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Biomedical subjects

R Krueger

Publications and source records attributed to R Krueger.

At least 19 recordsLinked to original sources
PubMed2006

Mutation analysis of the seven in absentia homolog 1 (SIAH1) gene in Parkinson's disease.

Seven in absentia homolog 1 (SIAH-1) is a member of the RING-finger-containing E3 ubiquitin ligases. Two substrates of SIAH-1 are alpha-synuclein and synphilin-1, both of these proteins are involved in Parkinson's disease (PD). Recently, mutations in Parkin, another E3 ubiquitin ligase which ubiquinates synphilin-1 and glycosylated alpha-synuclein, have been defined as a major cause of autosomal recessive PD. The potential role of SIAH-1 in PD is further underlined as SIAH-1 protein is a component of the Lewy bodies and as it plays a role in apoptosis caused by nitric oxide (NO) induced oxidative stress. Thus, we performed a mutation screening of the SIAH-1 gene in PD patients. However, screening a large sample of 209 familial and sporadic PD patients we could not find any disease causing mutation. We therefore conclude that genetic alterations of SIAH-1 do not significantly contribute to the pathogenesis of PD.

Aged↗
PubMed2005

The effect of combination antiretroviral therapy on CD5 B- cells, B-cell activation and hypergammaglobulinaemia in HIV-1-infected patients.

OBJECTIVES: This study assessed B-cell activation, CD5 B-cells and circulating immunoglobulin levels in HIV-infected patients treated with combination antiretroviral therapy (CART). METHODS: Measurement of plasma immunoglobulin levels and electrophoresis of plasma proteins, and analyses of total numbers of B-cells and B-cells expressing CD 38 and CD5 in whole blood, were undertaken in 47 consecutive HIV-1-infected patients attending an out-patient clinic. RESULTS: All HIV-infected patients had similar percentages and numbers of B-cells. Proportions of CD5 B-cells in all HIV-infected patients were significantly lower than those in HIV-negative controls. Aviraemic HIV-infected patients on CART had lower percentages of CD5, CD 38 and CD5 CD 38 B-cell subsets and lower plasma levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) than viraemic HIV-infected patients (untreated or on CART). However, 33-37% of aviraemic HIV-infected patients had IgG and IgA levels above the 95th percentile of the normal range defined in HIV-seronegative donors. In aviraemic HIV-infected patients, plasma IgA levels correlated only with proportions of activated (CD 38) B-cells. IgG levels did not correlate with the proportions of B-cell subsets or any marker of HIV disease activity. Monoclonal immunoglobulins were not detected in any plasma sample. CONCLUSIONS: Aviraemic HIV-infected patients on CART have lower plasma levels of IgG and IgA than viraemic HIV-infected patients, but levels are often above the normal range. CD5 B-cell numbers are depressed, so these cells are unlikely to contribute to hypergammaglobulinaemia in HIV-infected patients.

ADP-ribosyl Cyclase 1↗
PubMed2004

Graves' disease during immune reconstitution after highly active antiretroviral therapy for HIV infection: evidence of thymic dysfunction.

A patient with HIV infection who experienced immune reconstitution after highly active antiretroviral therapy (HAART) [increase in CD4 T cell count from <1/microl to >600/microl] presented with severe Graves' disease 32 months after commencing HAART. A comprehensive clinical and laboratory study demonstrated pronounced regional lymphadenopathy and thymic enlargement at presentation, and that the onset of thyrotropin receptor antibody production was associated with increased production of soluble CD30 (a marker of type 2 immune responses). Blood naive CD8 T cell counts and TREC levels in both CD4 and CD8 T cells were increased at multiple time points compared with carefully selected controls. We conclude that the Graves' disease in this patient was associated with abnormally high blood counts of thymus-derived T cells, and propose that Graves' disease after HAART in this and other HIV patients may result from failure to delete autoreactive T cell clones in the regenerating thymus.

Adult↗
PubMed2004

Community tobacco control leaders' perceptions of harm reduction.

