bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymorphisms within the angiotensinogen gene (GT‐Repeat) and the risk of stroke in pediatric patients with sickle cell disease: A case‐control study
Authors: Tang Delia C. , Prauner Ron , Liu Wenli , Kim Kye‐Hyun , Hirsch Robert P. , Driscoll M. Catherine , Rodgers Griffin P.
Published: August 2002

Stroke is one of the most devastating complications of patients with sickle cell disease (SCD). Currently, there are no known molecular or genetic markers that can be used to assess the risk of stroke in this population. We have previously shown that relative hypertension may be one risk factor for stroke in SCD. In a case‐control study, we investigated the association between GT‐repeat polymorphism within the angiotensinogen (AGT) gene and the risk of stroke in pediatric patients with SCD. After informed consent was obtained, 63 patients (21 stroke subjects and 42 nonstroke control subjects matched according to age and sex) with SCD followed at local pediatric hematology clinics were genotyped to test the association of specific GT‐repeat alleles of the AGT gene and occurrence of stroke. There were statistical differences in the distribution of the genotypes among stroke and nonstroke SCD patients (χ2 = 10.82, df = 11, P < 0.05). We also found GT‐repeat alleles A3 and/or A4 of the AGT gene conferred a four‐fold increase in the risk of stroke (odds ratio [OR] = 4, P < 0.05). The attributable odds ratio for allele A3 and A4 is 2.24 and 4.33, respectively (P < 0.005). Our results suggest that GT‐repeat within the AGT gene may be associated with risk of stroke in pediatric SCD. The relative risk of stroke in the presence of alleles A3 and/or A4 is fourfold greater than in the absence of these alleles. If these data are substantiated in a larger cohort of patients, our results indicate that the determination of GT‐repeat of AGT gene may be a useful genetic marker to assess the risk for stroke of patients with SCD. Am. J. Hematol. 68:164–169, 2001. Published 2001 Wiley‐Liss, Inc.
Menopausal experiences and bone density of Mayan women in Yucatan, Mexico
Authors: Beyene Yewoubdar , Martin Mary C.
Published: August 2002

This cross‐sectional study reports on the menopausal transition of Mayan women from Yucatan, Mexico. A total of 228 women completed the study, and 118 women were classified by history as postmenopausal; the others were premenopausal. Demographic information, reproductive history, physical examination, hormone concentrations, radial bone density, food samples, and history of physical activity were obtained. The average age at which menopause occurred by history was 44.3 ± 4.4 years; this is reflected in the distribution of FSH levels by age. None of the women reported symptoms of hot flashes, and none recalled any history of significant symptoms associated with their menopausal transition. Hormone levels were similar to U.S. reference values with elevated FSH (66.6 ± 29.1 mIU/ml), low estradiol (9.4 ± 8.3 pg/ml) and estrone (13.3 ± 7.8 pg/ml), E1 > E2, and normal levels of testosterone and androstenedione. BMD declined with age, and values were lower than reference values for United States women. Clinical evidence of fracture was not detected by history or physical examination even for those who were 20 years postmenopausal. The endocrine characteristics of menopause among Mayan women in Yucatan are similar to hormonal changes reported for women in the United States, but signs, symptoms, and apparent consequences are different in the two populations. Am. J. Hum. Biol. 13:505–511, 2001. © 2001 Wiley‐Liss, Inc.
Postmenopausal function in context: Biocultural observations on Amish, neighboring non‐Amish, and Ifugao household health
Authors: Hewner Sharon J.
Published: August 2002

Ecological approaches to female post‐reproductive function must consider the social context and microenvironment of the household. A model integrating these environmental factors into the analysis of late‐life well‐being (operationally defined as household health) is presented and explored in three settings: an Old Order Amish community, the neighboring community of non‐Amish, and an Ifugao community in the Philippine highlands. Intensive interview and observation of function were completed in a sample of at least 25 households in each community. The complex interaction of social and biological factors is explored in case studies and through multiple regression analysis with household health as the dependent variable. The results emphasize the importance of social support and assessing capabilities within the household. The results also suggest the need for natural field observation of work to better understand the influence of pacing and scheduling, necessity of work, and the role of environmental modification in postmenopausal function. Am. J. Hum. Biol. 13:521–530, 2001. © 2001 Wiley‐Liss, Inc.
Lung cancer risk, silica exposure, and silicosis in Chinese mines and pottery factories: The modifying role of other workplace lung carcinogens*
Authors: Cocco Pierluigi , Rice Carol H. , Chen Jing Qiong , McCawley Michael A. , McLaughlin Joseph K. , Dosemeci Mustafa
Published: August 2002

Background

Aims of our study were to explore whether and to what extent exposure to other lung carcinogens, or staging and clinical features of silicosis modify or confound the association between silica and lung cancer.

Methods

We used data from a nested case‐control study, conducted in the late 1980s in 29 Chinese mines and potteries (10 tungsten mines, 6 copper and iron mines, 4 tin mines, 8 pottery factories, and 1 clay mine), that included 316 lung cancer cases and 1,356 controls, matched by decade of birth and facility type. The previous analysis of these data presented results by type of mine or factory.

