bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for falls among Iowa farmers: A case‐control study nested in the Agricultural Health Study
Authors: Sprince Nancy L. , Zwerling Craig , Lynch Charles F. , Whitten Paul S. , Thu Kendall , Gillette Patricia P. , Burmeister Leon F. , Alavanja Michael C.R.
Published: August 2003

Background

Farmers are at increased risk for fall‐related injury compared with other occupations. Little is known about risk factors for non‐fatal falls on the farm. This case‐control study, nested within the Agricultural Health Study, aimed to assess risk factors for work‐related falls among Iowa farmers.

Methods

A screener questionnaire sent to 6,999 farmers in 1998 identified 79 farmers who reported a fall‐related farm injury that required medical advice or treatment in the previous year. Multivariable logistic regression analysis was used to assess several possible risk factors for injury among these farmers compared with 473 farmers with no injury in the previous year.

Results

There were significant associations between fall‐related farm injury and age between 40 and 64 years (OR = 2.21; 95% CI = 1.20–4.07), doctor‐diagnosed arthritis/rheumatism (OR = 2.05; 95% CI = 1.11–3.79), difficulty hearing normal conversation (even with a hearing aid, in the case of those who used one) (OR = 1.82; 95% CI = 1.07–3.08), and taking medications regularly (OR = 1.80; 95% CI = 1.02–3.18).

Conclusions

Aging and health impairments, such as arthritis and hearing difficulties, are risk factors for which accommodations and preventive strategies can be devised to prevent fall‐related injuries on the farm. Am. J. Ind. Med. 44:265–272, 2003. © 2003 Wiley‐Liss, Inc.
The Drake Health Registry Study: Cause‐specific mortality experience of workers potentially exposed to beta‐naphthylamine
Authors: Cassidy Laura D. , Youk Ada O. , Marsh Gary M.
Published: August 2003

Objective

To examine the cause‐specific mortality experience of an occupational cohort with probable past exposure to beta‐naphythylamine (BNA).

Methods

Subjects were 374 male and 26 female workers employed at a Pennsylvania chemical plant that produced or used beta‐naphthylamine (BNA) between 1940 and 1981. Vital status through 1998 was determined for 97.5% of the cohort and cause of death for 100% of 79 deaths. Limited industrial hygiene data and reports from former employees were used to categorize workers as high, medium, or low risk for BNA exposure. Statistical analyses included US and local county‐based standardized mortality ratios (SMRs).

Results

We observed statistically significantly elevated county rate‐based SMRs for all causes combined (SMR = 1.98, 95% confidence interval (CI) = 1.56–2.49), all malignant neoplasms combined (28 deaths, SMR = 3.08, 95% CI = 2.05–4.46), respiratory system cancer (12 deaths, SMR = 3.91, 95% CI = 2.02–6.83), and bladder cancer (four deaths, SMR = 16.83, 95% CI = 4.59–43.1). Three bladder cancer cases were classified as high risk (SMR = 26.79, 95% CI = 5.53–78.29). Mortality risks were also elevated for most other malignant and non‐malignant cause of death categories examined.

Conclusions

Bladder cancer risk remains highly elevated among Drake/Kilsdonk workers and appears to be causally related to past BNA exposure. While lifestyle and behavioral risk factors may explain some of the mortality excesses for non‐urological cancers, the possibility remains that BNA exposure may have also played a role in these and other observed cancer excesses. Am. J. Ind. Med. 44:282–290, 2003. © 2003 Wiley‐Liss, Inc.
Serum pneumoproteins: A cross‐sectional comparison of firefighters and police
Authors: Burgess Jefferey L. , Witten Mark L. , Nanson Christopher J. , Hysong Tracy A. , Sherrill Duane L. , Quan Stuart F. , Gerkin Richard , Bernard Alfred M.
Published: August 2003

Background

Serum pneumoproteins provide a measure of the permeability of the lower respiratory tract, and have shown promise as a biomarker of acute and chronic exposure to respiratory toxicants.

Methods

To evaluate the effects of chronic occupational smoke exposure, 105 firefighters were compared with 44 police controls in a cross‐sectional study using spirometry, diffusing capacity of the lung, serum Clara cell protein (CC16), and serum surfactant‐associated protein A (SP‐A) measurements.

Results

There were no significant differences in age, gender, height, spirometry (FVC and FEV1), and diffusing capacity between the two groups. Serum SP‐A was lower in firefighters (260.1 ± 121.2 μg/L) than police (316.0 ± 151.4 μg/L, P = 0.019). Serum CC16 was also lower in firefighters (8.39 ± 3.11 μg/L) than police (10.56 ± 4.20 μg/L, P < 0.001), although this difference lost statistical significance when adjusted for confounders.

Conclusions

Firefighters have lower serum concentrations of SP‐A than do police. Although the clinical significance of this finding is presently unknown, SP‐A deserves further study as a biomarker of toxic exposure to the lower respiratory tract. Am. J. Ind. Med. 44:246–253, 2003. © 2003 Wiley‐Liss, Inc.
Neurological symptoms among Sri Lankan farmers occupationally exposed to acetylcholinesterase‐inhibiting insecticides
Authors: Smit Lidwien A.M. , van‐Wendel‐de‐Joode Berna N. , Heederik Dick , Peiris‐John Roshini J. , van der Hoek Wim
Published: August 2003

Background

In many agricultural districts in Sri Lanka, pesticide poisoning is a leading cause of death. This study aims to evaluate the impact of pesticide use on Sri Lankan farmers' health.

Methods

A total of 260 subjects were surveyed in both a low and a high exposure period. Acetylcholinesterase activity was measured and data on symptoms were collected with questionnaires.

