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J Münch

Publications and source records attributed to J Münch.

At least 19 recordsLinked to original sources
PubMed2005

[Malaria in the emergency room. Results of the emergency treatment of 137 patients with symptomatic malaria].

OBJECTIVE: To assess characteristics and outcome of emergency patients with acute malaria. PATIENTS AND METHODS: We retrospectively assessed the clinical and laboratory parameters of 137 consecutive patients (87 males, 50 females; median age 37 years, range 17 - 67 years) presenting with acute malaria to our tertiary care center between 1992 and 2002. RESULTS: Falciparum malaria was diagnosed in 116/137 and tertian malaria in 19/137 patients; a single patient was infected with both parasites while in another case the type of parasite remained unclear. Infections were acquired in Africa (121), Asia , and in the Americas . One traveler visited multiple continents. Only 36 % (50/137) of patients had used malaria chemoprophylaxis. 128/137 patients were treated as in-patients; 22 of these had to be treated on an intensive care unit. According to the criteria of the German Society of Tropical Medicine, 44/137 (32 %; 95 % confidence interval (CI): 25 - 40 %) patients suffered from complicated malaria. The overall mortality rate was 2/137 (1.5 %; 95 % CI: 0,4 - 5.2 %); the mortality rate of complicated malaria tropica was 2/44 (4,5 %; 95 % CI 1,3 - 15 %). Patients with complicated malaria were significantly older than those with uncomplicated malaria. Median length of hospital stay was 4 days in uncomplicated and 9 days in complicated cases. Based on costs of EUR 2500 per case, an attack rate of > 3 % in East African travelers and a cost of EUR 55 for a chemoprophylaxis with mefloquine, chemoprophylaxis is cost-effective. CONCLUSION: In our retrospective analysis, complicated malaria tropica was associated with older age. Although malaria causes considerable morbidity, the overall mortality from severe malaria is low. Reinforcement of chemoprophylaxis especially in travelers to Africa could reduce malaria cases and is cost-effective.

Adolescent↗
PubMed2001

DC-SIGN interactions with human immunodeficiency virus type 1 and 2 and simian immunodeficiency virus.

Dendritic cells (DCs) efficiently bind and transmit human immunodeficiency virus (HIV) to cocultured T cells and so may play an important role in HIV transmission. DC-SIGN, a novel C-type lectin that is expressed in DCs, has recently been shown to bind R5 HIV type 1 (HIV-1) strains and a laboratory-adapted X4 strain. To characterize the interaction of DC-SIGN with primate lentiviruses, we investigated the structural determinants of DC-SIGN required for virus binding and transmission to permissive cells. We constructed a panel of DC-SIGN mutants and established conditions which allowed comparable cell surface expression of all mutants. We found that R5, X4, and R5X4 HIV-1 isolates as well as simian immunodeficiency and HIV-2 strains bound to DC-SIGN and could be transmitted to CD4/coreceptor-positive cell types. DC-SIGN contains a single N-linked carbohydrate chain that is important for efficient cell surface expression but is not required for DC-SIGN-mediated virus binding and transmission. In contrast, C-terminal deletions removing either the lectin binding domain or the repeat region abrogated DC-SIGN function. Trypsin-EDTA treatment inhibited DC-SIGN mediated infection, indicating that virus was maintained at the surface of the DC-SIGN-expressing cells used in this study. Finally, quantitative fluorescence-activated cell sorting analysis of AU1-tagged DC-SIGN revealed that the efficiency of virus transmission was strongly affected by variations in DC-SIGN expression levels. Thus, variations in DC-SIGN expression levels on DCs could greatly affect the susceptibility of human individuals to HIV infection.

Amino Acid Sequence↗
PubMed2001

Simian immunodeficiency virus in which nef and U3 sequences do not overlap replicates efficiently in vitro and in vivo in rhesus macaques.

