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Reliability of stimulated and spontaneous growth hormone (GH) levels for identifying the child with low GH secretion.

The reliability of stimulated and spontaneous GH levels for identifying the child with low GH secretion has been the subject of debate. We compared the ability of GH concentrations after pharmacological stimulation with levodopa and clonidine and of spontaneous peak and 12-h pooled GH concentrations during sleep on a single night to estimate the maximum spontaneous GH secretion from 2 nights in 55 children, aged 5-16 yr, with heights below the 3rd percentile and/or height velocities below the 25th percentile for age, who had two consecutive overnight GH secretory profiles. Maximum stimulated GH concentrations correctly categorized 80% of children who had maximum spontaneous GH concentrations above and below 4 micrograms/L using a double monoclonal immunoradiometric assay for GH (Tandem-R HGH, Hybritech). The remaining 20% of children had stimulated GH concentrations below but spontaneous GH concentrations above 4 micrograms/L. Using this cut-off, the maximum GH concentrations from the first and second nights correctly categorized 98% and 95% of the children, respectively. Night to night variation in GH secretion was low in children who had low spontaneous GH secretion (maximum spontaneous peak and pool GH concentrations, less than 4 and less than or equal to 0.7 micrograms/L, respectively), and pooled GH concentrations from the 2 nights were concordant in 98% of the cases. We conclude that it is not uncommon for stimulated GH concentrations to underestimate spontaneous GH secretion. Even without acclimatization to the hospital setting, measurement of spontaneous GH secretion on a single night was more reliable for identifying the child with low endogenous GH secretion than was GH stimulation testing alone.

Adolescent↗

Absence of protease-resistant prion protein in the cerebrospinal fluid of Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD), believed to be caused by a protease-resistant isoform of prion protein (PrP(Sc)), usually manifests itself as a clinically distinctive age-related dementia because of its rapid progression, occasionally accompanied by cerebellar ataxia. Recently, a variant CJD (vCJD) has been described, which has prominent early psychiatric symptoms and an earlier age of death. Although cerebrospinal fluid (CSF) is part of the extracellular fluid of the central nervous system (CNS), the bulk of its proteins are derived from the plasma and there is increasing concern about possible transmission of prion disease by blood. As investigation of CSF has played a significant role in the diagnosis and management of several neurological diseases, it was decided to characterize PrP present in the CSF of CJD individuals. Significant variation was observed in the level of PrP in the CSF from both non-CJD and CJD (including vCJD) patients, and the detected PrP forms are protease-sensitive. Using a conformation-dependent immunoassay, it was further demonstrated that the PrP detected in the CSF from CJD patients was broadly similar in conformation to that found in non-CJD patients. Taken together, the results of this study fail to demonstrate any correlation between the presence of protease-resistant PrP isoform (PrP(Sc)) in the CSF and disease manifestation.

Creutzfeldt-Jakob Syndrome↗

Effects of size and locomotor adaptations on the hominid pelvis: evaluation of australopithecine bipedality with a new multivariate method.

Three pelves and eight innominate bones belonging to the fossil species, Australopithecus africanus, Australopithecus robustus, Homo erectus, and Homo sapiens, have been studied biometrically and compared with those of recent humans and apes. A new method of logarithmic factorial analysis suppresses both the size effects and the size reference on pelvic proportions. In combination with principal component analysis it allows specializations to be dissociated from allometrical variations. Some morphological differences on the hominid pelvis prove to be mainly allometric. However, the pelvic morphology of australopithecines is clearly differentiated from that of the genus Homo (including H. erectus, OH 28, KNMER 3227). A. africanus (Sts 14, MLD 7, AL 288) is nearer the humans than is A. robustus (SK 50, SK 3155), which appears to be more specialized in the australopithecine lineage. The pelvic morphology of A. africanus, as integrated with the articular pelvic-femoral link, appears to be biometrically equivalent to that of humans.

Animals↗

Noise robustness of nonlinear filters for image recognition.

We analyze the performance of the Fourier plane nonlinear filters in terms of signal-to-noise ratio (SNR). We obtain a range of nonlinearities for which SNR is robust to the variations in input-noise bandwidth. This is shown both by analytical estimates of the SNR for nonlinear filters and by experimental simulations. Specifically, we analyze the SNR when Fourier plane nonlinearity is applied to the input signal. Using the Karhunen-Loève series expansion of the noise process, we obtain precise analytic expressions of the SNR for Fourier plane nonlinear filters in the presence of various types of additive-noise processes. We find a range of nonlinearities that need to be applied that keep the output SNR of the filter stable relative to changes in the noise bandwidth.

