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Biomedical subjects

H Arnold

Publications and source records attributed to H Arnold.

At least 37 records · Page 2Linked to original sources
PubMed2001

Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene.

Proteins encoded by the human CYP3A genes metabolize every second drug currently in use. The activity of CYP3A gene products in the general population is highly variable and may affect the efficacy and safety of drugs metabolized by these enzymes. The mechanisms underlying this variability are poorly understood, but they include gene induction, protein inhibition and unknown genetic polymorphisms. To better understand the regulation of CYP3A expression and to provide a basis for a screen of genetic polymorphisms, we determined and analysed the sequence of the human CYP3A locus. The 231 kb locus sequence contains the three CYP3A genes described previously (CYP3A4, CYP3A5 and CYP3A7), three pseudogenes as well as a novel CYP3A gene termed CYP3A43. The gene encodes a putative protein with between 71.5% and 75.8% identity to the other CYP3A proteins. The highest expression level of CYP3A43 mRNA is observed in the prostate, an organ with extensive steroid metabolism. CYP3A43 is also expressed in several other tissues including liver, where it can be induced by rifampicin. CYP3A43 transcripts undergo extensive splicing. The identification of a new member of the CYP3A family and the characterization of the full CYP3A locus will aid efforts to identify the genetic variants underlying its variable expression. This, in turn, will lead to a better optimization of therapies involving the numerous substrates of CYP3A proteins.

Amino Acid Sequence↗
PubMed2001

Evening shift.

Explore the source record for details and available documents.

Emergency Nursing↗
PubMed2000

Targeted disruption of the Nkx3.1 gene in mice results in morphogenetic defects of minor salivary glands: parallels to glandular duct morphogenesis in prostate.

To investigate functions of the homeodomain-containing transcription factor Nkx3.1 a null mutation was generated by targeted gene disruption introducing the bacterial LacZ gene as reporter into the locus. In addition to defects in duct morphogenesis of the prostate and bulbourethral gland displaying progressive epithelial hyperplasia and reduced ductal branching (Bhatia-Gaur, R., Donjacour, A.A., Sciavolino, P.J., Kim, M., Desai, N., Young, P., Norton, C.R., Gridley, T., Cardiff, R.D., Cunha, G.R., Abate-Shen, C., Shen, M.M., 1999. Genes Dev. 13, 966-977), we observed a novel phenotype in minor salivary glands of Nkx3.1 null mutants. Minor salivary glands in the oral cavity of mutant mice appeared reduced in size and exhibited severely altered duct morphology. Other Nkx3.1 expressing regions were unaffected by the mutation. The activity of the Nkx3. 1/LacZ allele faithfully reflected the known expression domains of Nkx3.1 in sclerotome, a subset of blood vessels, Rathke's pouch, and ductal epithelium in prostate and minor salivary glands during pre- and postnatal mouse development. However, it was additionally expressed in the heart, duodenum and lung. These ectopic expression domains resemble the pattern of the Nkx2.6 gene which is closely linked to Nkx3.1 in the mouse genome and its regulation may therefore be affected by the mutation. In Nkx3.1/Shh compound mutant mice we found that Nkx3.1 expression in sclerotome and prostate was strictly dependent on sonic hedgehog (Shh) signaling, while other expression domains including heart and gut were independent of Shh. Expression in lung appeared augmented in the absence of Shh. Our results suggest that Nkx3.1 plays a unique role in regulating proliferation of glandular epithelium and in the formation of ducts in prostate and minor salivary glands.

Animals↗
PubMed2000

Expression of the novel basic-helix-loop-helix transcription factor cMespo in presomitic mesoderm of chicken embryos.

