bluuebunny/crossref_metadata_2025 huggingface dataset:
Lafora disease is not linked to the Unverricht‐Lundborg locus
Authors: Labauge Pierre , Beck Corrine , Bellet Hélène , Coquillat Georges , Vespignani Hervé , Dulac Olivier , Gilgenkrantz Simone , Dravet Charlotte , Genton Pierre , Pellissier Jean‐François , Chery Michèle , Baldy‐Moulinier Michel , Malafosse Alain
Published: June 2005

Lafora disease and Unverricht‐Lundborg disease are two forms of progressive myoclonus epilepsies (PME). Recently the gene for Unverricht‐Lundborg disease (EPM1) was mapped to chromosome 21q22.3. Using three highly polymorphic DNA markers (D21S212, PFKL, and D21S171) which flank the EPM1 locus, we performed linkage analysis to investigate whether or not the EPM1 gene is also implicated in Lafora disease. Linkage was excluded in three North‐African pedigrees each comprising at least two affected individuals. This result suggests that differential diagnosis of Lafora disease and Unverricht‐Lundborg disease may be facilitated by molecular genetic analysis. © 1995 Wiley‐Liss, Inc.
Allelic association at the D14S43 locus in early onset Alzheimer's disease
Authors: Brice Alexis , Tardieu Sandrine , Campion Dominique , Guern Eric Le , Martinez Maria , Carpentier Alexandre , Penet Christiane , Dubois Bruno , Bellis Michel , Mallet Jacques , Hannequin Didier , Clerget‐Darpoux Françoise , Agid Yves
Published: June 2005

The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer's disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer's disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. © 1995 Wiley‐Liss, Inc.
Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early onset alcoholism/substance abuse
Authors: Vanyukov Michael M. , Moss Howard B. , Yu Ling Mei , Tarter Ralph E. , Deka Ranjan
Published: June 2005

An association between the liability to early onset alcoholism/substance abuse and a recently discovered dinucleotide repeat length polymorphism at the MAOA gene (MAOCA‐1) was examined using polymerase chain reaction (PCR). A significant correlation between the presence/absence of the disorder and the length of the MAOCA‐1 repeat was found in males, but not females, with “long” alleles (repeat length above 115 bp) associated with both increased risk for the disorder and lower age of onset of substance abuse. These preliminary data suggest that further exploration of the relationship between the MAOA gene and behavioral traits in an expanded sample is warranted. © 1995 Wiley‐Liss, Inc.
Two single base polymorphisms in introns 41 and 16 of the NF1 gene
Authors: Shen Ming Hong , Upadhyaya Meena
Published: June 2005

We have characterized two intragenic polymorphisms in the neurofibromatosis type 1 (NF1) gene by direct sequencing of PCR products. The variants for these polymorphisms were initially detected on Hydrolink gels. One of the polymorphisms involves a G to A transition in intron 41 at the 28th base upstream of exon 42 with an observed ‘G’/‘A’ heterozygosity of 0.42. The other polymorphism is a T to C transition in intron 16 at the 16th base upstream of exon 17 with an observed ‘T’/‘C’ heterozygosity of 0.09. In combination with other documented polymorphisms in the NF1 gene, these variants should assist in genetic analysis of NF1 families. © 1995 Wiley‐Liss, Inc.
Schizophrenia: Gender, family risk, and plasma homovanillic acid
Authors: Dávila Ricardo , Zumárraga Mercedes , González‐Torres Miguel A. , Andía Isabel , Zamalloa Maria I. , Basterreche Edurne , Guimón José , Friedhoff Arnold J.
Published: June 2005

Plasma homovanillic acid concentration was assessed in 60 young schizophrenic patients, with and without first‐degree relatives with schizophrenia, before treatment, and 3 days after starting haloperidol treatment. The baseline concentration of homovanillic acid in plasma was no different in the two groups before treatment; it was, however, significantly higher in the patients with relatives than in those without relatives diagnosed of schizophrenia after 3 days of haloperidol treatment. © 1995 Wiley‐Liss, Inc.
Automated linkage analysis in psychiatric disorders
Authors: He L. , Mansfield D. C. , Brown A. F. , Green D. K. , Morris S. W. , St. Clair D. M. , Muir W. J. , Maclean A. , Wright A. F. , Blackwood D. H. R.
Published: June 2005

A genome‐wide search for linkage of micro‐satellite markers to chromosomal loci containing genes responsible for the major psychoses is a laborious task which can be carried out with greater speed and economy by introducing automation to several steps in the procedure.

We describe the use of the Automated Linkage Preprocessor (ALP) program for the computer analysis of the waveform generated by fluorescein‐labelled markers after electrophoretic separation. (To obtain a copy send a request to A.F. Brown at the below MRC address or use Anonymous FTP to ftp.hgu.mrc.ac.uk. Software is in directory pub/ALP.) The program runs on a PC in the Microsoft Windows environment, and is used in conjunction with an automated laser fluorescence (ALF) sequencer (Pharmacia) and its Fragment Manager™ software to detect and size the PCR products, filter out peaks of fluorescence due to nonallele fragments, and generate genotypes in a format suitable for direct input to standard linkage analysis programs.

