[Cerebrospinal fluid-based diagnostics of CT-negative subarachnoid haemorrhage]. / Liquordiagnostik bei CT-negativer Subarachnoidalblutung.

The diagnostic investigation of CT-negative subarachnoid haemorrhage (SAH) is a particular challenge in clinical neurology. Cerebrospinal fluid (CSF) analysis via lumbar puncture is the method of choice. The diagnosis of SAH in CSF is based on a bloody or xanthochromic discoloration of the CSF as well as on findings in non-automated CSF cytology including the detection of erythrophages and siderophages. The automated determination of CSF ferritin concentrations or spectrophotometric detection of xanthochromia may contribute to the diagnosis but are only useful with regard to the overall clinical picture. Generally, the knowledge of the time flow of CSF changes associated with SAH is essential for a correct interpretation of CSF findings.

[Wilson's disease]. / Morbus Wilson.

Wilson's disease is a rare autosomal recessive disorder of hepatic copper transport leading to a biliary excretion inhibition of copper. Overload of the metal mainly in liver and basal ganglia leads to hepatic but also to extrapyramidal motor as well as psychiatric clinical symptoms. Diagnosis is based on clinical suspicion, parameters of copper metabolism, ophthalmic examination and a liver biopsy. A radiocopper test is able to identify patients even with inconsistent laboratory results. For initial assessment and follow-up neurophysiological investigation and MRI are recommended additionally. Genetic analysis can be helpful to detect asymptomatic relatives of the index patient. Dependent on the stage of the disease for therapy chelating drugs and zinc are possible but must be given lifelong without longer interruptions. With early diagnosis and consequent treatment the prognosis of Wilson's disease is excellent and usually the need for liver transplantation can be prevented.

[Correlation of clinical aspects as well as genotype and phenotype in Wilson's disease on the basis of epidemiologic, clinical and cranial MRI findings]. / Klinische und Genotyp-Phänotyp-Korrelation epidemiologischer, bildgebender und neurologischer Befunde bei Patienten mit Morbus Wilson.

Wilson's disease, a rare autosomal recessive disorder of hepatic copper transport, is characterized by a varying pattern of hepatic, neurologic and psychiatric symptoms. Currently, about 250 causative mutations of the ATP 7B gene are known. However, a correlation between genotype and phenotype according to these mutations is not yet clear. To elucidate a possible correlation in this study 39 patients with Wilson's disease were subdivided into three groups according to the underlying mutation in group I for homocygote respectively group II for compound heterocygote mutation in H1069Q and group III for other mutations. Clinical subtype and extent of neurologic disturbance as well as epidemiologic aspects, presence of psychiatric symptoms, results of acustically evoked potentials (Wave III, interpeak latency III-V) and findings of cranial MRI were considered. While psychopathological symptoms, the results of acustically evoked potentials and cranial MRI show a correlation to the clinical subtype of Wilson's disease there was no genotype-phenotype correlation on the basis of the mutation in H1069Q. The qualitative and quantitative pattern of results do not show any significant differences in the three groups of genotype. Thus, the time of treatment onset still has most influence on the extent of clinical manifestation and reversibility of the toxic copper accumulation.

Classification of fine-motoric disturbances in Wilson's disease using artificial neural networks.

Patients suffering from Wilson's disease are divided into several types according clinical symptoms only at time of manifestation. Thereby two main subgroups exist: neurologic and non-neurologic types. After long-term therapy the neurological symptoms occurring in hepatolenticular degeneration may be improved but frequently with remaining fine-motoric disturbances which should be used for evaluation of the actual patient state. These disturbances are difficult to assess in an exact and objective manner by clinical examination. Therefore we measured fine-motoric passive and active abilities based on a standardized test set using the VSCOPE-system. The parallel evaluation of all fine-motoric data using an artificial neural network leads to a reclassification of these patients based on actual fine-motoric abilities but not reflecting the clinical classification at time of manifestation.

[Wilson disease]. / Morbus Wilson.

