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Successful transplantation of human hepatoblastoma into immunodeficient mice.

Six hepatoblastomas (HBs) from pediatric patients were transplanted into immunodeficient NMRI nu/nu mice. Cells from two fetal HBs did not develop tumors. In contrast, xenografts derived from three nonpretreated HBs and one HB after three courses of chemotherapy, all comprising embryonal cells, showed growth after 8 to 10 weeks. The take rates of HB varied from 60% to 90% (mean, 80%). Histologically, they resembled their originals in the pattern of fetal and embryonal differentiated areas and contained hematopoietic foci. The tumors produced high levels of alpha-feto-protein in the patients and the animals. In contrast to the patients, tumor-bearing mice did not display elevated platelet counts. During serial grafting, growth rates of the tumors gradually increased, and hematopoiesis was no longer detectable; however, histologically, a dedifferentiation could not be clearly identified. The addition of viable human or murine fibroblasts to inoculated cells of three nude mouse HBs resulted in a significant increase in the growth rate of all tumors and reappearance of hematopoiesis in three of the examined 10 xenografts of one HB. The authors conclude that HB xenografts in immunodeficient mice are a feasible in vivo model for studies of the biological behavior of this tumor.

Animals↗

Light extinction by fine atmospheric particles in the White Mountains region of New Hampshire and its relationship to air mass transport.

Chemical, optical, and physical measurements of fine aerosols (aerodynamic diameter < or = 2.5 microm) have been performed at a mountaintop location adjacent to the White Mountain National Forest in northern NH, USA. A 1-month long sampling campaign was conducted at Cranmore Mountain during spring 2000. We report on the apportionment of light extinction by fine aerosols into its major chemical components, and relationships between variations in aerosol parameters and changes in air mass origin. Filter-based, 24-h integrated samples were collected and analyzed for major inorganic ions, as well as organic (OC), elemental (EC), and total carbon. Light scattering and light absorption coefficients were measured at 5-min intervals using an integrating nephelometer and a light absorption photometer. Fine particle number density was measured with a condensation particle counter. Air mass origins and transport patterns were investigated through the use of 3-day backward trajectories and a synoptic climate classification system. Two distinct transport regimes were observed: (1) flow from the north/northeast (N/NE) occurred during 9 out of 18 sample-days; and (2) flow from the west/southwest (W/SW) occurred 8 out of 18 sample-days. All measured and derived aerosol and meteorological parameters were separated into two categories based on these different flow scenarios. During W/SW flow, higher values of aerosol chemical concentration, absorption and scattering coefficients, number density, and haziness were observed compared to N/NE flow. The highest level of haziness was associated with the climate classification Frontal Atlantic Return, which brought polluted air into the region from the mid-Atlantic corridor. Fine particle mass scattering efficiencies of (NH4)2SO4 and OC were 5.35 +/- 0.42 m2 g(-1) and 1.56 +/- 0.40 m2 g(-1), respectively, when transport was out of the N/NE. When transport was from the W/SW the values were 4.94 +/- 0.68 m2 g(-1) for (NH4)2SO4 and 2.18 +/- 0.91 m2 g(-1) for OC. EC mass absorption efficiency when transport was from the N/NE was 9.66 +/- 1.06 m2 g(-1) and 10.80 +/- 1.76 m2 g(-1) when transport was from the W/SW. Results from this work can be used to predict visual air quality in the White Mountain National Forest based on a forecasted synoptic climate classification and its associated visibility.

Aerosols↗

Extractable organic matter in PM10 from LiWan district of Guangzhou City, PR China.

