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At least 271 records · Page 15Linked to original sources
PubMed2003

CpG island methylation in carcinoid and pancreatic endocrine tumors.

Carcinoid tumors and pancreatic endocrine tumors (PETs) are uncommon neuroendocrine neoplasms and their genetic alterations are not well characterized. CpG island methylation is a mechanism of gene silencing, and concordant methylation of multiple CpG islands as CpG island methylator phenotype (CIMP) has been described in tumors. The aim of this study was to evaluate CIMP in carcinoid tumors and PETs. We studied 16 carcinoid tumors, 11 PETs, and 22 associated normal mucosa or pancreas. Methylation status of the p14, p16, cyclo-oxygenase 2 (COX2), O(6)-methyl-guanine methyltransferase (MGMT), estrogen receptor (ER), thrombospondin 1 (THBS1), retinoic acid receptor beta 2 (RARbeta), T-type calcium channel (CACNA1G), and multiple endocrine neoplasia type-1 (MEN1) genes, and of MINT1, MINT2, MINT25, MINT27 and MINT31 loci was evaluated by methylation-specific-PCR (MSP) or combined bisulfite restriction analysis (COBRA). Carcinoid tumors were frequently methylated at RARbeta, MGMT, p16, COX2, p14, THBS1, and ER ranging from 25 to 63% of tumors. Other CpG islands were infrequently methylated or unmethylated. The adjoining normal mucosa was also methylated for ER, COX2, and RARbeta, but methylation at p14, p16, THBS1, and MGMT was tumor-specific. By contrast, PETs and normal pancreas were frequently methylated only at ER. Methylation was more frequent in carcinoid tumors than PETs at MGMT (25 versus 0%, p = 0.03), THBS1 (44 versus 9%, p = 0.04), p14 (44 versus 9%, p = 0.04) and RARbeta (25 versus 0%, p = 0.03). Loss of p16 protein expression correlated with methylation of p16 gene in carcinoid tumors (p = 0.006). Our study indicates that methylation profile of carcinoid tumors differs from PETs, reflecting different molecular pathogenesis.

Adult↗
PubMed2000

Reducing premature death and renal failure in Australian aboriginals. A community-based cardiovascular and renal protective program.

OBJECTIVE: To describe results of a systematic treatment program to modify renal and cardiovascular disease in an Aboriginal community whose rates of renal failure and cardiovascular deaths are among the highest in Australia. DESIGN: Longitudinal survey of people during treatment, and comparison of rates of natural death and renal failure with those in a historical control group. SETTING: Tiwi Islands (population, about 1800), November 1995 to December 1998. PARTICIPANTS: All adults with blood pressure > or = 140/90, with diabetes and urinary albumin/creatinine ratio (ACR) > or = 3.4 g/mol (microalbuminuria threshold), or with progressive overt albuminuria (ACR > or = 34 g/mol) were eligible for treatment. The historical control group comprised 229 people who satisfied these criteria in the pretreatment period 1992-1995. INTERVENTIONS: Perindopril, combined with calcium-channel blockers and diuretics if needed to achieve blood pressure goals; attempts to improve control of blood glucose and lipid levels; health education. MAIN OUTCOME MEASURES: Blood pressure, ACR, serum creatinine level and glomerular filtration rate (GFR) over two years of treatment; rates of renal failure and natural death compared with control group (analysed on intention-to-treat basis). RESULTS: 258 people enrolled in the program, and 118 had complete data for two years of treatment. In these 118, blood pressures fell significantly, while ACR and GFR stabilised. Rates of the combined endpoints of renal failure and natural death per 100 person-years were 2.9 for the treatment group (95% CI, 1.7-4.6) and 4.8 for the control group (95% CI, 3.3-7.0). After adjustment for baseline ACR category, the relative risk of the treatment group versus the control group for these combined endpoints was 0.47 (95% CI, 0.25-0.86; P = 0.013). Treatment benefit was especially marked in people with overt albuminuria or hypertension and in non-diabetic people. The estimates of benefit were supported by a fall in community rates of death and renal failure. CONCLUSIONS: Aboriginal people can participate enthusiastically in chronic disease management, with rapid, dramatic improvement in clinical profiles and mortality. Similar programs should be introduced urgently into other Aboriginal communities nationwide.

