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M Baier

Publications and source records attributed to M Baier.

At least 19 recordsLinked to original sources
PubMed2001

Use of the Multiple Sclerosis Functional Composite to predict disability in relapsing MS.

OBJECTIVE: To determine whether the MS Functional Composite (MSFC) can predict future disease progression in patients with relapsing remitting MS (RR-MS). BACKGROUND: The MSFC was recommended by the Clinical Outcomes Assessment Task Force of the National MS Society as a new clinical outcome measure for clinical trials. The MSFC, which contains a test of walking speed, arm dexterity, and cognitive function, is expressed as a single score on a continuous scale. It was thought to offer improved reliability and responsiveness compared with traditional clinical MS outcome measures. The predictive value of MSFC scores in RR-MS has not been determined. METHODS: The authors conducted a follow-up study of patients with RR-MS who participated in a phase III study of interferon beta-1a (AVONEX) to determine the predictive value of MSFC scores. MSFC scores were constructed from data obtained during the phase III trial. Patients were evaluated by neurologic and MRI examinations after an average interval of 8.1 years from the start of the clinical trial. The relationships between MSFC scores during the clinical trial and follow-up status were determined. RESULTS: MSFC scores from the phase III clinical trial strongly predicted clinical and MRI status at the follow-up visit. Baseline MSFC scores, and change in MSFC score over 2 years correlated with both disability status and the severity of whole brain atrophy at follow-up. There were also significant correlations between MSFC scores during the clinical trial and patient-reported quality of life at follow-up. The correlation with whole brain atrophy at follow-up was stronger for baseline MSFC than for baseline EDSS. CONCLUSION: MSFC scores in patients with RR-MS predict the level of disability and extent of brain atrophy 6 to 8 years later. MSFC scores may prove useful to assign prognosis, monitor patients during early stages of MS, and to assess treatment effects.

Adult↗
PubMed2000

Targeting human T cells by retroviral vectors displaying antibody domains selected from a phage display library.

To generate T cell-specific retroviral vectors an scFv phage display library derived from immunized mice was selected for binding to the human T cell line Molt-4/8. The scFv cDNAs recovered from the selected phages were transiently expressed as an N-terminal fusion of the spleen necrosis virus (SNV) transmembrane protein (TM) subunit of the viral envelope protein (Env) in the cell line DSH-cxl, which packages the beta-galactosidase gene into SNV particles. Screening of supernatants from about 150 transfections resulted in the identification of 5 scFvs that mediated efficient transduction of Molt-4/8 cells. Using stable packaging cell lines vector preparations with titers greater than 10(4) EFU/ml on human T cells were obtained. The scFv 7A5 in particular was able to mediate selective transduction of human T cells with high efficiency. Titers of up to 106 EFU/ml were reached on Molt-4/8, Jurkat, and A301 cells, while titers on HeLa cells, TE671 cells, 293T cells, and HT1080 cells were below 102 EFU/ml. Transduction of stimulated primary human peripheral blood cells, which consisted mainly of T cells, was about fivefold more efficient than transduction of B cells. Western blot analysis of supernatant from the 7A5 packaging cells demonstrated incorporation of 7A5-TM into vector particles and indicated proteolytic processing of the coexpressed unmodified TM during particle formation. Binding of bacterially expressed 7A5-scFv to a panel of cell lines correlated well with the transduction results. These data provide the first proof of concept that a general approach can be taken to obtain scFvs able to mediate selective gene transfer into target cells.

Amino Acid Sequence↗
PubMed2000

Clinical significance of the multiple sclerosis functional composite: relationship to patient-reported quality of life.

