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Biomedical subjects

Jan Klein

Publications and source records attributed to Jan Klein.

At least 55 records · Page 3Linked to original sources

Phylogenetic relationships among East African haplochromine fish as revealed by short interspersed elements (SINEs).

Genomic DNA libraries were prepared from two endemic species of Lake Victoria haplochromine (cichlid) fish and used to isolate and characterize a set of short interspersed elements (SINEs). The distribution and sequences of the SINEs were used to infer phylogenetic relationships among East African haplochromines. The SINE-based classification divides the fish into four groups, which, in order of their divergence from a stem lineage, are the endemic Lake Tanganyika flock (group 1); fish of the nonendemic, monotypic, widely distributed genus Astatoreochromis (group 2); the endemic Lake Malawi flock (group 3); and group 4, which contains fish from widely dispersed East African localities including Lakes Victoria, Edward, George, Albert, and Rukwa, as well as many rivers. The group 4 haplochromines are characterized by a subset of polymorphic SINEs, each of which is present in some individuals and absent in others of the same population at a given locality, the same morphologically defined species, and the same mtDNA-defined haplogroup. SINE-defined group 4 contains six of the seven previously described mtDNA haplogroups. One of the polymorphic SINEs appears to be fixed in the endemic Lake Victoria flock; four others display the presence-or-absence polymorphism within the species of this flock. These findings have implications for the origin of Lake Victoria cichlids and for their founding population sizes.

Africa↗

Ancestral population sizes and species divergence times in the primate lineage on the basis of intron and BAC end sequences.

The effective sizes of ancestral populations and species divergence times of six primate species (humans, chimpanzees, gorillas, orangutans, and representatives of Old World monkeys and New World monkeys) are estimated by applying the two-species maximum likelihood (ML) method to intron sequences of 20 different loci. Examination of rate heterogeneity of nucleotide substitutions and intragenic recombination identifies five outrageous loci (ODC1, GHR, HBE, INS, and HBG). The estimated ancestral polymorphism ranges from 0.21 to 0.96% at major divergences in primate evolution. One exceptionally low polymorphism occurs when African and Asian apes diverged. However, taking into consideration the possible short generation times in primate ancestors, it is concluded that the ancestral population size in the primate lineage was no smaller than that of extant humans. Furthermore, under the assumption of 6 million years (myr) divergence between humans and chimpanzees, the divergence time of humans from gorillas, orangutans. Old World monkeys, and New World monkeys is estimated as 7.2, 18, 34, and 65 myr ago, respectively, which are generally older than traditional estimates. Beside the intron sequences, three other data sets of orthologous sequences are used between the human and the chimpanzee comparison. The ML application to these data sets including 58,156 random BAC end sequences (BES) shows that the nucleotide substitution rate is as low as 0.6-0.8 x 10(-9) per site per year and the extent of ancestral polymorphism is 0.33-0.51%. With such a low substitution rate and short generation time, the relatively high extent of polymorphism suggests a fairly large effective population size in the ancestral lineage common to humans and chimpanzees.

Animals↗

Propofol-induced injection pain: comparison of a modified propofol emulsion to standard propofol with premixed lidocaine.

Propofol is well known for its association with pain on injection. The most frequently used method to reduce this pain is premixture with lidocaine. Recently, a modified lipid emulsion of propofol containing medium-chain triglycerides (MCT) with long-chain triglycerides (LCT), in contrast to the usual LCT formulation, has been advocated to alleviate pain. In a randomized, prospective, controlled, double-blind study on 222 surgical patients, we compared the effect of the two solutions on the incidence and intensity of injection pain. Patients were randomly allocated to receive either propofol MCT/LCT (group M; n = 109) or standard propofol LCT with the addition of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of propofol (group L; n = 113). Pain scores were assessed using a verbal analog scale (VAS) ranging from 0-10. Group L was found to have significantly less pain on the injection of propofol (mean VAS, 2.5 +/- 2.9) (mean +/- sd) than group M (mean VAS, 3.8 +/- 3.2; P = 0.002). Regarding postoperative recall of pain on injection, patients in group L indicated significantly less pain (mean VAS, 2.2 +/- 2.4) than patients in group M (mean VAS, 3.0 +/- 2.7; P = 0.02). Premixing of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of standard propofol LCT causes less pain on injection than propofol MCT/LCT and thus increases patient comfort.

Adolescent↗

A molecule bearing an immunoglobulin-like V region of the CTX subfamily in amphioxus.

