Biomedical subjects
Publications and source records attributed to M Johansson.
Cytogenetic investigation of short-term cultures from a parathyroid adenoma revealed a t(1;5)(p22;q32) as the sole clonal chromosomal aberration. Karyotypic abnormalities have not previously been described in this tumor type.
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System peaks created in a coupled column system, after transfer of the precolumn mobile phase to the analytical column have been investigated. Co-elution of an analyte with a system peak may affect the chromatographic performance of the analyte. The possibility of using the peak compression effect, in order to increase the detectability of the compounds noscapine, narcotoline and cotarnine, respectively, is studied. Three different mobile phases for the analytical column have been tested, the first contained a co-ion, the second a counter-ion and the last both a co-ion and a counter-ion. A compressed noscapine peak is obtained not only when it is eluted in a positive gradient of the co-ion in the first system, but also in a positive gradient of the counter-ion in the second system. Slightly compressed narcotoline and cotarnine peaks are obtained in the third system as long as they eluted before the deficiency peak of the counter-ion.
Lymphocytes from 21 male smokers, 10 untreated lung cancer patients, and 11 controls were cultured with and without exposure to mitomycin C. There were no differences between the chromosome aberration frequencies in the two groups: the spontaneous aberration frequency was 8.5% among patients and 8.4% among controls, whereas after mitomycin C induction the corresponding frequencies were 25.5% and 24.6%, respectively.
Noscapine, narcotoline and cotarnine were quantified in deproteinized plasma samples by using a coupled-column liquid chromatographic system. The drug and the metabolites were first separated into two groups on a short polar precolumn (-CN) with an acidic mobile phase, containing a low content of acetonitrile. The metabolites were transferred to a hydrophobic analytical column (C18) and separated with a mobile phase containing a counter ion and a co-ion in an acidic buffer with an high acetonitrile content. Noscapine was transferred to another hydrophobic analytical column (C18) with a mobile phase containing a counter ion in an acidic buffer with an high acetonitrile content. Ultraviolet detection at 310 nm was used for all three compounds. The limits of quantitation were 9 ng/ml for noscapine, 13 ng/ml for cotarnine and 20 ng/ml for narcotoline. The within-day precisions were better than 6% (relative standard deviation), and the absolute recoveries were above 82%.
Extraction of the hydrophobic tertiary amine bromhexine from plasma using cyclohexane-heptafluorobutanol (99.5:0.5, v/v) was studied at different pH values. The extraction yield from buffer solutions was quantitative at pH greater than 4.1, but from plasma the extraction yield decreased with increasing pH. Furthermore, at pH 8.4 the extraction yield varied greatly (56-99%) in different human plasma. The addition of lipoproteins to phosphate buffer, at pH 8.1, decreased the extraction yields considerably. Quantitative extraction from plasma was obtained by using a very long extraction time at pH 8.4 or by decreasing the pH to 5.4. The chromatographic system consisted of a reversed-phase column (Nucleosil C18, 5 microns) with an acidic mobile phase (methanol-phosphate buffer, pH 2) containing an aliphatic tertiary amine. UV detection at 308 or 254 nm was used. The limit of quantitation was 5 ng/ml using 3.00 ml of plasma and detection at 254 nm. The intra-assay precision for bromhexine was better than 3.6% at 5 ng/ml.
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System peaks were generated in an ion-pair reversed-phase system by co-injection of an alkylsulphate with the analytes. The acidic mobile phase contained acetonitrile and an aliphatic tertiary amine as a co-ion. The retention time of the system peak was regulated by the concentration and hydrophobicity of the co-ion and the alkylsulphate. The peak performance of the analytes was affected by co-elution with a system peak. Both peak distortions and improvements appeared, and the principles for the latter could be applied in a dual-column system involving trace enrichment and column switching.
