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Biomedical subjects

R Seeger

Publications and source records attributed to R Seeger.

At least 19 recordsLinked to original sources
PubMed1998

Accidents related to sleepiness: review of medical causes and prevention with special reference to Switzerland.

Sleepiness is a major cause of traffic accidents. Our purpose was to review determinants of accidents related to sleepiness and measures to prevent them. We performed a systematic literature review on the topic and studied official accident statistics and legislation regarding medical driving ability in Switzerland. In 1997, 79,178 road traffic accidents, each causing bodily injury or property damage in excess of 500 Swiss francs, occurred in Switzerland. According to official statistics, sleepiness accounted for only 1% of identified causes. However, scientific studies performed in other countries suggest that sleepiness is a contributing factor in up to 30% of traffic accidents. Causes of hypersomnolence are sleep restriction, sleep disturbance by external environmental factors, inappropriate sleep hygiene, and sleep disorders. Several reports suggest an increased crash rate in patients with obstructive sleep apnoea syndrome. At our clinic, every sixth sleep apnoea patient reports sleepiness-related driving problems which resulted in traffic accidents in one third of them. Long monotonous motorway drives, late night, early morning and late afternoon hours are associated with an increased crash rate. Drivers with excessive sleepiness should not drive until the cause of hypersomnolence is determined and treated appropriately. Medical assessment of driving ability in patients with sleep disorders involves a specific history including standardised questionnaires, sleep studies and vigilance tests. Swiss legislation authorizes physicians to report sleepy drivers to the authorities if they are thought to represent an accident risk for themselves or others. We conclude that sleepiness is a common but under-recognised cause of traffic accidents. Enhancing awareness of the problem in the public, early recognition and treatment of sleep disorders, and counselling of drivers with excessive sleepiness may contribute to prevention.

Accident Prevention↗
PubMed1997

[Problems in the assessment of driving capability in family practice].

More than half of the Swiss adult population possesses a valid driver's licence. To safely drive a car, certain medical demands are requested by law. Drivers of trucks, taxis and coaches and all drivers past the age of 70, must undergo a periodical medical examination. These examinations are usually performed by general practitioners. The most important legal foundations and the medical examination procedure are explained in this publication. Frequent diseases affecting the patient's driving ability such as poor vision, alcoholism, drug abuse, the early stages of dementia and other physical impairments are presented. Not to be neglected are the number of road traffic accidents resulting from medical reasons. The general practitioner is authorized to contact the authorities if he feels a patient is no longer capable of driving. For this reason, general practitioners should also be aware of the patient's driving capability other than during a periodical traffic examination. The individual's interests have to be carefully considered as opposed to that of society. The problems of general driving capability assessment performed by the general practitioner and possible procedures in case of patient's disagreement are presented.

Adult↗
PubMed1996

[Iatrogenic driving incapacity].

The most frequent reasons for iatrogenic incapacity to drive are unreported or untreated cases of alcohol and drug abuse, medication which impairs driving competence, and sleep-apnea syndrome. Some 50% of traffic injuries and fatalities in Switzerland would appear to be avoidable through a more consistent policy.

Adolescent↗
PubMed1994

Human dTMP kinase: gene expression and enzymatic activity coinciding with cell cycle progression and cell growth.

dTMP kinase (E.C.2.7.4.9.) catalyzes the phosphorylation of dTMP to the corresponding diphosphate. This enzyme is essential for DNA synthesis in vivo and is an important intermediate enzyme in the pathway of many pyrimidine analog drugs. In this report, we describe the isolation of the human dTMP kinase gene by functional complementation of a Saccharomyces cerevisiae cell cycle mutant, cdc8. The cDNA sequence revealed an open reading frame that encodes a protein with the molecular weight of 23,806. The deduced protein sequence was compared to known dTMP kinase sequences from different organisms. Although functionally complementary and structurally conserved, expressed human dTMP kinase in yeast shows little enzymatic activity. In contrast, active human dTMP kinase can be expressed from the gene cloned into the baculovirus expression system, as evidenced by increased enzymatic activity by four- to five-fold. Unlike yeast dTMP kinase, human dTMP kinase does not contain a cysteine residue after the conserved glycine-rich loop, but its enzymatic activity is still affected by the sulfhydryl inhibitor, 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB). The levels of dTMP kinase mRNA and its enzymatic activity fluctuate during the cell cycle, peaking at the S phase. Thus, like Saccharomyces cerevisiae CDC8 (encoding dTMP kinase), the human homolog mRNA and enzymatic activity are also cell cycle regulated. We have also examined four neuroblastoma cell lines for dTMP kinase mRNA levels and its kinase activities, which appear to vary according to cell growth rate. Our results suggest that the expression of the dTMP kinase gene and its activity coincide with various stages of cell growth. The identification of the human dTMP kinase gene and expression of its product in the baculovirus expression system should facilitate study of the mechanism of gene regulation and its role in pyrimidine metabolism.

