Biomedical subjects

Jan Klein

Publications and source records attributed to Jan Klein.

67 records · Page 4Linked to original sources

PubMed2002

The effect of selection on a long wavelength-sensitive (LWS) opsin gene of Lake Victoria cichlid fishes.

In East African Lake Victoria >200 endemic species of haplochromine fishes have been described on the basis of morphological and behavioral differences. Yet molecular analysis has failed to reveal any species-specific differences among these fishes in either mitochondrial or nuclear genes. Although the genes could be shown to vary, the variations represent trans-species polymorphisms not yet assorted along species lines. Nevertheless, fixed genetic differences must exist between the species at loci responsible for the adaptive characters distinguishing the various forms from one another. Here we describe variation and fixation at the long wavelength-sensitive (LWS) opsin locus, which is selection-driven, adaptive, and if not species- then at least population-specific. Because color is one of the characters distinguishing species of haplochromine fishes and color perception plays an important part in food acquisition and mate choice, we suggest that the observed variation and fixation at the LWS opsin locus may have been involved in the process that has led to the spectacular species divergence of haplochromine fishes in Lake Victoria.

Adaptation, Physiological↗

PubMed2002

Lamprey lymphocyte-like cells express homologs of genes involved in immunologically relevant activities of mammalian lymphocytes.

To shed light on the origin of adaptive immunity, a cDNA library was prepared from purified lymphocyte-like cells of a jawless vertebrate, the sea lamprey (Petromyzon marinus). Randomly selected cDNA clones were sequenced, and their homologies to proteins in the databases were determined. Of the sequences homologous to proteins involved in immune responses, five were selected for further characterization. Their encoding genes corresponded to loci that in jawed vertebrates are essential for activities of lymphocytes. These activities include regulation of T and B cell stimulation and proliferation (CD45); stabilization of molecular complexes involved in lymphocyte activation, adhesion, migration, and differentiation (CD9/CD81); adaptor functions in signaling leading to the activation of B lymphocytes (BCAP) and T lymphocytes (CAST); and amino acid transport associated with cell activation (CD98). The presence of these genes in the lamprey genome and their expression in lymphocyte-like cells support the notion that these cells perform many of the functions of gnathostome lymphocytes. It reopens the question of the stage jawless fishes reached in the evolution of their immune system.

Amino Acid Sequence↗

PubMed2002

Isolation and characterization of lymphocyte-like cells from a lamprey.

Lymphocyte-like cells in the intestine of the sea lamprey, Petromyzon marinus, were isolated by flow cytometry under light-scatter conditions used for the purification of mouse intestinal lymphocytes. The purified lamprey cells were morphologically indistinguishable from mammalian lymphocytes. A cDNA library was prepared from the lamprey lymphocyte-like cells, and more than 8,000 randomly selected clones were sequenced. Homology searches comparing these ESTs with sequences deposited in the databases led to the identification of numerous genes homologous to those predominantly or characteristically expressed in mammalian lymphocytes, which included genes controlling lymphopoiesis, intracellular signaling, proliferation, migration, and involvement of lymphocytes in innate immune responses. Genes closely related to those that in gnathostomes control antigen processing and transport of antigenic peptides could be ascertained, although no sequences with significant similarity to MHC, T cell receptor, or Ig genes were found. The data suggest that the evolution of lymphocytes in the lamprey has reached a stage poised for the emergence of adaptive immunity.

ATP-Binding Cassette Transporters↗

PubMed2002

Evidence that the separation of Mhc class II from class I loci in the zebrafish, Danio rerio, occurred by translocation.

In the zebrafish, Danio rerio, and other teleosts, the class I and class II loci of the major histocompatibility complex ( Mhc) reside on different chromosomes. To shed light on the events that might have generated this difference from tetrapods, in which these two types of loci are clustered in a single chromosomal region, the organization of the class II loci in linkage group 8 of the zebrafish was determined by the characterization of contigs of PAC clones. Three contigs were defined: DAB, DCB, and DBB. The 350-kb-long DAB contig contained only four genes: DDB, DAB, SLC7A4, and DAA. The 150-kb-long DCB contig contained the DCB, DCA, and fz10 genes at an undetermined distance from the DAB contig. And the 120-kb-long DBB contig comprised the DBB gene presumably in another linkage group. The low gene density of the linkage group 8 contigs, contrasting with the high gene density of the zebrafish class I region, and the close association with genes [ SLC7A4 coding for an amino acid transporter, and fz10 (frizzled 10) coding for a receptor of the WNT glycoprotein] that are not linked with the tetrapod Mhc, is interpreted to mean that the separation of the class II from class I loci in teleosts occurred by translocation rather than by genomic or chromosomal duplication.