We have identified a novel chicken gene, cMespo, which encodes a basic-helix-loop-helix (bHLH) protein with sequence homology to a subgroup of bHLH transcription factors that have been implicated in somitogenesis. cMespo transcripts are first found in the primitive streak of gastrulating chick embryos (HH stage 4) and continue to accumulate in presomitic mesoderm (PSM) until somite formation has been concluded. cMespo, however, is not expressed within somites or in tailbud mesoderm. The expression domain of cMespo in PSM largely overlaps with delta-1 but spares a region of several prospective somites at the rostral end of PSM in which c-Meso and Cek-8 are expressed.

Amino Acid Sequence↗
PubMed2000

Expression analysis of the chicken homologue of CITED2 during early stages of embryonic development.

Members of the Cited family are nuclear transactivators which bind to the coactivators p300 and CBP. While Cited1 also binds to the TGFbeta signal transducer Smad4, this has not been shown for Cited2. We isolated a chicken homologue of Cited2 from a HH stage 3-6 cDNA library and examined its expression pattern during early stages of embryonic development by whole-mount in situ hybridization. CITED2 expression is detectable in the epiblast as early as stage XI. From HH stage 2 onwards CITED2 is expressed in an anterior domain in the elongating primitive streak in cells which are fated to become heart. During gastrulation the expression pattern is highly dynamic and transiently displays left-right asymmetry with stronger expression on the right side. CITED2 expression appears at multiple sites of forming mesodermal structures. Most prominently, CITED2 is expressed in presomitic and lateral plate mesoderm, in the headfold (future forebrain), the head mesoderm, the pharyngeal floor, the ventral blood islands, somitomeres and the intermediate mesoderm which gives rise to the kidney anlagen.

Amino Acid Sequence↗
PubMed2000

[Endoscopic use of the water jet dissector in the cerebral ventricle system--an experimental study].

Endoscopic surgery in the cerebral ventricle is limited by the small number of suitable instruments and bleedings obscuring the visibility. The water jet cutter allows the dissection of tissue, generally leaving vessels intact. Therefore it could be an additional instrument for neuroendoscopic purposes. In this preclinical study the employment of the water jet dissector under endoscopic conditions was evaluated. Incision-experiments (n = 80) on the ventricular system of fresh porcine brain were carried out under endoscopic view. To achieve similarity to the ventricular system, specimens were dissected in liquid medium (Ringer's-lactate, 37 degrees C). The depths of incision were measured digitally and histological examination of the tissue was performed. Depending on the applied pressure, distance from cutting nozzle to tissue and cutting velocity, the depths of incision ranged from 0.12 mm up to 2.4 mm. The water jet dissector is good to handle under endoscopic conditions and vessels are preserved. Based on these factors, this instrument is predestinated for further neuroendoscopic application. Prior to clinical application our results will have to be tested on living, perfused cerebral tissue.

Animals↗
PubMed1999

Epidermal diseases in bottlenose dolphins: impacts of natural and anthropogenic factors.

Experimental studies have highlighted the potential influence of contaminants on marine mammal immune function and anthropogenic contaminants are commonly believed to influence the development of diseases observed in the wild. However, estimates of the impact of contaminants on wild populations are constrained by uncertainty over natural variation in disease patterns under different environmental conditions. We used photographic techniques to compare levels of epidermal disease in ten coastal populations of bottlenose dolphins (Tursiops truncatus) exposed to a wide range of natural and anthropogenic conditions. Epidermal lesions were common in all populations (affecting > 60% of individuals), but both the prevalence and severity of 15 lesion categories varied between populations. No relationships were found between epidermal disease and contaminant levels across the four populations for which toxicological data were available. In contrast, there were highly significant linear relationships with oceanographic variables. In particular, populations from areas of low water temperature and low salinity exhibited higher lesion prevalence and severity. Such conditions may impact on epidermal integrity or produce more general physiological stress, potentially making animals more vulnerable to natural infections or anthropogenic factors. These results show that variations in natural environmental factors must be accounted for when investigating the importance of anthropogenic impacts on disease in wild marine mammals.

Animals↗
PubMed1999

Dural arteriovenous malformation in the anterior cranial fossa.

