Factors related with metastasis of right retroesophageal lymph nodes in papillary thyroid cancer.

AIM: Right retroesophageal lymph nodes (RRLNs) should be involved in central lymph nodes (CLNs) dissection in patients with papillary thyroid cancer (PTC). This study assessed the incidence and factors related to RRLNs metastasis. METHODS: From January 2008 to March 2010, 129 patients who underwent total thyroidectomy with CLNs dissection including RRLNs were enrolled. The predictive value of RRLNs metastasis was assessed. RESULTS: Twenty six (20.1%) of 129 patients exhibited nodal metastasis in RRLNs. Metastasis of RRLNs was associated with large tumor size (>1 cm; P<0.01), multiplicity (P=0.03), preoperative LN enlargement (P<0.01), metastasis of non-retroesophageal lateral LN (P<0.01) and large number of CLNs metastases (P<0.01) in univariate analysis. Multivariate analysis revealed that tumor size (>1 cm) and metastasis of non-retroesophageal lateral LN were independent correlates of RRLNs metastases. CONCLUSION: RRLNs may be removed during operation for PTC, particularly in patients with tumor >1 cm and lateral LN metastases.

Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

A case of small cell lung cancer treated with chemoradiotherapy followed by photodynamic therapy.

Here, we present the case of a 51-year-old man with limited-stage small cell lung cancer (LS-SCLC) who received concurrent chemoradiotherapy and photodynamic therapy (PDT). The patient was diagnosed as having LS-SCLC with an endobronchial mass in the left main bronchus. Following concurrent chemoradiotherapy, a mass remaining in the left lingular division was treated with PDT. Clinical and histological data indicate that the patient has remained in complete response for 2 years without further treatment. This patient represents a rare case of complete response in LS-SCLC treated with PDT.

Molecular characterization of hepatitis A virus isolated from acute gastroenteritis patients in the Seoul region of Korea.

Hepatitis A virus (HAV) is a major public health problem throughout the world. As a result of declining HAV endemic in Korea, an increasing number of children and adolescents have become susceptible to HAV infection. HAV is related with sanitation conditions of the environment and is transmitted via the fecal-oral route, either through person-to-person contact or by contaminated water and food. The present study has been carried out to determine the phylogenetic analysis and circulating patterns of HAV strains detected from hospitalized patients with acute gastroenteritis (AGE) in the Seoul region of Korea. In total, 2,782 stool specimens from hospitalized patients with AGE collected in October 2006 to September 2007 in Seoul were tested for HAV. A pair comparison of the nucleic acid sequence of a 159-bp base region at the putative VP1/2A junction of 85 Seoul isolates revealed that the most common HAV strain circulating in the region during 2006-2007 was subgenotype IA. HAV phylogenetic studies can provide important information on the genetic characteristics of HAV from AGE patients who may subsequently become the source of infection in Korea.

Optical spectroscopy of PPV-based block copolymers of nanostructured supramolecular organic semiconductor.

The third-order nonlinearity of a PPV-based nanostructured supramolecular organic semiconductor (DBAB), with an electron donor (D) connected to an electron acceptor (A) via nonconjugated and flexible bridge (B) units, was investigated in this work at both near-resonant (532 nm) and nonresonant (1064 nm) wavelength by using degenerate four-wave mixing. The second hyperpolarizabilities of D, A, and DBAB at 532 nm were found to be approximately 2.42 x 10(-43) m2/V2, 7.75 x 10(-44) m2/V2, and 1.80 x 10(-43) m2/V2 in copolarization geometry, and approximately 1.59 x 10(-43) m2/V2, 2.59 x 10(-44) m2/V2, and 1.18 x 10(-43) m2/V2 in orthogonal polarization geometry, respectively. The second hyperpolarizabilities of DBAB at 1064 nm were approximately 1.66 x 10(-46) m2/V2 and approximately 8.77 x 10(-47) m2/V2 for parallel and orthogonal polarization cases.

Nonlinear optical properties of mushroom-shaped CdSe/CdS coreshells.

