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H Nilsson

Publications and source records attributed to H Nilsson.

At least 55 records · Page 3Linked to original sources

On the cellular mechanism for the effect of acidosis on vascular tone.

The role of smooth muscle [Ca2+]i and membrane potential for the relaxation to hypercapnic (increased CO2) and normocapnic (unchanged CO2) acidosis is not complete understood. It is often stated that membrane hyperpolarization plays an important role but this has not been vigorously tested. In this study we investigated isolated rat cerebral small arteries under isobaric conditions. Lumen diameter was measured simultaneously with either [Ca2+]i or membrane potential, and acidosis was induced by increasing PCO2 or reducing HCO3- of the bathing solution or by adding HCI to a nominally bicarbonate-free solution. Confocal microscopy verified loading of smooth muscle cells with fluorescent dyes. Acidosis always reduced myogenic tone at transmural pressures between 20 and 120 mmHg. Acidification at a transmural pressure of 40 mmHg caused an increase in diameter and a decrease in [Ca2+]i. This was also seen in the presence of L-NNA and after depolarization with 50 mM K+. The response to hypercapnic and normocapnic acidosis was similar. However, while hypercapnic acidosis caused hyperpolarization, normocapnic acidosis caused depolarization. Dilatation, decrease of [Ca2+]i and depolarization, was also seen with reduction of pH in bicarbonate-free solution. We conclude that the isobaric relaxation to both hypercapnic and normocapnic acidosis is most likely mediated by a reduction of [Ca2+]i. Membrane potential may on the other hand not play a major role for this reduction of [Ca2+]i and it is possible that molecular CO2 has an effect on the membrane potential.

Acidosis↗

Effect of acidosis on tension and [Ca2+]i in rat cerebral arteries: is there a role for membrane potential?

The cellular mechanism responsible for the reduction of tension in cerebral small arteries to acidosis is not known. In this study the role of smooth muscle intracellular Ca2+ concentration ([Ca2+]i) and membrane potential for the relaxation to acidosis was investigated in isolated rat cerebral small arteries. Isometric force was measured simultaneously with [Ca2+]i (fura 2) or with membrane potential (intracellular microelectrodes), and acidosis was induced by increasing PCO2 or reducing HCO3- of the bathing solution. Both hypercapnic and normocapnic acidosis were associated with a reduction of intracellular pH [measured with 2',7'-bis-(carboxyethyl)-5 (and -6)-carboxyfluorescein], caused relaxation, and reduced [Ca2+]i. However, whereas hypercapnic acidosis caused hyperpolarization, normocapnic acidosis was associated with depolarization. It is concluded that a reduction of [Ca2+]i is in part responsible for the direct effect of the acidosis on the vascular smooth muscle both during normo- and hypercapnia. The mechanism responsible for the reduction of [Ca2+]i differs between the hypercapnic and normocapnic acidosis, being partly explained by hyperpolarization during hypercapnic acidosis, whereas it is seen despite depolarization during normocapnic acidosis.

Acidosis↗

Absorption of solar radiation by an ellipsoid sensor simulated the human body.

Assessment of heat gain in man caused by solar radiation is one of the most important problems in research of the human heat balance outdoors. The purpose of the present study was to investigate a new method for estimation of solar heat income. Absorption of short wave radiation (direct, diffuse and reflected) was measured with an ellipsoid sensor representing a simple, physical model of man. Measurements were performed in climatic chamber with the use of an iodide CSI solar lamp. The absorbed quantity of solar radiation varied as a result of sun altitude as well as of a colour and insulation of fabric covering the ellipsoid sensor. The new coefficients derived from our investigations for estimating doses of absorbed solar radiation should be applicable for a standing man. They correlate better with mean skin temperature observed on subjects outdoor than previous results obtained based on a cylinder as an analogue model of man. The ellipsoid sensor covered by a black fabric absorbed about 6 times more of solar radiation than when covered by a white textile.

Absorption↗

Interactions between neuropeptide Y and the adenylate cyclase pathway in rat mesenteric small arteries: role of membrane potential.

