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Biomedical subjects

M Just

Publications and source records attributed to M Just.

At least 37 records · Page 2Linked to original sources
PubMed1995

Safety, immunogenicity, and pilot efficacy of Plasmodium falciparum sporozoite and asexual blood-stage combination vaccine in Swiss adults.

This study was part of a larger program to develop a vaccine effective against Plasmodium falciparum infection caused by sporozoites and clinical malaria caused by asexual blood stages. In a phase 1 study of safety and immunogenicity, two recombinant proteins (Ro 46-2717, a circumsporozoite [CS] protein) construct with a molecular mass of 35 kD, and Ro 46-2924, a merozoite surface antigen [MSA-2] construct with a molecular mass of 25 kD) adsorbed onto alum were injected in two low (20 micrograms) or two high (100 micrograms) doses in the right and left deltoid muscles of 33 healthy Swiss volunteers; six other volunteers received a placebo (alum alone). Twenty-six participants reported 51 immunization-related adverse events, mainly pain at the injection site. Mean antibody titers to CS protein and MSA-2 in an indirect immunofluorescence assay peaked four weeks after the second immunization without evidence of boosting (i.e., sharp increase in titer). By that time, 56% and 31% of the vaccinees seroconverted to CS protein and MSA-2, respectively, with the increase in MSA-2 titer being weaker than that for the CS protein. After a third immunization, five vaccinees volunteered to be challenged by three or four infective bites of Anopheles stephensi. Prepatent and incubation periods in all five were comparable with unvaccinated historic controls challenged under similar conditions, and all had symptoms of clinical falciparum malaria. We conclude that the vaccine components were safe and immunogenic but there was no evidence that this immunization regimen with the CS protein plus MSA-2 component was able to prevent infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

[Prevention of congenital toxoplasmosis in Europe].

To sound out prevalent opinions among health authorities in Europe concerning the control and prevention of congenital toxoplasmosis (CT), a questionnaire was sent to the 28 WHO member countries in Europe. The questionnaire was returned by 23 countries. Only 7 countries recommend systematic screening of pregnant women. The reasons given by the 14 countries which do not recommend systematic screening are diverse: recommendations are in preparation, unfavourable cost-benefit return, absence of satisfactory treatment, programme not possible, incidence level too low, etc. 11 countries have a surveillance system for CT, of which only 3 are among the countries which recommend systematic screening. However, the absence of a multidisciplinary approach does not permit proper surveillance of cases. It appears from this survey that control of CT is undertaken in a very heterogeneous manner in Europe and no country has a programme whose impact on CT can be measured. So far, the European experience does not permit conclusions either in favour of or against a programme for the systematic screening of CT. However, cost-benefit analysis plays a very important role in determining whether such a programme should be implemented. Parameters such as the security of diagnosis (standardization of methods, quality and experience of the laboratories) and the monitoring of cases (definition, multidisciplinary approach to the surveillance and long-term treatment of patients, national collection of case reports, evaluation of the programme) are indispensable for the implementation of an effective surveillance system.

Cost-Benefit Analysis↗
PubMed1994

[Immunogenicity and stability of an aluminum-free liposomal hepatitis A vaccine (Epaxal Berna)].

The high immunogenicity of the liposomal hepatitis A vaccine (Epaxal Berna) after a single dose and after a booster dose one year later has been confirmed in several studies with healthy adult volunteers: 95-100% and 96-100% seroconversion (> or = 20 mIE/ml) after 1 and 12 months respectively, as well as a booster effect in 100% of the cases after revaccination. The tolerability of this new, alum-free vaccine has been excellent with 6-25% local and 0-13% mild systemic reactions after a dose of 0.5 ml. Stability testing with and without detergent indicated partial internalization of the hepatitis A virions in the phospholipid bilayer of the liposome vesicles with storage. Immunization of 10 healthy adult volunteers with vaccine stored for 32 months at 4 degrees C showed, however, that the duration of storage has no influence on immunogenicity and tolerability of the vaccine.

