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Biomedical subjects

J Johansen

Publications and source records attributed to J Johansen.

At least 109 records · Page 6Linked to original sources

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↗

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↗

Effects of medazepam on voltage-gated ion currents of cultured chick sensory neurons.

The effects of the benzodiazepine, medazepam, were investigated in current and voltage-clamped cultured chick dorsal root ganglion neurons. Under current clamp, micromolar concentrations initially elevated the action potential threshold and blocked both the sodium and calcium components of the spike. In voltage clamp, low (I(Ca.T)) and high (I(CA.N/L)) threshold calcium, sodium (I(Na)) and the delayed rectifier potassium (I(K)) currents were isolated by the use of appropriate solutions and voltage command protocols. Medazepam depressed both subtypes of I(Ca) equally well with calculated half-maximal depression at 77 microM. At a fixed concentration of 200 microM, medazepam depressed I(Na) (70 +/- 9%) and I(K) (73 +/- 6%) to a degree comparable to I(Ca) (75 +/- 3%). The results show that benzodiazepines can modulate the activity of several voltage-gated ion currents in chick dorsal root ganglion neurons.

Animals↗

In situ patch-clamp recording of calcium-activated potassium channels from an identified leech neuron.

The paired anterior lateral giant cells of the leech Haementeria have only two active voltage gated ionic currents. We took advantage of this simple complement of ionic currents to investigate the single channel properties of this cells' calcium-activated K+ current (I(K,Ca) in situ. Cell-attached patch recordings showed large, bursting events with a conductance of approximately 90-100 pS which had extrapolated reversal potential consistent with K+ events. The channel open time distribution was well described by a single exponential process while the channel closed times were bi-exponentially distributed. The results show that the single channel properties of I(K,Ca) in annelids closely resemble those of similar currents described in vertebrates.

Animals↗

Whole body retention of 99mTc-diphosphonate. Relation to biochemical indices of bone turnover and to total body calcium.

Whole body retention (WBR) and urinary excretion (UE) of 99mTc-diphosphonate were determined in 161 healthy adults and the results were compared to accepted biochemical markers of bone turnover. WBR was corrected for total body bone mineral (TBBM) and UE for forearm bone mineral content (BMC). Both uncorrected and corrected retention measurements were highly significantly correlated to the biochemical markers (P less than 0.001), but the r values were low (0.22-0.64). All bone turnover variables demonstrated considerably higher levels of bone turnover in postmenopausal women than in premenopausal women (P less than 0.001), whereas the variables were unchanged with age in men. The correction of WBR for TBBM and UE for BMC increased the validity of the retention methods and the two calculations gave exactly the same results on a group basis, both demonstrating significantly higher bone turnover in women than in men in each age group (P less than 0.05-P less than 0.001). All the turnover variables were measured in a group of perimenopausal women (n = 33). The data clearly demonstrated that bone turnover is menopause dependent, whereas age in itself is of minor significance.

Adult↗

Proton magnetic resonance spectroscopy of leech muscle and nervous system.

1. Proton nuclear magnetic resonance spectroscopy (1H NMR) was used to measure the major intracellular metabolites in perchloric acid extracts of the Macrobdella decora muscle and nervous systems and the Oryctolagus cuniculus cerebrum. 2. Acetate, alanine, choline, glutamate, inositol, and lactate were assigned in the spectrum of leech ventral cord, leech muscle, and rabbit cerebrum. 3. Hirudonine and propionate were clearly observed only in the spectrum of leech muscle. 4. Creatine, N-acetyl aspartate, gamma aminobutyric acid, aspartate, and taurine, distinctive components of spectra of the mammalian cerebrum, were not seen in the invertebrate spectra. 5. 1H NMR spectroscopy provides a simple and rapid means of characterizing the major organic metabolites found in leech muscle and nervous tissues.

3-Hydroxybutyric Acid↗

The effects of procaine, strychnine and penicillin on nociceptive neurons in leech segmental ganglia.

