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9199330d-86a2-4cb5-8347-11df70b18d67
| 2 |
The former included antibodies of the IgG1 subclass which were considered to be particularly thymus dependent (1). The higher response of nu/nu mice was reflected mainly in the increased production of IgG antibodies. Under the influence of a graft-vs-host reaction, a 10-fold increase in antibody titers to DNP-AE-dextran was observed, due entirely to an enhanced IgG response.
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fc246427-c0c4-4db5-b39d-4a3fca590dff
| 0 |
Lymphoid cell fractionation by aggregated immunoglobulin-agarose columns. Fractionation by columns of aggregated rat immunoglobulin (Agg Ig)-agarose was investigated as a method of separating different populations of lymphoid cells. With rat spleen cells, Agg Ig columns retained phagocytes, IgM- and IgG-antibody-forming-cells, cells mediating antibody- or PHA-induced lysis of chicken erythrocytes, and specifically immune splenocytes lytic to chicken erythrocytes without exogenous antibody.
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fc246427-c0c4-4db5-b39d-4a3fca590dff
| 1 |
Agg Ig columns did not selectively remove 'B lymphocytes' (surface-Ig-bearing lymphocytes with or without EAC' receptors), or T lymphocytes capable of PHA-induced proliferation or graft-versus-host reactivity. With mouse spleen cells, Agg Ig columns retained alloimmune cytotoxic T cells.
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8c235f98-e06e-4c76-97e9-b55c334667e7
| 0 |
Rheological studies of Hb SS blood: influence of hematocrit, hypertonicity, separation of cells, deoxygenation, and mixture with normal cells. Studies of the rheological properties of Hb SS blood indicate that the marked increase in viscosity with deoxygenation is primarily due to cell-cell interaction of cells which were not permanently deformed.
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8c235f98-e06e-4c76-97e9-b55c334667e7
| 1 |
The permanently deformed cells, the bottom fraction of cells separated by centrifugation, show only a fraction of the increase in viscosity compared to top cells, when each was deoxygenated. Top cells showed a greater degree of morphologic change with deoxygenation compared to bottom cells. The viscosity of deoxygenated Hb SS blood was disproportionately reduced by the addition of compatible deoxygenated Hb AA cells.
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8c235f98-e06e-4c76-97e9-b55c334667e7
| 2 |
A mixture of 1/4 Hb AA cells and 3/4 Hb SS cells reduced the viscosity of deoxygenated Hb SS blood 50 per cent. Studies of Hb SS cells in hypertonic media indicate that hypertonicity per se does not cause sickling. Normal and Hb SS erythrocytes both show identical changes in rheological properties when suspended in hypertonic serum.
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8c235f98-e06e-4c76-97e9-b55c334667e7
| 3 |
However, changes in oxygen saturation due to a decrease in intracellular pH with certain hypertonic media may lead to sickling when Hb SS blood is at intermediate PO2 levels. The addition of x-ray contrast material to blood results in the changes due to hypertonicity but does not cause sickling of Hb SS cells.
|
8c235f98-e06e-4c76-97e9-b55c334667e7
| 4 |
The contrast material lowers the pH of the media and raises intracellular pH.
|
e603c297-edad-42ef-87c6-924e2d0b3735
| 0 |
Detection of pneumococcal polysaccharide in the sputum of patients with pneumococcal pneumonia by counterimmunoelectrophoresis. Each of 41 patients with bacterial pneumonia was placed into 1 of 4 categories based on the relative clinical certainty of the diagnosis of pneumococcal pneumonia. The frequency of pneumococcal polysaccharide in the sputum by counterimmunoelectrophoresis (CIE) was then noted for each diagnostic category of patients.
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e603c297-edad-42ef-87c6-924e2d0b3735
| 1 |
Detection of pneumococcal polysaccharide in sputum correlated with the diagnostic certainty of pneumococcal pneumonia, while results of culture of sputum were less indicative of pneumococcal infection. Saliva of 83 normal individuals failed to give positive tests for pneumococcal polysaccharide despite the presence of alpha-hemolytic streptococci on culture. Furthermore, the mere presence of pneumococci in cultures did not predict a positive test for polysaccharide by CIE nor did the absence of pneumococci mean that polysaccharide would not be detected.
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e603c297-edad-42ef-87c6-924e2d0b3735
| 2 |
This study suggests that detection of pneumococcal polysaccharide appears more rapid, more sensitive, and more specific than sputum cultures in diagnosing pneumococcal infection of the lung.
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b659f2b3-6803-4a92-a6b2-1eb86090caa2
| 0 |
The myofilament lattice: studies on isolated fibers. IV. Lattice equilibria in striated muscle. Accounts of similarities between the thick filament lattice of striated muscle and smectic liquid-crystalline structures have focused upon an equilibrium between electrostatic (repulsive) and van der Waal's (attractive) forces. In living, intact muscle the fiber volume constitutes an additional important parameter which influences the amount of interaxial separation between the filaments.
