Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine, 2016
Reduction of the vertical transmission of hepatitis B virus (HBV) is important. No difference exi... more Reduction of the vertical transmission of hepatitis B virus (HBV) is important. No difference exists in infection rates between breast-fed and formula-fed infants born to hepatitis B-infected women, as long as the infant receives hepatitis B immune globulin and hepatitis B vaccine at birth. Recently, an expert review from the Society for Maternal-Fetal Medicine stated, ‘‘We recommend that women with HBV infection be encouraged to breast feed as long as the infant receives immunoprophylaxis at birth (HBV vaccination and hepatitis B immunoglobulin).’’ Although LactMed generally does not provide specific treatment information, the importance of infants’ receiving these products and the negligible risk of vertical transmission if they are given are provided in the record for each drug used to treat hepatitis B. Lamivudine and tenofovir are commonly used to treat hepatitis B. These drugs have not been studied in nursing mothers who are being treated solely for hepatitis B infection. However, they have both been studied fairly well in nursing mothers who are HIV+ with and without HBV infection. FDA-approved labeling for these drugs is somewhat confusing. The lamivudine (Epivir-HBV) label discusses excretion of lamivudine into milk at three to six times the dose used to treat hepatitis B (i.e., the dose used for HIV infection) and then states, ‘‘Because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue Epivir-HBV taking into consideration the importance of continued hepatitis B therapy to the mother and the known benefits of breastfeeding.’’ The warning for tenofovir (Viread) is even stronger, although it confusingly intertwines HIV transmission with hepatitis B, stating, ‘‘Because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving Viread.’’ A recent expert review concluded that there is currently no justification for contraindicating the use of lamivudine or tenofovir for hepatitis B during breastfeeding. An accompanying editorial pointed out the inconsistencies between their use during pregnancy and during breastfeeding in both labeling and international guidelines. Labeling and guidelines both recommend using tenofovir and lamivudine during pregnancy (where fetal exposure is much greater than breastfeeding exposure) for both HIV and hepatitis B infections and recommend that the drugs be continued during breastfeeding in HIV+ mothers, but they recommend against breastfeeding in mothers who have only hepatitis B infections. Another recent expert review from Australia, New Zealand, and the UK also states that breastfeeding should not be contraindicated for mothers with HBV infection taking tenofovir.
mRNAs that contain premature stop codons are selectively degraded in all eukaryotes tested, a phe... more mRNAs that contain premature stop codons are selectively degraded in all eukaryotes tested, a phenomenon termed “nonsense-mediated mRNA decay” (NMD) or “mRNA surveillance.” NMD may function to eliminate aberrant mRNAs so that they are not translated, because such mRNAs might encode deleterious polypeptide fragments. In both yeasts and nematodes, NMD is a nonessential system. Mutations affecting three yeast UPF genes or seven nematode smg genes eliminate NMD. We report here the molecular analysis of smg-2 of Caenorhabditis elegans . smg-2 is homologous to UPF1 of yeast and to RENT1 (also called HUPF1), a human gene likely involved in NMD. The striking conservation of SMG-2, Upf1p, and RENT1/HUPF1 in both sequence and function suggests that NMD is an ancient system, predating the divergence of most eukaryotes. Despite similarities in the sequences of SMG-2 and Upf1p, expression of Upf1p in C. elegans does not rescue smg-2 mutants. We have prepared anti-SMG-2 polyclonal antibodies and ...
Proceedings of the National Academy of Sciences, 1981
A method is described to detect and measure the frequency of spontaneous tandem genetic duplicati... more A method is described to detect and measure the frequency of spontaneous tandem genetic duplications located throughout the Salmonella genome. The method is based on the ability of duplication-containing strains to inherit two selectable alleles of a single gene during generalized transductional crosses. One allele of the gene carries an insertion of the translocatable tetracycline-resistance element Tn10; the other allele is a wild-type copy of that gene. Using this technique, we have measured the frequency of tandem duplications at 38 chromosomal sites and the amount of material included in 199 independent duplications. These results suggest that, in one region of the chromosome, tandem duplications are particularly frequent events. Such duplications have end points within rRNA (rrn) cistrons and probably arise by unequal cross-over between these dispersed repeated sequences. Spontaneously duplications of this type are harbored by as much as 3% of the bacterial population. Prelimi...
