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Biomedical subjects

J Christensen

Publications and source records attributed to J Christensen.

At least 109 records · Page 6Linked to original sources
PubMed1995

Hypocomplementemic urticarial vasculitis syndrome. Clinical and serologic findings in 18 patients.

We identify and describe clinical findings in hypocomplementemic urticarial vasculitis syndrome (HUVS), an uncommon to rare illness related to systemic lupus erythematosus (SLE). A patient with recurrent, idiopathic urticaria-like lesions was diagnosed as having HUVS if a lesional biopsy showed leukocytoclastic vasculitis, the serum C1q was markedly decreased, and antibody to C1q was detected in the patient's serum. The clinical characteristics, serologic findings, and outcome of patients who met these criteria were determined from prospective and retrospective data, including hospital and office records, patient interviews, previously banked serum samples, and freshly drawn sera. Eighteen patients with HUVS were identified, and high incidences of angioedema, ocular inflammation, glomerulonephritis, and obstructive pulmonary disease were found. Renal and lung biopsies showed mesangial or membranoproliferative glomerulonephritis and severe pulmonary emphysema without vasculitis. Pulmonary function was measured in 17 patients, 11 of whom had dyspnea. All dyspneic patients had moderate to severe airflow obstruction, which progressed in all 11 and subsequently improved in only 1. Six of these 11 patients died of respiratory failure, 1 underwent lung transplantation, and 3 of the remaining 4 have moderately severe to life-threatening respiratory insufficiency. Treatment did not appear to alter the progression of obstructive lung disease. In contrast, renal insufficiency improved with treatment in 2 of 2 patients. Angioedema, ocular inflammation, obstructive lung disease, and glomerulonephritis appear to be common in HUVS, and lung disease causes substantial morbidity and mortality. The pathogenesis of HUVS may involve humoral autoimmunity, although it is not clear how autoimmunity would participate in development of obstructive lung disease. Cigarette smoking appears to be a risk factor for fatal lung disease in HUVS. All patients with HUVS should be made aware of this possibility and should be advised, encouraged, and helped to avoid tobacco smoke.

Adult↗
PubMed1995

The NS1 polypeptide of the murine parvovirus minute virus of mice binds to DNA sequences containing the motif [ACCA]2-3.

A DNA fragment containing the minute virus of mice 3' replication origin was specifically coprecipitated in immune complexes containing the virally coded NS1, but not the NS2, polypeptide. Antibodies directed against the amino- or carboxy-terminal regions of NS1 precipitated the NS1-origin complexes, but antibodies directed against NS1 amino acids 284 to 459 blocked complex formation. Using affinity-purified histidine-tagged NS1 preparations, we have shown that the specific protein-DNA interaction is of moderate affinity, being stable in 0.1 M salt but rapidly lost at higher salt concentrations. In contrast, generalized (or nonspecific) DNA binding by NS1 could be demonstrated only in low salt. Addition of ATP or gamma S-ATP enhanced specific DNA binding by wild-type NS1 severalfold, but binding was lost under conditions which favored ATP hydrolysis. NS1 molecules with mutations in a critical lysine residue (amino acid 405) in the consensus ATP-binding site bound to the origin, but this binding could not be enhanced by ATP addition. DNase I protection assays carried out with wild-type NS1 in the presence of gamma S-ATP gave footprints which extended over 43 nucleotides on both DNA strands, from the middle of the origin bubble sequence to a position some 14 bp beyond the nick site. The DNA-binding site for NS1 was mapped to a 22-bp fragment from the middle of the 3' replication origin which contains the sequence ACCAACCA. This conforms to a reiterated motif (ACCA)2-3, which occurs, in more or less degenerate form, at many sites throughout the minute virus of mice genome (J. W. Bodner, Virus Genes 2:167-182, 1989). Insertion of a single copy of the sequence (ACCA)3 was shown to be sufficient to confer NS1 binding on an otherwise unrecognized plasmid fragment. The functions of NS1 in the viral life cycle are reevaluated in the light of this result.

Adenosine Triphosphate↗
PubMed1995

Purification and characterization of the major nonstructural protein (NS-1) of Aleutian mink disease parvovirus.

