Biomedical subjects

J Klein

Publications and source records attributed to J Klein.

At least 253 records · Page 14Linked to original sources

PubMed1998

Pharmacokinetic predisposition to nicotine from environmental tobacco smoke: a risk factor for pediatric asthma.

During the last decade several studies have shown that children whose parents smoke have higher rates of asthma. Recently, hair concentrations of cotinine have been shown to reflect systemic exposure to this constituent of smoke in both children and adults. At the present time it is not known, however, why some children exposed to passive smoking have asthma while others, similarly exposed, do not. The present study aimed at verifying whether asthmatic children are different from nonasthmatic children exposed to similar degrees of passive smoking in the way their bodies handle nicotine, a constituent of cigarette smoke. Seventy-eight asthmatic children were compared to 86 control children, all attending a consulting pediatric clinic in Toronto. A questionnaire completed by the parents and children detailed the daily number of cigarettes the child was exposed to and the identity of the smokers. Clinical data were extracted from the patients' charts. Urinary (corrected for creatinine) and hair concentrations of cotinine were measured by radioimmunoassays. The asthmatic and control children were of similar age, gender, and ethnic distribution, parental education, and socioeconomic status. Parents of asthmatic children tended to report a lower daily number of cigarettes (7.4 +/- 1.3/day vs. 11.2 +/- 2.3/day, p = 0.14), and this report agreed with the trend of urinary cotinine (47.1 +/- 9.1 ng/mg vs. 62.6 +/- 11.5 ng/mg, respectively). Conversely, children with asthma had on average twofold higher concentrations of cotinine in their hair (0.696 +/- 0.742 ng/mg) than control children (0.386 +/- 0.383) (p = 0.0001). In a similar manner, the hair:urine concentration ratio was significantly higher in children with asthma (0.028 +/- 0.002) than in their controls (0.18 +/- 0.003) (p = 0.0001). These results suggest that under exposure to similar amounts of nicotine, children with asthma have on average twofold higher systemic exposure to this constituent of cigarette smoke. These data suggest that out of all children passively exposed to environmental tobacco smoke, those who exhibit asthma have a higher systemic exposure to nicotine, possibly due to lower clearance rate. This is the first evidence of pharmacokinetic predisposition to environmental tobacco smoke as an etiological factor in pediatric asthma.

Adult↗

PubMed1998

[Importance of examination of the portal circulation using contrast media when there are indications for surgical anastomosis].

In a group of 79 patients hospitalized on account of haemorrhage associated with portal hypertension the authors evaluate the diagnostic yield of radiological and sonographic methods. Sonography is a non-invasive procedure and is useful for routine checks of the function of the anastomosis. Direct contrast examinations are essential in preoperative reflections and for evaluation of possible complications of an already established shunt. Indirect procedures are in the latter two instances inadequate and unreliable.

Contrast Media↗

PubMed1998

Cloning of major histocompatibility complex (Mhc) genes from threespine stickleback, Gasterosteus aculeatus.

The threespine stickleback Gasterosteus aculeatus is an important model in evolutionary and ethologic studies. Its utility would greatly be increased by the availability of molecular markers distinguishing individuals and populations. Such markers can be provided by the major histocompatibility complex (Mhc) genes, which are well known for their extensive polymorphism. In the present study, both class I and class II B Mhc genes have been identified and sequenced. Fifteen distinct class I exon 2 and exon 3 sequences were obtained and assigned to 12 loci on the basis of intron 2 length differences. Some of the loci appear to be related to class I loci identified previously in cichlid fish. The intron 2 sequences and insertions/deletions in exon 2 group the loci into three families (with one family divided further into two subfamilies) derived from different ancestral genes. The ancestors presumably diverged from one another before the divergence of Gasterosteiformes from Perciformes. The 12 distinct class II B sequences may be derived from six loci, which are, however, closely related to one another in both exonic and intronic parts and may have diverged from a single common ancestor after the divergence of Gasterosteiformes from Perciformes. The intron 2 of some of the class I genes contains two microsatellites that can be used as markers, in addition to the polymorphism of the Mhc genes in their exonic regions.

