[Olfactory neuroblastoma in children: clinical analysis of five cases].

The clinical data of five patients diagnosed with olfactory neuroblastoma (ONB) who were admitted to the Department of Pediatrics, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2012 to January 2024 were retrospectively analyzed. Two males and three females aged 6.2 (5.7-15.8) years were included. The symptoms mainly covered nasal congestion, increased nasal secretions, headache, decreased vision and so on. Pathological grade Ⅱ, Ⅲ and Ⅳ was identified in two cases, one case and two cases, respectively. Modified Kadish stage B, C and D was detected in one case, two cases and two cases, respectively. All patients underwent surgery, chemotherapy, and radiation therapy. Among the five patients, four survived and one died. The follow-up time was 22.3 (10.4-56.4) months, and the recurrence rate was 0. ONB should be suspected when tumors are presented in the upper and middle parts of the nasal cavity, especially dumbbell shaped masses that grow towards the nasal cavity and intracranial area based on imaging. The multimodality therapy of ONB comprising of surgery and chemotherapy, can achieve good therapeutic effects and prognosis, but long-term follow-up is required.

[Establishment of a patient-derived xenograft humanized mouse model for hepatoblastoma in children].

Objective: To establish a patient-derived xenograft (PDX) humanized mouse model for hepatoblastoma in children. In addition, compare the biological consistency between successfully modeled PDX tumors and primary tumors in children while comparing and analyzing the influence of PDX model modeling success as a key factor. Methods: A PDX tumor model was constructed from fresh tumor tissue samples from 39 children with hepatoblastoma. The tumor growth time and volume size were recorded in detail. Simultaneously, 39 children's data were collected for experimental and clinical analysis. The difference in tumorigenesis rate between different parameters was analyzed by χ (2) test (categorical variable). Continuous variables with a normal distribution were compared using the t-test. Results: After cell passage and pathological diagnosis, 21 cases of hepatoblastoma PDX models were successfully constructed, with a success rate of 53.8% (21/39). Tumor samples from each generation of successfully modeled PDX models had pathology results that were consistent with those of the corresponding primary tumors. The analysis of the key factors affecting the tumor formation rate of PDX revealed that the metastasis rate was more successful in primary tumors than in liver in situ tumors (7/8 vs. 14/31, P = 0.049). However, there was no significant difference between tumor formation rates and pathological subtypes. According to the PDX tumor formation group comparison between the primary tumor and the metastatic tumor, there was no statistically significant difference between the two groups in terms of tumor formation time and tumor volume. Hematoxylin-eosin staining in hepatoblastoma's PDX mouse was consistent with the primary tumor. Immunohistochemistry positivity rates of four proteins, namely hepatocyte antigen (Hepatocyte), phosphatidylinositol glycan 3, ß-catenin, and alpha-fetoprotein, in primary tumor tissues and PDX mouse models were 100% vs. 100%, 100% vs. 95.24%, 100% vs. 100%, and 95.24% vs. 85.71%, respectively. Conclusion: A PDX mouse model for hepatoblastoma has been successfully established in children. The tumor formation rate is high, with metastatic tumors having a higher tumor formation rate than primary tumors and transplanted tumors retaining the biological characteristics of primary tumors.

[Tuberculosis screening in respiratory department inpatients in comprehensive medical institutions].

Objective: To explore the effect of screening tuberculosis patients in the respiratory department of general hospitals, and to provide a basis for the development of patient screening strategy. Methods: Clinical information and sputum samples of inpatients in the respiratory department of a general hospital in Longhua District, Shenzhen from December 2018 to December 2020 were collected. Sputum samples were sent to the tuberculosis laboratory of the Shenzhen Longhua Center for Chronic Disease Control (designated tuberculosis diagnosis and treatment institution) for sputum smear, liquid culture and Gene-Xpert test. Results: A total of 407 sputum samples (23 cases of suspected tuberculosis by chest imaging and 384 by clinical manifestations) were collected from 3 724 hospitalized patients. A total of 88 patients with positive etiology were detected by the three methods, and the positive rate was 21.6% (88/407), among which 15 patients with suspected tuberculosis were detected by imaging reports, and the positive rate of etiology was 19.0% (73/384) in the reported patients without imaging reports. At least 1.96% (73/3 724) of the hospitalized patients were estimated to be tuberculosis positive during the study. Pneumonia (30.1%,22/73), cough (15.1%,11/73) and pulmonary infection (15.1%,11/73) were the main characteristics in the patients with positive pathogens. Conclusions: Screening for tuberculosis among inpatients in the respiratory department of general hospitals is an effective way to detect patients who were radiographically reported to have probable tuberculosis. It is of great significance to carry out active screening in key departments of general hospitals for tuberculosis detection and control.