Wilson disease is an autosomal recessive inherited disorder of human copper metabolism that leads to neurological symptoms and hepatic damage of variable degree. The affected gene ATP7B encodes a hepatic copper transport protein, which plays a key role in human copper metabolism. Clinical symptoms are complex with neurologic symptoms such as tremor, dysarthria, psychiatric disorders etc., predominant hepatic disease or mixed forms. Copper deposition in the liver results in acute liver failure, chronic hepatitis or liver cirrhosis. Early recognition by means of clinical, biochemical or genetic examination and early initiation of therapy with chelators or zinc-salts are essential for outcome and prognosis. Liver transplantation is an alternative in cases with acute and chronic liver failure and cures the hepatic disease. Frequent monitoring of drug therapy, adverse effects, and compliance is critical for the prognosis of the disease.

[Neurosyphilis and neuroborreliosis. Retrospective evaluation of 22 cases]. / Neurosyphilis oder Neuroborreliose. Retrospektive Auswertung von 22 Kasuistiken.

We present laboratory data from 22 patients suspected of having neurosyphilis. In two cases the suspicion could not be confirmed, and in 20 cases neurosyphilis was detected. The sera from 17 patients were also assayed for Borrelia-specific antibodies. Suspicious immunoglobulin G antibody indices were detected in nine cases and a suspicious immunoglobulin M antibody index in one. In six of these, stored CSF/serum pairs were available to specify the antibodies by immunoblotting. This allowed for the identification of one patient apparently infected by both Borrelia spp. and Treponema pallidum. In all cases of newly suspected neurosyphilis, we recommend considering neuroborreliosis at the same time.

Vacuum-ultraviolet beam array generation by flat micro-optical structures.

Micro-optical structures for VUV laser beam shaping and wave-front sensing were manufactured by thin-film deposition onto CaF2 and transfer by etching. Arrays of Bessel-like F2 laser beams at a wavelength of 157 nm with extremely small conical angles were generated by microaxicon lenses. Beam propagation was studied in simulations and experiments. Apodization by absorbing layers is proposed for beam cleaning.

Expression patterns of erythropoietin and its receptor in the developing midbrain.

The expression patterns of erythropoietin (EPO) and its receptor (EPOR) were investigated in the midbrain and in adjacent parts of the synencephalon and hindbrain of embryonic C57Bl mice. On embryonic (E) day 8 (E8), virtually all neuroepithelial cells expressed EPOR. After neural tube closure, subsets of these cells downregulated EPOR. In contrast, radial glial cells were EPOR-immunolabeled from E11 onwards. Simultaneously, subpopulations of early developing neurons upregulated EPO and expressed HIF-1, known to transcriptionally activate EPO. Three-dimensional reconstructions revealed subpopulations of EPO-expressing neurons: (1) in the trigeminal mesencephalic nucleus (TMN), (2) at the rostral transition of the midbrain and synencephalon, (3) in the basal plate of the midbrain, (4) in the trigeminal motor nucleus, and (5) in the trigeminal principal sensory nucleus. In the rostral midbrain and synencephalon, EPO-immunoreactive neurons were attached to EPOR-expressing radial glial cells. The identity of radial glial cells was proven by their immunoreactivity for antibodies against astrocyte-specific glutamate transporter, brain lipid-binding protein, and nestin. From E12.5 onwards EPOR was downregulated in radial glial cells. Viable neurons of the TMN continued to express EPO and upregulated EPOR. Our findings provide new evidence that components of the EPO system are present in distinct locations of the embryonic brain and, by interactions between neurons and radial glial cells as well as among clustered TMN neurons, may contribute to its morphogenesis. Whether the observed expression patterns of EPO and EPOR may reflect EPO-mediated trophic and/or antiapoptotic effects on neurons is discussed.

Investigation of fine-motor disturbances in Wilson's disease.

