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Biomedical subjects

J Christensen

Publications and source records attributed to J Christensen.

At least 91 records · Page 5Linked to original sources
PubMed1997

The role of antioxidant enzymes in the control of opossum sphincter of Oddi motility.

Superoxide rapidly oxidizes nitric oxide (NO) to form peroxynitrite, thus terminating the biological activity of NO. The aims of our study were to determine if superoxide alters the motor function of the sphincter of Oddi and to localize the antioxidant enzymes in the sphincter of Oddi. Immunostaining was performed and enzyme activities were measured in the sphincter of Oddi. In physiological experiments, force-displacement transducers recorded tension in the spontaneously contracting sphincter of Oddi and after electrical field stimulation (EFS) of precontracted sphincter of Oddi. Superoxide was generated by the addition of xanthine with xanthine oxidase, superoxide radicals were scavenged by the addition of superoxide dismutase (SOD), and catalase or SOD was inhibited by diethyldithiocarbamic acid. Immunostaining demonstrated SOD and catalase immunoreactivity in ganglia situated at the serosal surface of the circular muscle. Total SOD activity was 202 +/- 12 U/mg. Generation of superoxide or inhibition of SOD increased the contractile frequency and decreased relaxation after EFS. We conclude that superoxide alters sphincter of Oddi motor function, and the presence of superoxide scavenging enzymes in enteric plexuses suggests that they may regulate sphincter of Oddi neuromuscular function by clearing endogenous superoxide.

Animals↗
PubMed1996

Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.

OBJECTIVE: To determine whether neuromuscular dysfunction of the esophagus causes chest pain in patients in whom no disease is found on cardiac work-up, upper gastrointestinal endoscopy, esophageal manometry, and 24-hour pH studies. DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: 24 consecutive patients and 12 healthy controls. MEASUREMENTS: A new technique, impedance planimetry, was used to measure the sensory, motor, and biomechanical properties of the human esophagus. The impendance planimeter, which consists of a probe with four ring electrodes, three pressure sensors, and a balloon, simultaneously measures intraluminal pressure and cross-sectional areas. This allows calculation of the biomechanical variables of the esophageal wall. RESULTS: Stepwise balloon distentions from 5 to 50 cm H2O induced a first sensation at a mean pressure (+/- SD) of 15 +/- 9 cm H2O in patients and 30 +/- 11 cm H2O in controls (P < 0.001). Moderate discomfort and pain were reported by 20 of 24 patients (83%) at 26 +/- 9 cm H2O and at 36 +/- 9 cm H2O, respectively, but by none of the controls (P < 0.001). Typical chest pain was reproduced in 20 of 24 patients (83%). In patients, the reactivity of the esophagus to balloon distention was greater (P = 0.01), the pressure elastic modulus was higher (P = 0.02), and the tension-strain association showed that the esophageal wall was less distensible (P = 0.02). Distention excited tertiary contractions and secondary peristalsis at a lower threshold of pressure (P = 0.05) and with a higher motility index in patients than in controls (P = 0.04). CONCLUSION: In patients with chest pain and normal cardiac and esophageal evaluations, impedance planimetry of the esophagus reproduces pain and is associated with a 50% lower sensory threshold for pain, a 50% lower threshold for reactive contractions, and reduced esophageal compliance.

Adult↗
PubMed1996

Repair-deficient 3-methyladenine DNA glycosylase homozygous mutant mouse cells have increased sensitivity to alkylation-induced chromosome damage and cell killing.

In Escherichia coli, the repair of 3-methyladenine (3MeA) DNA lesions prevents alkylation-induced cell death because unrepaired 3MeA blocks DNA replication. Whether this lesion is cytotoxic to mammalian cells has been difficult to establish in the absence of 3MeA repair-deficient cell lines. We previously isolated and characterized a mouse 3MeA DNA glycosylase cDNA (Aag) that provides resistance to killing by alkylating agents in E. coli. To determine the in vivo role of Aag, we cloned a large fragment of the Aag gene and used it to create Aag-deficient mouse cells by targeted homologous recombination. Aag null cells have no detectable Aag transcripts or 3MeA DNA glycosylase activity. The loss of Aag renders cells significantly more sensitive to methyl methanesulfonate-induced chromosome damage, and to cell killing induced by two methylating agents, one of which produces almost exclusively 3MeAs. Aag null embryonic stem cells become sensitive to two cancer chemotherapeutic alkylating agents, namely 1,3-bis(2-chloroethyl)-1-nitrosourea and mitomycin C, indicating that Aag status is an important determinant of cellular resistance to these agents. We conclude that this mammalian 3MeA DNA glycosylase plays a pivotal role in preventing alkylation-induced chromosome damage and cytotoxicity.

