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Biomedical subjects

M Behrens

Publications and source records attributed to M Behrens.

At least 19 recordsLinked to original sources

PET1402, a nuclear gene required for proteolytic processing of cytochrome oxidase subunit 2 in yeast.

The nuclear mutation pet ts1402 prevents proteolytic processing of the precursor of cytochrome oxidase subunit 2 (cox2) in Saccharomyces cerevisiae. The structural gene PET1402 was isolated by genetic complementation of the temperature-sensitive mutation. DNA sequence analysis identified a 1206-bp open reading frame, which is located 215 bp upstream of the PET122 gene. The DNA sequence of PET1402 predicts a hydrophobic, integral membrane protein with four transmembrane segments and a typical mitochondrial targeting sequence. Weak sequence similarity was found to two bacterial proteins of unknown function. Haploid cells containing a null allelle of PET1402 are respiratory deficient.

Alleles

A novel method for recording whole-cell and single-channel currents from differentiating cerebellar granule cells in situ.

A preparation procedure is described yielding very thin tissue layers (1-3 cells) of the rat cerebellum. One-week-old rat cerebellum was embedded in agarose and cut in 1 mm slices, which then were mounted by a fresh fibrin preparation on the bottom of a culture dish. After coagulation of the fibrin the slice was gently lifted, leaving a thin fingerprint-like layer of cells on the bottom of the dish. Individual cells could be identified by their topographical positions. From these preparations patch-clamp recordings were made of cells in the external and the internal granule layer and of migrating cells. Whole-cell currents of cells in the external granule layer, recorded using the perforated-patch method, show that these neuroblasts already possess a full complement of ionic currents, consisting of a transient sodium current and a transient and a sustained potassium current. Whereas the potassium currents are predominant, the maximum sodium peak currents are minute (42 +/- 5 pA, mean +/- S.E.M., n = 21), i.e. too small for generating action potentials. There were no significant differences between cells of the external and the internal granule layer. The ionic channels passing these currents were identified and characterized in single-channel studies on cell-attached patches. Two types of potassium channel were found: a non-inactivating channel with a single-channel conductance of 21 pS and an inactivating channel with a conductance of 6 pS.

Animals

Identification of 5'-regions affecting the expression of the human CR2 gene.

Human CR2 has a restricted cellular distribution, being expressed on B lymphocytes, dendritic cells of the spleen, pharyngeal epithelial cells, and at low levels on some T lymphocytes. CR2 is expressed by mature B lymphocytes, but not by pre-B cells or by plasma cells, suggesting that mechanisms exist for positive and negative regulation of CR2 gene expression during B cell development. S1 nuclease digestion and primer extension analysis positioned the transcriptional start site between 92 and 94 bp upstream of the ATG codon. Nucleotide sequence analysis identified several sequences within the CR2 promoter region with homology to other known promoter sequences. These included a site similar to an AP-1 site, a sequence with 10 of 13 nucleotides identical to the X box of class II genes, and a TATA box. Genomic DNA starting immediately 5' of the sequence encoding the CR2 signal peptide was subcloned upstream of the bacterial chloramphenicol acetyltransferase gene for analysis of functional promoter and enhancer sites. The functional boundaries of the CR2 promoter were determined by deletion analysis, with both the X box-like sequences and the TATA box required for CR2 expression. This analysis revealed sequences with regulatory effects on CR2 gene expression, however, these transcriptional controlling sequences did not act in a tissue specific fashion.

Antigens, Differentiation, B-Lymphocyte

Inner membrane protease I, an enzyme mediating intramitochondrial protein sorting in yeast.