[Clinical features and prognostic analysis of hepatoblastoma in children under six years old].

Objective: To summarize and analyze the clinical features, treatment effects and related factors affecting the prognosis of hepatoblastoma (HB) in children under six years old. Methods: Clinical data of 382 children with HB under six years old who were pathologically diagnosed at the Pediatric Single Center of Beijing Tongren Hospital from May 2005 to May 2019 were analyzed retrospectively. The factors affecting the treatment effect and survival rate of HB were analyzed. The independent risk factors affecting the prognosis of HB were studied by Cox regression model. The χ(2) test was used to compare the enumeration data between groups. Kaplan-Meier method was used for survival analysis. Log-rank test was used to compare the survival rates among subgroups. Results: Children enrolled were with median age of 1.75 (0.08 ~ 5.92) years old and a male to female ratio of 1.5. Alpha-fetoprotein (AFP) median level was 197 406.5 µg/L at initial diagnosis, and the pathological tissue type was mainly epithelial (55.8%). Preoperative PRETEXT stage was mostly stage III (58.6%). 86 cases (22.5%) had portal vein or hepatic vein, and vena cava invasion. 73 cases (19.1%) had extrahepatic adjacent tissues and organs invasion. Twenty-four cases (6.3%) had tumor rupture and bleeding. 171 cases (44.8%) had distant metastases, and 96 cases (25.1%) had multiple intrahepatic lesions. Patients were followed-up to May 2020 (median follow-up time was 56 months). After comprehensive treatment, 218 cases were completely relieved, and 69 cases were partially relieved, and the treatment efficiency was 75.1%. Kaplan-Meier survival analysis showed that the 1, 3, and 5-years overall survival rates (OS) were 93.7%, 84.0%, and 73.9%, respectively, and the event-free survival rates were 90.5%, 79.2%, and 67.5%, respectively. Comparison of the clinical factors of 5-year OS showed that AFP < 100 µg/L (HR = 3.341, P = 0.005), PRETEXT stage IV (HR = 4.026, P = 0.001), vascular invasion (HR = 2.178, P = 0.019) and distant metastasis (HR = 2.634, P = 0.010) were independent risk factors in each subgroup affecting the prognosis of children with HB, and the difference was statistically significant. Conclusion: HB prognosis is related to AFP level, PRETEXT stage, presence or absence of vascular invasion and distant metastasis. Therefore, its survival and prognosis will be different in the presence of different risk factors.

[Operative strategy and clinical results of complex four part distal radius fractures by combined palmar and dorsal internal fixation].

Objective: To explore a standard procedure for the treatment of combined dorsal and palmar internal fixation for complex four part distal radius fractures and assess its clinical results. Methods: From May 2009 to October 2016, 38 patients(39 sides)who suffered from complex four part distal radius fractures were performed operatively with open reduction and internal fixation via combined dorsal and palmar approach in Department of Orthopaedic Trauma, Qilu Hospital of Shandong University(Qingdao). The series included 22 males(22 sides) and 16 females(17 sides). Age of the patients was 53.5 years ranging from 25 to 79 years.According to Melone classification, there were 34 sides of type of Ⅳ, 5 of type Ⅴ.According to Frykman classification, there were 15 sides of type Ⅶ, 24 sides of type Ⅷ, and all the cases were type C3 according to AO/OTA classification.Preoperatively, the key articular fragments in four part distal radius fractures were identified and the individual fracture patterns from conventional X-ray and CT-scan were analyzed. All the patients were performed combined volar and dorsal fixation.Firstly, a palmar approach which gave access to and fix the palmar-ulnar fragment and the radial styloid fragment was performed.Then a limited dorsal approach across the third extensor compartment which gave access to the dorso-ulnar fragment and a limited dorsal arthrotomy to visualize the radiocarpal joint when necessary were performed.Through dorsal approach, we can address the dorso-ulnar fragment, free intra-articular fragment and direct visualize the joint.Use of a retinacular flap was routinely advocated to help prevent against tendon irritation and rupture.The follow-up control included conventional X-ray, range of motion(ROM), grip strength, and the disabilities of the arm, shoulder and hand index(DASH), as well as the patient-rated wrist evaluation(PRWE) score for functional outcome at 6 and 12 months. Results: Thirty-three patients(34 sides) were followed up for at least 12 months.The would healed well in all cases 2 weeks postoperatively, and no soft tissue infections, necrosis or neurovascular complications occurred.All the fractures of 38 cases(39 sides)healed averaged 3.6 months(ranging from 2.5-5.7 months), and no loss of reduction occurred postoperatively.Anatomic reconstruction with a step or gap of <1 mm was achieved in 37 cases(38 sides), Whereas 5 patients were lost to follow-up at 12 months postoperatively.ROM and grip strength were all recovered to over 85% of the unaffected side(exception of the bilateral patient). Median DASH-index and PRWE were 6.5(0-17) and 9.3(0-20)respectively. Conclusion: Combined volar and dorsal approaches allow achieving anatomic reconstruction in complex four part intra-articular distal radius fractures and reveal good functional outcomes at intermediate follow-up.

