bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital myopathy, recurrent secretory diarrhea, bullous eruption of skin, microcephaly, and deafness: A new genetic syndrome?
Authors: Levy J. , Chung W. , Garzon M. , Gallagher M.P. , Oberfield S.E. , Lieber E. , Anyane‐Yeboa K.
Published: December 2002

We describe three siblings with congenital myopathy, bullous eruption of the skin, secretory diarrhea, apparent zinc deficiency, failure to thrive, deafness, and microcephaly. The parents are not consanguineous and there are no other affected relatives. This new syndrome, which follows an apparent autosomal recessive pattern, appears to be distinct from known syndromes of secretory diarrhea, myopathy, deafness, microcephaly, and zinc deficiency. © 2003 Wiley‐Liss, Inc.
De novo dup(X)(q22.3q26) in a girl with evidence that functional disomy of X material is the cause of her abnormal phenotype
Authors: Armstrong Linlea , McGowan‐Jordan Jean , Brierley Kathleen , Allanson Judith E.
Published: December 2002

The relationship between phenotype and Xq duplications in females remains unclear. Some females are normal; some have short stature; and others have features such as microcephaly, developmental delay/mental retardation, body asymmetries, and gonadal dysgenesis. There are several hypotheses proposed in the literature to explain this variability. We describe a 7‐year‐old girl with dup(X)(q22.3q26). The pregnancy was complicated by intrauterine growth retardation, and she was distressed during labor. During her first year she fed poorly and failed to thrive. She has microcephaly, her height is at the 10th centile, and her hands and feet are strikingly small. She is hypotonic and delayed. Asymmetries of muscle power, and of leg and foot length have been noted. She has mild unilateral ptosis. She has some features of Turner syndrome, and multiple other minor anomalies such as flat labia. These are features common to other described females. This report describes our patient in detail and compares her phenotype to those of the other females with Xq duplications, displays our laboratory investigations, and discusses ideas regarding the pathogenesis of phenotype. The duplicated X is of paternal origin. It is inactivated in all cells; however, the distal duplicated portion appears to be active. We suggest that functional disomy of the duplicated X material, due to local escape from inactivation, may be responsible for the phenotype in the affected females. © 2002 Wiley‐Liss, Inc.
Humeroradial synostosis, ulnar aplasia and oligodactyly, with contralateral amelia, in a child with prenatal cocaine exposure
Authors: Marles Sandra L. , Reed Martin , Evans Jane A.
Published: December 2002

Humeral “bifurcation” due to humeroradial synostosis, and amelia are both very rare limb anomalies. We report on a Canadian. Aboriginal boy with both these limb deficiencies. The family history was unremarkable, but he was exposed prenatally to cocaine at the time of limb development. Humeroradial synostosis with ulnar aplasia has been reported by several authors. The majority of cases are unilateral. When both upper limbs arms are involved, cases with oligodactyly often have asymmetrical limb deficiencies and have all been sporadic to date. Some appear to represent cases of the femur–fibula–ulna or FFU complex. Affected individuals with normal hands usually have symmetrical defects and show an autosomal recessive pattern of inheritance. Limb deficiencies have been reported in several infants exposed prenatally to cocaine and have been inducible in animal models. Most are terminal transverse defects or deficiencies of middle digits. When more than one limb is involved, the defects are usually asymmetric. Our case appears to be one of the most severely affected children reported to date. © 2002 Wiley‐Liss, Inc.
Mesomelic and rhizomelic short stature: The phenotype of combined Leri‐Weill dyschondrosteosis and achondroplasia or hypochondroplasia
Authors: Ross Judith L. , Bellus Gary , Scott Charles I. , Abboudi Jack , Grigelioniene Giedre , Zinn Andrew R.
Published: December 2002

We studied two children with combined genetic skeletal disorders. Both had Leri‐Weill dyschondrosteosis (LWD); one also had achondroplasia and the other had hypochondroplasia. Both had severe short stature and evidence of rhizomelia and mesomelia as well as other phenotypic features of their individual genetic disorders. Achondroplasia was due to the G380R FGF3R mutation and hypochondroplasia to a N540K mutation in the same gene. The patient with hypochondroplasia had a heterozygous SHOX deletion; no SHOX mutation was identified in the child with achondroplasia. The phenotypes of combined LWD and achondroplasia or hypochondroplasia appeared to be less than additive, suggesting that SHOX and FGFR3 act on overlapping pathways of bone growth and development. © 2002 Wiley‐Liss, Inc.
Is immunosuppression therapy in renal allograft recipients teratogenic? A single‐center experience
Authors: Bar Jacob , Stahl Bracha , Hod Moshe , Wittenberg Clara , Pardo Joseph , Merlob Paul
Published: December 2002

The aim of the study was to determine whether immunosuppressive agents used in renal allograft recipients are teratogenic or otherwise associated with pregnancy outcome. The study population consisted of 38 renal allograft recipients treated with combinations of prednisone, azathioprine, cyclosporin A, and tacrolimus attending our Hypertension in Pregnancy Clinic. The 48 live offspring of 73 pregnancies in this group were evaluated for major congenital malformations and mild errors of morphogenesis. Findings were compared with those in 48 offspring of 41 women with primary renal disease not treated with immunosuppressive drugs. Pregnancy outcome parameters were also compared between the study and control groups in the perinatal period and on a long‐term basis (2–7 years after birth). Two major anomalies (4.2%), subcoronal hypospadias and rudimentary thumb, and 10 mild errors of morphogenesis (20.8%) were detected in the study group. These rates did not differ significantly from those in the control group (4.2% and 16.6%, respectively). Pregnancy outcome was worse in the renal transplant patients than in the women with primary renal disease in terms of prematurity (60% vs. 21%, P = 0.001), growth restriction (52% vs. 17%, P = 0.001), and hospitalization in a neonatal intensive care unit (35% vs. 6%, P = 0.01). In conclusion, the similar prevalence of major anomalies and mild errors of morphogenesis in offspring of the renal transplant patients and the women with primary renal disease suggests that immunosuppressive therapy is not a teratogenic factor. It may, however, be associated with worse pregnancy outcome. © 2002 Wiley‐Liss, Inc.
46,XY gonadal dysgenesis: Evidence for autosomal dominant transmission in a large kindred
Authors: Le Caignec Cédric , Baron Sabine , McElreavey Ken , Joubert Madeleine , Rival Jean‐Marie , Mechinaud Françoise , David Albert
Published: December 2002

