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Biomedical subjects

D G Fischer

Publications and source records attributed to D G Fischer.

At least 19 recordsLinked to original sources
PubMed2006

Do high-tannin leaves require more roots?

The well-known deceleration of nitrogen (N) cycling in the soil resulting from addition of large amounts of foliar condensed tannins may require increased fine-root growth in order to meet plant demands for N. We examined correlations between fine-root production, plant genetics, and leaf secondary compounds in Populus angustifolia, P. fremontii, and their hybrids. We measured fine-root (<2 mm) production and leaf chemistry along an experimental genetic gradient where leaf litter tannin concentrations are genetically based and exert strong control on net N mineralization in the soil. Fine-root production was highly correlated with leaf tannins and individual tree genetic composition based upon genetic marker estimates, suggesting potential genetic control of compensatory root growth in response to accumulation of foliar secondary compounds in soils. We suggest, based on previous studies in our system and the current study, that genes for tannin production could link foliar chemistry and root growth, which may provide a powerful setting for external feedbacks between above- and belowground processes.

Hybridization, Genetic↗
PubMed2004

Ecosystem implications of genetic variation in water-use of a dominant riparian tree.

Genetic variation in dominant species can affect plant and ecosystem functions in natural systems through multiple pathways. Our study focuses on how genetic variation in a dominant riparian tree ( Populus fremontii, P. angustifolia and their natural F(1) and backcross hybrids) affects whole-tree water use, and its potential ecosystem implications. Three major patterns were found. First, in a 12-year-old common garden with trees of known genetic makeup, hybrids had elevated daily integrated leaf-specific transpiration ( E(tl); P=0.013) and average canopy conductance ( G(c); P=0.037), with both E(tl) and G(c) approximately 30% higher in hybrid cross types than parental types. Second, delta(13)C values of leaves from these same trees were significantly more negative in hybrids ( P=0.004), and backcross hybrids had significantly more negative values than all other F(1) hybrid and parental types ( P<0.001). Third, in the wild, a similar pattern was found in leaf delta(13)C values where both hybrid cross types had the lowest values ( P<0.001) and backcross hybrids had lower delta(13)C values than any other tree type ( P<0.001). Our findings have two important implications: (1). the existence of a consistent genetic difference in whole-tree physiology suggests that whole-tree gas and water exchange could be another pathway through which genes could affect ecosystems; and (2). such studies are important because they seek to quantify the genetic variation that exists in basic physiological processes-such knowledge could ultimately place ecosystem studies within a genetic framework.

Carbon Isotopes↗
PubMed1998

Characteristics of intrafamilial and extrafamilial child sexual abuse.

OBJECTIVE: The precise nature of the differences between intrafamilial and extrafamilial child sexual abuse is not clear. The purpose of the present study is to provide clarification of these differences. METHOD: Archival data containing 1,037 cases of child sexual abuse were obtained from police files in two western Canadian cities with populations of about 180,000. Two trained research assistants coded and transcribed the data. RESULTS: Results showed: (1) earlier onset, longer duration, higher level of intrusion, and greater physical and emotional injury for intrafamilial victims; (2) less use of physical/verbal force, or enticements, and greater use of instructions "not to tell" by intrafamilial offenders; (3) more convictions and longer jail sentences for intrafamilial offenders; and (4) no intra-extrafamilial differences in victim sex preference. CONCLUSIONS: Boys are younger than girls at the time of first abuse in samples of criminal justice and hospital referrals, although only for older aged victims, for example, 8 to 17 years. Although statistically significant, there is little difference in level of intrusion perpetrated by intrafamilial and extrafamilial offenders, both are highly intrusive. Both intrafamilial and extrafamilial offenders use physical/verbal force, with older victims: extrafamilial offenders more often choose older victims, and therefore more often use force. Intrafamilial victims suffer greater physical and emotional injury, resulting from greater intrusion not duration of abuse. It's not clear that victim sex preferences of intra- and extrafamilial offenders exist.

Adolescent↗
PubMed1994

Isolation and characterization of a soluble form of the LDL receptor, an interferon-induced antiviral protein.

Interferons (IFNs) act by inducing several intracellular antiviral proteins. We report here that IFNs also induce an extracellular soluble protein that inhibits vesicular stomatitis virus (VSV) infection. This protein accounts for 25%-50% of the total antiviral activity elicited by IFN. The antiviral protein was purified to homogeneity from culture supernatants of IFN-treated cells by several chromatographic steps, to give a single 28-kDa active polypeptide. Upon sequencing, this novel protein corresponded to the N-terminal ligand-binding domain of the human 160-kDa low-density lipoprotein receptor (LDLR). In addition, we find that IFN induces the cell surface LDLR and this phenomenon may explain previous reports on reduction of serum cholesterol in IFN-treated patients. Viruses produce soluble cytokine receptors that inhibit their respective cytokines, thereby assisting virus infection. It appears now that host cells employ similar molecules for the opposite role of controlling virus infections.