PM10 (particulate matter with aerodynamic diameter <10 microm) samples were collected at LiWan District of Guangzhou, PR China during April and July 2001 using a high volume air sampler to determine the distributions of homologous compounds and biomarkers. Polycyclic aromatic hydrocarbons (PAHs) including non-alkylated PAHs, methyl-alkylated PAHs, and some PAHs containing S/O atoms and n-alkanes were measured using gas chromatography/mass spectrometry analysis. The sigma(n)-alkane and sigmaPAHs ranged from 26.4 to 719.2 ng/m3 and 7.4 to 159.4 ng/m3, respectively. A seasonal fluctuation was clearly evident with higher concentrations occurring during the colder months (April). In addition, some compositional differences are observed for the organic compounds in samples collected from different heights above ground level. Higher sites had a significant contribution from vascular plant wax. The presence of petroleum products with no carbon number preference, pristane, phytane and a significant unresolved complex mixture (UCM) with unresolved to resolved components ratio (U/R) of 6.2-13.2 confirm the petroleum component. The relative distribution of n-alkanes and the values of molecular diagnostic ratio, such as carbon preference index (CPI) values ranging from 1.0 to 1.4 (for the whole range of n-alkanes), indicated the importance of petroleum and diesel residues and gasoline emissions, as well as the minor contribution of n-alkanes emitted directly from epicuticular waxes. Indeed, the percent contribution of leaf 'wax' n-alkanes (5.2-19.4%) indicated a low contribution of biogenic sources. The fossil fuel biomarkers, hopanes and steranes were observed in the PM10 samples, which indicate a petroleum origin. The distribution pattern of PAHs was characteristic of anthropogenic emissions. Coupling carbon number maximum (Cmax), CPI, U/R values, molecular marker and molecular diagnostic ratios for alkanes and PAHs revealed a classification of natural biogenic and anthropogenic components of atmospheric aerosols. These analyses support the conclusion that vehicular emission was the major source of organic compounds during the study period, while the contribution of epicuticular waxes emitted by terrestrial plants was minor.

Air Pollutants↗

A preliminary study on the pathogenicity of a strain of caprine herpesvirus-1.

The strain BA-1 of caprine herpesvirus-1 (CpHV-1), isolated from latently infected goats, was inoculated intranasally into three five-year-old goats. The animals developed fever and leukopenia. The signs began on post-inoculation day (PID) 4 and lasted 7 days. In one goat herpes-like lesions appeared on the vulvar area on PID 7. Virus was consistently recovered from the nasal and the vaginal swabbings obtained from the three goats. Virus was never recovered from the ocular and rectal swabbings nor from any buffy coat samples. However, the buffy coats were positive for viral DNA detected by polymerase chain reaction (PCR). All isolates from the experimental goats were identical in their restriction patterns to the original BA-1 and were similar to the reference E/CH strains of CpHV-1.

Animals↗

Band-shaped and whorled microcystic dystrophy of the corneal epithelium.

OBJECTIVE: To report the clinical, histopathologic, and electron microscopic features of band-shaped and whorled microcystic corneal epithelial dystrophy. DESIGN: Two interventional case reports. PARTICIPANTS: Two patients, two eyes. INTERVENTION: The involved area of corneal epithelium was scraped from each cornea. RESULTS: Histopathologic examination showed microscopic vacuoles in the epithelial cytoplasm in both cases. Electron microscopic examination revealed mainly empty cytoplasmic vacuoles with scant nonspecific osmophilic material. The process recurred clinically in one patient. Changes in corneal topography are documented in one patient. CONCLUSION: Clinical findings and pathologic studies seem nearly identical to those in the original report. No pattern of systemic disorder or medication use was found. The cause of this condition remains unknown.

Aged↗

Masked bilateral superior oblique muscle paresis. A simple overcorrection phenomenon?