46,XY gonadal dysgenesis is characterized by abnormal testicular determination. We describe a large kindred in which various disorders of sexual development were observed, ranging from completely female phenotype without ambiguities of the external genitalia (five cases) to men with isolated penile or perineal hypospadias (four cases), including two cases with moderate virilization and one case with ambiguity of the external genitalia. Histologic examination of gonadal tissue was performed on seven subjects. These findings were suggestive of complete gonadal dysgenesis in one patient, partial gonadal dysgenesis in three patients, and mixed gonadal dysgenesis in three patients. Four patients developed gonadal tumors (two gonadoblastoma, two dysgerminoma, and one immature teratoma, i.e., one patient had a dysgerminoma with some areas of gonadoblastoma). All affected subjects had no other congenital anomalies or dysmorphic features. Analysis of families with several affected individuals with 46,XY gonadal dysgenesis implied an X‐linked mode of inheritance because of the apparent absence of male‐to‐male transmission. However, a sex‐limited autosomal dominant mode of inheritance affecting only XY individuals could not be ruled out. Analysis of the pedigree we report indicated an autosomal dominant mode of inheritance because of male‐to‐male transmission. This kindred supports the involvement of at least one autosomal gene in non‐syndromic 46,XY gonadal dysgenesis. © 2002 Wiley‐Liss, Inc.
First patient with trisomy 21 accompanied by an additional der(4)(:p11 → q11:) plus partial uniparental disomy 4p15‐16
Authors: Starke Heike , Mitulla Beate , Nietzel Angela , Heller Anita , Beensen Volkmar , Grosswendt Gisela , Claussen Uwe , von Eggeling Ferdinand , Liehr Thomas
Published: December 2002

We report on a rare additional numerical chromosomal aberration in a child with Down syndrome due to free trisomy 21. The karyotype showed 48,XY,+21,+mar after GTG banding, with the marker present in 80% of cells. The supernumerary marker chromosome (SMC) was as small as approximately one‐third of 18p, and with the recently developed centromere‐specific multi‐color fluorescence in situ hybridization (cenM‐FISH) technique, it was shown that the SMC was a derivative chromosome 4. The SMC was not specifically stained by arm‐specific probes for chromosome 4; thus, it has been described as der(4)(:p11 → q11:). Microsatellite analysis resulted in a partial maternal uniparental isodisomy (UPD) for chromosome 4p15–16 and a maternal origin for two chromosomes 21. Until now only two similar cases have been described in the literature, but without clarifying the origin of the SMC and without looking for an additional UPD. This is the only reported case of a UPD 4p in a liveborn child. © 2002 Wiley‐Liss, Inc.
Velocardiofacial syndrome in an unexplained XX male
Authors: Phelan Mary C. , Rogers R. Curtis , Crawford Eric C. , Brown Laura G. , Page David C.
Published: December 2002

We report the unusual finding of velocardiofacial syndrome (VCF) in an unexplained 46,XX male. A microdeletion of 22q11.2 was confirmed by fluorescence in situ hybridization (FISH) analysis. Routine G‐banded chromosome analysis revealed an XX sex chromosome constitution. FISH was performed using the SRY probe and failed to detect hybridization. The sex chromosome status of the patient was further investigated by PCR testing to screen for the presence of 24 distinct loci spanning the Y chromosome. PCR screening failed to detect any apparent Y chromosome material. © 2002 Wiley‐Liss, Inc.
Communication with close and distant relatives in the context of genetic testing for hereditary breast and ovarian cancer in cancer patients
Authors: Claes Erna , Evers‐Kiebooms Gerry , Boogaerts Andrea , Decruyenaere Marleen , Denayer Lieve , Legius Eric
Published: December 2002

The psychological aspects of genetic testing for hereditary breast and ovarian cancer (HBOC) in cancer patients (diagnostic genetic testing) have so far received less attention than predictive genetic testing in unaffected persons. Our study is aimed at gaining insight into the psychological aspects of diagnostic genetic testing and at formulating practical recommendations for counseling. Cancer patients often play a key role in the communication of information to relatives because they were the first individuals to be tested in the family. The present article focuses on the communication to close and distant relatives about the hereditary cancer, the genetic test and its result. Participants previously diagnosed with breast and/or ovarian cancer, with a family history of these cancers and who requested DNA‐testing, were eligible for the study. Of the 83 eligible patients who could be contacted, 63 participated (response rate = 76%). Twenty‐six participants were members of a family where a BRCA1 or BRCA2 mutation was detected. The DNA‐analysis in the family of 37 participants had not revealed any mutation. Data were collected by semi‐structured interviews and psychological tests and questionnaires. The dissemination of information was largely focused on first‐degree relatives. Communication to distant relatives about the genetic test and its result was problematic. Other than the genetic test result and age as “objective” predictors of informing distant relatives, little and/or superficial contact seemed to be the major subjective barrier to informing distant relatives. Furthermore, the knowledge about HBOC of these messengers reveals several shortcomings. Communication within the family should receive special attention during counseling. © 2002 Wiley‐Liss, Inc.
Further delineation of Wittwer syndrome and refinement of the mapping region
Authors: Wieland Ilse , Muschke Petra , Wieacker Peter
Published: December 2002

