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Jan Maehlen

Publications and source records attributed to Jan Maehlen.

17 recordsLinked to original sources
PubMed2006

Preconditioning with estradiol abolishes its neuroprotection in cerebellar neurons.

Certain steroids are neuroprotective because they are modulators of neuronal activity or ROS scavengers. We examined neuroprotection following glutamate-induced excitotoxicity in cerebellar granule neuron cultures. 17beta-Estradiol, 17alpha-estradiol (nonestrogenic), or vitamins C+E were equally neuroprotective when coadministered with glutamate, consistent with protection by ROS scavenging. Progesterone protected mainly by an action on GABA-A receptors. Since exogenous antioxidants may influence the level of glutathione, the main endogenous antioxidant in neurons, we investigated if a preconditioning period with the neuroprotectors changed their efficacy as protectors. The neuroprotection by 17beta-estradiol and 17alpha-estradiol, but not progesterone or vitamins C+E, was almost abolished following a preconditioning period of 24h. This reduction was accompanied by an inhibition of the gamma-glutamylcysteine synthetase promoter, and a reduced level of glutathione when preconditioning was combined with the subsequent glutamate exposure. Thus, vitamins C+E and progesterone were more effective long-term neuroprotectors, since preconditioning did not reduce glutathione.

Animals↗
PubMed2006

Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis.

Congenital neuronal ceroid-lipofuscinosis (NCL) is a devastating inherited neurodegenerative disorder of unknown metabolic basis. Eight patients with this rare disorder, all with similar clinical and neuropathological findings, have been reported, and here we describe two further patients. Previously, we showed that a mutation in the cathepsin D gene causes congenital NCL in sheep. On the basis of the neuropathological and ultrastructural similarities between the sheep and patients affected with congenital NCL, we screened the cathepsin D gene for mutations in a patient of Pakistani origin. We identified a nucleotide duplication, c.764dupA, in the cathepsin D gene in homozygous form in the patient, and in heterozygous form in his father. This duplication is likely to be disease-causing, as it creates a premature stop codon, predicting a truncation of the protein. When transiently expressed in cell cultures, the mutant protein was enzymatically inactive, but stable. In paraffin-embedded brain tissue samples of two affected siblings of the Pakistani patient, cathepsin D was absent, suggesting rapid degradation of the c.764dupA mutant cathepsin D at mRNA or protein level in vivo. Further, we were able to confirm lack of cathepsin D in the brain tissue of yet another, unrelated, patient of English origin with congenital NCL. On the basis of the present data, and the nearly identical clinical and/or pathological phenotype of the other reported cases of congenital NCL, it is reasonable to suggest that cathepsin D deficiency caused by mutations in the corresponding gene may underlie all cases of congenital NCL. The present observations also suggest that cathepsin D deficiency should be considered as a possible diagnosis in microcephalic neonates, who present with seizures at or before birth.

Animals↗
PubMed2006

Chicken cerebellar granule neurons rapidly develop excitotoxicity in culture.

Rat cerebellar granule cell culture is widely used as a model to study factors that control neuronal differentiation and death (e.g. excitotoxicity). However, a main drawback of this model is its dependence on depolarizing culture condition (25 mM potassium). In addition, it is quite expensive to maintain and requires animal facilities. Here we report that cerebellar granule neuron cultures from chicken may be used as an alternative model to study excitotoxicity. Surprisingly, fetal chicken cells may be grown in a physiological potassium concentration (5 mM potassium). They develop excitotoxicity rapidly in culture (fully developed at 3 days in vitro), and respond to glutamate excitotoxicity similar to rat cultures (ROS production and activation of caspase-3).

Animals↗
PubMed2006

Results of the Two-County trial of mammography screening are not compatible with contemporaneous official Swedish breast cancer statistics.

BACKGROUND: National mammography screening programmes are based on the results of randomised trials, but the quality of these trials has recently been questioned. The Swedish Two-County trial reported a 31% reduction in breast cancer mortality and was instrumental for the introduction of screening in many countries. In this trial, official Swedish health registries were used to identify breast cancers and breast cancer deaths in the study population. METHODS: We used data from the same registries to estimate the numbers of breast cancer cases and breast cancer deaths among the included women. RESULTS: Compared to official Swedish statistics we found that 192 breast cancer cases and 43 breast cancer deaths seem to be missing in the main publication of the Two-County trial; we found similar discrepancies in two updates of the trial. These large differences can hardly be explained by random fluctuations in the cancer occurrence. CONCLUSION: The data reported for the Two-County trial are incomplete. Other data indicate that the mortality results in a recent report were flawed.

