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Biomedical subjects

C Rosenberg

Publications and source records attributed to C Rosenberg.

At least 91 records · Page 5Linked to original sources

Screening and treating depressed patients. A comparison of two controlled citalopram trials across treatment settings: hospitalized patients vs. patients treated by their family doctors. Danish University Antidepressant Group.

This study is a comparison across treatment settings of two previously published trials, namely the Danish University Antidepressant Group (DUAG) study on citalopram vs. clomipramine in hospitalized patients with major depression, and the Nordic citalopram vs. imipramine study of depressed patients treated by their family doctors. The Hamilton Depression Scale (HAM-D) had the same level of inter-rater reliability and construct validity in the two settings. Using a HAM-D score of 7 or less as the criterion for full two remission, clomipramine was superior to imipramine and citalopram. Using a reduction of the baseline HAM-D score by 50% or more as a response criterion, there were no differences between the three antidepressants after 5 or 6 weeks of treatment. Citalopram showed superior tolerability to the tricyclic antidepressants.

Citalopram↗

FRAXF in a patient with chromosome 8 duplication.

We report on a folate sensitive fragile site at Xq27-28 in a girl with a multiple congenital anomalies and mental retardation syndrome, who also carries a duplication of the long arm of chromosome 8. The fragile site was shown by FISH to be distal to both FRAXA and FRAXE. DNA hybridisation with probe OxF14 showed the amplification of the CGG repeats of locus FRAXF in the patient and in her clinically normal mother.

Blotting, Southern↗

Alterations of yeast artificial chromosome transgenic sequences in stretched embryonic stem-cell chromatin visualized by fluorescence in situ hybridization.

Transgenic mice have been generated from embryonic stem (ES) cells carrying functional genes cloned within yeast artificial chromosomes (YACs). Information on the integrity and organization of the inserted sequences, including the number of copies and their orientation to each other, is still limited by current methods. We have applied fluorescence in situ hybridization to stretched chromatin preparations from YAC-transfected ES cells to analyze the organization and copy number of the integrated sequences.

Animals↗

Sleep, breathing, and cephalometrics in older children and young adults. Part I -- Normative values.

STUDY OBJECTIVES: Aims were (1) to provide normative values for sleep and sleep-related breathing variables and physical features (cephalometrics, body mass index [BMI], and tonsillar size) in older children/adolescents and young adults, (2) to describe sex and age group differences, and (3) to evaluate relationships between physical features and sleep-related breathing variables. DESIGN: Standard polysomnographic variables describing sleep and breathing were measured during a single night. Cephalometric measures were obtained from a standing lateral skull radiograph. SUBJECTS: Normal, healthy boys (n=23; mean age=13.3+/-2.1 years), girls (n=22; mean age =13.8+/-1.8 years), men (n=23; mean age=22.2+/-1.5 years), and women (n=24; mean age=22.4+/-1.8 years) with BMI less than 27 were evaluated. RESULTS: Sleep variables showed age group and sex differences consistent with published norms. Slow-wave sleep and rapid eye movement (REM) latency declined with age; transient arousals increased with age. Sleep-related breathing variables showed few changes related to age group or sex; small but statistically significant sex differences were found for arterial oxygen saturation nadir (lower in male subjects) and respiration disturbance index in non-REM sleep (greater in male subjects). Differences in cephalometric measures largely reflected normal growth and expected sex differences. No significant relationships between sleep-related breathing variables and physical findings were observed. CONCLUSIONS: These data provide well-controlled normative values for sleep, breathing, and cephalometrics in a group of normal older children, adolescents, and young adults. The data provide useful reference points for patients of these ages in whom sleep apnea is suspected, particularly since such clinical studies are normally based on first-night polysomnography. Furthermore, these values represent developmentally appropriate grouping of the data.

Adolescent↗

Sleep, breathing, and cephalometrics in older children and young adults. Part II -- Response to nasal occlusion.

