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Biomedical subjects

C C Williams

Publications and source records attributed to C C Williams.

At least 19 recordsLinked to original sources

Membrane macrophage colony-stimulating factor on MADB106 breast cancer cells does not activate cytotoxic macrophages but immunizes rats against breast cancer.

Weakly immunogenic, but highly malignant, rat MADB106 breast cancer cells were retrovirally transduced with the membrane form of macrophage colony-stimulating factor (mM-CSF). The cloned mM-CSF-transfected MADB106 cells physically conjugated with macrophages, but were not killed by the macrophages in 48-h cytotoxicity assays. Macrophages killed the mM-CSF-expressing tumors in the presence of noncytotoxic doses of either taxol or taxol plus cisplatin. This indicated that macrophages bind to the mM-CSF expressed on the tumor cells, but for successful macrophage cytotoxicity to occur against mM-CSF-transduced tumor cells other factors must be present. The mM-CSF-transfected tumor cells were rejected when inoculated subcutaneously into normal rats. Cloned MADB106 tumor cells which expressed high amount of mM-CSF were rejected, while tumor cells that displayed lower levels of mM-CSF grew in 60% of the inoculated rats. The mM-CSF-transfected tumors that grew were smaller and had a greater amount of necrosis, compared to the viral vector tumors. Rats that spontaneously rejected the mM-CSF-transfected MADB106 cells showed rechallenge resistance to unmodified parental MADB106 and R3230Ac breast cancers, but not to the F98 glioma. These observations suggest that breast cancer-specific immunity was induced by the inoculation of mM-CSF-expressing MADB106 tumor cells.

Animals↗

Dexamethasone increases the expression of membrane macrophage colony stimulating factor from retrovirally transduced tumor cells expressing macrophage colony stimulating factor.

Many different tumor cell types (breast, ovarian, glioma, liver and colon) were retrovirally transduced with the human macrophage colony stimulating factor (M-CSF) gene (either the membrane associated form [mM-CSF] or the secreted form [sM-CSF]). These cells were tested for their ability to display increased amounts of mM-CSF in response to dexamethasone. M-CSF-transfected tumor cells expressed additional mM-CSF in response to 18-72 h incubations with 3-15 microg/ml dexamethasone, while non-transfected parental cells were unaffected by this treatment. Increased mM-CSF protein expression on the M-CSF transduced cells was observed by flow cytometry and Western blotting using M-CSF specific antibodies. Northern blot analysis revealed an increase in the mM-CSF specific transcripts within the dexamethasone-treated mM-CSF transduced cells, but this was not seen within the non-transfected tumor cells that were treated with dexamethasone. ICAM-1 expression was unaffected by dexamethasone treatment, indicating that this response is mM-CSF specific. All trans-retinal and 1,25-dihydroxy vitamin D3 compounds that have been reported to induce M-CSF expression failed to increase mM-CSF. When dexamethasone-treated mM-CSF transfected clones were used as target cells for macrophage-mediated cytotoxicity assays, an increased killing with the dexamethasone-treated cells was seen. The macrophage-mediated cytotoxicity of these mM-CSF expressing tumor cells was blocked with excess recombinant M-CSF by saturating M-CSF receptors on the macrophage that is required for this form of tumor cell killing. This work suggests the possibility that dexamethasone may prove useful for vaccination purposes using mM-CSF retrovirally transfected tumor cells.

Animals↗

A limit on retrieval-induced forgetting.

Retrieving some members of a memory set impairs later recall of semantically related but not unrelated members (M. C. Anderson, R. A. Bjork, & E. L. Bjork, 1994; M. C. Anderson & B. A. Spellman, 1995). The authors investigated whether this retrieval-induced forgetting effect would generalize to testing procedures other than category-cued recall. Although the authors demonstrated a retrieval-induced forgetting effect using a category-cued recall task, they failed to show retrieval-induced forgetting on several different memory tests that used item-specific cues, including a category-plus-stem-cued recall test, a category-plus-fragment-cued recall test, a fragment-cued recall test, and a fragment completion task.