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b659f2b3-6803-4a92-a6b2-1eb86090caa2
| 1 |
This is demonstrable by comparison of the lattice behavior of living fibers with that of fibers from which the sarcolemma has either been removed or made leaky by glycerination. These comparisons were made mainly by low-angle X-ray diffraction under conditions of changes in sarcomere length, ionic strength or osmolarity, and pH.
|
b659f2b3-6803-4a92-a6b2-1eb86090caa2
| 2 |
Single fibers with the sarcolemma removed and glycerinated muscle have lattices which behave in accord with equilibrium liquid-crystalline systems in which the thick filament spacing is determined by the balance between electrostatic and van der Waal's forces. Conversely, osmotic and shortening studies demonstrate that the living, intact muscle has a lattice which behaves in accord with the so-called non-equilibrium (volume-constrained) liquid-crystalline condition in which the interaxial separation between the thick filaments is solely due to the amount of volume available as determined by the Donnan steady-state across the sarcolemma.
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cb8268a8-34e1-42e3-8499-b4af3175a1c3
| 0 |
The identification and subcellular localization of thrombosthenin "M", the myosin-like component of pig platelets. A protein has been studied which spontaneously precipitates from stored fractions of platelet soluble phase prepared by density gradient centrifugation. It is rich in a Ca2+ ATPase activity which displays an activity/pH profile resembling that of skeletal muscle myosin.
|
cb8268a8-34e1-42e3-8499-b4af3175a1c3
| 1 |
Adjustment of freshly prepared soluble phase fractions to 0.6 M with respect to KCl and dilution 1 in 3 results in the precipitations of a protein fraction with essentially the same enzymatic properties as the spontaneously precipitable protein. These two similar proteins represent between 9 and 13% of the soluble phase total protein and each account for almost the whole of divalent cation activated ATPase activity of the soluble phases from which they were derived.
|
cb8268a8-34e1-42e3-8499-b4af3175a1c3
| 2 |
The Mg2+ ATPase activity is only about twice purified with respect to the soluble phase enzyme activity, but the Ca2+ ATPase shows a 10-13-fold enrichment. Synthetic actomyosins can be prepared from the two proteins by addition of either platelet or skeletal muscle actin. These show significant increases in Mg2+ ATPase at the most favourable combination ratios.
|
cb8268a8-34e1-42e3-8499-b4af3175a1c3
| 3 |
The ratio between the yield of soluble phase protein obtained by dilution precipitation and the lactate dehydrogenase activity of the soluble phase remains constant under a wide range of homogenization and sonication conditions applied to the original whole platelet suspensions. This confirms our earlier view that the soluble phase is a valid intracellular compartment for a considerable proportion of the platelet contractile protein and that in the complex the myosin-like component predominates.
|
74105ec1-38c9-4a20-ab52-a3a72308ac7e
| 0 |
Control of mouth opening and pharynx protrusion during feeding in the sea anemone Calliactis parasitica. 1. Activity in all three known conducting systems (the nerve net, SS1, and SS2) may accompany feeding in Calliactis. The most marked response is an increase in pulse frequency in the SS2 (the endodermal slow conducting system) during mouth opening and pharynx protrusion.
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74105ec1-38c9-4a20-ab52-a3a72308ac7e
| 1 |
2. Electrical stimulation of the SS2 at a frequency of one shock every 5 s elicits mouth opening and pharynx protrusion in the absence of food. 3. A rise in SS2 pulse frequency is also evoked by food extracts, some amino acids, and in particular by the tripeptide reduced glutathione, which produces a response at a concentration of 10(-5) M.
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74105ec1-38c9-4a20-ab52-a3a72308ac7e
| 2 |
4. Although the SS2 is an endodermal system, the receptors involved in the response to food appear to be ectodermal. 5. The epithelium that lines the pharynx conducts SS1 pulses, but there is some evidence for polarization of conduction.
|
06f2a42e-8d90-4cd7-93d2-412b864f7260
| 0 |
Blood oxygen transport and metabolism of the confined lugworm Arenicola marina (L.). Oxygen consumption (MO2), haemoglobin oxygen saturation level (SVO2) and pH (pHv) in prebranchial blood were measured in lugworms experimentally confined in sea water at 15 degrees C. Total blood flow through the gills (Vb) was estimated.
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06f2a42e-8d90-4cd7-93d2-412b864f7260
| 1 |
For sea water oxygen partial pressure (PwO2) between 120 and 150 Torr MO2, SVO2 and Vb were high and nearly constant. For PwO2 less than 120 Torr, Vb fell quickly, MO2 progressively dropped, and metabolism remained aerobic at the expense of the prebrancial blood oxygen store.
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06f2a42e-8d90-4cd7-93d2-412b864f7260
| 2 |
For PwO2 less than 50 Torr, Vb and SvO2 values were extremely low, and the low pHv and the modified buffer power of the surrounding sea water showed that anaerobic metabolism was occurring. Changes in respiratory gas exchanges and metabolism during the tidal cycle are deduced from the comparison of these results with data obtained in the field.
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d4a2efb0-4480-4ee4-bec2-e7610afd80e2
| 0 |
Multiple sedimenting species of properdin in human serum and interaction of purified properdin with the third component of complement. Normal human serum subjected to sucrose density gradient analysis exhibited multiple sedimenting species of properdin antigen. Properdin antigen distribution was dependent on serum concentration, ionic strength, temperature, and the presence of C3, and was not dependent on the presence of divalent metal cations or blood coagulation.
