PubMed Health⌕ Search

Biomedical subjects

J Dean

Publications and source records attributed to J Dean.

At least 37 records · Page 2Linked to original sources
PubMed2001

Defective zonae pellucidae in Zp2-null mice disrupt folliculogenesis, fertility and development.

All vertebrate eggs are surrounded by an extracellular matrix. This matrix is known as the zona pellucida in mammals and is critically important for the survival of growing oocytes, successful fertilization and the passage of early embryos through the oviduct. The mouse zona pellucida is composed of three glycoproteins (ZP1, ZP2 and ZP3), each encoded by a single copy gene. Using targeted mutagenesis in embryonic stem cells, Zp2-null mouse lines have been established. ZP1 and ZP3 proteins continue to be synthesized and form a thin zona matrix in early follicles that is not sustained in pre-ovulatory follicles. The abnormal zona matrix does not affect initial folliculogenesis, but there is a significant decrease in the number of antral stage follicles in ovaries isolated from mice lacking a zona pellucida. Few eggs are detected in the oviduct after stimulation with gonadotropins, and no two-cell embryos are recovered after mating Zp2-null females with normal male mice. The structural defect is more severe than that observed in Zp1-null mice, which have decreased fecundity, but not quite as severe as that observed in Zp3-null mice, which never form a visible zona pellucida and are sterile. Although zona-free oocytes matured and fertilized in vitro can progress to the blastocyst stage, the developmental potential of blastocysts derived from either Zp2- or Zp3-null eggs appears compromised and, after transfer to foster mothers, live births have not been observed. Thus, in addition to its role in fertilization and protection of early embryos, these data are consistent with the zona pellucida maintaining interactions between granulosa cells and oocytes during folliculogenesis that are critical to maximize developmental competence of oocytes.

Animals↗
PubMed2001

A biologically inspired controller for hexapod walking: simple solutions by exploiting physical properties.

The locomotor system of slowly walking insects is well suited for coping with highly irregular terrain and therefore might represent a paragon for an artificial six-legged walking machine. Our investigations of the stick insect Carausius morosus indicate that these animals gain their adaptivity and flexibility mainly from the extremely decentralized organization of the control system that generates the leg movements. Neither the movement of a single leg nor the coordination of all six legs (i.e., the gait) appears to be centrally pre-programmed. Thus, instead of using a single, central controller with global knowledge, each leg appears to possess its own controller with only procedural knowledge for the generation of the leg's movement. This is possible because exploiting the physical properties avoids the need for complete information on the geometry of the system that would be a prerequisite for explicitly solving the problems. Hence, production of the gait is an emergent property of the whole system, in which each of the six single-leg controllers obeys a few simple and local rules in processing state-dependent information about its neighbors.

Animals↗
PubMed2000

Periconceptional vitamin use, dietary folate and occurrent neural tube defected pregnancies in a high risk population.

PURPOSE: This 5 year (1992-1997) population-based case control study was conducted to determine if supplemental or dietary folate taken during the periconceptional period reduces the risk of occurrent neural tube defect (NTD) affected pregnancies in a high risk population.METHODS: Cases were all NTD pregnancies including elective terminations, fetal deaths and live births in South Carolina. Only isolated, occurrent NTD affected pregnancies were included (N = 179). Controls (N = 288) were randomly selected from each hospital in proportion to the hospital's contribution to the total live births in the state for the previous year. All mothers were interviewed in person using a modified Centers for Disease Control and Prevention Birth Defect Risk Factor Surveillance Mother's Questionnaire and the Harvard Food Frequency Questionnaire.RESULTS: Women who used a vitamin with 0.4 mg or more of folate at least 3 times per week during the 3 months before and 3 months after conception had a lower risk of having an NTD affected pregnancy than women who took no folate supplementation at any time during pregnancy [adjusted odds ratio (AOR) = 0.42; 95% confidence interval (CI) = 0.19-0.94]; women who used a vitamin with 0.4 mg or more of folic acid for less than 3 times per week or in partial months during the 6 month periconceptional period also had a slightly lower risk of having an NTD affected pregnancy relative to women who used no folate supplementation at any time during pregnancy [AOR =.72; 95% CI = 0.41-1.30]. The risk of NTD affected pregnancy was also lower for women who daily consumed foods containing higher levels of folate: AORs were 0.36 (95% CI = 0.18-0.73), 0.72 (95% CI = 0.42-1.22), and 0.61 (95% CI 0.36-1.04) from the highest to lowest quartile of dietary folate which were 0.457-3.12 mg, 0.322-0.457 mg, and 0.236-0.322 mg respectively.CONCLUSIONS: A reduction in occurrent NTD risk associated with folate supplementation and dietary intake was observed.