OBJECTIVE: This study aimed to determine a mechanism by which the masked bilateral superior oblique muscle paresis phenomenon may be explained. DESIGN: A retrospective study of the authors' patients with the preoperative diagnosis of a unilateral superior oblique muscle paresis was performed. Patients in whom an apparent contralateral superior oblique muscle paresis developed after surgery (masked bilateral superior oblique muscle paresis) were compared with those patients in whom this condition did not develop. PARTICIPANTS: One hundred eight patients participated. RESULTS: Of the 108 patients studied, 30 (27.7%) patients had signs of an apparent superior oblique muscle paresis develop in the contralateral eye after surgery. In comparing those patients in whom an apparent contralateral superior oblique muscle paresis did develop after surgery with those patients in whom this finding did not develop, no significant differences were found in the age at surgery; etiology (traumatic vs. nontraumatic); average hyperdeviations in primary gaze, ipsilateral and contralateral gazes, and ipsilateral and contralateral head tilts; average V pattern; inferior and superior oblique muscle function; extorsion on double Maddox rod testing; and objective fundus extorsion. CONCLUSION: Analysis of the authors' data showed that a surgical overcorrection of a unilateral superior oblique muscle paresis can masquerade as an apparent contralateral superior oblique muscle paresis. This is caused by a persistence of the head tilt and side gaze misalignment pattern from the original superior oblique muscle paresis.

Adult↗

Molecular analysis of nematode diversity and the evolution of parasitism.

A thorough and coherent classification of the phylum Nematoda is essential if the evolution of countless phenotypes is to be understood. Here, Mark Dorris, Paul De Ley and Mark Blaxter discuss how the application of molecular phylogenetics is helping to resolve some of the inconsistencies in morphological classification and phylogeny by establishing relationships between free-living and parasitic groups, showing possible patterns underlying the origins of parasitism and placing key nematode species in an evolutionary context for comparative study.

Animals↗

The morphologic and biologic patterns of chemically induced pancreatic adenocarcinoma in Syrian golden hamsters after homologous transplantation.

A pancreatic adenocarcinoma induced by N-nitrosobis(2-oxopropyl)amine in the Syrian golden hamster was successfully transplanted to a homologous host by subcutaneous inoculation through 10 successive passages. The rate of 'tumor take' increased progressively with each generation from 60% to 100%, and the latency period after inoculation was reduced simultaneously from 6 weeks to 1 week in the second and following passages. The tumors grew rapidly, ulcerated the overlying skin, and metastasized to the regional lymph nodes and lungs. The animals usually died with multiple lung metastases between the 5th and 20th weeks. All transplanted tumors and their metastases retained the pattern of the original, well-differentiated adenocarcinomas.

Adenocarcinoma↗

Mechanisms and management of an incomplete epidural block for cesarean section.

Epidural blockade is an important option for anesthesia in parturients undergoing abdominal delivery. Despite the multiple benefits of this method, there is at least one significant downside--a relatively high occurrence of unsatisfactory anesthesia that requires intervention. Depending on the presumed mechanism of epidural block failure and other clinically relevant factors (e.g., timing of diagnosis, urgency of the procedure, and so forth), certain effective measures are recommended to successfully manage this demanding situation. In general, it is important to make every effort to make the pre-existing epidural effective or replace it with another regional technique, because overall, regional anesthesia is associated with significantly lower maternal mortality. It is important to identify a dysfunctional epidural block preoperatively before a maximum volume of local anesthetic has been administered. If catheter manipulation does not produce substantial improvement, and there is no time constraint, it is safe and reasonable to replace the epidural catheter. However, risks associated with excessive volume of local anesthetic should be kept in mind. Additional epidural injections or a second catheter placement might be considered under special circumstances. Single-shot spinal anesthesia after a failed epidural may provide fast onset and reliable surgical anesthesia. Available data, although limited and contradictory, suggest the possibility of unpredictably high or total spinal anesthesia. Many authors, however, believe that appropriate precautions and modifications in technique make this a safe alternative. These modifications include limiting the amount of epidural local anesthetic administered when diagnosing a nonfunctioning epidural and decreasing the dose of intrathecal local anesthetic by 20% to 30%. If there is no documented block when the spinal is inserted, and more than 30 minutes have passed from the last epidural dose, it is probably safe to use a normal dose of local anesthetic. Continuous spinal anesthesia with a macro catheter might be a dependable alternative, particularly if large amounts of local anesthetic have already been used or the patient's airway is a cause for concern. Although there are no reports of combined spinal epidural anesthesia being used in this context, it would appear to be an attractive alternative. It allows the anesthesiologist to give smaller doses intrathecally, while still offering the flexibility of augmenting the block if needed. When inadequate epidural block becomes apparent during surgery there are limited alternatives. Depending on the origin and the pattern of inadequate anesthesia, options may include psychological support, supplementation with a variety of inhalational and intravenous agents, and local anesthetic infiltration. Induction of general anesthesia is typically left as a backup option, but must be strongly considered if the patient continues to have pain/discomfort.