Several precursors transported from the cytoplasm to the intermembrane space of yeast mitochondria are first cleaved by the MAS-encoded protease in the matrix space and then by additional proteases that have not been characterized. We have now developed a specific assay for one of these other proteases. The enzyme is an integral protein of the inner membrane; it requires divalent cations and acidic phospholipid for activity, and is defective in yeast mutant pet ts2858 which accumulates an incompletely processed cytochrome b2 precursor. The protease contains a 21.4 kd subunit whose C-terminal part is exposed on the outer face of the inner membrane. An antibody against this polypeptide inhibits the activity of the protease. As overproduction of the polypeptide does not increase the activity of the protease in mitochondria, the enzyme may be a hetero-oligomer. This 'inner membrane protease I' shares several key features with the leader peptidase of Escherichia coli and the signal peptidase of the endoplasmic reticulum.

Amino Acid Sequence

Mitochondrial inner membrane protease 1 of Saccharomyces cerevisiae shows sequence similarity to the Escherichia coli leader peptidase.

The nuclear yeast mutant pet ts2858 is defective in the removal of pre-sequences from the mitochondrially encoded cytochrome oxidase subunit II (COXII) and the processing intermediate of cytochrome b2 (Cytb2), a nuclear gene product. In order to identify the genetic lesion in this mutant we have cloned and characterized a DNA region which complements the pet ts2858 mutation. The DNA sequence revealed three open reading frames, one of which is responsible for the complementation. A 570 bp reading frame represents the structural gene PET2858, as demonstrated by in vitro mutagenesis, gene expression from a foreign promoter, and allelism tests. PET2858 encodes a 21.4 kDa protein, which is essential for growth on non-fermentable carbon sources and for the proteolytic processing of COXII and the Cytb2 intermediate. When the N-terminus of the PET2858 protein is fused to a reporter protein, the resulting hybrid molecule is imported into mitochondria. Interestingly, the N-terminal half of the deduced PET2858 protein exhibits 30.7% amino acid identity to the leader peptidase of Escherichia coli. These results suggest that PET2858 codes for a mitochondrial inner membrane protease (IMP1) or at least a subunit of it. This protease is involved in protein processing and export from the mitochondrial matrix.

Alleles

Effects of yohimbine on isolation-induced aggression, social attraction, and conspecific odor preference in mice.

Yohimbine treatment inhibited isolation-induced attack in mice but had no effect on defense. The drug also increased social distances and produced a transient decrease in preference for conspecific male odors. The antiaggressive actions of yohimbine parallel those reported for the anxiogenic beta-carbolines and for phenylpiperazine "serenic" agents. The results emphasize the importance of supplementing conspecific agonistic encounters with additional behavioral measures such as nonagonistic social attraction in evaluating antiaggressive drugs. The decreased responsiveness to conspecific odors seen in Experiment 3 also suggests that increased conspecific avoidance may be mediated, in part at least, by altered olfactory processes.

Aggression

Comparison of myopotential interference in unipolar-bipolar programmable DDD pacemakers.

Myopotential interference (MPI) can inhibit or trigger single and dual chamber unipolar pacemakers while bipolar pacemakers are resistant. Twenty units of two different models of dual chamber pacemaker, each capable of being programmed to single chamber or dual chamber and unipolar or bipolar function were tested to provoke myopotential interference. No patient had evidence of myopotential interference at any sensitivity setting in the bipolar configuration either in atrium or in ventricle. All patients (20/20) interfered with pacemaker function at the highest atrial or ventricular sensitivity settings in the unipolar configuration. T wave sensing occurred at the 0.25 mV sensitivity setting in four patients in pacemaker model 925, in both bipolar and unipolar configurations. Twenty-five percent of patients had myopotential interference at the unipolar atrial sensing threshold and did not allow a setting which would reject myopotential interference while providing satisfactory atrial sensing. Twenty percent (2/10) had myopotential caused ventricular inhibition at the least sensitive ventricular channel setting in model 240G so that myopotential interference could not be avoided in that unit no matter how large the electrogram.

Arrhythmias, Cardiac

Retained pacemaker leads.