Adult↗

Predictors of success and satisfaction in the practice of psychiatry: a preliminary follow-up study.

BACKGROUND: Few studies have examined the predictors of psychiatrists' perceived success and personal satisfaction with their careers. The present study examines self-reported success and personal satisfaction with their careers in a cohort of psychiatrists followed for more than 20 years. METHODS: A total of 29 psychiatrists, all of whom had participated in a study during their residency 21 to 24 years earlier, completed a self-report questionnaire. The first set of questions addressed the type and characteristics of their professional practice; the second set assessed aspects of their nonprofessional practice; and the third set assessed aspects of their nonprofessional, personal lifestyles. The personality traits of neuroticism and extraversion were assessed during the residency years and were used as predictors. Composite measures of self-perceived external success and personal satisfaction were computed. Regression models were constructed to determine the best predictors of these composite measures. RESULTS: Neuroticism proved to be a significant predictor of external success but not of personal satisfaction, with higher scores predicting a lower rating of perceived external success. There were 2 practice characteristics--involvement with research and practising from an orientation other than psychoanalytic--that predicted perception of success. One personal lifestyle characteristic--the perception that one's nonprofessional life sustained professional life--also predicted perception of success. The best predictor of personal satisfaction was overall satisfaction with nonprofessional aspects of life. CONCLUSIONS: Personality, nonprofessional social support, and engaging in research are associated with greater perceived success and personal satisfaction with a career in psychiatry.

Career Choice↗

Optical dipole model for photodetection in the near field.

Near-field photodetection optical microscopy (NPOM) is a scanning probe technique that has been developed to perform nanometer-scale optical intensity mapping and spectroscopy. In NPOM a nanometer-scale photodiode detector absorbs power directly as it is scanned in the near field of an illuminated sample surface. A model of photodetection in the near and intermediate fields is presented. A brief review of far-field absorption is given for comparison. Far-field absorption measurements measure the imaginary part of the polarizability to first order. In contrast, photodetection in the near field measures the real part of the polarizability. Other aspects of near-field photodetection are also examined, including contrast mechanisms and lateral resolution. NPOM measurements performed on isolated 300-nm spheres show good agreement with the theory.

Journal Article↗

Effects of dietary protein on whole-body protein turnover and endocrine function in young-adult and aging dogs.

Thirty-six adult female Beagles averaging 2 (young-adult) or 8 (geriatric) yr of age were used to assess the effects of graded levels of dietary protein (16, 24, or 32%) on endocrine-controlled regulation of whole-body protein turnover. Rates of whole-body protein synthesis (WBPS) and whole-body protein degradation (WBPD) were estimated using orally administered 15N-glycine and total excreta collection. Although N balance was similar for all dogs, N flux through the metabolic pool increased linearly (P < 0.05) as protein intake increased. Rates of WBPS, WBPD, or the difference between them were not influenced by age (P > 0.10). A quadratic increase (P < 0.05) in WBPS and WBPD was observed in response to dietary protein. Serum insulin-like growth factor-I (IGF-I), IGF-I-binding protein 3, and total IGF-I-binding proteins were higher (P < 0.05) in geriatric dogs than in young-adult dogs regardless of protein intake. These results indicate that dietary protein in excess of 16% may not be required to maintain N balance in young-adult and aging dogs despite the linear increase in N flux through the metabolic pool. Furthermore, age-induced changes in endocrine functionality may differ between dogs and other species.

Administration, Oral↗

To see and remember: visually specific information is retained in memory from previously attended objects in natural scenes.

What is the nature of the representation formed during the viewing of natural scenes? We tested two competing hypotheses regarding the accumulation of visual information during scene viewing. The first holds that coherent visual representations disintegrate as soon as attention is withdrawn from an object and thus that the visual representation of a scene is exceedingly impoverished. The second holds that visual representations do not necessarily decay upon the withdrawal of attention, but instead can be accumulated in memory from previously attended regions. Target objects in line drawings of natural scenes were changed during a saccadic eye movement away from those objects. Three findings support the second hypothesis. First, changes to the visual form of target objects (token substitution) were successfully detected, as indicated by both explicit and implicit measures, even though the target object was not attended when the change occurred. Second, these detections were often delayed until well after the change. Third, changes to semantically inconsistent target objects were detected better than changes to semantically consistent objects.