BACKGROUND: The Multiple Sclerosis Functional Composite (MSFC) was recommended by a task force of the National Multiple Sclerosis Society as a new clinical outcome measure for clinical trials. The task force recommended that the MSFC be validated against other measures of the disease, such as patient-reported quality of life. METHODS: Three hundred patients with multiple sclerosis (MS) representing the spectrum of disease severity were included in this cross-sectional study. The MSFC and Kurtzke Expanded Disability Status Scale (EDSS) were used as measures of disease severity. Clinical relevance of the disease severity scores was analyzed using measures included in the Multiple Sclerosis Quality of Life Inventory. The MSFC and EDSS scores were correlated with self-reported employment status, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and the Sickness Impact Profile (SIP). RESULTS: The MSFC and EDSS scores were strongly correlated (r = -0.80, P<.001). The MSFC scores were correlated with patient-reported physical functioning (SIP Physical Summary Scale: r = -0.71, P<.001; SF-36 Physical Component Score: r = -0.41, P<.001). The MSFC scores were significantly but more weakly correlated with emotional functioning (SIP Psychosocial Summary Scale: r = -0.34, P<.001). After controlling for EDSS scores, there were significant residual correlations between the MSFC scores and measures of health-related quality of life, suggesting that the MSFC accounts for the variability in health-related quality of life measures not reflected by the EDSS. CONCLUSIONS: The observed strong correlations between MSFC scores and validated measures of self-reported quality of life indicate that the MSFC scores are clinically relevant. This study supports a recommendation by the National Multiple Sclerosis Society Task Force to use the MSFC as a clinical outcome measure.

Adult↗
PubMed2000

The relationship between insight and clinical factors for persons with schizophrenia.

This correlational study examined the relationship of insight with positive and negative symptoms and level of functioning among persons with schizophrenia or schizoaffective disorder. Poor insight as a symptom of schizophrenia is the conceptual framework. Thirty-seven people receiving assertive community treatment, inpatient hospitalization, or outpatient treatment were assessed using 2 self-rating insight scales, the Scale for Assessment of Positive Symptoms (SAPS), the Scale for Assessment of Negative Symptoms (SANS), and the Global Assessment of Functioning (GAF). A significant negative correlation was found between insight and positive formal thought disorder. No significant relationships were found between insight and negative symptoms or level of functioning. Reactions to the self-rating insight tools suggest necessary revisions of the insight tool.

Adult↗
PubMed2000

Membrane-type matrix metalloproteinase-9 activity in placental tissue from patients with pre-existing and gestational diabetes mellitus.

The activity of matrix metalloproteinase (MMP)-9 was evaluated in placental tissue from healthy subjects (controls) and from patients with gestational and pre-existing diabetes mellitus (GDM and PDM, respectively). Compared with controls, MMP-9 activity was greater in placental tissue from patients with PDM and lower in placental tissue from patients with GDM. The modulatory role of nitric oxide (NO) and reactive oxygen species (ROS) on MMP-9 activity in placental tissue was evaluated. In healthy placenta, NO synthase inhibitors diminished MMP-9 activity, whereas NO donors enhanced it. The addition of xanthine/xanthine oxidase or hydrogen peroxide to placental incubates enhanced MMP-9 activity, while the addition of superoxide dismutase (SOD) diminished it. In placental tissue from patients with PDM, MMP-9 activity was stimulated by NO and by ROS. In placental tissue from patients with PDM, concentrations of nitrates/nitrites and thiobarbituric acid-reactive substances (TBARS) were enhanced, whereas SOD activity was decreased, suggesting that elevated concentrations of NO and ROS may be related to the enhanced MMP-9 concentrations found in these tissues. In placenta from GDM patients, in which a diminished concentration of MMP-9 were detected, nitrate/nitrite concentrations were increased, but placental MMP-9 activity did not change in the presence of either NO donors or inhibitors. The activity of MMP-9 in placental tissue from patients with GDM was stimulated by ROS donor systems and was inhibited by the addition of SOD; however, TBARS and SOD concentrations were unchanged in these tissues compared with controls. These findings demonstrate that placental MMP-9 activity is modulated by NO and ROS and that, in diabetic pathology, NO and ROS may determine changes in MMP-9 activity, which are probably involved in the structural and functional abnormalities of diabetic placental tissue.

