Search PubMed⌕ Search

Biomedical subjects

M Nielsen

Publications and source records attributed to M Nielsen.

At least 307 records · Page 17Linked to original sources
PubMed1981

Metastases to the breast from extramammary carcinomas.

Metastases to the breast from extramammary carcinomas are rare. Only about 200 cases are reported in the literature. Fifteen additional cases are presented here and the literature is reviewed. Two of the patients has primary thyroid carcinoma, two adenocarcinoma of the colon, three bronchogenic carcinoma, four malignant melanoma, one a squamous cell carcinoma of the oesophagus, one an adenocarcinoma of the stomach, one a renal cell carcinoma and one a carcinoid of the terminal ileum. In three cases the breast lesion was the first manifestation of an extramammary cancer. Six of the patients died of disseminated cancer shortly after the breast metastasis was diagnosed. Although breast metastasis may be suspected clinically, exact histological diagnosis is important in order to avoid unnecessary surgical treatment and to guide further therapy.

Adult↗
PubMed1981

Basement membrane changes in breast cancer detected by immunohistochemical staining for laminin.

The distribution of the basement membrane glycoprotein laminin was studied by the immunoperoxidase technique in benign and malignant human breast tissue and in axillary lymph nodes from patients with breast cancer. An antiserum prepared against rat laminin was used. The specificity of this antiserum against human laminin was studied using the FL cell line of human epithelial-like cells derived from normal amniotic membrane. The antiserum reacted with these cells in immunoperoxidase staining and precipitated metabolically labeled secreted polypeptides which comigrated with polypeptides with molecular weights of 400,000 and 200,000 of rat laminin in sodium dodecyl sulfate:polyacrylamide gel electrophoresis. The neoplastic cells in malignant breast tissues showed strong cytoplasmic staining for laminin, and a positive reaction was aslo found in lymph node metastases. In some cases in which only micrometastases were present, these cells also stained strongly for laminin. In nonmalignant breast tissues, the epithelial cells of the duct were positive for laminin, but the staining was weaker than in the carcinomas. Pretreatment of the fixed tissue sections with trypsin markedly enhanced the staining of basement membranes for laminin. In trypsin-treated sections of normal breast tissue and benign lesions, the laminin staining delineated continuous basement membranes. In carcinomas representing the more differentiated types, basement membranes presumably produced by the tumor cells could be revealed by laminin staining, but they were thinner and discontinuous. The poorly differentiated carcinomas lacked organized basement membranes detectable by laminin staining. Our studies suggest that staining for laminin may be a useful adjunct test for detection of micrometatases in lymph nodes. The correlation of disintegration of the laminin-containing basement membranes of tumors with increasingly anaplastic appearance supports the notion that basement membranes may play a role in tumor invasion.

Basement Membrane↗
PubMed1980

Decreased spiroperidol and LSD binding in rat brain after continuous amphetamine.

Rats were implanted with a silicone tubing pellet continuously releasing amphetamine base for several days. After five days of this treatment specific binding of spiroperidol (dopamine receptors) and LSD (serotonin receptors) was decreased in the corpus striatum and frontal cortex. In the striatum the number of dopamine receptors was decreased while the affinity was unchanged. These results indicate that dopamine and serotonin receptors can be regulated by the release of their own neurotransmitter.

Amphetamine↗
PubMed1980

Ethyl beta-carboline-3-carboxylate shows differential benzodiazepine receptor interaction.