Adult↗
PubMed1994

Phosphorylation of focal adhesion vasodilator-stimulated phosphoprotein at Ser157 in intact human platelets correlates with fibrinogen receptor inhibition.

Integrins and other adhesion receptors are essential components for outside-in and inside-out signaling through the cell membrane. The platelet glycoprotein IIb-IIIa (also known as fibrinogen receptor or integrin alpha IIb beta 3) is activated by platelet agonists, inhibited by cyclic-nucleotide-elevating agents, and is involved in the activation of protein tyrosine kinases including the 125-kDa focal adhesion kinase (pp125FAK). However, the molecular details of glycoprotein IIb-IIIa regulation are not well understood. Here we report that in ADP-activated human platelets cAMP- and cGMP-dependent protein-kinase-mediated phosphorylation of the focal adhesion vasodilator-stimulated phosphoprotein (VASP) at Ser157 correlates well with glycoprotein IIb-IIIa inhibition. Human platelets contain similar concentrations of glycoprotein IIb-IIIa complexes (fibrinogen binding sites) and VASP. Using gel-filtered platelets, cAMP-elevating agents [e.g. prostaglandin E1 and the forskolin analog 6-(3-dimethylaminopropionyl)forskolin (NKH 477)] caused VASP Ser157 phosphorylation and inhibited glycoprotein IIb-IIIa activation up to 70-100%. NO-generating, cGMP-elevating agents [e.g. 3-morpholinosydnonimine hydrochloride (SIN1) and sodium nitroprusside] stimulated VASP Ser157 phosphorylation and inhibited glycoprotein IIb-IIIa activation up to a maximal extent of 30-50%. The effects of cAMP- and cGMP-elevating agents on VASP phosphorylation and fibrinogen binding were reversible and could be mimicked by membrane-permeant selective activators of platelet cAMP- or cGMP-dependent protein kinase, respectively. Using threshold concentrations, the nitrovasodilator SIN 1 potentiated the effects of the forskolin analog NKH 477 with respect to inhibition of platelet aggregation, VASP phosphorylation and glycoprotein IIb-IIIa inhibition. It is proposed that the inhibition of glycoprotein IIb-IIIa induced by cyclic nucleotide involves cAMP-and cGMP-dependent protein-kinase-mediated VASP phosphorylation at Ser157.

Adenosine Diphosphate↗
PubMed1994

[Cardiac tamponade and Kaposi's sarcoma].

The case of a 31 year-old intravenous drug addict female patient with infection by the human immunodeficiency virus who had recurrent cardiac tamponade and who was diagnosed by pericardic biopsy as Kaposi's sarcoma is reported. The patient demonstrated involvement by cutaneous, mucosal, lymph node and probably pleuropulmonary Kaposi's sarcoma. Thoracic radiography, computerized tomography and echocardiography only showed the presence of pericardic effusion. Neither did the pericardic fluid obtained by pericardiocentesis provide any significant ethiologic data. Only the pericardic biopsy showed the typical lesions of Kaposi's sarcoma in this localization confirming diagnosis. This is the first case of pericardic Kaposi's sarcoma described in an alive patient and the difficulties of achieving the diagnosis of the cardiac involvement by Kaposi's sarcoma in AIDS patients are commented upon.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Study of pertussis vaccines in infants: comparison of response to acellular pertussis DTP vaccines containing 25 micrograms of FHA and either 25 or 8 micrograms of PT with response to whole-cell pertussis DTP vaccine.

