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S J Thompson

Publications and source records attributed to S J Thompson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Enhanced immunogenicity of a recombinant genital warts vaccine adjuvanted with monophosphoryl lipid A.

The regression of genital warts is believed to be a T-cell-mediated immune effect. We have sought to enhance the immunogenicity of a therapeutic vaccine for the treatment of genital warts with the use of the adjuvant monophosphoryl lipid A (MPL-immunostimulant), a detoxified form of the lipopolysaccharide (LPS) of Salmonella minnesota R595. The comparative immunogenicity and reactogenicity of a recombinant human papillomavirus type 6 (HPV6) L2E7 fusion protein in either aqueous, oil-in-water emulsions or Alhydrogel formulations containing MPL was evaluated. We conclude that the simple addition of MPL to the L2E7 fusion protein already adsorbed onto Alhydrogel preferentially enhances antigen specific in vitro T-cell proliferative responses, IFN gamma production and in vivo delayed type hypersensitivity responses without increasing its reactogenicity.

Adjuvants, Immunologic↗
PubMed1998

Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6.

Acetaminophen (APAP), a widely used analgesic and antipyretic agent, is bioactivated by cytochromes P450 to cause severe hepatotoxicity. APAP is oxidized by two pathways to form a toxic intermediate, N-acetyl-p-benzoquinone imine (NAPQI), and a nontoxic catechol metabolite, 3-hydroxy-APAP (3-OH-APAP). We investigated the role of P450 2E1 and 2A6 in APAP oxidation by using baculovirus-expressed and highly purified forms of human P450 2E1 and 2A6. An electrochemical HPLC assay was developed to quantify both oxidative metabolites simultaneously. For the first time, it was demonstrated that human P450 2E1 selectively oxidized APAP to NAPQI (assayed as its glutathione conjugate, GS-APAP), whereas human P450 2A6 selectively oxidized APAP to 3-OH-APAP. At 1 mM APAP, the relative ratio for the formation of GS-APAP vs 3-OH-APAP with human P450 2E1 was approximately 6:1, whereas the ratio with human P450 2A6 was 1:3. Apparent Km and Vmax values for the formation of GS-APAP by human P450 2E1 were 1.3 mM and 6.9 nmol/min/nmol of P450, respectively, whereas they were 4.6 mM and 7.9 nmol/min/nmol of P450 for P450 2A6. Apparent Km and Vmax values for the formation of 3-OH-APAP by human P450 2E1 were 4.0 mM and 2.5 nmol/min/nmol of P450, respectively, whereas they were 2.2 mM and 14.2 nmol/min/nmol of P450, respectively, for P450 2A6. Thus, although at toxic doses of APAP P450 2E1 is the more efficient catalyst for the formation of the toxic metabolite NAPQI, P450 2A6 also can contribute significantly to NAPQI production.

Acetaminophen↗
PubMed1998

Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia.

The purpose of this study was to determine the incidence of and pharmacokinetic parameters associated with the development of transient encephalopathy following the administration of high-dose methotrexate and intrathecal chemotherapy in children with acute lymphoblastic leukemia (ALL). Two hundred and fifty-nine children with newly diagnosed ALL treated on one of two consecutive trials were analyzed. Presenting features in patients who developed transient encephalopathy were compared with those of patients who did not experience this event. For each patient who developed transient encephalopathy, methotrexate pharmacokinetic parameters were compared with those of matched controls. The cumulative incidence of acute encephalopathy was 3% (SE 1%) at 1 year and was associated with age greater than or equal to 10 years at diagnosis. Pharmacokinetic data did not differ between patients who developed transient encephalopathy and those who did not. The majority of patients had no long-term sequelae and were able to receive further courses of methotrexate without modification. Transient focal neurologic deficits occur in about 3% of children with ALL following the administration of intravenous and intrathecal methotrexate. These events cannot be predicted by pharmacokinetic parameters Of methotrexate disposition. However, these events are generally benign, suggesting that patients who experience acute encephalopathy should continue to receive this important chemotherapeutic agent.

Adolescent↗
PubMed1998

Effect of T-helper cytokine environment on specificity of T-cell responses to mycobacterial 65,000 MW heat-shock protein.