The nef genes of human immunodeficiency virus and simian immunodeficiency virus (SIV) overlap about 80% of the U3 region of the 3' long terminal repeat (LTR) and contain several essential cis-acting elements (here referred to as the TPI region): a T-rich region, the polypurine tract, and attachment (att) sequences required for integration. We inactivated the TPI region in the nef reading frame of the pathogenic SIVmac239 clone (239wt) by 13 silent point mutations. To restore viral infectivity, intact cis-regulatory elements were inserted just downstream of the mutated nef gene. The resulting SIV genome contains U3 regions that are 384 bp shorter than the 517-bp 239wt U3 region. Overall, elimination of the duplicated Nef coding sequences truncates the proviral genome by 350 bp. Nonetheless, it contains all known coding sequences and cis-acting elements. The TPI mutant virus expressed functional Nef and replicated like 239wt in all cell culture assays and in vivo in rhesus macaques. Notably, these SIVmac constructs allow us to study Nef function in the context of replication-competent viruses without the restrictions of overlapping LTR sequences and important cis-acting elements. The genomes of all known primate lentiviruses contain a large overlap between nef and the U3 region. We demonstrate that this conserved genomic organization is not obligatory for efficient viral replication and pathogenicity.

Animals↗
PubMed2001

CD4 down-modulation by human immunodeficiency virus type 1 Nef correlates with the efficiency of viral replication and with CD4(+) T-cell depletion in human lymphoid tissue ex vivo.

The human immunodeficiency virus type 1 (HIV-1) Nef protein is an important virulence factor. Nef has several functions, including down-modulation of CD4 and class I major histocompatibility complex cell surface expression, enhancement of virion infectivity, and stimulation of viral replication in peripheral blood mononuclear cells. Nef also increases HIV-1 replication in human lymphoid tissue (HLT) ex vivo. We analyzed recombinant and primary nef alleles with highly divergent activity in different in vitro assays to clarify which of these Nef activities are functionally linked. Our results demonstrate that Nef activity in CD4 down-regulation correlates significantly with the efficiency of HIV-1 replication and with the severity of CD4(+) T-cell depletion in HLT. In conclusion, HIV-1 Nef variants with increased activity in CD4 down-modulation would cause severe depletion of CD4(+) T cells in lymphoid tissues and accelerate AIDS progression.

CD4 Antigens↗
PubMed2001

Efficient class I major histocompatibility complex down-regulation by simian immunodeficiency virus Nef is associated with a strong selective advantage in infected rhesus macaques.

Substitution of Y223F disrupts the ability of simian immunodeficiency virus (SIV) Nef to down-modulate major histocompatibility complex (MHC) class I from the cell surface but has no effect on other Nef functions, such as down-regulation of CD4, CD28, and CD3 cell surface expression or stimulation of viral replication and enhancement of virion infectivity. Inoculation of three rhesus macaques with the SIVmac239 Y223F-Nef variant revealed that this point mutation consistently reverts and that Nef activity in MHC class I down-modulation is fully restored within 4 weeks after infection. Our results demonstrate a strong selective pressure for a tyrosine at amino acid position 223 in SIV Nef, and they constitute evidence that Nef-mediated MHC class I down-regulation provides a selective advantage for viral replication in vivo.

Animals↗
PubMed2000

Natural proteolytic processing of hemofiltrate CC chemokine 1 generates a potent CC chemokine receptor (CCR)1 and CCR5 agonist with anti-HIV properties.

Hemofiltrate CC chemokine (HCC)-1 is a recently described human chemokine that is constitutively expressed in numerous tissues and is present at high concentrations in normal plasma. Using a cell line expressing CC chemokine receptor (CCR)5 as a bioassay, we isolated from human hemofiltrate an HCC-1 variant lacking the first eight amino acids. HCC-1[9-74] was a potent agonist of CCR1, CCR3, and CCR5 and promoted calcium flux and chemotaxis of T lymphoblasts, monocytes, and eosinophils. It also blocked entry of HIV-1 strains using CCR5 as coreceptor. Limited tryptic digestion of HCC-1 generated the active variant. Conditioned media from several tumor cell lines activated HCC-1 with a high efficiency, and this activity could be inhibited by serine protease inhibitors. Our results indicate that HCC-1 represents a nonfunctional precursor that can be rapidly converted to the active chemokine by proteolytic processing. This process represents an additional mechanism by which tumor cells might generate chemoattractant molecules and recruit inflammatory cells. It might also affect HIV-1 replication in infected individuals and play an important role in AIDS pathogenesis.

