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Biomedical subjects

R Cole

Publications and source records attributed to R Cole.

At least 91 records · Page 5Linked to original sources

The induction of the major heat-stress protein in purified rat glial cells.

Cultured purified oligodendroglia and astroglia exposed to heat stress (45 degrees C, 10 or 20 min) synthesized a 68-kDa heat-stress protein, which migrates on two-dimensional gel electrophoresis and reacts with a specific monoclonal antibody suggesting it is similar to a major 72-kDa heat-shock protein previously reported in other cell types. This protein was not detected in control glial cultures. Actinomycin D prevented synthesis of this protein demonstrating an absolute requirement for newly synthesized mRNA. The response was prolonged by increasing the period of heat stress from 10 to 20 min. In addition to the 68-kDa HSP protein, the incorporation of radioactivity into 70-, 89-, and 97-kDa proteins was also increased after heating, but in contrast to the 68 kDa protein these proteins appeared to be made in control glial cultures.

Animals↗

Serum contains inducers and repressors of oligodendrocyte differentiation.

An important stage in oligodendrocyte development is the expression of galactocerebroside (GC), the major glycolipid in myelin. Although oligodendrocyte cell lineage and differentiation in vitro have been the object of many studies, to date there is sparse information on the regulation of GC expression in oligodendrocytes already committed to be positive for GC. We report here that GC expression in these cells is controlled by three serum factors. Two of these, possibly a lipoprotein and a mucoprotein, increase GC levels, whereas the third, probably a glycoprotein, exerts an inhibitory effect. The developmental increase of GC in postnatal rat brain cerebral cultures and its induction by serum factors are reversible phenomena. The isolation of the GC-regulatory factors would allow experimental manipulation of impaired GC expression by differentiated oligodendrocytes.

Animals↗

Calmodulin kinase II in pure cultured astrocytes.

Calcium- and calmodulin-dependent protein kinase activity was studied in pure neuronal and glial cultures. The addition of calcium and calmodulin stimulated 32P incorporation into several neuronal proteins including two in the 50- and 60-kilodalton (kD) region which comigrated with purified forebrain calmodulin kinase II subunits (CaM kinase II). In mature astrocytes, CaM kinase activity was also present, and was inhibited by trifluoroperazine and diazepam. Again in homogenates of these cells, two phosphoproteins of apparent molecular masses of 50 and 60 kD comigrated with purified CaM kinase. CaM kinase activity was absent in immature mixed glia and oligodendrocytes. The presence of CaM kinase in neurons and mature astrocytes was confirmed using monoclonal antibodies specific for the 50-kD subunit of the enzyme. No immunoreactivity was observed in oligodendrocytes. The presence of CaM kinase in astrocytes suggests a more ubiquitous role of this enzyme in regulating cellular processes than was previously recognized.

Animals↗

Wound prophylaxis with metronidazole in head and neck surgical oncology.

Anaerobic organisms are thought to be an important source of wound infection in head and neck oncologic surgery. Antibiotic prophylaxis consisting of agents specific for anaerobes combined with broad-spectrum agents that provide coverage for other well-recognized pathogens should be an effective combination regimen for this group of patients. We conducted a prospective, randomized study comparing the efficacy of prophylaxis using combination of metronidazole and cefazolin-designated group A, to prophylaxis using cefazolin alone-group B, for patients undergoing oncologic procedures of the head and neck. The rate of wound infection in the cefazolin-metronidazole group (158 patients) was 9.5%, compared with 18.6% in the cefazolin group (172 patients) (p = 0.03). Patients undergoing clean procedures had a 4.9% infection rate overall, compared with 17.9% for clean-contaminated procedures, and 33.3% for contaminated procedures. The average length of hospitalization was 20.7 days for patients who developed infections, compared with 8.9 days for patients without infection. Anaerobic organisms were cultured in 12 of 26 patients, ten of whom did not receive metronidazole. The lower rate of wound infection among patients who received metronidazole suggests that anaerobic organisms are an important source of wound infection in head and neck oncologic surgery. Chemoprophylaxis for these patients should, therefore, include specific anaerobic coverage in addition to the broad-spectrum agents that cover the more familiar aerobic organisms.

Bacteria, Anaerobic↗

Inositol phospholipid hydrolysis in cultured astrocytes and oligodendrocytes.

