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Biomedical subjects

F Müller

Publications and source records attributed to F Müller.

At least 163 records · Page 9Linked to original sources
PubMed1996

Chromatin diminution in nematodes.

The process of chromatin diminution in Parascaris and Ascaris is a developmentally controlled genome rearrangement, which results in quantitative and qualitative differences in DNA content between germ line and somatic cells. Chromatin diminution involves chromosomal breakage, new telomere formation and DNA degradation. The programmed elimination of chromatin in presomatic cells might serve as an alternative way of gene regulation. We put forward a new hypothesis of how an ancient partial genome duplication and chromatin diminution may have served to maintain the genetic balance in somatic cells and simultaneously endowed the germ line cells with a selective advantage.

Animals↗
PubMed1996

Abnormal levels of circulating adhesion molecules in HIV-1 infection with characteristic alterations in opportunistic infections.

Adhesion molecules enabling leukocytes to communicate and adhere are essential for immunological and inflammatory responses. Circulating forms of these adhesion molecules are detected, although their influence on immunological functions is unknown. We have measured soluble levels of E-selectin, vascular adhesion molecules-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in sera from 65 HIV-1-seropositive patients and controls. We found significantly higher levels of soluble VCAM-1 (sVCAM-1) and ICAM-1 (sICAM-1) in both symptomatic and asymptomatic HIV-1-infected patients than in controls (P <0.01). Both sICAM-1 and sVCAM-1 correlated to serum levels of neopterin (r = 0.40, P < 0.001; r = 0.46, P <0.001, respectively) and TNFalpha (r = 0.44, P < 0.01; r = 0.49, P < 0.001, respectively), while only sVCAM-1 correlated strongly to CD4+ lymphocyte count (r = -0.46, P < 0.001). Patients infected with Mycobacterium avium intracellular complex had significantly higher levels of sVCAM-1 and sICAM-1 than other AIDS patients (P < 0.05), while patients with cytomegalovirus disease had significantly lower levels both of sE-selectin and sICAM-1 (P < 0.05) than other AIDS patients. In conclusion, we found abnormal levels of circulating adhesion molecules in both symptomatic and asymptomatic HIV-1 infection including AIDS. The correlation to other parameters and clinical events may implicate involvement of circulating adhesion molecules in the immunopathogenesis of HIV-1 infection.

AIDS-Related Opportunistic Infections↗
PubMed1996

Regulation and expression of transgenes in fish -- a review.

Transgenic fish, owing to a number of advantages which they offer over other species, are proving to be valuable model systems for the study of gene regulation and development genetics in addition to being useful targets for the genetic manipulation of commercially important traits. Despite having begun only a decade ago, the production of transgenic fish has become commonplace in a number of laboratories world-wide and considerable progress has been made. In this review, we initially consider the various regulatory elements and coding genes which have been used in fish, and subsequently discuss and compare both the transient and long-term fate and expression patterns of injected DNA sequences in the context of the different factors which are likely to have an effect on the expression of transgenes.

Animals↗
PubMed1996

High transgene activity in the yolk syncytial layer affects quantitative transient expression assays in zebrafish Danio rerio) embryos.

For the purpose of studying the factors that cause wide variation in transient transgene expression in individual fish, a lacZ reporter gene linked to a carp beta-actin regulatory sequence was introduced into zebrafish embryos. As a general trend, a correlation between the number of transgene copies injected and the level of transgene expression was found. However, a substantial variation in the level of expression still occurred that could not be attributed to technical factors such as the difference in injected volume of the transgene. Co-injection of 32P-dCTP and transgene into the same embryo followed by detection of beta-galactosidase activity, has shown that the volume used for transgene injection, which was determined in terms of radioactivity, is not closely related to the level and location of transgene expression. Injection into the animal pole at zygote stage and the yolk cytoplasmic layer (YCL) at the 64-cell stage followed by determination of transgene expression in terms of unit injection volume, revealed that there are marked differences among tissues with regard to their capacity for transgene expression, and that the yolk syncytial layer is higher in this capacity. This high activity is assumed to be due to the high transcriptional activity or enhanced transgene replication in the syncytial layer, which is known to contain giant polyploid nuclei. The high levels of expression in the YSL may influence transient expression studies using quantitative comparative analyses and should be taken into consideration when expression data are derived from homogenates of yolk sac embryos.