Anesthesia, Epidural↗

Molecular and clinical studies of Polish patients with Prader-Willi syndrome.

A group of 30 patients clinically described as having the Prader-Willi Syndrome (PWS) were studied using microsatellites from 15q11-13 and methylation analysis with probe PW71B (D15S63). The patients were categorized according to clinical symptoms. 80% of all patients were informative using molecular and cytogenetic methods. Among 8 patients with an atypical PWS phenotype, 2 showed uniparental disomy, and 2 had a mosaic deletion for 15q. The last 4 atypical and 2 typical patients had neither molecular defects confirmed by microsatellite analysis nor a parent-of-origin-specific methylation pattern for PWS. Our results confirm that methylation pattern analysis provides an additional and alternative microsatellite analysis to diagnose PWS.

Adolescent↗

An examination of similarity neighbourhoods in young children's receptive vocabularies.

Based on an analysis of similarity neighbourhoods of worlds in children's lexicons, Dollaghan (1994) argues that because of the degree of phonological overlap among lexical items in memory, children must perform detailed acoustic-phonetic analyses in order to recognize spoken words. This is in contradiction to Charles-Luce & Luce (1990), who reported that the similarity neighbourhoods in younger children's expressive lexicons are sparse relative to older children's and adult lexicons and that young children may be able to use more global word recognition strategies. The current investigation re-examined these issues. Similarity neighbourhoods of young children's receptive vocabularies were analysed for three-phoneme, four-phoneme and five-phoneme words. The pattern of the original results from Charles-Luce & Luce (1990) was replicated.

Child↗

Intracellular UDP-N-acetylhexosamine pool affects N-glycan complexity: a mechanism of ammonium action on protein glycosylation.

Understanding the mechanisms by which ammonium ions affect glycosylation may suggest strategies for producing glycoproteins with homogeneous biological activity in the presence of undesirable byproducts of cellular energy metabolism. We have previously shown that ammonium ions cause an increase in the intracellular UDP-N-acetylhexosamine (UDPGNAc) pool, which may be responsible for the ammonium-induced increase in complexity and decrease in sialylation state of the N-linked oligosaccharide. To investigate this novel hypothesis, we induced an artificial increase in UDPGNAc pool by treating recombinant BHK cells expressing an IL-2 variant that features an artificial site for N-glycosylation, with glucosamine (1:2 molar ratio to glucose) and uridine (2 mmol L-1) in the absence of ammonium ions or glutamine. The product fractions collected during this treatment showed increased antennarity compared to product collected under control conditions. When this pool was returned to normal levels, the glycosylation pattern regained its original (control) features. However, the sialylation state remained unaffected, suggesting that the decreased sialylation observed under ammonium treatment is due to a different mechanism of action, possibly involving changes in intracellular pH. By pretreating the cells with 0.5 mmol L-1 adenosine, and exposing them continuously to NH4Cl and adenosine we were able to prevent the ammonium-induced increase in UDPGNAc. Product fractions collected during this treatment showed unchanged antennarity but decreased sialylation of the N-linked oligosaccharide, thus conclusively demonstrating that ammonium ions act on protein glycosylation by at least two independent mechanisms, one of which involves an increase in the UDPGNAc pool.