Cultures of astrocytes and oligodendrocytes were prelabeled with 3H-inositol and the accumulation of 3H-inositol phosphates was determined following stimulation with a number of neuroactive substances. In astrocytes, norepinephrine (NE) produced the greatest stimulation with significant increase also observed with bradykinin. In oligodendrocytes, the greatest stimulation was produced by carbachol with significant increase also produced by bradykinin, histamine and NE. Carbachol was found to be ineffective in producing stimulation in astrocytes. The accumulation of 3H-inositol phosphates in astrocytes in response to NE was found to be dependent on the presence of Li+. The NE stimulation in astrocytes was dose-dependent and had an EC50 of 1.2 microM. This stimulation was blocked by the low concentration of the alpha 1-adrenergic antagonist prazosin but not by the alpha 2-adrenergic antagonist yohimbine. The NE-stimulated accumulation of 3H-inositol phosphates in astrocytes was inhibited by the cyclic nucleotide phosphodiesterase inhibitor isobutylmethylxanthine as well as by the cAMP analog dibutyryl cAMP.

Animals↗

Ultrastructural and microprobe analysis of simian lung mite pigments.

Using light microscopy, polarizable amorphorous bodies with tinctorial characteristics of lipochromes and flocculent pigmental materials were found within the alveolar macrophages and peribronchiolar region of the lungs in a pig-tailed macaque (Macaca nemistrina) infected with simian lung mite (Pneumonyssus simicola). Examination of these pigmental bodies, using a high-voltage (1.2 meV) electron microscope and an energy-dispersive X-ray analysis system, indicated that the pigmental bodies contained a high concentration of silica. One female adult P simicola also was examined, and its digestive tract had visible, polarizable pigment and a high concentration of silica. Thus, lesions associated with lung mite infection in Old World monkeys may be superimposed by this silicotic condition, which may be associated with their arid, dusty, environment. Therefore, until the link between lung mite infection and silicosis is clarified, experimental inhalation toxicologic findings in mite-infected Old World monkeys should be interpreted cautiously.

Animals↗

Thyroid hormone deiodinases in purified primary glial cell cultures.

Iodothyronine metabolism was studied in neuroglial cells prepared from neonatal rat cerebri. Astrocytes account for nearly all of the deiodinase activity in mixed glial cell cultures. The predominant pathway is 5-deiodination, which closely resembles the enzyme activity in homogenates of cerebral cortex. Astrocytes cultured in serum-free chemically defined medium show a gradual decrease in 5-deiodination and an increase in 5'-deiodination. Exposure of cells to triiodothyronine partially reverses these changes. Thus, astrocytes contain enzymes for both major deiodinative pathways and may play a role in the regulation of thyroid hormone levels in the brain.

Animals↗

Changes in the cell wall of Clostridium species following passage in animals.

Morphological changes in clostridial isolates after animal passage with other flora in mixed infections were studied by utilizing a subcutaneous abscess model in mice. We used 26 isolates of 7 clostridial species, and one isolate each of Bacteroides fragilis and Klebsiella pneumoniae. Abscesses were induced by all 7 Clostridium perfringens and 3 Clostridium butyricum isolates and by some of the other isolates. A thick granular wall prior to animal inoculation was shown only in C. perfringens, C. butyricum, and C. difficile. This structure was observed in other clostridia only following their animal passage alone or when co-inoculated with K. pneumoniae or B. fragilis.

Animals↗

The violated neck: cervical node biopsy prior to definitive treatment.

The intent of this study was to determine whether open neck biopsy for patients with squamous cell carcinoma metastatic to the neck influenced the biologic course of the disease or the response to treatment. One hundred ninety-two patients, treated over a 10-year period at M.D. Anderson Hospital and Tumor Institute, were reviewed; 102 of the 139 patients, whose primary site of disease was identified prior to definitive treatment, were matched with a control group of 204 patients. The results showed no significant difference in wound complications, neck recurrence, distant metastases, and 5-year survival. Also, time interval from the biopsy to subsequent treatment and the type of node biopsy did not appear to have any significant detrimental effect. On the basis of these findings, we conclude that, although it is important to refrain from proceeding with an open biopsy until a complete head and neck evaluation has been done, violation of the neck does not signify a poorer prognosis--provided adequate treatment is subsequently given.

Adolescent↗

A double blind trial of nitroglycerin vasodilator ointment in patients undergoing cytotoxic chemotherapy.

A randomized double blind controlled trial has shown that topical, nitroglycerin vasodilator cream applied to the intended injection site in patients undergoing cytotoxic chemotherapy for various malignancies, produced detectable vasodilation and a decrease in minor aids to venepuncture compared to placebo. It did not decrease the number of attempts at cannulation needed nor the overall cannulation failure rate and cannot be recommended for general use in cytotoxic chemotherapy clinics.

Administration, Topical↗

Myelination of mouse cerebellar explants by rat cultured oligodendrocytes.

