Biomedical subjects

S Hartmann

Publications and source records attributed to S Hartmann.

At least 19 recordsLinked to original sources

PubMed2003

The hypothermic effect of 5-CT in mice is mediated through the 5-HT7 receptor.

The 5-HT(7) receptor is a recent addition to the 5-HT receptor family and to date there is no clear idea as to its potential role in the CNS. The receptor has been mapped by in situ hybridization and 5-HT(7)-like immunoreactivity and has been detected in discrete areas of the brain including the hypothalamus (Oliver et al., 1999). This suggests the receptor may be involved in temperature regulation and have shown that a selective 5-HT(7) receptor antagonist reverses the hypothermic effect of 5-CT in guinea-pigs. The current study confirmed that the 5-HT(7) receptor antagonists, SB-269970 (1-30 mg/kg, i.p.) and SB-258719 (5-20 mg/kg, i.p.), but not the 5-HT(1A) receptor antagonist, WAY 100635(0.1-1 mg/kg, s.c.), or the 5-HT(1B/D) antagonist, GR127935 (1.25-5 mg/kg, i.p.), reversed the hypothermic effect of 5-CT in mice. In addition the effect of 5-CT on body temperature was examined on 5-HT(7) receptor null mutant mice. 5-CT (0.1-1 mg/kg, i.p.) significantly reduced rectal temperature in wildtype but not 5-HT(7) receptor knockout mice. This suggests that the hypothermic effects of 5-CT are mediated through the 5-HT(7) receptor. All procedures were carried out in accordance with the UK Animals (Scientific Procedures) Act (1986).

Animals↗

PubMed2003

[Two rare complications in patients with bone-anchored hearing aids].

In our program of bone-anchored hearing aids we experienced two rare complications: a child with a hearing aid fell on her head and got an intrusion of the bone-screw into the intracranial space with a fracture of tabula externa and interna. There were no further intracranial complications, no hematoma or infection. The screw was explanted immediately with oto-microsurgical instruments and diamond burrs. The site of the screw was covered with a local skin flap. There were no complications in wound healing and the child got a second implant on the other side. A patient got an infection of his bone fixation screw and we took out the external fixation but left in place the bone screw, which was obviously still well fixed and the adjacent bone was without signs of infection. There was good secondary wound healing with local and systemic antibiotics. With almost completely healed external wound the patient got an intracranial abscess, that needed neurosurgical drainage. After long-time antibiotic treatment the patient is well again.

Abscess↗

PubMed2002

Immunomodulatory properties of cystatins.

Cystatins are natural tight-binding reversible inhibitors of cysteine proteases. Because these cysteine proteases exist in all living organisms and because they are involved in various biological and pathological processes, the control of these protease functions by cystatins is of cardinal importance. Cystatins are found in mammals but cystatin-like molecules are also present in mammals and parasites. In the immune system, cystatins modulate cathepsin activities and antigen presentation. They also induce tumor necrosis factor alpha and interleukin 10 synthesis, and they stimulate nitric oxide production by interferon gamma-activated murine macrophages. In turn, nitric oxide has inhibitory activity on cysteine proteases, especially those from parasitic protozoa. Cystatins isolated from parasitic nematodes also have immunomodulatory activities that are distinguishable from those induced by lipopolysacharide-like molecules from endosymbiotic bacteria. On the whole, cystatins and cystatin-like molecules belong to a new category of immunomodulatory molecules. Doubtless increasing data will improve our knowledge of this property, leading to practical applications in immunotherapy.

Amino Acid Sequence↗

PubMed2002

Protective immunity induced by irradiated third-stage larvae of the filaria Acanthocheilonema viteae is directed against challenge third-stage larvae before molting.

