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Biomedical subjects

A Bogucki

Publications and source records attributed to A Bogucki.

At least 19 recordsLinked to original sources
PubMed2006

A VEGF-A splice variant defective for heparan sulfate and neuropilin-1 binding shows attenuated signaling through VEGFR-2.

The development of functional blood and lymphatic vessels requires spatio-temporal coordination of the production and release of growth factors such as vascular endothelial growth factors (VEGFs). VEGF family proteins are produced in multiple isoforms with distinct biological properties and bind to three types of VEGF receptors. A VEGF-A splice variant, VEGF-A(165)b, has recently been isolated from kidney epithelial cells. This variant is identical to VEGF-A(165) except for the last six amino acids encoded by an alternative exon. VEGF-A(165)b and VEGF-A(165) bind VEGF receptors 1 and 2 with similar affinity. VEGF-A(165)b elicits drastically reduced activity in angiogenesis assays and even counteracts signaling by VEGF-A(165). VEGF-A(165)b weakly binds to heparan sulfate and does not interact with neuropilin-1, a coreceptor for VEGF receptor 2. To determine the molecular basis for altered signaling by VEGF-A(165)b we measured VEGF receptor 2 and ERK kinase activity in endothelial cells in culture. VEGF-A(165) induced strong and sustained activation of VEGF receptor 2 and ERK-1 and -2, while activation by VEGF-A(165)b was only weak and transient. Taken together these data show that VEGF-A(165)b has attenuated signaling potential through VEGF receptor 2 defining this new member of the VEGF family as a partial receptor agonist.

Alternative Splicing↗
PubMed2005

Botulinum toxin type A for upper limb spasticity following stroke: an open-label study with individualised, flexible injection regimens.

Current antispastic medications are unsatisfactory for spasticity treatment, but botulinum toxin type A (BTX-A) shows promise as a new therapeutic option. This open-label, prospective study aimed to assess the effectiveness of BTX-A in improving functional mobility in the early post-stroke population using an individualised, flexible range of doses and targeted muscle groups. Twenty-one stroke patients (13 male, 8 female) were enrolled and injected with BTX-A (Botox, Allergan, mean dose: 255 U; range: 185-300) according to individual spasticity patterns. Assessments were made at baseline and weeks 2, 4, 6, 10 and 16 post-treatment. Outcome measures comprised: Modified Ashworth Scale (MAS), finger flexion scale (Bhakta), MRC scale, Physician's Rating Scale (PRS), Nine Hole Peg Test (9HPT), Motor Assessment Scale, Clinical Global Impression (CGI), Global Assessment of Spasticity (GASS) and Visual Analogue Scale (VAS) for pain assessment. Statistically significant improvements in muscle tone as determined by the MAS were found in all areas (except arm) till week 16 (p<0.05). Finger positioning improved for the study duration, whilst muscle power increased only slightly in specific muscles. PRS revealed significant improvements to week 10 and slight improvement in 9HPT performance in selected patients was observed. Motor Assessment Scale results were statistically significant for arm, hand and advanced hand functions, although the overall functional benefit was mild. GASS and CGI results also showed improvement. Pain was present only in 11 patients and did not significantly improve following treatment. Individualised BTX-A injection regimens may be an effective, reversible and safe new treatment option for patients with spasticity. Nevertheless, functional improvement may be reached only in selected patients.

Adult↗
PubMed2001

Gene targeting in Arabidopsis.

Precise modification by gene targeting (GT) provides an important tool for studies of gene function in vivo. Although routine with many organisms, only isolated examples of GT events have been reported for flowering plants. These were at low frequencies precluding reliable estimation of targeting efficiency and evaluation of GT mechanisms. Here we present an unambiguous and straightforward system for detection of GT events in Arabidopsis using an endogenous nuclear gene encoding protoporphyrinogen oxidase (PPO), involved in chlorophyll and heme syntheses. Inhibition of PPO by the herbicide Butafenacil results in rapid plant death. However, the combination of two particular mutations renders PPO highly resistant to Butafenacil. We exploited this feature for selection of GT events by introducing the mutations into the PPO gene by homologous recombination. We have estimated the basal GT frequency to be 2.4 x 10(-3). Approximately one-third of events were true GT (TGT) leading to the anticipated modification of the chromosomal PPO copy. The remaining events could be classified as ectopic GT (EGT) arising by modification of vector DNA by the chromosomal template and its random integration into the Arabidopsis genome. Thus the TGT frequency in our experimental setup is 0.72 x 10(-3). In view of the high efficiency of Arabidopsis transformation, GT experiments of a reasonable size followed by a PCR screen for GT events should also allow for modification of non-selectable targets. Moreover, the system presented here should contribute significantly to future improvement of GT technology in plants.

Arabidopsis↗
PubMed2000

Elevated levels of intrachromosomal homologous recombination in Arabidopsis overexpressing the MIM gene.

