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Biomedical subjects

M Falk

Publications and source records attributed to M Falk.

At least 73 records · Page 4Linked to original sources
PubMed1994

Relationship between humoral response to Plasmodium falciparum merozoite surface antigen-2 and malaria morbidity in a highly endemic area of Papua New Guinea.

The prevalence and concentration of antibodies to merozoite surface antigen-2 (MSA-2) were measured in blood samples collected during a cross-sectional survey. Antibodies were measured by enzyme-linked immunosorbent assay using two recombinant proteins that closely approximated the full-length mature MSA-2 polypeptides expressed by the Plasmodium falciparum isolate FC27 and the cloned line 3D7 and that were representative of the dimorphic forms of MSA-2. Antibodies were also measured to a form of the 3D7 MSA-2 lacking the central repetitive sequences (d3D7). High antibody prevalence was observed to all three antigens: the overall prevalence of IgG to FC27, 3D7, and d3D7 was 91%, 90%, and 90%, respectively. The majority of individuals > or = 5 years of age had antibodies to both forms of MSA-2. The geometric mean antibody units increased with age with a plateau being reached by 15-20 years of age. There was a significant positive association of antibody prevalence with both the presence of the parasite and an enlarged spleen in children. This study provides the first evidence that antibodies against nonrepeat regions of MSA-2 are associated with fewer fever episodes and less anemia, both known to be indicators of malaria morbidity.

Adolescent↗
PubMed1994

Detection of HRX-FEL fusion transcripts in pre-pre-B-ALL with and without cytogenetic demonstration of t(4;11).

The t(4;11)(q21;q23) characterizes a distinct clinical entity of childhood and adult acute lymphoblastic leukemia (ALL) with a pre-pre-B-phenotype, monocytoid features, coexpression of CD15 and/or CDw65 and a dismal prognosis. The molecular correlate of the t(4;11) has been identified as a fusion transcript of HRX, a gene on 11q23 with homology to drosophila trithorax gene, and FEL, a serine-proline-rich gene on 4q21 of unknown function. The aim of the current study was to establish a reverse transcription-polymerase chain reaction (RT-PCR) approach for the rapid and sensitive detection of the HRX-FEL fusion transcript associated with the t(4;11). For this purpose, two groups of patients were studied: group A comprised cases with cytogenetically proven t(4;11) including three infant and four adult pre-pre-B-ALL, as well as the two cell lines RS4;11 and MV4;11. Group B consisted of ten adult pre-pre-B-ALL with the identical phenotype, but without cytogenetic confirmation of t(4;11). Using primers complementary to HRX and FEL cDNA sequences 300 to 500 bp 5' and 3' of published breakpoints, respectively, specific amplification products were obtained in all nine cases of group A and in nine of the ten cases of group B. Three different types of fusion transcripts were identified by sequence analysis with HRX breakpoints at nucleotides 4086 and 4218 and FEL breakpoints at nucleotides 1413, 1416, and 1458. These data indicate that RT-PCR allows the detection of HRX-FEL fusion transcripts in the vast majority of cytogenetically proven and immunophenotypically suspected t(4;11) ALL. Hence, this technique may allow identification of a further subset of high risk ALL and may also be useful for the monitoring of minimal residual disease in t(4;11) ALL.

Adult↗
PubMed1993

Reduced effect of inhaled beta 2-adrenergic agonists on lung mucociliary clearance in patients with cystic fibrosis.

