bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical activity at 9–12 months and fatness at 2 years of age
Authors: Wells J.C.K. , Ritz P.
Published: November 2004

Previous research has shown that physical activity in early infancy does not predict later fatness, whereas in preschool children, such a relationship is found. The objective of this study was to investigate whether total energy expenditure (TEE) and behavior in late infancy are related to subcutaneous and total fatness in early childhood. Twenty‐six infants were studied at 9–12 months and followed up at 2 years of age. Anthropometry, body composition, TEE, and behavior were measured in late infancy; skinfold thicknesses and total body fat were measured at 2 years of age. Infant TEE adjusted for fat‐free mass was not related to later fatness. Infant behavior was related to later subcutaneous fatness, but not to total body fatness. Lower levels of infant activity were associated with greater skinfold thicknesses in childhood. Thus, by late infancy, physical activity level is related to subsequent skinfold thickness. Particular aspects of infant behavior appear to be more important than the sum of energy expended on activity. However, the relationship did not extend to total body fat. Am. J. Hum. Biol. 13:384–389, 2001. © 2001 Wiley‐Liss, Inc.
Assessment of the growth of children and physical status of adults in two Aboriginal communities in South Australia
Authors: Henneberg Maciej , Schilitz Anja , Lambert Kosette M.
Published: November 2004

Growth of children and physical status of adults in two Aboriginal communities, Gerard and Raukkan, South Australia, were assessed. Height, weight, biepicondylar breadth of humerus, the triceps and subscapular skinfolds, and arm circumferences were measured on 110 children and 77 adults annually between 1996 and 2000. Data were transformed to z scores, using American reference data. In all groups height z scores are negative. In all but Raukkan boys, the z scores are significantly smaller than the reference. Body weight z scores lie above the reference, with the only exceptions being Gerard children. Still, in all cases BMI lies above the reference, being significantly greater than the reference, except in Gerard girls. z scores for the triceps skinfold are not consistently positive, but those for the subscapular skinfold are positive in all groups, indicating centralized fat accumulation. In both boys and girls, Raukkan men and Gerard women, biepicondylar breadth of the humerus is below the reference. Increased BMI and trunk fatness suggest that members of these communities are not only receiving adequate nutrition, but that in many cases there is also a caloric surplus, sometimes leading to obesity. Inadequate skeletal growth indicated by short stature and small biepicondylar breadths, on the other hand, suggests that the environment is less than optimal for growth. Factors such as disease load, psychosocial pressures, or specific nutrient shortages may be involved. Am. J. Hum. Biol. 13:603–611, 2001. © 2001 Wiley‐Liss, Inc.
Climate and head form in India
Authors: Bharati S. , Som S. , Bharati P. , Vasulu T.S.
Published: November 2004

The relationship between head form and climatic variation was investigated in different tribal and caste populations of India. The magnitude of the cephalic index varies significantly in different zones. In tropical zones, head form is longer (dolicocephalic), but in temperate zones, head form is more round (mesocephalic or brachycephalic), especially among Scheduled Tribes (ST) and Scheduled Castes (SC) than among other castes. These trends possibly support a climatic adaptation model in head form differences among ST and SC in India. Am. J. Hum. Biol. 13:626–634, 2001. Published 2001 Wiley‐Liss, Inc.
Nutritional status by socioeconomic level in an urban sample from Bilbao (Basque Country)
Authors: Rebato E. , Rosique J. , Vinagre A. , Salces I. , San Martín L. , Susanne C.
Published: November 2004

Anthropometry, records of food intake, and bioelectric impedance were gathered from a sample of 297 adults of both sexes who lived in marginal districts in the town of Bilbao and benefited from a program of social assistance. This survey aimed to determine present nutritional status and to ascertain the relationship between food intake and nutritional conditions. A comparative evaluation of anthropometry and food intake was then carried out using a reference from the Basque Country and a control sample from the same area but from better‐off nutritional and socioeconomic conditions. Males from low socioeconomic status (SES) displayed lower heights and weights compared to the local reference and control sample. They showed higher skinfold thickness than males in the local reference but lower thicknesses than those in the control sample. All anthropometric variables, except height, were higher in women of low socioeconomic status compared to the local reference and control sample. Low socioeconomic males had lower estimated percentage of body fat than the control sample, while females showed the opposite pattern. On the other hand, estimates of food intake in males did not reveal great differences among samples from different socioeconomic backgrounds, while low SES females had greater intakes of food than the better‐off control sample. Estimated zinc intake showed differences by SES in both sexes. Am. J. Hum. Biol. 13:668–678, 2001. © 2001 Wiley‐Liss, Inc.
Child abuse and the balance of power in parental relationships: An evolved domain‐independent mental mechanism that accounts for behavioral variation
Authors: Handwerker W. Penn
Published: November 2004