Jirds (Meriones unguiculatus) were vaccinated with irradiated L3 third-stage larvae (L3) of Acanthocheilonema viteae, and the time required for killing of the challenge L3 was determined. The number of parasites recovered from vaccinated jirds was reduced to about 10% of the control values on the second day after challenge infection and later on. Histological studies revealed an eosinophil-rich infiltrate containing macrophages, neutrophils, and mast cells in the vicinity of the L3 on day 2 after challenge and destruction of the worms by day 4 after challenge. Ultrastructural studies confirmed these data and showed that eosinophils, macrophages, and mast cells were close to the L3 on day 2 after challenge. Flattening of the eosinophils onto the surface of the worms, degranulation of electron-dense material, and rupture of the L3 surface was observed on day 4 after challenge, followed by invasion of the inner of the worms by phagocytic cells. These data show that immune attack against the challenge L3 in vaccinated jirds is initiated between the first and the second day after challenge and that killing occurs around the fourth day after challenge, before the worms undergo their first molt.

Animals↗

PubMed2001

Modulation of human T cell responses and macrophage functions by onchocystatin, a secreted protein of the filarial nematode Onchocerca volvulus.

Immune responses of individuals infected with filarial nematodes are characterized by a marked cellular hyporesponsiveness and a shift of the cytokine balance toward a Th2/Th3 response. This modulation of cellular immune responses is considered as an important mechanism to avoid inflammatory immune responses that could eliminate the parasites. We investigated the immunomodulatory potential of a secreted cysteine protease inhibitor (onchocystatin) of the human pathogenic filaria Onchocerca volvulus. Recombinant onchocystatin (rOv17), a biologically active cysteine protease inhibitor that inhibited among others the human cysteine proteases cathepsins L and S, suppressed the polyclonally stimulated and the Ag-driven proliferation of human PBMC. Stimulated as well as unstimulated PBMC in the presence of rOv17 produced significantly more IL-10, which was paralleled in some situations by a decrease of IL-12p40 and preceded by an increase of TNF-alpha. At the same time, rOv17 reduced the expression of HLA-DR proteins and of the costimulatory molecule CD86 on human monocytes. Neutralization of IL-10 by specific Abs restored the expression of HLA-DR and CD86, whereas the proliferative block remained unaffected. Depletion of monocytes from the PBMC reversed the rOv17-induced cellular hyporeactivity, indicating monocytes to be the target cells of immunomodulation. Therefore, onchocystatin has the potential to contribute to a state of cellular hyporesponsiveness and is a possible pathogenicity factor essential for the persistence of O. volvulus within its human host.

Animals↗

PubMed2001

Determination of retinol and retinyl esters in human plasma by high-performance liquid chromatography with automated column switching and ultraviolet detection.

A HPLC method with automated column switching and UV detection is described for the simultaneous determination of retinol and major retinyl esters (retinyl palmitate, retinyl stearate, retinyl oleate and retinyl linoleate) in human plasma. Plasma (0.2 ml) was deproteinized by adding ethanol (1.5 ml) containing the internal standard retinyl propionate. Following centrifugation the supernatant was directly injected onto the pre-column packed with LiChrospher 100 RP-18 using 1.2% ammonium acetate-acetic acid-ethanol (80:1:20, v/v) as mobile phase. The elution strength of the ethanol containing sample solution was reduced by on-line supply of 1% ammonium acetate-acetic acid-ethanol (100:2:4, v/v). The retained retinol and retinyl esters were then transferred to the analytical column (Superspher 100 RP-18, endcapped) in the backflush mode and chromatographed under isocratic conditions using acetonitrile-methanol-ethanol-2-propanol (1:1:1:1, v/v) as mobile phase. Compounds of interest were detected at 325 nm. The method was linear in the range 2.5-2000 ng/ml with a limit of quantification for retinol and retinyl esters of 2.5 ng/ml. Mean recoveries from plasma were 93.4-96.5% for retinol (range 100-1000 ng/ml) and 92.7-96.0% for retinyl palmitate (range 5-1000 ng/ml). Inter-assay precision was < or =5.1% and < or =6.3% for retinol and retinyl palmitate, respectively. The method was successfully applied to more than 2000 human plasma samples from clinical studies. Endogenous levels of retinol and retinyl esters determined in female volunteers were in good accordance with published data.

Automation↗

PubMed2001

Extensive ribosomal DNA genic variation in the columnar cactus Lophocereus.

