Biomedical subjects

L Johannsen

Publications and source records attributed to L Johannsen.

At least 19 recordsLinked to original sources

PubMed2006

Abnormally speeded saccades to ipsilesional targets in patients with spatial neglect.

We mapped the distribution of saccadic reaction times (SRTs) in the visual field of patients with spatial neglect in order to characterise the topography of the bias in spatial orientation peculiar to this disorder. LED-generated stimuli were lit randomly in one of four positions (+/-5 degrees , +/-10 degrees , +/-20 degrees , +/-30 degrees ) along the horizontal meridian in blocks of either ipsilesional or contralesional presentations. Patients were asked to move the gaze as quickly as possible from central fixation to target upon its appearance. Unlike control subjects, patients with neglect showed an asymmetric distribution of visuo-motor performance in the two hemifields with an increasing impairment in target detection and saccadic reaction at increasing eccentricities in the contralesional field. In contrast, in the ipsilesional field they showed abnormally speeded SRTs at 5 degrees and 10 degrees , outperforming even healthy subjects. Latency of saccades increased again at more peripheral ipsilesional locations (20 degrees and 30 degrees ) where there was also a tendency for a higher omission rate as compared to control groups. These results indicate that in neglect patients the spatial orientation bias, as witnessed by saccadic performance, specifically affects an off-centred sector of the ipsilesional space, and this is in keeping with evidence from a previous study using a manual RT paradigm. The generality of this phenomenon across different types of motor response suggests that it depends upon abnormal mechanisms of spatial coding interfering with perceptual processing and orienting behaviour.

Adult↗

PubMed2002

Prognosis of contraversive pushing.

Stroke patients with 'pusher syndrome' actively push away from the non-hemiparetic side leading to a loss of postural balance and falling towards the paralysed side. The behaviour is due to an altered perception of the body's orientation in relation to gravity. Here, we studied the prognosis of the disorder. Twelve pusher patients first investigated immediately after the stroke were re-examined 6 months later. Pusher symptoms had nearly completely recovered. The aim for physiotherapy of patients with contraversive pushing thus is to shorten the period of necessary treatment and enable earlier discharge from residential care.

Adult↗

PubMed2001

seco-Cyclothialidines: new concise synthesis, inhibitory activity toward bacterial and human DNA topoisomerases, and antibacterial properties.

seco-Cyclothialidines are a promising class of bacterial DNA gyrase B subunit inhibitors. A new seco-cyclothialidine derivative containing a dioxazine moiety, BAY 50-7952, was synthesized through a new concise pathway. One key step of the synthesis is the straightforward formation of the 2-aminothiazole derivative of S-tritylcysteine. In biological tests, BAY 50-7952 and other known seco-cyclothialidines exhibited high and selective activity toward bacterial DNA gyrase and toward Gram-positive bacteria. The dioxazine moiety and other similar groups were found to be important for the ability of the seco-cyclothialidines to penetrate bacterial membranes. The opposite enantiomer ((S)-form) of BAY 50-7952 was also synthesized, and neither significant target activity nor in vitro antibacterial activity were found, suggesting a highly selective fit of the (R)-form. Despite promising in vitro activity, only poor activity was found in the murine infection model.

Animals↗

PubMed2001

Diagnostic yield by testing small fiber function in patients examined for polyneuropathy.

We assessed the diagnostic yield of adding quantitative sensory testing to the standard work-up for polyneuropathy in unselected patients. All patients aged 18 to 70 years referred to our department for electrodiagnosis with a tentative diagnosis of polyneuropathy and symptoms complying with predefined criteria were included in the study. We performed near nerve conduction studies in 4 nerves and determined heat and cold detection thresholds on hand and foot with a Thermotest (Somedic AB, Sweden). In order to uncover CNS diseases, somatosensory-evoked potentials were recorded in patients with abnormal quantitative sensory testing and normal nerve conduction studies. A total of 198 patients completed the study and 149 were considered to have polyneuropathy. Twenty-five patients remained undiagnosed and in 24 patients, other diseases were responsible for the symptoms. Of the patients with either polyneuropathy or no other diagnosis, 76% (n = 174) had abnormal nerve conduction. Abnormal cold sensation, heat sensation or abnormality in at least 1 of these and normal nerve conduction were found in 14, 12 and 17 patients. Of the 174 patients, 86% (95% CI 80-90%) had an abnormality in at least 1 of the tests (i.e. abnormal nerve conduction and/or abnormal quantitative testing of temperature sensation). In conclusion, quantitative testing of temperature sensation improves the diagnostic yield in patients examined for chronic polyneuropathy.

