bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement precision and normal range of endometrial thickness in a postmenopausal population by transvaginal ultrasound
Authors: Warming L. , Ravn P. , Skouby S. , Christiansen C.
Published: March 2003

Objectives

The aim of this study was to examine the endometrial thickness (ET) in an asymptomatic postmenopausal population, and to assess the long‐term variability.

Design

A total of 1182 asymptomatic generally healthy postmenopausal women were enrolled into this cross‐sectional evaluation of the ET. Measurements were performed by transvaginal ultrasound. A subset of the women (n = 178) was examined twice 3 months to 2 years apart to assess the long‐term variability.

Results

Cross‐sectionally, ET varied with length of menopause. During the first 5 years after menopause (YSM) the mean ET was 2.3 mm but it decreased by 0.03 mm/year (P < 0.01). From 5 to 13 YSM the ET remained stable at a mean of 1.8 mm with no significant changes (P = 0.13). Thereafter there was a minimal increase of 0.01 mm/year (P < 0.05). In order to minimize the influence of natural changes on ET, only women who had reached the menopause more than 5 years earlier were entered into the subsequent long‐term study. The mean ET was 2.0 mm ± 1.0 mm with no significant differences within or between the observers' measurements. The precision errors were less than 1 mm.

Conclusions

The normal range of the thickness of the postmenopausal endometrium in asymptomatic women varies with YSM. There is a high long‐term agreement within and between observers in measuring the ET. Copyright © 2002 International Society of Ultrasound in Obstetrics and Gynecology
Fetal duodenal obstructions: increased risk of prenatal sudden death
Authors: Brantberg A. , Blaas H‐G. K. , Salvesen K. Å. , Haugen S. E. , Møllerløkken G. , Eik‐Nes S. H.
Published: March 2003

Objectives

The aim of this study was to describe the outcome of fetuses with duodenal obstruction diagnosed prenatally and to compare the outcome with the results of studies of newborns.

Methods

All fetuses with a prenatal diagnosis of duodenal obstruction were registered and evaluated prospectively from January 1985 to December 2000.

Results

Duodenal obstruction was found in 29 fetuses at a mean gestational age of 29+2 weeks. Polyhydramnios was found in 24 cases (83%). Six fetuses (21%) had trisomy 21. Associated anomalies, including trisomy 21, were found in 18 cases (62%). Four fetuses with normal karyotype died in utero at 31–35 gestational weeks. Two of them had associated anomalies, but the anomalies could not explain the prenatal deaths and the deaths occurred suddenly and unexpectedly. Three infants died postnatally; all three had associated anomalies. Four infants with normal karyotype had neurological impairment suggesting that they might have had intrauterine asphyxia.

Conclusions

The present study indicates that duodenal obstruction is a more serious condition than previously believed, with an increased risk of prenatal asphyxia and death, even when the karyotype is normal and no associated anomalies are present. We consider the possibility that it could be caused by bradycardia/asystole following vagal overactivity due to distension of the upper gastrointestinal tract. Copyright © 2002 International Society of Ultrasound in Obstetrics and Gynecology
Scale development in zebrafish (Danio rerio)
Authors: SIRE JEAN‐YVES , ALLIZARD FRANCOISE , BABIAR OLIVIER , BOURGUIGNON JACQUELINE , QUILHAC ALEXANDRA
Published: March 2003

In the course of an extensive comparative, structural and developmental study of the cranial and postcranial dermal skeleton (teeth and scales) in osteichthyan fishes, we have undertaken investigations on scale development in zebrafish (Danio (Brachydanio) rerio) using alizarin red staining, and light and transmission electron microscopy. The main goal was to know whether zebrafish scales can be used as a model for further research on the processes controlling the development of the dermal skeleton in general, especially epithelial–mesenchymal interactions. Growth series of laboratory bred specimens were used to study in detail: (1) the relationship of scale appearance with size and age; (2) the squamation pattern; and (3) the events taking place in the epidermis and in the dermis, before and during scale initiation and formation, with the aim of searching for morphological indications of epithelial‐mesenchymal interactions. Scales form late in ontogeny, generally when zebrafish are more than 8.0 mm in standard length. Within a population of zebrafish of the same age scale appearance is related to standard length, but when comparing populations of different age the size of the fish at scale appearance is also related to age. Scales always appear first in the posterior region of the body and the squamation then extends anteriorly. Scales develop in the dermis but closely apposed to the epidermal–dermal boundary. Cellular modifications occurring in the basal layer of the epidermis and in the dermis before scale formation clearly indicate that the basal epidermal cells differentiate first, before any evidence of differentiation of the progenitors of the scale‐forming cells in the dermis. This strongly suggests that scale differentiation could be initiated by the epidermal basal layer cells which probably produce a molecular signal towards the dermis below. Subsequently dermal cells accumulate close to the epidermis, and differentiate to form scale papillae. The late formation of the scales during ontogeny is due to a late colonisation of the dermis by the progenitors of the scale‐forming cells. Because of their late formation during ontogeny and of their regular pattern of development, scales in zebrafish represent a good model for further investigations on the general mechanisms of epithelial‐mesenchymal interactions during dermal skeleton development, and in particular for the study of the gene expression patterns.
Morphometric study of glycine‐immunoreactive neurons and terminals in the rat cuneate nucleus
Authors: LUE J. H. , SHIEH W. F. , CHEN S. H. , SHIEH J. Y. , WEN C. Y.
Published: March 2003