STUDY OBJECTIVES: We postulated that nasal occlusion would provide a challenge enabling us to assess factors predisposing development of sleep apnea in older children/adolescents and young adults. Factors of interest included sex, age, body mass index (BMI), tonsillar hypertrophy, and cephalometric measurements. DESIGN: Sleep and breathing variables were examined and compared for four groups of subjects between one baseline night and one night of nasal occlusion in a sleep research laboratory. SUBJECTS: Healthy, normal boys (n=23, mean age=13.3+/-2.1 years), girls (n=22, mean age=13.8+/-1.8 years), men (n=23, mean age=22.2+/-1.5 years), and women (n=24, mean age=22.4+/-1.8 years) were studied. MEASUREMENTS AND RESULTS: The following sleep and sleep-related breathing measures showed significant increases in all four groups from baseline to occlusion: percentage of stage 1, number of transient arousals, transient arousal index, apnea index, respiratory disturbance index (RDI), and mean apnea length. No significant relationships were found between occlusion-night RDI and tonsillar size, cephalometric variables, or BMI, either singly or in combination. CONCLUSIONS: Subjects' responses to nasal occlusion varied: most demonstrated a minimal and clinically insignificant increase in RDI; few showed a marked increase in RDI. Significant increases of sleep fragmentation -- even in the absence of frankly disturbed breathing -- indicate that nasal occlusion may secondarily affect waking function if prolonged over a series of nights.

Adolescent↗

Characteristics of subjects with chronic pain, in relation to local and widespread pain report. A prospective study of symptoms, clinical findings and blood tests in subgroups of a geographically defined population.

The relation between reported chronic pain and clinical findings was studied by comparing survey data six months before and eighteen months after a clinical examination. Studied individuals (n = 165) were randomly selected from subsamples of an initial survey (n = 1806) to a general population. Among individuals reporting chronic pain 85% were assessed to have chronic pain at the examination. Diagnoses were found in 22% of examined pain individuals. Myofascial pain syndrome and myalgia were the most common findings. Compared with located neck-shoulder pain, widespread pain had a greater impact on the individual, a worse prognosis regarding pain duration and working capacity, and revealed a raised serum urate level of unclear significance. Although no specific cause of pain is found in individuals with widespread pain it is important to identify and treat this group due to the great effects on functional capacity and the worse prognosis.

Adult↗

An STS-based map of the human genome.

A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.

Animals↗

Intron phase correlations and the evolution of the intron/exon structure of genes.

Two issues in the evolution of the intron/exon structure of genes are the role of exon shuffling and the origin of introns. Using a large data base of eukaryotic intron-containing genes, we have found that there are correlations between intron phases leading to an excess of symmetric exons and symmetric exon sets. We interpret these excesses as manifestations of exon shuffling and make a conservative estimate that at least 19% of the exons in the data base were involved in exon shuffling, suggesting an important role for exon shuffling in evolution. Furthermore, these excesses of symmetric exons appear also in those regions of eukaryotic genes that are homologous to prokaryotic genes: the ancient conserved regions. This last fact cannot be explained in terms of the insertional theory of introns but rather supports the concept that some of the introns were ancient, the exon theory of genes.

Amino Acid Sequence↗

The Rhizobium meliloti region located downstream of the nod box n6 is involved in the specific nodulation of Medicago lupulina.

Six nod box regulatory sequences are present in the Rhizobium meliloti genome. We have analysed the DNA region located downstream of nod box n6, and identified three open reading frames, designated nolQa, nolQb and nolS. LacZ fusions in these ORFs are not induced by classical nod gene inducers, which indicates that their expression either is not under the control of the nod box, or involves another regulatory mechanism acting in conjunction with the NodD/nod box regulatory circuit. Mutations in this n6 locus result in a delay in nodule formation on a particular host, Medicago lupulina. As this region is not strictly conserved among different R. meliloti strains, nolQa, nolQb and nolS may constitute auxiliary nodulation genes, for which the selection pressure is limited to particular host plants.

Gene Expression Regulation, Bacterial↗

TRPC1, a human homolog of a Drosophila store-operated channel.

