Identification of Tumor Antigens in the HLA Peptidome of Patient-derived Xenograft Tumors in Mouse

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Highlights

• •Sufficient tumor tissues are often unavailable large HLA peptidome discovery.
• •Using patient derived xenograft (PDX) tumors can overcome this limitation.
• •The large PDX HLA peptidomes expand significantly those of the original biopsies.
• •The HLA peptidomes of the PDX tumors included many tumor antigens.

     

Changing behavior of surface immunoglobulin on mouse B lymphocytes during immune development: I. LPS-induced changes in the lateral mobility of B lymphocyte surface immunoglobulins on two populations which express different surface immunoglobulin phenotypes

The redistribution of surface membrane immunoglobulin molecules (sIg) was studied in two functionally distinct populations of mouse splenic B lymphocytes, namely, those bearing membrane IgM(IgG^?) and those bearing IgG. Brief exposure to mitogenic doses of bacterial lipopolysaccharide (LPS) produced direct but differential effects on the subsequent ability of specific antibodies to induce this redistribution on each cell type. Studied as a function of temperature, antibody-induced redistribution of sIgM on cells previously exposed to LPS was observed to occur at temperatures lower than the temperatures required for similar sIgM redistribution on lymphocytes not exposed to LPS. In contrast, mitogen-treated sIgG⁺ cells demonstrated an opposite and long-lasting effect (at least 40 hr), requiring higher temperatures to allow sIgG movement comparable to that seen on untreated sIgG-bearing lymphocytes. Thus, we conclude that LPS interacts with both IgM⁺(IgG^?) and IgG⁺ lymphocytes, but that such interactions produced different membrane effects on each B-cell subset. This membrane change can therefore be useful as a quasi-functional differentiation marker. Furthermore, differences in sensitivity to cellular activation by LPS seen between sIgM-bearing (sIgG^?) and sIgG-bearing B cells may be a reflection of such direct, although different, membrane effects.     

Investigation of variation in phenotype and DNA content between single-conidium isolates of single Penicillium strains

Variation in phenotypic properties was examined in three strains of closely related fasciculate species of Penicillium using 114 morphological, physiological, and biochemical characters. Thirty-six of these characters showed variation within single-conidium isolates of the same strain. Conidial sizes and nuclear DNA contents were compared using flow microfluorimetry; these results suggested that significant differences in conidial DNA content are associated with phenotypic variation. The taxonomic significance of the results is discussed.     

Chemo-adoptive immunotherapy of nude mice implanted with human colorectal carcinoma and melanoma cell lines

Summary The antitumor effects of chemotherapy, recombinant human interleukin-2 (IL-2), recombinant human interferon A/D (IFN), allogeneic human lymphokine-activated killer (LAK) cells, and antitumor monoclonal antibody (mAb), administered alone and in various combinations, were tested in athymic nude mice carrying human tumor xenografts. Treatment began 6–18 days after i.v. or i.p. inoculation of colorectal carcinoma or melanoma cell lines, when macroscopic growths were evident. Chemotherapy consisted of two or three courses of 5-fluorouracil (5-FU) or dacarbazine. IL-2 and/or IFN were administered three to five times weekly for 1–3 weeks, usually starting 2–5 days after chemotherapy. Human LAK cells were infused once or twice weekly for 2 or 3 weeks concurrently with IL-2. In some experiments, murine anticolorectal carcinoma mAb (SF25) was administered. In both tumor systems, chemotherapy alone or immunotherapy alone (IL-2, IL-2 + LAK cells, IFN, IL-2 + IFN ± LAK cells) had little or no therapeutic effects. Additive effects were obtained by combining chemotherapy with IL-2 and LAK cells or with IL-2 and IFN. In the majority of the experiments, the most effective combination was chemotherapy + IL-2 + IFN + LAK cells. Treatment with mAb was beneficial in the colorectal carcinoma system when combined with 5-FU + IL-2 or 5-FU + IL-2 + IFN. Homing experiments with radiolabeled human and mouse LAK cells injected i.v. showed increased early accumulation in the liver and lungs, whereas freshly explanted mouse splenocytes localized mostly in the spleen and liver. The tissue distribution pattern of human LAK cells was similar in normal and tumor-bearing mice (with lung metastases). These findings suggest that combination of chemotherapy with cytokines and LAK cells can be partially effective for advanced solid human tumors even in the absence of the host's T-cell immune response. Preliminary experiments showed that tumor-specific, anti-melanoma T-cell clones were effective in local (s.c.) tumor growth inhibition (Winn assay) following coinjection with the autologous tumor cells.     

