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Biomedical subjects

C Beck

Publications and source records attributed to C Beck.

At least 37 records · Page 2Linked to original sources

The thymidine kinase/ganciclovir-mediated "suicide" effect is variable in different tumor cells.

The herpes simplex virus thymidine kinase (HSV-TK) converts ganciclovir (GCV) into a toxic product and allows selective elimination of TK+ cells in vitro and in vivo. It is currently being used in clinical gene therapy trials as a therapeutic gene or as a safety marker. We have analyzed the susceptibility of different tumor cell lines to the TK/GCV-mediated "suicide" effect. Therefore, tumor cells TSA, J558L, EB, and ESB and, as a control, NIH-3T3 cells were infected with a retrovirus containing a hygromycin/TK fusion gene. All cell lines were sensitive to GCV in vitro; however, the concentration of GCV and the time needed to eliminate tumor cells completely considerably varied between different tumor cell lines. TSA-TK cells were completely eliminated within 10 days in 1 microg/ml GCV, whereas ESB-TK cells required 22 days in 10 microg/ml GCV. When two cell lines were examined, the differing sensitivity to GCV in vitro correlated with the ability to eradicate TK+ tumors in vivo. TSA-TK tumors could be eliminated in almost all animals by systemic GCV administration, whereas ESB-TK tumors were completely resistant. Different sensitivity to GCV was not due to different TK expression levels because the cells were similarly resistant to hygromycin, and Western blot analysis with an anti-TK antiserum revealed similar protein amounts in TSA/TK and ESB-TK cells. Together, the results demonstrate that tumor cells are highly different concerning the susceptibility to the TK/GCV effect, which, however, may be tested for in vitro.

3T3 Cells

A single rRNA gene region in Bradyrhizobium japonicum.

Bradyrhizobium japonicum contains only a single rRNA (rrn) gene region, despite its comparatively large genome size of 8,700 kb. The nucleotide sequence revealed an organization of rRNA and tRNA genes that is frequently found in bacteria: 5'-rrs (16S rRNA)-ileT (tRNA(Ile))-alaT (tRNA(Ala))-rrl (23S rRNA)-rrf (5S rRNA)-3'. The 5' end of the primary transcript, one of the 16S rRNA processing sites, and the 5' end of the mature 16S rRNA were determined by primer extension. DNA hybridization experiments showed that the slowly growing Bradyrhizobium strains generally have only a single copy of the 16S rRNA gene, whereas the faster-growing Rhizobium species contain three rrs copies.

Base Sequence

Lymphotoxin-alpha/beta heterodimer is expressed on leukemic hairy cells and activated human B lymphocytes.

The expression of human lymphotoxin (LT) alpha/beta cell-surface complex was studied in human B-cell lines as well as in normal and neoplastic human B lymphocytes. In the absence of TNF receptors, only the human hairy-cell leukemia (HCL)-derived cell line JOK-I revealed constitutive cell-surface expression of LT but not TNF-alpha. Immunoprecipitation experiments with anti-LT monoclonal antibody (MAb) 9B9 from cell-surface radioiodinated JOK-I cells revealed that a cell-surface lymphotoxin molecule (25 kDa) is expressed in association with a 33-kDa molecule. Enzymatic digestion with F/N-glycosidase and O-glycosidase showed that both proteins contained N-linked carbohydrate residues, whereas only the 25-kDa molecule contained O-linked sugar residues. Analysis of mRNA expression revealed specific transcripts of LT-alpha and LT-beta in JOK-I cells. Resting tonsillar B cells did not express cell-surface LT. However, LT-beta mRNA was observable in unstimulated tonsillar B cells, whereas LT-alpha mRNA, cell-surface LT and LT secretion could only be detected upon in vitro activation. Thus LT-beta and alpha appear to be sequentially expressed in human B cells. Neoplastic B cells from chronic lymphocytic leukemia (BCLL), being devoid of constitutive cell-surface LT expression, could be induced to express surface LT by in vitro stimulation with Staphylococcus aureus Cowan I (SAC). Constitutive LT-beta transcripts, however, could also be detected in 4 out of 5 cases of BCLL. In contrast, human HCL cells displayed constitutive cell expression of lymphotoxin-alpha and beta. These findings demonstrate that cell-surface LT-alpha is expressed in association with LT-beta on activated normal B cells and neoplastic B cells representing an activated state.

B-Lymphocytes

Benign infantile familial convulsions are not an allelic form of the benign familial neonatal convulsions gene.

