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Biomedical subjects

H Köller

Publications and source records attributed to H Köller.

At least 19 recordsLinked to original sources
PubMed2005

[Myopathies under therapy with lipid-lowering agents].

Myopathies ranging from myalgia to clinically asymptomatic creatine kinase (CK) elevation and to life-threatening rhabdomyolysis belong to the most important complications of lipid-lowering therapies with fibrates and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, i.e., statins. Rhabdomyolysis is a rare side effect of statin therapy with an estimated incidence of 0.2/1 million prescriptions. Myalgia and muscle cramps were reported by up to 5% of patients, but they were observed with the same percentage in controls receiving placebo. Due to increasing numbers of patients under lipid-lowering therapy, however, more and more patients present in neuromuscular units with the differential diagnosis of a fibrate- or statin-induced myopathy.

Anticholesteremic Agents↗
PubMed2003

[Chronic inflammatory demyelinating polyneuropathy].

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated disease of the peripheral nervous system with a prevalence of 1-2/100,000. Clinical and experimental findings suggest a role of immune pathomechanisms;however, the target antigens are still unknown. Beside classic CIDP with symmetrical proximal and distal paresis, subgroups of CIDP with pure motor or sensory deficits have been described. Diagnostic criteria include evidence of demyelination in electrophysiological examination and biopsy as well as elevated protein content in the CSF. Magnetic resonance imaging of plexuses and roots extends the diagnostic armamentarium and may be helpful in differential diagnosis. The utility of immunosuppressant/immunomodulatory therapies has been demonstrated in several studies.

Autoantigens↗
PubMed2002

[Treatment of HIV infection from the neurologic viewpoint. Therapy must reach the brain].

An effective highly active antiretroviral therapy (HAART) can prevent the manifestation of HIV-1-associated encephalopathy. Also, HIV-1-associated minor cognitive/motor deficits--an early form of HIV-1-associated dementia--are improved. Clinically manifest HIV-1-associated encephalopathy is an indication for HAART treatment, irrespective of immune status. To date, minor cognitive and/or motor deficits in the presence of good immune status have not been identified as an indication for HAART treatment. Any CNS-effective treatment should be based on either zidovudine or stavudine, since these substances readily enter the CSF; however, NNRTI can also be applied. Side effects of HAART on the central and peripheral nervous system, as well as interactions with known neurological medicaments must be taken into account.

AIDS Dementia Complex↗
PubMed2001

Soluble cerebrospinal fluid factors induce Ca2+ dysregulation in rat cultured cortical astrocytes in HIV-1-associated dementia complex.

OBJECTIVES: To investigate the effect of cerebrospinal fluid (CSF) of HIV-1-seropositive patients with and without HIV-1-associated dementia complex (HADC) on the intracellular Ca2+ regulation of cultured cortical astrocytes. DESIGN: In a blinded study the effects of CSF samples from HADC patients and from HIV-1-seropositive but not demented patients on intracellular Ca2+ regulation of cultured cortical astrocytes were investigated. Astrocytes were chosen because they contribute to both electrophysiological and immunological processes within the brain. METHODS: Astrocytes were incubated in CSF samples for 1 h, loaded with the Ca2+ indicator dye Fura-2 and intracellular Ca2+ responses upon glutamate application were measured. RESULTS: CSF samples from 10 out of 11 HADC patients induced a significant reduction of the intracellular Ca2+ increase upon glutamate application. On the contrary, seven out of 10 CSF samples from HIV-1-seropositive patients without HADC as well as 10 out of 10 CSF samples from HIV-1-seronegative controls did not affect the intracellular Ca2+ response. CONCLUSIONS: Our data strongly confirm the hypothesis that CSF samples of HADC patients contain soluble factors which interfere with the function of astrocytes. These factors may include HIV-1 proteins, locally released cytokines or neurotoxins.

AIDS Dementia Complex↗
PubMed2001

TNFalpha reduces glutamate induced intracellular Ca(2+) increase in cultured cortical astrocytes.

The proinflammatory cytokine TNFalpha is locally released during various inflammatory CNS diseases and high cerebrospinal fluid (CSF) titers of TNFalpha were found in meningitis patients. We know from previous studies that TNFalpha also depolarizes astrocytes by reducing their inwardly rectifying K+ currents. We have now investigated the effect of TNFalpha on the glutamate induced intracellular Ca2+ increase in astrocytes, a process which seems to be involved in glial mediated modulation of neuronal synaptic transmisssion. Incubation with TNFalpha (50-1000 U/ml for 60 min) reduces the glutamate induced intracellular Ca2+ increase in astrocytes but not in neurons and this seems to be a phenomenon secondary to the TNFalpha induced depolarization. While other proinflammatory cytokines (interleukin 1beta, IL-2, IL-6) did not interfere with the astrocytic glutamate response, incubation in CSF from septic meningitis patients (CSF-SM) also reduced the glutamate induced intracellular Ca2+ increase. The application of a neutralizing anti-TNFalpha antibody to the CSF-SM prior to cell incubation partially restored the glutamate response. Our data suggest that inflammatory molecules such as TNFalpha impair astrocytes' response to glutamate and this may indirectly affect neuronal synaptic transmission.