STUDY OBJECTIVE: It has been suggested that the defective cyclic AMP-dependent Cl- secretion and the increased Na+ absorption from airway epithelia in cystic fibrosis (CF) may lead to dehydrated secretions and impaired mucociliary clearance. Beta 2-adrenergic agonists are unable to stimulate the Cl- transport in the airways in CF while being able to do so in normal airways. Thus, we questioned whether the beta 2-adrenergic agonist, terbutaline, would improve mucociliary clearance in patients with CF as it does in healthy subjects. DESIGN: A double-blind, randomized cross-over trial. SETTING: Whole lung and regional mucociliary clearance of a radioaerosol was measured for 3 h by gamma camera. One minute of cough clearance was measured at 3 h. Pulmonary function was measured before and after the gamma camera study. PATIENTS: Ten young patients with CF were studied; three were heterozygous for deletion of the phenylalanine at position 508 (delta F508), and seven were delta F508 homozygous. INTERVENTIONS: Inhalation of 1 mg of terbutaline (4 puffs) and placebo via a metered-dose inhaler by spacer. MEASUREMENTS AND RESULTS: The largest differences in tracheobronchial retention (percent) in the whole lung and regional lung zones were generally observed within 1 h after terbutaline and placebo treatment: whole lung (mean +/- SD), 60 +/- 22 percent and 63 +/- 20 percent; central zone, 41 +/- 19 percent and 50 +/- 25 percent; midzones, 65 +/- 27 percent and 63 +/- 19 percent; and peripheral zones, 77 +/- 28 percent and 72 +/- 28 percent, respectively [p > 0.1]. Whereas none of these differences was statistically significant, subanalyses suggested an improvement in mucociliary clearance by terbutaline in the three delta F508 heterozygous patients but not in the seven delta F508 homozygous patients. One minute of voluntary coughing resulted in clearance of less than 8 percent of the initial radioactivity, with a trend of more peripheral zone clearance after terbutaline compared with placebo. A small significant decrease in airway resistance was detected 3 h after terbutaline. CONCLUSIONS: We conclude that 1 mg of terbutaline did not improve mucociliary clearance significantly in the patients with CF. Also, the effect of terbutaline was much less than demonstrated earlier in healthy subjects. This is consistent with earlier findings of a lack of beta-adrenergic modulation of Cl- transport in CF. Thus, no rehydration of the dry mucus in CF is expected, and a possible beta 2-agonist-induced increase in ciliary beating would have only a minor effect on overall mucociliary clearance.

Administration, Inhalation↗
PubMed1993

[Bioprosthesis degeneration in the aortic and mitral valve position. Results and problems from the cardiosurgical viewpoint].

38 patients (20 men, 18 women) underwent reoperation between July 1989 to September 1992 because of degeneration of bioprosthetic valves implanted in aortic or/and mitral position. Retrospective analysis revealed a mean implantation time of 116.5 +/- 31.5 months for the bioprostheses (median 116). At reoperation 63.2% of them had a single valve replacement, 36.8% a more complex cardiac procedure (double or triple valve replacement, valve replacement and coronary bypass grafting). 50% (n = 9) of the reoperation cohort were symptomatic (NYHA III), 16 (42.1%) were serious symptomatic (NYHA IV). All deaths were NYHA IV preoperatively. Early mortality was 18.4% (n = 7). Mean age at the time of first operation was 51 +/- 10.7, mean age at reoperation was 60.5 +/- 10.6. There was a significantly longer aortic clamp time (AKT, p = 0.0005) and bypass time (BPT, p = 0.0000) compared to first operation, also a significantly longer BPT of the deads confronted with the survivors (p = 0.0075). Bioprosthetic valves in mitral position were significantly longer implanted (p = 0.0416) than in aortic position. But there was no difference in implantation time of commercially available Carpentier-Edwards- or Ionescu-Shiley grafts. At reoperation we changed more than 95% of the degenerated valves to mechanical devices--corresponding to international tendencies. We discuss the early tissue degeneration of bioprosthetic valves and their increasing problem during reoperation.

Adult↗
PubMed1993

Air pollution levels, meteorological conditions and asthma symptoms.