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d4a2efb0-4480-4ee4-bec2-e7610afd80e2
| 1 |
In mixtures of purified components, properdin sedimented heavier in the presence of C3, C3b, or C3c. Addition of factor B to mixtures containing C3 and properdin was without effect. These data provide insights into earlier discrepancies concerning the sedimentation behavior of partially purified properdin, indicate a propensity of some constituents of the alternative pathway to form protein-protein complexes, and suggest caution in interpretation of immunopathological studies in which properdin deposits are found in the presence of C3.
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1c278aec-368c-4655-86fb-7378ebe9cbad
| 0 |
[Cathepsin, phosphoprotein-phosphatase and acid phosphatase in the soluble fraction of the cattle brain cortex: purification and properties (author's transl)]. Cattle brain cortex was homogenised in 0, 29 mol/1 sucrose and centrifuged at 101 000 X g. The supernatant contains the majority of 3 enzymes participating in protein turnover:
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1c278aec-368c-4655-86fb-7378ebe9cbad
| 1 |
cathepsin (EC 3.4.4.23), phosphoprotein phosphatase (EC 3.1.3.16) and acid phosphatase (EC 3.1.3.2). They were separated by chromatography on Sephadex G 200 in neutral buffer. The cathepsin was purified up to 380 fold by gel filtration on Sephadex and column electrophoresis. The pH optimum of cathepsin was 5.7
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1c278aec-368c-4655-86fb-7378ebe9cbad
| 2 |
. At 37 degrees C no decrease of activity was measurable during 30 min. The Km was found to be 2.75 mg/ml Casein Hammarsten. The molecular weight by gel filtration and exclusion-gel electrophoresis was about 45 000, corresponding to the cathepsin from human liver (Barrett, A.
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1c278aec-368c-4655-86fb-7378ebe9cbad
| 3 |
J. (1970) Biochem. J. 117, 601-607). The sedimentation constant 3.0 S20,W is comparable with the values of proteinase of different origin, and the composition is similar with respect to the high proportion of acidic amino acids. The phosphoprotein phosphatase can be further purified by chromatography on hydroxyapatite and by column electrophoresis.
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1c278aec-368c-4655-86fb-7378ebe9cbad
| 4 |
The pH optimum of phosphoprotein phosphatase was about pH 5.5. At 45 degrees C no decrease of activity was measurable during 20 min; the Km was 1.43 mg/ml casein isoelectric. The pH optimum of acid phosphatase was about 5.6. At 54 degrees C NO DECREASE OF ACTIVITY WAs measurable during 30 min;
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1c278aec-368c-4655-86fb-7378ebe9cbad
| 5 |
the Km was 2 mumol/1 for Sodium phenolphthalein diphosphate. All three enzymes slowly lost their activity during several weeks at - 4 degrees C, apparently by self digestion in the cold.
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0010e3ad-e724-4029-8b6d-cf87357bb892
| 0 |
Polydipsia, hyponatremia, and seizures in psychotic patients. Case histories are presented for four psychotic patients who ingested large quantities of water and subsequently developed grand mal seizures and serum sodium levels of less than 121 meq/liter. The physiology of psychogenic polydipsia and related disorders is reviewed. The relation of this disorder to temporal lobe seizures and to the use of phenothiazines is considered.
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44fa1219-b1b7-4a79-ae04-06b1e341529b
| 0 |
Isolation from bovine brain of a fraction containing capillaries and a fraction containing membrane fragments of the choroid plexus. Combined differential and density gradient centrifugation was used for the isolation of a capillary-rich fraction from the cerebral cortex and a brush border containing fraction from the bovine choroid plexus.
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44fa1219-b1b7-4a79-ae04-06b1e341529b
| 1 |
The activities of gamma-glutamyl transpeptidase and several other marker enzymes were monitored during the fractionation procedure. Electron microscopic examination showed a membrane-rich fraction in the choroid plexus high in the gamma-glutamyl transpeptidase and 5'-nucleotidase activities. From the brain cortex, a capillary-rich fraction was obtained which was high in gamma-glutamyl transpeptidase and alkaline phosphatase activities.
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44fa1219-b1b7-4a79-ae04-06b1e341529b
| 2 |
A histochemical examination showed gamma-glutamyl transpeptidase activity localized in the capillary walls.
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fd26de4c-314c-4378-9f84-15eba34e3d5d
| 0 |
Ionic mechanism of 5-hydroxytryptamine induced hyperpolarization and inhibitory junctional potential in body wall muscle cells of Hirudo medicinalis. Five-hydroxytryptamine (5-HT) causes a hyperpolarization and increased conductance of the leech body wall muscle cell membrane. If 5-HT is applied in the absence of the Cl minus ion, the response appears as a depolarization, whereas if 5-HT is applied in the absence of the K+ ion, the response is a hyperpolarization.
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fd26de4c-314c-4378-9f84-15eba34e3d5d
| 1 |
In both cases, the conductance of the muscle cell membrane is increased. Stimulation of the peripheral nerve to the body wall muscle produces a complex junctional potential in muscle cells. Exposing the muscle to d-tubocurarine (d-TC) eliminates the excitatory component (EJP) of the complex potential.