Eye Movements↗

Increasing access and building equity into mental health services: an examination of the potential for change.

This article explores the use of mental health care services by ethnoracial people in Canada and distinguishes between the reasons for underutilization of services by ethnoracial groups and the barriers which prevent ethnoracial groups from accessing services. Research focusing on Canadian race relations is reviewed to reveal how they are paralleled in the functioning of mainstream mental health care organizations. Existing policies and attitudes are then considered in relation to how they support or impede interventions to increase accessibility to services. Finally, frameworks for organizational change based on multiculturalism and anti-racism are presented, and the advantages and disadvantages of both are articulated.

Canada↗

Is retrieval-induced forgetting an inhibitory process?

Three experiments investigated memory performance in the retrieval practice paradigm (Anderson, Bjork, & Bjork, 1994; Anderson & Spellman, 1995). This paradigm produces a retrieval-induced forgetting effect, wherein practicing some members of a studied category decreases the recall of other members of that category relative to a baseline. Our findings indicate that the retrieval-induced forgetting effect is replicable but that previous findings supporting an inhibitory account of this phenomenon may not be.

Humans↗

Styrene oxide in blood, hemoglobin adducts, and urinary metabolites in human volunteers exposed to (13)C(8)-styrene vapors.

Styrene is used in the manufacture of plastics and polymers and in the boat-building industry. The major metabolic route for styrene in rats, mice, and humans involves conversion to styrene-7,8-oxide (SO). The purpose of this study was to evaluate blood SO, SO-hemoglobin (SO-Hb) adducts, and urinary metabolites in styrene-exposed human volunteers and to compare these results with data previously obtained for rodents. Four healthy male volunteers were exposed for 2 h during light physical exercise to 50 ppm (13)C(8)-styrene vapor via a face mask. Levels and time profiles of styrene in exhaled air, blood, and urine (analyzed by GC) and urinary excretion patterns of mandelic acid and phenylglyoxylic acid in urine (analyzed by HPLC) were comparable to previously published volunteer studies. Maximum levels of SO in blood (measured by GC-MS) of 2.5-12.2 (average 6.7) nM were seen after 2 h, i.e., in the first sample collected after exposure had ended. The styrene blood level in humans was about 1.5 to 2 times higher than in rats and 4 times higher than in mice for equivalent styrene exposures. In contrast the SO levels in human blood was approximately fourfold lower than in mice. The level of hydroxyphenethylvaline (determined by GC-MS-MS) in pooled blood collected after exposure was estimated as 0.3 pmol/g globin corresponding to a SO-Hb adduct increment of about 0.003 pmol/g and ppmh. NMR analyses of urine showed that a major portion (> 95%) of the excreted (13)C-derived metabolites was derived from hydrolysis of SO, while only a small percentage of the excreted metabolites (< 5%) was derived from metabolism via phenylacetaldehyde. Signals consistent with metabolites derived from other pathways of styrene metabolism in rodents (such as glutathione conjugation with SO or ring epoxidation) were not detected.

Carbon Isotopes↗

Macrophages that kill glioma cells expressing the membrane form of macrophage colony stimulating factor are resistant to prostaglandin E2 and interleukin-10.

Malignant rat T9 glioma cells retrovirally transduced with the membrane form of macrophage colony stimulating factor (mM-CSF) were killed by bone marrow derived macrophages in 24 h cytotoxicity assays. Prostaglandin E2 (PGE) and interleukin-10 (IL10) were tested for their ability to block this tumoricidal reaction. Only at very high nonphysiological concentrations of PGE (10(-5) and 10(-6) M) was this cytotoxicity inhibited. Use of high doses of theophylline, a phosphodiesterase inhibitor, also prevented macrophages from killing the mM-CSF transduced target cells. IL10 did not alter the killing potential of the mM-CSF tumoricidal macrophages, even though IL10 reduced the production of nitric oxide by macrophages in response to tumor necrosis factor and lipopolysaccharide. IL10 enhanced the growth of bone marrow macrophages suggesting that IL10 has a complex role in the regulation of tumoricidal macrophages. Thus, the mM-CSF may be an ideal agent to treat tumors that utilize either of these two immunosuppressive defense mechanisms that may block other forms of treatment.

