Biomedical subjects

M Wahl

Publications and source records attributed to M Wahl.

At least 73 records · Page 4Linked to original sources

PubMed1995

Influence of high titers of maternal antibody on the serologic response of infants to diphtheria vaccination at three, five and twelve months of age.

Diphtheria antitoxin was determined in serum from 44 pregnant women, of whom 26 had received one injection of diphtheria toxoid during pregnancy. Their infants were vaccinated with a combined diphtheria-tetanus vaccine at 3, 5 and 12 months of age. This vaccination schedule has been used in Sweden since 1986, replacing the old schedule of vaccination at 3, 4.5 and 6 months of age originally designed for diphtheria-tetanus-pertussis vaccine, which had not been used after cessation of general vaccination against pertussis in 1979. Serum samples from the infants were obtained at 3, 7 and 18 months of age. After 2 injections infants of mothers with high antitoxin titers, > or = 0.1 IU/ml, tended to have lower antitoxin titers than infants of mothers with low antitoxin concentrations (P = 0.067). All children had, however, antitoxin above the minimum protective level of 0.01 IU/ml. Median antitoxin titers were 1.6 IU/ml in both groups after the third booster injection. Four infants of mothers who had been vaccinated during pregnancy and who had titers of > or = 0.4 IU/ml did not reach the 0.1 IU/ml level after 2 injections: all 4 responded with high antitoxin titers after the third dose. Thus all infants were primed by 2 doses of vaccine, irrespective of maternal antibody concentration. The repressive effect of maternal antibody on titers noted after 2 doses was no longer observed after the third, booster dose.

Antibodies, Viral↗

PubMed1995

Effects of potassium channel activators on isolated cerebral arteries of large and small diameter in the cat.

The smooth-muscle relaxant action of adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels in cerebral arteries of large diameter has been confirmed in a number of in vitro studies, but there is still debate about the presence of KATP channels in small cerebral arteries. In the present study, the authors compare the effects of cromakalim and bimakalim, two putative KATP channel activators, in different parts of the feline isolated middle cerebral artery (MCA) designated proximal, intermediate, and distal. The latter corresponds to those small pial arteries that are usually studied in vivo. In ring segments precontracted with 10(-5) M of uridine-5-triphosphate (UTP), both cromakalim and bimakalim induced concentration-related relaxation, with bimakalim being more potent than cromakalim, and no significant differences noted among segments obtained from the different regions of the MCA. In vessels precontracted by adding 30 mM KCl the potency of cromakalim and bimakalim was reduced compared with that obtained after UTP precontraction. In the presence of 10(-6) M glibenclamide, an antagonist of KATP channel activators, the concentration-effect curve to bimakalim was shifted to the right in the proximal and distal MCA, indicating a similar route of action for bimakalim and cromakalim in these arteries. The present study therefore indicates the presence of KATP channels in isolated small cerebral arteries according to results obtained in vivo. Activators of KATP channesl may prove helpful in the treatment of vasospasm, which may occur in large and small cerebral arteries after subarachnoid hemorrhage.

Animals↗

PubMed1995

Endothelin-1-induced contraction and relaxation of isolated rat basilar artery: effect of the endothelium.

In rat basilar artery ring segments precontracted with prostaglandin (PG)F2a, endothelin (ET)-3 induced a concentration-related relaxation at doses of 3 x 10(-10) to 1 x 10(-8) M, whereas contraction occurred at higher concentrations. In contrast, relaxation by ET-1 was observed only in the presence of an ETA receptor antagonist. The ET-induced relaxation could be blocked by an ETB receptor antagonist and by a nitric oxide (NO) synthase inhibitor, suggesting activation of an ETB receptor. This receptor, which may be located on the endothelium, is apparently coupled to release of NO. Under resting tension, ET-1 and ET-3 induced concentration-related contractions, which were enhanced after NO synthase inhibition or after de-endothelialization. These results suggest simultaneous induction of contraction and relaxation by the ETs. With ET-1, this occurs in the same concentration range, with the relaxing effect being masked by the contraction.

Animals↗

PubMed1995

Efficacy of human leucocyte alpha-interferon treatment for chronic hepatitis C virus infection.