Eukaryotic messenger RNAs containing premature stop codons are selectively and rapidly degraded, ... more Eukaryotic messenger RNAs containing premature stop codons are selectively and rapidly degraded, a phenomenon termed nonsense-mediated mRNA decay (NMD). Previous studies with both Caenohabditis elegans and mammalian cells indicate that SMG-2/human UPF1, a central regulator of NMD, is phosphorylated in an SMG-1-dependent manner. We report here that smg-1, which is required for NMD in C. elegans, encodes a protein kinase of the phosphatidylinositol kinase superfamily of protein kinases. We identify null alleles of smg-1 and demonstrate that SMG-1 kinase activity is required in vivo for NMD and in vitro for SMG-2 phosphorylation. SMG-1 and SMG-2 coimmunoprecipitate from crude extracts, and this interaction is maintained in smg-3 and smg-4 mutants, both of which are required for SMG-2 phosphorylation in vivo and in vitro. SMG-2 is located diffusely through the cytoplasm, and its location is unaltered in mutants that disrupt the cycle of SMG-2 phosphorylation. We discuss the role of SMG-...
The oxide superconductors, particularly those recently discovered that are based on La(2)CuO(4), ... more The oxide superconductors, particularly those recently discovered that are based on La(2)CuO(4), have a set of peculiarities that suggest a common, unique mechanism: they tend in every case to occur near a metal-insulator transition into an odd-electron insulator with peculiar magnetic properties. This insulating phase is proposed to be the long-sought "resonating-valence-bond" state or "quantum spin liquid" hypothesized in 1973. This insulating magnetic phase is favored by low spin, low dimensionality, and magnetic frustration. The preexisting magnetic singlet pairs of the insulating state become charged superconducting pairs when the insulator is doped sufficiently strongly. The mechanism for superconductivity is hence predominantly electronic and magnetic, although weak phonon interactions may favor the state. Many unusual properties are predicted, especially of the insulating state.
The division of one cell into two requires the coordination of multiple components. We describe a... more The division of one cell into two requires the coordination of multiple components. We describe a gene, car-1, whose product may provide a link between disparate cellular processes. Inhibition of car-1 expression in Caenorhabditis elegans embryos causes late cytokinesis failures: cleavage furrows ingress but subsequently regress and the spindle midzone fails to form, even though midzone components are present. The localized accumulation of membrane that normally develops at the apex of the cleavage furrow during the final phase of cytokinesis does not occur and organization of the endoplasmic reticulum is aberrant, indicative of a disruption in membrane trafficking. The car-1 gene has homologues in a number of species, including proteins that associate with RNA binding proteins. CAR-1 localizes to P-granules (germ-line specific ribonucleoprotein particles) and discrete, developmentally regulated cytoplasmic foci. These foci also contain DCAP-1, a protein involved in decapping mRNAs....
AUDs are increasingly recognized as common problems among older adults. The magnitude of this pro... more AUDs are increasingly recognized as common problems among older adults. The magnitude of this problem is likely to increase over ensuing decades as baby boomers reach retirement age with drinking habits that are significantly different from current cohorts of older adults. Barriers to detection are numerous and include nonspecificity of alcohol-related presentations, patient denial, and clinicians' unwillingness to recognize that patients can and do develop alcohol problems in later life. Despite the limitations of current screening and diagnostic instruments, the authors recommend use of the CAGE as a formal screening tool for older patients because of its brevity, demonstrated efficacy, and convenience. In patients who answer affirmatively to any CAGE question, diagnostic certainty can be increased by use of follow-up questions or referral to an alcohol treatment specialist. Referral of patients with established alcohol abuse or dependence is essential for definitive treatment, and successful outcomes can be expected and are gratifying once achieved. In patients with less severe AUDs, brief interventions with frequent follow-up are recommended. Age-specific screening and diagnostic instruments for older AUD patients, once fully developed and validated, will facilitate identification. Much less is known about other substance use disorders in older adults. Psychoactive drug use is not uncommon in this patient population and may result in adverse health outcomes. Treatment interventions proposed for AUDs are advocated for older adults found to have other substance use disorders as well and are likely to yield improved outcomes. Future investigations that better define the epidemiology, detection, and treatment of other substance use disorders in older populations are clearly warranted at this time.