Animals↗

Defining new frameworks for psychosocial intervention.

The personal experiences of individuals with schizophrenia have been neglected in the psychiatric literature. Disappointingly, ideas about the impact of the illness on the experience of "self" have either been devalued or based primarily on the impressions of theorists rarely collaborating with individuals with the illness. Rather than making assumptions about the subjective experience of mental illness, we must enter a meaningful dialogue with our clients so that they can tell us about their situations using their own voices. This study presents life-history interviews with 15 individuals diagnosed with schizophrenia and describes the explanatory models they use to give coherence to their experiences of psychosis. The struggle for control emerges as a central theme with effects on the management of symptoms, self-image, feelings of social competence, and dealing with others' expectations. Respondents speak about the possibility of recovery from illness through engaging in a process of internal and external reorganization. These individuals echo the assertions in the literature generated by consumers and other investigators of subjective experience and advocate for recovery-based models of care including therapeutic discourse with clients.

Adaptation, Psychological↗

Laminin-like proteins are differentially regulated during cerebellar development and stimulate granule cell neurite outgrowth in vitro.

The basement membrane glycoprotein laminin-1 is a potent stimulator of neurite outgrowth. Although a variety of laminin isoforms have been described in recent years, the role of alternative laminin isoforms in neural development remains largely uncharacterized. We found that a polyclonal antibody raised against the alpha1, beta1, and gamma1 chains of laminin-1 and a monoclonal antibody raised against the alpha2 chain of laminin-2 detect immunoreactive material in neuronal cell bodies in the developing mouse cerebellum. In addition, laminin-1-like immunoreactivity was found in cell types throughout the cerebellum, but laminin-alpha2-like immunoreactivity was restricted to the Purkinje cells. Purified laminin-1 and laminin-2 stimulated neurite outgrowth in primary cultures of mouse cerebellar granule neurons to a similar extent, whereas the synthetic peptides tested appeared to be active only for cell adhesion and not for stimulation of neurite outgrowth. The E8 proteolytic fragment of laminin-1 contained full neurite outgrowth activity. The identity of laminins expressed in granule neurons was also examined by Western blotting; laminin-like complexes were associated with the cell and appeared to have novel compositions. These results suggest that laminin-like complexes play important roles in cerebellar development.

Animals↗

Macrophages kill T9 glioma tumor cells bearing the membrane isoform of macrophage colony stimulating factor through a phagocytosis-dependent pathway.

Rat T9 glioma cells transfected with the gene for the membrane isoform of macrophage-CSF (mM-CSF) but not for the secreted isoform of M-CSF were directly killed by bone marrow-derived macrophages. Macrophage-mediated cytolysis of the mM-CSF-transfected clone was blocked by using chemical inhibitors of phagocytosis such as iodoacetate, 2-deoxyglucose, gadolinium chloride, and cytochalasin B. In contrast, macrophage-mediated killing of mM-CSF-expressing tumor cells was augmented by the microtubule inhibitor, colchicine. Use of nitric oxide and reactive oxygen intermediate inhibitors failed to alter the macrophage-mediated killing of the mM-CSF-transfected tumor cells. Photomicroscopy, using immunohistochemical staining with the anti-Hck Ab to distinguish macrophages from tumor cells, revealed that phagocytosis began within 2 h after addition of the mM-CSF-bearing tumor cells. Photocinematography confirmed that macrophages first phagocytosized and then lysed the internalized mM-CSF transfectant cells. Using annexin V and acridine orange staining techniques, macrophages phagocytosized living mM-CSF-transfected tumor cells.

