Biomedical subjects

K Müller

Publications and source records attributed to K Müller.

At least 19 recordsLinked to original sources

PubMed1992

Development of speed of repetitive movements in children is determined by structural changes in corticospinal efferents.

This study was aimed to determine the relationship between the maturation of corticospinal efferents, determined by transcranial stimulation of motor cortex, and the development of fastest repetitive voluntary motor activity in children. The development of fastest repetitive voluntary motor activity was assessed for 3 different types of movements including fastest repetitive tapping movements, aiming movements and a pegboard transportation task. These 3 motor activities were chosen as they were different as to their dependence on detailed sensory guidance. Despite these differences the speed of all 3 movements showed a very similar developmental profile, which was matched, however, by the developmental slope of the fastest cortico-motoneuronal efferents. Hence the development of central conduction times determines the speed of repetitive movements in children. In contrast, we could not observe significant effects of repetitive training on speed of these movements. We show for the first time that the development of fastest voluntary movements is a structure-bound phenomenon, being independent from learning.

Adolescent↗

PubMed1992

Inhibition of triosephosphate isomerase from Trypanosoma brucei with cyclic hexapeptides.

Two series of oligopeptides have been synthesized. Their effects on the activity of purified triosephosphate isomerase from Trypanosoma brucei and various other organisms have been studied. Using detailed three-dimensional structure information, the first series consisted of both cyclic and linear hydrophilic peptides that were designed to mimic the beta turns of the subunit interface loops of the trypanosome triosephosphate isomerase dimer. None of these exerted any inhibitory effect. The second series consisted of more hydrophobic cyclic peptides, originally designed to inhibit a hepatic transport system. Several of these were very effective in inhibiting the trypanosome triosephosphate isomerase, but not the homologous enzymes from rabbit, dog, yeast or Escherichia coli. The most active peptide, cyclo[-Trp-Phe-D-Pro-Phe-Phe-Lys(Z)-], exerted 50% inhibitory activity at a concentration of 3 microM. The nature of the inhibitory action of one of these compounds cyclo[-Trp-Tyr(OSO3Na)-D-Pro-Phe-Thr(OSO3Na)-Lys(Z)-] was studied in more detail. Its inhibition was noncompetitive and reversible and more than one peptide was able to bind/active site.

Amino Acid Sequence↗

PubMed1992

Lymphokines and soluble interleukin-2 receptors in juvenile chronic arthritis. Clinical and laboratory correlations.

Serum levels of interleukin (IL)-2, interferon gamma (IFNg) and soluble IL-2 receptors (sIL-2R) were determined in sera from 34 patients with poly- or pauciarticular juvenile chronic arthritis (JCA) by use of enzyme-linked immunosorbent assays (ELISAs). Levels of sIL-2R were elevated in the group of patients compared with those of healthy children and correlated significantly with several parameters of clinical activity, including the functional capacity, joint score, visual-analogue score and erythrocyte sedimentation rate (ESR). Serum IL-2 levels were also elevated in the JCA patients, correlating with the patients functional capacity. Serum levels of IFNg were below the detection limit of the assay. Our data supported the notion that T-cell activation plays a role in the immunopathologic processes leading to clinical JCA.

Adolescent↗

PubMed1992

1,25-Dihydroxyvitamin D3-mediated suppression of T lymphocyte functions and failure of T cell-activating cytokines to restore proliferation.

1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to be a potent inhibitor of lymphocyte proliferation in vitro. The present study was undertaken to determine if this is caused by a direct effect on the lymphocytes, and to evaluate to what degree this suppression may be restored by the addition of cytokines. 1,25-(OH)2D3, > or = 10(-10) M, significantly inhibited the proliferation of pokeweed mitogen (PWM)-driven human peripheral blood mononuclear cells (MNC). Depletion of monocytes did not alter the response to 1,25-(OH)2D3. The antiproliferative effect was preceded by decreased production of interleukin (IL)-1 alpha and lymphotoxin (LT), both of which are crucially involved in T cell activation. However, the suppressive effect of 1,25-(OH)2D3, seen in MNC cultures stimulated with PWM alone, was of the same magnitude as the effect seen in MNC cultures stimulated with a combination of PWM and recombinant (r)IL-1 alpha, rIL-6, recombinant tumour necrosis factor (rTNF) alpha, rIL-2 or rLT, as well as PWM plus conditioned medium. Although pretreatment of monocytes for 2 h with 1,25-(OH)2D3 caused significant reduction in the release of IL-1 alpha and TNF alpha, reconstitution of monocyte-depleted cultures with similarly treated monocytes had no inhibitory effect on the proliferative response. In conclusion, even though it cannot be excluded that a low but critical number of monocytes are essential for the suppressive effect of 1,25-(OH)2D3-mediated inhibition of MNC proliferation, the inhibition is most likely the result of a direct effect on the lymphocytes and independent of monocytes and exogenously added cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Genetic relatedness of the nucleoprotein (NP) of recent swine, turkey, and human influenza A virus (H1N1) isolates.

