bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal Mitochondrial Structure in Human Unfertilized Oocytes and Arrested Embryos
Authors: AU HENG‐KIEN , YEH TIEN‐SHUN , KAO SHU‐HUEI , TZENG CHII‐RUEY , HSIEH RONG‐HONG
Published: June 2005

Abstract: To clarify the relationship between mitochondria and embryo development, we collected human unfertilized oocytes, early embryos, and arrested embryos. Unfertilized oocytes and poor‐quality embryos were collected, and the ultrastructure of mitochondria was determined by transmission electron micrography. Four criteria for determining the mitochondrial state were mitochondrial morphology, cristae shape, location, and number of mitochondria. In mature oocytes, mitochondria were rounded with arched cristae and a dense matrix and were distributed evenly in the ooplasm. In pronuclear zygotes, the size and shape of mitochondria were similar to those in mature oocytes; however, mitochondria appeared to migrate and concentrate around pronuclei. In this study, 67% of examined unfertilized oocytes had fewer mitochondria in the cytoplasm. A decreased number of mitochondria located near the nucleus was also demonstrated in 60% of arrested embryos. Fewer differentiated cristae were determined in all three arrested blastocyst stages of embryos. The relative expressions of oxidative phosphorylation genes in oocytes and embryos were also determined. These data imply that inadequate redistribution of mitochondria, unsuccessful mitochondrial differentiation, or decreased mitochondrial transcription may result in poor oocyte fertilization and compromised embryo development.
Pravastatin Attenuates Ceramide‐Induced Cytotoxicity in Mouse Cerebral Endothelial Cells with HIF‐1 Activation and VEGF Upregulation
Authors: CHEN SHANG‐DER , HU CHAUR‐JONG , YANG DING‐I , NASSIEF ABDULLAH , CHEN HONG , YIN KEJIE , XU JAN , HSU CHUNG Y.
Published: June 2005

Abstract: Ceramide is a pro‐apoptotic lipid messenger that induces oxidative stress and may mediate apoptosis in cerebral endothelial cells (CECs) induced by TNF‐α/cycloheximide, lipopolysaccharide, oxidized LDL, IL‐1, and amyloid peptide. Exposure of CECs to C2 ceramide for 12 h caused cell death in a concentration‐dependent manner, with a LC50 of 30 μM. Statins are inhibitors of 3‐hydroxyl‐3‐methyl coenzyme A reductase which is the rate‐limiting enzyme for cholesterol biosynthesis. Pretreatment with pravastatin at 20 μM for 16 h substantially attenuated ceramide cytotoxicity in mouse CECs. Increases in vascular endothelial growth factor (VEGF) expression were detected within 1‐3 h after pravastatin treatment. This pravastatin action was accompanied by the activation of hypoxia‐inducible factor‐1 (HIF‐1), a transcription factor known to activate VEGF expression. These results raise the possibility that pravastatin may protect CECs against ceramide‐induced death via the HIF‐VEGF cascade.
Bcl‐2 Gene Family Expression in the Brain of Rat Offspring after Gestational and Lactational Dioxin Exposure
Authors: CHANG SHWU‐FEN , SUN YU‐YO , YANG LIANG‐YO , HU SSU‐YAO , TSAI SHIH‐YING , LEE WEN‐SEN , LEE YI‐HSUAN
Published: June 2005

Abstract: Recent epidemiological studies have shown that dioxin, a persistent organic pollutant, is related to cognitive and behavioral abnormalities in the offspring of exposed cohort. In order to investigate the possible impact of dioxin in survival gene expression during brain development, we established an animal model of gestational and lactational dioxin‐exposed rat offspring. The expressions of dioxin‐responsive gene cytochrome P450 1A1 (CYP1A1), apoptotic gene Bax, and anti‐apoptotic genes Bcl‐2 and Bcl‐xL were examined in rat liver and brains using Western blot analysis and RT‐PCR. The results showed that treatment of pregnant rats with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) (2 μg/kg body weight through oral delivery) at gestation day 15 resulted in an increase of Bcl‐xL in offspring male liver and cerebral cortex, but a decrease in female offspring. In contrast, the expression of Bcl‐xL in the cerebellum was decreased in male, but increased in female. Bcl‐2, another anti‐apoptotic gene, was also downregulated in P0 female liver, cerebral cortex, but was not observed in male. In the 4‐month‐old offspring, however, the Bcl‐2 protein levels in the liver and cerebellum of both male and female pups were higher in the TCDD group as compared with the control group. However, the Bcl‐2 level in the cerebral cortex of TCDD‐treated groups was higher than the control group only in female but not male offspring at 4 months old. The expression of Bax showed no significant changes upon TCDD exposure at P0 stage, but was significantly reduced in the 4‐month‐old male cortex. These results indicate that early exposure of dioxin could affect the development of certain brain regions with gender difference, in terms of its differential effect on expressions of Bcl‐xL, Bcl‐2, and Bax.
High Prevalence of the COII/tRNALys Intergenic 9‐bp Deletion in Mitochondrial DNA of Taiwanese Patients with MELAS or MERRF Syndrome
Authors: LIU CHIN‐SAN , CHENG WEN‐LING , CHEN YI‐YUN , MA YI‐SHING , PANG CHENG‐YOONG , WEI YAU‐HUEI
Published: June 2005

