Primary intraspinal soft-tissue sarcoma in childhood: Report of two cases with a review of the literature

Two young children who presented with lower spinal cord dysfunction manifested by bilateral leg weakness and urinary retention were diagnosed with intraspinal soft-tissue sarcoma. Neither patient had a significant extradural mass. Both tumors had histochemical features of rhabdomyosarcoma. Temporary responses were noted after combination chemotherapy either with vincristine, actinomycin D, and cyclophosphamide or with ifosfamide/mesna and etoposide. However, both patients developed uncontrollable cerebrospinal fluid (CSF) dissemination of tumor and died within 6 months of diagnosis, despite intrathecal chemotherapy and irradiation for one and very high-dose intravenous methotrexate (33 g/m²) for the other. This rare tumor can respond to parenteral antisarcoma chemotherapy, but better strategies are needed to prevent CSF spread and ultimate demise. Early institution of intrathecal cytostatic agents may retard or prevent CSF dissemination and prolong survival. © 1994 Wiley-Liss, Inc.     

Free serum amino acids in patients with advanced cervical carcinoma

Free serum amino acids were measured in patients with untreated advanced cervical carcinoma and compared to amino acid concentrations in normal patients. Of the 20 amino acids measured, 11 were significantly elevated in the patients with carcinoma.     

Recombinant allergens for immunotherapy.

Many of the problems associated with using natural allergenic products for allergy diagnosis and treatment can be overcome using genetically engineered recombinant allergens. Over the past 10 years, the most important allergens from mites, pollens, animal dander, insects, and foods have been cloned, sequenced, and expressed. Allergens have diverse biological functions (they may be enzymes, enzyme inhibitors, lipocalins, or structural proteins). High-level expression systems have been developed to produce recombinant allergens in bacteria, yeast, or insect cells. Recombinant allergens show comparable immunoglobulin E (IgE) antibody binding to natural allergens and show excellent reactivity on skin testing and in in vitro diagnostic tests. Recombinant allergens will enable innovative new strategies for allergen immunotherapy to be developed. These include peptide-based vaccines, engineered hypoallergens with reduced reactivity for IgE antibodies, nucleotide-conjugated vaccines that promote Th1 responses, and the possibility of developing prophylactic allergen vaccines.     

Use of Weighted p‐Values in Regional Inference Procedures

Our previous studies have demonstrated that the power to detect linkage was improved by calculating a moving average of consecutive p‐values in a small region as compared with testing all single p‐values. The goal of this study was to test whether the power can be improved further with an alternative method whereby the middle p‐values in the sequence were given more weight than the others. We also wanted to compare the moving average tests with multipoint linkage tests. The simulated extended pedigree data from the general population was analyzed to identify two major genes (MG1 and MG5) underlying two quantitative traits (Q1 and Q5). We used the variance components method implemented in the GENEHUNTER program to test for linkage of 14‐marker regions each on chromosome 19 and chromosome 1 to the adjusted quantitative traits Q1 and Q5, respectively, in all 50 replicates. As before, we found that the moving average test was more powerful than a test based on single p‐values. In some cases, the weighting procedure increased the power further and was similar to that of multipoint analysis, but this was not consistently found. In addition, all methods had low power and it is not possible to make a general conclusion that some weighting schemes are better than others. © 2001 Wiley‐Liss, Inc.     

Inhibition of Angiogenesis by Interleukin 4

Interleukin (IL)-4, a crucial modulator of the immune system and an active antitumor agent, is also a potent inhibitor of angiogenesis. When incorporated at concentrations of 10 ng/ml or more into pellets implanted into the rat cornea or when delivered systemically to the mouse by intraperitoneal injection, IL-4 blocked the induction of corneal neovascularization by basic fibroblast growth factor. IL-4 as well as IL-13 inhibited the migration of cultured bovine or human microvascular cells, showing unusual dose–response curves that were sharply stimulatory at a concentration of 0.01 ng/ml but inhibitory over a wide range of higher concentrations. Recombinant cytokine from mouse and from human worked equally well in vitro on bovine and human endothelial cells and in vivo in the rat, showing no species specificity. IL-4 was secreted at inhibitory levels by activated murine T helper (T_H0) cells and by a line of carcinoma cells whose tumorigenicity is known to be inhibited by IL-4. Its ability to cause media conditioned by these cells to be antiangiogenic suggested that the antiangiogenic activity of IL-4 may play a role in normal physiology and contribute significantly to its demonstrated antitumor activity.     

