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Biomedical subjects

W Falk

Publications and source records attributed to W Falk.

At least 127 records · Page 7Linked to original sources
PubMed1982

Only the chemotactic subpopulation of human blood monocytes expresses receptors for the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine.

Human peripheral blood monocytes comprise a subpopulation of 20 to 40% that is capable of responding to chemoattractants and a remaining subpopulation that cannot respond. We were able to obtain 99%-pure attractant-responsive monocytes by using a newly constructed separation chamber. The binding of the radioactive chemotactic peptide N-formylmethionyl-leucyl-[3H]phenylalanine to migrating and nonmigrating populations was then studied. The binding was saturable at room temperature in the presence of azide. Saturation occurred at 5 x 10(-8) M, and 50% of the maximal binding was obtained at 10(-8) M, the concentration that induced optimal chemotaxis. The nonmigrating monocytes did not bind the peptide under the same conditions, which shows that at least one reason for a nonresponsiveness to chemotaxin is apparently a lack of receptors. By Scatchard analysis we calculated an equilibrium dissociation constant ranging from 23 to 37 nM; the number of binding sites per cell ranged from 64,000 to 77,000. The binding was very rapid. Fifty percent of the optimal binding occurred at 3.5 min, and equilibrium was reached after 20 to 30 min. Chemotactic deactivation of the monocytes reduced the number of available binding sites by 60%.

Azides↗
PubMed1982

Chemotaxis of purified human monocytes in vitro: lack of accessory cell requirement.

This study was undertaken to determine whether cell cooperation, either among monocytes or between monocytes and lymphocytes, is a prerequisite for monocyte chemotactic responsiveness. We compared Ficoll-Hypaque-separated mononuclear cells and a preparation of 99% pure monocytes obtained by chemotaxis in a newly designed separation chamber. Monocytes of both preparations migrated to chemoattractants without a lag phase, and no further increase in migrated cells was observed after 70 min. The cell dose-response was linear for both preparations over a wide range of cell concentrations in the cell input well of the chemotaxis chamber, suggesting that no monocyte-monocyte interaction was required. Since only 20 to 60% of the monocytes purified by chemotaxis migrated a second time, the possibility of a requirement for an accessory cell was tested. The addition to purified monocytes of several different mononuclear cell preparations comprising lymphocytes or nonmigrating monocytes had no effect on monocyte migration. These experiments show that normal human blood monocytes in vitro do not require stimuli from other cells to respond to chemoattractants. Their behavior is profoundly different from that of mouse peritoneal macrophages, which exhibit a time lag in vitro before migration toward an attractant and become more responsive with either increasing cell concentration or addition of purified lymphocytes.

Cell Communication↗
PubMed1981

[Present and future of oral pertussis vaccination].

Parenteral immunization against whooping cough shows some disadvantages which led to proposals to curtail pertussis vaccination in some countries. As a result a striking rise in pertussis morbidity in these regions was noted, so vaccination against whooping cough is still indicated. We developed an oral vaccine for the neonate to achieve a protective immunity at a time when it is especially needed and to avoid side-reactions. Oral vaccine was given to more than 15,000 newborns, vaccination results of the last 3 years are reported.

Administration, Oral↗
PubMed1981

[BCG vaccination and manifest tuberculosis].

Due to the findings in 10 children with tuberculosis, which has been proved by cultural methods or animal test, it is advisable to take the following into consideration: The possibility of tuberculosis must be assumed for each BCG-vaccination child, that shows symptoms of disease of uncertain aetiology and that has had or might have had contact with a person with active tuberculosis. Among the diagnostic procedure proof and typing of the tubercle bacillus are considered to be most important.

Adolescent↗
PubMed1981

Specificity and reversibility of chemotactic deactivation of human monocytes.

The chemotactic deactivation of human monocytes was studied to provide insight into the mechanism of chemotaxis. Deactivation was dependent on the dose of chemoattractant and time of incubation. A concentration in the cell suspension of 10(-8) M N-formylmethionylleucyl phenylalanine (FMLP) for 45 min at 37 degrees C led to 60% suppression of the subsequent specific chemotactic response. Higher concentrations of FMLP led to almost 100% specific suppression. Deactivation was specific under all conditions used. The response to a nonrelated chemoattractant, human serum-derived C5a, was unaffected by incubation in FMLP. Deactivation was also transient. If cells were deactivated at 37 degrees C with FMLP, they recovered within 6 h at 37 degrees C from this deactivation. Both phenomena, deactivation and recovery from deactivation, were temperature dependent. Monocytes could not be deactivated at 0 degrees C, and they did not recover from deactivation when kept at 0 degrees C. Thus, specific deactivation appears to require cellular metabolism, involving loss of receptors or blocking of a step between receptor occupancy and response.

Anaphylatoxins↗
PubMed1981

Inhibition of nonspecific tumoricidal activity by activated macrophages with antiserum against a soluble cytotoxic factor.

Mouse peritoneal macrophages activated for tumor cytotoxicity by any of several in vivo or in vitro treatments released a soluble cytotoxin into culture fluids only after exposure to small amounts of bacterial lipopolysaccharides. This cytotoxic factor was physicochemically similar to the cytotoxic factor (tumor necrosis factor) in sera of BCG-infected mice injected with lipopolysaccharide. A rabbit antiserum against partially purified serum cytotoxic factor also inhibited the activity of macrophage-derived cytotoxic factor. Of special interest was the observation that rabbit anti-cytotoxic factor inhibited the cytotoxic activity of macrophages both in the presence and in the absence of exogenously added lipopolysaccharide. Inhibition was not complete but was consistent in all experiments. Thus, cytotoxic factor was implicated as a possible effector molecule in the nonspecific tumoricidal activity of activated macrophages.