Journal Article↗

The CT motion quantitation of lung lesions and its impact on PET-measured SUVs.

UNLABELLED: We previously reported that respiratory motion is a major source of error in quantitation of lesion activity using combined PET/CT units. CT acquisition of the lesion occurs in seconds, rather than the 4-6 min required for PET emission scans. Therefore, an incongruent lesion position during CT acquisition will bias activity estimates using PET. In this study, we systematically analyzed the range of activity concentration changes, hence SUV, for lung lesions. METHODS: Five lung cancer patients were scanned with PET/CT. In CT, data were acquired in correlation with the real-time positioning. CT images were acquired, in cine mode, at 0.45-s intervals for slightly longer (1 s) than a full respiratory cycle at each couch position. Other scanning parameters were a 0.5-s gantry rotation, 140 kVp, 175 mA, 10-mm couch increments, and a 2.5-mm slice thickness. PET data were acquired after intravenous injection of about 444-555 MBq of (18)F-FDG with a 1-h uptake period. The scanning time was 3 min per bed position for PET. Regularity in breathing was assisted by audio coaching. A commercial software program was then used to sort the acquired CT images into 10 phases, with 0% corresponding to end of inspiration (EI) and 50% corresponding to end of expiration (EE). Using the respiration-correlated CT data, images were rebinned to match the PET slice locations and thickness. RESULTS: We analyzed 8 lesions from 5 patients. Reconstructed PET emission data showed up to a 24% variation in the lesion maximum standardized uptake values (SUVs) between EI and EE phases. Examination of all the phases showed an SUV variation of up to 30%. Also, in some cases the lesion showed up to a 9-mm shift in location and up to a 21% reduction in size when measured from PET during the EI phase, compared with during the EE phase. CONCLUSION: Using respiration-correlated CT for attenuation correction, we were able to quantitate the fluctuations in PET SUVs. Because those changes may lead to estimates of lower SUVs, the respiratory phase during CT transmission scanning needs to be measured or lung motion has to be regulated for imaging lung cancer in routine clinical practice.

Aged↗

Identification and antigenic site analysis of foot-and-mouth disease virus from pigs and cattle in Korea.

From May to June 2002, a total of 16 foot-and mouth disease (FMD) outbreaks due to the serotype O virus, Pan Asia strain, were recorded in Korea. The viruses were identified by antigen ELISA, RT-PCR and sequence analysis. The overall nucleotide sequence divergence of the VP1 region among the 4 isolates in 2002 was 0 to 1.4%, but between O/SKR/2002 and O/SKR/2000 isolates was 1.9-4.9%. Phylogenetic analysis with the some known strains from East Asian countries showed that the 4 Korean isolates in 2002 formed one distinct cluster, which different from clusters of Korean isolates in 2000, with in the same lineage of the ME-SA topotype strains. Deduced amino acid sequences around neutralizable antigenic site on VP1 site of O/SKR/2002 isolates were aligned and compared with other strains. At the antigenic site 1, the replacements of the critical amino acid residues at position 144 from V to L and at position 152 from A to T were observed in O/SKR/2002 viruses. For antigenic site 2 and 4, there were not significant variations in general. At the antigenic site 3, the substitutions of amino acid residues were present at positions 54 and 56 in O/SKR/2002 isolates and an alternative residue I at position 54 are observed only at the sequence of O/SKR/AS/2002 (cow) virus. And the substitution (L-->P) of significant residue at position 144 was detected at the amino acid sequence of the O/SKR/2002 (cow) virus.

Amino Acid Sequence↗

Shape variation in the mandibular symphysis of apes: an application of a median axis method.

Symphyseal contours in a sample of living and fossil apes were assessed by application of the line skeleton, a form of median axis transformation. While the line skeleton offers novel opportunities for the analysis of shape, this study reaffirms previous observations that the shape of the symphysis is highly variable within great ape species, such that symphyseal morphology is not useful as a taxonomic marker. There is also little indication that symphyseal shape differs significantly between the sexes. The perception of what constitutes a salient superior or inferior transverse torus among living apes appears to be dependent on the expression of the genioglossal fossa.

Algorithms↗

Theoretical approach to evaluate thermodiffusion in aqueous alkanol solutions.

Flow due to thermodiffusion may change direction in fluid mixtures with the variation of composition and temperature. This occurrence remains an unraveled phenomenon in petroleum research. Using a modified theoretical approach, this paper evaluates the thermal diffusion factor in alkanol water mixtures, including methanol, ethanol, and isopropanol aqueous mixtures. By combining this approach with an equation of state perturbed chain statistical associating fluid theory and using two adjustable parameters calculated from experimental data, the present approach provides a good agreement for the prediction of thermal diffusion in alkanol water mixtures when compared with the available experimental data. This work reveals that the thermodiffusion in infinite dilutions may play an important role in understanding the thermodiffusion phenomena.