Amino Acid Sequence↗

PubMed1998

[Cervical deficit radiculopathy in 3 cases of vertebral artery dissection].

Three cases of extracranial vertebral artery dissections with upper limb peripheral motor deficit (C5-C6) are reported. Six similar cases were also found in the literature. Central neurological symptoms occurred in five of these nine cases, suggesting the diagnosis of dissection. The peripheral motor or sensorial deficit was strictly isolated in the four other cases, simulating radicular neuralgia due to discopathy or foraminal compression. In case of dissections, a precise analysis of pain is helpful to guide diagnosis; sharp, unbearable, continuous and extended neck pain without nocturnal paroxysms and posterior neck stiffness is typical. Analgesics or anti-inflammatory drugs are ineffective. Peripheral motor deficit is more common than sensory deficit. Recovery was complete in this series. In most cases, the radiculopathy appears to be due to cervical root compression in its extraforaminal course due to the dissection hematoma and rarely to radicular ischemia.

Adult↗

PubMed1997

Complex origin of the HLA-DR10 haplotype.

The region of the HLA complex occupied by the DRB genes has undergone many rearrangements in the course of primate evolution. The rearrangements have produced a number of haplotypes differing from one another in the number and composition of the DRB genes. Some of the rearrangements also affected the DRB genes themselves. Selective intron sequencing has revealed the DR10 haplotype to be composed of at least three segments, each of different origin. The haplotype carries three DRB genes (gene fragments): DRB1*10, DRB6, and DRB9. The 5' end of the DRB1*10 gene, from the promoter region to a site in intron 1 approximately 500 bp from the beginning of exon 2, is derived from a DRB1*03-like gene. The segment of the DR10 haplotype encompassing the rest of the DRB1*10 gene and extending to the region between the DRB1 and DRB6 genes is of independent origin; it diverged from other DRB genes (DRB1*01 and DRB1*03) approximately 30 million years ago. Finally, the third segment encompassing the remainder of the DR10 haplotype is derived from a DR1-like haplotype. Since the functional part of the DR10 haplotype is of independent origin, there is little justification for the currently common practice of placing the haplotype together with DR1 in the group of DR1 haplotypes. The rearrangements in the DR haplotypes may constitute one of several mechanisms for increasing diversity at the DRB loci. The region of high instability seems to be flanked by conservatively evolving regions.

Base Sequence↗

PubMed1997

Linkage of LMP, TAP, and RING3 with Mhc class I rather than class II genes in the zebrafish.

The LMP2 and LMP7 genes code for subunits of the proteasome, a multimeric enzymatic complex that degrades proteins into peptides. The two subunits replace corresponding constitutively expressed subunits during the immune response. Some of the peptides generated by the proteasome in the cytosol are transported by the products of the TAP1 and TAP2 genes into the lumen of the endoplasmic reticulum and are loaded onto the assembling MHC class I molecules. In mammals, the LMP2, LMP7, TAP1, and TAP2 genes reside in the class II region of the Mhc, closely linked to the RING3 gene. In the present study we identified, cloned, and sequenced the LMP, TAP2, and RING3 genes of the zebrafish, Danio rerio. We identified variants of these genes and used them in a segregation analysis of haploid embryos derived from heterozygous mothers. The analysis revealed that in zebrafish, the LMP2, LMP7, TAP12, and RING3 loci are closely linked but, in contrast to mammals, the LMP/TAP/RING3 cluster resides not in the Mhc class II but in the class I region. We also confirmed that in the zebrafish, the class I and class II regions are not linked to each other. In this species, therefore, the LMP/TAP/RING3 genes are clustered with the class I genes on a chromosome that apparently does not contain any class II genes. The linkage of LMP/TAP/RING3/class I may be the original and the LMP/TAP/RING3/class II a derived arrangement of these genes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Linkage of TATA-binding protein and proteasome subunit C5 genes in mice and humans reveals synteny conserved between mammals and invertebrates.