In 1996, Wittwer et al. described a XLMR‐syndrome mapping in Xp22.3. This family was reexamined. The spectrum of clinical symptoms now includes progressive skeletal lesions with osteoplastic and osteoclastic changes. Haplotype analysis using 23 microsatellite markers on Xp22 localized the disease locus between DXS8095 and DXS7108 comprising 3.9–6.1 Mb. This interval overlaps with known contiguous gene‐deletion syndromes. However, deletion analysis of identified genes and ESTs in the critical interval for Wittwer syndrome showed no loss of the corresponding marker sequences in the patients. © 2002 Wiley‐Liss, Inc.
Mild phenotype in a 15‐year‐old boy with Pallister–Killian syndrome
Authors: Genevieve D. , Cormier‐Daire V. , Sanlaville D. , Faivre L. , Gosset P. , Allart L. , Picq M. , Munnich A. , Romana S. , de Blois Mc. , Vekemans M.
Published: December 2002

Pallister–Killian syndrome is a rare disorder characterized by multiple congenital anomalies, coarse face, pigmentary skin changes, seizures, severe mental retardation, and the presence of an extra metacentric chromosome i(12p) confined to skin fibroblasts only. Here, we report on an unusual case of i(12p) in a 15‐year‐old boy presenting with mild mental retardation, minor facial features (long face, prognathism, short neck), normal weight, length, and OFC parameters as well as hyperpigmented streaks. The boy attended normal school until the age of 14 years. Because of hyperpigmented stripes, chromosome analysis was performed on skin fibroblasts. This study showed that 37% of the cells had an additional isochromosome for the short arm of chromosome 12. This observation illustrates the phenotypic variability of i(12p) and emphasizes the importance of skin fibroblasts chromosome analysis in patients with pigmentary skin changes. © 2002 Wiley‐Liss, Inc.
Molecular cytogenetic analysis of a constitutional de novo interstitial deletion of chromosome 12p in a boy with developmental delay and congenital anomalies
Authors: Gläser Birgitta , Rossier Eva , Barbi Gotthold , Chiaie Loredana Delle , Blank Christian , Vogel Walther , Kehrer‐Sawatzki Hildegard
Published: December 2002

We describe the case of a 6‐month‐old boy with psychomotor retardation, craniofacial dysmorphism, cleft lip and palate, as well as hearing and visual impairment. Analysis of G‐banded chromosomes of the propositus showed a de novo interstitial deletion of the short arm of chromosome 12, del(12)(p12.1p12.3). Molecular cytogenetic analysis with bacterial artificial chromosomes (BAC) clones was used to refine the extent of the deletion. The deleted segment encompasses about 12.5 Mb between markers D12S1832 and G62375. The phenotypic consequences of the deletion are discussed and compared with other cases of interstitial deletions of proximal chromosome 12p. © 2002 Wiley‐Liss, Inc.
G protein subunit Gγ13 is coexpressed with Gαo, Gβ3, and Gβ4 in retinal ON bipolar cells
Authors: Huang Liquan , Max Marianna , Margolskee Robert F. , Su Hui , Masland Richard H. , Euler Thomas
Published: December 2002

We investigated the expression of Gγ13, a recently discovered G protein subunit, and a selection of Gβ subunits in retinal bipolar cells, by using a transgenic mouse strain in which green fluorescent protein is strongly expressed in a single type of cone bipolar cell. The cells have ON morphology, and patch‐clamp recordings in slices confirmed that they are of the physiological ON type. Immunohistochemistry showed that Gγ13 is expressed in rod bipolar cells and ON cone bipolar cells, where it is colocalized in the dendrites with Gαo. ON and OFF cone bipolar cells and rod bipolar cells were identified among dissociated cells by their green fluorescence and/or distinct morphology. Hybridization of single‐cell polymerase chain reaction products with cDNA probes for G protein subunits Gβ1 to 5 showed that Gβ3, Gβ4, and Gγ13 are coexpressed in ON bipolar cells but not present in OFF bipolar cells. Gβ1, 2, and 5 are expressed in partially overlapping subpopulations of cone bipolar cells. Gγ13 and Gβ3 and/or Gβ4, thus, seem selectively to participate in signal transduction by ON bipolar cells. J. Comp. Neurol. 455:1–10, 2003. © 2002 Wiley‐Liss, Inc.
Morphological classification of the rat lateral cerebellar nuclear neurons by principal component analysis
Authors: Sultan Fahad , Czubayko Uwe , Thier Peter
Published: December 2002