Actins↗
PubMed1996

Biological monitoring of mercury vapour exposure by scalp hair analysis in comparison to blood and urine.

The reliability of human scalp hair as an indicator of mercury vapour exposure is contentious. In this study mercury concentrations in hair were compared with those in blood and urine of 20 dental students during their first "occupational" exposure to mercury vapour. Samples were collected before, at the end of the technical course of operating dentistry which lasted 6 weeks, and 3 months later. Mercury was measured by cold vapour atomic absorption spectrometry. In all biological media studied, mercury levels significantly (P < 0.05) reflected exposure to mercury vapour. After the time period without exposure mercury content decreased. Hair mercury levels were correlated to those in erythrocytes at sampling times 1 and 3 (r = 0.686 and r = 0.492) and to the frequency of fish consumption at sampling time 1. It is concluded that hair may be used as an indicator of internal uptake of mercury provided that it was not externally exposed to mercury vapour. In cases of occupational exposure to mercury vapour, hair is an useful tool for monitoring external exposure.

Adult↗
PubMed1996

Comparative analysis of tertiary structure elements in signal recognition particle RNA.

BACKGROUND: The signal recognition particle (SRP) is a ribonucleoprotein complex that associates with ribosomes to promote co-translational translocation of proteins across biological membranes. We have used comparative analysis of a large number of bacterial, archaeal, and eukaryotic SRP RNA sequences to derive shared tertiary SRP RNA structure elements. RESULTS: A representative three-dimensional model of the human SRP RNA is shown that includes single-stranded intrahelical and interhelical RNA loops and incorporates data from enzymatic and chemical modification, electron microscopy, and site-directed mutagenesis. Properties of the SRP RNA model are an overall extended dumbbell-shaped structure (260 A x 70 A) with a pseudoknot in the small SRP domain (a pairing of 12-UGGC-15 with 33-GCUA-36), and a tertiary interaction in the large SRP domain (198-GA-199 with 232-GU-233). CONCLUSIONS: The RNA 'knuckle' formed in helix 8 of SRP RNA appears to constitute the binding site for protein SRP54 or its bacterial equivalent, protein P48. A dynamic property of this feature may explain the hierarchial assembly of proteins SRP19 and SRP54 in the large SRP domain. Furthermore, the human SRP RNA model serves as a framework to understand details of the structure and function of SRP in all organisms and is presented to stimulate further experimentation in this area.

Animals↗
PubMed1996

Elevated plasma concentration of reduced homocysteine in patients with human immunodeficiency virus infection.

Oxidative stress has been suggested to be an important factor in the immunopathogenesis of human immunodeficiency virus (HIV) infection. Reduced plasma thiols may lead to production of reactive oxygen species, thus contributing to the oxidative stress. We quantified the total, reduced, and protein-bound forms of the thiols homocysteine, cysteine, cysteinylglycine, and methionine in plasma from 21 HIV-infected patients and 15 healthy control subjects and compared the results with clinical and immunologic indexes. The HIV-infected patients had significantly higher concentrations of reduced homocysteine in plasma compared with control subjects. No significant differences in reduced homocysteine concentrations were noted when asymptomatic and symptomatic HIV-infected patients were compared, and we did not find any relation between reduced homocysteine concentrations and other markers of immunodeficiency. The HIV-infected patients had normal total homocysteine concentrations. The reduced cysteinylglycine concentration tended to be elevated in the patient group. No differences between HIV-infected patients and control subjects were found for reduced or total cysteine. Compared with control subjects, the HIV-infected patients had lower concentrations of methionine in plasma, and a significant correlation was found between low concentrations of methionine and low CD4+ lymphocyte counts in blood. Elevated concentrations of reduced homocysteine could possibly contribute to formation of reactive oxygen species, leading to accelerated immunologic deterioration and increased HIV replication.

Adult↗
PubMed1996

Disseminated Mycobacterium avium complex infection in AIDS: immunopathogenic significance of an activated tumor necrosis factor system and depressed serum levels of 1,25 dihydroxyvitamin D.

