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Biomedical subjects

Peter Fischer

Publications and source records attributed to Peter Fischer.

At least 55 records · Page 3Linked to original sources

An aspartate aminotransferase of Wolbachia endobacteria from Onchocerca volvulus is recognized by IgG1 antibodies from residents of endemic areas.

Wolbachia are intracellular alpha-proteobacteria, closely related to Rickettsia, that infect various arthropods and filarial parasites. In the present study, the cDNA encoding the aspartate aminotransferase (AspAT) of Wolbachia from the human pathogenic filarial parasite Onchocerca volvulus (Ov-WolAspAT) was identified. At the amino acid level, the identity of the Ov-WolAspAT was 56% to Rickettsia prowazekii AspAT and 54% to the AspAT of the nitrogen-fixing bacterium Sinorhizobium meliloti, but the highest degree of identity was found to the putative AspAT of Wolbachia from Brugia malayi and Drosophila melanogaster (85%). All of these bacterial AspATs are members of the AspAT subclass Ib. A 35 kDa fragment of the Ov-WolAspAT was expressed in Escherichia coli, and immunolocalization using polyclonal antibodies against this antigen revealed that Ov-WolAspAT is present in a considerable proportion of the Wolbachia from O. volvulus, as well as in the endobacteria of several other filarial parasites. Western blot analysis using recombinant Ov-WolAspAT as antigen showed that IgG1 antibodies were present in 70 (51%) individuals living in areas endemic for O. volvulus, B. malayi or Wuchereria bancrofti and no IgG4 or IgE antibodies were found. Among 40 sera of persons from Uganda and Liberia who were putatively not infected with human filarial parasites, 11 (28%) individuals presented IgG1 antibodies, while none of the 33 sera from healthy Europeans and none of the 14 sera from patients with proven Rickettsia or Brucella infections reacted with the antigen. These results also show that an intracellular protein of Wolbachia endobacteria (WolAspAT) acts as antigen in human filariasis.

Amino Acid Sequence↗

Evaluation of the interface between bone and titanium surfaces being blasted by aluminium oxide or bioceramic particles.

The surface structure, in particular the surface roughness, and the surface chemistry of titanium implants influence their anchoring in bone. The aim of this study was to analyse metal-bone contact (MBC) after modification of the implant surface, using different materials for blasting. The surface modification of titanium was produced by blasting it with particles made of Al2O3 or bioceramics. The biological effects were then investigated experimentally using 27 rabbits, analysed after 7, 28 and 84 days after the implantation of titanium cylinders treated accordingly. The MBC showed a tendency for more bone after bioceramics were used as a blasting material, compared to Al2O3.

Aluminum Oxide↗

A dominant role for extracellular glutathione S-transferase from Onchocerca volvulus is the production of prostaglandin D2.

The extracellular glutathione S-transferase from the filarial parasite Onchocerca volvulus (Ov-GST1) is a glutathione-dependent prostaglandin D synthase. Ov-GST1, located in the outer hypodermal lamellae and in parts of the cuticle, produces prostaglandin D(2) directly at the parasite-host interface. Ov-GST1 therefore has the potential to participate in the modulation of the host immune response by contributing to the production of prostanoids; this supports the predominant hypothesis that parasite-derived eicosanoids influence host inflammatory and immune cells.

Animals↗

Polymerase chain reaction-based detection of lymphatic filariasis.

PCR-based diagnostic assays are promising tools for the monitoring and evaluation of the Global Programme for Elimination of Lymphatic Filariasis. Sensitive and specific assays have been described for the detection of Wuchereria bancrofti, Brugia malayi, or Brugia timori infection in blood, sputum, and vectors. These techniques can be most cost-effective when employed for pool screening, which is important in the later stages of control programs when infection rates of humans and vectors are low, and large numbers of samples must be examined.

Animals↗

A novel bornane synthesis by an old idea.

Aiming at a synthesis of spiro[2.4]hepta-4,6-dienes with a carbon substituent at C-4, we investigated solvolysis reactions of the thiatricycle 2, obtained from spiro[2.4]hepta-4,6-diene (1) and thiophosgene by [4 + 2] cycloaddition. With methanol or ethanol a mixture of the esters 7 and 8 was formed. Desulfurization of the thionoesters 8 gave methyl and ethyl spiro[2.4]hepta-4,6-diene-4-carboxylate (10a,b). The corresponding alcohol (11) was prepared from 10b by LiAlH(4) reduction. Ethenetetracarbonitrile combined with the 4-substituted spiro[2.4]hepta-4,6-dienes to give the [4 + 2] cycloadducts 12a-c. Diels-Alder reaction between 11 and 2-chloroacrylonitrile afforded the spiro(bicyclo[2.2.1]hept-5-ene-7,1'-cyclopropane) derivative 14a that was transformed in three steps to rac-10-hydroxycamphor (17). This synthesis of a bornane derivative opens opportunity for variations and thus may find further applications.

