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Human melanoma cells can process the MAGE-1 gene product and present the processed nonapeptide EADPTGHSY on their major histocompatibility complex class I molecules, HLA-A1, as a determinant for cytolytic T lymphocytes (CTLs). Considering that autologous antigen presenting cells (APCs) pulsed with the synthetic nonapeptide might, therefore, be immunogenic, melanoma patients whose tumor cells express the MAGE-1 gene and who are HLA-A1+were immunized with a vaccine made of cultured autologous APCs pulsed with the synthetic nonapeptide. Analyses of the nature of the in vivo host immune response to the vaccine revealed that the peptide-pulsed APCs are capable of inducing autologous melanoma-reactive and the nonapeptide-specific CTLs in situ at the immunization site and at distant metastatic disease sites.

The discoveries of human melanoma-associated antigens in molecular terms have renewed interest in peptide- or peptide- and antigen-presenting-cell (APC)-based cancer vaccines. Considering the limited scope of immunization using defined peptides, we have studied an alternative approach of specific immunization with tumor-lysate-loaded autologous APC (adherent peripheral mononuclear cells cultured in 1000 U granulocyte/macrophage-colony-stimulating factor for 14 days) as a surrogate vaccine. Seventeen patients (11 with active metastatic disease) were intradermally immunized with the vaccine in a phased dose escalation (10(5)-10(7) cells/injection) monthly for 4 months. Thirteen patients completed all four immunizations showing no toxicity (3 patients had to be taken off study because of progressive disease and 1 patient went off study as a result of myocardial infarction due to multi-vessel coronary artery disease). None has shown any immediate or delayed toxicity attributable to the immunization and none has shown any evidence of autoimmunity. One patient showed a partial regression of a subcutaneous nodule. Thirteen patients are alive after 4+ months to 30+ months (17-month median survival for the group). Nine patients showed evidence of delayed-type hypersensitivity at the vaccine sites. Monitoring of biological response in conventional natural killer or cytolytic T lymphocyte assays with pre- and post-immune peripheral blood lymphocytes revealed no consistent differences. The vaccine-infiltrating lymphocytes (VIL) from nine specimens were adequately expanded following in vitro stimulation with the respective autologous-lysate-loaded APC for phenotypic and functional analyses. Five of the nine ex vivo expanded VIL were predominantly CD8+. Evidence of an antigen-specific CD8+ T cell response (cytotoxicity and/or tumor necrosis factor production) was detected in three of the five CD8+ VIL. These observations suggest that this type of vaccine is feasible, that it has biological activity, and that the approach may be improved through additional strategic manipulations.

We report an unusual case of massive intraventricular spread of B-cell lymphoma of the breast, presenting with rapidly progressive ataxia and impaired cognition with need for ventriculostomy. Rapid resolution followed intravenous dexamethasone and radiation therapy.

The relative merits of a vascularized autogenous cartilage flap (VACF) are discussed in reconstruction of tracheal defects in rabbits. Sixteen albino Vienna rabbits were divided into two groups of eight animals each. In all rabbits, a rectangular tracheal defect was created. In the experimental group, a VACF was designed on the left auricle. This island flap was then transposed through a subcutaneous tunnel to the trachea and used to repair the defect. In the control group, tracheal defects were reconstructed with free cartilage grafts. In histologic evaluations, it was found that the reconstructed site showed a greater degree of vascularization when a VACF was used, and the gap between the trachea and flap was filled with new cartilage tissue, to a much greater extent than with the free cartilage grafts. It is concluded that use of the VACF is a relatively safe and effective procedure for repairing tracheal defects.

Recently the Galactic and Extra-galactic All-sky Murchison Widefield Array survey has published 27 new candidate radio supernova remnants (SNRs) which are located within the longitude ranges of 345{\\deg} < l < 60{\\deg} and 180{\\deg} < l < 240{\\deg}. To search for the gamma-ray counterparts of these candidate radio SNRs, we analyzed 14 years of {\\it Fermi}-LAT data in the energy range of 1 - 300 GeV. There are three promising SNRs; G18.9\\(-\\)1.2, G23.1\\(+\\)0.1, and G28.3\\(+\\)0.2, which we detected at a significance level of \\(\\sim\\)9\\(\\sigma\\), \\(\\sim\\)13\\(\\sigma\\), and \\(\\sim\\)12\\(\\sigma\\), respectively. Here we report the results of our morphological and spectral analyses of G18.9\\(-\\)1.2, G23.1\\(+\\)0.1, and G28.3\\(+\\)0.2. No extended gamma-ray emission is detected for any of these SNRs. Our analysis of the 3 SNRs' {\\it Fermi}-LAT gamma-ray emission showed that their best-fit positions (if assumed point-like) overlap with the locations of the corresponding GLEAM counterparts.