Results

Twenty‐four percent of surveyed farmers had suffered at least once from acute pesticide poisoning. Farmers showed significantly more inhibition of cholinesterase activity than controls. Acute symptoms indicative for exposure to cholinesterase‐inhibiting pesticides were associated with farming and a higher degree of cholinesterase suppression (more than 13% inhibition). Integrated Pest Management (IPM) training seemed to result in less insecticide use, and less cholinesterase inhibition.

Conclusions

Our results suggest that occupational acetylcholinesterase‐inhibiting insecticide exposures have a negative impact on Sri Lankan farmers' health. Overall reduction in pesticide use seems the best option to protect farmers from the adverse effects of pesticides. Am. J. Ind. Med. 44:254–264, 2003. © 2003 Wiley‐Liss, Inc.
Agricultural injury in California migrant Hispanic farm workers
Authors: McCurdy Stephen A. , Samuels Steven J. , Carroll Daniel J. , Beaumont James J. , Morrin Lynne A.
Published: August 2003

Background

Agriculture is among the most hazardous industries in the United States.

Methods

A longitudinal study of injury among migrant Hispanic farm workers residing in six Northern California Migrant Family Housing Centers (MHCs) during the 1997 harvest season was conducted. Participants completed an initial interviewer‐administered work‐and‐health questionnaire at the beginning of the harvest season addressing the preceding year; there were three periodic follow‐up surveys.

Results

There were 1,201 adult farm workers (participation 85.2%) who completed the initial questionnaire. Of these, 837 (69.7%) completed the final follow‐up survey. There were 86 agricultural injuries (incidence 9.3/100 full‐time equivalent employees (FTEs), 95% CI 7.5–11.5/100 FTE). Increased risk for agricultural injury occurred among women paid piece‐rate (RR 4.9, 95% CI 1.8–12.8). Sprains and strains were most common (31%), followed by lacerations (12%).

Conclusions

Agricultural injury experience in this cohort is comparable to that of agricultural workers in other U.S. settings. Increased risk among women paid piece‐rate suggests further study and potential policy changes regarding payment regimens. Heterogeneity of injury in this population presents a major prevention challenge. In view of high frequency of strain and sprain injuries, ergonomic interventions deserve further study. Am. J. Ind. Med. 44:225–235, 2003. © 2003 Wiley‐Liss, Inc.
Asthma following household exposure to hydrofluoric acid
Authors: Franzblau Alfred , Sahakian Nancy
Published: August 2003

Background

Almost all reports of respiratory health effects of hydrofluoric acid are derived from industrial settings and usually involved massive and conspicuous exposures. In the present report we describe a case of adult‐onset asthma immediately following use of a household rust stain remover that contained an 8–9% aqueous solution of hydrofluoric acid (HF).

Methods

This is a case‐report. A literature search of hydrogen fluoride, and reactive airways dysfunction syndrome (RADS) was performed.

Results

A previously healthy 26‐year‐old woman developed asthma immediately following inhalation exposure to hydrofluoric acid from a household cleaner, consistent with reactive airways dysfunction syndrome. The circumstances of exposure and possible mechanism of disease are discussed.

Conclusions

It is likely that this patient's use of the rust stain remover resulted in inhalation exposure to hydrofluoric acid well above any applicable standard, and hence constituted a ‘high level’ irritant exposure capable of inducing reactive airways dysfunction syndrome. In our opinion, the presence of this concentration hydrofluoric acid in a consumer product may be unduly hazardous. Am. J. Ind. Med. 44:321–324, 2003. © 2003 Wiley‐Liss, Inc
Sequence‐Based, in situ detection of chromosomal abnormalities at high resolution
Authors: Knoll Joan H.M. , Rogan Peter K.
Published: August 2003

We developed single copy probes from the draft genome sequence for fluorescence in situ hybridization (scFISH) which precisely delineate chromosome abnormalities at a resolution equivalent to genomic Southern analysis. This study illustrates how scFISH probes detect cryptic and subtle abnormalities and localize the sites of chromosome rearrangements. scFISH probes are substantially shorter than conventional recombinant DNA‐derived probes, and Cot1 DNA is not required to suppress repetitive sequence hybridization. In this study, 74 single copy sequence probes (>1,500 bp) have been developed from ≥100 kb genomic intervals associated with either constitutional or acquired disorders. Applications of these probes include detection of congenital microdeletion syndromes on chromosomes 1, 4, 7, 15, 17, 22 and submicroscopic deletions involving the imprinting center on chromosome 15q11.2q13. We demonstrate how hybridization with multiple combinations of probes derived from the Smith‐Magenis syndrome interval on chromosome 17 identified a patient with an atypical, proximal deletion breakpoint. A similar multi‐probe hybridization strategy has also been used to delineate the translocation breakpoint region on chromosome 9 in chronic myelogenous leukemia. Probes have also been designed to hybridize to multiple cis paralogs, both enhancing the chromosomal target size and detecting chromosome rearrangements, for example, by splitting and separating a family of related sequences flanking an inversion breakpoint on chromosome 16 in acute myelogenous leukemia. These novel strategies for rapid and precise characterization of cytogenetic abnormalities are feasible because of the sequence‐defined properties and dense euchromatic organization of single copy probes. © 2003 Wiley‐Liss, Inc.
Double heterozygosity in bone growth disorders: Four new observations and review
Authors: Flynn Maureen A. , Pauli Richard M.
Published: August 2003

Because matings between individuals of small stature is common, information regarding double heterozygosity for dominantly inherited bone growth disorders is of considerable importance. We summarize seven occurrences of four combinations of double heterozygosity (achondroplasia/spondyloepiphyseal dysplasia congenita, achondroplasia/pseudoachondroplasia, achondroplasia/osteogenesis imperfecta type I, achondroplasia/hypochondroplasia (non‐FGFR3)), and review additional reports from the literature. Each of the eight different examples of double heterozygosity for bone growth disorders now reported results in distinct phenotypic features, differing severity, and disparate expectations. We document the natural history of each. The genetic processes underlying these disorders also are examined to assess whether knowledge of molecular mechanisms can be used to predict clinical severity. © 2003 Wiley‐Liss, Inc.
Identification of four novel mutations in the alpha glucosidase gene in five Italian patients with infantile onset glycogen storage disease type II
Authors: Pittis Maria Gabriela , Montalvo Anna Lisa E. , Miocic Snjezana , Martini Cristina , Deganuto Marta , Candusso Manila , Ciana Giovanni , Bembi Bruno
Published: August 2003