A quantitative method for the analysis of flunixin, 2-(2-methyl-3-trifluoromethylanilino) nicotinic acid, in equine urine by gas chromatography with nitrogen-phosphorus detection has been developed. Flunixin and the internal standard, mefenamic acid, N-(2,3-xylyl) anthranilic acid, were analysed after extractive methylation of the carboxylic acid group using methyl iodide. The extraction and alkylation conditions of flunixin and mefenamic acid have been studied. The detection limit of the method was 0.25 mumol/l flunixin in urine (74 ng/ml). Flunixin was found to be conjugated to 96.5% in equine urine, and the conjugate was spontaneously hydrolysed to free flunixin. This approach can also be used to confirm the presence of flunixin or mefenamic acid in horse urine in the doping control of racehorses.
The pharmacokinetics and bioavailability of N-acetylcysteine (NAC) have been determined after its intravenous and oral administration to 6 healthy volunteers. According to a randomized cross-over design each subject received NAC 200 mg i.v. and 400 mg p.o., and blood samples were collected for 30 h. Reduced NAC had a volume of distribution (VSS) of 0.59 l.kg-1 and a plasma clearance of 0.84 l.h-1.kg-1. The terminal half-life after intravenous administration was 1.95 h. The oral bioavailability was 4.0%. Based on total NAC concentration, its volume of distribution (VSS) was 0.47 l.kg-1 and its plasma clearance was 0.11 l.h-1.kg-1. The terminal half-life was 5.58 h after intravenous administration and 6.25 h after oral administration. Oral bioavailability of total NAC was 9.1%.
Herpes simplex virus (HSV) type 1 was used to infect cultures of human embryonic dorsal root ganglion cells. Infected cultured were studied by electron microscopy. Viral nucleocapsids were observed to be internalized into neuronal cells bodies and neuritic extensions by fusion of the viral envelope and the plasma membrane. No signs of internalization by endocytosis were noted. Nucleocapsids were transported in neurites and were within 2 hrs postinfection found located near the microtubules and close to the nuclear pores in the perikaryon. A primary envelopment of nucleocapsids occurred at the inner lamina of the nuclear membrane and virions appeared between the two laminae. Presence of non-enveloped nucleocapsids outside the nuclear membrane and in close contact with the endoplasmic reticulum suggested that nucleocapsids could pass to the cytoplasmic side probably by de-envelopment at the outer nuclear membrane. A secondary envelopment occurred at the endoplasmic reticulum where the virions also became enclosed in transport vesicles. Enveloped virus appearing in the cytoplasm of neurons and neuritic extensions was always found only inside these transport vesicles. During their passage through the cytoplasm the virion-transport vesicle complexes were surrounded by smaller lysosome-like vesicles possibly derived from the Golgi apparatus. Fusion reactions between vesicles with virions and the smaller vesicles seemed to occur. We discuss if in this way the virion-transport vesicle complexes might be provided with glycosyl transferases and substrates necessary for maturation and completion of glycosylation of the viral envelope glycoproteins. The transport vesicles seemed essential for egress of virions from the infected cell by releasing virus when fusing with the plasma membrane.
Dextromethorphan and its metabolites were determined in plasma by a dual column liquid chromatographic switching system, after a prepurification on Sep-Pak C(18) cartridges. A polar precolumn (CN) and two hydrophobic analytical columns (C(18)) were used with mobile phases optimised regarding trace enrichment, selectivity and speed by the content of organic modifier. Dextromethorphan and its metabolites could be quantified at 5 ng ml(-1) with an intra-assay precision better than 6% (RSD).
The indirect fluorescent-antibody technique was compared with indirect and mu-capture enzyme-linked immunosorbent assays for the detection of respiratory syncytial virus (RSV) immunoglobulin M (IgM) in the elderly. Sera from 47 patients (mean age, 70 years) with acute lower respiratory tract infections caused by RSV were investigated. Specific IgM was detected in 81% (38 of 47) of the patients. The fluorescent-antibody technique, which gave 70% positive results, proved to be the most sensitive of the three methods. An IgM response was seldom seen in sera from the elderly within the first week of disease, but was present in 85% of sera (33 of 39) collected between days 11 and 30 of disease. In some patients it persisted for more than 6 weeks. Detection of IgM was found to be a useful tool for the diagnosis of RSV infections in elderly patients.
