Impact of Chemotherapy for Childhood Leukemia on Brain Morphology and Function

Objective

Using multidisciplinary treatment modalities the majority of children with cancer can be cured but we are increasingly faced with therapy-related toxicities. We studied brain morphology and neurocognitive functions in adolescent and young adult survivors of childhood acute, low and standard risk lymphoblastic leukemia (ALL), which was successfully treated with chemotherapy. We expected that intravenous and intrathecal chemotherapy administered in childhood will affect grey matter structures, including hippocampus and olfactory bulbs, areas where postnatal neurogenesis is ongoing.

Methods

We examined 27 ALL-survivors and 27 age-matched healthy controls, ages 15–22 years. ALL-survivors developed disease prior to their 11th birthday without central nervous system involvement, were treated with intrathecal and systemic chemotherapy and received no radiation. Volumes of grey, white matter and olfactory bulbs were measured on T1 and T2 magnetic resonance images manually, using FIRST (FMRIB’s integrated Registration and Segmentation Tool) and voxel-based morphometry (VBM). Memory, executive functions, attention, intelligence and olfaction were assessed.

Results

Mean volumes of left hippocampus, amygdala, thalamus and nucleus accumbens were smaller in the ALL group. VBM analysis revealed significantly smaller volumes of the left calcarine gyrus, both lingual gyri and the left precuneus. DTI data analysis provided no evidence for white matter pathology. Lower scores in hippocampus-dependent memory were measured in ALL-subjects, while lower figural memory correlated with smaller hippocampal volumes.

Interpretation

Findings demonstrate that childhood ALL, treated with chemotherapy, is associated with smaller grey matter volumes of neocortical and subcortical grey matter and lower hippocampal memory performance in adolescence and adulthood.     

Experimental studies on thermal behaviour and diurnal activity rhythms of juvenile European sturgeon (Acipenser sturio)

Experiments were performed to determine the temperature preference of juvenile sturgeons. The biorhythms of activity and the location of fish in a thermal gradient of an electronic shuttlebox were registered. The fish showed dominant 24 h activity rhythms with its maximum at the nighttime. A temperature preference range or an active thermoregulatory behavior could not be demonstrated by our experiments. The behavior of sturgeons was influenced by temperature: activity and swimming speed were positively correlated to rising temperatures. There are indications that the fish could have been attracted by low light intensities at night.     

Determination of biogenic amines in infusions of tea (Camellia sinensis) by HPLC after derivatization with 9-fluorenylmethoxycarbonyl chloride (Fmoc-Cl)

The reagent 9-fluorenylmethoxycarbonyl chloride (Fmoc-Cl) was used for the pre-column derivatization of the biogenic amines (BAs) cadaverine (Cad), histamine (Him), octopamine (Ocp), phenylethylamine (Pea), putrescine (Put), spermidine (Spd), spermine (Spm), tyramine (Tym) and the internal standard 1,6-diaminohexane (Dhx). The resulting Fmoc-derivatives were resolved by high-performance liquid chromatography on a Superspher^? C₁₈ column using a binary gradient generated from sodium acetate and acetonitrile. For quantification, the fluorescence of derivatives was used at 263?nm excitation and 313?nm emission wavelength. This approach was applied to free BAs extractable with boiling water from 14 black, 5 green, 1 Oolong, and 1 instant tea. Infusions were prepared by adding 35?ml boiling water to one gram of tea and extracted for 20?min. In the Oolong tea and two black teas, no BAs could be detected. Limits of detection were 0.07–1.0?pmol for BAs at signal-to-noise ratio 3:1. Besides most abundant Tym and Spm lower quantities of Pea, Put, and Spd were detected, albeit not in all teas. Quantities of Tym ranged from 16 to 431?μg Tym/L infusion (1.1–25.3?μgTym/g tea) and 31 to 319?μg Spm/L infusion (1.5–16.9?μg Spm/g tea). In none of the teas, Him was detected. Owing to the low amounts of free BAs in tea infusions, no health risks are to be expected even on consumption of large quantities of tea as beverage.     

Impact of C60 Adsorption on Surface Plasmon Polaritons on Self-Assembled Ag(111) Islands on Si(111)

The influence of C₆₀ adsorption on the properties of surface plasmon polaritons on small Ag islands is discussed. Under illumination with UV light as well as under illumination with femtosecond laser pulses, a decrease of the photoemission yield with increasing C₆₀ coverage is observed. With angular resolved measurements, changes of the band structure during deposition are studied. Based on these experiments, an increase of the work function with increasing coverage is measured. In two photon photoemission, the surface plasmons are imaged as a periodic moiré pattern, the wavelength of which changes because of a modified effective surface dielectric function. Our findings imply that the wavelength of the plasmon wave becomes shorter as a result. Finally, a decrease of the intensity of the moiré pattern maxima compared with the intensity of the first maximum with increasing C₆₀ coverage has been observed. Accordingly, the damping of the plasmon wave becomes stronger.     

