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Biomedical subjects

K Haase

Publications and source records attributed to K Haase.

9 recordsLinked to original sources

[Myxoma of the middle ear-a rare cause of facial palsy].

In case of the co-occurrence of facial palsy and inflammation-like symptoms of the same ear, the differential diagnosis is focused on viral (herpes zoster) or bacterial diseases. We report a patient for whom the surgical exploration of the middle ear revealed a benign tumor: a myxoma. These neoplasias are rare tumors in the head and neck region. The typical tumor site is the atrium of heart. In the ear, the tumor grows slowly and remains asymptomatic unless it irritates structures such as the facial nerve or the vestibular organ. Histologically, the tumor presents a "myxoid" matrix that is rich in acid mucopolysaccarides. The treatment of choice is complete surgical resection. Using the case presented, we discuss the causality between the tumor and the facial palsy, although during the operation the bony canal of the nerve was found to be intact. In any cases with clinically and radiologically unclear findings of the ear in connection with facial palsy, surgical exposure should be considered.

Aged↗

Determination of the relationship between T cell responsiveness and the number of MHC-peptide complexes using specific monoclonal antibodies.

We describe the generation of three mAbs that recognize the complex of the class II MHC molecule IEk bound to a peptide derived from the carboxyl terminus of moth cytochrome c (residues 95-103). Reactivities of these mAbs are sensitive to single alterations in the sequence of both helices of the MHC molecule and to the bound peptide. The epitopes of these reagents are distinct but overlap substantially. One of these mAbs specifically blocks lymphokine release by T cells responsive to this complex but not others. We have used another to examine how the number of complexes on an APC is related to its ability to stimulate T cells. We find that 200-400 complexes per cell are necessary and sufficient to induce a degree of stimulation, whereas maximum stimulation is achieved only if more than 5000 complexes are present. The analysis indicates that T cell activation is a stochastic process.

Amino Acid Sequence↗

An experimental model for interpreting percutaneous penetration of oligonucleotides that incorporates the role of keratinocytes.

Oligonucleotides have been extensively studied for their potential as therapeutic agents. Phosphorothioate oligonucleotides have been demonstrated to be particularly useful due to their stability against nucleases, their ability to be internalized by many cell types, and the ease with which they hybridize with target mRNA. These compounds have previously been delivered across the skin with the aid of iontophoresis. During transdermal delivery, the first viable cells exposed to the oligonucleotides are the keratinocytes. The purpose of this study was to determine the relationship between internalization of these compounds by keratinocytes and their transport across the skin. The in vitro uptake of 15 different fluorescently labeled phosphorothioate oligonucleotides into human keratinocytes was quantitatively measured with a fluorometer. Photomicrographs of keratinocytes indicate diffuse cytoplasmic and nuclear localization. The ability of these molecules to enter cells was linearly related to size. Cellular uptake data were inversely correlated with previously reported steady-state transport levels of oligonucleotides that had been transdermally delivered by iontophoresis across hairless mouse skin. Oligonucleotides that readily entered keratinocytes had a decreased ability to penetrate skin under iontophoretic conditions. The results indicate that oligonucleotide sequences may be designed for treating skin diseases (high uptake, low transport) or systemic disorders (low uptake, high transport).

Animals↗

Hallux hammer toe secondary to pseudomonas osteomyelitis.

The authors present two cases of resultant hallux hammer toe secondary to the definitive treatment of hallux sesamoidal osteomyelitis. Pseudomonas osteomyelitis developed in both cases following puncture wounds to the first metatarsophalangeal joint complex. The authors also review the literature on pseudomonas osteomyelitis secondary to puncture wounds and the development of hallux hammer toe after removal of the involved sesamoid bones.

Adolescent↗

Retrovirus-induced insertional mutation in Mov13 mice affects collagen I expression in a tissue-specific manner.

In the Mov13 mouse mutant, transcription of the alpha 1 (1) collagen gene is blocked by a retroviral insert in the first intron. We now report that teeth derived from homozygous embryos produce a dentin layer containing normal amounts of collagen 1. In situ hybridization and RNAase protection experiments indicate that the mutant allele is efficiently transcribed in odontoblasts, in contrast to other cell types. Correct splicing of the primary transcript containing the viral sequence results in a functional alpha 1 (1) collagen mRNA. The absence of a mutagenic effect in odontoblasts, as opposed to fibroblasts, suggests that the retroviral insert interferes with tissue-specific transcriptional control of the alpha 1 (1) collagen gene, most likely by inactivating cell-type-specific cis-acting regulatory elements.

Animals↗

Insertion of the bacterial gpt gene into the germ line of mice by retroviral infection.

Mouse substrains genetically transmitting the exogenous Moloney murine leukemia virus (Mo-MuLV) at a single locus have been derived previously by infection of preimplantation embryos. Here we explore the potential of retroviral vectors for transferring nonviral genes into the germ line of mice. Preimplantation mouse embryos were cocultivated with a cell line that produces a recombinant retrovirus whose genome carries the Escherichia coli gene gpt. We show that the vector sequence was inserted into the genome of the embryo and into the germ line at a frequency similar to that for the Mo-MuLV-helper sequence. A new mouse strain, Mgpt-1, was developed that is homozygous for a single MSVgpt proviral genome. The proviral sequences were highly methylated and not expressed in tissues of Mgpt-1 mice. When cells derived from transgeneic animals were treated with 5-azacytidine, the proviral sequences were not methylated and were transcriptionally activated. These results indicate that nonviral genes that are under the control of the viral long terminal repeat are inactivated when transferred into the germ line of animals.

Animals↗