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades mRNAs co... more Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades mRNAs containing premature translation termination codons (PTCs). SMG-1 and Upf1 transiently form a surveillance complex termed “SURF” that includes eRF1 and eRF3 on post-spliced mRNAs during recognition of PTC. If an exon junction complex (EJC) exists downstream from the SURF complex, SMG-1 phosphorylates Upf1, the step that is a rate-limiting for NMD. We provide evidence of an association between the SURF complex and the ribosome in association with mRNPs, and we suggest that the SURF complex functions as a translation termination complex during NMD. We identified SMG-8 and SMG-9 as novel subunits of the SMG-1 complex. SMG-8 and SMG-9 suppress SMG-1 kinase activity in the isolated SMG-1 complex and are involved in NMD in both mammals and nematodes. SMG-8 recruits SMG-1 to the mRNA surveillance complex, and inactivation of SMG-8 induces accumulation of a ribosome:Upf1:eRF1:eRF3:EJC complex on m...
Despite strong heritability, little is known about the genetic control of susceptibility to testi... more Despite strong heritability, little is known about the genetic control of susceptibility to testicular germ cell tumors (TGCT) in humans or mice. Although the mouse model of spontaneous TGCTs has been extensively studied, conventional linkage analysis has failed to locate the factors that control teratocarcinogenesis in the susceptible 129 family of inbred strains. As an alternative approach, we used both chromosome substitution strains (CSS) to identify individual chromosomes that harbor susceptibility genes and a panel of congenic strains derived from a selected CSS to determine the number and location of susceptibility variants on the substituted chromosome. We showed that 129-Chr 18MOLF males are resistant to spontaneous TGCTs and that at least four genetic variants control susceptibility in males with this substituted chromosome. In addition, early embryonic cells from this strain fail to establish embryonic stem cell lines as efficiently as those from the parental 129/Sv strai...
Testicular germ cell tumors (TGCT) are sex limited, occurring only in males with a Y chromosome. ... more Testicular germ cell tumors (TGCT) are sex limited, occurring only in males with a Y chromosome. Recently, the gr/gr deletion on the human Y chromosome was associated with increased risk of TGCTs. In addition, the presence of Y chromosome sequences is associated with TGCTs in cases of gonadal dysgenesis. TGCTs in strain 129 males recapitulate many aspects of testicular cancer in human infants and can be used to evaluate the role of the Y chromosome in TGCT risk. We used chromosome substitution strains and a sex-reversing mutant to test the role of the Y chromosome on TGCT susceptibility. Our results show that a Y-linked gene that does not differ among the tested strains is essential for tumorigenesis. [Cancer Res 2009;69(8):3614–8]
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine, 2016
Reduction of the vertical transmission of hepatitis B virus (HBV) is important. No difference exi... more Reduction of the vertical transmission of hepatitis B virus (HBV) is important. No difference exists in infection rates between breast-fed and formula-fed infants born to hepatitis B-infected women, as long as the infant receives hepatitis B immune globulin and hepatitis B vaccine at birth. Recently, an expert review from the Society for Maternal-Fetal Medicine stated, ‘‘We recommend that women with HBV infection be encouraged to breast feed as long as the infant receives immunoprophylaxis at birth (HBV vaccination and hepatitis B immunoglobulin).’’ Although LactMed generally does not provide specific treatment information, the importance of infants’ receiving these products and the negligible risk of vertical transmission if they are given are provided in the record for each drug used to treat hepatitis B. Lamivudine and tenofovir are commonly used to treat hepatitis B. These drugs have not been studied in nursing mothers who are being treated solely for hepatitis B infection. However, they have both been studied fairly well in nursing mothers who are HIV+ with and without HBV infection. FDA-approved labeling for these drugs is somewhat confusing. The lamivudine (Epivir-HBV) label discusses excretion of lamivudine into milk at three to six times the dose used to treat hepatitis B (i.e., the dose used for HIV infection) and then states, ‘‘Because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue Epivir-HBV taking into consideration the importance of continued hepatitis B therapy to the mother and the known benefits of breastfeeding.’’ The warning for tenofovir (Viread) is even stronger, although it confusingly intertwines HIV transmission with hepatitis B, stating, ‘‘Because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving Viread.’’ A recent expert review concluded that there is currently no justification for contraindicating the use of lamivudine or tenofovir for hepatitis B during breastfeeding. An accompanying editorial pointed out the inconsistencies between their use during pregnancy and during breastfeeding in both labeling and international guidelines. Labeling and guidelines both recommend using tenofovir and lamivudine during pregnancy (where fetal exposure is much greater than breastfeeding exposure) for both HIV and hepatitis B infections and recommend that the drugs be continued during breastfeeding in HIV+ mothers, but they recommend against breastfeeding in mothers who have only hepatitis B infections. Another recent expert review from Australia, New Zealand, and the UK also states that breastfeeding should not be contraindicated for mothers with HBV infection taking tenofovir.
