Heparin effect on hydrolysis of fibrin clots in a bull and a man with varying fibrinolytic systems

Heparin was studied for its effect on the hydrolysis time of clots from desAA fibrin (FB), desAABB fibrin (F0) and fibrinogen (Fg) of a bull and a man by gly-or lys-plasminogen which is activated by the tissue activator. It is shown that heparin in the concentration to 4.6 M does not affect that hydrolysis time of clots from human and bovine Fg and human Fg by gly-plasminogen which is activated by the tissue activator. Heparin increases the hydrolysis time of clots from bovine Fg and F0 by gly-and lys-plasminogen, the tissue activator being present. It firstly increases (in concentrations below 0.5 (microM), and then decreases (in concentrations above 0.5 (microM) the hydrolysis time of clots from human FB, F0 and Fg and bovine FB and F0 by plasmin. In concentration 4.6 microM heparin increases the hydrolysis time of clots from human fibrinogen by fibrinolytic systems. Effect of heparin on fibrinolytic process from the viewpoint of affine interactions between the components of fibrin clots is discussed.     

Recent developments in the understanding of antinuclear autoantibodies

Cytological identification of soybean mitotic metaphase chromosomes (2n = 40) has been severely limited by their small size and uniform karyomorphology. We have developed fluorescent in situ hybridization (FISH), PCR-primed in situ labelling (PCR-PRINS) procedures, and molecular probes for routine cytological identification and for the physical mapping of soybean somatic chromosomes. Chromosome preparation has been achieved by modifications of previous protocols and through the preparation of root-tip protoplasts prior to chromosome spreading. Initially our probe selection focused on highly repeated DNAs that provide very intense localized hybridization signals. Repetitive gene probes that have proven valuable include the rDNA loci (5S and 45S) which are chromosome specific. We have also developed satellite DNA probes for two different sequence families: the SB92 and the STR120 satellites. Both of these are tandemly arranged at multiple chromosomal loci. By using different cloned examples of each family, we have been able to selectively label unique subsets of soybean chromosomes. Double hybridization with biotin and digoxigenin labeled probes has allowed us to determine the chromosomal overlap between different probes. In addition, we have joined portions of the metaphase chromosome painting patterns with the genetic map by single-copy FISH and PCR-PRINS detection of the RFLP loci G8.15, G17.3, and A199a and A199b. Total genomic DNA in situ hybridization (GISH) patterns were also used to characterize the soybean chromosomes.     

Postural and symptomatic improvement after physiotherapy in patients with dizziness of suspected cervical origin

OBJECTIVE: To assess postural performance in patients with dizziness of suspected cervical origin in whom extracervical causes had been excluded, and to assess the effects of physiotherapy on postural performance and subjective complaints of neck pain and dizziness. DESIGN: Prospective, randomized, controlled trial. SETTING: Primary care centers and a tertiary referral center. PATIENTS AND SUBJECTS: Of 65 referrals, 43 patients were excluded because extracervical etiology was suspected. Of the remaining 22 patients, 17 completed the study (15 women, 2 men, x age 37 yr, range 26-49). The controls were 17 healthy subjects (15 women, 2 men, x age 36 yr, range 25-55). INTERVENTION: Physiotherapy based on analysis of symptoms and findings, and aimed to reduce cervical discomfort. Patients were randomized either to receive immediate physiotherapy (n = 9), or to wait 2 months, undergo repeat measurements, and then receive physiotherapy (n = 8). MAIN OUTCOME MEASURES: Posturography, measuring velocity and variance of vibration-induced body sway and variance of galvanically induced body sway. Subjective intensity of neck pain (Visual Analog Scale ratings, 0-100), intensity and frequency of dizziness (subjective score 0-4). RESULTS: The patients manifested significantly poorer postural performance than did healthy subjects (.05 > p > .0001). Physiotherapy significantly reduced neck pain and intensity and the frequency of dizziness (p < .01), and significantly improved postural performance (.05 > p > .0007). CONCLUSIONS: Patients with dizziness of suspected cervical origin are characterized by impaired postural performance. Physiotherapy reduces neck pain and dizziness and improves postural performance. Neck disorders should be considered when assessing patients complaining of dizziness, but alternative diagnoses are common.     

Management of upper and lower urinary tract infections in pregnant women

Nurse practitioners often manage pregnant women for many health problems. Early recognition, treatment, or timely referral of any infectious process, especially urinary tract infections, is crucial to an optimal pregnancy outcome. Knowledge of urinary tract anatomic and physiologic changes in pregnancy and bacterial features necessary for infection to occur expands understanding the foundation of urinary tract infection prevention and treatment. This article discusses urinary tract infections, specifically focusing on clinical features, diagnosis, and treatment measures among pregnant women.     