Disseminated Mycobacterium avium complex (MAC) infection is associated with considerable morbidity and mortality in patients with AIDS. Because both tumor necrosis factor-alpha (TNF-alpha) and 1,25-dihydroxyvitamin D3 (1,25D) may be involved in the normal control of MAC infection, these parameters were studied in AIDS patients with disseminated MAC infection. Of 53 AIDS patients studied, 24 had no clinical events, 11 had disseminated MAC infection, and 18 had other clinical events. Patients with disseminated MAC infection had significantly higher serum levels of both TNF-alpha and soluble TNF receptors compared with other AIDS patients; almost half of the MAC-infected patients had TNF bioactivity in serum. MAC-infected patients also had severely decreased serum 1,25D levels compared with all other AIDS patients. The activation of the TNF system was significantly correlated with the degree of 1,25D deficiency. These findings may reflect interaction between vitamin D and the TNF system in the pathophysiology of disseminated MAC infection in AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1996

Reduced, oxidized and protein-bound forms of homocysteine and other aminothiols in plasma comprise the redox thiol status--a possible element of the extracellular antioxidant defense system.

Reduced, oxidized and protein-bound forms of homocysteine (Hcy), cysteine and cysteinylglycine in plasma interact via redox and disulphide exchange reactions, and these aminothiol species comprise a dynamic system referred to as redox thiol status. Notably, in plasma reduced cysteine is the most abundant low molecular weight sulfhydryl compound. Elevation of plasma Hcy (hyperhomocysteinemia) causes changes in redox thiol status. Protein-bound Hcy increases up to a maximum capacity of about 140 micromol/L, and there is a concurrent displacement of protein-bound cysteine. When the Hcy binding approaches saturation, free oxidized and reduced Hcy show a substantial increase. The resulting increase in reduced/total ratio for Hcy causes a parallel change in this ratio for the other aminothiols. These dynamics were observed during both chronic hyperhomocysteinemia (due to cobalamin deficiency or homocystinuria) and acute hyperhomocysteinemia (induced by methionine or Hcy loading). In addition, changes in redox thiol status have been observed in patients with vascular disease (decreased reduced/total ratio for cysteine), renal failure (low reduced/total ratio for aminothiols) or HIV infection (high level of reduced Hcy), which suggest primary imbalance between prooxidant and antioxidant processes in these patients. In conclusion, redox thiol status is a dynamic system which is probably linked to the extracellular antioxidant defence system. This must be taken into account when designing future experimental or epidemiological studies on Hcy and cardiovascular disease.

Animals↗
PubMed1996

Intraepithelial gamma/delta T cells in duodenal mucosa are related to the immune state and survival time in AIDS.

The proportion of T-cell receptor gamma/delta+ cells and the CD4/CD8 ratio relative to all CD3+ intraepithelial lymphocytes (IEL) were determined by immunofluorescence in duodenal mucosa of late-stage (mostly CDC IVC1/D) subjects (n = 21) infected with human immunodeficiency virus type 1 (HIV-1). The gamma/delta fraction (median, 14.2%; range, 1.7 to 59.8%) was increased (P < 0.03) compared with that in HIV- controls (n = 11; median 2.8%; range, 0.3 to 38%). Also, the number of gamma/delta+ IEL per mucosal unit was increased (P < 0.05) in the HIV+ subjects (median, 11.1/U) compared with the controls (3.2/U). Approximately 100% of the gamma/delta+ IEL were CD8-, and most expressed the Vdelta1vJdelta1-encoded epitope (median, 90.9%). The total number of CD3+ IEL tended to be lower than in the controls (67.4 versus 72.9/U). Both the epithelium and the lamina propria contained mainly CD8+ T cells, the median ratios of CD4+ T cells being 1 and 7.6%, respectively. This result accorded with the reduced CD4 cell number in blood (median, 18 X 10(6)/liter). The HIV+ subjects had increased serum levels of neopterin and beta2-microglobulin (both P < 0.0001), probably reflecting immunostimulation. Serum neopterin and beta2-microglobulin were inversely related to duodenal gamma/delta IEL, particularly in the premortal group (r = -0.97 and r = -0.58, respectively). The increased gamma/delta IEL might reflect enhanced intestinal protection in late-phase HIV infection. Short survival expectancy (<7 months) was associated not only with high levels of neopterin and beta2-microglobulin but also with a reduced number of duodenal gamma/delta+ cells (P < 0.03).