Glycogen storage disease type II (GSDII) is an autosomal recessive disorder due to the deficiency of the lysosomal enzyme acid alpha glucosidase. Four novel mutations (C670T, G989A, G2188T, and Δ 23 nt 828‐850) were identified in five Italian patients with the infantile form of the disease. The C670T mutation was present in two unrelated patients in heterozygosity; the effect on enzyme activity was assessed by in vitro expression. COS‐1 cells expressing the C670T allele had a twofold higher activity than the negative control cells. The G989A and G2188T point mutations lead to the introduction of premature stop signals that results in truncated forms of alpha glucosidase. The in vitro expression of G2188T allele demonstrated no increment in activity compared to negative control. The frame shifting deletion of nucleotides 828–850 was identified in one patient in heterozygosity. The shift in the reading frame introduces a stop codon 135 nucleotides downstream the deletion junction that results in a truncated protein without catalytic activity. Nested PCR screening showed that the mutation was carried by the mother and was absent in the other members of the family. The four novel severe mutations herein described concerned only infantile onset GSDII patients; the loss of enzyme activity is correlated with the severity of the disease. © 2003 Wiley‐Liss, Inc.
Hyperechogenic fetal bowel: A large French collaborative study of 682 cases
Authors: Simon‐Bouy B. , Satre V. , Ferec C. , Malinge M.C. , Girodon E. , Denamur E. , Leporrier N. , Lewin P. , Forestier F. , Muller F. ,   and the French Collaborative Group
Published: August 2003

Hyperechogenic fetal bowel is detected in 0.1–1.8% of pregnancies during the second or third trimester. This ultrasound sign is associated with cystic fibrosis or other conditions (e.g., chromosomal anomalies, viral infection) but no large‐scale prospective studies have been conducted. This 1997–1998 multicenter study in 22 molecular biology laboratories identified 682 cases of hyperechogenic fetal bowel detected by routine ultrasound examination during the second (86%) or third trimester. The fetal bowel was considered hyperechogenic when its echogenicity was broadly similar to, or greater than, that of the surrounding bone. Karyotyping, screening for viral infection, and screening for cystic fibrosis mutations were performed in all cases. Pregnancy outcome and postnatal follow‐up were obtained in 656 of the 682 cases (91%). In 447 cases (65.5%), a normal birth was observed. Multiple malformations were observed in 47 cases (6.9%), a significant chromosomal anomaly was noted in 24 (3.5%), cystic fibrosis in 20 (3%), and viral infection in 19 (2.8%). In utero unexplained fetal death occurred in 1.9% of cases, toxemia in 1.2%, IUGR in 4.1%, and premature birth in 6.2%. This study demonstrates that this ultrasound sign is potentially associated with medically significant outcomes. Having established that the bowel is hyperechogenic, recommended investigations should include a detailed scan with Doppler measurements, fetal karyotyping, cystic fibrosis screening, and infectious disease screening. After birth, newborns require pediatric examination because a surgical treatment may be necessary. This should be combined with clear counseling of the parents. © 2003 Wiley‐Liss, Inc.
Partial hexasomy of chromosome 15
Authors: Huang Bing , Bartley James
Published: August 2003

Marker chromosomes originating from chromosome 15, often referred to as inv dup(15), is the most common marker chromosome found in humans. The large marker 15 that contains the Prader‐Willi syndrome (PWS)/Angelman syndrome (AS) chromosome region is usually associated with an abnormal phenotype of moderate to severe mental retardation, seizures, poor motor coordination, behavioral problems, and mild dysmorphic features. We report here an infant boy with two copies of the large inv dup(15). A 10‐day‐old infant was found to have infantile spasms, microcephaly, hypotonia, and lethargy. Lymphocyte chromosome analysis revealed a 48,XY, +2mar karyotype. Fluorescence in situ hybridization with probes rRNA, D15Z4, D15S11, and GABRB3 demonstrated that both markers were chromosome 15 in origin and contained the Prader‐Willi/Angelman syndrome chromosome region. Therefore, this patient is hexasomic for the PWS/AS region. The phenotype of this patient does not appear to be significantly more severe than patients with one copy of the large inv dup(15) at birth, however, follow‐up evaluation of the patient at 21 months of age shows that this patient has frequent and severe seizure activity, severe bilateral hearing loss, and cortical blindness. © 2003 Wiley‐Liss, Inc.
Association between mutations in the CARD15 (NOD2) gene and Crohn's disease in Israeli Jewish patients
Authors: Fidder Herma H. , Olschwang Sylviane , Avidan Benjamin , Zouali Habib , Lang Alon , Bardan Eytan , Picard Orit , Bar‐Meir Simon , Colombel Jean Frederic , Chowers Yehuda
Published: August 2003