Adult↗
PubMed2000

Antisense suppression of 2-cysteine peroxiredoxin in Arabidopsis specifically enhances the activities and expression of enzymes associated with ascorbate metabolism but not glutathione metabolism.

The aim of this study was to characterize the effect of decreased 2-cysteine peroxiredoxin (2-CP) on the leaf anti-oxidative system in Arabidopsis. At three stages of leaf development, two lines of transgenic Arabidopsis mutants with decreased contents of chloroplast 2-CP were compared with wild type and a control line transformed with an empty vector. Glutathione contents and redox state were similar in all plants, and no changes in transcript levels for enzymes involved in glutathione metabolism were observed. Transcript levels for chloroplastic glutathione peroxidase were much lower than those for 2-CP, and both cytosolic and chloroplastic glutathione peroxidase were not increased in the mutants. In contrast, the foliar ascorbate pool was more oxidized in the mutants, although the difference decreased with plant age. The activities of thylakoid and stromal ascorbate peroxidase and particularly monodehydroascorbate reductase were increased as were transcripts for these enzymes. No change in dehydroascorbate reductase activity was observed, and effects on transcript abundance for glutathione reductase, catalase, and superoxide dismutase were slight or absent. The results demonstrate that 2-CP forms an integral part of the anti-oxidant network of chloroplasts and is functionally interconnected with other defense systems. Suppression of 2-CP leads to increased expression of other anti-oxidative genes possibly mediated by increased oxidation state of the leaf ascorbate pool.

Antioxidants↗
PubMed2000

Identification of upregulated genes in scrapie-infected brain tissue.

The pathogenesis of scrapie, and of neurodegenerative diseases in general, is still insufficiently understood and is therefore being intensely researched. There is abundant evidence that the activation of glial cells precedes neurodegeneration and may thus play an important role in disease development and progression. The identification of genes with altered expression patterns in the diseased brain may provide insight on the molecular level into the process which ultimately leads to neuronal loss. Differentially expressed genes in scrapie-infected brain tissue were enriched by the suppression subtractive hybridization technique, molecularly cloned, and further characterized. Northern blotting and nucleotide sequencing confirmed the identities of 19 upregulated genes, 11 of which were unknown to be affected by scrapie. A considerable number of these 19 genes, namely those encoding interferon-inducible protein 10 (IP-10), 2',5'-oligo(A) synthetase, Mx protein, IIGP protein, major histocompatibility complex classes I and II, complement, and beta(2)-microglobulin, were inducible by interferons (IFNs), suggesting that an IFN response is a possible mechanism of gene activation in scrapie. Among the newly found genes, that coding for 2',5'-oligo(A) synthetase is of special interest because it could contribute to the apoptotic loss of neuronal cells via RNase L activation. In addition, upregulation of the chemokine IP-10 and B-lymphocyte chemoattractant mRNAs was seen at relatively early stages of the disease and was sustained throughout disease development.

Animals↗
PubMed2000

Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients.

Brain atrophy measurement can provide an estimate of the amount of tissue destruction due to the pathologic processes in multiple sclerosis. The potential usefulness of atrophy as a marker of disease progression depends upon the concurrent and predictive relationships between atrophy and disability. A follow-up study was performed to measure atrophy and disability scores in patients from the Multiple Sclerosis Collaborative Research Group's phase III trial of IFNbeta-1a (Avonex) in relapsing- remitting multiple sclerosis. New data were obtained on 160 out of 172 eligible patients from the original trial were enrolled in the follow-up study approximately 8 years after randomization. The follow-up visit consisted of several tests and questionnaires including a clinical exam to determine Expanded Disability Status Score (EDSS) and Multiple Sclerosis Functional Composite (MSFC), and a magnetic resonance imaging exam to calculate the brain parenchymal fraction. Brain parenchymal fraction was correlated with both EDSS and MSFC at each of the four time points for which data were available (baseline 1, 2 and 8 years). Furthermore, the change in BPF was correlated with the changes in disability scores from the end of the phase III trial to the follow-up exam. These data suggest that brain atrophy may be a useful and clinically relevant marker of disease progression in relapsing--remitting MS.