The Arabidopsis MIM gene encodes a protein belonging to the SMC family (structure maintenance of chromosomes) which is required for intrachromosomal homologous recombination (ICR). Both ICR and MIM gene expression are enhanced by DNA-damaging treatments, suggesting that MIM is a factor limiting DNA repair by homologous recombination (HR) under genotoxic stress. We tested this hypothesis by measuring the levels of recombination in the mim mutant under genotoxic stress, using methyl methanesulfonate. Although the mutant clearly showed diminished basal and induced levels of ICR, enhancement of ICR by DNA-damaging treatments was similar to that observed in the wild type. This suggests that the MIM gene product is required for DNA repair by HR, but is not critical for HR induction. To determine whether enhanced availability of MIM would increase basal HR levels in Arabidopsis, we examined ICR frequencies in transgenic Arabidopsis strains overexpressing the MIM gene after ectopic insertion of additional MIM copies. Two independent lines showed a twofold increase in ICR frequency relative to the wild type. Thus MIM is required for efficient ICR in plants, and its manipulation can be used to change homologous recombination frequencies. Since MIM is one of the components responsible for chromatin dynamics, our results suggest that the chromatin environment determines the frequency of homologous recombination.

Arabidopsis↗
PubMed1999

Serial SFEMG studies of orbicularis oculi muscle after the first administration of botulinum toxin.

Serial single fiber electromyography (SFEMG) examinations of orbicularis oculi muscle in patients with blepharospasm or hemifacial spasm treated with botulinum toxin injections were performed. The aim of the study was to evaluate the impairment of neuromuscular transmission, to follow reinnervation after botulinum toxin administration and to find out whether there was a relationship between SFEMG parameters and clinical symptoms. Examinations were performed before injection, during early and late remission of symptoms, and after recurrence of the involuntary movement. Severe impairment of neuromuscular transmission, as revealed by increased jitter and increased presence of abnormal potential pairs and pairs with blocking, was found in early remission, but fiber density remained unchanged when compared with pretreatment values. In late remission, increased fiber density was registered for the first time. The recurrence of involuntary movements was related to the further increase of fiber density and tendency to normalization of jitter parameters. The study therefore suggests that formation of new neuromuscular junctions and their functional maturation is responsible for muscle recovery after botulinum toxin administration.

Action Potentials↗
PubMed1999

[The phenomena of irradiating pain in rotator cuff tear: quantitative analysis].

The aim of this study was the quantitative analysis of the phenomena of pain radiation in the case of rotator cuff tear. The clinical material concerns 97 patients, age range from 45 to 86 years. Radiating pain was noted in 33 cases; radiation into distal part of arm--12.4%, elbow--9.3%, forearm--6.2%, hand--1%, hand and thumb 2.1%, 5th finger--1.0%, neck--1.0% and into axilla--1.0%. The radiation of pain was provoked by one finger pressure over tender point (84.8%) or by impingement sign (15.2%). Next the impingement test was performed and additionally supplemented by intraarticular lidocaine injection in 5 cases. Radiation of pain disappeared completely in 26 cases, partly in 6 and persisted in one.

Aged↗
PubMed1998

Function of the rabbit supraspinatus muscle after detachment of its tendon from the greater tubercle. Observations up to 6 months.

The supraspinatus tendon was detached from the greater tubercle in 30 rabbits. After 6 weeks (group A), 3 months (group B) and 6 months (group C) in vivo evaluation of the twitch-tension and fatigue index were done. Next the scapulas with muscles were examined by CT. During the first 6 weeks a marked reduction in power and fatigue index by about 20% and 10-15%, respectively, in comparison with the control side was noted. These findings remained unchanged at 3 and 6 months. The CT examination showed fatty muscle degeneration, mainly in the 1/3 distal part of supraspinatus, but not in the infraspinatus muscle.

Animals↗
PubMed1998

[Botulinum toxin: mechanism of action].

Inhibitory effect of botulinum toxin on acetylcholine release from the neurons of peripheral nervous system and morphological changes produced in neuro-muscular junction by administration of the toxin are discussed. Other possible mechanisms of action, which can be responsible for the therapeutic effect are presented. Two clinically important problems are discussed: spreading of the toxin from the site of injection, and immunization which is responsible for non-responsiveness in some cases.

Acetylcholine↗
PubMed1998

[Botulinum toxin injections under electromyographic guidance].

EMG can be used for both dystonic muscles selection and performing injections of botulinum toxin. The indications for performing injections under EMG guidance in different forms of movement disorders are discussed. There is no need of EMG control in the treatment of blepharospasm and hemifacial spasm. In cervical dystonia the use of EMG guidance can improve the results of treatment in cases of head tilt, retrocollis, shoulder elevation and in more complex forms of dystonia. The injections should be performed under EMG control in patients with limb, oro-mandibular and laryngeal dystonia and with palatal myoclonus.

Botulinum Toxins↗
PubMed1997

Comparative behavior of E. coli and S. aureus regarding attachment to and removal from a polymeric surface.

Staphylococcus aureus was found to attach more readily on polypropylene fibers with greater resistance to subsequent washing off than Escherichia coli after immersion of the fibers up to 300 s in pure culture suspensions in mineral salts medium. Each of five different washing solutions were effective against E. coli, whereas only a solution that contained SDS was effective against S. aureus. Placement of inoculated fibers on nutrient agar for longer periods of time resulted in greater resistance to washing by both organisms, although S. aureus remained more resistant than E. coli.