The distribution of glycine‐immunoreactive (glycine‐IR) neurons and their associated axon terminals in the rat cuneate nucleus was studied using antiglycine postembedding immunoperoxidase labelling and immunogold staining, respectively. The immunoperoxidase‐labelled glycine‐IR neurons were widely distributed in the entire rostrocaudal extent of the nucleus. They made up 30.8% (9671/31368) of the neurons surveyed. Quantitative evaluation showed that the percentage of glycine‐IR neurons in the caudal level was significantly higher than that in the middle and rostral levels. The glycine‐IR neurons were small cells (mean area=198±1.9 μm2, n=2862) with ovoid or spindle‐shaped somata. Statistical analysis showed that the size of the glycine‐IR neurons in the rostral level was significantly smaller than that in the middle and caudal levels. Immunogold labelled glycine‐IR terminals which contained predominantly pleomorphic synaptic vesicles were mostly small (mean area=1.24±0.03 μm2, n=286) and they constituted 24.7% (286/1158) of the total terminals surveyed. They formed axodendritic, axosomatic and axoaxonic synapses with unlabelled elements. It is suggested from this study that glycine is one of the major neurotransmitters involved in the depression of synaptic transmission in the cuneate nucleus.
Variation in the apparent density of human mandibular bone with age and dental status
Authors: KINGSMILL V. J. , BOYDE A.
Published: March 2003

This study examines the variability in the anatomy of mandibles of differing ages and different stages of tooth loss. Mandibles from individuals between 19 and 96 y were sectioned into 2 mm thick vertical plane‐parallel slices and cleaned of marrow and periosteum. The apparent density (mass per unit volume in g/ml) from midline (MID) and mental foramen region (MF) sites was determined by weighing the slices and dividing by a volume calculated as the product of section thickness and the mean area of the 2 sides of the section. The cortical thickness of the inferior border and the basal and alveolar bone heights were measured in radiographs of the slices. Mandibular apparent density was negatively correlated with the cross sectional area (midline r=−0.48, mental foramen r=−0.45), and at the midline was significantly greater in edentulous than in dentate individuals (means (±s.e.m.) edentulous n=13: 1.43 (±0.07) g/ml; dentate n=17: 1.27 (±0.04) g/ml, P<0.05). Where a large enough age range was available, mandibular apparent bone density showed a significant increase with age (midline males: r=0.53, n=18) especially for dentate individuals (r=0.91, n=8). There was a correlation between the apparent densities at the two sites in the same mandible (r=0.64), with the values obtained for the midline being significantly greater than for the mental foramen region (midline 1.34 (±0.04) g/ml; mental foramen 1.19 (±0.04) g/ml, P<0.001, paired t test). The mandible shows great interindividual variability, but there may be a considerable reduction in cross sectional girth of the mandible following tooth loss, and, unlike postcranial sites, an increase in apparent density with age.
In situ detection of apoptotic cells by TUNEL in the gill epithelium of the developing brown trout (Salmo trutta)
Authors: ROJO M. C. , GONZALEZ M. E.
Published: March 2003

Apoptosis is a form of naturally occurring cell death during development and it is characterised by extensive DNA fragmentation. Apoptosis is easily detected in the gill epithelium of brown trout embryos in ultrathin sections (Rojo et al. 1997). Here we provide the first biochemical evidence for apoptosis in the gill epithelium of brown trout embryos, using in situ end‐labelling of DNA breaks (Gavrieli et al. 1992). Embryos at d 57 of development as well as those at hatching, were processed to analyse the distribution of apoptotic cells in the gills. The extent of apoptosis revealed by the terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick end‐labelling method technique is considerably greater than apoptosis detected by nuclear morphology. This method revealed that apoptosis was frequent at hatching, although it was also present during embryonic development. The presence and distribution of stained nuclei were different depending on the developmental stage. In embryos of 57 d, apoptotic flattened nuclei were dispersed in the gill epithelium, whereas at hatching, they were mainly grouped in the tips of the filaments and in the gill arches. TUNEL also revealed a distinct pattern of nuclear staining: at hatching, the intense staining covered the entire cell, but in embryos it was restricted to the nucleus. These results show the functional relevance of apoptosis at hatching, when apoptosis seems to be the unique process by which cell numbers in the gill epithelium are adjusted, in order to prepare for the new extrinsic conditions affecting the free‐living life of alevins.
Stereological estimation of the volume weighted mean volumes of alveoli and acinar pathways in the rat lung to characterise alterations after ischaemia/reperfusion
Authors: FEHRENBACH ANTONIA , OCHS MATTHIAS , WITTWER THORSTEN , CORNELIUS JAN , FEHRENBACH HEINZ , WAHLERS THORSTEN , RICHTER JOACHIM
Published: March 2003