Increasingly, functionless pacemaker leads are being abandoned in place because they cannot be safely removed. One hundred eighty-nine intact or partially removed pacemaker leads were abandoned in situ in 152 patients between Jan. 1, 1965, and Dec. 31, 1985. The leads, sometimes several leads in a single patient, were deemed uninfected at the time of abandonment in 137 patients and contaminated with Staphylococcus epidermidis in 15 patients. All of the contaminated leads have remained clinically uninfected during follow-up. One clean lead became infected early after implantation and the patient died after an open cardiac operation to remove that lead and an adjacent abandoned lead that was adherent to the subclavian vein. No other patient has had a late complication during follow-up to 256 months (mean 47.6). Properly managed abandonment of an uninfected lead can carry a very low complication rate.

Electrodes, Implanted

Ocular neuromyotonia. A clinical description of six patients.

We report the cases of six patients with ocular neuromyotonia, a disorder believed to result from episodic involuntary discharge of ocular motor nerves producing sustained and inappropriate contraction of their respective ocular muscles. Transient disturbances of ocular motility and diplopia result. Four patients had involvement of ocular muscles supplied by the third cranial nerve: one had presumed involvement of the superior oblique muscle, and one the lateral rectus muscle, suggesting abnormal discharge in the fourth and sixth cranial nerves, respectively. Four of six patients received prior radiation therapy for pituitary tumors, implying a possible pathogenic link. Three patients improved after treatment with membrane-stabilizing medication, suggesting that unstable membranes of injured ocular motor axons may generate spontaneous impulses, which produce involuntary sustained and inappropriate ocular muscle contraction.

Abducens Nerve

Nystagmus in motor neuron disease: clinicopathological study of two cases.

Two patients with amyotrophic lateral sclerosis proved postmortem had nystagmus in addition to typical clinical signs of motor neuron disease. The first patient had gaze-evoked rotatory nystagmus that was followed by horizontal nystagmus in the primary position with supranuclear paresis of horizontal gaze and upgaze. The second patient had rotatory nystagmus that was evoked by lateral gaze, with normal range of eye movements. Nystagmus is so rare in motor neuron disease that these observations may imply another disease, but postmortem examination did not provide any other explanation. These two cases add to the increasing evidence that motor neuron disease comprises a heterogeneous group of disorders.

Abducens Nerve

Bilateral central and centrocaecal scotomata due to mass lesions.

Unilateral central or centrocaecal scotoma may result from optic nerve compression. However, such defects bilaterally usually indicate non-compressive optic neuropathy of toxic or nutritional, hereditary, or demyelinating origin. Three cases are reported of patients who presented with somewhat atypical bilateral central or centrocaecal scotomata and were found to have suprasellar mass lesions demonstrated by CT scan and confirmed neurosurgically.

Adult

Cytomegalovirus retinitis in a young homosexual male with acquired immunodeficiency.

A case is reported of histopathologically documented CMV retinitis. It is part of a recently appreciated syndrome in young homosexual men, in which cellular immune deficiency has been documented and in which CMV infection may play a role. This case demonstrates that CMV retinitis is not excluded by negative CMV serology or cultures.

Acquired Immunodeficiency Syndrome

Hypopigmented iris spot. An early sign of tuberous sclerosis.

Hypopigmented skin spots, resembling the mountain ash leaf, may represent the earliest sign in tuberous sclerosis. We examined two patients with hypopigmented iris spots who suffered from this systemic disease. These iris spots may be analogous to the skin lesions, which have decreased amount of melanin in the melanosomes.

Adult

Slowly alternating skew deviation: description of a pretectal syndrome in three patients.

Three patients who had slowly alternating skew deviation are described; each had elements of the Sylvian aqueduct syndrome. This combination of signs supports a pretectal location for lesions associated with alternating skew movements. Postmortem examination of a patient who died of chronic herpes simplex encephalitis showed extensive demyelination and periaqueductal spongiform degeneration; there was preservation of the oculomotor and trochlear nuclei, the medial longitudinal fasciculus, vestibular nuclei, and the interstitial nucleus of Cajal bilaterally. The slowly alternating dysconjugate vertical movements bear a resemblance to both see-saw nystagmus and the ocular tilt response.

Brain