Two cases of dural arteriovenous malformation (AVM) at the base of the anterior cranial fossa are described. In both cases an intracerebral hematoma following the rupture of the AVM was the first indication of the disease. In one case, the malformation was supplied both by the anterior ethmoidal artery and frontopolar artery draining into the superior sagittal sinus. In the second case, the right anterior ethmoidal artery with draining veins into the superior sagittal sinus and sphenoparietal sinus was the feeding vessel. Surgical evacuation of the hematoma and excision of the malformation was performed on both patients. The typical clinical signs and radiological findings are described. A review of the pertinent literature is given.

Adult↗
PubMed1999

A new technique for attaching a stereotactic frame to the head: technical note.

The aim of this study was to develop a device which allows an intermediate, painless fixation of a stereotactic frame prior to definite pin fixation. To stabilize the stereotactic frame rubber coated metal springs were used. By testing the springs on 30 volunteers with different head diameters and circumferences the optimal shape was determined. In the clinical setting 15 patients undergoing stereotactic surgery were tested, stability and patient's convenience were measured. The procedure was well tolerated and measurements revealed symmetric distances between head and frame. Therefore these metal springs are a useful accessory to the Leksell stereotactic system.

External Fixators↗
PubMed1998

Intracerebral hematomas caused by aneurysm rupture. Experience with 67 cases.

During a six-year (1986-1992) 334 patients with subarachnoid hemorrhage (SAH) were admitted to the Department of Neurosurgery. Medical University of Lübeck, Germany. In 281 patients the SAH was caused by rupture of an intracranial arterial aneurysm, verified by angiography, postmortem examination, or at emergency operation without angiography. In 67 (23.8%) of the 281 aneurysmal SAH patients the initial computerized tomography (CT) demonstrated an intracerebral hematoma (ICH). An ICH localized in the temporal lobe due to the rupture of a middle cerebral artery (MCA) aneurysm was found in 47 patients (70.2%). Forty-three patients were considered for surgery with a surgical mortality of 8 (18.6%). In the group of 19 ICH patients not operated upon, 16 individuals died (84.2%). We therefore advocate active surgical management of ICH patients: hematoma evacuation and aneurysm clipping at the same operation. Emergency surgery in younger patients (grade V) with temporal ICH suggesting the rupture of a MCA or internal carotid artery (ICA) aneurysm can be done without angiography.

Adult↗
PubMed1998

Preoperative functional magnetic resonance imaging (fMRI) of the motor system in patients with tumours in the parietal lobe.

Intracranial lesions may compromise structures critical for motor performance, and mapping of the cortex, especially of the motor hand area, is important to reduce postoperative morbidity. We investigated nine patients with parietal lobe tumours and used functional MRI sensitized to changes in blood oxygenation to define the different motor areas, especially the primary sensorimotor cortex, in relation to the localization of the tumour. Activation was determined by pixel-by-pixel correlation of the signal intensity time course with a reference waveform equivalent to the stimulus protocol. All subjects showed significant activation of the primary sensorimotor cortex while performing a finger opposition task with the affected and unaffected side. In five patients the finger opposition task additionally activated the ipsilateral sensorimotor cortex and the supplementary motor area (SMA). Extension and flexion of the foot, additionally performed in two patients, also activated the sensorimotor cortex, in one case within the perifocal oedema of the tumour. Tumour localization near the central sulcus induced displacement of the sensorimotor cortex as compared to the unaffected side in all patients with a relevant mass effect. The results of our study demonstrate that functional MRI at 1.5 T with a clinically used tomograph can reproducibly localize critical brain regions in patients with intracranial lesions.

Adult↗
PubMed1998

Spontaneous recovery of an aqueductal stenosis.

The case of a 17-year-old male with hydrocephalus caused by aqueductal obstruction is presented. A ventriculo-peritoneal shunt was implanted and later removed due to an infection. In the clinical follow-up no deterioration was observed. No further surgery was necessary. The repeat-MRI showed spontaneous resolution of the hydrocephalus with a normal aqueduct.