Procaine, strychnine and penicillin selectively depolarized the membrane potential and prolonged the action potential recorded in the lateral but not the medial nociceptive (N) cell in the hirudinid leech Macrobdella decora. In contrast, procaine did not differentiate between medial and lateral N cells in two other hirudinid leeches Hirudo medicinalis and Haemopis marmorata. In these species, the drug equally decreased the amplitude of action potentials in both types of N cells without effecting their resting membrane properties. In the nociceptive neurons of the glossiphoniid leech Haementeria ghilianii which possesses only one type of N cell, procaine produced a depolarization and prolonged the action potential. This finding indicates that the single pair of N cells in Haementeria is of the lateral type. The results suggest that the lateral type N cell in Macrobdella and Haementeria share a unique Na+-dependent conductance which is selectively opened by the local anesthetics procaine and strychnine as well as by penicillin. This conductance is either not present or insensitive to the drugs in the homologous N cells in the two other leech species examined.

Animals↗

Familial hypocalciuric hypercalcaemia. III: Bone mineral metabolism.

Bone mineral metabolism was studied in 10 subjects with familial hypocalciuric hypercalcaemia (FHH) and 10 age-, sex- and surface area matched healthy controls. Bone turnover was estimated by urinary calcium and hydroxyproline excretions relative to creatinine (Ca/Creat and OHPr/Creat, respectively), serum bone Gla-protein (S-BGP) and serum alkaline phosphatase (S-ALP). Bone status was evaluated by measurement of bone mineral content (BMC) on both forearms and X-ray examinations of the hands. Ca/Creat and OHPr/Creat (indices of bone resorption) were both significantly higher in the FHH group than in the controls. S-BGP and S-ALP (indices of bone formation) tended towards a higher level in the FHH subjects, but the differences were not significant. The BMC values were similar in the two study groups and did not change with time. We conclude that these patients with FHH might have a bone turnover higher than normal, and that the increased bone resorption must be paralleled by an increased bone formation.

Bone and Bones↗

Voltage-clamp analysis of the ionic conductances in a leech neuron with a purely calcium-dependent action potential.

1. The purely calcium-dependent action potential of the anterior lateral giant (ALG) cell in the leech Haementeria was examined under voltage clamp. 2. Analysis with ion substitutions showed that the ALG cell action potential is generated by only two time- and voltage-dependent conductance systems, an inward Ca-dependent current (ICa) and an outward Ca-dependent K current IK(Ca). 3. The kinetic properties of the inward current were examined both in Cs-loaded neurons with Ca as the current carrier as well as in Ba-containing Ringer solutions with Ba as the current carrier, since Ba effectively blocked all time- and voltage-dependent outward current. 4. During a maintained depolarization, Ba and Ca currents activated with a time constant tau m, they then inactivated with the decay following a single exponential time course with a time constant tau h. The time constants for decay of both Ba and Ca currents were comparable, suggesting that the mechanism of inactivation of ICa in the ALG cell is largely voltage dependent. In the range of potentials from 5 to 45 mV, tau m varied from 8 to 2 ms and tau h varied from 250 to 125 ms. 5. The activation of currents carried by Ba, after correction for inactivation, could be described reasonably well by the expression I'Ba = I'Ba(infinity) [1--exp(-t/tau m)]. 6. The steady-state activation of the Ba-conductance mBa(infinity) increased sigmoidally with voltage and was approximated by the equation mBa(infinity) = (1 + exp[(Vh-6)/3])-1. The steady-state inactivation hBa(infinity) varied with holding potential and could be described by the equation hBa(infinity) = [1 + exp(Vh + 10/7)]-1. Recovery from inactivation of IBa was best described by the sum of two exponential time courses with time constants of 300 ms and 1.75 s, respectively. 7. The outward current IK(Ca) developed very slowly (0.5-1 s to half-maximal amplitude) and did not inactivate during a 20-s depolarizing command pulse. Tail current decay of IK(Ca) followed a single exponential time course with voltage-dependent time constants of between 360 and 960 ms. The steady-state activation n infinity of IK(Ca) increased sigmoidally with depolarization as described by the equation n infinity = [1 + exp(Vh-13.5)/-8)]-1. 8. The reversal potentials of IK(Ca) tail currents were close to the expected equilibrium potential for potassium and they varied linearly with log [K]o with a slope of 51 mV. These results suggest a high selectivity of the conductance for K ions.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Saxitoxin differentiates between two types of Na+-dependent potentials in the Retzius cell of hirudinid leeches.

