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Biomedical subjects

R Hartmann

Publications and source records attributed to R Hartmann.

At least 19 recordsLinked to original sources
PubMed2006

Results of a randomised controlled cross-over trial on the effect of continuous subcutaneous glucose monitoring (CGMS) on glycaemic control in children and adolescents with type 1 diabetes.

OBJECTIVE: To study the feasibility and the influence on glycaemic control of continuous glucose monitoring (CGMS) in young patients with type 1 diabetes. DESIGN AND METHODS: A double-blinded, cross-over study was performed in 30 children (median age 11.1 years [range: 2.3 - 16.3], diabetes duration 2.1 years [0.2 - 7.1]). Patients were randomised into an open (A) or blind study arm (B). Both groups performed standardised self-monitoring blood glucose (SMBG) and received CGMS at the beginning of the study, at 3 and 6 months, each. In the blinded arm, patients and investigator were concealed from CGMS data. After 3 months, open and blinded study arms crossed over. Average glucose values and area under the glucose curve (AUC) per 24 h, above 180 and below 60 mg/dl were calculated from CGMS. Haemoglobin A1c (HbA1c) was measured at each study point. RESULTS: Despite comparable clinical characteristics between the 15 patients of each arm, mean HbA1c was slightly lower in arm A than in B at baseline (7.8 +/- 1.2 % vs. 8.4 +/- 1.1 %, p = 0.148), at 3 months (7.8 +/- 1.1 % vs. 8.3 +/- 1.1 %, p = 0.233), and significantly lower at 6 months (7.6 +/- 1.1 % vs. 8.5 +/- 0.9 %, p = 0.026). However, no significant change of HbA1c occurred within each arm (A, p = 0.183 and B, p = 0.823), irrespectively whether CGMS data were blinded or not. Likewise, mean glucose and hyper- or hypoglycaemia values did not change significantly. CONCLUSIONS: In this setting, CGMS did not decisively influence glycaemic control of a total study cohort. More frequent use of CGMS at shorter intervals in single patients with hyper- or hypoglycaemic problems may be of greater value than SMBG.

Adolescent↗
PubMed2005

Natural course of autoimmune thyroiditis in type 1 diabetes: association with gender, age, diabetes duration, and puberty.

AIMS: To investigate the natural history and incidence of autoimmune thyroiditis (AIT) in paediatric patients with type 1 diabetes (T1D). METHODS: Since 1990, annual screening for thyroid disease has been performed in children and adolescents with T1D. Antibodies against thyroperoxidase (anti-TPO) and thyroglobulin (anti-TG) as well as TSH were measured in 659 patients (54.3% boys). In 126 patients, anti-TPO and anti-TG levels were followed at yearly intervals from onset up to five years of T1D. Anti-TPO above 30 U/ml and anti-TG above 20 U/ml were considered positive, values above 100 U/ml as significantly raised and indicative of AIT. L-thyroxine treatment was started if TSH was higher than 4.5 microU/ml and/or thyroid gland enlargement on thyroid ultrasound was present. RESULTS: At initial screening, 15.4% of patients had raised anti-TPO and 14.4% anti-TG. Girls had more frequently raised antibodies than boys. Sixty two patients (9.4%, 61% girls) required treatment with L-thyroxine. The cumulative incidence (SE) of AIT after 10 years of diabetes was 0.14 (0.02), being significantly higher in females (0.18 (0.03)), particularly after the age of 12 years. At T1D onset, positive anti-TPO and anti-TG were present in 21 of 126 patients (16.7%), each. All patients with significantly increased values of anti-TPO (n = 17, 148-5340 U/ml) and anti-TG (n = 11, 140-2000 U/ml) at T1D onset remained positive during the following five years. CONCLUSIONS: For early detection of autoimmune thyroiditis in children with T1D, measurement of anti-TPO and TSH at T1D onset and in yearly intervals after the age of 12 years is recommended.

Adolescent↗
PubMed2004

Postnatal cortical development in congenital auditory deprivation.

The study investigates early postnatal development of local field potentials (LFPs) in the primary auditory cortex of hearing and congenitally deaf cats. In hearing cats, LFPs elicited by electrical intracochlear stimulation demonstrated developmental changes in mid-latency range, including reductions in peak and onset latencies of individual waves and a maturation of their shape and latencies during the first 2 months of life. In long latency range (>80 ms), the P(1)/N(1) response appeared after the fourth week of life and further increased in amplitude and decreased in latency, reaching mature shapes between the fourth and sixth months after birth (p.n.). Cortical activated areas became increasingly smaller during the first 3 months of life, reaching mature values at the fourth month p.n. The layer-specific pattern of synaptic activity matured 4 months p.n. In congenitally deaf cats, the developmental pattern was different. The lowest cortical LFP thresholds were significantly smaller than in hearing controls, demonstrating a "hypersensitivity" to sensory inputs. The development of N(b) waves was delayed and altered and the long latency responses became smaller than in controls at the second and third months. The activated areas remained smaller than in controls until the third month, then they increased rapidly and exceeded the activated areas of age-matched controls. From the fourth month on, the activated areas decreased again and smaller synaptic currents were found in deaf cats than in controls. The presented data demonstrate that functional development of the auditory cortex critically depends on auditory experience.

