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Biomedical subjects

M Franken

Publications and source records attributed to M Franken.

9 recordsLinked to original sources

Element concentrations in the archiacanthocephalan Macracanthorhynchus hirudinaceus compared with those in the porcine definitive host from a slaughterhouse in La Paz, Bolivia.

Concentrations of lead and cadmium, determined by electrothermal atomic absorption spectrometry, and concentrations of the elements barium, cadmium, copper, iron, magnesium, manganese, nickel, lead, selenium and strontium, determined by inductively coupled plasma mass spectrometry, in the acanthocephalan Macracanthorhynchus hirudinaceus and its porcine final host, sampled at a slaughterhouse in La Paz, Bolivia, were compared. Inductively coupled plasma mass spectrometry analysis revealed that most of the elements were found at higher concentrations in the acanthocephalan than in different tissues of its host. The bioconcentration of elements in M. hirudinaceus compared with the host intestine, listed in order of decreasing values, was as follows: Cd > Pb > Ni > Sr = Cu > Mg > Se > Fe = Mn = Ba. Analysis by electrothermal atomic absorption spectrometry showed that M. hirudinaceus contained 85, 85, 56 and 24 times higher lead levels compared with hosts muscle, liver, kidney and intestine, respectively. The mean cadmium concentration of the parasite was 32 times higher than that of the liver and five times higher compared with porcine kidney. The metal distribution within the body of M. hirudinaceus was as follows: cement gland > testes > lemnisci > eggs = tegument for lead and lemnisci > testes > cement gland > tegument > eggs for cadmium. Therefore, the hypothesis that parasites excrete toxic metals with the shells of their eggs seems not to be valid for M. hirudinaceus. It is concluded, that not only eoacanthocephalans and palaeacanthocephalans parasitising fish, but also archiacanthocephalans from mammalian hosts, are able to bioaccumulate metals.

Abattoirs↗

Pseudo-myocardial infarction during an episode of herpes zoster.

The patient arrived at the emergency unit with a history of acute myocardial infarction, for which she was treated. Without improvement in the pain, the patient developed heart failure and underwent a hemodynamic study, which showed normal coronary arteries and extensive ventricular impairment. During evolution, the clinical findings improved and herpes zoster appeared on the right shoulder. In a few months the clinical findings subsided, and the findings of the electrocardiogram, chest X-ray, and ventricular function were normal. The patient is currently asymptomatic.

Aged↗

[No adverse effects on intelligence 6 years after surgery for epilepsy].

OBJECTIVE: To evaluate the long-term effects of epilepsy surgery on intelligence. DESIGN: Prospective descriptive. METHOD: The group included 20 patients of the Instituut voor Epilepsiebestrijding, Heemstede, and the Epilepsiecentrum Kempenhaeghe, Heeze, the Netherlands, who suffered from medication-resistant epilepsy originating from the temporal lobe, in 9 patients from the left lobe (mean age: 33.1 years), in 11 from the right one (34.6 years). The epilepsy focus was removed surgically (Academic Hospital, Utrecht). The scores on the 'Wechsler adult intelligence scale' (WAIS) were determined before the operation and 6 months, 2 years and 6 years after operation. RESULTS: The mean WAIS IQs before operation were: verbal IQ (VIQ): 111.8 and performance IQ (PIQ): 117.7 in the group treated on the left and VIQ: 113.5 and PIQ: 112.4 in the group treated on the right. The mean gains 6 years after operation were 0.8 and 2.6 VIQ-points and 8.7 and 8.5 PIQ-points respectively. In the patients operated on the left the difference between VIQ and PIQ was significant 2 and 6 years after operation. The increase in IQs remained within what could be expected in retests. Only for the VIQ of patients treated on the left was a smaller retest effect found. CONCLUSION: These figures show that in the long term epilepsy surgery does not have an adverse outcome on the intelligence.

Adult↗

The Northern Bolivian Altiplano: a region highly endemic for human fascioliasis.