The deep cerebellar nuclei (DCN) constitute the major structures by which the cerebellum forwards its output to the rest of the brain. Although the connectivity of the DCN has been well studied, little is known about the interface—the neurons' soma and dendrites—between the DCN's inputs and outputs. We therefore decided to analyze the neurons' somatic and dendritic morphology by applying a multivariate approach (principal component analysis; PCA), in order to define morphological groups possibly related to distinct positions in the nuclear microcircuitry. The PCA was based on intracellularly stained neurons from the rat's lateral DCN and on 19 parameters that described the neurons' morphology. The PCA yielded two principal components that accounted for 46% of the variance. The first component, correlated with soma size, separated the majority of neurons (type I) from a population of small neurons (type II). The second component showed negative correlation with larger cells with more numerous primary dendrites and a more multipolar appearance (type Ia) and positive correlation with smaller neurons with asymmetric dendritic fields and tufted dendrites (type Ib). The preponderance of small somata in our type Ib neurons suggests that these neurons probably correspond to the inferior olive projection neurons. In summary, our results are in agreement with previous classifications, which distinguished projection neurons (type I) from local neurons (type II); furthermore, our results point to a hitherto undescribed dendritic morphological difference in the projection neurons. The latter may be important for understanding the phylogenetic changes seen in the mammalian lateral cerebellar nucleus. J. Comp. Neurol. 455:139–155, 2003. © 2002 Wiley‐Liss, Inc.
Projection neurons originating from thermo‐ and hygrosensory glomeruli in the antennal lobe of the cockroach
Authors: Nishino Hiroshi , Yamashita Shingo , Yamazaki Yoshiyuki , Nishikawa Michiko , Yokohari Fumio , Mizunami Makoto
Published: December 2002

Most insects are equipped with specialized thermo‐ and hygroreceptors to locate a permissible range of ambient temperature and distant water sources, respectively. In the cockroach, Periplaneta americana, cold, moist, and dry receptor cells in the antennae send axons to particular sets of two or three glomeruli in the dorsocentral part of the antennal lobe (primary olfactory center), designated DC1–3 glomeruli. However, it is not known how thermo‐ and hygrosensory signals from these glomeruli are represented in higher‐order centers, the protocerebrum, in any insect species. With the use of intracellular recording and staining techniques, we identified a new class of interneurons with dendrites almost exclusively in the DC1, DC2, or DC3 glomeruli and axons projecting to the protocerebrum in the cockroach. Remarkably, terminals of all these projection neurons (PNs) covered almost identical areas in the lateral protocerebrum (LP), although their termination areas outside the LP differed from neuron to neuron. The termination areas within the LP were distinct from, but close to, those of uniglomerular and macroglomerular PNs that transmitted signals concerning general odors and female sex pheromones, respectively. PNs originating from DC1, DC2, and DC3 glomeruli exhibited excitatory responses to cold, moist, and dry stimuli, respectively, probably due to excitatory synaptic input from cold, moist, and dry receptor cells, respectively, whereas their responses were often modulated by olfactory stimuli. These findings suggested that dorsocentral PNs participate in neural pathways that lead to behavioral responses to temperature or humidity changes. J. Comp. Neurol. 455:40–55, 2003. © 2002 Wiley‐Liss, Inc.
Anatomic mapping of neuronal odor responses in the developing rat olfactory bulb
Authors: Guthrie Kathleen M. , Gall Christine
Published: December 2002

Behavioral evidence indicates that altricial mammals possess olfactory function at early developmental ages, before the olfactory bulb has matured anatomically. We monitored the early anatomic and functional development of the olfactory bulb in rat pups stimulated with odors using in situ localization of c‐fos mRNA to identify responsive postsynaptic neurons. Odor‐specific spatial patterns of neuronal activation in the glomerular layer were evident from birth, were sharply defined rather than diffuse, and remained relatively unchanged in terms of their bulbar distribution during the first 3 postnatal weeks. In neonates, focal postsynaptic responses in the glomerular layer occurred in the form of clusters of activated tufted neurons. Broad zones of activated mitral cells were located beneath these cell clusters, with scattered neurons in the underlying granule cell layer also expressing c‐fos. The cellular composition of these functional neuronal groups shifted from predominantly output neurons at the earliest ages, to increasing incorporation of interneurons as they developed postnatally. The characteristic distribution of activated neurons in the mature glomerular layer, in which the boundaries of individual glomeruli are precisely defined by cells expressing c‐fos, emerged near the end of the first week. Broad zones of cRNA hybridization in the mitral cell layer became increasingly restricted as the size of the activated granule cell population increased postnatally, correlating with the functional maturation of inhibitory circuitry. These results provide evidence that the types and distributions of neurons collectively activated by sensory input to glomeruli change as the rat olfactory bulb matures and that distinct, functional odor maps in the glomerular layer are established from birth. J. Comp. Neurol. 455:56–71, 2003. © 2002 Wiley‐Liss, Inc.
Developmental expression of nicotinic receptors in the chick and human spinal cord
Authors: Keiger C. Jane H. , Prevette David , Conroy William G. , Oppenheim Ronald W.
Published: December 2002

Naturally occurring programmed cell death of lumbar motor neurons in the chick spinal cord occurs between embryonic day (E) 6 and E12; whereas, a peak of motor neuron degeneration in the human spinal cord occurs between 12 and 16 weeks gestation. One of the major neurotransmitters, acetylcholine, is released from the embryonic motor neuron early in development and is thought to be responsible for early muscle activity that serves as a signal for regulating motor neuron survival. The effects of acetylcholine are mediated by two functionally distinct classes of receptors; namely, muscarinic and nicotinic with nicotinic receptors being used at the neuromuscular synapse. In this study, we determined the developmental expression profile of nicotinic acetylcholine receptor subunits in the chick and human lumbar motor neurons and skeletal muscle using reverse transcription polymerase chain reaction, immunoblots, and immunocytochemistry. Our results show that, in the chick, nicotinic receptor subunits α1, α4, α7, α8, and β2 appear to be regulated during the process of naturally occurring motor neuron cell death in the spinal cord. A new finding was the expression of α8 mRNA and protein from E4.5 through E7 in chick motor neurons. Interestingly, we also found that, at E14, α8 protein was localized only in sensory dorsal horn neurons. In the developing human spinal cord, we determined that nicotinic receptor subunits α1, α2, α3, α4, α7, β2, and β3 were expressed before the programmed cell death period, and α2, α4, α7, β2, β3, and β4 were expressed during the programmed cell death period. Our data demonstrate that neuronal and muscle nicotinic receptor mRNAs and proteins are expressed during important embryonic periods. This finding raises the possibility that nicotinic receptors play an important role in the spinal cord and skeletal muscle during early development. J. Comp. Neurol. 455:86–99, 2003. © 2002 Wiley‐Liss, Inc.
Expression of AMPA‐type glutamate receptor subunit (GluR2) in ON‐bipolar neurons in the rat retina
Authors: Kamphuis Willem , Klooster Jan , Dijk Frederike
Published: December 2002