In many vertebrate and invertebrate cells, inositol 1,4,5-trisphospate production induces a biphasic Ca2+ signal. Mobilization of Ca2+ from internal stores drives the initial burst. The second phase, referred to as store-operated Ca2+ entry (formerly capacitative Ca2+ entry), occurs when depletion of intracellular Ca2+ pools activates a non-voltage-sensitive plasma membrane Ca2+ conductance. Despite the prevalence of store-operated Ca2+ entry, no vertebrate channel responsible for store-operated Ca2+ entry has been reported. trp (transient receptor potential), a Drosophila gene required in phototransduction, encodes the only known candidate for such a channel throughout phylogeny. In this report, we describe the molecular characterization of a human homolog of trp, TRPC1. TRPC1 (transient receptor potential channel-related protein 1) was 40% identical to Drosophila TRP over most of the protein and lacked the charged residues in the S4 transmembrane region proposed to be required for the voltage sensor in many voltage-gated ion channels. TRPC1 was expressed at the highest levels in the fetal brain and in the adult heart, brain, testis, and ovaries. Evidence is also presented that TRPC1 represents the archetype of a family of related human proteins.

Adult↗

PCDD/PCDF levels in the blood of workers at a pulp and paper mill.

Blood samples from 34 workers at a pulp and paper mill and from 14 control persons were analysed for 2,3,7,8-substituted PCDDs and PCDFs. There were no statistically significant differences in total lipid-adjusted PCDD/PCDF concentrations, expressed as toxic equivalents, in blood plasma between the potentially exposed bleaching plant or paper mill workers and the controls. The mean level was 61 pg/g I-TEQ in bleaching plant workers, 60 pg/g I-TEQ in paper mill workers and 49 I-TEQ pg/g in controls. Regarding the concentrations of individual isomers, however, there was an indication that the blood plasma concentrations might be affected by the living and working environment.

Adult↗

Selection of adrenal tumor cells in culture demonstrated by interphase cytogenetics.

Solid tumors often consist of an admixture of cell populations with different genome constitutions. Karyotyping of this material is complicated by the low mitotic index. Even when chromosome studies are feasible, altered representation of the original cell populations after cell cultivation is possible. We report a human adrenal carcinoma that exhibited a normal karyotype after cultivation but was shown to be highly aneuploid when investigated by fluorescence in situ hybridization (FISH) in direct preparations of uncultured cells with six different centromeric probes. The high frequencies of trisomy for the investigated chromosomes in these interphase cells indicate that most of the tumor cells were in the triploid range. Strong selection for disomic cells was detected in interphase preparations after one and two subcultures and was even stronger in the corresponding metaphase preparations. Trisomy for chromosome 15 appeared to be maintained independent of triploidy and might play a role in cultured cell survival. The number of chromosome 17 centromeres was not increased in polyploid cells, suggesting loss of this chromosome in the original cells of the tumor.

Adrenal Gland Neoplasms↗

High resolution DNA fiber-fish on yeast artificial chromosomes: direct visualization of DNA replication.

Fluorescent in situ hybridization (FISH) is a powerful, direct and sensitive technique with a wide resolution range that enables the simultaneous study of multiple targets, labelled in different colours. Spreading techniques, denoted here as 'Fiber-FISH', increase FISH-resolution to the DNA fiber, using decondensed nuclear DNA as hybridization target. FISH could be a powerful analytical tool for thorough physical examination of yeast artificial chromosomes (YACs) which are often chimaeric or contain internal deletions. However, with one exception restricted to meiotic yeast chromosomes, FISH has not been used successfully on yeast/YAC DNA. We have developed a fast and simple method that can be applied routinely for compositional and structural analysis of cosmid and YAC DNA in yeast. It enables precise localization and ordering of clones, resolves overlaps and distances and gives a detailed picture of the integrity and colinearity of both probe and target. The combination of high resolution, signal abundance and short yeast cell cycle allows direct visualization of replicating DNA fibers. In a 400 kb region of the human dystrophin gene, we identified two replication origins, demonstrating that human DNA cloned in yeast is capable of initiating its own replication.