Adult↗
PubMed2000

Development of a self-inactivating, minimal lentivirus vector based on simian immunodeficiency virus.

In contrast to oncoviruses, lentiviruses do not require target cell division for integration into the host genome. Lentiviral vectors can therefore expand the spectrum of target cells susceptible to retroviral gene transfer. To analyze whether vectors based on simian immunodeficiency viruses (SIVs) could be used for gene transfer, a three-plasmid vector-packaging system was developed, in which Gag-Pol and the vector itself are of SIV origin, while Env is derived either from SIV, amphotropic murine leukemia virus (MuLV), or the G glycoprotein of vesicular stomatitis virus (VSV-G). To increase the safety of the SIV vector system, a self-inactivating SIV vector was constructed. After optimization of the SIV gag-pol expression plasmid, a minimal SIV vector, which contained only SIV sequences present on the multiply spliced nef transcript, could still be produced at titers of 2 x 10(5) infectious units/ml. Growth-arrested cells could be transduced with this vector even if vif, vpr, vpx, and nef had been deleted from the packaging construct and the vector.

Animals↗
PubMed1999

Use of alpha-, beta- and gamma-hexachlorocyclohexane in Europe, 1970-1996.

Data on current and historical usage of alpha, beta, and gamma-hexachlorocyclohexane (HCH) in Europe are presented. The data were collected and estimated as a part of a project studying the regional cycling of persistent organic pollutants (POPs) in the Baltic environment (Popcycling-Baltic). Better data on sources, environmental discharges and atmospheric emissions of HCH and other POPs are needed to study, and hopefully reduce, the impact of these pollutants on the environment. Substantial uncertainties are assigned to the estimated data for individual countries and years, but it seems likely that the general trend of usage in Europe is captured. The quality of the estimates is thought to improve in general throughout the period, thus, reflecting the availability of reliable data. The results suggest that 382,000 t of technical HCH and 81,000 t of lindane were used in Europe from 1970 to 1996. This is equivalent to an estimated cumulative usage of 259,000 t alpha-HCH, 235,000 t gamma-HCH and 20,000 t beta-HCH. The usage of technical HCH was the major source of gamma-HCH until the late 1970s, and thereafter lindane became the dominating source of this isomer. The use of gamma-HCH in 1996 was estimated to still be nearly one-third of the European usage in 1970. The pattern of decreasing concentrations in biota follows the pattern of reductions in usage for the studied period within the Baltic area.

Environmental Monitoring↗
PubMed1999

Co-receptor usage of BOB/GPR15 in addition to CCR5 has no significant effect on replication of simian immunodeficiency virus in vivo.

Human immunodeficiency virus type 2 (HIV-2) and the closely related simian immunodeficiency viruses (SIVs) frequently use the orphan receptor BOB/GPR15 in addition to the chemokine receptor CCR5 for efficient entry and replication. However, the role of BOB/GPR15 in replication and pathogenesis of HIV-2 and SIV in vivo is unclear. This study shows that a single amino acid substitution in the V3 loop of the pathogenic SIVmac239 clone, 321P-->S, impaired the ability to use BOB/GPR15 for entry and replication but had little effect on the ability to use CCR5. This envelope variant replicated with an efficiency comparable with the parental SIVmac239 isolate in rhesus macaques. Furthermore, the mutant genotype and phenotype remained stable even after the onset of immunodeficiency. These results suggest that this cofactor plays only a minor role for the pathogenicity of the HIV-2/SIVmac/SIVsm group of primate lentiviruses.