1. Simultaneous measurements of membrane potential and tension were performed to investigate the intracellular mechanisms of neuropeptide Y (NPY) in rat mesenteric small arteries. 2. NPY (0.1 microM) depolarized arterial smooth muscle cells from -55 to -47 mV and increased wall tension by 0.22 N m-1, representing 11% of the contraction elicited by a high-potassium solution. Isoprenaline (1 microM) and acetylcholine (1 microM) evoked hyperpolarizations of 11 and 17 mV, respectively. NPY inhibited the isoprenaline-induced effects on membrane potential without affecting those of acetylcholine. 3. Forskolin evoked sustained concentration-dependent hyperpolarizations of small mesenteric arteries. NPY (0.1 microM) inhibited the responses to 1 microM forskolin, but did not alter the stable hyperpolarization elicited by the specific activator of protein kinase A (PKA) SP-5,6-DCl-cBIMPS (0.1 mM). Forskolin increased the cyclic AMP (cAMP) content of the arteries 21-fold, and NPY inhibited the forskolin-evoked increase in cAMP levels by 91%. 4. The hyperpolarization produced by 1 microM forskolin was not affected by either charybdotoxin (0.1 microM) or 4-aminopyridine (0.5 mM), but glibenclamide (5 microM) inhibited the hyperpolarization by 70%. Glibenclamide also inhibited the hyperpolarization evoked by SP-5,6-DCl-cBIMPS by 59%. 5. Neither depolarization nor contraction caused by NPY were significantly affected by either glibenclamide (5 microM) or nifedipine (1 microM), but they were reduced by gadolinium (10 microM). However, the blocking effect of NPY on forskolin-elicited hyperpolarization was not affected by gadolinium. 6. Charybdotoxin (0.1 microM) and 4-aminopyridine (0.5 mM) strongly enhanced the depolarization and contraction caused by NPY (0.1 microM), and nifedipine (1 microM) prevented the enhanced responses to NPY in the presence of charybdotoxin. 7. These findings suggest that NPY acts through at least two different intracellular mechanisms in mesenteric small arteries: a depolarization of arterial smooth muscle which is probably due to activation of non-selective cation channels, and a marked inhibition of adenylate cyclase activity, which in turn inhibits the hyperpolarization produced by cAMP accumulation in these arteries.

4-Aminopyridine↗

Evidence for several roles of dynein in pigment transport in melanophores.

Melanophores are specialized cells that transport pigment granules to and from the cell center, giving animals the ability to change skin color. A kinesin-related plus-end motor has previously been shown to be responsible for pigment granule dispersion [V.I. Rodionov, F.K. Gyoeva, and V.I. Gelfand. Proc. Natl. Acad. Sci. USA. 1991, 88:4956-4960]. Here, we have microinjected a dynein antibody (70.1) into cultured cod (Gadus morhua) melanophores and used the dynein inhibitor vanadate on permeabilized melanophores in skin pieces, to examine the role of the microtubule minus-end motor dynein in these cells. Both pigment granule aggregation and maintenance of the spherical central pigment mass (CPM) were inhibited by the antibody and by vanadate. Vanadate or antibody treatment of cells with aggregated pigment did not induce pigment dispersion. However, when the antibody-injected cells were induced to disperse pigment, the pigment moved farther to the cell periphery, which resulted in a depletion of pigment in the cell center. Similar superdispersion of previously uniformly distributed pigment was also seen when the antibody was injected in melanophores with dispersed pigment. Our results demonstrate that both pigment aggregation and maintenance of the CPM are dynein-dependent processes. Our data further show that dynein is involved in the homogeneous distribution of dispersed pigment. These results suggest that both dynein and kinesin are active in keeping pigment granules dispersed throughout the cytoplasm, transporting pigment granules in opposite directions. The possibility that dynein is continuously active during both aggregation and dispersion, while kinesin might be the target for regulation, is discussed.

Animals↗

Assessment of respiration during video fluoroscopy of dysphagic patients.

