Search PubMed⌕ Search

Biomedical subjects

M Møller

Publications and source records attributed to M Møller.

At least 217 records · Page 12Linked to original sources

Dose-dependent kinetics of imipramine in elderly patients.

In a group of elderly depressed patients treated with imipramine (50-200 mg/day), six patients had the dose changed after 1-3 weeks of treatment. In all cases an increased dose resulted in a considerably disproportional rise in the plasma level of the active metabolite desipramine. In a group of elderly depressed patients treated with nortriptyline (40-100 mg/day) the dose/plasma level ratio could be examined in 6 patients, and there was no tendency towards a disproportional rise in plasma level, when the dose was raised. Dose changes, thus, may result in unpredictable changes in plasma levels during imipramine treatment and therapy control by plasma level monitoring may be difficult in these patients. Additional treatment with perphenazine (8-16 mg/day) to patients on imipramine (N = 3) or nortriptyline (N = 2) caused a marked rise in drug levels for imipramine in particular affecting the desipramine levels.

Aged↗

Vesicular transport of cationized ferritin by the epithelium of the rat choroid plexus.

We have studied the transport of ferritin that was internalized by coated micropinocytic vesicles at the apical surface of the choroid plexus epithelium in situ. After ventriculocisternal perfusion of native ferritin (NF) or cationized ferritin (CF), three routes followed by the tracers are revealed: (a) to lysosomes, (b) to cisternal compartments, and (c) to the basolateral cell surface. (a) NF is micropinocytosed to a very limited degree and appears in a few lysosomal elements whereas CF is taken up in large amounts and can be followed, via endocytic vacuoles and light multivesicular bodies, to dark multivesicular bodies and dense bodies. (b) Occasionally, CF particles are found in cisterns that may represent GERL or trans-Golgi elements, whereas stacked Golgi cisterns never contain CF. (c) Transepithelial vesicular transport of CF is distinctly revealed. The intercellular spaces of the epithelium, below the apical tight junctions, contain numerous clusters of CF particles, often associated with surface-connected, coated vesicles. Vesicles in the process of exocytosis of CF are also present at the basal epithelial surface, whereas connective tissue elements below the epithelium are unlabeled. Our conclusion is that fluid and solutes removed from the cerebrospinal fluid by endocytosis either become sequestered in the lysosomal apparatus of the choroidal epithelium or are transported to the basolateral surface. However, our results do not indicate any significant recycling via Golgi complexes of internalized apical cell membrane.

Animals↗

QT interval in relation to ventricular arrhythmias and sudden cardiac death in postmyocardial infarction patients.

Ninety-one consecutive patients below the age of 70 years were subjected to a 60-second resting ECG and 24-hour ambulatory ECG monitoring two weeks and one, three and six months after an acute myocardial infarction. The corrected QT (QTc) interval decreased from the late hospital phase to the investigations three and six months after the infarction (p less than 0.01, less than 0.05). ECG monitorings showing complicated ventricular ectopic beats (multiform, repetitive, R-on-T) were associated with an insignificantly longer QTc than other recordings. Eleven patients suffered a sudden cardiac death during a median follow-up period of 24 months (range 22-27). The QTc intervals in patients who died suddenly were insignificantly longer than in the survivors. Only four patients, who all survived, had a constantly prolonged QTc. After exclusion of tracings during quinidine therapy, a QTc longer than 440 msec was found in 7 (23%) of 31 recordings from patients who suffered a sudden cardiac death compared to 29 (10%) of 287 recordings from the survivors (p less than 0.05). A combination of complicated ventricular ectopic beats and a QT longer than 440 msec was demonstrated in 5 (16%) of 31 and 14 (5%) of 287 recordings from the two groups of patients (p less than 0.05). A trend towards longer QTc intervals was observed in patients with complicated ventricular arrhythmias and in those who died suddenly, but no well defined high-risk groups could be identified.

Adult↗

Localization of sodium pump sites in cat pancreas.

