Metastatic hepatocellular carcinoma.
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Aged↗
Biomedical subjects
J Glass
Publications and source records attributed to J Glass.
Translational control during the acute phase response. Ferritin synthesis in response to interleukin-1.
Interleukin-1 (IL-1 beta) increases the synthesis of both heavy and light (L)-ferritin subunits when added to human hepatoma cells (HepG2) grown in culture. RNase protection and Northern blot analysis with L-ferritin probes revealed that no changes in L-ferritin mRNA levels occur after cytokine stimulation. However, the induction coincides with an increased association of the L-subunit mRNA with polyribosomes. Since the recruitment of stored ferritin mRNA onto polyribosomes is seen when iron enters the cell, the effect of IL-1 beta on iron uptake was tested and was found to be unaffected by the lymphokine. Neither transferrin receptor mRNA levels nor the number of receptors displayed on the cell surface was affected by IL-1 beta. However, the action of the cytokine on ferritin translation is inhibited by the action of the intracellular iron chelator deferoxamine. These data indicate that IL-1 beta induces ferritin gene expression by translational control of its mRNA. The pathway of induction is different from iron-dependent ferritin gene expression whereas regulation requires the background presence of cellular iron.
Acute-Phase Proteins↗
Mobilization of iron from endocytic vesicles. The effects of acidification and reduction.
The factors necessary to dissociate iron from transferrin in endocytic vesicles and to mobilize the iron across the vesicle membrane were studied in a preparation of endocytic vesicles markedly enriched in transferrin-transferrin receptor complexes isolated from rabbit reticulocytes. Vesicles were prepared with essentially fully saturated transferrin by incubating the reticulocytes with the protonophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone prior to incubation with 59Fe, 125I-transferrin with or without fluorescein isothiocyanate labeling. Initiation of acidification by the addition of ATP was sufficient to achieve dissociation of 59Fe from transferrin with a rate constant of 0.054 +/- 0.06 s-1. Mobilization of 59Fe out of the vesicles required, besides ATP, the addition of a reductant with 1 mM ascorbate, allowing approximately 60% mobilization at 10 min with a rate constant of 0.0038 +/- 0.0006 s-1. An NADH:ferricyanide reductase activity could be demonstrated in the vesicles with an activity of 7.1 x 10(-9) mol of NADH reduced per min/mg of vesicle protein. Both dissociation and mobilization were inhibited by N-ethylmaleimide, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, and monensin. Mobilization, but not dissociation, was inhibited by the permeant Fe(II) chelator alpha,alpha'-dipyridyl. The Fe(III) chelators deferoxamine, diethylenetriaminepentaacetic acid, and apotransferrin did not promote mobilization of dissociated iron in the absence of a reductant. This study establishes the basis for the cellular incorporation of iron through the endocytic pathway in which the endocytic vesicle membrane utilizes, in a sequential way, an acidification system, an iron reduction system, and an Fe(II) transporter system.
Animals↗
Aluminum inhibits hemoglobin synthesis but enhances iron uptake in Friend erythroleukemia cells.
Aluminum (Al) overload in dialysis patients and experimental animals is associated with the development of anemia. However, the precise mechanisms of erythrocyte Al uptake and toxicity are poorly understood. Al accumulation, hemoglobin (Hb) synthesis and cell growth were evaluated in dimethylsulfoxide (DMSO)-induced Friend erythroleukemia cells (FEC), a model system for erythroid differentiation. FEC were grown in media containing either Al citrate, transferrin-aluminum (Tf-Al), Tf or no additions. Al accumulation occurring only in cells grown in Tf-Al containing media was detected at 24 hours and increased linearly up to 96 hours after induction. By 96 hours, 200 +/- 36 micrograms Al/liter lysed cells were detected in Tf-Al grown cells versus 5 +/- 1 micrograms Al/liter lysed cells in cells grown in Al citrate (P less than 0.001). Tf-Al inhibited Hb synthesis at 72 hours after induction. At 96 hours 50 +/- 15% cells were benzidine positive when grown in Tf-Al compared to 76 +/- 15% in Al citrate (P less than 0.001). FEC grown in increasing concentrations of Tf-Al (100 to 500 micrograms/ml) showed inhibition of Hb synthesis at lower concentrations of Tf-Al at 100 micrograms/ml than for cell growth at 300 micrograms/ml. Higher concentrations of Tf-Al (greater than 300 micrograms/ml) did not further inhibit Hb synthesis or cell growth. Iron (Fe) and Tf uptake were increased in Al loaded FEC compared to control cells. The increased Tf uptake was probably the result of increased Tf receptor expression on FES since Tf cell cycling time was unchanged. These data indicate that Al utilizes the Tf uptake pathway for entry into erythrocyte precursors. Al is toxic at sites distal to Fe uptake, possibly at the heme and/or globin synthetic pathways, resulting in decreased Hb synthesis and cell growth.