The purpose of this work was to determine if the fine specificity of T cells differed between mice immunized with an antigen in a T helper 1 (Th1) cytokine-dominated environment as compared with a T helper 2 (Th2) cytokine-dominated environment. It was found that splenic T cells from mice immunized with mycobacterial heat-shock protein (hsp 65) and interleukin-12 (IL-12) produced less interleukin-4 (IL-4) and more interferon-gamma (IFN-gamma) in response to stimulation with hsp 65 in vitro than did T cells from mice immunized with hsp 65 alone. The T-cell proliferative response to hsp 65 did not differ between the two groups of mice, although the responses were higher than those of T cells from non-immunized mice. Strikingly, T cells from mice given hsp 65 and IL-12 gave significantly higher responses to six peptides (corresponding to the sequence of hsp 65) to which T cells from mice immunized with hsp 65 alone did not respond. It is considered that different epitopes are presented to T cells (possibly owing to changes in antigen processing) if the environment is shifted, by IL-12, from Th2 towards Th1 cytokines.

Animals↗
PubMed1998

Bithalamic involvement predicts poor outcome among children with thalamic glial tumors.

Clinical features and treatment of 36 consecutive pediatric patients with thalamic glial tumors confirmed by histology and characterized by neuroimaging were reviewed to identify prognostic factors. The median age at diagnosis was 10 years (range 1-18 years). Twenty-four patients had low-grade tumors (juvenile pilocytic astrocytoma n = 9, fibrillary astrocytoma n = 6, astrocytomas not otherwise specified n = 6, ganglioglioma n = 2 and oligodendroglioma n = 1) and 12 patients had high-grade tumors (glioblastoma multiforme n = 7, anaplastic astrocytoma n = 4 and unclassified malignant tumor n = 1). With a median follow-up of 4.3 years among survivors, estimates of 4-year progression-free survival (PFS) and overall survival (OS) for the entire group are 28+/-10 and 37 +/- 10%, respectively. Low-grade tumors were associated with a significantly better 4-year PFS (36 +/- 12 vs. 0% for the high-grade group; p = 0.03) and OS (52 +/- 12 vs. 0%; p < 0.001). This review identified that bithalamic involvement, characterized by neuroimaging, exerted an independent and significant negative impact on PFS and OS for patients with low-grade tumors. Estimates of 4-year PFS and OS among patients with tow-grade bithalamic versus monothalamic tumors were 58 +/- 15 vs. 0% and 85 +/- 11 vs. 0% (p < 0.00001), respectively. The presence of bithalamic involvement did not affect outcome among patients with high-grade tumors. Additionally, age at diagnosis, enhancement with neuroimaging contrast, extension beyond the thalamus and extent of surgical resection did not correlate with overall outcome. Because treatment approaches varied during the study period, the impact of radiation therapy or chemotherapy could not be assessed. This contemporary, single-institution series of pediatric thalamic glial tumors demonstrates, for the First time, the statistical significance of bithalamic involvement as a marker of poor prognosis among patients with low-grade glial lesions.

Adolescent↗
PubMed1998

Changes in the galactose content of IgG during humoral immune responses.

The Fc region of IgG bears two oligosaccharides of variable composition. The serum level of one variant which lacks terminal galactose and sialic acid (agalactosyl IgG) is raised in a number of autoimmune diseases and animal models thereof. Here it is shown that such changes in IgG glycosylation occur during non-pathological humoral immune responses. It was found that if specific pathogen free (SPF) CBA/Ca mice are transferred from a sterile to a conventional environment, their levels of total serum IgG rise whereas the degree of IgG galactosylation falls. Next, mice were immunised with bovine serum albumin (BSA) in incomplete Freund's adjuvant. As anti-BSA titres rose the antibodies became less galactosylated and later, as the titres fell, the antibodies became more galactosylated. By contrast, there was little or no variation in the relative galactosylation of total IgG. It is considered that the galactosylation of IgG antibodies varies during an immune response.

Animals↗
PubMed1997

CD4+ Th2 cells specific for mycobacterial 65-kilodalton heat shock protein protect against pristane-induced arthritis.

