Biomedical subjects
Publications and source records attributed to N Vogt.
We show that chloroacetaldehyde, a chemical compound known to be reactive with unpaired adenine and cytosine residues, reacts with adenine residues (syn conformation) but not with cytosine residues (anti conformation) within Z-DNA. These modified residues are sensitive to cleavage by piperidine, which allows mapping at the single nucleotide level.
The purpose of this work was to analyse at the molecular level the DNA recognized by the antibodies to Z-DNA in in situ experiments. Antibodies to Z-DNA interact strongly with R-band positive heterochromatic segments of fixed metaphase chromosomes of Cebus (Viegas-Pequignot et al., 1983). These segments are constituted of a satellite DNA the repeat unit of which is about 1520 base pairs long. The base sequence of the repeat unit has been determined. It contains a (AC)n rich region which, in vitro, adopts the Z conformation under topological constraints. Experiments with nuclei suggest that this sequence is not predominantly in the Z conformation in vivo. The polymorphic structure of the (AC)n rich region argues for an active recombination sequence.
With the tritium-Sephadex method, the hydrogen-exchange kinetics of the five NH protons of guanine and cytosine residues in Z-form poly(dG-dC) X poly (dG-dC) were measured as a function of temperature and catalyst concentration. Over the measured temperature range from 0 to 34 degrees C, two classes of protons with constant amplitudes are found. The three protons of the fast class, which were assigned to the guanine amino and imino protons, have an exchange half-time in the minute time range (at 20 degrees C the half-time is 2.5 min) and an activation energy of 18 kcal mol-1. Since these two types of protons exchange at the same rate in spite of their grossly different pK values, the exchange of these protons must be limited by the same nucleic acid conformational change. The two cytosine amino protons of the slow class are especially slow with exchange half-times in the hour time range (at 20 degrees C the exchange half-time is 1 h) and the activation energy is 20 kcal mol-1. The exchange of these two protons is not limited by some nucleic acid conformational change as shown by the marked exchange acceleration of these protons upon addition of 0.2 M imidazole. In addition, we have also reexamined the hydrogen-deuterium exchange kinetics of the amino protons of guanosine cyclic 2',3'-monophosphate by a spectral difference method using a stopped-flow spectrophotometer. The measured kinetic process is monophasic with a rate constant of 3 s-1 at 20 degrees C, which is in the same range as the predicted rate constant of the guanine amino protons.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma lipoprotein patterns currently employed in attempts to identify different forms of hyperlipoproteinemia have been investigated in 113 hospitalized diabetics. For classification two methods have been compared: The first is based on lipid electrophoresis pattern in agarose gel coupled with the measurement of triglycerides and cholesterol. The second is based on plasma lipoprotein pattern obtained by separation of lipoproteins on cellulose acetate and following densitometry combined with estimation of cholesterol and beta-cholesterol and triglycerides in plasma. It could be demonstrated, that the results obtained in agarose system are not convertible to data obtained with the method for quantifying lipoproteins. By quantitative analysis only 4 p.c. of diabetics had type IIa, 4 p.c. type V, the others type IIb or IV. Graphic plots and calculated concentrations of lipoproteins gave differences in lipoprotein profiles between compensated and acidotic diabetics. In diabetes stage 1 most values are in the normal range, in stage 2 prebetalipoproteins increase and betalipoproteins decrease. In some case betalipoproteins are elevated and prebetalipoproteins diminished. In stage 3 with metabolic acidosis we observed an altered lipoprotein profile with confluence of beta- and prebeta-peak. The calculated concentration profile was also different from the others and revealed no certain quantitative information described for other electropherograms containing alpha, beta- and prebeta-bands. This phenomenon was frequently observed in patients with acute viral hepatitis and severe chronic liver disease. The pattern in diabetics is representative for patients with an excess of plasma lipids (the 2.5 fold of normal values in the mean). It is characterised as a broad beta band on the electropherogram similar to type III pattern. Presence of beta migrating lipoproteins in the ultracentrifugal supernatand fraction of d = 1006 could not be demonstrated.
Lipoprotein electrophoresis with measurement of serum lipids was performed on 115 patients with various forms of liver disease. There was a reduction in alpha-lipoproteins and an increase in beta-lipoproteins, as well as a reduced separability of pre-beta and beta fractions in those with acute viral hepatitis. All these changes regressed completely with healing. Similar changes were shown also in chronic liver disease and were most marked in acute liver failure, but also marked in decompensated liver cirrhosis and chronic progressive hepatitis, while less marked in chronic persistent hepatitis and compensated liver cirrhosis. In patients with fatty livers there were no characteristic findings other than a slight increase in pre-beta lipoproteins. On the other hand, the lipoprotein pattern was markedly changed in cases with tumour in the region of the gallbladder, but similar changes were noted also with tumours at other sites. They are, therfore, unlikely to be liver-specific.