The role of glutamate receptors (GluR) in the signal pathways of the retina is widely recognized. Photoreceptors make synaptic contact with functionally different classes of bipolar cells. The OFF‐type bipolar cells mediate light offset‐evoked responses and use ionotropic α‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionate (AMPA)‐ or kainate‐type GluRs, whereas bipolars involved in the ON‐pathway use the metabotropic GluR6. This dichotomy predicts a defined expression pattern of AMPA‐type GluRs and mGluR6 in bipolar cell classes. This hypothesis was tested by performing immunocytochemical double labeling studies combining GluR‐specific antibodies with markers specific for the diverse bipolar cell populations in the rat retina. AMPA‐type receptors are composed of combinations of four types of subunits, GluR1–4. GluR1 is expressed by a few somata in the outer part of the inner nuclear layer (INL). Sparse colocalization with any of the bipolar markers used could be established. In contrast, GluR2 is expressed by many of the somata in the outer zone of the INL. At the transcript level, in situ hybridizations demonstrated abundant GluR2 expression over the complete width of the INL. In contrast to our expectations, approximately 70% of the somata labeled by the rod ON‐bipolar markers protein kinase C (PKC) or Goα, colocalized with GluR2. Approximately 90% of the OFF‐type bipolar cells, identified as recoverin‐positive, showed GluR2 immunoreactivity. At least 40% of the somata that were mGluR6‐immunoreactive, a both rod and cone ON‐type bipolar marker, were GluR2‐immunopositive. Ultrastructurally, examples were observed of GluR2 localization in bipolar processes with labeling outside the actual compartment associated with the synaptic complex of the rod terminal. No specific antibody was available against GluR3, but 74% of the PKC‐positive cells were GluR2/3‐positive. GluR4 did not show a somatic localization making double labeling impossible. On the basis of these results, we conclude that ionotropic GluRs are expressed by rod ON‐type bipolar cells (PKC‐ or Goα‐immunoreactive), and by cone ON‐ and OFF‐type bipolars based on a colocalization with nearly all of the present recoverin‐positive somata. Our observations show that the functional dichotomy in ON‐ and OFF‐type bipolars is not reflected in a matching expression pattern of ionotropic and metabotropic GluRs. This finding raises the intriguing possibility that the AMPA‐type GluRs are, in an as yet unclear manner, involved in the ON signaling pathways of rods and cones. J. Comp. Neurol. 455:172–186, 2003. © 2002 Wiley‐Liss, Inc.
Long‐term regeneration of abdominal vagus: Efferents fail while afferents succeed
Authors: Phillips Robert J. , Baronowsky Elizabeth A. , Powley Terry L.
Published: December 2002

Vagal afferents regenerate, by 18 weeks after subdiaphragmatic transection, to reinnervate the gut and to differentiate into the two types of terminals normally found in the smooth muscle wall of the gastrointestinal (GI) tract (Phillips et al. [2000] J Comp Neurol. 421:325–346). Regeneration, however, is neither complete nor entirely accurate by 18 weeks. Moreover, the capacity of the vagal efferents to reinnervate the GI tract under comparable conditions has not been evaluated. Therefore, to determine whether a more extended postaxotomy survival interval would (1) result in more extensive reinnervation of smooth muscle, (2) facilitate correction of the inaccuracies of the regenerated axons and terminals, and (3) yield motor as well as sensory reinnervation of GI targets, Sprague‐Dawley rats received either complete subdiaphragmatic vagotomies (n = 18) or sham surgeries (n = 12). Physiological endpoints that might normalize as vagal elements regenerated, including body weight, daily food intake, size of first daily meal, and metabolic efficiency, were monitored. At 45 weeks after the vagotomies, the animals were randomly assigned to afferent (wheat germ agglutinin–horseradish peroxidase) or efferent (cholera toxin subunit B–horseradish peroxidase) mapping conditions, and labeled axons and terminals in the stomach and first 8 cm of the small intestine were inventoried in whole‐mounts. Afferent regeneration was more extensive at 45 weeks than previously observed at 18 weeks after surgery; however, the amount of GI innervation was still not comparable to the intact pattern of the sham rats. Furthermore, abnormal patterns of sensory organization occurred throughout the reinnervated field, with small bundles of axons forming complex tangles and some individual axons terminating in ectopic locations. The presence of growth cone profiles suggested that vagal reorganization was ongoing even 45 weeks after surgery. In contrast to this relatively extensive, albeit incomplete, sensory reinnervation of the gut, motor fibers had failed to reinnervate the GI tract. Thus, dramatic differences exist in the regenerative capacities of the sensory and motor arms of the vagus under the same surgical and maintenance conditions. Furthermore, the functional measures of disordered energy regulation did not normalize over the 45 weeks during which afferent but not efferent innervation was restored. J. Comp. Neurol. 455:222–237, 2003. © 2002 Wiley‐Liss, Inc.
Expression of Ca2+‐activated BK channel mRNA and its splice variants in the rat cochlea
Authors: Langer Patricia , Gründer Stefan , Rüsch Alfons
Published: December 2002