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N-Acetylcysteine in plasma may exist as intact N-acetylcysteine (NAC) or be oxidized to disulphides, either as a dimer or mixed with other thiol-containing compounds. To prevent oxidation of NAC, whole blood was immediately centrifuged after collection and the plasma proteins were precipitated with perchloric acid. NAC was measured by direct injection of the supernatant into the chromatographic system and the oxidized forms, coupled to small sulphides (ONACS), were determined after reductive cleavage of all NAC disulphides in the supernatant with dithiothreitol before injection. The total plasma concentration of the compound, i.e., including the fraction coupled to proteins (ONACP), was assayed after an initial reduction of the disulphide linkages in plasma. After subsequent precipitation of proteins, the supernatant was directly injected. The chromatographic system was a reversed-phase column (C18) with an acidic mobile phase. After a fast (less than 6 s) post-column reaction with pyrenemaleimide, NAC was detected by fluorimetry. The contribution to the band broadening by the reactor was about 10%. The limit of quantification of NAC in plasma was 240 nM, with an intra-assay precision of 14%.
The 41 serotypes of human adenoviruses are classified into six subgenera (A-F) with different tropisms. Enteric infections are caused in children by serotypes Ad40 and Ad41 of subgenus F. Serotypes Ad40 and Ad41 transform embryonic cells but cannot induce tumours in newborn hamsters. They differ from all other (established) human adenoviruses by being unable to replicate in conventional cell cultures. Ad40 and Ad41 grow in 293 cells (human embryonic kidney cells immortalized by transfection with the E1A, E1B regions of Ad5). In spite of the difficulty of isolating Ad40 and Ad41 they can be directly identified in stools by enzyme-linked immunosorbent assay (ELISA) and solid-phase immuno-electron microscopy. The amount of viral DNA in stool preparations is sufficient for identification by DNA restriction or dot-blot analysis. Adenoviruses have been associated with 7-17% of cases of diarrhoea in children. Ad40 and Ad41 cause diarrhoea throughout the year. Clinical features are watery stools, vomiting and moderately elevated temperature; respiratory symptoms are infrequent. The diarrhoea is protracted (mean 8.6 and 12.2 days for Ad40 and Ad41 respectively). Children with rotavirus diarrhoea vomited more frequently and had a higher temperature and diarrhoea of shorter duration. The impact of enteric adenoviruses in the aetiology of diarrhoea world-wide is not known but is accessible to investigation.
A prospective study of the fetal heart rate pattern during labor before and after paracervical blockade (PCB) was performed. The material comprised 469 women in labor, or 28% of 1673 women delivered during a 6-month period. The majority of the anesthesias (87%) were administered by specially trained midwives. Bupivacain (Marcain) was the anesthetic used. The injections were made at four different points at a cervical diameter of 3-9 cm. The concentration of the anesthetic was 0.25 or 1.25% generally in 10 ml of normal saline. A second PCB was administered in 54 patients at least one hour after the preceding one. Fetal heart rate (FHR) was recorded via a scalp electrode and the pattern studied 15 min before and 30 min after the injection of the anesthetic. Bradycardia was defined as a persistent deceleration exceeding 3 min and occurring within 30 min of the PCB. Variability and acceleration pattern persisted independently of the PCB. Following PCB, decelerations of all types increased, while the basal rhythm decreased by on average 1.5 beats/min. Following PCB fetal bradycardia occurred in 1.9%. The bradycardia persisted on average for 6.5 min with a lowest average FHR of 73 beats/min. Retrospectively, 6 out of 9 infants exhibited recognized risk factors for bradycardia. All infants with bradycardia scored 9-10/5 min, according to the Apgar rating scale and all had a normal development with regard to growth, motor and speech development at the age of 2 years. There were no significant differences in vaginal operative deliveries between the PCB and the non-PCB group.(ABSTRACT TRUNCATED AT 250 WORDS)
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