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Biomedical subjects

M Kessel

Publications and source records attributed to M Kessel.

At least 73 records · Page 4Linked to original sources
PubMed1991

Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid.

Exposure of murine embryos to teratogenic doses of retinoic acid (RA) induced homeotic transformations of vertebrae. Posterior transformations occurred along the complete body axis after RA administration on day 7 of gestation and were accompanied by anterior shifts of Hox gene expression domains in embryos. Anterior transformations of vertebrae in the caudal half of the vertebral column were induced on day 8.5. We suggest that the identity of a vertebral segment is specified by a combination of functionally active Hox genes, a "Hox code." In this concept the sequential activation of Hox genes defines sequentially more posterior axial levels, while mesodermal cells leave the primitive streak. Exogenous RA interferes with the normal establishment of Hox codes and thus with axial specification.

Animals↗
PubMed1991

Axial specification in higher vertebrates.

The specification of the body axis in the embryo is reflected in the structure of the vertebral column. Expression patterns of Hox genes in the prevertebrae suggest their involvement in this specification process and in the maintenance of vertebral identities. A single, ectopically expressed Hox gene can reprogramme the rostral part of the vertebral column and induce phenotypic alterations interpretable as homeotic transformations.

Animals↗
PubMed1991

Purification and immunological characterization of a GroEL-like protein from Bordetella pertussis.

A GroEL-like protein from Bordetella pertussis was purified. This protein was found to have the tetradecameric subunit structure typical of the GroEL family of proteins and to contain epitopes similar to those of other members of this family, including a human GroEL-like protein. Active immunization of neonatal mice with the B. pertussis GroEL-like protein provided little protection against an aerosol challenge with B. pertussis. Antibodies to this protein were elicited in mice by a standard diphtheria-tetanus-pertussis (DTP) vaccine but not by an experimental acellular pertussis vaccine. Since the Bordetella GroEL-like protein was found to contain epitopes similar to those on the mammalian analog, the potential exists that vaccination with standard DTP vaccines may induce antibodies which react with the mammalian GroEL analog.

Animals↗
PubMed1991

Leukotriene B4 and tumor necrosis factor release from leukocytes: effect of peritoneal dialysate.

The effect of peritoneal dialysate on the capacity of peripheral blood polymorphonuclear (PMNL) and mononuclear leukocytes (MNC) to release leukotriene B4 (LTB4) and tumor necrosis factor alpha (TNF alpha) was investigated in vitro. Following density gradient separation, aliquots of 5 x 10(6) PMNL or MNC were incubated in peritoneal dialysis fluid containing 1.5% glucose or Hanks' buffer (= control) for 1-2 h at 37 degrees C. TNF alpha and LTB4 production was stimulated with Escherichia coli lipopolysaccharide (LPS) and calcium ionophore A23187, respectively. MNC incubated in buffer and LPS produced (mean +/- SD) 1,006 +/- 522 pg TNF alpha/5 x 10(6) cells; no significant amounts of TNF alpha were detectable in the presence of dialysate. An inhibition of TNF alpha release was also observed in MNC exposed to bicarbonate-buffered dialysates (pH 7.40) and 4.25% and 1.5% glucose solution with physiologic osmolality. Incubation of PMNL in Hanks' buffer followed by A23187 stimulation led to production of 29.1 +/- 19.2 ng LTB4/5 x 10(6) cells, whereas glucose-incubated cells were refractory to ionophore stimulation (less than 0.1 ng LTB4/5 x 10(6) cells). The failure of dialysate-exposed leukocytes to release inflammatory mediators in response to adequate stimuli may contribute to the impairment of cellular host defense in the setting of continuous ambulatory peritoneal dialysis.

Calcimycin↗
PubMed1990

Murine developmental control genes.