Patients suffering from Wilson's disease (WD) can be divided into two main subgroups: neurologic and nonneurologic WD. We measured passive and active fine-motor abilities of 37 WD patients and 24 randomly selected volunteers. The measurement was based on a standardized test set in a defined environment for detection of disturbed finemotor control. The set contains 5 tests comprising rest tremor, postural tremor, target tapping, forefinger tapping and spiral painting, reflecting different aspects of movement disorders. The tests showed significant differences between neurologic WD and volunteers, especially for tasks defining active control. In neurologic WD we found no differences between subgroups whereas for non-neurologic WD we often detected slight movement disorders. The detected movement disorders cam be interpreted as persistent disorders after long-term therapy.

Comparison of clinical types of Wilson's disease and glucose metabolism in extrapyramidal motor brain regions.

In Wilson's disease a disturbed glucose metabolism especially in striatal and cerebellar areas has been reported. This is correlated with the severity of extrapyramidal motor symptoms (EPS). These findings are only based on a small number of patients. Up to now it is unknown whether EPS are caused by various patterns of disturbed basal ganglia glucose metabolism. We investigated 37 patients and 9 normal volunteers to characterize the disturbed glucose metabolism in Wilson's disease more precisely. The glucose metabolism was determined in 5 cerebellar and cerebral areas (putamen, caput nuclei caudati, cerebellum, midbrain and thalamic area) by using (18)F-Fluorodesoxyglucose-Positron-Emission-Tomography ( [(18)F]FDG-PET). The database was evaluated by a cluster analysis. Additionally, the severity extrapyramidal motor symptoms were judged by a clinical score system. Three characteristic patterns of glucose metabolism in basal ganglia were obtained. Two of them may be assigned to patients with neurological symptoms whereas the third cluster corresponds to most patients without EPS or normal volunteers. The clusters can be identified by characteristic consumption rates in this 5 brain areas. The severity of EPS can not clearly be assigned to one of the clusters with disturbed glucose metabolism. However, the most severe cases are characterized by the lowest consumption in the striatal area. When there is marked improvement of EPS impaired glucose consumption reveals a persistent brain lesion. Finally, the neurological symptoms in Wilson's disease are caused by (at least) two different patterns of disturbed glucose metabolism in basal ganglia and cerebellum. The severity of EPS seems to be determined by a disturbed consumption in the striatal area.

Differential alteration of the nigrostriatal dopaminergic system in Wilson's disease investigated with [123I]ss-CIT and high-resolution SPET.

Wilson's disease (WD) is a copper deposition disorder which can result in a number of extrapyramidal motoric symptoms such as parkinsonism. Therefore, this study was carried out to investigate, for the first time, nigrostriatal dopaminergic function in WD in relation to different courses and severity of the disease. Using high-resolution single-photon emission tomography (SPET) after administration of 2ss-carbomethoxy-3ss-(4[123I]iodophenyl)tropane ([123I]ss-CIT), striatal dopamine transporters (DAT) were imaged in 43 WD patients and a control group of ten subjects. From the SPET images, specific [123I]ss-CIT binding ratios were obtained for the caudate heads, putamina and entire corpus striatum. In addition, to evaluate a putative dissociation between the caudate and putaminal [123I]ss-CIT binding ratios, the ratio between these binding ratios was calculated (CA/PU ratio). The SPET data were compared with clinical data on the course of the disease (CD), the severity of neurological symptoms and the degree of hepatic alteration. Whereas the specific regional [123I]ss-CIT binding ratios in patients with asymptomatic/hepatic CD did not differ from those in the control group (e.g. striatal ratios: 13.4+/-3.0 vs 11.7+/-2.8), in patients with neurological CD the ratios were significantly reduced for all striatal substructures (P=0.003 after one-factor ANOVA). For the different subgroups a tendency was detected towards a stepwise decrease in the specific [123I]ss-CIT binding ratios from pseudo-sclerosis CD (9.4+/-2.3), through pseudo-parkinsonian CD (9.1+/-2.1) to arrhythmic-hyperkinetic CD (8.5+/-1.6). However, these group differences reached significance only for the comparison with asymptomatic/hepatic CD (P=0.02). The CA/PU ratio was significantly higher in WD than in the control group (1.30+/-0.19 vs 1.11+/-0.08; P=0.003). Severity of neurological symptoms was significantly correlated with all specific regional [123I]ss-CIT binding ratios (r=-0.49 to -0.57). For degree of liver alteration, significant correlations were obtained with the putaminal binding ratio (r=-0.37) and the CA/PU ratio (r=0.44). From these results is concluded that in WD the nigrostriatal dopaminergic function is compromised to varying extents. The degree of this presynaptic alteration of dopaminergic neurotransmission depends on the clinical course and severity of this copper deposition brain disorder and also varies in the different striatal substructures.