Previous studies use zero‐order analyses to show a link between child abuse and exposure to “stepfathers.” These studies rest on a proposed evolved, domain‐specific cognitive mechanism that induces adult males to abuse or kill offspring not their own and, so, contribute directly to reproductive success. However, child abuse may reflect an evolved neurological mechanism that creates behavioral plasticity and adaptability by assigning emotional weights (which in consciousness appear rationalized as costs and benefits) to choice alternatives in all behavioral domains. This mechanism should act as a selective mechanism to create enhanced ability to avoid predation (social exploitation) and to obtain access to resources, given the properties of specific ecosystems, and should control behavioral responses to variation in the balance of power in social relationships. Power equalities should elicit good treatment for both parties; power inequalities, by contrast, should elicit exploitative and coercive behavior on the part of those who hold the balance of power. This paper reports a test of both hypotheses simultaneously, controlling for a standard social science risk factor (growing up in poverty). Once we control for the balance of power in parental relationships, exposure to a stepfather and growing up in poverty show no effect on the intensity of child abuse. Powerful women negotiated affectionate behavior from their partners for both themselves and their children; powerless women's negotiations with partners usually left both themselves and their children open to violence. Am. J. Hum. Biol. 13:679–689, 2001. © 2001 Wiley‐Liss, Inc.
Porotic hyperostosis as a marker of health and nutritional conditions during childhood: Studies at the transition between imperial rome and the early middle ages
Authors: Salvadei Loretana , Ricci Francesca , Manzi Giorgio
Published: November 2004

Porotic hyperostosis, characterized by small and localized perforations on the surface of cranial bones, is considered a good indicator for assessing the health and nutritional status of past human populations. The most widely accepted theory at present indicates that anemias, either acquired or of genetic origin, are responsible for the bony lesions described as porotic hyperostosis. In this paper, the prevalence of these lesions in two skeletal samples from Latium (central Italy) was used to evaluate health and life conditions in Italy after the collapse of the Roman Empire. One sample belongs to the Roman Imperial Age (1st–3rd centuries A.D.) rural town of Lucus Feroniae; the other comes from the 7th century A.D. Lombard necropolis of Selvicciola. The prevalence of cribra orbitalia and cribra cranii was quite similar in the two samples but slightly more frequent in the Medieval community. Differential diagnosis suggested iron deficiency anemia in early childhood as the causative agent of the hyperostotic lesions in both samples. These results may be interpreted in light of previous examinations of same samples and according to their respective historical and socio‐economical characteristics. Am. J. Hum. Biol. 13:709–717, 2001. © 2001 Wiley‐Liss, Inc.
Familial amyotrophic lateral sclerosis and parkinsonism‐dementia complex of the Kii peninsula of Japan: Clinical and neuropathological study and tau analysis
Authors: Kuzuhara Shigeki , Kokubo Yasumasa , Sasaki Ryogen , Narita Yugo , Yabana Tadashi , Hasegawa Masato , Iwatsubo Takeshi
Published: November 2004

We report the first case of neuropathologically verified parkinsonism‐dementia complex of the Kii peninsula, together with the patient's brother, who had amyotrophic lateral sclerosis. The propositus woman developed parkinsonism and dementia at 63 years of age and died at 70 without displaying clinical features of amyotrophic lateral sclerosis. The brain exhibited marked atrophy of the frontal and temporal lobes. Microscopically, there were many neurofibrillary tangles in the central nervous system, most markedly in the mesial temporal lobe and deep nuclei, as well as changes of amyotrophic lateral sclerosis but no senile plaques or Lewy bodies. Neurofibrillary tangles exhibited twisted tubule structures on electon microscopic examination, and an analysis of insoluble tau protein extracted from the fresh brain revealed a 60‐, 64‐, 68‐kD triplet. The tau gene exhibited no mutations. Her brother developed progressive bulbar palsy–type amyotrophic lateral sclerosis at 45 years of age and died at 49 without presenting with dementia or parkinsonism. Neuropathological examination revealed not only pathologic features of amyotrophic lateral sclerosis but also a moderate number of neurofibrillary tangles in the temporal cortex and deep nuclei. The siblings were neuropathologically similar despite their different clinical manifestations. These findings suggest that amyotrophic lateral sclerosis and parkinsonism‐dementia complex of this family may be phenotypic variants of a tauopathy caused by genetic abnormalities. Ann Neurol 2001;49:501–511
A novel TRK A (NTRK1) mutation associated with hereditary sensory and autonomic neuropathy type V
Authors: Houlden Henry , King R. H. M. , Hashemi‐Nejad A. , Wood N. W. , Mathias C. J. , Reilly Mary , Thomas P. K.
Published: November 2004

A boy with recurrent pyrexial episodes from early life sustained a painless ankle injury and was found to have a calcaneus fracture and, later, neuropathic joint degeneration of the tarsus. Examination revealed distal loss of pain and temperature sensation and widespread anhidrosis. Sural nerve biopsy demonstrated severe reduction in small‐caliber myelinated fiber density but only modest reduction in unmyelinated axons, the pattern of type V hereditary sensory and autonomic neuropathy (HSAN V). DNA analysis showed that he was homozygous for a mutation in the NTRK1/high‐affinity nerve growth factor (TrkA) gene, his parents being heterozygous. Mutations in this gene are known to be responsible for HSAN IV (congenital insensitivity to pain with anhidrosis). The two disorders are therefore likely to be allelic. Ann Neurol 2001;49:521–525
Effects of riluzole on cortical excitability in patients with amyotrophic lateral sclerosis
Authors: Stefan Katja , Kunesch Erwin , Benecke Reiner , Classen Joseph
Published: November 2004

2 Using transcranial magnetic stimulation, the effect of riluzole (RLZ) on cortical excitability was studied in patients with amyotrophic lateral sclerosis (ALS). Paired‐pulse inhibition (PPI) and paired‐pulse facilitation (PPF) were reduced. RLZ partially restored deficient PPI in the first of 4 consecutive 3‐month periods of testing, but left PPF unchanged. These findings substantiate the view that attenuation of glutamate‐related excitotoxicity is an important factor contributing to the beneficial effect of RLZ in ALS. Ann Neurol 2001;49:537–540
Gluten sensitivity in sporadic and hereditary cerebellar ataxia
Authors: Bushara Khalafalla O. , Goebel Stephan U. , Shill Holly , Goldfarb Lev G. , Hallett Mark
Published: November 2004