RATIONALE AND OBJECTIVES: The authors evaluated the coordination of swallowing and respiration in dysphagic patients. MATERIALS AND METHODS: Video fluoroscopy and respirometry were performed simultaneously during 98 swallows in 33 patients (18 women, 15 men) with a median age of 70 years (interquartile range, 52-78 years). Pharyngeal transit time, deglutition apnea, and the ratio between the two (swallowing safety index) were calculated. Presence of a misdirected swallow (aspiration or penetration) was indicated. RESULTS: Pharyngeal transit time was not associated with deglutition apnea. Misdirected swallow was associated with a slightly prolonged pharyngeal transit time, a slightly shorter deglutition apnea, and a significantly lower swallowing safety index (1.8 [1.0-4.2] vs 4.5 [2.4-6.7]; P < .001) compared with normally directed swallow. The association between misdirected swallow and lower swallowing safety index was independent of pharyngeal transit time. CONCLUSION: Assessment of respiration is important in the evaluation of dysphagia. Aspiration, especially in elderly dysphagic patients, may be a consequence of primarily disturbed respiration. A low swallowing safety index may indicate risk of misdirected swallow.

Aged↗

Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice.

The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.

Animals↗

Stiffness of the common carotid artery in healthy 50-year-old subjects.

We examined whether, in a group of healthy 50 year-old subjects, there was a relation between the stiffness of the common carotid artery and risk factors for atherosclerosis and, further, if there was a sex difference in these healthy individuals. A group of 248 healthy subjects (123 men and 125 women), all 50 years of age, were examined. The elastic properties of the common carotid artery, measured in terms of stiffness index, were investigated with an ultrasound technique. Men had significantly higher stiffness index than women (5.46 +/- 1.32 vs. 5.04 +/- 1.05, P < 0.01). The arterial diameter was significantly larger in men. When comparing stiffness index in a subgroup of 38 men and women with similar arterial diameters, no significant difference in stiffness index was found. Multivariate analysis showed that smoking habits, measured as pack-years, insulin levels and the low-density lipoprotein (LDL)-/high-density lipoprotein (HDL)-cholesterol ratio was independently significantly associated with the stiffness index. Sex did not emerge as a significant variable. In conclusion, there is a relation between the stiffness of the carotid arteries and risk factors for atherosclerosis such as smoking, insulin levels and LDL-/HDL-cholesterol ratio in healthy 50-year-old subjects. The stiffness is higher in men than in women, probably dependent on differences in arterial size and possibly also on risk factors.

Arteriosclerosis↗

Inositol 1,4,5-trisphosphate turnover enzymes--activities and subcellular distribution in hepatocarcinogenesis.

The metabolism of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in homogenates and sub-fractions from normal rat liver and premalignant liver nodules was investigated. The activities of 5-phosphatase, expressed as pmol converted substrate per minute and mg protein, were equal when using the two substrates, and did not differ between normal and nodular homogenates. Subcellular fractions were purified by sequential steps of differential centrifugation and density gradient fractionation procedures. The total phosphatase activity was found to be distributed between cytosol (15%) and membraneous fractions (75%), with most of the enzyme activity residing in the plasma membranes. A doubling of phosphatase specific activity was seen in the nodular low density membrane fraction, containing Golgi apparatus and endosomes, as compared with normal liver. Inositol 1,4,5-trisphosphate 3-kinase activity was found to be exclusively cytosolic. No difference in this enzyme was seen between the two tissue types studied. Vasopressin (0.2 or 2 microM) had no effect either on phosphatase or kinase activity. The compartmentalization of inositol polyphosphate 5-phosphatase activity presents a possible explanation of earlier findings that premalignant liver tissue was able to respond with inositol 1,4,5-trisphosphate, but not inositol 1,3,4,5-tetrakisphosphate formation after agonist stimulation.

Animals↗

KCa-channel blockade prevents sustained pressure-induced depolarization in rat mesenteric small arteries.