Results

In our study, pooling all 29 Chinese work sites, lung cancer risk showed a modest association with silica exposure. Risk did not vary after excluding subjects with silicosis or adjusting the risk estimates by radiological staging of silicosis. Strong correlation among exposures prevented a detailed evaluation of the role of individual exposures. However, lung cancer risk was for the most part absent when concomitant exposure to other workplace lung carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), nickel or radon‐daughters, was considered. The cross classification of lung cancer risk by categories of exposure to respirable silica and total respirable dust did not show an independent effect of total respirable dust. Silicosis showed a modest association with lung cancer, which did not vary by severity of radiological staging, or by radiological evidence of disease progression, or by level of silica exposure. However, among silicotic subjects, lung cancer risk was significantly elevated only when exposure to cadmium and PAH had occurred.

Conclusions

Our results suggest that, among silica‐exposed Chinese workers, numerous occupational and non‐occupational risk factors interact in a complex fashion to modify lung cancer risk. Future epidemiological studies on silica and lung cancer should incorporate detailed information on exposure to other workplace lung carcinogens, total respirable dust, and on surface size and age of silica particles to understand whether and to what extent they affect the carcinogenic potential of silica. Am. J. Ind. Med. 40:674–682, 2001. © 2001 Wiley‐Liss, Inc
Musculoskeletal problems of the neck, shoulder, and back and functional consequences in nurses
Authors: Trinkoff Alison M. , Lipscomb Jane A. , Geiger‐Brown Jeanne , Brady Barbara
Published: August 2002

Background

Though musculoskeletal disorders (MSDs) are highly prevalent among registered nurses (RNs), little is known about functional consequences of MSDs in nurses.

Methods

Data on neck, shoulder, and back MSD problems were analyzed in 1,163 working nurses (response rate = 74%). Cases had relevant symptoms lasting at least 1 week or occurring at least monthly in the past year, with at least moderate pain intensity, on average. MSD problems with a frequency, duration, or pain intensity below the level needed to meet the case definition were defined as MSD symptoms. Those who did not meet symptom or case criteria at any body site were defined as asymptomatic. Odds of consequences (e.g., saw a doctor/provider, missed work, reduced/modified work, non‐work activities, or recreation, medication use, inadequate sleep) were estimated for cases versus those with symptoms.

Results

We found 45.8, 35.1, and 47.0% of nurses had neck, shoulder, or back MSD problems (either at the case or symptom level), respectively, within the past year. Cases were far more likely to have seen a provider versus those with symptoms (adjusted odds ratio, aOR Neck: 4.33, 95% CI: 2.85–6.56; aOR Shoulder: 4.83, 95% CI: 3.00–7.77; aOR Back: 3.69, 95% CI: 2.47–5.49). Cases also were more likely to experience all other functional consequences.

Conclusions

MSD consequences are substantial and suggest opportunities for intervention. Future research will examine the impact of work organization and physical demands on MSDs. Am. J. Ind. Med. 41:170–178, 2002. © 2002 Wiley‐Liss, Inc.
Interstitial pulmonary fibrosis after severe exposure to welding fumes
Authors: Buerke U. , Schneider J. , Rösler J. , Woitowitz H.‐J.
Published: August 2002

Background

Interstitial pulmonary fibrosis (IPF) is reported after long term, severe exposure to welding fumes in poorly ventilated workplaces.

Methods

Fifteen welders with IPF were examined—13 in our outpatient clinic—from 1990 to 1997. Occupational histories and examinations, lung function analyses, symptoms and clinical findings, histological analyses in 13 patients partly including SEM/EDX‐analyses, chest X‐rays, chest computed tomographies were conducted.

Results

Duration of work as welders was 28 years and the cumulative dose of welding fumes 221 mg/m3 × years (median). Lung function studies found pattern of restriction or combined restriction‐obstruction, lower diffusion capacity, and reduced blood oxygen tension at exercise. Histologicallly, patchy interstitial fibrosis was noted. Accumulations of particulate matter typically for welding fume were detected. EDX showed increase of iron load and close topographical relationship to welding fume particles embedded in areas of scattered fibrosis.

Conclusion

While epidemiological data are limited, it is reasonable to conclude that a causal relationship exists between IPF in welders with long term exposure to high concentrations of welding fumes. Am. J. Ind. Med. 41:259–268, 2002. © 2002 Wiley‐Liss, Inc.
Capture–recapture estimation of unreported work‐related musculoskeletal disorders in Connecticut
Authors: Morse Timothy , Dillon Charles , Warren Nicholas , Hall Charles , Hovey Deborah
Published: August 2002

Background

Estimates of the extent of musculoskeletal disorders (MSD) are usually based upon workers' compensation reports, although recent reports indicate that there may be widespread under‐reporting of MSD.

Methods

An estimate of the incidence of arm and hand work‐related MSD was made using capture–recapture analysis of the overlap between state workers' compensation reports and physician reports in Connecticut for 1995. The resulting estimate was compared to a population‐based survey of MSD.

Results

There was very small overlap between the two state injury reporting systems: 6.7% of 793 reported workers' compensation cases, or 8% of 661 physician's reports. The estimate for MSD not captured by either system was 13,285, resulting in 14,686 (95% CI: 9,733–18,453) total reported and non‐reported cases. This compares to an estimate of 13,775 cases (95% CI: 8,800–18,800) based on a phone survey.