The third-order nonlinear optical susceptibilities of mushroom-shaped CdSe/CdS coreshells as a function of concentration have been investigated using polarization- and concentration-resolved degenerate four-wave mixing in a resonant region. The effective third-order nonlinear optical susceptibilities, /chi(3)xxxx/ and /chi(3)xyyx/ of CdSe/CdS coreshells were estimated to be approximately 1.86 x 10(-21)-1.03 x 10(-20) m2/V2, and approximately 0.45 x 10(-21)-6.15 x 10(-21) m2/V2, respectively, for various concentrations of approximately 0.64 x 10(-3)-4.95 x 10(-3) mol/m3. The second hyperpolarizabilities, /xxxx/ and /xyyx/, of CdSe/CdS coreshells were extracted to be approximately 2.37 x 10(-41) m5/V2 and approximately 1.29 x 10(-41) m5/V2, respectively.

Mutations of tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2) genes in metastatic breast cancers.

Several lines of evidence suggest that apoptosis dysregulation plays an important role in cancer metastasis. In this study, to explore the possibility that the mutations of death receptors are involved in the metastasis mechanism, we analyzed the death domains of Fas and tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 and -2 (TRAIL-R1 and -R2) genes for the detection of somatic mutations in 57 breast cancers with (n = 34) or without (n = 23) metastasis to the regional lymph nodes. We found seven mutations (three TRAIL-R1 and four TRAIL-R2 mutations), and these mutations were detected only in the breast cancers with metastasis. Furthermore, we also analyzed the allelic losses of chromosome 8p21-22, where TRAIL-R1 and R2 reside in the same series of breast cancers, and found that the allelic losses were significantly higher in metastatic breast cancers. We expressed the tumor-derived TRAIL-R1 and TRAIL-R2 mutants in 293 cells and found that apoptosis was suppressed. These data suggest that TRAIL-R1 and R2 genes are relevant to the frequent loss of chromosome 8p21-22 in breast cancer and that the inactivating mutations of TRAIL-R1 and -R2 genes play a role in the metastasis of breast cancer.

Intracerebral adenovirus-mediated p53 tumor suppressor gene therapy for experimental human glioma.

Malignant gliomas of astrocytic origin are good candidates for gene therapy because they have proven incurable with conventional treatments. Although mutation or inactivation of the p53 tumor suppressor gene occurs at early stages in gliomas and is associated with tumor progression, many tumors including high-grade glioblastoma multiforme carry a functionally intact p53 gene. To evaluate the effectiveness of p53-based therapy in glioma cells that contain endogenous wild-type p53, a clinically relevant model of malignant human glioma was established in athymic nu/nu mice. Intracerebral, rapidly growing tumors were produced by stereotactic injection of the human U87 MG glioma cell line that had been genetically modified for tracking purposes to express the Escherichia coli lacZ gene encoding beta-galactosidase. Overexpression of the p53 gene by adenovirus-mediated delivery into the tumor mass resulted in rapid cell death with the eradication of beta-galactosidase-expressing glioma cells through apoptosis. In long-term experiments, the survival of mice treated with the p53 adenoviral recombinant was significantly longer than that of mice that had received control adenoviral recombinant. During the observation period of 1 year, a complete cure was achieved in 27% of animals after a single injection of p53 adenoviral recombinant, and 38% of the animals were tumor free in the group receiving multiple injections of p53 adenoviral recombinant into a larger tumor mass. These experiments demonstrate that overexpression of p53 in gliomas, even in the presence of endogenous functional wildtype p53, leads to efficient elimination of tumor cells. These results point to the potential therapeutic usefulness of this approach for all astrocytic brain tumors.

Beta-amyloid precursor protein is detectable on monocytes and is increased in Alzheimer's disease.

Using the anti-beta-amyloid precursor protein (betaAPP) monoclonal antibodies 4G8, 6E10 and 22C11 and flow cytometry, we report that human circulating peripheral blood monocytes display surface immunoreactivity for betaAPP. In contrast, circulating lymphocytes do not possess cell surface betaAPP immunoreactivity, despite similar levels of betaAPP expression. Immunoblotting analysis showed that monocytes, but not lymphocytes, possess an 82 kDa C-terminal betaAPP fragment consistent with a processed transmembrane species. Monocyte surface betaAPP was upregulated approximately threefold by activation with lipopolysaccharide and interferon-gamma, activation did not produce detectable betaAPP on the cell surface of lymphocytes. Surface betaAPP immunoreactivity was reduced in a normal aged population compared to normal young controls (Young = 81.07 +/- 13.67 mean fluorescence units, Aged = 36.74 +/- 3.81, p < 0.01), but was significantly increased in AD subjects compared to age-matched healthy controls (AD = 60.31 +/- 7.42, p < 0.05). Our data suggest that a proportion of peripheral A beta may be derived from monocyte/macrophages, and that defects in brain cell processing of betaAPP in AD may be shared by this readily accessible peripheral cell.

