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Biomedical subjects

J Johansen

Publications and source records attributed to J Johansen.

At least 19 recordsLinked to original sources
PubMed1992

Barbiturate depression of a K+ dependent inhibitory synapse is independent of dendritic cable filtering.

Technical limitations with intracellular electrophysiological methods usually restrict recording of postsynaptic potentials only from neuronal soma, a site remote from the actual synapse. The intervening dendritic cable interposed between the actual synapse and the site of recording can significantly filter the synaptic signal. Therefore, investigations of drug effect on synaptic mechanisms, based on postsynaptic recordings obtained at the soma, must be interpreted with care. The potential role of dendritic cable filtering in the atypical pentobarbital depression of a K(+)-dependent inhibitory synapse between the P to Nut cell in the posterior packet of the leech was investigated. The effective electrical geometry under the conditions of control and 0.5 mM PNB sufficient to completely abolish the postsynaptic potential were determined from analyses of the membrane charging curves assuming the lumped-soma-short-cable model. Under the control condition, the postsynaptic Nut cell exhibits dendritic dominance with rho = 2.52, normalized equivalent cable length L = 1.08, and a membrane time constant tau o = 52 ms. With phenobarbital application, changes in the geometrical parameters consistent with a decrease in the specific membrane resistance Rm are observed. Simulation of the drug induced change in the electrical geometry demonstrates that the decrease in the post synaptic potential is largely due to the decrease in the soma input resistance and an increase in the cable filter contributes little to the observed depression of the postsynaptic potential. However, the combined effect of the decrease in the input resistance and the increase in the cable filtering of synaptic current is insufficient in explaining the observed total block of the synaptic potential by PNB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Tract formation and axon fasciculation of molecularly distinct peripheral neuron subpopulations during leech embryogenesis.

In leech, the central projections of peripheral sensory neurons segregate into specific axonal tracts, which are distinguished by differential expression of surface antigens recognized by the monoclonal antibodies Lan3-2 and Lan4-2. Lan3-2 recognizes an epitope expressed on axons that segregate into three distinct axon fascicles. In contrast, the Lan4-2-positive axons selectively project into only one of the Lan3-2-positive axon tracts. These observations provide evidence for a hierarchy of guidance cues mediating specific pathway formation in this system. Since the Lan3-2 antibody has been shown to perturb this process and since, as shown here, the Lan3-2 and Lan4-2 antigens are closely molecularly interrelated, these antibodies may help define molecules and epitopes mediating neuronal recognition and axonal guidance.

Afferent Pathways↗
PubMed1992

Visual outcome following complicated extracapsular cataract extraction.

In a prospective study of 1,597 consecutive extracapsular cataract extractions (ECCE), we review 49 cases complicated by capsular or zonular rupture with or without vitreous loss. The ECCEs were divided into two groups depending on the type of intraocular lens (IOL) implanted. In Group A, whose patients received an anterior chamber lens, we found a significantly (P < .05, t-test) worse postoperative visual acuity than in Group B whose patients received a posterior chamber lens. We therefore suggest that in the presence of a capsular tear and vitreous loss, one should try to implant a posterior chamber lens rather than an anterior chamber lens to obtain as good a visual acuity as possible.

Aged↗
PubMed1992

High-signal foci on MR images of the brain: observer variability in their quantification.

Foci of high signal in the cerebral white matter are common incidental findings on MR images of the brain of control subjects or patients with a variety of diseases. Although the number of foci has been reported to correlate with age and several risk factors, the degree of observer variability in quantifying foci has not been reported. We used kappa statistics to determine radiologists' agreement in counting high-signal-intensity foci on MR images obtained in healthy volunteers and in patients with hypertension. Before interpreting the images, one pair of radiologists studied 30 routine MR images and reached consensus on differentiating high-signal foci from other foci of high intensity caused by normal structures (e.g., deep gyri or Virchow-Robin spaces). These two observers than independently determined the number of foci in the study group. Using their own criteria, other radiologists independently counted the foci. Agreement between observers was determined with the kappa statistic. The results showed fair agreement between the radiologists who first reached a consensus in counting foci of hyperintensity and poor agreement between the other observers. We conclude that in order to compare the frequency of foci of hyperintensity in different groups of patients, observer variability must be controlled. Studies without proper control subjects may lead to incorrect conclusions regarding the correlation of focal hyperintensities and various risk factors.

Alzheimer Disease↗
PubMed1992

Lymph node metastases in the neck from unknown primary tumour.