Voltage‐activated K+ channels are important for shaping the receptor potentials of cochlear hair cells. In particular, the functional maturation of inner hair cells in mice around the onset of hearing coincides with the expression of a large, fast K+ conductance, probably mediated by Ca2+‐activated K+ (BK) channels. In hearing organs of lower vertebrates, frequency tuning depends on BK‐type K+ channels with different kinetics. Kinetics are varied by alternative splicing of the channels' α subunits and combination with modulating β subunits. It is unclear whether similar mechanisms “fine tune” mammalian hair cells. We used various polymerase chain reaction (PCR) approaches to screen rat cochleae for splice variants of BK‐type α subunits. We isolated mainly minimal variants and only occasionally splice variants with additional inserts. We conclude that α subunits with different kinetics are not substantially used in the rat cochlea. However, we isolated six variants differing in their extreme C‐terminal sequences, which may be involved in the targeting of the channel protein. By using reverse transcriptase‐PCR, we demonstrated also the expression of transcripts for several β subunits. In situ hybridization experiments revealed strict coexpression of α with β1 transcripts. In inner hair cells, strong labeling emerged shortly before the onset of hearing. Labeling of outer hair cells appeared later and generally weaker. Thus, our molecular data confirm electrophysiological results that suggested that BK channels underlie the large K+ conductance in inner hair cells of mammals. Extensive splicing of BK channel transcripts, however, does not seem to be used in mammalian hair cells as is done in lower vertebrates. J. Comp. Neurol. 455:198–209, 2003. © 2002 Wiley‐Liss, Inc.
Topographical and laminar organization of subicular projections to the parahippocampal region of the rat
Authors: Kloosterman Fabian , Witter Menno P. , Van Haeften Theo
Published: December 2002

In this study, we analyzed in detail the topographic organization of the subiculoparahippocampal projection in the rat. The anterograde tracers Phaseolus vulgaris leucoagglutinin‐L and biotinylated dextran amine were injected into the subiculum at different septotemporal and transverse levels. Deep layers of the ento‐, peri‐, and postrhinal cortices are the main recipients of subicular projections, but in all cases we noted that a small fraction of the projections also terminates in the superficial layers II and III. Analysis of the fiber patterns in the parahippocampal region revealed a topographic organization, depending on the location of the cells of origin along both the transverse and the septotemporal axes of the subiculum. Projections originating from subicular cells close to CA1, i.e., proximal part of subiculum, terminate exclusively in the lateral entorhinal cortex and in the perirhinal cortex. In contrast, projections from cells closer to the subiculum‐presubiculum border, i.e., distal part of subiculum, terminate in the medial entorhinal cortex and in the postrhinal cortex. In addition, cells in septal portions of the subiculum project to a lateral band of entorhinal cortex parallel to the rhinal sulcus and to peri‐ or postrhinal cortices, whereas cells in more temporal portions project to more medial parts of the entorhinal cortex. These results indicate that subicular projections to the parahippocampal region precisely reciprocate the known inputs from this region to the hippocampal formation. We thus suggest that the reciprocal connectivity between the subiculum and the parahippocampal region is organized as parallel pathways that serve to segregate information flow and thus maintain the identity of processed information. Although this parallel organization is comparable to that of the CA1‐parahippocampal projections, differences exist with respect to the degree of collateralization. J. Comp. Neurol. 455:156–171, 2003. © 2002 Wiley‐Liss, Inc.
Calbindin and calretinin immunoreactivities identify different types of neurons in the adult lamprey spinal cord
Authors: Megías Manuel , Álvarez‐Otero Rosa , Pombal Manuel A.
Published: December 2002

The central pattern generator for locomotion in vertebrates is composed of different spinal neuronal populations that generate locomotor movement. In the lamprey spinal cord, several classes of interneurons have been identified based on morphologic and physiological criteria and integrated in the spinal cord circuits implicated in the generation of locomotion. However, the lack of histochemical markers for most of the interneurons makes it difficult to study whole populations along the spinal cord. We have investigated the immunoreactivity with antibodies raised against calbindin and calretinin. Several types of neurons could be classified: (1) strongly immunoreactive neurons located dorsomedially, (2) moderately immunoreactive neurons located laterally, (3) small weakly immunoreactive neurons, d) ventromedial neurons, (4) liquor contacting cells, and (5) motoneurons. The ventromedial group of calbindin‐immunoreactive neurons also is immunoreactive for serotonin and, therefore, represents the ventromedial group of dopamine/serotonin spinal neurons. Some of the lateral calbindin‐immunoreactive neurons may be CC‐type cells (cells with caudal‐crossed axons), because they are retrogradely labeled by tracer injections into the contralateral spinal cord. Other well‐characterized cell types, such as sensory dorsal cells, lateral interneurons, descending propriospinal edge cells, and spinobulbar giant interneurons are negative for both calbindin and calretinin. Therefore, calbindin and calretinin are useful markers for the study of cell populations that may be integrated in locomotor circuits. J. Comp. Neurol. 455:72–85, 2003. © 2002 Wiley‐Liss, Inc.
Ecological, evolutionary, and functional correlates of sensilla number and glomerular density in the olfactory system of decapod crustaceans
Authors: Beltz Barbara S. , Kordas Kashka , Lee Monaya M. , Long Jennifer B. , Benton Jeanne L. , Sandeman David C.
Published: December 2002