In small blood vessels, elevation of transmural pressure induces myogenic constrictions and smooth muscle depolarization. The role of calcium-activated K+ channels (KCa channels) in these responses was examined in cannulated rat mesenteric small arteries. Inner and outer diameter were continuously monitored with a video technique. Smooth muscle membrane potential was recorded simultaneously using microelectrodes. To test for myogenic responsiveness, the transmural pressure was changed stepwise in the range between 10 and 120 mmHg. Pressure elevation induced moderate myogenic responses and significant depolarization, from -54.5 +/- 0.4 (SE) mV (n = 56) at 10 mmHg to -47.3 +/- 1.8 mV (n = 12) at 120 mmHg. Norepinephrine (NE, 0.67 and 10 microM) induced constriction and vasomotion, augmented myogenic responsiveness, and shifted the pressure-membrane potential relation to more depolarized values. Blockade of the Kca channels with charybdotoxin (ChTX) suppressed the responsiveness to pressure. In the absence of ChTX, with 0.67 microM NE, pressure elevation from 10 to 120 mmHg induced depolarization from -46.9 +/- 1.0 (n = 16) to -35.8 +/- 0.7 (n = 12) mV, whereas because of the myogenic response, the diameter increased only by 7%. In the presence of ChTX, with 0.3 microM NE, pressure changed the membrane potential from -41.0 +/- 1.1 (n = 12) to -37.8 +/- 0.7 mV (n = 4), which was not significant, and the diameter increased by 28%. These results demonstrate that blockade of KCa channels reduces responsiveness to pressure elevation. This suggests that pressure may induce depolarization and concomitant myogenic responsiveness by closure of KCa channels.

Animals↗

Localization of kinesin and cytoplasmic dynein in cultured melanophores from Atlantic cod, Gadus morhua.

In this study we have analyzed pigment translocation in cultured melanophores from the cold-tempered Atlantic cod, Gadus morhua. The transport process was found to be cold-adapted, as it proceeded at low temperatures. Both the typical morphology of the melanophores with long cytoplasmic processes, and the ability to translocate pigment granules, were found to be highly dependent on microtubules. Microtubules in melanophores were relatively stable to vinblastine treatment compared to microtubules in other skin cells. Extensive posttranslational modifications of tubulin were found. Detyrosinated and polyglutamylated microtubules were frequent, while acetylated microtubules only comprised a subpopulation or domains of microtubules. Both cod kinesin and dynein were distributed in a punctate pattern throughout the melanophores in close proximity to microtubules. The motors accumulated together with pigment granules during aggregation and were dispersed during translocation of pigment granules to the periphery. Individual melanosomes were occasionally found to rapidly change direction during translocation. Our data raise the interesting possibility that both kinesin and dynein are bound to pigment granules. This is of functional significance, since pigment granules are transported back and forth in the melanophores, and may be activated differently during aggregation and dispersion to generate translocation.

Animals↗

Quantitative aspects of swallowing in an elderly nondysphagic population.

The prevalence of swallowing impairment increases with age and is a major health care problem in the elderly. It has been assumed that age-related changes in nerves and muscles hamper muscle strength and coordination of swallowing. However, it is unclear what impairment is related to primary aging and what is the consequence of diseases prevalent in the elderly (secondary aging). In order to quantify swallowing in nondysphagic elderly we used the noninvasive ROSS (Repetitive Oral Suction Swallow) test. A total of 53 individuals aged 76 +/- 5 years (mean +/- SD) were examined. We found that the nondysphagic elderly demonstrated significant differences compared with young individuals in 10 of 17 measured variables, i.e., decreased peak suction pressure, increased frequency of multiple swallows after one ingestion, increased frequency of polyphasic laryngeal movements, increased frequency of inspiration after swallowing, and increased frequency of coughing during or after swallowing. Therefore, primary aging mainly seems to influence coordination of swallowing, but oral and pharyngeal swallow per se seem to be unaffected.

Adult↗

Quantitative assessment of swallowing in healthy adults.