We have previously described the expression of the major nonstructural protein (NS-1) of Aleutian mink disease parvovirus (ADV) in insect cells by using a baculovirus vector (J. Christensen, T. Storgaard, B. Bloch, S. Alexandersen, and B. Aasted, J. Virol. 67:229-238, 1993). To study its biochemical properties, ADV NS-1 was expressed in Sf9 insect cells and purified to apparent homogeneity with a combination of nuclear extraction, Zn2+ ion chromatography, and immunoaffinity chromatography on monoclonal antibodies. The purified protein showed ATP binding and ATPase- and ATP- or dATP-dependent helicase activity requiring either Mg2+ or Mn2+ as a cofactor. The ATPase activity of NS-1 was efficiently stimulated by single-stranded DNA and, to a lesser extent, double-stranded DNA. We also describe the expression, purification, and characterization of a mutant NS-1 protein, in which a lysine in the putative nucleotide binding consensus sequence of the molecule was replaced with serine. The mutated NS-1 was expressed at 10-fold higher levels than wild-type NS-1, but it exhibited no ATP binding. ATPase, or helicase activity. The availability of large amounts of purified functional NS-1 protein will facilitate studies of the biochemistry of ADV replication and gene regulation leading to disease in mink.

Adenosine Triphosphatases↗
PubMed1995

Minute virus of mice transcriptional activator protein NS1 binds directly to the transactivation region of the viral P38 promoter in a strictly ATP-dependent manner.

The NS1 polypeptide of minute virus of mice (MVM) is a potent transcriptional activator of the MVM P38 promoter. The minimum region of this promoter required for transactivation has been identified and termed the transactivation region (tar). However, the function of tar and the biochemical steps involved in NS1-mediated transactivation are not well understood. Here we provide evidence that NS1 binds directly and specifically to tar in a strictly ATP-dependent manner. A DNA fragment containing tar was specifically coimmunoprecipitated with purified baculovirus-expressed MVM NS1, using antibodies directed against NS1 amino- or carboxy-terminal peptides. Using this immunoprecipitation assay, we found that the NS1-tar interaction was enhanced approximately 10-fold by ATP, but subsequent incubation at elevated temperatures in the presence, but not the absence, of MgCl2 caused rapid loss of tar binding. This finding suggests that the tar-NS1 complex has a short half-life under assay conditions which favor ATP hydrolysis. Specific binding was efficiently inhibited by self-ligated oligonucleotides containing the core DNA sequence (ACCA)3, but the same nonligated 20- and 21-mer oligonucleotides were unable to compete effectively, indicating that NS1 only binds to its cognate site when this site is presented on DNA fragments of sufficient size. DNase I footprinting experiments performed in the presence of gamma S-ATP revealed that NS1 protects a 43-bp sequence extending asymmetrically from the (ACCA)2 sequence toward the TATA box of the promoter. NS1 footprints obtained at other sites in the MVM genome were similarly large and asymmetric, all extending approximately 31 bp 5' from the core (ACCA)2-3 sequence. Surprisingly, no footprints were obtained in the absence of gamma S-ATP even under low-stringency binding conditions. However, ATP could be omitted from the reactions if NS1 was first incubated with antibodies directed against its 16-amino-acid carboxy-terminal peptide. Since these antibodies probably create intermolecular cross-links, this finding suggests that NS1 may only bind its cognate site efficiently, or perhaps at all, if the transactivator is first induced to form oligomers. From these data, we hypothesize that ATP binding may also induce NS1 to oligomerize and that such assembly is required before the protein can bind effectively to the tar sequence. The functional implications of the NS1-tar interaction will be discussed.

Adenosine Triphosphate↗
PubMed1995

Ultrasonographic in vitro examination of nonpalpable breast masses. A new method.

Specimen radiology is necessary for ensuring successful surgical excision of nonpalpable, clinically occult breast masses discovered by mammography. However, occasionally nonpalpable lesions are only detected by sonography. A simple method of ultrasonographic in vitro identification of nonpalpable lesions invisible on specimen radiographs is presented.

Adult↗
PubMed1995

Co-localization of manganese superoxide dismutase and NADH diaphorase.