Gluten sensitivity, with or without classical celiac disease symptoms and intestinal pathology, has been suggested as a potentially treatable cause of sporadic cerebellar ataxia. Here, we investigated the prevalence of abnormally high serum immunoglobulin A (IgA) and IgG anti‐gliadin antibody titers and typical human lymphocyte antigen (HLA) genotypes in 50 patients presenting with cerebellar ataxia who were tested for molecularly characterized hereditary ataxias. A high prevalence of gluten sensitivity was found in patients with sporadic (7/26; 27%) and autosomal dominant (9/24; 37%) ataxias, including patients with known ataxia genotypes indicating a hitherto unrecognized association between hereditary ataxias and gluten sensitivity. Further studies are needed to determine whether gluten sensitivity contributes to cerebellar degeneration in patients with hereditary cerebellar ataxia. Patients with hereditary ataxia (including asymptomatic patients with known ataxia genotype) should be considered for screening for gluten sensitivity and gluten‐free diet trials. Ann Neurol 2001;49:540–543
Attention and cognition in bradykinetic‐rigid syndromes: An event‐related potential study
Authors: Pirtošek Zvezdan , Jahanshahi Marjan , Barrett Geoff , Lees Andrew J.
Published: November 2004

Bradykinetic‐rigid syndromes are often accompanied by cognitive impairment. Because prominent motor involvement in these disorders may interfere with neuropsychological testing, we used event‐related potentials (ERPs) for the assessment of cognition and attention in 41 patients with various bradykinetic‐rigid syndromes of less than 5 years duration: idiopathic Parkinson's disease corticobasal degeneration, Steele‐Richardson‐Olszewski syndrome (SRO), and multiple system atrophy. Patients were compared with matched normals. ERP abnormalities in the auditory “oddball” paradigm were found only in corticobasal degeneration and SRO. ERP abnormalities in selective attention tasks were present in all patient groups, changes in SRO being the most prevalent. Abnormalities in corticobasal degeneration were present under “less‐attention‐demanding” conditions and suggested involvement of posterior parts of the brain. Multiple system atrophy and idiopathic Parkinson's disease patient groups had minimal ERP abnormalities. However, reaction times in MSA were longer in all paradigms. The results of the study support the view that bradykinetic‐rigid syndromes involve some attentional deficits, but also have distinct reaction time and ERP characteristics, which may be helpful in differential diagnosis.
Endocytic disturbances distinguish among subtypes of alzheimer's disease and related disorders
Authors: Cataldo Anne , Rebeck G. William , Ghetti Bernadino , Hulette Christine , Lippa Carol , Van Broeckhoven Christine , Van Duijn Cornelia , Cras Patrick , Bogdanovic Nenad , Bird Thomas , Peterhoff Corrinne , Nixon Ralph
Published: November 2004

The endocytic pathway is important in amyloid precursor protein (APP) processing and β‐amyloid formation. Our studies have shown that endocytic pathway activation is a prominent and early feature of neurons in vulnerable regions of the brain in sporadic Alzheimer's disease. We report that endocytic pathway abnormalities are present not only in neurons, but in cerebral endothelia in Alzheimer's disease caused by certain APP mutations. The presence or absence of endocytic abnormalities distinguish subtypes of familial Alzheimer's disease linked to APP mutations from presenilin mutations, supporting the notion that different cellular pathways are involved in the altered processing of APP leading to increased β‐amyloid generation in certain of these different Alzheimer's disease subtypes.
Nonprogressive autosomal recessive ataxia maps to chromosome 9q34‐9qter in a large consanguineous lebanese family
Authors: Delague Valérie , Bareil Corinne , Bouvagnet Patrice , Salem Nabiha , Chouery Eliane , Loiselet Jacques , Mégarbané André , Claustres Mireille
Published: November 2004

Congenital ataxias are a heterogeneous group of predominantly nonprogressive disorders characterized by hypotonia, developmental delay followed by the appearance of ataxia, and often associated with dysarthria, mental retardation, and atrophy of the cerebellum. We performed a genome‐wide screen on a large inbred Lebanese family presenting a nonprogressive autosomal recessive congenital cerebellar ataxia associated with short stature (MIM 213200), already described by Mégarbané and colleagues.1 The disease locus was assigned to a 12.1 cM interval on chromosome 9q34‐9qter between D9S67 and D9S312. Differential diagnosis with other hereditary ataxias linked to the same region is discussed.
Central and peripheral nervous system infection, immunity, and inflammation in the nonhuman primate model of lyme borreliosis
Authors: Pachner Andrew R. , Cadavid Diego , Shu Gale , Dail Donna , Pachner Sarah , Hodzic Emir , Barthold Stephen W.
Published: November 2004