The method should offer the advantages of speed, accuracy, and reduced cost. Its use in linkage studies in a large family with manic‐depressive illness is discussed. © 1995 Wiley‐Liss, Inc.
DRD4 dopamine receptor genotype and CSF monoamine metabolites in Finnish alcoholics and controls
Authors: Adamson M. D. , Kennedy J. , Petronis A. , Dean M. , Virkkunen M. , Linnoila M. , Goldman D.
Published: June 2005

The DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in having a highly polymorphic gene structure that has been reported to produce altered receptor functioning. These allelic variations are caused by a 48‐bp segment in exon III of the coding region which may be repeated from 2–10 times. Varying the numbers of repeated segments changes the length, structure, and, possibly, the functional efficiency of the receptor, which makes this gene an intriguing candidate for variations in dopamine‐related behaviors, such as alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated for association with schizophrenia, bipolar disorder, Parkinson's disease, and chronic alcoholism, and all have been largely negative for a direct association.

We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were alcoholics, many of the early onset type with features of impulsivity and antisocial traits. Genotype frequencies were compared to 113 Finnish controls who were free of alcohol abuse, substance abuse, and major mental illness. In 70 alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major metabolite of dopamine, and 5‐hydroxyindoleacetic acid (5‐HIAA). No association was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF concentrations of the monoamine metabolites showed no significant difference among the DRD4 genotypes.

This study of the DRD4 dopamine receptor in alcoholics is the first to be conducted in a clinically and ethnically homogeneous population and to relate the DRD4 genotype to CSF monoamine concentrations. The results indicate that there is no association of the DRD4 receptor with alcoholism. © 1995 Wiley‐Liss, Inc.
Central pontine myelinolysis as a complication of partial ornithine carbamoyl transferase deficiency
Authors: Mattson Lisa R. , Lindor Noralane M. , Goldman Deborah H. , Goodwin Jeffrey T. , Groover Robert V. , Vockley Jerry
Published: June 2005

Central pontine myelinolysis (CPM) is a demyelinating condition of the central pons with or without associated foci of demyelination in extrapontine areas. We present a case of partial ornithine carbamoyl transferase deficiency in a 5‐year‐old girl which was complicated by CPM. The patient was a previously undiagnosed girl who presented with mild hyperammonemic encephalopathy with a maximum plasma ammonia level of 376 μM on admission. Laboratory testing established the diagnosis of OCT deficiency, and therapy with hydration and protein restriction was successful in returning the plasma ammonia levels to normal. Five days after correction of her hyperammonemia, the patient developed intractable seizures and coma. Serial MRI scans of the brain revealed the evolution of the characteristic findings of CPM. Plasma ammonia and electrolyte concentrations were well controlled throughout this time. This represents the first description of CPM in a patient with a urea cycle defect. © 1995 Wiley‐Liss, Inc.
Characteristics of familial aggregation in early‐onset Alzheimer's disease: Evidence of subgroups
Authors: Campion D. , Martinez M. , Hannequin D. , Brice A. , Thomas‐Anterion C. , Michon A. , Babron M. C. , Dubois B. , Goas Y. , Jaillard‐Serradt A. , Ledoze F. , Pasquier F. , Puel M. , Zimmerman M. A. , Bellis M. , Mallet J. , Agid Y. , Clerget‐Darpoux F.
Published: June 2005

Characteristics of familial aggregation of Alzheimer's Disease were studied in 92 families ascertained through a clinically diagnosed proband with an onset below age 60 years. In each family data were systematically collected on the sibships of the proband, of his father, and of his mother. A total of 926 relatives were included and 81% of the living relatives (i.e., 251 individuals) were directly examined. The estimated cumulative risk among first degree relatives was equal to 35% by age 89 years (95% confidence interval 22 to 47%). This result does not support the hypothesis that an autosomal dominant gene, fully penetrant by age 90 years, is segregating within all these pedigrees.

Despite the fact that all probands were selected for an onset before age 60 years it was shown that two types of families could be delineated with respect to age at onset among affected relatives: all secondary cases with an onset below age 60 years were contributed by a particular group of families (type 1 families), whereas all secondary cases with an onset after age 60 years were contributed by another group of families (type 2 families). Although genetic interpretation of these findings is not straightforward, they support the hypothesis of etiologic heterogeneity in the determinism of early‐onset Alzheimer's disease. © 1995 Wiley‐Liss, Inc.
Towards the finer mapping of facioscapulohumeral muscular dystrophy at 4q35: Construction of a laser microdissection library
Authors: Upadhyaya M. , Osborn M. , Maynard J. , Altherr M. , Ikeda J. , Harper P. S.
Published: June 2005

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal‐dominant disorder which has been mapped to the 4q35 region. In order to saturate this distal 4q region with DNA markers, a laser‐based chromosomal microdissection and microcloning procedure was used to construct a genomic library from the distal 20% of chromosome 4, derived from a single human metaphase spread.

Of the 100 microclones analyzed from this library, 94 clones contained inserts sized from 80–800 bp, with an average size of 340 bp. Less than 20% of these clones hybridized to human repeat sequences. Seventy‐two single‐copy clones were further characterized by Southern blot hybridization against a DNA panel of somatic cell hybrids, containing various regions of chromosome 4. Forty‐two clones mapped to chromosome 4, of which 8 clones mapped into the relevant 4q35 region. Twenty of these chromosome 4‐specific clones were screened against “zoo‐blots”; 11 clones, of which 3 mapped to 4q35, identified conserved sequences.