Journal Article↗

Number of ancestral human species: a molecular perspective.

Despite the remarkable developments in molecular biology over the past three decades, anthropological genetics has had only limited impact on systematics in human evolution. Genetics offers the opportunity to objectively test taxonomies based on morphology and may be used to supplement conventional approaches to hominid systematics. Our analyses, examining chromosomes and 46 estimates of genetic distance, indicate there may have been only around 4 species on the direct line to modern humans and 5 species in total. This contrasts with current taxonomies recognising up to 23 species. The genetic proximity of humans and chimpanzees has been used to suggest these species are congeneric. Our analysis of genetic distances between them is consistent with this proposal. It is time that chimpanzees, living humans and all fossil humans be classified in Homo. The creation of new genera can no longer be a solution to the complexities of fossil morphologies. Published genetic distances between common chimpanzees and bonobos, along with evidence for interbreeding, suggest they should be assigned to a single species. The short distance between humans and chimpanzees also places a strict limit on the number of possible evolutionary 'side branches' that might be recognised on the human lineage. All fossil taxa were genetically very close to each other and likely to have been below congeneric genetic distances seen for many mammals. Our estimates of genetic divergence suggest that periods of around 2 million years are required to produce sufficient genetic distance to represent speciation. Therefore, Neanderthals and so-called H. erectus were genetically so close to contemporary H. sapiens they were unlikely to have been separate species. Thus, it is likely there was only one species of human (H. sapiens) for most of the last 2 million years. We estimate the divergence time of H. sapiens from 16 genetic distances to be around 1.7 Ma which is consistent with evidence for the earliest migration out of Africa. These findings call into question the mitochondrial "African Eve" hypothesis based on a far more recent origin for H. sapiens and show that humans did not go through a bottleneck in their recent evolutionary history. Given the large offset in evolutionary rates of molecules and morphology seen in human evolution, Homo species are likely to be characterised by high levels of morphological variation and low levels of genetic variability. Thus, molecular data suggest the limits for intraspecific morphological variation used by many palaeoanthropologists have been set too low. The role of phenotypic plasticity has been greatly underestimated in human evolution. We call into question the use of mtDNA for studies of human evolution. This DNA is under strong selection, which violates the assumption of selective neutrality. This issue should be addressed by geneticists, including a reassessment of its use for molecular clocks. There is a need for greater cooperation between palaeoanthropologists and anthropological geneticists to better understand human evolution and to bring palaeoanthropology into the mainstream of evolutionary biology.

Animals↗

Associations in the hominoid facial skeleton.

A comparative study has been made of the correlations between numerous linear and angular dimensions of the facial skeleton of man and the three great apes. The Varimax (rotated orthogonal) factor analysis was found to be an essential aid in analysing the very large correlation matrices obtained. It indicated that three groups of association can be identified in the hominoid skull. The first reflects co-ordonated variation in total skull size; the second, co-ordinated variation within common anatomical regions; the third, co-ordination between the jaws and dentition. A broadly similar pattern was found in each group for all four genera. The principal contrasts between man, on the one hand, and the apes, on the other, were found in groups 1 and 2. The most prominent of these was a generally much tighter degree of association between the size and position of upper and lower jaws in the apes, and a consequently reduced tendency for disruption of the occlusal relationship of the teeth.

Animals↗

Ongoing mutation in MALT lymphoma immunoglobulin gene suggests that antigen stimulation plays a role in the clonal expansion.

Indirect antigenic stimulation by H. pylori-specific T cells is implicated in the development of low-grade gastric lymphoma of mucosa-associated lymphoid tissue (MALT), however, the role of direct antigen stimulation is unknown. To study the role of direct antigen stimulation in MALT lymphomagenesis and its relationship with the pathogenesis of distinct pathological lesions, which represent different stages of the tumour progression, we cloned and sequenced the rearranged immunoglobulin (Ig) heavy chain gene in three low-grade (two from the lung, one from the stomach) and one high-grade (from the stomach) cases. In the low-grade gastric case, we studied the Ig sequence in primary as well as its disseminated and recurrent tumours. In the high-grade gastric case, we analysed the Ig sequence in tumour cell populations microdissected from the residual diffuse low-grade lesions, diffuse high-grade areas from follicles colonized by high-grade blasts. Compared with the published germline sequences, the heavy chain variable (VH) genes of three MALT lymphomas, in which the putative germline was identified, contained frequent somatic mutations, showing a much higher ratio of replacement/silent mutations in the complementarity determining regions (CDRs) than the framework regions (FRs). Ongoing mutation as indicated by intraclonal variation of the Ig sequence clearly existed in low-grade tumour including its dissemination and recurrence, but was not evident in high-grade tumour cell populations including those microdissected from independent colonized follicles. In addition, the germlines of VH genes used by the three MALT lymphomas are frequently found in autoreactive antibodies. Our results suggest that MALT lymphoma derives from postgerminal centre memory B cells, possibly autoreactive B cell clones, and that direct antigen stimulation may play an important role in the clonal expansion of low-grade MALT lymphoma.