The relationship between chronic infection, antispirochetal immunity, and inflammation is unknown in Lyme neuroborreliosis. In the nonhuman primate (NHP) model of Lyme neuroborreliosis, we measured spirochetal density in the nervous system and other tissues by polymerase chain reaction and correlated these values to anti‐B. burgdorferi antibody in the serum and cerebrospinal fluid, and to inflammation in tissues. Despite substantial presence of B. burgdorferi, the causative agent of Lyme borreliosis, in the central nervous system, only minor inflammation was present there, though skeletal and cardiac muscle, which contained similar levels of spirochete, were highly inflamed. Anti‐B. burgdorferi antibody was present in the cerebrospinal fluid but was not selectively concentrated. All infected animals developed anti‐B. burgdorferi antibody in the serum, but increased amplitude of antibody was not predictive of higher levels of infection. These data demonstrate that Lyme neuroborreliosis is a persistent infection, that spirochetal presence is a necessary but not sufficient condition for inflammation, and that antibody measured in serum may not predict the severity of infection.
European/Canadian multicenter, double‐blind, randomized, placebo‐controlled study of the effects of glatiramer acetate on magnetic resonance imaging–measured disease activity and burden in patients with relapsing multiple sclerosis
Authors: Comi Giancarlo , Filippi Massimo , Wolinsky Jerry S. ,   European/Canadian Glatiramer Acetate Study Group
Published: November 2004

Two prior double‐blind, placebo‐controlled, randomized trials demonstrated that glatiramer acetate (GA) reduces relapse rates in patients with relapsing remitting multiple sclerosis (RRMS). This study was designed to determine the effect, onset, and durability of any effect of GA on disease activity monitored with magnetic resonance imaging (MRI) in patients with RRMS. Two hundred thirty‐nine eligible patients were randomized to receive either 20 mg GA (n = 119) or placebo (n = 120) by daily subcutaneous injection. Eligibility required one or more relapses in the 2 years before entry and at least one enhancing lesion on a screening MRI. The study was a randomized, double‐blind, placebo‐controlled phase during which all patients studied underwent monthly MRI scans and clinical assessments over 9 months. The primary outcome measure was the total number of enhancing lesions on T1‐weighted images. Secondary outcome measures included the proportion of patients with enhancing lesions, the number of new enhancing lesions and change in their volume; the number of new lesions detected on T2‐weighted images and change in their volume, and the change in volume of hypointense lesions seen on unenhanced T1‐weighted images. Clinical measures of disease activity were also evaluated. The active treatment and placebo groups were comparable at entry for all demographic, clinical, and MRI variables. Treatment with GA showed a significant reduction in the total number of enhancing lesions compared with placebo (−10.8, 95% confidence interval −18.0 to −3.7; p = 0.003). Consistent differences favoring treatment with GA were seen for almost all secondary end points examined: number of new enhancing lesions (p < 0.003), monthly change in the volume of enhancing lesions (p = 0.01), and change in volume (p = 0.006) and number of new lesions seen on T2‐weighted images (p < 0.003). The relapse rate was also significantly reduced by 33% for GA‐treated patients (p = 0.012). All effects increased over time. Glatiramer acetate significantly reduced MRI‐measured disease activity and burden. Ann Neurol 2001;49:290–297
Differences in sensory and motor cortical organization following brain injury early in life
Authors: Thickbroom Gary W. , Byrnes Michelle L. , Archer Sarah A. , Nagarajan Lakshmi , Mastaglia Frank L.
Published: November 2004

There have been a number of physiological studies of motor recovery in hemiplegic cerebral palsy which have identified the presence of novel ipsilateral projections from the undamaged hemisphere to the affected hand. However, little is known regarding the afferent projection to sensory cortex and its relationship to the reorganized cortical motor output. We used transcranial magnetic stimulation (TMS) to investigate the corticomotor projection to the affected and unaffected hands in a group of subjects with hemiplegic cerebral palsy, and also performed functional magnetic resonance imaging (fMRI) studies of the patterns of activation in cortical motor and sensory areas following active and passive movement of the hands. Both TMS and fMRI demonstrated a normal contralateral motor and sensory projection between the unaffected hand and the cerebral hemisphere. However, in the case of the affected hand, the TMS results indicated either a purely ipsilateral projection or a bilateral projection in which the ipsilateral pathway had the lower motor threshold, whereas passive movement resulted in fMRI activation in the contralateral hemisphere. These results demonstrate that there is a significant fast‐conducting corticomotor projection to the affected hand from the ipsilateral hemisphere in this group of subjects, but that the predominant afferent projection from the hand is still directed to the affected contralateral hemisphere, resulting in an interhemispheric dissociation between afferent kinesthetic inputs and efferent corticomotor output. The findings indicate that there can be differences in the organization of sensory and motor pathways in cerebral palsy, and suggest that some of the residual motor dysfunction experienced by these subjects could be due to an impairment of sensorimotor integration at cortical level as a result of reorganization in the motor system. Ann Neurol 2001;49:320–327
Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial Parkinsonism associated with mutations in the Parkin gene
Authors: Hilker Ruediger , Klein Christine , Ghaemi Mehran , Kis Bernhard , Strotmann Tim , Ozelius Laurie J. , Lenz Olaf , Vieregge Peter , Herholz Karl , Heiss Wolf‐Dieter , Pramstaller Peter P.
Published: November 2004