Journal Article↗
PubMed2000

Gpbox (Psx2), a homeobox gene preferentially expressed in female germ cells at the onset of sexual dimorphism in mice.

XX gonads differentiate into ovaries, a morphologic event evident by embryonic day 13.5 (E13.5) in mice. To identify early markers of oogenesis, sex-specific urogenital ridge cDNA libraries were constructed from E12-13 embryos. After mass excision and isolation of plasmid DNA, approximately 4800 expressed sequence tags were determined and compared to existing databases. Few cDNAs were specifically expressed in the urogenital ridge, but one, designated GPBOX, encodes a 227-amino-acid homeobox protein that is first expressed at E10.5 in the embryo as well as in the extraembryonic tissues. The Gpbox gene is single copy in the mouse genome and is located on the X chromosome in close proximity to two other homeobox genes, Pem and Psx1. Within the embryo, its expression is limited to the gonad, and transcripts are not detected in adult tissues. Although comparable levels are initially present in both sexes, GPBOX transcripts accumulate faster in female germ cells and peak at E12.5 when they are present in fivefold greater abundance than in males. The persistence of GPBOX transcripts in female germ cells until E15.5 and their virtual disappearance in males by E13.5 suggest that Gpbox may play a role in mammalian oogenesis.

Amino Acid Sequence↗
PubMed2000

The mouse zona pellucida: folliculogenesis, fertility and pre-implantation development.

Perinatally, oocytes within the mouse ovary become surrounded by a layer of flattened granulosa cells and form primordial follicles. The subsequent accretion of the zona pellucida between the oocytes and granulosa cells provides a biochemical marker of folliculogenesis. In mice, the zona matrix is composed of three proteins (ZP1, ZP2, ZP3). Mouse lines lacking either ZP1 or ZP3 have been established and have abnormal folliculogenesis. Without ZP1, structurally defective zonae are formed resulting in decreased fecundity due to early embryonic loss. More strikingly, without ZP3, the zona matrix is absent, no 2-cell embryos are formed and females are infertile. The structural integrity of the zona matrix can be restored by substituting human homologues for the missing mouse protein and these 'humanized' zona matrices should prove useful in investigating the molecular basis of fertilization.

Animals↗
PubMed2000

Tumor necrosis factor receptor-associated periodic syndrome: a novel syndrome with cutaneous manifestations.

BACKGROUND: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an inflammatory disorder characterized by prolonged episodes of periodic fever and localized inflammation and dominantly inherited mutations in TNFRSF1A, the gene encoding the 55-kDa tumor necrosis factor receptor. To our knowledge, the cutaneous pathologic characteristics of TRAPS have not been described previously. OBJECTIVES: To characterize the dermatologic manifestations of TRAPS by clinical, microscopic, and molecular methods, and to investigate its immunophenotype. DESIGN, SETTING, AND PATIENTS: At the National Institutes of Health Clinical Center, Bethesda, Md, a tertiary care referral center, 25 patients with a clinical and molecular diagnosis of TRAPS were evaluated clinically and 10 biopsy specimens of lesional skin were examined by light microscopy and immunohistochemistry. Patients were screened for mutations in TNFRSF1A, the gene coding for the p55 tumor necrosis factor receptor. MAIN OUTCOME MEASURES: Clinical, light microscopic, and immunohistochemical features. RESULTS: The skin eruption usually lasted 4 to 21 days (mean, 13 days). Of 25 patients, 21 (84%) presented with migratory erythematous macules and patches and 10 (40%) had edematous dermal plaques. Conjunctivitis, characterized by pain and redness and/or periorbital edema, was present in 11 patients (44%). Most patients had their first skin eruption during the first 2 years of life. All patients had fever associated with the skin eruption. Most patients had associated abdominal pain (22 [88%]) and myalgia (20 [80%]). Other symptoms included arthralgia (13 [52%]), pleuritic chest pain (10 [40%]), and headache (17 [68%]). Microscopic examination of 10 biopsy specimens of lesional skin showed a superficial and deep perivascular and interstitial infiltrate of lymphocytes and monocytes. None of the biopsy specimens showed multinucleated macrophages or granulomatous or leukocytoclastic vasculitis. The results of immunohistochemistry showed a perivascular infiltrate of CD3+, CD4+, CD8+, CD68+, CD79a-, and CD20- cells. All the mutations were missense mutations in exons 2 through 4 of TNFRSF1A, directly affecting the extracellular domain of the protein. CONCLUSIONS: TRAPS is characterized by a spectrum of dermatologic findings, including migratory patches, edematous plaques, periorbital edema, and/or conjunctivitis. TRAPS is characterized by a perivascular dermal infiltrate of lymphocytes and monocytes.