The TATA-binding protein (TBP) is a factor required for the transcription of all classes of eukaryotic genes. Here, we demonstrate that in the mouse the TBP-encoding gene (Tbp) resides next to the proteasomal subunit C5-encoding gene (Psmb1). The genes are located on mouse chromosome 17 in the t complex within the Hybrid sterility 1 (Hst1) region. We demonstrate that the homologous human genes (TBP AND PSMB1) are tightly linked on the long arm of chromosome 6, in a region syntenic with the proximal part of mouse chromosome 17. The mouse Tbp and Psmb1 and the human TBP and PSMB1 genes are transcribed in the opposite orientation. The TATA-binding protein and proteasomal subunit C5 genes are also linked on chromosome III of Caenorhabditis elegans, and together they are linked to other genes whose homologs map to human chromosome 6 and mouse chromosome 17. In the Drosophila genome, the housekeeping TATA-binding protein gene maps close to two other genes with homologs in the mammalian major histocompatibility complex. There thus exists conserved synteny of unrelated genes between mammals and invertebrates.

Animals↗

PubMed1997

Modulation of hippocampal acetylcholine release after fimbria-fornix lesions and septal transplantation in rats.

Female Long-Evans rats sustained electrolytic lesions of the fimbria and the dorsal fornix causing a partial lesion of the septohippocampal pathway. Two weeks later, the rats received intra-hippocampal grafts of fetal septal cell suspensions. Nine to twelve months later, the release of acetylcholine (ACh) in the hippocampus of sham-operated, lesion-only and grafted rats was measured by microdialysis. The extent of cholinergic (re)innervation was determined by acetylcholinesterase (AChE) staining and densitometry. In both lesion-only and grafted rats, the ratio of ACh release to AChE staining intensity was increased as compared to sham-operated rats, indicating a loss of endogenous inhibitory mechanisms. Scopolamine (0.5 mg/kg i.p.), a muscarinic antagonist, increased ACh release in all treatment groups. 8-OH-DPAT (0.5 mg/kg s.c.), an agonist at serotonergic 5HT1A-receptors, induced an increase of hippocampal ACh release in sham-operated rats. This effect was lost in lesion-only rats, but was fully restored by neuronal grafting. As 8-OH-DPAT influences hippocampal ACh release by a postsynaptic action, this finding indicates that the host brain exerts a serotonergic influence on the grafted cholinergic neurons.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1997

Phospholipid breakdown and choline release under hypoxic conditions: inhibition by bilobalide, a constituent of Ginkgo biloba.

A marked increase of choline release from rat hippocampal slices was observed when the slices were superfused with oxygen-free buffer, indicating hypoxia-induced hydrolysis of choline-containing phospholipids. This increase of choline release was suppressed by bilobalide, an ingredient of Ginkgo biloba, but not by a mixture of ginkgolides. The EC50 value for bilobalide was 0.38 microM. In ex vivo experiments, bilobalide also inhibited hypoxia-induced choline release when given p.o. in doses of 2-20 mg/kg 1 h prior to slice preparation. The half-maximum effect was observed with 6 mg/kg bilobalide. A similar effect was noted after p.o. administration of 200 mg/kg EGb 761, a ginkgo extract containing approximately 3% of bilobalide. We conclude that ginkgo extracts can suppress hypoxia-induced membrane breakdown in the brain, and that bilobalide is the active constituent for this effect.

Animals↗

PubMed1997

Polymorphism of the HLA-DRB1 locus in Colombian, Ecuadorian, and Chilean Amerinds.

We have characterized the DRB1 genotypes in a sample of 64 South American Indians drawn from populations in Chile, Colombia, and Ecuador. No novel DRB1 alleles were found in the total of 17 different alleles characterized, indicating that rapid allelic generation does not occur at the DRB1 loci, in contrast to HLA-B. Comparison between Chilean and Colombian/Ecuadorian samples revealed no major differences in their allelic frequencies. In the combined Amerind sample the HLA-DRB1*0407 and HLA-DRB1*1402 alleles occurred in the highest frequencies (38% and 22%, respectively). Genetic distance measurement showed the HLA-DRB1 frequencies reported here to agree with findings in other Amerind groups. The high frequencies of both HLA-DRB1*0407 and HLA-DRB1*1602 alleles, in conjunction with their absence in Siberian samples, suggest that migratory groups other than Siberians may have been involved in the peopling of the Americas.

