Amyloid associated with elastin-staining laminar aggregates in the lungs of patients diagnosed with acute respiratory distress syndrome.

Background: The heterogeneity of conditions underlying respiratory distress, whether classified clinically as acute lung injury (ALI) or the more severe acute respiratory distress syndrome (ARDS), has hampered efforts to identify and more successfully treat these patients. Examination of postmortem lungs among cases clinically diagnosed as ARDS identified a cohort that showed a consistent morphology at the light and electron microscope levels, and featured pathognomonic structures which we termed elastin-staining laminar structures (ELS).

Methods: Postmortem tissues were stained using the Verhoeff-Van Gieson procedure for elastic fibers, and with Congo red for examination under a polarizing microscope.

Stress proteins and glycoproteins (Review).

Proteins represent both structural and functional elements of biological organisms, however, their structural and catalytic function is directly linked to the acquisition and maintenance of a complex three-dimensional conformation. A molecular machinery to accomplish protein folding and maintenance in vivo is provided by a variety of molecular chaperones that include both heat shock proteins (Hsps), glucose-regulated proteins (Grps), and a separate class of stress glycoproteins (S-Gps). Different chaperones associate to form functional complexes (chaperone) and work coordinately to accomplish specific functions during the folding of particular proteins.

Partial characterization of a Cisplatin-resistant subline of murine rif-1 tumor-cells.

We have developed a drug-resistant cell line (RIF/Ptr1) (R) from the murine radiation-induced fibrosarcoma (RIF-1) also designated Pts or (S). This subline has been characterized previously by an increased resistance to cisplatin (cis-diamminedichloroplatinum(II) or CDDP), lowered intracellular CDDP concentrations, and elevated intracellular glutathione (GSH) levels (1.4-2.

Tumor drug-resistance: a challenge to therapists and biologists.

Cancer is the second largest cause of death after cardiovascular disease in the United States. Systemic chemotherapy is the major treatment modality for a number of common cancers, such as lymphomas, leukemias, and for the majority of disseminated tumors. The emergence of drug-resistant tumor cells is the major cause of subsequent cancer treatment failures.

Heat shock glycoprotein GP50: product of the retinoic acid-inducible J6 gene.

High intracellular levels of heat shock proteins and enhanced protein glycosylation are two phenomena closely associated with the cellular stress response. GP50 is the major heat-induced glycoprotein in Chinese hamster ovary (CHO) cells; however, GP50 is not well characterized, and its function is unknown. J6 is a gene originally identified in F9 murine teratocarcinoma cells after exposure to retinoic acid.

Prompt protein glycosylation during acute heat stress.

Constitutive patterns of protein synthesis and protein glycosylation are severely disrupted by acute heat stress. Stressed cells respond by preferential synthesis of specific proteins, e.g.

Multidrug resistance: prospects for clinical management.

Clinical success in the treatment of tumors with chemotherapy has significantly improved over the past several years. However, treatment failures due to drug resistance of cancer cells has remained a major problem. The classical form of multiple drug resistance is perhaps also the most common type of drug resistance, and represents the overexpression of a transmembrane glycoprotein pump (P-170) that mediates the efflux of a spectrum of structurally and functionally unrelated drugs.

Inhibition of heat shock protein synthesis and protein glycosylation by stepdown heating.

Mammalian cells exhibit increased sensitivity to hyperthermic temperatures of 38-43 degrees C after an acute high-temperature heat shock; this phenomenon is known as the stepdown heating (SDH) effect. We characterized the SDH effect on (1) the synthesis of major heat shock proteins, HSP110, 90, 72/70, 60 (35S-amino acids label), (2) on heat-induced protein glycosylation (3H-D-mannose label), and (3) on thermotolerance expression, using cell survival as an endpoint. Partitioning of label between soluble and insoluble cell fractions was separately examined.

Tumor-targeted delivery of 8-hydroxyquinoline.

RIF-1 mouse tumors express high levels of beta-glucuronidase activity relative to most normal tissues. The high activity can be exploited for targeting specific drugs preferentially to tumor tissues. In this study we examined the kinetics of 8-hydroxyquinoline (8-OHQ) accumulation in tumor and in several normal tissues resulting from the in vivo deconjugation of 8-hydroxyquinolyl-glucuronide (8-OHQ-GlcA).

