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Biomedical subjects

M Møller

Publications and source records attributed to M Møller.

At least 145 records · Page 8Linked to original sources

Direct projections from the anterior and tuberal regions of the lateral hypothalamus to the rostral part of the pineal complex of the rat. An anterograde neuron-tracing study by using Phaseolus vulgaris leucoagglutinin.

The anterograde tracer, Phaseolus vulgaris leucoagglutinin, was injected into the lateral hypothalamic division of the Wistar rat. After 7 days of survival the animals were fixed by perfusion, and cryostat sections processed for visualization of the tracer by immunohistochemistry. Injections into the anterior and tuberal regions of the lateral hypothalamic division labeled neurons which projected caudally to the rostral part of the pineal complex, e.g. the deep pineal gland and the pineal stalk. Labeled fibers were in this study not observed in the superficial pineal gland. Due to the direct innervation of the lateral hypothalamic region from the retina and the involvement of this area in circadian rhythmicity, the projections, demonstrated in this study, from the lateral hypothalamic region to the pineal gland are suggested to transmit impulses which modulate the circadian activity of the rat pineal gland.

Animals↗

A direct neural projection from the intergeniculate leaflet of the lateral geniculate nucleus to the deep pineal gland of the rat, demonstrated with Phaseolus vulgaris leucoagglutinin.

The anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was injected into different subregions of the rat lateral geniculate nucleus. After a survival for 5-10 days, the rats were fixed by perfusion with 4% paraformaldehyde, whereafter the brains were cut in a cryostat and the tracer was localized by immunohistochemistry. After deposits of PHA-L involving the intergeniculate leaflet, a high number of PHA-L-immunoreactive fibers were observed to project directly into the posterior commissure. From the posterior commissure, some nerve fibers turned dorsally and entered into the deep pineal gland, a part of the pineal complex located in between the posterior and the habenular commissure. A few PHA-L-immunoreactive fibers were observed in the pineal stalk, but no fibers were detected in the superficial pineal gland. In cases where the injections were placed in the dorsal or ventral subnuclei, no immunoreactive nerve fibers were observed to enter the pineal complex. These results indicate that the intergeniculate leaflet of the lateral geniculate nucleus, a nucleus considered to be involved in circadian rhythmicity, might influence the pineal gland, via a neural projection to the rostral part of the pineal complex.

Animals↗

Innervation of the mink pineal gland with neuropeptide Y (NPY)-containing nerve fibers. An experimental immunohistochemical study.

An immunohistochemical investigation of the mink pineal gland was performed by use of antibodies raised in rabbits against neuropeptide Y (NPY) and Cys-NPY (32-36)-amide recognizing neuropeptide Y with an amidation at position 36 (NPYamide). NPY-immunoreactive nerve fibers were located predominantly in the rostral part of the pineal gland and in the pineal stalk. Immunoreactive nerve fibers were found throughout the pineal gland, but the number of fibers in the caudal part of the gland was low. The fibers were present both in the perivascular spaces and between the pinealocytes. Many NPY-immunoreactive fibers were also located in the posterior and habenular commissures; some of these fibers were connected with the fibers in the rostral part of the mink pineal gland, indicating that at least some of the NPY-immunoreactive nerve fibers are of central origin. The nerve fibers immunoreactive to amidated NPY were distributed in a similar manner. However, the number of fibers immunoreactive to NPYamide was lower than the number of fibers immunoreactive to NPY itself. After removal of the superior cervical ganglia bilaterally 22 days or 12 months before sacrifice, NPY-immunoreactive nerve fibers remained in the gland. This immunohistochemical study of the mink pineal gland therefore shows that the NPY/NPYamide-immunoreactive nerve fibers innervating the pineal gland in this species are a component of the central innervation or originate from extracerebral parasympathetic ganglia.

Animals↗

Somatostatin and prosomatostatin in the retina of the rat: an immunohistochemical, in-situ hybridization, and chromatographic study.