Journal Article↗

Paranoid delusions and hallucinations and bright light therapy in Alzheimer's disease.

INTRODUCTION: Bright light therapy (BLT) is becoming increasingly popular as an adjunct in the treatment of non-SAD depression and circadian rhythm disturbances in demented patients. Although the rate of side-effects is low, special attention should be paid when treating new groups of patients. We present the case of an 80-year-old woman suffering from dementia of Alzheimer's type (DAT). METHOD: Bright light (2.500 lux) was administered two hours daily between 10 and 12 a.m. for 14 days. Changes in delusion or agitation were recorded using the confusion rating scale (CRS). RESULTS: Out of five patients, three already had delusional symptoms which slightly improved during the course of BLT, one patient never showed delusions before or during BLT, and one patient, which we present here, showed an increase in agitation and developed delusional symptoms. After eight days of treatment, the patient developed conjunctival irritation with marked red eyes and complained about blurred vision. After 12 days of treatment, the patient was disorientated in time and place and after 14 days the patient started to hallucinate and BLT had to be discontinued. The paranoid delusions and hallucinations stopped one day after treatment discontinuation. CONCLUSION: Looking at all the presented evidence, BLT seems to be a useful treatment supplement in DAT patients, when suffering from delusions or agitation. On the other hand, caution should be used when using BLT in demented patients if agitation develops or increases during BLT.

Aged↗

Treatment of Brugia timori and Wuchereria bancrofti infections in Indonesia using DEC or a combination of DEC and albendazole: adverse reactions and short-term effects on microfilariae.

Filariasis caused by Brugia timori and Wuchereria bancrofti is an important public health problem on Alor island, East Nusa Tenggara, Indonesia. To implement a control programme, adverse reactions and short-term effects on the microfilaria (mf) density were studied following a divided dose of diethylcarbamazine (DEC, 6 mg/kg body weight - 100 mg on day 1 and the rest on day 3) or a single dose of DEC (6 mg/kg body weight on day 3) and albendazole (Alb, 400 mg). In order to define the most appropriate regimen, 30 persons infected with B. timori were treated in the hospital and results were compared with those obtained from the treatment of 27 persons infected with W. bancrofti. Adverse reactions consisted of systemic reactions such as fever, headache, myalgia, itching and local reactions such as adenolymphangitis. Fever experienced by a number of patients in both treatment groups generally occurred 12-24 h after drug administration and lasted up to 2 days. Adenolymphangitis tended to occur later and was resolved within 4 days. The number of W. bancrofti patients suffering from adverse reactions was lower and the reactions were milder than those of the B. timori patients. There was no difference in adverse reactions between DEC alone and DEC-Alb treatment for either infection. The geometric mean mf count decreased on day 7 in the B. timori infected patients from 234 mf/ml in the DEC group and from 257 mf/ml in the DEC-Alb group to 7 and 8 mf/ml, respectively. The mf densities of the W. bancrofti infected patients decreased on day 7 from 214 mf/ml in the DEC group and from 559 mf/ml in the DEC-Alb group to 15 and 14 mf/ml, respectively. Our data indicate that the microfilaricidal effect of the drugs is achieved more rapidly for B. timori, which is associated with more adverse reactions than W. bancrofti. In addition, 111 B. timori infected persons were treated in the community with DEC-Alb in one selected village. The adverse reactions and the reduction of mf density was similar to the findings of the hospital-based study. In this group, there was a strong correlation of mf density with the frequency and severity of adverse reactions. The addition of Alb resulted in no additional adverse reactions compared with DEC treatment alone and can also be used for the treatment of B. timori infection. In Indonesia, where the prevalence of intestinal helminths is high, the use of a combination of DEC and Alb to control lymphatic filariasis may also have impact on the control of intestinal helminths.

Adolescent↗

High prevalence of Brugia timori infection in the highland of Alor Island, Indonesia.