The aim of this study was to characterise pulmonary reimplantation injury in isolated, perfused rat lungs following 2 h of cold ischaemia, and 50 min. of in vitro reperfusion. The effects of 2 differently composed lung preservation solutions (low potassium Euro‐Collins and Celsior; each n=5) were examined in comparison with untreated, nonischaemic control lungs (n=3). After fixation by vascular perfusion and tissue collection by systematic random sampling, the volume weighted mean volume (v) of alveoli and acinar pathways was estimated by light microscopic stereology using the method of point sampled intercepts in plastic embedded, Azan‐stained material. Significantly higher v of alveoli and acinar paths was found in the Celsior group than in Euro‐Collins preserved lungs. However, in the controls the size of acinar pathways was similar to Celsior preserved lungs whereas alveolar size was comparable to preservation with Euro‐Collins. The between‐animal coefficient of variation of alveoli was very low in controls and Celsior preserved but higher in the Euro‐Collins group. Size distribution of alveoli and acinar paths in 15 size classes was largely homogeneous in all groups tested. In the Euro‐Collins group the fractions of both class 1‐alveoli and class 1‐acinar paths significantly exceeded those of the other groups. Widely expanded alveoli (size classes 13–15) only occurred after preservation with Celsior whereas wider acinar paths (size class 15) were found in the Celsior group and in the controls. It is concluded that lung preservation with low‐potassium Euro‐Collins and Celsior solutions may act differently on distinct spaces in the distal gas‐exchange regions of lungs. This may be due to selective effects on pulmonary surfactant activity and on elastic tissue elements in the alveolar ducts, respectively. Additionally, the method of point sampled intercepts is considered to be an efficient tool to evaluate the effects of different preservation solutions on lung parenchyma.
Expression of parathyroid hormone‐related protein and the parathyroid hormone/parathyroid hormone‐related protein receptor in rat thymic epithelial cells
Authors: FUNK JANET L. , JONES GERAINT V. , BOTHAM CATHERINE A. , MORGAN GEOFFREY , WOODING PETER , KENDALL MARION D.
Published: March 2003

Thymic epithelial cells are an important source of cytokines and other regulatory peptides which guide thymocyte proliferation and maturation. Parathyroid hormone‐related protein (PTHrP), a cytokine‐like peptide, has been reported to affect the proliferation of lymphocytes in vitro. The studies presented here were undertaken to test the hypotheses that PTHrP is produced locally within the thymus where it could influence thymocyte maturation and, more specifically, that thymic epithelial cells (TEC) could be the intrathymic source of PTHrP expression. To this end, immunohistochemical studies were performed to localise PTHrP and the PTH/PTHrP receptor within the adult rat thymus. Antibodies directed against 2 different PTHrP epitopes, PTHrP(1–34) and PTHrP(34–53), demonstrated prominent specific PTHrP immunoreactivity in both subcapsular and medullary TEC. In addition, faint but specific staining for PTHrP was seen in the cortex, interdigitating between cortical lymphocytes while sparing epithelial‐free subcapsular areas, thus suggesting that cortical TEC could also be a source of PTHrP immunoreactivity. In contrast, PTH/PTHrP receptor immunoreactivity was only seen in medullary and occasional septal TEC; no evidence of cortical or lymphocytic PTH/PTHrP receptor immunoreactivity was detected. Immunohistochemical studies of cultured cytokeratin‐positive rat TEC confirmed the results of these in situ studies as cultured TEC were immunoreactive both for PTHrP and the PTH/PTHrP receptor. Thus these results demonstrate that PTHrP is produced by the epithelial cells of the mature rat thymus. This suggests that PTHrP, a peptide with known cytokine, growth factor and neuroendocrine actions, could exert important intrathymic effects mediated by direct interactions with TEC, or indirect effects on PTH/PTHrP receptor‐negative thymocytes.
Endothelial glycoconjugates: a comparative lectin study of the brain, retina and myocardium
Authors: LAWRENSON J. G. , CASSELLA J. P. , HAYES A. J. , FIRTH J. A. , ALLT G.
Published: March 2003

There is evidence that the endothelial cell (EC) glycocalyx is a significant determinant of vascular permeability, acting as a charge‐size filter to permeant molecules. We have therefore examined its oligosaccharide composition in 3 classes of microvessel with differing permeabilities. EC in rat brain, retina and myocardium were labelled with a panel of lectins and subjected to a semiquantitative analysis. Surprisingly, no substantial differences were evident for any lectin labelling between the 3 microvessel types despite their marked morphophysiological diversity. In particular, all showed substantial sialic acid expression, with Maackia amurensis (MAA) labelling sialic acid in an α2–3 linkage to β‐galactose and Sambucus nigra (SNA) recognising sialic acid in an α2–6 linkage to β‐galactose. Arachis hypogaea (PNA) binding after neuraminidase digestion indicated the presence of Gal β1–3GalNAc attached to terminal sialic acid. The results therefore show that the sequences NeuNAc α2–3Gal β1–3GalNAc and NeuNAc α2–6Gal β1–3GalNAc are strongly expressed in the 3 microvessel types irrespective of their permeability properties. This homogeneity suggests that these lectin ligands may be involved in a common set of EC functions, e.g. cell∶cell and cell∶matrix interactions. However, we cannot rule out the possibility that glycocalyx differences may exist between vessels in the paracellular cleft which may alter its filtration properties.
Bcl‐2, tissue transglutaminase and p53 protein expression in the apoptotic cascade in ribs of premature infants
Authors: STEVENS H. Y. , REEVE J. , NOBLE B. S.
Published: March 2003