Alkylating Agents↗
PubMed1996

NMDA and kainate-evoked release of nitric oxide and classical transmitters in the rat striatum: in vivo evidence that nitric oxide may play a neuroprotective role.

The effects of N-methyl-D-aspartate (NMDA), kainate, S-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and KCl on striatal nitric oxide (NO), acetylcholine (ACh), dopamine (DA), serotonin (5-HT), aspartate (ASP), glutamate (GLU) and gamma-aminobutyric acid (GABA) release were measured in anaesthetized rats in vivo by microdialysis and in vitro in organotypic slice cultures. Local NMDA (1-100 microM) infusion by retrodialysis dose-dependently increased levels of classical transmitters, NO2-, NO3-, citrulline and arginine at similar thresholds (10 microM). Similar patterns of NMDA-evoked (50 microM) release were seen in striatal cultures. NMDA-evoked changes were all calcium-dependent and blocked by NMDA (APV or MK-801) but not AMPA/kainate (DNQX) receptor antagonists, excepting DA which could be prevented by both. In vivo, kainate increased NO2-, NO3-, CIT and ARG levels at 50 and 100 microM but was less potent than NMDA. Kainate also evoked significant ACh, DA and GLU release dose-dependently starting at 1-10 microM whereas 5-HT, ASP and GABA required 50 or 100 microM doses. Kainate effects were inhibited by DNQX, but not by APV, and were calcium-dependent, AMPA failed to alter NO2-, NO3-, CIT or ARG levels at 50 or 100 microM doses but dose-dependently increased ACh and DA. Similar results were seen with kainate (50 microM) and AMPA (50 microM) in vitro. KCl evoked NO2-, NO3-, CIT and ARG release as well as that of the classical transmitters in vivo and in vitro. In vivo administration of the NO synthase inhibitor L-nitroarginine (L-NARG; 100 microM) significantly reduced NO2-, NO3- and CIT levels and prevented NMDA, kainate or KCl-evoked increases. It also potentiated ACh, ASP, GLU and GABA release and reduced that of DA in response to 50 microM NMDA whereas treatment with an NO-donor (SNAP; 10 microM) significantly reduced evoked ACh, ASP and GLU release. The NO synthase inhibitor L-NARG potentiated kainate-evoked ACh release and reduced that of DA, although less potently than NMDA, but it had no effect on KCl-evoked transmitter release. Overall, these results show that both NMDA and kainate increase striatal NO release at similar dose-thresholds as for classical transmitter release suggesting that NO is dynamically released under physiological and not just pathological conditions. Reductions of striatal NO levels also potentiates calcium-dependent transmitter release in response to NMDA and, to a lesser extent, kainate, whereas increasing them reduces it. This is consistent with a role for NO as a neuroprotective agent in this region acting to desensitize NMDA receptors.

Animals↗
PubMed1996

Acute and transient psychotic disorder: comorbidity with personality disorder.

A study sample of 51 patients with acute and transient psychotic disorder (ATPD) (ICD-10) is presented. The findings suggest that, in hospital settings, ATPD is a non-frequent condition with onset in early adult life and most often associated with female sex, good premorbid social functioning and no or minor/moderate psychosocial stressors. The DSM-IV criteria distribute the patients into three diagnostic categories: schizophreniform disorder (41%), brief psychotic disorder (33%) and psychotic disorder not otherwise classified (25%). A high prevalence (63%) of personality disorders (PD) is revealed after recovery from the psychotic episode. The ATPD is not related to any specific PD, and in a substantial minority (37%) of cases no PD is found. The unspecified category is by far the most frequent PD in patients with ATPD. The sample will be followed up and reassessed.