[Clinical features, treatment and prognosis of retinoblastoma in distant metastasis stage].

Objective: To summarize the clinical features, treatment and prognosis of retinoblastoma (RB) patients in distant metastasis stage. Methods: Retrospective case series study. Clinical data of 24 cases (30 eyes) with diagnosis of distant metastasis stage RB were collected in pediatrics department of Beijing Tongren Hospital affiliated with Capital Medical University, from September 2005 to December 2013. In these cases, including 11 male cases and 13 female cases, the treatment age ranged from 7 months to 9 years with the median of 26 months. There were 18 unilateral cases (12 cases of right eye and 6 cases of left eye) and 6 bilateral cases. All cases were treated with surgery, chemotherapy and radiotherapy. The adverse reaction, blood routine and biochemical routine were monitored dynamically and regularly during treatment. The clinical manifestations and auxiliary examination were combined to evaluate the therapeutic effect. Determining the prognosis with death and survival, the survival curve and the median survival time were calculated by the product limit method. Results: The results of pathologic examination of 13 cases showed 11 cases of optic nerve involvement, 6 cases of optic nerve and choroid involvement, 1 case of post laminar involvement, 1 case of cornea and conjunctiva involvement. The most common metastatic site was central nerve system (CNS) (23 cases), followed by orbital involvement (10 cases). Other metastatic sites included bone (9 cases), bone marrow (1 case), pleura (1 case) and lymph node (1 case). 23 patients with CNS metastasis underwent systemic chemotherapy and intrathecal injection. The toxicity and side effects of radiotherapy and chemotherapy were evaluated and classified as grade I-II. Those adverse effects were tolerated by all cases. Followed up to December 31, 2015, all patients with CNS metastasis died and the median survival time was 6 months. Only 1 patient without CNS metastasis disease-free survived for 64 months. Conclusions: The most common metastasis site of RB was CNS. The overall prognosis of RB with distant metastasis was poor, in spite of given combined treatment mainly including surgery, chemotherapy and radiotherapy. But the prognosis of RB patients without CNS metastasis in distant metastasis stage was better than with CNS metastasis. (Chin J Ophthalmol, 2017, 53: 121-126).

Metastatic melanoma to the ovary in pregnancy: A case report.

Metastatic melanoma to the ovary is an uncommon presentation. We report a case of metastatic melanoma to the ovary that presented as a growing left adnexal mass during pregnancy and was thought to be benign by imaging and frozen section pathology. Here we discuss the challenges in radiologic and pathologic diagnosis, as well as considerations for the mother and newborn.

[Clinical features and treatment efficacy of infantile renal tumors: a multicenter retrospective study].