Manganese superoxide dismutase (Mn SOD), mitochondrial enzyme, defends against the toxic effects of superoxide radical (O2.-) in pathological processes by catalyzing the conversion of O2.- to hydrogen peroxide (H2O2). The activity of another enzyme, NADH diaphorase, forms the basis for a histochemical method used commonly to demonstrate nerve cell bodies in the enteric plexuses. We found identical patterns of localization of Mn SOD immunoreactivity and NADH diaphorase activity in brain, esophagus, stomach, colon, liver, and kidney. NADH diaphorase enzymatic activity co-migrated with complexes of Mn SOD on a non-denaturing gel. This suggests that the NADH diaphorase may in some way be related to Mn SOD.

Animals↗
PubMed1995

Ultrasound-guided renal biopsy with biopsy gun technique--efficacy and complications.

One hundred and thirty-one ultrasound-guided renal biopsies performed in 127 patients with automated spring-loaded biopsy technique were evaluated. Adequate tissue for histologic diagnosis was obtained in 92% of the procedures (94% of the patients). The mean glomerular yield was 16.8 glomeruli. Complications were seen in 21% of the patients, 18% having minor and 3% having major complications. Patients with severe hypertension had significantly more complications than the rest of the patients. The rate of complications in patients who had 3 or 4 biopsy passes was not increased compared to patients who had one or 2 biopsy passes. Thus, this study indicates that the risk of complications and the safety of the procedure is not influenced by increasing the number of biopsy passes in order to obtain representative specimens.

Acute Kidney Injury↗
PubMed1995

Iodide mumps after intravascular administration of a nonionic contrast medium. Case report and review of the literature.

Swelling of the submandibular, sublingual and/or parotid glands ("iodide mumps") is an uncommon complication to intravascular administration of contrast material. The etiology remains unclear, but the reaction seems to be idiosyncratic or related to toxic accumulation of iodide in the ductal systems of the salivary glands. The introduction of nonionic contrast media has not eliminated the risk of developing iodide mumps. The first reported case of iodide mumps after intravascular administration of iopromide (Ultravist 300) is presented.

Contrast Media↗
PubMed1995

Chronic intestinal pseudo-obstruction: diagnosis and treatment.

Chronic intestinal pseudo-obstruction (CIP), a syndrome of disordered intestinal motility, is characterized by failure of the intestine to propel its contents through an unobstructed lumen. The symptoms and signs of CIP can be very similar to those of mechanical bowel obstruction. The two disease states differ in management, however; therefore, clinicians must differentiate the two. Abnormal propulsion can result from many causes. Cases can be classified as primary or secondary, and identifiable causes can be subdivided into those affecting neuronal control of motility and those directly affecting intestinal muscle function. Careful history, physical examination, and investigations help identify causative factors. The secondary forms of CIP are more common than the primary, and many cases are reversible by correction of the causative factor (e.g., drugs, metabolic abnormalities, or infection). Management of CIP depends on the cause of the disorder, the extent and location of intestine involved, and the severity of symptoms; general measures include dietary changes, prokinetic agents, and, rarely, surgical interventions. Some children with severe, refractory CIP who are wholly dependent on parenteral nutrition are candidates for consideration of intestinal transplantation.

Chronic Disease↗
PubMed1994

Sensitive gas-liquid chromatographic method for the determination of loratadine and its major active metabolite, descarboethoxyloratadine, in human plasma using a nitrogen-phosphorus detector.

A sensitive gas-liquid chromatographic (GLC) method was developed for the determination of loratadine, a long-acting tricyclic antihistamine, and its active metabolite, descarboethoxyloratadine, in human plasma. The method involved extraction with organic solvent at neutral and alkaline pH. The organic layer from the neutral pH extraction was evaporated to dryness, reconstituted and injected into the GLC system. On the other hand, to the organic layer from the alkaline pH extraction trifluoroacetic anhydride was added. Following addition of H2O, the mixture was centrifuged and the organic layer was evaporated to dryness, reconstituted and injected onto the GLC system that was equipped with a nitrogen specific detector and a fused-silica capillary column. The linearity for both loratadine and descarboxyloratadine were demonstrated with r > or = 0.998 at concentrations ranging from 0.1 to 30 ng/ml. The results showed that the GLC method was accurate (bias < or = 12%) and precise (coefficient of variation, C.V., < or = 12%) for loratadine and descarboethoxyloratadine. The limit of quantitation was 0.1 ng/ml for loratadine with a C.V. of 9.2% and for descarboethoxyloratadine with a C.V. of 5.3%. The GLC method described has been demonstrated to be useful for the determination of loratadine and descarboethoxyloratadine in plasma samples of pediatric volunteers following oral administration of a single dose of 10 mg of loratadine syrup.

