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Biomedical subjects

P Lundgren

Publications and source records attributed to P Lundgren.

At least 19 recordsLinked to original sources
PubMed2006

Neurosteroid modulation of allopregnanolone and GABA effect on the GABA-A receptor.

The neurosteroid allopregnanolone (ALLO) or 3alpha-OH-5alpha-pregnane-20-one interacts with the GABA type A receptor chloride ion channel complex and enhances the effect of GABA. Animal and human studies suggest that ALLO plays an important role in several disorders including premenstrual syndrome, anxiety, and memory impairment. In contrast to ALLO, steroids with a hydroxy group in the 3beta position usually exert a reducing effect and have recently attracted interest due to their suggested role in counteracting the negative action of ALLO. In this study, five different 3beta-steroids were tested for their ability to modulate GABA-mediated chloride ion uptake in the absence and presence of ALLO in rat brain microsacs preparations. In addition, the effects of the 3beta-steroids and their interaction with ALLO were investigated by patch-clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) in rat hypothalamic neurons from the medial preoptic nucleus (MPN). All tested 3beta-steroids reduced the ALLO-enhanced GABA response in cerebral cortex, in hippocampus and in MPN. In cerebellum, only one had this effect. However, in the absence of ALLO, two of the 3beta-steroids potentiated GABA-evoked chloride ion uptake and prolonged the sIPSCs decay time, whereas the others had little or no effect. Therefore, it is possible that at least some 3beta-steroids can act as positive GABA(A) receptor modulators as well as negative modulators depending on whether or not ALLO is present. Finally, these results suggest that the 3beta-steroids could be of interest as pharmacological agents that could counteract the negative effects of ALLO.

Analysis of Variance↗
PubMed2005

Rapid non-genomic effect of glucocorticoid metabolites and neurosteroids on the gamma-aminobutyric acid-A receptor.

Glucocorticoids and neurosteroids, such as allopregnanolone and tetrahydrodeoxycorticosterone, are released during stress. A non-genomic effect of glucocorticoids has been established but is not yet fully understood. We have studied the effect of glucocorticoid metabolites on the gamma-aminobutyric acid (GABA) system. In these experiments we studied the effects of the glucocorticoid metabolites allotetrahydrocortisol, tetrahydrocortisol, allotetrahydrocortisone and tetrahydrocortisone in rat cortical microsacs. Our results showed that both these cortisol and cortisone metabolites reduce GABA-mediated chloride ion uptake. This reduction was not observed in the presence of allopregnanolone but allotetrahydrocortisol interacts with allopregnanolone, enhancing the allopregnanolone-stimulated potentiation of GABA-mediated chloride ion uptake. This enhanced effect was completely blocked by the addition of 30 microm of the 3beta-isomer of allopregnanolone, isoallopregnanolone. Our findings show that steroids released during stress interact with each other and GABA in the GABA system.

Animals↗
PubMed2001

Segregation of nitrogen fixation and oxygenic photosynthesis in the marine cyanobacterium Trichodesmium.

In the modern ocean, a significant amount of nitrogen fixation is attributed to filamentous, nonheterocystous cyanobacteria of the genus Trichodesmium. In these organisms, nitrogen fixation is confined to the photoperiod and occurs simultaneously with oxygenic photosynthesis. Nitrogenase, the enzyme responsible for biological N2 fixation, is irreversibly inhibited by oxygen in vitro. How nitrogenase is protected from damage by photosynthetically produced O2 was once an enigma. Using fast repetition rate fluorometry and fluorescence kinetic microscopy, we show that there is both temporal and spatial segregation of N2 fixation and photosynthesis within the photoperiod. Linear photosynthetic electron transport protects nitrogenase by reducing photosynthetically evolved O2 in photosystem I (PSI). We postulate that in the early evolutionary phase of oxygenic photosynthesis, nitrogenase served as an electron acceptor for anaerobic heterotrophic metabolism and that PSI was favored by selection because it provided a micro-anaerobic environment for N2 fixation in cyanobacteria.

Aerobiosis↗
PubMed2001

A novel monoclonal antibody specific for the N-terminal end of GAD65.

We describe a novel monoclonal antibody raised towards the N-terminus of the 65 kDa isoform of glutamate decarboxylase (GAD65). This N-GAD65 mAb is highly specific for GAD65 and can be used in a wide range of applications such as Western blot analysis, immunoprecipitation and immunocytochemistry. Full-length cDNAs coding for N-GAD65 mAb heavy and light chains were cloned and characterized by nucleotide sequence analysis. Both heavy and light chain-specific cDNAs are functional and are members of mouse heavy chain subgroup IgG1 and kappa chain group 2, respectively. Comparing the N-GAD65 mAb gene sequences with GenBank shows that the cDNAs were not reported previously.

