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Biomedical subjects

E Mueller

Publications and source records attributed to E Mueller.

At least 19 recordsLinked to original sources
PubMed1995

c-fos is required for malignant progression of skin tumors.

The proto-oncogene c-fos is a major nuclear target for signal transduction pathways involved in the regulation of cell growth, differentiation, and transformation. Using the multistep skin carcinogenesis model, we have directly tested the ability of c-fos-deficient mice to develop cancer. Upon treatment with a tumor promoter, c-fos knockout mice carrying a v-H-ras transgene were able to develop benign tumors with similar kinetics and relative incidence as wild-type animals. However, c-fos-deficient papillomas quickly became very dry and hyperkeratinized, taking on an elongated, horny appearance. While wild-type papillomas eventually progressed into malignant tumors, c-fos-deficient tumors failed to undergo malignant conversion. Experiments in which v-H-ras-expressing keratinocytes were grafted onto nude mice suggest that c-fos-deficient cells have an intrinsic defect that hinders tumorigenesis. These results demonstrate that a member of the AP-1 family of transcription factors is required for the development of a malignant tumor.

Animals↗
PubMed1994

Targeted disruption of the c-fos gene demonstrates c-fos-dependent and -independent pathways for gene expression stimulated by growth factors or oncogenes.

The c-fos proto-oncogene is believed to play a pivotal role in transducing growth factor-mediated signals from the extracellular milieu into the nucleus. c-fos protein dimerizes with c-jun and related proteins and mediates transcription via AP-1 sites. Using c-fos-deficient mice generated through gene knockout techniques, we derived 3T3-type cell lines from primary embryonic fibroblasts. The c-fos-deficient cells grow normally under optimal culture conditions and show only a slight reduction in growth rate in low serum culture compared with control cells. They also express mRNA for most of the Fos and Jun family members at normal levels. The overall levels of AP-1 DNA binding activity are normal and several genes (c-jun, MCP1, metallothionein) known to contain functional AP-1 sites are expressed normally in the c-fos-deficient and control cells. In contrast, mRNA for the metalloproteases stromelysin (MMP-3) and type I collagenase (MMP-1), which are often induced by oncogenes and growth factors and have been implicated in tumor invasiveness, cannot be induced by epidermal growth factor or platelet-derived growth factor in c-fos-deficient cells. Transformation of mutant cells with polyoma middle T oncogene essentially restores wild-type levels of stromelysin expression, while transformation with v-src leads to only a weak induction of the metalloprotease. These results clearly demonstrate that some AP-1-dependent genes require c-fos for full expression while others do not; oncogenes may activate expression of metalloproteases via either fos-dependent or fos-independent mechanisms. These results also imply that c-fos may play an important regulatory role in the invasive behavior of malignant tumors, independent of any role this proto-oncogene might play in cell growth per se.

3T3 Cells↗
PubMed1994

Induced hyperthermia in brain tissue in vivo.

Concerning hypothermia treatment, knowledge of time-temperature and of temperature distributions within tumor volumes is essential in order to obtain the maximal therapeutic effect. New techniques are being developed to overcome these difficulties. Two different heat sources, a contact Nd:YAG laser system and an automatically controlled high-frequency current system were investigated on 15 rabbits. Changes of the intracerebral temperature were registered at 4 different distances from the energy source. The intracerebral temperature was increased to 42.5 degrees C at a distance of 5 mm to the heat source and maintained at this level for a period of 60 min. The contact Nd:YAG laser system reached 42.5 degrees C at 3 W of output power. Using higher laser output power, brain tissue herniation (brain edema) through the burrhole was observed. The automatically controlled high-frequency current system reached 42.5 degrees C at 18.75 W of output current. A very small herniation of brain tissue could be observed using higher output current. Both heat sources presented an exponential decrease of the temperature profile depending on the distance. The tissue heat clearance was compensated for by intermittent laser or high-frequency current application. Both systems proved efficient for inducing hyperthermia as needed for antitumoral therapy.

Animals↗
PubMed1994

Ifosfamide induced depletion of glutathione in human peripheral blood lymphocytes and protection by mesna.

We studied the effects of ifosfamide and major metabolites on intracellular glutathione (GSH) levels in human peripheral blood lymphocytes (PBL). In vitro exposure of PBL to 4-hydroperoxyifosfamide (4-OOH-IF), acrolein or chloroacetaldehyde at 37 degrees C for 60 min led to a concentration dependent depletion of intracellular GSH. The concentration of the three metabolites to cause a 50% depletion of GSH in PBL was in the micromolar range (acrolein: 16 +/- 4 microM; 4-OOH-IF: 22 +/- 9 microM; chloroacetaldehyde: 30 +/- 7 microM). Exposure to ifosfamide, the non-activated drug, had no effects on the intracellular GSH levels. Pretreatment with 4-OOH-IF suppressed dose-dependently the interleukin-2-induced proliferation of PBL. Incubation of PBL together with 2-mercaptoethanesulfonate (mesna) and 4-OOH-IF, acrolein or chloroacetaldehyde prevented the GSH depletion. The protecting effect of mesna in combination with 4-OOH-IF was independent of GSH biosynthesis, because addition of buthionine sulfoximine had no significant influence on this effect. These findings indicate a novel protective mechanism of mesna against intracellular GSH depletion of PBL during exposure to metabolites of ifosfamide.