Adolescent↗
PubMed2000

Mater encodes a maternal protein in mice with a leucine-rich repeat domain homologous to porcine ribonuclease inhibitor.

MATER (Maternal Antigen That Embryos Require) is an ooplasm-specific protein first identified as an antigen (OP1) associated with ovarian autoimmunity in mice. Its primary structure has been deduced from full-length cDNA that encodes a 125-kDa protein required for progression of the mouse embryo beyond two cells. Expression of the gene encoding MATER is restricted to the oocyte, which makes it one of a growing, but still limited, number of maternal-effect genes in mammals. To further investigate the function of MATER during oogenesis and early development, we have characterized the gene and resultant protein. Mater is a single-copy gene in the genome of 129/Sv mice and is located at the proximal end of Chromosome (Chr) 7. The gene, spanning approximately 32 kbp, contains 15 exons ranging in size from 48 to 1576 bp, which together encode the 111 amino acid MATER protein. The first five exons encode 26-27 amino acid hydrophilic repeats and exons 8-14 encode 14 leucine-rich repeats. The three-dimensional structure of the latter domain can be closely modeled on the previously determined X-ray crystallographic coordinates of porcine ribonuclease inhibitor. These characterizations of the gene and protein provide the basis for genetic investigations of MATER function in early mammalian development.

Amino Acid Sequence↗
PubMed2000

Expression of receptor protein tyrosine phosphatase alpha mRNA in human prostate cancer cell lines.

Receptor protein tyrosine phosphatase alpha (RPTPalpha) is a transmembrane protein phosphatase, and has been proposed to be involved in the differentiation of the neuronal system. In the present study, we demonstrated the expression of RPTPalpha mRNA in several normal human tissues. We further investigated the regulation of expression of RPTPalpha mRNA in epithelial cells utilizing three commercially available human prostate cancer cell lines LNCaP, PC-3 and DU145. This is because these cells exhibit different levels of differentiation, defined by the expression of a tissue-specific differentiation antigen, prostatic acid phosphatase (PAcP), and their androgen sensitivity. LNCaP cells express PAcP and are androgen-sensitive cells, while PC-3 and DU145 cells do not express PAcP and are androgen-insensitive cells. Northern blot analyses revealed that, in LNCaP cells, fetal bovine serum (FBS) and 5alpha-dihydrotestosterone (DHT) down-regulates RPTPalpha mRNA expression, similar to the effect on PAcP. Contrarily, FBS up-regulated the RPTPalpha mRNA level in PC-3 and DU145 cells. In LNCaP cells, sodium butyrate inhibited cell growth and up-regulated RPTPalpha as well as PAcP mRNA expression. Although, sodium butyrate also inhibited the growth of PC-3 and DU145 cells, the level of RPTPalpha mRNA was decreased in PC-3, while increased in DU145 cells. Thus, data taken together indicate that the expression of RPTPalpha is apparently regulated by a similar mechanism to that of PAcP in LNCaP cells.

Acid Phosphatase↗
PubMed2000

Mater, a maternal effect gene required for early embryonic development in mice.

Maternal effect genes produce mRNA or proteins that accumulate in the egg during oogenesis. We show here that Mater, a mouse oocyte protein dependent on the maternal genome, is essential for embryonic development beyond the two-cell stage. Females lacking the maternal effect gene Mater are sterile. Null males are fertile.

Animals↗
PubMed2000

Elastin: mutational spectrum in supravalvular aortic stenosis.

