It's Erren's brainchild, folks!
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Breast Neoplasms↗
Biomedical subjects
Alexander Lerchl
Publications and source records attributed to Alexander Lerchl.
Adult sertoli cells are not terminally differentiated in the Djungarian hamster: effect of FSH on proliferation and junction protein organization.
Sertoli cell number is considered to be stable and unmodifiable by hormones after puberty in mammals, although recent data using the seasonal breeding adult Djungarian hamster (Phodopus sungorus) model challenged this assertion by demonstrating a decrease in Sertoli cell number after gonadotropin depletion and a return to control levels following 7 days of FSH replacement. The present study aimed to determine whether adult Sertoli cells are terminally differentiated using known characteristics of cellular differentiation, including proliferation, junction protein localization, and expression of particular maturational markers, in the Djungarian hamster model. Adult long-day (LD) photoperiod (16L:8D) hamsters were exposed to short-day (SD) photoperiod (8L:16D) for 11 wk to suppress gonadotropins and then received exogenous FSH for up to 10 days. Sertoli cell proliferation was assessed by immunofluorescence by the colocalization of GATA4 and proliferating cell nuclear antigen and quantified by stereology. Markers of Sertoli cell maturation (immature, cytokeratin 18 [KRT18]; mature, GATA1) and junction proteins (actin, espin, claudin 11 [CLDN11], and tight junction protein 1 [TJP1, also known as ZO-1]) also were localized using confocal immunofluorescence. In response to FSH treatment, proliferation was upregulated within 2 days compared with SD controls (90% vs. 0.2%, P < 0.001) and declined gradually thereafter. In LD hamsters, junction proteins colocalized at the basal aspect of Sertoli cells, consistent with inter-Sertoli cell junctions, and were disordered within the Sertoli cell cytoplasm in SD animals. Exogenous FSH treatment promptly restored localization of these junction markers to the LD phenotype. Protein markers of maturity remain consistent with those of adult Sertoli cells. It is concluded that adult Sertoli cells are not terminally differentiated in the Djungarian hamster and that FSH plays an important role in governing the differentiation process. It is proposed that Sertoli cells can enter a transitional state, exhibiting features common to both undifferentiated and differentiated Sertoli cells.
Actins↗
1800 MHz electromagnetic field effects on melatonin release from isolated pineal glands.
Isolated pineal glands of Djungarian hamsters (Phodopus sungorus) were continuously perifused by Krebs-Ringer buffer, stimulated with the beta-adrenergic receptor agonist isoproterenol to induce melatonin synthesis, and exposed for 7 hr to a 1800 MHz continuous wave (CW) or pulsed GSM (Global System for Mobile Communications)-modulated electromagnetic signal at specific absorption rate (SAR) rates of 8, 80, 800, and 2700 mW/kg. Experiments were performed in a blind fashion. Perifusate samples were collected every hour, and melatonin concentrations were measured by a specific radioimmunoassay. Both types of signal significantly enhanced melatonin release at 800 mW/kg SAR, while at 2700 mW/kg SAR, melatonin levels were elevated in the CW, but suppressed in the GSM-exposed pineal glands. As a temperature rise of approximately 1.2 degrees C was measured at 2700 mW/kg SAR, effects at this level are thermal. With regard to radiofrequency electromagnetic fields, the data do not support the 'melatonin hypothesis,' according to which nonthermal exposure suppresses melatonin synthesis.
Animals↗
50 Hz magnetic fields of 1 mT do not promote lymphoma development in AKR/J mice.
Some epidemiological studies suggest that exposure to power-frequency magnetic fields increases the risk of leukemia, especially in children with high residential exposures. In contrast, most animal studies did not find a correlation between magnetic-field exposure and hematopoietic diseases. The present study was performed to investigate whether chronic, high-level (1 mT) magnetic-field exposure had an influence on lymphoma development in a mouse strain that is genetically predisposed to thymic lymphoblastic lymphoma. Three groups of 160 unrestrained female AKR/J mice were sham-exposed or exposed to sinusoidal 50 Hz magnetic fields beginning at the age of 12 weeks for 32 weeks, 7 days per week, either for 24 h per day or only during nighttime (12 h). Exposure was carried out in a blind design. Exposure did not affect survival time, body weight, lymphoma development or hematological parameters. The resulting data do not support the hypothesis that exposure to sinusoidal 50 Hz magnetic fields is a significant risk factor for hematopoietic diseases, even at this relatively high exposure level.