One of the features common among olfactory systems for vertebrate and invertebrate species is the division of the primary processing area into distinct clumps of synaptic neuropil, called glomeruli. The olfactory glomeruli appear to serve as functional units of olfaction and are the location of the primary processing between chemosensory afferents and second‐order neurons. Although glomeruli are found across all phyla, their numbers and size appear to be characteristic for each species, giving rise to the speculation that there is a relationship between glomerular number and function. It has been hypothesized, for example, that animals with more glomeruli may be able to resolve a wider range of odors. Crustacean species are distributed among freshwater, marine, and terrestrial habitats in arctic, temperate, and tropical climates. They also exhibit a variety of lifestyles and behaviors in which olfaction may play a dominant role. Feeding, for example, ranges from carnivorous, through subaquatic and terrestrial omnivorous scavenging, to filter feeding. Mating and territorial behaviors also are known to involve chemical signals. The current study examines glomerular numbers in the olfactory lobes of 17 crustacean species from six of the seven taxa now included in the reptantian decapods. Estimates of the glomerular numbers were obtained from the analysis of sectioned material treated immunocytochemically with an antibody against synapsin that labels proteins contained in neuronal terminals. The numbers of glomeruli found in the different species were then compared with the volume of the glomerular neuropil, numbers of olfactory sensilla, life styles, habitat, and phylogenetic affinities. The picture that emerges from these correlations is that the decapod crustaceans have exploited various strategies in the construction of their olfactory systems in which the problems of size, sensitivity, and selectivity have all interacted. We find a continuum across the groups ranging from those that favor a high convergence of receptor neurons onto a few glomeruli to those that share a small number of receptor neurons among many glomeruli. The potential functional consequences of these differences are discussed. J. Comp. Neurol. 455:260–269, 2003. © 2002 Wiley‐Liss, Inc.
Loss of calbindin‐D28k from aging human cholinergic basal forebrain: Relation to neuronal loss
Authors: Geula Changiz , Bu Jing , Nagykery Nicholas , Scinto Leonard F.M. , Chan Jennifer , Joseph Jeffrey , Parker Robert , Wu Chuang‐Kuo
Published: December 2002

Cholinergic neurons of the basal forebrain (BFCN) are selectively vulnerable in neurodegenerative disorders of the elderly, particularly in Alzheimer's disease (AD). We investigated age‐related changes in the BFCN that may serve as a substrate for this vulnerability. We report a substantial and selective age‐related loss of the calcium binding protein calbindin‐D28K (CB) from the human BFCN. Unbiased stereological estimation indicated that, in individuals under age 65 years, 72% of the choline acetyltransferase (ChAT)‐positive BFCN contained CB immunoreactivity. In individuals over age 65 years, only 28% of the BFCN contained CB immunoreactivity, a dramatic loss of 61%. Similar results were obtained using neuronal counts from matching single‐ or double‐stained sections in a larger cohort. The loss of CB immunoreactivity was neurochemically specific. No age‐related changes were observed in the number of ChAT‐ or low‐affinity nerve growth factor receptor (p75NTR)‐immunoreactive profiles. The loss of CB was greatest in very old individuals, in whom a small loss of BFCN was observed. Furthermore, the loss of CB displayed the same pattern as the loss of BFCN in AD and was more substantial in the posterior compared with the anterior BFCN sector, suggesting a role for CB in the selective vulnerability of BFCN in AD. The depletion of CB from the BFCN is likely to deprive these neurons of the capacity to buffer high levels of intracellular Ca2+ and thus to leave them vulnerable to pathological processes, such as those in neurodegenerative disorders, which can cause increased intracellular Ca2+, thus leading to their degeneration. J. Comp. Neurol. 455:249–259, 2003. © 2002 Wiley‐Liss, Inc.
Evidence that Sema3A and Sema3F regulate the migration of GABAergic neurons in the developing neocortex
Authors: Tamamaki Nobuaki , Fujimori Kazuhiro , Nojyo Yoshiaki , Kaneko Takeshi , Takauji Rumiko
Published: December 2002

The ganglionic eminence (GE) supplies neurons containing γ‐aminobutyric acid (GABA) to the pallium of the telencephalon. We investigated the molecular guidance mechanisms of GE cell migration in the neocortex and found neuropilin‐1 (Npn‐1) or neuropilin‐2 (Npn‐2) on the GE cells. Ectopic Sema3A or ‐3F expression by COS1 cell clusters placed on embryo neocortical slices reduced the cell migration but did not block it completely. However, the cell migration was almost completely blocked by COS1 cell clusters expressing both Sema3A and ‐3F. The direction of cell migration could be reversed by placing Sema3A‐ and ‐3F‐coexpressing COS1 cell clusters at the distal cut end of the neocortical slices. Further slice experiments revealed that migration of half of the GE cells in the neocortex was regulated by Sema3A and that migration of the other half of the GE cells in the neocortex was regulated by Sema3F. When the cells responding to Sema3A were diverted by ectopic Sema3A expression in vivo, Dlx2‐positive cells were found predominantly in the lower intermediate zone (IZ). When the cells responding to Sema3F were diverted by ectopic Sema3F expression in vivo, Dlx2‐positive cells were found predominantly in the upper IZ. It was speculated that the semaphorin–neuropilin interactions distribute the GABAergic GE cells evenly in the neocortex as well as guide the GE cells from the GE to the neocortex. The Sema3A expression site under the subplate extended dorsally as the embryo developed. The Sema3A expression seemed to block the Npn‐1‐positive GE cells in the neocortex from entering the cortical plate (CP) and guide them to the dorsal cortex and the hippocampus. Sema3F expression in the CP continued through the embryonic stages. The expression seemed to block Npn‐2‐positive GE cells in the neocortex from entering the CP and make them migrate into the lower IZ. Finally, the semaphorin–neuropilin interactions sorted GABAergic inteneurons into the CP and white matter neurons into the IZ. J. Comp. Neurol. 455:238–248, 2003. © 2002 Wiley‐Liss, Inc.
Inspiratory augmenting bulbospinal neurons express both glutamatergic and enkephalinergic phenotypes
Authors: Stornetta Ruth L. , Sevigny Charles P. , Guyenet Patrice G.
Published: December 2002