Sequence analysis of the hypervariable internal transcribed spacer (ITS) regions of ribosomal DNA (rDNA) is commonly used to gain insights into plant and animal population structure and phylogeny. We characterized ITS1, ITS2, and the 5.8S coding region of 18 senita (Lophocereus) individuals from 12 different populations in Baja as well as from closely related cactus species. Analyses of multiple clones demonstrated extensive paralogy in the senita rDNA gene family. We identified at least two putatively non-recombining rDNA operons in senita as well as multiple paralogous sequences within each operon. Usage of PCR, reverse transcriptase (RT)-PCR, Southern blot, primary sequence analyses of the 18S rDNA gene, and secondary structure analyses of the 5.8S rRNA showed that one of the operons encodes rDNA pseudogenes in a low copy-number (Truncated), whereas the second operon encodes an expressed rRNA (Functional). Surprisingly, we found extensive paralogy not only in the ITS regions but also in the 5.8S coding regions in senita both within and between operons. Phylogenetic analyses suggest that the second rDNA operon originated prior to the divergence of Lophocereus. A significant (p < 0.05) divergence-rate acceleration was found in the Lophocereus 5.8S rDNA coding region in the Functional operon in comparison to Pereskiopsis porteri (Cactaceae) and Portulaca molokiniensis (Portulacaceae) with Silene dioica and Spinacia oleracea as the outgroups.

Base Sequence↗

PubMed2000

Properdin, the positive regulator of complement, is highly C-mannosylated.

Properdin is the positive regulator of the alternative pathway of complement activation. The 53-kDa protein is essentially composed of six thrombospondin type 1 repeats, all of which contain the WXXW motif, the recognition sequence for C-mannosylation. C-Mannosylation is a post-translational modification of tryptophan residues in which, in contrast to the well known N- and O-glycosylation, the carbohydrate is attached via a C-C bond to C-2 of the indole moiety of tryptophan. C-Mannosylation was first found in human RNase 2 and interleukin-12. The terminal complement proteins C6-C9 also carry this modification as part of their thrombospondin type 1 repeats. We studied the C-mannosylation pattern of human properdin by mass spectrometry and Edman degradation. Properdin contains 20 tryptophans of which 17 are part of a WXXW motif. Fourteen tryptophans were found to be modified 100%. This is the first example of a protein in which the majority of tryptophan residues occurs in the C-mannosylated form. These results show that C-mannosylated proteins occur at several steps along the complement activation cascade. Therefore, this system would be ideal to investigate the function of C-mannosylation.

Amino Acid Sequence↗

PubMed2000

EPC syntheses and structure-activity relationships of hypoglycaemic semicyclic amidines.

A series of homochiral sterically hindered mono- and bicyclic amidines was prepared as hypoglycaemic agents by lethargic reaction of O-methylcaprolactim and 3-ethoxy-2-azabicyclo[2.2.2]oct-2-ene, respectively, with homochiral cis-2-substituted cyclopentane amines provided by asymmetrical reductive amination of racemic 2-substituted cyclopentanones. All compounds, except the cyclohexylmethyl-isoquinuclidone derivative which inhibited secretion at 100 microM, significantly stimulated insulin secretion 2-8-fold at 10 microM and 100 microM in INS-1 cells. The most potent activator was the 2-cyclopentyl-substituted caprolactam derivative 5e. The stimulatory effects on secretion increased with rising steric hindrance of both the amidine alpha-carbon and the bicyclic amidine moiety itself. Enantiomeric discrimination was observed for the 2-¿(cis-2-bulkysubstituted cyclopentyl)iminohexahydroazepine halides 5e and 5f and for the 3-¿(cis-2-substituted cyclopentyl)imino-2-azabicyclo¿2.2.2ŏctane halides 6a and 6c. The amidines depolarized INS-1 cells and generated action potentials, accompanied by a decrease of membrane conductance. Simultaneously [Ca(2+)](i) increased, probably due to Ca(2+)-entry through voltage-dependent Ca(2+)-channels. At high concentrations, where inhibition of secretion was observed, ¿Ca(2+)(i) still rose upon application of the amidines, indicating an additional inhibitory pathway downstream to the elevation of ¿Ca(2+)(i). Even at high concentrations (100 microM), the amidines had no toxic effects on insulin secreting INS-1 cells.