Adult↗

PubMed1996

Microglia digest Staphylococcus aureus into low molecular weight biologically active compounds.

Excess sleep and fever are central nervous system (CNS) facets of the acute phase response; these responses are induced by microbial products, such as muramyl peptides, via their ability to enhance cytokine production. Although peripheral macrophages are known to digest bacteria, thereby releasing muramyl peptides that, in turn, stimulate cytokine production, it was unknown whether CNS phagocytes such as microglia also had this capacity. Primary cultures of microglia were allowed to phagocytize and digest Staphylococcus aureus radiolabeled with a cell wall-specific marker. Radiolabeled low molecular weight substances released into the culture medium were partially purified and tested for the ability to induce excess sleep, fever, and cytokine production. These substances increased non-rapid eye movement sleep, electroencephalographic slow-wave activity, and brain temperature after intracerebroventricular injection into rabbits. They also induced interleukin-1, tumor necrosis factor, and the interleukin-1 receptor antagonist production in human monocytes. Results suggest that microglia perform fundamental macrophage functions and further implicate microglia as resident immunocompetent cells.

Animals↗

PubMed1994

Somnogenic activity of muramyl peptide-derived immune adjuvants.

Muramyl peptides (MPs) possess immunostimulatory, pyrogenic and somnogenic activities. The structural requirements of MPs for each of these activities are different though certain MPs, e.g. muramyl dipeptide (NAM-L-ala-D-isogln) possess all three activities. Several MPs are proposed for use as immune adjuvants; somnogenic and pyrogenic activities would be considered adverse side effects of such compounds. We report here that some of the putative adjuvants, GIF101, WG209 and MDP-threonine lack somnogenic and pyrogenic activities. Current results also expand our understanding of the structural requirements for these activities. Major findings are that the addition of the dipeptide L-ala-D-isogln to NAG-NAM-L-ala-D-isogln blocks the activity of the latter compound and that the amino sugar moiety of MPs, NAM, is unnecessary for somnogenic and pyrogenic activity.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1994

[Muramyl peptides and sleep].

Effects of muramyl peptides from bacterial cell walls (MDP and GMDP), their fragments, steric isomers and structural analogues were studied on sleep in rabbits. An increase in the SWS, decrease in PS, rise in body temperature were found following minimal doses, whereas pathological responses in the EEG and sleep as well as pyrogenic effects occurred after higher doses. The GMDP analogues affected sleep weakly, and isomers and fragments were inactive. Possible role of muramyl peptides in normal and pathological regulation of sleep is discussed.

Animals↗

PubMed1993

Radiation-induced brachial plexopathy: neurological follow-up in 161 recurrence-free breast cancer patients.