Apoptotic cells of the human growth plate have not previously been demonstrated in situ. We have investigated the distribution of apoptotic cells in costosternal growth plates and bone of premature infants aged 4–11 d with a gestational age of ∼ 26 wk. In addition, we investigated the immunolocalisation of apoptosis‐related proteins within the growth plates and associated bone. A proportion of late hypertrophic chondrocytes and osteocytes within newly formed primary spongiosa showed evidence of highly fragmented DNA. The incidence of osteocyte apoptosis decreased as the distance from the chondroosseous junction increased. Tissue transglutaminase (tTG) expression was associated with apoptosis of osteocytes and hypertrophic chondrocytes. In contrast the presence of tTG was demonstrated in osteoblasts and bone lining cells but it did not colocalise with evidence of apoptosis. The anti‐apoptotic gene product Bcl‐2 was absent from the growth plate but was present in osteocytes. Visual assessment indicated a greater occurrence of the protein in cells occupying regions of low apoptosis. P53 was not demonstrated in the growth plate or bone. These findings would indicate that human growth plate chondrocytes appear to show little provision for ensuring cell longevity. In contrast osteocyte apoptosis appears negatively correlated with the skeletal distribution of Bcl‐2 protein in the human infant, implying a potential selective vulnerability in individual cells. Lack of Bcl‐2 and the high incidence of osteocyte apoptosis in the more rapidly remodelling bone of the human infant suggest a potential role of osteocyte apoptosis in the remodelling process.
Effects of chronic oestrogen treatment are not selective for uterine noradrenaline‐containing sympathetic nerves: a transplantation study
Authors: BRAUER M. MONICA , CHAVEZ‐GENARO REBECA , LLODRA JAIME , RICHERI ANALIA , SCORZA M. CECILIA
Published: March 2003

Previous studies have shown that chronic administration of oestrogen during postnatal rat development dramatically reduces the total content of noradrenaline in the uterine horn, abolishes myometrial noradrenergic innervation and reduces noradrenaline‐fluorescence intensity of intrauterine perivascular nerve fibres. In the present study we analysed if this response is due to a direct and selective effect of oestrogen on the uterine noradrenaline‐containing sympathetic nerves, using the in oculo transplantation method. Small pieces of myometrium from prepubertal rats were transplanted into the anterior eye chamber of adult ovariectomised host rats. The effect of systemic chronic oestrogen treatment on the reinnervation of the transplants by noradrenaline‐containing sympathetic fibres from the superior cervical ganglion was analysed on cryostat tissue sections processed by the glyoxylic acid technique. In addition, the innervation of the host iris was assessed histochemically and biochemically. The histology of the transplants and irises was examined in toluidine blue‐stained semithin sections. These studies showed that after 5 wk in oculo, the overall size of the oestrogen‐treated transplants was substantially larger than controls, and histology showed that this change was related to an increase in the size and number of smooth muscle cells within the transplant. Chronic oestrogen treatment did not provoke trophic changes in the irideal muscle. Histochemistry showed that control transplants had a rich noradrenergic innervation, associated with both myometrium and blood vessels. Conversely, in oestrogen‐treated transplants only occasional fibres were recognised, showing a reduced NA fluorescence intensity. No changes in the pattern and density of innervation or in the total content of noradrenaline of the host irises were detected after chronic exposure to oestrogen. We interpreted these results to indicate that the effects of oestrogen on uterine noradrenaline‐containing sympathetic nerves are neither selective or direct, but result from an interaction between sympathetic nerve fibres with the oestradiol‐primed uterine tissue. A potential effect of oestrogen on the neurotrophic capacity of the uterus is discussed.
Corticofugal axons from adjacent ‘barrel’ columns of rat somatosensory cortex: cortical and thalamic terminal patterns
Authors: WRIGHT A. K. , NORRIE L. , ARBUTHNOTT G. W.
Published: March 2003

The cortical representations of the vibrissae of the rat form a matrix in which each whisker has its own area of cortex, called a ‘barrel’. The afferent pathways from the periphery travel first to the trigeminal nuclei and thence via the ventroposteromedial thalamus (VPM) to the cortical barrels have been described in detail. We have studied the output from barrels by filling adjacent areas of the primary somatosensory cortex (SI) with either Phaseolus vulgaris leucoagglutinin (PHA‐L) or biotinylated dextran amine (BDA) and demonstrating the course and terminations of the axons that arise within the barrel fields. The method not only dramatically illustrates the previously described corticothalamic pathway to VPM but also demonstrates a strict topography in the cortical afferents to the thalamic reticular nucleus (RT). Cells supplying the RT projection are found below the barrels in layer IV. Connections to the posterior thalamus, on the other hand, have no discernible topography and are derived from cortical areas surrounding the barrels. Thus the outputs of these ‘septal’ areas return to the region from which they receive thalamic input. The corticocortical connections are also visible in the same material. Contralateral cortical connections arise from the cells of the septa between barrels. The projections to secondary somatosensory area (SII) are mirror images of the barrel pattern in SI with rather more overlap but nonetheless a recognisable topography.
Determination of age at death using combined morphology and histology of the femur
Authors: THOMAS C. D. L. , STEIN M. S. , FEIK S. A. , WARK J. D. , CLEMENT J. G.
Published: March 2003

