Photochemotherapy and photodynamic toxicity: simple methods for identifying potentially active agents.
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Biomedical subjects
Publications and source records attributed to I Diamond.
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Endogenous membrane protein kinase activity and protein kinase substrates have been found in membrane fractions enriched in the acetylcholine receptor that were prepared from the electric organ of Torpedo californica. Phosphorylation of four polypeptides is stimulated 9-fold by K+. The specific cholinergic ligand, carbachol, inhibited phosphorylation of these four polypeptides by 72% in the presence of 1mM Na+ and 100 mM K+. The 65,000-dalton component of the acetylcholine receptor in the membrane fraction appears to be phosphorylated by the endogenous protein kinase. These results suggest that protein phosphorylation may play an important role in synaptic events at nicotinic cholinergic synapses.
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Magnesium-deficient fetuses exhibited malformations (44%), anemia, and edema. Maternal plasma magnesium levels at day 21 of pregnancy reflected the level of dietary magnesium (2.43 +/- 0.09 mg Mg/100 ml, control; 0.74 +/- 0.02 mg Mg/100 ml, deficient). Plasma magnesium levels of deficient fetuses showed similar decreases although all fetal magnesium values at term were hihger than maternal values from the same group (3.29 +/- 0.22 mg Mg/100 ml, control; 1.78 +/- 0.07 mg Mg/100 ml, deficient). Magnesium deficiency did not appear to affect the maternal blood parameters. However, when fetal blood was examined, all of the parameters measured were altered in magnesum-deficient fetuses (Table 2). No abnormalities in hemoglobin bands or plasma proteins were seen between any groups by electrophoresis. Measurement of total protein contents showed no differences between maternal blood protein contents, but total plasma protein from magnesium-deficient fetuses was significantly lower than controls (2.00 +/- 0.14 versus 2.62 +/- 0.13 g/100 ml), thus establishing a factor in fetal edema production. Morphologic data showed that in magnesium-deficient fetuses, fetal erythropoiesis was significantly greater in liver, adrenal glands, and spleen than in controls and that maturation was normoblastic. Stained and unstained peripheral blood smears of magnesium-deficient fetuses showed and obvious macrocytosis and at least 50% of the red cells stained abnormally, exhibiting pale areas. Erythrocytic morphology seen in fetal magnesium deficiency is consistent with inadequate filling of the cell by hemoglobin as suggested by Cohlan et al. (5), a probable cause of membrane collapse. The inadequate filling of magnesium-deficient red blood cells (RBC) with hemoglobin might be explained by a reduction in hemoglobin synthesis which is consistent with the reduced mean corpuscular hemoglobin (MCH) and MCH concentration (MCHC) of the deficient fetal red cells. The role of magnesium in protein synthesis is also compatible with a reduction in hemoglobin synthesis, yet may not completely explain the abnormalities and resultant shortened lifespan of the red cells.
Thyroid glands of 36 chickens of the obese strain with hereditary spontaneous autoimmune thyroiditis were examined by electron microscopy at 1, 3, 5, 7, 10, and 14 weeks of age with particular emphasis on basal lamina changes. All chickens were of the B1B1 genotype. The electron microscopic results were compared with six normal White Leghorn chickens of the same age. The major abnormality observed in obese strain chickens was the persistent presence of electron-dense deposits along the follicular basal lamina in the thyroid beginning with 7-week-old chickens. The deposits morphologically comparable to immune complexes were noted either between the basal plasma membrane and the follicular basal lamina or below the follicular basal lamina. In 14-week-old chickens, the electron-dense deposits were observed within abnormally thickened basal lamina. The deposits were not present in the vascular basal lamina adjacent to the thyroid follicles and were not observed in the thyroids of 1- to 5-week old chickens and were also not encountered in normal White Leghorn chickens. Indirect morphologic evidence suggests that these may be antigen-antibody complexes, but characterization of these deposits and their role remain to be determined.
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Statistically significant cerebral arteriovenous differences of D-beta-hydroxybutyrate were found in rats made diabetic by administration of streptozotocin. The amount of D-beta-hydroxybutyrate extracted by the brain in diabetic animals increased with increasing arterial concentrations and the extraction ratios were comparable to those found in animals and humans with ketosis due to other causes.
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1. The limited bilirubin binding capacity of human serum albumin, and the fact that kernicterus can occur once the serum unconjugated bilirubin concentration exceeds this capacity, makes the assessment of non-albumin bound free bilirubin valuable in cases of severe neonatal hyperbilirubinemia. 2. Present methodology for this assessment utilizes Sephadex column chromatography, and is somewhat tedious and slow. 3. We have developed a procedure for assessing the albumin binding capacity of serum by titrating a sample of the serum with T-20 Dextran coated charcoal. 4. The method requires 2 ml of serum, takes 90 minutes to complete and is highly reproducible. 5. By this method, we can determine the reported secondary loose binding capacity of the albumin as well as the tight binding capacity which is determined by existing methods. 6. The tight binding capacity of a pool of normal adult human serum was found to be 20 mg/dl of serum. 7. This is in agreement with existing methods. The loose binding capacity was found to be an additional 10 mg/dl of serum. Added phenobarbital was found to lower the tight binding capacity, but not the secondary capacity.
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Malignant tumors take up and retain hematoporphyrin to a much greater extent than do normal tissues. Porphyrins are photodynamic agents that sensitize cells so that they are damaged by exposure to light. Treatment with hematoporphyrin followed by irradiation with light can destroy glioma cells in culture in less than 8 min and gliomas growing s.c. in rats in about 40 min. Photochemotherapy may become useful in the management of malignant tumors that are resistant to current methods of treatment.
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1. The role of muscle mass and function in the regulation of choline acetyltransferase activity at the neuromuscular junction has been investigated in the rat.2. Choline acetyltransferase (ChAc) is located in presynaptic nerve terminals and is a specific enzymatic marker of cholinergic innervation in muscle.3. ChAc activity increased co-ordinately with developmental growth of the soleus muscle. However, another form of muscle growth, work hypertrophy, did not produce an increase in ChAc.4. Growth arrest of muscle by hypophysectomy did not alter the normal development of ChAc activity, and cortisone-induced muscle atrophy did not reduce ChAc activity in the soleus or plantaris.5. Tenotomy-induced muscle atrophy provoked a significant fall in ChAc in the soleus and plantaris.6. The tonic soleus had significantly greater ChAc activity than the phasic plantaris.7. These observations suggest that muscle mass per se does not influence the development and regulation of ChAc in muscle but that the quality of muscle contraction may modulate enzyme activity.
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