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Biomedical subjects

R Lutz

Publications and source records attributed to R Lutz.

At least 19 recordsLinked to original sources
PubMed1995

Investigation of coronary vessels in microscopic dimensions by two- and three-dimensional NMR microscopic imaging in the isolated rat heart. Visualization of vasoactive effects of endothelin 1.

BACKGROUND: Nuclear magnetic resonance (NMR) imaging of macroscopic coronary vessels is rapidly advancing, whereas little attention has focused on development of NMR techniques for investigation of coronary microvessels. Such techniques would be of particular importance, since conventional methods to visualize coronary microvessels have specific limitations. The aim of our study was to develop two- and three-dimensional (2D and 3D) high-resolution imaging of coronary microvessels. Quantitative analysis of vessel size was performed in tomograms and applied to evaluate the vasoconstrictor effect of endothelin 1. METHODS AND RESULTS: Angiographic imaging was performed on an 11.75-T magnet by 2D and 3D gradient-echo pulse sequences. In tomograms, the validity of this method in providing correct vessel size was tested by phantom experiments. Experiments were carried out in the isolated constant-pressure-perfused rat heart with continuous registration of coronary flow and left ventricular pressure. NMR pulse sequences were pressure-triggered in mid diastole. Four groups of hearts were studied. In group 1 (n = 20), 2D imaging perpendicular and parallel to the long axis of the heart was performed. Cross sections of vessels with diameter > 140 microns were clearly detectable. In group 2 (control, n = 5) and group 3 (n = 13), tomograms perpendicular to the long axis were obtained before and after administration of vehicle (group 2) and 200 pmol endothelin 1 bolus (group 3). Vehicle had no effect on vessel cross section. Endothelin 1, which decreased global coronary flow by 47%, reduced vessel cross section by 38 +/- 19%. A weak but, on average, significant inverse correlation between area of cross section and vessel size was found. In group 4 (n = 10), 3D imaging was performed in 7 normal hearts and 3 hearts with anterior myocardial infarction. A 3D image of the entire coronary artery tree was obtained, revealing excellent agreement with anatomic studies. In infarcted rat hearts, occlusion of the left coronary artery was demonstrated. CONCLUSIONS: Visualization and quantification of coronary microvessels are feasible by NMR microscopy. NMR microscopy bears the potential of becoming a powerful tool for the investigation of the coronary microcirculation.

Animals↗
PubMed1995

Flow instabilities induced by coronary artery stents: assessment with an in vitro pulse duplicator.

An in vitro pulse duplicator system was used to investigate whether coronary artery stents induce downstream flow instabilities. Hot film or electrochemical probes were used to measure wall shear stress before and after deployment of both single and multiple (overlapping) stents in normal and diseased coronary geometries. Left main coronary diameters ranged from 4 to 5 mm, whereas left anterior descending (LAD) and left circumflex (LCX) diameters ranged from 2 to 4 mm. Under resting conditions, all coronary flow waveforms remained laminar, even after stent placement. However, disturbances were found downstream from a stent placed in the proximal LAD under mild exercise conditions. These disturbances were found 5 mm distal to the stent, in both the LAD and the proximal LCX. Turbulence intensities of order 5% were induced by a single slotted stent in a normal LAD geometry. In cases of distal disease, the turbulence intensity was 9% with one stent and 11% with tandem stents. In cases of proximal disease, these values were 19 and 25%, respectively. The shear stress from these disturbances (20-200 dynes cm-2) is sufficient to delay re-endothelialization and promote restenosis. Therefore, the disturbances could contribute to the increased incidence of restenosis reported with multiple stents, and with stents used in cases of diffuse coronary disease.

Aorta↗
PubMed1995

Correlation of severity and outcome with plasma sterol levels in variants of the Smith-Lemli-Opitz syndrome.