Adjuvants, Immunologic↗
PubMed2000

Validity of self-reported colorectal cancer screening behavior.

End points for trials promoting cancer screening are often based on self-reported screening behavior. This study was designed to evaluate and optimize the reliability of a computer-assisted telephone interview for collecting self-reported colorectal cancer screening behavior. Cases who had received a fecal occult blood test (FOBT), flexible sigmoidoscopy, and/or colonoscopy, and controls who had no record of colorectal screening were identified among 40-75-year-old members of the Denver Kaiser Permanente Health Care Program and were contacted by telephone. Sensitivities and specificities of self-reported screening were calculated by comparison of subjects' recall with Kaiser Permanente records. The questionnaire was revised based upon results of the pilot phase of the study. Using the revised questionnaire, the sensitivity of self-reported screening was 96.2% for the FOBT, 94.9% for flexible sigmoidoscopy, 88.7% for colonoscopy, and 96.2% for either endoscopic screening test. The specificity of self-reported screening was 85.9% for the FOBT, 92.2% for flexible sigmoidoscopy, 96.8% for colonoscopy, and 92.0% for either endoscopic screening test. No marked differences in the accuracy of the self-reports were detected as a function of gender, age, ethnicity, or family history of colorectal cancer of the participants. Self-reports of colon cancer screening behavior can be reliably used as end points for intervention trials when carefully phrased questions are used.

Adult↗
PubMed2000

Changes in functional status related to health maintenance visits to family physicians.

BACKGROUND: Physicians do not provide preventive care at the level recommended by national organizations. This may be because of physicians' lack of training or low level of confidence or because of patients' fears, beliefs, and lack of health knowledge. METHODS: We used an observational prospective cohort study in an academic family practice office to investigate changes in patients' functional status associated with receiving recommendations to change behavior from family physicians. Patients 18 years and older presenting for health maintenance visits to family physicians completed a functional status instrument and a brief intake questionnaire by telephone before their visit. After the visit patients were randomized to a debriefing interview or an observation-only group. The interview included the Patient/Doctor Interaction Scale and an assessment of whether patients received a recommendation to change behavior. RESULTS: One hundred thirty-two patients were randomized to the debriefing group, and of those, 92% completed assessments at 3 months. Patients reporting recommendations to change behavior had lower scores at 1 and 3 months for mental health, social health, and self-esteem and higher anxiety and depression scores than patients not receiving these recommendations. CONCLUSIONS: There are declines in social and emotional functional status in patients presenting to family practice clinicians for health maintenance visits during which recommendations for behavioral change were made. Such declines may inhibit physicians from making recommendations for behavioral change or patients from accepting them.

Adaptation, Psychological↗
PubMed1999

Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial.

BACKGROUND: Inhaled nitric oxide improves oxygenation and lessens the need for extracorporeal-membrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease. METHODS: We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age < or = 34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age. FINDINGS: The two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0.03). Survival at discharge was 52% in the inhaled-nitric-oxide group and 47% in controls (p=0.65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%). INTERPRETATION: Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury.

Administration, Inhalation↗
PubMed1999

Efficiency of prostate-specific antigen and digital rectal examination in screening, using 4.0 ng/ml and age-specific reference range as a cutoff for abnormal values.