We wanted to assess relations between the daily occurrence of asthma symptoms and fluctuations of air pollution concentrations and meteorological conditions. In a panel of 31 asthmatic patients residing in the town of Piteå in northern Sweden, severe symptoms of shortness of breath, wheeze, cough and phlegm were recorded in an asthma diary together with suspected causes. Sulphur dioxide, nitrogen dioxide, black smoke, relative humidity and temperature were used to evaluate the relationship to the environment. By using multivariate analyses, we found that daily variations in the particulate pollution levels, indicated by black smoke levels below the criteria limits, had significant effects on the risk of developing severe symptoms of shortness of breath. This association was stronger among 10 subjects, who had at least five incident days with severe shortness of breath. Meteorological conditions were not significant in the multivariate models. Cough and phlegm did not show significant relationships to any environmental condition that was evaluated. Only one-third of the subjects reported, at least once during the study, symptoms believed to be related to air pollutants, although we found significant correlations between the pollution levels and the frequency of pollution-related symptoms. We conclude that an association has been established for black smoke as pollutant and shortness of breath as respiratory symptom, and that in certain asthmatics, effects were occurring at lower particulate levels than suggested previously.

Adolescent↗
PubMed1992

V delta 1+ subset of human gamma delta T cells responds to ligands expressed by EBV-infected Burkitt lymphoma cells and transformed B lymphocytes.

Human gamma delta T cells of peripheral blood can be divided in two groups in terms of their TCR as well as their behavior upon in vitro stimulation. The major subset expresses the TCR V-segments V gamma 9 and V delta 2 and proliferates in response to ligands revealed by various microorganisms, and the cell line Daudi in addition. The minor group is less homogenous on the gamma-chain but is almost completely identified by mAb against the V delta 1 segment; there is no ligand known to promote growth of these cells. Here we demonstrate that gamma delta T cells out of this subgroup are strongly stimulated in vitro by cells from several Burkitt's lymphoma cell lines. EBV infection of the Burkitt's lymphoma cell lines enhanced the stimulatory ability towards the T cells. Although EBV infection influenced the expression of a variety of cell surface molecules including ICAM-1 and LFA-3, no correlation to the gamma delta T cell-stimulating capacity became apparent. We conclude that Burkitt's lymphoma cells and transformed B cells express ligands of cellular origin for a hitherto poorly characterized subgroup of human gamma delta T cells.

B-Lymphocytes↗
PubMed1992

The calcium-binding proteins MRP8 and MRP14 form a membrane-associated heterodimer in a subset of monocytes/macrophages present in acute but absent in chronic inflammatory lesions.

Monocytes/macrophages expressing an epitope recognized by a monoclonal antibody 27E10 are present in acute but are absent in chronic inflammatory disorders. This report shows that the 27E10 antigen is formed by noncovalent association of the two Ca(2+)-binding proteins MRP8 and MRP14 which belong to the S100 protein family. Identification has been confirmed immunochemically, by matrix-assisted UV-laser desorption/ionization spectrometry and by partial amino acid sequencing. Surface expression of the MRP8/MRP14 complex on a subset of monocytes is reported for the first time and shown to be up-regulated in a Ca(2+)-dependent manner. The 27E10 surface-positive monocytes isolated by cell separation techniques release high amounts of tumor necrosis factor-alpha and interleukin-1 beta in contrast to their 27E10 surface-negative counterparts thus emphasizing their role in inflammation.

Acute Disease↗
PubMed1992

"Milky" urine--a child with chyluria.

A 10-year-old boy with chyluria due to a congenital fistulous communication between the lymphatic system and the bladder is described. Chyluria can be parasitic or non-parasitic. Many causes of non-parasitic chyluria have been reported. Lymphography is the preoperative imaging procedure of choice since it demonstrates the site, the calibre and the number of the fistulous communications. Lymphoscintigraphy shows very well the site of the fistula but is not as precise as lymphography. However, it has the advantage to be less invasive and is an excellent alternative in the non-surgical cases. The prognosis of non-parasitic chyluria is usually very good and the treatment is mostly conservative.

Child↗
PubMed1992

[New perspectives of avalanche disasters. Phase classification using pathophysiologic considerations].