A unique proteolytic fragment of human fibrinogen containing the A alpha COOH-terminal domain of the native molecule

The COOH-terminal portion of the A alpha chain of human fibrinogen is highly susceptible to proteolytic degradation. This property has prevented isolation of the COOH-terminal domain of fibrinogen for the direct investigation of its functional characteristics. Human fibrinogen was degraded with hementin, a fibrinogen-olytic protease from the posterior salivary glands of the leech, Haementeria ghilianii. Two initial fragments, Yhem1 and Dhem1, produced by cleavage through the three polypeptide chains in the connector region, were characterized and shown to retain the entire A alpha COOH-terminal domain. Late cleavages by hementin occurred in the A alpha chain COOH-terminal region to produce fragments Yhem and Dhem with shorter A alpha chain remnants. Fragments Dhem were isolated from an intermediate hementin digest of fibrinogen using anion-exchange chromatography. Fragment Dhem1 was separated further from Dhem fragments with shorter alpha chain remnants by affinity chromatography on immobilized plasma fibronectin. Fragment Dhem1 represents a unique proteolytic fragment of fibrinogen containing an intact A alpha chain COOH-terminal region. NH2-terminal sequence analysis of isolated chains from fragment Dhem1 located hementin cleavage sites in the connector region to A alpha Asn102-Asn103, B beta Lys130-Gln131, and gamma Pro76-Asn77. The specific interaction of fragment Dhem1 with immobilized fibronectin indicated that the binding site probably was located within the COOH-terminal 111 amino acids of the A alpha chain. The overall pattern of fibrinogen cleavage by hementin is similar to that of plasmin, yet hementin cleaves preferably in the coiled-coil connector, sparing the A alpha COOH-terminal domain.     

Control of Gonadal Maturation and Regression by Experimental Variation of Environmental Factors in the Mormyrid Fish, Mormyrus rume proboscirostris

We used spawning, external appearance of the females and in part histology of gonads of the African mormyrid fish Mormyrus rume proboscirostris to evaluate the reaction of the fish to experimental variation of environmental factors. Conductivity changes are sufficient to induce gonadal maturation (decrease of conductivity) and regression (increase of conductivity), respectively. Increase of water level and simulation of rain at constant conductivity values did not induce gonadal maturation and spawning. Neither males nor females of M. rume proboscirostris showed postbreeding refractoriness. Social stress apparently prevented complete gonadal maturation and successful spawning. The females laid on average 364 eggs per fractional spawning; the spawning intervals were 21 days. Hatching rate amounted to about 40% in all experiments taken together.     

Does conversion of forest to agricultural land change soil carbon and nitrogen? a review of the literature

Soil carbon is a large component of the global carbon cycle and its management can significantly affect the atmospheric CO₂ concentration. An important management issue is the extent of soil carbon (C) release when forest is converted to agricultural land. We reviewed the literature to assess changes in soil C upon conversion of forests to agricultural land. Analyses are confounded by changes in soil bulk density upon land‐use change, with agricultural soils on average having 13% higher bulk density. Consistent with earlier reviews, we found that conversion of forest to cultivated land led to an average loss of approximately 30% of soil C. When we restricted our analysis to studies that had used appropriate corrections for changes in bulk density, soil C loss was 22%. When, from all the studies compiled, we considered only studies reporting both soil C and nitrogen (N), average losses of C and N were 24% and 15%, respectively, hence showing a decrease in the average C : N ratio. The magnitude of these changes in the C : N ratio did not correlate with either C or N changes. When considering the transition from forest to pasture, there was no significant change in either soil C or N, even though reported changes in soil C ranged from ?50% to +160%. Among studies that reported changes in soil N as well as soil C, C : N ratios both increased and decreased, with trends depending on changes in system N. Systems with increasing soil N generally had decreased C : N ratios, whereas systems with decreasing soil N had increased C : N ratios. Our survey confirmed earlier findings that conversion of forest to cropland generally leads to a loss of soil carbon, although the magnitude of change might have been inflated in many studies by the confounding influence of bulk‐density changes. In contrast, conversion of forest to uncultivated grazing land did not, on average, lead to loss of soil carbon, although individual sites may lose or gain soil C, depending on specific circumstances, such as application of fertiliser or retention or removal of plant residues.