1. Cat pancreases were exposed to [3H]ouabain either by perfusion, or by incubation of slices, with Krebs--Henseleit bicarbonate solution containing [3H]ouabain, and [3H]ouabain binding sites were localized by light microscopical autoradiography. 2. Acinar cells were found to possess only a few [3H]ouabain binding sites located on the basolateral plasma membranes. 3. The epithelial cells lining the intercalated and interlobular ducts were heavily labelled. The [3H]ouabain binding sites were located on the basolateral membranes. 4. Since secretion of pancreatic juice can be abolished by ouabain, it is concluded that the duct cells, especially those of the numerous small (intercalated) and intermediate-sized (interlobular) ducts are responsible for pancreatic secretion of electrolytes and water. 5. The localization of the (Na+ + K+)-activated ATPase to the basolateral membranes of the cells excludes a direct role of the transport enzyme in the secretion of Na+. However, a model is proposed where the Na+ + K+)-activated ATPase plays a crucial, though indirect role in pancreatic secretion of electrolytes and water.

Animals↗

Lacrimal gland electrolyte and water secretion in the rabbit: localization and role of (Na+ + K+)-activated ATPase.

1. The rate of acetylcholine (ACh)-induced fluid secretion was measured from the main secretory duct of rabbit lacrimal glands perfused in vivo with Krebs Henseleit bicarbonate solutions. 2. Perfusion with ouabain (10(-5) M) decreased the rate of lacrimal gland fluid secretion to 23% of the control value. 3. Perfusion with furosemide (10(-4) and 10(-3) M), which has been shown to inhibit the coupled transport of Na+ and Cl-, reversibly decreased the rate of secretion to 43 and 33% of the control value respectively. 4. (Na+ + K+)-activated ATPase was localized in slices of rabbit lacrimal gland using autoradiography with [3H]ouabain. 5. A high density of [3H]ouabain binding sites was present on ductal cells, whereas a very low density was found on acinar cells. For both types of cells the [3H]ouabain binding sites were located on the basolateral plasma membranes. 6. It is concluded that ACh-induced secretion of electrolytes and water is dependent upon (Na+ + K+)-activated ATPase. In addition, coupled transport of Na+ and Cl- appears to be involved in secretion. 7. Basolateral location of the (Na+ + K+)-activated ATPase implies that it plays an indirect role in electrolyte and water secretion. A possible role may be to energize a secondary active transport of Cl- that is mediated by a NaCl cotransport system.

Acetylcholine↗

Horseradish peroxidase and microperoxidase. Their purity and binding to serum proteins.

Buffer solutions of commercially available batches of the electron microscopic enzyme tracers, horseradish peroxidase (HRP, mol wt = 40,000) and microperoxidase (MP, mol wt = 2,000), were investigated by gel filtration. The elution profiles of the HRP and MP solutions together with estimates of the peroxidatic activity of the collected fractions indicated that HRP was homogeneous with respect to molecular weight, while MP contained high molecular weight impurities with peroxidatic activity. Serum samples from four different species of tracer-injected animals (hagfish, lamprey, frog, mouse) and from control animals were investigated with the same techniques. No binding between HRP and the serum proteins or degradation of HRP was detected; whereas, MP circulated predominantly bound to serum proteins in all the investigated animals. The number average molecular weights of aqueous solutions of HRP and MP determined by vapor osmometry were 9,000 and 1,000, respectively. The results emphasize that protein binding should be evaluated when MP is used as an electron microscopic tracer. In addition, the finding that HRP and MP solutions have a much higher osmotic activity than the molecular weights of the tracers would suggest should be taken into consideration, especially when bolus injections into animals are performed.

Animals↗

Method for direct induction of serotonin fluorescence in a carcinoid tumor after embedding in hydroxyethyl methacrylate.

Tissue slices from a carcinoid tumor were fixed in formalin and after dehydration embedded in hydroxyethyl methacrylate. Sections, 5 micrometers in thickness, were cut with a D-knife mounted on a serial microtome. Some sections were stained with either hematoxylin and eosin or by azo-coupling with fast garnet GBC, whereas others were reacted for catecholamines and indolamines either by exposing them to formaldehyde vapor for 1 hour at 80 degrees C. or by dipping them into a sucrose-phosphate buffer-glyoxylic acid solution followed by heating at 80 degrees C. for 15 minutes. Fluorescence intensities and the spectra of the fluorophores were recorded on 5-micrometers thick formaldehyde-reacted sections by microspectrofluorometry. With both the formaldehyde vapor method and the glyoxylic acid solution method, an intense yellow fluorescence was obtained from the carcinoid tumor cells, as well as from normal enterochromaffin cells. The excitation and emission maxima obtained by microspectrofluorometry from these cells indicated the presence of a fluorophore originating from serotonin.