Specific antisera, raised in rabbits, against somatostatin 1-14, somatostatin 1-28, the fragment 1-12 of somatostatin 1-28, and prosomatostatin 20-36 were used for immunohistochemistry and gel filtration of the rat retina. With all antisera, immunoreactive perikarya could be located in the inner nuclear and ganglion cell layers. In the inner nuclear layer, amacrine cells with processes extending predominantly into the first sublayer of the inner plexiform layer were observed. Some processes extended also to the ganglion cell layer. In addition, somatostatin-immunoreactive interplexiform cells were present in the inner nuclear layer. In the ganglion cell layer, perikarya were found located in the midperiphery and in the far periphery of the retina. The neurons located in the midperiphery of the retina possessed a round perikaryon from which processes could be followed going into the inner plexiform layer, where they dichotomized in the third and first sublayers. The perikarya in the far periphery of the retina near the ora serrata exhibited an ovoid-shaped cell body from which processes extended horizontally in a bipolar manner in the layer itself. By use of an [35S]-labeled antisense oligonucleotide probe, in situ hybridization of the rat retina showed the presence of perikarya in the inner nuclear layer and ganglion cell layer containing mRNA encoding for prosomatostatin. Gel filtration of the retinal extracts followed by radioimmunoassay showed the presence of somatostatin 1-14, the fragment 1-12 of somatostatin 1-28, and prosomatostatin 1-64. However, somatostatin 1-28 was not detected. The results obtained in this study verify the presence of somatostatin 1-14 in the rat retina located in perikarya and processes in the inner nuclear and ganglion cell layers. The positive in-situ hybridization signals show that the intraneuronal somatostatin immunoreactivity is due to synthesis of the peptide and not uptake in the neurons. The presence of the somatostatin propeptide and fragments of this propeptide, in both intraretinal perikarya and fibers, indicate a posttranslational modification of this neuropeptide in the perikarya and the processes as well.

Animals↗

Vasoactive intestinal peptide-like immunoreactive nerve fibers in the pineal gland of the sheep.

Vasoactive intestinal peptide (VIP)-like immunoreactive nerve fibers were demonstrated by peroxidase antiperoxidase (PAP) immunohistochemistry to be distributed throughout the entire pineal gland of the sheep. VIP-containing fibers were observed along the blood vessels, penetrating into the gland from the pial capsule and also in the capsule itself. Some fibers left the perivascular position and entered the pineal parenchyma, where they were located among pinealocytes. This suggested that the VIPergic fibers might influence both pinealocytes and blood vessels of the gland. The location of VIP-containing fibers in the capsule of the pineal gland indicates that the fibers originate from perikarya located in a peripheral ganglion.

Animals↗

Antiarrhythmic treatment with flecainide (Tambocor). Clinical experience from 107 patients.

The long-term clinical effect of oral flecainide treatment was evaluated in 107 pts (10-82 yrs). Indications for treatment were: atrial fibrillation 38%, atrial flutter 16%, ventricular tachycardia 24%, ventricular ectopic beats 10% and supraventricular tachycardia 12%. Daily flecainide dosage was 200 (100-400) mg. Follow-up period 3 mths (15 days-15 mths). Based on the history and ECG flecainide had been effective in 51 pts. The improvement was most pronounced in pts suffering from supraventricular tachycardia involving an accessory bypass tract (84-92%). Flecainide had been discontinued in 50 pts due to: insufficient effect in 28, side effects in 17 and for other reasons in 5. The side effects indicating flecainide withdrawal (pts) were: cerebral symptoms (4), gastrointestinal complaints (2), bradyarrhythmias (2), heart failure (3) and suspected pro-arrhythmia (4). (Ventricular tachycardia in 3, 1:1 AV-conducting during atrial flutter in 1).

Administration, Oral↗

Characterization of serotonin N-acetyltransferase activity in the retina of the Mongolian gerbil, Meriones unguiculates.

In order to better understand the nature of melatonin synthesis in the mammalian retina, characterization of the enzyme serotonin N-acetyltransferase (NAT; EC 2.3.1.87) was undertaken in the Mongolian gerbil. Retinal and pineal homogenates were assayed for NAT activity by means of the radiometric method of Deguchi and Axelrod (1972). The activities of the retinal and pineal enzymes were similar with regard to pH optima and reaction rate. However, enzyme product formation by retinal NAT under varying substrate concentrations (including no substrate) remained virtually constant, hence preventing the determination of retinal NAT kinetics. In contrast, the pineal enzyme was determined to have a maximal velocity of 1 pmol/min and an apparent Michaelis constant of 100.7 microM, which agrees well with earlier reports in the rat. A daily rhythm of retinal NAT activity was observed with low levels during the daytime, early nighttime and very late nighttime hours. Peak levels were observed at 01.00 h in darkness. Acute light exposure reduced nocturnal NAT activity significantly within 10 min. This is the first demonstration of such an effect on retinal NAT activity in a mammalian species.