Aluminum↗
[Neurologic symptoms and their topical classification in neurosarcoidosis: studies in patients with pulmonary sarcoidosis].
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Adult↗
Assay and characteristics of the iron binding moiety of reticulocyte endocytic vesicles.
A 59Fe assay was designed to detect an Fe(III) binding capacity in NP-40 solubilized proteins from rabbit reticulocyte endocytic vesicles. The iron binding capacity had an apparent molecular weight as determined by gel exclusion chromatography of 450,000 daltons. The iron binding moiety coincided with the major nontransferrin iron-containing material of endocytic vesicles labeled in vivo by incubation of cells with 59Fe, 125I-labeled transferrin. The material solubilized from vesicles with NP-40 exhibited two classes of saturable binding sites, one with an association constant for 59Fe-citrate of 3.63 x 10(9) M-1 and with 6.6 x 10(-12) moles of iron bound per mg protein and the other with a constant of 3.96 x 10(8) M-1 and 1.0 x 10(-12) moles of iron bound per mg protein. These affinities are sufficient to satisfy the solubility characteristics of Fe(III) at pH 5.0. Most of the 59Fe bound both in vivo and in vitro to the iron binding moiety could be displaced with 56Fe and an equivalent amount of 59Fe could subsequently be rebound in vitro. The iron binding assay was adopted to vesicle proteins separated by SDS-polyacrylamide gel electrophoresis with subsequent transfer to nitrocellulose and revealed an iron binding activity of molecular weight approximately 95,000 daltons.
Animals↗
Synthesis and biological activities of oxytocin and lysine vasopressin analogs containing glutamic acid gamma-hydrazide in position 4.
Solution methods, using N-hydroxysuccinimide esters, were used to synthesize [Glu(NHNH2)4] oxytocin and [Glu(NHNH2)4, Lys8] vasopressin. In these analogs of neurohypophyseal hormones, the side-chain carboxamide function of a glutamine residue is formally replaced by a hydrazide group at position 4. The hormone analogs were assayed for uterototonic activity, milk ejection activity, antidiuretic activity, and rat pressor activity. The specific biological activities of the oxytocin and vasopressin analogs were decreased compared to the respective parent hormones in all assay systems.
Animals↗
Hereditary hemorrhagic telangiectasia and danazol.
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Adult↗
Diagnosis of silent myocardial ischemia in women.
The diagnosis of silent ischaemic heart disease may be important in men as well as in women. However, diagnosing women by exercise ECG is limited due to the higher rate of false positive results. For improving diagnostic validity the following investigations were done. In 310 women, aged 41-63 years (mean age 47 years', revealing 'pathological' exercise ECG, further testing was performed using nitroglycerin (NTG 0.8 mg). As a reference method, pulmonary artery (PA) pressure measurement was used. As a result of NTG testing, two groups could be separated: (a) those in whom ST segment depression remained constant (N = 217, NTG negatives = 70%). Since the end-diastolic PA pressure was found normal, these results were interpreted to be false-positive. (b) NTG effected a reduction or normalization of exercise induced ST segment changes (N = 93, NTG positives = 30%). There was a correspondence with exercise inducible end-diastolic PA pressure decrease. Consequently, true positives were assumed. Analysis of angina pectoris history indicated typical chest pain in 2% of NTG negatives only, but in 16% of NTG positives. In agreement with this during exercise, angina was reported by NTG negatives in 3% of cases and by NTG positive in 17%. The rest of this group (83%) is considered having exercise induceable silent myocardial ischaemia. When checking-up after five years, exercised-induced angina could be found in 4% of NTG negatives again, but in 36% of NTG positives. It was concluded that exercise testing by additionally using nitroglycerin is a rather important approach for diagnosing myocardial ischaemia in women.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Cerebrovascular insufficiency caused by extracranial vascular changes--results of surgical therapy].
