Biomedical subjects
Publications and source records attributed to J Rodriguez.
The novel fatty acids (Z)-6-nonadecenoic acid (1) and (Z)-17-pentacosenoic acid (2) were characterized in the sponge Geodia gibberosa. These fatty acids were mainly found in phosphatidylethanolamine and phosphatidylcholine.
1. The phospholipid fatty acid compositions of the sponges Ircinia strobilina, Ircinia felix, Ircinia campana, Ircinia sp., Spongia tubulifera and Dysidea etherea were studied, revealing the presence, besides other common fatty acids, of considerable amounts (2-5%) of the novel 23-methyl-5,9-tetracosadienoic acid (1). 2. The demospongic acids 5,9-tetracosadienoic acid, 23-methyl-5,9-tetracosadienoic acid (1), and 5,9-pentacosadienoic acid, were particularly abundant in sponges of the genus Ircinia, in contrast to the most common 5,9-hexacosadienoic acid found in other species. These findings are discussed in terms of the taxonomy of the Dictyoceratida. 3. The complete characterization of the novel phospholipid fatty acid 23-methyl-5,9-tetracosadienoic acid (1) is presented.
A 21-month-old girl presented with ureteral triplication, representing an exceptional variant of Smith's type 1. One ureter was intravesical and the other 2 were extravesical (bladder neck and vaginal).
Stimulation of the quisqualate (QA) subtype of glutamate receptor increased the expression of phosphate activated glutaminase (needed for neurotransmitter glutamate synthesis) and the ability to release neurotransmitter glutamate in cultures of glutamatergic cerebellar granule neurons. In contrast, QA had no significant effects on the lactate dehydrogenase activity and amount of protein. The QA-mediated elevation in glutaminase activity was blocked by the ionotropic QA receptor antagonist CNQX and mimicked by the ionotropic QA receptor agonist AMPA, but not by the metatropic QA receptor agonist t-ACPD. The increase in Ca2+ influx essentially through activation of L-type channels, and not the mobilization of internal Ca2+ stores, was responsible for these QA receptor-mediated long-term changes in cerebellar granule neurons.
Using a recombinant vaccinia virus (VV) that expresses E. coli beta galactosidase (beta-Gal) to infect lymphocytes, we show that enzymometrically or immunologically detectable beta-Gal expression is less pronounced among T cells than among B cells. VV infection caused growth inhibition of B cells, but barely affected T-cell proliferation in vitro. Moreover, the production of infectious viral particles was less pronounced in T lymphocytes. Kinetic studies revealed that after an initial dose-dependent growth inhibition, T cells continued to proliferate without the doubling time being affected by VV infection. Nonetheless, the T cells do express proteins encoded by recombinant VV, such as beta-Gal, or secrete soluble proteins such as interleukin-4, though at a lower efficiency at the per cell level than B lymphocytes. In conclusion, the physiology of T cells appears to be less perturbed by VV than that of B cells, although the virus is capable of directing expression of recombinant genes to T lymphocytes.
In a previous work we have shown that histidine decarboxylase (HD) activity is found in a soluble and a membrane-bound form. A major part (82%) of the membrane-bound HD activity in the crude mitochondrial fraction (P2) was present in the synaptic plasma membrane-containing subfraction. Physiological concentrations of Ca2+ had no direct effect on HD activity but caused a solubilization of approximately 50% of membrane-bound HD in the P2 fraction. Mg2+ had similar but lower effects (20% solubilization) than Ca2+. Incubation with depolarizing concentrations of K+ in the presence of 1 mM CaCl2 caused a significant (30%) solubilization of HD.
The various components required for individualising clinical drug dosage regimens are reviewed, including a study of 3 types of fitting procedures, 2 types of gentamicin pharmacokinetic model and the utility of D-optimal times for obtaining serum gentamicin concentrations. The combination of the current Bayesian fitting procedure, the kslope pharmacokinetic model [in which the elimination rate constant (kel) can change from dose to dose with changing creatinine clearance] and the explicit measurement of the assay error pattern yielded predictions of future serum gentamicin concentrations which were (a) slightly better than those found using weighted nonlinear least squares; (b) somewhat better than those found with Bayesian fitting and a fixed-kel model; (c) better than those found using the traditional linear regression fitting procedure and a fixed kel model. D-Optimally timed pairs of concentrations also predicted future concentrations at least as well, and more cost effectively.