During a 12-year period a total of 203 patients were referred to the oncologic center of Odense with lymph node metastases in the neck. Routine examinations on admission failed to detect the primary tumour in 37 patients. During follow-up, the primary was revealed in 18 of these patients, and in a further 8 cases it was found at autopsy. The primary was most often located in the head and neck region with a possibility of curative therapy. Patients with small neck node metastases responded well to treatment with neck dissection and radiotherapy, resulting in a 5-year crude survival rate of 53%.

Adenocarcinoma↗
PubMed1991

[Neck lymph node metastases from an unknown primary tumor].

During a period of 12 years, a total of 203 patients with lymph node metastases in the neck were referred. At the conclusion of the programme of investigation, the primary tumours remained undiagnosed in 37 patients. The primary tumours were diagnosed in 18 patients, ten of these were alive. The primary tumours were most commonly localized in the head and neck region with the possibility for curative treatment. Patients with small metastases experienced good effects from regional treatment in the form of cervical dissection and radiotherapy with a five-year crude survival of 53%

Female↗
PubMed1991

Epidermoid carcinoma of the pharynx. Therapeutic results in a series of 221 patients.

Two hundred and twenty-one cases of epidermoid carcinoma of the pharynx diagnosed between 1965 and 1984 were analysed. Fifty-seven per cent of the carcinomas were poorly differentiated and 57% of the patients had stage IV disease; 65% had lymph node metastases at the time of diagnosis. Radiotherapy was the primary treatment. Between 1977 and 1979, preirradiation chemotherapy was used and from 1979 the effect of the radiosensitizer misonidazole was investigated in split-course radiotherapy. Loco-regional failure occurred in 60% after primary treatment. No changes in treatment results were observed during four consecutive 5-year periods. The five-year corrected actuarial survival rate in the whole series was 33%. It is concluded that the treatment results are still unsatisfactory, and that chemotherapy, optimized radiotherapy, and radiosensitizers as used in the present series did not seem to improve the results. Alcohol and tobacco restriction is emphasized for prevention.

Adolescent↗
PubMed1991

Growth cone behavior underlying the development of stereotypic synaptic connections in Drosophila embryos.

Each muscle fiber in the segmented body wall of Drosophila larvae is innervated by anatomically stereotyped neuromuscular junctions. These synapses arise through the selective choices of motoneuronal growth cones at their peripheral targets. Using digital optical microscopy of staged intracellular dye fills, we have singly identified embryonic motoneurons and have examined individual growth cones when they contact and differentiate at the target cells. There is a precise connectivity between motoneuron and muscle fiber, which is the direct consequence of growth cone behavior. We have also found that Drosophila muscle fibers possess molecularly heterogeneous cell surfaces that may be involved in growth cone recognition of appropriate targets. Fasciclin III, a homophilic adhesion molecule, is coexpressed by several of the efferent growth cones and in a site-specific fashion by the target muscle fiber's membrane. The fasciclin III expression is transient, corresponding to the period in embryogenesis when the first neuromuscular contacts are made. Upon encountering the target cell surface, the growth cones can sprout stereotypically arrayed filopodial processes, orient along the anterior-posterior axis, and turn in predictable directions. Subsequently, terminal branches are established in a nonrandom order. These phenomena were found to occur in two motoneurons that innervate adjacent muscle fiber targets, and may be general features of neuromuscular synaptogenesis in Drosophila.

Aging↗
PubMed1990

Ionic conductances in two types of sensory neurons in the leech, Macrobdella decora.

1. Ion conductances were investigated in two kinds of leech sensory neurons (PM and N1 cells) which differ in their membrane excitability and action potential. 2. In the PM cell body excitable membrane behavior is dominated by only two currents, a sodium current (INa) and a delayed rectifier (IK). 3. In contrast, in the N1 cell INa and IK is supplemented with the presence of a transient potassium current, IA. 4. A comparison between INa and IK in the two cell types did not reveal any significant difference in activation and inactivation kinetics of either current between neurons. 5. Thus, the properties and presence of the A-current in the N1 cell and not in the PM cell may account for the functional difference in excitability of the two kinds of neurons.

Action Potentials↗
PubMed1989

Different actions of a short-acting barbiturate on sodium and potassium conductances in invertebrate and vertebrate neurons.

