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Biomedical subjects

K Baier

Publications and source records attributed to K Baier.

At least 19 recordsLinked to original sources
PubMed2006

Thrombin generation in factor VIII-depleted neonatal plasma: nearly normal because of physiologically low antithrombin and tissue factor pathway inhibitor.

BACKGROUND: Bleeding in hemophilic neonates has a low incidence. A possible explanation for this could be the peculiarities of the neonatal hemostatic system, especially low levels of the inhibitors tissue factor pathway inhibitor (TFPI) and antithrombin (AT). OBJECTIVE: We investigated the influence of an elevation of these inhibitors to adult levels on the thrombin generation (TG) in normal neonatal plasma and factor (F) VIII-depleted neonatal plasma by means of incubation with anti-FVIII-antibodies. PATIENTS/METHODS: TG was measured after activation with low amounts of tissue factor (TF) by using Calibrated Automated Thrombography. RESULTS: TG in FVIII-depleted neonatal plasma was nearly as high as in normal neonatal plasma. TG decreased after elevation of AT in both neonatal plasmas. After elevation of TFPI TG decreased much more in FVIII-depleted neonatal plasma than in normal neonatal plasma. After elevation of both inhibitors their synergistic effect led to a stronger decrease of TG in FVIII-depleted neonatal plasma. TG measured in plasma of one hemophilic newborn showed the same pattern as in FVIII-depleted neonatal plasma. CONCLUSION: Our observation provides a biochemical basis for the rare bleeding in hemophilic neonates and shows the important role of the natural inhibitors in the hemostatic system of hemophilic patients.

Adult↗
PubMed2005

The tumor suppressor RASSF1A in human carcinogenesis: an update.

Loss of heterozygosity of the small arm of chromosome 3 is one of the most common alterations in human cancer. Most notably, a segment in 3p21.3 is frequently lost in lung cancer and several other carcinomas. We and others have identified a novel Ras effector at this segment, which was termed Ras Association Domain family 1 (RASSF1A) gene. RASSF1 consists of two main variants (RASSF1A and RASSF1C), which are transcribed from distinct CpG island promoters. Aberrant methylation of the RASSF1A promoter region is one of the most frequent epigenetic inactivation events detected in human cancer and leads to silencing of RASSF1A. Hypermethylation of RASSF1A was commonly observed in primary tumors including lung, breast, pancreas, kidney, liver, cervix, nasopharyngeal, prostate, thyroid and other cancers. Moreover, RASSF1A methylation was frequently detected in body fluids including blood, urine, nipple aspirates, sputum and bronchial alveolar lavages. Inactivation of RASSF1A was associated with an advanced tumor stage (e.g. bladder, brain, prostate, gastric tumors) and poor prognosis (e.g. lung, sarcoma and breast cancer). Detection of aberrant RASSF1A methylation may serve as a diagnostic and prognostic marker. The functional analyses of RASSF1A reveal an involvement in apoptotic signaling, microtubule stabilization and mitotic progression. The tumor suppressor RASSF1A may act as a negative Ras effector inhibiting cell growth and inducing cell death. Thus, RASSF1A may represent an epigenetically inactivated bona fide tumor suppressor in human carcinogenesis.

Chromosomes, Human, Pair 3↗
PubMed2003

Induction of mucosal tolerance with recombinant Hev b 1 and recombinant Hev b 3 for prevention of latex allergy in BALB/c mice.

The prevalence of type I allergy to Hevea brasiliensis latex is particularly high among individuals with frequent exposure to latex products, such as health-care workers (HCW) and patients with spina bifida (SB). Treatment of latex allergy seems problematic as preventive measures, such as allergen avoidance, are not always possible and conventional immunotherapy with standardized latex extracts is not performed routinely. Thus, the aim of the present study was to establish a mouse model of latex allergy using two major latex allergens for HCWs and SB patients, Hev b 1 and Hev b 3, for sensitization. Prophylactic measures on the basis of mucosal tolerance induction with the recombinant allergens were tested in this model. Female BALB/c mice immunized intraperitoneally with recombinant (r)Hev b 1 or rHev b 3 displayed strong immune responses in vivo and in vitro. Intranasal treatment with rHev b 1 and rHev b 3 prior to sensitization led to reduced allergen-specific IgG1/IgE levels and significantly suppressed allergen-induced basophil degranulation. Moreover, lymphocyte proliferation and cytokine production (IL-4, IL-5, IFN-gamma) in vitro were significantly suppressed after pretreatment with both allergens. Suppressive cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF)-beta, remained unchanged after the intranasal pretreatment, indicating mechanism of anergy rather than active immunosuppression. Taken together, these results suggest that mucosal tolerance induction with recombinant allergens could present a promising prevention strategy against latex allergy.