Acquired Immunodeficiency Syndrome↗
PubMed1996

[Emergency carotid endarterectomy in acute infarction--case report and literature review].

Elective operation of carotid stenosis over 70% is uncontested since publication of the interim results of NASCET and ECST [1,2] trials. Even though emergency carotid endarterectomy for rapidly progressing cerebral infarction (stroke in evolution) remains very controversial outcome depends on how fast cerebral perfusion is reestablished, complete recovery is possible if carotid thrombendarterectomy is successfully performed in between the first 6-8 hours. We report the case of a female patient developing a cerebral infarction on the first postoperative day after femoropopliteal bypass grafting. Diagnosis of an acute carotid occlusion was established by cerebral duplex sonography, intracerebral hemorrhage was excluded by emergency computed tomography. Emergency thrombendarterectomy successfully reverted all cerebral symptoms. Postoperative course was uneventful, the patient was dismissed on the 12th postoperative day without any neurological residual deficit.

Arterial Occlusive Diseases↗
PubMed1995

R4, a non-LTR retrotransposon specific to the large subunit rRNA genes of nematodes.

A 4.7 kb sequence-specific insertion in the 26S ribosomal RNA gene of Ascaris lumbricoides, named R4, is shown to be a non-long terminal repeat (non-LTR) retrotransposable element. The R4 element inserts at a site in the large subunit rRNA gene which is midway between two other sequence-specific non-LTR retrotransposable elements, R1 and R2, found in most insect species. Based on the structure of its open reading frame and the sequence of its reverse transcriptase domain, R4 elements do not appear to be a family of R1 or R2 elements that have changed their insertion site. R4 is most similar in structure and in sequence to the element Dong, which is not specialized for insertion into rRNA units. Thus R4 represents a separate non-LTR retrotransposable element that has become specialized for insertion in the rRNA genes of its host. Using oligonucleotide primers directed to a conserved region of the reverse transcriptase encoding domain, insertions in the R4 site were also amplified from Parascaris equorum and Haemonchus contortus. Why several non-LTR retrotransposable elements have become specialized for insertion into a short (87 bp) region of the large subunit rRNA gene is discussed.

Amino Acid Sequence↗
PubMed1995

[Pathogenesis of infections--a complex interplay between microbes and the immune defence].

The pathogenesis of infectious diseases is regulated by a complex interplay between microbes and the immune system. To function well, the immune system is dependent on factors in both the internal and the external environment. Behavioural, social and cultural factors are all important. Increasing resistance to drugs and greater awareness of other side effects of antibiotics have led to greater recognition by doctors of the need to use alternative ways of treating and preventing infections, particularly by modulating the immune response. Important elements of the defence against various types of infectious agents are outlined. This is intended as a framework for understanding how infectious diseases can be dealt with by modulating the immune response instead of only attempting to kill the microbe. This is particularly important in patients with serious infections and in groups of patients specially predisposed to infections.

Animals↗
PubMed1995

[New immunopathogenetic aspects of infectious diseases].

The clinical course of infectious diseases depends on the complicated interaction between the microorganism and the immune system of the host. The vast amount of knowledge acquired during recent years in the field of immunology will probably lead to new ways of treating infectious diseases by selective immunomodulation. In this paper, we review some newer aspects of host defence mechanisms of relevance to immunomodulation of infectious diseases. The cytokine network, apoptosis, superantigens, and oxidative stress are all discussed with reference to various infectious diseases. Furthermore, the possible role of physical and psychological stress in the immunopathogenesis of infectious disease is discussed in the light of the interplay between the immune system and the neuroendocrine system.

Antigens, Bacterial↗
PubMed1995

Decreased levels of total and reduced glutathione in CD4+ lymphocytes in common variable immunodeficiency are associated with activation of the tumor necrosis factor system: possible immunopathogenic role of oxidative stress.

