD4 T-cell counts < 500/mm3 significantly predicted a poor magnitude of neutralizing antibodies against WT, omicron BA.5, and XBB 1.5 strains among PLWH. Multivariable linear regression adjusting for age and gender revealed that LCDR was associated with reduced neutralizing activity (P = 0.017) and interferon-γ-producing T-cell responses (P = 0.049 for CD T-cell; P = 0.014 for CD8 T-cell) against WT, and strongly associated with more decreased cross-neutralization against omicron BA.5 strains (P < 0.001). Conclusion HCDR demonstrated robust humoral and cell-mediated immune responses after a booster dose of ancestral SARS-CoV-2 vaccine, whereas LCDR showed diminished immune responses against WT virus and more impaired cross-neutralization against omicron BA.5 strain.