Adult↗
PubMed2005

Development of a cryogen-free concentration system for measurements of volatile organic compounds.

An innovative cryogen-free concentrator system for measurement of atmospheric trace gases at the parts per trillion level has been developed with detection by routinely used gas chromatographic methods. The first-generation system was capable of reaching a trapping temperature of -186 degrees C, while the current version can reach -195 degrees C. A Kleemenko cooler is used to create liquid nitrogen equivalent trapping conditions and eliminate the use of solid absorbents, a potential source of artifacts. The method utilizes dual-stage trapping with individual cold regions. The two stages are cooled to -20 and -175 degrees C for water management and sample enrichment, respectively. Both stages house a Silonite-coated stainless steel sample loop; the second stage loop is filled with 1-mm-diameter glass beads, which provide an inert surface area for analyte concentration. In our application, the complete system employed four channels utilizing two flame ionization detectors, one electron capture detector, and a mass spectrometer. The system was automated for unattended operation and was deployed off the New England east coast on Appledore Island to measure a suite of ambient non-methane hydrocarbons, halocarbons, alkyl nitrates, and oxygenated volatile organic compounds during the International Consortium for Atmospheric Research on Transport and Transformation field campaign in summer 2004. This robust system quantified 98 ambient volatile organic compounds with precisions ranging from 0.3 to 15%.

Journal Article↗
PubMedDate not supplied

Cellular interactions promote tissue-specific function, biomatrix deposition and junctional communication of primary cultured hepatocytes.

Hepatocytes, prepared from normal adult rat liver, were seeded onto a collagen substratum and cultured alone or in the presence of rat liver endothelial cells. When hepatocytes were cultured alone in a hormonally defined serum-free medium, decreased albumin production and rapid morphological deterioration of bile canaliculi structures and gap junctions occurred within 4 to 5 days. In contrast, hepatocytes cocultured with liver mesenchymal cells remained morphologically intact and biochemically functional for at least 4 weeks. They reorganized into small islands, continued to secrete high levels of albumin, did not express alpha-fetoprotein (a fetal marker), and remained strongly dye coupled. All of the hepatocytes synthesized albumin and retained their gap junctional channels. No junctional communication was observed between hepatocytes and endothelial cells. Long fibers containing fibronectin, Type I collagen and laminin distributed over the hepatocytes were induced in coculture but never appeared in hepatocytes cultured alone. Moreover, supplementation of the hormonally defined medium with phenobarbital and dimethyl sulfoxide, both of which improve the life span and functional activities of cultured hepatocytes, failed to induce reticulin fiber formation in pure culture of hepatocytes. The modulation of albumin secretion, biomatrix deposition and junctional communication observed in hepatocytes cultured with sinusoidal liver cells was also obtained when hepatocytes were in association with various epithelial or mesenchymal cells [rat liver epithelial cells (T51B), mouse embryonic fibroblasts (NIH 3T3), human or rat dermal fibroblasts and bovine aorta endothelial cells (AG 4762)].

Albumins↗
PubMed2001

Smoking-cessation counseling in the home. Attitudes, beliefs, and behaviors of home healthcare nurses.