OBJECTIVES: To determine whether type I and the more severe type II variant of Smith-Lemli-Opitz syndrome have the same metabolic defect and to learn which plasma sterol measurements best predict survival. METHODS: Plasma sterols were measured in 33 individuals (24 type I, 9 type II) with a clinical diagnosis of the syndrome. RESULTS: Cholesterol levels were abnormally low (61 +/- 34 mg/dl) in type I subjects, whereas concentrations of the cholesterol precursor 7-dehydrocholesterol and its isomer 8-dehydrocholesterol were elevated 40- to 10,000-fold. Plasma cholesterol levels were significantly lower and total dehydrocholesterol levels higher in type II than in type I. Six children with the type II variant died by 13 weeks with mean plasma cholesterol levels 6.2 +/- 3.1 mg/dl, versus 17 +/- 11 mg/dl in the three surviving children with type II (p < 0.05). No child with a cholesterol level 7 mg/dl or less lived longer than 13 weeks. CONCLUSIONS: Patients with type I and type II variants of Smith-Lemli-Opitz syndrome have markedly reduced activity of the enzyme that converts 7-dehydrocholesterol to cholesterol, but the extent of the block is far more complete in type II. Survival correlates strongly with higher plasma cholesterol concentrations.

Abnormalities, Multiple↗
PubMed1994

DNA primers for amplification of mitochondrial cytochrome c oxidase subunit I from diverse metazoan invertebrates.

We describe "universal" DNA primers for polymerase chain reaction (PCR) amplification of a 710-bp fragment of the mitochondrial cytochrome c oxidase subunit I gene (COI) from 11 invertebrate phyla: Echinodermata, Mollusca, Annelida, Pogonophora, Arthropoda, Nemertinea, Echiura, Sipuncula, Platyhelminthes, Tardigrada, and Coelenterata, as well as the putative phylum Vestimentifera. Preliminary comparisons revealed that these COI primers generate informative sequences for phylogenetic analyses at the species and higher taxonomic levels.

Amino Acid Sequence↗
PubMed1992

p23rab2, a ras-like GTPase with a -GGGCC C-terminus, is isoprenylated but not detectably carboxymethylated in NIH3T3 cells.

With the development of a specific anti-rab2 antiserum, p23rab2, a ras-like GTPase with a -GGGCC C-terminus, has been localized mainly to the particulate (P100) fraction in NIH3T3 cells, although a small amount of this protein also appears in the soluble fraction. The endogenous p23rab2 is isoprenylated in intact cells, and recombinant murine p23rab2 is also isoprenylated in an in vitro system using reticulocyte lysate. Both the cytosolic and membrane-bound forms of p23rab2 are isoprenylated in intact cells. Recombinant p23rab2 is specifically geranylgeranylated at one or both of the C-terminal cysteine residues in the in vitro system. Blocking isoprenoid synthesis with lovastatin results in an accumulation of a totally cytosolic unisoprenylated form, indicating that isoprenylation is a prerequisite for membrane association of p23rab2. Surprisingly, unlike p21ras and p25rab3A, no carboxymethylation of p23rab2 is detectable in either the soluble or particulate fractions.

3T3 Cells↗
PubMed1991

An atypical case of cytochrome c oxidase deficiency with biochemical heterogeneity in fibroblasts.

A patient presenting in the first year of life with feeding difficulties and failure to grow had variable but persistent lactic acidemia noted at age 20 months. Nonspecific nutritional and biochemical therapy was accompanied by improvement in general clinical status, growth, gait, and development. However, she died in a catastrophic illness at the end of the third year of life. Studies in intact fibroblast mitochondria were consistent with an isolated but partial defect in cytochrome c oxidase. On direct assay of this enzyme complex in fibroblast homogenates and mitochondria, activity was much more severely depressed (less than or equal to 8% of control). Her fibroblasts normally synthesized the three cytochrome c oxidase subunits encoded on the mitochondrial genome. These data confirm that this patient had cytochrome c oxidase deficiency and demonstrate significant biochemical heterogeneity, since the results of the intact mitochondrial studies correlate better with her clinical course than do those of the direct enzymatic assays.

Cells, Cultured↗
PubMed1991

Intravascular streaming during carotid artery infusions. Demonstration in humans and reduction using diastole-phased pulsatile administration.