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An automatic procedure for defining recurrent folding motifs in proteins of known structure is described. These motifs are formed by short polypeptide fragments of equal size containing between four and seven residues. The method applies a classical clustering algorithm that operates on distances between selected backbone atoms. In one application, we use it to cluster all protein fragments into only four structural classes. This classification is rough considering the observed diversity of local structures, but comparable in homogeneity to the four classes of secondary structure (alpha-helix, beta-strand, turn and coil). Yet, it discriminates between extended and curved coil and distinguishes beta-bulges from beta-strands. In a second application, the clustering procedure is combined with assignment of backbone dihedral angles to allowed regions in the Ramachandran map. This produces an exhaustive repertoire of highly homogeneous families of structural motifs that contains all the beta-hairpins, beta alpha- and alpha beta-loops previously defined by manual procedures, and new structural families of which two examples, a beta alpha-loop and an alpha-helix beginning, are analyzed in detail. The described automatic procedures should be useful in categorizing structure information in proteins, thereby increasing our ability to analyze relations between structure and sequence.
The relation between amino acid sequence and local structure in proteins is investigated. The local structures considered are either the four classes of secondary structure (H, E, T and C) or four classes of local conformations defined using measures of conformational similarity based on distances between C alpha atoms. The classes are obtained by applying an automatic clustering procedure to short polypeptide fragments of uniform length from a database of 75 known protein structures. The thrust of our investigation consists of systematically searching the database for simple amino acid patterns of the type Gly-X-Ala-X-X-Val, where X denotes an arbitrary residue. Patterns that are nearly always associated with the same structure are retained. Finding many such associations, we then evaluate by a statistical approach how many among them are non-random and compare the results for different definitions of local structure. A similar comparison is made for the predictive value of retained associations, which is assessed using an internal test based on dividing the database into "learning" and "test" subsets. While we find that local structures defined by conformational similarity are not superior to secondary structure for prediction purposes, they help us gain insight into the factors that influence the predictive value of derived associations. A major conclusion is that the number of retained associations is in large excess over the number expected from a random correlation between sequence and structure, irrespective of how local conformation is defined. However, only a very small number of these associations can be earmarked as reliable using statistical criteria, due to the limited size of the database. We find, for instance, that the pattern Ala-Ala-X-X-Lys reliably characterizes helix, and the pattern Val-X-Val-X-X-X-Ala reliably characterizes extended structure and beta-strand. The possibility is discussed that these and other reliable associations correspond to regions of the polypeptide chain whose conformations are locally determined and that these regions may play a role in folding.
The effect of histamine on the activity of ornithine decarboxylase (ODC) of cerebellar granule neurons was studied using primary cultures grown both in serum-containing medium and in chemically defined medium. In comparison with granule neurons grown in chemically defined medium, the activity of ODC was about twice as great in the neurons grown in serum-containing medium. Treatment of cultured cerebellar neurons with histamine caused a dose-dependent increase in ODC activity. The maximum elevation was observed at 500 nM of histamine, when the increase in ODC activity was about 50% and 120% over controls in granule cells grown in serum-containing medium and in chemically defined medium, respectively. Histamine had no significant effect on the activity of lactate dehydrogenase in these cultures. The present findings provided direct evidence for the involvement of histamine in the regulation of ODC-related non-mitotic growth of granule neurons in the cerebellum.