Lymphocyte content of amyloid precursor protein is increased in Down's syndrome and aging.

We quantified cellular amyloid precursor protein (APP) in ethanol-permeabilized peripheral lymphocytes from 13 subjects with Alzheimer's disease (AD), 11 subjects with Down's syndrome (DS), and 13 healthy elderly and 31 healthy young controls. APP content was analyzed by indirect immunofluorescence and flow cytometry, using the 22C11 monoclonal antibody (mAb) directed against an N-terminal domain of APP. Authenticity of 22C11 APP signal was confirmed by immunoblotting and flow cytometry studies with the mAb 6E10, directed against the A beta domain of APP. Consistent with gene dosage, patients with DS had 1.51-fold higher lymphocyte APP signal than age-matched normal young subjects (corrected p < 0.05). Both AD patients and elderly control groups had significantly increased lymphocyte APP signal compared to young controls (either comparison corrected p < 0.01). Indeed, increasing age in non-DS subjects was significantly correlated with lymphocyte APP (r = 0.508, p < 0.0001), such that APP immunoreactivity more than doubled from 20 to 80 years. Lymphocyte APP was nonsignificantly higher in AD vs. aged controls in this small sample. Increased cellular APP content in DS and aging may correspond to generalized alterations in expression or processing of this molecule, and suggests a novel determinant for the timing of AD onset.

Chemokine-enhanced migration of human peripheral blood mononuclear cells is antagonized by interferon beta-1b through an effect on matrix metalloproteinase-9.

The increased migration of peripheral blood mononuclear cells (PBMNCs) across a fibronectin (FN) matrix in response to the chemokines RANTES, MIP-1 alpha and MCP-1 is antagonized by interferon-beta-1b (IFN beta-1b). MCP-1 treatment of PBMNCs elevates their mRNA level and secretion of a matrix degrading enzyme, matrix metalloproteinase (MMP)-9, which is abrogated by IFN beta-1b. The clinical benefits of IFN beta-1b treatment in multiple sclerosis patients may in part be a result of this drug's ability to decrease the migration of PBMNCs in spite of a chemotactic gradient. Furthermore, the elevation of MMP-9 production by PBMNCs may be an important mechanism of action of chemokines.

Processing of the beta-amyloid precursor protein in ex vivo human brain cells.

We studied distribution and processing of the Alzheimer's beta-amyloid precursor protein (betaAPP) in immediately ex vivo human brain cells obtained during neurosurgical procedures. Immunoblotting and flow cytometry studies revealed that brain cells supported betaAPP as a transmembrane holoprotein. Brain cells in short-term suspension culture were competent to process betaAPP into Abeta as shown by [35S]methionine pulse-chase studies. Brain cell Abeta was immunoprecipitated as SDS-stable dimers and higher-order multimers. Cleavage of cell surface betaAPP with trypsin prior to metabolic labeling reduced cellular Abeta by approximately 50%. We conclude that plasmalemmal betaAPP in human brain cells is a source of cellular Abeta, presumably via endosomal-lysosomal processing.

Ubiquitin and Alzheimer's amyloid beta precursor protein colocalize to endosomes-lysosomes in cultured human cells.

Chloroquine (CHQ)-sensitive cellular compartments, identified as endosomes-lysosomes (ELs), have been implicated in the proteolysis of amyloid beta precursor protein (A beta PP) in Alzheimer's disease. Here we show using immunocytochemistry and immunogold electron microscopy that not only A beta PP but also ubiquitin (Ub) co-localize to ELs in CHQ-treated human neuroblastoma (SK-N-SH) and glioblastoma (U-373). Immunoblotting analysis of cell lysates indicated a significant degree of CHQ-mediated interference in A beta PP metabolism in a time- and concentration-dependent manner. The implication is that abnormal intracellular accumulation of A beta PP and its C-terminal fragments beyond a certain threshold may trigger the Ub response. We hypothesize that Ub may play a role in A beta PP processing and/or trafficking to ELs, particularly in stress-related conditions.

Serum pancreastatin levels predict response to hepatic artery chemoembolization and somatostatin analogue therapy in metastatic neuroendocrine tumors.