Alleles↗

PubMed1997

Genetically modified Escherichia coli for colorimetric detection of inorganic and organic Hg compounds.

A sensitive colorimetric bacterial system was developed for the detection of Hg(II) and organomercury compounds. The bioactive species, a recombinant Escherichia coli, produces proportionally elevated levels of the enzyme beta-galactosidase with increasing amounts of Hg. This is due to a reporter plasmid which carriers a Hg(II)-inducible promoter (mer promoter) from the Hg resistance transposon Tn501 regulating the transcription of a promoterless lacZ gene. Additionally, a pMB1 origin of replication without the natural RNA polymerase start site is fused downstream of the mer promoter leading to a Hg(II)-inducible plasmid replication, which results in an improved signal-to-noise ratio. To enhance the sensitivity of this cellular biosensor, the transport proteins for Hg(II) uptake are constitutively produced by a helper plasmid. To enable the detection of organically bound Hg, the Streptomyces lividans organomercurical lyase, an enzyme which catalyses the cleavage of C-Hg-bonds of organomercurial compounds, is also provided by the helper plasmid. Hg(II) and phenylmercuric acetate (PMA) concentrations as low as 5 x 10(-10) M (0.1 ppb) may be detected within a few minutes.

Biological Transport↗

PubMed1997

Class I mhc genes of cichlid fishes: identification, expression, and polymorphism.

Cichlid fishes of the East African Rift Valley lakes constitute an important model of adaptive radiation. Explosive speciation in the Great Lakes, in some cases as recently as 12 400 years ago, generated large species flocks that have been the focus of evolutionary studies for some time. The studies have, however, been hampered by the paucity of biochemical markers for phylogenetic reconstruction. Here, we describe a set of markers which should help to alleviate this problem. They are the class I genes of the major histocompatibility complex. We provide evidence for the existence of at least 17 class I loci in cichlid fishes, and for extensive polymorphism of three of these loci. Since the polymorphism has a trans-species character, it will be possible to use it in investigating the founding events of the individual species. The sequences of the cichlid class I fishes support the monophyly of actinopterygian fish on the one hand, and of tetrapods on the other.

Animals↗

PubMed1997

Mapping of mhc class I and class II regions to different linkage groups in the zebrafish, Danio rerio.

The mammalian major histocompatibility complex (Mhc) consists of three closely linked regions, I, II, and III, occupying a single chromosomal segment. The class I loci in region I and the class II loci in region II are related in their structure, function, and evolution. Region III, which is intercalated between regions I and II, contains loci unrelated to the class I and II loci, and to one another. There are indications that a similar Mhc organization exists in birds and amphibians. Here, we demonstrate that in the zebrafish (Danio rerio), a representative of the teleost fishes, the class II loci are divided between two linkage groups which are distinct from the linkage group containing the class I loci. The beta2-microglobulin-encoding gene is loosely linked to one of the class II loci. The gene coding for complement factor B, which is one of the region III genes in mammals, is linked neither to the class I nor to the class II loci in the zebrafish. These results, combined with preliminary data suggesting that the class I and class II regions in another order of teleost fish are also in different linkage groups, indicate that close linkage of the two regions is not necessary either for regulation of expression or for co-evolution of the class I and class II loci. They also raise the question of whether linkage of the class I and class II loci in tetrapods is a primitive or derived character.

Animals↗

PubMed1997

Isolation of candidate hybrid sterility 1 genes by cDNA selection in a 1.1 megabase pair region on mouse chromosome 17.