The sequences of nucleoprotein (NP) genes of recent human and turkey isolates of influenza A viruses, which serologically could be correlated to contemporary swine viruses, were determined. These sequences were closely related to the NPs of these swine viruses and they formed a separate branch on the phylogenetic tree. While the early swine virus from 1931 resembled the avian strains in consensus amino acids of the NP and in its ability to rescue NP ts mutants of fowl plague virus in chicken embryo cells, the later strains on that branch were different: at 15 positions they have their own amino acids and they rescued the NP ts mutants only poorly. Of the NPs of the human New Jersey/76 isolates analysed, one clustered with the recent H1N1 swine viruses of the U.S.A., the other one with contemporary human strains. Since the NP is one of the main determinants of species specificity it is concluded that, although the H1N1 swine isolates from the U.S.A. form their own branch in the phylogenetic tree, they can be transmitted to humans and turkeys, but they do not spread further in these populations and so far have not contributed to human pandemics. It is not very likely that they will do so in future, since its branch in the phylogenetic tree develops further away from the human and avian branch.

Animals↗

PubMed1992

Magnetoelectrical stimulation of motor cortex in children with motor disturbances.

Transcranial magnetoelectrical stimulation (TMS) is now widely used as a diagnostic tool in adults. In this study we report our experiences with this technique in children with central motor disturbances. We used a Cadwell MES10 magnetoelectrical stimulator with a maximal magnetic field of 2 tesla. The stimulation procedure followed a standardized protocol, with the patients being as relaxed as possible in order to avoid contamination of parameters with different preinnervational levels. Stimulation data were compared to a data base obtained in 58 normal children. The first group of patients consisted of 20 children aged from 7 months to 16 years with hemiparesis of different etiologies. Neuroimaging data were correlated with the results of magnetoelectrical stimulation. In 13 patients a pathological pattern of TMS could be detected, and in 7 of these a corresponding lesion of the cortico-spinal tract was found in CT or MRI scans. In 7 children TMS was normal, in spite of a clear-cut lesion of the cortico-spinal tract in CT or MRI scans in 4 of them. The second group of patients consisted of 16 children with extrapyramidal disease, mostly of hereditary origin, such as DOPA-responsive dystonia or benign hereditary chorea. TMS showed a normal response pattern in this group. We discuss problems and possible pitfalls in TMS in childhood in evaluating the diagnostic value of TMS. At the moment the diagnostic usefulness of TMS in children with motor disturbances appears limited and calls for careful interpretation.

Adolescent↗

PubMed1992

1,25-Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level.

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibits lymphocyte proliferation and production of antibodies and lymphokines such as interleukin (IL)-2 and interferon gamma. These lymphocyte functions are dependent upon cytokines, including IL-1 alpha, IL-1 beta, IL-6 and tumour necrosis factor alpha (TNF-alpha), produced by the antigen presenting cells. In the present study we examined the effect of 1,25-(OH)2D3 on the production of these cytokines, as well as superoxide generation by freshly isolated mononuclear cells and partially purified monocytes. The immediate precursor of 1,25(OH)2D3, 25-OH D3, and the synthetic analogue MC 903 ('Calcipotriol') were examined in parallel. 1,25-(OH)2D3 dose-dependently inhibited the production of IL-alpha, IL-6 and TNF-alpha by Escherichia coli lipopolysaccharide (LPS)-stimulated monocytes, without affecting superoxide production. MC 903 had comparable effects while 25-OH D3 was ineffective. The inhibition caused by 1,25-(OH)2D3 was not abolished by supraoptimal concentrations of LPS or indomethacin. 1,25-(OH)2D3 had similar effects on secreted and cell-associated IL-alpha. Nuclear run-off analysis indicated that inhibition of these cytokines was not caused by impaired production of mRNA. Taken together, the study demonstrates a vitamin D-induced inhibitory effect of LPS-driven monokine production, which is most likely a vitamin D-receptor mediated phenomenon exerted at a post-transcriptional, presecretory level. Impaired monokine production may be of importance in 1,25-(OH)2D3-mediated inhibition of lymphocyte functions in vitro.