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Adult↗
Management of the neuropathic bladder by clean intermittent catheterisation: 5 year outcomes.
Based on a telephone interview and medical record review of the urological outcomes among 40 spinal cord injury patients with a neuropathic bladder at discharge who were an average of 60 months post-injury and who were all initially managed by chronic clean intermittent catheterisation (CCIC), the following conclusions were made: Over 80% of patients using CCIC at discharge continued to use it, suggesting low morbidity and high patient acceptance; Urological complications in patients using CCIC were more frequent in the lower urinary tract than in the upper urinary tract, were more frequent in men than women, and had a low morbidity; Urological complications and hospitalisations were more frequent among the 41% of patients using CCIC who had frequent SxUTIs; SxUTIs were common in patients using CCIC but rates may be comparable with other methods; Although 44% of CCIC patients were hospitalised at least once in 5 years for urological complications, this is comparable to reported multi-centre outcomes in the U.S.A. (Young, 1982).
Female↗
Evoked release of methionine enkephalin from tolerant/dependent enteric ganglia: paradoxical dependence on morphine.
Experiments were performed in order to determine whether the state of tolerance to and dependence upon opiates is associated with changes in one or more of the characteristics of the electrically induced release of methionine enkephalin from enteric ganglia. Acute morphine pretreatment substantially reduces the magnitude of the evoked release of this peptide from opiate-naive ilea. However, the rate of the evoked release of enkephalin from morphine-pretreated, tolerant/dependent preparations is indistinguishable from that observed for untreated, naive ilea. Paradoxically, 15 min after acute in vitro withdrawal of morphine form such preparations, the presence of morphine appears to be prerequisite for the manifestation of electrically evoked release of methionine enkephalin. The evoked release of this peptide from ilea 60 min after withdrawal is no longer dependent upon morphine. Moreover, the magnitude of the increase in the rate of enkephalin release from these preparations is almost double that observed for opiate-naive ilea. These data indicate that the manifestation of opiate tolerance/dependence for the release of methionine enkephalin from enteric ganglia comprises several adaptive processes, the consequences of which can be observed at different stages of withdrawal.
Animals↗
Rabbit reticulocyte coated vesicles carrying the transferrin-transferrin receptor complex: I. Purification and partial characterization.
Coated vesicles bearing the transferrin-transferrin receptor complex were isolated from rabbit reticulocytes by freeze-thaw cell lysis, followed by differential centrifugation with pelleting of vesicles at 100,000 g. Electronmicroscopy demonstrated the vesicles to have the characteristic morphology of coated vesicles, including the appearance of triskelions. The protein composition of the vesicles as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis included transferrin, transferrin receptor, and proteins of apparent mol wt of approximately 180,000, 140,000, 100,000, and 47,000 daltons. The 180,000 and 100,000 mol wt proteins were identified as clathrin and coated vesicle assembly factor proteins, respectively, by Western blot analyses. The vesicles had a Mg2+-dependent ATPase with a specific activity of approximately 8.5 nmoles ATP converted/min/mg vesicle protein. The vesicles could acidify the intravesicular space, as evidenced by the stimulation of the Mg2+-ATPase by the protonophore FCCP. Reticulocytes appear to be an excellent source of coated vesicles and as such should provide a model for studying the endocytosis of transferrin and the steps of iron uptake that proceed in these vesicles.
Acid-Base Equilibrium↗
Amines as inhibitors of iron transport in rabbit reticulocytes.
The effect of the known inhibitors of iron uptake, n-butylamine and NH4Cl, was examined at the molecular level to more precisely define the mechanisms by which these lysosomotropic agents block iron uptake by rabbit reticulocytes. Utilizing a rapid pulse-chase technique to follow the handling of a cohort of 59Fe, 125I-transferrin bound to rabbit reticulocytes, both amines were observed to have no effect on the cell-mediated release of 59Fe from internalized transferrin. The results indicated, however, that both agents acted to 1) retard the internalization of transferrin bound to transferrin receptors on the plasma membrane of reticulocytes, 2) retard the externalization of internalized transferrin, and 3) block the transport into the cytosol of iron released from transferrin.
Ammonium Chloride↗
Short-term nerve stimulation increases enkephalin production and content in the guinea pig myenteric plexus.
