Biomedical subjects

M Keller

Publications and source records attributed to M Keller.

At least 109 records · Page 6Linked to original sources

PubMed1997

Lithium and recurrence in a long-term follow-up of bipolar affective disorder.

BACKGROUND: Though previous studies have clearly shown that lithium affords prophylaxis in bipolar affective disorder, these studies have not demonstrated the persistence of this prophylactic effect beyond the first year of recovery. METHODS: One hundred and eighty-one patients with bipolar affective disorder recovered during 5 years of semi-annual follow-up. After 8 weeks of recovery, 139 were taking lithium prophylaxis and 42 were not. Analyses used drug status (lithium v. no-lithium) as a censoring variable to compare these two groups by interval-specific probabilities of recurrence. RESULTS: Recurrence was initially less likely in the lithium group but interval-specific probabilities of recurrence did not consistently favour either group after the first 32 weeks of recovery. CONCLUSIONS: Biases in treatment decisions may have both reduced the size and altered the specificity of the lithium effects seen here. Nevertheless, the apparent transience of lithium prophylactic effects is unexplained and may reflect important, physiological differences between relapse and recurrence. This possibility invites a controlled lithium discontinuation study, with gradual taper, of patients who have had at least 8 months of sustained euthymia.

Adult↗

PubMed1997

The relation of childhood personality types to adolescent behavior and development: a longitudinal study of Icelandic children.

The relation of childhood personality types, or configurations of personality traits, to adolescent development was examined. Three personality types were identified in an inverse factor analysis of California Child Q-Sort data on 128 Icelandic 7-year-olds: resilient, overcontrolled, and undercontrolled. Growth curve analyses demonstrated that in comparison to children of the other 2 types, children of the resilient personality type had higher levels of academic achievement and lower levels of concentration problems throughout adolescence; resilient children also developed sophisticated friendship reasoning and an internal locus of control more quickly. Children of the overcontrolled type were found to be more prone to social withdrawal and low levels of self-esteem during adolescence than children of the other 2 types. In contrast to the other 2 types, children classified as undercontrolled showed an increase in aggressive behavior in adolescence. Implications of the findings for research on personality development are discussed.

Adolescent↗

PubMed1997

Prevention of coronary vascular abnormalities early in reperfusion with TGF-beta may not prevent late coronary vascular injury.

Endothelial injury, manifest by increased protein leak and decreased endothelium-dependent relaxation, occurs during reperfusion after ischemia. Transforming growth factor-beta (TGF-beta) has been shown to improve endothelium-dependent relaxation and reduce infarct size after short periods (from 20 min to 4.5 h) of reperfusion even when administered 24 h before the ischemic period. However, whether this represents a transient delay in the process leading to endothelial injury or prevention of injury has not been clear. To examine this issue, we measured protein leak, an index of coronary microvascular permeability, and endothelium-dependent relaxation, a measure of coronary endothelial function, after brief (1-h) and lengthy (48-h) reperfusion periods in dogs treated 30 min before ischemia with TGF-beta (30 microg/kg, i.v.) and control dogs. The left anterior descending coronary artery (LAD) was ligated for 1 h followed by 1 h of reperfusion (n = 10) or 48 h of reperfusion (n = 12). Protein leak was assessed by a dual-isotope technique by using radiolabeled transferrin and erythrocytes, and endothelium-dependent relaxation was assessed in epicardial coronary rings by using adenosine diphosphate (ADP), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent dilator. In control animals, there was a marked increase in the protein leak index (PLI) in the infarct zone (8.3 +/- 1.4 in 1-h dogs, and 8.7 +/- 0.9 in 48-h dogs) compared with the nonischemic myocardium (3.1 +/- 0.8 at 1 h, and 3.8 +/- 0.9 at 48 h). In TGF-beta treated dogs, there was a marked improvement in PLI in the infarct zone in 1-h dogs (PLI, 4.1 +/- 1.1; p < 0.05; or a 50% reduction compared with untreated dogs). However, the 48-h dogs treated with TGF-beta failed to demonstrate an improvement in PLI (PLI, 8.5 +/- 0.9; p = NS). Endothelium-dependent relaxation was impaired in the LAD in control dogs, and treatment with TGF-beta failed to improve relaxation after 1 or 48 h of reperfusion. Microvascular permeability was increased and endothelium-dependent relaxation was decreased after ischemia at both 1 and 48 h of reperfusion. Pretreatment with TGF-beta reduced the increase in permeability at 1 h of reperfusion but not at 48 h.