Previous studies showed that mice with pristane-induced arthritis (PIA) and those protected from the disease by preimmunization with mycobacterial 65-kDa heat shock protein (hsp65), possess raised immune responses to hsp65. Thus, a paradox exists whereby T cells from both arthritic and hsp65-protected animals proliferate vigorously in response to the same Ag. Here we demonstrate that T cells from mice with PIA and hsp65-protected mice produce different cytokines in vitro in response to hsp65. The use of a sensitive CelELISA to measure Ag-driven lymphokine production revealed that spleen cells from hsp65-protected mice, but not those from pristane-injected or normal mice, produced the Th2-associated cytokines IL-4, IL-5, and IL-10 in response to stimulation with hsp65. By contrast, the Th1-associated cytokines IL-2 and IFN-gamma were produced by spleen cells from mice of all groups in response to hsp65. Furthermore, there was a dramatic increase in the IgG1 to IgG2a ratio of anti-hsp65 Abs from arthritic to protected mice. Thus, it appears that a Th2 response is protective against PIA. To examine this theory, a regimen of IL-12 administration which polarizes the hsp65-specific (Th2) immune response toward Th1 was identified. This regime abolished hsp65-mediated protection against PIA. Other experiments revealed that the specificity of the response to hsp65 was important, as other bacterial proteins known not to protect against PIA induced similar Th2-associated cytokines in vitro. It is considered that the protection afforded by hsp65 preimmunization is mediated by Th2-associated cytokines produced by hsp65-specific CD4+ T cells.

Animals↗
PubMed1997

Incorporation of cells into an ELISA system enhances antigen-driven lymphokine detection.

The ability to measure successfully the levels of Th1 or Th2 cytokines during an in vitro antigen-driven, polyclonal T-cell response has proven to be more difficult than expected. Here we describe the development of a highly sensitive cell-based ELISA (celELISA) technique for the detection of murine Th1 and Th2 cytokines. The celELISA combines the quantification aspects of the conventional sandwich ELISA with the sensitivity of the ELISPOT assay. The celELISA was particularly useful for the improved detection of IL-2, IL-4, and to a lessor extent, IFN-gamma.

Animals↗
PubMed1997

A diagnostic comparison of homeless and nonhomeless patients in an urban mental health clinic.

This study compared demographic and diagnostic characteristics of a sample of homeless outpatient mental health clinic attenders with a domiciled comparison group from the same clinic. Data on demographic variables and DSM-III-R psychiatric diagnoses were collected over a two-year period on a consecutive sample of 166 homeless and 117 nonhomeless clinic attenders. Data on demographics and psychiatric diagnoses of the homeless clinic attenders were further compared with data collected systematically from 900 homeless individuals in the same city. In the clinic, homeless subjects were more often members of ethnic minorities, and homeless women were significantly younger and better educated than their nonhomeless counterparts. Rates of schizophrenia, bipolar disorder, and somatization disorder were not significantly different between homeless and nonhomeless groups. Major depression was about four times as prevalent in nonhomeless men as in homeless men. Homeless men were significantly more likely than nonhomeless men to qualify for a diagnosis of alcohol use disorder, and homeless women were more likely than other women to qualify for a diagnosis of drug use disorder. Both homeless men and women were significantly more likely than their domiciled counterparts to meet criteria for antisocial personality disorder. Personality disorder other than antisocial was more prevalent in nonhomeless men than in homeless men. Combined rates of personality disorder were significantly higher among homeless than nonhomeless women, but not men. Homeless clinic attenders were demographically and diagnostically very similar to a general homeless population in the same city. The only diagnosis that was more prevalent in the homeless clinic than in the homeless community was antisocial personality disorder. We concluded that because of difference in diagnostic prevalence, homeless and nonhomeless individuals in mental health clinics need to be considered independently. Clinicians treating homeless outpatients may benefit from having special facility in diagnosis and management of antisocial personality disorder and substance abuse, along with expertise in other psychiatric disorders in this population.

Adult↗
PubMed1997

Deficits, delays, and distractions: an evaluation of symbolic play and memory in children with autism.