The worldwide importance of human infection by Fasciola hepatica has been recognized in recent years. The endemic region between Lake Titicaca and the valley of La Paz, Bolivia, at 3800-4100 m altitude, presents the highest prevalences and intensities recorded. Large geographical studies involving Lymnaea truncatula snails (malacological, physico-chemical, and botanic studies of 59, 28 and 30 water bodies, respectively, inhabited by lymnaeids; environmental mean temperature studies covering a 40-year period), livestock (5491 cattle) and human coprological surveys (2723 subjects, 2521 of whom were school children) were conducted during 1991-97 to establish the boundaries and distributional characteristics of this endemic Northern Altiplano region. The endemic area covers part of the Los Andes, Ingavi, Omasuyos and Murillo provinces of the La Paz Department. The human endemic zone is stable, isolated and apparently fixed in its present outline, the boundaries being marked by geographical, climatic and soil-water chemical characteristics. The parasite distribution is irregular in the endemic area, the transmission foci being patchily distributed and linked to the presence of appropriate water bodies. Prevalences in school children are related to snail population distribution and extent. Altiplanic lymnaeids mainly inhabit permanent water bodies, which enables parasite transmission during the whole year. A confluence of several factors mitigates the negative effects of the high altitude.

Adolescent↗

Pharmacokinetics and cognitive effects of carbamazepine formulations with different dissolution rates.

OBJECTIVE: In this study our aim was to assess pharmacokinetic effects and adverse cognitive effects of switches between generic and branded formulations of carbamazepine (CBZ). METHOD: Twelve patients were included in a randomized open-label, observer-blind, cross-over design with a double-baseline period, comparing three different formulations of carbamazepine in monotherapy--the innovatory branded form Tegretol and two generic forms, CBZ Pharmachemie and CBZ Pharbita. Cognitive assessment was carried out at baseline and 3 days after a cross-over. RESULTS: Area under the curve and a number of pharmacokinetic properties (serum concentration day curves, change in serum concentration (delta scores), peak/trough concentrations and peak time) did not differ among the three CBZ formulations. Therefore, the basic assumption for this study, i.e. to test pharmacokinetic-related differences in cognitive profile, was not met. In line with these findings, none of the cognitive variables showed statistically significant differences with respect to the cognitive profile during the day. CONCLUSION: Switches between the investigated generic CBZ formulations and the branded product did not result in any difference in cognitive profiles. These results are not necessarily valid, though, for other generic forms of CBZ, for other types of antiepileptic drugs or for CBZ treatment in higher doses or in polytherapy.

Adult↗

Epstein-Barr virus-driven gene therapy for EBV-related lymphomas.

Genetic alterations in malignant tissues are potential targets for gene-based cancer therapies. Alternatively, aberrant expression of certain specific genes associated with malignant transformation may be envisioned to enhance the expression of chemosensitizing drugs. Epstein-Barr virus (EBV)-related B-cell lymphomas are fatal complications of immunosuppression due to AIDS, organ transplantation or congenital immune abnormalities. The malignant cells latently infected with EBV typically express the transcription factor EBNA2 as one of nine latent viral genes. We tested whether an EBNA2-responsive EBV promoter may selectively target EBV-related lymphoma cells by virus-regulated expression of a suicide gene. Using the BamC promoter driving a hygromycin-thymidine kinase fusion gene or controls, we demonstrated that sensitivity to ganciclovir was selectively enhanced in cells expressing EBNA2. Further, there was complete macroscopic regression of established B-cell lymphomas in mice with severe combined immunodeficiency disease (SCID mice) treated with a single course of ganciclovir. These data provide in vitro and in vivo support for a model of exploiting the molecular basis of tumor development to enhance the specificity of gene therapy.

Animals↗

Comparative analysis identifies conserved tumor necrosis factor receptor-associated factor 3 binding sites in the human and simian Epstein-Barr virus oncogene LMP1.