The Hybrid sterility 1 (Hst1) gene causes male infertility in crosses between certain inbred strains of the laboratory and wild mouse, Mus musculus. To identify the causative gene, we have searched YAC clones encompassing the Hst1 region for testis-expressed sequences, using the cDNA selection method. We isolated 12 non-overlapping cDNA clones, sequenced them, and placed them on a physical map based on the analysis of YAC clones and total genomic DNA. The cDNA clones map to ten loci. Three cDNA sequences correspond to the proteasome subunit C5 (locus Psmb1), ornithine decarboxylase (Odc-rs15), and penta-zinc finger (Zfp91-rs1) transcripts. Three of the ten testis-expressed loci described in this report (D17Ph4e, Psmb1, and Zfp91-rs1) co-segregate with all Hst1 recombinants and, together with the Tbp gene, are therefore potential candidates for the Hst1 gene. The presented physical and genetic mapping data indicate there are no gross rearrangements distinguishing the Hst1(f) and Hst1(s) alleles.

Animals↗

PubMed1997

Evidence for convergent evolution of A and B blood group antigens in primates.

To determine whether convergent or trans-specific evolution is responsible for the persistence of the ABO polymorphism in apes, we have sequenced segments of introns 5 and 6 of the ABO gene. Four substitutions and one insertion or deletion group human A, B, and O alleles together, separate from their chimpanzee A and gorilla B counterparts. No shared substitutions support a trans-species mode of evolution for any of the alleles examined. We conclude that the A and B antigens of the chimpanzee and gorilla, respectively, have arisen by convergent evolution. Phylogenetic analysis suggests that the human A and B alleles are ancient, having diverged at least 3 million years ago. These alleles must have therefore been trans-specifically inherited within the genus Homo.

ABO Blood-Group System↗

PubMed1997

Activation of phospholipases C and D by the novel metabotropic glutamate receptor agonist tADA.

In hippocampal slices taken from 8-day-old rats, trans-azetidine-2,4-dicarboxylic acid (tADA), a novel glutamatergic agonist acting preferentially at class I mGluR receptors, activates phosphoinositide and phosphatidylcholine hydrolysis with widely different potencies. Inositol phosphate formation was maximally increased at 10 microM tADA (EC50: 1.2 microM), while phospholipase D activation was observed at a tADA concentration of 1 mM. This is the first report of a tADA-induced phospholipase D activity.

Animals↗

PubMed1997

Ontogenetic and pharmacological studies on metabotropic glutamate receptors coupled to phospholipase D activation.

The present study was aimed at characterizing the metabotropic receptor subtype which is involved in the activation of phospholipase D (PLD) by glutamate in rat hippocampal slices. We first observed that the ontogenetic profile of glutamate-induced hydrolysis of phosphoinositides and of phosphatidylcholine was strikingly similar. Both pathways were significantly activated by glutamate in tissue taken from 3-, 8- and 15-day old rats, but not in adult rats. PLD activation was strongest in slices taken from 8-day old rats. At this age, quisqualate had a higher potency for PLD activation (EC50: 0.6 microM) than 1S,3R-ACPD (EC50: 16 microM) and DHPG, a specific activator of group I mGluR, was a full agonist at PLD activation (EC50: 3.5 microM) indicating an involvement of a group I mGluR (mGluR1 and 5). MCPG and AIDA, two putative antagonists at mGluR1 receptors, caused a small but (in the case of MCPG) significant inhibition. DCG-IV, an activator of group II mGluR, was a weak partial agonist at PLD activation (EC50: 22 nM) while L-AP 4, an activator at group III mGluR, was totally inactive. Likewise, forskolin, a stimulant of cyclic AMP formation, was inactive either alone, or in combination with glutamatergic agonists. Pretreatment of the slices with pertussis toxin did not affect PLD activation. In summary, the glutamate-mediated activation of hippocampal PLD, which occurs transiently during postnatal development, is mediated by a group I mGluR, possibly involving mGluR5.

Animals↗

PubMed1997

Noninvasive methods for drug measurement in pediatrics.

Infants and children present a special challenge to drug monitoring because the disposition of drugs differs from adults and because there are far fewer clinical studies designed for children than for adults. The excuse for this unfortunate situation is the imposition of severe technical and ethical constraints caused by blood sampling; however, in the past two decades, several new noninvasive methods to measure drugs have been tested and implemented in therapeutic drug monitoring. It is our hope that these new techniques will help advance the ability to diagnose and manage infants and young children.

Adolescent↗