An expressed sequence tag with significant similarity to a vertebrate T-cell receptor (Tcr) sequence was found in a cDNA library prepared from the posterior part of the adult amphioxus, Branchiostoma lanceolatum ( Brla). Characterization of the corresponding cDNA clone revealed the presence of an open reading frame encoding a 351 amino acid residue-long polypeptide. The putative protein, tentatively designated Brla-VDB for "V-domain bearing", appears to consist of two domains. The N-terminal domain begins with a putative leader peptide followed by a sequence resembling the V domain of the CTX protein originally found to be expressed in the cortical thymocytes of the clawed frog Xenopus. The C-terminal domain of the VDB protein does not show significant sequence similarity to any entry in the databases and contains five hydrophobic segments separated by short intervening hydrophilic stretches. It may therefore belong to a protein that crosses the plasma membrane five times. These findings support the notion that V domains resembling those found in Tcrs evolved in nonvertebrates before the emergence of the adaptive immune system and may have participated in functions not involved directly in immunity.

Amino Acid Sequence↗

Genes encoding putative natural killer cell C-type lectin receptors in teleostean fishes.

Mammalian natural killer (NK) cells are cytotoxic lymphocytes that express receptors specific for MHC class I molecules. The NK cell receptors belong to two structurally unrelated families, the killer cell Ig-like receptors and the killer cell C-type lectin receptors. We describe a cDNA clone derived from the bony (cichlid) fish Paralabidochromis chilotes and show that it encodes a protein related to the CD94/NK cell group 2 (NKG2) subfamily of the killer cell C-type lectin receptors. The gene encoding this receptor in a related species, Oreochromis niloticus, has a similar structure to the human CD94/NKG2 genes and is a member of a multigene cluster that resembles the mammalian NK cell gene complex. Thus, the CD94/NKG2 subfamily of NK cell receptors must have arisen before the divergence of fish and tetrapods and may have retained its function (possibly monitoring the expression of MHC class I molecules) for >400 million years.

Amino Acid Sequence↗

Origin and speciation of haplochromine fishes in East African crater lakes investigated by the analysis of their mtDNA, Mhc genes, and SINEs.

The Western Branch of the East African Great Rift Valley is pocketed with craters of extinct or dormant volcanoes. Many of the craters are filled with water, and the lakes are inhabited by fishes. The objective of the present study was to determine the amount and nature of genetic variation in haplochromine fishes inhabiting two of these crater lakes, Lake Lutoto and Lake Nshere, and to use this information to infer the origin and history of the two populations. To this end, sequences of mitochondrial (mt) DNA control region, exon 2 of major histocompatibility complex (Mhc) class II B genes, and short interspersed elements (SINEs) were analyzed. The results indicate that the Lake Nshere and Lake Lutoto fishes originated from different but related large founding populations derived from the Kazinga Channel, which connects Lake Edward and Lake George. Some of the genetic polymorphism that existed in the ancestral populations was lost in the populations of the two lakes. The polymorphism that has been retained has persisted for some 50000 generations (years). During this time, new mutations arose and became fixed in each of the two populations in the mtDNA, giving rise to sets of diagnostic substitutions. Each population evolved in isolation after the colonization of the lakes less than 50000 years ago. There appears to be no population structure within the crater lake fishes, and their present effective population sizes are in the order of 104 to 105 individuals. Comparisons with the endemic haplochromine species of Lake Victoria reveal interesting parallels, as well as differences, which may help to understand the nature of the speciation process.

Africa, Eastern↗

Statins are associated with a reduced incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery.

BACKGROUND: Patients undergoing major vascular surgery are at increased risk of perioperative mortality due to underlying coronary artery disease. Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (statins) may reduce perioperative mortality through the improvement of lipid profile, but also through the stabilization of coronary plaques on the vascular wall. METHODS AND RESULTS: To evaluate the association between statin use and perioperative mortality, we performed a case-controlled study among the 2816 patients who underwent major vascular surgery from 1991 to 2000 at the Erasmus Medical Center. Case subjects were all 160 (5.8%) patients who died during the hospital stay after surgery. From the remaining patients, 2 controls were selected for each case and were stratified according to calendar year and type of surgery. For cases and controls, information was obtained regarding statin use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. A vascular complication during the perioperative phase was the primary cause of death in 104 (65%) case subjects. Statin therapy was significantly less common in cases than in controls (8% versus 25%; P<0.001). The adjusted odds ratio for perioperative mortality among statin users as compared with nonusers was 0.22 (95% confidence interval 0.10 to 0.47). Similar results were obtained in subgroups of patients according to the use of cardiovascular therapy and the presence of cardiac risk factors. CONCLUSIONS: This case-controlled study provides evidence that statin use reduces perioperative mortality in patients undergoing major vascular surgery.