Abstract: The COII/tRNALys intergenic 9‐bp deletion (MIC9D) of mitochondrial DNA (mtDNA) has been established as a genetic polymorphism for Asian‐Pacific populations. We investigated whether this small mtDNA deletion is co‐transmitted with human diseases such as mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes (MELAS) and myoclonic epilepsy with ragged‐red fibers (MERRF) syndromes. Forty unrelated Taiwanese families, including 12 families with MERRF and A8344G mtDNA mutation and 28 families with MELAS and A3243G mutation of mtDNA, respectively, were recruited in this study. In addition, 199 healthy subjects were recruited as control. We found that the frequency of occurrence of mtDNA with the MIC9D polymorphism in healthy subjects was 21% (41/199). However, the incidence of the MIC9D polymorphism was 67% (8/12) among the probands of all the families with MERRF syndrome (P= 0.001; OR = 8) and 39% (11/28) among the probands of the families with MELAS syndrome (P= 0.038; OR = 2). This finding indicates that the frequency of occurrence of mtDNA with the MIC9D polymorphism in patients with MERRF or MELAS syndrome is higher than that of healthy subjects. The prevalence of mitochondrial encephalomyopathies in relation to the MIC9D polymorphism of mtDNA in Taiwanese population is discussed.
Raffinee in the Treatment of Spinal Cord Injury: An Open‐Labeled Clinical Trial
Authors: CHEN HSIN‐YING , LIN JER‐MIN , CHUANG HUNG‐YI , CHIU WEN‐TA
Published: June 2005

Abstract: The purpose of this preliminary clinical trial was to assess the safety and therapeutic trend of Raffinee, a mixture of free radical scavengers derived from natural products, on subacute spinal cord injury (SCI). SCI patients (three females and seven males) were enrolled from three medical centers in Taiwan. Their ages ranged from 18 to 76 years, with an average of 47.6 ± 19.0 years. There were four incomplete and six complete cases in this study. Standard regimens for SCI at acute stage were given at each hospital. Approximately 7 weeks (35.4 ± 13.9 days) after SCI, 2 U of Raffinee was given orally before meals three times a day for 6 weeks. Patients received motor, sensory, and activities of daily living (ADL) assessments before and after the treatment with Raffinee every week for 6 weeks. The Wilcoxon signed‐ranks test was used for statistical analysis. Significant motor and sensory recovery began in the second week of Raffinee treatment, and significant ADL recovery was also noted in the third week. Functional recovery was more prominent in incomplete cases. Raffinee appeared to be safe in the subacute stage of SCI and may be an effective adjuvant therapy for enhancing functional recovery. Further clinical studies including double‐blinded randomized placebo‐controlled trials with follow‐up for more than 1 year are necessary to validate the effectiveness of Raffinee in SCI.
Cyclin D1 in Breast Cancer Pathogenesis
Authors: Arnold Andrew , Papanikolaou Alexandros
Published: June 2005

Taking a perspective on available evidence that emphasizes relevance to human disease, cyclin D1 is solidly established as an oncogene with an important pathogenetic role in breast cancer and other human tumors. However, the precise cellular mechanisms through which aberrant cyclin D1 expression drives human neoplasia are less well established. Indeed, emerging evidence suggests that cyclin D1 might act, predominantly or at least in part, through pathways that do not involve its widely accepted function as a cell cycle regulator. Although therapeutic exploitation of the role of cyclin D1 as a molecular driver of breast cancer carries great promise, it is also suggested that direct targeting of the cyclin D1 gene or gene products may prove more successful than approaches that rely on arguably incomplete knowledge of the oncogenic mechanisms of cyclin D1.
Colony-Stimulating Factors for Chemotherapy-Induced Febrile Neutropenia: A Meta-Analysis of Randomized Controlled Trials
Authors: Clark Otavio A.C. , Lyman Gary H. , Castro Aldemar A. , Clark Luciana G.O. , Djulbegovic Benjamin
Published: June 2005

Purpose

Current treatment for febrile neutropenia (FN) includes hospitalization for evaluation, empiric broad-spectrum antibiotics, and other supportive care. Clinical trials have reported conflicting results when studying whether the colony-stimulating factors (CSFs) improve outcomes in patients with FN. This Cochrane Collaboration review was undertaken to further evaluate the safety and efficacy of the CSFs in patients with FN.

Methods

An exhaustive literature search was undertaken including major electronic databases (CANCERLIT, EMBASE, LILACS, MEDLINE, SCI, and the Cochrane Controlled Trials Register). All randomized controlled trials that compare CSFs plus antibiotics versus antibiotics alone for the treatment of established FN in adults and children were sought. A meta-analysis of the selected studies was performed.

Results

More than 8,000 references were screened, with 13 studies meeting eligibility criteria for inclusion. The overall mortality was not influenced significantly by the use of CSF (odds ratio [OR] = 0.68; 95% CI, 0.43 to 1.08; P = .1). A marginally significant result was obtained for the use of CSF in reducing infection-related mortality (OR = 0.51; 95% CI, 0.26 to 1.00; P = .05). Patients treated with CSFs had a shorter length of hospitalization (hazard ratio [HR] = 0.63; 95% CI, 0.49 to 0.82; P = .0006) and a shorter time to neutrophil recovery (HR = 0.32; 95% CI, 0.23 to 0.46; P < .00001).