Acetaldehyde↗
PubMed1994

Effects of thermocycling and occlusal force on adhesive composite crowns.

The aim of this in vitro study was to provide first quantitative data on the marginal adaptation and the required load to fracture of adhesive composite crowns with and without adhesive composite cores. Eighteen caries-free extracted human premolars were restored using fine hybrid composite crowns with margins located entirely in dentin. Six crowns were adhesively luted to dentin stubs, six to endodontically treated teeth with adhesive titanium posts and adhesive composite cores, and six to adhesive composite cores without posts. Another ten unprepared teeth served as a control. All restored teeth were subjected to long-term occlusal and thermal stresses. The marginal adaptation was evaluated in the SEM before and after loading. Load to fracture was recorded at the end of the stress. Before stressing, 72.2 to 85.0%, and after stressing, 51.9 to 66.2% of "continuous margin" were recorded at the dentin-luting composite interface. The best results after stressing were achieved with crowns luted to adhesive composite cores without titanium posts. At the luting composite-composite crown interface, 61.6 to 88.7% of "continuous margin" before and 57.7 to 75.5% after stressing were recorded. The required load to fracture the restored teeth ranged from 72.0 to 89.2% of the unrestored, unloaded control. Adhesive composite cores without titanium posts yielded the best results.

Bite Force↗
PubMed1994

Intratracheal pulmonary ventilation (ITPV): control of positive end-expiratory pressure at the level of the carina through the use of a novel ITPV catheter design.

A new mode of pulmonary ventilation called intratracheal pulmonary ventilation (ITPV) was studied. Briefly, a continuous flow of air/oxygen is introduced through a small catheter, the tip of which is positioned at the carina, with a diffuser mounted at its distal end. A timed expiration valve, when closed, provides for inspiration; when open, it provides for expiration. The system as first described had a potential for significant back pressure at the level of the carina, which was more at rapid gas flows and with smaller endotracheal tubes. We have now mounted a venturi on the tip of the catheter (reverse thrust catheter [RTC]) that avoids back pressure, and which facilitates expiration. At respiratory rates from 10 to 120/min, the ITPV system with the RTC maintained end-expiratory pressure at the level of the carina at, or near 0 cm H2O. Compared to conventional mechanical ventilation, at identical respiratory rates, this system reduced tidal volume by one half at the lowest respiratory rates, and by as much as two thirds at the highest respiratory rates, with a proportional decrease in peak inspiratory pressure. ITPV has the smallest minute volume ventilation of any conventional or nonconventional mode of pulmonary ventilation.

Animals↗
PubMed1993

FTIR spectroscopic analysis of the amide and acid bands of ganglioside GM1, in pure form and in mixtures with DMPC.

The amide I bands of sphingolipids show complicated patterns due to intra- and intermolecular interactions via hydrogen bonds. In order to assign the amide I absorption bands of the ganglioside GM1 to the different amide groups in the headgroup and back bone, the compounds N-acetylgalactosamine, N-acetylneuraminic acid, glucocerebroside and ceramide III were examined as reference systems. The frequencies of the COOH and COO- bands of the sialic acid residue of GM1 were determined by pH-titration and were found to absorb at 1729 cm-1 and 1605 cm-1, respectively. In D2O the three amide groups of GM1 give one broad absorption band at 1627 cm-1, whereas in the glucocerebroside intra- and intermolecular interactions of the amide group give rise to three distinct amide I bands. For a solid sample of GM1 in KBr also one broad band was observed in the amide I region. We also studied the influence of the ganglioside GM1 on model membranes of DMPC as host lipid. The change of the CH2 stretching vibrational absorption bands as a function of temperature reveal that addition of GM1 to DMPC leads to increased phase transition temperatures Tm with increasing ganglioside content. No Ca2+ binding to the COO- group of GM1 was observed.

Acetylgalactosamine↗
PubMed1993

Adsorption and modification of calcium salt crystal growth by anionic peptides and spermine.