Animals↗
PubMed1999

The human immunodeficiency virus type 1 nef gene can to a large extent replace simian immunodeficiency virus nef in vivo.

The nef gene of the pathogenic simian immunodeficiency virus (SIV) 239 clone was replaced with primary human immunodeficiency virus type 1 (HIV-1) nef alleles to investigate whether HIV-1 Nef can substitute for SIV Nef in vivo. Initially, two rhesus macaques were infected with the chimeric viruses (Nef-SHIVs). Most of the nef alleles obtained from both animals predicted intact open reading frames. Furthermore, forms containing upstream nucleotide substitutions that enhanced expression of the inserted gene became predominant. One animal maintained high viral loads and slowly progressed to immunodeficiency. nef long terminal repeat sequences amplified from this animal were used to generate a second generation of Nef-SHIVs. Two macaques, which were subsequently infected with a mixture of cloned chimeric viruses, showed high viral loads and progressed to fatal immunodeficiency. Five macaques received a single molecular clone, named SHIV-40K6. The SHIV-40K6 nef allele was active in CD4 and class I major histocompatibility complex downregulation and enhanced viral infectivity and replication. Notably, all of the macaques inoculated with SHIV-40K6 showed high levels of viral replication early in infection. During later stages, however, the course of infection was variable. Three animals maintained high viral loads and developed immunodeficiency. Of the remaining two macaques, which showed decreasing viral loads after the acute phase of infection, only one efficiently controlled viral replication and remained asymptomatic during 1.5 years of follow-up. The other animal showed an increasing viral load and developed signs of progressive infection during later stages. Our data demonstrate that HIV-1 nef can, to a large extent, functionally replace SIVmac nef in vivo.

Alleles↗
PubMed1995

[Psychosomatic aspects of multiple sclerosis].

Multiple sclerosis is one of the most frequent neurological diseases. Till today too little attention has been laid upon its psychosomatic aspects. In the psychosomatic-somatopsychic-global sense of a therapy a differentiated enlightenment performed step by step, is recommended in the first part of this article. This includes a differentiation of the melting-pot-like unspecific diagnoses into subdiagnoses with different prognoses. This is important for the coping-mechanisms to be performed by the patient, in which necessarily he must be supported by his doctor. The second part shows a psychodynamic factor to the onset of this disease which is caused by several different factors. This psychodynamic factor is characterized by the shift of an intraindividual struggle of power into the soma and it performs a dispute between two parts of the self, Introjects asking for performance on one side, the unfulfilled wish of love and bestowal on the other side. This wish is fulfilled directly by the symptoms of multiple scleroses--at a high price. As a conclusion of this article a giving up of the artificial distinction between psychosomatic and somatic diseases is suggested by taking MS as an example.

Adaptation, Psychological↗
PubMed1976

[Incidence and damages inflicted by simuliid flies in the GDR district of Schwerin].

Systematic faunal studies in the district Schwerin showed at the present time there are 3 more or less damage-biotopes existing in the districts of Perleberg, Ludwigslust and Parchim; 5 river sources can be considered as potential sources, 5 are temporary and 2 are ephemeral whilst in 3 further areas environmental influences such as effluent impairs the flow of the river and the developmental stages of Simuliidae were not observed.--The following species were found: Boophthora erythrocephala, Wilhelmia salopiensis, Wilhelmia equina, Odagmia ornata, Eusimulium aureum and Eusimulium lundstroemi.--The damage statistics covering the period 1966--1971 showed in the district of Schwerin, due to Simuliid attacks, 38 cattle died, 170 were seriously ill; in 1967 5 horses were seriously ill; in 1971, 3 pigs died and 27 were seriously ill.--The symptoms were manifested by pathological petechiae, scabs and oedema, also by insufficiency of the heart and circulatory system, diminished performance and growth disturbance. In severe cases heart and circulation failure occurred, paresis, coma and death followed.--The real economic significance of the Simuliid attacks rest with its strong and prolonged distrubance in young animals, as well as in pronounced irreparable diminished performance in diseased dairy cattle.

Animals↗