Biomedical subjects
Publications and source records attributed to W Arnold.
Depressive symptoms were rated during a double-blind placebo-controlled trial of nadolol for chronic aggression. Depressive symptoms were not significantly different in nadolol and placebo groups during any phase of the drug trial.
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Despite numerous scientific efforts, the etiology of otosclerosis still remains unknown. Pathogenically, there are several signs of a chronic inflammatory process of the bony otic capsule. In this study, we tried to characterize the components of chronic inflammation by immunohistochemical techniques. Within otosclerotic lesions a mixed cellular infiltrate can be observed, consisting of lymphocytes, macrophages and plasma cells. Macrophages which are capable of presenting antigen in association with major histocompatibility antigens (MHC) class I and class II to CD8(+)-, and CD4(+)-T cells, respectively, were found in otosclerotic lesions based on their expression of the MAC387 antigen. Furthermore, HLA-DR positive cells and complement C3 have been found in resorption lacunae of otosclerotic lesions. Several osteoblasts and chondrocytes in active otosclerotic lesions reveal a strong surface expression of beta-2-microglobulin, indicating an increased MHC class I antigen expression in active otosclerotic lesions. In agreement with recently published data we found that a large fraction of the lymphoid cells are antigen-primed T-cells expressing an alpha/beta T-cell receptor in association with CD3 molecules on their surfaces. CD4+ lymphocytes which functionally represent lymphokine-secreting cells are activated through the specific recognition of antigen, presented in context with MHC class II molecules such as HLA-DR. Therefore, the presence of MHC class II positive cells are crucial for the initiation of a local immune response. Thus, our observation of HLA-DR positive cells in otosclerotic lesions is of particular interest.(ABSTRACT TRUNCATED AT 250 WORDS)
Circumstantial evidence supports a role for the retinoblastoma susceptibility gene, Rb-1, in the maintenance of normal cell growth, in that loss of its function results in abnormal growth and malignancy. Here we report that a high rate of mitosis and efficient dense focus formation in human embryonic lung fibroblasts (HEL cells) is induced by antisense oligonucleotide-directed inhibition of synthesis of p105-Rb, the product of the Rb-1 gene. mRNA specific for p105-Rb is truncated at the site of base pairing with the antisense oligonucleotide, and no synthesis of p105-Rb is observed. The rate of mitosis is considerably increased and the frequency of dense focus formation is extremely high in treated cells. However, although phosphothioate oligodeoxyribonucleotides taken up by the cells remain stable for at least 4 weeks, the recipient cells do not become immortal; nor are they able to induce tumor formation in nude mice. Thus, loss of Rb-1 function is not sufficient per se to allow malignant transformation.
The pace analysis of patients with a total hip replacement has been carried out by means of the electroichnograph EKIG-3 of the Riga Institute of Orthopaedics and Traumatology. It comprises foot analysis (heel torsion, sole exercise, ball torsion, contact ability by using special sandals) on an electrically flowed carpet. Furthermore, angular changes in the knee-joint have been registered by means of goniometers, and the trunk deviation to the lateral an sagittal direction has also been measured.
35 patients have been examined before the implantation of a total hip replacement, about 7 days postoperatively and again after 12 weeks by means of the electro-ichnograph EKIG-3 of the Riga Institute of Orthopaedics and Traumatology. Before the hip-joint substitution the normal values could not approximately be attained. The step duration has postoperatively increased, and it has decreased to pre-operative values by the time of the follow-up examination. The best results were obtained concerning the change of the trunk deviation in the frontal plane. The hip mobility measured passively was remarkably better after the operation and almost reached normal values. Regarding the results it should above all be taken into consideration, that the most important fact for the patient is the alleviation and elimination of pain, respectively.
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DNA fragments carrying the recA genes of Rhizobium meliloti and Rhizobium leguminosarum biovar viciae were isolated by complementing a UV-sensitive recA- Escherichia coli strain. Sequence analysis revealed that the coding region of the R. meliloti recA gene consists of 1044 bp coding for 348 amino acids whereas the coding region of the R. leguminosarum bv. viciae recA gene has 1053 bp specifying 351 amino acids. The R. meliloti and R. leguminosarum bv. viciae recA genes show 84.8% homology at the DNA sequence level and of 90.1% at the amino acid sequence level. recA- mutant strains of both Rhizobium species were constructed by inserting a gentamicin resistance cassette into the respective recA gene. The resulting recA mutants exhibited an increased sensitivity to UV irradiation, were impaired in their ability to perform homologous recombination and showed a slightly reduced growth rate when compared with the respective wild-type strains. The Rhizobium recA strains did not have altered symbiotic nitrogen fixation capacity. Therefore, they represent ideal candidates for release experiments with impaired strains.