Differential cellular response within the rabbit tendon unit following tendon injury

Since 1975, 340 patients were treated by tracheal sleeve resection for tracheal or subglottic laryngeal iatrogenic stenoses in our unit. Preoperative iterative Nd YAG laser sessions have usually been performed, without success. The length of the sleeve specimen was an average of 3 1/4 cm. Twelve patients died on the post operative course (3.5%), 3 more patients died later after failure of the procedure (0.9%) and nineteen had recurrent stenoses treated with use of a tracheostomy tube, a permanent Montgomery tube, or an endotracheal stent (5.6%). Three hundred and six patients are definitely cured (90%), at the first attempt for 265 patients, after a laser session for granulomas for 20 patients, after a second tracheal resection for 6 patients and after a temporary Montgomery tube for 15 patients. Providing there is a good selection of the patients, tracheal sleeve resection is the best treatment for iatrogenic stenosis.     

Molecular basis and species specificity of high affinity binding of vasoactive intestinal polypeptide by the rat secretin receptor

The affinity and specificity of the binding interaction between ligands and their receptors are key for appropriate hormonal regulation of target tissues. However, it is now apparent that vasoactive intestinal polypeptide (VIP) binds to the rat secretin receptor with similar affinity to that for its natural ligand, secretin (Holtmann et al., 1995). In this report, we establish that this is not a characteristic of the human secretin receptor, and use rat-human secretin receptor chimeras, site mutants and truncated receptor constructs to establish the molecular basis for this unusual binding interaction. Of note, isolated N-terminal domains of the rat secretin and the VIP receptors are capable of high affinity binding of VIP. In the recently recognized secretin family of receptors, this domain has six conserved cysteine residues and disulfide bonds that are likely important to achieve the complex conformation critical for this binding. A single acidic residue (Asp98) present in the rat secretin receptor appears to be critical, because a site-mutant changing this to the polar, but uncharged residue present in that position in the human receptor (Asn) eliminates the high affinity binding of VIP. Of interest, a previously identified critical basic residue in VIP (Lys15) provides a candidate for charge-pairing with this residue, potentially aligning the peptide ligand in a nonproductive orientation within this receptor.     

A questionnaire study among 171 medical candidates enrolled in a PhD program. Three elements in the PhD education: supervision, research courses and international relations

One hundred and seventy-one medical doctors (median age 34 years) registered as Ph.D.-students at the Medical Faculty, University of Aarhus, were given a questionnaire concerning the Ph.D-program (91% reply rate). The Ph.D.-students had typically graduated four years before enrollment and had gained basic clinical experience. Eighty-four percent had been involved in research projects prior to their formal research education. In general, the Ph.D.-students found the supervision offered by senior researchers adequate, although, more Ph.D.-students in clinical than in preclinical departments would have liked their main supervisor to be more enthusiastic and have more specific expertise. By tradition, the Medical Faculty in Aarhus offers a broad introductory course on research methodology, this was appreciated by the Ph.D.-students. However, they found that too much time was allocated for this purpose. The Ministry of Education recommends that Ph.D.-students gain experience from international collaboration, preferably from a stay abroad. However, only 24% of Ph.D.-students had stayed at an international collaborating institution. Although the overall evaluation of the medical Ph.d.-program was positive, the Ph.D.-students pointed out weaknesses and conflicts requiring adjustment.     

Macrophage formation of angiostatin during inflammation. A byproduct of the activation of plasminogen

Angiostatin is a potent inhibitor of tumor angiogenesis and the growth of metastatic foci. Recent studies have indicated that neoplastic cells can generate angiostatin directly or in cooperation with tumor-associated macrophages. In studies reported here, we determined whether angiostatin is generated in mice under non-neoplastic settings. Utilizing murine RAW264.7 macrophages and thioglycollate-elicited peritoneal macrophages, we demonstrate that angiostatin-like fragments are generated as a byproduct of the proteolytic regulation of membrane-bound plasmin. Plasmin proteolysis and subsequent loss in membrane-bound plasmin activity requires active plasmin but was unaffected by inhibitors of metalloproteinases. Lysine binding fragments of plasmin, isolated from macrophage-conditioned media utilizing affinity chromatography, appeared as a major (48 kDa) and two minor bands (42 and 50 kDa) in SDS-polyacrylamide gel electrophoresis and were immunoreactive with anti-kringle 1-3 IgG. Each peptide begins with Lys77 and contains the entire sequence of angiostatin. The affinity isolated plasmin fragments inhibited bFGF-induced endothelial cell proliferation. Lavage fluid recovered from the peritoneal cavities of mice previously injected with thioglycollate contained angiostatin-like plasmin fragments similar to those generated in vitro. This is the first demonstration that angiostatin-like plasmin fragments are generated in a non-neoplastic inflammatory setting. Thus, in addition to regulating pericellular plasmin activity, proteolysis of plasmin generates inactive kringle-containing fragments expressing angiostatic properties.