Agar↗
PubMed1993

Stress-induced intrachromosomal recombination in plant somatic cells.

Levels of induced homologous recombination between chromosomal repeats in plant somatic cells were examined. Transgenic plants of Nicotiana tabacum hemi- or homozygous for pairs of deletion derivatives of the neomycin phosphotransferase (nptII) marker gene integrated at a single genomic locus were produced. Homologous recombination within the overlapping parts of the nptII gene restored the function and the resulting kanamycin resistance was used for scoring recombination frequency. The recombination events were confirmed by the appearance of a characteristic 1245-base-pair EcoRV fragment detected in all kanamycin-resistant clones tested. The rate of spontaneous recombination was found to be related to the copy number of recombination substrates and was 9 x 10(-5) and 19 x 10(-5) for hemi- and homozygote strains, respectively. Ionizing radiation, mitomycin C, and heat shock markedly increased the frequency of intrachromosomal recombination. Low doses of x-rays (1.25 Gy) enhanced the relative recombination frequency to approximately twice the spontaneous value. The presence of mitomycin C increased the frequency of recombination 9-fold and exposure to an elevated temperature (50 degrees C) increased it 6.5-fold. The x-ray and heat shock treatments reduced cell viability to 53% and 8%, respectively. Mitomycin C treatment had no effect on cell survival.

Journal Article↗
PubMed1992

Single-stranded DNA as a recombination substrate in plants as assessed by stable and transient recombination assays.

Two separate assays, one that requires stable integration of recombination products and one that does not, were employed to elucidate the role of single-stranded DNA in extrachromosomal homologous recombination in Nicotiana tabacum. Both assays revealed that single-stranded DNA in linear and in circular forms was an efficient substrate for recombination, provided that the cotransformed recombination substrates were of complementary sequence, so that direct annealing was possible. Recombination was inefficient when both single-stranded recombination partners contained homologous regions of identical sequence and generation of a double-stranded DNA was required prior to heteroduplex formation. These results indicate that direct annealing of single strands is an important initial step for intermolecular recombination in tobacco cells. Annealed cotransformed single-stranded molecules yielded intermediates that could be further processed by either continuous or discontinuous second-strand synthesis. The type of intermediate had no influence on the recombination efficiency. Double-stranded circles were unable to recombine efficiently either with each other or with single-stranded DNA. Our results suggest that a helicase activity is involved in the initial steps of double-stranded DNA recombination which unwinds duplex molecules at the site of double-strand breaks.

Base Sequence↗
PubMed1991

Amyloid beta-protein in cerebral amyloid angiopathy, senile plaques, and preamyloidotic lesions in subcortical arteriosclerotic encephalopathy (Binswanger disease).

Cerebral vascular amyloid deposits, senile plaques and neurofibrillary tangles have been found in subcortical arteriosclerotic encephalopathy (Binswanger disease). A mouse antiserum, prepared against a 43-amino acid synthetic peptide homologous to the amyloid beta-protein of Alzheimer disease (anti-SP43), revealed immunoreactive amyloid deposits in meningeal and intracortical blood vessels, senile plaques, intraneuronal amyloid and preamyloid in a neuropathologically confirmed case of Binswanger disease previously reported to have cerebral vascular amyloid deposits. These lesions contained sulfated glycosaminoglycans as determined by the Alcian blue/critical electrolyte concentration method. Similar findings were not observed in a case of Binswanger encephalopathy without cerebral amyloid deposits. Our study indicates that amyloidotic lesions in Binswanger encephalopathy with cerebral amyloid deposits contain amyloid beta-protein and sulfated glycosaminoglycans.

Amyloid beta-Peptides↗
PubMed1991

Evaluation of dementia in subcortical arteriosclerotic encephalopathy (Binswanger's disease).

Sixteen patients with a clinical diagnosis of subcortical arteriosclerotic encephalopathy (Binswanger's disease) were studied. Mild or moderate dementia was found in 14 cases, with characteristic disturbances of concentration, and psychic retardation with apathy. Neuropsychological studies revealed that signs of diffuse lesions in the frontal lobes dominated. Impairment of memory was significant in all cases. Although intellectual impairment in subcortical arteriosclerotic encephalopathy resembled subcortical dementia, some significant differences were found.

Activities of Daily Living↗
PubMed1990

Studies on nitroglycerin and histamine provoked cluster headache attacks.

Attacks of cluster headache provoked by the administration of nitroglycerin (1 mg sublingually) or histamine (0.01 mg/kg subcutaneously) were studied. The constant latency time in individual patients during nitroglycerin and histamine provocation suggested that the same mechanism is involved in both methods of headache induction. Repeated nitroglycerin provocation revealed its tendency to lengthen duration of the refractory period at the end of the bout, when the attacks were less frequent. The "cross studies" on spontaneous and nitroglycerin provoked attacks indicated that the underlying mechanism of both is at least partially the same.

Adult↗