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Biomedical subjects

L Johansson

Publications and source records attributed to L Johansson.

At least 199 records · Page 11Linked to original sources
PubMed1987

Characterization of monoclonal anti-DNA antibodies and visualization of binding to chromosomes and cell nuclei.

Monoclonal antibodies against DNA from two hybridoma cell lines were produced and characterized. One had specificity for single stranded (ss) DNA with some cross-reactivity to RNA, while the other was specific for both single (ss) and double stranded (ds) DNA. The latter ds and ss DNA-binding antibody was used as a model for analysing the distribution of the epitope in chromosomes and cell nuclei. A linear correlation between antibody binding and propidium iodide counterstaining was found on flow cytometric analysis of suspended chromosomes. Immunofluorescence of rat myoblast cells showed a speckled distribution of the antibody in the nucleus with a variability between the cells. Using electron microscopy to visualize antibody binding with gold particles, codistribution with uranyl acetate staining of leucocytes was found. These results suggested that the antibody preferentially binds to condensed chromatin in cells and chromosomes.

Animals↗
PubMed1987

Comparison of high-selectivity gas chromatographic methods, including column switching, for the determination of felodipine in plasma.

The selectivity required for the determination of low concentrations of felodipine in plasma was achieved by either mass-selective detection, optimization of stationary phase selectivity or column-switching gas chromatography (GC) with a dual-oven chromatograph, the latter two with electron-capture detection. The three approaches were evaluated in terms of selectivity, detectability, precision and suitability for routine applications with automated injection. Using mass-selective detection, the detectability in plasma samples was limited by the performance of the mass spectrometer. The detection limit (signal-to-noise ratio = 3) was 4.7 pmol (1.8 pg) of felodipine. Pre-concentration of extracts permitted quantitation in plasma down to 0.2 nmol/1. Using electron-capture detection, the detectability was determined by the selectivity and bleeding characteristics of the columns. For single-column separation, a 35% phenyl phase was selected. The detection limit was 3.0 fmol (1.2 pg). The limit of quantitation in plasma was 1 nmol/1. In column-switching GC, bleeding products from the first column will separate on the second column and may interfere in separations for trace analysis. Bleeding products from a 50% phenyl phase (DB-17) were characterised by GC-mass spectrometry. With a dual-column system, employing a DB-17 (50% phenyl) column for selective introduction on to a CP-Sil 5 (0% phenyl) column, the signal-to-noise ratio was limited by the low-bleeding second column, provided that the bleeding products from the first column were adequately separated from felodipine. The detection limit in this instance was significantly lower 0.35 fmol (0.13 pg). Direct injection of plasma extracts permitted quantitation down to 0.4 nmol/l. All three methods were well suited for use with autosamplers.

Chromatography, Gas↗
PubMed1987

Effects of lead on the male mouse as investigated by in vitro fertilization and blastocyst culture.

Long-term exposure of male mice to inorganic lead (lead chloride, 1 g/liter) in the drinking water reduces their fertility. The cause of this reduction, expressed as a decrease in the number of mated females showing implantations, was investigated, using an in vitro fertilization method. It was found that spermatozoa from lead-exposed males had a significantly lower ability to fertilize mouse eggs than those from unexposed males. Preimplantation embryos, isolated from uterine horns of mice mated with lead-exposed males, were examined. No morphologically abnormal embryos were found. However, when cultured in vitro over the implantation period, blastocysts of the group mated with lead-exposed males showed an increased frequency of delayed hatching from the zona pellucida or an inability to hatch. Among blastocysts from this group a decreased frequency of inner cell mass development was also found.

Animals↗
PubMed1987

Distribution of natural killer cells and lymphocyte subclasses in Jessner's lymphocytic infiltration of the skin and in cutaneous lesions of discoid and systemic lupus erythematosus.

We studied the cell infiltrates in biopsies from lymphocytic infiltration of the skin (LIS), with six monoclonal T cell antigen-specific antibodies and compared the reactivity pattern with those in biopsies from discoid and systemic lupus erythematosus skin lesions and allergic contact skin reactions. A newly described antibody (NK9) recognizing natural killer (NK) cells and activated cytotoxic T lymphocytes was included, and the numbers and activity of circulating NK cells was determined. Immunohistochemical staining revealed that the numbers of NK9-positive cells were highest in LIS. The distribution of T lymphocytes (OKTII + ve), helper T cells (OKT4 + ve), suppressor T cells (OKT8 + ve), Langerhans cells (OKT6 + ve) and activated T cells (anti-Tac + ve) in LIS differed from those in DLE,SLE and allergic contact reactions. However, the number of circulating NK cells (large granular lymphocytes) and the NK activity in peripheral blood were normal in LIS. We conclude that in LIS a distinct type of T cell activation occurs; the cause of this remains to be determined.

Adult↗
PubMed1986

Long-term exposure of the male mouse to lead: effects on fertility.