Animals↗

PubMed1997

The 32-kilobase exp gene cluster of Rhizobium meliloti directing the biosynthesis of galactoglucan: genetic organization and properties of the encoded gene products.

Proteins directing the biosynthesis of galactoglucan (exopolysaccharide II) in Rhizobium meliloti Rm2011 are encoded by the exp genes. Sequence analysis of a 32-kb DNA fragment of megaplasmid 2 containing the exp gene cluster identified previously (J. Glazebrook and G. C. Walker, Cell 56:661-672, 1989) revealed the presence of 25 open reading frames. Homologies of the deduced exp gene products to proteins of known function suggested that the exp genes encoded four proteins involved in the biosynthesis of dTDP-glucose and dTDP-rhamnose, six glycosyltransferases, an ABC transporter complex homologous to the subfamily of peptide and protein export complexes, and a protein homologous to Rhizobium NodO proteins. In addition, homologies of three Exp proteins to transcriptional regulators, methyltransferases, and periplasmic binding proteins were found. The positions of 26 Tn5 insertions in the exp gene cluster were determined, thus allowing the previously described genetic map to be correlated with the sequence. Operon analysis revealed that the exp gene cluster consists of five complementation groups. In comparison to the wild-type background, all exp complementation groups were transcribed at a substantially elevated level in the regulatory mucR mutant.

Amino Acid Sequence↗

PubMed1997

Hb Osler [beta 145(HC2)Tyr-->Asp] results from posttranslational modification.

We studied two members of an African American family with erythrocytosis. An abnormal hemoglobin variant with an electrophoretic pattern on cellulose acetate similar to Hb J was identified. The oxygen dissociation curve using whole blood was biphasic, dramatically left-shifted, and hyperbolic. Sequence analysis of DNA from the proband showed heterozygosity for a T-->A change at the first position of codon 145 in the beta-globin gene which results in the substitution of an asparagine residue for normal tyrosine. The second cycle of C-terminal amino acid sequence analysis of a mixture of alpha- and beta-globin chains showed tyrosine, aspartic acid, and small amounts of asparagine. Collectively, these results indicate the existence of a mutation at codon 145 of the beta-globin gene which encodes for asparagine instead of tyrosine, and that asparagine then undergoes a partial posttranslational deamidation to aspartic acid. This amino acid substitution corresponds to Hb Osler, which is a high oxygen affinity hemoglobin variant, initially described to be caused by a substitution of Tyr-->Asp at beta 145. Posttranslational amino acid modification may constitute an important component in the pathophysiology of hemoglobinopathies.

Adult↗

PubMed1996

A synthetic cryIC gene, encoding a Bacillus thuringiensis delta-endotoxin, confers Spodoptera resistance in alfalfa and tobacco.

Spodoptera species, representing widespread polyphagous insect pests, are resistant to Bacillus thuringiensis delta-endotoxins used thus far as insecticides in transgenic plants. Here we describe the chemical synthesis of a cryIC gene by a novel template directed ligation-PCR method. This simple and economical method to construct large synthetic genes can be used when routine resynthesis of genes is required. Chemically phosphorylated adjacent oligonucleotides of the gene to be synthesized are assembled and ligated on a single-stranded, partially homologous template derived from a wild-type gene (cryIC in our case) by a thermostable pfu DNA ligase using repeated cycles of melting, annealing, and ligation. The resulting synthetic DNA strands are selectively amplified by PCR with short specific flanking primers that are complementary only to the new synthetic DNA. Optimized expression of the synthetic cryIC gene in alfalfa and tobacco results in the production of 0.01-0.2% of total soluble proteins as CryIC toxin and provides protection against the Egyptian cotton leafworm (Spodoptera littoralis) and the beet armyworm (Spodoptera exigua). To facilitate selection and breeding of Spodoptera-resistant plants, the cryIC gene was linked to a pat gene, conferring resistance to the herbicide BASTA.

Amino Acid Sequence↗

PubMed1996

Mapping of the entomocidal fragment of Spodoptera-specific Bacillus thuringiensis toxin CryIC.