Acoustic Stimulation↗
PubMed2004

Caseinophosphopeptides and their cell modulating potential.

In the context of the EU research project FAIR-CT 98-3077, studies were carried out to investigate caseinophosphopeptides (CPP) as potential ingredients for functional food and pharmaceutical applications. CPP preparations were produced by enrichment of CPP from hydrolytic casein digests. Enzyme preparations used for hydrolysis were PTN 3.0 S, Alcalase, Bioprotease P conc, Proteinase DS. Cytochemical studies were carried out to examine the cytotoxic potential or cell modulating activities of CPP using human cancer cell lines (HL-60, Caco-2) and non-malignant polymorphonuclear leukocytes (PML) from oral cavity. PML cells isolated by magnetic cell sorting using CD-15-antibody-labelled paramagnetic beads were used for the first time for testing food-derived peptides. Cell activity was measured by formazan dye formation. Effects on enterocytic differentiation properties of Caco-2 cells were examined by transepithelial membrane resistance of Caco-2 cell monolayers and brush border associated alkaline phosphatase activity. In conclusion, (1) no deleterious cytochemical consequences (apoptotic, antiproliferative or general cytotoxic effects) were observed on presenting a range of CPP preparations to various human cell systems, indicating that these compounds can be rated harmless at a cellular level, (2) stimulation of IgG-secretion into culture supernatant of PBL points to possible immunoenhancing properties of CPP preparations.

B-Lymphocytes↗
PubMed2003

Effects of the isolation methodology on protein profiles of blood trypomastigotes of Trypanosoma cruzi.

Blood trypomastigotes of Trypanosoma cruzi were isolated from infected athymic rnu/rnu rats and purified by an improved procedure of DEAE-Sephacel ion-exchange chromatography. Elution into a buffer supplemented with bovine serum albumin avoided column-induced changes on the surface of the parasites. Biotin-labelled bovine serum albumin, fluorescence microscopy, flow cytometry and Western blot analysis revealed a very intense binding of albumin to the parasite. Incubation and washing of cells without protein supplementation did not result in any damage or lysis of parasites but it did cause extensive shedding of cellular and surface proteins into the supernatant which could be prevented by using the protein-supplemented buffer. A decreasing yield of high molecular weight cellular proteins in relation to centrifugal force was a general phenomenon observed in scanning densitometry of SDS gels after isolation in either protein-supplemented buffer or protein-free buffer. The quantity of shed cellular components increased with increasing centrifugal force. In contrast, quantities of high molecular weight, biotin-labelled surface proteins increased with greater centrifugal force, indicating labelling of otherwise inaccessible residues. These data emphasize the importance of protein supplementation of buffers with proteins and of choosing low centrifugation forces (<400 g) during investigations of T. cruzi.

Animals↗
PubMed2003

Detection of caseinophosphopeptides in the distal ileostomy fluid of human subjects.

Caseinophosphopeptides (CPP) were detected for the first time in ileostomy fluid, collected at 2 h intervals for 10 h post milk and CPP ingestion, from human volunteers with an ileostomy. The level of CPP present in ileostomy fluid obtained from milk-fed volunteers was markedly higher than that from volunteers fed with selected CPP preparations. The findings are based on HPLC analysis in combination with peptide-bound P determination, thin-layer electrophoresis and amino acid analysis, together with ELISA studies using polyclonal antibodies raised against a set of CPP to detect immunoreactive CPP in ileostomy fluid. These procedures allowed the detection of nm concentrations of CPP. CPP, which can be released during intestinal digestion, may function as bioactive constituents and carriers for different minerals, especially Ca, and may be used as ingredients in functional foods or pharmaceutical preparations.

Adult↗
PubMed2002

Gene structure of the murine 2'-5'-oligoadenylate synthetase family.

The 2'-5'-oligoadenylate synthetases (OASs) are members of a family of interferon-induced proteins playing an important role in the antiviral effect of interferons as well as being involved in apoptosis and control of cellular growth. Based on sequence data from the murine BAC clone (RP23-39M18), and a number of EST and IMAGE clones and the Celera Mouse database, we identified twelve Oas genes in the mouse genome, all localized to the chromosome 5F region. In contrast to the single OAS1 gene found in humans, we identified eight closely linked Oas1 genes in the murine genome, together with the genes of Oas2 and Oas3. Compared to the single OASL gene found in humans, two genes of OAS-like proteins, Oasl1 and Oasl2, were identified. All the putative genes seem to be transcribed. The exon/intron structures of the murine Oas genes were found to be identical to those of the human genes.