INTRODUCTION: Neuroendocrine tumors often metastasize to the liver and present with disabling hormonal symptoms. Hepatic artery chemoembolization (HACE) combined with somatostatin therapy, pre-embolization, peri-embolization and post-embolization, at doses to control symptoms, is an aggressive approach that can relieve hormonal symptoms with minimal morbidity and mortality. METHODS: Chemoembolization was performed using 30 mg of adriamycin, 50 mg of mitomycin, 12 ml of hexabrix, 10 ml of ethiodol, and 360-500-microm particles. Pancreastatin, a split product of chromogranin A, was measured pre-HACE and post-HACE in all patients. RESULTS: Forty-three chemoebolization procedures were performed in 34 symptomatic patients from December 1995 to August 1999. Seventeen patients had intestinal primaries (50%), seven had pancreatic primaries (20%), five had bronchial primaries (15%), and five had unknown primaries (15%). Systemic pancreastatin levels were improved or stable in 31 patients (78%). Symptoms were improved in these 31 patients (78%). Systemic serotonin levels were improved or stable in 24 patients (60%). Radiographic improvement or stability was seen in 18 patients (45%). Procedural related morbidity included pain, fevers, nausea, vomiting, and transient elevations of liver function studies in 75-100% of patients. There was one procedural related mortality (2%). Less than 20% improvement in pancreastatin levels from baseline was associated with death in five of five patients (100%). This was not observed with serotonin levels. CONCLUSION: Measurement of serum pancreastatin levels is an easy and useful method to predict success in patients who undergo HACE plus somatostatin therapy for metastatic neuroendocrine tumors to the liver. This therapeutic approach is effective in relieving symptoms in 78% of patients, with minimal major morbidity or mortality.

High toxicity of sulfasalazine in adult-onset Still's disease.

OBJECTIVE: Sulfasalazine (SSZ) is an anti-rheumatic drug that has been used to treat chronic arthritis. In many reports, the use of SSZ in children with systemic onset juvenile rheumatoid arthritis (JRA) revealed frequent side effects which required discontinuation of the drug. We examined whether there were frequent side effects of SSZ in patients with adult-onset Still's Disease (AOSD). METHODS: From July 1990 to April 1998, we followed 41 AOSD patients. Ten were given SSZ for the treatment of arthritis and the side effects were studied. We also studied 109 consecutive patients with RA who had been given SSZ, as a control group. In addition, we retrospectively studied the side effects and efficacy of SSZ in both groups through their medical records. RESULTS: Six patients (60%, p < 0.01) with AOSD experienced side effects ranging from mild ones like abdominal pain, nausea and vomiting, urticaria, and facial flushing to severe ones such as high fever, hypotension, and severe myelosuppression as well as fulminant hepatitis, which led to the death of one patient. However, 16 patients (14.7%) with RA stopped using SSZ due to mild side effects such as rash, urticaria, gastrointestinal troubles, mild leukopenia, and fever. Three AOSD patients (30%, p = 0.053) and 15 RA patients (13.8%) stopped using SSZ due to its inefficacy. CONCLUSION: We conclude that SSZ appears to have frequent severe side effects in AOSD, as in systemic onset JRA. These potential adverse effects of SSZ should be considered when it is used to treat chronic arthritides with systemic symptoms. Further study of SSZ in the treatment of AOSD in a multi-center, placebo-controlled environment is needed.

Transverse myelitis in a patient with long-standing ankylosing spondylitis.

Ankylosing spondylitis is reported to involve not only the joints but other organs as well. Among these extra-articular involvements, uncommon complications associated with nervous system such as single root lesions, compression of the myelum and cauda equina syndrome have also been documented. Here we present a patient with long-standing ankylosing spondylitis who developed spastic paraparesis. Extensive study to find the cause of a spastic paraparesis failed and therefore led to the conclusion that this patient was suffering from transverse myelitis. Similar reports in the past have been attributed to an association with multiple sclerosis; however, we suggest that the findings support the diagnosis of a rare complication of ankylosing spondylitis with an unknown etiology.

Coexistence of coronary aneurysms and total occlusion of coronary arteries in systemic lupus erythematosus.