Objective: To further understand the clinical features, treatment efficacy and risk factors for poor prognosis in infantile-onset renal tumors. Methods: Clinical data of 45 cases of infantile-onset renal tumors from June 2011 to November 2019 in Peking University First Hospital, Beijing Children's Hospital, Beijing Tongren Hospital and Beijing Shijitan Hospital were analyzed retrospectively. The clinical features were summarized and the prognoses were evaluated. Multi-disciplinary diagnosis and treatment was used, including surgery, chemotherapy and radiotherapy. Kaplan-Meier analysis was used to calculate the overall survival rate and the event-free survival rate, while the chi-square test was used to analyze the risk factors for poor prognosis. Results: Among 45 patients, 24 were males and 21 females. The age of onset was 7 (ranged 3-11) months, and the length of tumor at initial diagnosis was 9.7 (ranged 4.9-25.0)cm. The International Society of Pediatric Oncology (SIOP) staging: 5 cases (11%) were in stage Ⅰ, 22 cases in stage Ⅱ (49%), 8 cases in stage Ⅲ (18%), 6 cases in stage Ⅳ (13%), and 4 cases in stage Ⅴ (9%). Risk groups included 5 cases (11%) in the low-risk group, 22 cases (49%) in the intermediate-risk group, and 18 cases (40%) in the high-risk group. Forty-four cases (98%) did not receive preoperative biopsy, 26 cases (58%) received preoperative chemotherapy, 39 cases (87%) received postoperative chemotherapy, and 2 cases (4%) received three-dimensional conformal radiotherapy. The 5-year overall survival rate was (83±7)%, and the 5-year event-free survival rate was (76±8)%. Hematuria as the first symptom (3/8 vs. 83% (30/36), χ²=7.005, P=0.024), tumor long diameter≤8 cm (5/11 vs. 85% (28/33), χ²=5.606, P=0.027) and high-risk pathological group (7/18 vs.100% (26/26), χ²=21.928, P<0.01) were risk factors for poor prognosis of children with renal tumors in this group. Conclusion: The prognosis of children with infantile-onset renal tumors is fairly well, nevertheless the prognosis is poor in patients with hematuria as the first symptom and in high-risk pathological group.

Immunocytochemical colocalization of specific immunoglobulin A with sendai virus protein in infected polarized epithelium.

Immunoglobulin (Ig)A provides the initial immune barrier to viruses at mucosal surfaces. Specific IgA interrupts viral replication in polarized epithelium during receptor-mediated transport, probably by binding to newly synthesized viral proteins. Here, we demonstrate by immunoelectron microscopy that specific IgA monoclonal antibodies (mAbs) accumulate within Sendai virus-infected polarized cell monolayers and colocalize with the hemagglutinin- neuraminidase (HN) viral protein in a novel intracellular structure. Neither IgG specific for HN nor irrelevant IgA mAbs colocalize with viral protein. Treatment of cultures with viral-specific IgA but not with viral-specific IgG or irrelevant IgA decreases viral titers. These observations provide definitive ultrastructural evidence of a subcellular compartment in which specific IgA and viral envelope proteins interact, further strengthening our hypothesis of intracellular neutralization of virus by specific IgA antibodies. Our results have important implications for intracellular protein trafficking, viral replication, and viral vaccine development.

[Expression and significance of programmed cell death ligand-1 in neuroblastoma tissues].