Conclusion

The use of the CSFs in patients with established FN caused by cancer chemotherapy reduces the amount of time spent in hospital and the neutrophil recovery period. The possible influence of the CSFs on infection-related mortality requires further investigation.
Transforming Growth Factor-β3 Increases Gap-Junctional Communication among Folliculostellate Cells to Release Basic Fibroblast Growth Factor
Authors: Kabir Nurul , Chaturvedi Kirti , Liu Lian Sheng , Sarkar Dipak K.
Published: June 2005

Folliculostellate (FS) cells are known to communicate with each other and with endocrine cells via gap junctions in the anterior pituitary. We investigated whether TGFβ3 and estradiol, known to regulate FS cell production and secretion of basic fibroblast growth factor (bFGF), increases gap junctional communication to alter bFGF secretion from FS cells. FS cells in monolayer cultures were treated with TGFβ3 or vehicle alone for 24 h and then microinjected with Lucifer Yellow and high-molecular-weight Texas Red dextran. Ten minutes later the transfer of dye among adjacent cells was recorded with a digital microscope. TGFβ3 increased the transfer of dye. The TGFβ3-neutralizing antibody and the gap junction inhibitor octanol reduced the effect of TGFβ3 on the transfer of dye. The TGFβ3-induced transfer of dye was unaltered by simultaneous treatment with estradiol. The steroid alone also had no effect. TGFβ3 increased total and phosphorylated levels of connexin 43. Estradiol treatment did not produce any significant changes on basal or TGFβ3-induced increases in connexin 43 levels. The gap-junction inhibitor octanol reduced TGFβ3-increased levels of bFGF in FS cells. Taken together, these results suggest that TGFβ3 may act on FS cells to increase gap-junctional communication to maximize its effect on bFGF secretion.
Dopamine, Dopamine D2 Receptor Short Isoform, Transforming Growth Factor (TGF)-β1, and TGF-β Type II Receptor Interact to Inhibit the Growth of Pituitary Lactotropes
Authors: Sarkar D. K. , Chaturvedi K. , Oomizu S. , Boyadjieva N. I. , Chen C. P.
Published: June 2005

The neurotransmitter dopamine is known to inhibit prolactin secretion and the proliferation of lactotropes in the pituitary gland. In this study, we determined whether dopamine and TGFβ1 interact to regulate lactotropic cell proliferation. We found that dopamine and the dopamine agonist bromocriptine stimulated TGFβ1 secretion and TGFβ1 mRNA expression but inhibited lactotropic cell proliferation both in vivo and in vitro. The dopamine’s inhibitory action on lactotropic cell proliferation was blocked by a TGFβ1-neutralizing antibody. We also found that PR1 cells, which express low amounts of the dopamine D2 receptor, demonstrated reduced expression of TGFβ1 type II receptor and TGFβ1 mRNA levels and had undetectable levels of TGFβ1 protein. These cells showed a reduced TGFβ1 growth-inhibitory response. Constitutive expression of the D2 receptor short isoform, but not the D2 receptor long isoform, induced TGFβ1 and TGFβ1 type II receptor gene expression and recovered dopamine- and TGFβ1-induced growth inhibition in PR1 cells. The constitutive expression of D2 receptor short isoform also reduced the tumor cell growth rate. These data suggest that a TGFβ1 system may mediate, in part, the growth-inhibitory action of dopamine on lactotropes.
A Ftz-F1-Containing Yeast Artificial Chromosome Recapitulates Expression of Steroidogenic Factor 1 in Vivo
Authors: Karpova Tatiana , Presley Jeremy , Manimaran Rengasamy R. , Scherrer Serge P. , Tejada Lovella , Peterson Kenneth R. , Heckert Leslie L.
Published: June 2005

Steroidogenic factor 1 (SF-1/Nr5a1) is an orphan nuclear receptor encoded by the Ftz-F1 gene and is required for gonad and adrenal development and regulation of hormone production within the reproductive and adrenal axes. To extend our understanding of Ftz-F1 and its role in SF-1 expression, we identified and characterized a yeast artificial chromosome (YAC) containing Ftz-F1. Within this YAC, Ftz-F1 is centrally located and flanked by genes encoding a second orphan nuclear receptor, germ cell nuclear factor, and proteasome (prosome, macropain) subunit β type 7. Three lines of transgenic mice carrying the YAC were generated and in two lines (lines 7 and 14), RT-PCR and ribonuclease protection analysis showed that expression of transgenic SF-1 mimicked that of endogenous SF-1, both spatially and quantitatively. In the third line (line 15), pituitary and hypothalamic expression were absent. Comparison of the integrated transgenes revealed that line 15 was truncated at the end of intron 4 and revealed a region within the locus that is responsible for SF-1 expression in the pituitary and hypothalamus. The line 14 transgene was introduced into a mouse strain lacking functional SF-1. Examination of SF-1-deficient, transgene-positive mice revealed that the YAC was able to rescue adrenal and gonad development, which normally arrests in the SF-1-null embryos and showed that the 153-kb transgene integrated in line 14 is sufficient to properly direct SF-1 expression and support its biological activity. Thus, the study defines a region of Ftz-F1 that contains the requisite set of regulatory elements to direct SF-1 cell-specific expression and all temporal and quantitative changes need for its biological activity.
Identification of the cyclic-nucleotide-binding domain as a conserved determinant of ion-channel cell-surface localization
Authors: Akhavan Armin , Atanasiu Roxana , Noguchi Tomohiro , Han Wei , Holder Natasha , Shrier Alvin
Published: June 2005