mRNAs that contain premature stop codons are selectively degraded in all eukaryotes tested, a phe... more mRNAs that contain premature stop codons are selectively degraded in all eukaryotes tested, a phenomenon termed “nonsense-mediated mRNA decay” (NMD) or “mRNA surveillance.” NMD may function to eliminate aberrant mRNAs so that they are not translated, because such mRNAs might encode deleterious polypeptide fragments. In both yeasts and nematodes, NMD is a nonessential system. Mutations affecting three yeast UPF genes or seven nematode smg genes eliminate NMD. We report here the molecular analysis of smg-2 of Caenorhabditis elegans . smg-2 is homologous to UPF1 of yeast and to RENT1 (also called HUPF1), a human gene likely involved in NMD. The striking conservation of SMG-2, Upf1p, and RENT1/HUPF1 in both sequence and function suggests that NMD is an ancient system, predating the divergence of most eukaryotes. Despite similarities in the sequences of SMG-2 and Upf1p, expression of Upf1p in C. elegans does not rescue smg-2 mutants. We have prepared anti-SMG-2 polyclonal antibodies and ...
Proceedings of the National Academy of Sciences, 1981
A method is described to detect and measure the frequency of spontaneous tandem genetic duplicati... more A method is described to detect and measure the frequency of spontaneous tandem genetic duplications located throughout the Salmonella genome. The method is based on the ability of duplication-containing strains to inherit two selectable alleles of a single gene during generalized transductional crosses. One allele of the gene carries an insertion of the translocatable tetracycline-resistance element Tn10; the other allele is a wild-type copy of that gene. Using this technique, we have measured the frequency of tandem duplications at 38 chromosomal sites and the amount of material included in 199 independent duplications. These results suggest that, in one region of the chromosome, tandem duplications are particularly frequent events. Such duplications have end points within rRNA (rrn) cistrons and probably arise by unequal cross-over between these dispersed repeated sequences. Spontaneously duplications of this type are harbored by as much as 3% of the bacterial population. Prelimi...
Eukaryotic messenger RNAs containing premature stop codons are selectively and rapidly degraded, ... more Eukaryotic messenger RNAs containing premature stop codons are selectively and rapidly degraded, a phenomenon termed nonsense-mediated mRNA decay (NMD). Previous studies with both Caenohabditis elegans and mammalian cells indicate that SMG-2/human UPF1, a central regulator of NMD, is phosphorylated in an SMG-1-dependent manner. We report here that smg-1, which is required for NMD in C. elegans, encodes a protein kinase of the phosphatidylinositol kinase superfamily of protein kinases. We identify null alleles of smg-1 and demonstrate that SMG-1 kinase activity is required in vivo for NMD and in vitro for SMG-2 phosphorylation. SMG-1 and SMG-2 coimmunoprecipitate from crude extracts, and this interaction is maintained in smg-3 and smg-4 mutants, both of which are required for SMG-2 phosphorylation in vivo and in vitro. SMG-2 is located diffusely through the cytoplasm, and its location is unaltered in mutants that disrupt the cycle of SMG-2 phosphorylation. We discuss the role of SMG-...
The oxide superconductors, particularly those recently discovered that are based on La(2)CuO(4), ... more The oxide superconductors, particularly those recently discovered that are based on La(2)CuO(4), have a set of peculiarities that suggest a common, unique mechanism: they tend in every case to occur near a metal-insulator transition into an odd-electron insulator with peculiar magnetic properties. This insulating phase is proposed to be the long-sought "resonating-valence-bond" state or "quantum spin liquid" hypothesized in 1973. This insulating magnetic phase is favored by low spin, low dimensionality, and magnetic frustration. The preexisting magnetic singlet pairs of the insulating state become charged superconducting pairs when the insulator is doped sufficiently strongly. The mechanism for superconductivity is hence predominantly electronic and magnetic, although weak phonon interactions may favor the state. Many unusual properties are predicted, especially of the insulating state.
The division of one cell into two requires the coordination of multiple components. We describe a... more The division of one cell into two requires the coordination of multiple components. We describe a gene, car-1, whose product may provide a link between disparate cellular processes. Inhibition of car-1 expression in Caenorhabditis elegans embryos causes late cytokinesis failures: cleavage furrows ingress but subsequently regress and the spindle midzone fails to form, even though midzone components are present. The localized accumulation of membrane that normally develops at the apex of the cleavage furrow during the final phase of cytokinesis does not occur and organization of the endoplasmic reticulum is aberrant, indicative of a disruption in membrane trafficking. The car-1 gene has homologues in a number of species, including proteins that associate with RNA binding proteins. CAR-1 localizes to P-granules (germ-line specific ribonucleoprotein particles) and discrete, developmentally regulated cytoplasmic foci. These foci also contain DCAP-1, a protein involved in decapping mRNAs....