Calcifediol↗

PubMed1992

Isolation of Mycobacterium simiae from the environment.

An examination of 18 sphagnum samples collected in two different biotopes of the coastal region of southeastern Madagascar revealed an unexpectedly high positivity for mycobacteria (83.3%). The concentration of alcohol acid-fast bacilli reached a high level of 10(5) and 10(6)/g, respectively, compared with the sphagnum biotopes in moderate climates. Besides the habitat-specific mycobacterial species in sphagnum vegetation, like M. sphagni, M. gordonae and M. madagascariense, potentially pathogenic species, like M. avium, M. scrofulaceum and M. xenopi and M. marinum, were found. Furthermore, pathogenic M. simiae was found in sphagnum vegetation of Madagascar, first time isolated in the environment until now. It should be considered as a potential source of infection for human and animals.

Animals↗

PubMed1992

[Success of retinal surgery comparing phakic and pseudophakic eyes with reference to preoperative findings and the kind of lens implant].

We analyzed retrospectively 597 eyes over a minimum follow-up of 6 months and compared the results of pseudophakic eyes with phakic eyes. The repair of pseudophakic retinal detachment is more difficult than the surgery in aphakic retinal detachment. Pseudophakic retinal detachment had a more advanced retinal detachment and PVR-stages at the time of diagnosis. Localisation of the tear was more complicated and the surgery was more invasive than in phakic eyes. In 61.2% the repair was for pseudophakic eyes with posterior chamber lens 78%, with anterior chamber lens 81.8% and for iris-fixated IOL's 75%. Compared to this, the anatomic reattachment rate in phakic eyes was 94.8%. The pseudophakic group had less favorable visual results.

Follow-Up Studies↗

PubMed1992

Maturation of set-modulation of lower extremity EMG responses to postural perturbations.

To analyse the influence of different "postural sets" on stance stabilizing EMG responses in children, EMG responses to toe-up tilt perturbations were recorded in 70 children between the age of 9 months and 10 years, as well as in a control group of 10 adults under different postural set conditions, using either bilateral destabilization with eyes opened, eyes closed, or introducing additional minute upper extremity support. Recordings were also made with the children seated in front of the platform with the ankle joint angle being identical to that in the standing condition. Also recordings were made after unilateral destabilization in bilateral lower leg muscles, to determine if there is a generalization of EMG response patterns to the mechanically not disturbed side. Across all age-groups the principal modulation of EMG response changes according to postural conditions was identical. Long latency (LL) EMG responses were down-regulated when additional upper extremity support was provided. LL-responses were abolished in the sitting condition. With unilateral destabilizations throughout all age-groups short latency responses were restricted to the perturbed side, whereas long latency responses could be obtained symmetrically. The proximal to distal gradient of recruitment of muscle groups, remained identical across all age-groups. The data indicate that the basic organizational principle of stance stabilizing EMG responses and their modification by postural sets remains invariant across development. This indicates that the involved organizational principles are present as soon as a child is able to stand upright and are not subject to further shaping by motor learning.

Child↗

PubMed1992

Inhibition of human T lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3. Differential effects on CD45RA+ and CD45R0+ cells.