High prevalence of the H1069Q mutation in East German patients with Wilson disease: rapid detection of mutations by limited sequencing and phenotype-genotype analysis.

BACKGROUND/AIMS: Wilson disease is caused by a large number of different mutations in the ATP7B gene. Wilson disease patients from a homogeneous ethnical background (Saxonia) were studied for distribution and phenotypes of ATP7B mutations. METHODS: Eighty-two patients were analyzed. The H1069Q mutation was assayed by a polymerase chain reaction-based restriction fragment length polymorphism test. Exons 8 and 15 were sequenced in all, and the entire gene in 30, non-H1069Q-homozygotes. RESULTS: Four novel and 12 known mutations were found. Thirty-two (39%) Wilson disease patients were homozygous and 39 (48%) heterozygous for the H1069Q mutation (allele frequency 63%). Together with sequence analysis of exons 8 and 15 mutations in both alleles were identified in 65% of patients. Only one patient had both mutations at other locations. In H1069Q homozygotes symptoms started later (21.3+/-7.2 years) than in H1069Q compound heterozygotes (14.6+/-5.8, P<0.001) or H1069Q negatives (10+/-4.4, P<0.001), and they had more frequently neurologic symptoms (93 vs. 47%, P<0.001) and Kayser-Fleischer rings (82 vs. 51%, P<0.001). Mutation status did not correlate with liver biopsy findings, serum ceruloplasmin levels or (64)Cu-assay results. CONCLUSIONS: In spite of many known ATP7B mutations, only few occur in this homogeneous population. Limited genetic testing is useful to confirm Wilson disease in this population.

Pattern of calretinin immunoreactivity in the main olfactory system and the vomeronasal system of the tree shrew, Tupaia belangeri.

The distribution of the calcium-binding protein calretinin was studied in peripheral and central parts of the main olfactory system (MOS) and the vomeronasal system (VNS) of adult tree shrew Tupaia belangeri. The calretinin immunoreaction was carried out with a peroxidase-coupled polyclonal antibody. In the VNS, complete labeling of all receptor cells and vomeronasal nerve fibers was observed, whereas only a subset of the somata and dendrites of receptor cells and of the olfactory nerve fibers of the MOS was immunoreactive. From the immunoreactive dendritic clubs of vomeronasal receptor cells, calretinin-labeled structures, presumably clumps of microvilli, arose that terminated within immunopositive portions of the mucus. In the main olfactory bulb, the neuropil of some of the glomeruli was immunoreactive. All periglomerular and many mitral cells were labeled. The external plexiform layer was subdivided into a faintly immunoreactive superficial half and a strongly immunoreactive deep half. Immunoreactive basal dendrites of mitral cells could be followed into either the deep half or the superficial half. In the laminated internal granular layer, a subset of immunopositive granule cells extended dendrites into the external plexiform layer. Mitral cells and granule cells with dendrites ascending to different levels of the external plexiform layer may represent functional subclasses. In the accessory olfactory bulb, all vomeronasal nerve fibers, glomeruli, and mitral/tufted cells were labeled, whereas immunoreactive periglomerular cells and internal granule cells were only scattered. In Tupaia, calretinin immunoreactivity is a more general property of the primary projecting neurons of the VNS than of the MOS and possibly indicates the involvement of calretinin in the perception of certain of the olfactory qualities.

Capillary-contacting horizontal cells in the retina of the tree shrew Tupaia belangeri belong to the mammalian type A.