A total of 42 Swedish patients with biopsy-proven chronic hepatitis C virus (HCV) infection were treated with a natural human leucocyte alpha-interferon (HuIFN-alpha-Le), Alfanative (BioNative AB, Umeå, Sweden) in an open uncontrolled study. Two patients were withdrawn from treatment within 2 weeks due to non-compliance and were omitted from further analysis, and 40 patients (17 females), mean age 39 years (range 24-71) completed the study. All patients were HCV RNA-positive in serum prior to treatment, with raised alanine aminotransferase (ALT) levels > 1.5 times the upper normal limit known for more than 6 months. Interferon was given at a dose of 3 MU t.i.w. for an intended 24 weeks and follow-up was a further 24 weeks after treatment. Biochemical non-responders were withdrawn from treatment within 12-16 weeks but continued follow-up. Overall 21/40 (52.5%) patients had a complete biochemical response with normal ALT levels at the end of treatment. Sustained response during follow-up was seen in 8 (20%) whereas 13 (32.5%) had a non-sustained response. At the end of treatment 23 (58%) patients had undetectable serum HCV RNA and 9 (23%) at follow-up. Patients with sustained, non-sustained and non-response had a mean pretreatment HCV RNA level of 3.2 x 10(5), 2.5 x 10(6) and 3.2 x 10(6) genomes/ml, respectively, differences that did not reach statistical significance. Of the patients 3, 9, 10 and 14 had genotype 1b, 3a, 1a, and 2b, respectively, and 4 had mixed genotypes. Of the 23 patients with genotype 2b or 3a, 7 had a sustained response vs. none of the 13 patients with genotype 1a or 1b (p = 0.03). No patients with cirrhosis had a sustained response whereas 4/18 with chronic persistent and 4/18 with chronic active hepatitis had such a response. It is concluded that some 50% of patients treated with HuIFN-alpha-Le responded with normalisation of ALT levels but that only 20% had a durable response 24 weeks post-treatment, and that patients with genotypes 3a or 2b seem to respond better than patients with other genotypes.

Adult↗

PubMed1995

Efficacy of human leucocyte alpha-interferon treatment for chronic hepatitis C virus infection.

Adult↗

PubMed1994

Opening of the blood-brain barrier during cortical superfusion with histamine.

Histamine may influence cerebral microcirculation from the intravascular and parenchymal side. The latter route can be simulated by cortical superfusion. The effect of cortical superfusion with histamine (10(-9)-10(-3) M) on blood-brain barrier (BBB) permeability was studied in the cat by measuring extravasation of the tracers Na(+)-fluorescein (MW 376) or fluorescein isothiocyanate (FITC) labelled dextran (MW 62,000 or 145,000) by intravital fluorescence microscopy. Histamine induced an opening of BBB resulting in extravasation of small and large molecular weight tracers with threshold concentrations of 10(-9), 10(-8) and 10(-6) M for Na(+)-fluorescein, FITC-dextran 62,000 and 145,000, respectively. Once tracer extravasation had started the degree of extravasation increased with increasing concentrations of histamine in the superfusion fluid. Similar to histamine the H2 agonist impromidine (3 x 10(-12)-3 x 10(-9) M) induced a concentration dependent extravasation of Na(+)-fluorescein. 2-Pyridylethylamine which is 3-4 times more selective for H1 than for H2 receptors also induced an extravasation of Na(+)-fluorescein. Cortical superfusion with mepyramine (10(-7) M) or cimetidine (10(-4) M), which block the H1 and H2 receptors, respectively, already induced significant extravasation of Na(+)-fluorescein by themselves. These compounds could thus not be used as competitive antagonists to block histamine-induced extravasation. However, our data are in accord with data obtained during intravascular and topical application of histamine and support the hypothesis that H2 receptors at the luminal and abluminal membrane of the endothelium mediate the opening of the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Involvement of calcitonin gene-related peptide (CGRP) and nitric oxide (NO) in the pial artery dilatation elicited by cortical spreading depression.