Amino Acid Sequence↗
PubMed1988

Characterization of N-myc amplification units in human neuroblastoma cells.

A set of DNA clones comprising 48 independent HindIII fragments (215 kilobases of sequence) was derived from the N-myc amplification unit of the neuroblastoma cell line NGP. These clones were used to investigate N-myc amplification units in NGP cells and 12 primary neuroblastoma tumors. Three parameters were evaluated: (i) the number of rearrangements from germ line configuration that had occurred during the amplification process; (ii) the homogeneity of amplification units within individual tumors; and (iii) the conservation of amplified sequences among different tumors. The results indicated that remarkably few rearrangements had occurred during amplification, that the amplification units within any one tumor were quite homogeneous, and that although each tumor contained a unique pattern of amplified DNA fragments, there was considerable similarity between the amplification units of different tumors. In particular, the amplification units were strikingly similar over a contiguous domain of at least 140 kilobases surrounding the N-myc structural gene.

Cell Line↗
PubMed1987

Shedding of GD2 ganglioside by human neuroblastoma.

Substantial concentrations of the cell-surface glycosphingolipid, the disialoganglioside GD2, are uniformly present in human neuroblastoma tumors. This ganglioside can also be detected in the plasma of patients with neuroblastoma by direct thin-layer chromatographic analysis. Among 32 neuroblastoma patients in all clinical stages studied prior to the initiation of treatment, 27 (84%) showed measurably elevated plasma concentrations of GD2 (greater than or equal to 50 pmol/ml). The mean level (545 +/- 108 pmol/ml) was more than 50 times the normal plasma GD2 concentration of less than or equal to 10 pmol/ml. Circulating GD2 was not detected in the plasma of patients with the related, more differentiated tumors, ganglioneuroblastoma and ganglioneuroma, indicating an association of the shedding of this ganglioside with the undifferentiated phenotype. Circulating GD2 diminished in patients in response to therapy, and reappeared in patients whose disease recurred. The results suggest that the sequential determination of circulating GD2 will be of value in monitoring individual patients with neuroblastoma.

Antibodies, Monoclonal↗
PubMed1987

Immune interventions in disease.

Three therapeutic areas of clinical immunology that have seen active development recently are immunopharmacology of immunosuppressive drugs; clinical use of the alpha-, beta-, and gamma-interferons and interleukin-2; and monoclonal antibody applications in marrow transplantation and antitumor therapy. Understanding of the immune regulatory systems and of the soluble factors that convey information between immune and related cells (for example, lymphokines and cytokines and their receptors) has improved substantially. New information about established immunosuppressive drugs and the introduction of new drugs are providing new opportunities for effective treatment of autoimmune diseases and improved effectiveness of organ transplantation. Clinical trials are evaluating the use of interleukin-2 in immunodeficiency disorders and neoplastic disease. Monoclonal antibodies, which have been successfully applied to diagnostic procedures, have been shown to be useful for therapeutic applications in marrow transplantation and antitumor treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Expression of GD2 ganglioside by untreated primary human neuroblastomas.

Primary neuroblastomas obtained before therapy from 36 patients were studied to determine the frequency of tumors expressing a specific glycosphingolipid, GD2 ganglioside. Total tissue gangliosides were purified by a new partition method, quantitated, and analyzed by high-performance thin-layer chromatography. All 36 neuroblastoma tumors, representing all clinical stages, contained GD2 ganglioside. The mean relative and absolute concentrations of GD2 were substantial (12% of the total tissue gangliosides and 50 nmol/g of tissue) and were independent of the clinical stage of the tumor. In contrast, 6 samples of related but more differentiated tumors (ganglioneuroblastoma and ganglioneuroma) had little or no detectable GD2 (less than or equal to 1.5% of total gangliosides and less than or equal to 4 nmol/g of tissue). These results suggest that GD2 is a sensitive marker for neuroblastoma tissue and may be an excellent target antigen for immunotherapy of this tumor.