Mutations of a putative cyclic-nucleotide-binding domain (CNBD) can disrupt the function of the hyperpolarization-activated cyclic-nucleotide-gated channel (HCN2) and the human ether-a-go-go-related gene potassium channel (HERG). Loss of function caused by C-terminal truncation, which includes all or part of the CNBD in HCN and HERG, has been related to abnormal channel trafficking. Similar defects have been reported for several of the missense mutations of HERG associated with long QT syndrome type 2 (LQT2). Thus, we postulate that normal processing of these channels depends upon the presence of the CNBD. Here, we show that removal of the entire CNBD prevents Golgi transit, surface localization and function of HERG channel tetramers. This is also true when any of the structural motifs of the CNBD is deleted, suggesting that deletion of any highly conserved region along the entire length of the CNBD can disrupt channel trafficking. Furthermore, we demonstrate that defective trafficking is a consequence of all LQT2 mutations in the CNBD, including two mutations not previously assessed and two others for which there are conflicting results in the literature. The trafficking sensitivity of the CNBD might be of general significance for other ion channels because complete deletion of the CNBD or mutations at highly conserved residues within the CNBD of the related ERG3 channel and HCN2 also prevent Golgi transit. These results broadly implicate the CNBD in ion-channel trafficking that accounts for the commonly observed loss of function associated with CNBD mutants and provides a rationale for distinct genetic disorders.
Refrigeration systems with minimized refrigerant charge: System design and performance
Authors: Primal F , Lundqvist P
Published: June 2005

Independently of the choice of refrigerant, environmental and/or safety issues can be minimized by reducing leakage and the amount of refrigerant charge in heat pump or refrigeration systems, preferably both. In the investigation reported here, a laboratory test rig was built, simulating a water-to-water heat pump with a heating capacity of 5 kW. The system was designed to minimize the charge of refrigerant mainly by use of minichannel aluminium heat exchangers and a compact system design. It was shown that the system could be run with 200 g of propane at typical domestic heat pump operating conditions without reduction in the heating coefficient of performance (COP1) compared with a traditional design. Additional charge reduction is possible by selecting proper compressor lubrication oils or by employing a compressor simply using less lubrication oil.
Theoretical performance of transcritical carbon dioxide cycle with two-stage compression and intercooling
Authors: Baek J. S. , Groll E. A. , Lawless P. B.
Published: June 2005

A computer model was developed to perform a thermodynamic analysis of the transcritical carbon dioxide cycle with two-stage compression and intercooling. In typical two-stage compression with intercooling applications, the intercooler serves the purpose of cooling the fluid to the lowest possible temperature before it enters the second-stage compressor. This paper presents the results of the system analysis of the transcritical carbon dioxide cycle with two-stage compression and intercooling (intercooler cycle) and identifies the pressure ratios that provide maximum system efficiency. The results show that the coefficient of performance (COP), curves of the intercooler cycle are different from the ‘typical bell curve behaviours’ that are observed when plotting the COP versus the intermediate pressure with assumptions of isentropic and real compression process.
Modelling and experimental validation of advanced refrigeration systems in supermarkets
Authors: Arias J , Lundqvist P
Published: June 2005

The effective use of energy and the replacement of CFC and HCFC refrigerants are two factors that have influenced the design and operation of refrigeration systems in supermarkets during recent years. The potential for increasing energy efficiency in refrigeration systems, indoor climate and refrigerated cabinets is large. Since the energy systems of a supermarket are relatively complex, improvements in one subsystem affect other systems, thus making analysis of potential improvements non-additive. A computer model, CyberMart, that predicts building heating and cooling loads, HVAC (heating, ventilation, and air conditioning), and refrigeration system performances of a supermarket, has been developed. The focus of the model is on energy use, environmental impact (TEWI), and life cycle cost (LCC) of the refngeration system. The refrigeration system solutions included in the model are: direct system, completely indirect system, partially indirect system, cascade system, parallel system with mechanical sub-cooling (where the refrigerant in the low-temperature system is sub-cooled with the brine of the intermediate temperature level), and district cooling (that cools the condenser of the refrigeration machines). Measurements of different parameters such as outdoor and indoor temperatures, relative humidity, and compressor power have been carried out in several stores to validate the model. A theoretical description of the model and results from the model and measurements are presented in this paper.
Case–Control and Two-Gate Designs in Diagnostic Accuracy Studies
Authors: Rutjes Anne WS , Reitsma Johannes B , Vandenbroucke Jan P , Glas Afina S , Bossuyt Patrick MM
Published: June 2005

Background: In some diagnostic accuracy studies, the test results of a series of patients with an established diagnosis are compared with those of a control group. Such case–control designs are intuitively appealing, but they have also been criticized for leading to inflated estimates of accuracy.

Methods: We discuss similarities and differences between diagnostic and etiologic case–control studies, as well as the mechanisms that can lead to variation in estimates of diagnostic accuracy in studies with separate sampling schemes (“gates”) for diseased (cases) and nondiseased individuals (controls).

Results: Diagnostic accuracy studies are cross-sectional and descriptive in nature. Etiologic case–control studies aim to quantify the effect of potential causal exposures on disease occurrence, which inherently involves a time window between exposure and disease occurrence. Researchers and readers should be aware of spectrum effects in diagnostic case–control studies as a result of the restricted sampling of cases and/or controls, which can lead to changes in estimates of diagnostic accuracy. These spectrum effects may be advantageous in the early investigation of a new diagnostic test, but for an overall evaluation of the clinical performance of a test, case–control studies should closely mimic cross-sectional diagnostic studies.