Animals↗
Where are the Sunday babies? Observations on a marked decline in weekend births in Germany.
In 5-year intervals, data from 722,306 individuals born between 1988 and 2003 in North Rhine Westphalia, Germany's largest state, were analyzed for the weekday of birth. In contrast to data from 1900 to 1950 (n=149,267), serving as historical controls, a very marked nonrandom distribution was discovered, with decreasing numbers of births on weekends, especially on Sundays, reaching deviations from the expected distribution of -17.8% in 2003, while births on weekdays are more frequent than expected (Fridays: +8.1% in 2003). The increasing avoidance of births during weekends by elective labor induction on weekdays is discussed as a consequence of practical and increasing financial constraints of hospitals.
Birth Rate↗
5-hydroxytryptophan is a more potent in vitro hydroxyl radical scavenger than melatonin or vitamin C.
Hydroxyl radicals are involved in direct damage of important biomolecules. Potent radical scavengers such as vitamin C and indoles of the tryptophan family can avert the potential damage. Melatonin and its precursor 5-hydroxytryptophan (5-HTP) were compared with water-soluble vitamin C. Different scavenger concentrations were measured in a steady-state luminol chemiluminescence system (SLCL-system) with combined Fe(II) chloride (0.1 mm) and hydrogen peroxide (1.0 mm) as hydroxyl radical generators. 5-HTP showed highest hydroxyl radical scavenging effects with a 50% inhibition concentration (IC50) of 1.8 microm. For vitamin C an IC50 of 12.7 microm was measured, whereas melatonin in pure demineralized water was much less efficient (IC50=724 microm). A comparison between melatonin in aqueous solution and melatonin in ethanol solution revealed that melatonin was significantly more effective in pure demineralized water.
5-Hydroxytryptophan↗
Predicted 3D-structure of melanopsin, the non-rod, non-cone photopigment of the mammalian circadian clock, from Djungarian hamsters (Phodopus sungorus).
Melanopsin is the photopigment of the retinal ganglion cells, which are involved in the synchronization of the biological clock in the suprachiasmatic nucleus (SCN) of mammals with the exogenous photoperiod. So far, no information about the three-dimensional (3D) structure of melanopsin is available. Here we report the predicted structure based on the protein-coding region of the nucleotide sequence of the gene for melanopsin, originating from isolated mRNA from the eyes of Djungarian hamsters (Phodopus sungorus). The nucleotide sequence shares the largest homologies with melanopsin of mice and rats (each 89%) and humans (84%). Based on the amino-acid sequence, and in comparison with the known structure of bovine rhodopsin, the three-dimensional melanopsin protein structure was modeled by using automated homology modeling approaches that were subsequently refined. Melanopsin consists of highly conserved seven-transmembrane domains and a long cytoplasmatic tail with multiple putative phosphorylation sites. In the binding site of the chromophore, a 11-cis-retinal is likely to be bound to lysine at position 336 as Schiff's base. The modeling results may indicate different photoisomerization within the melanopsin molecule compared with bovine rhodopsin.
Amino Acid Sequence↗
No effects of GSM-modulated 900 MHz electromagnetic fields on survival rate and spontaneous development of lymphoma in female AKR/J mice.