Clinical and serological responses of infants to primary vaccination with diphtheria-tetanus-acellular pertussis (DTPa) vaccines containing 25 micrograms of filamentous haemagglutinin (FHA) and either 25 or 8 micrograms of pertussis toxoid (PT) were compared in a double-blind randomized study with responses of infants receiving whole-cell pertussis DTP vaccine (DTPw). In total, 308 healthy infants were enrolled to receive three vaccine doses at 3, 4 and 5 months of age. DTPa recipients had significantly lower incidences of local reactions and fever than the DTPw recipients. No differences in reactogenicity were observed between DTPa groups receiving 8 and 25 micrograms doses of PT. After vaccination, an immune response to PT was seen in 96% of 25 micrograms PT DTPa recipients, 94% of DTPw recipients and 86% of 8 micrograms PT DTPa recipients. The geometric mean anti-PT neutralizing antibody titre was significantly higher for 25 micrograms PT dose recipients (34.9 Chinese hamster ovary (CHO)) as compared with 8 micrograms PT dose recipients (21.0 CHO). The results support the use of the higher dose of PT in acellular pertussis vaccine preparations.

Adhesins, Bacterial↗
PubMed1994

[In vitro NMR spectroscopy of healthy, pathologically changed and carcinomatous breast tissue samples correlated with histological findings].

Of 57 patients with clinically suspected mamma carcinoma 121 samples were analysed by in vitro 1H-NMR spectroscopy at 300 MHz and correlated with histological data. Within the relevant spectral region between 2.7 and 4.1 ppm strong signals were observed from fat, (phosphoryl-) choline, (phospho-) creatine, and carnitine. Furthermore, with high regularity, 8 weak, partly overlapping signals were resolved and attributed to glucose, glycine, threonine, serine, inositol, and sucrose. Their intensities were determined by an iterative fitness program. From the intensity ratios, different kinds of tissue could be distinguished based on spectroscopic criteria. Healthy or mastopathically modified tissue could be discriminated from more than 50% carcinoma affected tissue with a specificity of better than 99.5%. This fact is explained by the lower content of fatty acids in the malignant tissue. Differences between spectra of healthy of mastopathically affected tissue were only small.

Breast↗
PubMed1993

Use of the polymerase chain reaction to detect Bordetella pertussis in patients with mild or atypical symptoms of infection.

Nasopharyngeal aspirates and nasopharyngeal swabs from 177 children exhibiting mild to severe clinical symptoms of whooping cough were tested by the polymerase chain reaction (PCR) and culture for the presence of Bordetella pertussis. In the PCR analysis amplifications of samples prepared with and without DNA extraction were compared. In 26% of samples prepared without DNA extraction, the PCR was found to be inhibited, whereas no inhibition was detected after DNA extraction. Twelve percent (21/177) of the samples were positive in both culture and the PCR, and an additional 49% (87/177) of the samples were positive exclusively in the PCR. Thirty-eight percent (8/21) of culture-positive patients and 63% (55/87) of the patients in whom infection was detected only by PCR had mild or atypical clinical symptoms. Of these groups 26% (5/19) and 50% (39/78), respectively, had been fully vaccinated with three or more doses of diphtheria, tetanus and pertussis vaccine.

Bacteriological Techniques↗
PubMed1993

Time course of hepatitis A antibody production after active, passive and active/passive immunisation: the results are highly dependent on the antibody test system used.

Two commercially available automated test systems for hepatitis A antibody, HAVAB IMX (Abbott) and ENZYMUN Anti-HAV (Boehringer) were evaluated in a study of active, passive and active/passive immunisation against hepatitis A. The inactivated hepatitis A vaccine Epaxal Berna and the hepatitis A immunoglobulin preparation Globuman were products of the Swiss Serum and Vaccine Institute. Although both hepatitis A antibody test kits were standardised with the same international WHO standard hepatitis A immunoglobulin preparation, divergent results were obtained for the level of circulating hepatitis A antibody after vaccination. One month after the vaccination the mean geometric antibody titres were 315 mIU/ml after active, 253 mIU after active/passive and 22 mIU after passive immunisation when measured with the Enzymun assay. In the same sera 70 mIU/ml after active, 60 mIU after active/passive and 18 mIU after passive immunisation could be detected with the IMX test. Antibody avidity studies could not explain the differences obtained by the two test methods. The neutralization test is the standard method for the estimation of protection against hepatitis A. This test is not suitable for large series of serum samples, and enzyme immunoassays are indispensable for vaccination studies. To be suitable for monitoring antibody development in phase I and II clinical trials as well as in postmarketing studies, EIA tests for hepatitis A antibodies must be commercially available and of known sensitivity. The Enzymun anti-HAV test developed by Boehringer Mannheim (Germany) offers the possibility to measure antibody titres around the protective level of 20 mIU/ml which is reached by the passive immunisation with immunoglobulin preparations or within two weeks after active vaccination with an inactivated hepatitis A vaccine. The Abbott IMX test system is more useful for the detection of natural infections by the hepatitis A virus.