Conclusions: As the accuracy of a test is likely to vary across subgroups of patients, researchers and clinicians might carefully consider the potential for spectrum effects in all designs and analyses, particularly in diagnostic accuracy studies with differential sampling schemes for diseased (cases) and nondiseased individuals (controls).
Maternal Serum Invasive Trophoblast Antigen and First-Trimester Down Syndrome Screening
Authors: Palomaki Glenn E , Knight George J , Neveux Louis M , Pandian Raj , Haddow James E
Published: June 2005

Background: In the United States, Down syndrome screening is still performed mainly in the second trimester, using 3 or 4 markers. Moving screening into the first trimester has the advantage of earlier diagnosis. Currently, first-trimester screening typically includes maternal serum pregnancy-associated plasma protein-A (PAPP-A), the free β-subunit of human chorionic gonadotropin (free β), and ultrasound measurement of nuchal translucency thickness (NT). The current report describes a case–control study of serum invasive trophoblast antigen (ITA) and its possible inclusion in first-trimester screening for Down syndrome.

Methods: As part of an earlier observational study, serum samples from 54 Down syndrome and 276 matched unaffected pregnancies were collected between 9 and 15 weeks of gestation. Samples had been aliquoted and stored at −20 °C for 8 years. ITA was measured and converted to weight-adjusted multiples of the median (MoM). The distributions of other first-trimester markers are from a single published study.

Results: Median ITA MoM in Down syndrome pregnancies increase as gestational age increases (2.02 MoM at 11 and 2.44 MoM at 13 completed weeks). At 75% detection, maternal age in combination with ITA and PAPP-A measurements have an 8.0% false-positive rate, slightly lower than the 8.8% found for the free β and PAPP-A combination; adding NT measurements reduces false positives for the 2 combinations to 2.0% and 1.8%, respectively.

Conclusion: Serum ITA appears to be a useful first-trimester Down syndrome marker that could replace free β measurements while maintaining performance.
Factors Affecting Survival and Growth of Juvenile Freshwater Mussels Cultured in Recirculating Aquaculture Systems
Authors: Jones Jess W , Mair Rachel A , Neves Richard J
Published: June 2005

Seasonal differences in glochidial maturity, substrate, and diet were studied to determine how these factors affect the survival and growth of juvenile freshwater mussels. Comparisons were made between juveniles produced in the fall and spring of the year; cultured in sediment, sand, or without substrate; and fed either of two species of small (5–10-μm) green algae. The survival and growth of endangered juveniles of oyster mussel Epioblasma capsaeformis were compared with those of a common, seemingly more robust species, the rainbow mussel Villosa iris. The growth of rainbow mussel juveniles was significantly greater than that of oyster mussel juveniles (P < 0.001). The survival and growth of oyster mussel juveniles were significantly greater when propagated in the spring, that is, when glochidia were mature and would normally be released, than in fall (P < 0.001). Survival and growth of juveniles of both species were significantly greater when they were cultured in a sediment substratum rather than sand or no substratum (P < 0.001). No differences (P > 0.05) were observed in survival and growth of juveniles fed algal species Neochloris oleoabundans or Nannochloropsis oculata. In the spring of the year, juvenile oyster mussels achieved a survival of 29.6% and mean length of 664 μm at 60 d of age, whereas at the same age rainbow mussel juveniles exhibited a survival of 25.1% and a mean length of 1,447 μm.
Enhanced physical education and body fat in the primary school child
Authors: Shephard Roy J. , Lavallée Hugues
Published: June 2005

The influence of 1 hr/day of required physical education upon body skinfold readings was examined in 546 children recruited from an urban and a rural primary school in Québec. Two chorts of experimental students began the enhanced program in grade 1, with immediately preceding and succeeding clases serving as controls. The same observer took nine skinfold readings each year, within 2 weeks of each child's birthday. The data showed a significicant and relatively consistent effect of gender (females 10–19% greater than males, with a slightly larger accumulation on the trunk than on the limbs) throughout the 6 years of observation. There was also a trend to an environmental effect (rural > urban), but the experimental students did not differ significantly from their peers in control classes. It is concluded that the energy expenditure added by even a well‐designed physical education program is insufficient to influence the body fatness of free‐living children. © 1993 Wiley‐Liss, Inc.
Parity, adiposity, and body fat distribution among Hispanic women
Authors: Ness Roberta B.
Published: June 2005

The relationship between parity and body fat distribution was investigated in a sample of 1,590 Mexican American, 411 Cuban American, and 657 Puerto Rican women, aged 20–74 years. Participants were interviewed and examined as part of the Hispanic Health and Nutrition Examination Survey, a cross‐sectional study of a representative sample of Hispanic populations residing in the United States. In each ethnic group, there was an increase with greater parity in overall body fat (body mass index [BMI], or triceps plus subscapular skinfolds), central vs. peripheral skinfold thicknesses (subscapular/triceps ratio), and upper vs. lower body skinfold thicknesses (subscapular/calf ratio). These positive associations remained after adjusting for age, income, marital status, smoking, menopausal status, and education. They were statistically significant only in the Mexican American group. After controlling for the BMI, the association between parity and the subscapular/ calf ratio remained significant in Mexican Americans, suggesting a relationship between parity and upper body fat distribution independent of body size. © 1995 Wiley‐Liss, Inc.
An unusual dysplasia‐malformation‐cancer syndrome in two patients
Authors: Durkin‐Stamm M. Virginia , Gilbert Enid F. , Ganick Dorothy J. , Opitz John M. , Miller Robert W.
Published: June 2005

We report two patients with a similar syndrome of gross malformation of a lower limb and contiguous structures due to involvement with dysplastic, teratomatous tissue. This dysplasia seems to have arisen in a paramedian position in the embryonic hindquarter at the time of lower limb‐bud differentiation. Malignant degeneration at 5–7 months led to metastases and death in both cases around 1 year of age. The behavior of the dysplastic/oncoplastic tissue suggests a 2‐“mutational” causal model. This is an apparently previously undescribed formal genesis syndrome.
5α‐Reductase activity of genital and nongenital skin fibroblasts from patients with 5α‐reductase deficiency, androgen insensitivity, or unknown forms of male pseudohermaphroditism
Authors: Pinsky Leonard , Kaufman Morris , Straisfeld Cipia , Zilahi Barbara , Hall Conrad St.‐G. , Opitz John M.
Published: June 2005