Acute Disease↗
PubMed1996

Antioxidant enzymes in intramural nerves of the opossum esophagus.

Superoxide radical (O2-.) combines with nitric oxide (NO) to form peroxynitrite, thereby nullifying the biological activity of NO. Superoxide dismutase (SOD) prevents this reaction by converting O2-. to H2O2. We tested the hypotheses that the antioxidant enzymes catalase (CAT), Mn SOD, and Cu/Zn SOD are present in enteric neurons of the opossum esophagus, and that O2-. alters esophageal motor function. Immunostaining demonstrated CAT, Mn SOD, and Cu/Zn SOD immunoreactivity in interganglionic nerve bundles and ganglia of the myenteric and submucosal plexuses. Western blot analysis confirmed the presence of these enzymes in homogenates of esophageal muscularis propria, and enzyme assays demonstrated Cu/Zn SOD and Mn SOD activities of 262 and 73 U/mg protein, respectively. Both diethyldithiocarbamic acid, an inhibitor of Cu/Zn SOD, and xanthine (X) with xanthine oxidase (XO), which generate O2-., shortened the latency of the nerve-mediated contraction of circular esophageal muscle, the off response, by 20.2 and 23.4%, respectively. SOD alone did not affect the latency, but it inhibited the effect of X with XO on the latency. Antioxidant enzymes found in intramural esophageal nerves may play a role in regulating NO-mediated neuromuscular communication in the esophagus.

Animals↗
PubMed1996

Ultrasonographically guided fine-needle aspiration biopsy of intrathoracic tumors.

PURPOSE: Evaluation of diagnostic accuracy and complication frequency at ultrasonographically guided fine-needle aspiration biopsy of intrathoracic tumors. MATERIAL AND METHODS: A total of 134 ultrasonographically guided percutaneous fine-needle aspiration biopsies were performed on 128 patients with intrathoracic tumors abutting on the pleura. A cytologic diagnosis was obtained in 119 patients (93%). RESULTS: In 83 patients, cytologic malignancy was found; in 34, benignity; and in 2, cellular atypia. A total of 117 diagnoses were correct and 2 diagnoses were false-positive. A malignancy subtyping based on the cytologic aspirates was made in 80 patients. In 40 (93%) of 43 histologically proven subtypes, the subtyping was correct. The complication frequency in terms of pneumothorax was 3.7%. CONCLUSION: Ultrasonographically guided percutaneous fine-needle aspiration biopsy is a safe and reliable method of establishing the cytologic diagnosis of intrathoracic tumors.

Biopsy, Needle↗
PubMed1996

Circadian variation of DNA replication in hamster cheek pouch epithelium analysed by tritiated thymidine labelling, flow sorting and autoradiography: no resting S phase cells in the normal epithelium.

In the normal hamster cheek pouch epithelium, cell proliferation takes place with a pronounced circadian rhythm. We tested our previous hypothesis that all cells having S phase DNA content are actively synthesizing DNA and thus participating in the daily cohort of proliferating cells. We found no evidence of resting S phase cells in the normal epithelium. Using labelling with tritiated thymidine followed by fluorescence activated cell sorting according to DNA content and by autoradiography of the sorted nuclei, it was demonstrated that during the 24 h period almost all cells with mid S phase DNA content were active in DNA synthesis.

Animals↗
PubMed1995

[Primary intracranial and intraspinal neoplasms in Denmark 1943-1987].

This is a descriptive study of primary intracranial and intraspinal tumours notified to the national Danish Cancer Registry during the years 1943-1987. A total of 19,317 cases of benign and malignant neoplasms were included over these 45 years with a doubling of the age-standardized incidence rates for both men and women from start till end of the registration period. The trend was mainly explained by markedly increasing rates in the age groups 60 years or above at diagnosis. Approximately some 74% of tumours were derived from the brain tissues and 19% from the intracranial and intraspinal meninges. Meningiomas predominate among women with a male:female ratio of 0.5, while tumours of the brain tissues predominate among men (ratio 1.3). Meningiomas are more frequently encountered as a chance finding at autopsy compared to other types of intracranial and intraspinal tumours. The above-mentioned increase in age-specific incidence is due mainly to improved diagnostic capabilities over the period and a subsequent decrease in the underreporting of these tumour types.