Animals↗

Ontogeny of locomotion in mountain gorillas and chimpanzees.

The African apes are a group of closely related taxa that differ considerably in body size. In spite of the large body size difference, the African apes are similar in many aspects of their morphology; it has been suggested that most of their differences result from selection for these body size differences (Shea, 1988). The influence of body size on locomotion has been well-documented, but what is less clear, is whether these behavioral differences occur throughout ontogeny because few studies have directly addressed the influence of ontogeny (and changing body size) on locomotion. This study documents the ontogeny of mountain gorilla locomotion and compares it with that of chimpanzees in order to consider how changing body size during ontogeny influences locomotion in the two species. Results indicate that gorilla locomotor development is greatly accelerated compared with chimpanzees, and that much of the interspecific variation in age can be explained by body size. When chimpanzees and gorillas are at similar sizes (although widely disparate ages), they perform very similar locomotor activities. However, it is incorrect to view a gorilla as a faster growing and ultimately larger chimpanzee. Throughout ontogeny, gorillas have broader scapulae and relatively shorter phalanges and metacarpals than chimpanzees (Susman, 1979; Shea, 1981; Jungers & Susman, 1984; Inouye, 1992) which are associated differences in mountain gorilla and chimpanzee suspensory behavior; gorillas never show as high an incidence of suspensory behavior as chimpanzees during ontogeny.

Aging↗

The 5-HT transporter gene-linked polymorphic region (5-HTTLPR) in evolutionary perspective: alternative biallelic variation in rhesus monkeys. Rapid communication.

By conferring allele-specific transcriptional activity on the 5-HT transporter gene promoter in humans, the 5-HT transporter gene-linked polymorphic region (5-HTTLPR) influences a constellation of personality traits related to anxiety and increases the risk for neurodevelopmental, neurodegenerative, and psychiatric disorders. Here we have analyzed the presence and variability of the 5-HTTLPR in several species of primates including humans, and other mammals. PCR, Southern blot, and sequence analyses of the 5-HT transporter gene's 5'-flanking region in different mammalian species confirmed the presence of the 5-HTTLPR in platyrrhini and catarrhini (hominoids, cercopithecoids) but not in prosimian primates and other mammals. Since the 5-HTTLPR is unique to humans and simian primates, a progenitor 5-HTTLPR sequence may have been introduced into the genome some 40 Mio, years ago. In humans the majority of alleles are composed of either 14 or 16 repeat elements, while alleles with 18 or 20 repeat elements are rare. In contrast, great apes including orang-utan, gorilla, and chimpanzee display a high prevalence of alleles with 18 and 20 repeat elements. In hominoids all alleles originate from variation at a single locus (polymorphic locus 1). In the 5-HTTLPR of rhesus monkeys (rh5-HTTLPR) we found an alternative locus for length variation (polymorphic locus 2) generated by a 21 bp insertion/deletion event. The existence of a distinct biallelic variation of the 5-HTTLPR in rhesus monkeys but similar allele and genotype frequencies in this species and humans supports the notion that there may be a relationship between functional 5-HT transporter expression, anxiety-related traits, and the complexity of socialization in human and non-human primate populations.

Alleles↗

Patterns of size sexual dimorphism in Australopithecus afarensis: another look.

Size sexual dimorphism is one of the major components of morphological variation and has been associated with socio-ecology and behavioral variables such as mating patterns. Although several studies have addressed the magnitude and pattern of sexual dimorphism in Australopithecus afarensis, one of the earliest hominids, consensus has yet to be reached. This paper uses assigned re-sampling method, a data re-sampling method to estimate the magnitude of sexual dimorphism without relying on individual sex assessments, to examine the fossil hominid sample from Hadar. Two questions are asked: first, whether sexual dimorphism in a selected sample of skeletal elements of A. afarensis is the same as that in living humans, chimpanzees, or gorillas; and second, whether different skeletal elements reflect variation in sexual dimorphism in the same way. All possible metric variables were used as data in applying the method, including seven variables from three elements (mandibular canine, humerus, femur). Analyses show that A. afarensis is similar in size sexual dimorphism to gorillas in femoral variables, to humans in humeral variables, and to chimpanzees in canine variables. The results of this study are compatible with the hypothesis that the pattern of sexual dimorphism in A. afarensis is different from any that are observed in living humans or apes.