Adolescent↗

Identification and characterization of a TAP-family gene in the lamprey.

An expressed sequence tag obtained from a sea lamprey ( Petromyzon marinus) cDNA library was used to obtain a full-length coding sequence showing significant similarity to ABCB transporter proteins. The sequence is closely related to the mammalian ABCB9 protein and the TAP1 and TAP2 proteins that transport peptides for loading onto nascent Mhc class I molecules. The Pema-ABCB9 gene has an exon-intron organization similar to that of the mammalian TAP genes, with the exception of exon 2, which in the lamprey is split into two by a 949-bp long intron. The gene probably occurs in a single copy in the haploid lamprey genome. The ABCB9 genes appear to be evolving four-to-ten times slower than the TAP1 and TAP2 genes. Six putative transmembrane helices and the nucleotide-binding domain of the lamprey ABCB9 protein show high sequence similarity with the TAP1 and TAP2 molecules. The lamprey protein also contains sequence stretches that resemble the putative peptide interacting parts of the TAP1 and TAP2 molecules, but are peppered with ABCB9-specific residues.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Identification of chemokines and a chemokine receptor in cichlid fish, shark, and lamprey.

Chemokines are small, inducible, structurally related proteins that guide cells expressing the right chemokine receptors to sites of immune response. They have been identified and studied extensively in mammals, but little is known about their presence in other vertebrate groups. Here we describe seven new chemokines in bony fish and one in a cartilaginous fish, as well as one chemokine receptor in a jawless vertebrate. All eight chemokines belong to the SCYA (CC) subfamily characterized by four conserved cysteine residues of which the first two are adjacent. The chemokine receptor is of the CXCR4 type. Phylogenetic analysis does not reveal any clear evidence of orthology of fish and human chemokines. Although the divergence of the subfamilies began before the fish-tetrapod split, much of the divergence within the subfamilies took place separately in the two vertebrate groups. The existence of a chemokine receptor in the lamprey indicates that chemokines are apparently also present in the Agnatha.

Amino Acid Sequence↗

Macrophage migration inhibitory factor (MIF) of jawed and jawless fishes: implications for its evolutionary origin.

The macrophage migration inhibitory factor (MIF) is a cytokine produced by T lymphocytes and macrophages in response to inflammatory stimuli. We sequenced MIF cDNA clones of two jawless fishes, the sea lamprey (Petromyzon marinus) and the North Atlantic hagfish (Myxine glutinosa), as well as of the jawed (cichlid) fish Paralabidochromis chilotes. The fish MIF-encoding genes have the same exon-intron organization as the mammalian MIF genes and are present in one copy per haploid genome. Secondary and tertiary structure predictions suggest that the fish MIF proteins have a topology characteristic of the entire MIF-family of proteins. Phylogenetic analysis separates the known nematode members of the family into two groups, one having a sister group relationship with the mammalian D-dopachrome tautomerase (DDT) proteins and the other being related to vertebrate MIFs. It also reveals a high degree of convergent evolution among the members of the family. Finally, it suggests that the divergence of MIF and DDT occurred before the emergence of nematodes in metazoan evolution.

Amino Acid Sequence↗

Oxygen tension under hyperbaric conditions in healthy pig brain.

OBJECTIVE: To investigate the effect of hyperbaric conditions on brain oxygenation, intracranial pressure and brain glucose/lactate levels in healthy non-brain-traumatized animals. DESIGN AND SETTING: Prospective animal study in a hyperbaric chamber. SUBJECTS: Twelve adult Landrace/Yorkshire pigs. INTERVENTIONS: The animals were normoventilated in a pressure-controlled mode according to the open lung concept first at normobaric pressures (FiO2 of 0.4 and 1.0) and subsequently in the hyperbaric chamber at 1.9 and 2.8 bar (both at an FiO2 of 1.0). Under these conditions brain oxygen tension and intracranial pressure were recorded and brain glucose/lactate levels were measured by microdialysis. RESULTS: At normobaric conditions, increasing the FiO2 from 0.4 (baseline) to 1.0 resulted in a significant increase in brain oxygen tension from 33 +/- 14 to 63 +/- 28 mmHg (P<0.05). Compared with baseline, both hyperbaric conditions (at an FiO2 of 1.0) led to a significant increase in brain oxygen tension to 151 +/- 65 mmHg (P<0.001) at 1.9 bar and to 294 +/- 134 mmHg (P<0.001) at 2.8 bar. CONCLUSIONS: If there is a need for increased oxygenation in the brain, then one way to achieve this is to apply hyperbaric conditions at 100% oxygen. Compared with an atmospheric pressure with a FiO2 of 0.4, a nine-fold increase (900%) in PbrO2 values can be reached by increasing the FiO2 to 1.0 and the pressure to 2.8 bar. In this study, hyperbaric oxygen pressure in the brain did not lead to changes in intracranial pressure or in brain glucose/lactate levels.