Allergens↗
PubMed2002

Mucosal tolerance as therapy of type I allergy: intranasal application of recombinant Bet v 1, the major birch pollen allergen, leads to the suppression of allergic immune responses and airway inflammation in sensitized mice.

BACKGROUND: Several studies have demonstrated that mucosal administration of soluble antigens can prevent the onset or reduce the severity of certain autoimmune diseases or allergies. Few studies exist showing the efficacy of mucosal tolerance for therapy of such diseases. OBJECTIVE: The aim of the present study was to modulate an allergic immune response by intranasal antigen administration in an already sensitized organism. METHODS: A murine model of allergic asthma to birch pollen (BP) and its major allergen Bet v 1 was utilized. Sensitized mice were intranasally treated with recombinant (r)Bet v 1 in different concentrations and at different intervals. On the day the mice were killed, blood and bronchoalveolar lavage fluids were taken and immediate type I skin tests were performed. T cell proliferation and cytokine production (interleukin (IL)-5, interferon (IFN)-gamma) were measured in spleen and lung cell cultures. RESULTS: Mucosal treatment with rBet v 1 (3 x 50 microg in 4 day intervals) led to a reduction of type I skin reactions, suppressed immunoglobulin (Ig)G1/IgE antibody levels and markedly decreased IL-5 and IFN-gamma production in vitro in spleen and lung cell cultures. Moreover, lung inflammation (i.e. eosinophilia and IL-5 levels in bronchoalveolar lavage fluids) was significantly suppressed by the treatment. CONCLUSION: Our results demonstrate that intranasal treatment with rBet v 1 reduced systemic allergic immune responses as well as airway inflammation in BP-sensitized mice. We therefore suggest that mucosal tolerance induction with recombinant allergens could be a promising concept for the therapy of allergic diseases.

Administration, Intranasal↗
PubMed2002

Phage-displayed Bet mim 1, a mimotope of the major birch pollen allergen Bet v 1, induces B cell responses to the natural antigen using bystander T cell help.

BACKGROUND AND OBJECTIVE: In previous studies we have generated mimotopes of Bet v 1, the major birch pollen allergen, by biopannings of phage-display random peptide libraries. In the present study, we analysed the humoral and cellular immune response to Bet v 1-mimotopes. METHODS: The mimotope CFPYCYPSESA, designated Bet mim 1, was used for intraperitoneal immunizations of BALB/c mice in phage-displayed form. For examination of the humoral immune response, enzyme-linked immunosorbent assay (ELISA) experiments were applied. Stimulation capacities were investigated in cultured mouse splenocytes and in humoral Bet v 1-specific T cell clones. RESULTS: We demonstrated that the Bet mim 1-induced murine antibody response against Bet v 1 was predominated by the IgG1 isotype. In these mice only the phage-displayed mimotopes, but neither the allergen nor the synthetic Bet mim 1-mimotopes were able to stimulate proliferation of cultured splenocytes. Using Bet v 1-specific T cell clones of allergic patients, phage-displayed and synthetic mimotopes were unable to stimulate T cell proliferation. Moreover, tolerance induction to Bet v 1 in mice by intranasal administration of Bet mim 1-phages or Bet mim 1-peptide failed. CONCLUSION: Taking these results together, our data indicate that Bet mim 1 mimics a Bet v 1-epitope on the B cell but not on the T cell level. We suggest that the phage itself is responsible for the recruitment of T cells providing bystander help in the formation of a mimotope-specific humoral response.

Allergens↗
PubMed2002

In vitro radiosensitivity measured in lymphocytes and fibroblasts by colony formation and comet assay: comparison with clinical acute reactions to radiotherapy in breast cancer patients.