Amino Acid Sequence↗

PubMed2002

Origin and affinities of indigenous Siberian populations as revealed by HLA class II gene frequencies.

Gene frequencies of eight Siberian populations (Mansi, Tuva, Todja, Tofalar, Buryat, Okhotsk Evenki, Ulchi, and Negidal) were determined for the three most polymorphic HLA class II loci ( DRB1, DQA1, and DQB1) by a combination of single-stranded conformational polymorphism typing and DNA sequencing. The number of alleles per population ranged from 16 to 25, from seven to eight, and from nine to 14 for the DRB1, DQA1, and DQB1 loci, respectively. The alleles at the three loci occurred in 66 different combinations (haplotypes), most of which appeared to be of ancient origin, but some may have arisen within the Siberian populations. Phylogenetic analysis of the frequency data suggests that the HLA genes of Asian and indigenous American populations stem from a single pool distinct from the gene pools of European and African populations. The Asian populations separate into two clusters, one of which encompasses nearly all the Siberian populations and all the indigenous American populations tested, while the other consists of Central, Eastern, and Southeastern Asian populations. The position of the Tuva people appears to be near the node from which the two clusters diverge. The divergence time of the two clusters is estimated to be 21,000-24,000 years BP. Three different branches of the native Siberian peoples seem to have contributed founders for the indigenous American ethnic groups.

Alleles↗

PubMed2002

Evidence for local inflammation in complex regional pain syndrome type 1.

BACKGROUND: The pathophysiology of complex regional pain syndrome type 1 (CRPS 1) is still a matter of debate. Peripheral afferent, efferent and central mechanisms are supposed. Based on clinical signs and symptoms (e.g. oedema, local temperature changes and chronic pain) local inflammation is suspected. AIM: To determine the involvement of neuropetides, cytokines and eicosanoids as locally formed mediators of inflammation. METHODS: In this study, nine patients with proven CRPS 1 were included. Disease activity and impairment was determined by means of a Visual Analogue Scale, the McGill Pain Questionnaire, the difference in volume and temperature between involved and uninvolved extremities, and the reduction in active range of motion of the involved extremity. Venous blood was sampled from and suction blisters made on the involved and uninvolved extremities for measurement of cytokines interleukin (IL)-6, II-1beta and tumour necrosis factor-alpha (TNF-alpha), the neuropetides NPY and CRGP, and prostaglandin E2 RESULTS: The patients included in this study did have a moderate to serious disease activity and impairment. In plasma, no changes of mediators of inflammation were observed. In blister fluid, however, significantly higher levels of IL-6 and TNF-alpha in the involved extremity were observed in comparison with the uninvolved extremity. CONCLUSIONS: This is the first time that involvement of mediators of inflammation in CRPS 1 has been so clearly and directly demonstrated. This observation opens new approaches for the succesful use and development of immunosuppressives in CRPS 1.

Blister↗

PubMed2002

Persistence of Mhc heterozygosity in homozygous clonal killifish, Rivulus marmoratus: implications for the origin of hermaphroditism.

The mangrove killifish Rivulus marmoratus, a neotropical fish in the order Cyprinodontiformes, is the only known obligatorily selfing, synchronous hermaphroditic vertebrate. To shed light on its population structure and the origin of hermaphroditism, major histocompatibility complex (Mhc) class I genes of the killifish from seven different localities in Florida, Belize, and the Bahamas were cloned and sequenced. Thirteen loci and their alleles were identified and classified into eight groups. The loci apparently arose approximately 20 million years ago (MYA) by gene duplications from a single common progenitor in the ancestors of R. marmoratus and its closest relatives. Distinct loci were found to be restricted to different populations and different individuals in the same population. Up to 44% of the fish were heterozygotes at Mhc loci, as compared to near homozygosity at non-Mhc loci. Large genetic distances between some of the Mhc alleles revealed the presence of ancestral allelic lineages. Computer simulation designed to explain these findings indicated that selfing is incomplete in R. marmoratus populations, that Mhc allelic lineages must have diverged before the onset of selfing, and that the hermaphroditism arose in a population containing multiple ancestral Mhc lineages. A model is proposed in which hermaphroditism arose stage-wise by mutations, each of which spread through the entire population and was fixed independently in the emerging clones.

Alleles↗

PubMed2002

Contribution of homoplasy and of ancestral polymorphism to the evolution of genes in anthropoid primates.