We have previously shown chronic immune activation and enhanced generation of reactive oxygen species in common variable immunodeficiency (CVI). In the present study, we examined levels of glutathione, the dominant intracellular thiol, that play an important protective role against oxidative and inflammatory stress in plasma and in monocytes and lymphocyte subsets in 20 CVI patients and in 16 healthy controls. CD4+ lymphocytes from CVI patients had significantly lower levels of both total and reduced glutathione as well as a lower ratio of reduced to total glutathione compared with healthy controls. This decrease in glutathione levels in CD4+ lymphocytes was most pronounced in the CD45RA+ subset. Plasma levels of total glutathione were also significantly decreased in CVI. In contrast, monocytes from CVI patients exhibited increased levels of both total and reduced glutathione compared with blood donor monocytes. CVI patients had significantly raised serum levels of tumor necrosis factor alpha (TNF alpha) and TNF alpha concentration was strongly associated with glutathione depletion in CD4+ lymphocytes. Furthermore, the lowest levels of both total and reduced glutathione were found in a subgroup of CVI patients characterized by persistent immune activation in vivo, decreased numbers of CD4+ lymphocytes in peripheral blood, and splenomegaly. Finally, supplementation of cell cultures with glutathione-monoethyl ester did significantly enhance interleukin-2 production from peripheral blood mononuclear cells in CVI patients. These glutathione abnormalities in CVI indicate increased oxidative stress, particularly in CD4+ lymphocytes, and intracellular depletion of reduced glutathione of the demonstrated magnitude may have profound implications for CD4+ lymphocyte function and the immunodeficiency in CVI.

Adult↗
PubMed1995

The cpc-2 gene of Neurospora crassa encodes a protein entirely composed of WD-repeat segments that is involved in general amino acid control and female fertility.

Phenotypic and molecular studies of the mutation U142 indicate that the cpc-2+ gene is required to activate general amino acid control under conditions of amino acid limitation in the vegetative growth phase, and for formation of protoperithecia in preparation for the sexual phase of the life cycle of Neurospora crassa. The cpc-2 gene was cloned by complementation of the cpc-2 mutation in a his-2ts bradytrophic background. Genomic and cDNA sequence analysis indicated a 1636 bp long open reading frame interrupted by four introns. The deduced 316 amino acid polypeptide reveals 70% positional identity over its full length with G-protein beta-subunit-related polypeptides found in humans, rat (RACK1), chicken, tobacco and Chlamydomonas. With the exception of RACK1 the function of these proteins is obscure. All are entirely made up of seven WD-repeats. Expression studies of cpc-2 revealed one abundant transcript in the wild type; in the mutant its level is drastically reduced. In mutant cells transformed with the complementing sequence, the transcript level, enzyme regulation and female fertility are restored. In the wild type the cpc-2 transcript is down-regulated under conditions of amino acid limitation. With cpc-2 a new element involved in general amino acid control has been identified, indicating a function for a WD-repeat protein that belongs to a class that is conserved throughout the evolution of eukaryotes.

Amino Acid Sequence↗
PubMed1995

Increased levels of oxidized glutathione in CD4+ lymphocytes associated with disturbed intracellular redox balance in human immunodeficiency virus type 1 infection.

We investigated the intracellular glutathione redox status in isolated lymphocyte subpopulations and monocytes in patients with human immunodeficiency virus type 1 (HIV-1) infection and in healthy controls. CD4+ lymphocytes from HIV-1-infected patients were primarily characterized by a substantial increase in oxidized glutathione levels and a considerable decrease in the ratio of reduced to total glutathione, in most cases below 0.5 in patients with symptomatic HIV-1 infection, rather than decreased levels of reduced glutathione. The increase in oxidized glutathione was strongly correlated with low numbers of CD4+ lymphocytes in peripheral blood and impaired stimulated interleukin-2 production and proliferation in peripheral blood mononuclear cells, which is compatible with an immunopathogenic role for these redox disturbances. The HIV-1-infected patients with the most advanced clinical and immunologic disease were also characterized by an increase in levels of reduced glutathione in monocytes, suggesting that the glutathione redox cycle may be differentially regulated in CD4+ lymphocytes and monocytes. We could not confirm previous reports suggesting cysteine deficiency as a major cause of disturbed glutathione homeostasis during HIV-1 infection. The demonstrated glutathione abnormalities were correlated with raised serum levels of tumor necrosis factor alpha. These findings suggest that a therapeutical approach, which can restore the glutathione redox dysbalance in CD4+ lymphocytes and decrease the inflammatory stress, may be worthwhile exploring in HIV-1 infection.

CD4-Positive T-Lymphocytes↗