Prenatal MRI diagnosis and outcomes of abdominal or sacrococcygeal teratomas and parasitic fetuses.

Objective: To investigate the MRI findings of fetal abdominal or sacrococcygeal teratomas and parasitic fetuses and analyze the outcomes on the basis of follow-up assessments. Methods: The MRI data of 60 cases of abdominal or sacrococcygeal masses were examined. The outcomes were followed up and compared with the prenatal MRI diagnoses. Results: The 60 cases included 52 cases of sacrococcygeal teratomas and eight cases of abdominal lesions. The common types of sacrococcygeal teratomas were type I (21/52, 40.4%) and type II (20/52, 38.5%); type III sacrococcygeal teratomas were rarer (8/52, 15.4%), while type IV tumors (3/52, 5.7%) were frequently complicated with hydronephrosis. Other complications included polyhydramnios in 22 cases, placental edema in six cases, and fetal hydronephrosis in three cases (all type IV). Seven of the eight parasitic fetuses were located in the abdominal cavity, and one was located in the sacrococcygeal region. Postnatal surgery was performed in 51 cases (51/60), including 44 with teratomas and seven with parasitic fetuses. In one case with hydronephrosis, peritoneal effusion, and subcutaneous edema, treatment was discontinued after birth (1/60). Fetal induction of labor was observed in eight cases (8/60). Prenatal ultrasound yielded incorrect or ambiguous diagnoses in 11 cases, while 51 cases showed a favorable course after surgery. Conclusions: MRI shows high accuracy in the diagnosis of fetal sacrococcygeal teratomas and parasitic fetuses. The prognosis in these cases is generally good. However, type IV sacrococcygeal teratomas are prone to fetal hydronephrosis and misdiagnosis and show a poorer prognosis.

The magnetic resonance enterography imaging features of symptomatic Meckel's diverticulum in pediatric patients: a retrospective observational study of 31 cases.

BACKGROUND: The aim of this study was to explore the magnetic resonance enterography (MRE) imaging manifestations of a symptomatic Meckel's diverticulum (MD) in pediatric patients in order to provide a reference for the diagnosis of the condition. METHODS: The medical records of 31 pediatric patients with MD from May 2014 to October 2020 were retrospectively analyzed. The inclusion criteria were patients with MD accompanied by unexplained gastrointestinal bleeding, anemia (except hematological diseases), chronic persistent abdominal pain, repeated intussusception, or intussusception in older pediatric patients during surgery. The clinical variables (age, sex, and hemoglobin) and imaging, surgical, and pathological findings were recorded. RESULTS: MD was definitively identified in 28 patients, with the following characteristics: a blind-ending fluid-filled and/or gas-filled structure (n=23), an elongated shape (n=1), a dumbbell shape (n=1), and a solid mass (n=3). The diverticula were located in the right lower quadrant (n=16), the right abdomen at the level of the umbilicus (n=3), the right upper quadrant (n=2), the left upper quadrant (n=2), and the midline lower abdomen (n=5). Supply arteries were visualized in nine cases. In all cases, mural enhancement was comparable to that of the adjacent small-bowel (SB). Extravasation of the intravascular contrast medium was seen in two cases. Peripheral structural abnormalities included mesenteric fat stranding (n=7), hemorrhage in the adjacent lumen (n=3), free intraperitoneal gas (n=1), abnormal fluid retention (n=2), intestinal obstruction (n=1), and lymph node enlargement (n=7). A normal appendix was identified in 18 cases. CONCLUSIONS: MRE is an appropriate method of diagnosing symptomatic MD in pediatric patients and is particularly useful in the assessment of complications.

Brucine inhibits bone metastasis of breast cancer cells by suppressing Jagged1/Notch1 signaling pathways.

OBJECTIVE: To examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis. METHODS: The osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0.08 mmol/L), or 10 µmol/L zoledronic acid as positive control. The migration and bone resorption were measured by transwell assay and in vitro bone resorption assay. The protein expressions of Jagged1 and Notch1 were investigated by Western blot. The expressions of transforming growth factor-ß1 (TGF-ß1), nuclear factor-kappa B (NF-κB) and Hes1 were determined by enzyme-linked immunosorbent assay. RESULTS: Compared with the model group, brucine led to a dose-dependent decrease on migration of MDA-MB-231 cells, inhibited RANKL-induced osteoclastogenesis and bone resorption of RAW264.7 cells (P<0.01). Furthermore, brucine decreased the protein levels of Jagged1 and Notch1 in MDA-MB-231 cells and RAW264.7 cells co-cultured system as well as the expressions of TGF-ß1, NF-κB and Hes1 (P<0.05 or P<0.01). CONCLUSION: Brucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.

The immunomodulating properties of human respiratory syncytial virus and immunostimulating complexes containing Quillaja saponin components QH-A, QH-C and ISCOPREP703.

A successful vaccine against human RSV (HRSV) is likely to induce a Th1 or a balanced Th1/TH2 cytokine response. We tested a panel of HRSV immunostimulating complexes (ISCOMs) containing different Quillaja saponin fractions (QH-A, QH-C, and 703: a mixture of 70% QH-A and 30% QH-C) with different immunological properties for their capacity of inducing innate and acquired immune responses. The HRSV 703 ISCOMs induced the strongest innate and acquired immune responses, followed by RSV QH-C and QH-A ISCOMs. All three formulations induced various degrees of Th1 bias response with prominent production of IFN-gamma being 10-50 times higher than that of IL-4 and IL-5. The HRSV specific IgG isotype profile correlated with the predominant secretion of Th1 cytokines, with strong induction of IgG2a antibodies. The 703 ISCOMs induced the most pronounced Th1 profile followed by QH-C and QH-A ISCOMs. The high incorporation of F protein in these ISCOMs compared to G protein combined with the Th1 biased nature of ISCOM are likely to be the causes to promote a Th1 type of profile. The prospect to formulate an RSV ISCOM formulation with an optimal Th1/Th2 balance is in reach particularly in view of the versatile properties of the ISCOM concept.

