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Biomedical subjects

J Wolff

Publications and source records attributed to J Wolff.

At least 19 recordsLinked to original sources
PubMed2006

Direct interaction of Bcl-2 proteins with tubulin.

A direct interaction between tubulin and several pro-apoptotic and anti-apoptotic members of the Bcl-2 family has been demonstrated by effects on the assembly of microtubules from pure rat brain tubulin. Bcl-2, Bid, and Bad inhibit assembly sub-stoichiometrically, whereas peptides from Bak and Bax promote tubulin polymerization at near stoichiometric concentrations. These opposite effects on microtubule assembly are mutually antagonistic. The BH3 homology domains, common to all members of the family, are involved in the interaction with tubulin but do not themselves affect polymerization. Pelleting experiments with paclitaxel-stabilized microtubules show that Bak is associated with the microtubule pellet, whereas Bid remains primarily with the unpolymerized fraction. These interactions require the presence of the anionic C-termini of alpha- and beta-tubulin as they do not occur with tubulin S in which the C-termini have been removed. While in no way ruling out other pathways, such direct associations are the simplest potential regulatory mechanism for apoptosis resulting from disturbances in microtubule or tubulin function.

Amino Acid Sequence↗
PubMed2005

Thiol-disulphide interchange in tubulin: kinetics and the effect on polymerization.

All 20 cysteine residues are accessible to disulphide reagents in the tubulin dimer, whereas only four are accessible in taxol-stabilized microtubules. Reaction rates with disulphide reagents are a function of the reagent, are decreased by G nucleotides, and increased with increase in pH and urea. With transient (stop-flow) kinetics, DTNB [5,5'-dithiobis-(2-nitrobenzoic acid)] and 2,2'-dithiodipyridine progress curves cannot be fitted by the sum of exponential terms based only on classes of cysteines. The mixed disulphide products react further to form both intra- and intermonomer disulphide bonds that can be reversed by reducing agents. With MMTS (methyl methanethiosulphonate) or ODNB (n-octyl-dithio-2-nitrobenzoate), virtually no protein-protein disulphide bonds are formed and the ODNB reaction can be given as the sum of three exponential terms with pseudo-first-order rate constants of 0.206, 0.069 and 0.010 s(-1) at pH 6.5, suggesting three classes of thiol reactivities. Limited cysteine substitution leads to only small changes in tryptophan or CD spectra, whereas complete substitution leads to loss of the helix content. MMTS-induced loss of SH groups leads to progressive increases in the critical concentration and loss of polymerization competence that can be reversed by assembly promoters such as higher protein concentration, taxol or high ionic strength. Under such conditions, the substituted tubulin forms protofilament-based structures such as microtubules, open tubules, sheets and/or bundles.

2,2'-Dipyridyl↗
PubMed2005

The clinical and genetic spectrum of spinocerebellar ataxia 14.

Spinocerebellar ataxia 14 (SCA14) is associated with missense mutations in the protein kinase C gamma gene (PRKCG), rather than a nucleotide repeat expansion. In this large-scale study of PRKCG in patients with ataxia, two new missense mutations, an in-frame deletion, and a possible splice site mutation were found and can now be added to the four previously described missense mutations. The genotype/phenotype correlations in these families are described.

Adolescent↗
PubMed2005

EAU guidelines on prostate cancer.

OBJECTIVES: The first summary of the European Association of Urology (EAU) guidelines on prostate cancer was published in 2001. These guidelines have been continuously updated since many important changes affecting the clinical management of patients with prostate cancer have occurred over the past years. The aim of this paper is to present a summary of the 2005 update of the EAU guidelines on prostate cancer. METHODS: A literature review of the new data has been performed by the working panel. The guidelines have been updated and level of evidence/grade of recommendation added to the text. This enables readers to better understand the quality of the data forming the basis of the recommendations. RESULTS: A full version is available at the EAU Office or at . Systemic prostate biopsies under ultrasound guidance is the preferred diagnostic method and the use of periprostatic injection of a local anaesthetic can significantly reduce pain/discomfort associated with the procedure. Active treatment (surgery or radiation) is mostly recommended for patients with localized disease and a long life expectancy with radical prostatectomy being the only treatment evaluated in a randomized controlled trial. Follow-up is at large based on prostate specific antigen (PSA) and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy has become an option for selected patients with hormone refractory prostate cancer. CONCLUSION: The knowledge in the field of prostate cancer is rapidly changing. These EAU guidelines on prostate cancer summarize the most recent findings and put them into clinical practice.