BACKGROUND: Several reports indicated that non-thermal electromagnetic radiation such as from mobile phones and base stations may promote cancer. Therefore, it was investigated experimentally, whether 900 MHz electromagnetic field exposure influences lymphoma development in a mouse strain that is genetically predisposed to this disease. The AKR/J mice genome carries the AK-virus, which leads within one year to spontaneous development of thymic lymphoblastic lymphoma. METHODS: 320 unrestrained female mice were sham-exposed or exposed (each n = 160 animals) to GSM like 900 MHz electromagnetic fields for 24 hours per day, 7 days per week, at an average whole body specific absorption rate (SAR) value of 0.4 W/kg. Animals were visually checked daily and were weighed and palpated weekly. Starting with an age of 6 months, blood samples were taken monthly from the tail. Animals with signs of disease or with an age of about 46 weeks were sacrificed and a gross necropsy was performed. RESULTS: Electromagnetic field exposure had a significant effect on body weight gain, with higher values in exposed than in sham-exposed animals. However, survival rate and lymphoma incidence did not differ between exposed and sham-exposed mice. CONCLUSION: These data do not support the hypothesis that exposure to 900 MHz electromagnetic fields is a significant risk factor for developing lymphoma in a genetically predisposed species, even at a relatively high exposure level.
Animals↗
Month of birth and life expectancy: role of gender and age in a comparative approach.
The effects of month of birth (MOB) on life expectancy of a German subpopulation was investigated. Data from people who died in North Rhine Westphalia in the years 1984 ( n=188,515) and 1999 ( n=188,850) were analyzed. For comparative purposes, all deaths that occurred at an age of <50 years were excluded (1984: 8.4%; 1999: 6.2%). In general, individuals born in May through July had the lowest age at death (1984: 75.27+/-0.09 years; 1999: 77.58+/-0.09 years), while those born between October and December had the highest (1984: 75.98+/-0.08 years; 1999: 78.35+/-0.09 years), supporting earlier findings. The observed amplitudes (differences between highest and lowest values) were more pronounced in men than in women. When comparing these data of MOB effects on life expectancy with earlier findings in Australia, Austria, Denmark, Ukraine, and the USA, it is evident that a negative correlation exists between the average age at death and the MOB amplitudes. Separate analyses by gender, possible for the data from Germany, the Ukraine, and the USA, revealed a significant negative correlation for men, but not for women. A new hypothesis is therefore presented describing an influence of life quality, as reflected by average life expectancy, on the extent of MOB effects; for example, seasonally variable sensitivities during pregnancy/early childhood.
Aged↗
The risk of lymphoma in AKR/J mice does not rise with chronic exposure to 50 Hz magnetic fields (1 microT and 100 microT).
Some epidemiological studies suggest that exposure to 50 or 60 Hz magnetic fields might increase the risk of leukemia, especially in children with a comparable high residential exposure. To investigate this possibility experimentally, the influence of 50 Hz magnetic-field exposure on lymphoma induction was determined in a mouse strain that is genetically predisposed to this disease. The AKR/J mouse genome carries the AK virus, which leads within 1 year to spontaneous development of thymic lymphoblastic lymphoma. Beginning at an age of 4-5 weeks, groups of 160 female mice were sham-exposed or exposed to 50 Hz magnetic fields at 1 or 100 microT for 24 h per day, 7 days per week, for 38 weeks. Animals were checked visually daily and were weighed and palpated weekly. There was no effect of magnetic-field exposure on body weight gain or survival rate, and lymphoma incidence did not differ between exposed and sham-exposed animals. Therefore, these data do not support the hypothesis that chronic exposure to 50 Hz magnetic fields is a significant risk factor for developing hematopoietic malignancy.
Animals↗
Comments on the recent publication on microwave effects on Emicro-Pim1 transgenic mice (Utteridge et al., Radiat. Res. 158, 357-364, 2002).
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Animals↗
Spontaneous central melatonin secretion and resorption kinetics of exogenous melatonin: a ventricular CSF study.