Benign infantile familial convulsions (BIFC) and benign familial neonatal convulsions (BFNC) are two forms of familial convulsions having an age of onset within the first year of life. The gene responsible for BFNC has been mapped to chromosome 20q in the close vicinity of D20S19 and D20S20 markers. We performed linkage analysis between BIFC and D20S19-D20S20 in eight families in order to know whether the BFNC gene is also implicated in BIFC. Several apparent obligate crossovers between affected members were detected. The data here presented demonstrate that the BFNC gene is not responsible for BIFC.

Age of Onset

A nonsense mutation in the alpha4 subunit of the nicotinic acetylcholine receptor (CHRNA4) cosegregates with 20q-linked benign neonatal familial convulsions (EBNI)

Benign Familial Neonatal Convulsions (BFNC) is an epileptic disorder with an autosomal dominant mode of transmission. It has been shown that about 80% of BFNC pedigrees are linked to a genetic defect on chromosome 20q13.3. A candidate gene for the epilepsies, the gene coding for the alpha4 subunit of the nicotinic cholinergic receptor (CHRNA4), has previously been localized on chromosome 20. Here we report a single point mutation converting a serine codon to a stop codon in the exon 5 of CHRNA4, in one BFNC family. Identification of CHRNA4 as the defective gene in 20q-BFNC represents the first example of a human idiopathic epilepsy caused by a mutation directly affecting a neurotransmitter receptor in the central nervous system.

DNA Probes

[Ginkgo extract EGb 761 (tenobin)/HAES versus naftidrofuryl (Dusodril)/HAES. A randomized study of therapy of sudden deafness].

80 patients with idiopathic sudden hearing loss existing no longer than 10 days were included in a randomised reference-controlled study. The therapeutic value of Ginkgo EGb 761 (Tebonin) + HAES was compared to that of Naftidrofuryl (Dusodril)+HAES. The main mechanisms of action of EGb 761 are a vasoregulating activity (increased blood flow), the platelet activating factor antagonism and a prevention of membrane damage caused by free radicals. Naftidrofuryl has antiserotonergic and therefore vasodilatory properties. The statistical analysis of the audiometric data was performed in measuring the relative hearing gain as described by Eibach 1979. After one week of observation, 40% of the patients in each group showed a complete remission of hearing loss. This was also observed by other authors who had compared other drugs. Therefore, in these cases, it is most likely that spontaneous recovery is the most important factor. After two and three weeks of observation, measuring the relative hearing gain, there was a significant borderline benefit of EGb 761 (p = 0.06) without any side effects. Some patients of the reference group developed side effects such as orthostatic dysregulation or headache or sleep disturbances. Minimising side effects should be one of the most important goals in therapy of sudden hearing loss until the efficiency of infusion therapy is proved.

Adult

[Effects of therapy of laryngeal and hypopharyngeal cancers on eustachian tube function].

In a prospective investigation Eustachian tube function was tested before and after surgery and irradiation of patients suffering from carcinoma of the larynx or hypopharynx. Passive and active tubal parameters were determined using the dual-impedance method in a pressure chamber. In this test, passive tubal function is described by the spontaneous opening and closing characteristics of the tube by an overpressure in the middle ear. Active tubal parameters are determined by the facility of the tube to equalize an over- and underpressure in the middle ear by swallowing. Statistic evaluation was performed with Student's t-test. There were no significant alterations of passive or active tubal function after neck dissection with or without surgery of the primary tumour. On the other hand we observed significant deterioration of all tubal parameters immediately after a series of fractionated percutaneous telecobalt therapy (60 Gy). 2 out of 18 patients developed unilateral middle ear effusion during irradiation which was reversible within 6 months. In most patients we observed a total or at least partial restitution of passive tubal parameters during this time, which was statistically significant. The active tubal function was of minor reversibility. Whereas the facility to equalize a positive pressure in the middle ear was quite good after 6 months, only few patients were able to equalize a negative pressure. The temporary deterioration of passive tubal function may be caused by a marginal implication of the tube at the edge of the irradiation field and by increased lymphatic pressure in tubal tissue following a radiogenic swelling of the lymphatic vessels of the neck.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy

On the localization of voltage-sensitive calcium channels in the flagella of Chlamydomonas reinhardtii.