Air Pressure↗

Gas embolism: pathophysiology and treatment.

Based on a literature search, an overview is presented of the pathophysiology of venous and arterial gas embolism in the experimental and clinical environment, as well as the relevance and aims of diagnostics and treatment of gas embolism. The review starts with a few historical observations and then addresses venous air embolism by discussing pulmonary vascular filtration, entrapment, and the clinical occurrence of venous air emboli. The section on arterial gas embolism deals with the main mechanisms involved, coronary and cerebral air embolism (CAE), and the effects of bubbles on the blood-brain barrier. The diagnosis of CAE uses various techniques including ultrasound, perioperative monitoring, computed tomography, brain magnetic resonance imaging and other modalities. The section on therapy starts by addressing the primary treatment goals and the roles of adequate oxygenation and ventilation. Then the rationale for hyperbaric oxygen as a therapy for CAE based on its physiological mode of action is discussed, as well as some aspects of adjuvant drug therapy. A few animal studies are presented, which emphasize the importance of the timing of therapy, and the outcome of patients with air embolism (including clinical patients, divers and submariners) is described.

Animals↗

Anti-inflammatory actions of acupuncture.

Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of beta-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-alpha and interleukin-10 are discussed.

Acupuncture Therapy↗

Molecular phylogeny of early vertebrates: monophyly of the agnathans as revealed by sequences of 35 genes.

Extant vertebrates are divided into three major groups: hagfishes (Hyperotreti, myxinoids), lampreys (Hyperoartia, petromyzontids), and jawed vertebrates (Gnathostomata). The phylogenetic relationships among the groups and within the jawed vertebrates are controversial, for both morphological and molecular studies have rendered themselves to conflicting interpretations. Here, we use the sequences of 35 nuclear protein-encoding genes to provide definitive evidence for the monophyly of the Agnatha (jawless vertebrates, a group encompassing the hagfishes and lampreys). Our analyses also give a strong support for the separation of Chondrichthyes (cartilaginous fishes) before the divergence of Osteichthyes (bony fishes) from the other gnathostomes.

Animals↗

Awareness: Monitoring versus remembering what happened.

BACKGROUND: Awareness during anesthesia is foremost assessed with postoperative interviews, which may underestimate its incidence. On-line monitors such as the Bispectral Index and patient response to verbal command are not necessarily commonly used. This study investigated response to command during deep sedation (Bispectral Index 60-70) and the ability of prevailing monitoring techniques to indicate awareness and predict recall. METHODS: The authors systematically assessed the response to command using the isolated forearm technique while monitoring electroencephalographic and hemodynamic variables. Fifty-six elective surgical patients were repeatedly given verbal instructions to squeeze the observer's hand during target-controlled infusion with propofol and alfentanil. After recovery, conscious recall was assessed with a short structured interview. RESULTS: Overall, 1,082 commands were given. No response was observed to 887 (82%) commands, an equivocal response was observed to 56 (5%) commands, and an unequivocal response was observed to 139 (13%) commands. Of the 37 patients (66%) with an unequivocal response to command ("awareness"), nine (25%) reported conscious recall after recovery. Their reports provided valuable insights as to how awareness may be adequately addressed. Hemodynamic variables poorly predicted awareness, whereas parameters derived from the encephalogram, especially the Bispectral Index, were highly significant predictors (P < 0.0001). Electroencephalographic parameters did not discriminate between patients with or without conscious recall, whereas heart rate and responsiveness to command did. CONCLUSIONS: The incidence of awareness is underestimated when conscious recall is taken as evidence. Awareness can be monitored on-line with behavioral and modern neurophysiologic measures. Providing feedback during intra-anesthetic awareness helps patients to cope with a potentially stressful situation.

Adult↗