1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3), the biologically active form of vitamin D3, has been shown to modulate lymphocyte functions in vitro. These effects are exerted through binding to specific receptors that are expressed in activated, but not in resting lymphocytes. 1,25-(OH)2 D3 inhibits lymphocyte proliferation, immunoglobulin production and the release of cytokines including interleukin-2 (IL-2) and interferon gamma (IFN gamma) by mitogen driven blood mononuclear cells (MNC). A distinction between CD45RA+ and CD45R0+ subsets of T cells has, however, proven extremely relevant in terms of immunoactivation and immunopathology. The present study was undertaken to evaluate effects of 1,25-(OH)2 D3 on proliferation and cytokine production by purified CD45RA+ and CD45R0+ T cells. 1,25-(OH)2 D3 caused a dose- and time-dependent reduction in phytohemagglutinin-(PHA) and poke-weed mitogen (PWM)-driven proliferation of purified CD45R0+ T cells. In contrast, proliferation of the CD45RA+ subset was unaffected by this treatment. Comparable levels of lymphotoxin (LT), IFN gamma and IL-2 were obtained in cultures of both subsets. 1,25-(OH)2 D3 reduced these levels, but the suppressive effect of the hormone was delayed in cultures of CD45RA+ T cells. The results suggest that the CD45R0+ subset is relatively more sensitive than CD45RA+ subset to the inhibitory effects of 1,25-(OH)2 D3. This finding may be of pharmacological interest, because the CD45R0+ subset plays a key role in immune activation and because these cells have been associated with the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.

Adult↗

PubMed1992

Accurate diagnosis of acute appendicitis: a retrospective and prospective analysis of 686 patients.

OBJECTIVE: To formulate a score system that would make the preoperative diagnosis of acute appendicitis more accurate. DESIGN: Retrospective then prospective study. SETTING: City University Hospital. SUBJECTS: 536 patients who had their appendixes removed between 1981 and 1986 (retrospective study), and 150 consecutive patients admitted with a presumptive diagnosis of appendicitis between 1987 and 1988 (prospective study). MAIN OUTCOME MEASURES: Correlation between the histological diagnosis of appendicitis and variables representing history, clinical examination, and laboratory investigations. RESULTS: The rate of histologically proven negative appendicectomies in the retrospective series was 40% and in the prospective series 33%. The variables that were thought to be predictive were: male sex, white cell count of greater than 11 x 10(9)/l, history of less than 24 hours with no previous complaints, rebound tenderness, shift of pain from the epigastrium, and localised guarding, but all criteria had low specificities and sensitivities when applied prospectively, and combining the scores did not improve them. CONCLUSION: The accurate diagnosis of appendicitis depends largely on the experience of the surgeon and is not improved by the application of a score system that includes the above variables.

Acute Disease↗

PubMed1992

Adaptational increase of liver glutathione content during long-term application of cyclosporine A may attenuate toxic side effects.

The concentrations of reduced and oxidized glutathione and of adenine nucleotides were determined in liver, kidney and heart of rats during long-term (four weeks), high-dose therapy with cyclosporine A. In liver and kidney the concentration of oxidized glutathione increased following 4 weeks-therapy suggesting increased formation of free radicals and accelerated lipid peroxidation processes. These processes may be due to an increased activity of the cytochrome P-450 system. Compensatory levels of reduced glutathione were also increased. The adaptational increase of the tissue level of reduced glutathione, presumably the response to a chronic oxidative stress, was more distinct in the liver. The liver did not lose adenine nucleotides. In contrast the kidney, after 4 weeks of cyclosporine A therapy, lost 25% of the adenine nucleotides. These findings suggest that the liver is characterized by a greater potential for effective adaptation to oxidative stress conditions compared to the kidney. These adaptations may prevent distortions of energy and nucleotide metabolism in the liver which is in agreement with the minor ultrastructural changes we have observed.

Adaptation, Physiological↗

PubMed1992

[Intraoperative monitoring of early auditory evoked potentials in hearing acoustic neuroma patients complemented by cochlear nerve action potentials].

Hearing preservation was attempted in eight cases of acoustic neurinomas with good preoperative hearing. This was successful in 3 cases. Brain-stem auditory evoked potentials (BAEP0 were monitored in all cases, and compound nerve action potentials (CNAP) were recorded from the cochlear nerve in the last 3 cases. The BAEP was extremely sensitive to intraoperative manipulation. Intraoperative loss of wave V in BAEP was observed not only in all 5 cases with postoperative hearing loss, but also in 2 out of 3 cases with successful hearing preservation. CNAP correlated better with the hearing outcome than BAEP. In the cases where hearing was preserved, intact CNAP responses were demonstrated at the end of the operation. Conversely, deterioration of CNAP was seen in a case of postoperative hearing loss. CNAP was 10-15 times larger in amplitude than BAEP, so that the new responses were obtainable in shorter intervals. This capability of frequent examination seemed to increase the possibility of avoiding irreversible damage to the hearing by changing surgical tactics. The addition of CNAP monitoring is a good supplement to conventional BAEP monitoring in acoustic neurinoma surgery.