Bone is characterised by age‐related morphological and histological changes. We have previously established an automated method of recording bone morphometry and histology from entire transverse sections of cortical bone. Our aim was to determine whether data acquired using this automated system were useful in the prediction of age. Ninety‐six specimens of human femoral middiaphysis were studied from subjects aged 21–92 y. Equations predicting specimen age were constructed using macroscopic data (total subperiosteal area (TSPA), periosteal perimeter (PP), endosteal perimeter (EP), cortical bone area (CA) and moments of area) and microscopic data (the number, size and diversity of pores and intracortical porosity) together with sex, height and weight. Both TSPA and PP were independent predictors of age but the number of pores was not a significant predictor of age in any equation. The age predicted by these equations was inaccurate by more than 8 y in over half the subjects. We conclude that we could not predict age at a clinically acceptable level using data from our automated system. This most likely reflects an insensitivity to regional age‐related changes in bone histology because we recorded data from each entire cortex. Automated bone measurement according to cortical region might be more useful in the prediction of age. The inclusion of TSPA together with PP as independent predictors of age raises the possibility that a future measure of periosteal shape at the femoral diaphysis could also be helpful in the prediction of age. The accuracy reached with the relatively simple methods described here is sufficient to encourage the development of image‐analysis systems for the automatic detection of more complex features.
Human evolution: taxonomy and paleobiology
Authors: WOOD BERNARD , RICHMOND BRIAN G.
Published: March 2003

This review begins by setting out the context and the scope of human evolution. Several classes of evidence, morphological, molecular, and genetic, support a particularly close relationship between modern humans and the species within the genus Pan, the chimpanzee. Thus human evolution is the study of the lineage, or clade, comprising species more closely related to modern humans than to chimpanzees. Its stem species is the so‐called ‘common hominin ancestor’, and its only extant member is Homo sapiens. This clade contains all the species more closely‐related to modern humans than to any other living primate. Until recently, these species were all subsumed into a family, Hominidae, but this group is now more usually recognised as a tribe, the Hominini. The rest of the review sets out the formal nomenclature, history of discovery, and information about the characteristic morphology, and its behavioural implications, of the species presently included in the human clade. The taxa are considered within their assigned genera, beginning with the most primitive and finishing with Homo. Within genera, species are presented in order of geological age. The entries conclude with a list of the more important items of fossil evidence, and a summary of relevant taxonomic issues.
Progress in understanding hominoid dental development
Authors: DEAN CHRISTOPHER
Published: March 2003

Teeth preserve a record of the way they grow in the form of incremental markings in enamel, dentine and cementum. These make it possible to reconstruct cellular activity and the timing of dental development in living and fossil primates, including hominids. They also provide a way of exploring the mechanisms that underlie morphological change during evolution and the nature of the relationship between ontogeny and phylogeny. All living great apes are dentally mature by about 11 y, irrespective of their body mass. While the early period of root formation in living great apes is shorter than in modern humans, enamel takes approximately the same time to form, irrespective of how thick it is. In general, differences in the total time taken to form enamel seem not to be due to differences in the rate at which enamel and dentine are secreted, but rather to faster or slower rates of differentiation of ameloblasts and odontoblasts and therefore to the number of secretory cells active at any one time during tooth formation. Tooth size, especially height, may influence the sequence of appearance of tooth mineralisation stages. The space available in the jaws may also have an influence on both the timing of tooth bud/crypt appearance and the sequence of gingival emergence. When each of these potential influences on dental development are carefully considered, and incremental markings used to calibrate key events, the developing dentition can provide an estimate of the period of dental maturation in fossil hominoids. However, the influence of body mass on the period of dental development among primates remains unclear. The earliest hominoids, dated at around 18 Mya, may still have had modern monkey‐like maturational profiles, and the earliest hominids, dated between 1.8 and 3.7 Mya, modern great ape‐like maturational profiles. Exactly when the extended or prolonged modern human‐like maturational profile first appeared remains debatable, but the most secure suggestion might be at the time of the appearance of the earliest archaic Homo sapiens, when brain size and body mass were finally both within the ranges known for modern humans. But at present we should not reject the hypothesis that an extended, modern human‐like, maturational profile arose more than once during human evolution in parallel with an increase in brain size.
Structural and spatial organisation of brain parenchymal vessels in the lizard, Podarcis sicula: a light, transmission and scanning electron microscopy study
Authors: LAZZARI MAURIZIO , FRANCESCHINI VALERIA
Published: March 2003

