Stability of systems of three arbitrary charges: General properties.
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Biomedical subjects
Publications and source records attributed to A Martin.
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1. We tested the ability of ouabain to cause chronic hypertension by continuously infusing ouabain for 28 days (miniosmotic pump implantation; i.p.). The blood pressure and metabolic effects of sham (150 mmol/L NaCl; n = 12) or ouabain infusion (10 micrograms/kg per day; n = 14; 100 micrograms/kg per day; n = 14) were examined in conscious Sprague-Dawley rats. 2. Plasma ouabain concentrations measured after 28 days of ouabain infusion were as follows: sham, not detectable (n = 11); ouabain 10 micrograms/kg per day, 0.60 +/- 0.07 nmol/L (n = 14); and ouabain 100 micrograms/kg per day, 7.17 +/- 0.57 nmol/L (n = 14; P < 0.001). 3. Sham or ouabain infusion did not alter food intake, bodyweight, water intake or urine output in conscious rats. 4. Blood pressure was not altered by sham treatment. Ouabain at 10 micrograms/kg per day or 100 micrograms/kg per day did not produce consistent rises in blood pressure. Ouabain at 10 micrograms/kg per day increased blood pressure on treatment day 12 only (+6 mmHg; P < 0.05), while at 100 micrograms/kg per day blood pressure increased on treatment days 16 (+9 mmHg; P < 0.05) and day 18 (+8 mmHg; P < 0.05) only. There was no significant difference in blood pressure between sham and ouabain groups. 5. Renal blood flow was decreased in rats infused with ouabain at 10 micrograms/kg per day (2.0 +/- 0.3 mL/min per 100 g bodyweight; n = 5; P < 0.01) and 100 micrograms/kg per day (2.2 +/- 0.4 mL/min per 100 g bodyweight; n = 7; P < 0.05) compared with sham treatment (3.5 +/- 0.2 mL/min per 100 g bodyweight; n = 6). Renal vascular resistance was increased in rats treated with ouabain at 10 micrograms/kg per day (65.5 +/- 12.6 mmHg/mL per min per 100 g bodyweight; n = 5; P < 0.01) and 100 micrograms/kg per day (66.0 +/- 15.6 mmHg/mL per min per 100 g bodyweight; n = 7; P < 0.05) compared with sham treatment (32.6 +/- 2.5 mmHg/mL per min per 100 g bodyweight; n = 6). 6. High plasma concentrations of ouabain do not cause consistent increases in blood pressure in conscious Sprague-Dawley rats.
1. SCA40 (1nM-10 microM), isoprenaline (1-300 nM) and levcromakalim (100 nM-10 microM) each produced concentration-dependent suppression of the spontaneous tone of guinea-pig isolated trachea. Propranolol (1 microM) markedly (approximately 150 fold) antagonized isoprenaline but did not antagonize SCA40. The tracheal relaxant action of SCA40 was unaffected by suramin (100 microM) or 8-(p)-sulphophenyltheophylline (8-SPT; 140 microM). 2. An isosmolar, K(+)-rich (80 mM) Krebs solution increased tracheal tone, antagonized SCA40 (approximately 60 fold), antagonized isoprenaline (approximately 20 fold) and very profoundly depressed the log concentration-effect curve for levcromakalim. Nifedipine (1 microM) did not itself modify the relaxant actions of SCA40, isoprenaline or levcromakalim. However, nifedipine prevented the rise in tissue tone and the antagonism of SCA40 and isoprenaline induced by the K(+)-rich medium. In contrast, nifedipine did not prevent the equivalent antagonism of levcromakalim. 3. Charybdotoxin (100 nM) increased tracheal tone, antagonized SCA40 (approximately 4 fold) and antagonized isoprenaline (approximately 3 fold). Nifedipine (1 microM) prevented the rise in tissue tone and the antagonism of SCA40 and isoprenaline induced by charybdotoxin. 4. Quinine (30 microM) caused little or no change in tissue tone and did not modify the relaxant action of isoprenaline. However, quinine antagonized SCA40 (approximately 2 fold). Nifedipine (1 microM) prevented the antagonism of SCA40 induced by quinine. 5. Tested on spontaneously-beating guinea-pig isolated atria SCA40 (1 nM-10 microM) increased the rate of beating in a concentration-dependent manner. Over the concentration-range 1 microM-10 microM, SCA40 also caused an increase in the force of atrial contraction. 