Cell Differentiation↗
PubMed1985

Immunodiagnosis and immunotherapy of childhood malignancies.

Recent advances in immunologic techniques have allowed the generation of monoclonal antibodies against antigens on tumor cells and their normal counterparts. Monoclonal antibodies useful for diagnosing and defining subtypes of acute leukemias and neuroblastoma have been prepared, although the prognostic significance of the subtypes defined by such antibodies remains to be determined. The usefulness of these reagents for therapeutic purposes either ex vivo, in association with autologous bone marrow transplantation, or in vivo, as carriers of cytotoxic agents, is currently under investigation.

Acute Disease↗
PubMed1985

Differential amplification, assembly, and relocation of multiple DNA sequences in human neuroblastomas and neuroblastoma cell lines.

DNA amplification, manifested by homogeneously staining regions in chromosomes and by extrachromosomal, double minute bodies, is characteristic of many neuroblastoma cell lines. Sequences recruited from a specific domain on the short arm of chromosome 2 (2p) are amplified in advanced-stage primary neuroblastomas, whereas sequences from distinctly different regions of 2p are amplified in the neuroblastoma cell line IMR-32. Five different DNA segments, which include the oncogene N-myc, three other fragments derived from the homogeneously staining region of the neuroblastoma cell line IMR-32, and a fifth fragment, derived from the neuroblastoma cell line NB-9, showed differential and variable amplification in 24 advanced-stage neuroblastoma tumors out of 112 tested specimens. All five fragments were mapped within the chromosomal region 2p23-2p25 by three different approaches. However, eight other fragments cloned from the homogeneously staining region of IMR-32 cells, which were not amplified in the tumor tissues examined, were mapped to two more proximal domains of 2p, thousands of kilobases apart from each other and from the chromosomal domain that is amplified in the tumors. These results establish the amplification, to different degrees, of a variable-sized segment of one domain near the terminus of 2p in advanced neuroblastomas. These tumors might ultimately be distinguished according to the pattern of amplification of DNA segments within this domain. The data presented also indicate the existence of a new and complex amplification mechanism in at least one neuroblastoma cell line (IMR-32), which involves not only relocation of DNA from specific genomic domains but also the formation of novel units by splicing together very distant DNA segments.

Base Sequence↗
PubMed1982

Damage in vitro to various organs and tissues by rubescenslysin from the edible mushroom Amanita rubescens.

Rubescenslysin, a haemolytic protein from Amanita rubescens, disrupted the cytoplasmic membrane of human leucocytes which were more sensitive than erythrocytes. In the isolated hearts of rats and guinea pigs it caused systolic contracture, which was preceded by potassium outflow and sometimes by a transient positive inotropic effect. On the electrically stimulated guinea-pig left atrium it showed at first a positive, followed by a negative inotropic effect; on the spontaneously beating right atrium it produced transient positive followed by negative inotropic and chronotropic effects. Atria were less sensitive than intact hearts. In the isolated rat phrenic nerve-diaphragm preparation it produced a contracture, which was associated with reduction of indirect and direct contractility. In the isolated guinea-pig ileum it produced a slow contraction followed by tachyphylaxis. As excitability declined due to rubescenslysin, so did excitability by acetylcholine and potassium. Atropine and pheniramine had only feeble antagonistic effects, but papaverine was more powerful. In isolated rat hepatocytes, rubescenslysin caused a rapid outflow of potassium and coarse cell protrusions while later the cells became stainable with trypan blue. In the isolated perfused rat liver it produced a rapid outflow of potassium and of cytoplasmic and mitochondrial enzymes, and a somewhat slower outflow of lysosomal beta-glucuronidase, accompanied by a rise in the lactate/pyruvate ratio and a decrease in bile production. In the isolated perfused rat kidney it caused an outflow of cytoplasmic and mitochondrial enzymes, together with massive proteinuria and serious restriction of sodium and potassium reabsorption and of urine output. In all the tissues investigated the effects of rubescenslysin began within a few min, were dose-dependent and practically irreversible. There were only minor differences in sensitivity between various organs and species. The observations indicate that the toxin is relatively nonspecific in its attack on components of cell membranes.

Amanitins↗