This study was undertaken to prove that voltage-sensitive calcium channels controlling the photophobic stop response of the unicellular green alga Chlamydomonas reinhardtii are exclusively found in the flagellar region of the cell and to answer the question as to their exact localization within the flagellar membrane. The strategy used was to amputate flagella to a variable degree without perturbing the electrical properties of the cell and measure flagellar currents shortly after amputation and during the subsequent regeneration process. Under all conditions, a close correlation was found between current size and flagellar length, strongly suggesting that the channels that mediate increases in intraflagellar calcium concentration are confined to and distributed over the total flagellar length. Bald mutants yielded tiny flagellar currents, in agreement with the existence of residual flagellar stubs. In the presence of the protein synthesis inhibitor cycloheximide, flagellar length and flagellar currents also recovered in parallel. Recovery came to an earlier end, however, leveling off at a time when in the absence of cycloheximide only half maximal values were achieved. This suggests the existence of a pool of precursors, which permits the maintenance of a constant ratio between voltage-sensitive calcium channels and other intraflagellar proteins.

Animals

The ccoNOQP gene cluster codes for a cb-type cytochrome oxidase that functions in aerobic respiration of Rhodobacter capsulatus.

The genes for a new type of a haem-copper cytochrome oxidase were cloned from Rhodobacter capsulatus strain 37b4, using the Bradyrhizobium japonicum fixNOQP gene region as a hybridizing probe. Four genes, probably organized in an operon (ccoNOQP), were identified; their products share extensive amino acid sequence similarity with the FixN, O, Q and P proteins that have recently been shown to be the subunits of a cb-type oxidase. CcoN is a b-type cytochrome, CcoO and CcoP are membrane-bound mono- and dihaem c-type cytochromes and CcoQ is a small membrane protein of unknown function. Genes for a similar oxidase are also present in other non-rhizobial bacterial species such as Azotobacter vinelandii, Agrobacterium tumefaciens and Pseudomonas aeruginosa, as revealed by polymerase chain reaction analysis. A ccoN mutant was constructed whose phenotype, in combination with the structural information on the gene products, provides evidence that the CcoNOQP oxidase is a cytochrome c oxidase of the cb type, which supports aerobic respiration in R. capsulatus and which is probably identical to the cbb3-type oxidase that was recently purified from a different strain of the same species. Mutant analysis also showed that this oxidase has no influence on photosynthetic growth and nitrogen-fixation activity.

Aerobiosis

[Effects of a change in environmental pressure on spontaneous nystagmus in patients with cochleovestibular diseases].

Cochlear and vestibular effects of variation of middle ear pressure have been discussed for more than 50 years. In 1975, Densert reported on temporary improvement of hearing threshold in patients suffering from Ménière's disease after reduction of air pressure in a pressure chamber. One year later Ingelstedt observed reduction of spontaneous nystagmus under this condition. The transmission of relative overpressure from the middle ear to the labyrinth with consecutive decongestion of the hydropic endolymphatic system to the saccus was thought to be the cause of this phenomenon. Meanwhile a direct effect of labyrinthine pressure on the activity of the inner ear and labyrinth in healthy subjects and animals has been described. In order to gain further information on the phenomenon observed by Densert and Ingelstedt we performed investigations on patients suffering from several cochleovestibular diseases. Chamber pressure was altered and simultaneous electronystagmographic recording was performed. As a striking result, we observed a reduction of the pathological spontaneous nystagmus in a majority of patients with vestibular damage during and after the reduction of chamber pressure. Many of these subjects showed a partial restitution of nystagmus if the chamber pressure was increased again. This observation was made in patients with Méni ere's disease, vestibular neuritis and sudden hearing loss with vestibular involvement. Hence, we conclude that this phenomenon is not specific for Ménière's disease. A transmission of middle ear pressure to the labyrinth may be an explanation of our observations.

Air Pressure

Cognitively impaired elders. Using research findings to improve nursing care.

1. Cognitive changes may be similar in people with Alzheimer's disease, but each person loses abilities differently, and each individual responds differently to interventions. 2. Assessment of cognitive function is needed in order to design appropriate interventions that will be specific in facilitating independence in cognitively impaired elders. 3. Research findings suggest that functional ability in cognitively impaired elders can be maximized by assessing cognitive abilities and using this information to tailor specific interventions that will facilitate independence.

Aged

[Subablative gentamycin therapy in Menière's disease].