6. Intracellular electrophysiological recording from guinea-pig isolated trachealis showed that the relaxant effects of SCA40 (1 micro M) were often accompanied by the suppression of spontaneous electrical slow waves but no change in resting membrane potential. When the concentration of SCA40 was raised to 10 micro M, its relaxant activity was accompanied both by slow wave suppression and by plasmalemmal hyperpolarization.7. SCA40 (10 nM- 100 micro M) more potently inhibited the activity of cyclic AMP phosphodiesterase (PDE)than that of cyclic GMP PDE derived from homogenates of guinea-pig trachealis. Theophylline(1 micro M- 1O mM) also inhibited these enzymes but was less potent than SCA40 in each case and did not exhibit selectivity for inhibition of cyclic AMP hydrolysis.8. Tested against the activity of the isoenzymes of cyclic nucleotide PDE derived from human blood cells and lung tissue, SCA40 proved highly potent against the type III isoenzyme. It was markedly less potent against the type IV and type V isoenzymes and even less potent against the isoenzymes types I and II.9. It is concluded that the tracheal relaxant action of SCA40 (1 nM- 1 micro M) does not involve the activation of beta-adrenoceptors or P1 or P2 purinoceptors. Furthermore, this action is unlikely to depend upon the opening of BKca channels with consequent cellular hyperpolarization and voltage-dependent inhibition of Ca2+ influx. The tracheal relaxant action of SCA40 (up to 1 micro M) is more likely to depend upon its selective inhibition of the type III isoenzyme of cyclic nucleotide PDE. At concentrations above 1 micro M, SCA40 exerts more general inhibition of the isoenzymes of cyclic nucleotide PDE and may then promote the opening of BKca channels.
The concentrations of clavulanic acid and amoxicillin were determined in sera and different abdominal tissues of 17 patients who underwent elective colorectal surgery. Patients were randomly allocated to two groups. At the time of induction of anesthesia, patients in group 1 were given 200 mg of clavulanic acid with 2,000 mg of amoxicillin and patients in group 2 received 400 mg of clavulanic acid with 2,000 mg of amoxicillin. In both groups, the initial dose was administered again after 2 h. Blood samples were collected to determine peak and trough antibiotic levels. Serial blood samples were also collected at predetermined periods (opening and closure of the abdominal cavity and surgical anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously. Antibiotic concentrations were determined by high-performance liquid chromatography. Increasing the dose of clavulanic acid to 400 mg resulted in significantly higher peak and trough levels in serum (P < 0.03). Following the injection of 400 mg, mean concentrations of clavulanic acid in the fatty tissues were significantly increased at the time of opening (P < 0.02). The concentrations of clavulanic acid and amoxicillin in fatty tissues were 17 to 52% and 12 to 23% of the levels in sera, respectively. In the colonic wall, the concentrations of clavulanic acid and amoxicillin were 52 to 63% and 49 and 27% of the levels in sera, respectively. In sera, clavulanic acid given at a dose of 200 or 400 mg reached or exceeded the concentrations found to be effective in vitro to reduce the MICs of amoxicillin from the resistant to the susceptible category for 90% of the potential pathogens. In most of the tissues investigated, increased the dose of clavulanic acid to 400 mg resulted in a significantly higher number of samples with concentrations found to be effective in vitro (72 versus 11%; P < 0.05). In conclusion, increasing the dose of clavulanic acid to 400 mg resulted in higher levels in sera and improved penetration into the abdominal tissues in patients undergoing colorectal surgery.
Using gas chromatography-isotope ratio mass spectrometry, the detection, with a good reproducibility and in a single step, of the 13C content of glycoprotein neutral sugars, glycogen glucose, and ribonucleic acid ribose allowed us to trace incorporation into intestinal macromolecules of sugars derived from dietary glucose, labeled either naturally (as corn starch) or artificially. The 13C enrichment of glycoprotein neutral sugars was strong and rapid and plateaued up to the end of the experiment, whereas the 13C content of ribose increased linearly with time. By contrast, with artificially enriched dietary glucose, no significant 13C enrichment was detected in glycogen, suggesting that this macromolecule does not directly derive from dietary glucose. These results suggest differential control of sugars involved in the synthesis of intestinal macromolecules and demonstrate that this technique would be sensitive and reliable enough to be applied in man for serum glycoprotein sugar determinations.