In this study, the effects of methohexital are compared on the voltage-gated sodium (Na+) and potassium ion (K+) conductances of Retzius cells in the leech Macrobdella and of dorsal root cells of the chick in culture. Under current-clamp conditions methohexital prolonged the Na+-dependent action potential of neurons in the leech. This prolongation occurred in the absence of changes in resting membrane potential or the maximum rate of depolarization of the spike. The prolonged action potentials were identical to those recorded in the same neurons in the absence of outward currents [i.e. in Ca2+-free Ringer's solution containing Mn2+, tetraethylammonium chloride (TEA) and 4-aminopyridine (4-AP)]. They consisted of an initial spike, followed by a plateau lasting several hundreds of milliseconds. Both components of the action potential were Na+-dependent and resistant to tetrodotoxin (TTX), while the plateau was selectively blocked by saxitoxin (STX), suggesting that it originated from the flow of Na+ through a conductance different from that underlying the spike potential (Johansen and Kleinhaus, 1987). Similarly, the plateau of the action potential prolonged by methohexital, described in this study was abolished by 50 microM saxitoxin. These results suggest that the action of the drug resulted from a block of repolarizing K+-conductances. This was confirmed by voltage-clamp experiments which showed that methohexital (100-1000 microM) reduced both IK and IA in the Retzius cell, essential mimicking the combined effects of TEA and 4-AP (Johansen and Kleinhaus, 1986b). In contrast, in dorsal root cells, methohexital decreased the amplitude of Na+ and K+ currents equally. This modulation of ionic conductances by methohexital may be important for the sedative and anesthetic actions of the drug.

4-Aminopyridine↗
PubMed1989

Axonal guidance and the development of muscle fiber-specific innervation in Drosophila embryos.

The outgrowth of peripheral nerves and the development of muscle fiber-specific neuromuscular junctions were examined in Drosophila embryos using immunocytochemistry and computer-enhanced digital optical microscopy. We find that the pioneering of the peripheral nerves and the formation of the neuromuscular junctions occur through a precisely orchestrated sequence of stereotyped axonal trajectories, mediated by the selective growth cone choices of pioneer motoneurons. We have also examined the establishment of the embryonic muscle fibers and, using intracellular dye fills, have identified cells that are putative muscle pioneers. The muscle fibers of the bodywall have completed their morphogenesis prior to the initiation of synaptic contacts, and owing to the timing of neurite outgrowth from the CNS, synaptogenesis is synchronous at muscle fibers throughout the bodywall. At each muscle fiber the innervating axons make their initial contacts on a characteristic surface domain of the target cell's membrane. Through stereotyped growth cone-mediated trajectories the motoneurons actively establish the basic anatomical features of the mature neuromuscular junction, including the stereotyped, muscle fiber-specific branch anatomy. These events occur without significant process pruning or apparent synapse elimination. Our results suggest that the basic elements of the mature neuromuscular innervation, including the details of the ending trajectory on the target cell's surface, are formed by the precise navigation and presumed recognition by the motoneuron growth cones of muscle membrane surface features.

Animals↗
PubMed1989

Stereotypic morphology of glutamatergic synapses on identified muscle cells of Drosophila larvae.

The distribution and morphology of glutamatergic synapses on Drosophila bodywall muscle fibers were examined at the single-synapse level using immunocytochemistry and electrophysiology. We find that glutamate-immunoreactive motor endings innervate the entire larval bodywall musculature, with each muscle fiber receiving at least one glutamatergic ending. The innervation is initiated at stereotyped locations on each muscle fiber from where moderately branched varicose nerve processes project over the internally facing muscle surface. Individual muscle fibers have distinct stereotypic patterns of nerve endings that occupy characteristic regions on the cell surface. The muscle-specific branching pattern of motor endings is reiterated by segmentally homologous fibers. Two morphological types of innervating nerve processes can be distinguished by their bouton size distributions: (1) Type I processes, which have localized branching and a broad size distribution of relatively large varicosities ranging up to 8 microns (mean diameter, 3.1 +/- 1.6 microns; +/- SD, n = 521), and (2) thinner Type II processes, which have a narrower distribution of small varicosities with a mean diameter of only 1.4 +/- 0.6 microns (+/- SD, n = 214). Immunoelectron microscopy with peroxidase-labeled second antibody demonstrates that the varicosities are surrounded by a subsynaptic reticulum, that they contain immunoreactive vesicles of about 30-50 nm, and thus probably represent synaptic release sites. By iontophoretic application of glutamate we mapped the responsive sites on the muscle surface and found an excellent correspondence between transmitter sensitivity and the patterns of endings as described by immunocytochemistry. In contrast to our finding of numerous glutamate iontophoresis-sensitive sites, we did not detect any aspartate-responsive muscles. These data provide strong new evidence for glutamate being an endogenous transmitter at the Drosophila larval neuromuscular junction.