BACKGROUND: Despite advances in smoking treatment, cessation rates remain stagnant, possibly a function of the lack of new channels to reach heavily addicted smokers. This cross-sectional study examined home care nurses' attitudes, beliefs, and counseling behaviors regarding counseling their home care patients who smoke. METHODS: Home healthcare nurses (N=98) from the Visiting Nurse Association of Rhode Island were randomly selected to participate in a study helping home-bound medically ill smokers to quit. At baseline, nurses completed a questionnaire that assessed a constellation of cognitive factors (self-efficacy, outcome expectations, perceived effectiveness, risk perception, motivation, and perceived patient adherence) as correlates of self-reported nurse counseling behaviors. RESULTS: Nurses with higher outcome expectations spent more time counseling their patients about quitting (p<0.04). Nurses' self-efficacy was the only variable associated with consistent counseling (p<0.05). While the majority of nurses "asked and advised" their patients, a minority of nurses "assisted or arranged" follow-up. Perceived importance of counseling was associated with a greater likelihood of asking, advising and assisting (p<0.05). None of the nurses who currently smoked (n=13) provided follow-up to their patients. Nurses who reported higher levels of both risk perception (regarding the harmful effects of smoking) and perceived effectiveness were more likely to recommend the nicotine patch. CONCLUSIONS: Attitudes and beliefs about smoking are significantly associated with nurse counseling behaviors. Helping nurses to overcome their barriers to smoking counseling may open up new channels for smoking intervention.

Adult↗
PubMed2000

The human and mouse methylenetetrahydrofolate reductase (MTHFR) genes: genomic organization, mRNA structure and linkage to the CLCN6 gene.

Methylenetetrahydrofolate reductase (MTHFR), a pivotal enzyme in folate metabolism, regulates the proportional distribution of one-carbon moieties between cellular methylation reactions and nucleic acid synthesis. The organization of the MTHFR gene and the structure of its mRNA were characterized in human and mouse. There are three mRNA transcripts of 2.8, 7.2 and 9.8 kb in human and two of 3.2 and 7.5 kb in mouse. Northern blot analysis revealed that human MTHFR MRNA is only present at low abundance in most tissues tested. Five kilobases of sequence flanking the 3' end of the human gene were isolated, and polyadenylation sites were defined by 3' RACE. The shorter 2.8 kb transcript and the two larger 7.2 and 9.8 kb transcripts utilize different polyadenylation signal sequences, 629 and 4937 bp downstream of the stop codon, respectively. The two mRNA species in mouse also result from differential polyadenylation. Approximately 7 and 3.5 kb upstream of the human and mouse genes, respectively, were isolated and sequenced. Transcription start sites in human MTHFR were mapped using 5' RACE. The 2.8 and 7.2 kb mRNAs originate from one of two transcription start sites that are 206 and 243 bp upstream of the ATG initiation codon, whereas transcription of the 9.8 kb mRNA is initiated at a start site located 2.8 kb upstream of the translation start codon. The putative MTHFR promoter does not have a TATA box but contains CpG islands and multiple potential Sp1 binding sites. The MTHFR gene was finely mapped to interval 16 of chromosome 1p36.3, a region deleted in many tumors, by establishing a close linkage to CLCN6, a putative chloride channel gene. A novel CA-repeat polymorphism identified within intron 2 of the CLCN6 gene may be useful in assessing loss of heterozygosity in such tumors. The multiple MTHFR mRNA species identified in this report may reflect an underlying complex set of gene regulatory mechanisms acting through an alternative transcription start site and/or polyadenylation signal sequence utilization.

3' Untranslated Regions↗
PubMed2001

Outcomes of an ecological and participatory approach to prevent alcohol and other drug "abuse" among multiethnic adolescents.

This study presents outcomes related to adolescents' alcohol use from an evaluation study testing the effectiveness of The Coalition for Youth Quality of Life Project (Le Regroupement pour la qualité de vie des jeunes). This project is an ecological and participatory approach developed to prevent alcohol and other drug use and misuse among multiethnic youth. The intervention was implemented through four channels of program delivery: families, schools, community organizations, and local government. The study involved 411 sixth graders from eight elementary schools and 380 eighth graders from two junior high schools, in two school districts of the Island of Montreal (province of Quebec, Canada). All students were enrolled in regular classes. Follow-up data were collected 18 months and 30 months after pre-test using a school survey. The findings indicated that the program had no significant impact on alcohol use. The program was, however, capable of producing a significant effect on several hypothesized mediating variables. At first follow-up, the sixth graders showed a higher self-esteem, better peer pressure resistance skills, and a more positive relationship with their father than the controls. The eighth graders were also more inclined to get involved in community activities related to substance abuse prevention and to choose more alternatives to "substance abuse" in their leisure time than the controls. The results are discussed by examining attrition effects and also reasons for program failure. Issues are raised about the evaluation of an ecological and participatory approach.