Bias↗
PubMed2005

Brain stem encephalitis in listeriosis.

Serious infection with the bacterium L. monocytogenes mainly manifests as sepsis and/or meningitis. A particular entity is Listeria brain stem encephalitis, which is characterized by progressive brain stem deficits. The condition is fatal unless early treated. The purpose of the present study was to assess the incidence of brain stem encephalitis in a population-based listeriosis material. Medical records from 212 of the 240 patients with serious listeriosis reported in Norway from 1977 to 2000, as well as autopsy material from 8 of these patients, were available. This material was searched for clinical and neuropathological evidence of brain stem infection. Findings indicating brain stem encephalitis were present in 19 of the 172 patients with adult listeriosis (11%) but none of the 40 pregnancy-related listeriosis cases. None of the 19 patients had been diagnosed with Listeria brain stem infection originally. We conclude that brain stem encephalitis is relatively common in this Norwegian listeriosis material.

Adolescent↗
PubMed2005

Neuropathological findings in 9 cases of listeria monocytogenes brain stem encephalitis.

Brain stem encephalitis is a particular manifestation of infection with the bacterium Listeria monocytogenes. Here, we present the neuropathological findings in 9 such cases. In the brain stem, the inflammatory infiltrates were located predominantly within nuclei and tracts of cranial nerves innervating the oropharynx. These findings support the hypothesis that the food-borne bacterium Listeria monocytogenes invades the brain stem along cranial nerves.

Adolescent↗
PubMed2004

[Overdiagnosis in mammography screening].

BACKGROUND: In Norway and Sweden, the introduction of mammography screening programmes has been associated with about a 50% increase in breast cancer incidence for the screened age groups and almost stable incidence in higher age groups. This suggests that mammography screening results in a substantial degree of overdiagnosis. MATERIAL AND METHODS: In a prospective cohort study of the Norwegian mammography programme we recorded the incidence of breast cancer among women aged 50 to 69 years offered mammography screening as well as the incidence of interval cancer among those attending, and breast cancer among those not attending. We used these data to calculate the incidence of cancer detected by screening among those screened. RESULTS: The incidence of invasive cancer at second and third screening is 2.4 times higher than expected. We estimated that only 42% of the screening-detected invasive cancers would have developed into clinical disease in the absence of a screening programme. When ductal carcinoma in situ is added, only 34% of the screening-detected cancers would have developed into clinical disease. INTERPRETATION: Two thirds of breast cancers detected by screening are overdiagnosed.

Aged↗
PubMed2004

Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study.

OBJECTIVE: To determine whether any increase in the incidence of breast cancer in women detected by mammography is compensated for by a drop in the incidence after age 69, years when women are no longer invited for screening. DESIGN: Population based cohort study of incidence of breast cancer during the introduction of nationwide screening programmes. SETTING: Norway and Sweden. PARTICIPANTS: All women aged above 30 years (1.4 and 2.9 million, respectively, in 2000). MAIN OUTCOME MEASURES: Changes in age specific incidence rates of invasive breast cancer associated with the introduction of the screening programmes. RESULTS: As a result of screening the recorded incidence of breast cancer in women aged 50-69 years increased by 54% in Norway and 45% in Sweden. There was no corresponding decline in incidence after the age of 69 years. CONCLUSIONS: Without screening one third of all invasive breast cancers in the age group 50-69 years would not have been detected in the patients' lifetime. This level of overdiagnosis is larger than previously reported.

Adult↗
PubMed2002

Allele frequencies of apolipoprotein E gene polymorphisms in the protein coding region and promoter region (-491A/T) in a healthy Norwegian population.

This study examines the distribution of apolipoprotein E (APOE) alleles in a population of healthy male and female Norwegians (n = 798) below the age of 40. The -491A/T polymorphism of the promoter region of the APOE gene was also examined. A seminested polymerase chain reaction was applied in the genotyping. The results showed that the E3 allele had the highest frequency (0.744), followed by E4 (0.198) and E2 (0.058). The APOE frequencies found in this study differ significantly from those obtained in earlier Norwegian APOE phenotypings. The allele frequencies in the -491 site of the promoter region were 0.845 for the A allele and 0.155 for the T allele. The genotype frequency was highest for AA (0.707), followed by AT (0.277) and TT (0.016). Moreover, the A allele was in linkage disequilibrium to E4.

Adult↗