OBJECTIVE: To investigate community tobacco control leaders' attitudes toward harm reduction approaches to tobacco use, in order to assess benefits and risks associated with these strategies. DESIGN: Cross sectional design involving qualitative outcomes from nine structured focus groups. SUBJECTS: 47 community tobacco control leaders in Minnesota working in the areas of public policy, clinical treatment of nicotine dependence and youth development participated. OUTCOME MEASURES: Participants discussed definitions of harm reduction; benefits and risks of harm reduction methods; and how funds for tobacco control research and programmes should be allocated. RESULTS: Results indicated inconsistency about the definition of harm reduction: most groups included a broad range of strategies that extended beyond those typically referenced in the scientific literature. Many participants stated that harm reduction might be beneficial, particularly for smokers who could not or would not quit. However, most also expressed concern about a number of risks, including delivering a mixed message about tobacco, inadvertently benefiting the tobacco industry, and causing unanticipated negative health effects. Participants were inclined to suggest public policy measures (for example, smoking bans, increased taxes) as means for reducing harm. CONCLUSIONS: Results indicate that even among tobacco control leaders there is a need for common terminology to describe harm reduction approaches and that public policy approaches to harm reduction are considered more dependable than strategies that involve pharmaceutical treatment or rely on the tobacco industry, such as product modification.

Attitude of Health Personnel↗
PubMed2001

Percentage of CD3+CD4-CD8-gammadeltaTCR- T cells is increased HIV disease.

HIV patients given highly active antiretroviral therapy (HAART) experience a rapid rise in alphabetaT cell numbers, but changes in gammadeltaT cell populations have not been described. Here we investigate the effects of immune reconstitution and immune restoration diseases (IRDs) on expression of a pan-gammadeltaT cell receptor (TCR) marker on double-negative (CD3(+)CD4(-)CD8(-)) T cells and T cells expressing CD4 or CD8. IRDs are inflammatory disorders associated with preexisting infections in patients who have achieved immune reconstitution after HAART. Proportions of CD3(+)CD4(-)CD8(-) T cells and total gammadeltaT cells were not affected by CD4(+) T cell counts, HAART, or a history of IRD, but levels of CD4(-)CD8(-)gammadeltaTCR(-) T cells were higher in patients with <15% CD4(+) T cells.

Adult↗
PubMed2001

What is a good public participation process? Five perspectives from the public.

It is now widely accepted that members of the public should be involved in environmental decision-making. This has inspired many to search for principles that characterize good public participation processes. In this paper we report on a study that identifies discourses about what defines a good process. Our case study was a forest planning process in northern New England and New York. We employed Q methodology to learn how participants characterize a good process differently, by selecting, defining, and privileging different principles. Five discourses, or perspectives, about good process emerged from our study. One perspective emphasizes that a good process acquires and maintains popular legitimacy. A second sees a good process as one that facilitates an ideological discussion. A third focuses on the fairness of the process. A fourth perspective conceptualizes participatory processes as a power struggle--in this instance a power play between local land-owning interests and outsiders. A fifth perspective highlights the need for leadership and compromise. Dramatic differences among these views suggest an important challenge for those responsible for designing and carrying out public participation processes. Conflicts may emerge about process designs because people disagree about what is good in specific contexts.

Conflict of Interest↗
PubMed2001

Immune dysfunction and immune restoration disease in HIV patients given highly active antiretroviral therapy.

BACKGROUND: Some immune defects caused by HIV infection resolve following treatment with highly active antiretroviral therapy (HAART), but residual immune dysfunction may cause disease. Problems with the regulation of the restored immune system in the first six months of treatment can lead to atypical presentations of mycobacterial, cytomegalovirus (CMV), hepatitis B virus or hepatitis C virus (HCV) disease. We defined these conditions as immune restoration diseases (IRD) and showed that they occur in 30-40% of individuals who begin HAART from low CD4 T cell counts. OBJECTIVES: Analysis of immune dysregulation in patients who have responded to HAART. STUDY DESIGN: Patients with successful immune reconstitution following HAART were selected from a database containing details of all patients managed at Royal Perth Hospital (Western Australia) on the basis a CD4 T cell count <100/microl before HAART and an increase of >4-fold or to >200 CD4 T cells/microl. RESULTS: Patients who had experienced an IRD demonstrated increased levels of bioavailable IL-6 and increased expression of CCR5 and CCR3 on monocytes and granulocytes, but numbers of gammadeltaT-cells were similar to patients with similar CD4 T cell counts without an IRD. Carriage of HLA-A2, -B44 was associated with a history of CMV retinitis and/or encephalomyelitis as an IRD, but not with IRD initiated by Mycobacterium sp., cutaneous varicella zoster or herpes simplex infections or HCV. We also identified a patient with Graves' thyrotoxicosis and pronounced lymphadenopathy after HAART, and demonstrated that thyroid stimulating hormone receptor antibody production was associated with an increase in serum soluble CD30, suggesting acquired immune dysregulation. CONCLUSIONS: IRD are associated with persistent immune activation, where differences in genetic profiles suggest that distinct pathological mechanisms are responsible for retinitis/encephalomyelitis IRD. Further studies are important as dysregulated T-cell responses may cause disease later in the course of immune reconstitution.