The effects of tetrodotoxin (TTX) and saxitoxin (STX) on the action potentials recorded in Ca2+-free solution in the absence of Ca2+ and K+ currents were investigated in the Retzius cell of three hirudinid leech species (Hirudo medicinalis, Macrobdella decora and Poecilobdella granulosa) and in the glossiphoniid leech Haementeria ghilianii. In the four leech species, stimulation of the Retzius cell in the presence of 25 mmol l-1 tetraethylammonium chloride (TEA), 3 mmol l-1 4-aminopyridine (4-AP) and 2mmol l-1 Mn2+ evoked prolonged action potentials consisting of an initial fast-rising spike followed by a plateau lasting several hundreds of milliseconds. The amplitude and duration of both components of action potentials recorded under these conditions were dependent on [Na+]o. In the hirudinid leeches the initial spike was unaffected by TTX and STX whereas the plateau was selectively blocked by micromolar concentration of STX. In Haementeria both the initial spike and the subsequent plateau were sensitive to nanomolar concentrations of STX and TTX with an estimated ED50 of approximately 20 nmol l-1 for inhibition of Vmax of the fast spike. The results suggest that there are two types of ionic currents mediating the two distinct components of Na+-dependent action potentials in the Retzius cell: (1) a fast-inactivating one, presumably underlying the normal spike which is TTX- and STX-resistant in hirudinid leeches but sensitive to both agents in Haementeria and (2) a low-threshold, prolonged current which underlies the plateau recorded from these cells in the absence of Ca2+ and K+ currents and which is selectively blocked by STX in hirudinid leeches but sensitive to both STX and TTX in Haementeria. It is likely that the variable kinetic and pharmacological properties that characterize the various Na+ potentials in these identified homologous neurones may be of functional significance and result from differences in the molecular structure of their Na+ channels.

4-Aminopyridine↗

Late diagnosed congenital dislocation of the hip.

During the years 1975 to 1979, 82,574 children from five counties in southeast Norway were live-born, 197 of whom were treated for late detected CDH, for an incidence of 2.4 per 1,000 live births, i.e., 0.4 promille dislocation, 0.6 promille subluxation, and 1.4 promille dysplasia of the acetabulum without dislocation. All the hips had been found stable at birth. Eighty-six percent were girls, and the left hip was affected in 48 percent, the right hip in 31 perent, and both hips in 21 percent. Only 6.5 percent were delivered in the breech position. This and the stability found neonatally may indicate an etiologic difference between neonatally and late diagnosed CDH.

Breech Presentation↗

Barbiturates block divalent cation action potentials in leech nociceptive cells.

Phenobarbital (PNB), pentobarbital (PTB) and methohexital (MTX) decreased the maximum rate of depolarization Vmax and duration of divalent cation action potentials elicited in leech nociceptive neurons in Na+-free solutions containing the K+-channel blocker TEA, without significantly affecting resting membrane potential or conductance. The block of the divalent cation action potentials was reversible and dose-dependent, ED50 for inhibition of Vmax being 560 microM for MTX, 800 microM for PTB and 3000 microM for PNB. This order of potency correlated well with the ratio of unchanged/charged form of the drugs at physiological pH suggesting that in leech, as in other preparations, the non-ionized form was the active one. In Na+-containing Ringer, the 3 barbiturates depolarized and decreased membrane resistance in the lateral nociceptive cells, but not the medial nociceptive cells. These results provide additional information regarding the newly described pharmacological differences among closely related neurons. These membrane actions may be related to some of the excitatory properties described for other barbiturates in invertebrate and mammalian preparations.

Action Potentials↗

Transient and delayed potassium currents in the Retzius cell of the leech, Macrobdella decora.