Synthetic polyanions, including peptide analogs of naturally occurring proteins, have been shown to inhibit the nucleation and growth of calcium salt crystals. The binding characteristics of polyaspartate and aspartate-serine copolymers to calcium carbonate (calcite) and hydroxyapatite (HAP) are presented here. The binding is related to dose-dependent inhibition of crystal growth measured by constant composition assay. Peptide phosphorylation had little effect on binding affinity or crystal growth inhibition with either calcium salt. Spermine was able to reduce hydroxyapatite crystal growth but with lower efficacy than the polyanionic peptides. Spermine reversed some of the HAP growth inhibition produced by an anionic peptide. Binding of a labeled polyanion was reduced by a similar anionic peptide at all concentrations of the label, however, spermine reduced binding only at higher concentrations of the labeled polyanion. The data support the presence of multiple binding site classes on HAP surfaces, some inaccessible to polycations and some at which both polyanions and polycations can bind.

Adsorption↗
PubMed1993

Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-beta.

Previous studies by our group have demonstrated that angiotensin II (ANG II), as a single factor in serum-free medium, induces cellular hypertrophy of a cultured murine proximal tubular cell line (MCT). The present study was performed to test the hypothesis that this growth effect was mediated by activation of endogenous transforming growth factor-beta (TGF-beta). Exogenous TGF-beta 1 (1 ng/ml) mimicked the growth effects observed with 10(-8) M ANG II (inhibition of DNA synthesis and induction of cellular hypertrophy). A neutralizing anti-TGF-beta antibody attenuated the ANG II-induced increase in de novo protein and total RNA synthesis as well as total protein content. This antibody also abolished the ANG II-mediated inhibition of [3H]thymidine incorporation into quiescent MCT cells. Control IgG or an unrelated antibody had no effect. A bioassay for TGF-beta using mink lung epithelial cells revealed that MCT cells treated with ANG II released active TGF-beta into the cell culture supernatant. Northern blot analysis and semi-quantitative cDNA amplification demonstrated increases in steady-state levels for TGF-beta 1 mRNA after ANG II stimulation of MCT cells, but not in a syngeneic murine mesangial cell line. Our data indicate that the ANG II-induced hypertrophy in MCT cells is mediated by synthesis and activation of endogenous TGF-beta. It is intriguing to speculate that TGF-beta may play a role in the early tubular cell hypertrophy and the subsequent interstitial scarring observed in several models of chronic renal injury that are characterized by increased activity of intrarenal ANG II.

Angiotensin II↗
PubMed1992

Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomised double blind European Cooperative Study Group trial.

OBJECTIVE: To determine whether concomitant treatment with intravenous heparin affects coronary patency and outcome in patients treated with alteplase thrombolysis for acute myocardial infarction. DESIGN: Double blind randomised trial. TREATMENT REGIMENS: Alteplase 100 mg (not weight adjusted) plus aspirin (250 mg intravenously followed by 75-125 mg on alternate days) plus heparin (5000 units intravenously followed by 1000 units hourly without dose adjustment) was compared with alteplase plus aspirin plus placebo for heparin. SETTING: 19 cardiac centres in six European countries. SUBJECTS: 652 patients aged 21-70 years with clinical and electrocardiographic features of infarcting myocardium in whom thrombolytic therapy could be started within six hours of the onset of major symptoms. MAIN OUTCOME MEASURE: Angiographic coronary patency 48-120 hours after randomisation. RESULTS: Coronary patency (TIMI grades 2 or 3) was 83.4% in the heparin group and 74.7% in the group given placebo for heparin. The relative risk of an occluded vessel in the heparin treated group was 0.66 (95% confidence interval 0.47 to 0.93). Mortality was the same in both groups. There were non-significant trends towards a smaller enzymatic infarct size and a higher incidence of bleeding complications in the group treated with heparin. CONCLUSIONS: Concomitant intravenous heparin improves coronary patency in patients with alteplase. Whether this can be translated into improved clinical benefit needs to be to be tested in a larger trial.

Adult↗
PubMed1990

The Bears' Picnic: children's representations of themselves and their families.

The Bears' Picnic, a new test of preschoolers' representations of self and family, was given to four-year-olds who had been observed with their mothers at twenty months of age. Observed maternal sensitivity and the affective quality of both partners were related to the child's later valuing versus devaluing of self and others.

Child, Preschool↗
PubMed1989

Formylglycinamide ribonucleotide synthetase from Escherichia coli: cloning, sequencing, overproduction, isolation, and characterization.