The structure and 3‐dimensional pattern of the intraparenchymal microvessels in the brain of the lizard, Podarcis sicula, were studied by a combination of light and transmission electron microscopy as well as scanning electron microscopy of vascular corrosion casts. The angioarchitecture pattern consists of narrow hairpin‐shaped microvascular loops of different length originating from the meningeal surface. In each loop, descending and ascending vessels are closely apposed to one another throughout their length and are connected by a narrow U‐shaped terminal loop at their tips. The 2 limbs of the vessel pairs show a slightly different diameter but lack other structural differences. While some paired vessels give rise to a secondary hairpin‐shaped loop with 2 possible branching patterns, there are no anastomotic intraparenchymal connections with analogous neighbouring structures. The cerebral vascular pattern of Podarcis sicula resembles that found in a few representatives of other vertebrate classes. All cerebral vessels structurally appear to be capillaries. Also the observations carried out on semithin and thin sections strongly support the capillary loop model in the Podarcis brain vasculature and, in accordance with studies carried out on various vertebrates, the general submicroscopic features of the brain capillary wall suggest the presence of an endothelial type blood‐brain barrier.
Intact myelinated fibres in biopsies of ventral spinal roots after preganglionic traction injury to the brachial plexus. A proof that Sherrington's ‘wrong way afferents’ exist in man?
Authors: SCHENKER MICHAEL , BIRCH ROLFE
Published: March 2003

Bell‐Magendie's law of separation of spinal function states that afferent and efferent fibres join the spinal cord separately in ventral and dorsal spinal nerve roots. For over 100 years there have been reports that challenge the exclusiveness of this law in mammals; very few studies have referred to man. We conducted a prospective morphological study in patients with preganglionic traction injuries of the brachial plexus to address this question. Avulsed ventral and dorsal roots were examined after variable intervals from the injury for histological and ultrastructural evidence for myelinated afferent fibres entering the cord via the ventral roots. Intact myelinated fibres were found in all ventral root specimens, but the majority of fibres in later biopsies are regenerative. A small number of fibres could be demonstrated that are likely to be ‘wrong way ventral afferents’. Their number is falsely low due to wallerian degeneration of dorsal and ventral afferents following the mechanical and ischaemic effects of traction injury. Our findings are the first morphological evidence in human material that Bell‐Magendie's law might not entirely be correct and they underline the difficulties in comparing traumatic with experimental rhizotomy.
Reproduction in the Noughties: will the scientists have all the fun?
Authors: JOHNSON MARTIN H.
Published: March 2003

The past 20–30 years have seen major advances in our understanding of human reproduction and in our ability to manipulate it, as well as major social changes in human reproductive and sexual attitudes. Many of these advances and changes developed out of the first successful in vitro fertilisation (IVF) of the human oocyte. It is also the case that 30 years ago few foresaw what was to come, and many were at best doubtful and often were very critical of the scientific work which led to human IVF and to many of the subsequent developments. This lack of foresight provides us with a lesson about the dangers that we face in looking forward and attempting to predict the future. This review will try to convey, not comprehensively but through examples, the flavour of current activities in Assisted Reproduction clinics and research laboratories around the world and what is being talked about for the future in respect of emergent patient demands and anticipated clinical needs. This clinically driven approach will form the basis for consideration of some underlying scientific aspects of reproductive research, some of the ethicolegal issues that may arise, and the implications of this anticipated future for our current approaches to medical education. The future will be considered not simply in terms of the New Reproduction itself but also in its interaction with the opportunities and challenges presented by the New Genetics. It is perhaps in the interaction between these two fields of endeavour that some of the most difficult challenges ahead lie.
Size of neocortical neurons in control subjects and in Alzheimer's disease
Authors: BUNDGAARD M. J. , REGEUR L. , GUNDERSEN H. J. G. , PAKKENBERG B.
Published: March 2003

The aim of the present study was to estimate mean neuronal volume and absolute size distributions of the neocortical neurons in brains from controls and AD patients using stereological methods based on unbiased principles to determine whether changes in absolute cell size are part of the neuropathological pattern of Alzheimer's disease. The neocortex of 8 patients with Alzheimer's disease (AD), mean age 81·1 (68–94) y was compared with 9 nondemented controls, mean age 80·9 (65–101) y. The brains came from Johns Hopkins University Hospital (JHUH) in Baltimore, USA, the Netherlands Brain Bank (NBB), and from a large brain repository in Denmark. The rotator method was used to obtain an estimate of cell volumes providing absolute size distributions of the volume of both cell perikaryon and cell nuclei. The geometric mean volume of cell nuclei in neocortical neurons was 328 μm3 (interindividual CV = 0·15) in the Alzheimer group compared with 277 μm3 (interindividual CV = 0·17) in controls which was a statistically significant increase (P= 0·049). The perikaryal volume was 1117 μm3 in the Alzheimer group compared with 999 μm3 in controls which was a nonsignificant difference (P= 0·20). There was a highly significant correlation between the nuclear and perikaryal volumes in all individuals. The average slope of the regression lines was significantly higher in the Alzheimer patients than in the controls, illustrating that nuclear hypertrophy was more pronounced in the largest neurons.
Intrathymic lymph nodes in humans
Authors: TANEGASHIMA A. , USHIYAMA I. , KIKUI Y. , YAMAMOTO H.
Published: March 2003