The Oregon plan has had a significant impact in the U.S., sparking a public debate over issues such as cost-containment and access. This paper follows the Oregon health care plan from its beginnings in 1987 to the present, discussing the plan's pros and cons, the final outcome of the proposed legislation, and its relation to the national health care reform package proposed by President Clinton. Arguments for the plan have included: its innovativeness, its plans to expand accessibility and contain health care costs, and its encouragement of public involvement in health care issues. Arguments against the plan are: it provides no guarantee of a minimal level of services for medical recipients and it rations health care for the poor based on prioritization of condition-treatment pairs.
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BACKGROUND: Common etiopathogenic factors may explain the association of systemic sarcoidosis with inflammatory bowel disease. METHODS: We report two cases of such an association: one of sarcoidosis that developed 2 years after proctocolectomy for ulcerative colitis and one of sarcoidosis and Crohn's colitis. Factors like increased cellular immunity or circulating immunocomplexes or autoantibodies may have a role. Exogenous agents or familiarity may also be involved. CONCLUSIONS: It is postulated that the association between sarcoidosis and inflammatory bowel disease (both ulcerative colitis and Crohn's disease) does not occur by chance alone and that the two conditions may share some genetic or immunologic alterations. The two diseases, however, follow an independent clinical course.
Seven human T cell lines from a patient with Graves' disease were raised against endogenously generated human thyroid peroxidase (hTPO) with stimulation indices ranging from 2.1 to 7.6. Clonal expansion within these T cell lines was demonstrated by sequencing multiple bacterial colonies containing RT-PCR-generated fragments derived from the expressed hTcRs. Some lines had more than one human T cell receptor (hTcR) alpha and beta chain mRNAs as judged by RT-PCR. Stopcodons present in several hTcR sequences indicated that only one V alpha and one V beta gene were translated. Both the V alpha/beta gene families and the J alpha/beta gene segments differed amongst the lines and no characteristic recognition sequences were discernable in the CDR3 regions. Using Kyte-Doolittle analysis we found hydrophobic peaks in most N alpha-regions (but not N beta regions) suggesting that hydrophobic interactions may be important in the recognition of hTPO. However, increasing affinity values, as measured by SI, were strongly correlated with decreasing hydrophobicity in the N alpha region (1st order regression, r = -0.93138, p < 0.01). Thus, lower affinity, self-reactive, T cells may be more hydrophobic ('sticky') in their N alpha regions while higher affinity cells may be characterized by TcRs with lower hydrophobicity. These findings demonstrate a substantial role for hydrophobic interactions in hTPO-reactive T cell receptors and further support a role for the TcR alpha chain in the recognition of thyroid autoantigen.
In 54 patients with malignant lymphoma, haematopoietic recovery after high-dose chemotherapy and autologous bone marrow transplantation (BMT) was compared between patients randomised to receive 10 or 30 micrograms/kg/day of r-metHuG-CSF (filgrastim) or no growth factor. After standard high-dose chemotherapy with cyclophosphamide, etoposide and BCNU (CVB regimen for patients with Hodgkin's disease) or BCNU, etoposide, cytosine arabinoside and melphalan (BEAM regimen for patients suffering from non-Hodgkin's lymphoma) followed by autologous BMT, r-metHuG-CSF was administered by continuous intravenous infusion from the first day after autologous BMT until neutrophil recovery. When the r-metHuG-CSF groups were compared with the control group the major findings were: the median time to reach an absolute neutrophil count (ANC) > or = 0.5 x 10(9)/L was 20 days in the control group and 12 and 14 days, respectively, in the r-metHuG-CSF groups (P = 0.0004). The duration of neutropenia (ANC < 0.5 x 10(9)/L) was reduced from 27 days in the control group to 11 and 13 days in the r-metHuG-CSF groups (P = 0.0001). In addition, fewer days of febrile neutropenia were observed in the r-metHuG-CSF groups (5 and 6 days) than in the control group (10 days; P = 0.036). No significant effects of r-metHuG-CSF administration on the number of days with fever, the use of intravenous antibiotics and hospitalisation were detected. R-metHuG-CSF was well tolerated without any serious side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors report a case of recurrent pigmented intraspinal schwannoma with malignant progression. Electron-microscopic study confirmed that melanin pigment was produced by tumor cells and that these cells were derived from the nerve sheath. The histogenesis of pigmented tumors is explained by their neural crest origin and the problem of differential diagnosis of the malignant form with melanoma is discussed.