Adult↗

PubMed1991

[Basel Project of comprehensive and interdisciplinary rehabilitation of neurological patients. An action concept].

As a consequence of progress in modern medicine an increase in the number of handicapped individuals and the need for rehabilitation are noted in demographic studies during the last years. The offered facilities, however, did not keep pace with the actual demand; therefore, in the canton of Basel-Stadt a multidisciplinary project is actually under development, aiming at an adequate, mostly regionally orientated socio-medical rehabilitation. The article summarizes the well known therapeutic goals of comprehensive neurologic rehabilitation and compares them with the results of a study on the actual situation in the canton. Thus fundamental basic information on future infrastructure needs for neurologic rehabilitation in the canton of Basel-Stadt area are furnished.

Education, Medical, Continuing↗

PubMed1991

[Systemic lupus erythematosus. 1. Disease manifestations, infections, thrombotic episodes, causes of death and survival in a case load of 173 patients followed for 13.9 years].

One hundred and seventy-three patients had systemic lupus erythematosus according to the 1982-ARA-criteria. The mean disease duration at the time of the study was 16.4 years, and the patients were followed by three Copenhagen clinics for a mean of 13.9 years until 1987/88 or death. Half of the patients had nephropathy, 61 patients developed severe infections, and 39 patients had thrombotic episodes. Fifty-six patients died during the observation period, 24 due to active lupus (12 of kidney failure), 12 because of infections, and 11 because of atherosclerotic cardio-vascular disease. The patients had 10-, 15- and 20-year survival rates of 80, 65 and 48 per cent. The deaths were evenly distributed throughout the observation period.

Adult↗

PubMed1991

[Systemic lupus erythematosus. 2. Factors of predictive significance for survival].

Sixty-one of 173 patients with systemic lupus erythematosus followed for a mean of 13.9 years had severe infections which influenced their survival more than could be accounted for by the mortality (20 per cent) caused by the infections. Patients with infections had more SLE manifestations than patients without infections, and they died of lupus manifestations more often than patients without infections. Patients who went into a permanent remission and patients who died of lupus differed most markedly by the rates of infection. The rate of infection was increased more than tenfold in patients treated with high dosages of glucocorticoid compared with patients who received low dosages. Treatment with cytostatics influenced the rate of infections to a moderate degree. Nephropathy also influenced survival but half of the patients with nephropathy maintained a normal plasma creatinine in spite of the long observation period. 16 per cent of the patients with nephropathy died of kidney failure or are receiving chronic hemodialysis.

Adult↗

PubMed1991

The alkaline phosphatase from bone: transphosphorylating activity and kinetic mechanism.

For the purified alkaline phosphatase from bone, the ability to catalyze a phosphate transfer reaction from p-nitrophenyl phosphate to two different hydroxy acceptor compounds, ethanolamine and glycerol, was established by identification of the formed phosphorylated products, phosphoethanolamine and glycerol 3-phosphate, respectively. In addition, a steady-state kinetic analysis of the hydrolysis of p-nitrophenyl phosphate in the presence of an added nucleophile, diethanolamine, gave rise to the proposal of a simple model for the kinetic mechanism of the enzyme. This mechanism includes a covalent phosphoryl enzyme intermediate, the dephosphorylation of which by water (k3) or a nucleophile (k4) is rate-determining. According to this model, in the presence of diethanolamine, k3 and k4 were determined to be 4.44 s-1 M-1 and 1000 s-1 M-1, respectively. Therefore, in vitro a suitable nucleophile, such as diethanolamine, seems to be a better phosphate acceptor than water. These results may suggest that alkaline phosphatase from bone could be well suited for catalyzing phosphate transfer reactions in vivo as well.

Alkaline Phosphatase↗