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fd26de4c-314c-4378-9f84-15eba34e3d5d
| 2 |
The inhibitory potential (IJP) that remains has an equilibrium potential at approximately 65 mV. Furthermore, this IJP appears as a depolarization when the nerve is stimulated in the presence of d-TC and low CL minus, whereas this is not the case if the nerve is stimulated in the presence of d-TC and low K+.
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fd26de4c-314c-4378-9f84-15eba34e3d5d
| 3 |
The drugs BOL-148 and cyproheptadine block the IJP's in the body wall muscle. These data are interpreted as indicating that 5-HT acts on leech body wall muscle cells by increasing the conductance to the Cl minus ion and that the IJP's caused by nerve stimulation are probably the result of 5-HT release at nerve terminals.
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fd26de4c-314c-4378-9f84-15eba34e3d5d
| 4 |
As a final point, it has been shown that the inhibition by 5-HT of the spontaneous EJP's that occur on the leech body wall muscle results from an inhibition of central neurons and not from any direct effect on the muscle cell or on peripheral synapses.
|
740f7182-a120-4c95-9af8-86056b0ce66d
| 0 |
Cerebrospinal fluid lactate and lactate/pyruvate ratios in hydrocephalus. Cerebral metabolism in 21 hydrocephalic patients was studied. Preoperative and postoperative specimens of cerebrospinal fluid (CSF) were obtained and the cerebral perfusion pressure (CPP) was calculated in each instance. The specimens of CSF were analyzed for lactate and pyruvate and the lactate/pyruvate (L/P) ratio was calculated for each sample.
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740f7182-a120-4c95-9af8-86056b0ce66d
| 1 |
The L/P ratio, which reflects the redox state of the cell, was used to determine the extent of anaerobic metabolism. An inverse relationship was noted between CPP and lactate as well as the L/P ratio. In general, the level of anaerobic metabolism was decreased after insertion of a shunt.
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5a247d90-cd79-4f5e-bc00-144af7884ddc
| 0 |
Effects of hyperventilation, CO2, and CSF pressure on internal carotid blood flow in the baboon. The combined effect upon cerebral blood flow (CBF) of an elevation of cerebrospinal fluid pressure (CSFP) and changes in respiratory CO2 was studied in nine baboons under chloralose anesthesia. The animals were mildly hyperventilated and provided with increasing amounts of CO2 in O2-air.
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5a247d90-cd79-4f5e-bc00-144af7884ddc
| 1 |
Arterial CO2 tensions (PaCO2) increased from 17 to 58 mm Hg. Internal carotid blood flow (ICBF) was measured at normal CSFP and at hydrostatically maintained 50 mm Hg CSFP. It was found that: 1) end-tidal CO2 may be used as a substitute for arterial PaCO2 determinations;
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5a247d90-cd79-4f5e-bc00-144af7884ddc
| 2 |
2) this elevation of CSFP has little effect on ICBF during hypercapnia and normocapnia; however, 3) during hypocapnia the ICBF is reduced an additional 20% when CSFP is elevated; that is, ICBF is reduced 50% from normal when end-tidal CO2 is reduced to 2% at this elevated level of CSFP.
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5a247d90-cd79-4f5e-bc00-144af7884ddc
| 3 |
Caution should be exercised during hyperventilation therapy particularly if the elevated CSFP or intracranial pressure (ICP) is not reduced to approach normal levels; in these conditions, the combination of decreasing PaCO2 and elevated ICP may reduce CBF below critical levels and thus lead to cerebral hypoxia.
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bdcee5d5-ae17-4317-a6b9-ace1ceb5a537
| 0 |
The effect of dietary vanadium on fatty acid and cholesterol synthesis and turnover in the chick. Day-old male, broiler type chicks were used to study the effect of 100 ppm dietary vanadium on fatty acid and cholesterol synthesis and turnover in vivo. After feeding the experimental diets for 4 weeks body weight and liver weight of chicks fed 100 ppm vanadium were significantly less than those of the control chicks and liver total lipid and cholesterol tended to be slightly higher than the levels of the control chicks.
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bdcee5d5-ae17-4317-a6b9-ace1ceb5a537
| 1 |
[1-14C] Acetate was administered intravenously and the specific activities of plasma and liver total lipid, cholesterol and fatty acid were determined at 0.25, 0.50, 1.0, 4.0, 8.0 and 15.0 hours after the injection. Plasma total lipid and cholesterol were significantly higher than the levels in the control chicks.
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bdcee5d5-ae17-4317-a6b9-ace1ceb5a537
| 2 |
The rate of incorporation of [1-14C]acetate into plasma and liver total lipid, cholesterol and fatty acid was higher in chicks fed vanadium than the control group at any of the time being tested after the injection. There was a significant increase in the hepatic citrate cleavage enzyme activity among chicks fed 100 ppm vanadium, whereas, there was no significant change in acetate thiokinase activity.
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bdcee5d5-ae17-4317-a6b9-ace1ceb5a537
| 3 |
Turnover rate of plasma total lipid and fatty acid in vanadium fed chicks was lower than the control. The turnover rate of plasma cholesterol determined by administering [4-14C]cholesterol and periodically measuring the specific activity of plasma cholesterol was higher in chicks fed vanadium than in those fed the basal diet.