This is the first report to describe the isolation of potential expressed sequences derived from the FSHD region. These chromosome region‐specific microclones will be useful in the construction of the physical map of the region, the positional cloning of potential disease‐associated genes, and the identification of additional polymorphic markers from within the distal 4q region. © 1995 Wiley‐Liss, Inc.
Complex segregation analyses of Old Order Amish families ascertained through bipolar i individuals
Authors: Pauls David L. , Bailey Julia N. , Carter Alice S. , Allen Cleona R. , Egeland Janice A.
Published: June 2005

Specific genetic hypotheses about the mode of transmission of bipolar affective disorders were examined by performing complex segregation analyses of Old Order Amish families. The analyses were performed on (1) the total set of 42 families including 689 relatives, 2) a subset of 19 families consisting of those kindreds sharing common ancestors within three generations that contained 333 relatives, and 3) a subset of 23 more distantly related families with 356 relatives. When all 42 families were included in the analyses, the specific mode of transmission that could be distinguished was dependent upon the diagnostic scheme used in the analysis. An autosomal dominant mode of inheritance could be rejected when relatives with bipolar I, atypical bipolar, major depressive disorder, and hypomania were included as affected. When analyses included only the subset of families more closely related, an autosomal dominant inheritance model was found to be consistent with transmission of BP I disorder. It was not possible to distinguish between other transmission models with broader diagnostic schemes in this subset of families. Finally, results of analyses on the subset of more distantly related families suggest that there is a significant proportion of Old Order Amish families in which the genetic factors contributing to the expression of bipolar illness are either polygenic or oligogenic. © 1995 Wiley‐Liss, Inc.
Adrenocorticotropin receptor/melanocortin receptor‐2 maps within a reported susceptibility region for bipolar illness on chromosome 18
Authors: Detera‐Wadleigh Sevilla D. , Yoon Sung W. , Berrettini Wade H. , Goldin Lynn R. , Turner Gordon , Yoshikawa Takeo , Rollins Denise Y. , Muniec David , Nurnberger John I. , Gershon Elliot S.
Published: June 2005

We have examined the possible linkage of adrenocorticotropin receptor/melanocortin receptor‐2 (ACTHR/MC‐2) to a reported putative susceptibility locus for bipolar illness (BP) in 20 affected pedigrees. Initially, allelic variants of the gene were identified by polymerase chain reaction‐single stranded conformation polymorphism (PCR‐SSCP) and the gene was genetically mapped using both the Centre d'Etudes du Polymorphisme Humain (CEPH) pedigrees and the BP pedigrees used in this study. We found that the ACTHR/MC‐2 gene maps between D18S53 and D18S66. These loci span a region of chromosome 18 which, in a previous study (Berrettini et al.: Proc Natl Acad Sci USA 91:5918–5921, 1994) revealed a putative predisposing locus to BP through nonparametric methods of linkage analysis. Linkage of ACTHR/MC‐2 to BP was not demonstrable under parametric and nonparametric methods of analyses, although affected sib‐pair (ASP) method revealed an increase in allele sharing among ill individuals, P=0.023. Since this receptor is within a potential linkage region, ACTHR/MC‐2 could be considered a candidate gene for BP. © 1995 Wiley‐Liss, Inc.

This Article is a U.S. Government work and, such as, is in the public domain in the United State of America.
No evidence for allelic association between bipolar disorder and monoamine oxidase a gene polymorphisms
Authors: Craddock Nick , Daniels Johanna , Roberts Enriqueta , Rees Mark , McGuffin Peter , Owen Michael J.
Published: June 2005

We have tested the hypothesis that DNA markers in the MAOA gene show allelic association with bipolar affective disorder. Eighty‐four unrelated Caucasian patients with DSM III‐R bipolar disorder and 84 Caucasian controls were typed for three markers in MAOA: a dinucleotide repeat in intron 2, a VNTR in intron 1, and an Fnu4HI RFLP in exon 8. No evidence for allelic association was observed between any of the markers and bipolar disorder. © 1995 Wiley‐Liss, Inc.
Evidence for a genetic association between alleles of monoamine oxidase a gene and bipolar affective disorder
Authors: Lim Lionel C. C. , Powell John , Sham Pak , Castle David , Hunt Neil , Murray Robin , Gill Michael
Published: June 2005

We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significant only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant. © 1995 Wiley‐Liss, Inc.
Bipolar disorder: Evidence for a major locus
Authors: Spence M. Anne , Flodman Pamela L. , Sadovnick A. Dessa , Bailey‐Wilson Joan E. , Ameli Hossein , Remick Ronald A.
Published: June 2005

Complex segregation analyses were conducted on families of bipolar I and bipolar II probands to delineate the mode of inheritance. The probands were ascertained from consecutive referrals to the Mood Disorder Service, University Hospital, University of British Columbia and diagnosed by DSM‐III‐R and Research Diagnostic Criteria. Data were available on over 1,500 first‐degree relatives of the 186 Caucasian probands.

The purpose of the analyses was to determine if, after correcting for age and birth cohort, there was evidence for a single major locus. Five models were fit to the data using the statistical package SAGE: (i) dominant, (ii) recessive, (iii) arbitrary mendelian inheritance, (iv) environmental, and (v) no major effects.