Amino Acid Sequence↗
PubMed1993

An antiviral soluble form of the LDL receptor induced by interferon.

Interferons, which induce several intracellular antiviral proteins, also induce an extracellular soluble protein that inhibits vesicular stomatitis virus (VSV) infection. This 28-kilodalton soluble protein was purified to homogeneity and identified by protein sequencing as the ligand-binding domain of the human 160-kilodalton low density lipoprotein receptor (LDLR). The existence of an antiviral soluble LDLR was confirmed by immunoaffinity chromatography with monoclonal antibody to LDLR. This soluble receptor mediates most of the interferon-triggered antiviral activity against VSV, apparently by interfering with virus assembly or budding, and not by inhibiting virus attachment to cells.

Amino Acid Sequence↗
PubMed1993

Inflammatory bowel disease impact and patient characteristics.

A major purpose of this survey was to describe the impact of inflammatory bowel disease on the daily life of 150 nonhospitalized adults. A complementary purpose was to examine patient characteristics and their relationship to perceived impact. Self-report questionnaires and interviews were used to collect the data. Most patients reported a low to moderate impact of the disease on daily life. Greatest impact was reported in the areas of elimination, worry, recreation and leisure activities, sleep and rest. Among patient characteristics that correlated positively with the impact variable were age, under 35 years, female gender, depressed mood, and affective-oriented coping style. The findings suggest that nurses and other health professionals may enhance patient adaptation and life satisfaction by focusing efforts on patient characteristics that are amenable to change and on areas of life where the disease impact is experienced most intensively.

Activities of Daily Living↗
PubMed1991

Cyclosporin A regulates the expression of HLA-DR on human monocytes by two different mechanisms.

Cyclosporin A (CsA), but not its nonimmunosuppressive analog cyclosporin H (CsH), inhibited the expression of HLA-DR in human monocytes. Induction of HLA-DR by interferon (IFN)-gamma in fresh monocytes was also inhibited by CsA and not by CsH. However, when monocytes were pretreated with either CsA or CsH for 16 hr prior to the addition of IFN-gamma, HLA-DR expression was increased, probably because of a cyclosporin-induced increase in the number of IFN-gamma receptors. Down-regulation of the HLA-DR mRNA by CsA was found to be dependent on continuous protein synthesis. IFN-alpha also inhibited the IFN-gamma-induced HLA-DR mRNA expression and showed synergy with CsA at low concentrations but not at high concentrations of the drugs. A common mechanistic element in the pathways of CsA and IFN-alpha is proposed.

Cycloheximide↗
PubMed1990

A factor analytic study of two scales measuring dissociation.

The present study was designed to investigate the construct validity of dissociation. We administered the PAS and the DES to 507 male (48%) and female (52%) undergraduate students. Factor analysis on each scale separately showed that neither the PAS nor the DES adequately measures the three dimensions hypothesized to underlie dissociative experience. For both scales, a single factor emerged as replicable and reliable. Use of the scales, in their present form, therefore, should be limited to a single dimension representing disturbances in affect-control in the case of the PAS and disturbances in cognition-control if the DES is used at least with normal populations. Analysis of the combined items showed that the scales are measuring conceptually different but statistically correlated dimensions of dissociation. Further development of both scales is desirable, and further research should investigate the effect of different response formats on the internal structure of the scales.

Adolescent↗
PubMed1989

Characterization of human IFN-gamma response using somatic cell hybrids of hematopoietic and nonhematopoietic origin.

A panel of 27 rodent-human somatic cell hybrids composed of cells of hematopoietic (nonadherent cells) and nonhematopoietic origin (adherent cells) was used to identify the chromosomes involved in the biological response to human IFN-gamma (Hu-IFN-gamma). We found that the stimulation of class-I histocompatibility antigen expression correlates with the presence of human chromosomes 6 and 21 in adherent cell hybrids, while human chromosome 6 alone is sufficient in nonadherent hybrids. Scatchard analysis of the binding of radiolabeled Hu-IFN-gamma to nonadherent cell hybrids gave a Kd value similar to that found on human cell lines. Induction of a reporter gene placed under the transcriptional control of the interferon responsive sequence (IRS) in adherent cell hybrids requires both chromosomes 6 and 21. The antiviral protection by Hu-IFN-gamma in adherent cell hybrids was reached at physiological doses (2 units/ml) when human chromosomes 6 and 21 were present, while higher doses of Hu-IFN-gamma (5000 units/ml) were required for hybrids lacking chromosome 21. Thus, we demonstrate that differences exit in the response to Hu-IFN-gamma depending on the origin of the cell type.