Intra-arterial carotid artery chemotherapy for malignant gliomas is limited by focal injuries to the eye and brain which may be caused by poor mixing of the drug with blood at the infusion site. This inadequate mixing can be eliminated in animal models with diastole-phased pulsatile infusion (DPPI) which creates 1-ml/sec spurts during the slow blood flow phase of diastole. Before treatment with intracarotid cisplatin, 10 patients with malignant gliomas were studied to determine whether intravascular streaming occurs after intracarotid infusion in humans, and if so, if it is reduced with DPPI. Regional cerebral blood flow (rCBF) studies were performed by intravenous injection of H2(15)O and positron emission tomography. This was followed by supra- or infraophthalmic internal carotid artery (ICA) injections of H2(15)O with either continuous infusion or DPPI. Local H2(15)O concentration in the brain was determined and the images of radiotracer distribution in the continuous infusion and DPPI studies were compared to the rCBF images. Intravascular streaming of the infusate was identified by a heterogeneous distribution of the infused H2(15)O in brain compared to rCBF. Extensive and variable intravascular streaming occurred in three patients who received infusions into the supraophthalmic segment of the ICA. Some brain areas received up to 11 times the expected radiotracer delivery, while other regions received as little as one-tenth. This streaming pattern was markedly reduced or eliminated by DPPI. In the five patients who received infraophthalmic infusions, a minimally heterogeneous distribution of the infusate was detected. The authors conclude that extensive intravascular streaming accompanies supraophthalmic ICA infusions in patients. The magnitude of streaming can be substantially reduced or eliminated with DPPI. Those who perform intra-arterial infusion should consider using DPPI to assure uniform drug delivery to brain.

Analysis of Variance↗
PubMed1989

X-linked olivopontocerebellar atrophy.

We present a kindred with a relatively pure cerebellar degeneration that demonstrates X-linked recessive inheritance. The unique clinical picture of affected patients in our kindred is characterized by an infantile onset of ataxia; very slow rate of progression; normal strength, reflexes, and sensation; and cerebellar degeneration with involvement of the olive and pons demonstrated by neuroimaging techniques. The distinction between this and other reported olivopontocerebellar degenerations is made on the basis of the clinical features and mode of inheritance. It is not clear if the distinct clinical pattern in this kindred represents variable expression of a previously reported condition, allelic variance of previously reported kindreds, or a separate clinical entity. Molecular analysis, currently underway, may help settle the issue.

Adult↗
PubMed1985

Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates.

We have studied the effects of methotrexate (MTX-Glu1) and the polyglutamate derivatives of methotrexate (MTXPGs) with 2, 3, 4, and 5 glutamyl residues on the catalytic activity of thymidylate synthase purified from MCF-7 human breast cancer cells and on the kinetics of the ternary complex formation by 5-fluoro-2'-deoxyuridine 5'-monophosphate, folate cofactor, and thymidylate synthase. MTX-Glu1 exhibited uncompetitive inhibition of thymidylate synthase when reaction kinetics were analyzed by either double reciprocal plots or a computerized mathematical model based on nonlinear least-squares curve fitting. The Ki for MTX-Glu1 inhibition was 13 microM and the I50 was 22 microM, irrespective of the degree of polyglutamation of the folate. In contrast, the polyglutamated derivatives of MTX all acted as noncompetitive inhibitors. The MTXPGs had 75-300-fold greater potency than MTX-Glu1 as inhibitors of thymidylate synthase catalytic activity, with Ki values from 0.17 to 0.047 microM for MTX-Glu2 to MTX-Glu5, respectively. Neither MTX-Glu1 nor MTXPGs promoted the formation of a charcoal-stable ternary complex with thymidylate synthase and 5-fluoro-2'-deoxyuridine 5'-monophosphate. CH2-H4PteGlu5 (where PteGlu represents pteroylglutamic acid) was found to be 40-fold more potent than CH2-H4PteGlu1 in participating in the formation of a ternary complex, and 10 microM MTX-Glu5 significantly inhibited the formation of a ternary complex containing this folate as cofactor. The inhibition was determined to be due to a reduction in the kon. The potency of this inhibition was markedly greater in the presence of CH2-H4PteGlu1 as compared to CH2-H4PteGlu5. This finding suggests that the degree of interference with complex formation in intact cells would depend on the state of polyglutamation of available folate cofactor. Ternary complex formation with H2PteGlu5 as the folate cofactor was also investigated, and a 50% reduction in complex formation was found in the presence of a 2 microM concentration of MTX-Glu5. These findings have significant implications regarding the mechanism of action of MTX-Glu1 and contribute to an understanding of the complex interactions of MTX-Glu1 and 5-fluorouracil.