Objective: To investigate the relationship between expression of programmed cell death ligand-1(PD-L1) in the tissue of neuroblastoma (NB) and patient's clinical characteristics and prognosis. Methods: Clinical data and surgical tissue paraffin blocks of 100 newly diagnosed NB children at Sun Yat-sen University Cancer Center between January 2000 and December 2015 were collected and the expression level of PD-L1 and its' relationship with pathological parameters and survival rate were analyzed retrospectively. The ratio between groups was compared by chi-square test. Kaplan-Meier method was used for survival analysis and COX regression model was used for multivariate analysis. Results: Among 100 cases, 71 were males and 29 females; there were 5 cases of stageⅠ, 4 cases of stageⅡ, 19 cases of stage Ⅲ, 65 cases of stage Ⅳ and 7 cases of stage Ⅳs. Ten out of 62 cases (16%) were N-MYC amplified; 15 cases were in low-risk group, 18 were in medium-risk group and 67 were in high-risk group. The positive rate of PD-L1 in NB tumor tissue was 57% (57/100), of which 55 were weakly positive, 1 was moderately positive and 1 was strongly positive. The positive rates of PD-L1 expression in tumor tissues without bone metastasis were higher than those with bone metastasis(66%(39/59)vs.44%(18/41), χ(2)=4.864, P=0.027), the positive rates of PD-L1 expression in tumor tissues pathologically diagnosed as neuroblastoma were higher than those pathologically diagnosed as ganglioneuroblastoma (61%(53/87) vs.31%(4/13), χ(2)=4.195, P=0.041), the positive rates of PD-L1 expression in tumor tissues originated from abdominal cavity were higher than those originated from other places (61% (51/83)vs.35%(6/17), χ(2)=3.937,P=0.047).The 4-year event-free survival (EFS) rates of patients with PD-L1 negative and positive were 40% and 33% (χ(2)=0.009, P=0.923), respectively. The 4-year overall survival (OS) rates of patients with PD-L1 negative and positive were 62% and 58% (χ(2)=0.294, P=0.587). Among 33 non-high-risk patients, the 4-year EFS rates of patients with PD-L1 negative and positive were 89% and 78% (χ(2)=0.001, P=0.965), the 4-year OS rates of patients with PD-L1 negative and positive were 100% and 96% (χ(2)=0.500, P=0.480). Among 67 high-risk patients, the 4-year EFS rates of patients with PD-L1 negative and positive were 24% and 11% (χ(2)=1.154, P=0.282), the 4-year OS rates of patients with PD-L1 negative and positive were 48% and 41% (χ(2)=0.692, P=0.405). Multivariate analysis showed that N-MYC gene amplification was an independent adverse prognostic factor for OS and EFS rates of NB patients (RR: 1.726,95%CI:1.209-2.466; RR:1.326,95%CI:1.014-1.736) and advanced clinical stage was an independent adverse prognostic factor for EFS rates of NB patients (RR: 26.498, 95%CI:3.518-199.614). Conclusions: The expression of PD-L1 in NB tumor tissues was correlated with the clinical characteristics of children. However, there were no significant differences in the prognosis of patients with or without PD-L1 expression.

Intracellular IL-37b interacts with Smad3 to suppress multiple signaling pathways and the metastatic phenotype of tumor cells.

Multiple signaling pathways that promote tumor cell metastasis are differentially activated in low/non-metastatic and metastatic tumor cells, resulting in the differential expression of metastasis-related genes. The underlying mechanism may involve the alterations of the intrinsic negative regulation in tumor cells. Here we report that the differential expression of interleukin-37b (IL-37b) in tumor cells alters the intrinsic negative regulation of signaling pathways, resulting in the difference of metastatic capacity. IL-37b could bind Smad3 and suppress Smad pathway by interfering with the formation and nuclear translocation of Smad2/3/4 complex. In turn, Smad3 could function as a co-regulator, enabling IL-37b to suppress multiple non-Smad pathways. IL-37b-Smad3 translocated into nucleus to upregulate the expression of non-receptor protein tyrosine phosphatases (PTPNs), thus promoting dephosphorylation to suppress the activation of tyrosine phosphorylation-dependent signaling pathways such as ERK, p38 MAPK, JNK, PI3K, NF-κB, and STAT3 pathways. Intriguingly, 13 of 17 PTPNs, most of which are metastasis suppressors, were downregulated in metastatic tumor cells because of the low expression of IL-37b. The marked decrease of intracellular IL-37b attenuated the intrinsic negative regulation in tumor cells, resulting in the enhanced activation of multiple signaling pathways and the increased capacity of invasiveness and metastatic colonization. Consistently, low expression of IL-37b in tumors was significantly associated with poor prognosis of cancer patients. Taken together, these findings reveal that intracellular IL-37b is a critical factor in the negative regulation of multiple signaling pathways that modulate the expression of metastasis-related genes, and suggest that IL-37b expression in tumor cells can potentially be a histopathological prognostic parameter for cancer patients and a therapeutic target for preventing tumor metastasis.

Effects of feed particle size and feed form on survival of Salmonella typhimurium in the alimentary tract and cecal S. typhimurium reduction in growing broilers.