New approaches to the study of tumor drug resistance.

The development of tumor drug resistance is the major obstacle to successful systemic chemotherapy. Therefore, devising methods for reversing drug resistance is a high priority and could lead to significant improvements in cancer treatment. The mechanisms of tumor drug resistance are manifold and are not well understood.

Cultured Chinese hamster cells undergo apoptosis after exposure to cold but nonfreezing temperatures.

Cultured Chinese hamster V79 fibroblast cells at the transition from logarithmic to stationary growth have been shown to undergo apoptosis (programmed cell death) after cold shock [B. L. Soloff, W.

Protein glycosylation in heat-sensitive and thermotolerance-deficient mutants of Chinese hamster ovary cells.

Chinese hamster ovary (CHO) cells are capable of developing a high degree of thermotolerance in response to appropriate heat conditioning. In this study we examined the relationship between thermotolerance development and protein glycosylation using four sublines of CHO cells. Two of these CHO sublines are characterized by an increased heat sensitivity and impaired cellular capacity for thermotolerance development.

Tumor cell drug resistance and its reversal.

Tumors that formerly were uniformly fatal can now be cured by cancer chemotherapy. However, successful anticancer therapy is faced by many obstacles, such as excessive normal tissue toxicity and drug resistance. Tumor drug resistance may be either intrinsic or acquired.

Characterization of a cisplatin-resistant subline of murine RIF-1 cells and reversal of drug resistance by hyperthermia.

The development of tumor cell drug resistance is a major obstacle which often leads to failure of cancer chemotherapy. Therefore, reversing the cell drug resistance would have important implications in cancer treatment. We have developed a cisplatin-resistant mouse tumor cell line from the radiation induced fibrosarcoma (RIF-1) parental line; this line is named RIF/ptr1 versus the parental line RIF/pts1.

In vitro antiproliferative activity of 4-substituted 2-(2-hydroxyphenyl)thiazolines on murine leukemia cells.

Two previously synthesized and two structurally novel thiazoline iron chelators are described. N4-Benzyl-N1,N8-bis[[2-(2-hydroxyphenyl)thiazolin-4-yl]carbonyl] homospermidine (5) proved to be the most potent antiproliferative and cytocidal compound in the series with in vitro IC50 values of 3 and 1 microM on L1210 and P388 murine cell lines. The N4-acetyl analogue 7 was considerably less active than 5 with IC50 and cell viability values that were similar to those of the structurally simple thiazolines 2 and 3.

Immunochemical quantitation of DNA adducts derived from the human bladder carcinogen 4-aminobiphenyl.

To assess target-tissue exposure to the human urinary bladder carcinogen 4-aminobiphenyl (ABP), we have developed a sensitive immunochemical method for measuring the major arylamine-DNA adduct formed, N-(guan-8-yl)-ABP (Gua-C8-ABP). High-affinity polyclonal antisera from rabbits immunized with N-(guanosin-8-yl)-ABP coupled to keyhole limpet hemocyanin were characterized and shown to have high specificity for antigenic determinants on the purine and biphenyl rings of Gua-C8-ABP and minimal cross-reactivity with ABP, deoxyguanosine, or hydrolyzed DNA. Assay standards containing ABP-modified DNA were prepared by reacting [3H]N-hydroxy-ABP with calf thymus DNA.

Tumor-targeted cell killing with 8-hydroxyquinolyl-glucuronide.

Many tumors show elevated levels of hydrolytic enzymes that may be associated with invasive processes. The RIF-1 murine tumor has levels of beta-glucuronidase that are more than four times higher than those in liver. Elevated tumor glucuronidase levels can be used as a basis for tumor-targeted therapy when systemically administered glucuronides of cytotoxic drugs are deconjugated preferentially at the tumor site.

Uncoupling of oxidative phosphorylation does not induce thermotolerance in cultured Chinese hamster cells.