Animals↗

Induction of Arabidopsis tryptophan pathway enzymes and camalexin by amino acid starvation, oxidative stress, and an abiotic elicitor.

The tryptophan (Trp) biosynthetic pathway leads to the production of many secondary metabolites with diverse functions, and its regulation is predicted to respond to the needs for both protein synthesis and secondary metabolism. We have tested the response of the Trp pathway enzymes and three other amino acid biosynthetic enzymes to starvation for aromatic amino acids, branched-chain amino acids, or methionine. The Trp pathway enzymes and cytosolic glutamine synthetase were induced under all of the amino acid starvation test conditions, whereas methionine synthase and acetolactate synthase were not. The mRNAs for two stress-inducible enzymes unrelated to amino acid biosynthesis and accumulation of the indolic phytoalexin camalexin were also induced by amino acid starvation. These results suggest that regulation of the Trp pathway enzymes under amino acid deprivation conditions is largely a stress response to allow for increased biosynthesis of secondary metabolites. Consistent with this hypothesis, treatments with the oxidative stress-inducing herbicide acifluorfen and the abiotic elicitor alpha-amino butyric acid induced responses similar to those induced by the amino acid starvation treatments. The role of salicylic acid in herbicide-mediated Trp and camalexin induction was investigated.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Preliminary investigation of the use of dried-blood spots for the assessment of in utero exposure to environmental pollutants.

We determined the concentration of dichlorodiphenyldichloroethylene (p,p'-DDE) in dried-blood spot specimens from 2-day-old infants from rural Texas who had never been breast fed. Anonymous, residual whole blood spots on filter paper, previously used for routine newborn screening procedures, were soaked in a phosphate buffer, extracted with an organic solvent, and eluted through silica gel. The concentrated eluates were analyzed by capillary gas chromatography with electron capture detection (ECD). The blood collected from 10 newborns was analyzed and found to contain DDE concentrations ranging from 0.13 to 1.87 pg/microliter with a mean of 0.72 pg/microliter. One of the 10 newborns had a whole blood DDE concentration of 1.87 pg/microliter, which was greater than the concentration of 1.34 pg/microliter in a freshly drawn sample from an adult donor whose blood serum was shown to contain DDE. With improvement in detection limits, this approach has the potential to displace the analyses of mothers' blood (as a surrogate indicator of infants' exposures) and cord blood as standard procedures for determining the newborns' body burden of environmental pollutants.

Adult↗

Nitrogen metabolism and hormonal responses of steers fed wheat silage and infused with amino acids or casein.

Four Holstein steers (159 kg) surgically fitted with abomasal-infusion cannulas were used in a 4 x 4 Latin square study to test amino acid (AA) and casein (CAS) infusions on nitrogen balance and hormonal status of steers consuming vegetative wheat (Triticum aestivum L.) silage (12.3% CP). Treatments were 5-d infusions of 1) water (CONT), 2) arginine (ARG; 13.69 g/d), 3) limiting amino acids (LAA, 13.69 g/d arginine + 10.92 g/d histidine + 28.97 g/d lysine + 10.88 g/d methionine + 16.96 g/d threonine, and 4) Na-CAS (300 g/d). Whole blood was collected for plasma AA, growth hormone (GH), insulin, and IGF-I concentrations. Data were analyzed by ANOVA, and the following orthogonal contrasts were used to separate treatment means: CONT vs ARG; ARG vs LAA; and LAA vs CAS. Urinary N increased (P < .02) for CAS vs LAA. Arginine increased N retention, as did CAS, compared to LAA. Total plasma essential AA were decreased by arginine. Mean plasma insulin concentrations were increased by CAS (P < .034). Arginine increased mean plasma GH levels, but not IGF-I. The CAS treatment increased (P < .015) IGF-I levels, but not GH. These data suggest that performance of steers fed wheat silage was limited by duodenal AA flow and that arginine was the first-limiting AA. Casein infusion increased plasma insulin and IGF-I, which would explain the improved growth noted in calves and lambs fed forages supplemented with ruminally undegraded protein.

Amino Acids↗