The purL gene of Escherichia coli encoding the enzyme formylglycinamidine ribonucleotide (FGAM) synthetase which catalyzes the conversion of formylglycinamide ribonucleotide (FGAR), glutamine, and MgATP to FGAM, glutamate, ADP, and Pi has been cloned and sequenced. The mature protein, as deduced by the structural gene sequence, contains 1628 amino acids and has a calculated Mr of 141,418. Comparison of the purL control region to other pur loci control regions reveals a common region of dyad symmetry which may be the binding site for the "putative" repressor protein. Construction of an overproducing strain permitted purification of the protein to homogeneity. N-Terminal sequence analysis and comparison of glutamine binding domain sequences (Ebbole & Zalkin, 1987) confirm the amino acid sequence deduced from the gene sequence. The purified protein exhibits glutaminase activity of 0.02% the normal turnover, and NH3 can replace glutamine as a nitrogen donor with a Km = 1 M and a turnover of 3 min-1 (2% glutamine turnover). The enzyme forms an isolable (1:1) complex with glutamine: t1/2 is 22 min at 4 degrees C. This isolated complex is not chemically competent to complete turnover when FGAR and ATP are added, demonstrating that ammonia and glutamine are not covalently bound as a thiohemiaminal available to complete the chemical conversion to FGAM. hydroxylamine trapping experiments indicate that glutamine is bound covalently to the enzyme as a thiol ester. Initial velocity and dead-end inhibition kinetic studies on FGAM synthetase are most consistent with a sequential mechanism in which glutamine binds followed by rapid equilibrium binding of MgATP and then FGAR. Incubation of [18O]FGAR with enzyme, ATP, and glutamine results in quantitative transfer of the 18O to Pi.

Amino Acid Sequence↗
PubMed1988

Changes in accommodation with age: static and dynamic.

Accommodative amplitude decreases with age, not with aging. The decrease is largely completed by age 40 years; only minor residual accommodation is present in most subjects after the mid-40s. Dynamical measurements show the accommodative response of subjects over 30 years of age to be significantly slowed (time constants of accommodation increases). Accommodation amplitude is less than 3 D by 30 years of age. Thus prepresbyopia is a sign of continual development, not of deterioration of the accommodative mechanism. Accommodation, or the change of clear vision with change in lens power, has been studied by many distinguished scientists including Descartes and Thomas Young. Helmholtz's "Theory of Accommodation" is a dual, indirect, active theory. There are both lenticular, including lens and capsule, and also extralenticular mechanisms, comprised of the zonule of Zinn or suspensory ciliary ligament and the ciliary muscle itself. The ciliary muscle does not act directly on the lens but indirectly through its action on the zonule of Zinn. Active contraction of the ciliary muscle, a unified muscle, produces accommodation; relaxation of the ciliary muscle permits relaxation of accommodation.

Accommodation, Ocular↗
PubMed1986

MR imaging of the normal shoulder.

Magnetic resonance (MR) images of the shoulders of a healthy volunteer were obtained in axial, sagittal, and coronal orientations using a 0.5-T imaging system. Multiple high-resolution spin-echo images were generated using an off-center zoom technique and a specially designed surface coil. Several anatomic structures, including the rotator cuff, long biceps tendon, articular capsule, muscles, and bones, were visualized. The coronal and sagittal views were the most useful for demonstrating the rotator cuff. MR imaging has potential as a new non-invasive tool for the evaluation of the shoulder region.

Adult↗
PubMed1986

Description of flow phenomena in magnetic resonance imaging.

The magnetic resonance (MR) signal from the hydrogen nuclei of blood is not only determined by the MR parameters T1, T2 and proton density, but is strongly dependent on the movement of the protons. Magnetic resonance imaging (MRI) offers therefore the possibility to visualize the distribution of moving spins, especially blood flow, noninvasively and without contrast agents; moreover, the velocity of the moving spins can be quantified. Flow phenomena in MRI are a pretentious field because the complicated hydrodynamics of the living system is coded in the MR signal; therefore, an understanding of the underlying physical principle of the MR signal is required to interpret and extract flow information from the image. However, rather simple theoretical and experimental models of fluid transport in vessels allow to explain the main features of various effects observed in images.

Blood Circulation↗
PubMed1986

The nonlaboring transverse lie. A management dilemma.

During a one-year period, 29 patients at 37 weeks' gestation or later were referred to the breech version clinic at Los Angeles County/University of Southern California Medical Center and found to have sonographic evidence of a transverse lie. Because of the relative instability of the lie and the high probability of spontaneous conversion, the patients were not considered candidates for version and were returned to their referral agencies for subsequent prenatal care. The subsequent outcomes in these patients were reviewed. Twenty-four (83%) spontaneously converted to a longitudinal lie and presented in labor with either a vertex (15 [52%]) or breech (9 [31%]) presentation. The five (17%) remaining patients presented in labor with a persistent transverse lie. Overall, the cesarean section rate was 13 of 29, or 45%. The indications for cesarean section were breech presentation, eight (62%), and transverse lie, five (38%). Major complications included two prolapsed cords, one spontaneous uterine rupture and one neonatal death. Based on a review of our experience, it appears reasonable to consider external version in any patient with a persistent transverse lie around 39 weeks. The high rate of subsequent cesarean section and major morbidity associated with expectant management of these patients suggests that if version is unsuccessful, strong consideration should be given to elective cesarean section.

Adolescent↗