PURPOSE: To compare colony-forming and comet assays on fibroblasts and lymphocytes of 32 breast cancer patients irradiated after breast-conserving operations and to correlate the results with acute clinical radiation reactions in the skin. MATERIAL AND METHODS: Skin fibroblasts were isolated and cultivated before radiotherapy and lymphocytes were drawn prior to the first and directly after the final external irradiation. The colony-forming assay was performed with fibroblasts and the comet assay with lymphocytes and fibroblasts of breast cancer patients according to standard protocols. The clinical radiation reactions of the patients were graded according to the RTOG system. RESULTS: No significant correlation (p =0.09) was detected between clinical acute skin reactions and the in vitro clonogenic data in fibroblasts. Results of the comet assay in lymphocytes, however, showed a significant correlation (p <0.05) with the clinical data when patients were divided into two groups with average and elevated acute reactions. Apart from initial damage, fibroblasts did not show significant differences between the two patient groups. Repeated comet assays in lymphocytes of the same patient drawn before treatment and before and after external radiotherapy demonstrated good reproducibility of the test and no significant impact of preceding radiation treatment. There was a good correlation (r =0.65) between the comet assay results in fibroblasts and lymphocytes of the same individual. CONCLUSIONS: In this cohort of patients, a significant correlation between the in vitro results of the comet assay in lymphocytes and clinical acute reactions was detected. The results of the comet assay and of fibroblast colony formation did not correlate with in vitro radiosensitivity.

Breast Neoplasms↗
PubMed2001

Expression of two nblA-homologous genes is required for phycobilisome degradation in nitrogen-starved Synechocystis sp. PCC6803.

One of the responses exhibited by cyanobacteria when they are limited for an essential nutrient is the rapid degradation of their light-harvesting complex, the phycobilisome. Phycobilisome degradation is an ordered proteolytic process, visible by a color change of the cyanobacterial cell from blue-green to yellow-green (chlorosis). The small polypeptide NblA plays a key role in degradation of phycobilisomes in Synechococcus sp. PCC7942. Unlike Synechococcus, Synechocystis sp. PCC6803 has two nblA-homologous genes, nblA1 and nblA2, which are contiguous on the genome. Here we show that nblA1 and nblA2 are simultaneously expressed in Synechocystis 6803 upon nitrogen deprivation, and are both required for phycobilisome degradation.

Amino Acid Sequence↗
PubMed2001

A low-cost intervention for cleaner drinking water in Karachi, Pakistan.

OBJECTIVE: To pilot test an inexpensive, home-based water decontamination and storage system in a low-income neighborhood of Karachi. METHODS: Fifty households received a 20-L plastic water storage vessel with a high-quality spout and a regular supply of diluted hypochlorite solution. Twenty-five control households were recruited. Water samples were collected at baseline and during unannounced follow-up visits 1, 3, 6, and 10 weeks later. RESULTS: Baseline drinking water samples among intervention households were contaminated with a mean 9397 colony-forming units (cfu)/100 mL of thermotolerant coliforms compared with a mean 10,990 cfu/100 mL from controls. After intervention the mean concentration of thermotolerant coliforms decreased by 99.8% among the intervention households compared with an 8% reduction among controls. Two years after vessel distribution, 34 (68%) of the families were still using the vessel. Thirteen of the households had stopped using their vessel because it had broken after more than 6 months of use, a pattern most consistent with ultraviolet radiation-induced degradation of the plastic. CONCLUSIONS: In a highly contaminated environment, a specifically designed water storage container and in-home water chlorination was acceptable and markedly improved water quality. Where plastic water vessels will be exposed to substantial sunlight, ultraviolet light stabilizers should be incorporated into the plastic.

Costs and Cost Analysis↗
PubMed2001

Microbiologic effectiveness of hand washing with soap in an urban squatter settlement, Karachi, Pakistan.

We conducted a study in a squatter settlement in Karachi, Pakistan where residents report commonly washing their hands to determine if providing soap, encouraging hand washing, and improving wash-water quality would improve hand cleanliness. We allocated interventions to 75 mothers and collected hand-rinse samples on unannounced visits. In the final model compared with mothers who received no hand-washing intervention, mothers who received soap would be expected to have 65% fewer thermotolerant coliform bacteria on their hands (95% CI 40%, 79%) and mothers who received soap, a safe water storage vessel, hypochlorite for water treatment, and instructions to wash their hands with soap and chlorinated water would be expected to have 74% fewer (95% CI 57%, 84%). The difference between those who received soap alone, and those who received soap plus the safe water vessel was not significant (P = 0.26). Providing soap and promoting hand washing measurably improved mothers' hand cleanliness even when used with contaminated water.

Female↗
PubMed2001

[Carcinoma of the external ear canal and middle ear as interdisciplinary challenge for ear surgery and radiotherapy].