High-affinity binding of 3H-diazepam and 3H-flunitrazepam has provided evidence for the presence of benzodiazepine receptors on brain neurones. Pharmacological evidence showing a clear correlation between receptor affinity and in vivo pharmacological potency for several benzodiazepines and a link between benzodiazepine receptors and GABA (gamma-amino-butyric acid) receptors at the molecular level, indicates that these receptors are relevant to the pharmacological and clinical effects of benzodiazepines. In searching for possible endogeneous ligands for benzodiazepine receptors we have recently isolated ethyl beta-carboline-3-carboxylate (beta-CCE) found human urine and brain, and shown that beta-CCE has a higher affinity than diazepam for brain benzodiazepine receptors. beta-CCE itself is probably not present in the brain, but may be closely related to an endogenous benzodiazepine receptor ligand. We report here that beta-CCE, in contrast to benzodiazepines, can distinguish clearly between benzodiazepine receptors in cerebellum and hippocampus. This result strongly indicates that benzodiazepine receptors are not a single class of non-interacting entities. It has not been possible to determine whether two distinct receptors are present and/or whether true negative cooperativity exists among hippocampal, but not cerebellar, benzodiazepine receptors.

Allosteric Regulation↗
PubMed1980

Urinary and brain beta-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors.

Benzodiazepines probably exert their anxiolytic, hypnotic, and anticonvulsant effects by interacting with brain-specific high-affinity benzodiazepine receptors. In searching for possible endogenous ligands for these receptors we have purified a compound 10(7)-fold from human urine by extractions, treatment with hot ethanol, and column chromatography. The compound was identified as beta-carboline-3-carboxylic acid ethyl ester (IIc) by mass spectrometry, NMR spectrometry, and synthesis; IIc was also isolated from brain tissues (20 ng/g) by similar procedures. Very small concentrations of IIc displaced [3H]diazepam completely from specific cerebral receptors, but not from liver and kidney binding sites; the concentration causing 50% inhibition of specific [3H]diazepam binding (IC50) was 4-7 nM compared to ca. 5 nM for the potent benzodiazepine lorazepam. Specific binding sites for quinuclidinyl benzilate, naloxone, spiroperidol, serotonin, muscimol, and WB 4101 were not affected by IIc. In contrast to benzodiazepines, IIc exhibits "mixed type" competitive inhibition of forebrain benzodiazepine receptors (negative cooperativity). We surmise that an endogenous ligand for benzodiazepine receptors may be a derivative of beta-carboline-3-carboxylic acid.

Binding, Competitive↗
PubMed1980

Benzodiazepine receptors.

It appeared recently that the important group of psychoactive drugs, the benzodiazepines, binds with high affinity to a single class of saturable sites on brain membranes of all higher vertebrates including man. There was a good correlation between the pharmacological effects of different benzodiazepines and their affinity for 3H-diazepam and 3H-flunitrazepam binding sites, indicating that the binding site is the physiological relevant receptor upon which benzodiazepines act. The most active benzodiazepines, like lorazepam and triazolam, act in concentrations of about 1 nmol/l. The highest concentration of benzodiazepine receptors in human brain was found in cerebral cortical regions, intermediate levels were found in midbrain and some limbic structures, while white matter areas exhibit low levels. This indicates that benzodiazepines act preferentially in cortical areas. The presence of benzodiazepine receptors suggests that there may an endogenous ligand for these receptors. Hypoxanthine, inosine and nicotinamide have been isolated from brain tissue and proposed as endogenous ligands. These three compounds are very weak on benzodiazepine receptors. The most promising compound has been isolated from human urine and brain and is a lipophilic, small-molecular weight aromatic compound, which exhibits very high affinity (Ki congruent to 0.003 mumol/l) for benzodiazepine receptors.

Animals↗
PubMed1980

The value of the micromethod erythrocyte sedimentation rate in the diagnosis of infections in newborns.

200 newborns, gestational age between 27 and 43 weeks (mean 39 weeks) and a birth weight between 900 and 4600 g (mean 2600 g) were studied. 18 patients had severe infections, 20 topical infections, 11 had signs of infection but negative microbiological cultures, 26 had positive cultures but no clinical signs of infection, and 125 patients had no sign of infection at all. In the group without infection (125 patients), the micromethod erythrocyte sedimentation rate (MESR) raised slowly from 2 mm/h at birth (95% upper limit 8 mm/h) to 4 mm/h 8 days after delivery. The MESR of the patients with respiratory distress, asphyxia, intubated children and patients with umbilical catheter, who had no infection, did not differ from other patients in this group. In patients with focal and general infections, rapidly rising MESR within wide limits was observed. Thus, in the individual newborn a high MESR supports the diagnosis of severe infection, whereas a low MESR does not exclude this diagnosis.