Acetyltransferases↗

The effect of carotid sinus massage is independent of posture in patients with heart disease.

The influence of posture on the effect of carotid sinus massage (CSM) in patients with heart disease has not been systematically evaluated. In the present study CSM was performed in 80 patients (mean age 55 +/- 10 (SD) years) suffering from various cardiovascular diseases. Each subject had unilateral right- and left-sided CSM performed in the supine and in the sitting position, while heart rate and systolic blood pressure were monitored. No statistically significant differences in the CSM-induced response in systolic blood pressure or heart rate were found between the two postures. In the supine position the drop in heart rate was significantly greater after right-sided than after left-sided CSM (P less than 0.05). In only one patient (1%) was a significant carotid sinus reflex evoked. The response was cardioinhibitory with asystole for 3700 ms during right-sided, supine CSM. These results imply that posture does not influence the effect of CSM in patients suffering from heart disease.

Aged↗

Stimulation of serotonin-N-acetyltransferase activity in the pineal gland of the mongolian gerbil (Meriones unguiculatus) by intracerebroventricular injection of vasoactive intestinal polypeptide.

There is ever-increasing evidence that intrapineal peptides have an important role in the modulation of pineal melatonin synthesis. In the pineal gland of the Mongolian gerbil (Meriones unguiculatus), we have previously shown the presence of VIP-immunoreactive nerve fibers as well as pinealocytic VIP receptors. To assess the functional significance of these findings, 10 microliters of a 1 microM or 1 nM solution of VIP were injected into the lateral ventricle of gerbils over a period of 10 min. Animals were killed 1.5 hr after injection, and the superficial pineal glands were excised and assayed for N-acetyltransferase (NAT) activity. Injection of the 1 microM VIP solution stimulated the NAT activity to values four times the control values. The results are compatible with an in vivo influence on the pineal gland indole metabolism of the nonsympathetic VIP-containing nerve fibers via VIP-receptors present in the gland.

Acetyltransferases↗

Epididymitis caused by treatment with amiodarone.

Epididymitis is described in a man aged 33 who had been treated with the antiarrhythmic agent, amiodarone. No signs of bacterial infection or anatomical abnormalities were found. Amiodarone as the cause of non-infectious epididymitis has been reported. This additional case stresses the importance of considering an adverse effect of amiodarone treatment as a cause when making a differential diagnosis of epididymitis.

Adult↗

Substance p in the median eminence and pituitary of the rat: demonstration of immunoreactive fibers and specific binding sites.

The distribution of substance P was demonstrated by immunohistochemical methods, and receptor binding with 125I-8-iodinated 8-tyrosine-substance P as an analog was used to describe possible specific binding sites in the hypothalamo-hypophysial system of the rat. The immunohistochemical experiments showed fibers exhibiting substance P-immunoreactivity in the external and internal layer of the median eminence. In the external layer some of the fibers were located in apposition to the portal capillaries. In the posterior pituitary substance P-immunoreactive fibers were identified. These terminals varied in size and were located near the capillaries as well as in the neuropil. The anterior lobe contained a number of substance P-immunoreactive fibers distributed around the pituitary cells. The kinetic analysis on crude membrane fractions from anterior and posterior pituitaries revealed the presence of a specific binding site for substance P in the anterior pituitary. These data indicate that substance P may be released from the median eminence and posterior pituitary to the vascular system and reach specific receptors in the anterior pituitary. However, a direct innervation of the anterior pituitary is possible. The lack of binding sites in the posterior pituitary indicates that fibers in this organ release substance P into the blood stream.

Animals↗

Vasoactive intestinal peptide in the hypothalamohypophysial system of the Mongolian gerbil.