To identify areas endemic for Brugia timori infection, a field survey was carried out in 2001 on Alor, East Nusa Tenggara Timor, Indonesia. Elephantiasis was reported on this island by villagers as a major health problem. Bancroftian filariasis was detected in four villages in the coastal area, whereas B. timori was identified in four rice-farming villages. No mixed infections with both species were found. In the highland village Mainang (elevation = 880 m), 586 individuals were examined for B. timori infection and 157 (27%) microfilaria carriers were detected. The prevalence of microfilaremic individuals standardized by sex and age was 25%. The geometric mean microfilarial density of microfilaremic individuals was 138 microfilariae/ml. Among teenagers and adults, males tended to have a higher microfilarial prevalence than females. Microfilaria prevalence increased with age and a maximum was observed in the fifth decade of life. In infected individuals, the microfilarial density increased rapidly and high levels were observed in those individuals 11-20 years old. The highest microfilaria density was found in a 27-year-old woman (6,028 microfilariae/ml). Brugia timori on Alor was nocturnally periodic, but in patients with high parasite loads, a small number of microfilariae was also detected in the day blood. The disease rate was high and many persons reported a history of acute filarial attacks. Seventy-seven (13%) individuals showed lymphedema of the leg that occasionally presented severe elephantiasis. No hydrocele or genital lymphedema were observed. This study showed that B. timori infection is not restricted to the lowland and indicated that it might have a wider distribution in the lesser Sunda archipelago than previously assumed.

Adolescent↗

Jenfluor ap--a novel fluorogenic substrate for in situ detection of alkaline phosphatase activity.

Alkaline phosphatase (AP) activity is often targeted in enzyme-related histochemistry as probe enzyme to detect neoplastic cells, as marker for primordial germ cells as well as in preimplantation studies, osteoblast differentiation, phosphate starvation in bacteria, yeast and phytoplankton. Moreover, AP-marker activity is a very useful tool in immunohistochemistry to detect gene sequences, antigens and antibodies. Here we describe a novel high resolution fluorescence method to localize AP-activity in cells and tissue sections based on a naphthol-AS azo coupling procedure (Jenfluor ap). This method provides amorphous photostable fluorescent final reaction products without any diffusion artifacts which are visible in conventional fluorescence microscopes as well as in confocal laser scanning and near infrared multiphoton laser scanning microscopes. The superiority of the Jenfluor ap method in comparison to the known Fast Red TR salt as well as the ELF stains is discussed.

Alkaline Phosphatase↗

Pressure Dependence Investigation of the Low-Temperature Structure of TlAu(CN)(2) by High-Resolution Neutron Powder Diffraction and Optical Studies.

In contrast to the anomalous increase of the lattice parameter b and associated reorientation of the [Au(3)(CN)(2)](-) ion with decreasing temperature, the unit cell volume and the lattice parameters of TlAu(CN)(2) are found to decrease (at T = 62 K) linearly for external hydrostatic pressures up to 4.5 kbar. The [Au(CN)(2)](-) ions do not essentially change orientation with pressure. The structural results suggest that the change in luminescence energy with pressure is due to changes in Tl.Au as well as in Au.Au interatomic separations, which again illustrates the importance of Tl.Au covalent interactions in this compound.

Journal Article↗

Molecular-Based Magnetism in Bimetallic Two-Dimensional Oxalate-Bridged Networks. An X-ray and Neutron Diffraction Study.

Bimetallic, oxalate-bridged compounds with bi- and trivalent transition metals comprise a class of layered materials which express a large variety in their molecular-based magnetic behavior. Because of this, the availability of the corresponding single-crystal structural data is essential to the successful interpretation of the experimental magnetic results. We report in this paper the crystal structure and magnetic properties of the ferromagnetic compound {[N(n-C(3)H(7))(4)][Mn(II)Cr(III)(C(2)O(4))(3)]}(n)() (1), the crystal structure of the antiferromagnetic compound {[N(n-C(4)H(9))(4)][Mn(II)Fe(III)(C(2)O(4))(3)]}(n)() (2), and the results of a neutron diffraction study of a polycrystalline sample of the ferromagnetic compound {[P(C(6)D(5))(4)][Mn(II)Cr(III)(C(2)O(4))(3)]}(n)() (3). Crystal data: 1, rhombohedral, R3c, a = 9.363(3) Å, c = 49.207(27) Å, Z = 6; 2, hexagonal, P6(3), a = 9.482(2) Å, c = 17.827(8) Å, Z = 2. The structures consist of anionic, two-dimensional, honeycomb networks formed by the oxalate-bridged metal ions, interleaved by the templating cations. Single-crystal field dependent magnetization measurements as well as elastic neutron scattering experiments on the manganese(II)-chromium(III) samples show the existence of long-range ferromagnetic ordering behavior below T(c) = 6 K. The magnetic structure corresponds to an alignment of the spins perpendicular to the network layers. In contrast, the manganese(II)-iron(III) compound expresses a two-dimensional antiferromagnetic ordering.