Ulcerative colitis (UC) and Crohn's disease (CD) are heterogeneous disorders characterized by chronic intestinal inflammation. Genetic predisposition is a major risk factor in both diseases. The CARD15 (NOD2) gene has been implied as a candidate gene in the pathogenesis CD. Our aim was to delineate the frequency of three missense and one frameshift variant of CARD15 in Israeli Jewish CD and UC patients. DNA was extracted from blood samples from 238 unrelated inflammatory bowel disease (IBD) patients, 68 with UC and 170 with CD. The DNA was genotyped for two missense mutations, R675W and G881R, and one frameshift mutation, 980FS981X. Mutations in CARD15 were observed with significantly greater frequency in CD patients (46/170, 27%) than in UC patients (7/68, 10%) (P = 0.005). Homozygous and compound heterozygous carriers were restricted to seven (4%) patients with CD as compared to none of the UC patients (P = 0.01). Similar rates in Ashkenazi and non‐Ashkenazi Jewish patients were observed. Age‐of‐onset of disease was lower in Ashkenazi mutation carriers as compared to non‐carriers of Ashkenazi origin (18.7 ± 8.6 years vs. 25.8 ± 13.4 years, respectively, P = 0.03). No other phenotypic characteristics could distinguish mutation carriers from non‐carriers. We conclude that germline mutations in the CARD15 gene are more frequently found in CD than UC patients and appear to predict an earlier age‐of‐onset in Ashkenazi Jewish patients. No association could be demonstrated between CARD15 mutations and specific disease course or behavior. © 2003 Wiley‐Liss, Inc.
Vasomotor instability in neonates with chromosome 22q11 deletion syndrome
Authors: Shashi Vandana , Berry Margaret N. , Hines Michael H.
Published: August 2003

Approximately 70% of individuals with chromosome 22q11 deletion syndrome (22q11DS) have congenital heart defects. A host of other vascular problems in these patients, such as tortuous carotid arteries, Raynaud's phenomenon, unexplained hypotension, hypertension, and hypothermia, raise the possibility that there may be abnormal autonomic regulation of the vascular system. So far, however, there has been no formal report of autonomic dysfunction in patients with 22q11 deletion. We present two infants with 22q11DS, who had profound hypotension after uncomplicated surgeries for congenital heart disease. The hypotension was not responsive to vasopressor treatment (and extracorporeal membrane oxygenation in one infant) and resulted in death, due to multiorgan system failure. Obvious causes, such as poor cardiac contractility, prolonged circulatory arrest, neurological abnormality, sepsis and blood loss were excluded. On autopsy, no abnormalities were found that could explain the hypotension. We hypothesize that these infants died of severe hypotension due to abnormal vascular tone and that this is a variable feature in individuals with 22q11 deletion. The autonomic nervous system, which is responsible for the regulation of vasomotor tone, may be variably affected in 22q11DS. This could have implications for the surgical management of patients with 22q11DS. Further studies on this topic would establish or refute the association between 22q11DS and dysautonomia.© 2003 Wiley‐Liss, Inc.
Blepharocheilodontic (BCD) syndrome: Expanding the phenotype?
Authors: Lopes Vera Lúcia Gil da Silva , Guion‐Almeida Maria Leine , Rodini Elaine Sbroggio de Oliveira
Published: August 2003

We describe affected individuals in three generations of a family and another sporadic case, all Brazilian patients, with a combination of signs that diagnose the BCD syndrome. In addition to the cardinal signs, the sporadic case has hypothyroidism and imperforate anus, which was observed previously in one patient. The broadened phenotype and the possibility of involvement of p63 and IRF6 genes in this condition are discussed. © 2003 Wiley‐Liss, Inc.
Novel deletion in the pre‐mRNA splicing gene PRPF31 causes autosomal dominant retinitis pigmentosa in a large Chinese family
Authors: Wang Lejin , Ribaudo Michael , Zhao Kanxing , Yu Ning , Chen Qiuyun , Sun Qiuxiang , Wang Liming , Wang Qing
Published: August 2003

We report the identification of a novel 12 bp deletion of the pre‐mRNA splicing gene PRPF31 in a large Chinese family with autosomal dominant retinitis pigmentosa (adRP). This mutation results in the deletion of four amino acids (ΔH111K112F113I114) including H111, an amino acid residue that is highly conserved throughout evolution. The 12 bp deletion co‐segregates with the disease phenotype in 19 RP patients in the family, but is not present in unaffected relatives or 100 normal individuals. Our data indicate that the novel 12 bp deletion in PRPF31 causes retinitis pigementosa in this Chinese adRP family. In contrast to the incomplete penetrance observed in most adRP families linked to chromosome band 19q13.4 (RP11), the 12 bp PRPF31 deletion identified in this study appears to show high penetrance. These data expand the spectrum of PRPF31 mutations causing adRP, and confirm the role of PRPF31 in the pathogenesis of RP. © 2003 Wiley‐Liss, Inc.
Methionine synthase (MTR) 2756 (A → G) polymorphism, double heterozygosity methionine synthase 2756 AG/methionine synthase reductase (MTRR) 66 AG, and elevated homocysteinemia are three risk factors for having a child with Down syndrome
Authors: Bosco Paolo , Guéant‐Rodriguez Rosa‐Maria , Anello Guido , Barone Concetta , Namour Farès , Caraci Filippo , Romano Antonino , Romano Corrado , Guéant Jean‐Louis
Published: August 2003

Contradictory findings have been recently published on the evaluation of genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR 677 C→T) and methionine synthase reductase (MTRR 66 A→G) as risk factors for having a child with Down syndrome (DS); however, the influence of polymorphisms of methionine synthase (MTR 2756 A→G) and of MTHFR 1298 A→C has never been evaluated. In this study, the risk of being a DS case or having a DS child (case mother) was studied by multiple logistic regression analysis of the independent and combined genotypes and of plasma homocysteine, folates, and vitamin B12 in 92 DS cases and 140 control subjects as well as in 63 case mothers and 72 age‐matched control mothers from Sicily. (The MTHFR 677 T allele frequency was not different in DS cases and case mothers, compared to the respective control groups). After adjustment for age, total homocysteine (t‐Hcys) and MTR 2756 AG/GG genotype were significant risk factors for having a DS child, with odds ratio (OR) of 6.7 (95% CI: 1.4–32.0, P = 0.016) and of 3.5 (95% CI: 1.2–10.9, P = 0.028), respectively. By comparison, MTR 2756 AG/GG genotype increased significantly the risk of being a DS case, with an OR of 3.8 (95% CI: 1.4–10.5, P = 0.009). The double heterozygosity MTR 2756 AG/MTRR 66 AG was the single combined genotype that was a significant risk factor for having a DS child, with an OR estimated at 5.0 (95% CI: 1.1–24.1), after adjustment for t‐Hcys. In conclusion, our results provide evidences that homocysteine and MTR genetic polymorphism are two potent risk factors for mothers to have a DS child in Sicily. © 2003 Wiley‐Liss, Inc.
Familial optic atrophy with white matter changes
Authors: Vinkler Chana , Lev Dorit , Kalish Hadas , Watemberg Nathan , Yanoov‐Sharav Miri , Leshinsky‐Silver Esther , Lerman‐Sagie Tally
Published: August 2003