An in vitro experiment and an in vivo experiment were conducted to investigate the effects of feed particle size (coarse and fine) and feed form (mash and pellet) on the survival of Salmonella typhimurium (ST) in the alimentary tract, and the reduction of cecal ST in growing broilers in a 2 x 2 factorial design. All diets in the 2 trials were corn and soybean meal-based diets that differed only in physical characteristics. Diets were provided for birds from d 1 to 22 of age. In the in vitro trial, the relative gizzard weight was lower in birds that were fed the pellet diet (P < 0.01), whereas the relative weight of the cecum was higher in these birds (P < 0.01). Broilers receiving the pellet diet had enhanced concentrations of volatile fatty acids in contents from both the gizzards and the ceca. In addition, there was an increase in gizzard pH (P < 0.01) with the pellet diet, but a reduction in cecal pH (P < 0.05). Pellet-fed birds showed a significantly decreased and increased in vitro death rate of ST in the contents from gizzards (P < 0.01) and ceca (P < 0.05), respectively. A higher in vitro ST death rate in the gizzard was observed in birds given the coarse mash diet compared with those given the fine mash diet. In the in vivo experiment, cecal volatile fatty acid concentrations were increased, whereas cecal pH was decreased significantly (P < 0.05) when birds were fed the pellet diet compared with the mash diet. Furthermore, cecal ST concentrations were higher (P < 0.05) in broilers fed the pellet diet than in those fed the mash diet. Results indicated that the pellet diet increases the incidence of ST in gizzards and ceca in growing broilers and provide evidence demonstrating that the gizzard may play a critical role in reducing ST contamination in growing broilers.

Effects of particle size and physical form of diets on mast cell numbers, histamine, and stem cell factor concentration in the small intestine of broiler chickens.

The aim of this study was to investigate the hypothesis that particle size and diet form may affect the growth of mast cells and histamine release from the small intestine of broiler chickens. A total of 288, day-old male broiler chicks were randomly allocated to 1 of 4 corn-soy diets in a 2 x 2 factorial design. The factors included particle size (coarse vs. fine) and physical form (mash vs. pellet). The birds were housed in 90 x 60 cm pens containing 12 birds, and each treatment contained 6 replicate pens of birds from d 1 to 22. On d 22, 6 broilers from each treatment were slaughtered. Tissues from the small intestine (duodenum, jejunum, and ileum) were obtained to quantify mast cells using the toluidine blue staining technique. The results showed that mast cells in the jejunum were concentrated in the upper part of the villus in birds fed the coarsely ground mash diet, whereas mast cells were evenly distributed throughout the intestine in birds fed the other 3 diets. The number of mast cells was significantly lower in the duodenum (P = 0.04), jejunum (P < 0.01), and ileum (P = 0.01) of birds fed coarsely ground diets compared with finely ground diets, and there was no difference in mast cell numbers between birds fed mashed or pelleted diets at any site in the intestine. The histamine content (P = 0.02) and stem cell factor concentration (P = 0.03) were markedly lower in the jejunum of birds that were fed coarsely ground diets compared with finely ground diets. The stem cell factor concentration in the duodenum (P < 0.01) and jejunum (P = 0.05) was higher in birds fed pelleted compared with mash diets. The overall results of this experiment suggest that particle size and diet form affect mast cell number and histamine content in the small intestine by regulation of stem cell factor concentration.

[Treatment and prognostic analysis of retinoblastoma patients with choroid invasion].

Objective: To observe the treatment and prognosis of choroid invasion of retinoblastoma (RB) in children. Method: A total of 149 children who had been diagnosed with unilateral RB and received enucleation disclosing tumor invasion to choroid from January 2006 to December 2013 in Beijing Tongren Hospital were recruited in this study. Choroid involvement was classified as massive choroid invasion and focal choroid invasion. Massive choroid invasion was defined as a maximum diameter of invasive tumor focus of 3 mm or more in diameter that might reach the scleral tissue. Focal choroid invasion was defined as a tumor focus of less than 3 mm in diameter without involvement of sclera. The treatment was delivered according to the invasive status of tumor with combination of histopathological high risk factors. The prognosis of different degrees of choroid invasion was observed. They were divided into two groups according to whether the merger of other high histopathologic risk factors, the survival situation was compared. The subjects were followed up for 1 to 9 years (the median follow-up time: 4 years and 1 month). Result: Among the 149 subjects, 90 were boys and 59 were girls. The right eye was affected in 81 patients and the left eye in 68 patients. Sixteen patients died, resulting in an overall survival rate of 89.3%. Among massive choroid invasion in 47 cases, 9 patients experienced disease recurrence and death resulting in a survival rate of 80.9%. While the focal choroid invasion was found in 102 cases, only 7 children had disease relapsed and died resulting in a survival rate of 93.1% which was statistically significant (χ2=5.067, P=0.024). Among 8 patients with massive choroid invasion without pathological high-risk factors, no death occurred, while in other 39 patients with high-risk factors, 9 died with a mortality rate of 23.1%, however, the difference was not statistically significant (Fisher's exact probability method, P=0.323). Among 60 patients with focal choroid invasion without pathological high-risk factors, no death was observed, while among the other 42 patients presenting high-risk factors, 7 of them died with a mortality rate of 16.7% (Fisher's exact probability method, P=0.003). Cox multivariate analysis showed that massive choroid invasion and surgical margin of the optic nerve were influential factors of prognosis. Conclusion: Patients with focal choroid invasion have a low disease recurrence and may not receive adjuvant chemotherapy. Patients with massive choroid invasion without presenting pathological high-risk factors warrant further prospective study to assess whether adjuvant chemotherapy is needed. However chemotherapy is recommended for those with massive choroid invasion presenting with risk factors to avoid the high disease recurrence in such patients.