We have treated 20 patients suffering from unilateral Morbus Meniere (2 x 12 mg gentamicin for 7 days). These patients were controlled for 24 months. In 95% we regarded a complete or substantial control of definitive spells ("American Committee on Hearing and Equilibrium guidelines for reporting treatment results in Meniere's disease", Otolaryngol. Head and Neck Surg. 10/19-85). Only 1 patient with pretherapeutic equal caloric response showed a post-therapeutic destroyed vestibular apparatus on the treated ear. In the other 7 patients (35%), who had a loss of vestibular function after therapy, there was an already pretherapeutic more or less noticeable caloric hypoexcitability. It is possible to induce an only subablative damage with a clinical success in 95%.

Audiometry, Pure-Tone

Classification of autonomic disorders.

Recent advances in our understanding of the pathophysiology of cardiovascular regulation and the metabolism of catecholamines have enabled us to develop an improved system of classification of autonomic disorders. Patients with autonomic impairment, clinically unassociated with other neurological abnormalities, are considered to have the Bradbury-Eggleston syndrome (idiopathic orthostatic hypotension, pure autonomic failure). Individuals whose autonomic failure is accompanied by degeneration in other neurological systems are classified as having the Shy-Drager syndrome (multiple system atrophy with autonomic failure). Patients in whom a deficiency of the enzyme dopamine-beta-hydroxylase is present from birth have many features suggestive of the Bradbury-Eggleston syndrome but manifest normal sweating and biochemically have an elevated plasma and urinary dopamine level. Recognition of these individuals is of particular importance because they are uniquely responsive to treatment with oral dihydroxyphenylserine (L-DOPS). A fourth disorder is baroreflex failure; this disorder is usually due to surgery, trauma, radiation or other injury to the ninth or tenth cranial nerves or the medullary nuclei which their fibers innervate. Patients with baroreflex failure have oscillations between hypertension and hypotension, but these alterations are poorly correlated with posture. Very high levels of plasma norepinephrine are found during the hypertensive phase of baroreflex failure. Baroreflex failure is generally responsive to treatment with clonidine. In conclusion, the diagnosis and therapy of autonomic disorders has improved due to the more precise taxonomy now current.

Autonomic Nervous System Diseases

Confirmation of linkage of benign familial neonatal convulsions to D20S19 and D20S20.

Benign familial neonatal convulsions (BFNC) is an idiopathic form of epilepsy beginning within the first six months of life. Its genetic origin and autosomal dominant mode of inheritance have been suspected since its first description. Recently, the BFNC gene has been localised within chromosome 20q in one large pedigree. For the first time, we confirm here (with D20S19 and D20S20) the close linkage of BFNC to chromosome 20q in six French pedigrees. In addition, the existence in these families of several cases of febrile convulsions (FC), another epileptic syndrome with an autosomal dominant genetic component, led us to study the possibility of a genetic background identical to BFNC. Our results suggest the existence of different susceptibility genes for BFNC and FC.

Blotting, Southern

Disruptive behaviors of a cognitively impaired nursing home resident.

The descriptive case study of a 71-year-old man with Primary Degenerative Alzheimer's Dementia identifies and describes specific disruptive behaviors exhibited by a demented, disruptive nursing home resident and the biopsychosocial characteristics of these behaviors. The Disruptive Behavior Scale (Beck, Baldwin, Heithoff, & Cuffel, 1990) measured disruptive behaviors. Data collected included chart review, interviews, testing, and observation. The majority of observed disruptive behaviors fell under four categories: (1) walks aimlessly, (2) makes repetitive noises, (3) uses obscene/profane language, and (4) makes repetitive movements. Staff members and chart notes reported the same categories, except for "makes repetitive noises." All aggressive behavior toward the staff occurred during assistance with activities of daily living (ADLs).

Activities of Daily Living

[Laryngeal cancer following gunshot injury and paraffin injection].

Subcutaneous and submucosal injections of paraffin were a wide-spread technique in plastic and reconstructive surgery during the early decades of this century. Intralaryngeal injections were applied to patients suffering from paralysis of one vocal cord or a defect resulting from perforating trauma, intending improvement of the voice. This method was widely abandoned within the fifties when severe complications like foreign-body granuloma and carcinoma developed in patients undergoing paraffin injections. The development of cancer after a trauma is a common question in expert reports. We report the case of a patient who developed carcinoma of the vocal cord 49 years after perforation of the larynx by a shot with consecutive injection of paraffin. The relationship between trauma, injections of paraffin and cancer is discussed and consequences on diagnostics and treatment of risk patients are outlined.

Aged