Child↗
PubMed1994

Intestinal pseudo-obstruction in adult spinal muscular atrophy.

A 42-year-old woman with negative family history had the insidious onset of weakness in her lower extremities 8 years before, in 1983. The disorder slowly progressed to include cramps and muscle twitches. The diagnosis of adult spinal muscular atrophy (SMA) was made when electromyography showed large rapidly firing motor unit-potentials, positive waves, and fibrillation potentials, and when muscle biopsy of the quadriceps revealed severe alterations consistent with neurogenic atrophy. The patient also had severe chronic constipation for many years. More recently she had developed unremitting diarrhea. Gastrointestinal studies showed no evidence of peristaltic contractions in the rectum, delayed gastric emptying, and abnormal jejunal manometry with altered propagation of the migrating myoelectrical complex.

Adult↗
PubMed1994

Colocalization of NADPH-diaphorase activity and certain neuropeptides in the esophagus of opossum (Didelphis virginiana).

Nitric oxide and various neuropeptides in the myenteric plexus regulate esophageal motility. We sought colocalization of nitric oxide synthase and neuropeptides in frozen sections of mid-portion of smooth-muscled opossum esophagus using NADPH-diaphorase activity to mark the synthase and immunoreactivity to detect peptides. The peptides, all with demonstrated physiological activity in this organ, were calcitonin gene-related peptide, galanin, neuropeptide Y, substance P, and vasoactive intestinal polypeptide. The ExtrAvidin Peroxidase immunostain for each peptide was carried up to the final peroxidase reaction with 3-amino-9-ethyl-carbazole. The NADPH-diaphorase reaction was applied with short incubation to provide light staining just before the peroxidase reaction was performed. We examined sections for the proportions of singly and dually labeled nerve cells in the myenteric plexus. NADPH-diaphorase activity was highly colocalized with calcitonin gene-related peptide (59%), galanin (54%), and vasoactive intestinal polypeptide (53%). It showed little colocalization with neuropeptide Y (10%) and substance P (8%). The proportions of all nerve cells containing each of the substances were: NADPH-diaphorase--33%, calcitonin gene-related peptide--30%, galanin--55%, neuropeptide Y--16%, substance P--35%, and vasoactive intestinal polypeptide--58%. We conclude that the nerves responsible for peristalsis in the esophagus may act by releasing nitric oxide along with other inhibitory substances, calcitonin gene-related peptide, galanin, and vasoactive intestinal polypeptide, but not excitatory substances, neuropeptide Y and substance P.

Animals↗
PubMed1994

Vasoactive intestinal contractor: localization in the opossum esophagus and effects on motor functions.

BACKGROUND/AIMS: Vasoactive intestinal contractor (VIC), an endothelinlike peptide and a putative gastrointestinal hormone, contracts gastrointestinal smooth muscle. The aim was to study VIC in relation to esophageal function. METHODS: Intramural nerves in opossum esophageal smooth muscle strips were stimulated in the presence of various concentrations of VIC and were stained for VIC immunoreactivity. RESULTS: VIC caused an atropine-resistant increase in the amplitude of nerve-induced contractions of the circular muscle. VIC alone contracted longitudinal muscle, and this effect was nearly eliminated by 1 mmol/L atropine. VIC caused an atropine-resistant increase in the resting tone of the lower esophageal sphincter muscle, but it did not affect nerve-induced relaxation of that muscle. VIC-immunoreactive nerve fibers occurred in the longitudinal muscle layer, in the muscularis mucosae, and around the ducts of esophageal glands. A few such fibers were found in the circular muscle layer. Nerve fibers and cell bodies of the myenteric plexus showed VIC immunoreactivity. In the stomach, immunoreactive nerve fibers occurred in muscularis mucosae and circular muscle but not in longitudinal muscle. CONCLUSIONS: VIC is localized in neuronal elements of the opossum esophagus and excites contractions in esophageal smooth muscle.

Animals↗
PubMed1994

Interstitial cells of Cajal in the rat colon are damaged by mild hypoxia.