BACKGROUND: The purpose of this study was to examine the diagnostic efficiency of prostate-specific antigen (PSA) and digital rectal examination (DRE) testing when using either 4.0 ng/ml or an age-specific reference range (ASRR) as an abnormal cutoff PSA value. METHODS: Between 1992-1995, 116,073 men, aged 40-79 years, were screened during Prostate Cancer Awareness Week. When using a 4.0-ng/ml cutoff PSA value, 22,014 had either an abnormal PSA, an abnormal DRE, or both. When using an ASRR cutoff PSA value, 17,561 had either an abnormal PSA, an abnormal DRE, or both. The positive predictive value (PPV), sensitivity, and specificity of PSA, DRE, and combined PSA and DRE tests were evaluated. RESULTS: When using a 4.0-ng/ml cutoff PSA value, the PPVs of abnormal PSA alone, abnormal DRE alone, and combined abnormal PSA and DRE tests were 27.7%, 17.7%, and 56.0%, respectively. Sensitivities were 34.9%, 27.1%, and 38.0%, respectively. Specificities were 63.1%, 49.0%, and 87.9%, respectively. When using an ASRR cutoff PSA value, the PPVs of each category were 31.8%, 20.8%, and 63.7%, respectively. Sensitivities were 27.1%, 41.0%, and 31.8%, respectively. Specificities were 75.0%, 32.8%, and 92.2%, respectively. The PPVs of the PSA test were higher than those of the DRE. The PPVs of combined tests were highest when using either a 4.0-ng/ml cutoff PSA value or an ASRR cutoff PSA value (all P < 0.001). When using an ASRR, the PPVs of PSA, DRE, and combined tests were higher than those when using a 4.0-ng/ml without statistical significance (all P > 0.05). Sensitivity of PSA when using an ASRR was lower than when using 4.0 ng/ml. CONCLUSIONS: Significantly higher PPVs indicated that utilizing both a PSA test and a DRE is most effective in screening for the early detection of prostate cancer. Although higher PPVs when using an ASRR cutoff PSA value suggested fewer unnecessary biopsies, lower sensitivities resulted in fewer cancers detected. Thus, we recommend that the combination of a PSA test with a cutoff value of 4.0 ng/ml and a DRE should continue to be utilized in the screening programs.

Adult↗
PubMed1999

GA-binding protein factors, in concert with the coactivator CREB binding protein/p300, control the induction of the interleukin 16 promoter in T lymphocytes.

Interleukin 16 (IL-16) is a chemotactic cytokine that binds to the CD4 receptor and affects the activation of T cells and replication of HIV. It is expressed as a large 67-kDa precursor protein (pro-IL-16) in lymphocytes, macrophages, and mast cells, as well as in airway epithelial cells from asthmatics after challenge with allergen. This pro-IL-16 is subsequently processed to the mature cytokine of 13 kDa. To study the expression of IL-16 at the transcriptional level, we cloned the human chromosomal IL-16 gene and analyzed its promoter. The human IL-16 gene consists of seven exons and six introns. The 5' sequences up to nucleotide -120 of the human and murine IL-16 genes share >84% sequence homology and harbor promoter elements for constitutive and inducible transcription in T cells. Although both promoters lack any TATA box, they contain two CAAT box-like motifs and three binding sites of GA-binding protein (GABP) transcription factors. Two of these motifs are part of a highly conserved and inducible dyad symmetry element shown previously to control a remote IL-2 enhancer and the CD18 promoter. In concert with the coactivator CREB binding protein/p300, which interacts with GABPalpha, the binding of GABPalpha and -beta to the dyad symmetry element controls the induction of IL-16 promoter in T cells. Supplementing the data on the processing of pro-IL-16, our results indicate the complexity of IL-16 expression, which is tightly controlled at the transcriptional and posttranslational levels in T lymphocytes.

Animals↗
PubMed1999

Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure.