Acrylates↗

Immunocytochemical demonstration of the D2 protein in the presynaptic complex.

A monospecific antiserum against the rat brain synaptic plasma membrane protein D2 was produced by sequential immunization of rabbits with immunoprecipitates. This antiserum was used for immunoperoxidase localization of D2 in adult rat brain at both the light and the electron microscopal level. D2 was located in the presynaptic complex of neurons distributed ubiquitously in the brain. By gel electrophoresis D2 was demonstrated to exist in a perinatal form, which was desialylated during the ontogenetic period of maximal synaptogenesis.

Animals↗

The pineal complex of the three-spined stickleback, Gasterosteus aculeatus L.: a light-, electron microscopic and fluorescence histochemical investigation.

The pineal complex of the three-spined stickleback (Gasterosteus aculeatus L.) was investigated by light and electron microscopy, as well as fluorescence histochemistry for demonstration of catecholamines and indolamines. The pineal complex of the stickleback consists of a pineal organ and a small parapineal organ situated on the left side of the pineal stalk. The pineal organ, including the entire stalk, is comprised mainly of ependymal-type interstitial cells and photoreceptor cells with well-developed outer segments. Both unmyelinated and myelinated nerve fibres are present in the pineal organ. Nerve tracts from the stalk enter the habenular and posterior commissures. A small bundle of nerve fibres connects the parapineal organ and the left habenular body. The presence of indolamines (5-HTP, 5-HT) was demonstrated in cell bodies of both the pineal body and the pineal stalk, and catecholaminergic nerve fibres surround the pineal complex.

5-Hydroxytryptophan↗

Ventricular arrhythmias during exercise testing and 24-hour ECG tape recording in patients with ischaemic heart disease and in normal individuals.

The occurrence of ventricular arrhythmias (VA) during resting ECG, maximal bicycle exercise testing and 24-hour ECG tape recording (24-ETR) was studied in 24 patients and 24 matched normal persons. The patients were on treatment with beta-receptor blocking agents or verapamil for ischaemic heart disease (IHD), verified by coronary angiography. The matched persons showed no signs of heart disease. VA did not occur in any of those studied on a 60-second resting ECG. During exercise testing, one patient and six normal subjects had VA. During 24-ETR, VA were found in 16 patients and 11 normal persons. The maximum heart rate during exercise and the average heart rate during ETR did not differ significantly between individuals with and without VA in the groups of patients and normal subjects, respectively. It is concluded that in IHD patients receiving beta-blocking agents or verapamil, 24-ETR is a more reliable indicator of VA than exercise ECG testing. In normal individuals the two methods are of similar value.

Arrhythmias, Cardiac↗

Mutagenicity studies with urine concentrates from coke plant workers.

Urine from coke plant workers, collected before and after work, were tested for the content of mutagenic substances in the Salmonella test system. Urine extracts from exposed smokers showed mutagenic activity, whereas urine from exposed nonsmokers did not. The mutagenicity of exposed smoker's urine was not significantly different from that of urine from nonexposed smokers. Mutagenicity of smokers' urine was only evident in the presence of a rat liver metabolic activation system. The addition of beta-glucuronidase did not enhance the mutagenic effect. The facts that coke plant workers are exposed to very high levels of polycyclic aromatic hydrocarbons (PAH) and that there is no observed enhanced mutagenicity of their urine indicate that the mutagenicity observed with urine from smokers is not due to conventional PAH.

Coal↗

The spontaneous variation in the pattern of ventricular extrasystoles in patients recently recovered from an acute myocardial infarction.

