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H Klima

Publications and source records attributed to H Klima.

At least 19 recordsLinked to original sources

Biophotons, microtubules and CNS, is our brain a "holographic computer"?

Several experiments show that there is a cell to cell communication by light in different cell types. This article describes theoretical mechanisms and subcellular structures that could be involved in this phenomenon. Special consideration is given to the nervous system, since it would have excellent conditions for such mechanisms. Neurons are large colourless cells with wide arborisations, have an active metabolism generating photons, contain little pigment, and have a prominent cytoskeleton consisting of hollow microtubules. As brain and spinal cord are protected from environmental light by bone and connective tissue, the signal to noise ratio should be high for photons as signal. Fluorescent and absorbing substances should interfere with such a communication system. Of all biogenic amines nature has chosen the ones with the strongest fluorescence as neurotransmitters for mood reactions: serotonin, dopamine and norepinephrine. If these mechanisms are of relevance our brain would have to be looked upon as a "holographic computer".

Animals↗

Elektromagnetische Bioinformation im Frequenzbereich von 100 Hz bis 100 kHz?

Electromagnetic Bioinformation in the Frequency Region between 100 Hz and 100 kHz? A highly sensitive measurement amplifier (BIT device) was constructed in order to detect possible electromagnetic biosignals in the frequency region between 100 Hz and 100 kHz. Even when working with the highest amplification mode of the BIT device, no endogenous electromagnetic biosignals could be detected on the test persons, but only well-known EMG signals. If the BIT device worked in a feedback mode, electromagnetic oscillations beween 1.7 and 2.9 kHz could be generated and oscilloscopically detected; these oscillations are caused by the oscillator system 'BIT - man', depending on the impedance of the human body. Biological effects of the impedance-depending oscillations were investigated in a simple randomized double-blind study. Three anamnestically healthy persons were treated 20 times with their specific oscillations. The physiological effects of this treatment were measured by pulse plethysmography. Nonlinear analysis of the time series indicated significant changes in pulse dynamics of one person. Linear analysis of heart rate variability showed no statistical significance. Our device was only designed for the project described below. It is, therefore, evident that the research results presented in this paper cannot be applied to any of the therapy devices at present on the market.

Journal Article↗

Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity.

Cholesteryl ester storage disease (CESD) and Wolman disease are both autosomal recessive disorders associated with reduced activity and genetic defects of lysosomal acid lipase (LAL). We provide evidence that the strikingly more severe course of Wolman disease is caused by genetic defects of LAL that leave no residual enzyme activity. In a CESD patient, a G --> A mutation at position -1 of the exon 8 splice donor site results in skipping of exon 8 in 97% of the LAL hnRNA originating from this allele, while 3% are spliced correctly, resulting in full-length LAL enzyme. The mutant LAL mRNA codes for a protein lacking amino acids 254 to 277. On the other allele, a G --> T mutation leads to a premature stop codon at Gly245, resulting in inactive LAL enzyme. In addition, the previously identified Leu179 --> Pro mutation is present on this allele, and the LAL mRNA is rendered unstable by the premature stop codon. Analysis of two children with Wolman disease showed that both were homozygous for a G --> A mutation at position +1 of the same splice donor site as for the CESD patient, leading to skipping of exon 8. In contrast to the CESD patient, no correctly spliced mRNA was detectable. We have also expressed a wildtype LAL cDNA and the mutant LAL cDNA from one Wolman patient in Sf9 and H5 insect cells. We demonstrate that the LAL enzyme generated from the wildtype LAL cDNA was active in homogenates from Sf9 and H5 cells, while the enzyme with the internal deletion of 24 amino acids originating from the LAL cDNA of the Wolman patient was not. The combined data provide evidence that the only functionally relevant genetic difference between the Wolman patients and the CESD patient is that the splice defect in Wolman, which affects one of the invariable nucleotides of the splice consensus sequences (position +1), does not permit any correct splicing, whereas the defect observed in CESD (position -1) allows some correct splicing (3% of total LAL mRNA) and therefore the synthesis of functional enzyme.

Alternative Splicing↗

Genomic organization of the human lysosomal acid lipase gene (LIPA).

Defects in the human lysosomal acid lipase gene are responsible for cholesteryl ester storage disease (CESD) and Wolman disease. Exon skipping as the cause for CESD has been demonstrated. We present here a summary of the exon structure of the entire human lysosomal acid lipase gene consisting of 10 exons, together with the sizes of genomic EcoRI and SacI fragments hybridizing to each exon. In addition, the DNA sequence of the putative promoter region is presented. The EMBL accession numbers for adjacent intron sequences are given.

Base Sequence↗

[Etiopathogenetic aspects of osteochondrosis dissecans of the femoral condyles].