Amidines↗

PubMed2000

Randomized, double-blind, placebo-controlled trial of interferon alfa2a with and without amantadine as initial treatment for chronic hepatitis C.

Although the antiviral effects of amantadine sulphate (1-aminoadamantan sulphate) have not been characterized for the hepatitis C virus (HCV), previous pilot studies have suggested promising results in patients with chronic hepatitis C. The aim of the present study was to compare the efficacy, safety, and health-related quality of life (HRQOL) of interferon alfa (IFN-alpha) alone or in combination with oral amantadine for treatment of chronic hepatitis C. One hundred nineteen previously untreated patients with chronic hepatitis C were randomly allocated to treatment with IFN-alpha2a at a dose of 6 megaunits 3 times a week subcutaneously for 24 weeks, followed by 3 megaunits thrice weekly for an additional 24 weeks plus amantadine sulphate administered orally 100 mg twice a day for 48 weeks or the same IFN regimen plus a matched placebo. The primary endpoint was undectable serum HCV RNA (<1,000 copies/mL) at week 24 after treatment. At the end of treatment and the 24-week follow-up period serum HCV RNA was undetectable in 20 (34%) and 6 (10%) of the 59 patients treated with the combination IFN-alpha plus amantadine and in 20 (33%) and 13 (22%) of the 60 patients treated with IFN-alpha alone, respectively (P = n.s.). Discontinuation of therapy for adverse events was similar in both treatment groups. Although treatment with IFN-alpha worsened HRQOL, combination with amantadine showed a substantial trend to improve fatigue and vigor. In conclusion, combination therapy IFN-alpha plus amantadine is as effective as IFN-alpha monotherapy in previously untreated patients with chronic hepatitis C.

Adolescent↗

PubMed2000

Efficacy of botulinum toxin A for treatment of upper esophageal sphincter dysfunction.

OBJECTIVES: To investigate the efficacy of botulinum toxin A (BTA)-induced chemodenervation of the upper esophageal sphincter (UES) in patients with dysphagia and UES dysfunction. STUDY DESIGN: Prospective clinical trial in 10 selected patients with pure UES dysfunction. METHODS: In each patient 30 units of BTA were injected into the UES under brief general anesthesia. Videofluoroscopic swallowing study (VSS) was done and a clinical symptom score was determined before and after treatment. RESULTS: On VSS relative opening of the UES improved in all patients (mean +/- SD: 47 +/- 14% before versus 71 +/- 24% after treatment; P < .01). Hypopharyngeal retention or laryngeal penetration of barium was significantly reduced in four of seven patients. Clinical symptom scores improved in all patients. One patient was free of symptoms, mild dysphagia persisted in six patients, and moderate dysphagia persisted in three patients. CONCLUSIONS: Our results support the use of BTA in selected patients with pure UES dysfunction. Its efficacy is limited by the possibility of a persistent structural stenosis of the UES and the risk of BTA diffusion into the larynx or hypopharynx.

Adult↗

PubMed1999

Hearing screening in healthy newborns: feasibility of different methods with regard to test time.

Clicked-evoked otoacoustic emissions and automated auditory brainstem response are both considered appropriate hearing screening tools. The aim of this study was to compare their practicability with respect to test duration. In the first part of the study, clicked-evoked otoacoustic emissions were recorded in 388 healthy infants on the newborn ward in the first days of life. To reduce false positive rates of screening, clicked-evoked otoacoustic emissions combined with automated auditory brainstem response measurement (A-ABR, Algo 1E and Algo 2) were used in a second investigation. Fifty-five newborns screened by this two-stage method recorded an increased pass rate. The new digital technique of automated auditory brainstem response measurement (Algo 1E and Algo 2) employed in the second part of the study has a test time even shorter than that of clicked-evoked otoacoustic emissions and is no longer a time-consuming test due to improved technology of the second generation of automated auditory brainstem response equipment. Screening including preparation and follow-up time took 9.43 min (Algo 1E) and 8.26 min (Algo 2) respectively and was thus less time-consuming than reported in former studies.

Audiometry, Evoked Response↗

PubMed1999

NIH shift in flavin-dependent monooxygenation: mechanistic studies with 2-aminobenzoyl-CoA monooxygenase/reductase.