Pneumocystis carinii shows DNA homology with the ustomycetous red yeast fungi

Pneumocystis carinii causes life-threatening pneumonia in T-lymphocyte-immunodeficient subjects in transplant and oncology units or with acquired immune deficiency syndrome (AIDS). Recent DNA homology studies show P. carinii to be a fungus. To investigate the biology and epidemiology of this parasite further, we elected to determine for it a more precise taxonomic assignment within the fungal kingdom. We screened a wide range of organisms representing the major orders of fungi using DNA amplification and subsequently sequenced a portion of the mitochondrial gene encoding the large subunit ribosomal RNA. Our data show that the opportunistic pulmonary pathogen P. carinii is closely related to the ustomycetous red yeast fungi, a group which includes organisms that are extensively distributed throughout the environment and which release many widely dispersed airborne spores.     

Seasonal changes in the photosynthetic response ofMercurialis perennis plants from different light regime conditions

Curves relating net photosynthetic rate to irradiance [P(I) curve relation] were estimated and analysed inMercurialis perennis L. plants stemming from three forest (spruce, beech and ash) stands with different tree leaf canopy development and different light regime. The saturating irradiance (I_s) reached the highest values in plants of all three stands in spring (spruce forest: 438 W m⁻², beech forest: 440 W m⁻² and ash forest: 367 W m⁻²), it declined sharply in the middle of the growing season (283, 285 and 297 W m^-2, respectively) and this I_s level persisted until autumn. A pronounced dynamics in plants from spruce and beech forests made itself manifest also in the adaptation (I_a) and compensating (I_c) irradiances, respectively. After a sudden decline in summer, values in autumn were close to those of the vernal season. The most pronounced parameter, which optimally expressed the adaptation ofMercurialis perennis to various light conditions, was the photosynthetic efficiency (α) calculated as the slope of the linear part of the curve relating net photosynthetic rate to irradiance. At the time of the highest P_{N sat.} value in course of the growing season (August) (spruce forest: 100, beech forest: 98.7 and ash forest: 85.8 μg CO₂ m⁻² s⁻¹), R_D was in its minimum; in autumn P_{N sat.} reached the lowest values which corresponded to the most intensive R_D. It was found thatMercurialis perennis plants stemming from forest stands with different light conditions did not make use equally of the altering light conditions in the course of the growing season. By the underlying analysis of P(I) curves this rhizomatous perennial herb (geophyte) may be characterized as a shade tolerant species.     

Endogenous γ-Hydroxybutyrate in Rat Brain Areas: Postmortem Changes and Effects of Drugs Interfering with γ-Aminobutyric Acid Metabolism

Abstract: The possibility that γ-hydroxybutyrate (GHB), a metabolite of γ-aminobutyric acid (GABA), may play a role in the CNS has recently come to attention. We describe here a sensitive and specific mass fragmento-graphic technique that allows the measurement of picomole amounts of GHB in single rat brain areas. Moreover, we show that GHB can accumulate postmortem, an effect that is blocked by the use of microwave irradiation to kill the animals. To understand further the relationship between GABA and GHB formation, we treated rats with drugs known to inferfere with GABA metabolism at different levels and concomitantly measured GABA and GHB in cerebral cortex and cerebellum. Isoniazide, which blocks the formation of GABA, also decreases GHB. Blockers of the catabolism of GABA, such as aminooxyacetic acid and γ-acetylenic GABA, increase GABA levels and decrease those of GHB. Sodium dipropylacetate increases both GABA and GHB, supporting the hypothesis that this effective antiepileptic drug also blocks in vivo the enzyme that converts succinic semialdehyde to succinic acid.     

The occurrence of fungi in activated sludge

The population of a biological system in a sewage treatment plant is formed of a fortuitous assemblage of microorganisms, members of which are continually dropped out while additional members are recruited. Many of these organisms are active throughout the year. Fewer yeasts than filamentous fungi are found by the plating technique. The population is about evenly divided between species producing their spores in dry states and in wet states. The fungus population includes species which under certain circumstances are able to use a wide variety of substrates from simple sugars to complex carbohydrates and hydrocarbons.

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Zusammenfassung Die Population eines biologischen Systems in einem Kloakenwasser-Behandlungs-werk ist durch ein zufälliges Zusammentreffen von Mikroorganismen geformt, deren Mitglieder fortwährend ausfallen, während andere hinzukommen. Viele dieser Mikroorganismen sind während des ganzen Jahres aktiv. Weniger Hefen denn Fadenpilze sind mit der Plattentechnique gefunden. Die Population ist ungefähr gleichmäßig unter den Arten verteilt, die die Sporen in trockenem wie in feuchtem Zustand produzieren. Die Pilzpopulation umfaßt Arten, die unter gewissen Umständen fähig sind, eine große Varietät von Nährmaterial, von einfachen wie auch komplexen Kohlenstoffhydraten und Kohlenstoffhydraten zu benutzen.

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Much of the material included here was Presented at the 23rd Industrial Waste Conference Purdue University, Lafayette, Indiana May 7–9, 1968