Endothelial Cell Proliferation is Enhanced by Low Dose Non-Thermal Plasma Through Fibroblast Growth Factor-2 Release

Non-thermal dielectric barrier discharge plasma is being developed for a wide range of medical applications, including wound healing, blood coagulation, and malignant cell apoptosis. However, the effect of non-thermal plasma on the vasculature is unclear. Blood vessels are affected during plasma treatment of many tissues and may be an important potential target for clinical plasma therapy. Porcine aortic endothelial cells were treated in vitro with a custom non-thermal plasma device. Low dose plasma (up to 30 s or 4 J cm⁻²) was relatively non-toxic to endothelial cells while treatment at longer exposures (60 s and higher or 8 J cm⁻²) led to cell death. Endothelial cells treated with plasma for 30 s demonstrated twice as much proliferation as untreated cells five days after plasma treatment. Endothelial cell release of fibroblast growth factor-2 (FGF2) peaked 3 h after plasma treatment. The plasma proliferative effect was abrogated by an FGF2 neutralizing antibody, and FGF2 release was blocked by reactive oxygen species scavengers. These data suggest that low dose non-thermal plasma enhances endothelial cell proliferation due to reactive oxygen species mediated FGF2 release. Plasma may be a novel therapy for dose-dependent promotion or inhibition of endothelial cell mediated angiogenesis.     

Prospective validation of a perinatal bacterial vaginosis screening risk score.

OBJECTIVE: Prospectively validate an antenatal bacterial vaginosis (BV) risk score at two public health department obstetrics clinics. STUDY DESIGN: Women (n=409) entering prenatal care received a BV risk score (range 0 to 16) at their first visit and at 24 to 28 weeks' gestation. BV was measured with Gram-stained vaginal smears. Normal discharge was used as a surrogate for being asymptomatic. RESULTS: Approximately half of the women scored > or =3 at each assessment. In total 29% had true BV at the first assessment (13% at the second assessment). The BV risk score (> or =3) had 91% sensitivity and 63% specificity, and the BV risk score (> or =5) had 88% sensitivity and 76% specificity. Among true cases, 42% were asymptomatic, of which 77% had risk scores > or =3. All symptomatic BV cases had risk scores > or =3. CONCLUSION: In practice, the risk score identified both asymptomatic and symptomatic cases. Asymptomatic women are of particular interest because they are not screened for BV under current practice guidelines.     

Nitric oxide reduces bacterial superantigen-immune cell activation and consequent epithelial abnormalities

Inhibition of the inducible form of nitric oxide (NO) synthase prolonged the murine enteropathy evoked by the bacterial superantigen, Staphylococcus aureus enterotoxin B (SEB). We examined the ability of NO to alleviate SEB-induced epithelial dysfunction and immune cell activation. Human peripheral blood mononuclear cells (PBMC) were activated by SEB for 24 h +/- the NO donors, S-nitroso-N-acetylpenicillamine and spermine-NONOate. The conditioned medium (CM) was collected and applied to T84 epithelial monolayers, and permeability [i.e., transepithelial resistance (TER)] and stimulated ion transport (i.e., short-circuit current responses to carbachol and forskolin) were assessed 24 h later. Exposure to CM led to an approximately 40% drop in TER and hyporesponsiveness to both secretagogues. CM made in the presence of NO donors (10(-4) M) had no significant effect on epithelial barrier or ion transport parameters. NO donors alone had no effect on naive epithelia, and addition of the NO donors to previously made CM did not affect the ability of this CM to alter epithelial function. Moreover, the NO donors dose-dependently reduced SEB-evoked PBMC proliferation and cytokine production (i.e., interferon-gamma, tumor necrosis factor alpha) but did not affect viability. These findings suggest a beneficial role for NO in inflammation by reducing immune cell activation and thus ameliorating consequent physiological abnormalities, in this instance, perturbed epithelial permeability and active ion transport.