OBJECTIVES AND BACKGROUND: To determine whether inhaled nitric oxide (iNO) therapy can attenuate the progression of lung disease in acute hypoxemic respiratory failure, we performed a multicenter, randomized, masked, controlled study of the effects of prolonged iNO therapy on oxygenation. We hypothesized that iNO therapy would improve oxygenation in an acute manner, slow the rate of decline in gas exchange, and decrease the number of patients who meet pre-established oxygenation failure criteria. STUDY DESIGN: A total of 108 children (median age 2.5 years) with severe acute hypoxemic respiratory failure from 7 centers were enrolled. After consent was obtained, patients were randomized to treatment with iNO (10 ppm) or mechanical ventilation alone for at least 72 hours. Patients with an oxygenation index >/=40 for 3 hours or >/=25 for 6 hours were considered treatment failures and exited the study. RESULTS: Patient age, primary diagnosis, pediatric risk of mortality score, mode of ventilation, and median oxygenation index (35 +/- 22 vs 30 +/- 15; iNO vs control; mean +/- SEM) were not different between groups at study entry. Comparisons of oxygenation indexes during the first 12 hours demonstrated an acute improvement in oxygenation in the iNO group at 4 hours (-10.2 vs -2.7, mean values; P <.014) and at 12 hours (-9.2 vs -2.8; P <.007). At 12 hours 36% of the control group met failure criteria in contrast with 16% in the iNO group (P <.05). During prolonged therapy the failure rate was reduced in the iNO group in patients whose entry oxygenation index was >/=25 (P <.04) and in immunocompromised patients (P <.03). CONCLUSIONS: We conclude that iNO causes an acute improvement in oxygenation in children with severe AHRF. Two subgroups (immunocompromised and an entry oxygen index >/=25) appear to have a more sustained improvement in oxygenation, and we speculate that these subgroups may benefit from prolonged therapy.

Administration, Inhalation↗
PubMed1999

Late increase of serum S100 beta protein levels in hamsters after oral or intraperitoneal infection with scrapie.

Following recent reports of elevated serum S100 beta protein (S100 beta) levels in patients with genetic and sporadic Creutzfeldt-Jakob disease and in rodents parenterally infected with scrapie, the suitability of serum S100 beta as a preclinical marker for transmissible spongiform encephalopathies was assessed in time-course studies. Syrian hamsters were orally and intraperitoneally challenged with scrapie and assayed for serum S100 beta levels at various times after infection. Although elevated serum S100 beta levels were consistently observed in terminally ill animals for both routes of infection, the experiments failed to detect significantly increased S100 beta serum concentrations prior to the manifestation of clinical symptoms. Thus, in this animal model, serum S100 beta does not appear to be an appropriate marker for the preclinical detection of scrapie, but it may provide a convenient laboratory aid for the diagnosis of transmissible spongiform encephalopathy in naturally or accidentally infected animals and humans.

Administration, Oral↗
PubMed1999

Protective function of chloroplast 2-cysteine peroxiredoxin in photosynthesis. Evidence from transgenic Arabidopsis.

2-Cysteine peroxiredoxins (2-CPs) constitute a ubiquitous group of peroxidases that reduce cell-toxic alkyl hydroperoxides to their corresponding alcohols. Recently, we cloned 2-CP cDNAs from plants and characterized them as chloroplast proteins. To elucidate the physiological function of the 2-CP in plant metabolism, we generated antisense mutants in Arabidopsis. In the mutant lines a 2-CP deficiency developed during early leaf and plant development and eventually the protein accumulated to wild-type levels. In young mutants with reduced amounts of 2-CP, photosynthesis was impaired and the levels of D1 protein, the light-harvesting protein complex associated with photosystem II, chloroplast ATP synthase, and ribulose-1,5-bisphosphate carboxylase/oxygenase were decreased. Photoinhibition was particularly pronounced after the application of the protein synthesis inhibitor, lincomycin. We concluded that the photosynthetic machinery needs high levels of 2-CP during leaf development to protect it from oxidative damage and that the damage is reduced by the accumulation of 2-CP protein, by the de novo synthesis and replacement of damaged proteins, and by the induction of other antioxidant defenses in 2-CP mutants.

Antioxidants↗