Adolescent↗
PubMed1995

NADPH-diaphorase-positive nerve fibers in smooth muscle layers of opossum esophagus: gradients in density.

Nitric-oxide-releasing nerves regulate esophageal smooth muscle function. The density of such nerve fibers may differ in the different functional parts of the esophagus. We used both inspection and gray-scale analysis of digitized images to seek differences in density of such nerve fibers, stained for reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase), between esophageal body and esophago-gastric sphincter and between smooth muscle layers in the opossum esophagus. Sections of Swiss roll preparations of the entire organ were stained for NADPH-diaphorase and for immunoreactivity to vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), galanin (GAL), substance P (SP) and constitutive nitric oxide synthase (cNOS). In the circular muscle layer, NADPH-diaphorase-positive fibers were most abundant at the cephalic end of the esophageal body with a significant decline toward and through the esophago-gastric sphincter. In the longitudinal muscle layer and the longitudinally-oriented muscularis mucosae, NADPH-diaphorase-positive nerve fibers were most abundant at the esophago-gastric sphincter with a significant decline toward and through the striated-smooth muscle junction. cNOS immunoreactivity co-localized with NADPH-diaphorase activity. Fibers stained for CGRP immunoreactivity were distributed like the NADPH-diaphorase-positive fibers. Fibers stained for immunoreactivity to the other peptides (VIP, GAL, SP) showed no clear differences in distribution along the esophagus in any of the muscle layers.

Amino Acid Oxidoreductases↗
PubMed1995

Zinc-containing telencephalic connections to the rat striatum: a combined Fluoro-Gold tracing and histochemical study.

The organization of telencephalic zinc-containing neurons projecting to the rat striatum was investigated by combining intrastriatal injections of the retrograde fluorescent tracer Fluoro-Gold with histochemistry revealing zinc-containing neurons and terminals. Throughout the ipsilateral and contralateral neocortex, corticostriatal zinc-containing neurons with striatal projections were located predominantly at the border between deep layer V and superficial layer VI. Additional, but fewer zinc-containing neurons were located in layers II, III and deep layer VI of the ipsilateral neocortex. The main neocortical source of zinc-containing afferents to the striatum were the frontal motor cortices. Smaller contingents of zinc-containing projections arose from the motor cortical forelimb and hindlimb areas and the parietal cortical areas. In the cingulate cortex, zinc-containing neurons with striatal projections were found predominantly in the ipsilateral layers II and III, with only few neurons in the ipsilateral layer VI and in the contralateral layers II, III and VI. Subcortically, zinc-containing neurons belonging to the amygdalostriatal projection were found bilaterally in the basolateral and basomedial nuclei of the amygdala. Zinc has been found to modulate the response of many ligand- and voltage-gated ion channels, including both GABA receptors and NMDA-, AMPA- and kainate-type glutamate receptors. The present findings raise the possibility that zinc in the corticostriatal projections might play a role in the selective, possibly excitotoxic, cell death of GABAergic projections seen in Huntington's disease.

Animals↗
PubMed1995

Effect of nitroblue tetrazolium on NO synthase and motor function of opossum esophagus.

Nitric oxide mediates neuromuscular events in the opossum esophagus. The NADPH diaphorase stain is used to localize nitric oxide synthase-containing enteric neurons. Cells stain by the NADPH diaphorase technique because they reduce nitroblue tetrazolium to the visible formazan. The effects of nitroblue tetrazolium on neuromuscular function and nitric oxide synthase of esophageal muscle were studied. The NADPH diaphorase stain was performed. Nitroblue tetrazolium inhibited lower esophageal sphincter relaxation, abolished the latency gradient of the off response, and inhibited nitric oxide synthase. The NADPH diaphorase technique stained myenteric plexus nerve cell bodies and nerve processes. Nitroblue tetrazolium is not a nonspecific muscle or nerve toxin, as nerve-mediated cholinergic responses, responses to exogenous nitric oxide, and responses to myogenic stimulation were maintained after nitroblue tetrazolium abolished the off response and lower esophageal sphincter relaxation. Nitroblue tetrazolium inhibits nitric oxide-mediated events and nitric oxide synthase. It stains neurons in the esophageal myenteric plexus.