The characteristic EPR doublet of tyrosine radicals of the growth-regulating enzyme ribonucleotide reductase was detected in human melanoma tissue grown in nude mice. This was possible through the use of an amelanotic melanoma that does not exhibit disturbing EPR signals from melanin. The content of tyrosine radicals is higher in young tumor tissues than in older ones. The clinically applied antimelanotic drug, 4-hydroxyanisole, inhibits ribonucleotide reductase in Ehrlich ascites tumor cells as demonstrated by a pronounced quenching of tyrosine radicals (IC50 = 5 microM). In amelanotic melanoma tissue tyrosine radicals of the enzyme are also quenched by 4-hydroxyanisole in concentrations down to 50 microM. Thus, the inactivation of ribonucleotide reductase, which provides deoxyribonucleotides for DNA synthesis, may be a hitherto unexpected mechanism for the antitumor action of 4-hydroxyanisole.
To facilitate the clinical application of dot-blot hybridization for assaying hepatitis B virus (HBV) DNA, we compared the ability of nucleic acid probes labelled with 32P or with various non-radioactive markers to detect HBV DNA in patient serum. Cloned HBV DNA was hybridized with (1) 32P-labelled HBV DNA cloned in M13, (2) the 32P-labelled HBV RNA probe included in the HepProbe kit, (3) an alkaline phosphatase-labelled synthetic oligonucleotide of HBV, (4) biotin-labelled HBV DNA, and (5) sulphonated HBV DNA. Detection was either by autoradiography or an enzymatic colour reaction. The lowest level of detection of cloned HBV DNA was achieved with the 32P-labelled HBV RNA probe (0.3 pg HBV DNA, corresponding to 3 x 10(4) genomes in 50 microliters), followed by the 32P-labelled DNA probe (0.3-2 pg), sulphonated DNA (1-2 pg), biotin-labelled DNA (4 pg), and an alkaline phosphatase-labelled synthetic oligonucleotide (30 pg). Subsequently, sera from 159 patients with various constellations of HBsAg, HBeAg, and anti-HBe were tested with the most sensitive radioactive method (HepProbe) and the corresponding nonradioactive method (sulphonation). The overall concordance rate was 71% (r = 0.42). Compared with HepProbe results, sulphonation showed a sensitivity of 80% and a specificity of 67%. We conclude that radiolabelling (in particular 32P-labelling of HBV RNA) still allows the most sensitive and reliable detection of HBV DNA in patient serum using conventional dot-blot hybridization.
Our previous immunofluorescence studies support the conclusion that the temporal appearance and subcellular distribution of TS28 (a marker of transverse (T) tubules and caveolae in adult skeletal muscle [Jorgensen, A. O., W. Arnold, A. C.-Y. Shen. S. Yuan, M. Gover, and K. P. Campbell, 1990, J. Cell Biol. 110:1173-1185]), correspond very closely to those of T-tubules forming de novo in developing rabbit skeletal muscle (Yuan, S., W. Arnold, and A. O. Jorgensen, 1990, J. Cell Biol. 110:1187-1198). To extend our morphological studies of the biogenesis of T-tubules and triads, the temporal appearance and subcellular distribution of the alpha 1-subunit of the 1,4-dihydropyridine receptor (a marker of the T-tubules and caveolae) was compared to (a) that of TS28; and (b) that of the ryanodine receptor (a marker of the junctional sarcoplasmic reticulum) in rabbit skeletal muscle cells developing in situ (day 19 of gestation to 10 d newborn) by double immunofluorescence labeling. The results presented show that the temporal appearance and relative subcellular distribution of the alpha 1-subunit of the 1,4-dihydropyridine receptor (alpha 1-DHPR) are distinct from those of TS28 at the onset of the biogenesis of T-tubules. Thus, in a particular developing myotube the alpha 1-DHPR appeared before TS28 (secondary myotubes; day 19-24 of gestation). Furthermore, the alpha 1-DHPR was distributed in discrete foci at the outer zone of the cytosol, while TS28 was confined to foci and rod-like structures at the cell periphery. As development proceeded (primary myotubes; day 24 of gestation) approximately 50% of the foci were positively labeled for both TS28 and the alpha 1-DHPR, while approximately 20 and 30% of the foci were uniquely labeled for TS28 and the alpha 1-DHPR, respectively. The foci labeled for both TS28 and the alpha 1-DHPR and the foci uniquely labeled for TS28 were generally confined to the cell periphery, while the foci uniquely labeled for the alpha 1-DHPR were mostly confined to the outer zone of the cytosol. 1-2 d after birth, TS28 was distributed in a chickenwire-like network throughout the cytosol, while the alpha 1-DHPR was confined to cytosolic foci. In contrast, the temporal appearance and subcellular distribution of the alpha 1-DHPR and the ryanodine receptor were very similar, if not identical, throughout all the stages of the de novo biogenesis of T-tubules and triads examined.(ABSTRACT TRUNCATED AT 400 WORDS)
A 2.6 kb ClaI-BamHI DNA fragment of megaplasmid 2 of Rhizobium meliloti 2011 was found to carry genes involved in exopolysaccharide synthesis and infection of alfalfa nodules. The analysis of the nucleotide sequence of this DNA fragment revealed the existence of two open reading frames (ORFs) running in opposite directions. Plasmid integration mutagenesis showed that these ORFs are organized as two monocistronic transcription units. One of the ORFs represents a new exo gene designated exoZ, which is involved in, but not essential for, the production of acidic exopolysaccharide. However, exoZ is not necessary for nodule formation with alfalfa. The ExoZ protein was found to show homology (23.3%) to the NodX protein of the R. leguminosarum biovar viciae strain TOM, known to be essential for nodulating the primitive Afghanistan pea. The second identified ORF corresponds to the exoB locus. The deduced amino acid sequence of the ExoB protein is homologous (39.6%) to that of the Escherichia coli GalE protein. In R. meliloti, exoB codes for a UDP-glucose 4-epimerase. A deficiency in the activity of this enzyme fully accounts for all the multiple carbohydrate defects that have been observed in exoB mutants.