Serially subcultured fibroblast strains from genital (foreskin, labium majus) skin, as a group, have considerably more steroid (testosterone) 5α‐reductase activity than those from nongenital skin. Foreskin strains varied 40‐fold and labial strains even more. Labial strains overlapped nongenital strains of either sex more frequently than did prepuce strains. The activity of foreskin strains from two siblings with proven 5α‐reductase deficiency was clearly lower than that of any of 18 control strains. The comparative behavior of the various strain types indicates that labial and nongenital strains should not be used to support a clinical suspicion of male pseudohermaphroditism due to 5α‐reductase deficiency.

The activities of labial strains from patients with complete androgen insensitivity (testicular feminization) – five with the recptor‐negative variety and two with the receptor‐positive type – were as variable as those of control labial strains. The decreased 5α‐reductase activity observed in fresh skin slices of some patients is probably an expression of their functional estrogen/ androgen imbalance in vivo.
A detailed description of mothers' knowledge before genetic counseling for down syndrome: Part I
Authors: Antely R. M. , Seidenfeld M. J. , Jackson Laird G.
Published: June 2005

This study focuses on counselees' knowledge of the Down syndrome before receiving genetic counseling. Data were collected from 47 mothers of children with the Down syndrome using a structured interview of 13 open‐ended questions. This instrument was found to be both internally reliable and consistent. Results of this study document the enormous variation of counselees' knowledge of the Down syndrome before genetic counseling and show that this is positively associated with their educational background. Counselees with more than a high school education knew about 60% of the genetic information pertaining to the diagnosis before genetic counseling, while those with less than a high school education knew only 23% of this information before counseling. These results indicate that the better educated counselees are less apt to need to learn basic genetic information and may seek out genetic counseling services for other reasons. Possible motives are seeking knowledge confirmation, emotional support, and personalization of the information.
Triplication of chromosome Arm 20p due to inherited translocation and secondary nondisjunction
Authors: Marcus E. S. , Fuller B. , Riccardi V. M.
Published: June 2005

A patient with triplication of all of chromosome arm 20p is presented to illustrate the relatively modest degree of developmental delay that can result from autosomal triplication and the role of nondisjunction as a mechanism for deriving a partial triplication status.
Christ‐Siemens‐Touraine syndrome—a clinical and genetic analysis of a large Brazilian kindred: II. Affected males
Authors: Pinheiro M. , Freire‐Maia N.
Published: June 2005

We describe 13 males with Christ‐Siemens‐Touraine syndrome from one family. History and examination were supplemented by three sweat tests and dermatoglyphic analysis. Some of the patients had two uncommon findings (onychodystrophy and excessive lacrimation), and five had an “incomplete” form of the syndrome. Four signs (distal phalanges of fingers and toes radially and tibially deviated, respectively; facial hypochromic spots; large occipitofrontal circumference) seem to be here described for the first time. The segregation proportion in the sibships with at least an affected male was found to be normal (1:1) in 44 series of data (43 from the literature), where a high ascertainment bias was present ( 155 affected and 68 normal males).
H–Y gene expression in apparent absence of the long arm of the Y chromosome
Authors: Moreira‐Filho Carlos Alberto , Otto Priscilla G. , Frota‐Pessoa Oswaldo
Published: June 2005

H‐Y antigen expression was detected on cells from an individual having a presumptive 45,X/46,X,i(Yp) karyotype, but was absent on cells from another person having a 46,X,i(Yq) karyotype. This suggests that the short arm of the human Y chromosome is essential for H‐Y antigen expression, at least in the subjects studied.
Segregation of noisy Mendelian traits and the effect of age‐dependence: A prolegomenon
Authors: Murphy Edmond A.
Published: June 2005

A discussion of the primordial confusion between the multiplicative Galtonian (“lognormal”) trait and the imperfectly segregating Mendelian trait is laid out form a probabilitic standpoint. Several criteria used in comparing them (bimodality; bitangentiality; goodness of fit to the multinomialized form of the distribution; cumulants of the distributions) are reviewed and the inadequacy of their probabilistic properties discussed in some detail. The logical asymmetry of the normalized score (“Roberts' correction”) and hence its invalidity as a criterion for distinguishing between the models is pointed out. The form of a mixture of two Gaussian distributions with fixed and equal variances but with differing age‐dependent means (“the Platt model”) is explored. The epistemological implications are exhibited. As a first step to restoring symmetry, a general model is proposed of which these and other models in wide use emerge as special cases. No attempt is made to deal here with the statistical aspects of the problem.
Brief historical note: The concept of “gonadal dysgenesis”
Authors: Opitz John M. , Pallister Philip D.
Published: June 2005

The history of gonadal dysgenesis cautions against overinterpretation of data: The streak gonads are neither the result of dysgenesis nor of embryonic origin but represent late fetal/neonatal degeneration; the X‐chromatin‐negative character of the buccal smear and the frequency of color vision defects did not indicate male sex in the Ullrich‐Turner syndrome but rather an XO constitution; severity of dysgenesis did not correlate with risk of gonadal neoplasia but with genotype; the gonadal lesion in the Ullrich‐Turner syndrome was not due to a pituitary defect but a primary ovarian lesion; patients with the Noonan syndrome do not have the Turner phenotype.