Amino Acid Sequence↗
PubMed2001

Distribution and properties of neutral ceramidase activity in rat intestinal tract.

Ceramide plays an important role in regulating cell proliferation and apoptosis. Recent studies indicate that generation of ceramide in the intestine from sphingomyelin hydrolysis may be implicated in colon cancer development. The enzymes that catalyze the further hydrolysis of ceramide in the intestine have, however, not been well investigated. Our data reveal the existence of a ceramidase (EC 3.5.1.23) in rat intestinal mucosa with an optimal pH of 7.0. One milligram of mucosal protein is able to hydrolyze 44.0+/-9.6 nmol of ceramide in 1 hr. The activity is low in the proximal duodenum and increases to a plateau in the proximal jejunum. The activity is then similar throughout the small intestine, until it declines in the distal part of ileum. Some activity is also detectable in the colon. The activity increases slightly in the presence of monomeric bile salt concentrations and sharply at the critical micellar concentration. Similar patterns were observed for both primary (taurocholate) and secondary (taurodeoxycholate) bile salts. The addition of Triton X-100 enhances the ceramidase activity at optimal bile salt concentration. The reaction is linear with time for the first 20 min and the hydrolytic rate declines slowly thereafter. Finally, the activity shows a considerable resistance against tryptic degradation, as 71% of the ceramidase activity remained when the homogenates were preincubated with high concentrations of trypsin. Intestinal mucosa also has a ceramide synthesis activity, with a distribution pattern generally paralleling ceramide hydrolysis activity. In conclusion, intestinal neutral ceramidase has a distinct distribution pattern and bile salt dependence, which enables it to collaborate with intestinal sphingomyelinase in hydrolysis of sphingomyelin.

Amidohydrolases↗
PubMed1998

Whole-cell immunolocalization of nitrogenase in marine diazotrophic cyanobacteria, trichodesmium spp

The mechanism by which planktonic marine cyanobacteria of the genus Trichodesmium fix N2 aerobically during photosynthesis without heterocysts is unknown. As an aid in understanding how these species protect nitrogenase, we have developed an immunofluorescence technique coupled to light microscopy (IF-LM) with which intact cyanobacteria can be immunolabeled and the distribution patterns of nitrogenase and other proteins can be described and semiquantified. Chilled ethanol was used to fix the cells, which were subsequently made permeable to antibodies by using dimethyl sulfoxide. Use of this technique demonstrated that about 3 to 20 cells (mean +/- standard deviation, 9 +/- 4) consecutively arranged in a Trichodesmium trichome were labeled with the nitrogenase antibody. The nitrogenase-containing cells were distributed more frequently around the center of the trichome and were rarely found at the ends. On average 15% of over 300 randomly encountered cells examined contained nitrogenase. The percentage of nitrogenase-containing cells (nitrogenase index [NI]) in an exponential culture was higher early in the light period than during the rest of the light-dark cycle, while that for a stationary culture was somewhat constant at a lower level throughout the light-dark cycle. The NI was not affected by treatment of the cultures with the photosynthetic inhibitor dichloro 1,3'-dimethyl urea or with low concentrations of ammonium (NH4Cl). However, incubation of cultures with 0.5 &mgr;M NH4Cl over 2 days reduced the NI. The IF technique combined with 14C autoradiography showed that the CO2 fixation rate was lower in nitrogenase-containing cells. The results of the present study suggest that (i) the IF-LM technique may be a useful tool for in situ protein localization in cyanobacteria, (ii) cell differentiation occurs in Trichodesmium and only a small fraction of cells in a colony have the potential to fix nitrogen, (iii) the photosynthetic activity (CO2 uptake) is reduced if not absent in N2-fixing cells, and (iv) variation in the NI may be a modulator of nitrogen-fixing activity.

Journal Article↗
PubMed1997

Expression pattern of glutamate decarboxylase (GAD) in the developing cortex of the embryonic chick brain.