Clinical Trials as Topic↗
PubMed2005

Non-viral approaches for gene transfer.

Gene therapy has great potential to treat or prevent a variety of both genetic and acquired conditions that include neuromuscular disorders, cardiovascular disease, cancer, and infectious diseases. For recessive genetic disorders such as Duchenne muscular dystrophy, delivery of the normal dystrophin gene to muscle should prevent the myofibers from dying. Despite the great promise and sound principles of gene therapy, its application to humans have been hampered by the inability to safely and effectively deliver genes to the target tissues. Among the several gene transfer methods under development, the use of non-viral delivery methods and specifically naked DNA is particularly attractive in that many of the concerns over the use of viral-mediated methods, such as immunogenicity of viral packaging proteins and cost of viral vector production can be avoided. Recently we used limb veins for efficient, repeatable, and safe delivery of nucleic acids to skeletal myofibers throughout the limb muscles of mammals in vivo. Promising results have been obtained in both rodents and larger animals including non-human primates. Studies in the mdx mouse model indicate that the approach should be of use for patients with Duchenne muscular dystrophy. Based upon these encouraging results, a human clinical trial to deliver the human dystrophin gene to patients with DMD is being planned. The initial objective is to preserve hand and forearm function to increase the quality of life.

Dystrophin↗
PubMed2004

[Anaesthesia for radiation therapy of brain tumours in children. A multidisciplinary challenge].

Radiation therapy of childhood intracranial malignancies is always a challenge for radiation oncologists, anaesthetists and paediatric oncologists. Detailed knowledge of the course of the disease prior to radiation therapy and a critical evaluation of the child's actual physical status are mandatory in each case. Furthermore the anaesthetist should be informed about the child's individual preferences and aversions. The optimum prearrangement of the radiation therapy is of paramount importance. Interdisciplinary communication structures which must always involve the child's parents have to be established. Perfect adjustment of the mask that fixes the head during each radiation procedure is necessary to give the child the possibility to breathe spontaneously without an endotracheal tube or a laryngeal mask. Two case reports highlight these aspects of the complex procedure of paediatric radiation therapy which are relevant for the anaesthetist.

Anesthesia↗
PubMed2004

Neutrophil CD177 (NB1 gp, HNA-2a) expression is increased in severe bacterial infections and polycythaemia vera.

The NB1 glycoprotein (CD177, HNA-2a antigen) is exclusively expressed on human neutrophils. As the clinical significance of CD177 expression is unknown, we investigated its expression in healthy individuals before and after stimulation with granulocyte colony-stimulating factor (G-CSF), in patients with rheumatoid arthritis, viral hepatitis, severe bacterial infections and polycythaemia vera. Expression was quantitatively determined by flow cytometry and by real time polymerase chain reaction. Only G-CSF-stimulated individuals and patients with severe bacterial infections and polycythaemia showed a significantly (P < 0.001) increased CD177 expression compared with healthy individuals, indicating that neutrophil CD177 expression can increase significantly in certain clinical conditions.

Adult↗
PubMed2003

Intrinsic proportions of the human tarsus: an original approach to tarsal biometry.