The concept of gonadal dysgenesis, introduced by Kermauner in 1912, has outlived its usefulness. Improved methods of phenotype analysis, family studies, and endocrine and cytogenetic methods have shown it to be causally and pathogenetically heterogeneous and have contributed to a better identification and delineation of the several different genetic entities which it formerly comprised.
Discriminant analysis of ribosomal protein synthesis findings in carrier detection of duchenne muscular dystrophy
Authors: Ionasescu V. , Burmeister L. , Hanson J.
Published: June 2005

Previous studies have shown that in vitro muscle ribosomal protein synthesis (RPS) by monomeric ribosomes (MR) and total polyribosomes (TPR) and collagen synthesis (CS) are significantly increased (P < 0.01) in 47 known carriers of Duchenne muscular dystrophy as compared to 60 age‐matched controls. However, there was considerable overlap of the distribution of controls and carriers, particularly for monomeric ribosomal protein synthesis and collagen synthesis. To improve detection of carriers we used discriminant analysis utilizing logs of each measurement as superior to a univariate or bivariate scheme. This study considered four groups: proven carriers (30) (group 1), presumptive carriers (female relatives of Duchenne patients with high serum creatine kinase (CK) levels) (32) (group 2), controls ≥ 20 years old (42) (group 3) and controls < 20 years (36) (group 4).

Comparison of groups
Misclassification (%)

1 versus 3
1.4

1 versus 3 and 4
0.9

2 versus 4
4.4

2 versus 3 and 4
1.8

1 and 2 versus 3 and 4
2.9

These results suggest that discriminant analysis reduces the misclassification rates as compared with univariate or bivariate analysis and confirm the superiority of RPS measurements as a carrier test for Duchenne muscular dystrophy.
Malignant melanoma and charcot‐marie‐tooth disease
Authors: Greene Mark H. , Mead Gene D. , Reimer Ronald R. , Bergfeld Wilma F. , Fraumeni Joseph F.
Published: June 2005

Two patients with Charco‐Marie‐Tooth disease subsequently developed cutaneous malignant melanoma. This constellation of diseases may be due to chance, but raises the possibility of a shared neural crest defect or genetic linkage.
Female pseudohermaphroditism and associated anomalies
Authors: Lubinsky Mark S. , Opitz John M.
Published: June 2005

A patient was observed with female pseudohermaphroditism (FPH) and the “Prune Belly Syndrome” (PBS) – abdominal muscle hypoplasia and urinary tract abnormalities – findings seen in three previously reported cases. A review of cases of FPH with additional anomalies suggests a spectrum of primary, and possibly derived, malformations with Prune Belly Syndrome at one extreme.

These findings can best be understood as disturbance of a specific embryological developmental field of which FPH is a marker, although not an invariable expression. The field includes anorectal, urogenital, sacral‐spinal, and ventral wall structures. FPH is a rare manifestation, and the cases reviewed suggest that it can appear as a developmental anomaly without apparent hormonal trigger.

Malformations of this field are understandable on the basis of a multifactorial model, with male sex as a predisposing factor. The caudal defects of the cryptophthalmos syndrome offer a paradigm for a spectrum of field anomalies.
Kniest dysplasia: Neonatal death with necropsy
Authors: Chen Harold , Yang S. Samuel , Gonzalez Enrique , Opitz John M.
Published: June 2005

We describe a premature female infant with Kniest dysplasia, who died shortly after birth. This appears to be the first autopsy performed in this condition. Manifestations included neonatal respiratory distress, large head, midface hypoplasia, flat nasal bridge, short nose, micrognathia, cleft palate, short neck, micromelia, and mildly bowed limbs. Roentgenologic findings included short, slightly bowed tubular bones with metaphyseal flare; mild platyspondyly, with vertical clefts of vertebral bodies; small iliac bones with increased acetabular angles; and inadequate ossification of pubic rami. Histopathologic findings of cartilage included focal “Swiss‐cheese” pattern; disorganized physeal growth zone; and PAS‐positive, diastase‐resistant intracytoplasmic inclusions, which corresponded to finely granular material accumulated in dilated cisterns of rough endoplasmic reticulum.
Discriminating among single locus models using small pedigrees
Authors: Beaty T. H. , Murphy Edmond A.
Published: June 2005

Simulated small pedigrees (2 parents, 4 offspring) were used to illustrate the applications and limitations of a “model choice” approach designed to detect genetic heterogeneity in familial diseases. While it is possible to identify groups of pedigrees which have different genetic causes for quantitative phenotypic trait(s), theoretical limitations on discriminating between 4 single locus models exist for certain pedigree structures. These limitations originate from the overlapping phenotypic predictions of the various genetic models. Such limitations must be carefully considered in the design of genetic studies. Studies aimed at detecting genetic heterogeneity in familial diseases should limit the different genetic models being considered and tailor the sampling strategy to avoid collecting pedigrees which are non‐informative for certain comparisons.
Short stature, psychomotor retardation, and unusual facial appearance in two brothers
Authors: Smith Richard D. , Fineman Robert M. , Myers Garth G. , Optiz John M.
Published: June 2005

Described here are clinical, radiological, and morphological studies of two brothers with an apparently previously undescribed mental retardation syndrome.
Short rib‐polydactyly syndrome, type 3 with chondrocytic inclusions: Report of a case and review of the literature
Authors: Yang S. Samuel , Lin Ching‐Shen , Al Saadi A. , Nangia Bhim Sen , Bernstein Jay , Herrmann Jürgen
Published: June 2005