BACKGROUND: Carcinoma of the external auditory canal are tumours considered to have a poor prognosis. Improvement of the survival rate by surgical means alone is not possible. Individual therapy modalities as a result of an interdisciplinary approach between otosurgeon and radiotherapist are necessary. PATIENTS AND METHODS: A series of 30 patients (3 patients pretreated at other institutions) with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions was analysed with particular reference to tumour size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques. Clinical endpoints were freedom from local failure, overall survival, disease-free survival. The mean follow-up was 4.7 years (range: 0.1 to 18.8 years), median 3 years. RESULTS: Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 51%. According to Pittsburgh classification the 5-year survival rate for early disease (T1- and T2-tumours) was 89%, for stage III 67% and for stage IV 39%. Most important prognostic factors were dural infiltration (all patients with dural invasion died within 2.2 years) and the infiltration of surgical margins (the 5-year survival rate of patients with complete tumour resection was 100%, but 54% in patients with tumour beyond surgical margins). 192-iridium HDR afterloading brachytherapy based on 3D CT-treatment planning is an effective tool in the management of local recurrences following surgery and a full course of external beam radiotherapy. CONCLUSIONS: Surgical resection followed by radiotherapy adapted to the stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

Adult↗
PubMed2001

The in vitro colony assay: a predictor of clinical outcome.

PURPOSE: To determine the predictive power of an in vitro colony assay on the clinical normal-tissue complication rate. MATERIAL AND METHODS: Primary skin fibroblasts from 88 individuals were generated from the skin biopsies of patients who received a standardized radiotherapy. Tissue was cultured for three to six passages, irradiated with doses between 1 and 8 Gy under defined conditions, seeded and finally the colonies were stained and counted after 10-14 days. The survival curves were fitted by the L-Q model and the SF2, alpha/beta and plating efficiency were calculated. RESULTS: The parameters SF2 and plating efficiency were stable throughout the 4-year test period. Intra-individual differences between repeated experiments were significantly lower than inter-individual test results. For the observed acute skin and late normal-tissue reactions other than skin the in vitro parameter SF2 correlated significantly (p<0.005). For late skin reactions this correlation was not found. DISCUSSION: In contrast to other publications, a clear correlation was found between the in vitro test results and clinically observed early reactions. The lack of correlation for late skin reactions suggests that the combination of intrinsic radiation sensitivity and exogenous factors may alter the clinically observed reaction of certain tissues to a different extent.

Breast Neoplasms↗
PubMed2001

Intranasal treatment with a recombinant hypoallergenic derivative of the major birch pollen allergen Bet v 1 prevents allergic sensitization and airway inflammation in mice.

BACKGROUND: The major birch pollen allergen Bet v 1 represents one of the most prevalent environmental allergens responsible for allergic airway inflammation. OBJECTIVE: In the present study we sought to compare the complete recombinant Bet v 1 allergen molecule with genetically produced hypoallergenic fragments of Bet v 1 regarding mucosal tolerance induction in a mouse model of allergic asthma. METHODS: BALB/c mice were intranasally treated with recombinant Bet v 1 or with two recombinant Bet v 1 fragments (F I: aa 1-74; F II: aa 75-160) prior to aerosol sensitization with birch pollen and Bet v 1. RESULTS: Intranasal application of F II, containing the major T cell epitope, led to significant reduction of IgE/IgG1 antibody responses, in vitro cytokine production (IL-5, IFN-gamma, IL-10) and negative immediate cutaneous hypersensitivity reactions comparable to the pretreatment with the complete rBet v 1 allergen. Moreover, airway inflammation (eosinophilia, IL-5) was inhibited by the pretreatment with either the complete Bet v 1 or F II. However, for prevention of airway hyperresponsiveness the complete molecule was required. The mechanisms leading to immunosuppression seemed to differ in their dependence on the conformation of the molecules, since tolerance induced with the complete Bet v 1, but not with F II, was transferable with spleen cells and associated with increased TGF-beta mRNA levels. CONCLUSION: We conclude that mucosal tolerance induction with recombinant allergens and genetically engineered hypoallergenic derivatives thereof could provide a convenient and safe intervention strategy against type I allergy.

Administration, Intranasal↗
PubMed2001

African-European differences in the capacity of T-cell cytokine production.

Regional differences in immune responsiveness have been studied by comparing the frequency of cytokine producing T cells in healthy African children and adults and their age-matched European counterparts. By use of flow cytometry for the intracellular detection of cytokines an overall expansion of CD4+ and CD8+ T cells producing the Type 1 cytokines interleukin (IL)-2 and interferon (IFN)-gamma was observed in adults when compared with children, giving credit to the cumulative effect of contacts with environmental antigens. The CD4+ cells expressing the Type 2 cytokines IL-4 and IL-13, however, increased only in Africans, probably reflecting continuously present challenges with antigens that preferentially drive Type 2 responses. A striking increased frequency of both Type 1 and Type 2 cytokines producing T cells was found in African adults when compared with their European counterparts. The quantitative and qualitative regional differences in immune reactivity are likely to be of significance for all immune intervention strategies, especially for the design of vaccines.