Conclusions

This analysis points to substantial under‐reporting of MSD in Connecticut: estimates of unreported cases exceed those officially reported by a factor of 11:1. The findings have an important bearing on injury prevention programs and policy making. Am. J. Ind. Med. 39:636–642, 2001. © 2001 Wiley‐Liss, Inc.
Advent of occupational health services research*
Authors: Deitchman Scott , Dembe Allard E. , Himmelstein Jay
Published: August 2002

After lagging behind health services research in general health care, research is now examining health services provided to workers suffering occupational injuries and illnesses. The National Institute for Occupational Safety and Health, the Robert Wood Johnson Foundation Workers' Compensation Health Initiative, the Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality), and the Canadian Institute for Work and Health co‐sponsored a June, 1999, conference to explore research needs in this area. Fundamental tenets for advancing occupational health services research include: adopting the goal of improving occupational health care, including better integration of preventive and curative care; creating standardized interstate occupational health care data sets that include medical, economic, and patient perspectives; better defining quality in occupational care and developing appropriate performance measures; in addition to medical costs, assessing social, economic, medical and functional outcomes of care; considering the connections between work and health, including general health services; and addressing the need to train qualified occupational health services researchers. Am. J. Ind. Med. 40:291–294, 2001. Published 2001 Wiley‐Liss, Inc.
Determinants of duration of disability and return‐to‐work after work‐related injury and illness: Challenges for future research
Authors: Krause Niklas , Frank John W. , Dasinger Lisa K. , Sullivan Terry J. , Sinclair Sandra J.
Published: August 2002

Background

The purpose of this review was to identify critical data and research needs in addressing the following question: What are the primary factors that affect the time lost from work, return‐to‐work (RTW), subsequent unemployment, and changes in occupation after disabling illness or injury?

Methods

Review of the literature to identify research challenges originating from the multitude of disciplines, data sources, outcome measures, and methodological and analytical problems.

Results

About 100 different determinants of RTW outcomes were identified. Their impact varies across different phases of the disablement process. Recommendations are provided for addressing five selected research challenges.

Conclusion

Interdisciplinary research needs to develop a comprehensive conceptual framework. Priority should be given to studies on specific domains of risk factors meeting five selection criteria: amenability to change; relevance to users of research; generalizability across health conditions, disability phases, and settings; “degree of promise” as derived from qualitative exploratory studies; and capacity to improve measurement instruments. Combining qualitative and quantitative research methods is necessary to bridge existing knowledge gaps. Am. J. Ind. Med. 40:464–484, 2001. © 2001 Wiley‐Liss, Inc.
Different familial transmission patterns in bipolar I disorder with onset before and after age 25
Authors: Grigoroiu‐Serbanescu Maria , Martinez Maria , Nöthen Markus M. , Grinberg Mihaela , Sima Dorina , Propping Peter , Marinescu Elvira , Hrestic Mihaela
Published: August 2002

Gene identification in common disorders such as Alzheimer disease and breast cancer has greatly profited from the use of age of onset as criterion to delineate subgroups of disease characterized by different inheritance patterns. In bipolar affective disorder, where the majority of linkage studies have produced conflicting results, studies reporting clinical characteristics and familial occurrence of disease have suggested that age of onset might serve as an indicator for identifying more homogeneous subgroups of disease. Our study was the first to examine this hypothesis by the means of segregation analysis. We investigated a sample of 177 bipolar I probands recruited from consecutive admissions and their first‐ and second‐degree relatives (2,407 subjects). Probands were subdivided into an early‐onset (n = 107) and a late‐onset group (n = 70) using an age of onset of 25 as a cut‐off point. This age was chosen because the observed age of onset distribution was bimodal with a cut‐off of 25 years. Morbid risks for affective disorder were found significantly higher (P = 0.01) in relatives of probands with an early onset than in probands with late onset of disease. The segregation analysis showed that the disease is transmitted differently in early‐ and late‐onset groups. In the early‐onset group, a non‐Mendelian major gene with a polygenic component was favored while the data in the late‐onset group were compatible with a multifactorial model. This result may have important implications for future molecular studies aiming at the identification of disease‐associated genes. © 2001 Wiley‐Liss, Inc.
Serotonin transporter promoter polymorphism, peripheral indexes of serotonin function, and personality measures in families with alcoholism
Authors: Stoltenberg Scott F. , Twitchell Geoffrey R. , Hanna Gregory L. , Cook Edwin H. , Fitzgerald Hiram E. , Zucker Robert A. , Little Karley Y.
Published: August 2002

A functional polymorphism in the regulatory region of the serotonin transporter gene (5‐HTTLPR) is considered to be a plausible candidate gene for anxiety‐related personality traits and for alcoholism. Empirical support for the association between 5‐HTTLPR and psychological traits has been somewhat inconsistent; however, observations of the functional dominance of the low‐activity s‐allele over the l‐allele have been more consistent. When studying the influence of particular genes on psychological traits, it seems useful also to assess more biological intermediate traits that may mediate the effects of those genes on the traits of interest. The present study examined relationships between 5‐HTTLPR genotype, whole blood serotonin (5‐HT) level, and platelet 5‐HT binding in 150 Caucasian subjects from 50 biological families. Individuals with the s‐allele had lower average platelet 5‐HT binding availability than those with the l/l genotype (P < 0.025). Whole blood 5‐HT level was not associated with 5‐HTTLPR genotype. In adult men, those with the s‐allele had higher mean scores on the NEO‐FFI personality trait of openness than did those with the l/l genotype (P = 0.002). The effect was not statistically significant in women (P = 0.42), although it was in the same direction. Our findings do not support an association of 5‐HTTLPR genotype with alcoholism diagnosis, alcoholism subtype, or the personality trait of neuroticism. The results of this pilot study suggest that further work should examine the mediation of the genetic effects on personality traits by biochemical measures and their moderation by gender. © 2002 Wiley‐Liss, Inc.
Genetic study of Apolipoprotein E gene, alpha‐1 antichymotrypsin gene in sporadic Parkinson disease
Authors: Tang Guomei , Xie Huijun , Xu Lin , Hao Yixin , Lin Dayu , Ren Daming
Published: August 2002