Animals↗
PubMed1989

Monoclonal antibodies to the human interferon-gamma receptor: blocking of the biological activities of interferon-gamma and purification of the receptor.

Monoclonal antibodies against the human interferon-gamma (IFN-gamma) receptor were developed by injecting mice with a preparation of receptor that was purified from solubilized placental membranes by ligand affinity chromatography. Three antibodies were identified by their ability to block the binding of 125I-labeled IFN-gamma to its receptor on HeLa cells at 4 degrees C. One of these antibodies blocked several biological activities of IFN-gamma, including its antiviral activity, its ability to induce HLA-DR surface antigens, and its ability to protect cells from NK cell-mediated cytotoxicity. This antibody exhibited higher binding capacity to cells at 37 degrees C and was significantly less displaceable by an excess of IFN-gamma as compared with the other two antibodies. Immunoaffinity chromatography of solubilized crude placental membrane preparation yielded a purified receptor that exhibited a molecular weight of 88,000. The purified receptor retained its ability to bind 125I-labeled IFN-gamma in solution.

Animals↗
PubMed1988

Two molecular forms of the human interferon-gamma receptor. Ligand binding, internalization, and down-regulation.

The receptors for human interferon-gamma (IFN-gamma) on peripheral blood monocytes and various cells of nonhematopoietic origin were thoroughly characterized and compared. The receptors of all cell types exhibited a similar affinity for IFN-gamma (Kd approximately 1 x 10(-10) M), and in all cases receptor-mediated endocytosis and ligand degradation were demonstrated. However, the receptors differed in their molecular weights (95,000 in HeLa cells and 140,000 in monocytes, assuming a 1:1 ligand to receptor ratio) as concluded from experiments of cross-linking to 125I-IFN-gamma. Lower molecular weight species were obtained as well, particularly in monocytes. Such species could represent either degradation products or subunit structures. The monocyte and HeLa receptor responded differently to an excess of ligand. A significant receptor down-regulation was observed when monocytes were incubated with an excess of 125I-IFN-gamma, whereas no such down-regulation was observed in HeLa cells or in normal fibroblasts. This differential response was observed both in the presence or in the absence of a protein synthesis inhibitor. The receptor on monocytes was found to be acid-labile whereas that on HeLa cells was resistant to acid treatment. These and additional experiments indicate that the monocyte receptor is inactivated following internalization, whereas the HeLa receptor retains its structure and recycles back to the cell surface. The difference in the properties and fate of these two receptor subtypes is probably related to the differential functions of IFN-gamma in various cell types.

Binding Sites↗
PubMed1988

Regulation of cytoplasmic pH of cultured bovine corneal endothelial cells in the absence and presence of bicarbonate.

Intracellular pH (pHi) in confluent monolayers of cultured bovine corneal endothelial cells was determined using the pH-dependent absorbance of intracellularly trapped 5(and 6)carboxy-4',5'-dimethylfluorescein. Steady-state pH was 7.05 +/- 0.1 in the nominal absence of bicarbonate, and 7.15 +/- 0.1 in the presence of 28 mM HCO3-/5% CO2. Following an acid load imposed by a NH4Cl prepulse, pHi was regulated in the absence of HCO3- by a Na+-dependent process inhibitable to a large extent by 1 mM amiloride and 0.1 mM dimethylamiloride. In the presence of 28 mM HCO3-/5% CO2, this regulation was still dependent on Na+, but the inhibitory potency of amiloride was less. DIDS (1 mM) partially inhibited this regulation in the presence, but not in the absence of bicarbonate. With cells pretreated with DIDS, amiloride was as effective in inhibiting recovery from acid load as in the absence of HCO3-. The presence of intracellular Cl- did not appreciably affect this recovery, which was still sensitive to DIDS in the absence of Cl-. Removal of extracellular Na+ led to a fall of pHi, which was greatly attenuated in the absence of HCO3-. This acidification was largely reduced by 1 mM DIDS, but not by amiloride. Cl removal led to an intracellular alkalinization in the presence of HCO3-. The presence of a Cl-/HCO3- exchanger was supported by demonstrating DIDS-sensitive 36Cl- uptake into confluent cell monolayers. Thus, bovine corneal endothelial cells express three processes involved in intracellular pH regulation: an amiloride-sensitive Na+/H+ antiport, a Na+-HCO3- symport and a Cl-/HCO3- exchange, the latter two being DIDS sensitive.

Acid-Base Equilibrium↗
PubMed1988

The protective effect of interferon against natural killing activity is not mediated via the expression of class I MHC antigens.

