Explaining relapse to opiate addiction following successful completion of treatment.
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Biomedical subjects
Publications and source records attributed to B Feldman.
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The effect of low-molecular-weight dextran and aspirin on platelet deposition after transluminal coronary angioplasty was studied in a normal canine model. Eighteen anesthetized, open-chest dogs were separated into 4 groups. All dogs received 3,000 units of intravenous heparin 10 to 20 minutes before the procedure. Dogs in Group 1 served as controls and were given no further treatment. Dogs in Group 2 received low-molecular-weight dextran by continuous intravenous infusion at a rate of 20 ml/hour for 1 hour before balloon inflation. Dogs in Group 3 were given 500 ml of low-molecular-weight dextran as an intravenous bolus over 1 hour, beginning 4 hours before the procedure. Dogs in Group 4 were fed 20 mg/kg of aspirin 3 hours before angioplasty. The dogs were killed 10 minutes after angioplasty and the arterial segments subjected to balloon inflation submitted for electron microscopic analysis. An additional group of 10 dogs was used to assess the bleeding times and platelet counts from control and drug-treated dogs. Drug treatment was associated with significant prolongation of the bleeding time and reduction in platelet number. Extensive endothelial desquamation in the area of balloon angioplasty was observed in all dogs. However, no appreciable qualitative difference in either the degree or extent of rapid platelet deposition to the exposed subendothelium was discernible between the control and any of the treatment groups. These results do not confirm previous observations with low-molecular-weight dextran. Further work on the initial and long-term platelet response after endothelial injury should be undertaken in a primate atherosclerotic model.
An important portion of the protein kinase activity in the 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary tumour is inhibited by the bioflavonoid quercetin (10(-4) M). By partial purification on a DEAE Cellulose column it was shown that the quercetin-inhibitable enzyme activity can be eluted in a separate peak which contains markedly reduced cAMP-dependent protein kinase activity. Since quercetin does not affect the cAMP-dependent protein kinase activity, this drug becomes a potent tool for the quantitation of this special activity in the tumor. By hormonal manipulation, namely ovariectomy and estrogen treatment, it was shown that changes in the growth rate of the tumour were closely correlated with the magnitude of these special protein kinase activities. These results suggest a possible cause-and-effect relationship between cyclic AMP-independent protein kinase activity and tumour malignancy in this chemically induced tumor. These data are similar to recent findings in viral-induced malignant transformation.
An in vitro system of human nasal turbinate tissue culture has been developed. Nasal turbinate tissue resected during surgery for nasal obstruction is dissected free of bone, placed on absorbable gelatin sponges, and cultured with CMRL-1066 medium containing antibiotics. Viability of explants may be demonstrated both physiologically and histologically through a period of 4 weeks. 3H-glucosamine added to the medium is biosynthetically incorporated into mucous glycoprotein (MGP). Gel filtration column chromatography on Sephacryl S-1000 in 6M urea in 0.005M phosphate buffer demonstrates human turbinate MGP to fractionate with 85% of the radiolabel filtered and 15% excluded by the column. The excluded MGP fractionates with globular proteins of greater than 20 X 10(6) daltons, while the fractions that enter the column filter with molecular sizes of 0.4 X 10(6) to 20 X 10(6) daltons. MGP synthesized by human lung airways has comparable sizing characteristics, suggesting a similarity in upper and lower airway mucus chemistry.