Bovine respiratory syncytial virus ISCOMs--protection in the presence of maternal antibodies.

The protection induced by immunostimulating complexes (ISCOMs) against bovine respiratory syncytial virus (BRSV) was evaluated and compared to that of a commercial inactivated vaccine (CV) in calves with BRSV-specific maternal antibodies. Following experimental challenge, controls (n = 4) and animals immunized with CV (n = 5) developed moderate to severe respiratory disease, whereas calves immunized with ISCOMs (n = 5) remained clinically healthy. BRSV was re-isolated from the nasopharynx of all controls and from all calves immunized with CV, but from none of the calves immunized with ISCOMs. BRSV-RNA was detected by real-time PCR from a single animal in this group. Significantly higher BRSV-specific nasal IgG, serum IgG1 and IgG2 titers were detected before and after challenge in animals immunized with ISCOMs versus CV. In conclusion, the ISCOMs overcame the suppressive effect of maternal antibodies in calves and induced strong clinical and virological protection against a BRSV challenge.

Current status and potential application of ISCOMs in veterinary medicine.

The immune stimulating complex (ISCOM) is a 40 nm nanoparticle used as a delivery system for vaccine antigens, targeting the immune system both after parenteral and mucosal administration. The ISCOM is made up of saponin, lipids and antigen usually held together by hydrophobic interaction between these three components. The compulsory elements to form the ISCOM structure are cholesterol and saponin. When the antigen is omitted the ISCOM-MATRIX is formed. There are a number of saponins that can form ISCOMs, and many other substances (including antigens, targeting and immuno-modulating molecules) can be incorporated into the ISCOM provided they are hydrophobic or rendered to be hydrophobic. Thus, it is possible to create ISCOM particles with different properties. After parenteral immunisation of the ISCOM, the T cell response is first detected in the draining lymph node. Subsequently, the T cell response is localised to the spleen, while the B cell response is first found both in the draining lymph nodes and in the spleen. Up to 50 days later, the majority of the antibody producing cells is found in the bone marrow (BM). In contrast, antigens that have been adjuvanted in an oil emulsion, limit the T cell response to the draining lymph nodes while the B cell response is found in the draining lymph nodes and spleen, but not in the BM. The ISCOM efficiently evokes CD8+, MHC class 1 restricted T cell response. The deposit of antigens both to the endosomal vesicles and to the cytosol of antigen presenting cells (APCs) explains why both T helper cells (vesicles) and cytotoxic T lymphocytes (cytosol) are efficiently induced by ISCOMs. The T helper (Th) cell response is balanced in the sense that both Th1 and Th2 cells are induced. Prominent IL-12 production by cells in the innate system is a characteristic reaction induced by ISCOMs, promoting the development of a strong Th1 response. After mucosal administration by the intranasal or the intestinal routes, the ISCOM induces strong specific mucosal IgA responses in local and remote mucosal surfaces. Also T cell responses are evoked by the mucosal administration. A large number of experimental ISCOM vaccines have been tested and protection has been induced against a number of pathogens in various species including chronic and persistent infections exemplified by human immune deficiency virus 1 (HIV-1), and 2 (HIV-2) and simian immune deficiency virus (SIV) in primates, and various herpes virus infections in several species. In contrast to a conventional rabies virus vaccine the ISCOM rabies formulation protected mice after exposure to the virulent virus. Recently, experimental ISCOM vaccines were shown to efficiently induce immune response in newborns of murine and bovine species in the presence of maternal antibodies, while conventional vaccines have failed. ISCOM vaccines are on the market for horses and cattle and several other ISCOM vaccines are under development. Since the ISCOM and the ISCOM-MATRIX can be blended with live attenuated vaccine antigens without hampering the proliferation of the live vaccine antigens, it opens the possibility to use the ISCOM adjuvant system in a mixture of live and killed vaccine antigens.

Vaccination with recombinant alphavirus or immune-stimulating complex antigen against respiratory syncytial virus.

Respiratory syncytial virus (RSV) causes severe respiratory diseases in infants and young children. Inappropriate immunity to the virus can lead to disease enhancement upon subsequent infection. In this study, we have characterized the antiviral immunity elicited by the recombinant Semliki Forest virus (SFV) encoding the RSV fusion (F) and attachment (G) protein, and compared with that induced by the immune-stimulating complex (ISCOM)-incorporated FG proteins. Antiviral immunity against RSV elicited nasally or parentally by either of the immunogen having divergent profiles could reduce lung RSV titers upon challenge. However, resistance to RSV without disease enhancement was only observed in those vaccinated with SFV recombinants via nasal route. Presence of postvaccination pulmonary IFN-gamma response to the H-2K(d)-restricted T cell epitope (F(85-93); KYKNAVTEL) was found to be associated with absence of enhanced pulmonary disease and goblet cell hyperplasia as well as reduced Th2-cytokine expression. This result demonstrates that the SFV recombinants can result in enhanced clearance of RSV without enhancing the RSV-associated disease, and underlines the importance in priming pulmonary MHC class I-restricted T cells when RSV FG-based vaccines are used.