Nonhuman primates are naturally infected with a B-lymphotropic herpesvirus closely related to Epstein-Barr virus (EBV). These simian EBV share considerable genetic, biologic, and epidemiologic features with human EBV, including virus-induced tumorigenesis. However, latent, transformation-associated viral genes demonstrate marked sequence divergence among species despite the conserved functions. We have cloned the latent membrane protein 1 (LMP1) homologs from the simian EBV naturally infecting baboons (cercopithicine herpesvirus 12, herpesvirus papio) and rhesus monkeys (cercopithicine herpesvirus 15) for a comparative study with the human EBV oncogene. The transmembrane domains are well conserved, but there is striking sequence divergence of the carboxy-terminal cytoplasmic domain essential for B-cell immortalization and interaction with the tumor necrosis factor receptor signaling pathway. Nevertheless, the simian EBV LMP1s retain most functions in common with EBV LMP1, including the ability to induce NF-(kappa)B activity in human cells, to bind the tumor necrosis factor-associated factor 3 (TRAF3) in vitro, and to induce expression of tumor necrosis factor-responsive genes, such as ICAM1, in human B lymphocytes. Multiple TRAF3 binding sites containing a PXQXT/S core sequence can be identified in the simian EBV LMP1s by an in vitro binding assay. A PXQXT/S-containing sequence is also present in the cytoplasmic domain of the Hodgkin's disease marker, CD30, and binds TRAF3 in vitro. The last 13 amino acids containing a PXQXT/S sequence are highly conserved in human and simian EBV LMP1 but do not bind TRAF3, suggesting a distinct role for this conserved region of LMP1. The conserved TRAF3 binding sites in LMP1 and the CD30 Hodgkin's disease marker provides further evidence that a TRAF3-mediated signal transduction pathway may be important in malignant transformation.

Amino Acid Sequence↗

5' Coding and regulatory region sequence divergence with conserved function of the Epstein-Barr virus LMP2A homolog in herpesvirus papio.

B-lymphotropic herpesviruses naturally infecting Old World primates share biologic, epidemiologic, pathogenic, and molecular features with the human pathogen Epstein-Barr virus (EBV). These related gammaherpesviruses have colinear genomes with considerable nucleotide homology. The replicative cycle genes share a high degree of homology across species, whereas the transformation-associated EBV latent genes appear to be much more divergent. For example, the EBV BamHI Nhet fragment, which encodes all or part of the EBV latent infection membrane proteins, cross-hybridizes poorly to DNA from nonhuman primate B-lymphotropic herpesviruses. A viral DNA fragment corresponding to this region of the EBV genome was isolated from the baboon B-lymphotropic herpesvirus, herpesvirus papio, and used to clone a herpesvirus papio cDNA corresponding to EBV LMP2A. At least three tyrosine kinase interaction motifs are conserved despite significant amino acid divergence of the herpesvirus papio LMP2A first exon from the EBV homolog. Functionally, the herpesvirus papio LMP2A is tyrosine phosphorylated and induces tyrosine phosphorylation of cell proteins similar to EBV LMP2A. The 12 hydrophobic LMP2 transmembrane domains are well conserved. Two CBP (Jk) binding sites important for EBNA-2-induced transactivation of the LMP2A promoter are also present in the herpesvirus papio LMP2A promoter, and the simian LMP2A promoter is also responsive to EBV EBNA-2-induced transactivation in human B cells. Thus, transcriptional regulation, splicing, kinase interaction sites, and tyrosine phosphorylation of the LMP2A homologs have been conserved despite significant sequences heterogeneity in the preterminal repeat regions of these human and nonhuman primate EBVs. The conservation of the LMP2 gene, despite its apparent nonessential role for in vitro EBV infection, suggests an important role for LMP2A in vivo. The similarities between these human and simian B-lymphotropic herpesviruses, and the LMP2 genes in particular, suggest that the function of LMP2 in vivo could be addressed by using recombinant LMP2A-mutant simian viruses and experimental infection of Old World primates.

Amino Acid Sequence↗