Adolescent↗
PubMed1998

Effects of DFMO on glioma cell proliferation, migration and invasion in vitro.

The polyamine inhibitor DL-alpha-difluoromethylornithine (DFMO) is a specific irreversible inhibitor of ornithine decarboxylase which is a rate-limiting enzyme in the polyamine bio-synthesis pathway. The present study describes the effects of DFMO on glioma cell proliferation, migration and invasion using multicellular spheroids from three glioma cell lines (GaMg, U-251 Mg and U-87 Mg). 10 mM DFMO reduced cell migration in the three cell lines by about 30-50%. 1 mM putrescine, added together with DFMO inhibited the DFMO effect. A stronger effect was observed in the growth assay where 10 mM DFMO reduced the spheroid growth, for all cell lines, by 90%. This effect was also reversed by adding 1 mM of putrescine. In vitro tumor cell invasion experiments indicated after 3 days of confrontation, an extensive invasion also after 10 mM DFMO treatment. The brain aggregate volumes were reduced to about the same extent as in the absence of drug, suggesting essentially no effects of DFMO on the invasive process. It is concluded that the tumor spheroids retained their ability to invade normal brain tissue even after DFMO exposure. However, DFMO inhibited spheroid growth and cell migration which supports the notion that cell growth, migration and invasion are biological properties that are not necessarily related to each other.

Adult↗
PubMed1998

How to perforate safely a resistant floor of the 3rd ventricle? Technical note.

Third ventriculostomy for acquired non-communicating hydrocephalus is an excellent alternative to shunting procedures. Nevertheless, complications can be severe and even fatal (e.g., lesion of the basilar artery), especially if the floor of the 3rd ventricle is very tough and/or opaque. The authors describe a safe method of sharp perforation of the floor, which should be applied if blunt fenestration cannot be achieved easily.

Endoscopes↗
PubMed1997

Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro.

Paclitaxel (Taxol), an anti-cancer drug derived from Taxus species, was tested for its anti-migrational, anti-invasive and anti-proliferative effect on two human glioma cell lines (GaMg and D-54Mg) grown as multicellular tumour spheroids. In addition, the direct effect of paclitaxel on glioma cells was studied using flow cytometry and scanning confocal microscopy. Both cell lines showed a dose-dependent growth and migratory response to paclitaxel. The GaMg cells were found to be 5-10 times more sensitive to paclitaxel than D-54Mg cells. Paclitaxel also proved to be remarkably effective in preventing invasion in a co-culture system in which tumour spheroids were confronted with fetal rat brain cell aggregates. Control experiments with Cremophor EL (the solvent of paclitaxel for clinical use) in this study showed no effect on tumour cell migration, cell proliferation or cell invasion. Scanning confocal microscopy of both cell lines showed an extensive random organization of the microtubules in the cytoplasm. After paclitaxel exposure, the GaMg and the D-54Mg cells exhibited a fragmentation of the nuclear material, indicating a possible induction of apoptosis. In line with this, flow cytometric DNA histograms showed an accumulation of cells in the G2/M phase of the cell cycle after 24 h of paclitaxel exposure. After 48 h, a deterioration of the DNA histograms was observed indicating nuclear fragmentation.

Adult↗
PubMed1997

Asymmetric hydrocephalus: safe endoscopic perforation of septum pellucidum: technical note.

Asymmetric and/or loculated hydrocephalus can be treated with endoscopic septum fenestration to avoid or to simplify a shunt (1,2). In asymmetric lateral ventricles the septum pellucidum is dislocated to the opposite side and may even be in contact with the lateral wall of the contralateral ventricle (i.e., the thalamus). Perforating the septum with a catheter or a laser beam may damage the underlying tissue. The authors show a safe perforation technique: the septum is pulled towards the tip of the endoscope to enlarge the underlying space. Now the catheter can perforate the septum without the risk of damage to the underlying tissue.

Endoscopy↗