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L-Arginine is the substrate for the nitric oxide synthase (NOS) pathway that is essential for gastrointestinal wound healing. L-Arginine is also the substrate for the enzyme arginase which metabolizes L-arginine to ornithine and subsequently to proline and polyamines both known to interact in cell proliferation and collagen synthesis. Two distinct isoforms of arginase exist. The temporal expression of the L-arginine metabolism in experimental colon anastomosis was investigated. Male Lewis rats underwent laparotomy. A left-sided colotomy was performed and the colon reanastomosed using 6-0 prolene. Sham operation was performed in controls. On days 2, 5, 10, 14, and 28 after the surgery the anastomosis was excised. The tissue at the anastomosis (ANAST) as well as above and below the anastomosis (PDC) and from sham colon was harvested and analyzed for distinct arginase isoform I (AI) and arginase isoform II (AII) activity, protein and mRNA expression as well as immunohistochemistry. iNOS protein and mRNA expression were investigated in parallel. A mean of 3 to 4 separate rats were analyzed per time point. Statistical analysis was performed by student's t-test, significance was reached when P < 0.05. AI activity, protein, and mRNA expression were significantly upregulated at the anastomosis compared to sham controls and PDC colons at all time points. The maximum was achieved at days 10 to 14 after wounding, and decreased to baseline levels thereafter. Inflammatory cells stained positive for AI. AII protein was not detectable. However RT-PCR showed low baseline expression. iNOS expression was upregulated early but for a shorter time period after wounding and reverted quickly to undetectable levels. In anastomotic healing, AI upregulation suggests a prolonged metabolism of arginine via arginase to polyamines and proline to provide substrate for collagen synthesis and cell proliferation. The functional implication of this arginase pathway further needs to be elucidated.
OBJECTIVE: To describe a reversible hypersensitivity reaction characterized by pericardial effusion and acute mixed liver injury in a woman treated with minocycline. CASE SUMMARY: A 39-year-old white woman developed dyspnea and chest pain with pericardial effusion on echocardiography approximately 20 days after starting minocycline treatment. Additional manifestations consisted of eosinophilia and liver injury. No lung, skin, or joint involvement was noted; antinuclear antibody testing was negative. DISCUSSION: Minocycline has been associated with rare but severe hypersensitivity reactions and autoimmune disorders, generally involving the lungs, skin, or joints. We observed a patient with an unusual minocycline-induced reaction with pericardial effusion and acute mixed liver injury. The number of spontaneously reported cases in national and international databases indicates that minocycline-induced pericardial effusion is very rare as a main clinical manifestation. CONCLUSIONS: Clinicians should be aware of the possibility of pericardial effusion without lung, skin, or joint involvement as an adverse effect of minocycline.
Numerous spontaneous reports of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have followed the increased use of selective serotonin reuptake inhibitors (SSRI). It has been estimated that 1 in 200 patients treated per year developed SIADH, age and low body weight being particular risk factors. No clear gender effect has been detected when confounding factors such as body weight or antidepressant consumption are taken into account. Age-related susceptibility to hyponatraemia may be explained by physiological changes in renal and endocrine function. The high prevalence of polymedication and pluripathology in the elderly may be a contributing factor as well. To date, no study has demonstrated how SSRIs affect the regulation of fluid/sodium balance nor whether they have an independent effect on this regulation in depressed subjects.
Recent research has revealed the presence of opioid receptors in inflamed peripheral tissues. This gives rise to the possibility of treating the pain caused by wounds with the advantage of reducing the secondary effects related to the use of opioids and at the same time rendering their use more efficacious. The theory of a peripheral analgesic action of opioids has been tested in a variety of situations, in particular in brachial plexus blocks and intra-articular injections. In addition, the analgesic effect of opioids has been tested by cutaneous application for various conditions but on only a limited number of patients. On the basis of these case reports, we cannot conclude that the peripheral use of opioids is efficacious and the topical use of opioids cannot be recommended unless done within the framework of a controlled clinical trial.
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Collaboration between industry and clinical sites is an excellent way to foster research and improve patient care. A seven-step program for collaboration was illustrated by a clinical trial of a new dressing, Ventex (Kendall Health Care Products Co.). The seven steps are (1) Establish basis for collaboration; (2)sign agreements or contracts; (3) develop a project plan; (4) develop the protocol; (5) implement the study; (6) analyze the data and report results; and (7) present conclusions and publish results. Dressing performance, clinician and patient acceptance, and healing indicate that the dressing is feasible for a variety of wounds in a variety of settings.
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