We report two brothers who suffer from infantile onset optic atrophy and blindness. MRI of the brain demonstrated periventricular white matter changes in both children. Neurological and develelopmental examination are normal. Extensive laboratory investigations rule out metabolic disorders that can be associated with optic atrophy. No mutations associated with Leber hereditary optic neuropathy (LHON) were found and sequencing of the mitochondrially encoded complex 1 subunits was normal. We suggest that this family represents either an atypical variant of LHON with a yet undescribed mtDNA mutation or a new syndrome. © 2003 Wiley‐Liss, Inc.
Congenital generalized lipodystrophy, mental retardation, deafness, short stature, and slender bones: A newly recognized syndrome?
Authors: Rajab A. , Khaburi M. , Spranger S. , Kunze J. , Spranger J.
Published: August 2003

We present three patients with congenital generalized lipodystrophy, sensorineural deafness, low birth weight, short stature, delayed cognitive development, and progressive bone changes characterized by overtubulation and rarefaction of long bones with dense metaphyseal striations occurring in adolescence. Abnormalities of lipid and carbohydrate metabolism, hepatosplenomegaly, acanthosis nigricans, and hirsutism were not found. Comparison of the condition of these patients with known syndromic lipodystrophies suggests that they represent a previously unrecognized genetic disorder. The occurrence in sibs born to consanguineous parents and a third patient from the same tribal unit suggest autosomal recessive inheritance. © 2003 Wiley‐Liss, Inc.
Utilization of genetic counseling by parents of a child or fetus with congenital malformation in North‐East Italy
Authors: Isabella Mammi , Teresa Basile Rosaria , Silvano Bellato , Serena Belli , Francesco Benedicenti , Stefania Boni , Claudio Castellan , Maurizio Clementi , Elena Di Gianantonio , Marilena Petrella , Licia Turolla , Romano Tenconi
Published: August 2003

Congenital malformations (CM) affect 2–3% of all births, the cause of which, when known, is genetic in 80–90% of cases. A genetic consultation (GC) is indicated for the parents of a child affected by a CM. This study analyzes the parental utilization of genetic counseling (GCU) and its possible influencing factors after termination of pregnancy (TOP) because of fetal anomalies or after the birth of a child affected by a major malformation. The study concerns cases in North‐East Italy where there is a CM registry and a center‐satellite system for genetic counseling. The results of this analysis are also compared to other similar studies, which address the same topic. Between 1981 and 2000, 1,235 out of 14,888 GC were performed because of the presence of a CM in a child/fetus. In the same period, 4,933 births and 1,112 TOPs were registered. The overall GCU was 19%, with significant differences according to malformative phenotype, severity of the malformative condition, type of birth, and viability. Genetic counseling was performed significantly sooner following TOP than after the birth of a malformed child. GCU showed an unequal distribution according to the parents' place of residence, suggesting that easy and equal access to the genetic service was probably not well provided for. Our results suggest that genetic services should be integrated with related services, and that the public and physicians need a greater awareness of these services. © 2003 Wiley‐Liss, Inc.
Donnai‐Barrow syndrome: Four additional patients
Authors: Chassaing Nicolas , Lacombe Didier , Carles Dominique , Calvas Patrick , Saura Robert , Bieth Eric
Published: August 2003

In 1993, Donnai and Barrow reported a new syndrome in two sets of sibs and in an unrelated child, including diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness. Since then, only four similar patients have been documented. We describe four additional patients, including two sibling pairs from healthy parents. This report firmly establishes this syndrome as a distinct clinical entity and provides further evidence for its previously postulated autosomal recessive inheritance. © 2003 Wiley‐Liss, Inc.
Macrocephaly, distinct craniofacial appearance, and spastic paraplegia: A new case and expansion of the phenotype
Authors: Williams Marc S. , Josephson Kevin D.
Published: August 2003

An adult female patient is presented with macrocephaly, mental retardation, seizures, spastic paraplegia and distinctive craniofacial appearance. We believe she represents the fourth case of the Fryns macrocephaly, distinct craniofacial appearance and spastic paraplegia syndrome. Cardinal features are discussed and additional phenotypic manifestations are discussed. © 2003 Wiley‐Liss, Inc.
Wirt‐Gast‐Antennenmaterialien
Authors: Calzaferri Gion , Huber Stefan , Maas Huub , Minkowski Claudia
Published: August 2003