Chromosomes, Artificial, Yeast↗

Gas chromatographic-mass spectrometric determination of chlorophenols in the urine of sawmill workers with past use of chlorophenol-containing anti-stain agents.

The aim of this work was to establish whether workers at sawmills where chlorophenol-containing anti-stain agents had been previously used were still exposed to chlorophenols. A gas chromatographic-mass spectrometric (GC-MS) procedure for the determination of chlorophenols in urine was developed. Chlorophenols were determined from hydrolysed urine as acetylated derivatives and determined by GC-MS using selected ion monitoring (SIM). Isolation of the chlorophenols with toluene gave the best extraction efficiencies (65-119%). Stability tests at -20 degrees C showed no degradation of the chlorophenols studied during 6 months. The limit of quantification was 3.6 ng mg-1 creatinine for 2,4,6-trichlorophenol, 5.5 ng mg-1 for 2,3,4,6-tetrachlorophenol and 3.6 ng mg-1 for pentachlorophenol. Traces of 2,4,6-trichlorophenol, 2,3,4,6-tetrachlorophenol and pentachlorophenol were found both in previously exposed workers and in non-exposed controls, the urinary concentrations ranging from 1.1 to 15.9 ng mg-1 creatinine. The concentrations of urinary chlorophenols in previously exposed workers were of the same magnitude as those found in non-exposed controls and in the general population. The results show that it is unlikely that sawmill workers would be currently occupationally exposed to chlorophenols or polychlorinated dibenzo-p-dioxins and dibenzofurans via a contaminated work environment.

Acetylation↗

In Rhizobium meliloti, the operon associated with the nod box n5 comprises nodL, noeA and noeB, three host-range genes specifically required for the nodulation of particular Medicago species.

In Rhizobium meliloti, the genes required for nodulation of legume hosts are under the control of DNA regulatory sequences called nod boxes. In this paper, we have characterized three host-specific nodulation genes, which form a flavonoid-inducible operon down-stream of the nod box n5. The first gene of this operon is identical to the nodL gene identified by Baev and Kondorosi (1992) in R. meliloti strain AK631. The product of the second gene, NoeA, presents some homology with a methyltransferase. nodL mutants synthesize Nod factors lacking the O-acetate substituent. In contrast, in strains carrying a mutation in either noeA or noeB, no modification in Nod-factor structure or production could be detected. On particular hosts, such as Medicago littoralis, mutants of the n5 operon showed a very weak nodule-forming ability, associated with a drastic decrease in the number of infection threads, while nodulation of Medicago truncatula or Melilotus alba was not affected. Thus, nodL noeA and noeB are host-specific nodulation genes. By using a gain-of-function approach, we showed that the presence of nodL, and hence of O-acetylated Nod factors, is a major prerequisite for confering the ability to nodulate alfalfa upon the heterologous bacterium Rhizobium tropici.

Acetylation↗

The effect of zidovudine and 2'3'-dideoxyinosine on human trophoblast in culture.

Trophoblast from term and first trimester placenta, maintained in culture, were exposed to 20 mumoles/l zidovudine or 2'3'dideoxyinosine. Several indices of function were measured and compared to control trophoblast in parallel culture. The results from individual placentas were examined by Student's t-test and cumulative results by ANOVA. Neither zidovudine or 2'3'-dideoxyinosine had statistically significant effects on the function of term trophoblast, following a 48 hr exposure to the drug as indicated by hCG secretion, protein synthesis and glucose consumption. In one of five placentas exposed to zidovudine, progesterone secretion was reduced as compared to its control but remained in the high range. Zidovudine had no significant effect on cultured trophoblast isolated from first trimester placenta even after prolonged exposure to the drug for eleven days. Both term and first trimester trophoblast in culture tolerate prolonged exposure to high concentrations of zidovudine or 2'3'-dideoxyinosine. Human trophoblast in culture provides a safe in vitro model for the screening of drugs intended for use during pregnancy.

Analysis of Variance↗