AUDs are increasingly recognized as common problems among older adults. The magnitude of this pro... more AUDs are increasingly recognized as common problems among older adults. The magnitude of this problem is likely to increase over ensuing decades as baby boomers reach retirement age with drinking habits that are significantly different from current cohorts of older adults. Barriers to detection are numerous and include nonspecificity of alcohol-related presentations, patient denial, and clinicians' unwillingness to recognize that patients can and do develop alcohol problems in later life. Despite the limitations of current screening and diagnostic instruments, the authors recommend use of the CAGE as a formal screening tool for older patients because of its brevity, demonstrated efficacy, and convenience. In patients who answer affirmatively to any CAGE question, diagnostic certainty can be increased by use of follow-up questions or referral to an alcohol treatment specialist. Referral of patients with established alcohol abuse or dependence is essential for definitive treatment, and successful outcomes can be expected and are gratifying once achieved. In patients with less severe AUDs, brief interventions with frequent follow-up are recommended. Age-specific screening and diagnostic instruments for older AUD patients, once fully developed and validated, will facilitate identification. Much less is known about other substance use disorders in older adults. Psychoactive drug use is not uncommon in this patient population and may result in adverse health outcomes. Treatment interventions proposed for AUDs are advocated for older adults found to have other substance use disorders as well and are likely to yield improved outcomes. Future investigations that better define the epidemiology, detection, and treatment of other substance use disorders in older populations are clearly warranted at this time.
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades mRNAs co... more Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades mRNAs containing premature translation termination codons (PTCs). SMG-1 and Upf1 transiently form a surveillance complex termed “SURF” that includes eRF1 and eRF3 on post-spliced mRNAs during recognition of PTC. If an exon junction complex (EJC) exists downstream from the SURF complex, SMG-1 phosphorylates Upf1, the step that is a rate-limiting for NMD. We provide evidence of an association between the SURF complex and the ribosome in association with mRNPs, and we suggest that the SURF complex functions as a translation termination complex during NMD. We identified SMG-8 and SMG-9 as novel subunits of the SMG-1 complex. SMG-8 and SMG-9 suppress SMG-1 kinase activity in the isolated SMG-1 complex and are involved in NMD in both mammals and nematodes. SMG-8 recruits SMG-1 to the mRNA surveillance complex, and inactivation of SMG-8 induces accumulation of a ribosome:Upf1:eRF1:eRF3:EJC complex on m...
Despite strong heritability, little is known about the genetic control of susceptibility to testi... more Despite strong heritability, little is known about the genetic control of susceptibility to testicular germ cell tumors (TGCT) in humans or mice. Although the mouse model of spontaneous TGCTs has been extensively studied, conventional linkage analysis has failed to locate the factors that control teratocarcinogenesis in the susceptible 129 family of inbred strains. As an alternative approach, we used both chromosome substitution strains (CSS) to identify individual chromosomes that harbor susceptibility genes and a panel of congenic strains derived from a selected CSS to determine the number and location of susceptibility variants on the substituted chromosome. We showed that 129-Chr 18MOLF males are resistant to spontaneous TGCTs and that at least four genetic variants control susceptibility in males with this substituted chromosome. In addition, early embryonic cells from this strain fail to establish embryonic stem cell lines as efficiently as those from the parental 129/Sv strai...
Testicular germ cell tumors (TGCT) are sex limited, occurring only in males with a Y chromosome. ... more Testicular germ cell tumors (TGCT) are sex limited, occurring only in males with a Y chromosome. Recently, the gr/gr deletion on the human Y chromosome was associated with increased risk of TGCTs. In addition, the presence of Y chromosome sequences is associated with TGCTs in cases of gonadal dysgenesis. TGCTs in strain 129 males recapitulate many aspects of testicular cancer in human infants and can be used to evaluate the role of the Y chromosome in TGCT risk. We used chromosome substitution strains and a sex-reversing mutant to test the role of the Y chromosome on TGCT susceptibility. Our results show that a Y-linked gene that does not differ among the tested strains is essential for tumorigenesis. [Cancer Res 2009;69(8):3614–8]
Uploads
Papers by philip anderson