Adult↗
PubMed1993

[Magnetic resonance tomography of chronic aortic dissection].

17 patients with chronic aortic dissection were examined by MRI. In 12 patients, comparison between gradient echo sequences and SE sequences was possible. Gradient echo sequences, unlike SE sequences, permitted evaluation of flow in the true and false lumen, reliable differentiation between thrombus and flowing blood and clear delineation of the intimal flap. An additional comparison between transoesophageal ultrasound and MRT in 15 patients showed significant advantages in favour of MRI. In three patients MRI was able to detect more proximal origins of the dissection. Moreover, MRI allowed evaluation of the major aortic branches and their relation to the dissection; this was not possible with ultrasound. MRI plays an important role in the follow-up of chronic aortic dissections.

Adult↗
PubMed1993

[MR tomographic functional analysis of the left ventricle].

The following contribution presents a continuous MRT analysis of the contraction and relaxation processes of healthy left ventricles giving reference values for contraction and relaxation velocities. For the total ventricle we have Vsyst. r. total = 342 +/- 47% LVEDV/sec and Vdiast. r. total = 303 +/- 59% LVEDV/sec. In relation to the end-diastolic (tomographic) volume (EDSV) significantly greater changes in volume per unit of time were measured apically compared to basal (systolic: 411 +/- 89% EDSV/sec apical vs 261 +/- 35% EDSV/sec basal; diastolic: 810 +/- 145% EDSV/sec apical vs 245 +/- 70% EDSV/sec basal). Occurrence of the end-systolic minimal volumes of apical tomographic layers was delayed against the total ventricle by 22.4 +/- 7.9% t syst. Within the ventricle there was systolically a redistribution of the proportions of volume from apical to basal.

Adult↗
PubMed1993

[MR tomographic measurement of the diastolic relaxation of the hypertrophied left ventricle with the single-slice-multiphase technic].

In order to assess diastolic ventricular function in hypertensive patients, a single-slice multiphase sequence was used in order to measure contraction and early diastolic relaxation. There was no difference in the contraction velocity between hypertensives and normals (Vsys. n.r. = 56.1 +/- 13.8% LVDV/s vs. 51.7 +/- 8.6% LVEDV/s, stat, n. sign.). Early diastolic relaxation velocity in hypertensives was reduced as compared with the control group (Vdiast. 1n.r. = 37.9 +/- 13.1% LVEDV/s vs. 47.1 +/- 9.6% LVEDV/s, p < 0.05). There was no linear relation between abnormal relaxation and the extent of myocardial hypertrophy. Hypertensives with myocardial hypertrophy frequently had reduced early diastolic relaxation velocity. Regression analysis for estimating left ventricular volumes derived from single-slice measurements were confirmed by additional multislice measurements. The calculated LVEDV correlated at r = 0.956 with multi-slice measurements and tended to show lower values (LVEDV n.r. = 104.6 +/- 30.8 ml vs. LVEDV = 102.1 +/- 28.8 ml, r = 0.956, p < 0.05). The LVESV was overestimated by the multi-slice technique, the calculated regression volume averaged 23% lower, realistic values (LVESV n.r. = 28.5 +/- 15.3 ml vs. LVESV = 37.1 +/- 15.6 ml, r = 0.887, p < 0.001).