Various strategies have been used to isolate genes that participate in the regulation of mouse development. Gene families that have been identified on the basis of their homology to motifs within Drosophila control genes or human transcription factor genes, namely homeobox (Hox), paired-box (Pax), and POU genes, can be compared with respect to gene organization, structure, and expression patterns. The functions of these genes can be analyzed molecularly in vitro and in vivo with the use of available mouse mutants or transgenic mice. In addition, it has been possible to generate gain- or loss-of-function mutations by random or targeted introduction of transgenes. Models derived from these studies can reveal the successive steps of developmental control on a genetic level.

Animals↗
PubMed1990

Variations of cervical vertebrae after expression of a Hox-1.1 transgene in mice.

To understand the function of murine homeobox genes, a genetic analysis is mandatory. We generated gain-of-function mutants by introducing genomic sequences of the Hox-1.1 gene under the control of a chicken beta-actin promoter into mice. Our previous data had shown that these transgenic mice are nonviable after birth and are born with craniofacial abnormalities. In a subsequent detailed analysis of severely affected animals, malformations of the basioccipital bone, the atlas, and the axis were observed. Manifestation of an additional vertebra, a proatlas, occurred at the craniocervical transition. The dominant interference of the Hox-1.1 transgene with developmental programs seems to occur around day 9 of gestation, the time of neural crest migration and somite differentiation. We discuss the resulting phenotype with respect to a developmental control function of Hox-1.1.

Animals↗
PubMed1990

Anti-TNP antibody localization of the reactive lysine residues in myosin.

Myosin contains reactive lysine residues which are trinitrophenylated by 2,4,6-trinitrobenzene sulfonate much faster than the rest of the lysines. Here we find the location of these residues in the primary and spatial structure of myosin with the help of an anti-trinitrophenyl antibody. This antibody was raised against trinitrophenyl hemocyanin in rabbits. It reacted with trinitrophenylated myosin, and with some of the tryptic fragments of trinitrophenylated myosin. By analyzing the reaction with Western blots, it was found that the antibody preferentially reacts with the 27 kDa N-terminal fragment of the myosin head, and more weakly with the light meromyosin region of the myosin rod. The 27 kDa fragment contains the most reactive lysine residue, while the intermediate lysine residue is located in the light meromyosin region. The locations of the epitopes of the antibody were visualized on electron microscope images of rotary-shadowed trinitrophenylated myosin-antibody complexes. The distances of the epitopes to the head-rod junction of myosin were measured as 13 and 113 nm for the epitope on the head (reactive lysine residue) and for that on the rod (intermediary reactive lysine residue), respectively.

Antibodies↗
PubMed1990

Localization of epitopes and functional effects of two novel monoclonal antibodies against skeletal muscle myosin.

Two skeletal myosin monoclonal antibodies, raised against human skeletal myosin, were used to study the correlation between function, primary and tertiary structure of S-1 prepared from rabbit skeletal myosin. The heavy chain of S-1 is cleaved into three fragments by trypsin--27 kDa, 50 kDa and 20 kDa--aligned in this order from the N-terminus. The epitope of the first antibody was assigned to the N-terminal 1-23 amino acid stretch of S-1, since it reacted with the 27 kDa N-terminal tryptic fragment of S-1 but not with a derivative of the 27 kDa fragment, which lacks the above amino acid stretch. The epitope of the second antibody was assigned to the 3 kDa N-terminal region of the central 50 kDa domain of S-1. This assignment was based on proteolytic and photochemical cleavage of S-1 and on the labelling of its N-terminus by a specific antibody. The antibodies were visualized binding to the myosin head on electron micrographs of rotary-shadowed complexes of antibodies with myosin. Measurements on the micrographs indicated that the distances between the head-tail junction of myosin and the 'anti-27 K' and 'anti-50 K' epitopes are 14 nm and 17 nm, respectively. Both antibodies have a high affinity to S-1. The affinity of the 'anti-50 K' to S-1 decreased upon actin binding, while that of the 'anti-27 K' was not affected by binding of S-1 to F-actin. The 'anti-50 K' antibody inhibited the K+ (EDTA) and the actin-activated ATPase activity of S-1, while the 'anti-27 K' had no effect. The results indicate that either the epitope of the 'anti-50 K' is near to the actin or to the ATP-binding sites of S-1, or that there is communication, expressed as propagated conformational changes, between these sites and the epitope.