Wir stellen Wirt‐Gast‐Materialien vor, aufgebaut aus zylindrischen Zeolith‐L‐Kristallen, deren Kanäle mit Farbstoffmolekülen gefüllt sind. Die Synthese dieser Stoffe beruht auf der Eigenschaft der Moleküle, in einzelne Kanäle zu diffundieren. Der umgekehrte Prozess, das Herausdiffundieren der Farbstoffe, kann mithilfe eines molekularen “Korkens” unterdrückt werden. Durch Funktionalisierung dieser zapfenförmigen Moleküle lassen sich Eigenschaften wie Benetzbarkeit, Brechungsindex und chemische Reaktivität einstellen. Die supramolekulare Organisation der Farbstoffe innerhalb der Kanäle entspricht einer ersten Organisationsstufe. Damit gelingt es, Licht im Volumen eines Nanokristalls zu sammeln und Anregungsenergie strahlungslos an die Enden des Zylinders oder umgekehrt von dort zur Mitte zu transportieren. Eine zweite Organisationsstufe ist die Kupplung an einen externen Acceptor‐ oder Donor‐Zapfenfluorophor an den Kanalenden, der elektronische Anregungsenergie abfängt oder einspeist. Die dritte, zum Teil noch hypothetische Stufe umfasst die Kupplung an eine externe Funktionseinheit über Zapfenmoleküle. Die Abstimmbarkeit dieser hochorganisierten Materialien bietet attraktive Möglichkeiten zur Untersuchung von elektronischen Energieübertragungsphänomenen und zur Entwicklung von neuen photonischen Funktionseinheiten.
Carbonylmetallkomplexe – eine neue Klasse von Pharmazeutika?
Authors: Johnson Tony R. , Mann Brian E. , Clark James E. , Foresti Roberta , Green Colin J. , Motterlini Roberto
Published: August 2003

Mittlerweile steht fest, dass NO trotz seiner hohen Toxizität in Säugetieren als Botenstoff fungiert. Da NO+ und CO isoelektronisch sind, sollte es nicht überraschen, dass CO eine gleichartige Funktion zukommt. Der Mensch produziert selbst etwa 3–6 cm3 CO pro Tag, wobei bestimmte Entzündungszustände sowie pathologische Bedingungen, die mit der Hämolyse der roten Blutkörperchen verbunden sind, die produzierte Menge merklich erhöhen. In den letzten zehn Jahren ist das Interesse an den biologischen Wirkungen von CO stark gestiegen und inzwischen gilt es in der medizinischen Literatur als gesichert, dass CO in Säugetieren eine wesentliche Rolle als Signalmolekül spielt. Dabei ist der Hauptwirkungsbereich das Herz‐Kreislauf‐System, z. B. bei der Unterdrückung von Abstoßungsreaktionen bei Organtransplantationen und beim Schutz des Gewebes vor ischämischer Schädigung und Apoptose. Vor kurzem wurde gezeigt, dass Carbonylmetallkomplexe im Organismus CO freisetzen und ähnliche biologische Wirkungen wie CO selbst zeigen können. Dies eröffnet die Möglichkeit, pharmazeutisch wichtige Carbonylmetallkomplexe zu entwickeln.
Titelbild: Templating of Silsesquioxane Cross‐Linking Using Unimolecular Self‐Organizing Polymers (Angew. Chem. 32/2003)
Authors: Connor Eric F. , Sundberg Linda K. , Kim Ho‐Cheol , Cornelissen Jeroen J. , Magbitang Teddie , Rice Phil M. , Lee Victor Y. , Hawker Craig J. , Volksen Willi , Hedrick James L. , Miller Robert D.
Published: August 2003

Nanowissenschaft wird Nanotechnologie: Nanoporöse Filme eines wärmehärtenden organischen Silsesquioxans zur Isolierung von Schaltungen auf Chips entstehen mit amphiphilen sternförmigen Polymertemplaten, die anschließend thermisch entfernt werden können. Durch lebende Polymerisation bei der Synthese des Templats werden Porengröße und ‐form beeinflusst. R. D. Miller, J. L. Hedrick et al. beschreiben diese Methode in ihrer Zuschrift auf S. 3915 ff.
Host–Guest Antenna Materials
Authors: Calzaferri Gion , Huber Stefan , Maas Huub , Minkowski Claudia
Published: August 2003

The focus of this review is on host–guest composites with photonic antenna properties. The material generally consists of cylindrical zeolite L crystals the channels of which are filled with dye molecules. The synthesis is based on the fact that molecules can diffuse into individual channels. This means that, under the appropriate conditions, they can also leave the zeolite by the same way. In some cases, however, it is desirable to block their way out by adding a closure molecule. Functionalization of the closure molecules allows tuning of, for example, wettability, refractive index, and chemical reactivity. The supramolecular organization of the dyes inside the channels is a first stage of organization. It allows light harvesting within a certain volume of a dye‐loaded nanocrystalline zeolite and radiationless transport to both ends of the cylinder or from the ends to the center. The second stage of organization is the coupling to an external acceptor or donor stopcock fluorophore at the ends of the channels, which can trap or inject electronic excitation energy. The third stage of organization is the coupling to an external device through a stopcock molecule. The wide‐ranging tunability of these highly organized materials offers fascinating new possibilities for exploring excitation‐energy‐transfer phenomena, and challenges for developing new photonic devices.
Metal Carbonyls: A New Class of Pharmaceuticals?
Authors: Johnson Tony R. , Mann Brian E. , Clark James E. , Foresti Roberta , Green Colin J. , Motterlini Roberto
Published: August 2003

It is now established that NO is a messenger molecule in mammals despite its high toxicity. As NO+ and CO are isoelectronic, it should not be unexpected that CO could also have a role as a messenger. CO is produced naturally in humans at a rate of between 3 and 6 cm3 per day, and this rate is increased markedly by certain inflammatory states and pathological conditions associated with red blood cell hemolysis. Over the last 10 years, the interest in the biological effects of CO has greatly increased, and it is now established in the medical literature that CO does have a major role as a signaling molecule in mammals. It is particularly active within the cardiovascular system, for example, in suppressing organ graft rejection and protecting tissues from ischemic injury and apoptosis. Recently it has been shown that metal carbonyls can also function as CO‐releasing molecules and provide similar biological activities. This opens the possibility to develop pharmaceutically important metal carbonyls.
Cover Picture: Templating of Silsesquioxane Cross‐Linking Using Unimolecular Self‐Organizing Polymers (Angew. Chem. Int. Ed. 32/2003)
Authors: Connor Eric F. , Sundberg Linda K. , Kim Ho‐Cheol , Cornelissen Jeroen J. , Magbitang Teddie , Rice Phil M. , Lee Victor Y. , Hawker Craig J. , Volksen Willi , Hedrick James L. , Miller Robert D.
Published: August 2003