Molecular phylogenies of lineages that split from one another in short succession are often difficult to resolve because different loci and different sites within the same locus yield incongruent relationships. The incongruity is commonly attributed to two causes: differential assortment of ancestral polymorphisms and homoplasy. To assess the relative contribution of these two causes, sequences of 57 segments from 51 loci in six primate lineages (human, chimpanzee, gorilla, orangutan, macaque, and tamarin, abbreviated as H, C, G, O, M, and T, respectively) were subjected to "partitioning" analysis, in which phylogenetically informative sites were identified in all 15 pairwise comparisons of each of the 57 segments and tallied for their support or lack thereof for each of the theoretically possible phylogenies. The six lineages include one of the best known cases of a difficult-to-resolve phylogeny: the trichotomy (H, C, G), in which the three lineages may have diverged from each other within a short period of time. In this period many of the ancestral polymorphisms apparently persisted and yielded phylogenetically incongruent signals. By contrast, no ancestral polymorphism is expected to have survived during the interval separating the divergences of the O, M, and T lineages from the ancestor of the (H, C, G) group. Any phylogenetic incompatibilities at sites in the O, M, and T lineages relative to the (H, C, G) group are therefore presumably the result of homoplasy. The frequency of homoplasy estimated in this manner is unexpectedly high: 12% for the (H, C, G) clade and 19% for the (H, C, G, O) clade. At least three-quarters of the 48% incompatibility observed in the (H, C) clade is attributable to the sorting out of ancestral polymorphisms coupled with intragenic recombination. Possible reasons for this high level of homoplasy in the O, M, and T lineages are discussed, and a computer simulation has been carried out to produce a model explaining the observed data.

Animals↗

PubMed2002

Memory function during propofol and alfentanil anesthesia: predictive value of individual differences.

BACKGROUND: Conscious recall and implicit memory have been shown to depend on hypnotic state as measured by electroencephalographic (EEG) bispectral index (BIS). A third expression of memory (unconscious-controlled memory) was recently observed after moderate to light sedation (BIS, 70-80). The present study investigated memory function during deep sedation (BIS, 60-70). As memory effects are small, the authors studied potential predictors of individual differences in memory performance. METHODS: Memory function and speed of information processing were assessed in 56 outpatients before surgery. During propofol anesthesia supplemented with alfentanil, patients heard a series of words while anesthesia was titrated to BIS, 60-70. In between words, response to command was assessed using the Isolated Forearm Technique. The authors tested memory with a word stem completion task and process dissociation procedure to distinguish explicit from implicit effects. RESULTS: Mean (+/- SD) BIS during word presentation was 64.0 +/- 3. Patients with conscious recall of verbal commands (n = 9) did not recall or recognize presented words. Even so, the process dissociation procedure revealed evidence of memory by a significantly higher hit rate in the inclusion condition (0.26) than in the exclusion condition (0.12). Patients without conscious recall showed no evidence of memory for presented words. Hit scores correlated significantly with scores in the preoperative memory test (r = 0.35). CONCLUSIONS: The authors found evidence of weak explicit memory function during anesthesia titrated to BIS, 60-70. The observations strongly suggest that postoperative memory relates to awareness during anesthesia, but the nature of this relation remains unclear. Memory seems more likely in patients with good preoperative memory performance.

Adult↗

PubMed2000

Linkage Relationships and Haplotype Variation of the Major Histocompatibility Complex Class I A Genes in the Cichlid Fish Oreochromis niloticus.

The haplochromine cichlid species flocks of the East African Great Lakes are one of the best examples of adaptive radiation. Analysis of genetic variation among these species provides valuable information on species relationships and timing of speciation events. Although the haplochromine cichlids generally display little genetic variation, the major histocompatibility complex (Mhc) genes have been found to be highly variable. A study of the linkage relationships of the Mhc class I A genes in the cichlid fish Oreochromis niloticus was therefore undertaken. Class I loci were identified, and their segregation in seven mothers and their haploid embryos was determined. In total, 56 class I A sequences were found among the seven families. A strong concordance of segregation was observed in five haplotypes among the embryos, indicating a close linkage of all loci. The number of loci per haplotype varied from 11 to 17, while the total number of distinct loci found among all families was 22. These findings show that all class I A loci are linked in a single genetic cluster in O. niloticus.

Journal Article↗

PubMedDate not supplied

Predicting perioperative cardiac risk.