Several lines of evidence have suggested some common genetic risk factors for Alzheimer disease (AD) and Parkinson disease (PD) because there are some overlapping pathologies in these two neurodegenerative diseases. In the present study, we investigated the role of Apolipoprotein E gene polymorphism and the signal peptide polymorphism in alpha‐1 antichymotrypsin (ACT) gene in idiopathic sporadic PD. The study was performed in a sample consisting of 68 PD cases and 160 healthy subjects in Shanghai China. We found no significant differences of ACT gene polymorphic distribution between PD cases and controls. The ApoE gene ε2/ε4 genotype was significantly more frequent in PD subjects (χ2 = 7.126, df = 1, P = 0.008) and conferred a 12.70 times susceptibility for PD (OR = 12.62, 95% CI: 1.445–110.17, χ2 = 5.259, P < 0.05, AF = 4.59%). No interaction of ApoE and ACT genes was detected in PD. Therefore, our data suggested that the ApoE ε2/ε4 genotype might be a susceptibility variant of moderate effect for sporadic idiopathic PD in our samples, whereas the ACT gene signal peptide polymorphism might not. © 2002 Wiley‐Liss, Inc.
Segregation analysis of Parkinson disease revealing evidence for a major causative gene
Authors: Maher N.E. , Currie L.J. , Lazzarini A.M. , Wilk J.B. , Taylor C.A. , Saint‐Hilaire M.H. , Feldman R.G. , Golbe L.I. , Wooten G.F. , Myers R.H.
Published: August 2002

The role of genetics in Parkinson disease (PD) continues to be an area of considerable interest and controversy. We collected information involving the nuclear families of 948 consecutively ascertained PD index cases from the University of Virginia (UVA) Health System, the University of Medicine and Dentistry of New Jersey–Robert Wood Johnson (RWJ) School of Medicine, and Boston University (BU) School of Medicine. We performed a segregation analysis to assess evidence for the presence of a Mendelian pattern of familial transmission. The proportion of male (60.4%) and female (39.6%) cases, the mean age of onset (57.7 years), and the proportion of affected fathers (4.7%), mothers (6.6%), brothers (2.9%), and sisters (3.2%) were similar across the three sites. While most of the index cases were male, modestly more of the reported affected relatives were female. These analyses support the presence of a rare major Mendelian gene for PD in both the age‐of‐onset and susceptibility model. The age‐of‐onset model provides evidence for a gene that influences age‐dependent penetrance of PD, influencing age of onset rather than susceptibility. We also found evidence for a Mendelian gene influencing susceptibility to the disease. It is not evident whether these two analyses are modeling the same gene or different genes with different effects on PD. The finding of significant genes influencing penetrance for PD raises the question of whether these may interact with environmental factors or other genes to increase the risk for PD. Such gene environment interactions, involving reduced penetrance in PD, may explain the low concordance rates among monozygotic twins for this disease. © 2002 Wiley‐Liss, Inc.
Polymorphism R25P in the gene encoding transforming growth factor‐beta (TGF‐β1) is a newly identified risk factor for proliferative diabetic retinopathy
Authors: Beránek Michal , Kan̆ková Kater̆ina , Benes̆ Petr , Izakovic̆ová‐Hollá Lydie , Znojil Vladimír , Hájek Dobroslav , Vlková Eva , Vácha Jir̆í
Published: August 2002

Associations of the genetic polymorphisms in the promoter region and the signal peptide sequence of the transforming growth factor‐beta (TGF‐β1) gene with proliferative diabetic retinopathy (PDR) in patients with non‐insulin‐dependent diabetes mellitus (NIDDM) were studied. A total of 245 Caucasian subjects comprised the two groups: NIDDM patients with PDR (n = 73) and NIDDM patients without PDR (n = 172). Allele frequencies of common TGF‐β1 polymorphisms (at positions −988C/A, −800G/A, −509C/T, +869T/C (L10P), and +915G/C (R25P)) were determined by PCR‐based methodology. All polymorphisms were in strong linkage disequilibrium (P < 10−2). Significantly higher frequencies of both the L allele and the R allele of the signal sequence polymorphisms in PDR subjects were found (after a correction for multiple comparisons, Pcorr < 10−2 and Pcorr < 10−4, respectively). Calculated odds ratios (ORs) for the LL and RR genotypes were 2.89 (95% confidence interval (CI), 1.6–5.1) and 19.73 (95% CI, 2.6−146.8), respectively. No significant differences between groups were found for the −800G/A and −509C/T polymorphisms. The −988A allele was not represented in our sample. Multiple logistic regression identified age, diabetes duration, and R25P polymorphism as significant predictors (P = 0.002, P = 0.000003, and P = 0.007, respectively). The frequencies of genotype combinations of the −800G/A, −509C/T, L10P, and R25P TGF‐β1 polymorphisms were significantly different between the PDR and non‐PDR groups (χ2 = 37.83, df = 20, P < 10−2). The frequency of haplotype consisting of majority alleles was found significantly associated with PDR (P < 0.03). The presented data indicate that the R25P polymorphisms in the TGF‐β1 gene could be regarded as a strong genetic risk factor for PDR. © 2002 Wiley‐Liss, Inc.
CUX2, a potential regulator of NCAM expression: Genomic characterization and analysis as a positional candidate susceptibility gene for bipolar disorder
Authors: Jacobsen Nick J.O. , Elvidge Gareth , Franks Emily K.E. , O'Donovan Michael C. , Craddock Nick , Owen Michael J.
Published: August 2002