From Nanoscience to Nanotechnology: Sacrificial micellar star‐shaped polymers template their image in a thermosetting resin to generate a nanoporous film for the insulation of on‐chip metal wiring. The uniform pore size and shape of the pores is solely determined by the molecular weight of the polymer, which is, in turn, controlled by using living polymerization techniques. More about this methodology is given in the Communication by R. D. Miller, J. L. Hedrick, and co‐workers on page 3785 ff.
Wax moth, Galleria mellonella fat body receptor for high‐density lipophorin (HDLp)
Authors: Lee Chang Seok , Han Jik Hyon , Lee Sang Mong , Hwang Jae Sam , Kang Seok Woo , Lee Bong Hee , Kim Hak R.
Published: August 2003

To identify and characterize the HDLp (high‐density lipophorin) receptor from Galleria mellonella (LpRGm), we used techniques of ligand blotting. This method was, to our knowledge, first used to characterize the lipophorin receptor (LpR) in insects. LpRGm had an approximate molecular weight of 97 kDa under non‐reducing conditions and bound the HDLp specifically. The time‐course of lipophorin binding to their receptor protein was rapid. The binding of lipophorins to their receptors was saturable with a Kd of 34.33 ± 4.67 μg/ml. Although Ca2+ was essentially required in the binding of HDLp to their receptors, interestingly increasing concentration of Ca2+ has shown to have a slight inhibitory effect. EDTA was used here as Ca2+ chelating reagent, because Mg2+ in the binding buffer did not affect the binding of HDLp to their receptors, and inhibited the binding of HDLp and LpRGm absolutely. Suramin (polysulfated polycyclic hydrocarbon), known to inhibit the binding of lipoproteins to their receptors, effectively abolished the binding of HDLp to their receptors. LpRGm showed the stage specific binding activity especially in day 1–3 last instar larval, prepupal, and day 1–3 adult stages. Arch. Insect Biochem. Physiol. 54:14–24, 2003. © 2003 Wiley‐Liss, Inc.
Evidence for a LPS‐binding protein in medfly hemocyte surface: Mediation in LPS internalization but not in LPS signaling
Authors: Metheniti Aristea , Giannakas Nikos , Katsoulas Haralabos L. , Soldatos Anastasios N. , Tsakas Sotiris , Lambropoulou Maria
Published: August 2003

A doublet of medfly hemocyte proteins with a molecular mass of about 55 and 50 kDa were precipitated with LPS. Antibodies raised against human CD14 recognize the same doublet of proteins. These results support that mammalian CD14 and the doublet of protein bands in medfly hemocytes share common epitopes. This doublet of protein bands is released from hemocytes upon LPS triggering. A portion of the released protein is clustered on the surface of a distinct hemocyte type and the other remains soluble. The membrane‐bound LPS‐binding protein is involved in LPS internalization and Escherichia coli phagocytosis but not in LPS signaling. Arch. Insect Biochem. Physiol. 54:25–36, 2003. © 2003 Wiley‐Liss, Inc.
Carminic acid dye from the homopteran Dactylopius coccus hemolymph is consumed during treatment with different microbial elicitors
Authors: de la Cruz Hernández‐Hernández Fidel , de Muñoz Fernando García‐Gil , Rojas‐Martínez Alberto , Hernández‐Martínez Salvador , Lanz‐Mendoza Humberto
Published: August 2003

The activation of Dactylopius coccus (Costa) hemolymph with microbial polysaccharide molecules was studied. Hemolymph incubated in the presence of laminarin, zymosan, and N‐acetyl glucosamine produced a dark fibrillar precipitated, and the red pigment (carminic acid) was consumed (measured spectrophotometrically at 495 nm). Lipopolysaccharide (LPS) did not induce any response. The reaction was inhibited with millimolar concentrations of serine and cysteine protease inhibitors, EGTA and phenyl thiourea. It was also diminished by prostaglandin synthesis inhibitors: dexamethasone, acetylsalicylic acid, and indomethacin. However, Mg2+ chelator EDTA did not inhibit hemolymph activation. Hemolymph proteins were depleted from soluble phase during treatment with laminarin, but a group of around 34 kDa remained unmodified. These results showed that D. coccus hemolymph is activated by microbial elicitors, its activation depends on eicosanoids, and suggest participation of a prophenoloxidase (PPO)‐like activation system that could consume carminic acid. We are currently dissecting the molecular factors involved in D. coccus hemolymph activation to determine homologies and differences with other arthropods immune response pathways. Arch. Insect Biochem. Physiol. 54:37–45, 2003. © 2003 Wiley‐Liss, Inc.
Tyramine and octopamine: Antagonistic modulators of behavior and metabolism
Authors: Roeder Thomas , Seifert Mark , Kähler Christian , Gewecke Michael
Published: August 2003

The phenolamines tyramine and octopamine are decarboxylation products of the amino acid tyrosine. Although tyramine is the biological precursor of octopamine, both compounds are independent neurotransmitters, acting through various G‐protein coupled receptors. Especially, octopamine modulates a plethora of behaviors, peripheral and sense organs. Both compounds are believed to be homologues of their vertebrate counterparts adrenaline and noradrenaline. They modulate behaviors and organs in a coordinated way, which allows the insects to respond to external stimuli with a fine tuned adequate response. As these two phenolamines are the only biogenic amines whose physiological significance is restricted to invertebrates, the attention of pharmacologists was focused on the corresponding receptors, which are still believed to represent promising targets for new insecticides. Recent progress made on all levels of octopamine/tyramine research enabled us to better understand the molecular events underlying the control of complex behaviors. Arch. Insect Biochem. Physiol. 54:1–13, 2003. © 2003 Wiley‐Liss, Inc.
Selection of normalizer genes in conducting relative gene expression analysis of embryos
Authors: Zhang Qin J. , Chadderton Antony , Clark Robert L. , Augustine‐Rauch Karen A.
Published: August 2003

BACKGROUND

In relative gene expression analysis, a reference gene for sample normalization is required for determining target expression changes among experimental treatment groups. Since some developmental toxicants secondarily cause general growth retardation and/or other general biological changes, commonly used housekeeping genes may not serve as accurate normalizers.