2',5'-Oligoadenylate Synthetase↗
PubMed2002

Hearing after congenital deafness: central auditory plasticity and sensory deprivation.

The congenitally deaf cat suffers from a degeneration of the inner ear. The organ of Corti bears no hair cells, yet the auditory afferents are preserved. Since these animals have no auditory experience, they were used as a model for congenital deafness. Kittens were equipped with a cochlear implant at different ages and electro-stimulated over a period of 2.0-5.5 months using a monopolar single-channel compressed analogue stimulation strategy (VIENNA-type signal processor). Following a period of auditory experience, we investigated cortical field potentials in response to electrical biphasic pulses applied by means of the cochlear implant. In comparison to naive unstimulated deaf cats and normal hearing cats, the chronically stimulated animals showed larger cortical regions producing middle-latency responses at or above 300 microV amplitude at the contralateral as well as the ipsilateral auditory cortex. The cortex ipsilateral to the chronically stimulated ear did not show any signs of reduced responsiveness when stimulating the 'untrained' ear through a second cochlear implant inserted in the final experiment. With comparable duration of auditory training, the activated cortical area was substantially smaller if implantation had been performed at an older age of 5-6 months. The data emphasize that young sensory systems in cats have a higher capacity for plasticity than older ones and that there is a sensitive period for the cat's auditory system.

Age Factors↗
PubMed2002

[Results of the treatment of childhood acute lymphoblastic leukemia according to the Berlin-Moscow-91 protocol in 1991-2000].

The report deals with the results of application of an original protocol--the Berlin-Moscow-91 (BM-91)--for the treatment of acute lymphoblastic leukemia (ALL) in children. The researchers' major concern was to improve survival and cut down side-effects incidence as well as to prevent and successfully manage occult neuroleukemia as a potential source of relapse. Patients aged 5 months-15 years received the BM-91 and ALL BFM-90m treatment first at one clinic and later at several centers. Out of 852 children with primary diagnosis of ALL admitted to Russian hematological hospitals (March 2, 1991-November 3, 2000), 687 were included into the study; 329 received the MB-91 protocol. Nine-year recurrence-free survival was 73% while overall survival--80%. Toxic side-effects after L-asparaginase were reported in 27 (7.9%). It is concluded that good results in childhood ALL treatment can be achieved without resorting to high-dosage chemotherapy and radiation in most cases.

Adolescent↗
PubMed2002

[Treatment of acute lymphoblastic leukemia in children according to the ALL-BFM-90m protocol in the Russian Federation and the Republic of Belarus].

Prognosis for children treated according to the BFM-90m protocol (Berlin-Frankfurt-Munster Group) for acute lymphoblastic leukemia (ALL) improved significantly as compared with previous modalities. Methotrexate was used in the dose of 1,000 mg/m2, 36 h. The paper presents the 10-year results for this modification. Patients aged 0-15 years were treated at hematological hospitals of Moscow, other Russian towns and in Minsk, Belarus, (July 5, 1990-November 11, 2000). BFM-90m treatment was given to 682 children out of 1,326 with primary diagnosis of ALL; a comparative trial of the MB-91 protocol hed been carried out at the same clinics since 1991. During 10 years, recurrence-free survival was 72% while overall survival--77%. Toxicity of side-effects was tolerable. The BFM-90m treatment showed significantly better results in both countries.

Adolescent↗
PubMed2001

Inhibition of 2'-5' oligoadenylate synthetase by divalent metal ions.

OAS1 is the small form and OAS2 is the medium form of the human interferon-induced 2'-5' oligoadenylate synthetases. The p42 isoform of OAS1 and the p69 isoform of OAS2 have been expressed in insect cells and purified to give pure, highly active 2'-5' oligoadenylate synthetase. The catalysis of 2'-5' oligoadenylate synthesis is strictly dependent on double-stranded RNA and magnesium ions. We have examined the effect of a series of divalent metal ions: copper, iron and zinc ions strongly inhibited the enzymatic activity, cobalt and nickel ions were partly inhibitory whereas calcium and manganese ions were without effect. However, manganese ions can replace magnesium ions as activator. The inhibitory effect of zinc ions was characterised in detail. The inhibitory constants of Zn(2+) were estimated to be 0.10 mM for OAS1p42 and to 0.02 mM for OAS2p69. Cross-linking experiments showed that zinc ions can control the oligomerisation by enhancing the formation of tetrameric forms of OAS1p42

2',5'-Oligoadenylate Synthetase↗
PubMed2001

Prognostic value of minimal residual disease in relapsed childhood acute lymphoblastic leukaemia.