A single dominant, mendelian major locus was the best fitting of these models for the sample of bipolar I and II probands when only bipolar relatives were defined as affected (polygenic inheritance could not be tested). Adding recurrent major depression to the diagnosis “affected” for relatives reduced the evidence for a major locus effect. Our findings support the undertaking of linkage studies and are consistent with the analyses of the National Institutes of Mental Health (NIMH) Collaborative Study data by Rice et al. (Arch Gen Psychiatry 44: 441–447, 1987) and Blangero and Elston (Genet Epidemiol 6:221–227, 1989). © 1995 Wiley‐Liss, Inc.
Schizophrenia and the androgen receptor gene: Report of a sibship showing co‐segregation with reifenstein syndrome but no evidence for linkage in 23 multiply affected families
Authors: Arranz Maria , Sharma Tonmoy , Sham Pak , Kerwin Robert , Nanko Shin , Owen Michael , Gill Michael , Collier David
Published: June 2005

Crow et al. [1993: Am J Med Genet (Neuro‐psychiatr Genet) 48:159–160] have reported excess sharing of alleles by male sibling pairs with schizophrenia, at a triplet repeat marker within the androgen receptor gene, indicating that mutations at or near this gene may be a risk factor for males. In this report, we describe a pair of male siblings concordant for both schizophrenia and Reifenstein syndrome, which is caused by a mutation in this gene. This provides support for the hypothesis that the androgen receptor may contribute to liability to develop schizophrenia. Because of this, we have examined a collection of 23 pedigrees multiply affected by schizophrenia for linkage to the androgen receptor. We have found no evidence for linkage by both the LOD score and affected sibling‐pair methods, under a range of genetic models with a broad and narrow definition of phenotype, and when families with male‐to‐male transmission are excluded. However, because of the small number of informative male‐male pairs in our sample, we cannot confirm or refute the excess allele sharing for males reported by Crow. © 1995 Wiley‐Liss, Inc.
Linkage analysis between manic‐depressive illness and markers on the long arm of chromosome 11
Authors: Ewald Henrik , Mors Ole , Flint Tracey , Friedrich Ursula , Eiberg Hans , Kruse Torben A.
Published: June 2005

The long arm of chromosome 11 is one of the most interesting regions in the search for major genes involved in the etiology of manic‐depressive illness. Several candidate genes have been identified, including the gene encoding the dopamine D2 receptor, the M1 muscarinic receptor, and porfobillinogen deaminase. Furthermore, different families with co‐segregation of psychiatric illness and structural chromosome abnormalities involving regions 11q21, 11q22.3, and 11q25 have been reported. Using narrow as well as broad phenotypic models, conservative genetic parameters, models with dominant or recessive modes of inheritance, and various methods to reduce misclassification, the present study did not find evidence for a major gene causing manic‐depressive illness on the long arm of chromosome 11. In the broader phenotypic models multi‐point analyses excluded at least 11q14 to 11q23.3, approximately 60 cM, even in one large family. Assuming homogeneity close linkage to DRD2 was excluded for all dominant models, and also in the affecteds‐only analyses in the large family alone. © 1995 Wiley‐Liss, Inc.
Monoamine oxidases and alcoholism. I. Studies in unrelated alcoholics and normal controls
Authors: Parsian A. , Suarez B. K. , Tabakoff B. , Hoffman P. , Ovchinnikova L. , Fisher L. , Cloninger C. R.
Published: June 2005

Low platelet MAO activity has been associated with alcoholism. In order to evaluate the role of MAO genes in susceptibility to alcoholism, we have taken a biochemical and molecular genetic approach. The sample consisted of 133 alcoholic probands who were classified by subtypes of alcoholism and 92 normal controls. For those subjects typed for platelet MAO activity, alcoholics (N = 74) were found not to differ from the non‐alcoholics controls (N = 34). Neither was there a significant difference between type I and type II alcoholics or between either subtype and normal controls. However, we do find significant differences between male and female alcoholics, but not between male and female controls. The allele frequency distribution for the MAO‐A and MAO‐B dinucleotide repeats is different between the alcoholic sample (N = 133) and the normal control sample (N = 92). In a two‐way analysis of variance of MAO‐B activity as a function of the allelic variation of each marker locus and diagnosis, there is no evidence for mean differences in activity levels for the different alleles. Our findings do not rule out a role for the MAO‐B gene in controlling the enzyme activity because the dinucleotide repeats are located in introns. © 1995 Wiley‐Liss, Inc.
Lack of association between manic‐depressive illness and a highly polymorphic marker from GABRA3 gene
Authors: Puertollano Rosa , Visedo Gillermo , Saiz‐Ruiz Jerónimo , Llinares Consuelo , Fernández‐Piqueras José
Published: June 2005

We have carried out an association study between a dinucleotide repeat polymorphism in GABRA3 gene and manic‐depressive illness in a Spanish population. This may be an important candidate gene for bipolar affective disorders since it is located in the Xq28 region, previously implicated in linkage studies. In addition, severe GABergic alterations have been reported in patients. We have not found significant differences between controls and patients in allele frequencies or genotypes. © 1995 Wiley‐Liss, Inc.
Family patterns of developmental dyslexia, part II: Behavioral phenotypes
Authors: Wolff Peter H. , Melngailis Ilze , Obregon Mateo , Bedrosian Martha
Published: June 2005

The motor control of bimanual coordination and motor speech was compared between first degree relatives from families with at least 2 dyslexic family members, and families where probands were the only affected family members. Half of affected relatives had motor coordination deficits; and they came from families in which probands also showed impaired motor coordination. By contrast, affected relatives without motor deficits came from dyslexia families where probands did not have motor deficits. Motor coordination deficits were more common and more severe among affected offspring in families where both parents were affected than among affected offspring in families where only one parent was affected. However, motor coordination deficits were also more common and more severe in affected parents when both parents were affected than among affected parents in families where only one parent was affected.