We have previously reported cosegregation of bipolar affective disorder and Darier disease, a dominant skin disorder with a neuropsychiatric component. The gene for Darier disease was mapped to chromosome 12q23–q24.1 and linkage studies have subsequently implicated this region as harboring a susceptibility gene for bipolar affective disorder. We have genomically characterized the human homologue of murine Cux‐2, a neuronal‐specific transcription factor potentially involved in the regulation of neural cell adhesion molecule expression that maps to this region. Also, in a panel of 15 unrelated bipolar patients from multiply affected families showing increased allele sharing at markers in the 12q23–q24.1 region, we performed mutational screening of the CUX2 coding sequence, and 5′ untranslated region (5′ UTR). Resulting sequence were analyzed in a large sample of bipolar patients (n = 218) and control subjects (n = 218). No evidence was found for the involvement of variants within the CUX2 coding, or 5′ UTR sequence in producing susceptibility to bipolar disorder. © 2001 Wiley‐Liss, Inc.
Association of a polymorphism of the dopamine transporter gene with externalizing behavior problems and associated temperament traits: A longitudinal study from infancy to the mid‐teens
Authors: Jorm Anthony F. , Prior Margot , Sanson Ann , Smart Diana , Zhang Yafei , Easteal Simon
Published: August 2002

There have been reports that a variable number of tandem repeats (VNTR) polymorphism situated in the 3′ untranslated region of the dopamine transporter gene is associated with attention‐deficit hyperactivity disorder. On the basis of these findings, we predicted an association of this polymorphism with hyperactivity, other externalizing behavior problems, and related temperament traits in a general population sample. The association was investigated using children participating in a longitudinal study of childhood temperament and development. DNA was taken from 660 children who had been assessed for temperament from 4–8 months to 15–16 years, and for behavior problems from 3–4 to 15–16 years. No significant associations were found at any age. There are a number of methodological differences from earlier studies that might explain the lack of associations with hyperactivity. It is also possible that the earlier findings are not replicable. © 2001 Wiley‐Liss, Inc.
Malignancy of recurrent, early‐onset major depression: A family study
Authors: Zubenko George S. , Zubenko Wendy N. , Spiker Duane G. , Giles Donna E. , Kaplan Barry B.
Published: August 2002

Coordinated efforts to identify susceptibility genes for unipolar major depressive disorder (MDD) and related disorders are now underway. These studies have focused on recurrent, early‐onset MDD (RE‐MDD), the most heritable form of this disorder. The goal of this study was to characterize the burden of MDD and other mood disorders, comorbid mental disorders, and excess mortality in RE‐MDD families. A total of 81 families were identified through probands over the age of 18, who met criteria for recurrent (≥ 2 episodes), early‐onset (≤ 25 years), nonpsychotic, unipolar MDD (RE‐MDD), and included 407 first‐degree relatives and 835 extended relatives. Psychiatric diagnoses for probands and their family members who provided blood samples were formulated from structured personal interviews, structured family history assessments, and available medical records. The remaining family members who participated and those who were deceased were evaluated through the family history method augmented by available medical records. Best estimate diagnoses were made during a consensus conference according to established diagnostic criteria. Approximately half of the first‐degree relatives and a quarter of extended relatives of RE‐MDD probands suffered from at least one mood disorder, typically MDD. As commonly observed for other oligogenic, multifactorial disorders, the severity of MDD reflected by age at onset and number of episodes attenuated with increasing familial/genetic distance from the proband. A substantial fraction of RE‐MDD probands and their first‐degree relatives met diagnostic criteria for additional psychiatric disorders that include prominent disturbances of mood. The deceased relatives of RE‐MDD probands died at a median age that was 8 years earlier than for the local population; over 40% died before reaching age 65. These differences in mortality statistics resulted from a shift toward younger ages at death across the lifespan, including a fivefold increase in the proportion of individuals who died in the first year of life. Several‐fold increases in the proportion of deaths by suicide, homicide, and liver disease were observed among the relatives of RE‐MDD probands. However, the rank order of the three most common causes of death—heart disease, cancer, and stroke—remained unchanged and differences in the proportions of deaths from the remaining causes were small. RE‐MDD is a strongly familial condition with a high rate of psychiatric comorbidity, whose malignant effects have a significant negative impact on the health and longevity of patients and their family members. © 2001 Wiley‐Liss, Inc.
Motor immaturity and specific speech and language impairment: Evidence for a common genetic basis
Authors: Bishop Dorothy V.M.
Published: August 2002