Molecular monitoring by quantitative PCR techniques of residual leukaemia cells during the first phases of treatment can predict outcome in children with acute lymphoblastic leukaemia. We did a retrospective study of 30 children who had been treated according to the ALL-REZ BFM trials to assess whether amount of minimal residual disease during the first stages of treatment for relapsed acute lymphoblastic leukaemia could predict outcome. In children with minimal residual disease of less than 10(-3) at day 36, probability of event-free survival was 0.86 (95% CI 0.77-0.95), compared with 0 in children with minimal residual disease of 10(-3) or greater (p<0.001). Our results suggest that information about molecular response to treatment can be used to predict long-term outcome in relapsed childhood acute lymphoblastic leukaemia.

Antineoplastic Agents↗
PubMed2001

Composted grape marc as growing medium for hypostases (Hypostases phyllostagya).

The use of composted grape marc (CGM) as a plant growth medium was investigated with Hypostases (Hypostases phyllostagya). Seven media were prepared using CGM mixed, in different ratios, with native peat and perlite. The following mixtures were used: 100% CGM, 75% CGM + 25% peat, 50% CGM + 50% perlite, 25% CGM + 75% peat, 50% CGM + 25%) peat + 25% perlite, 25%, CGM + 50%, peat + 25% perlite and 100% peat. The experiment was arranged in a randomized plot design with four replicates under greenhouse conditions. After a growing period of three months, some horticultural parameters were measured. Besides, some physical and chemical properties of the growing medium were determined. The mixtures of 50% CGM + 50% peat, 25% CGM + 75% peat and 100% peat were found to be most suitable based on the horticultural parameters. This was confirmed through the physical characteristics. Up to 50% composted grape marc can be used in mixtures with peat on account of its low cost and high nutrient content.

Botany↗
PubMed2001

Modular structure of PACT: distinct domains for binding and activating PKR.

PACT is a 35-kDa human protein that can directly bind and activate the latent protein kinase, PKR. Here we report that PKR activation by PACT causes cellular apoptosis in addition to PKR autophosphorylation and translation inhibition. We analyzed the structure-function relationship of PACT by measuring its ability to bind and activate PKR in vitro and in vivo. Our studies revealed that among three domains of PACT, the presence of either domain 1 or domain 2 was sufficient for high-affinity binding of PACT to PKR. On the other hand, domain 3, consisting of 66 residues, was absolutely required for PKR activation in vitro and in vivo. When fused to maltose-binding protein, domain 3 was also sufficient for efficiently activating PKR in vitro. However, it bound poorly to PKR at the physiological salt concentration and consequently could not activate it properly in vivo. As anticipated, activation of PKR by domain 3 in vivo could be restored by attaching it to a heterologous PKR-binding domain. These results demonstrated that the structure of PACT is modular: it is composed of a distinct PKR-activation domain and two mutually redundant PKR-interacting domains.

2',5'-Oligoadenylate Synthetase↗
PubMed2000

Selective degradation of 2'-adenylated diadenosine tri- and tetraphosphates, Ap(3)A and Ap(4)A, by two specific human dinucleoside polyphosphate hydrolases.

It is known that the interferon-inducible 2',5'-oligoadenylate synthetase can catalyze the 2'-adenylation of various diadenosine polyphosphates. However, catabolism of those 2'-adenylated compounds has not been investigated so far. This study shows that the mono- and bis-adenylated (or mono- and bis-deoxyadenylated) diadenosine triphosphates are not substrates of the human Fhit (fragile histidine triad) protein, which acts as a typical dinucleoside triphosphate hydrolase (EC 3.6.1.29). In contrast, the diadenosine tetraphosphate counterparts are substrates for the human (asymmetrical) Ap(4)A hydrolase (EC 3.6.1.17). The relative rates of the hydrolysis of 0.15 mM AppppA, (2'-pdA)AppppA, and (2'-pdA)AppppA(2"'-pdA) catalyzed by the latter enzyme were determined as 100:232:38, respectively. The asymmetrical substrate was hydrolyzed to ATP + (2'-pdA)AMP (80%) and to (2'-pdA)ATP + AMP (20%). The human Fhit protein, for which Ap(4)A is a poor substrate, did not degrade the 2'-adenylated diadenosine tetraphosphates either. The preference of the interferon-inducible 2'-5' oligoadenylate synthetase to use Ap(3)A over Ap(4)A as a primer for 2'-adenylation and the difference in the recognition of the 2'-adenylated diadenosine triphosphates versus the 2'-adenylated diadenosine tetraphosphates by the dinucleoside polyphosphate hydrolases described here provide a mechanism by which the ratio of the 2'-adenylated forms of the signalling molecules, Ap(3)A and Ap(4)A, could be regulated in vivo.

Acid Anhydride Hydrolases↗