Methionine-enkephalin content in the guinea pig myenteric plexus was determined before and after acute, short-term electrical or chemical stimulation. Stimulation at 20 Hz for 30 s or exposure to high potassium, the calcium channel agonist, CGP28 392, or the narcotic antagonist, (-)-naloxone, resulted in a significant increase in the content of myenteric methionine-enkephalin. The increase produced by electrical stimulation is dependent upon functional sodium channels and the presence of extracellular calcium. These results indicate that tissue levels of enkephalin are not fixed but can fluctuate in response to nerve stimulation and suggest a mechanism whereby the rate of production of this opioid peptide is coupled to neuronal activity. Furthermore, the ability of (-)-naloxone but not (+)-naloxone to almost double myenteric enkephalin content suggests that the neurons in which this increase occurs are under tonic modulation (direct or indirect) by opioids.
Animals↗
Personal therapy and the student therapist.
The effect of a therapist's personal psychotherapy on patient therapy outcome appears to be mixed. Some studies have shown that experienced, analysed therapists obtain better clinical results, but experience seems to be the important factor. Others have found no difference regardless of the therapist's personal therapy. Considerations favoring personal therapy include: awareness of the unconscious and of countertransference, increased empathy, minimizing blind spots, validating theory and method by first hand experience, and understanding how one's own defenses interfere with the therapeutic process. Those against personal therapy affirm there is no direct effect on competence, and there may even be detrimental effects (during residency); for example, inexperienced therapists in personal therapy appear to be less available to their patients because of their own preoccupations. Students' tendencies to identify with their analysts and pressure to conform in an analytic milieu might tend to decrease the number of therapists with varied orientations. The boundary between supervision and personal therapy is often unclear. In both, similar techniques may be used, but the goal of supervision should be to help the student to understand emotional problems and resistances which might interfere with the therapeutic process. Supervisors should make a compromise between purely didactic and therapeutic approaches. Despite the lack of conclusive evidence, supervisors should be encouraged to be less neutral and give advice and information to trainees who are in need of or who ask about personal therapy.
Adult↗
Microtopography of growth of normal and leukemic murine cells in diffusion-chamber cultures.
Histologic examination of "suspension" diffusion-chamber (DC) cultures of normal murine bone marrow cells demonstrates that hemopoietic cell growth in this system takes place in clonal form. Soon after implantation, marrow cells are arrayed on the filter membranes in a circumferential fashion adjacent to the surrounding lucite ring. Colonies of granulocytic cells soon form in this location and increase in size and number with increasing time of culture. Eventually cells begin to approach confluence over the entire filter membrane. Growth of C1498 murine acute myelogenous leukemic cells in DC cultures also takes place on the filter membranes and begins in a circumferential pattern. However, the leukemic cells grow diffusely and soon overspread the entire filter membrane, often growing several layers thick. Thus, although normal marrow cells are implanted into and are harvested from DC cultures in liquid-suspension form, they grow in a clonal pattern similar to that observed with the plasma-clot and fibrin-clot DC culture methods.
Animals↗
Direct analysis of the release of methionine-enkephalin from guinea pig myenteric plexus: modulation by endogenous opioids and exogenous morphine.
The in vitro release of methionine-enkephalin (met-enkephalin) from two longitudinal muscle myenteric plexus strips from guinea pig ileum has been obtained during continuous superfusion and quantitated directly using a radioimmunoassay specific for this opioid peptide. Electrical stimulation (5-80 Hz) produced a significant increase in the rate of release of met-enkephalin the magnitude of which was not dependent on the frequency of stimulation. Analysis of the release of met-enkephalin per pulse as a function of the frequency of stimulation indicated that the release of this opioid peptide from the myenteric plexus is inversely proportional to the frequency of stimulation. Electrically evoked release (40 Hz) of met-enkephalin was reduced by greater than 80% by substituting CoCl2 for CaCl2 or by pretreatment with tetrodotoxin (1 microgram/ml for 15 min). Evoked release was also reduced substantially by pretreatment with morphine (1 microM, 1.5 min). Alternatively, pretreatment of naive longitudinal muscle myenteric plexus strips with the opiate antagonist (-)-naloxone caused a significant increase in the rate of met-enkephalin release in the absence of electrical stimulation. In contrast, (+)-naloxone was devoid of any activity. These data, in combination with indirect pharmacological experiments, strongly indicate that met-enkephalin functions as a neurotransmitter in the enteric nervous system. Moreover, the activity of neurons that transmit via met-enkephalin appears to be under opioid regulation.
Animals↗