Previous studies have found an association between motor immaturity and specific language impairment in children. Data from two twin studies were used to address the question of whether these linked deficits have a common etiology. Study 1 involved 57 MZ and 22 DZ pairs where one or both twins had specific speech/language impairment. A control group of 173 single‐born children was also tested. Motor skill was assessed using a tapping task, which was carried out with left and right hands. Tapping scores were converted to scaled scores adjusted for age and sex. Unaffected twins and single‐born controls did not differ in motor skill, but twins with speech and/or language impairments obtained significantly poorer tapping scores than controls. Bivariate DeFries‐Fulker analysis pointed to shared genetic influence on tapping speed and a measure of speech production accuracy. In study 2, 37 twin pairs from study 1 were retested 2–3 years later and combined with 100 twin pairs from a general population sample. A timed peg‐moving task was used to assess motor skill. Children with combined speech and language impairments obtained poorer peg‐moving scores than unaffected children. Bivariate DeFries‐Fulker analysis found significant shared genetic variance for impairments on peg‐moving and on a test of nonword repetition. It is concluded that genes that put the child at risk for communicative problems also affect motor development, with the association being most evident when speech production is affected. © 2001 Wiley‐Liss, Inc.
Fecal analysis of ovarian cycles in female black‐handed spider monkeys (Ateles geoffroyi)
Authors: Campbell C.J. , Shideler S.E. , Todd H.E. , Lasley B.L.
Published: August 2002

An enzyme immunoassay (EIA) was applied to characterize the reproductive endocrinology of adult female black‐handed spider monkeys (Ateles geoffroyi). Analysis of paired urine and fecal samples, collected from two females housed at San Diego Zoo, confirmed that the EIAs employed provided quantitative measurements of ovarian sex steroid hormones. Fecal metabolite levels were significantly correlated with those in urine, confirming that feces are a valid source of steroid metabolites in this species. The excretion of these metabolites in feces lagged urinary excretion by 1–2 days. The ovarian cycle profiles of the two captive females and five free‐ranging females are comparable, with an average length of approximately 20–23 days. Cyclical bleeding, as previously reported, was observed in one of the two captive females. Pregnancy was detected in four free‐ranging females, and early fetal loss for one female was indicated by hormonal data. Am. J. Primatol. 54:79–89, 2001. © 2001 Wiley‐Liss, Inc.
Status and distribution of golden langurs (Trachypithecus geei) in Assam, India
Authors: Srivastava A. , Biswas J. , Das J. , Bujarbarua P.
Published: August 2002

The distribution of golden langurs (Trachypithecus geei) is limited to a small area of western Assam in northeast India and Bhutan between the rivers Manas in the east, Sankosh in the west, and Brahmaputra in the south. It is one of the most seriously endangered primate species of India. A comparative analysis based on satellite images taken in 1988 and 1998 showed a 50% loss of original golden langur habitat. Data on population dynamics collected using line transect and total count methods are presented here. An average group size of 8.2 (range 4.0–22.0) individuals was recorded. A total of 1,064 individuals were counted living in 130 groups. The sex ratio was 1.9–2.5 adult females for each adult male. A low percentage of juveniles and infants suggests that the population is unstable. Most of the groups had only one adult male. Small group sizes, isolated distribution, proportionately few infants and juveniles, and degrading habitat are all causes of concern. Demographic trends indicate a decline in the golden langur population. Am. J. Primatol. 55:15–23, 2001. © 2001 Wiley‐Liss, Inc.
Mitochondrial DNA variability of West New Guinea populations
Authors: Tommaseo‐Ponzetta M. , Attimonelli M. , De Robertis M. , Tanzariello F. , Saccone C.
Published: August 2002

This paper reports human mitochondrial DNA variability in West New Guinea (the least known, western side of the island of New Guinea), not yet described from a molecular perspective. The study was carried out on 202 subjects from 12 ethnic groups, belonging to six different Papuan language families, representative of both mountain and coastal plain areas. Mitochondrial DNA hypervariable region 1 (HVS 1) and the presence of the 9‐bp deletion (intergenic region COII‐tRNALys) were investigated. HVS 1 sequencing identified 73 polymorphic sites defining 89 haplotypes; the 9‐bp deletion, which is considered a marker of Austronesian migration in the Pacific, was found to be absent in the whole West New Guinea study sample.

Statistical analysis applied to the resulting haplotypes reveal high heterogeneity and an intersecting distribution of genetic variability in these populations, despite their cultural and geographic diversity. The results of subsequent phylogenetic approaches subdivide mtDNA diversity in West New Guinea into three main clusters (groups I–III), defined by sets of polymorphisms which are also shared by some individuals from Papua New Guinea. Comparisons with worldwide HVS 1 sequences stored in the MitBASE database show the absence of these patterns outside Oceania and a few Indonesian subjects, who also lack the 9‐bp deletion. This finding, which is consistent with the effects of genetic drift and prolonged isolation of West New Guinea populations, lead us to regard these patterns as New Guinea population markers, which may harbor the genetic memory of the earliest human migrations to the island. Am J Phys Anthropol 117:49–67, 2002. © 2002 Wiley‐Liss, Inc.
Genetic and environmental correlations between various anthropometric and blood pressure traits among adult Samoans
Authors: Choh A.C. , Gage T.B. , McGarvey S.T. , Comuzzie A.G.
Published: August 2002