The flavoprotein 2-aminobenzoyl-CoA monooxygenase/reductase from the eubacterium Azoarcus evansii catalyzes the dearomatization of 2-aminobenzoyl-CoA. The reaction consists in an O2-dependent monooxygenation at the benzene position 5, which is followed immediately by an NADH-dependent hydrogenation of the intermediate at the same catalytic locus. The reaction was studied by 1H, 2H, and 13C NMR spectroscopy of the products. The main product was characterized as 5-oxo-2-aminocyclohex-1-ene-1-carboxyl-CoA by two-dimensional NMR spectroscopy. Thus, [5-2H]2-aminobenzoyl-CoA was converted into [6-2H]5-oxo-2-aminocyclohex-1-ene-1-carboxyl-CoA, indicating a 5 --> 6 shift of the [5-2H] label. Label from NAD2H was transferred to the 3 position of the cyclic eneamine, whereas label from solvent D2O was incorporated into the 4 and the 6 positions of 5-oxo-2-aminocyclohex-1-ene-1-carboxyl-CoA. The labeling pattern is compatible with the monooxygenation proceeding via what is formally an NIH shift, yielding 5-oxo-2-aminocyclohex-1, 3-diene-1-carboxyl-CoA as a protein-bound intermediate. It is suggested that this shift in flavin-dependent monooxygenation may have general validity.

Acyl Coenzyme A↗

PubMed1999

Physical exercise during pregnancy--physiological considerations and recommendations.

Controversial findings in numerous studies involving physiological and endocrinological parameters indicate that physical exercise during pregnancy is complex and somewhat poorly understood. But despite this reservation, it is safe to say that on the basis of the current state of scientific research in this area, physical exercise is to be recommended during pregnancy so long as women are aware of potential dangers and contraindications. Due to thermoregulatory advantages, the beneficials effects of immersion and its joint protective character "aquatic exercise" can be highly recommended during pregnancy. Psychologically speaking, physical exercise offers a variety of benefits such as the encouragement of cooperation and competition which can be experienced as fun and gratifying. The physiological and psychological benefits of physical exercise are not only available to healthy women, but have also proven to be valuable for the prevention and treatment of illnesses such as gestational diabetes. The activation of large groups of muscles allow for an improved glucose utilization by simultaneously increasing insulin sensitivity.

Body Temperature Regulation↗

PubMed1999

Neonatal screening for hearing disorders in infants at risk: incidence, risk factors, and follow-up.

OBJECTIVE: To determine the incidence and risk factors for hearing disorders in a selected group of neonates and the feasibility of selective hearing screening. SETTINGS: Multicenter prospective trial at five centers in Germany. METHODS: Enrollment criteria: in addition to previously defined risk factors by the Joint Committee on Infant Hearing (family history of hearing loss, in utero infections, craniofacial anomalies, birth weight <1500 g, critical hyperbilirubinemia, ototoxic medications, bacterial meningitis, postnatal asphyxia, mechanical ventilation >5 days, stigmata, or syndromes associated with hearing loss), the impact of maternal drug abuse, birth weight <10th percentile, persistent pulmonary hypertension, and intracranial hemorrhage more than or equal to grade III or periventricular leukomalacia on infant hearing were evaluated. The screening procedure was performed by automated auditory brainstem response (A-ABR; ALGO 1-plus; Natus Med Inc, San Carlos, CA). STATISTICS: univariate analyses of risk factors versus A-ABR results and a multivariate regression analysis were used; additionally, the total test time was recorded. RESULTS: Seven hundred seventy recordings from 777 infants enrolled consecutively constitute the basis of this analysis. Mean gestational age was 33.8 +/- 4.3 weeks, birth weight 2141 +/- 968 g; 431 infants being male and 339 female; 41 (5.3%) infants exhibited pathologic A-ABR results (16 bilateral and 25 unilateral). Meningitis or sepsis, craniofacial malformations, and familial hearing loss were independent significant risk factors. Median total test time was 25 minutes. Follow-up examinations in 31 infants revealed persistent hearing loss in 18 infants (13 infants sensorineural, 5 from mixed disorders), 7 requiring amplification. CONCLUSION: Hearing screening in high-risk neonates revealed a total of 5% of infants with pathologic A-ABR (bilateral 2%). Significant risk factors were familial hearing loss, bacterial infections, and craniofacial abnormalities. Other perinatal complications did not significantly influence screening results indicating improved perinatal handling in a neonatal population at risk for hearing disorders.