Adolescent↗
PubMed1993

[Diagnosis of anorectal fistula using magnetic resonance tomography].

In 17 patients with anorectal fistulae the pelvis was examined by magnetic resonance imaging (MRI). The extent and the course of the fistulae and abscesses could be visualized by proton-density- and T2-weighted images. In 6 of 17 patients fistulae were seen that could not be detected by clinical investigation. In 2 cases additional pelvirectal abscesses were found. Most of the fistulae (5 of 6) had a complicated high suprasphincteric or rectovaginal course. It is concluded that with MRI anorectal fistulae and abscesses can be visualized and that this method is a worthful additional diagnostic tool in patients with complicated fistula-in-ano.

Adult↗
PubMed1992

Synthesis of undulin by rat liver fat-storing cells: comparison with fibronectin and tenascin.

Fat-storing cells (FSCs) are known to synthesize various components of the hepatic extracellular matrix and thereby play an important role during liver fibrogenesis. The aim of our study was to investigate the synthesis of undulin, a recently described connective tissue protein belonging to the fibronectin-tenascin superfamily of glycoproteins, by fat-storing cells in primary culture. SDS-PAGE analysis of immunoprecipitates from cell layer lysates or media pulse-labeled with radioactive methionine revealed undulin-specific bands A (270 kDa), B1 (190 kDa), and B2 (180 kDa) after reduction. A single undulin-specific transcript was detected at about 7 kb. Undulin synthesized by cell-free translation revealed two polypeptides migrating about 5000 Da below the B1 and B2 subunits. Treatment of FSCs with tunicamycin created two novel bands slightly below the B2 chain. Since the electrophoretic patterns of undulin chains recovered by cell-free translation and tunicamycin treatment of cells were very similar we suggest that N-glycosylation is the major post-translational processing event. Newly synthesized undulin was detected after 30 min of pulse labeling in the cell layer fraction and was secreted into the medium at a slower rate than fibronectin. In contrast to fibronectin and tenascin, undulin was already synthesized by freshly isolated FSCs and during the early stage of primary FSC culture ("resting" cells), supporting the hypothesis that undulin is associated with a differentiated mesenchyma. However, in analogy to fibronectin and tenascin, undulin was also synthesized by "activated" FSCs, indicating that undulin might also be of importance in dedifferentiated tissues.

Animals↗
PubMed1992

A single vaccination with an inactivated hepatitis A liposome vaccine induces protective antibodies after only two weeks.

In the near future an inactivated hepatitis A vaccine will be commercially available. The recommended vaccination schedule will include at least two vaccinations 1 month apart. Giving two doses of vaccine on the same day in one injection results in protection after 2-4 weeks dependent on the adjuvant used. Hepatitis A virus incorporated into liposomes proved to be a suitable formulation in term of rapid seroconversion, high level of mean antibody content and low reactogenicity.

Adult↗
PubMed1992

Reactogenicity and immunogenicity of inactivated hepatitis A vaccines.

Two inactivated hepatitis A virus (HAV) candidate vaccine strain were tested, derived from strains CLF and HM175. Neither vaccine increased liver enzymes levels and reactogenicity was similar to that observed with other alum-absorbed products. Antibody responses were dose-dependent and protection against HAV can be presumed to last for at least three years. All persons receiving 720 ELISA units (El.U) of the CLF vaccine seroconverted after one dose. For the HM175 vaccine, anti-HAV persisted until month 12 after injections at months 0 and 1, suggesting that the third dose of vaccine could be given at any time from month 6 to 12. A double dose of HM175 vaccine (1440 El.U) given as a single bolus resulted in 100% seroconversion by day 14 with a geometric mean anti-HAV level of 121 mIU/ml. This implies that rapid protection can be induced using large doses of inactivated HAV vaccine should time constraints dictate such an approach.

Adult↗