In an analysis of results from a biostatic examination on the pressure distribution at the weight-bearing femoral condyles under different conditions compared with results from a follow-up examination of patients with osteochondritis dissecans of the knee, we discuss the most likely etiology of this disease, namely mechanical induction. From this comparison it is deduced that the biomechanical impact is the most important factor for the initiation of osteochondritis dissecans at the femoral condyles.

Biomechanical Phenomena↗

Over-expression of a functionally active human GM2-activator protein in Escherichia coli.

The cDNA of the human GM2-activator protein was cloned into the expression vector pHX17. The plasmid encodes a fusion protein with a hexahistidine tail and a Factor Xa cleavage site at its N-terminus. The recombinant protein was purified from cell homogenates under denaturing conditions by metal-ion affinity chromatography in a single step and then was refolded. The hexahistidine tail could be removed when desired by digestion with Factor Xa. In a functional assay, the GM2-activator thus generated from Escherichia coli and renatured, with or without the hexahistidine tail, was as active as the native GM2-activator protein that was purified from human tissue. When added to the culture medium, the recombinant carbohydrate-free GM2-activator, carrying the hexahistidine tail, could be taken up efficiently and restored the degradation of ganglioside GM2 to normal rates in mutant fibroblasts with the AB variant of GM2-gangliosidosis, which is characterized by a genetic defect in the GM2-activator protein. The prokaryotic expression system is useful for producing milligram quantities of a pure and functionally active GM2-activator.

Amino Acid Sequence↗

[Long-term results after gluing of osteochondral fragments and osteochondrosis dissecans].

Long-term results after surgical treatment of osteochondritis dissecans of the talar dome and joint knee are dependent on the stage of cartilage damage, the age at operation and on the surgical technique. In cases of osteochondritis dissecans of the talar dome the only loosening of a refixed osteochondral fragment was seen after glueing with acrylate. Using the classification of Arcq in 59.6% an excellent and in 18.3% a good result was observed in cases of osteochondritis dissecans at the femoral condyles. In regard to the development of osteoarthritis in 56% no signs of osteoarthritis were visible. Worst results were obtained in knee joints in which acrylate glue was used for refixation of the osteochondral fragments. In conclusion we recommend the use of fibrin glue for refixation of osteochondral fragments in cases of osteochondritis dissecans even when early mobilisation follows the operation. Because of the long-lasting resorption and barrier effect to ingrowing tissue the use of cyanoacrylate should be avoided.

Adolescent↗

[Osteochondrosis dissecans of the knee and sports].

Osteochondritis dissecans (O.d.) of the knee is a common disease, but the aetiological factors are still controversial. With a follow-up examination of 97 surgically treated patients (109 lesions) we looked for the influence of preoperative sports activities as a possible aetiological factor. Most of the patients complained first symptoms at puberty age between 10 and 15 years, girls with a mean age of 12.4 years and boys with a mean age of 15 years. Because of that, humoral factors are supposed to have influence on the onset of this lesion. Also patients with O.d. of the knee demonstrated a high rate of sports activities and/or trauma prior to the onset of symptoms. There was also a good correlation between lesions at the medial condyle with varus malalignment. Additionally, in most of the patients a high grade of general ligament laxity could be observed at the follow-up examination. It seems that biomechanical factors have an important aetiological influence on the initiation of O.d. at the knee. At the date of follow-up examination all patients reported on a minor sports activity in comparison to sports activities prior to the onset of symptoms. The amount of postoperative sports activities depends on the level of the resulting Lysholm score and on the grade of osteoarthritis.

Adolescent↗

Regional localization of the gene coding for the GM2 activator protein (GM2A) to chromosome 5q32-33 and confirmation of the assignment of GM2AP to chromosome 3.

The gene coding for the GM2 activator protein (GM2A) was previously mapped by us to chromosome 5 by an ELISA-based technique. Here we confirm this assignment using a PCR analysis of somatic cell hybrids and describe a regional localization to chromosome 5q32-33 by in situ hybridization. We also confirm the assignment of a pseudogene GM2AP to chromosome 3.

Animals↗

A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.