Twelve patients between the ages of 40 and 68 years with myocardial infarction 1-6 months earlier were subjected to 24 h of ambulatory ECG monitoring for 2 consecutive d. In six patients with an average of less than 5 ventricular extrasystoles (VE) per hour during the first day, the pattern of the arrhythmias was both quantitatively and qualitatively unchanged from day to day. In six patients with an average of greater than 60 VE/h the first day, the number of VE were reduced significantly from the first to second day--in four patients by greater than 50%. The variation was greater after a day-to-day comparison than within the individual days following the division of the 24 h into 6-h periods. In general, the ventricular arrhythmias varied less following a qualitative rather than a quantitative evaluation. The evaluation of the effect of an antiarrhythmic drug in postmyocardial infarction patients requires that a considerable spontaneous variation should be taken into account when the patient is to be used as his own control. If a duration of monitoring of 24 h is employed both prior to and after the commencement of treatment, then the ventricular arrhythmias must practically disappear before the antiarrhythmic effect may be said to be documented.

Adult↗

Effect of superior cervical ganglionectomy on monoamine content in the epithalamic area of the Mongolian gerbil (Meriones unguiculatus): a fluorescence histochemical study.

Extirpation of the superior cervical ganglion was performed in a series of Mongolian gerbils. One or two weeks after the ganglionectomy the animals were injected with a monoamine oxidase inhibitor. Subsequently perfusion fixation was performed using the glyoxylic acid-paraformaldehydr-magnesium method (Lorén et al., 1976) for fluorescence histochemical investigation of the monoamines of the pineal complex. In the ganglionectomized animals all of the blue-fluorescent sympathetic fibers in the pineal complex (superficial pineal gland, deep pineal gland and the pineal stalk) completely disappeared. The yellow indolamine fluorescence of the cells in the superficial pineal and the deep pineal, as well as in the pineal stalk, was markedly reduced after ganglionectomy. No change in the morphology or number of sympathetic fibers in the medial habenular nucleus was observed. These results indicate that the presence of sympathetic nerve fibers with perikarya in the superior cervical ganglion is necessary for maintaining a high indolamine content in all three parts of the pineal complex. In addition, the results also indicate that the deep pineal gland is a functional part of the pineal complex. The presence of a functionally active deep pineal, bordering the pineal recess, suggests that part of the pineal hormones might be secreted into the cerebrospinal fluid.

Adrenergic Fibers↗

Histochemical demonstration of a circadian rhythm of succinate dehydrogenase in rat pineal gland. Influence of coenzyme Q10 addition.

Succinate dehydrogenase activity was investigated histochemically in the rat pineal gland. The influence of fixation on the activity pattern, the possible diffusion of enzyme, the nothing dehydrogenase reaction, and the substantivity of the tetrazolium salts and formazans were investigated in control experiments. In rats maintained on a 17/7 h light/dark schedule a distinct circadian rhythm of the succinate dehydrogenase was demonstrated in the pineal gland. Activity was lowest during the day and highest during the night. The dorsocaudal part of the gland showed the highest activity and within the same part of the gland the activity varied between individual pinealocytes. A relative lack of endogenous coenzyme Q, as well as a circadian rhythm of this coenzyme, highly influenced the activity of succinate dehydrogenase. It is concluded that succinate dehydrogenase activity in the pineal gland of the rat is regulated by changing the concentration of the active enzyme itself as well as the level of the endogenous coenzyme Q. Whether this is caused by a circadian rhythm in the synthesis or in the catabolism of the enzyme and the coenzyme was not revealed by the present study .

Animals↗

Brain-pineal nervous connections in the rat: an ultrastructure study following habenular lesion.

The neural connections of the pineal gland with the central nervous system (CNS) were studied in rats by stereotaxic lesioning followed by electron microscopic determination of nerve terminal degeneration. Electrolytic lesions were placed in the right medial habenular nucleus and after 3--14 days survival, the animals were prepared for electron microscopy. Control animals contained nerve terminals with 40--60 nm dense core vesicles located in the perivascular space of the pineal and in the intraparenchymal area. In the lesioned animals many electron-lucent degenerating nerve terminals could be observed intermingled with normal nerve terminals in the perivascular spaces. These degenerating terminals were often swollen and contained one side of the terminal. Both normal and degenerating nerve terminals were also observed in the parenchyma between the pinealocytes. The present findings indicate that nerve fibers from the habenular area actually terminate in the rat pineal gland.

Animals↗