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297ce047-969a-4bbd-a28d-51c08be58ff3
| 0 |
Changes of pH-values during storage of fetal blood samples. In recent years increased attention has been given to the degree of acidity of fetal blood during the course of labor or immediately after delivery. As it is not always possible to measure the blood pH immediately after sampling, it is important to know whether or not the pH is likely to change if the blood sample is stored for some time.
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297ce047-969a-4bbd-a28d-51c08be58ff3
| 1 |
30 heparinized whole blood samples were collected from the umbilical artery of 30 newborn infants immediately after delivery and were stored at room temperature. pH -measurements were made every 5 minutes up to 80 minutes. In a second group the same number of samples were stored in a refrigator.
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297ce047-969a-4bbd-a28d-51c08be58ff3
| 2 |
pH-measurements were performed after 30 minutes and then every hour for up to 7 hours, and finally after 24 hours. The pHact-values did not change at room temperature (about 24 degrees C) for up to 25 minutes; pHqu40-values decreased initially more rapidly but at 50 minutes the decrease was the same as in pHact-values namely 0.02
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297ce047-969a-4bbd-a28d-51c08be58ff3
| 3 |
units. Afterwards the pHact-values decreased at a mena rate of about 0.03 units per hour and pHqu40-values at a mean rate of about 0.017 units per hour. If the storage temperature was lowered by refrigeration (about 6 degrees C) the pHact-values remained between 0 and -0.02
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297ce047-969a-4bbd-a28d-51c08be58ff3
| 4 |
units for 6 hours and pHqu40-values for 3 hours. From these experiments it can be concluded that fetal blood samples must be kept in a refrigerator in order to inhibit autoxidation, if they have to be stored for longer than 50 minutes.
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bb66d091-8919-4c65-8769-63453b323fe4
| 0 |
Inhibition of drug-induced anorexia in rats by methysergide. Iproniazid was found to reduce food consumption in fasting rats. Combined treatment of iproniazid with tryptophan resulted in a significantly greater anorexic action whilst tryptophan alone had no effect on food consumption. Iproniazid treatment was associated with a significant increase in brain 5-hydroxytryptamine (5-HT) concentration but in association with tryptophan higher brain 5-HT concentrations were recorded.
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bb66d091-8919-4c65-8769-63453b323fe4
| 1 |
The anorexic action of the iproniazid-tryptophan combination was antagonized in a dose-dependent fashion by methysergide. Equivalent levels of anorexia induced by fenfluramine and mazindol were similarly antagonized by methysergide in a dose-related manner. The results suggest a common role of 5-HT in the inhibition of eating behaviour in fasting rats when anorexia is induced by iproniazid, fenfluramine or mazindol, sensitive to a specific 5-HT antagonist.
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e5513e1b-1e9b-4030-8cc1-2765803bbc93
| 0 |
Cerebral monoamine metabolism in guinea-pigs with ascorbic acid deficiency. Guinea-pigs kept on a diet deficient in vitamin C showed, after 3 weeks, a marked decrease of ascorbic acid in brain and blood leucocytes as well as of the activity of alkaline phosphatase in blood plasma. Pair-fed animals did not exhibit these changes.
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e5513e1b-1e9b-4030-8cc1-2765803bbc93
| 1 |
The alpha-methyl-p-tyrosine (alpha MpT)-induced diminution of noradrenaline in the hypothalamus and the rest of the brain was attenuated in pair-fed animals, but restored in guinea-pigs deficient in ascorbic acid. The cerebral noradrenaline content (without administration of alpha MpT) showed a decrease in both pair-fed and ascorbic acid deficient animals.
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e5513e1b-1e9b-4030-8cc1-2765803bbc93
| 2 |
The noradrenaline of the heart exhibited a similar tendency. The alpha MpT-induced dopamine decrease in the striatum of ascorbic acid deficient animals was attenuated and the dopamine content (without alpha MpT administration) decreased. Pair-fed animals showed a similar tendency. The striatal concentration of homovanillic acid (HVA) was diminished in both pair-fed and ascorbic acid deficient guinea-pigs.
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e5513e1b-1e9b-4030-8cc1-2765803bbc93
| 3 |
The cerebral content of 5-hydroxyindoleacetic acid showed a decrease in pair-fed as well as in ascorbic acid deficient animals. It is concluded that ascorbic acid deficiency enhances the turnover of brain noradrenaline, whereas under-nutrition without ascorbic acid deficiency (pair-feeding) diminishes the turnover of cerebral noradrenaline, 5-hydroxytryptamine and striatal dopamine.
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a09c29df-ace0-426e-8477-9e134052583d
| 0 |
The effect of an aldosterone antagonist on the protective action of carbenoxolone on the gastric mucosal barrier. The effect of an aldosterone antagonist on the protective action of carbenoxolone sodium on the gastric mucosal barrier has been studied in three dogs with Heidenhain pouches.
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a09c29df-ace0-426e-8477-9e134052583d
| 1 |
The net fluxes of hydrogen ion and sodium ion were measured before, during, and after contact with a 10 mM bile acid solution at pH 2, in pouches which had not been treated with drugs, in pouches treated with carbenoxolone sodium and in pouches treated with both carbenoxolone sodium and the aldosterone antagonist, spironolactone. Hydrogen ion back diffusion from, and sodium ion gain by the untreated pouch was increased by 10 mM bile acid solution.