We conclude that impaired temporal resolution in motor action identifies a behavioral phenotype in some subtypes of developmental dyslexia. The observed pattern of transmission for motor deficits and reading impairment in about half of dyslexia families was most congruent with a genetic model of dyslexia in which 2 codominant major genes cosegregate in dyslexia pedigrees where the proband is also motorically impaired. © 1995 Wiley‐Liss, Inc.
Failure to find a chromosome 18 pericentric linkage in families with schizophrenia
Authors: DeLisi Lynn E. , Lofthouse Ray , Lehner Thomas , Morganti Carla , Vita Antonio , Shields Gail , Bass Nicholas , Ott Jurg , Crow Timothy J.
Published: June 2005

A recent report of a possible linkage of bipolar affective disorder to a pericentric region of chromosome 18 initiated the present investigation to search for a similar linkage in 32 families with schizophrenia. The results of a study using 5 markers mapped to this region show negative lod scores and only weak evidence for any linkage by nonparametric analyses. If the previously reported finding is a true positive linkage for bipolar disorder, then either it is unlikely to be related to the genetics of schizophrenia, or the proportion of families linked to this region is small. © 1995 Wiley‐Liss, Inc.
Neurodevelopmental profile of infants and toddlers with oculo‐auriculo‐vertebral spectrum and the correlation of prognosis with physical findings
Authors: Cohen M. S. , Samango‐Sprouse C. A. , Stern H. J. , Custer D. A. , Vaught D. R. , Saal H. M. , Tifft C. J. , Rosenbaum K. N.
Published: June 2005

We studied the neurodevelopmental profile of infants and toddlers with oculo‐auriculo‐vertebral spectrum (OAV) and determined if certain physical manifestations were indicative of a poor neurodevelopmental prognosis. Twenty‐four patients with OAV, aged birth to 57 months, were seen in the Department of Medical Genetics at Children's National Medical Center for multidisciplinary evaluations, including neurodevelopmental assessments.

Fifty‐eight percent of these children scored more than 2 standard deviations below the mean in at least one domain of development. There was no difference in developmental outcome of boys versus girls, children affected unilaterally on the right side versus left side, and those with severe clinical manifestations versus those with a milder form. Children with OAV and abnormal muscle tone had lower cognitive, gross motor, and expressive language scores (P = 0.05, P = 0.002, and P = 0.02, respectively). Those affected bilaterally had lower cognitive, fine motor, receptive language, and expressive language scores (P = 0.06, P = 0.03, P = 0.03, P = 0.02, respectively). Children with cervical spine abnormalities had lower cognitive, fine motor, and expressive language scores (P = 0.02, P = 0.04, and P = 0.04, respectively).

We conclude that infants and toddlers with OAV are at increased risk for neurodevelopmental delay, especially those with abnormal muscle tone, bilateral involvement, and cervical vertebral anomalies. The complexity of the neurodevelopmental problems is strongly suggestive of central nervous system disturbances. Patients with OAV need comprehensive evaluation by a multi‐disciplinary team to define potential neurodevelopmental delays, allow for early intervention services, and promote an optimal developmental outcome. © 1995 Wiley‐Liss, Inc.
Adenylosuccinate lyase (ADSL) and infantile autism: Absence of previously reported point mutation
Authors: Fon Edward A. , Sarrazin Julie , Meunier Catherine , Alarcia Julio , Shevell Michael I. , Philippe Anne , Leboyer Marion , Rouleau Guy A.
Published: June 2005

Autism is a heterogeneous neuropsychiatric syndrome of unknown etiology. There is evidence that a deficiency in the enzyme adenylosuccinate lyase (ADSL), essential for de novo purine biosynthesis, could be involved in the pathogenesis of certain cases. A point mutation in the ADSL gene, resulting in a predicted serine‐to‐proline substitution and conferring structural instability to the mutant enzyme, has been reported previously in 3 affected siblings. In order to determine the prevalence of the mutation, we PCR‐amplified the exon spanning the site of this mutation from the genomic DNA of patients fulfilling DSM‐III‐R criteria for autistic disorder. None of the 119 patients tested were found to have this mutation. Furthermore, on preliminary screening using single‐strand conformation polymorphism (SSCP), no novel mutations were detected in the coding sequence of four ADSL exons, spanning approximately 50% of the cDNA. In light of these findings, it appears that mutations in the ADSL gene represent a distinctly uncommon cause of autism. © 1995 Wiley‐Liss, Inc.
Absence of linkage of apparently single gene mediated ADHD with the human syntenic region of the mouse mutantColoboma
Authors: Hess Ellen J. , Rogan Peter K. , Domoto Mark , Tinker Dorris E. , Ladda Roger L. , Ramer Jeanette C.
Published: June 2005