The aim of the present study was to examine whether the initial transient arterial dilatation during cortical spreading depression (CSD) was mediated by the release of calcitonin gene-related peptide (CGRP) and/or nitric oxide (NO). This question is of interest as the initial phase of CSD appears to be a model of events occurring during functional hyperemia and during the first period of classic migraine. Using an open cranial window technique, pial arterial diameter in the parietal cortex of cats was recorded with an image splitting method. Employing micropuncture technique, perivascularly applied CGRP8-37 did not alter the resting diameter of pial arteries but antagonized concentration dependently (5 x 10(-9)-10(-6) M) the dilatation (35%) due to 5 x 10(-8) M CGRP. NG-Nitro-L-Arginine (NOLAG, 10(-4) M) also had no effect on resting diameter of pial arteries, indicating that their resting tone is neither mediated by a continuous release of CGRP nor of NO. CSD was triggered by a remote intracortical injection of KCl (150 mM) and recorded by a microelectrode placed adjacent to the artery under investigation. CSD elicited a transient negative DC shift which was accompanied by a peak dilatation of 44 +/- 5.2% (S.E.M.). This dilatation was reduced by approximately 50% during topical application of 10(-7) M CGRP8-37 and 10(-4) M NOLAG each. A 75% inhibition of the CSD-induced dilatation was found during simultaneous application of both compounds. These data indicate that the initial dilatation during CSD is mediated, at least in part, by a release of CGRP and NO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effects of antihistaminics on experimental brain edema.

Histamine has potent effects on cerebral blood vessels which include increased permeability and dilatation. Since its concentrations are found to be increased in brain tissue in different experimental models of brain injury, histamine may act as a mediator of secondary brain damage. Using the cold-lesion model of vasogenic brain edema the effects of application of antihistaminics were studied in rats. Neither mepyramine, an H1 receptor blocker nor zolantidine, an H2 blocker provided any decrease in brain swelling or water content. Experiments with application of dexamethasone yielded a small non-significant decrease of edema while the amino-steroid U74389F did not reduce swelling. The results indicate that histamine is obviously not involved in mediating cold lesion-induced brain edema. Furthermore, generation of lipid peroxides after activation of phospholipase A2 also appears not to have a significant influence on edema in the present study.

Animals↗

PubMed1994

Computerised image analysis in conjunction with fluorescence microscopy for the study of blood-brain barrier permeability in vivo.

The present paper describes a new method using computerised image analysis techniques for quantification of tracer extravasation over the blood-brain barrier as studied by intravital fluorescence microscopy. Cats were equipped with an open cranial window and continuously infused with fluorescein isothiocyanate-labelled dextran (FITC-dextran, mol. wt. 70,000) to maintain a steady plasma concentration. Several cortical fields were recorded in each experiment and the images stored on video tape for off-line analysis. This procedure, which largely eliminates the superficial pial vasculature and allows extraction of the extravasation areas, consists of the following steps: (1) averaging of images, (2) software shading correction based on the original images for compensation of optical non-uniformity, (3) correction of displacement artefacts, (4) intensity adjustment, (5) generation of subtraction images by subtracting the first image of a series from the subsequent ones, (6) median filtering and thresholding, (7) a length recognition algorithm, and (8) elimination of small areas. Compared to the previously described method, step (2) has been newly developed and steps (4) and (8) added to enhance sensitivity for detecting tracer extravasation. The degree of extravasation in a cortical field at a given time point [E(f) value] was calculated as the mean intensity of the remaining pixels. The E(f) is a quantitative value computed by a fully automatised procedure which takes into account the number, as well as the size and intensity, of extravasation areas in a given cortical field. The E(f) values obtained at different times in a series of experiments were averaged to give the E(I) value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1994

Endothelin-induced contraction and relaxation of rat isolated basilar artery: effect of BQ-123.