Actins↗
PubMed1989

Craniofacial abnormalities induced by ectopic expression of the homeobox gene Hox-1.1 in transgenic mice.

Hox-1.1 is a murine homeobox-containing gene expressed in a time- and cell-specific manner during embryogenesis. We have generated transgenic mice that ectopically express Hox-1.1 from the chicken beta-actin promoter. In these mice Hox-1.1 expression was changed to an almost ubiquitous pattern. Ectopic expression of Hox-1.1 leads to death of the transgenic animals shortly after birth and is associated with multiple craniofacial anomalies, such as cleft palate, open eyes at birth, and nonfused pinnae. This phenotype is similar to the effects seen after systemic administration of retinoic acid during gestation. This suggests that retinoic acid embryopathy and the specific developmental defects caused by ectopic expression of a potential developmental control gene share a common pathogenic mechanism.

Abnormalities, Multiple↗
PubMed1989

Eicosanoid release as laboratory indicator of biocompatibility.

Biocompatibility evaluation of extracorporeal devices requires the establishment of sensitive indicators of blood cells/surface interactions. Among others, arachidonic acid derivatives, such as prostaglandins and thromboxanes, play an important role in the cell control systems. Hence, the release of eicosanoids during blood exposure to dialyzer membranes was investigated. Experiments included in vitro incubation of human blood with flat membranes (FM), as well as ex vivo perfusion of hollow fiber membranes (HFM) with blood from healthy volunteers in single-pass fashion. In both models, a significant release of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was detected. In addition, the amount of eicosanoid release depended on the type of membrane tested. After a 10-min FM incubation with fresh blood, plasma concentrations of TXB2 and PGE2 were pronounced by polycarbonate when compared to Cuprophan and polyacrylonitrile. During 10 min of open loop perfusion of HFM, polymethylmethacrylate was the most active biomaterial, whereas the reactivity of Cuprophan was significantly lower. Among HFM, Hemophan was by far the less active. These results indicate that the release of eicosanoids represents a sensitive parameter of blood cells/membrane reactivity. Thus, the question arises as to whether or not the extracorporeal process of cyclooxygenase activity could contribute to the clinical side effects of chronical hemodialysis.

Biocompatible Materials↗
PubMed1989

The 5'-flanking region of the gene encoding the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase is crucial for growth of the cyanobacterium Synechococcus sp. strain PCC 7942 at the level of CO2 in air.

Transformation of the high-CO2-requiring mutants (hcr) O221 and E1 derived from the cyanobacterium Synechococcus sp. strain PCC 7942 by a wild-type DNA library restored their ability to grow at the level of CO2 in air. A plasmid (pE12) containing a 10-kilobase DNA insert was rescued from a O221 heterogenote and proved to transform both O221 and E1 to the wild-type phenotype. The capacity of the pE12 subclones to confer the wild-type phenotype to O221 transformants enabled the mapping of the mutation in O221 (designated hcrO221) within a 232-base-pair PstI-BstXI DNA restriction fragment. Sequence analysis revealed two open reading frames (ORFs) at positions -1745 to -1262 (ORFI) and -1218 to -393 (ORFII) upstream of the rbcL gene. A 3-kilobase PstI fragment of O221 was cloned, and hcrO221 was found to be a point mutation within the PstI-BstXI region -1309 nucleotides upstream of the rbcL gene. The significance of this flanking region for adaptation to air levels of CO2 was further demonstrated by the generation of new hcr mutants following insertional inactivation of wild-type DNA in the BstXI site. Electron microscopy revealed aberrant carboxysome structures in growing cells of the hcr mutants, a defect that was possibly related to the mutation, since transformation with pE12 derivatives restored the carboxysome structure to normal.