Few precise biometrical data on human tarsal bones are available, and those published consist principally of linear and angular measurements made on dried bones or on radiographs. The material consisted of 86 complete adult human tarsi (dried bones). The tarsal proportions were determined using the relative tarsal weights (Weight of each of the seven tarsal bones/Weight of the total tarsusx100). The calcaneus was the greatest tarsal bone (41.95%), and the talus the second-largest (28.45%). The medial cuneiform, the cuboid, and the navicular had very similar proportions (7.00-8.38%), as did the intermediate and lateral cuneiforms (2.98% and 3.81%). The study of the ranks of each bone by decreasing proportion allowed the determination of individual variability. The posterior tarsal row was considerably larger (70.40%) than the anterior row (29.60%), resulting in an antero-posterior ratio of 0.42. The medial and lateral tarsal columns had quite similar proportions (50.63% and 49.37%), resulting in a latero-medial ratio of 0.98. The intrinsic tarsal proportions are fundamental biometrical data which seem to be of interest for a better characterization of the human foot in clinical practice and for quantitative approaches in functional and comparative morphology and in paleontology.

Adult↗
PubMed2003

Wave initiation through spatiotemporally controllable perturbations.

We study the initiation of pulses and fronts in a two-dimensional catalytic reaction-diffusion system: CO oxidation on Pt(110). Using a computer-controlled mobile focused laser beam, we impart various patterns (in space and time) of localized temperature "kicks" to the surface. We explore, and also rationalize through modeling, the cooperativity of such individually subcritical perturbations in both the excitable and the bistable regime.

Journal Article↗
PubMed2003

Gentle dragging of reaction waves.

Using a recently realized "addressable catalyst surface" [Science 294, 134 (2001)]] we study the interaction of chemical reaction waves with prescribed spatiotemporal fields. In particular, we study how a traveling chemical pulse is "dragged" by a localized, moving temperature heterogeneity as a function of its intensity and speed. The acceleration and eventual "detachment" of the wave from the heterogeneity is also explored through simulation and stability analysis.

Journal Article↗
PubMed2003

Anion selectivity by the sodium iodide symporter.

The iodide transporter of the thyroid (NIS) has been cloned by the group of Carrasco. The NIS-mediated transport was studied by electrophysiological methods in NIS-expressing Xenopus oocytes. Using this method, the anion selectivity of NIS was different from that previously reported for thyroid cells, whereas perchlorate and perrhenate were found not transported. In this study we compared the properties of human NIS, stably transfected in COS-7 cells to those of the transport in a thyroid cell line, the FRTL5 cells, by measuring the transport directly. We measured the uptake of (125)I(-), (186)ReO(4)(-), and (99m)TcO(4)(-) and studied the effect on it of known competing anions, i.e. ClO(4)(-), SCN(-), ClO(3)(-), ReO(4)(-), and Br(-). We conclude that the properties of the NIS transporter account by themselves for the properties of the thyroid iodide transporter as described previously in thyroid slices. The order of affinity was: ClO(4)(-) > ReO(4)(-) > I(-) >/= SCN(-) > ClO(3)(-) > Br(-). NIS is also inhibited by dysidenin (as in dog thyroid).

Animals↗
PubMed2002

Charge variants of tubulin, tubulin S, membrane-bound and palmitoylated tubulin from brain and pheochromocytoma cells.

Isoelectric focusing (IEF) of only approximately 1 microg of rat brain tubulin yields 27-30 distinct charge variants in the pH range of 4.5-5.4 with band separations of 0.01-0.02 pH units as detected by silver staining. Variants can be efficiently transferred from the immobilized gradient strip to polyvinylidene difluoride (PVDF) membranes for reaction with monoclonal antibodies. C-terminal-directed antibodies to alpha- and beta-tubulin yield patterns similar to N-terminal-directed antibodies. Removal of the acidic C-termini with subtilisin to form tubulin S increases the pI values by approximately 1 pH unit, leads to a loss in the isoelectric distinction between the alpha- and beta-tubulin variants seen by N-terminal-directed antibodies, and abolishes reactions with all beta-variants and all but three alpha variants by C-terminal-directed antibodies (TU-04 and TU-14). Many, but not all, of the variants are substrates for autopalmitoylation of rat brain tubulin. The distribution of isoelectric variants differs between cytoplasm and membrane fractions from PC12 pheochromocytoma cells. A potential role for different variants is suggested.