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The colon of 32 healthy Sprague-Dawley rats was studied microradiographically. The colonic arterial distribution of 18 rats was examined after injecting barium sulfate into the isolated aorta. The mucosal surface in 9 rats was studied using double-contrast technique after colon explantation. In 5 animals arterial and mucosal studies were carried out simultaneously. The radiographic thickness of the colonic wall was measured using a comparative microscope. The specimens were observed, photographed and examined histologically. Unlike the cecum and distal colon which, when insufflated, do not have mucosal folds, the proximal colon exhibits folds in an oblique direction corresponding to that of the arteries, and the colonic wall in this region is thicker. Comparison between arterial and mucosal microradiographic anatomy and wall thickness enables the proposition of a simple nontopographic division of the rat colon into cecum, proximal colon and distal colon.
Ceramide and ceramide-1-phosphate are sphingolipid analogues of diacylglycerol and phosphatidate, respectively, and they are putative second messengers of agonist-stimulated sphingomyelin metabolism. The interactions of exogenous cell-permeable ceramides and ceramide-1-phosphates in modifying DNA synthesis and signal transduction were investigated in Rat-1 fibroblasts. C2- and C8-Ceramide-1-phosphates (N-acetylsphingosine-1-phosphate and N-octanoylsphingosine-1-phosphate, respectively) at 1-10 microM stimulated DNA synthesis and cell division. This effect was blocked by cell-permeable ceramides. C2-Ceramide stimulated the conversion of exogenous C8-ceramide-1-phosphate to C8-ceramide, with very little production of sphingosine or sphingosine-1-phosphate. This mechanism may be partly responsible for preventing the stimulation of DNA synthesis. Unlike phosphatidate or lyso-phosphatidate, concentrations of C8-ceramide-1-phosphate that stimulated DNA synthesis did not inhibit adenylate cyclase activity, nor did they increase the activities of phospholipase D or mitogen-activated protein kinases (42- and 44 kDa isoforms). Although ceramide-1-phosphate can be considered as an analogue of phosphatidate, the effects of this compound on signal transduction differ considerably from those of phosphatidate. This work demonstrates that short-chain ceramide-1-phosphates can be used as novel external agonists that can stimulate DNA synthesis. This effect can be counteracted by short-chain ceramides.
A micromethod was developed to assay the hepatic activity and subcellular distribution of phosphatidate phosphohydrolase (PAH, EC 3.1.3.4), an important regulatory enzyme in triacylglycerol synthesis, in human needle biopsy specimens. In normal liver PAH is predominantly cytosolic in distribution, but on treatment with oleic acid it shifts to the membranous compartments of the cell, its physiologically active site. The hepatic specific activity of PAH was similar in controls and patients with fatty liver but significantly more of the enzyme was associated with the membranous compartments in patients with severe alcoholic fatty liver. These observations may explain the enhanced rates of triacylglycerol synthesis observed in these patients and may be implicated in the pathogenesis of alcoholic fatty liver.
During pregnancy, the human placenta secretes a variant of pituitary growth hormone (hGH-V) differing in sequence from the pituitary growth hormone (hGH-N) by 13 amino acids substitutions. HGH-V replaces hGH-N in the maternal bloodstream during the second half of pregnancy. HGH-V is produced in two, possibly three, isoforms: a 22 kDa form, a glycosylated 25 kDa form, and a probable 26 kDa form resulting from alternative splicing of the mRNA. Here we have studied the somatogenic and lactogenic activity of recombinant 22 kDa hGH-V isoform produced in Escherichia coli and compared it with the 22 kDa form of hGH-N. The two variants exert a similar somatogenic effect on rabbit and rat cells, but differ as regards their lactogenic activity in the rat.
The purpose of the study was to examine the influence of a 3-wk period of electrostimulation training on the strength of the latissimus dorsi m. and the swimming performances of 14 competitive swimmers divided into 7 electrostimulated (EG) and 7 control swimmers (CG). The peak torques registered during the flexion-extension of the arm was determined with the help of an isokinetic dynamometer at different velocities (from -60 degrees.s(-1) to 360 degrees.s(-1)). Performances were measured over a 25-m pull buoy and a 50-m freestyle swim. For EG, a significant increase of the peak torques was measured in isometric, eccentric, and concentric conditions (P < 0.5). The swimming times declined significantly (P < 0.01) by 0.19 +/- 0.14 s, for the 25-m pull-buoy, and by 0.38 +/- 0.24 s, for the 50-m freestyle. For CG, no significant difference was found for any of the tests. For the whole group, the variations of the peak torques, measured in eccentric condition (-60 degrees.s(-1)) were related to the variations of the performances (r = 0.77; P < 0.01). These results showed that an electrostimulation program of the latissimus dorsi increased the strength and swimming performances of a group of competitive swimmers.