The genetic defect leading to cholesteryl ester storage disease (CESD) has been determined in a 12-yr-old patient. Lysosomal acid lipase (LAL) activity in cultured skin fibroblasts was reduced to approximately 9% of control fibroblasts. Plasma cholesterol (255 mg/dl) and LDL-cholesterol (215 mg/dl) were elevated whereas HDL-cholesterol was reduced (19 mg/dl). Triglycerides were moderately elevated (141 mg/dl). There were no clinical abnormalities with the exception of hepatosplenomegaly. Both parents have reduced LAL activity in white blood cells. PCR analysis of the LAL mRNA from the propositus revealed a single slightly smaller mRNA species in skin fibroblasts as well as in leukocytes. The mother of the patient and his older brother had two mRNA species: one of normal size and one of the same size as the propositus. The father has a LAL mRNA of normal size only. Sequence analysis of a PCR-amplified cDNA fragment showed a 72-bp in-frame deletion resulting in the loss of the codons for amino acids 254-277. Analysis of genomic DNA revealed that the 72 bp represent an exon, indicating that the deletion in the mRNA is caused by defective splicing. Sequence analysis of the patient's genomic DNA revealed a G-->A substitution in the last nucleotide of the 72-bp exon in one of his alleles. The mutant allele was shown to cosegregate with the truncated mRNA in the pedigree, providing further evidence that the G-->A substitution causes aberrant splicing and exon skipping. No normal-sized mRNA is detectable in the propositus even though he is not homozygous for the splice site mutation. This can be only accounted for by assuming that he is a compound heterozygote with a null allele inherited from his father. In summary, the data presented provide evidence that deletion of the codons for amino acids 254-277 in the LAL mRNA in combination with a null allele cause the clinical expression of CESD in our patient.

Adolescent↗

Characterization of full-length cDNAs and the gene coding for the human GM2 activator protein.

Full-length cDNAs coding for the human GM2-activator protein has been isolated and characterized, and its genomic structure studied in two overlapping clones in lambda-EMBL-4 isolated from a human brain genomic library. Two different cDNAs were found that were identical to the 5'-terminus to nt 1311 (counted from the A of the initiation codon, ATG) including the entire protein coding sequence. However, they were entirely dissimilar in the 3'-non-coding sequences. The genomic clones covered 94% of the full-length cDNA sequence. Three introns were found. The last exon spans contiguously the carboxyl terminus of the protein and the entire 3'-untranslated region of one of the two cDNAs with different 3'-ends. The origin of the 3'-portion of the other cDNA clone is not clear at this time.

Base Sequence↗

Isolation of a cDNA encoding the human GM2 activator protein.

The GM2 activator protein is a glycolipid-binding protein required for the lysosomal degradation of ganglioside GM2. A human fibroblast cDNA library was screened with mixtures of oligonucleotide probes corresponding to four different areas of the amino acid sequence. A putative clone (821 bp) which gave positive signals to all four probe mixtures was purified and sequenced. The sequence was colinear with the sequence of 160 amino acids of the mature GM2 activator protein. Availability of the cDNA clone should facilitate investigation into function of the GM2 activator protein and also into genetic abnormalities underlying GM2 gangliosidosis AB variant.

Amino Acid Sequence↗

[Liver dystrophy in hares. Pathology and epidemiologic studies of the death of hares in central Hesse].

In the area of Central Hesse we observed an unusual frequency of deaths of hares. The characteristic pathological alterations included general icterus, acute liver dystrophy, chromoproteinemic nephrosis, hyperemia in the tracheal mucosa and in the lungs, and splenic vascular congestion and necroses. Affected animals showed an altered behaviour with a diminished escape range and escape distance. Some animals had lost orientation completely. On the basis of sender questioning it appears probable that rape cultivation, as intensified in 1986--particularly newly generated 00-sorts--can be held responsible.

Animals↗

Simultaneous detection of native and luminol-dependent luminescence of stimulated human polymorphonuclear leukocytes.

A method for investigating the cellular response of polymorphonuclear leukocytes to various stimuli was introduced using simultaneously native (luminol-independent) and luminol dependent luminescence as an indicator for myeloperoxidase (MPO)-H2O2-halide and O2- mediated reactions. In experimental systems containing low concentrations of luminol the total light emission was separated into contributions of native and luminol-dependent luminescence by making use of the different spectral behaviour of the two kinds of luminescence. Consequently the MPO-H2O2-halide system could be distinguished from the O2- dependent system by interpreting the recorded temporal traces of the emitted light.

Chemotaxis, Leukocyte↗

Cost-benefit analysis of BCG-vaccination in Austria.

BCG-vaccination in Austria is performed generally in newborn, but only partially in school children. A cost-benefit analysis was performed considering age-dependent immunizations, tuberculosis morbidity, protection rate and duration of protection, costs of vaccination, costs of tuberculosis therapy, frequency of complications due to vaccination and costs for treatment of these complications. This analysis shows an economic balance between costs and benefits with regard to immunication of newborn, i. e., costs of vaccination are approximately compensated by the saved costs of prevented diseases. In contrary vaccination of school children reveals a considerable economic gain. General revaccination of schoolchildren would make BCG-vaccination much more effective in an economic respect.

Adolescent↗