A kindred from South Tyrol (northern Italy) with familial, adult‐onset parkinsonism of pseudo‐dominant inheritance and mutations in the parkin gene was recently described. To gain insight into basal ganglia dysfunction in this form of hereditary parkinsonism, positron emission tomography (PET) with 18‐fluorodopa (FDOPA) and 11C‐raclopride (RAC) was performed in 5 affected family members and 5 asymptomatic relatives with proven compound heterozygous or heterozygous parkin mutations. Results were compared to findings in healthy control subjects and patients with typical sporadic, idiopathic Parkinson‘s disease. Similar to findings in the sporadic Parkinson’s disease group, presynaptic striatal FDOPA storage was decreased in patients with compound heterozygous parkin mutations, with the most prominent reduction in the posterior part of the putamen. Along with the presynaptic lowered FDOPA uptake, we found a uniform reduction of the striatal 11C‐raclopride binding index in all affected family members as compared to asymptomatic family members carrying a heterozygous parkin mutation, sporadic Parkinson's disease, and control subjects. Our PET data provide evidence that parkinsonism in this family is associated with presynaptic dopaminergic dysfunction similar to idiopathic Parkinson's disease pathophysiology, along with alterations at the postsynaptic D2 receptor level. In asymptomatic carriers of a single parkin mutation with an apparently normal allele, we found a mild but statistically significant decrease of mean FDOPA uptake compared to control subjects in all striatal regions. These data indicate a preclinical disease process in these subjects. Ann Neurol 2001;49:367–376
The incidence of mitochondrial encephalomyopathies in childhood: Clinical features and morphological, biochemical, and DNA abnormalities
Authors: Darin Niklas , Oldfors Anders , Moslemi Ali‐Reza , Holme Elisabeth , Tulinius Már
Published: November 2004

In this study we present incidence, point prevalence, and mortality figures of mitochondrial encephalomyopathies in a population‐based study of children from western Sweden. Through the screening of registers and review of medical records, we identified 32 patients under 16 years of age from the study population who were diagnosed between January 1, 1984, and December 31, 1998. The incidence of mitochondrial encephalomyopathies in preschool children (<6 years of age) was 1 out of 11,000. The preschool incidence of Leigh's syndrome was 1 out of 32,000, and the preschool incidences of both Alper's syndrome and infantile mitochondrial myopathy with cytochrome C oxidase deficiency were 1 out of 51,000. The point prevalence (January 1, 1999) of mitochondrial encephalomyopathies in children under 16 years of age was 1 out of 21,000. The median survival for patients with infantile onset was until 12 years of age. We identified 4 cases with mitochondrial DNA point mutations, 2 cases with mitochondrial DNA deletions, and 2 cases with nuclear mutations in the SURF1 gene. We conclude that mitochondrial encephalomyopathies are relatively common neurometabolic disorders in childhood. Ann Neurol 2001;49:377–383
Neurological and neuropathologic heterogeneity in two brothers with cobalamin C deficiency
Authors: Powers James M. , Rosenblatt David S. , Schmidt Robert E. , Cross Anne H. , Black Joseph T. , Moser Ann B. , Moser Hugo W. , Morgan Daniel J.
Published: November 2004

Two adult brothers, one documented to have methylmalonic acidemia with homocystinuria, or cobalamin C deficiency, after autopsy, displayed severe but divergent neurological presentations. One exhibited a myelopathy and the other chronic endocrine problems (Schmidt's syndrome) followed by a neuropsychiatric and dementing disorder owing to cerebral perivascular demyelination. The recognition of cobalamin C deficiency has practical implications because it is one of the few inherited diseases of central white matter that is treatable. Ann Neurol 2001;49:396–400
Anticardiolipin antibodies are not a useful screening tool in a nonselected large group of patients with multiple sclerosis
Authors: Sastre‐Garriga Jaume , Reverter Juan Carlos , Font Josep , Tintoré Mar , Espinosa Gerard , Montalban Xavier
Published: November 2004

Recent works claiming that primary antiphospholipid syndrome (PAPS) cannot be clinically distinguished from multiple sclerosis (MS) recommend that MS patients be screened for anticardiolipin antibodies (ACA). In this study 296 randomly selected patients with MS and clinically isolated syndromes and 51 healthy controls were analyzed; ACA, anti‐β2‐glycoprotein I, or antiprothrombin was found in 6 patients. No predominance of any kind of clinical manifestations and no cardinal manifestations of PAPS were found in these patients. ACA tests should be performed only when a suspicion of PAPS is raised and atypical clinical presentation for MS is found. Ann Neurol 2001;49:408–411
Primary progressive aphasia
Authors: Mesulam M.‐Marsel
Published: November 2004

Primary progressive aphasia (PPA) is a focal dementia characterized by an isolated and gradual dissolution of language function. The disease starts with word‐finding disturbances (anomia) and frequently proceeds to impair the grammatical structure (syntax) and comprehension (semantics) of language. The speech output in PPA can be fluent or nonfluent. Memory, visual processing, and personality remain relatively well‐preserved until the advanced stages and help to distiguish PPA from frontal lobe dementia and the typical forms of Alzheimer's disease. The term “semantic dementia” was originally introduced to designate a different group of patients with a combination of verbal and visual processing deficits. In practice, however, this diagnosis is also being used in a variant sense to denote a subtype of PPA with fluent speech and impaired comprehension, even in the absence of visual processing deficits. Insofar as the diagnosis of semantic dementia can have these two different meanings, it is important to specify whether it is being used in the original sense or to denote a subtype of PPA. Structural and physiological neuroimaging confirms the selective predilection of PPA for the left hemisphere, especially for its language‐related cortices. A few patients with PPA display the neuropathological markers of Alzheimer's disease, but in an unusual distribution. The majority of the autopsies in PPA have shown either Pick's disease or lobar atrophy without distinctive histopathology. The suggestion has been made that PPA and frontal lobe dementia constitute phenotypical variations of a unitary disease process within the “Pick‐lobar atrophy” spectrum. Recent advances in chromosome 17‐linked dementias justify a rigorous search for tau polymorphisms and tauopathy in sporadic PPA. An informed approach to this syndrome will increase the effectiveness with which clinicians can address the unique challenges associated with the diagnosis and care of PPA. Ann Neurol 2001;49:425–432
Familial dyskinesia and facial myokymia (FDFM): A novel movement disorder
Authors: Fernandez Magali , Raskind Wendy , Wolff John , Matsushita Mark , Yuen Eric , Graf William , Lipe Hillary , Bird Thomas
Published: November 2004