Previously, ultrastructural evidence has been presented that, in the retina of adult Tupaia belangeri, the perikarya and processes of horizontal cells extensively ensheath the basal lamina of capillary cross sections located between the inner nuclear layer and the outer plexiform layer. The present study tests whether these horizontal cells can be further characterized by applying a polyclonal antibody against glial fibrillary acidic protein (GFAP). GFAP-immunoreactivity was noted in the astrocytic plexus ensheathing retinofugal axons in the nerve fiber layer. The vitreal endfeet and parts of the trunks of M*uller cells were also labelled. Moreover, a large subpopulation of vessel-contacting horizontal cells was strongly GFAP-immunoreactive. Immunoreactivity was found in the perinuclear cytoplasm and in the sturdy primary dendrites of these cells. The somata of GFAP-immunoreactive horizontal cells were unevenly distributed. These cells had three to seven primary dendrites that showed considerable overlap with the dendrites of neighbouring horizontal cells. For these reasons, GFAP-immunoreactive horizontal cells were classified as belonging to the mammalian type A. Whether the simultaneous occurrence of two glial features, viz. extensive ensheathment of retinal capillaries and immunoreactivity for a polyclonal antibody towards GFAP, supports the view that retinal horizontal cells represent a cell type intermediate between neurons and glial cells is discussed.

The patterns of cell death and of macrophages in the developing forebrain of the tree shrew Tupaia belangeri.

The patterns of cell death and of macrophages were investigated in the forebrain and eyes of the tree shrew Tupaia belangeri during five phases of optic cup formation. Seventeen embryos were studied. Three- dimensional reconstructions were made from one embryo of each phase. In phase 1 (V-shaped optic evagination) a midline band of cell death passes through the closing anterior neuroporus. From phases 2 (optic vesicle) to 5 (far-advanced invagination) the midline band of cell death extends in the dorsal wall of the forebrain to its rostral pole and, further, into its ventral wall. At the approximate future position of the optic chiasm this ventral pycnotic area, predicted but so far unidentified by others, is connected to a previously described second band of cell death passing through the optic anlagen. Recently, evidence has been presented that chicken embryos develop holoprosencephaly and cyclopia when ventral forebrain structures are lost secondary to experimentally induced apoptosis. Our findings in Tupaia suggest that, in cases of spontaneous malformations of this kind, such an atypical pycnotic area in the ventral telencephalon might result from the defective regulation of cell death processes during optic cup formation. In the forebrain and eyes of Tupaia, the occurrence of bands of cell death precedes the appearance of the earliest intraepithelial macrophages. From phase 3 (onset of invagination) onwards almost all of them are concentrated along the band of cell death.

Acute and long-term results after transcoronary ablation of septal hypertrophy (TASH). Catheter interventional treatment for hypertrophic obstructive cardiomyopathy.

AIMS: To evaluate acute and long-term symptomatic, haemodynamic (at rest and during exercise) and electrophysiological results of transcoronary ablation of septal hypertrophy (TASH), a catheter interventional treatment for hypertrophic obstructive cardiomyopathy. METHODS AND RESULTS: Sixty-two transcoronary ablations of septal hypertrophy were performed by injection of 4.6+/-2.6 ml 96% ethanol into septal branches in 50 patients with hypertrophic obstructive cardiomyopathy and severe symptoms. Serial left and right heart catheterization, transoesophageal echocardiography and electrophysiological investigations were repeated 2 weeks and 7+/-1 months (n=37) after intervention. Transcoronary ablation of septal hypertrophy led to a reduction in septal thickness, sustained elimination of the outflow obstruction (51+/-41 vs 6+/-10 mmHg at rest, P<0.001; 134+/-48 vs 28+/-32 mmHg, P<0.001, post-extrasystolic), a decrease in left ventricular filling pressures at rest and during exercise and a pronounced clinical improvement. There was no evidence for the creation of an arrhythmogenic substrate as assessed by serial programmed electrical stimulation in 39 patients. However, permanent high-grade atrioventricular block occurred in 17% of the patients. There were two early, but no late deaths during a mean follow-up time of 10. 6+/-5.6 months. CONCLUSION: Transcoronary ablation of septal hypertrophy is a promising new treatment for hypertrophic obstructive cardiomyopathy in patients with severe symptoms. It should now be compared with alternative treatment strategies in prospective randomized studies.