Air↗
PubMed1989

Ultrafiltration and absorption characteristics of hydroxyethylstarch and dextran during long dwell peritoneal dialysis exchanges in rats.

Glucose has several disadvantages such as low pH, high osmolality and hyperglycemia. Rapid glucose absorption contributes to hyperlipidemia, obesity and ultrafiltration failure in peritoneal dialysis patients. Two commercially available plasma substitutes 10% hydroxyethylstarch (HES) and 6% dextran were studied for ultrafiltration and absorption patterns. 18 ml of each solution were instilled into the peritoneal cavity of 6 non-uremic rats. HES yielded a significantly (p less than 0.02) greater ultrafiltration after 6 h of dwell, whereas 2.3% glucose solution showed the typical ultrafiltration pattern of an easily absorbable osmotic agent. With 6% dextran ultrafiltration was markedly lower. At the end of cycle time the mean absorption rates for HES were 62.7% and 41.5% for dextran. It is concluded that HES is a potent osmotic agent due to sustained colloidal ultrafiltration. However, despite their high molecular weights both solutions were markedly absorbed probably by lymphatics. However, accumulation in tissues and undefined metabolic pathways might prove disadvantageous in patients with ESRD.

Absorption↗
PubMed1989

Correction of amino acid metabolism by recombinant human erythropoietin therapy in hemodialysis patients.

We assessed the effect of correction of anemia with recombinant human erythropoietin (rhEPO) on plasma amino acid levels in maintenance hemodialysis patients. The plasma amino acid pattern was estimated by high performance liquid chromatography in 18 healthy persons and 14 hemodialysis patients before and up to 12 weeks after rhEPO therapy. There was a correction of the plasma serine values (67 +/- 16 to 87 +/- 22; P less than 0.05) and a corresponding decrease in the serine precursors, glycine (317 +/- 113 to 228 +/- 56; P less than 0.05) and hydroxyproline (26 +/- 21 to 15 +/- 13; P less than 0.10). The low plasma branched-chain amino acids, valine (137 +/- 33 to 154 +/- 50; P less than 0.10) and leucine (72 +/- 22 to 80 +/- 27; P less than 0.20), also were corrected. The elevated values of ornithine (78 +/- 16 to 62 +/- 19; P less than 0.1) and arginine (94 +/- 14 to 72 +/- 14; P less than 0.1) fell. The diminished glutamine values (470 +/- 125 to 563 +/- 115; P less than 0.1) and the decreased tyrosine/phenylalanine ratio (0.78 +/- 0.17 to 0.98 +/- 0.21; P less than 0.05) rose. Thus, the administration of rhEPO not only affects erythropoiesis, but also corrects the plasma amino acid pattern towards normal.

Adult↗
PubMed1988

Naturally crystalline porin in the outer membrane of Bordetella pertussis.

The Gram-negative bacterium Bordetella pertussis is the agent responsible for whooping-cough, and much interest has focused on the functions, structures and immunological properties of the molecules exposed at its outer surface. We have found by electron microscopy that cells of two strains of B. pertussis are covered with a crystalline surface lattice. This lattice is not an extrinsic layer of high molecular weight glycoproteins, such as occur on many other bacteria, but is a natural crystal of an intrinsic membrane protein of 40,000 Mr. This molecule has been shown to be an anion-selective member of an extensive family of proteins ("porins") that render Gram-negative outer membranes permeable to solutes of up to approximately 650 Mr. Computer image processing reveals a trimeric channel-like structure that closely resembles other porins visualized in artificial arrays after treatment with detergents, but in a novel (p2) crystal form. This correlation provides a "missing link" between earlier structural studies based on artificial arrays of porins (of undefined physiological status), and membrane-permeabilization experiments with solubilized porins (in undefined structural states). For the strains characterized so far, crystallinity of the porin surface lattice shows an intriguing correlation with nonpathogenicity.

Bacterial Outer Membrane Proteins↗