Animals↗

Liquid-phase parallel synthesis of combinatorial libraries of substituted 6-carbamoyl-3,4-dihydro-2H-benzo[1,4]thiazines.

In this work, we explored several original combinatorial derivatization patterns for the 3,4-dihydro-2H-1,4-benzothiazine scaffold. The synthesis begins with commercially available 4-chloro- and 4-fluoro-3-nitrobenzoates and employs a sequence of moderate and high-yielding reactions that display a relatively high substituent tolerance. Simple manual techniques for parallel reactions were coupled with easy workup and purification procedures to give high-purity final products. The developed approach was easily adaptable for parallel synthesis of more than 2600 novel 2H-benzo[1,4]thiazine-6-carboxylic acid amides, which were efficiently prepared in a semiautomatic fashion using special CombiSyn synthesizers.

Chromatography, Liquid↗

Transcription of prostanoid receptor genes and cyclooxygenase enzyme genes in cultivated human iridial melanocytes from eyes of different colours.

Several prostaglandin analogues used for glaucoma treatment have been shown to cause increased iridial pigmentation as side-effect. In the present study we identified the types of prostanoid receptors and cyclooxygenase (COX) enzymes that are expressed in human iridial melanocytes isolated from eyes of different colours. Iris specimens were obtained during trabeculectomy surgery, or from enucleated eyes, and the iridial melanocytes were isolated and cultivated. The transcription of the DP, EP1, EP2, EP3, EP4, FP, IP and TP prostanoid receptor genes as well as the COX-1 and COX-2 enzyme genes was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR). Of the prostanoid receptors the FP receptor gene was found to be most consistently transcribed in the melanocytes isolated from both blue- and hazel-coloured eyes. No RNA of the DP, EP2 and TP receptor genes could be detected, whereas the EP1, EP3, EP4 and IP receptor genes were found to be transcribed in melanocytes from some eyes. The COX-2 gene was found to be transcribed, but the COX-1 gene less consistently. There was no difference in gene transcription pattern between melanocytes originating from eyes treated with latanoprost, and eyes not previously treated with the prostaglandin. These results indicate that the FP prostanoid receptor gene is transcribed in cultivated human iridial melanocytes of both blue and hazel eyes, whereas the other prostanoid receptor genes seem to be transcribed much less frequently, or not at all. Surprisingly, the COX-2 rather than the COX-1 gene, was found to be transcribed in the melanocytes.

Aged↗

Episodic inhibition.

Six experiments examined the proposal that an item of long-term knowledge can be simultaneously inhibited and activated. In 2 directed forgetting experiments items to-be-forgotten were found to be inhibited in list-cued recall but activated in lexical decision tasks. In 3 retrieval practice experiments, unpracticed items from practiced categories were found to be inhibited in category-cued recall but were primed in lexical decision. If, however, the primes and targets in lexical decision were taken directly from the study list, inhibition was observed. Finally, it was found that when items highly associated with a study list were processed in between study and test, no inhibition in recall was present. These, and a broad range of other findings, can be explained by the concept of "episodic inhibition," which proposes that episodic memories retain copies of semantic knowledge structures that preserve patterns of activation/inhibition originally generated in those structures during encoding. ((c) 2006 APA, all rights reserved).

Adolescent↗

Childhood cancer and ethnic group in Britain: a United Kingdom children's Cancer Study Group (UKCCSG) study.