A 22-year-old woman with known SLE and chronic hepatitis B developed anginal pain. During this period there was serologic but no other clinical evidence of active SLE. Myocardial perfusion SPECT showed a severe reversible perfusion defect in the posterior wall, and coronary angiography revealed multiple coronary aneurysms in the left anterior descending artery and circumflex artery and total occlusion of the proximal right coronary artery. This case suggests that coronary aneurysms and total occlusion may represent a sequela of arteritis, or of a combination of underlying vasculitis and a recent thrombotic obstruction due to antiphospholipid syndrome.

Anticlastogenic effects of galangin against mitomycin C-induced micronuclei in reticulocytes of mice.

We investigated the suppressive effect of galangin on the induction of micronucleated reticulocytes (MNRETs) by mitomycin C (MMC) in mouse peripheral blood. When galangin was given to mice 24 h before the intraperitoneal injection of MMC (1 mg/kg), a more marked decrease in the frequency of MNRETs was observed than in mice with simultaneous and post-treatment of galangin. On the other hand, when galangin was given to mice for 7 consecutive days before MMC injection, galangin showed potent anticlastogenic effects, even at the lowest dose level of 0.1 mg/kg. Results from our in vivo studies indicate that galangin is capable of suppressing the clastogenic activity of the direct acting MMC. Together with our earlier observations, it appears that galangin is capable of protecting cells from the toxic effects of a variety of hazardous chemicals. Therefore, galangin may be an useful chemopreventive compound.

Primary gastric lymphoma and pseudolymphoma.

Eighteen patients with primary gastric lymphomas and two with pseudolymphomas treated at the University of Louisville affiliated hospitals were analyzed in order to develop a more precise understanding of these rare diseases. Abdominal pain and weight loss were the most common initial symptoms. Only one patient presented with an abdominal mass. Upper GI series were helpful but failed to show a definite abnormality in two of 18 cases. Endoscopic examinations in all 18 were compatible with malignancy on gross finding, but six out of 15 endoscopic biopsies were not conclusive. All four cases, which proved fatal in less than two years, showed serosal invasion and diffuse histological pattern. On the basis of our analysis, we suggest that in patients with abdominal pain and weight loss of more than two months duration an aggressive course of evaluation should include upper gastrointestinal x ray and repeated endoscopic biopsy. If symptoms persist, laparotomy and biopsy may be warranted even if endoscopic biopsy shows no neoplasm. Curative surgery is the treatment of choice, but radiation therapy should be added in patients with serosal involvement. Very careful histological assessment of pseudolymphomas is necessary, because they may contain malignant lymphoma.

Radiologic changes of cervical spine in ankylosing spondylitis.

Ankylosing spondylitis (AS) is characterised by its effects on the axial skeleton. The cervical spine is also vulnerable to the disease process. Our aim was to determine the frequency of radiologic changes to the cervical spine and their correlation with clinical variables. We also used the Bath Ankylosing Spondylitis Radiology Index (BASRI) system, which is one of the reliable scoring systems of radiography, to score the global radiologic changes to the cervical and lumbar spine and the hip joints in our AS cohort. There were 181 patients with anteroposterior and lateral full-flexion views on radiography of the cervical spine here included in the study. A radiologist examined the radiologic changes to all anatomical compartments of the cervical spine in detail and graded them according to the BASRI system. We used the clinical and demographic data of our AS cohort to determine their relation to the radiographic changes. Eighty-eight patients (48.6%) showed radiological changes to the cervical spine; to the discovertebral joint 35.9%; the apophyseal joint 26.0%; atlantoaxial articulation 22.1% (atlantoaxial subluxation 13.8%); the costovertebral joint 18.2%; and to the posterior ligamentous attachment 11.6%. Using the BASRI system, 73 patients (40.3%) showed radiologic changes to the cervical spine and were graded as score 1 (1.7%), 2 (22.7%), 3 (6.6%) or 4 (9.4%). Among those graded as normal by the BASRI system, 17 showed some changes the cervical spine, such as atlantoaxial joint subluxation or narrowing, and severe osteoporosis with no other radiographic changes. Current age, disease duration, inflammatory back pain and cervical symptoms were associated with the radiographic changes to the cervical spine. The BASRI-cervical spine score correlated with the BASRI-lumbar spine and hip joint score, sacroiliitis, disease duration, and duration of inflammatory back pain and cervical symptoms. Our data suggest that radiographic changes to the cervical spine are frequent in AS, and can be predicted in the patients with old age, long duration of disease and inflammatory back pain, and cervical symptoms. Also, the BASRI scoring system showed similar results as a detailed assessment of the cervical spine in our study.