Shared polygenic effects (i.e., pleiotropy) are assumed to exist for such obesity‐related phenotypes as blood pressure and adiposity. It is possible to identify these shared genetic effects through bivariate genetic analyses. This analysis of 1,342 adult Samoans, across 801 pedigrees, indicates that significant heritable components (P < 0.05) ranging from 29–58% exist for weight, height, systolic blood pressure, diastolic blood pressure, triceps skinfold, subscapular skinfold, body mass index, and sum of skinfolds. In general, the anthropometric measurements share additive genetic effects, as do the anthropometric measures, with blood pressure. Heritabilities for central fat distribution are not significant in this population, which could be due to a lack of power. On the other hand, heritabilities have been found in Hispanics; hence the genes responsible for central fat distribution may not be evenly distributed among populations. Am J Phys Anthropol 115:304–311, 2001. © 2001 Wiley‐Liss, Inc.
Evolution of dentition in prehistoric Ohio Valley Native Americans III. Metrics of deciduous dentition
Authors: Sciulli Paul W.
Published: August 2002

Deciduous tooth size in Native Americans of the Ohio Valley area is fairly stable from the terminal Late Archaic (3200 BP) through the Late Prehistoric (350 BP) periods. Some fluctuation in average size did occur during this time. These fluctuations most likely reflect random changes due to gene drift. However, no difference in the pattern of interactions among the sizes of teeth (covariance structures) can be demonstrated during this period. Principal components analysis of the buccolingual and mesiodistal dimensions in the total sample indicate that the major axis of deciduous tooth size in the Ohio Valley population shows an allometric relationship, with the dimensions of the anterior teeth increasing (or decreasing) as the 1.33 power of the dimension of m and as the 2.0 power of the dimension of m. Comparison of the Ohio Valley samples with other samples from the Eastern Woodlands suggests that geography may have played a minor role in structuring deciduous tooth size variation. For the most part, however, widely separated Eastern Woodlands populations appear to have been evolving independently with respect to deciduous tooth size. Am J Phys Anthropol 116:140–153, 2001. © 2001 Wiley‐Liss, Inc.
Molecular and clinical correlation in five Indian families with spinocerebellar ataxia 12
Authors: Srivastava Achal K. , Choudhry Shweta , Gopinath Musuwadi S. , Roy Sanghamitra , Tripathi Manjari , Brahmachari Samir K. , Jain Satish
Published: August 2002

Spinocerebellar ataxia 12 (SCA12) is a recently identified form of autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5′ untranslated region of the gene PPP2R2B. We analyzed 77 Indian families with autosomal dominant cerebellar ataxia phenotype and confirmed the diagnosis of SCA12 in 5 families, which included a total of 6 patients and 21 family members. The sizes of the expanded alleles ranged from 55 to 69 CAG repeats, and the sizes of the normal alleles ranged from 7 to 31 repeats. We believe our study is the first to demonstrate that SCA12 may not be as rare in some populations as previously thought.
Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment
Authors: DeKosky Steven T. , Ikonomovic Milos D. , Styren Scot D. , Beckett Laurel , Wisniewski Stephen , Bennett David A. , Cochran Elizabeth J. , Kordower Jeffrey H. , Mufson Elliott J.
Published: August 2002

In Alzheimer's disease (AD), loss of cortical and hippocampal choline acetyltransferase (ChAT) activity has been correlated with dementia severity and disease duration, and it forms the basis for current therapies. However, the extent to which reductions in ChAT activity are associated with early cognitive decline has not been well established. We quantified ChAT activity in the hippocampus and four cortical regions (superior frontal, inferior parietal, superior temporal, and anterior cingulate) of 58 individuals diagnosed with no cognitive impairment (NCI; n = 26; mean age 81.4 ± 7.3 years), mild cognitive impairment (MCI; n = 18; mean age 84.5 ± 5.7), or mild AD (n =14; mean age 86.3 ± 6.6). Inferior parietal cortex ChAT activity was also assessed in 12 subjects with end‐stage AD (mean age 81.4 ± 4.3 years) and compared to inferior parietal cortex ChAT levels of the other three groups. Only the end‐stage AD group had ChAT levels reduced below normal. In individuals with MCI and mild AD, ChAT activity was unchanged in the inferior parietal, superior temporal, and anterior cingulate cortices compared to NCI. In contrast, ChAT activity in the superior frontal cortex was significantly elevated above normal controls in MCI subjects, whereas the mild AD group was not different from NCI or MCI. Hippocampal ChAT activity was significantly higher in MCI subjects than in either NCI or AD. Our results suggest that cognitive deficits in MCI and early AD are not associated with the loss of ChAT and occur despite regionally specific upregulation. Thus, the earliest cognitive deficits in AD involve brain changes other than simply cholinergic system loss. Of importance, the cholinergic system is capable of compensatory responses during the early stage of dementia. The upregulation in frontal cortex and hippocampal ChAT activity could be an important factor in preventing the transition of MCI subjects to AD.
Insular cortex involvement in mesiotemporal lobe epilepsy: A positron emission tomography study
Authors: Bouilleret Viviane , Dupont Sophie , Spelle Laurent , Baulac Michel , Samson Yves , Semah Frank
Published: August 2002