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a09c29df-ace0-426e-8477-9e134052583d
| 2 |
Addition to the pouches of either carbenoxolone sodium alone or carbenoxolone sodium and spironolactone reduced the hydrogen ion back diffusion after exposure to the bile acid solution. The spironolactone did not change the protective effect of carbenoxolone on the gastric mucosal barrier. Carbenoxolone did not change the increased sodium ion diffusion caused by bile.
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493e2d52-1564-4840-921c-491d2afb31db
| 0 |
The quantification of kanamycin ototoxicity in the rat using conditioned tone discrimination. Twelve male Lister hooded rats were conditioned to discriminate an 8 kHz tone (56.5 +/- 0.5 dB re 0.0002 dyne cm-2) and were subsequently injected subcutaneously with kanamycin (400 mg kg-1 day-1) for 28 days; during this time and for five weeks after dosage was stopped, the nature and extent of the resultant hearing deficits were studied.
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493e2d52-1564-4840-921c-491d2afb31db
| 1 |
The animals' Preyer reflex thresholds were determined at intervals during the study. Only one rat was unaffected by the kanamycin dosage. The onset of hearing impairment (reduced discrimination performance), which was gradual in some rats and sudden in others, generally occurred during the fourth week of kanamycin dosage although the earliest onset was towards the end of the second week.
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493e2d52-1564-4840-921c-491d2afb31db
| 2 |
In most animals the hearing impairment progressed after kanamycin was stopped and in one rat there was a latency between the end of drug dosage and onset of hearing impairment. Hearing impairment was irreversible in five rats. One rat, whose impairment was slight, recovered normal hearing. Some rats showed a reduced discrimination performance at a time when their Preyer reflex threshold showed no elevation suggesting that kanamycin, at least initially, caused a threshold elevation rather than reduced sensitivity to intense sounds.
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c712d55a-f80f-4524-a20d-e522fe3566a3
| 0 |
The bioavailability in man of ICRF-159 a new oral antineoplastic agent. The bioavailability of the antineoplastic agent, ICRF-159, has been examined in 12 patients receiving the drug in single and subdivided dose schedules in an attempt to account for the differences in toxicity found with the different schedules clinically.
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c712d55a-f80f-4524-a20d-e522fe3566a3
| 1 |
Recovery of radioactivity in the urine after single large doses (13.3-19.4 g) was 8.5 +/- 3.0% of the administered dose. After doses of 3.8-5.55 g recovery was 22.7 +/- 10.5% and after the same dose subdivided into 3 equal aliquots it was 52 +/- 8.7
|
c712d55a-f80f-4524-a20d-e522fe3566a3
| 2 |
%. Unrecovered radioactivity was largely accounted for in the faeces. Plasma radioactivity levels in 2 patients after high and low dose were equivalent. Toxicity of the drug paralleled urinary recovery of radioactivity. It is concluded that schedule dependence of toxicity of ICRF-159 is at least partly due to bioavailability factors.
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65ee2ef9-28b0-459c-9420-91cfe1b1d09e
| 0 |
Cornea preparation for in vitro bio-pharmaceutical evaluation of ophthalmic dosage forms. A system has been developed for a specific biopharmaceutical purpose: testing for ophthalmic preparations, the influence of formulation on drug transport through the cornea. The apparatus is a lucite cell, divided in two compartments by a clamped rabbit cornea. Physiological conditions are ensured by a supply of oxygenated perfusion medium. They are monitored by electrical conductivity and corneal thickness measurements. Reliability of the system was tested in a set of experiments.
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957c48a0-cde8-4c0b-9432-a00f95a263c5
| 0 |
A study of the human metabolism of secbutobarbitone. The urinary excretion of secbutobarbitone (I) and its metabolites has been studied quantitatively using combined gas chromatography-mass spectrometry. After a single oral dose was given to healthy male volunteers, unchanged drug (5-9%), 2'-hydroxysecbutobarbitone (II, 1.7-3.2%), 2'-oxosecbutobarbitone (III, less than 1%), and the carboxylic acid (IV, 24-34%) were found. The kinetics of the excretion process were studied.
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9ef467eb-ee92-43f9-809b-a62ac0e865f9
| 0 |
The identification and analysis of the metabolic products of mephentermine. Phentermine (Ib), N-hydroxymephentermine (Ic) and N-hydroxyphentermine (Id) were identified as metabolic products after in vitro incubation of mephentermine (Ia) with rabbit liver microsomal fractions. Compounds Ia, Ib and Ic were also identified as excretion products in the urine of a human subject given a single dose of mephentermine (Ia) sulphate.