Insecticidal CryI protoxins of Bacillus thuringiensis are activated by proteolysis in the midgut of insects. A conservation of proteolytic cleavage sites in the CryI proteins facilitates the expression of active toxins in transgenic plants to obtain protection from various insects. However, the engineering of CryIC toxins has, thus far, failed to yield applicable resistance to armyworms of Spodoptera species representing common insect pests worldwide. To improve the production of recombinant CryIC toxins, we established a CryIC consensus sequence by comparative analysis of three cryIC genes and tested the stability and protease sensitivity of truncated CryIC toxins in Escherichia coli and in vitro. In contrast to previous data, the boundaries of trypsin-resistant CryIC core toxin were mapped to amino acid residues I28 and R627. Proteolysis of the truncated CryIC proteins showed that Spodoptera midgut proteases may further shorten the C-terminus of CryIC toxin to residue A615. However, C-terminal truncation of CryIC to residue L614, and a mutation causing amino acid replacement I610T, abolished the insecticidal activity of CryIC toxin to S. littoralis larvae, as well as its resistance to trypsin and Spodoptera midgut proteases. Because no CryIC toxin carrying a proteolytically processed N-terminus could be stably expressed in bacteria, our data indicate that, in contrast to other CryI proteins, an entomocidal fragment located between amino acid positions 1 and 627 is required for stable production of recombinant CryIC toxins.

Amino Acid Sequence↗

PubMed1996

Five-year course of major depression: effects of comorbid alcoholism.

Some patients enter psychiatric treatment with clear cases of both major depression and alcoholism. While assumptions are often made about the relationships of these two conditions, little empirical evidence exists on the effects of sustained remissions in alcoholism on sustained remissions in depression. 127 patients with both disorders at treatment entry were studied over a 5-year period. Survival analyses with time-dependent covariates indicating alcoholism status were used to investigate remissions and relapses in major depression. Remission in alcoholism strongly and significantly increased the chances of remission in depression and were also related to reduced chances of depression relapse, although at a weaker level.

Adult↗

PubMed1996

Familial alcoholism in manic-depressive (bipolar) disease.

A previous analysis found a relatively high rate of alcoholism in a cohort of bipolar I subjects, and a trend for increased rates of alcoholism in relatives of subjects with both bipolar I disorder and alcoholism, compared to relatives of subjects with bipolar I disorder and no alcoholism. The sample of subjects with bipolar I disorder has been enlarged through continued follow-up, permitting new analyses to address the association and heritability of bipolar I disorder with alcoholism. Probands with bipolar I disorder were followed for 10 years as part of the NIMH Collaborative Depression Study. The rate of alcoholism in relatives of probands with both bipolar I disorder and alcoholism was compared to the rate of alcoholism in relatives of probands with bipolar disorder and no alcoholism. The prevalence of alcoholism in relatives of subjects with bipolar I disorder was compared to the rate of alcoholism in relatives of control subjects. Relatives of probands with bipolar I disorder showed a higher rate of alcoholism than relatives of controls. Relatives of probands with bipolar I disorder and alcoholism showed a higher rate of alcoholism than relatives of probands with bipolar I disorder without alcoholism. These data suggest that familial alcoholism may contribute to a vulnerability to bipolar I disorder, and that there is a shared heritability for the two disorders.

Adult↗

PubMed1996

Identification of levels of maternal HIV-1 RNA associated with risk of perinatal transmission. Effect of maternal zidovudine treatment on viral load.