Two experiments were conducted to evaluate symbolic-deficit and memory-deficit hypotheses to account for the cognitive problems seen in children with autism. Experiment 1 tested imitation, in immediate and deferred conditions, of familiar actions with different sets of objects representing the developmental progression from functional to symbolic play. The results showed that the autism group and both their receptive language and nonverbal IQ-matched controls imitated familiar actions with realistic objects (evidence for functional play) and placeholder objects (evidence for symbolic play) after delays ranging from 24 hr to 3 weeks. Experiment 2 tested familiar three-step event sequences in which a placeholder object was substituted for the second step in half the events. The results showed that the autism group remembered as many of the actions with the placeholder objects as their language-matched controls and as many correctly ordered sequences, a finding that supports a symbolic-delay (rather than deficit) hypothesis. These results were obtained in highly structured test situations and sharply contrast with the impairments seen in children with autism who are observed in naturalistic settings. Two interpretations of these findings are offered. First, structured test settings minimize distractions that typically occur in naturalistic settings that may interfere or disrupt symbolic play in children with autism. Second, the results are consistent with an executive function deficit in that the autistic group demonstrated more knowledge in the test settings than they demonstrate spontaneously in naturalistic ones.

Attention↗
PubMed1997

A comparison of clinical and structured interview diagnoses in a homeless mental health clinic.

OBJECTIVE: This study compared psychiatric diagnoses ascertained by independent clinicians with structured research interviews of homeless psychiatric patients assessed in a mental health clinic and in the community. Problems of both overdiagnosis and underdiagnosis in structured research interviews compared to clinician assessment were predicted. METHOD: Over a period of a year, 97 patients referred to a mental health clinic for homeless people were assessed with the Diagnostic Interview Schedule (DIS) administered by a clinical social worker who then completed a full clinical psychiatric social work assessment. These same patients received a thorough and systematic clinical psychiatric evaluation by a psychiatrist or psychologist, both experienced with this population. These clinicians gathered data from multiple sources, often with extended observation over time. The DIS and clinician diagnoses were made blind to one another and then compared; the clinician was often made aware of some of the symptoms that the social worker had elicited, but not whether the elicited material was from the DIS or from the clinical assessment. Diagnoses of 33 clinic patients previously assessed by trained nonclinician DIS interviews in an epidemiologic study of the homeless population in the community were also compared to clinician diagnoses, and no information from these patients' survey DIS interviews was made available to the clinicians. RESULTS: Compared to clinician assessment, structured interviews underdiagnosed antisocial personality disorder (ASPD) and overdiagnosed major depression. Alcohol use disorder and schizophrenia showed only small discrepancies by assessment method. Drug use disorder revealed no bias according to method of ascertainment, but showed very discrepant kappa levels comparing DIS to clinician assessment in the two different comparison contexts. CONCLUSIONS: If structured research methods assessing the homeless population actually overestimate depression, underestimate ASPD, and misclassify drug abuse, then policies stemming from structured interview research recommendations may call for levels and types of services not optimally suited to the reality of this population's needs. Because mental illness and substance abuse are thought to be critical factors in the generation and perpetuation of homelessness, the issue of accurate diagnosis is tantamount to understanding and providing workable solutions to the problem of homelessness. Further research is needed to untangle potential confounders of the homeless situation to psychiatric diagnosis.

Community Mental Health Centers↗
PubMed1997

Pristane-induced arthritis is CD4+ T-cell dependent.

The development of arthritis induced in mice by intraperitoneal injection of the non-antigenic mineral oil pristane (2,6,10,14-tetramethylpentadecane) was shown to depend on the presence of CD4+ T cells. Initial experiments assessed the influx of lymphoid cells into the peritoneal cavity of CBA/Igb mice after pristane injection. Both CD4+ and CD8+ cell numbers were maximal around 50 days. Other experiments confirmed our original observation that irradiated pristane-treated mice failed to develop arthritis unless they were reconstituted with spleen cells from normal donors. This finding has been extended by showing that the population of transferred splenic lymphoid cells must contain CD4+ T cells, while CD8+ T cells and B cells were not required for reconstitution. Conventionally housed and hsp 65-immunized animals are known to harbour T cells reactive with hsp 65. In addition, hsp 65-immunized mice are resistant to the development of pristane-induced arthritis (PIA). Thus, additional experiments assessed the population of splenic T cells activated and proliferating against mycobacterial 65,000 MW heat shock protein (hsp 65). In cultures of purified splenic T cells derived from both conventional and hsp 65-immunized mice, removal of CD4+ T cells significantly reduced the proliferative response to hsp 65, while removal of CD8+ T cells often enhanced the response. These proliferative responses were also shown to be major histocompatibility complex (MHC) class II restricted. The present findings demonstrate that PIA is CD4+ T-cell mediated, and immunodominant environmental antigens such as hsp 65 activate this population of lymphocytes. The CD4+ hsp 65-reactive population may be pathogenic or protective in PIA, depending upon the route of sensitization.