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9ef467eb-ee92-43f9-809b-a62ac0e865f9
| 1 |
Derivatization with acetic anhydride, trifluoroacetic anhydride and the trimethylsilyl donor reagent N,O-bis-(trimethylsilyl)-trifluoroacetamide (BSTFA) or hexamethyldisilazane (HMDS) were used for qualitative identification of the metabolic products Ib-Id by g.l.c.-mass spectrometry and for quantitative determination of Ia-Id after extraction from rabbit hepatic homogenates.
|
9ef467eb-ee92-43f9-809b-a62ac0e865f9
| 2 |
The synthesis of N-hydroxymephentermine (Ic) and the properties of the metabolic products are reported.
|
a6629c07-40e6-41a5-9bcc-bdb9b10bfa5e
| 0 |
A rapid g.l.c. procedure for the determination of codeine and norcodeine in biological fluids based on micro-phase extraction techniques. Therapeutic serum concentrations of codeine can be virtually completely extracted and obtained sufficiently concentrated for g.c. measurement without distillation, by acid extraction of the drug from the initial crude organic extracts of alkalinized serum followed by a micro-phase back extraction step.
|
a6629c07-40e6-41a5-9bcc-bdb9b10bfa5e
| 1 |
The procedure has simplicity, rapidity and eliminates concentration by distillation and background interference. The method can be readily adapted for the seperate measurements of codeine and norcodeine and it can also be used for similar analysis of other body fluids.
|
d42a231e-f4b4-43dd-a6ac-20be5abe2b2b
| 0 |
Plasma sodium concentration and sodium excretion in the anaesthetized dog. 1. The effect of acute alterations of plasma sodium concentration (PNa) on renal sodium excretion (UNaV) was investigated by three types of experiments on anaesthetized dogs: (a) A local increase in PNa at one kidney was produced by infusion of hypertonic saline directly into its artery while systemic levels of PNa were stabilized by haemodialysis.
|
d42a231e-f4b4-43dd-a6ac-20be5abe2b2b
| 1 |
(b) Systemic levels of PNa were lowered by exchange transfusion of blood for an equal volume of salt-free dextran-in-dextrose solution. The results were contrasted with those observed after similar exchanges, but using dextran-in-saline solution. (c) The level of PNa was altered by varying the sodium concentration of a saline solution infused at a fixed rate either intravenously or into one renal artery.
|
d42a231e-f4b4-43dd-a6ac-20be5abe2b2b
| 2 |
2. All three types of experiment suggest a dependence of UNaV on PNa Analysis demonstrated that this relationship was not due to contemporary changes in: packed cell volume; plasma solids concentration; plasma potassium concentration; blood pressure or plasma hydrogen ion concentration. The distribution of these variables did not change with PNa except for plasma hydrogen ion concentration.
|
d42a231e-f4b4-43dd-a6ac-20be5abe2b2b
| 3 |
Moreover, the relationship persisted when data were selected to exclude clearance periods in which the value for any variable had shifted past the group mean obtained before PNa was altered. 3. The fall in UNaV at low levels of PNa could be attributed to a fall in glomerular filtration rate (GFR), but the progressive rise in UNaV seen as PNa exceeded 150 m-mole 1(-1) occurred despite a fall in GFR and no apparent change in the mean filtered load of sodium.
|
d42a231e-f4b4-43dd-a6ac-20be5abe2b2b
| 4 |
These results suggest that the increased sodium excretion accompanying raised levels of PNa is due to reduced tubular re-absorption of sodium.
|
002730ef-2b14-4cb9-8c7f-0480d2989300
| 0 |
Synthesis of angiotensin II antagonists containing N- and O-methylated and other amino acid residues. [1-N-Methylisoasparagine,8-isoleucine]- (I), [1-sarcosine,4-N-methyltyrosine,8-isoleucine]- (II), [1-sarcosine,5-N-methylisoleucine,8-isoleucine]- (III), [1-sarcosine,8-N-methylisoleucine]- (IV), [1-sarcosine8k-N-methylisoleucine,8-N-methylisoleucine]- (V), [1-sarcosine,8-O-methylthreonine]- (VI), [1-sarcosine,8-methionine]- (VII), and [1-sarcosine,8-serine]angiotensin II (VIII), synthesized by Merrifield's solid-phase procedure, possess respectively 0.8
|
002730ef-2b14-4cb9-8c7f-0480d2989300
| 1 |
, 0.3, 0.5, 1.0, 0.0, 0.5, 3.7, and 0.7% pressor activity of angiotensin II (vagotomized, ganglion-blocked rats). They caused an initial rise in blood pressure (30 min of infusion, 250 ng/kg/min in vagotomized, ganglion-blocked rats) of 16.57, 9.80, 22.80
|
002730ef-2b14-4cb9-8c7f-0480d2989300
| 2 |
, 32.00, 7.00, 15.06, 32.50, and 11.42 mmHg and showed secretory activity (isolated cat adrenal medulla) of 1.0, 0.1, 0.01, 0.1, less than 0.01, 0.1, less than 0.01, and 0.05% of angiotensin II. On isolated organs pA2 values (rabbit aortic strips) of 8.74
|
002730ef-2b14-4cb9-8c7f-0480d2989300
| 3 |
, 7.44, 7.64, 7.85, 7.89, 8.76, 8.63, and 8.08, and pA2 values (cat adrenal medulla of 8.16, 9.16, 9.31, 8.00, 8.00, 7.00, 9.16, and 9.33 were obtained. Dose ratios (ratio of ED20 of angiotensin II during infusion of the antagonist and before infusion of the antagonist) in vagotomized, ganglion-blocked rats, infused at 250 ng/kg/min, were 33.43
|
002730ef-2b14-4cb9-8c7f-0480d2989300
| 4 |
, 2.14, 3.26, 2.99, 0.62, 62.52, incalculable, and 11.15, respectively. The results obtained suggest that (a) analogs I and VI are potent antagonists of the pressor response of angiotensin II in normal rat, VI being the most potent antagonist thus far synthesized;
|
002730ef-2b14-4cb9-8c7f-0480d2989300
| 5 |
(b) replacement of position 4 (Tyr) with MeTyr or position 5 and/or 8 (Ile) with Melle in [1-sarcosine,8-isoleucine]angiotensin II reduced the antagonist activity of this peptide (rabbit aortic strips and rats), indicating that steric hindrance imposed due to N-methylation in positions 4, 5, or 8 was not favorable in eliminating the initial pressor activity or prolonging the duration of action of [Sar1, Ile8]angiotensin II without reducing its antagonistic properties;
|
002730ef-2b14-4cb9-8c7f-0480d2989300
| 6 |
(c) except II, none of the analogs showed any enhanced duration of action, suggesting that N-methylation in positions 5 or 8 did not afford protection against proteolytic enzymes; and (d) perfusion studies in cat adrenals indicated that all of these analogs are only very weak secretagogues.