Adult↗
PubMed2000

Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin): mechanism of the cyanophycin synthetase reaction studied with synthetic primers.

Biosynthesis of the cyanobacterial nitrogen reserve cyanophycin (multi-L-arginyl-poly-L-aspartic acid) is catalysed by cyanophycin synthetase, an enzyme that consists of a single kind of polypeptide. Efficient synthesis of the polymer requires ATP, the constituent amino acids aspartic acid and arginine, and a primer like cyanophycin. Using synthetic peptide primers, the course of the biosynthetic reaction was studied. The following results were obtained: (a) sequence analysis suggests that cyanophycin synthetase has two ATP-binding sites and hence probably two active sites; (b) the enzyme catalyses the formation of cyanophycin-like polymers of 25-30 kDa apparent molecular mass in vitro; (c) primers are elongated at their C-terminus; (d) the constituent amino acids are incorporated stepwise, in the order aspartic acid followed by arginine, into the growing polymer. A mechanism for the cyanophycin synthetase reaction is proposed; (e) the specificity of the enzyme for its amino-acid substrates was also studied. Glutamic acid cannot replace aspartic acid as the acidic amino acid, whereas lysine can replace arginine but is incorporated into cyanophycin at a much lower rate.

Adenosine Triphosphate↗
PubMed1999

A novel high-purity isolation method for human peripheral blood neutrophils permitting polymerase chain reaction-based mRNA studies.

In the past few years, the role of polymorphonuclear neutrophils (PMN) in specific immune responses has gained significance due to their ability to express a variety of immunoregulatory molecules. However, controversial results concerning the potential of neutrophils for cytokine production have been obtained by sensitive molecular biological techniques. This problem might be related to contaminating leukocytes in conventionally isolated neutrophil suspensions as outlined by our study. We have established a novel method yielding highly purified neutrophils by combining a discontinuous Percoll gradient with fluorescence activated cell sorting of CD16bright cells. The latter step exploits the exceptionally high expression of Fc gammaRIIIB on PMN. Neutrophils could be enriched to homogeneity (> 99.9%) with a viability exceeding 90%. Contamination with NK cells or other lymphocytes, monocytes and eosinophils could be excluded as evaluated by reverse transcription-polymerase chain reaction (RT-PCR) with primers for HLA-DR, c-fms and CD52. The transcriptional potential of such purified neutrophils was confirmed by their ability to express MHC class II molecules after stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF). Our method should permit studies of PMN at the mRNA level and future investigations concerning the specificity of immunoregulatory molecule synthesis by neutrophils.

Cell Separation↗
PubMed1999

Carcinoma of the external auditory canal and middle ear.

PURPOSE: To evaluate therapeutic modalities used at our institutions regarding local control, disease-free survival and actuarial survival in carcinoma of the external auditory canal and middle ear, in an attempt to provide guidelines for therapy. METHODS AND MATERIALS: A series of 27 patients with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions were analyzed with particular reference to tumor size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques employed. Clinical endpoints were freedom from local failure, overall survival, and disease-free survival. The median follow-up was 2.7 years (range 0.1-17.9 years). RESULTS: Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 61%. According to the Pittsburgh classification, the actuarial 5-year survival rate for early disease (T1 and T2 tumors) was 86%, for T3 tumors 50%, and T4 stages 41%. Patients with tumors limited to the external auditory canal had a 5-year survival rate of 100%, patients with tumor invasion of the temporal bone 63%, and patients with tumor infiltration beyond the temporal bone 38%. The rate of freedom from local recurrence was 50% at 5 years. Unresectability by dural and cerebral infiltration, and treatment factors such as complete resection or resection with tumor beyond surgical margins are of prognostic relevance. All patients with dural invasion died within 2.2 years. The actuarial 5-year survival rate of patients with complete tumor resection was 100%, but 66% in patients with tumor beyond surgical margins. 192Iridium high-dose-rate (HDR) afterloading brachytherapy based on three-dimensional computed tomography (3D CT)-treatment planning was an effective tool in management of local recurrences following surgery and a full course of external beam radiotherapy. CONCLUSION: Surgical resection followed by radiotherapy adapted to stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

Adult↗