OBJECTIVE: To determine if there are levels of human immunodeficiency virus type 1 (HIV-1) associated with a high or low risk of perinatal transmission and to ascertain the mechanism by which zidovudine treatment reduces perinatal transmission. DESIGN: A nonrandomized prospective cohort study. SETTING: University medical center and two general hospital affiliates from May 1989 to September 1994. PATIENTS: Ninety-two HIV-1-seropositive women (95 pregnancies) and their 97 infants. INTERVENTION: Forty-two mothers (43 pregnancies) received zidovudine therapy during pregnancy and/or during labor and delivery. Eleven infants received prophylactic zidovudine for the first 6 weeks after delivery. MAIN OUTCOME MEASURE: HIV-1 infection status of the infant. RESULTS: Twenty of the 97 infants were perinatally infected with HIV-1. Transmitting mothers were more likely to have plasma HIV-1 RNA levels higher than 50000 copies per milliliter at delivery than nontransmitting mothers (15 [75.0%] of 20 transmitters vs four [5.3%] of 75 nontransmitters; P < .001). None of the 63 women with less than 20000 HIV-1 RNA copies per milliliter transmitted. Twenty-two women treated with open-label oral zidovudine during gestation showed an eightfold median decrease in plasma RNA levels (median [25th and 75th percentile], 43043 [5699 and 63053] copies per milliliter before zidovudine vs 4238 [603 and 5116] HIV-1 RNA copies per milliliter at delivery; P < .001) and none transmitted. Four zidovudine-treated women with high HIV-1 levels transmitted despite the presence of zidovudine-sensitive virus in vitro in both the mothers and their infants. CONCLUSIONS: Maternal HIV-1 RNA levels were highly predictive of perinatal transmission risk and suggest that certain levels of virus late in gestation and/or during labor and delivery are associated with both a high risk and a low risk of transmission. Our results also suggest that zidovudine exerts a major protective effect by reducing maternal HIV-1 RNA levels prior to delivery and that further strategies are needed to prevent perinatal transmission in women with high or increasing virus levels and/or zidovudine-resistant virus.

AIDS Serodiagnosis↗

PubMed1996

Characterization of two bioluminescent Rhizobium meliloti strains constructed for field releases.

The deliberate release of genetically engineered microorganisms requires a thorough characterization of the microbes in question. For the two bioluminescent Rhizobium meliloti strains, L1 and L33 [Selbitschka et al. (1992) Mol Ecol 1:9-19; Selbitschka et al. (1995) FEMS Microbiol Ecol 16:223-232], designated for field release, the sites of genetic modifications in the chromosomes were sequenced from amplified genomic DNA. This indicated no unexpected alterations in the nucleotide sequence. The bioluminescent phenotype was stably inherited over more than 100 generations in liquid cultures. The presence of the luciferase gene in both strains did not have secondary effects on a variety of metabolic pathways as assessed by the Biolog GN system. A specific polymerase chain reaction amplification, based on the chromosomal insertion site of the luc cassette, allowed the discrimination between the two strains and thus simplifies monitoring. The RecA-deficient strain L1 showed a strongly (more than 90%) reduced ability to nodulate alfalfa in competition with its parent strain R. meliloti 2011 and its RecA+ counterpart L33.

Bacterial Proteins↗

PubMed1996

Utilisation of amino acid mixtures in adolescents with phenylketonuria.

The nutritional regimen of patients with phenylketonuria (PKU) comprises a diet of natural proteins and phenylalanine (Phe)-free amino acid (AA) mixture. The main daily protein requirement is covered by a Phe-free AA mixture. In an adult with PKU, the consumption of the daily AA requirement in one single dose at breakfast caused nausea and vomiting. Therefore, four studies were designed to investigate the adverse and metabolic effects resulting from large intakes of AA mixtures used in the treatment of PKU patients with respect to the following: (1) biochemical effects following consumption of one single dose of Phe-free AA mixture in healthy persons; (2) transient metabolic changes caused by different individual regimens of AA intake in healthy persons and in one PKU patient; (3) nitrogen excretion in PKU patients taking the AA mixture in two or three portions; and (4) catabolic metabolism of AA in a PKU patient. In healthy subjects following the ingestion of the AA mixture in one bolus there was an increase in the blood levels of the given AA and also an increase in blood insulin concentration and a decrease in blood glucose concentration. These changes were less marked when the AA mixture was divided into three portions per day. In contrast, in a PKU patient following the ingestion of AA there was an increase in blood glucose. The urinary nitrogen excretion was greater in PKU patients when one compared to three portions of AA mixture was taken. The consumption of the daily requirement of AA mixture in one single does produced increased catabolism in a PKU patient. In conclusion it is recommended that the total daily amount of AA mixture should be divided into a minimum of three portions.

Adolescent↗

PubMed1996

Ferroglobus placidus gen. nov., sp. nov., A novel hyperthermophilic archaeum that oxidizes Fe2+ at neutral pH under anoxic conditions.