An unusual lymph node exists in the centre of the human thymus. This lymph node, which we call an intrathymic lymph node (ITLN), possesses some interesting morphological characteristics. In ontogeny, this node seems to appear at the latter half of fetal period. The function of the ITLN is still unknown, but it is assumed that it may play a different role in the immune system than other peripheral lymph nodes by its characteristics.
Conserved developmental processes constrain evolution of lungfish dentitions
Authors: SMITH MOYA MEREDITH , KRUPINA NATASHA I.
Published: March 2003

abstract

Although the 3 genera of living lungfish have different‐shaped adult tooth plates, their larval stages have similar patterns of development. The sequence in the pattern of initiation of teeth and their modification through ontogeny in Neoceratodus hatchlings provides a developmental model for fossil hatchling tooth plates (smallest 1–2 mm) recovered as 3‐dimensional dentitions from Andreyevichthys. This Late Devonian lungfish demonstrates that these also have a similar dentition pattern and suggests strongly conserved developmental processes. We postulate that a specific pattern of development, derived within lungfish, has been conserved in extant forms through evolution from the earliest known lungfish. The most basal early dipnoan, Diabolepis speratus, is also known from juveniles with tooth plates formed in this pattern.

The lungfish pattern is in marked contrast to the typical linear rows of teeth with lingual replacement for each tooth position, characteristic of most osteichthyan and chondrichthyan dentitions. Uniquely for lungfish, teeth are only added to the lateral ends of the radial rows in the palatal and lingual dentition and are consolidated into dental plates without loss through shedding. It is proposed that this tooth pattern is set up from primordial teeth at the patterning stage of the dentition, one in each dentate region of the larval jaws. Although in post‐Devonian lungfish marginal dentate bones are absent in the adult, in both the fossil and extant hatchling, teeth are present and function on some of the marginal bones. This pattern of development and loss is described and we conclude that in both forms it is also based on a radial pattern of successive tooth initiation. We propose that this ontogenetic pattern constrained the phylogenetic pattern of adult form, through evolution of dipnoan dentitions from 360 MYBP until the present. The universality amongst dipnoans and the implications for such a conserved constraint in the developmental module for the dentition is discussed.
The vertebrate segmentation clock
Authors: POURQUIE OLIVIER
Published: March 2003

abstract

Vertebrate somitogenesis has been shown to be associated with a molecular oscillator, the segmentation clock, whose periodicity matches that of the process of somitogenesis. The existence of such a clock in presomitic mesoderm (PSM) cells was originally proposed in theoretical models such as the ‘clock and wavefront’. Molecular evidence for the existence of this clock in vertebrates has been obtained on the basis of the periodic expression of several genes, most of which are related to the Notch signalling pathway. These genes are expressed in a dynamic sequence which appears as a wave sweeping caudo‐rostrally along the whole PSM once during each somite formation. Notch‐pathway mouse and fish mutants lose the dynamic expression of the cycling genes, indicating that Notch signalling is required for their periodic expression, or is required to coordinate the oscillations between PSM cells. Therefore Notch signalling is either part of the mechanism of the oscillator itself or acts as a cofactor required for cycling gene expression. A further potentially important role for the segmentation clock is to periodically activate Notch signalling in the rostral presomitic mesoderm, thereby generating the periodic formation of somite boundaries.
The role of Bapx1 (Nkx3.2) in the development and evolution of the axial skeleton
Authors: LETTICE LAURA , HECKSHER‐SØRENSEN JACOB , HILL ROBERT
Published: March 2003

abstract

The bagpipe‐related homeobox‐containing genes are members of the NK family. bagpipe (bap) was first identified in Drosophila and there are three different bagpipe‐related genes in vertebrates. Only two of these are found in mammals, the Nkx3.1 and the Bapx1 (Nkx3.2) gene. The targeted mutation in the mouse Bapx1 gene shows a vertebral phenotype in which the ventromedial elements are lacking; these are the centra and the intervertebral discs. In addition, a region of gastric mesenchyme is abnormal. This mesenchyme surrounds the posterior region of the presumptive stomach and duodenum, and in the mutant fails to support normal development of the spleen. In Drosophila, bagpipe has a role in gut mesoderm and the mutant embryos have no midgut musculature. Thus bap related genes in mouse and Drosophila have roles in patterning gut mesoderm; however, neither of the mammalian genes has a discernible role in the gut musculature. In contrast, both mammalian genes have roles in developmental processes that have appeared recently in evolution. The Bapx1 gene found in fish, amphibians, birds and mammals appears to have derived vertebrate specific functions sometime after the split between the jawless fish and gnathostomes.
Androgen receptor (AR), estrogen receptor‐alpha (ER‐α) and estrogen receptor‐beta (ER‐β) expression in the testis of the newt, Triturus marmoratus marmoratus during the annual cycle
Authors: ARENAS M. I. , ROYUELA M. , LOBO M. V. T. , ALFARO J. M. , FRAILE B. , PANIAGUA R.
Published: March 2003