Adolescent↗
PubMed2002

Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19.

Recent data in humans and animals suggest that assisted reproductive technology (ART) might affect the epigenetics of early embryogenesis and might cause birth defects. We report the first evidence, to our knowledge, that ART is associated with a human overgrowth syndrome-namely, Beckwith-Wiedemann syndrome (BWS). In a prospective study, the prevalence of ART was 4.6% (3 of 65), versus the background rate of 0.8% in the United States. A total of seven children with BWS were born after ART-five of whom were conceived after intracytoplasmic sperm injection. Molecular studies of six of the children indicate that five of the six have specific epigenetic alterations associated with BWS-four at LIT1 and one at both LIT1 and H19. We discuss the implications of our finding that ART is associated with human overgrowth, similar to the large offspring syndrome reported in ruminants.

Adult↗
PubMed2004

Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma.

Kaposiform hemangioendothelioma (KH) is a rare tumor of childhood often associated with Kasabach-Merritt phenomenon (KMP) and occasionally lymphangiomatosis. Although generally considered distinct from other vascular neoplasms, its rarity has precluded a thorough study of its immunophenotypic profile and long-term behavior. Thirty-three cases of KH were reviewed and immunostained for alpha-smooth muscle actin, various endothelial markers (CD31, CD34, vWf, FLI1), a platelet marker (CD61), and the juvenile hemangioma-associated markers GLUT-1 and Lewis Y antigen (LeY). In addition, the presence of HHV-8 was evaluated by RT-PCR. The patients (20 males and 13 females) ranged in age from 2 weeks to 20 years (mean 3 years 9 months). Tumors developed on the extremities (17 cases), head/neck (8 cases), and other sites (8 cases) and affected both superficial and deep soft tissue. Those in the skin presented as slightly raised blue-red lesions. More than half of the patients presented with KMP (14 of 25). Tumors consisted of irregular, infiltrating nodules of compressed vessels, which modulated between areas resembling a capillary hemangioma and Kaposi sarcoma (KS). Endothelial cells in nodules were CD31, CD34, and FLI1 positive but negative for GLUT1 and LeY. Scattered "epithelioid" or glomeruloid islands featuring endothelium associated with clusters of plump alpha-smooth muscle actin-positive pericytes, stippled hemosiderin, and CD61-positive fibrin thrombi likely represent the morphologic sites of platelet consumption. Small and large lymphatic channels occurred in 22 of 33 cases and were typically seen peripheral or deep to the main tumor mass. HHV-8 transcripts were not identified (0 of 3 cases). Follow-up information was available in 22 patients (range 8 months to 15 years; mean 2 years) and indicated that 3 died of disease, 8 were alive with disease, and 10 were alive without residual disease. Two patients developed regional perinodal soft tissue involvement, but none developed distant metastases. KH is a lesion having both a vascular and lymphatic component. Its common association with KMP probably relates in part to unique architectural features that favor turbulent blood flow and platelet activation. KH can also be reliably separated from JH by GLUT-1 and LeY immunostaining, indicating differences in the morphologic and functional attributes of the endothelium between the two lesions. The absence of HHV-8 in KH underscores a different pathogenesis from Kaposi sarcoma. Our study, the largest to date, emphasizes that mortality is due to KMP and not metastatic disease, which appears limited to regional perinodal soft tissue. Given this behavior, its continued classification as a vascular tumor of intermediate malignancy is warranted.

Adolescent↗
PubMed1997

Recombinational and physical mapping of the locus for primary open-angle glaucoma (GLC1A) on chromosome 1q23-q25.