In ring segments from rat basilar artery (BA) the endothelin (ET) peptides ET-1, ET-2, and ET-3 induced concentration-related contractions. The order of potency was ET-1 = ET-2 > ET-3, while no differences occurred in the maximum contraction. The selective ETA receptor antagonist, BQ-123 (10(-10)-10(-4) M) alone elicited a small contraction only at 10(-4) M. In the presence of BQ-123 (10(-7)-10(-5) M), the concentration-response curve for ET-1 was shifted to the right without any decrease in maximum contraction, indicating competitive inhibition of ET-1 binding to the ETA receptor by BQ-123. The pA2 value calculated for BQ-123 was 6.935; the slope of the regression curve was 0.734. In contrast to ET-1, the contractile action of ET-3 was abolished by 10(-5) M BQ-123. In segments precontracted with 10(-6) M serotonin, ET-3, but not ET-1, induced relaxation at low concentrations (10(-11)-10(-8) M), with maximum relaxation amounting to 17.8 +/- 14.7% of precontraction (mean +/- SD; n = 16). The relaxant action of ET-3 was abolished in vessels incubated with NG-nitro-L-arginine (10(-5) M), an inhibitor of nitric oxide synthase. These results indicate that the ET-induced contraction of the isolated rat BA involves activation of the ETA receptor. The ET-3-induced relaxation of precontracted rat BA is apparently mediated by release of nitric oxide from the endothelium.

Animals↗

PubMed1994

Dilating effect of perivascularly applied potassium channel openers cromakalim and pinacidil in rat and cat pial arteries in situ.

OBJECTIVE: The aim was to test the vasodilator effect of perivascularly applied potassium channel openers cromakalim and pinacidil in pial arteries of cat and rat. METHODS: Using an open cranial window technique the diameter of pial arteries in the parietal cortex of rat and cat was recorded with an image splitting method. Employing micropuncture techniques, test compounds were dissolved in inert cerebrospinal fluid and infused into the perivascular space of individual arteries. RESULTS: Cromakalim (7 x 10(-18)-7 x 10(-13) M) induced concentration dependent dilatation of feline pial arteries with a maximum effect of 26.8(SEM 3.2)% at 7 x 10(-15) M. In rat arteries, cromakalim had a maximum effect of 32.1(4.97)% at 10(-15) M, while pinacidil (10(-10)-10(7) M) exerted a maximum dilatation of 29.5(3.3)% at 10(-8) M. The latter is consistent with previous findings in feline pial arteries. The sulphonylurea glibenclamide (10(-8)-10(-6) M) had no effect on the resting diameter of rat and cat pial arteries, indicating that their resting tone is not influenced by mechanisms involving ATP sensitive potassium channels. However, glibenclamide reduced the dilating effect of cromakalim and pinacidil in rat and cat in a dose dependent manner. CONCLUSIONS: A comparison with previously published data obtained in isolated middle cerebral and basilar arteries showed that potassium channel openers of the benzopyrane and cyanoguanidine type are much more potent in pial arteries than in peripheral arteries in situ or in isolated arteries of the circle of Willis and of peripheral vascular beds.

Animals↗

PubMed1994

Immune status and booster effects of low doses of tetanus toxoid in Swedish medical personnel.

Of 102 medical staff at a Swedish hospital, 81% had tetanus antitoxin titres > or = 0.01 IU/ml in 1984-85. The unprotected individuals (antitoxin titre < 0.01 IU/ml) were all > 30 years of age. Of this group, one-third lacked a protective antibody level against tetanus toxin. Low booster doses of tetanus toxoid (0.75 or 1.9 Lf) were given to 66 vaccinees with a history of previous basic vaccination and no history of booster vaccination within the previous 5 years. The median titre increased from 0.26 IU/ml before to 3.3 IU/ml after vaccination. Low doses of tetanus toxoid may thus still provide an adequate immune response when given as a booster vaccination to individuals with a reliable history of basic immunization.

Adult↗

PubMed1994

Investigation of blood-brain barrier permeability by means of computerized image analysis.

Intravital fluorescence microscopy has been widely used to study changes of blood-brain barrier (BBB) permeability in vivo. However, quantification of tracer extravasation by counting leaky spots provides only a rough estimate of permeability increase. We have therefore developed a new method for measurement of tracer extravasation from cerebral blood vessels by combining image analysis techniques with intravital fluorescence microscopy. This method is based on generation of subtraction images after shading and displacement correction. Subtraction images are further processed to eliminate noise and diminish artefacts due to vessel distortion and/or dilatation. The "degree of extravasation" (E(f) value) which is then calculated takes into account the number and size of leaky spots as well as their intensities. Examples are shown to illustrate that pure vasodilatation does not increase E(f) as long as the BBB-permeability is not disturbed. This newly developed method may prove helpful for comparison of tracer extravasation under different experimental conditions.