Supravalvular aortic stenosis (SVAS) is a congenital narrowing of the ascending aorta which can occur sporadically, as an autosomal dominant condition, or as one component of Williams syndrome. SVAS is caused by translocations, gross deletions and point mutations that disrupt the elastin gene (ELN) on 7q11.23. Functional hemizygosity for elastin is known to be the cause of SVAS in patients with gross chromosomal abnormalities involving ELN. However, the pathogenic mechanisms of point mutations are less clear. One hundred patients with diagnosed SVAS and normal karyotypes were screened for mutations in the elastin gene to further elucidate the molecular pathology of the disorder. Mutations associated with the vascular disease were detected in 35 patients, and included nonsense, frameshift, translation initiation and splice site mutations. The four missense mutations identified are the first of this type to be associated with SVAS. Here we describe the spectrum of mutations occurring in familial and sporadic SVAS and attempt to define the mutational mechanisms involved in SVAS. SVAS shows variable penetrance within families but the progressive nature of the disorder in some cases, makes identification of the molecular lesions important for future preventative treatments.

Alternative Splicing↗
PubMed2000

Five cases of isolated glycerol kinase deficiency, including two families: failure to find genotype:phenotype correlation.

Little is understood of the genotype/phenotype correlations in X linked glycerol kinase deficiency (GKD) where most cases are caused by extensive deletions of Xp21, which often include genes flanking the GK locus. Few cases of isolated GKD have been investigated where the phenotype is not influenced by neighbouring genes. In this paper, we present the mutation data from four confirmed and one suspected case of non-deletion, isolated, X linked GKD and therefore extend the base of patients that can allow an assessment of genotype/phenotype correlations for this disease. The mutations found were two terminations leading to premature truncation of the GK polypeptide chain, one insertion, and an amino acid substitution. Phenotypic variation was observed in two families, where there was more than one affected subject carrying the same mutation, confirming previous studies that suggest there is no correlation between disease severity and genotype. Furthermore, the nature of the mutation in different families does not appear to influence the spectrum of phenotypic variation. In addition, one coding polymorphism in exon 3 has been found. The characterisation of the gene structure has been completed and shows that instead of 19 there are 21 exons.

Amino Acid Sequence↗
PubMed2000

Evidence based medicine in practice: lessons from a Scottish clinical genetics project.

OBJECTIVE: To establish national clinical guidelines and integrated care pathways for five conditions (tuberous sclerosis (TS), Huntington's disease (HD), myotonic dystrophy (MD), neurofibromatosis type 1 (NF1), and Marfan syndrome (MS)) and audit their use in Scotland. DESIGN: Systematic review of published reports followed by consensus conferences to prepare clinical guidelines and integrated care pathways. Structured review of medical records before and after introduction of integrated care pathways to document changes in practice. Survey of staff views on procedures adopted. SETTING: All four clinical genetics centres in Scotland. RESULTS: Project resulted in reduced variation in practice across centres, improved data recording in medical records, and improved communication with other professional groups. A very poor evidence base for management of patients with the conditions studied was found. CONCLUSIONS: A collaborative structure for undertaking clinical research would improve the evidence base for current practice. National discussion of the boundaries of responsibility of care for the long term management of patients with these disorders is required. The integrated care pathway approach shows promise as a means of facilitating the development of audit within clinical genetics services.

Evidence-Based Medicine↗
PubMed2000

FIGalpha, a germ cell-specific transcription factor required for ovarian follicle formation.

Primordial follicles are formed perinatally in mammalian ovaries and at birth represent the lifetime complement of germ cells. With cyclic periodicity, cohorts enter into a growth phase that culminates in ovulation of mature eggs, but little is known about the regulatory cascades that govern these events. FIGalpha, a transcription factor implicated in postnatal oocyte-specific gene expression, is detected as early as embryonic day 13. Mouse lines lacking FIGalpha were established by targeted mutagenesis in embryonic stem cells. Although embryonic gonadogenesis appeared normal, primordial follicles were not formed at birth, and massive depletion of oocytes resulted in shrunken ovaries and female sterility. Fig(&agr;) (the gene for FIGalpha null males have normal fertility. The additional observation that null females do not express Zp1, Zp2 or Zp3 indicates that FIGalpha plays a key regulatory role in the expression of multiple oocyte-specific genes, including those that initiate folliculogenesis and those that encode the zona pellucida required for fertilization and early embryonic survival. The persistence of FIGalpha in adult females suggests that it may regulate additional pathways that are essential for normal ovarian development.

Aging↗
PubMed2000

The zona pellucida: using molecular genetics to study the mammalian egg coat.