Animals↗
PubMed1988

Voltage clamp characterization of a calcium-dependent chloride conductance in a putative invertebrate motoneuron.

1. The properties of a Ca-activated Cl-current ICl(Ca) were investigated with the two electrode voltage clamp technique in the AL1 cell of the leech Haementeria ghilianii. 2. ICl(Ca) was revealed after Cl-loading of the cells, with outward K-currents eliminated by replacement of intra- and extracellular K with Cs, and with Na currents blocked by 1 microM TTX. CsCl-containing electrodes were used for recording and current passing. 3. In response to depolarizing voltage steps the cells exhibited sustained Cl-dependent currents the size and polarity of which varied with [Cl]0. The reversal potentials of tail currents of this conductance varied with [Cl]0 as predicted for the equilibrium potential of Cl by the Nernst equation and were unaffected by changes in extracellular cation concentration. 4. The decay of the Cl-dependent tail-currents followed a process which could be described by the sum of two exponentials with time constants tau 1 and tau 2 on the order of about 100 ms and 800 ms, respectively. No voltage-dependence of the time constants was apparent; however, tau 1 varied with the amount of Ca-influx. 5. The Cl-current required Ca for its activation. All current flow was abolished in Mn-containing Ringer solutions and when Ba was substituted for Ca. However, Sr could partially substitute for Ca as an activator of the current. 6. The activation curve for Cl-dependent tail currents was U-shaped directly paralleling the amount of Ca-influx, and no Cl-current flow could be induced a depolarizations below the activation threshold or beyond the apparent reversal potential for the Ca-current.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Continuous oestrogen-progestogen treatment and bone metabolism in post-menopausal women.

The suggestion that norethisterone acetate (NETA) stimulates bone formation prompted us to investigate calcium and bone metabolism in post-menopausal women treated with a continuous combination of oestrogen and NETA. The study included 49 healthy post-menopausal women. After an initial examination the women were randomly allocated to 2 yr of treatment with either hormones or placebo; 43 women completed the study. Within the first year of treatment the hormone group showed a slight, but significant, increase in bone mineral content in the forearms (single photon absorptiometry) and in the total skeleton (dual photon absorptiometry). After this initial increase the bone mass remained constant throughout the trial. Bone mineral density of the spine (dual photon absorptiometry) showed a significant increase of more than 5% in the hormone group. There were significant decreases of 4-7% in bone mass in the placebo group over 2 yr. Biochemical estimates of bone turnover (plasma bone Gla protein, serum alkaline phosphatase, fasting urinary calcium and fasting urinary hydroxyproline) fell significantly in the hormone group, but remained unchanged in the placebo group. We conclude that continuous administration of NETA in combination with oestrogen provides effective prophylaxis against post-menopausal bone loss, although it does not produce a persistent positive calcium balance in early post-menopausal women.

Alkaline Phosphatase↗
PubMed1988

Pigmented paravenous chorioretinal atrophy.

Two patients with pigmented paravenous chorioretinal atrophy are presented. Both patients had chorioretinal atrophy with pigment clusters located in the paravenous areas, and one of the patients had macular affection. This patient had exotropia and juvenile cataract, the other patient had senile cataract. Electroretinography showed decreased, but not totally extinguished potentials. Automatic and manual perimetry revealed relative and absolute scotomas corresponding to the atrophic paravenous areas. To our knowledge this is only the sixth report of pigmented paravenous chorioretinal atrophy with macular affection.

Adult↗
PubMed1988

Secondary lens implantation.

A retrospective study is presented of a series of anterior chamber lens implantation in 64 eyes of 54 patients after an earlier cataract extraction. Best corrected final post-operative visual acuity was better or the same of best corrected pre-operative vision in 93.8% of eyes. Vision deteriorated significantly in 4 eyes, in 3 eyes cystoid macular oedema was suspected clinically, and in 1 because of open angle glaucoma. Patients requiring anterior vitrectomy had the least favourable outcome with retinal complications in 33%. Secondary lens implantation is safe. However, great caution is recommended for patients who will require anterior vitrectomy on account of the higher rate of retinal complications.

Adult↗