METHODS

We conducted real‐time polymerase chain reaction (PCR) with normalization to calculate relative target transcriptional change, using housekeeping and structure‐specific expression genes as normalizers. Relative levels of Hoxb1 expression were measured in cultured rodent embryos at 24 hr post retinoic acid (RA) administration. Transcriptional response was also evaluated using two novel compounds that produced posterior axial and growth defects in rat whole‐embryo culture. Embryos treated with these compounds were evaluated for general biological processes, and their respective biological states were considered in the context of the relative gene expression change calculated with the housekeeping normalizers.

RESULTS

Normalized RA‐induced Hoxb1 expression demonstrated that only some reference genes accurately quantitated the expected 1.5‐ to 2‐fold increase in Hoxb1 expression. Evaluation of the test compounds demonstrated that only normalization with the spatially‐restricted hindbrain gene, Krox‐20, calculated significant expression decreases of T‐gene, a gene known to be functionally relevant in posterior axial development. Reduction in T‐gene expression was confirmed qualitatively by whole‐mount in situ hybridization.

CONCLUSIONS

Prudent reference gene selection is important in evaluating relative gene expression in embryos. An experimental control design is proposed to facilitate the identification of normalizing genes that will accurately calculate relative gene expression change in treated embryos. Birth Defects Research (Part A), 2003. © 2003 Wiley‐Liss, Inc.
Genotype frequencies and linkage disequilibrium in the CEPH human diversity panel for variants in folate pathway genes MTHFR, MTHFD, MTRR, RFC1, and GCP2
Authors: Shi Min , Caprau Diana , Romitti Paul , Christensen Kaare , Murray Jeffrey C.
Published: August 2003

BACKGROUND

Genetic variation in enzymes involved in vitamin metabolism is a candidate for analysis in studies of how nutritional covariates may impact a disease state. The role of folate pathway genes in birth defects and cardiovascular disease in humans has been widely studied. Since incidence rates for these disorders vary by geographic origins, it is useful to know which variants are the best candidates for studies based on genotype and allele frequency, as well as linkage disequilibrium (LD) in founder populations.

METHODS

Six polymorphisms in five folate metabolism‐related genes (MTHFR, MTHFD, MTRR, GCP2, and RFC1) were genotyped on a collection of 1064 DNA samples from populations around the world, which were made available by the Centre d'Étude du Polymorphisme Humain (CEPH) consortium for analysis.

RESULTS

In this study we report the genotype frequencies for variants in the MTHFR, MTHFD, MTRR, GCP2, and RFC1 genes, and the LD for two variants (C677T and A1298C) in MTHFR.

CONCLUSIONS

The rare allele frequency for each of the five genes studied varied widely. LD is strongest in Pakistani and Brazilian populations (D′ = 1.0) and weakest in Mexican populations (D′ = 0.45). These findings will allow the selection of variants that will provide the most power in studies of folate pathway genes involving different ancestral populations, and contribute to our knowledge of the population distribution of selected nutritional gene variants. Birth Defects Research (Part A), 2003. © 2003 Wiley‐Liss, Inc.
Subfertility and prepregnancy overweight/obesity: Possible interaction between these risk factors in the etiology of congenital renal anomalies
Authors: Honein Margaret A. , Moore Cynthia A. , Watkins Margaret L.
Published: August 2003

BACKGROUND

Maternal subfertility and high body mass index (BMI) are both associated with adverse reproductive outcomes, including some birth defects. One study reported an association between subfertility and renal anomalies (Li, 1999).

METHODS

We defined subfertility as the mother's report that she sought fertility treatment from a doctor/clinic, and high BMI as a prepregnancy BMI ≥25. We included 169 infants with renal anomalies (renal agenesis [n = 41], obstructive defects [n = 117], and duplication defects [n = 11]) and 2763 infants without defects who were born in 1968–1980 in metropolitan Atlanta, after excluding mothers who reported diabetes. Conditional logistic regression (matching variables: race, birth hospital, and birth period) was used to obtain effect estimates (adjusted for maternal age and gestational age).

RESULTS

Subfertility was more common among case‐mothers (11.8%) than control‐mothers (7.8%), high BMI was similar among case‐mothers (11.2%) and control‐mothers (10.9%), and joint exposure (subfertility and high BMI) was reported by 3% case‐mothers and 0.7% of control‐mothers. Joint exposure to subfertility and high BMI was associated with renal anomalies (odds ratio [OR] = 5.8; 95% confidence interval [CI] = 2.0–16.3). All case‐mothers who reported a joint exposure had infants with obstructive renal anomalies (OR = 8.5; 95% CI = 2.9–24.7). There was no association observed for either exposure alone (subfertility and low BMI, or high BMI and no subfertility) for either all renal anomalies or obstructive defects.

CONCLUSIONS

Women who are overweight/obese and experience subfertility may be more likely to have an infant with an obstructive renal anomaly. Further exploration of possible biologic mechanisms is needed. Birth Defects Research (Part A), 2003. Published © 2003 Wiley‐Liss, Inc.