Somesthetic and emotional symptoms that are common in patients with mesial temporal lobe epilepsy are usually related to hippocampo‐amygdalar complex involvement. Recent stereo‐electroencephalographic studies have shown a relationship between such symptoms and epileptic insular discharges. To further investigate this problem, we carried out a positron emission tomography study using fluorodeoxyglucose (18F‐FDG) and flumazenil (11C‐FMZ) in mesial temporal lobe epilepsy patients. The aim of our study was to assess the existence of a cortical insular involvement in order to examine its clinical correlates and the relationship between the postoperative outcome and the insular involvement. Fluorodeoxyglucose and flumazenil‐positron emission tomography studies were carried out in 18 patients with mesial temporal lobe epilepsy patients. A statistical parametric mapping (SPM96) was performed to analyze the data in comparison to 18 healthy volunteers. For each set of fluorodeoxyglucose and flumazenil images a group and an individual analysis were performed. In addition, a region of interest analysis was performed to validate the results. Focusing on the metabolic abnormalities, we also investigated the role of insular cortex in the symptoms experienced by the patients and the prognostic value of insular metabolic abnormalities. Highly significant hypometabolism and BZR binding decreases were detected in the insular cortex. Results were similar using the region of interest approach. Insular involvement (mainly ipsilateral to the seizure focus) was present in 60% of the patients. Emotional symptoms correlated with hypometabolism in the anterior part of the ipsilateral insular cortex, whereas somesthetic symptoms correlated with hypometabolism in the posterior part. No relationship between postoperative outcome and ipsilateral insular hypometabolism was found. Unilateral mesial temporal lobe epilepsy is associated with insular hypometabolism and benzodiazepine receptor loss. Our results also suggest that the anterior part of the insular cortex is involved in the emotional symptoms and the posterior insular cortex is involved in the somesthetic symptoms. Hypometabolism located in the insula did not influence postoperative outcome after anterior lobectomy.
Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients
Authors: Wintermark Max , Reichhart Marc , Thiran Jean‐Philippe , Maeder Philippe , Chalaron Marc , Schnyder Pierre , Bogousslavsky Julien , Meuli Reto
Published: August 2002

The purpose of this study was to determine the prognostic accuracy of perfusion computed tomography (CT), performed at the time of emergency room admission, in acute stroke patients. Accuracy was determined by comparison of perfusion CT with delayed magnetic resonance (MR) and by monitoring the evolution of each patient's clinical condition. Twenty‐two acute stroke patients underwent perfusion CT covering four contiguous 10mm slices on admission, as well as delayed MR, performed after a median interval of 3 days after emergency room admission. Eight were treated with thrombolytic agents. Infarct size on the admission perfusion CT was compared with that on the delayed diffusion‐weighted (DWI)–MR, chosen as the gold standard. Delayed magnetic resonance angiography and perfusion‐weighted MR were used to detect recanalization. A potential recuperation ratio, defined as PRR = penumbra size/(penumbra size + infarct size) on the admission perfusion CT, was compared with the evolution in each patient's clinical condition, defined by the National Institutes of Health Stroke Scale (NIHSS). In the 8 cases with arterial recanalization, the size of the cerebral infarct on the delayed DWI‐MR was larger than or equal to that of the infarct on the admission perfusion CT, but smaller than or equal to that of the ischemic lesion on the admission perfusion CT; and the observed improvement in the NIHSS correlated with the PRR (correlation coefficient = 0.833). In the 14 cases with persistent arterial occlusion, infarct size on the delayed DWI‐MR correlated with ischemic lesion size on the admission perfusion CT (r = 0.958). In all 22 patients, the admission NIHSS correlated with the size of the ischemic area on the admission perfusion CT (r = 0.627). Based on these findings, we conclude that perfusion CT allows the accurate prediction of the final infarct size and the evaluation of clinical prognosis for acute stroke patients at the time of emergency evaluation. It may also provide information about the extent of the penumbra. Perfusion CT could therefore be a valuable tool in the early management of acute stroke patients.
Sporadic Pick's disease: A tauopathy characterized by a spectrum of pathological τ isoforms in gray and white matter
Authors: Zhukareva Victoria , Mann David , Pickering‐Brown Stuart , Uryu Kunihiro , Shuck Theresa , Shah Keyur , Grossman Murray , Miller Bruce L. , Hulette Christine M. , Feinstein Stuart C. , Trojanowski John Q. , Lee Virginia M.‐Y.
Published: August 2002

Pick's disease is characterized neuropathologically by distinct τ‐immunoreactive intraneuronal inclusions known as Pick bodies and by insoluble τ proteins with predominantly three microtubule‐binding repeat τ isoforms. However, recent immunohistochemical studies showed that the antibody specific for exon 10, which encodes the fourth microtubule‐binding repeat, detected other τ lesions in Pick's disease. To better define the spectrum of τ pathology in Pick's disease, we used biochemical, immunohistochemical, and ultrastructural techniques to analyze the τ isoform composition in 14 Pick's disease brains. Western blot analysis showed that both three and four microtubule‐binding repeat pathological τ isoforms are present in gray and white matter of various brain regions. Using phosphorylation‐dependent anti‐τ antibodies, we show that major τ phosphoepitopes are present in sarcosyl‐insoluble gray and white matter regions of Pick's disease brains. Also, for the first time to our knowledge, we demonstrated that isoforms with four microtubule‐binding repeat τ isoforms are present in Pick bodies from selected brains. Isolated τ filaments were straight or twisted and formed by three microtubule‐binding repeat or four microtubule‐binding repeat τ isoforms. Major τ phosphorylation–dependent and exon 10–specific epitopes were present in filaments. Therefore, Pick's disease is characterized by an accumulations of Pick bodies in the hippocampal region and cortex as well as the presence of three and four microtubule‐binding repeat τ pathology in both cortical gray and white matter that distinguish this tauopathy from other neurodegenerative disorders.