A protein kinase activity fraction was defined in cytosols and membranes of mammary tissue isolated from rats during pregnancy lactation, and weaning. By partial purification on DEAE-cellulose columns, it was shown that this protein kinase activity is cAMP independent and that its preferential substrate is casein and not histone. This protein kinase activity is inhibited by the bioflavonoid quercetin at doses that do not inhibit cAMP-dependent protein kinase activity. The enzyme requires Mg2+ and is inactive in the presence of 10 mM Ca+2; these properties distinguish this activity from casein kinase activity found in the Golgi fraction and involved in milk protein processing. By following the physiological cycle of mammary gland development during pregnancy, lactation, and weaning, we found a close correlation between proliferation, expressed as the DNA content per gland, and quercetin-inhibited cytosolic protein kinase activity. Moreover, changes in this phosphorylating activity preceded the glandular growth changes. There was a less significant correlation between the growth process and protein kinase activity in the membrane fraction. The cytosolic cAMP-dependent protein kinase activity showed (only partial) correlation with growth only during pregnancy. Cytosolic progesterone receptor levels in mammary tissue were used as an estrogenic marker. Tissue growth correlated with progesterone receptor levels during pregnancy, where estrogens are the predominant hormones affecting tissue proliferation. However, no such correlation was found during lactation and weaning, when PRL is the major hormone affecting mammary gland growth. These results suggest that quercetin-inhibitable protein kinase activity is not merely another estrogenic marker, but represents more general regulatory activity which might be connected to growth processes of breast tissue.
A protein kinase activity was defined in cytosols and membranes of rat uterus by using two types of enzyme inhibitors. The heat stable protein kinase inhibitor inhibited the cAMP-stimulated protein kinase but not the basal activity measured in the absence of the cyclic nucleotide. However, this basal activity was inhibited by quercetin in a dose-dependent manner, whereas the cAMP-stimulated protein kinase was not inhibited by this bioflavonoid. Thus, quercetin can be used as a tool to define a specific fraction of cAMP-independent protein kinase activity in rat uterine cytosols and membranes. The mature rat uterus is characterized by short (4 days) cyclic changes in tissue growth. Cell proliferation expressed as total uterine DNA content is observed on proestrus, reaches its peak at estrus, and declines sharply during metestrus and diestrus. The quercetin-inhibited protein kinase activity in the membranes of this tissue also changes cyclically and precedes by one phase the cyclic change in tissue proliferation. The clearest effect was seen when the protein substrates for this protein kinase activity were endogenous membrane proteins partially solubilized by Triton X-100 treatment. In contrast no change was observed in cytosolic, quercetin-inhibited protein kinase activity. The cAMP-stimulated protein kinase activity decreased slightly on diestrus. These results support our working hypothesis that tissue proliferation in the uterus and other tissues such as rat mammary gland and mammary tumors, correlates with cAMP-independent, quercetin-inhibited, protein kinase activity in these tissues.
Thirty-five cholesteatomas medial to intact eardrums were treated in 34 children between 1976 and 1982. Six (18%) children had never had a documented episode of otitis media. Seventeen (50%) children, in whom the lesion was diagnosed at an early stage, underwent simple excision of the cholesteatoma without the need for extensive middle ear surgery. Findings from postoperative audiograms were normal for all such children. Cholesteatoma has recurred in eight (23%) children to date. Most recurrences were diagnosed 15 months or less after surgery. Routine careful otoscopic examination is essential in order to discover cholesteatoma at an early stage and to avoid hearing loss and the need for extensive otomastoid surgery. In order to perform an accurate examination of the eardrum, a halogen-illuminated otoscope and pneumo-otoscopy should be used by the pediatrician routinely. Particular attention should be paid to the posterior-superior quadrant of the tympanic membrane where a cholesteatoma is usually located.
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Cyclic AMP-independent protein kinase activities from Ehrlich ascites tumor cells, partially purified by DEAE-cellulose and phosphocellulose chromatography were inhibited by quercetin. The cyclic AMP in the tumor ascites cells and the cyclic AMP-dependent protein activity from this tumor and from bovine and mouse tissues were unaffected by this drug. Since we reported that quercetin elevates cyclic AMP level in Ehrlich ascites tumor cells, this bioflavonoid may have a dual effect on the protein kinase activities in these cells, thus, increasing the cyclic AMP-dependent and decreasing the cyclic AMP-independent protein kinase activities.
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