Pineal secretion of melatonin, a potential sleep-inducing agent, is stimulated by nighttime darkness. To gain better insight into the control of melatonin physiology in man, we studied melatonin concentrations in ventricular cerebrospinal fluid (v-CSF). In four patients aged 1-4 yr with therapeutic v-CSF drainage, including one with lumbar CSF (l-CSF) drainage, CSF samples were collected sequentially over 24-hr periods. One further patient with severe sleep disturbance had one collection period under chloral hydrate and another after oral melatonin administration. Reduction of light intensity or night periods, respectively, led to increased melatonin levels. At the moment of falling asleep, additional melatonin peaks were observed in v-CSF but not in l-CSF. Oral melatonin, but not chloral hydrate, caused a rapid increase in CSF melatonin between 10 and 80 min after intake, raising levels far beyond physiological concentrations. The commencement of sleep is associated with an additional melatonin peak v-CSF which is independent of baseline secretion during the day-night cycle. The possibility is discussed that the induction of sleep might depend on a critical level or increased melatonin concentrations, which can be achieved with orally administered melatonin.
Cerebral Ventricles↗
Effects of electromagnetic radiation (bright light, extremely low-frequency magnetic fields, infrared radiation) on the circadian rhythm of melatonin synthesis, rectal temperature, and heart rate.
Electromagnetic spectra reduce melatonin production and delay the nadirs of rectal temperature and heart rate. Seven healthy men (16-22 yrs) completed 4 permuted sessions. The control session consisted of a 24-hours bedrest at < 30 lux, 18 degrees C, and < 50 dBA. In the experimental sessions, either light (1500 lux), magnetic field (16.7 Hz, 0.2 mT), or infrared radiation (65 degrees C) was applied from 5 pm to 1 am. Salivary melatonin level was determined hourly, rectal temperature and heart rate were continuously recorded. Melatonin synthesis was completely suppressed by light but resumed thereafter. The nadirs of rectal temperature and heart rate were delayed. The magnetic field had no effect. Infrared radiation elevated rectal temperature and heart rate. Only bright light affected the circadian rhythms of melatonin synthesis, rectal temperature, and heart rate, however, differently thus causing a dissociation, which might enhance the adverse effects of shiftwork in the long run.
Adolescent↗
Melatonin and magnetic fields.
There is public health concern raised by epidemiological studies indicating that extremely low frequency electric and magnetic fields generated by electric power distribution systems in the environment may be hazardous. Possible carcinogenic effects of magnetic field in combination with suggested oncostatic action of melatonin lead to the hypothesis that the primary effects of electric and magnetic fields exposure is a reduction of melatonin synthesis which, in turn, may promote cancer growth. In this review the data on the influence of magnetic fields on melatonin synthesis, both in the animals and humans, are briefly presented and discussed.
Animals↗
Biological rhythms in the context of light at night (LAN).
In mammals including man, the most important zeitgeber for endogenous rhythms is the environmental light/dark cycle. Mammals perceive light through the eyes and that perception is relayed to the suprachiasmatic nucleus (SCN) by means of neuronal signals. The SCN, in turn, innervates the pineal gland, resulting in the production and release of melatonin almost exclusively during night-time hours. Thus, besides object recognition, eyes serve as the sensory organ for detecting the presence or absence of light. The way that light entrains the SCN is still a matter of intense research. It has been shown, for example, that the light intensities required for affecting melatonin rhythms are much higher than the intensities needed for object identification. On the other hand, even in rodents who completely lack the "classical" photoreceptors of the retina, their endogenous rhythms still can be synchronized by normal light/dark cycles. These two observations led to the hypothesis that there must be photoreceptors, apart from the known (object-identifying) retinal photoreceptors, which are responsible for the entrainment of internal rhythms. Very recently, a number of reports showed that in fact a completely new type of retinal photoreceptor, located in ganglion cells, may be responsible for entraining the SCN. It contains a photopigment, melanopsin, which shares homologies with rhodopsin, but also is evolutionarily older. Compared to rods or cones, the melanopsin-containing neurons are rare, but evenly distributed within the retina, indicating that they serve as a global, integrating light sensor. These ganglion cells apparently project directly into the SCN. Taken together, these new developments in photo-chronobiology open new areas of research. It will be of special interest, for example, to determine how the photosensitive ganglion cells and their dendrites integrate the environmental light stimuli.
Animals↗
Melatonin administration alters semen quality in normal men.
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Circadian Rhythm↗