Sexually mature male mice, exposed to lead in the drinking water for 3 months, attained a mean blood level of 32 micrograms/100 ml. In control mice, given deionized water, blood lead levels were less than 0.5 microgram/100 ml. At the end of the exposure period, each male was caged with three untreated females. On Day 17 after mating, the frequency of pregnant females and the number of fetuses and resorptions were recorded. Females without implantations were significantly more numerous (P less than 0.05) in the group that had been mated with the lead-exposed males. The frequencies of resorptions and fetal malformations were similar in the two groups. The two groups of males were compared with respect to body weight, plasma level of testosterone, number of epididymal sperms, and weight of reproductive organs. No statistically significant differences were found. Increased tissue concentrations of lead were noted for all the male reproductive organs, as well as the hypothalamus. It cannot be decided at present whether the decrease in the number of pregnant females was due to a reduction in the ability of spermatozoa from the lead-exposed males to fertilize or to a preimplantation loss of fertilized ova.

Animals↗
PubMed1986

Potential neuroleptic agents. 4. Chemistry, behavioral pharmacology, and inhibition of [3H]spiperone binding of 3,5-disubstituted N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamides.

A series of 3,5-disubstituted N-[(1-ethyl-2-pyrrolidinyl) methyl]-6-methoxysalicylamides was synthesized, starting from the 2,6-dimethoxybenzoic acids, by boron tribromide demethylation of the corresponding 3,5-disubstituted 2,6-dimethoxybenzamides and separation of the two positional isomers. The correct structure assignments were based on selective decoupling studies on their 13C NMR spectra. The salicylamide derivatives were tested for antidopamine activity in vivo by their ability to inhibit the apomorphine syndrome in the rat and in vitro by their ability to displace [3H]spiperone from striatal preparations of the rat brain. The activity seems to reside exclusively in the S enantiomer. Several compounds were considerably more potent than haloperidol, particularly those having an ethyl group in the 3-position and a halogen atom in the 5-position of the aromatic ring. The corresponding 5-alkyl-3-halogen-substituted compounds were much less active. A low acute toxicity was found for the most potent compounds. Some of the salicylamides displayed a 10-20-fold separation between the dose which blocks apomorphine-induced hyperactivity and that which blocks apomorphine-induced stereotypy. One compound, S-(-)-3,5-dichloro-N-[(1-ethyl-2-pyrrolidinyl) methyl]-6-methoxysalicylamide (raclopride, FLA 870) (13) had a stereotypy--hyperactivity separation more than twice that of sulpiride while being 100 times more potent in blocking the apomorphine effects. On this basis, 13 was selected for clinical trials against schizophrenia.

Animals↗
PubMed1986

Malignant cystosarcoma phyllodes in a man treated with polyestradiolphosphate. Case report.

Cystosarcoma phyllodes is a rare breast tumor and only five cases have been previously reported in males. A case of cystosarcoma phyllodes in a man treated with polyestradiolphosphate for prostatic carcinoma and by radiation because of breast tenderness is presented. The tumor showed a malignant stroma histologically and the epithelial component was similar to a ductal carcinoma in situ. Electron microscopy revealed several cell types. The possible relationship to radiation and estrogen therapy is discussed.

Aged↗
PubMed1985

Potential neuroleptic agents. 3. Chemistry and antidopaminergic properties of substituted 6-methoxysalicylamides.

A series of substituted 6-methoxysalicylamides were synthesized from their corresponding 2,6-dimethoxybenzamides by demethylation of one methoxy group with boron tribromide. Substituted 6-methoxysalicylamides having a lipophilic aromatic substituent in the 3-position para with respect to the methoxy group, e.g. a bromo or an iodo atom or an ethyl or a propyl group, and having an (S)-N-(1-alkyl-2-pyrrolidinyl)methyl moiety as the side chain were found to be potent blockers of [3H]spiperone binding in vitro and potent inhibitors of the apomorphine syndrome in the rat. Similar to remoxipride but in contrast to haloperidol, some of the substituted salicylamides show a 10-20-fold separation between the dose that inhibits hyperactivity and that which inhibits stereotypy. It was concluded that, besides the requirement of a lipophilic substituent in the position para to the methoxy group for antidopamine activity in vivo, the formation of a coplanar six-membered pseudoring involving the amide moiety and the methoxy group is a structural requirement for activity in vitro.

Animals↗
PubMed1985

Felodipine kinetics in healthy men.