Attention deficit disorder (ADHD) is a complex biobehavioral phenotype which affects up to 8% of the general population and often impairs social, academic, and job performance. Its origins are heterogeneous, but a significant genetic component is suggested by family and twin studies. The murine strain,coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD.Colobomais a semi‐dominant mutation that is caused by a hemizygous deletion of the SNAP‐25 and other genes on mouse chromosome 2q. To test the possibility that the human homolog of the mouse coloboma gene(s) could be responsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (20p11–p12). Five families in which the pattern of inheritance of ADHD appears to be autosomal dominant were studied. Segregation analysis of the traits studied suggested that the best fitting model was a sex‐influenced, single gene, Mendelian pattern. Several genetic models were evaluated based on estimates of penetrance, phenocopy rate, and allele frequency derived from our patient population and those of other investigators. No significant linkage was detected between the disease locus and markers spanning this chromosome 20 interval. © 1995 Wiley‐Liss, Inc.
Orgasm in female primates
Authors: Allen M. L. , Lemmon W. B.
Published: June 2005

The major genital responses of arousal in women are vasocongestion, resulting in tumescence of the vaginal walls, and vaginal lubrication, facilitating penile intromission and thrusting. During orgasm, several involuntary muscular reactions occur, the most adaptive being in the outer third of the vagina and the uterus. Uterine suction of the ejaculate seems to occur when the reproductive apparatus is functioning at full efficiency. Coitus may result in reflex ovulation. Indices of female nonhuman primate orgasm thus far proposed include rhythmic vaginal and anal contractions, hyperventilation, involuntary muscle tension, arm and leg spasms, grimacing, and uterine contractions. Orgasm in our species may exist as a result of phylogenetic inertia, not as a novel response selected during protohominid or hominid evolution. A theory for the evolutionary nature of orgasm in women states that the orgasmic vaginal contractions stimulate ejaculation. Reasons for the common asynchrony of this adaptive pattern are the usually lowered ejaculatory threshold because of non‐species‐typical orgasmic frequency in the male, and the frequently delayed female orgasm because of psychological inhibition and/or inadequate control and development of the pubococcygeus.
Abnormal behaviors in nursery‐reared squirrel monkeys (Saimiri sciureus)
Authors: Roy M. Aaron
Published: June 2005

Seventeen squirrel monkeys (Saimiri sciureus), 11 nursery‐reared and six mother‐reared, were monitored to clarify the type and degree of deviant behaviors that result from rearing this species in the nursery. Two observation periods were used: the first when the subjects averaged 6.7 months of age, the second when they averaged 15.5 months. Thirteen activities involving variations of nonnutritive orality, stereotypic posturing, and agitated behaviors were seen in the nursery‐reared subjects, but never in the mother‐reared subjects. No consistent gender, subspecies, or age differences were evident. Squirrel monkeys, like chimpanzees and some Old World monkeys, do develop atypical self‐directed behaviors when deprived of normal stimulation during early development.
Primate phonation: Anterior cingulate lesion effects on response rate and acoustical structure
Authors: Trachy Ronald E. , Sutton Dwight , Lindeman Roger C.
Published: June 2005

Four juvenile rhesus monkeys (Macaca mulatta) that were conditioned to emit a discriminative vocal response underwent unilateral and bilateral lesions of anterior cingulate gyrus in stepwise sequence. Pre‐ and post‐lesion measures of vocal response rate and acoustical features (call duration, amplitude, and fundamental frequency) were obtained for the conditioned task and for vocalization in the home colony (spontaneous vocalization). Unilateral lesions produced little consistent change in spontaneous “coo” vocalization rate and call duration. Conditioned vocalization of the monkeys exhibited no significant change in rate at this stage, although call duration was reduced significantly. Bilateral lesions produced no further modifications in acoustic properties of spontaneous calls, while the vocal rate decreased slightly. Conditioned calls were not significantly altered in acoustic features at this stage, although the discriminative vocalization rate was significantly decreased for all monkeys. The results indicate limited control over vocal motor systems by anterior cingulate cortex, while suggesting that this region participates in initiation of voluntary phonation.
The association between rank and reproductive success of male rhesus monkeys
Authors: Smith David Glenn
Published: June 2005

The paternity of 202 of 220 offspring of rhesus monkeys housed in six separate half‐acre field cages at the California Primate Research Center was determined by genetic marker techniques. Reproductive success of the adult males was statistically significantly correlated (r = 0.76, P <0.0005) with rank. Marked systematic changes in reproductive success were, however, observed for two adult males during the three years covered by this study. Based upon these results and those of another study, it is argued that changes in rank position typically follow, rather than precede, changes in reproductive success.
Technical note: Urine collection from vervet monkeys by instrumental conditioning
Authors: Kelley T. M. , Bramblett C. A.
Published: June 2005

Gang‐caged adult male vervet monkeys were trained to urinate on demand into a plastic beaker by positive reinforcement (peanut rewards). The animals were not separated from their social group during training or sampling.
The interrelationship between sex skin swelling and the urinary excretion of LH, estrone, and pregnanediol by the cycling female chimpanzee
Authors: McArthur J. W. , Beitins I. Z. , Gorman A. , Collins D. C. , Preedy J. R. K. , Graham C. E.
Published: June 2005