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness in industrialized countries. A locus for juvenile-onset POAG, GLC1A, has been mapped to 1q21-q31 in a 9-cM interval. With recombinant haplotypes, we have now reduced the GLC1A interval to a maximum of 3 cM, between the D1S452/NGA1/D1S210 and NGA5 loci. These loci are 2.8 Mb apart on a 4.7-Mb contig that we have completed between the D1S2851 and D1S218 loci and that includes 96 YAC clones and 48 STSs. The new GLC1A interval itself is now covered by 25 YACs, 30 STSs, and 16 restriction enzyme site landmarks. The lack of a NotI site suggests that the region has few CpG islands and a low gene content. This is compatible with its predominant cytogenetic location on the 1q24 G-band. Finally, we have excluded important candidate genes, including genes coding for three ATPases (ATP1B1, ATP2B4, ATP1A2), an ion channel (VDAC4), antithrombine III (AT3), and prostaglandin synthase (PTGS2). Our results provide a basis to identify the GLC1A gene.

Chromosome Mapping↗
PubMed1990

Intermingling of central and peripheral nervous tissues in rat dorsolateral vagal rootlet transitional zones.

The morphology of the CNS-PNS transitional zone of adult rat dorsolateral vagus nerve rootlets is uniquely complex. A typical rootlet contains a transitional zone over 300 microns long, consisting of a central tissue projection extending distally into each rootlet and a peripheral tissue insertion extending for a longer distance deep into the brainstem. The peripheral tissue insertion is continuous with the peripheral tissue of the free rootlet through channels traversing or running parallel to the central tissue projection. Accordingly, the vagal CNS-PNS interface is topologically much more complex than that found elsewhere. In some rootlets the peripheral tissue in the brainstem constitutes an isolated island deep within the neuraxis. In others, peripheral continuity is established only through a cross connection with the peripheral tissue insertion of a neighbouring rootlet. About one fifth of all vagal myelinated axons alternate between the CNS and PNS tissue compartments. This distinguishes the vagus from all other nerves studied to date. These axons are myelinated by Schwann cells distal to the transitional zone, by oligodendrocytes in the central tissue projection and by one or more short intercalated Schwann internodes further centrally, mostly in the peripheral tissue insertion, where their perikarya commonly form closely apposed aggregates. More than four fifths of all unmyelinated axon bundles alternate between central and peripheral tissue compartments, commonly more than once. In the peripheral tissue insertion axons are enveloped by series of non-myelinating Schwann cells. Schwann processes commonly extend for over 50 microns into the central compartment at each central-peripheral transition. Around one fifth of peripherally unmyelinated axons have an oligodendrocytic sheath in the central compartment. Of these axons possessing more than one intercalated Schwann internode, over one quarter display alternation of myelinated and unmyelinated segments in the peripheral tissue insertion. Astrocytes in the transitional zone segregate PNS tissue, a role played by sheath cells further peripherally in the vagal rootlets. Astrocytes form the surface limiting membranes of the central tissue projection and the barrier between the peripheral tissue insertion and the surrounding brainstem. The barrier consists only of an attenuated layer of processes. This is deficient in places, where oligodendrocytic myelin sheaths are directly exposed to the endoneurial space of the peripheral tissue insertion and in some instances are apposed to myelinating or non-myelinating Schwann cells. Such communication between the central and peripheral compartments is unique to the vagal transitional zone. The findings are consistent with a range of possible events during development.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

On site photosynthetic performance of Atlantic green algae.

Photosynthetic performance was measured on site in four common Atlantic green algae, Asparagopsis taxiforme, Valonia utricularia, Caulerpa racemosa and Codium taylori, in Gran Canaria, Canary Islands. The photosynthetic quantum yield was determined with a portable PAM instrument and with a diving PAM in the water column. Solar radiation was measured continuously above and in the water column by means of two three-channel dosimeters, ELDONET (Real Time Computer, Möhrendorf, Germany), in the UV-A, UV-B and PAR ranges. The effective photosynthetic quantum yield was found to be affected by exposure to solar radiation in as short as 15 min but recovered in the shade in most species within several hours. Only A. taxiforme failed to recover completely, and a 30-min exposure caused severe photoinhibition from which the algae recovered only partially. While most of the effect was due to the PAR wavelength range, the UV, and especially the UV-B, range considerably enhanced photoinhibition. In all four species, a significant inhibition was found even at their growth sites in the water column, measured with the diving PAM, at high solar angles.