|
002730ef-2b14-4cb9-8c7f-0480d2989300
| 7 |
With the exception of [Sar1,Thr(ObetaMe)8]angiotensin II, which gave lower antagonistic properties, all other analogs had either similar antagonistic properties or were better antagonists in adrenal medulla than in smooth muscle.
|
8c141db3-a979-47ab-a47b-fd29ed03988f
| 0 |
Synthesis and enzymic activity of some novel xanthine oxidase inhibitors. 3-Substituted 5,7-dihydroxypyrazolo(1,5-alpha)pyrimidines.
|
8c141db3-a979-47ab-a47b-fd29ed03988f
| 1 |
A series of 3-substituted 5,7-dihydroxypyrazolo[1,5-alpha]pyrimidines containing various aromatic [phenyl- (3e), 3-pyridyl- (3f), p-bromophenyl- (3g), p-chlorophenyl- (3h), p-acetamidophenyl- (3i), p-tolyl- (3j), m-tolyl- (3k), 3,4-methylenedioxyphenyl- (3m), or naphthyl- (3n)] or nonaromatic [hydrogen- (3a), nitro- (3b), bromo- (3c), or chloro- (3d)] substituents in the 3 position was synthesized and tested as inhibitors of xanthine oxidase.
|
8c141db3-a979-47ab-a47b-fd29ed03988f
| 2 |
The compounds (3a-m) were synthesized by condensation of the appropriate 3-amino-4-substituted pyrazole with diethyl malonate in alcoholic sodium methoxide and neutralization of the resulting enol sodium salts. As inhibitors of xanthine oxidase, 3e-n greater than 3a,c,d congruent to allopurinol greater than 3b.
|
8c141db3-a979-47ab-a47b-fd29ed03988f
| 3 |
The 3-aryl-substituted compounds 3e-n were 30-160 times better xanthine oxidase inhibitors than allopurinol using hypoxanthine as substrate and 10-80 times better using xanthine as substrate, as evidenced by a comparison of Ki values. The inhibition by all compounds (3a-n) was totally reversible and of the noncompetitive or mixed type.
|
8c141db3-a979-47ab-a47b-fd29ed03988f
| 4 |
A study of the pH dependence of xanthine oxidase inhibition by 3a,e,g and allopurinol indicated that the 3-aryl substituents facilitated binding to the enzyme. These and the above results show that the compounds reported here inhibit xanthine oxidase by a mechanism which is significantly different from that of allopurinol.
|
96dee860-e70d-443d-ac8e-8252f50b6bf3
| 0 |
Immobilized glucuronosyltransferase for the synthesis of conjugates. Partially purified rabbit liver UDPglucuronosyltransferase is immobilized on agarose by the cyanogen bromide activation method. Both soluble and matrix-bound enzyme preparations display very similar Km and pH optimum. The storage stability of the immobilized enzyme at 4 degrees is 5-10 times improved over the soluble preparations.
|
96dee860-e70d-443d-ac8e-8252f50b6bf3
| 1 |
The agarose-bound UDPglucuronosyltransferase is successfully used in the synthesis of p-nitrophenyl glucuronide in an overall yield of 50-70%. The matrix-bound enzyme is reusable over an extended period of time and offers an easy and convenient synthetic tool for various drug glucuronides.
|
0bd4c115-3b7e-4e51-b9fd-8ef5814e82be
| 0 |
The limits of informed consent. The patient, a 59-year-old man, was referred to a psychiatric hospital with what appeared initially to be the signs and symptoms of mental disorder. In hospital a lesion of the brain was diagnosed and surgery was proposed to relieve the condition.
|
0bd4c115-3b7e-4e51-b9fd-8ef5814e82be
| 1 |
The patient, however, during this and subsequent admissions to hospital, refused operation. His refusal to consent was regarded as valid as he seemed to have good insight into his condition. Finally, under section 26 of the Mental Health Act, he was treated surgically. Unfortunately the patient died six weeks later of intracranial haemorrhage.
|
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