FMRFamide immunoreactivity and the invasion of adenohypophyseal cells into the neural lobe in the developing pituitary of the tree shrew Tupaia belangeri.

Ontogenetic development of FMRFamide immunoreactivity in the cells and nerve fibers of the pituitary was studied in the tree shrew Tupaia belangeri. Up to the 26th day of gestation (E26), no FMRFamide immunoreactivity was visible. From E27 onwards it increased continuously until prenatally, on E41, the adult pattern was reached in the adenohypophysis, although at a lower intensity. In the adult Tupaia, as in the other mammals studied so far, a finely stained FMRFamide-immunoreactive fiber network was visible in the neural lobe and the infundibular stalk. As in several other adult mammals including man, endocrine cells in the pars intermedia and numerous scattered cells in the pars distalis were labeled, in contrast to several reports on rats and our studies on Galago, showing no FMRFamide-immunoreactive cells in these locations of the pituitary. With reference to the 'basophil invasion', we found FMRFamide-immunoreactive endocrine cells invading the neural lobe from the pars intermedia during the pituitary development. The distribution pattern of FMRFamide immunoreactivity in Tupaia indicates that the mammalian counterparts of FMRFamide may function as neuromodulators, neurotransmitters or as hormones already in defined prenatal stages.

Lectin binding sites in the vomeronasal organ and the olfactory epithelium of the tree shrew tupaia belangeri.

Lectin binding histochemistry was performed on the peripheral parts of the vomeronasal and olfactory system of Tupaia belangeri to investigate the distribution and density of defined carbohydrate terminals on the cell surface glycoproteins of the specific receptors, nerves and associated glands. Dolichus biflorus lectin staining was identifiable in all cells of the sensory epithelia of both systems, with the exception of the olfactory basal cells. The vomeronasal nerve expressed alpha-N-acetylgalactosamine, the olfactory nerve did not. Differences in the Dolichus biflorus lectin staining pattern were noted in the sensory and the non-sensory epithelium of the vomeronasal organ of pregnant and non-pregnant Tupaia belangeri. Like in other mammals examined so far, the systems were characterized by a moderate to high alpha-fucose density, only the supporting cells of the olfactory epithelium remaining unstained by Ulex europaeus I lectin. Bandeiraea simplicifolia II lectin binding was moderate in the olfactory glands and the brush border. In the vomeronasal organ, sugar residues of alpha- and beta-N-acetyl-D-glucosamine were found selectively in the transition zone between the two vomeronasal epithelia, where regeneration should take place. We tentatively conclude that specific glycoproteins, whose terminal sugars were detected by lectin binding, might be related to the chemoreception and transduction of the olfactory/pheromonal message into a nervous signal or to the histogenesis of the olfactory/vomeronasal system. This study showed that beside the species, pregnancy might play a role in these processes in the vomeronasal organ.

The morphogenesis of the arteries of the pelvic extremity. A comparative study of mammals with special reference to the tree shrew Tupaia belangeri (Tupaiidae, Scandentia, Mammalia).