The interrelationship between sex skin swelling and the urinary excretion of luteinizing hormone and sex steroids was investigated during ovulatory menstrual cycles in adult female chimpanzees. Estrone was excreted in two peaks, one during the preovulatory and the other during the midluteal phase. Maximum swelling of the sex skin was attained several days before the preovulatory estrone peak. The LH surge preceded or accompanied beginning detumescence of the sex skin which, in turn, was closely correlated with a rising excretion of pregnanediol. Urinary measurements provide integrated estimates of the concentration of fluctuating hormones and, in addition, are safer and easier to make than blood measurements in this species.
Physical maturation and age estimates of yellow baboons, Papio cynocephalus, in Amboseli National Park, Kenya
Authors: Altmann Jeanne , Altmann Stuart , Hausfater Glenn
Published: June 2005

In a longitudinal study of individually identified wild baboons in Amboseli National Park, Kenya, we collected data on physical development and reproductive maturation. Confirming and extending our earlier results, we demonstrated that the ratio of ages at which developmental milestones occur in the field as compared to those under extensive provisioning or in captivity were approximately 5:3. The age range for some developmental milestones was quite narrow and discrete, while for others there was considerable between‐individual variability and more gradual changes. For infants, only the change from pink to gray of the paracallosal skin occurred within a brief age span. For older animals two important developmental events are readily identified and occur within a fairly narrow age range: Rapid enlargement of testes at 5 to 6 years for males and onset of menarche at 4 to 5 ½ years for females. In the present report, we considered some consequences of accelerated or delayed maturation. We further explored the need to employ different age‐class criteria for different research problems.
Effects of rearing on aggression and subordination in papio monkeys
Authors: Coelho Anthony M. , Bramblett Claud A.
Published: June 2005

The objective of this study is to assess the effects of short‐term maternal deprivation (birth to 12 weeks) followed by peer group rearing on the development of aggressive and subordinate behaviors in papio monkeys (superspecies – Papio cynocephalus). Nursery reared monkeys (34 males and 30 females) were compared with mother‐peer reared monkeys (11 males and 12 females) in late infancy (6 to 12 months of age) and at the end of their juvenile stage (36 to 42 months of age) in social groups composed of 75% nursery reared subjects and 25% mother reared subjects. Focal animal data were analyzed with a repeated measure ANOVA model. In general, the nursery reared infants tended to be less aggressive than mother‐peer reared infants and performed less dominance behaviors, such as displace. Significant sex differences were present in the performance of aggressive (♂ > ♀) and subordinate (♂ > ♀) behaviors. Significant age differences were observed, with infants having consistently higher rates of performance.
Diurnal variations in serum testosterone concentrations of captive adult male chacma baboons (Papio ursinus)
Authors: Bielert C. , Howard‐Tripp M. E. , van der Walt L. A.
Published: June 2005

Captive adult male chacma baboons (Papio ursinus) housed with natural lighting exposure and blood sampled at 3‐hr intervals showed significant diurnal variations in serum testosterone concentrations. Low mean concentrations were found at 0800 hr approximately 1 hr after sunrise and mean concentrations were their highest at 2000 hr approximately 1 ¼ hr after sunset.
A description of the upper thoracic autonomic nervous system in the rhesus monkey (Macaca mulatta)
Authors: Billman George E. , Dickey D. Thomas , Stone H. Lowell
Published: June 2005

The purpose of this study was to describe the autonomic innervation of the carotid sinus and heart in the rhesus monkey. Nine male rhesus monkeys (Macaca mulatta) and one male crab‐eating macaque (M. fascicularis) were carefully dissected from the origin of the vagus nerves and superior cervical ganglia to the level of the fourth thoracic ganglion. The specimens were either freshly killed or obtained no later than 24 hours post mortem. The macaque monkeys were found to possess an innervation pattern that displayed features common to dog (connections between the vagus nerves and middle cervical ganglia), baboon (distinct cervical sympathetic and cervical vagal nerve trunks), and man (nerves projecting from the middle cervical and stellate ganglia to the heart). Distinct inferior cervical and first thoracic ganglia were never seen, but rather, large and well defined stellate ganglia were found. The macaque innervation pattern, when considered as a whole, most closely resembled the baboon.
Spontaneous malignomas in Tupaia (tree shrew)
Authors: Darai G. , Zöller L. , Hofmann W. , Möller P. , Schwaier A. , Flügel R. M.
Published: June 2005

Nine spontaneous malignomas of the tree shrew were detected and analysed during an observation period of nine years. The tumours were histopathologically examined and classified. All malignomas developed in imported Tupaia only. From the tumour cells of two different animals new Tupaia herpesviruses were isolated. This is the first. report on spontaneous malignomas of Tupaia in captivity.
A statistical analysis of the social behavior of the male stumptail macaque (Macaca arctoides)
Authors: Adams David H. , Schoel W. Michael
Published: June 2005