3C 400.2 belongs to the mixed morphology supernova remnant class, showing center-filled X-ray and shell-like radio morphology. We present a study of 3C 400.2 with archival Suzaku and Fermi-LAT observations. We find recombining plasma (RP) in the Suzaku spectra of north-east and south-east regions. The spectra of these regions are well described by two-component thermal plasma models: The hard component is in RP, while the soft component is in collisional ionization equilibrium (CIE) conditions. The RP has enhanced abundances indicating that the X-ray emission has an ejecta origin, while the CIE has solar abundances associated with the interstellar material. The X-ray spectra of north-west and south-west regions are best fitted by a two-component thermal plasma model: an ionizing and a CIE plasma. We have detected GeV gamma-ray emission from 3C 400.2 at the level of \\(\\sim\\)5\\(\\sigma\\) assuming a point-like source model with a power-law (PL) type spectrum. We have also detected a new GeV source at the level of \\(\\sim\\)13\\(\\sigma\\) assuming a Gaussian extension model with a PL type spectrum in the neighborhood of the SNR. We report the analysis results of 3C 400.2 and the new extended gamma-ray source and discuss the nature of gamma-ray emission of 3C 400.2 in the context of existing NANTEN CO data, DRAO HI data, and the Suzaku X-ray analysis results.

Pregnancy in women having chronic renal insufficiency and undergoing hemodialysis is a rare event with a poor outcome. This is the 1st case in whom pre- and posthemodialysis fetal renal artery Doppler flow velocimetry was used in conjunction with fetal blood sampling which was performed to assess fetal karyotype and blood chemistry. Uteroplacental Doppler measurements were also performed, and a close correlation between maternal-fetal blood creatinine and urea nitrogen levels and fetal renal, umbilical, and uterine artery resistance indexes was observed.

Millisecond pulsars (MSPs) are observed to emit multi-wavelength radiation, from radio to GeV. Spider MSPs, which interact with their low-mass companion in close orbit (orbital periods \\(< 1\\) day), may lead to strong intrabinary shocks that can further accelerate electron and positron pairs produced in the magnetosphere, possibly emitting very-high-energy (0.1--100 TeV; VHE) photons through inverse Compton scattering. Using 2565 days of HAWC Pass 5 data, we search for VHE emission from spider MSPs and present upper limits on individual sources. We also perform a stacking analysis to examine whether the two sets of spider systems, classified as redbacks and black widows depending on the companion mass, exhibit different spectral properties. Our study places constraints on TeV emission from MSPs and suggests that they are unlikely to contribute significantly to the Galactic diffuse emission at TeV and higher energies.

The last five years have shown us that ultra-high-energy (UHE; \\(>\\)100 TeV) gamma-ray sources are ubiquitous, but the nature of these sources remain highly uncertain. UHE gamma rays can be produced via either leptonic (Inverse compton) or hadronic (pion decay) emission mechanisms. To decisively determine the emission mechanisms, multimessenger searches are essential. Neutrinos are of particular interest as they are only created via hadronic channels. In this work, we describe a metric to select high-quality UHE events from the High Altitude Water Cherenkov (HAWC) Observatory. We use this metric to search for correlations between HAWC archival data and IceCube public neutrino alerts. 24 spatial coincidences are found, which is higher than the number of events expected by random chance. Therefore, we conclude that there are likely associations between HAWC gamma rays and IceCube neutrinos, but the angular resolutions of the two instruments prevent us from conclusively making any definitive associations between the coincidences and specific astrophysical sources. More sensitive detectors are needed.

Multi-TeV gamma-ray emission around eHWC J1850+001 (a source from the first HAWC catalog of gamma-ray sources emitting above 56 TeV) is spatially coincident with the pulsar wind nebula (PWN) G32.64+0.53, powered by PSR J1849-0001. The absence of counterparts in radio, optical, and GeV energy ranges, contrasted with clear detections in X-rays and very-high-energy (VHE) gamma-rays, is indicative of a non-thermal leptonic origin for the nebula. We apply a systematic analysis pipeline, including a sophisticated model for the Galactic diffuse emission, to 2860 days of data from the HAWC Observatory. Our detailed analysis confirms that the ultra-high-energy (UHE) emission originates from G32.64+0.53, and we measure its spectrum up to 270 TeV with significant emission well beyond 100 TeV. We fit the multi-wavelength observations with a time-dependent leptonic model powered by the pulsar's rotational energy, and the results establish the nebula as a leptonic PeV accelerator, capable of accelerating electrons to a maximum energy of \\(E_{\\mathrm{cut}}=1.5_{-0.6}^{+1.7}~\\mathrm{PeV}\\). The model also constrains the true age of the system to \\(26.8~\\mathrm{kyr}\\) and the nebular magnetic field to a low value of \\(2.5 ~\\mathrm{\\mu G}\\), supporting a leptonic PWN origin for the observed UHE emission.