Analysis of Variance↗

PubMed1999

[Melancholia and neurotic depression].

The author considers the psychopathological distinction between endogenous and neurotic depression as one of differing psychodynamics. In so doing he embeds both illnesses within psychoanalytic theory while at the same time allowing a sharp differentiation. Even the premorbid personalities of patients with endogenous and neurotic depression are different. The personalities of those with endogenous depression bear a similarity to those with obsessional character and betray a pathological super-ego monopolized by defence mechanisms. The personalities of patients with neurotic depression show an oral-dependent structure characterised by a structural deficit of the ego functions and of an autonomous super-ego. These factors are responsible for the greatly differing pathodynamics found in these illnesses and point to different etiological factors in socialization.

Depressive Disorder↗

PubMed1998

Modulation of NMDA receptors by glycine--introduction to some basic aspects and recent developments.

Glycine is a co-agonist at NMDA receptors and it's presence is a prerequisite for channel activation by glutamate or NMDA. Physiological concentrations reduce one form of NMDA receptor-desensitization. Interactions between the glycineB site and other domains of the NMDA receptor are complex and include the glutamate, Mg2+ and polyamines sites. Glycine shows different affinities at various NMDA receptor subtypes probably via to allosteric interactions between NMDA2 subunits and the glycine recognition site on the NMDAR1 subunit. There is still some debate whether the glycineB site is saturated in vivo but it seems likely that this depends on regional differences in receptor subtype expression, local glycine or D-serine concentrations and the expression of specific glycine transporters. GlycineB antagonists and partial agonists have been reported to have good therapeutic indices as neuroprotective agents against focal ischaemia and trauma, anti-epileptics, anxiolytics, anti-psychotomimetics and in models of chronic pain. They clearly lack two potentially serious side effects classically associated with NMDA receptor blockade, namely neurodegenerative changes in the cingulate/retrosplenial cortex and psychotomimetic-like effects. This improved therapeutic profile may be partially due to the ability of full glycineB antagonists to reveal glycine-sensitive desensitization and possibly also via functional and/or regional NMDA receptor subtype selectivity.

Animals↗

PubMed1998

Budipine is a low affinity, N-methyl-D-aspartate receptor antagonist: patch clamp studies in cultured striatal, hippocampal, cortical and superior colliculus neurones.

The NMDA receptor antagonistic effects of budipine were assessed using concentration- and patch-clamp techniques on cultured striatal, hippocampal, cortical and superior colliculus neurones. Inward current responses of striatal neurones to NMDA (200 microM) at -70 mV were antagonized by budipine in a concentration-dependent manner (50% inhibitory concentration (IC50) 59.4 +/- 10.7 microM, n = 17) with 24 times lower potency than memantine but similar potency to amantadine. In striatal neurones, budipine blocked outward currents at +70 mV with an IC50 of 827 microM, suggesting that the binding site is less deep in the channel (delta = 0.45) than for memantine. However, more detailed analysis of the fractional block by budipine 300 microM in hippocampal neurones gave a delta-value of 0.90, but revealed that 28% block is mediated at a voltage-independent site. This voltage-insensitive site was accessible in the absence of agonist. Budipine exhibited concentration-dependent open channel blocking kinetics (kappa(on) = 0.71 x 10(4) M(-1) s(-1)) whereas the fast offset rate was concentration-independent (kappa(off) = 0.63 s(-1)). Calculation of the ratio kappa(off)/kappa(on) revealed an apparent Kd value of 88.7 microM. Budipine, memantine and amantadine had similar effects against NMDA-induced currents in cultured hippocampal, cortical and superior colliculus neurones, although amantadine was somewhat more potent in cultured striatal neurones. The relevance of NMDA receptor antagonism to the anti-Parkinsonian effects of budipine remains to be established.

Amantadine↗