Chlorophyta↗
PubMed2003

Epigenetic and genetic alterations in duodenal carcinomas are distinct from biliary and ampullary carcinomas.

BACKGROUND & AIMS: Carcinomas of the extrahepatic bile ducts, ampulla of Vater, and duodenum are uncommon, and their epigenetic and genetic alterations are not well characterized. METHODS: We therefore compared the methylation profile and genetic alterations in 18 extrahepatic biliary, 9 ampullary, and 12 duodenal carcinomas. We evaluated methylation at p16, p14, and human Mut L homologue (hMLH1) by methylation- specific PCR (MSP), and at cyclooxygenase 2 (COX2), O(6)-methyl-guanine methyltransferase (MGMT), estrogen receptor (ER), retinoic acid receptor beta 2 (RAR beta), and T-type calcium channel (CACNA1G) genes, and methylated in tumor 1 (MINT1), MINT2, MINT25, MINT27, and MINT31 loci by combined bisulfite restriction analysis (COBRA); mutation of K-ras, p53, p16, and p14 genes by sequencing; loss of heterozygosity of chromosome 9p; and microsatellite instability (MSI). RESULTS: Duodenal carcinomas were methylated more frequently or had increased methylation densities than biliary carcinomas at p14 (P = 0.04), hMLH1 (P = 0.04), MGMT (P = 0.01), MINT1 (P = 0.01), MINT25 (P = 0.01), MINT27 (P = 0.001), RAR beta (P = 0.03), and ER (P = 0.001), and than ampullary carcinomas at RAR beta (P = 0.02) and ER (P = 0.03). In contrast, the methylation profiles of biliary and ampullary carcinomas were not statistically different. Simultaneous methylation of 3 or more CpG islands (CpG island methylator phenotype-high) was more common in duodenal cancers (P = 0.004). MGMT methylation was associated with G-to-A mutation in K-ras (P = 0.006), and hMLH1 methylation was associated with MSI-high (P = 0.01). CONCLUSIONS: Our findings indicate that the methylation profile and genetic alterations of duodenal carcinomas are distinct from biliary and ampullary carcinomas, and that tumor-specific methylation is associated with gene mutation and MSI.

Adaptor Proteins, Signal Transducing↗
PubMed1989

Putting a premium on medical staffs. A novel way to insure physician liability (and loyalty).

The physician malpractice insurance crisis is having an adverse financial impact on both hospitals and their medical staffs. Innovative hospitals are exploring ways to create insurance arrangements to cover the professional liability of their medical staffs. Hospital risk managers often have theorized that if the same insurer covered both hospitals and their staff physicians, providers and their patients would benefit. These programs--often referred to as "channeling" or "channeled programs"--use a common risk management program, common claims administration, and a common claims defense for insured hospitals and their medical staffs, reducing costs, unfavorable verdicts, and, thus, premiums. Unfortunately only a few commercial carriers now offer such a program. Some hospitals and systems have therefore turned to "captive" insurance companies to provide the benefits of a channeled program. Hospitals or systems and their medical staffs can establish a captive (i.e., a controlled insurance company designed to insure its owners and their affiliates) either offshore (typically in a tax-free jurisdiction such as the Cayman Islands, Barbados, or Bermuda) or onshore (typically in a state with facilitating legislation). The Tax Reform Act of 1986, together with the Liability Risk Retention Act of 1986, generally tips the regulatory balance in favor of onshore captives by allowing these entities to operate as risk retention groups (RRGs).

Financial Management↗
PubMed2000

Relaxation of insulin-like growth factor 2 imprinting and discordant methylation at KvDMR1 in two first cousins affected by Beckwith-Wiedemann and Klippel-Trenaunay-Weber syndromes.