PURPOSE: The purpose was to assess the incidence and clinical manifestations of radiation-induced brachial plexopathy in breast cancer patients, treated according to the Danish Breast Cancer Cooperative Group protocols. METHODS AND MATERIALS: One hundred and sixty-one recurrence-free breast cancer patients were examined for radiation-induced brachial plexopathy after a median follow-up period of 50 months (13-99 months). After total mastectomy and axillary node sampling, high-risk patients were randomized to adjuvant therapy. One hundred twenty-eight patients were treated with postoperative radiotherapy with 50 Gy in 25 daily fractions over 5 weeks. In addition, 82 of these patients received cytotoxic therapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and 46 received tamoxifen. RESULTS: Five percent and 9% of the patients receiving radiotherapy had disabling and mild radiation-induced brachial plexopathy, respectively. Radiation-induced brachial plexopathy was more frequent in patients receiving cytotoxic therapy (p = 0.04) and in younger patients (p = 0.04). The clinical manifestations were paraesthesia (100%), hypaesthesia (74%), weakness (58%), decreased muscle stretch reflexes (47%), and pain (47%). CONCLUSION: The brachial plexus is more vulnerable to large fraction size. Fractions of 2 Gy or less are advisable. Cytotoxic therapy adds to the damaging effect of radiotherapy. Peripheral nerves in younger patients seems more vulnerable. Radiation-induced brachial plexopathy occurs mainly as diffuse damage to the brachial plexus.

Adult↗

PubMed1993

Calcitonin gene-related peptide in small cell lung carcinomas.

OBJECTIVE: Calcitonin gene-related peptide (CGRP) is a regulatory peptide encoded by the calcitonin gene. CGRP is expressed in increased amounts by the cells of medullary thyroid carcinomas and has been demonstrated by immunohistochemistry to occur in neuroendocrine cells and nerve fibres of lung tissue. MEASUREMENTS: Serum CGRP levels were measured in patients with small cell lung carcinomas before treatment (n = 74) and immediately before the second course of chemotherapy (n = 30). In-situ hybridization and immunohistochemistry were performed on tumour tissue and CGRP was extracted from two tumours and characterized by gel chromatography and high pressure liquid chromatography. RESULTS: Serum CGRP levels were elevated in small cell lung carcinomas when compared with healthy controls of similar age and sex (median values 55.0 vs 36.6 pmol/l, P < 0.001), and 27% had levels above the upper normal range. Serum CGRP levels decreased following the initial course of chemotherapy (P < 0.05) but remained elevated when compared to the controls (P < 0.001). In-situ hybridization for CGRP mRNA was positive in three of 17 tumours and immunohistochemistry was positive in seven of 31 tumours investigated. CGRP immunoreactivity extracted from two tumours was characterized by gel chromatography and high pressure liquid chromatography. A major part of the immunoreactivity was demonstrated to represent the intact molecule. CONCLUSIONS: We found that patients with small cell lung carcinomas had elevated concentration of serum calcitonin gene-related peptide but only 27% had values above the upper normal range. Serum CGRP is therefore of limited value as a tumour marker. Intact CGRP can be extracted from tumour tissue, but in-situ hybridization and immunohistochemistry showed positive reactions in only a few of the tumours investigated. The elevated serum CGRP levels are therefore likely to be largely of extratumoral origin.

Adult↗

PubMed1993

Biological properties of bacterial peptidoglycan.

Synthetic and natural muramyl peptides have a variety of biological actions in mammals, including the abilities to enhance sleep and body temperature. Although muramyl peptides can be detected constitutively in mammalian organisms, no biochemical synthetic pathways are known for muramyl peptides in mammals. However, muramyl peptides are well known as components of bacterial cell wall peptidoglycan (synonym: murein). Isolated bacterial cell walls elicit host responses similar to those produced by bacterial infections or by purified muramyl peptides. Mammalian cells which phagocytize bacteria can digest bacterial cell walls and release biologically active muramyl peptides. The released muramyl peptides then express some or all of the biological effects observed with synthetic muramyl peptides. Also, cell-free systems consisting of isolated bacterial cell walls and lysozyme produce substances with similar biological activities.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1991

Intraperitoneal injection of cholecystokinin elicits sleep in rabbits.