Journal Article↗

Compact multiphoton/single photon laser scanning microscope for spectral imaging and fluorescence lifetime imaging.

An inverted fluorescence microscope was upgraded into a compact three-dimensional laser scanning microscope (LSM) of 65 x 62 x 48 cm dimensions by means of a fast kHz galvoscanner unit, a piezodriven z-stage, and a picosecond (ps) 50 MHz laser diode at 405 nm. In addition, compact turn-key near infrared femtosecond lasers have been employed to perform multiphoton fluorescence and second harmonic generation (SHG) microscopy. To expand the features of the compact LSM, a time-correlated single photon counting unit as well as a Sagnac interferometer have been added to realize fluorescence lifetime imaging (FLIM) and spectral imaging. Using this unique five-dimensional microscope, TauMap, single-photon excited (SPE), and two-photon excited (TPE) cellular fluorescence as well as intratissue autofluorescence of water plant leaves have been investigated with submicron spatial resolution, <270 ps temporal resolution, and 10 nm spectral resolution.

Animals↗

High infection rate of Wolbachia endobacteria in the sand flea Tunga penetrans from Brazil.

Tunga penetrans is an ectoparasite causing considerable morbidity in endemic communities. Recently, endobacteria of the genus Wolbachia were identified also in T. penetrans. Since Wolbachia were suggested as targets for intervention of insect pests and human filariasis, sand fleas were collected from infested humans, dogs and rats in a hyperendemic area in northeastern Brazil, and screened for Wolbachia infections. Twenty-one adult fleas and four batches of flea eggs were examined by PCR using primers targeting the 16S rDNA, the DNA coding for FtsZ cell-cycle protein or a Wolbachia surface protein (WSP-1). Wolbachia were detected in all examined samples from eggs, free-living male and female fleas and from neosomic female fleas. No Wolbachia DNA was detected in two samples containing flea faeces. In addition, Wolbachia were labelled by immunohistology in the ovaries of 37 female fleas using antisera raised against WSP-1 of Wolbachia the filarial parasite Dirofilaria immitis. In the vicinity of the embedded fleas containing the Wolbachia, infiltrations of neutrophils and macrophages were observed. This study showed that Wolbachia endobacteria are abundant in T. penetrans and that all examined fleas were infected by these endobacteria. Our findings may have important implications for the future development of control strategies for human tungiasis.

Animals↗

Onchocerca volvulus: expression and immunolocalization of a nematode cathepsin D-like lysosomal aspartic protease.

The N-terminal region of the cathepsin D-like aspartic protease from the human filarial parasite Onchocerca volvulus was expressed as His-tag fusion protein. Light and electron microscopic immunohistology using antibodies against the recombinant protein showed labeling of lysosomes in the hypodermis and epithelia of the intestine and the reproductive organs of Onchocerca. While developing oocytes were negative, mature oocytes and early morulae showed strong labeling. In older embryos and mature microfilariae, stained lysosomes were only found in a few cells. Cell death in degenerating microfilariae of patients untreated and treated with microfilaricidal drugs was associated with strong expression of aspartic protease. IgG1, IgG4, and IgE antibodies reactive with the recombinant protein were demonstrated in sera from onchocerciasis patients indicating exposure and recognition of the enzyme by the host's defence system. The aspartic protease of O. volvulus appears to function in intestinal digestion and tissue degradation of the filaria.

Animals↗

Tunga penetrans: molecular identification of Wolbachia endobacteria and their recognition by antibodies against proteins of endobacteria from filarial parasites.

In search of Wolbachia in human parasites, Wolbachia were identified in the sand flea Tunga penetrans. PCR and DNA sequencing of the bacterial 16S rDNA, the ftsZ cell division protein, the Wolbachia surface protein (wsp) and the Wolbachia aspartate aminotransferase genes revealed a high similarity to the respective sequences of endosymbionts of filarial nematodes. Using these sequences a phylogenetic tree was generated, that indicates a close relationship between Wolbachia from T. penetrans and from filarial parasites, but possibly as a member of a new supergroup. Ultrastructural studies showed that Wolbachia are abundant in the ovaries of neosomic fleas, whereas other, smaller and morphologically distinct, bacteria were observed in the lumen of the intestine. Wolbachia were labeled by immunohistology and immunogold electron microscopy using polyclonal antibodies against wsp of Drosophila, of the filarial parasite Dirofilaria immitis, or against hsp 60 from Yersinia enterocolitica. These results show that as in filariasis, humans with tungiasis are exposed to Wolbachia. Furthermore, antisera raised against proteins of Wolbachia from arthropods or from filarial parasites can be immunologically cross-reactive.

Amino Acid Sequence↗