Animals↗

PubMed1993

Mediators of vascular and parenchymal mechanisms in secondary brain damage.

Several putative mediators of vasogenic brain edema will be considered with respect to the following criteria: 1) their effect on blood-brain barrier (BBB) permeability, 2) their vasomotor actions which may increase driving forces for transmural bulk flow, 3) their influence on edema formation, 4) their actual tissue concentration in pathological states, and 5) the therapeutic results after specific treatment. Bradykinin (BK) can induce brain edema by increasing BBB permeability to small solutes and enhancing blood pressure in the microcirculation due to arterial dilatation and venous constriction. Its interstitial concentration is enhanced after experimental trauma. Since kallikrein inhibitors reduce brain swelling all criteria favour BK as a mediator of vasogenic edema. Arachidonic acid (AA) opens BBB also for large tracers but exerts only small vasomotor effects. The edema formation is associated with an increase of the AA concentration in the interstitial space. However, convincing therapeutic results on inhibition of AA are still lacking. In addition to the formation of vasogenic edema AA has been found to induce cytotoxic edema. From experiments dealing with the vasomotor effects Ellis et al. (Am J Physiol 255: H397-H400, 1988) concluded an interaction of BK and AA in brain injury. However, our own results do not favour this hypothesis since we found divergent vasomotor and permeability effects of BK and AA. Histamine (HA) opens BBB unspecifically and dilates cerebral vessels, mechanisms by which edema formation can be explained.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗

PubMed1993

Regulation of cerebral blood flow--a brief review.

Cerebral blood flow is largely independent of perfusion pressure when autoregulation is intact. Cerebral circulation is regulated mainly by changes of vascular resistance. Resistance can be modulated by local-chemical and endothelial factors, by autacoids, and by release of transmitters from perivascular nerves. Local-chemical factors such as H(+)-, K(+)-, Ca(2+)-ions, adenosine, and osmolarity are involved in the regulation of cerebrovascular resistance during cortical activation and under pathological conditions such as hypoxia or ischaemia. Endothelial factors such as thromboxane A2, endothelin (ET), endothelium derived constrictor factor and endothelium derived relaxing (EDRF, identified as nitric oxide, NO) or hyperpolarizing (EDHF) factor, and prostacyclin (PGI2), can be released by physical stimuli such as shear stress or haemorrhage, by autacoids, by neurotransmitters, and by cytokines. Several of these factors (NO, PGI2, ET) can also be released from neurons and astrocytes thus enabling a coupling between parenchymal function and flow. Autacoids like histamine, bradykinin, eicosanoids, and free radicals influence cerebrovascular resistance, capacitance vessels and the permeability of the blood-brain barrier under pathological conditions. They are released by trauma, ischaemia, seizures and inflammation. Cerebral arteries are innervated by several systems. The sympathetic-noradrenergic fibres originate from the superior cervical ganglion. By releasing the constricting transmitters norepinephrine and neuropeptide Y this system extends the range of autoregulation. The parasympathetic cholinergic system with the dilating transmitters acetylcholine and vasoactive intestinal polypeptide may prevent ischaemia. Besides the intracerebral noradrenergic and serotonergic perivascular innervation with an unclear function, a trigeminal innervation has been described.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Intracellular free Ca2+ in the cell cycle in human fibroblasts: transitions between G1 and G0 and progression into S phase.