A novel coccoid, anaerobic, Fe2+-oxidizing archaeum was isolated from a shallow submarine hydrothermal system at Vulcano, Italy. In addition to ferrous iron, H2 and sulfide served as electron donors. NO3- was used as electron acceptor. In the presence of H2, also S2O32- could serve as electron acceptor. The isolate was a neutrophilic hyperthermophile that grew between 65 degrees C and 95 degrees C. It represents a novel genus among the Archaeoglobales that we name Ferroglobus. The type species is Ferroglobus placidus (DSM 10642).

Archaea↗

PubMed1996

Digestion of delta-endotoxin by gut proteases may explain reduced sensitivity of advanced instar larvae of Spodoptera littoralis to CryIC.

The present study describes the correlation between gut protease activity of lepidopteran larvae of different instars, the inactivation of Bacillus thuringiensis delta-endotoxins in crystalline and noncrystalline forms, and the reduced susceptibility of advanced larval instars of Spodoptera littoralis to the toxin. The original assembly of delta-endotoxins in a crystal structure is essential for causing efficient larval mortality. Denaturation and renaturation (D/R) of delta-endotoxin crystals increased the vulnerability of the toxin molecules to proteolysis, reduced their capability to kill neonate larvae of S. littoralis, but sustained most of their larval growth-inhibition activity. E. coli-produced CryIC delta-endotoxin applied as a fraction of inclusion bodies exerted a growth inhibition effect, similar to the molecules released from the crystals by denaturation and subsequent renaturation. Incubation of CryIC with gut juice of 1st or 2nd instar larvae, left part of the CryIC toxin intact, while the toxin was completely degraded when incubated with gut juice of 5th instar larvae. The degradation rate was consistent with the increase of protease specific activity of the gut juice during larval development. This increase in toxin degradation may account for the loss of sensitivity of 5th instar larvae to CryIC. Specific protease inhibitors such as PMSF and Leupeptin were shown to inhibit gut proteases activity in all instar larvae, while, 1,10 phenanthroline, TLCK and TPCK were effective only in young instar larvae. The differential effect of protease inhibitors on proteases obtained from different larval instars indicated that gut juice protease profiles change with larval age. The observed quantitative and qualitative differences in degradation of delta-endotoxin by larval gut proteases that occur during larval maturation may account for the difference in susceptibility to the delta-endotoxin. This finding should be taken into consideration when designing strategies for the development of transgenic crops expressing delta-endotoxins as potent insecticidal proteins.

Animals↗

PubMed1996

Frequent recurrence and persistence of varicella-zoster virus infections in children infected with human immunodeficiency virus type 1.

OBJECTIVE: To examine complications and treatment of varicella-zoster virus (VZV) infections in children infected with human immunodeficiency virus type 1 (HIV-1). METHODS: Cases of VZV infection were identified retrospectively by reports to the department of health services and review of medical charts. The CD4+ cell counts were correlated with severity and frequency of VZV episodes. RESULTS: We identified 117 episodes of VZV infection in 73 HIV-1-infected children between Aug. 21, 1986, and Dec. 1, 1993. The most common complications were recurrence and persistence; 38 children (53%) had 69 recurrent episodes of VZV infection. The majority of children (61%) had zoster during the first recurrent episode, and 32% had a disseminated eruption typical of varicella. There was a strong association between an increasing number of episodes of VZV infection and low CD4+ cell count (p = 0.0008). In a subgroup followed for at least 2 years after their primary varicella episode, 10 of 22 children had a recurrence. Persistence of VZV infection was documented in 10 of 73 children, whereas other complications were rare. Thirty-three children (45%) were hospitalized and received acyclovir intravenously. CONCLUSION: Primary, recurrent, and persistent VZV infections are a frequent cause of morbidity and hospitalization for HIV-1-infected children. Studies of improved preventive and therapeutic agents are urgently needed in this population.

AIDS-Related Opportunistic Infections↗

PubMed1996

Is the fetal brain-sparing effect a risk factor for the development of intraventricular hemorrhage in the preterm infant?