We examined the hypothesis that vacuolation is a normal feature of interstitial cells of Cajal. With the zinc iodide-osmic acid stain, and using light microscopy, we examined the interstitial cells in Stach's plexus on the submucosal surface of the circular muscle layer of the colon in the rat. We subjected tissues to seven treatments designed to produce different degrees of damage from hypoxia. In the least-damaged colons (fixed immediately after dissection) about 20% of interstitial cells showed vacuoles. In the most damaged colons (immersed for 30 min in Krebs' solution equilibrated with 95% N2/5% CO2 at 37 degrees C) about 96% of cells showed vacuoles. Less drastic treatments produced fewer vacuoles, but even colons immersed for 30 min in Krebs' solution equilibrated with 95% O2/5% CO2 at 37 degrees C showed vacuolation in about 28% of cells. The light microscopic impression was confirmed by electronmicroscopy, but cells subjected to even the most severe treatment retained a recognizable ultrastructure. Vacuolation in interstitial cells is probably artifactual, a consequence of hypoxia.

Animals↗
PubMed1994

Production of mink enteritis parvovirus empty capsids by expression in a baculovirus vector system: a recombinant vaccine for mink enteritis parvovirus in mink.

The VP-2 gene of mink enteritis parvovirus (MEV) was amplified by the polymerase chain reaction using MEV DNA isolated from the faeces of a naturally infected mink. Subsequently the VP-2 gene was cloned into a baculovirus expression vector. Recombinant baculoviruses were isolated and the MEV VP-2 gene product was characterized after expression in Sf9 insect cells. The MEV VP-2 product had the same size as that reported for the wild-type MEV VP-2 protein and was recognized by convalescent sera from MEV-infected mink and a panel of monoclonal antibodies reactive to MEV. Furthermore, the VP-2 protein was able to form parvovirus-like particles, which had haemagglutinating properties comparable with the wild-type MEV. The cloned VP-2 gene was sequenced and only five nucleotide differences were found after alignment with the known sequences of the MEV type 1 and type 2 isolates. Surprisingly, the VP-2 gene encoded a valine and a tyrosine at amino acid positions 232 and 234, identical to the situation found in MEV type 1, but at position 300 there was a valine which is a determinant of MEV type 2. Immunization of mink with approximately 40,000 haemagglutinating units of recombinant MEV VP-2 induced a measurable antibody response as tested by haemagglutination inhibition. Furthermore, the immunized mink did not excrete virus and did not develop clinical disease upon challenge with a virulent isolate of MEV.

Animals↗
PubMed1994

Neuromuscular control of the oropharynx and esophagus in health and disease.

The oropharynx and esophagus convey swallowed materials from the mouth to the stomach and protect the airways from aspiration. These functions are subserved by complex neuromuscular interactions that coordinate the timing of the peristaltic contractions of the swallowing organs. The oropharynx and upper esophagus are composed of striated muscle, whereas the distal esophagus is composed of smooth muscle. The central nervous system completely controls peristalsis in the striated muscle organs. In the distal esophagus, neuromuscular mechanisms intrinsic to the esophagus control peristalsis. Diseases of the striated muscle, of the smooth muscle, or of the nervous system can lead to a derangement of peristalsis and disrupt the propulsion of swallowed materials to the stomach.

Deglutition↗
PubMed1994

Roles of Triton X-100 in NADPH-diaphorase histochemistry.

Triton X-100 is widely but not universally used in NADPH-diaphorase histochemical staining. We investigated its effect on the staining and examined nitroblue diformazan (NBF) production under the influence of Triton X-100. Exposure of opossum esophagus, intestine, and colon tissues to Triton X-100 before staining enhanced staining of nerve cells and fibers and suppressed staining of non-neural structures. Long exposures and high concentrations nearly abolished the staining of non-neural structures and decreased the staining of nerves. The use of an incubation medium containing Triton X-100 achieved the best staining of nerve cells and fibers. Addition of Triton X-100 to the incubation medium changed its color from yellow to purple; in the presence of tissues, this color change occurred much more quickly. Spectral analysis showed that Triton X-100 increases the rate of NBF formation in the presence of tissue supernatant. Triton X-100 increases it less in the absence of tissue supernatant. Therefore, Triton X-100 improves the histochemical staining, probably by catalyzing the activity of NADPH-diaphorase, by keeping the extracellular NBF in solution and thus suppressing the staining of non-neural structures, and by increasing the permeability of cell membranes.

Animals↗