Animals↗
PubMed1995

Clozapine serum levels and side effects during steady state treatment of schizophrenic patients: a cross-sectional study.

Serum clozapine (S-Cloza) and serum desmethyl-clozapine concentrations (S-Descloza) were measured in 30 chronic schizophrenic in- and out-patients on a variable dose regimen. All patients were in steady state with respect to clozapine therapy and in a stable condition with respect to psychotic illness. The 24-h clozapine dose (median with interquartile range in parenthesis) was 350 (228-425) mg/24 h (range 100-700). There was a weak positive correlation between doses and the BPRS total score (r = 0.44, P < 0.05). The median S-Cloza was 1076 (706-1882) nmol/l (range 196-5581 corresponding to 64-1824 ng/ml). The S-Cloza was linearly correlated to dose but with a high interindividual variation at equal doses, e.g. a factor of 8 at 400 mg/24 h, but a low intraindividual variability of 20%. The S-Descloza averaged 77% of the S-Cloza and was highly correlated to S-Cloza (r = 0.90; P < 0.001). The S-Descloza/dose ratio increased with age and duration of treatment. The side effects registered were EEG abnormalities (83%), tachycardia (23%), increased liver enzyme activity (60%), orthostatic hypotension (17%), and moderate leucocytosis (17%). Only EEG changes were correlated to S-Cloza (r = 0.43; P < 0.05). The score values of the UKU Side Effect Scale were weakly (r = 0.36) correlated to S-Cloza. No side effects were correlated to S-Descloza, doses, or treatment duration. The frequency of side effects was higher than in studies using lower mean doses indicating a correlation between doses or S-Cloza and the frequency of side effects. It is concluded that clozapine fulfils the criteria for therapeutic drug monitoring. TDM may contribute to finding the lowest effective dose with the fewest possible side effects.

Adolescent↗
PubMed1995

Manganese superoxide dismutase and reduced nicotinamide adenine dinucleotide diaphorase colocalize in the rat gut.

BACKGROUND & AIMS: Superoxide and other free radicals participate in inflammatory bowel disease and ischemia-reperfusion injury. Manganese superoxide dismutase (SOD) scavenges superoxide. Mn SOD is colocalized with reduced nicotinamide adenine dinucleotide (NADH) diaphorase in some tissues. NADH diaphorase histochemistry selectively stains enteric nerves. The aim of this study was to seek colocalization of Mn SOD with NADH diaphorase in the gut, especially in enteric nerves. METHODS: Indirect immunofluorescent staining and histochemistry were used to localize Mn SOD and NADH diaphorase in rat gut. RESULTS: Strong Mn SOD immunoreactivity was found in parietal cells, most intramural nerve cell bodies, the colonic interstitial cells of Cajal (at the submucosa-circular muscle layer interface), and intestinal epithelium cells. Weak to moderate Mn SOD immunoreactivity characterized smooth muscle cells, small submucosal arteries, esophageal striated muscle, esophageal epithelium, gastric epithelium, and intestinal glands. NADH diaphorase histochemistry (with Triton X-100) resulted in identical staining. CONCLUSIONS: Mn SOD and NADH diaphorase are colocalized throughout rat gut with strong activity in enteric nerves and colonic interstitial cells of Cajal.

Animals↗
PubMed1995

Measurement of monochromatic ocular aberrations of human eyes as a function of accommodation by the Howland aberroscope technique.

Further development of the objective version of the Howland and Howland [(1976) Science, 193, 580-582; (1977) Journal of the Optical Society of America, 67, 1508-1518] aberroscope technique for measuring ocular aberrations is described. Compensation for refractive corrections and calibration is discussed. The technique was used to investigate the effect of accommodation upon the monochromatic aberrations of the right eyes of 15 subjects. Coma and coma-like aberrations were the dominant aberrations for most people at different accommodation levels, thus confirming previous findings. Variations in aberrations were considerable between subjects. About half the subjects showed the classical trend towards negative spherical aberration with accommodation. Changes in spherical aberration with accommodation in this study were less than found in previous studies where all monochromatic aberration was considered to be spherical aberration.

Accommodation, Ocular↗