Two uncouplers of oxidative phosphorylation, 2,4-dinitrophenol (DNP) and carbonyl cyanide m-chlorophenylhydrazone (CCCP), were tested for their ability to modify the survival of cultured Chinese hamster ovary (CHO) and Chinese hamster V79 cells treated with hyperthermia. The uncouplers were used under conditions that inhibit oxidative ATP synthesis, as judged from measurements of cellular ATP levels. Incubation of CHO cells in glucose-free Hanks' balanced salt solution (HBSS) containing 1 mM DNP for 1 h at 37 degrees C followed by reincubation at 37 degrees C in complete growth medium for 3 or 16 h, showed no substantial changes in the 45 degrees C heat survival curve as compared to heated cells not exposed to DNP.

Protection against heat-induced cell killing by alanine.

When L-alanine was added either to full growth medium or to Hanks' balanced salt solution (HBSS) prior to hyperthermia, survival of heated cells was significantly increased in a concentration-dependent manner. Maximal heat protection was not immediate, but required at least 1 h at 37 degrees C incubation prior to heating. Heat protection was principally reflected in an increased Dq on the 45 degrees C survival curve; for example, with 100 mM L-alanine, the Dq increased from approximately equal to 20 (control) to 30 min at 45 degrees C.

Enhanced glycosylation of a 50 kD protein during development of thermotolerance in CHO cells.

During the development of thermotolerance, Chinese hamster ovary cells not only synthesized classical heat shock proteins, but also incorporated [3H]D-glucose or mannose into a glycoprotein with a Mr of approximately 50 kD. The glycosylation of the 50 kD protein correlated with the expression of thermotolerance under conditions when tolerance was induced either by acute or chronic heat conditioning. A phosphoprotein with the same molecular weight as the 50 kD glycoprotein was dephosphorylated immediately after heat conditioning.

Interactions of BCNU, low pH, glucose and hyperthermia in cultured RIF cells.

The interactions of BCNU (1,3-bis[2-chloroethyl]-1-nitrosourea) with low pH, glucose and hyperthermia were studied in cultured RIF tumor cells. The effect of a mild heat treatment of 43 degrees C, 1 h at pH 7.4 on cell killing [surviving fraction (S) = 0.

Apoptosis induced by cold shock in vitro is dependent on cell growth phase.

Chinese hamster V79 fibroblast cells were exposed to brief periods of cold but non-freezing temperatures at different points on the population growth curve. Upon rewarming, cells at the transition from logarithmic to stationary growth exhibited apoptosis (programmed cell death). Cells in other stages of growth, or after reentry into logarithmic growth by refeeding, did not exhibit apoptosis.

Development of thermotolerance in CHO cells: modification by procaine.

We have tested the reported ability of procaine to inhibit the induction and the development of thermotolerance in Chinese hamster ovary cells. Thermotolerance was induced either by hyperthermia alone (10 min, 45 degrees C) or by combining hyperthermia and procaine (5 min, 45 degrees C + 10 mM procaine) with heating times adjusted to yield similar cell survival after the conditioning treatments. Both the kinetics of thermotolerance development in fresh medium without procaine and the magnitude of thermotolerance 6 h after heat conditioning were similar for the two treatment groups.

Temperature-dependent induction of thermotolerance by ethanol.

Ethanol (1 M) cytotoxicity in asynchronous Chinese hamster ovary cells was strongly temperature dependent, yielding families of cell survival curves between 34 and 39 degrees C that were similar to those obtained at hyperthermic temperatures in medium without ethanol. Below 36 degrees C, survival curves were biphasic, indicating the development of thermotolerance during ethanol exposures. At room temperature (22 degrees C) ethanol was completely nontoxic with incubation periods up to 6 h.

Cytotoxicity of hyperthermia combined with bleomycin or cis-platinum in cultured RIF cells: modification by thermotolerance and by polyhydroxy compounds.

The effect of thermotolerance and of polyhydroxy compounds on the cytotoxicity of bleomycin and cis-platinum was studied in cultured RIF tumor cells. Cell survival in response to drug-heat treatments was compared in cells not previously exposed to hyperthermia and in preheated cells that had developed thermotolerance. Since cellular accumulation of polyhydroxy compounds is a potential mechanistic basis of thermotolerance, we also compared cell survival of thermotolerant cells and chemically heat-protected cells.