The intrauterine identification of fetuses at risk of developing intraventricular hemorrhage would be helpful to the perinatologist, in light of the recent results which suggest that indomethacin given to the infant reduces the risk of developing intraventricular hemorrhage. We hypothesized that fetuses undergoing brain sparing, as identified by a lowered pulsatility index (PI) in the middle cerebral artery, and delivered prior to 34 weeks may differ in terms of being at risk for intraventricular hemorrhage from those fetuses without the brain-sparing effect. The middle cerebral artery PI was studied in 43 fetuses between 25 and 33.6 weeks' gestation. The pregnancies were complicated by pre-eclampsia, intrauterine growth restriction (IUGR) and preterm labor. A cranial sonogram was performed during the first postnatal week in all the neonates. Intraventricular hemorrhage was present in 6/22 infants with a normal middle cerebral artery PI (group A) and 0/21 with an abnormal middle cerebral artery PI (group B) (p < 0.05). The mothers of the six fetuses who developed intraventricular hemorrhage underwent preterm labor. IUGR fetuses and pre-eclampsia were more common in group B. No difference was found between the two groups when the following variables were compared: (1) gestational age at the time of the Doppler study; (2) gestational age at delivery; (3) antenatal exposure to steroids; (4) antenatal exposure to magnesium; (5) Apgar score greater than 6 at 5 min; (6) respiratory distress syndrome in the newborn; (7) necrotizing enterocolitis; (8) Cesarean section; and (9) sepsis in the infant. Although the mean birth weight was significantly lower in group B than group A, no fetus in this group developed intraventricular hemorrhage. The fetal brain-sparing effect, pre-eclampsia and IUGR were associated with a lower risk of neonatal intraventricular hemorrhage than was preterm labor. Preterm labor appears to be a key factor in the development of intraventricular hemorrhage and must be included when testing associations with intraventricular hemorrhage.

Cerebral Arteries↗

PubMed1996

Synergistic activity of a Bacillus thuringiensis delta-endotoxin and a bacterial endochitinase against Spodoptera littoralis larvae.

In an attempt to increase the insecticidal effect of the delta-endotoxin crystal protein CryIC on the relatively Cry-insensitive larvae of Spodoptera littoralis, a combination of CryIC and endochitinase was used. CryIC comprising the first 756 amino acids from Bacillus thuringiensis K26-21 and endochitinase ChiAII encoded by Serratia marcescens were separately produced in Escherichia coli carrying the genes in overexpression vectors. The endochitinase on its own, even at very low concentrations (0.1 microgram/ml), perforated the larval midgut peritrophic membrane. When applied together with low concentrations of CryIC, a synergistic toxic effect was obtained. In the absence of chitinase, about 20 micrograms of CryIC per ml was required to obtain maximal reduction in larval weight, while only 3.0 micrograms of CryIC per ml caused a similar toxic effect in the presence of endochitinase. Thus, a combination of the Cry protein and an endochitinase could result in effective insect control in transgenic systems in which the Cry protein is not expressed in a crystalline form.

Animals↗

PubMed1996

Importance of psychotic features to long-term course in major depressive disorder.

OBJECTIVE: Most efforts to describe the prognostic significance of psychotic features in depression have been limited to single assessments 1 year or less after the initial evaluation. However, the various biological and treatment response differences between patients with psychotic and nonpsychotic depression suggest that prognostic differences may be very long-term. METHOD: The 787 patients described here entered the study as they sought treatment at one of five academic medical centers; they had either RDC major depressive disorder or schizo-affective depression (other than the mainly schizophrenic subtype) and completed at least 6 months of follow-up. Of these, 144 (18.3%) had psychotic depression as defined here. Patients provided follow-up interviews at 6-month intervals for 5 years and annually thereafter; 98 of those with psychotic depression and 434 of those with non-psychotic depression were followed for 10 years. RESULTS: Those who began follow-up with psychotic depression had fewer weeks with minimal symptoms in each of the 10 years of follow-up and reported more psychosocial impairment at both 5 and 10 years. Both the index episode and the first recurrence of psychotic depression lasted longer than nonpsychotic episodes, but nonpsychotic episodes among previously psychotic individuals were relatively brief. Intervals between episodes were significantly shorter for patients who had ever been psychotic. CONCLUSIONS: Together with evidence that psychotic features are highly recurrent, these data show 1) that psychotic features denote a lifetime illness of greater severity and 2) that within individuals, psychotic features may emerge in only the more severe episodes.

Adult↗