By use of the indirect peroxidase-antiperoxidase immunohistochemical technique the location of perikarya and fibers exhibiting vasoactive intestinal peptide (VIP)-like immunoreactivity was investigated in the hypothalamus and the posterior pituitary of the Mongolian gerbil (Meriones unguiculatus), because of the involvement of VIP in several neuroendocrine functions. In the hypothalamus, a large number of VIP-immunoreactive perikarya were seen in the ventromedial part of the suprachiasmatic nucleus. Few VIP-positive perikarya were present in the periventricular, paraventricular, and supraoptic nuclei and in the medial preoptic area close to the third ventricle. The perikarya in the paraventricular nucleus projected fibers in the direction of the median eminence. In the median eminence VIP-immunoreactive fibers were present especially in the external layer, concentrated in the perivascular spaces surrounding the portal vessels. Scattered VIP-immunoreactive fibers were also located in the internal layer of the median eminence as well as in the posterior pituitary lobe. In the latter, large VIP-positive Herring-like bodies were observed. With receptor autoradiography a large number of grains were demonstrated in the anterior pituitary lobe in contrast to the neural lobe. Many VIP-positive fibers and some perikarya were observed within the ependyma covering the rostroventral part of the third ventricle. Finally, fibers exhibiting VIP immunoreactivity were also seen in the organum vasculosum laminae terminalis (OVLT). These results support the concept that VIP is released into the portal vascular system and plays a role in the regulation of the activity of the anterior pituitary. In addition, VIP might be secreted into the cerebrospinal fluid of the third ventricle.

Animals↗

Indications for the presence of two populations of serotonin-containing pinealocytes in the pineal complex of the golden hamster (Mesocricetus auratus). An immunohistochemical study.

Serotonin-like immunoreactivity was investigated in the pineal complex of the golden hamster by use of the indirect immunohistochemical technique. The superficial and deep portions of the pineal gland, and also the pineal stalk exhibited an intense cellular immunoreaction for serotonin. In addition, perivascular serotonin-immunoreactive nerve fibers were observed. Some serotonin-immunoreactive processes of the pinealocytes terminated on the surface of the ventricular lumen in the pineal and suprapineal recesses, indicating a receptive or secretory function of these cells. Several serotonin-immunoreactive processes connected the deep pineal with the habenular area. One week after bilateral removal of both superior cervical ganglia the serotonin immunoreaction of the entire pineal complex was greatly decreased. However, some cells in the pineal complex, of which several exhibited a neuron-like morphology, remained intensively stained after ganglionectomy. This indicates that the indoleamine content of some cells in the pineal complex of the golden hamster is independent of the sympathetic innervation.

Animals↗

Low-affinity uptake of [3H]choline by rat neurointermediate lobe in vitro.

Uptake of [3H]choline by rat neurointermediate lobes in vitro was investigated. The rate of uptake showed saturation with concentration of [3H]choline above 120 microM. Lowering of the incubation temperature from 32 to 4 degrees C, or increasing the concentration of K+ in the incubation medium from 5 to 100 mM, diminished the rate of uptake by 83.8% (SEM 6.9%, n = 3) or 43.1% (SEM 13.5%, n = 3), respectively. Following preloading with [3H]choline, a slow efflux (1% of the content every 20 min) of [3H]radioactivity was observed from the perifused glands. This efflux was enhanced 10-fold by increasing the concentration of K+ in the perifusion medium to 100 mM. Neither the uptake of [3H]choline, nor the subsequent basal or potassium-enhanced efflux of [3H]radioactivity were affected by reducing the concentration of Na+ from 125 to 19 mM, or by including 10 microM hemicholinium-3 in the medium during preincubation and perifusion. Replacing Ca2+ by 0.5 mM EGTA during perifusion resulted in a minor decrease (28%, SEM 7.3%, n = 7) in the potassium-enhanced [3H]radioactivity efflux. This decrease occurred only in one of the two high-potassium periods during the perifusion. In conclusion, uptake of [3H]choline by rat neurointermediate lobes was due to a low-affinity, saturable mechanism, with the efflux of [3H]radioactivity most likely representing the depolarization-facilitated outflow of [3H]choline. Autoradiography of the tissue sections showed this uptake to be localized to both neuronal and glial elements of the neural lobe, in contrast to sparse labelling of pars intermedia.

Animals↗