A beta-glucosidase from the medium of an autolyzed culture of Penicillium oxalicum has been purified by tannic acid precipitation, sephacryl S-200, DEAE-Biogel, CM-Biogel and Mono Q successively. The purification process produced a homogeneous band in the SDS-PAGE that correspond to a Mr of 133,500. The enzyme had a pl of 4, and the active optima were found at pH 5.5 and 55 degrees C. The enzyme hydrolyzed different substrates showing maximum affinity against p-nitrophenyl-beta-D-glucoside with a Km value of 0.37 mM. The beta-glucosidase was inhibited by Glucono-D-lactone but not by glucose in the concentration range of 1 to 10 mM. The enzyme was adsorbed by Concanavalin-A-Sepharose.
To assess the efficacy of the simultaneous application of chest and abdominal compression (SCAC) in cardiopulmonary resuscitation (CPR), we performed a prospective study on 18 patients shortly after cardiac arrest. Three different CPR procedures were carried out consecutively: (1) Standard CPR; (2) CPR interposed with abdominal compression (IAC-CPR); and (3) SCAC-CPR. Standard CPR was repeated at the end of each sequence. Thoracic aortic and right atrial pressures were recorded during maneuvers and no vasoactive drugs were administered. Systolic aortic pressures were 39.02 +/- 21 mmHg, 63.6 +/- 21 mmHg and 94.04 +/- 21 mmHg during standard CPR, IAC-CPR and SCAC-CPR, respectively (P less than 0.001). There was no evidence of intra-abdominal injury in the eight autopsies performed. We have reached the conclusion that the use of SCAC-CPR on humans does produce greater intravascular pressure and we recommend this technique as a possible alternative to standard CPR.
Within a group of 271 patients with pelvic fracture, 69 patients met criteria for severe hemorrhage. Sixty consecutive patients were treated by a combined multispecialty musculoskeletal trauma service using a protocol designed to control bleeding, rapidly diagnose and control associated injuries, as well as to prepare the patient for open reduction of the pelvic fracture, if appropriate. The pneumatic antishock garment, external fixation, and angiography were selectively used to control bleeding. Abdominal injuries were diagnosed using clinical examination and diagnostic peritoneal lavage. When lavage aspirate was grossly bloody, patients had no negative explorations. Microscopically positive lavages were associated with a 50% false-negative rate. Using the protocol, the mortality rate was 5%. Overall mortality rate was 10%. The combination of a trauma team approach and a specifically designed protocol reduces the number of deaths from pelvic fracture.
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Ultrasound scans of a preterm neonate (27 weeks gestation) at seven weeks of age showed periventricular echo-free cavities, but these were no longer visible at 15 weeks, three weeks before the infant died. At autopsy, a linear glial scar, extending from the periventricular white-matter into the white axis of the parasagittal gyrus, was found in the area occupied by the periventricular cysts. The larger cavity was reduced to a slit-like excavation in the midst of glial tissue. Unsuspected focal infarcts in the cerebral cortex were also found. This observation demonstrates that transient echo-free cavities represent foci of cystic necrosis, which are subject to secondary collapse. In the authors' experience, the linear extension of periventricular leukomalacia (PVL) into the core of parasagittal gyri is a frequent feature of PVL, and one which cannot easily be accounted for by the usual explanations of border-zone ischaemic softening.
One of the causes of auxiliary liver transplantation failure is the inter-liver competition between the host liver and the graft for the hepatotrophic factors of the portal blood. We have developed an experimental model of heterotopic partial (30%) liver isotransplant using Wistar rats so as to study this competition. Splenoportography and dissection demonstrate the existence of collateral circulation. The collaterals at 90 days post-transplant (PT) consisted of veins from the portal vein to the host liver (PR), paraesophageal veins (PE) and splenorenal veins (SR). At 60 days P.T., PR and SR veins but not PE ones appeared, and at 30 days P.T., there were only PR veins. Graft atrophy at 90 days P.T. was associated with a severe degree of bile duct proliferation. The gradual development of portal hypertension causes porto-systemic collateral circulation and the graft loses the portal hepatotrophic factors. The late development of the portal hypertension and the biliary proliferation could be caused by the hepatic arterial ischemia in this experimental model. Thus, as has been described in the orthotopic liver transplantation, the heterotopic one might require a double vascularization, both portal and arterial.
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