We describe here familial dyskinesia and facial myokymia (FDFM), a novel autosomal dominant disorder characterized by adventitious movements that sometimes appear choreiform and that are associated with perioral and periorbital myokymia. We report a 5‐generation family with 18 affected members (10 males and 8 females) with FDFM. The disorder has an early childhood or adolescent onset. The involuntary movements are paroxysmal at early ages, increase in frequency and severity, and may become constant in the third decade. Thereafter, there is no further deterioration, and there may even be improvement in old age. The adventitious movements are worsened by anxiety but not by voluntary movement, startle, caffeine, or alcohol. The disease is socially disabling, but there is no intellectual impairment or decrease in lifespan. A candidate gene and haplotype analysis was performed in 9 affected and 3 unaffected members from 3 generations of this family using primers for polymorphic loci closely flanking or within genes of interest. We excluded linkage to 11 regions containing genes associated with chorea and myokymia: 1) the Huntington disease gene on chromosome 4p; 2) the paroxysmal dystonic choreoathetosis gene at 2q34; 3) the dentatorubral‐pallidoluysian atrophy gene at 12p13; 4) the choreoathetosis/spasticity disease locus on 1p that lies in a region containing a cluster of potassium (K+) channel genes; 5) the episodic ataxia type 1 (EA1) locus on 12p that contains the KCNA1 gene and two other voltage‐gated K+ channel genes, KCNA5 and KCNA6; 6) the chorea‐acanthocytosis locus on 9q21; 7) the Huntington‐like syndrome on 20p; 8) the paroxysmal kinesigenic dyskinesia locus on 16p11.2‐q11.2; 9) the benign hereditary chorea locus on 14q; 10) the SCA type 5 locus on chromosome 11; and 11) the chromosome 19 region that contains several ion channels and the CACNA1A gene, a brain‐specific P/Q‐type calcium channel gene associated with ataxia and hemiplegic migraine. Our results provide further evidence of genetic heterogeneity in autosomal dominant movement disorders and suggest that a novel gene underlies this new condition. Ann Neurol 2001;49:486–492
Spectroscopic studies of interaction of chlorobenzylidine with DNA
Authors: Zhong Wenying , Yu Jun‐Sheng , Huang Wenlong , Ni Kunyi , Liang Yingqiu
Published: November 2004

Electronic absorbance and fluorescence titrations are used to probe the interaction of chlorobenzylidine with DNA. The binding of chlorobenzylidine to DNA results in hypochromism, a small shift to a longer wavelength in the absorption spectra, and emission quenching in the fluorescence spectra. These spectral characteristics suggest that chlorobenzylidine binds to DNA by an intercalative mode. This conclusion is reinforced by fluorescence polarization measurements. Scatchard plots constructed from fluorescence titration data give a binding constant of 1.3 × 105 M−1 and a binding site size of 10 base pairs. This indicates that chlorobenzylidine has a high affinity with DNA. The intercalative interaction is exothermic with a Van't Hoff enthalpy of −143 kJ/mol. This result is obtained from the temperature dependence of the binding constant. The interaction of chlorobenzylidine with DNA is affected by the pH value of the solution. The binding constant has its maximum at pH 3.0. Upon binding to DNA, the fluorescence from chlorobenzylidine is quenched efficiently by the DNA bases and the fluorescence intensity tends to be constant at high concentrations of DNA when the binding is saturated. The Stern–Volmer quenching constant obtained from the linear quenching plot is 1.6 × 104 M−1 at 25°C. The measurements of the fluorescence lifetime and the dependence of the quenching constant on the temperature indicate that the fluorescence quenching process is static. The fluorescence lifetime of chlorobenzylidine is 1.9 ± 0.4 ns. © 2001 John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 62: 315–323, 2001
Expression of GnTIII in a recombinant anti‐CD20 CHO production cell line: Expression of antibodies with altered glycoforms leads to an increase in ADCC through higher affinity for FCγRIII
Authors: Davies Julian , Jiang LiYing , Pan Li‐Zhen , LaBarre Michael J. , Anderson Darrell , Reff Mitchell
Published: November 2004

The gene encoding the rat glycosylation enzyme β1–4‐N‐acetylglucosaminyltransferase III (GnTIII) was cloned and coexpressed in a recombinant production Chinese hamster ovary (CHO) cell line expressing a chimeric mouse/human anti‐CD20 IgG1 antibody. The new cell lines expressed high levels of antibody and have growth kinetics similar to that of the parent. Relative QPCR showed the cell lines to express varying levels of mRNA. High‐performance liquid chromatography (HPLC) analysis showed the enzyme to have added bisecting N‐acetylglucosamine (GlcNAc) residues in most (48% to 71%) of the N‐linked oligosaccharides isolated from antibody preparations purified from the cell lines. In an ADCC assay the new antibody preparations promoted killing of CD20‐positive target cells at approximately 10‐ to 20‐fold lower concentrations than the parent. This activity was blocked using an anti‐FcγRIII antibody, supporting the role of FcγRIII binding in this increase. In addition, cell binding assays showed the modified antibody bound better to FcγRIII‐expressing cells. The increase in ADCC activity is therefore likely due to an increased affinity of the modified antibody for the FcγRIII receptor. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 288–294, 2001.
Continuous production of (R)‐phenylacetylcarbinol in an enzyme‐membrane reactor using a potent mutant of pyruvate decarboxylase from Zymomonas mobilis
Authors: Goetz Günter , Iwan Peter , Hauer Bernhard , Breuer Michael , Pohl Martina
Published: November 2004