Many of the inspiratory augmenting (I‐AUG) neurons of the rostral ventral respiratory group (rVRG) are premotor neurons that excite phrenic motor neurons during inspiration, probably by releasing glutamate. In the present study, we demonstrate that these neurons are indeed glutamatergic, in that their cell bodies contain vesicular glutamate transporter‐2 (VGLUT2) mRNA and spinal terminals from neurons in the region of the rVRG contain VGLUT2 protein. We also demonstrate by using parallel in situ hybridization and immunocytochemical evidence that most rVRG inspiratory premotor neurons are enkephalinergic. After iontophoretic deposits of biotinylated dextran amine (BDA) in the area of the rVRG, many BDA‐labeled terminals in the ventral horn of cervical spinal cord (C4–C5) were immunoreactive for enkephalin and VGLUT2. Injections of Fluoro‐Gold amidst phrenic motor neurons in C4–C5 labeled neurons in the area of the rVRG that contained both VGLUT2 mRNA and preproenkephalin (PPE) mRNA as revealed by double in situ hybridization. Thirty‐eight bulbospinal I‐AUG neurons were recorded in the rVRG and filled with biotinamide by using the juxtacellular labeling technique. Every biotinamide‐filled cell tested was positively labeled for VGLUT2 mRNA (n = 14), and most of the cells tested in a separate population exhibited PPE mRNA (16/18). We conclude that most of the phrenic inspiratory premotor neurons of the rVRG are glutamatergic neurons that may also release enkephalins. J. Comp. Neurol. 455:113–124, 2003. © 2002 Wiley‐Liss, Inc.
Olfactory‐enriched transcripts are cell‐specific markers in the lobster olfactory organ
Authors: Hollins Bettye , Hardin Debra , Gimelbrant Alexander A. , McClintock Timothy S.
Published: December 2002

Genes expressed specifically in a tissue are often involved in the defining functions of that tissue. We used representational difference analysis of cDNA to amplify 20 cDNA fragments representing transcripts that were more abundant in the lobster olfactory organ than in brain, eye/eyestalk, dactyl, pereiopod, or second antenna. We then independently confirmed that the transcripts represented by these clones were enriched in the olfactory organ. The 20 cDNA fragments represent between 6 and 15 different genes. Six of the cDNAs contained sequences highly similar to known gene families. We performed in situ hybridization with these six and found that all were expressed in subsets of cells associated with the aesthetasc sensilla in the olfactory organ. Clones OET‐07, an ionotropic receptor, and OET‐10, an α tubulin, were specific to the olfactory receptor neurons. OET‐02, a monooxygenase, was expressed only in the outer auxiliary cells. OET‐03, a serine protease, was specific to the collar cells. OET‐11, an α2 macroglobulin, was expressed by the receptor neurons and the collar cells. OET‐17, a calcyphosine, was expressed in the receptor neurons, inner auxiliary cells, and collar cells. The identities and expression patterns of these six transcripts predict involvement in both known and novel properties of the lobster olfactory organ. J. Comp. Neurol. 455:125–138, 2003. © 2002 Wiley‐Liss, Inc.
Ultrastructural localization of serotonin 2A and N‐methyl‐D‐aspartate receptors in somata and dendrites of single neurons within rat dorsal motor nucleus of the vagus
Authors: Huang Jie , Pickel Virginia M.
Published: December 2002

Both glutamate and serotonin are potent modulators of autonomic functions involving the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMNV) at the level of the area postrema. Moreover, many of the dendrites in this NTS region express both N‐methyl‐D‐aspartate (NMDA) and serotonin (5HT) 2A receptors, and some of these dendrites may arise from the adjacent DMNV. Thus, single neurons in DMNV may also express both receptors. To test this hypothesis, we used electron microscopic immunocytochemistry for dual localization of the essential R1 subunit of the NMDA receptor (NR1) and the 5HT2A receptor in rat intermediate DMNV, a region serving mainly gastrointestinal functions. Gold particles representing NR1 and peroxidase reaction product for 5HT2A receptors were seen in the cytoplasm, as well as on distinct segments of the plasma membrane of many dendrites. Of the NR1‐labeled dendrites, 31% (254/814) also contained 5HT2A immunoreactivity; among the 5HT2A‐labeled dendrites, 52% (254/485) expressed NR1. The 5HT2A labeling was also present in numerous small unmyelinated axons, axon terminals, and glial processes. These profiles were largely without NR1 immunoreactivity, although NR1 was detected in some of the dendrites postsynaptic to 5HT2A‐labeled terminals. Our results suggest that calcium entry through NMDA channels and 5HT2A receptor activation may dramatically affect postsynaptic excitability of single neurons in the DMNV. In addition, the findings also indicate that the 5HT2A receptor is strategically positioned for involvement in modulation of the presynaptic release of neurotransmitters affecting the postsynaptic activity of DMNV neurons responsive to NMDA activation. J. Comp. Neurol. 455:270–280, 2003. © 2002 Wiley‐Liss, Inc.