Animals↗
PubMed2001

Basal ganglia metabolite abnormalities in minor motor disorders associated with human immunodeficiency virus type 1.

BACKGROUND: Minor motor disorders (MMDs) associated with human immunodeficiency virus type 1 (HIV-1) predict HIV-1 dementia and death. Little is known about the time course and neuropathologic mechanisms of HIV-1 MMDs. OBJECTIVE: To investigate the relationship between HIV-1 MMDs, as assessed by psychomotor speed, and metabolic alterations in the basal ganglia, as detected by proton magnetic resonance spectroscopy. PATIENTS AND METHODS: A total of 32 HIV-1-seropositive patients (10 with no MMD, 8 with incipient MMD, and 14 with sustained MMD, assessed through electrophysiologic testing of psychomotor speed including contraction times; 29 treated with highly active antiretroviral therapy) and 14 HIV-1-seronegative control subjects were examined for cerebral metabolite abnormalities in the basal ganglia by means of magnetic resonance spectroscopy. RESULTS: The 3 patient groups showed significantly different ratios of myoinositol/creatine (P =.02) in the basal ganglia. Whereas patients with no MMD or incipient MMD showed normal ratios, patients with sustained MMD showed higher values for myoinositol/creatine as a sign of glial proliferation. No differences in N-acetyl compounds, indicative of neuronal loss, were found. CONCLUSION: Whereas metabolic alterations in the basal ganglia were not detected in patients with incipient HIV-1 MMD, patients with sustained HIV-1 MMD did have significantly altered metabolic spectra indicative of glial proliferation.

AIDS Dementia Complex↗
PubMed2001

[Reversible multifocal encephalopathy in fulminant eclampsia].

Fulminant eclampsia characterised by the onset of focal neurological signs and convulsions is a rare complication of normal pregnancy in the third trimenon. We report on eight women (22-35 years old) with fulminant eclampsia who were admitted to our hospital due to seizures and central pareses. The patients presented with multifocal lesions involving grey and white matter preferentially of the occipital lobes, as evidenced by neuroimaging. Transcranial Doppler sonography revealed increased cerebral blood flow velocities. Treatment consisted of antihypertensive and anticonvulsive medication and operative termination of pregnancy. The patients normalised within 14 days. Our data show that fulminant eclampsia can induce a severe multifocal encephalopathy that can be reversible when treatment and termination of pregnancy are initiated immediately.

Acute Disease↗
PubMed2001

HIV-1 protein Tat reduces the glutamate-induced intracellular Ca2+ increase in cultured cortical astrocytes.

The trans-activator protein Tat of the human immunodeficiency virus type 1 (HIV-1) is regarded as an injurious molecule in the pathogenesis of HIV-1 associated encephalopathy (HIVE). We investigated the effects of Tat on neuroligand-induced intracellular Ca2+ increase in cultured astroglial cells. Rat cortical astrocytes, human glioblastoma cells and glial restricted precursor cells, from a human embryonic teratocarcinoma cell line, were incubated with recombinant Tat (100 ng/mL for 60 min) which induced a significant reduction of glutamate or ATP-induced intracellular Ca2+ increase ("glutamate response", "ATP response"). The reduction of the glutamate response was also observed following cell incubation with cell extracts of HeLa-T4+ cells transiently transfected with an expression plasmid coding for Tat. However, inactivation of the transcriptional trans-activity of Tat, by using a mutant form of Tat, as well as inhibition of de novo protein synthesis by cycloheximide abolished the effect on the glutamate response. This suggests that Tat acts upon induction of a so far unknown cellular gene whose gene product causes the reduction of glutamate responses. As the effect of Tat resembles the effect of TNFalpha on glutamate responses [Köller et al. (2001) Brain Res., 893, 237-243] which is locally released within the brains of HIVE patients, we also tested for synergistic effects of Tat and TNFalpha on the glutamate response. Low concentrations of Tat in combination with subthreshold concentrations of TNFalpha also elicited a marked reduction of astroglial glutamate responses. Our data suggest that Tat and TNFalpha, both by itself and synergistically, induce astroglial dysfunction.

AIDS Dementia Complex↗
PubMed2000

Time course of inwardly rectifying K(+) current reduction in glial cells surrounding ischemic brain lesions.