This study comprises an analysis of the data on 332 persons totally buried by avalanches in Switzerland between 1981 and 1989. The survival rate was calculated with the aid of a computer-assisted estimation procedure according to Turnbull. The curve pattern was interpreted according to pathophysiological considerations, on the basis of which the time course of the battle for survival was divided into 4 phases: 1) Survival phase: until 15 minutes after burial under the snow masses. The survival probability amounts to 93% and is, thus, higher than so far assumed. Almost all those buried survived this period of the time provided they were not fatally injured and received first aid. 2) Asphyxia phase: duration of burial under the avalanche from 15 to 45 minutes. The probability of survival sank dramatically during this period from 93% to about 25% (fatal kink of the survival probability curve). Those buried under the snow without an air pocket die of acute asphyxia (the point of no return) and the mortality rate reaches its maximum in this phase. 3) Latent phase: the period as from 45 minutes following the avalanche until the time of rescue. This phase is survived only in the presence of an air pocket. With sufficient oxygen reserves and freedom of thoracic movement a "phase of relative safety" occurs, whereby the survival probability diminishes further only slowly. The first deaths due to hypothermia arise after 90 minutes. 4) Rescue phase: from the time of extrication from the snow until arrival in hospital. There is an increased risk of a fatal outcome during the rescue procedure and immediately afterwards through augmented hypothermia.(ABSTRACT TRUNCATED AT 250 WORDS)

Asphyxia↗
PubMed1991

Comparison of the automated vision screening test to the Snellen test.

The comparison of an automatic vision screening machine using the Landolt rings and the usual Snellen Chart was carried out among 123 second grade and 149 fifth grade students in an elementary school in Jerusalem. The sensitivity of the test for a cut-off point of greater than or equal to 6/12 according to the Snellen test was 41.7% (CI = 16.5-71.4) and the specificity was 86.5% (CI 78.1-92.2) for second graders. For fifth graders the values were 50.0% (CI = 20.1-79.9) and 90.6% (CI 83.7-94.8) respectively. Diagnosis by a specialist decreased the number of 'false negatives' and confirmed the pathological cases. The automatic test was well accepted by the children. Though more time is needed for assessment using the automatic test, its advantage is that no professional staff are required.

Child↗
PubMed1991

The effects of postural drainage and positive expiratory pressure physiotherapy on tracheobronchial clearance in cystic fibrosis.

We studied the effects of two chest physiotherapy regimens on whole lung and regional tracheobronchial clearance (TBC) in ten patients with cystic fibrosis. The regimens were given on two separate days and consisted of 20 min of (1) postural drainage and the forced expiration technique (PD + FET), and (2) positive expiratory pressure (PEP-mask) and FET (PEP + FET). A third day served as control. The study days were randomized. Each day, the clearance of lung radioactivity was measured for 3 h by gamma camera. The number of spontaneous coughs was recorded and the sputum expectorated was sampled. We found that both PD + FET and PEP + FET improved whole lung TBC at 30 minutes and 1 h four or fivefold (p less than 0.01) compared with control, whereas at 2 h and 3 h only the improvement following PEP + FET (approximately 1.4 times) was significant (p less than 0.05). There was no significant difference in whole lung or regional TBC between the PD + FET and PEP + FET treatments. The correlations between TBC and the radioactivity content in sputum expectorated (rs2 = 0.76) and between TBC and numbers of coughs (rs2 = 0.65) were better than between TBC and the weight of sputum expectorated (Rs = 0.39). We conclude that PD or PEP when combined with FET have similar effects on short-term whole lung and regional TBC in patients with cystic fibrosis. Evaluation of TBC during chest physiotherapy when only based on the weight of sputum expectorated seems inadequate.

Adolescent↗
PubMed1990

[Genetic counseling in relation to drug intake in early pregnancy].