The development of the GABAergic system in the chick embryo telencephalon has been studied. Special emphasis was placed on the development of glutamate decarboxylase (GAD) between embryonic day 8 (E8) and E17. The GABA immunoreactivity and neuron-specific enolase expression was detected simultaneously in glutardialdehyde fixed sections, which confirmed that GABAergic cells exhibit neuronal phenotype. The GAD expression was studied by means of immunohistochemistry on cryo-sectioned material both at the light and electron microscopic levels. Furthermore, the presence and localization of GAD65 and GAD67 mRNAs were studied with an in situ hybridization technique with digoxigenin-labeled RNA probes. Protein expression as well as mRNA appearance mostly coincided both temporally and spatially. In the parahippocampal area, as well as in other regions of the developing cortex, GAD staining was seen from E8 onwards. The number of positive cells increased as did the intensity of staining up to E14. As observed in the electron microscope, the GAD protein was co-localized with GABA in most cases, although some GAD-positive cells devoid of GABA-staining also were observed. The pattern of GAD mRNA expression was in general similar to that of GAD immunostaining. Both GAD65 and GAD67 mRNA were detected during the entire period. Furthermore, GAD67 mRNA localization spatially was more correlated with GAD protein expression. The study provides evidence for the notion that development of the GABAergic system occurs rapidly during embryogenesis and, as suggested from mRNA data, that two forms of GAD with slight difference in distribution can contribute to this.

Animals↗
PubMed1996

Early 99mTc dimercaptosuccinic acid (DMSA) scintigraphy in symptomatic first-time urinary tract infection.

During a 2 year period, 175 children below 6 years of age (median 0.4 year) with non-obstructive symptomatic urinary tract infection were studied by 99mTc dimercaptosuccinic acid (DMSA) scintigraphy. DMSA scintigraphy was performed at a median of 10 days after the start of treatment and was abnormal in 73 children (42%), equivocal in 29 (16%) and normal in 73 (42%). Reflux was seen in 27% of all children and in 38% of the renal units that were abnormal at DMSA scintigraphy. A decreasing frequency of abnormalities at DMSA scintigraphy was seen within the first 14 days after the start of treatment. C-reactive protein and grade of reflux correlated significantly with abnormal DMSA studies. To demonstrate renal involvement in acute urinary tract infection, DMSA scintigraphy should be performed within days after the start of treatment. It is noteworthy that reflux was seen in less than half of renal units with abnormal DMSA scintigraphy.

Acute Disease↗
PubMed1995

Morphological and GABA-immunoreactive development of the embryonic chick telencephalon.

The development of neurons utilizing gamma-aminobutyric acid (GABAergic neurons) in prosencephalon and telencephalon from chicken embryonic days 4-14 (E4-E14) was studied by means of immunohistochemistry. Furthermore, routine histology and transmission electron microscopy. respectively, were performed in order to study the morphological development in the designated area. The main finding is that development of GABAergic neurons in the chick telencephalon is rapid; the GABA neurons are appearing in bulk at day 8, being "overexpressed" at days 10-11, decreasing in numbers thereafter and achieving mature morphology on day 14, which is considerably faster than in the rodent. Morphological analysis revealed that the prosencephalon mainly consisted of a thin layer of undifferentiated neuroblasts in the E4 embryo. By E6, the prosencephalon had increased in thickness and occasional cells outside the neuroepithelium showed a more mature morphology with a few cells weakly staining positive for GABA. At E8, the prospective granular and subventricular layers had developed. At E14, the appearance of the telencephalon is approximating that of the adult since both ependymal cells and morphologically mature neurons can be seen.

Animals↗
PubMed1989

In vitro release of anthralin from white petrolatum and an o/w cream.

A method to study the in vitro release of anthralin from ointments was developed. A diffusion cell with an artificial membrane (dialysis membrane) was used. As the solubility of anthralin in water is extremely low, methanol was chosen as receptor phase. The temperature at the membrane was kept constant at 32 degrees C during the release study. At appropriate intervals samples were withdrawn and assayed by HPLC. The in vitro release of anthralin from white petrolatum and a cream containing 70% oil in water (Locobase) was studied in a concentration range of 0.04-3.0%. Both ointments showed a faster release with increasing concentration of anthralin. The in vitro release of anthralin from the cream was significantly faster than from white petrolatum.

Anthralin↗
PubMed1986

Studies on the evaluation of preservative efficacy--II. The determination of antimicrobial characteristics of benzylalcohol.

A successful kinetic approach to the screening of preservation efficacy of benzylalcohol--a neutral-type preservative--is described. The D-value, activation energy (Ea), temperature coefficient (Q10) and concentration exponent (n) were used as parameters in determining the influence of different factors on the efficacy of benzylalcohol. Factors, such as the pH of the solution, temperature and concentration of the preservative were investigated. The study was carried out using five micro-organisms: Aspergillus niger, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus.

Bacteria↗