It has been shown that transplanted central nervous system tissue containing oligodendrocytes will myelinate neuronal processes in vitro and in situ. In this study we propose to show that cultured rat oligodendrocytes have the capacity to myelinate mouse cerebellar neuronal processes in vitro. Cultured rat oligodendrocytes were transplanted to cytosine arabinoside-treated mouse cerebellar explant cultures, then observed for myelination. Ultrastructural examination showed myelin and myelin-like figures in co-cultures. Control cytosine arabinoside-treated cultures and cultured oligodendroglia were without compact myelin.

Animals↗

Benzodiazepine binding characteristics of embryonic rat brain neurons grown in culture.

The binding of [3H]diazepam to cell homogenates of embryonic rat brain neurons grown in culture was examined. Under the conditions used to prepare and maintain these neurons, only a single, saturable, high-affinity binding site was observed. The binding of [3H]diazepam was potently inhibited by the CNS-specific benzodiazepine clonazepam (Ki = 0.56 +/- 0.08 nM) but was not affected by the peripheral-type receptor ligand Ro5-4864. The KD for [3H]diazepam bound specifically to cell homogenates was 2.64 +/- 0.24 nM, and the Bmax was 952 +/- 43 fmol/mg of protein. [3H]Diazepam binding to cell membranes washed three times was stimulated dose-dependently by gamma-aminobutyric acid (GABA), reaching 112 +/- 7.5% above control values at 10(-4) M. The rank order for potency of drug binding to the benzodiazepine receptor site in cultured neurons was clonazepam greater than diazepam greater than beta-carboline-3-carboxylate ethyl ester greater than Ro15-1788 greater than CL218,872 much greater than Ro5-4864. The binding characteristics of this site are very similar to those of the Type II benzodiazepine receptors present in rat brain. These data demonstrate that part, if not all, of the benzodiazepine-GABA-chloride ionophore receptor complex is being expressed by cultured embryonic rat brain neurons in the absence of accompanying glial cells and suggest that these cultures may serve as a model system for the study of Type II benzodiazepine receptor function.

Animals↗

Treatment of glaucoma using minidrops of clonidine.

A single regular (70 microL) or mini (15 microL) eyedrop of 0% (placebo), 0.25%, and 0.50% strengths of clonidine hydrochloride was administered to 16 patients with open-angle glaucoma in a double-masked crossover study. Both the regular drops and minidrops of 0.25% and 0.50% concentrations of the drug substantially lowered the intraocular pressure over a five-hour period as compared with the placebo. Only the regular drops of 0.50% clonidine substantially lowered the systemic BP. These results indicate the value of using a smaller volume of clonidine drop as an ocular hypotensive agent to avoid systemic effects.

Adult↗

Sister-chromatid exchange and micronucleus induction as indicators of genetic damage in maternal and foetal cells.

The effectiveness of 3 compounds, procarbazine, mitomycin C and cyclophosphamide as inducers of sister-chromatid exchanges (SCEs) in granulocyte-macrophage progenitor cells, in foetal liver and bone marrow from pregnant mice at day 17 of gestation were determined. Cyclophosphamide and procarbazine induced similar SCE frequencies in maternal and foetal cells. Mitomycin C was slightly less effective in foetal liver than in maternal bone marrow. In contrast to the results of SCE induction, cyclophosphamide produced more micronucleated polychromatic erythrocytes in foetal liver than in bone marrow. The SCE results for mitomycin C and procarbazine are compared with results obtained previously for micronuclei induction in 15-day pregnant animals.

Animals↗

Analysis of contaminants in factor VIII preparations administered to patients with hemophilia.

Cryoprecipitate and the more purified factor VIII concentrates are all heterogeneous preparations that contain not only a high concentration of factor VIII but also various other materials, some of which might be injurious, causing liver damage after long-term exposure. The efficiency of three standard cryoprecipitate filters, two microaggregate filters and the appropriate factor VIII concentrate filters in reducing the amount of particulate matter delivered to the patient was assessed. Filtration of cryoprecipitate through the standard filters removed less than 20% of the contaminating microaggregates and very few of the large number of intact platelets, although the total dose of factor VIII was delivered. Microaggregate filters were no better in reducing the platelet contamination, although the total number of particles delivered was halved. However, 25% of the factor VIII was retained in the bed volume of the filter. The concentrate preparations also contained significant amounts of particulate matter that was unrelated to factor VIII and was not removed following filtration through the designated filter. These findings indicate that a new filter should be developed for administration of factor VIII concentrate that would remove the particulate matter while delivering all of the factor VIII to the patient.

Diethylhexyl Phthalate↗