Animals↗
PubMed1997

Mothers' satisfaction with medical care: perceptions of racism, family stress, and medical outcomes in children with diabetes.

Patient satisfaction is an important indicator of medical outcomes. This study used an ecological framework to identify sociodemographic, family, and community predictors of mothers' satisfaction with their children's medical care and to determine the extent to which satisfaction is associated with medical outcomes such as adherence to treatment and health status of children with diabetes. Although individual demographics have little influence on satisfaction, family and community stressors are significant predictors of mothers' satisfaction with medical care. Mothers who reported greater perceptions of racism and family stress were significantly less satisfied with their children's medical care than those from less stressful environments. Mothers' satisfaction with medical care was significantly associated with adherence but was not significantly related to the children's health status.

Adolescent↗
PubMed1997

Mechanism-based inactivation of human liver cytochrome P450 2A6 by 8-methoxypsoralen.

The P450 2A6 catalyzed 7-hydroxylation of coumarin proceeded with a mean Km of 0.40 (+/-0.13) microM and Vmax of 6.34 nmol/nmol P450/min (36-fold variation) in microsomal preparations from a panel of 12 human livers. Substrate depletion was avoided during the kinetic determinations. 8-Methoxypsoralen (8-MOP) is a potent mechanism-based inactivator of human liver P450 2A6 and reconstituted purified recombinant P450 2A6 based on the following evidence: 1) 8-MOP causes time, concentration, and NADPH-dependent loss of P450 2A6 activity that is not reversed by potassium ferricyanide or extensive dialysis, 2) loss of P450 2A6 activity is associated with a loss of spectrally observable P450, 3) addition of nucleophiles or reactive oxygen scavengers to the incubations does not prevent inactivation of P450 2A6, and 4) 8-MOP-dependent P450 2A6 inactivation is inhibited (concentration dependent) by the addition of a competitive inhibitor (pilocarpine). Inactivation is selective for P450 2A6 at low concentrations of 8-MOP (2.5 microM) after short incubation time periods (3 min) and was characterized by a KI of 0.8 and 1.9 microM in a reconstituted and microsomal system, respectively, and a kinact of 1 min-1 and 2 min-1 in a reconstituted and microsomal system, respectively. A substrate depletion partition ratio of 21 was calculated for the inactivation of recombinant P450 2A6. Potency and selectivity suggest that 8-MOP could be a useful tool in vitro for evaluating P450 2A6 activity in various enzyme preparations.

Adolescent↗
PubMed1997

Body fat distribution and race differences in apolipoprotein A1.

OBJECTIVE: This is the first study to assess the role of waist-to-hip ratio in explaining race differences in levels of serum apolipoprotein A1, a protective risk factor for atherosclerosis. METHODS: Linear regression analyses were used in a community-based survey of 3,043 adults (23.5% African-American) to assess associations of race, age, anthropometric measures, education, diabetes, blood pressure medication use, cigarette smoking, and leisure-time physical activity with apolipoprotein A1 levels. RESULTS: Higher apolipoprotein A1 levels were observed among African-American than among white adults (African-American men: +15.6 mg/dl than white men, African-American women: +3.1 mg/dl more than white women; p < 0.05). Waist-to-hip ratio and other variables did not account for race differences among men. African-American women had +8.6 mg/dl higher levels than white women after adjustment for differing distributions of waist-to-hip ratio, age, body mass index and education. Cigarette smoking, physical activity, and medical history accounted for no further differences among women. CONCLUSIONS: Higher levels of obesity indicators and lower educational attainment among African-American women reduced a potentially greater beneficial race difference in apolipoprotein A1. These findings also suggest that other environmental and biochemical factors may play roles in explaining the higher protective levels of apolipoprotein A1 observed among African-American children and adults.

Adipose Tissue↗