Animals↗

Mortality rates among wild chimpanzees.

In order to compare evolved human and chimpanzees' life histories we present a synthetic life table for free-living chimpanzees, derived from data collected in five study populations (Gombe, Taï, Kibale, Mahale, Bossou). The combined data from all populations represent 3711 chimpanzee years at risk and 278 deaths. Males show higher mortality than females and data suggest some inter-site variation in mortality. Despite this variation, however, wild chimpanzees generally have a life expectancy at birth of less than 15 years and mean adult lifespan (after sexual maturity) is only about 15 years. This is considerably lower survival than that reported for chimpanzees in zoos or captive breeding colonies, or that measured among modern human hunter-gatherers. The low mortality rate of human foragers relative to chimpanzees in the early adult years may partially explain why humans have evolved to senesce later than chimpanzees, and have a longer juvenile period.

Animals↗

Technical efficiency of nursing units in a tertiary care hospital in Taiwan.

The variation in productivity and cost efficiency has been observed among 57 nursing units in a large tertiary care hospital. The inefficient units can achieve the same level of efficiency as the efficient units by altering their inputs (either nursing hours or patient costs). The optimization can be achieved through proper reallocations of nursing resources such as nursing hours or costs. However, the resource reallocation to achieve high efficiency should not be at the expense of quality of care. Future efficiency studies should incorporate the nursing sensitive measures of quality in the analysis.

Data Collection↗

Insights into the Holley- and Joseph- phenotypes.

BACKGROUND: The Dombrock blood group system consists of two antithetical antigens (Do(a) and Do(b)) and three high-incidence antigens (Gregory [Gy(a)], Holley [Hy], and Joseph [Jo(a)]). Hy and Jo(a) have an unusual phenotypic relationship. All Hy- RBCs are Jo(a-), but not all Jo(a-) RBCs are Hy-. The molecular background associated with Hy- and Jo(a-) phenotypes is reported. STUDY DESIGN AND METHODS: DNA from 18 probands with Gy(a+(w)) Hy- Jo(a-) RBCs (Hy- phenotype) and from 13 probands with Gy(a+) Hy+(w) Jo(a-) RBCs (Jo[a-] phenotype) was tested. RESULTS: Sequencing and PCR-RFLP revealed 323 G>T (Gly 108Val) and 378 T>C (silent mutation) changes on a DOB background (HY) associated with the Hy- samples. The sister of the original Hy- proband and the majority of samples had an additional mutation of 898 C>G (Leu300Val) (HY1); others had 898C (300Leu) (HY2). In the Jo(a-) phenotype, there is a 350 C>T (Thr1 17Ile) and a 378 C>T (silent mutation) change on a DOA background (JO). CONCLUSION: The results provide an explanation for the variation in typing results in antibody producers. The ablation of Jo(a) in the Hy- phenotype and the weakening of Hy in the Jo(a-) phenotype may be due to the close proximity of these antigens. The 898 C>G mutation, within the sequence motif for glycosylphosphatidylinositol linkage, may cause reduced efficiency of anchoring the protein to the RBC membrane, thereby weakening the expression of Gy(a) and Do(b).

Amino Acid Sequence↗

Nucleotide sequence analyses of human complement 6 (C6) gene suggest balancing selection.

The sixth complement component (C6) has a common charge polymorphism, C6A and C6B, with similar gene frequencies in all major populations. In addition, C6B2 is also found in Japanese populations at a frequency of about 6%. Sequence analyses of the coding region of three human and ape C6 alleles indicated four nonsynonymous and three synonymous changes in C6*B2 relative to C6*A, suggesting that a recombination event occurred between C6*B2 and C6*A to give rise to C6*B. Sequence variation in a 3.86 kb region encompassing exon 3, where the causal base change of the common C6 polymorphism is found, indicated that several single nucleotide polymorphisms (SNPs) were in extensive linkage disequilibrium (LD), with little differentiation among populations. Sliding window estimates of two test statistics for neutrality revealed significant values in a subregion where the replacement coding polymorphism resides, in all three human populations. These results raise the possibility that the two common C6 alleles in human populations are maintained by balancing selection.

Animals↗