AIDS-Related Opportunistic Infections↗
PubMed1998

Steep central islands after myopic photorefractive keratectomy.

PURPOSE: To investigate the formation of steep central islands and their reduction under modified experimental conditions. SETTING: University Eye Hospital Münster and Schwind Co., Kleinostheim, Germany. METHODS: Corneas of enucleated intact bovine eyes were treated with the Schwind Keratom. All experimental conditions were repeated six times in six different corneas. Eight experimental groups were looked at. Fluence was 180 to 200 mJ/cm2. Ablation mode (phototherapeutic keratectomy ([PTK] and standard myopic photorefractive keratectomy [PRK]), internal repetition rate (3 to 30 Hz), and ablation diameter (5 to 8 mm) and depth (4 to 15 diopters [D] in PRK) were varied. Modifications to reduce or avoid steep central islands included blowing nitrogen gas and aerosol over the cornea, cleaning the cornea of fluid, and using an anti-central-island software program. RESULTS: In PTK, an increase in the internal repetition rate resulted in a decrease in the height of the steep central island. In standard PRK, increasing refractive correction up to -8.0 D and increasing the ablation diameter resulted in an increase in steep central island power. The anti-central-island program, blowing aerosol, and cleaning the cornea reduced the formation of steep central islands and blowing nitrogen gas eliminated them. CONCLUSION: Steep central islands are created by a wide-field ablation process and are probably caused by many factors. Both software and hardware modifications can be used to reduce their formation.

Animals↗
PubMed1992

Relationship between chronic ovine dermatophilosis and levels of T6 lymphocyte antigen staining in peripheral blood mononuclear cells.

Quantification of a T6-lymphocyte antigen in peripheral blood mononuclear cells of sheep was used to select 15 from 48 one year old Merino ewes not previously exposed to Dermatophilus congolensis infection. These sheep were compared in response to challenge with D. congolensis zoospores and levels of T-6 lymphocyte antigen in peripheral blood mononuclear cells with 15 Merino ewes of similar age and strain from a different site that had been treated and recovered from chronic dermatophilosis. The T-6 lymphocyte antigen levels were significantly lower in the chronic dermatophilosis sheep and they developed significantly more severe lesions than the selected, previously unexposed sheep despite the former sheep having high serum antibody levels to D. congolensis. Measurement of the fleece characteristics, wax and suint concentration showed no differences between the groups that might have explained the considerable differences in their susceptibility to dermatophilosis.

Actinomycetales↗
PubMed1989

Anti-class II antibody production prolongs renal allograft survival.

It is widely accepted that transfusions are beneficial to the outcome of renal allotransplantation. Whereas some investigators suggested that transfusions may induce both specific and nonspecific suppression of the cell-mediated immune response, others disagree. To lend clarity to this discrepancy, we collected 40 serum samples before and after blood transfusion therapy of first-time cadaveric renal allograft recipients and evaluated each for T cell and B cell cytotoxic antibodies using an Amos modified complement-dependent microlymphocytotoxicity assay. When greater than 10% of the panel cells reacted with a grade 4 or better, the panel was considered significant, and when a lymphocyte specificity was lysed by antibody-rich serum greater than 50% of the time, the antibody was considered specific. Control T and B cell PRA assays employed sera from 27 normal nontransfused volunteers of similar age and sex. Survival distributions of differences in the PRA before and after blood transfusions and posttransfusion PRA levels were compared using the Gehan generalized Wilcoxon test. Other factors which influence allograft survival such as HLA-A, -B and -DR matches, number of blood transfusions, immunosuppressive therapy, age, sex, parity, previous positive crossmatch, circulating cytotoxic antibodies matching the graft, prior dialysis, length of time on the waiting list, lapse of time between transfusion and transplantation and the underlying primary diagnosis were also considered using the Gehan generalized Wilcoxon test or the chi 2 approximation. Transfusion-related B cell cytotoxic antibodies, HLA-DR monospecific or multispecific antibodies and HLA-A, -B matching extended graft survival in a significant manner. Sex influenced the production of B and T cell transfusion-related cytotoxic antibodies with females producing greater quantities of antibodies than males. Parity and the production of monospecific or multispecific antibody were associated with an increase in transfusion-related B cell cytotoxic antibody. A difference in sex was not linked to the production of monospecific or multispecific HLA-DR antibodies. The majority of males failed to respond to multiple blood transfusions with the production of B cell cytotoxic antibodies although more than half were successfully grafted. All females and males who responded with the production of B cell cytotoxic antibodies monospecific or multispecific, with the exception of 1 female, demonstrated an allograft survival of greater than 1 year. In conclusion, differences between pre- and post-transfusion B cell PRAs and monospecific or multispecific HLA-DR antibodies identified in patient sera following transfusions were good predictors of renal allograft survival in both males and females.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Transfusion↗
PubMed1988

15 years of experience with renal replacement therapy in patients starting therapy before age 20.