Adrenal Gland Neoplasms↗
PubMed2002

Complex evolution of vitellogenin genes in salmonid fishes.

Vitellogenins (Vtg) are usually encoded by small multigene families containing up to six genes. With 20 tandemly arranged genes, the rainbow trout ( Oncorhynchus mykiss) is an exception to this rule. PCR amplification, cloning and sequence analysis of Vtg genes in other salmonid species revealed the existence of two paralogous gene clusters, designated Vtg-A and Vtg-B. Southern hybridization showed that the number of genes varies from 2 to 30 copies from one species to another, as well as between the two gene clusters. All Coregonus, Thymallus, Salmo and Salvelinus species studied have both gene clusters, while Oncorhynchus species possess only the Vtg-A locus. Phylogenetic trees constructed from Vtg sequences revealed conflicting nodes with the consensus tree based on morphological and anatomical data. Vtg sequences support the grouping ( Salmo, ( Salvelinus, Oncorhynchus)) instead of the accepted consensus ( Salvelinus, ( Salmo, Oncorhynchus)). Structural data on gene organization also support the contention that Salvelinus and Oncorhynchus are sister taxa. Evolutionary implications for the Vtg gene clusters in salmonids are discussed.

Animals↗
PubMed2002

The local electrostatic environment determines cysteine reactivity of tubulin.

Of the 20 cysteines of rat brain tubulin, some react rapidly with sulfhydryl reagents, and some react slowly. The fast reacting cysteines cannot be distinguished with [14C]iodoacetamide, N-[(14)C]ethylmaleimide, or IAEDANS ([5-((((2-iodoacetyl)amino)ethyl)amino) naphthalene-1-sulfonic acid]), since modification to mole ratios 1 cysteine/dimer always leads to labeling of 6-7 cysteine residues. These have been identified as Cys-305alpha, Cys-315alpha, Cys-316alpha, Cys-347alpha, Cys-376alpha, Cys-241beta, and Cys-356beta by mass spectroscopy and sequencing. This lack of specificity can be ascribed to reagents that are too reactive; only with the relatively inactive chloroacetamide could we identify Cys-347alpha as the most reactive cysteine of tubulin. Using the 3.5-A electron diffraction structure, it could be shown that the reactive cysteines were within 6.5 A of positively charged arginines and lysines or the positive edges of aromatic rings, presumably promoting dissociation of the thiol to the thiolate anion. By the same reasoning the inactivity of a number of less reactive cysteines could be ascribed to inhibition of modification by negatively charged local environments, even with some surface-exposed cysteines. We conclude that the local electrostatic environment of cysteine is an important, although not necessarily the only, determinant of its reactivity.

Acetamides↗
PubMed2002

2',3'-Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin.

2',3'-Cyclic nucleotide-3'-phosphodiesterase (CNP) is firmly associated with tubulin from brain tissue and FRTL-5 thyroid cells as demonstrated by copolymerization with microtubules through several warm/cold cycles, the presence of CNP activity in purified tubulin preparations, and identical behavior during various extraction procedures. CNP acts as a microtubule-associated protein in promoting microtubule assembly at low mole ratios. This activity resides in the C terminus of the enzyme, which, by itself, promotes microtubule assembly at higher mole ratios. Phosphorylation of CNP interferes with its assembly-promoting activity, as does deletion of the C terminus, which leads to abnormal microtubule distribution in the cell. Submembranous colocalization of the proteins and CNP-dependent microtubule organization suggest that CNP is a membrane-bound microtubule-associated protein that can link tubulin to membranes and may regulate cytoplasmic microtubule distribution.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2002

Phenylketonuria in adulthood: a collaborative study.

During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural problems.

Adult↗