Bacterial Infections↗
PubMed1980

Netilmicin: efficacy and tolerance in the treatment of systemic infections in neonates.

38 newborn infants, 28 males and 10 females, were treated with netilmicin in doses 6-7 mg/kg/day for suspected or verified infections. 19 patients were mature (mean birth weight 3169 g) and 19 were premature (mean birth weight 1864 g). 32 had moderate or severe underlying diseases. 37 babies survived, 33 were cured or improved markedly and in 4 the results were indeterminate. Pathogenic bacteria were demonstrated in 24 cases and were eliminated in 15. Only one baby died. He suffered from severe respiratory distress syndrome and Escherichia coli septicemia. No E. coli was isolated at autopsy. The mean netilmicin peak serum value was 7.7 micrograms/ml (range 1.0-30.0) and the mean trough concentration 2.1 micrograms/ml (range 0.0-9.2). No adverse effects were seen.

Bacterial Infections↗
PubMed1979

Benzodiazepine receptors in the brain as affected by different experimental stresses: the changes are small and not undirectional.

Rats and mice were exposed to several different stress situations to investigate whether brain benzodiazepine receptors were sensitive to altered external or internal environmental circumstances. All stresses were applied for several days. Electrical foot shock and post-natal isolation of newborn pups resulted in small (7--25%; P less than 0.05--0.001) decreases in benzodiazepine receptor binding in some cerebral cortex or hippocampal areas while immobilization stress resulted in a small (9%; P less than 0.05) increase in frontal cortex. Other brain areas (i.e., striatum, cerebellum, pons-medulla, and occipital cortex) and other stress forms (isolation of male mice, forced swimming in cold water, or chronic amphetamine intoxication) did not change receptor binding. The effect of prolonged stress on benzodiazepine receptors is complex and not very pronounced.

Aggression↗
PubMed1979

Method of estimating the disposition of drugs in the Danish population by sampling reimbursed prescriptions.

A method by which for a small cost it is possible to obtain a quantitative expression for the utilization, disposition and cost of drugs in a Danish county of 500,000 inhabitants. The procedure makes it possible to follow reimbursed preparations, i. e., drugs considered essential for the treatment of diseases. The sale, in D kr., of reimbursed preparations to individuals comprises about 80% of the sale of preparations requiring prescription. And in turn the sale of the latter amounts to 80% of total drug sales to single subjects. The method is based on systematic utilization of all the information available on each prescription; concepts of 'Entry Parameters', 'Calculated Units' and 'Derived Units' was discussed; the 'units' concern frequency of prescription and age- and sex specific dose-frequencies (weight units or defined daily doses -- DDD's). The possibility of creating a base for calculation of the frequency of certain diseases and of side-effects of drugs is mentioned, and examples of the application of the method to certain categories of patients and to certain drugs are given. From limitations of the method it is concluded that it should be considered as a supplement to other complete methods for the study of drug consumption.

Age Factors↗
PubMed1979

Neuronal localisation of benzodiazepine receptors in cerebellum.

The cellular localisation of benzodiazepine receptors was studied. Kainic acid induced neuronal lesions (2 x 0.25-2 x 2 micrograms; 2-26 days in rat cerebellum decreased specific binding of [3H]flunitrazepam down to 35% of controls. Specific binding of [3H]flunitrazepam was also decreased (to 80% of controls) in the cerebllum of mutant nervous mouse (nr/nr) where Purkinje cells are degenerated but in the mutant weaver mouse where granule cells are degenerated. These results show that benzodiazepine receptors are located mainly on neurons; both on Purkinje cells and other neurons, but not to a great extent on granule cells.

Animals↗