In a randomized, crossover study, the absorption, distribution, and elimination of intravenous and oral felodipine were investigated in eight healthy men 22 to 31 years old. Felodipine was given as a 2.5 mg iv infusion over 30 minutes and as a 27.5 mg oral solution. Both doses were labeled with 25 microCi 14C-felodipine. Given as an oral solution, felodipine is rapidly (mean time to peak concentration 64 minutes; range 30 to 90 minutes) and completely absorbed. Presystemic elimination reduced the availability to 16% (range 10% to 25%). Felodipine kinetics can be described by a multicompartmental model with three distinct phases. The t1/2 for the initial phase was 6.4 minutes (range 1.7 to 10.4 minutes) and felodipine was distributed to a volume of 0.6 L/kg (range 0.4 to 0.9 L/kg), which approximately corresponds to the total body water. The second distribution phase reached pseudoequilibrium with a t1/2 of 1.6 hours (range 1.3 to 2.2 hours). The volume of distribution at the end of this phase was 9.7 L/kg (range 6.0 to 18.2 L/kg). The terminal phase had t1/2 of 10.2 hours (range 6.7 to 20.7 hours). The contribution of the three phases to the AUC was 15%, 40%, and 45% in the order of increased t1/2. Total body clearance of felodipine was 1.2 L/min (range 0.9 to 1.6 L/min). Within 72 hours after drug dosing, 62% to 81% of the felodipine doses were excreted in the urine and feces as metabolites. The rate of excretion by the kidneys had a biphasic pattern, with t1/2 values of 4 and 18 hours. Approximately 10% of the doses was excreted in the feces.

Administration, Oral↗
PubMed1985

Microbiologic progression of post-traumatic peritonitis.

The natural course of post-traumatic peritonitis was studied in 17 pigs. Following a standardized missile wound to the abdomen the pigs were operated on and observed in continuous anesthesia for periods up to 3 days. Bacterial density was measured in peritoneal exudate, parietal peritoneum, laparotomy wound, and projectile entrance and exit wounds at this operation and also at relaparotomy, which terminated the experiments. The bacterial density showed significant perioperative fall, averaging X 1,905 in peritoneal exudate and X 40 in parietal peritoneum. From a low postoperative level (mean c. 10(2)/ml or /gm), bacterial density increased significantly in the observation period. In peritoneal exudate the increase was X 4,073 and in peritoneum X 2,630. In laparotomy and projectile entrance and exit wounds the corresponding figures were X 234, X 126, and X 15. The bacterial population's perioperative reduction and subsequent proliferation were interpreted as reflecting the host defense, which accordingly was limited in capacity and duration.

Abdominal Injuries↗
PubMed1985

Excretion of radionuclides in human breast milk after the administration of radiopharmaceuticals.

The fraction of injected activity that was excreted through the breast milk of nursing mothers at different times after the injection of various radiopharmaceuticals has been measured in 21 patients. For 99mTc-labeled radiopharmaceuticals the total excreted fraction was 10% for pertechnetate and 1.5-3% for MAA, plasmin, diethylenetriaminepentaacetic acid (DTPA), and methylene diphosphonate (MDP). For [125I]hippuran and [131I]hippuran the corresponding value was 3%. For the above mentioned radiopharmaceuticals the activity concentration in the milk decreased exponentially with an effective half-life of approximately 4 hr. For chromium-51 ethylenediaminetetraacetic acid ([51Cr]EDTA) and [99mTc]RBC, much smaller amounts were excreted in the breast milk. The absorbed dose to various organs of the baby has been calculated. We conclude that when [99mTc]pertechnetate, [99mTc]MAA, [99mTc]plasmin, [125I]hippuran, or [131I]hippuran are used the child should be fed just before the administration of the radionuclide to the mother and the next three milk fractions should not be used. For [99mTc]DTPA and [99mTc]MDP as well as [51Cr]EDTA, only the first fraction should not be used. According to our earlier investigations breast feeding has to be stopped for at least 3 wk after investigations with [125I]fibrinogen.

Breast Feeding↗
PubMed1984

Monitoring of S- and R-tocainide in human plasma after heptafluorobutyrylation, separation on Chirasil-Val and electron-capture detection.

The conditions for the heptafluorobutyrylation of tocainide have been studied. An almost instantaneous reaction was obtained with 0.01% of heptafluorobutyric anhydride in toluene at 40 degrees C. Higher anhydride concentration caused degradation of the initially formed derivative, mainly by the loss of water, as shown by mass spectral analysis. Tocainide was isolated from plasma by extraction into dichloromethane at alkaline pH. Gas chromatographic separation was performed with a fused-silica capillary column coated with a methyl silicone gum. The enantiomers were separated on a glass capillary column coated with Chirasil-Val. Upon analysing 0.1 ml of plasma eight times the precision was 4.7% at the 10 mumol/1 level for the S-form of tocainide.

Acylation↗
PubMed1984

A filter paper dry blood spot procedure for acute intermittent porphyria population screening by use of whole blood uroporphyrinogen-I-synthase assay.

A filter paper dry blood spot procedure for the determination of whole blood uroporphyrinogen-I-synthase (UIS) activity is presented. The method is based on the concept of enzyme specific activity, the enzyme activity being related to the haemoglobin concentration of the assay sample. The diagnostic capacity with regard to the acute intermittent porphyria (AIP) gene carrier state is shown to be equivalent to that of a washed red cell reference method. On grounds of easy capillary blood sampling, uncomplicated and safe mail specimen transport and simple laboratory reception routines, the method is stated to be well adapted for use in AIP preadolescent population screening.

Adolescent↗