The properties of a quickly inactivating transient K current (IA) and a slowly inactivating delayed K current (IK) were investigated with two-electrode voltage-clamp techniques in the isolated soma of the Retzius cell of the leech, Macrobdella decora. The two currents could be pharmacologically separated according to their different sensitivities to tetraethylammonium ions (TEA) and 4-aminopyridine (4-AP). IA was totally blocked by 3 mM 4-AP but not affected by 25 mM TEA. IK was suppressed almost completely by 25 mM TEA, whereas its peak amplitude only decreased by 10-15% in 3 mM 4-AP. IA was activated at membrane potentials more positive than -35 to -30 mV, whereas the threshold for IK was at more positive potentials of approximately -20 to -15 mV. The activation of IA was rapid with a voltage-dependent time constant [tau m(A)] that varied from 6 to 2 ms for command potentials between -20 and 10 mV (at 22-24 degrees C). The inactivation, which was independent of voltage, was somewhat slower with a time constant (tau A) of approximately 90-110 ms. The time constants for activation [tau m(K)] and the early inactivation phase (tau K) of IK were both voltage dependent. In the range of potential steps from 0 to 30 mV, tau m(K) varied from 12 to 4.5 ms and tau K from 1,500 to 700 ms. The steady-state inactivation of IA varied with holding potential and was complete at potentials more positive than -30 mV. IA was fully available from potentials more negative than -70 mV. IK did not show steady-state inactivation below its threshold of activation. The time course of IA during a maintained depolarization could be reasonably described by the expression IA(t) = IA(infinity) [1-exp(-t/tau m(A))]2 exp(-t/tau A). The time course of activation of IK without allowance for inactivation was approximated by the expression IK(t) = IK(infinity) [1-exp(-t/tau m(K))]2. The reversal potentials and magnitude of both IA and IK were dependent on extra-cellular K concentration, which suggest that a substantial part of the two currents was carried by K ions.

4-Aminopyridine↗

Snapping hip.

Thirty-one snapping hips in 24 patients were followed for 4 (1-11) years after operation. At follow-up, snapping persisted in nine hips, in three cases accompanied by pain. The femoral neck angle was less in the patients (128 degrees) than in a control group (134 degrees).

Adolescent↗

Differential sensitivity of tetrodotoxin of nociceptive neurons in 4 species of leeches.

We have recently shown that the nociceptive neurons (N cells) in the leech can be segregated into a medial type (Nmed) and a lateral type (Nlat) according to their physiological and pharmacological properties. We now report that the Na-dependent action potential (AP) of the 2 cell types in Macrobdella have differential sensitivities to tetrodotoxin and that the APs of the N-cell homologs from different leech species also vary considerably in their response to TTX. The normal AP of the N cells in the 4 leech species was exclusively Na-dependent; its overshoot varied logarithmically with [Na]0, was unaffected by the presence of Mn and absence of Ca, and could not be elicited in Na-free Ringer's solutions. The decrease in the maximal rate of depolarization (Vmax) of the Na-dependent AP of the Nmed cell in Macrobdella produced by TTX followed a reverse Langmuir curve for bimolecular reaction with an ED50 of 9 microM. Almost complete blockage was obtained at 50 microM. In contrast, TTX inhibition of Vmax in the Nlat cell reached saturation at a level of only 55% reduction in Vmax even at doses in excess of 200 microM TTX. The simplest interpretation of these data is that there are 2 types of Na channels in the Nlat cell. This is further supported by the fact that the dose-response data could be well fitted by a Langmuir curve, assuming that the Nlat cell possesses 2 populations of Na conductances--one insensitive to TTX and one (like the Nmed cell) with an ED50 to TTX of 9 microM, the 2 populations being present in a 0.45:0.55 ratio, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Expression of surface antigens recognized by the monoclonal antibody lan 3-2 during embryonic development in the leech.

The monoclonal antibody lan 3-2 was used as a marker for the developmental expression of surface antigens which are specific for the two pairs of nociceptive neurons and a subset of axons in the adult CNS of the leech. In Haemopis embryos labeling of both nerve fibers and cell bodies with the antibody appears as expected for a metameric animal in a rostrocaudal temporal gradient from about day 5-6. Surprisingly, all central cell bodies are stained by the antibody in early development. However, later in embryogenesis around day 17 the staining intensity of most cells decreases except for the nociceptive cells, which remain antibody-positive, and the adult staining pattern gradually emerges. In addition to describing the central staining pattern, we show that specific peripheral neurons associated with the segmental sensilla also are antibody-positive during development. The distribution and developmental expression of the lan 3-2-positive antigens are compared between two phylogenetically different species of leeches and the diversity of the staining pattern of the monoclonal antibody is discussed.

Animals↗