Cholecystokinin (CCK) reduces food intake and promotes non-rapid-eye-movement sleep (NREMS) in rats. The purpose of present experiments was to determine if CCK is somnogenic in rabbits; another species in which CCK suppresses feeding. White New Zealand rabbits were treated intracerebroventricularly (ICV; 0.05, 0.5 and 2 micrograms) or intraperitoneally (IP; 2.5, 10 and 40 micrograms/kg) with CCK or saline, and sleep-wake activity and brain temperature (Tbr) were recorded for 6 h. Injections of 10 and 40 micrograms/kg CCK IP elicited a decrease in wakefulness and an increase in NREMS during the first hour postinjection. The hypnogenic effects were accompanied by a decrease in Tbr. After the IP injection of a lower dose (2.5 micrograms/kg) a slight, nonsignificant increase in NREMS during the first hour postinjection was followed by a decrease in NREMS. ICV injections of CCK had relatively small inhibitory effects on sleep. We conclude that circulating, hormone CCK might be a hypnogenic signal with a peripheral site of action.

Animals↗

PubMed1991

Modulation of human leukocyte antigenDR expression in glioblastoma cells by interferon gamma and other cytokines.

To study the regulation of major histocompatibility complex class II antigen by central nervous system cells, the expression of one of these antigens, human leukocyte antigenDR (HLADR) in three human glioblastoma cell lines (HTB14, 16 and 17) and a neuroblastoma cell line (HTB11) was determined. Interferon-gamma (IFN gamma) induced HTB16 and HTB17 cells to express HLADR, and enhanced the antigen expression in HTB14 cells, but it failed to induce HLADR expression in HTB11 cells. Tumor necrosis factor-alpha amplified and accelerated the expression of HLADR induced by IFN gamma in HTB16 cells. Interleukin-1 beta, prostaglandin E2 and transforming growth factor-beta suppressed IFN gamma-induced HLADR expression in HTB16 cells. Several other substances tested did not affect HLADR expression or IFN gamma-induced HLADR. These findings confirm that IFN gamma plays a role in the regulation of HLADR expression in cells derived from the brain and that some other cytokines modify IFN gamma-HLADR interactions.

Cytokines↗

PubMed1991

Somnogenic activity of pseudomurein in rabbits.

Pseudomurein is a major cell wall component of some archaebacteria that chemically differs from but morphologically, functionally, and structurally resembles eubacterial peptidoglycan. Eubacterial cell wall components, e.g., peptidoglycan, induce changes in sleep and body temperature. We now report that intravenous injections of rabbits with a suspension of pseudomurein from Methanobacterium thermoautotrophicum also induce similar central nervous system effects.

Animals↗

PubMed1991

Macrophages produce somnogenic and pyrogenic muramyl peptides during digestion of staphylococci.

Muramyl peptides have a variety of biological effects in mammals, including enhancement of the immune response, sleep, and body temperature. Although mammals lack biosynthetic pathways for muramyl peptides, they are found in mammals and are well known as components of bacterial cell walls. This suggests that phagocytic mammalian cells digest bacterial cell walls and produce biologically active muramyl peptides. Staphylococcal cell walls were radioactively labeled during growth of the bacteria. During the digestion of these radiolabeled bacteria, murine bone marrow macrophages produced low-molecular-weight substances that coeluted chromatographically with the radioactive cell wall marker. Further separation of these substances using reversed-phase high-performance liquid chromatography resulted in the isolation of substances with high specific biological activity. Intracerebroventricular injection of rabbits with these substances induced an increase in slow-wave sleep and body temperature and a suppression of rapid-eye-movement sleep. The characteristics of the biological responses and the chromatographic behavior of the active components are consistent with those of muramyl peptides. The ability of macrophages to tailor muramyl peptides from peptidoglycan may provide an amplification step for the immune response. Muramyl peptides released by macrophages may also act as mediators for various facets of the acute phase response elicited by bacterial infections such as fever and sleep.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1991

Sleep in diabetic rats: effects of interleukin 1.