An extracellular matrix that mediates critical steps in fertilization and early development surrounds all vertebrate eggs. In mice and humans, this matrix is known as the zona pellucida and comprises three glycoproteins: ZP1, ZP2 and ZP3. Homologues of these proteins isolated from other vertebrates have conserved protein motifs that may be important for establishing a common fibrillar structure. However, specific but contradictory biological roles have been assigned to individual egg coat proteins based on assays in vitro in a wide range of species. Mouse lines lacking either ZP1 or ZP3 have been established with abnormal or absent zona matrices and varying degrees of infertility to examine zona structure and function in vivo. By crossing mouse lines lacking individual zona proteins with those expressing human homologues, the structural integrity of the zona matrix can be restored. Because mouse and human spermatozoa exhibit order-specific binding to the zona pellucida, mice with 'humanized' chimaeric zonae may provide an experimental system to elucidate the molecular basis of sperm-zona interaction.

Amino Acid Motifs↗
PubMed2000

Decline in prevalence of neural tube defects in a high-risk region of the United States.

OBJECTIVES: To conduct surveillance for neural tube defects (NTDs) in a high-risk region of the United States and to prevent occurrence and recurrence of NTDs through the periconceptional use of folic acid supplements. DESIGN: Active and passive methods were used for surveillance of NTD-affected pregnancies and births during a 6-year period (October 1992-September 1998). Individual genetic counseling was used to prevent NTD recurrences and a public awareness campaign was used to reduce NTD occurrences. SETTING: State of South Carolina. PATIENTS: All cases of spina bifida, anencephaly, and encephalocele identified among 278 122 live births and fetal deaths to South Carolina residents during 1992-1998 were included. MAIN OUTCOME MEASURE: Changes in occurrence and recurrence rates during a 6-year period. RESULTS: Over the 6 years of surveillance, the prevalence rates for NTDs decreased from 1.89 to.95 cases per 1000 live births and fetal deaths. The prevalence decrease is explained primarily by a decrease in cases of spina bifida. Isolated NTDs accounted for 297/360 (82%) NTDs and 63/360 (18%) had at least 1 other structural anomaly. Females predominated among isolated NTDs but the sex distribution was equal among NTD cases with other anomalies. Prevalence rates for whites (1.48 cases per 1000 live births and fetal deaths) were higher than rates for blacks (.87 cases per 1000 live births and fetal deaths). There were no NTD recurrences in 113 subsequent pregnancies to mothers of infants with isolated NTDs who took periconceptional folic acid. The rate of periconceptional folic acid use among women of childbearing years increased from 8% to 35% during the 6-year project period. CONCLUSION: The prevalence of NTDs in a high-risk region has declined coincident with the increased periconceptional use of folic acid supplements among women of childbearing age.neural tube defects, high-risk region, birth defects, folic acid, spina bifida, anencephaly, encephalocele.

Adolescent↗
PubMed1999

Incorporation of mouse zona pellucida proteins into the envelope of Xenopus laevis oocytes.

All vertebrate eggs have extracellular matrices, referred to as the zona pellucida in Mus musculus and the vitelline envelope in Xenopus laevis. The mouse zona, composed of three sulfated glycoproteins (ZP1, ZP2, ZP3), is critical for fertilization and early development, and mice lacking a zona pellucida produce no live offspring. The primary structures of mouse ZP1 (623 amino acids), ZP2 (713 amino acids) and ZP3 (424 amino acids) have been deduced from full-length cDNAs, but posttranslational modifications result in mature zona proteins with molecular masses of 200-180 kDa, 140-120 kDa, and 83 kDa, respectively. The vitelline envelope forms a similar structure around Xenopus eggs and contains three glycoproteins that are structurally related (39-48% amino acid similarity) to the three mouse zona proteins. To investigate whether the structural semblances are sufficient to allow incorporation of the mouse zona proteins into the Xenopus vitelline envelope, capped synthetic mRNAs encoding ZP1, ZP2, and ZP3 proteins were injected into the cytoplasm of stage VI Xenopus oocytes. After 20 h of incubation the oocytes were harvested, and posttranslationally modified zona proteins were detected with monoclonal antibodies specific to mouse ZP1, ZP2, and ZP3. The oocytes were imaged with confocal microscopy to detect individual zona proteins in the extracellular matrix of the oocytes, and this localization was confirmed biochemically. Thus the mouse zona proteins appear to have been sufficiently conserved through 350 million years of evolution to be incorporated into the extracellular envelope surrounding Xenopus eggs.

Animals↗