The optimization of a continuous enzymatic reaction yielding (R)‐phenylacetylcarbinol (PAC), an intermediate of the L‐ephedrine synthesis, is presented. We compare the suitability of three pyruvate decarboxylases (PDC), PDC from Saccharomyces cerevisiae, PDC from Zymomonas mobilis, and a potent mutant of the latter, PDCW392M, with respect to their application in the biotransformation using acetaldehyde and benzaldehyde as substrates. Among these, the mutant enzyme was the most active and most stable one. The reaction conditions of the carboligation reaction were investigated by determining initial rate velocities with varying substrate concentrations of both aldehydes. From the resulting data a kinetic model was inferred which fits the experimental data with sufficient reliability to deduce the optimal concentrations of both substrates for the enzymatic process. The results demonstrate that the carboligation is most efficiently performed using a continuous reaction system and feeding both aldehydes in equimolar concentration. Initial studies using a continuously operated enzyme‐membrane reactor gave (R)‐PAC with a space–time yield of 81 g L‐1 · d‐1 using a substrate concentration of 50 mM of both aldehydes. The yield was easily increased by cascadation of enzyme‐membrane reactors. The new strategy allows the synthesis of (R)‐PAC from cheap substrates in an aqueous reaction system. It thereby overcomes the limitation of by‐product formation that severely limits the current fermentative process. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 317–325, 2001.
Linkers for improved cleavage of fusion proteins with an engineered α‐lytic protease
Authors: Lien Samantha , Milner Steven J. , Graham Lloyd D. , Wallace John C. , Francis Geoffrey L.
Published: November 2004

Addition of an N‐terminal fusion partner can greatly aid the expression and purification of a recombinant protein in Escherichia coli. We investigated two genetically engineered proteases designed to remove the fusion partner after the protein of interest has been expressed. Recombinant human insulin‐like growth factor‐II (hIGF‐II) has been produced from E. coli‐derived fusion proteins using a novel enzymatic cleavage system that uses a mutant of α‐lytic protease. Initially, two potential fusion protein linkers were designed, Pro‐Ala‐Pro‐His (PAPH) and Pro‐Ala‐Pro‐Met (PAPM), and were tested as substrates in the form of synthetic dodecapeptides. Using mass spectrometry and reverse‐phase HPLC, the position of cleavage was confirmed and the kinetics of synthetic peptide cleavage were examined. Use of the linkers in hIGF‐II fusion proteins produced in E. coli was then evaluated. The fusion proteins constructed consist of the first 11 amino acids of porcine growth hormone linked N‐terminally to hIGF‐II by six amino acids that include the dipeptide Val‐Asn followed by a variable tetrapeptide protease cleavage motif. Mass spectrometry and N‐terminal sequencing confirmed that proteolytic cleavage of the fusion proteins had occurred at the predicted sites. Using the fusion proteins as substrates, the cleavage of the rationally designed motifs by the α‐lytic protease mutant was compared. The fusion protein containing the motif PAPM had a kcat/KM ratio indicating a 1.6‐fold preference over the PAPH fusion protein for cleavage by this enzyme. Furthermore, when hIGF‐II fusion proteins containing the designed cleavable linkers were processed with the engineered α‐lytic protease, they gave greatly improved yields of native hIGF‐II compared to an analogous fusion protein cleaved by H64A subtilisin. Comparison of the peptide and protein cleavage studies shows that the efficient proteolysis of the cleavage motifs is an inherent property of the designed sequences and is not determined by secondary or tertiary structure in the fusion proteins. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 335–343, 2001.
Abnormal dispersion of a purkinje cell subset in the mouse mutant cerebellar deficient folia (cdf)
Authors: Beierbach Elaine , Park Chankyu , Ackerman Susan L. , Goldowitz Dan , Hawkes Richard
Published: November 2004

Purkinje cells of different molecular phenotypes subdivide the cortex of the cerebellum both rostrocaudally into parasagittal bands and mediolaterally into transverse zones. Superimposed on the Purkinje cell compartmentation, the cerebellar cortex is pleated into a reproducible array of lobes and lobules. During cerebellar development, Purkinje cell bands are formed through the rostrocaudal dispersal of embryonic clusters, triggered primarily by a Reelin‐dependent signaling pathway. In the naturally occurring mouse mutant cerebellar deficient folia (cdf), there is a failure of Purkinje cell dispersion that results in widespread Purkinje cell ectopia in the adult. The ectopia is restricted primarily to that subset of Purkinje cells that does not express zebrin II/aldolase C and that forms ectopic clusters in among the cerebellar nuclei. Most Purkinje cells that express zebrin II are located normally in a monolayer. Thus, the cerebellum of cdf mutants has a failure of Purkinje cell dispersion that is confined primarily to a zebrin II‐negative (zebrin II−) subpopulation. Despite the Purkinje cell ectopia, the parasagittal band organization of the cerebellum is still clear. The shortening of the cortex is distributed evenly over all lobules, with the result that transverse expression boundaries are relocated with respect to the lobules and fissures. The number of Purkinje cells in the cdf/cdf cerebellum is similar to the number in littermate controls. Therefore, it appears that the lesion in cdf results in the failure of a zebrin II− Purkinje cell subset to disperse either due to a cell intrinsic defect or due to an abnormal interaction between the Purkinje cells and either granule cells or afferent inputs. J. Comp. Neurol. 436:42–51, 2001. © 2001 Wiley‐Liss, Inc.
Distribution of estrogen receptor β immunoreactivity in the rat central nervous system
Authors: Shughrue Paul J. , Merchenthaler Istvan
Published: November 2004