Expression of androgen receptor (AR), estrogen receptor alpha (ER‐α) and estrogen receptor beta (ER‐β) in the testis of the marbled newt (Triturus marmoratus marmoratus) was investigated, with special attention to changes during the annual testicular cycle, using light microscopy immunohistochemistry and Western blot analysis. Primordial germ cells, primary and secondary spermatogonia and spermatocytes showed a positive reaction to the 3 receptor antibodies during the annual reproductive cycle. Follicular cells were positive to AR, ER‐α and ER‐β during the spermiogenesis and quiescence periods in the glandular tissue. Interstitial cells showed reactivity to AR, ER‐α and ER‐β in the spermiogenesis and the quiescence periods, and presented no labelling to these receptors in the proliferative period. These findings suggest that, as in mammals, there is an androgen‐estrogen regulation of the function and development of the newt testis.
Effects of the curly tail genotype on neuroepithelial integrity and cell proliferation during late stages of primary neurulation
Authors: HALL MATHEW , GOFFLOT FRANÇZOISE , ISEKI SACHIKO , MORRISS‐KAY GILLIAN M.
Published: March 2003

The curly tail (ct/ct) mouse mutant shows a high frequency of delay or failure of neural tube closure, and is a good model for human neural tube defects, particularly spina bifida. In a previous study we defined distinct domains of gene expression in the caudal region of non‐mutant embryos during posterior (caudal) neuropore closure (Gofflot et al. Developmental Dynamics210, 431–445, 1997). Here we use BrdU incorporation into S‐phase nuclei to investigate the relationship between cell proliferation and the previously described gene expression domains in ct/ct mutant embryos. The BrdU‐immunostained sections were also examined for abnormalities of tissue structure; immunohistochemical detection of perlecan (an extracellular heparan sulphate proteoglycan) was used as an indicator of neuroepithelial basement membrane structure and function. Quantitation of BrdU uptake revealed that at early stages of neurulation, cell proliferation was specifically reduced in the paraxial mesoderm of all ct/ct embryos compared with wild type controls, but at later stages (more cranial levels) it was increased. Those ct/ct embryos with enlarged posterior neuropore (indicating delay of closure) additionally showed an increased BrdU labelling index within the open neuroepithelium at all axial levels; however, this tissue was highly abnormal with respect to cell and nuclear morphology. It showed cell death and loss of cells from the apical surface, basement membrane defects including increased perlecan immunoreactivity, and increased separation from the underlying mesenchyme and notochord. These observations suggest that the mechanism of delay or failure of neuroepithelial curvature that leads to neural tube defects in curly tail embryos involves abnormalities of neuroepithelial‐mesenchymal interactions that may be initiated by abnormal cellular function within the neuroepithelium. Minor histological and proliferation abnormalities are present in all ct/ct embryos, regardless of phenotype.
Ultrastructural study of Betz cells in the primary motor cortex of the human brain
Authors: SASAKI SHOICHI , IWATA MAKOTO
Published: March 2003

The ultrastructure of Betz cells in the 5th layer of the primary motor cortex of 17 neurologically and psychiatrically normal control individuals was studied. Normal‐appearing Betz cells showed a wide range of features including novel electron‐dense inclusion bodies (Bunina‐like bodies) resembling Bunina bodies characteristic of amyotrophic lateral sclerosis (ALS), accumulations of neurofilaments (10 nm in diameter), bundles of filaments (20–25 nm in diameter) thicker than neurofilaments, lamellar structures, lamellar bodies and structures similar to Hirano bodies. Among these ‘abnormal’ features, the presence of Bunina‐like bodies may be an age‐related nonspecific degenerative change, since they appeared more frequently in elderly individuals. The presence of these abnormal features—particularly the Bunina‐like bodies—in the Betz cells of normal human brains must be considered in the assessment of the pathognomonic significance of such structures in ALS and other neurological diseases that affect the motor cortex.
Comparison of a new pmp22 transgenic mouse line with other mouse models and human patients with CMT1A*
Authors: Robertson A. M. , Perea J. , McGuigan A. , King R. H. M. , Muddle J. R. , Gabreëls‐Festen A. A. , Thomas P. K. , Huxley C.
Published: March 2003

Charcot‐Marie‐Tooth disease type 1A is a dominantly inherited demyelinating disorder of the peripheral nervous system. It is most frequently caused by overexpression of peripheral myelin protein 22 (PMP22), but is also caused by point mutations in the PMP22 gene. We describe a new transgenic mouse model (My41) carrying the mouse, rather than the human, pmp22 gene. The My41 strain has a severe phenotype consisting of unstable gait and weakness of the hind limbs that becomes obvious during the first 3 weeks of life. My41 mice have a shortened life span and breed poorly. Pathologically, My41 mice have a demyelinating peripheral neuropathy in which 75% of axons do not have a measurable amount of myelin. We compare the peripheral nerve pathology seen in My41 mice, which carry the mouse pmp22 gene, with previously described transgenic mice over‐expressing the human PMP22 protein and Trembler‐J (TrJ) mice which have a P16L substitution. We also look at the differences between CMT1A duplication patients, patients with the P16L mutation and their appropriate mouse models.