Previous observations indicate that both interleukin 1 beta (IL-1 beta) and insulin are involved in sleep regulation. IL-1 beta has been reported to stimulate insulin secretion, suggesting that some of the effects of IL-1 beta are mediated by insulin. The purpose of the current experiments was to study the possible role of endogenous insulin in physiological sleep regulation and in the hypnogenic effects of exogenously administered IL-1 beta. Isotonic saline or IL-1 beta (2.5 ng) was intracerebroventricularly injected into normal and streptozocin-diabetic rats at dark onset, and sleep-wake activity and brain temperature were recorded for 24 h. Blood samples were collected every 20 min during the first hour postinjection for plasma insulin measurement. In diabetic rats, rapid-eye-movement (REM) and non-REM sleep were significantly decreased during the second part of the light period on the baseline day. IL-1 beta elicited a biphasic sleep response in both normal and diabetic rats. This initial increase in non-REM sleep during the first 4 h postinjection was followed by significant sleep suppression in both groups. Brain temperature was not affected in either group. Plasma insulin concentration decreased in response to IL-1 beta in normal rats, whereas insulin was below the level of detection in the diabetic rats. These results indicate that, although sleep is disturbed in diabetic rats, pancreatic insulin might not have a decisive role in the regulation of sleep in rats, and it does not mediate the effects of IL-1 beta on sleep-wake activity.

Animals↗

PubMed1990

Penicillin-induced changes in the cell wall composition of Staphylococcus aureus before the onset of bacteriolysis.

To analyze if chemical cell wall alterations contribute to penicillin-induced bacteriolysis, changes in the amount, stability, and chemical composition of staphylococcal cell walls were investigated. All analyses were performed before onset of bacteriolysis i.e. during the first 60 min following addition of different penicillin G doses. Only a slight reduction of the amount of cell wall material incorporated after penicillin addition at the optimal lytic concentration was observed as compared to control cells. However, the presence of higher penicillin G concentrations reduced the incorporation of wall material progressively without bacteriolysis. Losses of wall material during isolation of dodecylsulfate insoluble cell walls were monitored to assess the stability of the wall material following penicillin addition. Wall material grown at the lytic penicillin concentration was least stable but about 30% of the newly incorporated wall material withstood even the harsh conditions of mechanical breakage and dodecylsulfate treatment. Dodecylsulfate insoluble cell walls were used for chemical analyses. While peptidoglycan chain length was unaffected in the presence of penicillin, other wall parameters were considerably altered: peptide cross-linking was reduced in the wall material synthesized after addition of penicillin; reductions from approx. 85% in controls to about 60% were similar for lytic and also for very high penicillin concentrations leading to nonlytic death. O-acetylation was also reduced after treatment with penicillin; this effect paralleled the occurrence of subsequent bacteriolysis at different drug concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

PubMed1990

Reduction of wall degradability of clindamycin-treated staphylococci within macrophages.

Clindamycin treatment of Staphylococcus aureus caused a remarkable thickening of the bacterial cell wall and made the bacterial wall much more resistant against lytic enzymes within bone marrow-derived macrophages as revealed by electron microscopy and radiolabeling experiments. This reduced wall degradability resulted from an increased number of O-acetyl groups in the murein. Furthermore, such clindamycin-treated bacteria were ingested by adherent bone marrow-derived macrophages at a higher rate than untreated bacteria. The medical aspects of these results are discussed.

Animals↗

PubMed1990

Somnogenic, pyrogenic, and hematologic effects of bacterial peptidoglycan.

Bacterial infections and certain muramyl peptides elicit a variety of pathophysiological effects including increases in body temperature and slow-wave sleep. Bacterial cell wall peptidoglycan is composed of muramyl peptides. To investigate the ability of isolated bacterial cell walls to enhance slow-wave sleep, rabbits were injected intravenously with cell walls isolated from Staphylococcus aureus or with soluble peptidoglycan prepared from Neisseria gonorrhoeae. These injections increased slow-wave sleep, electroencephalographic delta-wave amplitudes, and body temperature, reduced rapid-eye-movement sleep, and induced neutrophilia and lymphopenia. The somnogenic and pyrogenic effects of S. aureus cell walls developed within 1 h and persisted throughout the recording period. Injections of N. gonorrhoeae peptidoglycan induced similar effects but of larger magnitude and shorter duration. We conclude that peptidoglycan is a bacterial component that mediates the increased sleep observed during infectious disease.

Animals↗