A newborn with severely shortened ribs, short limbs, and postaxial polydactyly died shortly after birth. Postmortem roentgenograms established the diagnosis of type 3 short rib‐polydactyly (SRP) syndrome as described by Naumoff and associates. Histopathologic study showed the chondrocytes to contain previously undescribed cytoplasmic inclusion bodies that were PAS‐positive and diastase‐resistant. The material appeared by staining reactions to be a glycoprotein that was seen electron microscopically to accumulate within dilated cisterns of rough endoplasmic reticulum. Similar cytoplasmic inclusions have not been seen in other short rib‐polydactyly syndromes, including SRP types 1 and 2, Jeune syndrome, and Ellis‐van Creveld syndrome. It is often difficult to differentiate cases of type 3 and type 1 (Saldino‐Noonan) syndrome, and in the past the diagnosis has sometimes been confused. A review of previously reported cases showed that type 3 syndrome rarely (1 in 13) had cloacal developmental abnormalities, which are invariably present in patients with type 1 syndrome. Type 3 is also associated with a lower incidence of congenital heart disease, and cardiac malformations, when present, differ from those associated with type 1 syndrome. Both type 3 and type 1 SRP syndromes are transmitted in autosomal recessive fashion. Type 3 SRP syndrome has had an equal sex distribution, although type 1 has so far been reported to occur only in girls. Further investigation with additional patients is necessary to verify the above preliminary findings.
Human chromosome heteromorphisms in American blacks: II. Higher incidence of pericentric inversions of secondary constriction regions (h)
Authors: Verma Ram S. , Rodriguez Jorge , Dosik Harvey , Francke Uta
Published: June 2005

Eighty normal American blacks were studied by the CBG technique (C‐bands by barium hydroxide using Giemsa) for estimation of size and inversion heteromorphisms of chromosomes 1, 9, and 16, and the data were compared to those of whites using subjectively defined criteria. Size and inversion heteromorphisms were classified into 5 levels. The frequencies of size heteromorphisms of chromosomes 1 and 16 were 10.63% and 6.88%, respectively, which are not significantly different from those of a normal population of whites. A higher incidence of size heteromorphisms for chromosome 9 was noted in whites (47.5% vs 30%). The frequencies of inversion heteromorphism of chromosomes 1, 9, and 16 were 17.5%, 21.9%, and 0.0%, respectively. Overall, 61 chromosomes were found to have an inversion. Of these, 28 were in chromosome 1, and 33 were in chromosome 9. A higher incidence of inversion heteromorphisms of chromosomes 1 and 9 was noted in American blacks, while no inversions were found in chromosome 16 in either population. A significant association of increased size of the h region with inversion (r = 0.99 P < 0.01) is demonstrated, ie, enlarged h regions have a higher frequency of inversions.
Genetic polymorphisms among Iranian Jews in Israel
Authors: Cohen T. , Simhai B. , Steinberg A. G. , Levene C. , Opitz John M.
Published: June 2005

Iranian Jews represent a very ancient Jewish community with a high frequency of in breeding. A sample of Iranian Jews, mainly unrelated students, was tested for genetic markers of red blood cells and serum. The frequency of glucose‐6‐phosphate dehydrogenase deficiency was not uniform among Jews who had lived in different areas of Iran; it was lower among those from central Iran (6.7%) than in those from southern and western Iran (16.7% and 20.6%, respectively). The frequencies of B, CDe, cDE, S, and K alleles were among the highest recorded in Jewish ethnic groups. Iranian Jews were similar to Iraqi Jews with respect to the frequencies of the blood markers B, CDe, cde, cDe, ACP, PGM1 ADA, and Hp; however, the B and CDe markers occur with similar frequencies among indigenous Iranians. The presence of the cDe allele and the Gm,1,5,13,14,17 haplotype in low frequencies indicates black admixture. Mongoloid admixture is indicated by the polymorphism of the Gm1,13,15,16,17 haplotype. The very rare phenotype Gm(3,5,13,14,17) was observed in 4.8% of 167 individuals tested. This phenotype has not been previously observed among Jews.
Inherited translocation t(4;5) discovered on prenatal diagnosis
Authors: Nien‐hu Sun , Fon‐yen Wang , Jin‐xia Li , Xian‐ting Zhou , Shun Tang Huo , Omenn Gilbert S. , Opitz John M.
Published: June 2005

We report an apparently balanced reciprocal t(4q;5q) translocation ascertained coincidentally on amniocentesis in a phenotypically normal male fetus and found to be inherited in his mother and maternal grandmother. No banding study was available at the time of the amniocentesis, and the chromosomal status of his parents was unknown. Because of the possibility that this finding might be a de novo, unbalanced translocation, the pregnancy was terminated. Subsequently, the translocation was found to be apparently balanced, but so unequal that both unbalanced translocation products are presumed to be lethal. Thus, it is predicted that only carriers and normal individuals will be conceived and viable in this family. We are unaware of previously published observations on a similar (4q;5q) translocation.
Inheritance of Kartagener syndrome
Authors: Moreno Adolfo , Murphy Edmond A.
Published: June 2005

The surmised autosomal recessive inheritance of situs inversus of Kartagener syndrome is re‐examined on the hypothesis that the homozygous state replaces lateralization of the viscera in normal ontogeny by an indifferent lateralization. The segregation ratio in the progeny of two carrier parents (if there were no ascertainment bias) would then be 1/8. The estimated segregation ratio under the assumption of complete (truncate) ascertainment is 0.124.

The implications for genetic counseling are discussed.