The discovery of estrogen receptor β (ERβ) and subsequent localization of its mRNA in the rat central nervous system (CNS) has provided new insights about estrogen action in brain. A critical step in understanding the role of ERβ is demonstrating that the mRNA is translated into functional protein. The present study used a new ERβ‐specific polyclonal antiserum (Z8P) and immunocytochemistry (ICC) to investigate the distribution of ERβ in the rat CNS. Ovariectomized female rats were perfusion fixed, and free‐floating sections were incubated with Z8P. After visualization with a standard ABC method, nuclear immunoreactivity was seen in neurons throughout the brain, including the olfactory nuclei, laminae IV–VI of the cerebral cortex, medial septum, preoptic area, bed nucleus of the stria terminalis, supraoptic nucleus, paraventricular nucleus, zona incerta, medial and cortical amygdaloid nuclei, cerebellum, nucleus of the solitary tract, ventral tegmental area, and spinal trigeminal nucleus. Moreover, the results of a double‐label ICC/ in situ hybridization study revealed that ERβ mRNA and immunoreactivity were colocalized in neurons of the brain, thus confirming the specificity of the antiserum. Through the use of Western blot analysis, Z8P was shown to recognize in vitro translated ERβ, but not ERα, as well as a 60‐kDa protein from rat granulosa cells and ovary extracts. The results of these studies have demonstrated that (1) ERβ mRNA is translated into immunoreactive protein throughout the rat brain, and (2) ERβ resides in the cell nucleus. Together, these data provide an anatomic foundation for future studies and advance our understanding of estrogen action in hypothalamic and extrahypothalamic brain regions. J. Comp. Neurol. 436:64–81, 2001. © 2001 Wiley‐Liss, Inc.
Quantitative assessment of retinoid signaling pathways in the developing eye and retina of the chicken embryo
Authors: Hoover Frank , Gundersen Thomas E. , Ulven Stine M. , Michaille Jean‐Jacques , Blanchet Sandrine , Blomhoff Rune , Glover Joel C.
Published: November 2004

Retinoid signaling has been implicated as an important regulator of retinal development and differentiation. We have used state of the art high‐pressure liquid chromatography to identify and quantitate biologically active retinoids, immunohistochemistry to localize the retinoic acid synthetic enzyme retinaldehyde dehydrogenase 2 (RALDH2), and nucleic acid assays to quantitate and localize retinoid receptor gene transcripts in the developing eye and retina of the chicken. Our results demonstrate spatial distinctions in retinoid synthesis and signaling that may be related to laminar differentiation in the developing retina. Retinoic acids (RAs) and their precursor retinols (ROHs) are the predominant retinoids in the developing eye. All‐trans‐RA and all‐trans‐3,4‐didehydro‐RA are present in the neuroepithelium in approximately equal amounts from early stages of neurogenesis until shortly before hatching. The retinoid X receptor (RXR) ligand 9‐cis‐RA is undetectable at all stages; if present, it cannot exceed a small percentage of the total RA content. RAs are not detected in the pigment epithelium. All‐trans‐ROH is present in the neuroepithelium and pigment epithelium, whereas all‐trans‐3,4‐didehydro‐ROH is detected only in the pigment epithelium and/or the choroid and sclera. RALDH2 immunoreactivity is intense in the choroid, low or absent in the pigment epithelium, and moderate in the neuroepithelium, where it is highest in the outer layers. Transcripts of all five chicken retinoid receptor genes are present in the neural retina and eye throughout development. During the period of neurogenesis, at least three of the receptors (RARγ, RXRγ, RXRα), exhibit dynamic patterns of differential localization within the depths of the neural retina. J. Comp. Neurol. 436:324–335, 2001. © 2001 Wiley‐Liss, Inc.
Variability of position of the P2 glomerulus within a map of the mouse olfactory bulb
Authors: Schaefer Michele L. , Finger Thomas E. , Restrepo Diego
Published: November 2004

Olfactory receptor neurons (ORNs) that express a common odorant receptor molecule target specific glomeruli in the olfactory bulb. We systematically assessed the location of the olfactory glomeruli that receive input from ORNs expressing P2 receptors in the P2‐internal ribosome entry site‐tau‐lacZ mouse. We present a new mapping method that includes an Internet‐accessible computer program for generating two‐ and three‐dimensional maps of the glomerular sheet in the olfactory bulbs of mice. Cylindrical coordinates were used to define glomerular location: The coordinates were given as the anteroposterior (AP) distance parallel to the long axis of the bulb (rostrocaudal; RC) and angular measurements with origin defined by the remnant ependymal layer in the center of the granule cell layer in the bulb. Using this method, we can apply rigorous statistical methods to give objective estimates of position and variability. At the 95% confidence interval, the lateral P2 glomerulus lies at coordinates 1,008 μm ± 306 μm AP × 146° ± 12°, and the medial P2 glomerulus lies at 1,828 μm ± 196 μm AP × 204° ± 8°. We estimate that these coordinates encompass a domain containing 29 and 37 of the 1,800 glomeruli (∼2%) for the lateral and medial glomeruli, respectively. Furthermore, the data reported here demonstrate that the rostrocaudal position of small P2 glomeruli is three times more variable than that of large glomeruli. J. Comp. Neurol. 436:351–362, 2001. © 2001 Wiley‐Liss, Inc.