Production of tumor necrosis factor alpha by resident and activated murine macrophages.

Alveolar macrophages (Am phi s), resident peritoneal macrophages (RPm phi s), and thioglycolate-elicited peritoneal macrophages (TGPm phi s) were isolated from C57BL/6 mice and incubated with lipopolysaccharide (LPS), stimulated cell supernatant, or recombinant interferon gamma (IFN-gamma) for 24 h. Tumor necrosis factor (TNF) in cell-free supernatants was measured by enzyme-linked immunosorbent assay. Amo phi s incubated with 10(3) ng/ml LPS produced 50 times more TNF than RPm phi s and 5 times more than TGPm phi s, and LPS alone induced maximum TNF production by Am phi s. Stimulated cell supernatant or recombinant IFN-gamma alone did not induce TNF production. A combination of LPS with stimulated cell supernatant or IFN-gamma had only a limited synergistic effect on TNF production by Am phi s. However, both LPS and stimulated cell supernatant or recombinant IFN-gamma induced maximum TNF production by RPm phi s and TGPm phi s. TGPm phi s showed greater sensitivity to LPS and stimulated cell supernatant or IFN-gamma with regard to TNF production than the other macrophage populations investigated.

Assessment of baseline toxicity of mono-cyclic aromatic compounds by pseudomonas initial oxygen uptake assay.

The objective of this study was to develop quantitative structure-activity relationships (QSARs) for the toxicity of mono-cyclic aromatic compounds in the Pseudomonas putida initial oxygen uptake assay. The QSARs were developed using response-surface based on descriptors for chemical hydrophobicity (logP) and electrophilicity (LUMO). The model log (Ki(-1)=0.434 (+/-0.011) log P-0.389 (+/-0.013) LUMO - 2.13(+/-0.031); n=155, r2=0.941, r2(adj)=0.940, s=0.119, F=1206 led us to conclude that the polar and non-polar narcotics were statistically indistinguishable. Pentafluorophenol, pentachlorophenol and most dinitrophenols classified as weak acid respiratory uncouplers in literature fit well into this model when they were treated as their corresponding phenoxides. This latter result suggests that the action mechanism of these phenols should be reevaluated.

Vitamin E supplementation modulates cytokine production by thymocytes during murine AIDS.

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS, which is functionally similar to human AIDS. Retrovirus infection targeted the thymus, producing altered T cell differentiation via the dysregulation of thymocyte cytokine production. Human AIDS causes vitamin deficiencies, therefore the effects of dietary vitamin E supplementation were determined on the kinetics of cytokine production by concanavalin A-stimulated thymocytes in uninfected normal mice and mice with murine AIDS. Dietary supplementation, with a 15-fold increase in vitamin E (160 IU/l) in the liquid diet (National Research Council), modulated interleukin-2 (IL) production in both uninfected mice and retrovirus-infected mice. Vitamin E significantly reduced the level of IL-4 secretion in the uninfected mice at 4 and 8 weeks, but not at 12 and 16 weeks. It also significantly reduced IL-4 production, elevated by retrovirus infection. Vitamin E significantly reduced IL-6, and interferon-gamma production increased in murine AIDS. The effects of dietary vitamin E on concanavalin A-induced proliferation of thymocytes were consistent with the finding of changes in IL-2 secretion. No effects of dietary vitamin E on thymus weight were observed in uninfected or retrovirus-infected mice, whereas vitamin E significantly increased serum and thymic vitamin E concentration, which had been reduced by retrovirus infection. These data indicate that dietary vitamin E supplementation can modulate cytokine production by thymocytes, affecting T cell differentiation, especially during retrovirus-induced immune dysfunction.