This study retrospectively evaluates the survival on renal replacement therapy among patients starting dialysis before their twentieth birthday. The cohort included all patients starting therapy from 1972 through August, 1987 at the University of Mississippi or Kidney Care, Inc. Fifty-five patients, median age 17 years, range 5-19 years, underwent 335 patient years of therapy. Nineteen initially received CAPD; 12 home hemodialysis, 2 were transplanted prior to dialysis, and the remaining 22 patients were entered into dialysis in a free standing facility. Thirty-one patients received a cadaveric transplant and four patients received a living related transplant. The median transplant survival was 1360 days. There were 10 patients on renal replacement therapy over 10 years and a survival plot projected a 70% survival at 10 years. Nine patients died. Three percent of the time on renal replacement therapy was spent hospitalized. Although the hospitalization rate is significant, the pediatric patient may be expected to have a long survival on renal replacement therapy.

Adolescent↗
PubMed1987

Self-concept changes during youth-home placement of adolescents.

Youth status offenders typically present both mental health and behavior problems. This study describes a youth placement program and demonstrates self-concept enhancement through the program. Specific changes for boys and girls and different family structures are discussed.

Adaptation, Psychological↗
PubMed1986

Purification to homogeneity of pyrroline-5-carboxylate reductase of barley.

An enzyme has been purified to homogeneity from barley seedlings which has ;proline dehydrogenase' and the pyrroline-5-carboxylic acid reductase activities. The purification achieved is 39,000-fold as calculated from the proline dehydrogenase activity. The subunit molecular weight of the protein is 30 kilodaltons. The native enzyme has molecular weights up to 480 kilodaltons, depending on the buffer environment. From the pH profiles, the specific activities and thermodynamic considerations, it is concluded that the plant proline dehydrogenase functions in vivo as a pyrroline-5-carboxylate reductase.

Journal Article↗
PubMed1985

Deglycosylation of chondroitin sulfate proteoglycan by hydrogen fluoride in pyridine.

The original deglycosylation procedure using HF/pyridine has been modified for maximal removal of carbohydrate from chondroitin sulfate proteoglycan, with minimal alteration of the core protein. Gas-liquid chromatography analysis after treatment for various times showed that 95% of xylose and mannose and 70-85% of other sugars were removed within 30 min, indicating that almost all chondroitin sulfate chains and about 80% of N- and O-linked oligosaccharides were removed. In contrast to the loss of carbohydrate, no change in amino acid composition or loss of immunoreactivity occurred. Longer treatment of up to 16 h resulted in little additional removal of carbohydrate, but did cause a significant decrease in solubility and recovery of the deglycosylated product. Optimal removal of xylose residues after about 1 h was also shown by maximal acceptor activity of the product in a xylosyltransferase assay. Rapid removal of the HF reagent by vacuum evacuation and ion-exchange chromatography, coupled with the reduced time of treatment allowed recovery of an intact, homogenous protein core that is amenable to structural and sequence studies.

Amino Acids↗
PubMed1985

Double-blind comparison of haloperidol decanoate and fluphenazine decanoate effectiveness, side-effects, dosage and serum levels during a six months' treatment for relapse prevention.

In this present study 31 schizophrenic patients were treated for six months for relapse prevention under double-blind conditions with either haloperidol decanoate (22) or fluphenazine decanoate (9). In respect of the prophylactic action, both depot neuroleptics proved to be equal during the comparatively short period of observation. In both groups a psychotic relapse occurred that could not be managed by increasing the depot dosage. No side-effects worth mentioning appeared in either group of patients; patients under haloperidol decanoate, however, only required half the quantity of anti-parkinson medication as compared with patients treated with fluphenazine decanoate, and also displayed extrapyramidal motor symptoms (EPMS) to a lesser degree. Patients received a mean monthly injection of 80 mg of Haloperidol, reaching steady-state serum levels of about 3 ng/ml in the third injection interval. Fluphenazine serum levels known so far for seven patients amount to 0.8 ng/ml after fluphenazine injections of 21 mg every 14 days.

Adult↗