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The FITC technique using alpha-bungarotoxin visualized the staining pattern of acetylcholine (ACh) receptors in adult human cochlear and vestibular hair cells (HCs) in normal labyrinths and in cochleae with sensorineural hearing loss. Flourescence staining occurred in the cuticular plates of all HCs, indicating that the micromechanics of their suprastructures can act under cholinergic control. Quantitative differences of the fluorescence of ACh receptors occurred between the three rows of outer HCs at the same level in the cochlea and decreasing along a base-to-apex directed gradient. There is strong evidence that the subsurface cisterns are integrated in the efferent nerve system. In the degenerating organ of Corti an uncoupling of the efferent system takes places adjacent to disintegrating HCs, though the staining in the cuticular plates remains until a very late stage in HC disintegration. In vestibular HCs type I, fluorescence is emitted in the supranuclear area of the cytoplasm below the cuticular plate probably indicating an efferent guidance on the afferent nerve transmission directly via the HC itself.
It can be assumed, that the morphological structures of the blood-brain-barrier (BBB) and blood-cerebrospinal fluid-barrier (BCB) are built at the same principle and stops considerably the transport of water soluble substances to the cells of the brain. To these belong polar groups of active substances, which improve their water solubility (OH-, COOH-, CO-, NH2- and SH-substitutes). On the other side lipophilic solvents as vehicles support the penetration of such polar substances into the brain. Our aim in this paper was to investigate the distribution of unchanged barbiturates and their polar metabolites in the brain within the scope of animal experiments. All the animals (cats) got an overdose of Pentobarbital, to which a small quantity of the hypnotic marked with a 14C atom was added. Pentobarbital metabolizes in the organism in short times to hydroxy- and carboxy-pentobarbital. After different times of killing the organs and body fluids, especially the brain were examined and the results compared. It could be shown that in the brain of all animals in spite of different killing times 75-90 per cent of the unchanged barbiturate has been found. On the other side, only a maximum of 20 per cent of the pentobarbital metabolites was found in the brain cells. In the other organs and body fluids the part of the unchanged barbiturate was much lower, between 10 and 50 per cent, depending on the killing time. The quantity of the metabolites was essential higher, with variations between 50 and 90 per cent.(ABSTRACT TRUNCATED AT 250 WORDS)
This report is based on experience with the treatment of 135 patients who had sustained mainly gunshot injuries but also injuries from mines and hand grenades. The different sorts of the therapy were directly dependent on the different injury causes. Second- and third-grade fractures caused by middle and high velocity projectiles were treated by the open method, external fixation, debridement and draining. The therapy of choice is the application of a fixateur externe (external fixation). The prognosis after fixation with further treatment as needed was very good, even when not performed until several weeks after the injury, especially in the restitution of extremity continuity, which can sometimes help to prevent unnecessary amputations, especially of the upper extremities.
Transient evoked otoacoustic emissions (TEOAE) of 153 patients of various ages with normal or nearly normal hearing in the low, high or middle frequency ranges (different aetiologies) have been recorded. We found that the rate of detection of otoacoustic emissions depends on the width of the frequency range of preserved hearing. Single cases of narrow bands of hearing in the middle frequency region showed this region's significance for the high detectability of TEOAE. Although the investigated population consists mainly of adults, conclusions for the use of the TEOAE method for infant screening are drawn.
Dysphagia is a terminus which describes problems during the action of swallowing of fluids and/or food. The diagnosis is made by a detailed history according to a standard questionnaire, which then allows to distinguish between oropharyngeal and esophageal dysphagia.