The ontogeny of the arteries of the pelvic extremity of Tupaia belangeri was investigated by light microscopy on the basis of serial sections of 30 embryos, dating from day 17 to day 42 post-copulation. In Tupaia, the gestational period takes approximately 43 days. Additionally, a 3-D reconstruction of the pelvic region and the right leg of a 22-day embryo was prepared. The arteries of an adult Tupaia were studied on the basis of a corrosion cast. The results were compared with the ontogeny of the arterial system of other mammals. In the 17-day embryo, the anlage of the pelvic extremity is penetrated by a capillary plexus. In the 18-day embryo, the a. ischiadica reaches the pelvic limb bud, representing the primary axial artery. On day 19, its r. perforans tarsi extends from the plantar to the dorsal aspect of the foot plate. The a. ischiadica is the main artery of the leg until the stage of the 22-day embryo. Afterwards, the peripheral arteries supplied by it are taken over by the a. iliaca externa and its extension, the a. femoralis. The a. iliaca externa springs from the a. iliaca communis in the 19-day embryo. From day 21 to day 22, the capillary plexus, which is nourished by the a. femoralis, closely approaches the a. ischiadica, and finally, a connecting branch joins the a. ischiadica. The a. ischiadica is then reduced to the a. glutea caudalis, and the aa. femoralis, poplitea profunda (at the cranial aspect of the m. popliteus), and interossea become the main arteries of the pelvic extremity. The a. poplitea superficialis, lying at the caudal aspect of the m. popliteus, and its continuation in the crural region, the a. peronea, develop until the 25-day embryo. The a. peronea gives rise to an r. perforans which penetrates the membrana interossea towards the dorsum of the foot. As a result of a shift of the origin of the a. iliaca externa in the proximal direction, the length of the a. iliaca communis gradually decreases until, on day 24, the a. iliaca externa springs directly from the lateral wall of the aorta. In the 20-day embryo, the a. iliaca externa gives rise to an a. circumflexa ilium profunda towards the lateral pelvic wall, and in 23-day embryos, to the a. profunda femoris. The main branches of the a. profunda femoris develop until day 24. At the same time, the aa. circumflexa femoris lateralis and nutricia ossis femoris arise from the a. femoralis. The a. saphena, which is already recognizable in the 23-day embryo, gives rise to the a. genus descendens, and as an a. plantaris medialis, to four aa. digitales plantares communes (I-IV) at the planta pedis. The development of the a. tibialis cranialis on day 25 takes place independently and without any topographic relation to the a. saphena, which functionally replaces the a. tibialis cranialis in some other mammals. In the 26-day embryo, the aa. peronea and tibialis cranialis extend to the dorsum of the foot where they continue as the aa. dorsales pedis profunda and superficialis. The fourth main artery of the lower leg, the a. caudalis femoris, which is first observed in the 20-day embryo, reaches the lateral aspect of the foot on day 24. Its r. calcaneus runs to the planta pedis. In 30-day embryos, the aa. digitales plantares propriae have differentiated. The corresponding dorsal arteries and the superficial plantar vascular are develop until day 35, so that all important arteries of the pelvic extremity, which are seen in the corrosion cast of the adult, are recognizable. Among the embryos and the adult Tupaia studied, individual variation is minimal. The developmental stage at which the arteries of the leg acquired a secondary vascular wall was ascertained. Only a vessel with a primary vascular wall can dissolve into a capillary plexus later on (e.g., a. interossea). In contrast, the course of an artery which has acquired a secondary vascular wall is determined, because modifications of the course of a vessel often need a capillary plexus as an intermediate st

Pattern of cell death during optic cup formation in the tree shrew Tupaia belangeri.

Developmental cell death during optic cup formation was investigated in the tree shrew Tupaia belangeri. Twenty-six embryos from days 12 to 16 of prenatal ontogenesis were studied by light microscopy. Prior to the optic vesicle stage, a dorsal area of cell death surrounded the lumen of the V-shaped optic evagination (phase 1). A ventral band of dead cells, found in the optic vesicle (phase 2), preceded a dorsal focus of cell death (phase 3) previously described as a characteristic avian feature. During further invagination (phase 4), a peak of cell death was represented by a ventrodorsal band extending from the diencephalon over the complete optic anlage. The main areas of cell death found in phases 2 to 4 were, topographically, segments of this band. Also, the distinct areas of cell death reported in the literature for the vertebrate species studied so far fit well into this ventrodorsal band found in Tupaia. Thus, most probably, a common spatio-temporal sequence of cell death exists in all of them. In Tupaia, dead cells concentrated at the diencephalic insertion of the optic stalk, the suboptic necrotic center (SONC) reported by several authors, were part of the early ventral band of cell death originating from the median floor of the prosencephalon (phase 2). During optic cup formation, the SONC was part of the ventrodorsal band and, thus, was not secondarily formed by the subdivision of a pre-existing distal ventral area of cell death as reported for several other vertebrates.