In a series of 153 women with intake of drugs during early pregnancy the pregnancy was terminated in 22% of all cases. There were the following results of the 119 non-terminated pregnancies: delivery of a normal, healthy baby: 84%; abortion: 5%; still birth and premature birth, respectively: 3,5%. An abnormal phenotype was seen in 7% of the newborns, but only 3 cases with major malformation (cleft lip, club-foot, cataract) could be noted. Compared with normal pregnancies the results do not confirm an enhanced risk for malformations by intake of drugs during early pregnancy. Unfounded anxiety of physicians as well as of pregnant women with indicated pharmacotherapy should be reduced by better information and education.

Abnormalities, Drug-Induced↗
PubMed1989

Prevalence of peritonitis-associated coagulase-negative staphylococci on the skin of continuous ambulatory peritoneal dialysis patients.

The predominance of coagulase-negative staphylococci as normal skin flora is thought to be a factor in their association with episodes of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. We investigated the prevalence of peritonitis-associated strains on the skin of 28 patients undergoing peritoneal dialysis. Coagulase-negative staphylococci were the most frequently isolated organisms, comprising 47% of peritoneal dialysis fluid isolates and 59% of body site isolates. A total of 142 coagulase-negative staphylococci were speciated, tested for their antimicrobial sensitivity and slime production, and identified by phage typing and plasmid-profile analysis. Staphylococcus epidermidis was the most commonly identified species from both peritoneal dialysis fluid (73%) and body sites (53%). Multiple antibiotic resistance was common, and the greater proportion of isolates were resistant to methicillin; 63.6% of peritoneal dialysis fluid isolates and 61.7% of body-site isolates. S. haemolyticus isolates were significantly more resistant to methicillin than other species. By phage typing and plasmid-profile analysis it was shown that peritonitis was rarely caused by skin-colonizing strains. In only 3 of 14 patients were peritonitis-associated strains isolated as skin colonizers, and no patients developed peritonitis due to organisms previously isolated as skin colonizers.

Bacteriophage Typing↗
PubMed1988

Membrane integration and intracellular transport of the coronavirus glycoprotein E1, a class III membrane glycoprotein.

The E1-glycoprotein (Mr = 26,014; 228 amino acids) of mouse hepatitis virus A59 is a class III membrane glycoprotein which has been used in this study as a model system in the study of membrane integration and protein transport. The protein lacks an NH2-terminal cleavable signal sequence and spans the viral membrane three times. Hydrophobic domains I and III could serve as signal sequences for cotranslational membrane integration. Domain I alone was sufficient to translocate the hydrophilic NH2 terminus of E1 across the membranes as evidenced by glycosylation of a newly introduced N-glycosylation site. The COOH-terminal part of E1 involving amino acids Leu124 to Thr228 was found to associate tightly with membranes at the post-translational level, although this part of the molecule lacks pronounced hydrophobic sequences. Membrane protection assays with proteinase K showed that a 2-kDa hydrophilic fragment was removed from the COOH terminus of E1 indicating that the protein is largely embedded into the membrane. Microinjection of in vitro transcribed capped and polyadenylated mRNA into CV-1 cells or into secretory AtT20 pituitary tumor cells showed that the E1-protein accumulated in the Golgi but was not detectable at the plasma membrane or in secretory granules. The 28 NH2-terminal hydrophilic amino acid residues play no role in membrane assembly or in intracellular targeting. Various NH2-terminal portions of E1 were fused to Ile145 of the cytoplasmic N-protein of mouse hepatitis virus. The resulting hybrid proteins were shown to assemble into membranes in vitro and were detected either in the rough endoplasmic reticulum or transient vesicles of microinjected cells.

Amino Acid Sequence↗
PubMed1988

[Mechanism of the action of tenside on permeation through lipid membranes].

The permeability of lipid-collodium membranes is altered by the effect of cationic and anionic tensids. Then ionic and nonionic substances may permeate unselectively. This alteration is irreversible. Three ways of transport across membranes exists in presence of tensids: permeation by solubility into the lipid, transport into water on ionized groups of tensids and with water into micells of tensids, which permeate the membranes.

Chemical Phenomena↗