Biomedical subjects

W Bohne

Publications and source records attributed to W Bohne.

6 recordsLinked to original sources

PubMed1992

[New views on the pathogenesis and diagnosis of toxoplasmosis].

T. gondii is one of the most occurring human pathogenic parasites in Europe. While the majority of immunocompetent individuals with T. gondii infection do not present clinical symptoms, congenital toxoplasmosis and reactivation of a latent infection in immunocompromised patients (i. e. patients with AIDS) are of high clinical relevance. A classification of T. gondii isolates is not available so far, although it was possible to demonstrate strain differences by the use of several methods, i. e. by using monoclonal antibodies. T. gondii seems to be able to infect any mammalian cell. Host cell-derived as well as parasite-derived factors seem to be important for the contact between host cell and parasite and the subsequent internalization. Following invasion, T. gondii is located within a parasitophorous vacuole that does not fuse with lysosomes. The multiplication rate of these obligately intracellular growing parasites decreases during conversion from the tachyzoite stage to the bradyzoite stage. Finally, the bradyzoites-harbouring cysts persist for the lifetime of the host. Reconversion from bradyzoites to tachyzoites may occur in immunocompromised patients. Probably, IFN-gamma is involved in this process. In addition to serological methods, direct detection of T. gondii using PCR or demonstration of circulating antigens might be routinely used as diagnostical tools in the future. Determination of specific IgA antibodies, which can be evaluated using the immunoblot technique, seem to be important for early serological diagnosis. The use of recombinant antigens might be helpful in future diagnosis to circumvent discrepancies between serological test results which could have resulted from strain-specific differences.

Animals↗

PubMed1991

An 11-bp deletion in the arylsulfatase A gene of a patient with late infantile metachromatic leukodystrophy.

Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A. Examination of the arylsulfatase A gene in a patient suffering from late infantile metachromatic leukodystrophy revealed an 11-bp deletion in exon 8. Although this allele produces normal amounts of ASA mRNA, no arylsulfatase A cross-reacting material could be detected in cultured fibroblasts from the patient. The patient was found to be a compound heterozygote, the other allele is also known to generate no ASA polypeptides. This patient is another example where absence of ASA polypeptides correlates with the severe late infantile form of metachromatic leukodystrophy.

Amino Acid Sequence↗

PubMed1991

Two new arylsulfatase A (ARSA) mutations in a juvenile metachromatic leukodystrophy (MLD) patient.

Fragments of the arylsulfatase A (ARSA) gene from a patient with juvenile-onset metachromatic leukodystrophy (MLD) were amplified by PCR and ligated into MP13 cloning vectors. Clones hybridizing with cDNA for human ARSA were selected, examined for appropriate size inserts, and used to prepare single-stranded phage DNA. Examination of the entire coding and most of the intronic sequence revealed two putative disease-related mutations. One, a point mutation in exon 3, resulted in the substitution of isoleucine by serine. Introduction of this alteration into the normal ARSA cDNA sequence resulted in a substantial decrease in ARSA activity on transient expression in cultured baby hamster kidney cells. About 5% of the control expression was observed, suggesting a small residual activity in the mutated ARSA. The second mutation, a G-to-A transition, occurred in the other allele and resulted in an altered splice-recognition sequence between exon 7 and the following intron. The mutation also resulted in the loss of a restriction site. Apparently normal levels of mRNA were generated from this allele, but no ARSA activity or immuno-cross-reactive material could be detected. A collection of DNA samples from known or suspected MLD patients, members of their families, and normal controls was screened for these mutations. Four additional individuals carrying each of the mutations were found among the nearly 100 MLD patients in the sample. Gene segregation in the original patient's family was consistent with available clinical and biochemical data. No individuals homozygous for either of these two mutations were identified. However, combinations with other MLD mutations suggest that the point mutation in exon 3 does result in some residual enzyme activity and is associated with late-onset forms of the disease. The splice-site mutation following exon 7 produces late-infantile MLD when combined with other enzyme-null mutations, implying that it is completely silent enzymatically.

Adolescent↗

PubMed1990

Light and ultrastructural studies of human chronic periapical lesions.

Forty clinically chronic periapical granulomas and cysts and their corresponding teeth were removed. Diagnosis was by light and transmission electron microscopy. Ultrastructural features of the root surfaces concerned and the corresponding soft tissue were detected by scanning electron microscopy. Chronic periapical inflammation had caused root resorption which affected the cementum and/or the dentin. There were no ultrastructural differences between granuloma- and cyst-induced root resorption. Resorption lacunae were devoid of epithelial and connective tissue attachment. However, root surface exposed to granulomas and cysts also indicated spontaneous cementum repair. Moreover, at their periphery, cellular debris, cells defined as fibroblasts, and cell projections and fibrils could be seen which were continuations of the periodontal ligament.

Adolescent↗

PubMed1977

Diphosphonate therapy of paget's disease of bone.

The use of disodium ethane-1 hydroxy-1, 1-diphosphonate (EHDP) therapy for Paget's disease of bone was examined in 75 affected patients. Forty-eight patients received randomly assigned oral doses of either 0, 2.5, 5, 10, or 20 mg/kg/day in a controlled, double-blind protocol, and the remainder received either 10 or 20 mg/kg/day in a non-random protocol. The clinical status of the patients and appropriate laboratory tests were evaluated before treatment and at frequent intervals during a six-month period of initial therapy. There were no significant changes in either urinary hydroxyproline or serum alkaline phosphatase in those patients receiving placebos, while both these parameters decreased significantly at all dose levels of EHDP, with the greatest decline noted in the highest dose group. However, statistical analysis of the data related to changes in symptoms in the double-blind study revealed that patients receiving the higher dose of EHDP (10 or 20 mg/kg/day) had less favorable outcomes than those receiving the lower doses (2.5 or 5 mg/kg/day). The high does group had a relatively lower rate of symptom improvement and a relatively greater rate of deterioration than did the low dose group. Twenty-one of forty-nine patients followed for at least 18 months have shown a sustained suppression of their serum alkaline phosphatase and urinary hydroxyproline values for 12 months following cessation of EHDP, while therapy has been reinstituted for the other 28 patients because of increases in these measurements, with or without accompanying symptomatic deterioration. Eight patients sustained fractures through Pagetic bone during the period of study and all of these were treated with higher doses of EHDP. On the basis of the biochemical and clinical data in this study it appears that initial therapy of Paget's disease of bone with 5 mg EHDP/kg/day maximizes benefits while minimizing possible adverse effects.

Alkaline Phosphatase↗

PubMed1976

Ulnar dysmelia.

Eleven patients with hypoplasia and partial or complete aplasia of the ulna (examples of a complex spectrum of postaxial forearm and hand abnormalities) were reviewed. Three types of ulnar deformity were observed: (1) hypoplasia, (2) partial aplasia (ossification of the proximal part of the ulna present at birth); and (3) total aplasia (ossification not development). The roentgenographically "absent" segment of the ulna may be a large fibrocartilaginous anlage attached distally to the distal radial epiphysis or the ulnar side of the carpus, or both. The tethering effect of this band may cause ulnar deviation of the wrist (and hand) and dislocation of th badial head in utero as well as progression of these deformities after birth. Resection of the distal end of the fibrocartilaginous anlage during the first to second year of life is recommended, since the results of this procedure suggest that it reduces the angular growth deformities. It is also suggested that if the one-bone-forearm operation is indicated, it should be deferred until a later age, since complications may be less likely to occur then than at the time that the anlage is resected.

Abnormalities, Multiple↗