Swallowing has hitherto been evaluated during physical examination, radiologic barium studies, manometry, and cervical auscultation. Radiography principally demonstrates qualitative aspects of oral and pharyngeal function, whereas quantitative aspects have primarily been documented by manometry. To evaluate swallowing quantitatively, without using invasive methods or radiation, we have applied a combined test of water drinking, i.e., the Repetitive Oral Suction Swallow test (ROSS). The test provides reliable measurements of suction pressure, bolus volume, timing of important events in oral and pharyngeal swallow, and respiration. The test is described and results from 292 healthy, non-dysphagic subjects are presented. We found a mean bolus volume of 25.6 +/- 8.5 ml during single swallow and 21.1 +/- 8.2 ml during stress (forced, repetitive swallow). During forced, repetitive swallow, the bolus volume was more strongly associated with suction time (r2 = 0.55) than with peak suction pressure (r2 = 0.04), indicating that suction time is more important than suction pressure in determining the bolus volume. The oral-pharyngeal transit time decreased: single swallow 0.56 +/- 0.36 sec, forced repetitive swallow 0.23 +/- 0.11 sec, as did the coefficient of variation (48% and 64%, respectively) indicating a more automatic neural process for pharyngeal function in forced, repetitive swallow. The postswallow respiration started with inspiration in 10% of studied individuals, but did not correlate with deviations in other variables in the test. Thus, postswallow inspiration must be considered as normal. The ROSS test offers a rapid and easy quantitative assessment of swallowing.

Adolescent↗

Swallowing in hereditary sensory ataxia.

The oral, pharyngeal, and esophageal stages of swallowing were evaluated in 8 patients with recessively or dominantly inherited pure sensory ataxia. Six patients had swallowing difficulties: solid bolus obstruction, coughs during eating, and choking episodes. One patient had chronic bronchitis and another had recurrent pneumonia. The patients underwent a biphasic radiological barium swallow, including videofluoroscopy. No patient had a completely normal swallow. All had normal oral function, whereas pharyngeal function was abnormal in 6 patients. Esophageal function was abnormal in 6 patients. The swallowing dysfunction did not correlate with the severity of motor or sensory dysfunction in the limbs, nor with age or duration of ataxia. Our study shows that swallowing dysfunction is common in hereditary sensory ataxia. This dysfunction is likely to be due to involvement of the nucleus of the solitary tract in the brainstem. Despite some of the patients having suffered from choking episodes and others from bronchopulmonary complications, they did not spontaneously admit dysphagia. Swallowing should be evaluated thoroughly in patients with hereditary sensory ataxia since dysphagia in these patients might bring serious and potentially fatal complications.

Adult↗

Quantitative assessment of oral and pharyngeal function in Parkinson's disease.

Oral and pharyngeal dysfunction is common in Parkinson's disease. To reveal the frequency of swallowing dysfunction and correlate swallowing dysfunction with locomotor disturbances, we studied 75 patients with Parkinson's disease staged I-IV according to the Hoehn and Yahr score. We assessed oral and pharyngeal swallow during optimal medication by a quantitative test of swallowing (the ROSS test) measuring the suction pressure, bolus volume, swallowing capacity, and time for important events in the swallowing cycle. We found abnormal results in 7/12 patients (58%) in stage 1 of the Hoehn and Yahr score, in 13/14 patients (93%) in stage 2, in 29/32 patients (91%) in stage 3, and in 16/17 patients (94%) in stage 4. Abnormal test results in stages, 1, 2, and 3 were seldom related to swallowing difficulties noticed by the patients. In advanced disease (Hoehn and Yahr stage 4), the abnormal results were often considerable, with swallowing difficulties obvious to the patient. Two of 17 patients coughed during or immediately after the test and 3/ 17 patients were unable to complete the test. The degree of swallowing disturbance increased during stress (forced, repetitive swallow). The Hoehn and Yahr score and the results in the ROSS test did not correlate, indicating that swallowing disturbances are due to nondopaminergic degeneration. Silent swallowing impairment may interfere with the nutrition and quality of life in Parkinson's disease, thus it is of interest to monitor this in clinical practice.

Adult↗