Intracellular free calcium ([Ca2+]i) has been proposed to play an important part in the regulation of the cell cycle. Although a number of studies have shown that stimulation of quiescent cells with growth factors causes an immediate rise in [Ca2+]i (Rabinovitch et al., 1986; Vincentini and Villereal, 1986; Hesketh et al., 1988; Tucker et al., 1989, Wahl et al., 1990), a causal relationship between the [Ca2+]i transient and the ability of the cells to reenter the cell cycle has not been firmly established. We have found that blocking the mitogen-induced elevation of [Ca2+]i with the cytoplasmic [Ca2+]i buffer dimethyl BAPTA (dmBAPTA) also blocks subsequent entry of cells into S phase. The dose response curves for inhibition of serum stimulation of [Ca2+]i and DNA synthesis by dmBAPTA are virtually identical including an anomalous stimulation observed at low levels of dmBAPTA. Reversal of the [Ca2+]i buffering effect of dmBAPTA by transient exposure of the cells to the Ca2+ ionophore ionomycin also reverses the inhibition of DNA synthesis 20-24 h later. Ionomycin by itself does not stimulate DNA synthesis. These data are consistent with the conclusion that a transient increase in [Ca2+]i occurring shortly after serum stimulation of quiescent fibroblasts is necessary but not sufficient for subsequent entry of the cells into S phase. This study is the first to show a direct relationship between early serum stimulated Cai2+ increase and subsequent DNA synthesis in human cells. It also goes beyond recent studies on BALB/3T3 cells by providing dose response data and demonstrating reversibility, which are strong indications of a cause and effect relationship.

Buffers↗

PubMed1992

Acute and long-term effects on myocardial ischemia of intermittent and continuous transdermal nitrate therapy in stable angina.

The aim of this study was to compare the efficacy and safety of continuous and intermittent transdermal nitrate therapy using ambulatory electrocardiographic (Holter) monitoring. Eighty-five patients with stable angina pectoris and positive exercise test results participated during their concomitant antiischemic medication in a randomized open trial lasting 12 weeks. After a 3-week run-in period with continuous therapy (10 mg/24 hours), patients were randomized to either continuous- or intermittent-therapy groups. In the intermittent-therapy group the patients removed their patch at night (the mean patch-off period was 10 hours). Forty-eight-hour Holter monitoring was performed in each patient after randomization, and again after 2 and 12 weeks. Eighteen patients withdrew, 9 in each group. A total of 11,194 hours of electrocardiography were recorded and 607 ischemic episodes were detected, of which 79% were asymptomatic and 95% appeared during daytime. The number of ischemic episodes per 48 hours with intermittent therapy was 3.1 +/- 0.7 (mean +/- SEM) after randomization, 1.8 +/- 0.4 at 2 weeks and 2.0 +/- 0.6 at 12 weeks. With continuous therapy the respective numbers were 3.8 +/- 1.1, 3.5 +/- 0.9 and 4.2 +/- 1.2. The differences were not statistically significant because a large number of patients (30%) had no ischemic episodes on Holter recording. However, when examining 47 patients with episodes during the study, the number of episodes was significantly reduced in the intermittent-therapy group (p less than 0.05 at 12 weeks). The changes in asymptomatic and symptomatic episodes were concordant. No changes and differences between the treatment groups were seen in nighttime episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

PubMed1992

Association of cytoplasmic free Ca2+ gradients with subcellular organelles.

Previous investigations have identified gradients of intracellular free (Ca2+)i (Ca2+i) in the cytoplasm of human fibroblasts. In this study we have compared the spatial distribution of these gradients with the subcellular distribution of cytoplasmic organelles. Using the Ca(2+)-sensitive dye fura-2 and organelle-specific fluorescent dyes, we have found that the highest Ca2+ concentrations are found in the perinuclear cytoplasm and that these regions co-localize with the Golgi apparatus. The area occupied by the endoplasmic reticulum, which includes the Golgi region plus an adjacent area, is also significantly elevated above the average cellular (Ca2+)i. Most mitochondria are located in regions different from those with the highest (Ca2+)i. A variety of phenomena which could have given rise to artifactual (Ca2+)i gradients have been ruled out, including compartmentalization of fura-2 in subcellular organelles, incomplete hydrolysis of fura-2AM esters, and the presence of pH gradients which might change the Ca2+ binding characteristics of fura-2. The existence of gradients in (Ca2+)i between ER and Golgi containing regions of the cytoplasm supports the hypothesis (Sambrook: Cell 61:197-199, 1990) that the traffic of membrane bound vesicles from ER to Golgi is directed by local variations in (Ca2+)i.

Calcium↗