K(+) currents of activated glial cells surrounding ischemic infarcts are investigated using acutely dissociated cells from the periinfarct area after permanent middle cerebral artery occlusion in rats. Inwardly rectifying K(+) currents (K(IR)) were markedly reduced in cells neighboring infarcts with maximal alteration at day 3 after infarct followed by a partial recovery. This reduction of glial K(IR) currents may contribute to the functional disturbances in the periinfarct area.

Animals↗
PubMed1999

[Ciguatera poisoning. Growing differential diagnostic significance in the age of foreign tourism].

BACKGROUND: In the tropic sea there are carnivore fishes, e.g. the "peak bass", that incorporate toxin producing seaweed and can cause the ciguatera intoxication. Due to the frequent tourism to tropic regions even more cases of ciguatera intoxication can be seen in Europe. The late phase of ciguatera intoxication has hardly been recognized due to its different unspecific symptoms. In some cases ciguatera intoxication can even grow a vital threatening. CASE DESCRIPTION: Four patients from a travel group addressed us 4 and 14 days after breaking off their holidays in the Dominican republic. They presented complex neurological symptoms including paraesthesia, nervousness, inverse temperature perception, muscle cramps, headache and dizziness. The physical and apparative investigation of the patients, whose age ranked between 22 and 31 years, was totally unobtrusive. Essential for the diagnosis of ciguatera intoxication was the clue to the symptom causing dinner at their holiday location existing of "peak bass and lemon sauce". First symptoms in all members of the travel group were diarrhea, sickness and sweating. In this late phase only a symptomatic therapy could be offered. CONCLUSION: The here described cases show the importance of a comprehensive information for tropic travellers as for physicians accounted to in the acute phase of ciguatera intoxication, because recognized early enough (within the first 24 hours) the total symptomatology of ciguatera intoxication can be prevented effectively by intravenous infusions of mannitol.

Adult↗
PubMed1998

TNF alpha induces a protein kinase C-dependent reduction in astroglial K+ conductance.

Incubation of cultured cortical astrocytes with tumor necrosis factor alpha (TNF alpha) led to a marked reduction of membrane potential. Here we report that this depolarization depends on activation of protein kinase C (PKC), since it could be blocked by the PKC antagonists staurosporine and H7 and it could be mimicked by direct activation of PKC using the phorbol ester phorbol 12-myristate 13 acetate (PMA). Analyses of whole cell currents revealed a reduction of inwardly rectifying K+ currents whereas K+ outward currents were not affected. We conclude that TNF alpha induces changes of basic electrophysiological properties of astrocytes which are similar to those induced by proliferation or an in vitro model of traumatic injury.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Ammonia-induced depolarization of cultured rat cortical astrocytes.

Exposure of cultured rat cortical astrocytes to increased concentrations of ammonia has been shown to induce morphological and biochemical changes similar to those found in hyperammonemic (e.g., hepatic) encephalopathy in vivo. Alterations of electrophysiological properties are not well investigated. In this study, we examined the effect of ammonia on the astrocyte membrane potential by means of perforated patch recordings. Exposure to millimolar concentrations of NH4Cl induced a slow dose-dependent and reversible depolarization. At steady state, i.e., after several tens of minutes, the cells were significantly depolarized from a resting membrane potential of -96.2 +/- 0.6 mV (n = 83, S.E.M.) to -89.1 +/- 1.6 mV (n = 7, S.E.M.) at 5 mM NH4Cl, -66.3 +/- 3.6 mV (n = 9, S.E.M.) at 10 mM NH4Cl and -50.4 +/- 2.5 mV (n = 12, S.E.M.) at 20 mM NH4Cl, respectively. In order to examine the underlying depolarizing mechanisms we determined changes in the fractional ion conductances for potassium, chloride and sodium induced by 20 mM NH4Cl. No significant changes were found in the fractional sodium or chloride conductances, but the dominating fractional potassium conductance decreased slightly from a calculated 0.86 +/- 0.04 to 0.77 +/- 0.04 (n = 9, S.E.M.). Correspondingly, we found a significant fractional ammonium ion (NH4+) conductance of 0.23 +/- 0.02 (n = 10, S.E.M.) which was blocked by the potassium channel blocker barium and, hence, most likely mediated by barium-sensitive potassium channels. Our data suggest that the sustained depolarization induced by NH4Cl depended on changes in intracellular ion concentrations rather than changes in ion conductances. Driven by the high membrane potential NH4+ accumulated intracellularly via a barium-sensitive potassium conductance. The concomitant decrease in the intracellular potassium concentration was primarily responsible for the observed slow depolarization.

Ammonia↗