Cardiovascular complications are the major cause of perioperative morbidity and mortality of patients undergoing major vascular surgery. This is related to the frequent presence of an underlying coronary artery disease. This paper reviews the pathology of perioperative cardiac complications and cardiac risk assessment and risk reduction strategies. Guidelines of the American College of Cardiology and American Heart Association for the evaluation of cardiac risk for noncardiac surgery may provide the necessary framework for the assessment and management of patients undergoing major vascular surgery. Based on the American College of Cardiology and American Heart Association guidelines and data from contemporary studies, patients without risk factors are considered to be at low risk and do not require additional evaluations for coronary artery disease. Patients with 1 or 2 cardiac risk factors represent an intermediate-risk group for perioperative cardiac complications. If beta-blockers are prescribed, the probability of cardiac complications is low and there is no need for further noninvasive testing. Patients with 3 or more risk factors are at high risk for cardiac complications and the use of noninvasive testing may help further refine cardiac risk based on the presence and absence of test-induced myocardial ischemia. beta-Blockers should be prescribed to all patients, and coronary revascularization should be reserved for high-risk patients who have a clearly defined need for revascularization independent of the need for major vascular surgery.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Vertical infraclavicular block of the brachial plexus: effects on hemidiaphragmatic movement and ventilatory function.

BACKGROUND AND OBJECTIVES: Several case reports have suggested that block of the brachial plexus by the vertical infraclavicular approach influences hemidiaphragmatic movement and ventilatory function. These effects have not been evaluated in a prospective study. METHODS: Thirty-five consecutive patients scheduled for elective surgery under brachial plexus anesthesia were included. A vertical infraclavicular block was performed with ropivacaine 0.75%, 0.5 mL/kg. Ipsilateral hemidiaphragmatic movement was measured by ultrasonography at maximal forced inspiration and sniff. Forced vital capacity (FVC) and forced expiratory volume (FEV(1)) were measured by a portable vitalograph. All measurements were performed before the block procedure and at 5, 10, 30, and 60 minutes after the block. RESULTS: The block was successful in 34 of 35 patients. In 9 patients (26%), a change in hemidiaphragmatic movement (reduced or paradoxical) was observed. A significant decrease in ventilatory function was found in 8 of these 9 patients between baseline and at 60 minutes: FVC = -0.8 +/- 0.4 L and FEV(1) = -0.7 +/- 0.3 L, mean +/- SD (relative decrease: FVC = 30 +/- 14% and FEV(1) = 32 +/- 13%, mean +/- SD). Horner's syndrome was seen in 4 patients (12%), and in all, a change in hemidiaphragmatic movement was observed. No clinical signs of ventilatory dysfunction were noticed. CONCLUSION: The vertical infraclavicular block can result in a change in ipsilateral hemidiaphragmatic movement, with a decrease of ventilatory function. Although a correlation between the presence of Horner's syndrome and hemidiaphragmatic dysfunction was observed, hemidiaphragmatic dysfunction also occurred independently.

Amides↗

PubMedDate not supplied

A comparison of the lateral and posterior approach for brachial plexus block.

BACKGROUND: Brachial plexus block by the posterior approach described by Pippa is not widely used in contrast to the lateral approach of Winnie. We compared the clinical efficacy of both approaches in a randomized prospective study. METHODS: Eighty patients, American Society of Anesthesiologists physical status I or II, scheduled for surgery of the shoulder or upper arm were randomized in 2 groups: lateral (Winnie, n = 40) or posterior approach (Pippa, n = 40). A single injection of ropivacaine 7.5 mg/mL, 0.5 mL/kg, was made after obtaining a motor response in the distribution of the axillary nerve at a current below 0.5 mA (2 Hz, 0.1 millisecond). Onset and distribution of analgesia and motor block were assessed at 5, 10, 15, 20, 30, and 60 minutes after the local anesthetic injection. Complete block was defined as anesthesia in all dermatomes C3-C6 at 60 minutes after injection. RESULTS: The posterior approach provided complete block in 36 patients (90%) and the lateral approach in 33 patients (83%). Corresponding motor block was similar in both approaches, but the block procedure time was faster in the posterior approach (6.2 [5.2-7.2] minutes v 8.4 [7.1-10.2] minutes; P < .001). Surgical success rate (posterior 95% v lateral 93%) and side effects were similar in both approaches. One complication (thoracic epidural block) was seen using the lateral approach, whereas none occurred in the posterior approach. There was no difference in patient satisfaction scores of the 2 approaches, which were equally high in both groups (posterior 98% v lateral 95%). CONCLUSION: Both approaches are comparable regarding clinical efficacy for anesthesia of the shoulder and upper arm.

Adult↗