Breast Neoplasms↗
PubMed1982

Spatial memory in older adults: effects of intentionality.

College students and elderly adults were presented with drawings for study that were placed on the left or right side of a photographic slide. Persons in the items-only condition studied only the target drawings, whereas persons in the items-position condition studied both the target drawing and its location to determine whether intentionality affected picture recognition or position recall. Half of the drawings were presented with an irrelevant adjacent drawing to assess the effect of presenting the target item relative to another drawing. The principal finding was that, although special memory was well above chance, the Hasher and Zack's criteria for automatic processing of this dimension were not met. Specifically, an age-related decline in spatial memory was observed, and intentionality to learn position affected item recognition and position recall. It was also found that older persons' memory for position was enhanced by the irrelevant drawings. Results are discussed primarily in terms of the Hasher and Zacks model of automatic processing and possible encoding strategies utilized by the elderly.

Adult↗
PubMed1981

A fast interval processor (FIP) for cervical prescreening.

A cervical prescreening device (FIP: fast interval processor) designed to scan and classify a slide-mounted specimen within two minutes is described. The image analysis techniques are based directly on the MRC Cerviscan equipment with the minimal conversion needed to adapt these techniques for interval processing. A high scanning rate is achieved by scanning with a charge-coupled diode linear image sensor along one axis and by stepping the microscope stage continuously along the other axis. High processing rates are achieved using an asynchronous pipeline approach. Operations on pixels are carried out by parallel dedicated hardware units, while operations on intervals (segments) are carrie out using a dual microprocessing configuration. A determined attempt has been made to minimize the cost of the components required. Preliminary results showing scanning and processing performance are given.

Cervix Uteri↗
PubMed1975

Benzopyranopyridine derivatives. 1. Aminoalkyl derivatives of the azaxanthenes as bronchodilating agents.

The preparation of the four isomeric azaxanthones 3 and a number of their aromatic ring substituted derivatives is described. These ketones were converted into the title compounds which were examined for their biological properties. The most interesting compound in this series, the 1-methyl-4-piperidylidene derivative of 1-azaxanthene, shows the profile of an orally effective potent bronchodilating agent as well as a moderate antihistamine. Biological properties of this compound were compared to a number of antihistamines as well as known bronchodilating agents. Structure-activity relationships are also discussed.

Airway Resistance↗
PubMedDate not supplied

Expression of the proliferation-associated Ki-67 antigen in bovine testicular tubular cells during the seminiferous epithelial cycle, demonstrated with the MIB-1 antibody.

Ki-67 expression in the seminiferous tubule of the bovine testis was studied by immunohistochemistry during the seminiferous epithelial cycle using the monoclonal antibody MIB-1. Spermatogonial proliferation is most obvious in stages 5-7, and 8, when B-spermatogonia divide. A lower rate of spermatogonial propagation is observed preceding or during meiosis in stages 1-4. The MIB-1 antibody also gives positive results with some post-spermatogonial tubular cells. Preleptotenes passing through S-phase in stage 1 reveal positive nuclei. During prophase of meiosis I pachytenes react strongly, diplotenes react in an attenuated manner, while leptotenes and zygotenes stay negative. Secondary spermatocytes seen in stage 4 are positive as are the chromosomes during meta- and anaphase of the meiotic divisions. Post-meiotic spermatids are also decorated but stop Ki-67 expression abruptly at the end of stage 4. Sertoli cells are negative.

Animals↗