Effects of sulfur-containing analogues of stearic acid on growth and fatty acid biosynthesis in the protozoan Crithidia fasciculata.

A variety of analogues of stearic acid in which one of the methylene groups was replaced by a sulfur atom were examined as inhibitors of growth and fatty acid biosynthesis in the trypanosomatid protozoan Crithidia fasciculata. The 8-, 9-, 10-, and 11-thiastearic acids were found to suppress the synthesis of the cyclopropane-containing fatty acid dihydrosterculic acid (9,10-methyleneoctadecanoic acid) at micromolar concentrations in the growth medium, and all but the 9-thiastearate were found to inhibit the growth of the protozoa at concentrations. The most potent inhibitor, 8-thiastearic acid (I50 for growth = 0.8 microM; I50 dihydrosterculate synthesis = 0.4 microM), was also observed to inhibit the synthesis of gamma-linolenic acid at a similar concentration. The sulfoxide derivatives of the 9- and 10-thiastearates were found to have little effect on growth or fatty acid synthesis, and several long-chain amides of 3-amino-1,2-propanediol were found to have effects similar to those of the fatty acids from which they were derived.

Kinetics of cytokine production by thymocytes during murine AIDS caused by LP-BM5 retrovirus infection.

C57BL 6 mice inoculated with the murine leukemia retrovirus mixture, LP-BM5, rapidly produce murine AIDS with many functional similarities to human AIDS. Human HIV infection has recently been shown to inhibit thymocyte maturation. Therefore, the kinetics of the proliferation of thymocytes induced by Con-canavalin A (ConA) and levels of cytokines produced by in vitro ConA-stimulated thymocytes were examined during the progression of murine AIDS. The proliferation of thymocytes induced by ConA was significantly enhanced by retrovirus infection at 4 weeks post-infection compared to control, but significantly inhibited during 8-12 weeks post-infection. Release of IL-2 by ConA-stimulated thymocytes was significantly increased by retrovirus infection during 2-5 weeks post-infection and 11-18 weeks post-infection compared to control, but significantly decreased during 7-9 weeks post-infection. Secretion of IL-4 by ConA-stimulated thymocytes was significantly enhanced by retrovirus infection from 5 to 18 weeks post-infection compared to control. The level of IL-6 produced by ConA-stimulated thymocytes was significantly inhibited by retrovirus infection at the beginning of retrovirus infection (2-9 weeks), but significantly elevated after 11 weeks post-infection compared to control. Release of IFNgamma by ConA-stimulated thymocytes, however, was significantly enhanced during the whole period of retrovirus infection compared to control, while it surged at 13 weeks post-infection. We conclude that retrovirus infection affects the thymus, producing altered T-cell differentiation via the dysregulation of thymocyte cytokine secretion.

Inhibitory effects of canthaxanthin on in vitro growth of murine tumor cells.

The antitumorigenic effects of carotenoids, in addition to their immuno-enhancing effects, may occur by their direct action on growing tumor cells. To test this hypothesis the direct inhibitory effect of various concentrations of canthaxanthin (CX; 4,4'-diketo-beta-carotene), a non-provitamin A carotenoid, was tested on the in vitro growth of JB/MS, B16F10 melanomas and PYB6 fibrosarcoma and murine non-transformed NIH-3T3 (ATCC CRL 1658) cells. At concentrations of 1 x 10(-8) M up to 1 x 10(-4) M, CX significantly reduced the overall number of tumor cells. The greatest inhibition was observed at a CX concentration of 1 x 10(-4) M after 72 h and 96 h of incubation. However, CX had no inhibitory effect on the growth of the non-transformed NIH-3T3 cell line; rather it significantly enhanced growth of this cell line (P less than 0.05) after 96 h of incubation. Thus, the inhibitory action of CX on growing tumor cells appears to be due to its direct actions on tumor cells and not via its conversion to vitamin A or its immuno-enhancing effects.