Natural-killer cell mediated cytotoxicity (NK-CMC) is modulated by interferons both at the effector cell and at the target cell levels. Pretreatment of effector cells with interferon increases their cytotoxicity while pretreatment of target cells with interferons decreases their sensitivity to NK-CMC. Interferons are inducers of several genes including those of the major histocompatibility complex (MHC) and several earlier studies have established a circumstantial correlation between induction of class I MHC gene products and induction of resistance to NK-CMC. In the present study we demonstrate that interferon-alpha renders Daudi cells resistant to NK-CMC without inducing the surface expression of class I MHC antigens. Therefore we suggest that these two phenomena are independent responses to interferon treatment.

Cytotoxicity, Immunologic↗
PubMed1987

The relationship between agoraphobia, social phobia and blood-injury phobia in phobic and anxious-depressed patients.

This paper reports the results of principal components and stepwise discriminant analyses of anxiety, depression and fear scores for 74 phobic and anxious-depressed psychiatric patients. Factor analysis indicated a coherent agoraphobia factor, with less coherent blood-injury and social phobia factors. Discriminant analysis showed a high degree of correct classification of diagnosed agoraphobic, blood-injury and social phobic patients particularly for agoraphobia. A frequency distribution of the phobia scores indicated an all or nothing quality to agoraphobic fears. The results indicate that agoraphobia is a fairly coherent syndrome, but that more work is needed on the concepts and measurement of blood-injury and social phobias.

Adult↗
PubMed1986

Priming of leukocytes selectively increases the level of some interferon-alpha subtypes and not others.

The effect of pretreatment with interferon (IFN) ('priming') on the production of individual IFN subtypes was studied in subpopulations of human peripheral blood mononuclear cells and in the myeloid cell line KG-1. It was found that priming had a selective enhancing effect on the production of certain IFN-alpha subtypes (IFN-alpha 20K and IFN-alpha 21K) and not on others. KG-1 cells produce both IFN-alpha and -beta; however, only the production of IFN-alpha was enhanced by priming with either IFN-alpha, beta or gamma.

Animals↗
PubMed1986

Human monocytes tumoricidal activity: the role of interferon-gamma and bacterial lipopolysaccharide in its stimulation, preservation and decay.

The effect of interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS) on the cytotoxic activity of cultured monocytes was studied in a 6-h51Cr release assay with Actinomycin-D-treated tumor cells as targets. In this system, the lysis of target cells is mediated by a soluble factor (CF) which is similar or identical to human tumor necrosis factor (TNF). The spontaneous cytotoxic activity of freshly isolated monocytes declined after their maturation to macrophages during in vitro culturing. The decrease in the ability of cultured monocytes to lyse the targets is explained by a decrease in their ability to produce the soluble cytolytic factor. Both LPS and IFN-gamma modulated the effect of culturing. LPS exhibited a dual effect. Within 2-3 h after its addition, LPS enhanced the cytotoxic activity of monocytes by increasing the synthesis of CF. However, upon a longer incubation, the decay of the activity was more pronounced in the presence of LPS. IFN-gamma did not augment the cytotoxic activity of monocytes above the basal level, yet it prevented the loss of activity which accompanies the process of monocyte maturation to macrophages.

Animals↗
PubMed1986

Efficient constitutive production of human IFN-gamma in Chinese hamster ovary cells.

A human genomic DNA segment of 5.6 kb containing the entire gene for immune interferon-gamma was fused through its 5'-untranslated region to the corresponding region of the simian virus 40 (SV40) T-antigen gene. The SV40 early promoter used contained a modified transcriptional enhancer element with a 93-bp repeat. Supercoiled plasmid DNA was used to transfect Chinese hamster ovary (CHO) cells, the selectable marker being a SV40-dihydrofolate gene construct. Constitutive expression of the IFN-gamma gene in primary transformants was high, especially if a Harvey murine sarcoma virus long terminal repeat (LTR) was present in addition to the SV40 promoter. After gene amplification by methotrexate selection, CHO-gamma cell lines were obtained that produce 1.5-2 million units of IFN-gamma per million cells and per day (200,000 molecules per cell per minute). Metabolic labeling showed that over 90% of the protein secreted by such cells is human IFN-gamma. A one-step immuno-affinity chromatography on monoclonal antibodies yielded pure IFN-gamma with 1-2 X 10(8) units/mg protein. Like IFN-gamma from human white blood cells, the IFN-gamma from CHO-gamma cells is a mixture of two glycoproteins of 26,000 and 20,000 daltons with traces of the unglycosylated 17,000-dalton polypeptide. Large-scale cultures in 1% serum routinely yield over 600,000 units of human IFN-gamma/ml culture per day.

Animals↗