Beckwith-Wiedeman syndrome (BWS) and Klippel-Trenaunay-Weber syndrome (KTWS) are different human disorders characterized, among other features, by tissue overgrowth. Deregulation of one or more imprinted genes located at chromosome 11p15.5, of which insulin-like growth factor 2 (IGF2) is the most likely candidate, is believed to cause BWS, whereas the etiology of KTWS is completely obscure. We report a case of BWS and a case of KTWS in a single family. The probands, sons of two sisters, showed relaxation of the maternal IGF2 imprinting, although they inherited different 11p15.5 alleles from their mothers and did not show any chromosome rearrangement. The patient with BWS also displayed hypomethylation at KvDMR1, a maternally methylated CpG island within an intron of the KvLQT1 gene. The unaffected brother of the BWS proband shared the same maternal and paternal 11p15.5 haplotype with his brother, but the KvDMR1 locus was normally methylated. Methylation of the H19 gene was normal in both the BWS and KTWS probands. Linkage between the insulin-like growth factor 2 receptor (IGF2R) gene and the tissue overgrowth was also excluded. These results raise the possibility that a defective modifier or regulatory gene unlinked to 11p15.5 caused a spectrum of epigenetic alterations in the germ line or early development of both cousins, ranging from the relaxation of IGF2 imprinting in the KTWS proband to disruption of both the imprinted expression of IGF2 and the imprinted methylation of KvDMR1 in the BWS proband. Analysis of these data also indicates that loss of IGF2 imprinting is not necessarily linked to alteration of methylation at the KvDMR1 or H19 loci and supports the notion that IGF2 overexpression is involved in the etiology of the tissue hypertrophy observed in different overgrowth disorders, including KTWS.

3' Untranslated Regions↗
PubMed2000

Sequence and functional comparison in the Beckwith-Wiedemann region: implications for a novel imprinting centre and extended imprinting.

The clustered organization of most imprinted genes in mammals suggests coordinated genetic and epigenetic control mechanisms. Comparisons between human and mouse will help in elucidating these mechanisms by identifying structural and functional similarities. Previously we reported on such a comparison in the central part of the mouse imprinting cluster on distal chromosome 7 with the homologous Beckwith-Wiedemann syndrome (BWS) gene cluster on human chromosome 11p15.5. Here we focus on the adjacent sequences of 0.5 Mb including the KCNQ1/Kcnq1 and CDKN1C/Cdkn1c genes, which are implicated in BWS, and on one of the proposed boundary regions of the imprinting cluster. As in the previously analysed central region, this part of the cluster exhibits a highly conserved arrangement and structure of genes. The most striking similarity is found in the 3' part of the KCNQ1/Kcnq1 genes in large stretches of mostly non-coding sequences. The conserved region includes the recently identified KCNQ1OT1/Kcnq1ot1 antisense transcripts, flanked by a strikingly conserved cluster of LINE/Line elements and a CpG island which we show to carry a maternal germline methylation imprint. This region is likely to be the proposed second imprinting centre (IC2) in the BWS cluster. We also identified several novel genes inside and outside the previously proposed boundaries of the imprinting cluster. One of the genes outside the cluster, Obph1, is imprinted in mouse placenta indicating that at least in extra-embryonic tissues the imprinting cluster extends into a larger domain.

Alternative Splicing↗
PubMed1982

Microsurgical one-stage repair of hypospadias with a rectangular transverse dorsal preputial vascularized skin flap.

A microsurgical technique for one-stage repair of hypospadias using a rectangular transverse dorsal preputial island skin flap is presented. The use of optical magnification, atraumatic technique, and microsurgical instruments allows a vascularized preputial skin flap to be raised and isolated on the dorsum of the penis and then rotated ventrally and tubulized into a neourethral channel. The meatus of the new urethral channel lies at the tip of the glans. Cover for the penis is simply obtained and does not require a longitudinal row of sutures. The need to remove the distal stenotic portion of the urethra and to correct any degree of chordee is outlined and emphasized. Good cosmetic and functional results demonstrate the efficacy of such a technique.

Child↗