We present here the results of the largest study of childhood cancer and ethnic group in Britain, based on 7,658 children treated at paediatric oncology centres throughout the country. Incidence rates could not be calculated and so relative frequencies were analysed by the log-linear modelling method of Kaldor et al. (1990) with allowance made for regional variations in the ages and diagnostic groups of the children included in the study. Children of Asian (Indian sub-continent) and West Indian ethnic origin had similar patterns of incidence for acute lymphoblastic leukaemia to White Caucasians. There was a significant excess of Hodgkin's disease among Asian children compared with Caucasians with an estimated relative risk (RR) of 2.09; this excess was greatest in the 0-4 age group (RR = 6.67). There were significant deficits of Wilms' tumour and rhabdomyosarcoma among Asian children, each with a frequency around half that among Caucasians, whereas West Indians had a significant excess of Wilms' tumour (RR = 2.55). Asian and West Indian children each had a non-significant twofold RR for unilateral retinoblastoma. The results suggest that the incidence of childhood acute lymphoblastic leukaemia is associated with environmental determinants in the country of residence which are most likely to relate to lifestyle factors. The occurrence of retinoblastoma, Wilms' tumour and Hodgkin's disease in early childhood is apparently related more to ethnicity than to geographical location and may reflect genetic factors or environmental exposures specific to the lifestyle of particular ethnic groups.

Central Nervous System Neoplasms↗

Expansion of satellite DNAs derived from transposable elements in beetles with reduced diploid numbers.

Repetitive DNA sequences are ubiquitous in eukaryotic genomes, significantly influencing their structure, function, and evolution. They can facilitate genomic rearrangements, contributing to chromosomal and genomic diversity. Chrysomelidae (Coleoptera) beetles are known for their highly diverse karyotypes and heterochromatin distribution. In this study, we advanced the understanding of the intricate relationship between satellite DNA-like sequences (named here solely as satDNA) and genome organization/reshuffling using three species of Eumolpinae chrysomelids. We investigated the satellitomes of three species with divergent karyotypes that had undergone independent chromosomal fusions: Colaspis laeta (2n&#x2009;=&#x2009;22, Xyp), with a conserved karyotype; Endocephalus bigatus (2n&#x2009;=&#x2009;10, neo-XY); and Iphimeis dives (2n&#x2009;=&#x2009;14, neo-XY). Our comparative analysis revealed highly divergent patterns of satDNA origin, organization, and evolution. In species with reduced chromosome numbers and neo-sex chromosomes, we observed a high abundance of transposable element-related (TE-related) satDNAs. In Colaspis laeta, the sex chromosomes (Xyp) showed an advanced level of differentiation. However, in the species with a reduction in diploid number, such a level of differential enrichment of repetitive DNAs was not observed in the sex chromosomes, indicating an early stage of differentiation. Our findings support the hypothesis that chromosomal rearrangements and reorganization of repetitive DNA sequences are connected, with extensive reshuffling observed in species with reduced diploid numbers. Moreover, the data reinforce the involvement of TEs in satDNA origin, which could spread widely throughout the genome, including euchromatic areas. This study provides new insights into the evolutionary dynamics of repetitive DNAs in non-model species, emphasizing the impact of chromosomal rearrangements on genome architecture and evolution.

Animals↗

mtDNA hypervariable region II (HVII) sequences in human evolution studies.

Variation in human mitochondrial DNA (mtDNA) has been used to infer the origin and migration patterns in human populations. mtDNA analysis has been focused mainly on the first hypervariable region (HVI). Nevertheless, although many studies of the second hypervariable region (HVII) have been carried out during recent years, the correlation between the first and the second hypervariable regions has not been well established. We have analysed 71 individuals from a relatively isolated region at the westernmost edge of continental Europe (Galicia, NW Iberian peninsula) and we have used available HVII sequence information from another 17 European and African populations. The results show high concordance between the two hypervariable regions, not only in variability levels but also in other phylogenetic aspects. The study of the population structure through an AMOVA analysis shows a low level of heterogeneity in the European populations. Nevertheless, we have found some inconsistency in the results, which are related to the mutation rate in these two hypervariable regions. These results are compatible with a high heterogeneity of mutation rates across the HVII region and stress the interest of HVII in population and forensic genetics.

Base Sequence↗