The social behavior of male stumptail macaques was analyzed in terms of behavioral sequences recorded during paired encounters in a large test cage. Recurrent patterns of behavioral sequences were sought and used to hypothesize the structure of motivational systems of social behavior as has been done previously for other species. In addition to traditional statistical analyses to determine which dyadic behavioral sequences were nonrandom, there were several methodological innovations. Instead of analyzing behavior as a single channel of communications, we analyzed three independent channels and considered their inter‐correlations: 1) acts and postures; 2) vocalizations; and 3) facial expressions. Also, we analyzed not only within‐animal behavioral sequences but between‐animal sequences as well. Results were derived from 40 tests, most of which included vigorous agonistic and sexual interactions and a behavioral repertoire similar to that of adult male stumptail macaques observed by previous investigators. There were 30 acts and postures, eight facial expressions, and seven vocalizations that occurred more than five times. Many acts and postures occurred in nonrandom sequences, 43 such sequences within‐animal and 40 between‐animal. From these sequences and their correlations with specific vocalizations and facial expressions, it was possible to differentiate six categories of social behavior that may correspond to six different motivational systems: offense, defense, submission, groom and contact, male sexual behavior, and display. Both the frequency of behaviors in each category and the nature of the behavioral sequences were affected by the relative dominance of the two animals.
Validation of radioimmunoassays for LH and FSH in the sooty mangabey (Cercocebus atys): Characterization of LH and the response to GnRH
Authors: Mann David R. , Blank Michael S. , Gould Kenneth G. , Collins Delwood C.
Published: June 2005

Heterologous radioimmunoassays (RIA) for macaque LH and FSH were validated for the measurement of these hormones in the sooty mangabey and mangabey pituitary LH was characterized relative to rhesus monkey LH. Dilutions of a pituitary mangabey extract and a partially purified preparation of mangabey LH ran parallel to a rhesus monkey standard (LER 1909‐2) in the ovine‐ovine (o‐o) LH assay but showed some deviation from parallelism in the rhesus monkey FSH assay. The LH potency of the mangabey extract and standard were six and 190 times more potent, respectively, than LER 1909‐2 in the LH RIA. Mangabey LH was estimated to have a molecular weight of 40,000–42,000 daltons vs 35,000–38,000 daltons for rhesus LH on Sephadex G‐100 chromatography.

Plasma levels of radioimmunoreactive LH, FSH, and testosterone were assayed before and after a bolus administration of 25, 50, or 100 μg synthetic go‐nadotropin releasing hormone (GnRH) to adult male mangabeys. A significant increase in serum levels of LH was seen within 30 min with levels more than fourfold higher than the basal level of LH after administration of 100 μg GnRH. However, no consistent increases in plasma FSH values were detected. The integrated mean LH response above preinjection levels following 25, 50, or 100 μg GnRH was dose related. Serum levels of testosterone were also elevated after administration of GnRH, but peak concentrations of testosterone lagged behind peak levels of LH by approximately 30 min.

These studies indicate that the heterologous RIAs may be used for measuring gonadotropins in the mangabey and that the male mangabey is apparently more sensitive to GnRH than the rhesus monkey.
Clinical note: Calcium bilirubinate gallstones in an aged rhesus monkey (Macaca mulatta)
Authors: Kessler M. J.
Published: June 2005

Severe gallstone disease was found at necropsy in a 24‐year‐old female monkey which died of pyelonephritis. Reports of spontaneous cholelithiasis in rhesus monkeys are rare. This is the first description of gallstone disease in a non‐human primate caused by calcium bilirubinate choleliths.
Fertility in the male gorilla (Gorilla gorilla): Relationship to semen parameters and serum hormones
Authors: Gould K. G. , Kling O. R.
Published: June 2005

Circulating levels of steroid and protein hormones were measured in 17 adult male lowland gorillas (Gorilla gorilla). The population included both fertile and infertile males as identified by previous siring of offspring and presence or absence of spermatozoa in the ejaculate obtained by rectal probe electrostimulation.

Correlations were sought between levels of testosterone, dihydrotestosterone, androstenedione, estrone, estradiol, progesterone, 170H‐progesterone, dihydroepiandrosterone, luteinizing hormone, follicle‐stimulating hormone (FSH), and potential fertility status.

The results identify normal circulating levels of these hormones, and indicate that aspermatogenesis and infertility are not necessarily associated with any alteration in levels of gonadal steroids. There is an association of aspermatogenesis with elevation of FSH. Levels of adrenal androgens are more similar to other non‐human primates than to the human, which is of interest because in other aspects of reproductive physiology so far investigated the gorilla has proved to resemble the human more closely than it does the other nonhuman primates.
Survey and census of howler monkeys (Alouatta palliata) in the rain forest of “Los Tuxtlas,” Veracruz, Mexico
Authors: Estrada Alejandro
Published: June 2005

Howler monkey troops were censused at the biological reserve “Los Tuxtlas” in Veracruz, Mexico. The reserve includes 700 ha of rain forest. Twenty howler monkeys were also trapped, measured, marked, and released. Censuses were conducted for a period of 26 months, and they indicated the existence of 17 troops. The mean troop size was 9.12 (SD ± 2.93), and mean troop composition was 3.0 adult males, 4.12 females, 1.56 juveniles, and 1.54 infants. Ecological density was 0.23 howlers/ha or 23.29 howlers/km2. The male to female ratio was 1:1.37. No discrete seasonality in births was noted. Howler monkeys in this locality inhabit the northernmost limit of the neotropical rain forest. The population parameters fall within those reported for Alouatta palliata at other sites.