Animals↗
PubMed1981

Chemotaxis by mouse macrophage cell lines.

Five mouse macrophage cell lines were tested for chemotaxis and phagocytosis. All 5 cell lines ingested sheep red cells coated with rabbit IgG anti-Forssman antibody and exhibited chemotaxis to endotoxin-activated mouse serum (EAMS) and lymphocyte-derived chemotactic factor. Two cell lines were tested for chemotaxis to f-Met-Leu-Phe and neither responded. Four of the cell lines (RAW264, RAW309CR, PU5-1R, and WR19M.1) exhibited chemotaxis to C5a. These cell lines displayed a 1- to 2-hr lag before migrating toward EAMS, and chemotaxis was dependent upon cell density. When fewer than 10(3) cells were present per mm2 of filter surface, less than 10% of the cells migrated; however, at a density of 5 X 10(3) cells/mm2 50 to 70% of the cells migrated. WEHI-3 differed from the other cell lines in that there was no chemotaxis to C5a, migration to EAMS did not have a detectable lag, and there was no cell density dependence for chemotaxis. Comparison of these chemotactic properties with those reported in the literature for mouse macrophages and monocytes suggests that RAW264, RAW309CR, PU5-1R, and WR19M.1 have properties that are similar to those of mouse resident macrophages, whereas WEHI-3 may have some of the properties of mouse monocytes.

Animals↗
PubMed1980

Rapid quantitation of neutrophil chemotaxis: use of a polyvinylpyrrolidone-free polycarbonate membrane in a multiwell assembly.

A neutrophil chemotaxis assay was developd which permits rapid, quantitative assessment of migration across a membrane filter. The critical factor in the assay was the use of a 10 microns thick polycarbonate membrane without the usual polyvinylpyrrolidone coating. Migrated neutrophils remain adherent to the uncoated membrane, whereas 20-50% fall off polyvinylpyrrolidone-coated membranes. A major advantage of the method is that neutrophil chemotaxis can be readily quantified, since the migrated cells adhere to the membrane surface and are in one optical plane for counting. A 25 mm x 80 mm membrane sheet was used in a 48-well micro chemotaxis assembly, which requires only 20,000 neutrophils and 25 microliters of attractant per assay well. Neutrophil chemotaxis was complete within 10-20 min at 37 degrees C, with 20-30% of the cells migrating to N-formyl-methionyl-leucyl-phenylalanine and 40-50% migrating to complement derived C5a.

Carbonates↗
PubMed1980

A 48-well micro chemotaxis assembly for rapid and accurate measurement of leukocyte migration.

We designed a 48-well chemotaxis chamber to minimize manipulation time and amount of material required by the larger blindwell or Boyden chemotaxis chamber. Cell and chemoattractant dose-response curves showed that results were comparable to our better than those obtained with blindwell chambers. The volume of chemoattractant per well is 25 microliter; the number of cells can be as low as 10,000. The time needed for setting up this multiwell unit and for staining the membrane filter sheet is negligible. Combined with the use of an image analyzer to count the number of migrated cells, the method is suitable for clinical research on the functional state of monocytes in large groups of patients.

Chemotactic Factors↗
PubMed1980

Human monocyte chemotaxis: migrating cells are a subpopulation with multiple chemotaxin specificities on each cell.

Only 20 to 40% of human blood monocytes were capable of responding to chemotaxins in vitro. This limit is not due to restrictions of the in vitro system, but is due to the existence of a migrating subpopulation. Over a wide range, the number of cells migrating toward a given concentration of chemotaxin was directly proportional to the number added to the chemotaxis chamber. These monocytes responded to all of the three stimuli used: human serum-derived C5a, human lymphocyte-derived chemotactic factor, and a synthetic peptide. It was possible to deactivate cells to one attractant, leaving the response to other attractants intact. This suggested that these attractants were recognized by different receptors. Several lines of evidence showed that most migrating cells had receptors for all three chemotaxins tested. Thus, if cells were assayed for migration to one attractant, no additional migration occurred when the remaining cells were assayed for migration to a different attractant. Furthermore, the same cells that had migrated toward one attractant were able to respond to other chemotaxins. We also found that a single attractant attracted as many cells as a combination of two or three attractants. Calculations from these data showed that at least 75% of the migrating monocytes have different receptors for all three attractants.

Cell Movement↗
PubMed1980

[Normal values for circulating thyroid hormones, T3 uptake and thyrotropin before and after TRH. Radioimmunoassay determinations on 182 euthyroid children (author's transl)].

Measurements of T4, T3, rT3, T3U, and TSH (before and after TRH stimulation) were performed by RIA. 182 children, apparently euthyroid, age 2/12--14 years, were investigated in a cross sectional study. Free T4RIA and free T3RIA Indices and the ratio rT3/T3 and T4/T3 were calculated. Statistical analysis showed the following results: 1. Geometric mean serum concentrations of T4, T3, rT3 and TSH (basal) show no age related differences; T4 showed a not significant negative slope with age.--2. The ratio rT3/T3 and T4/T3 remains constant.--3. TRH induced TSH release (indicating the activity of the regulatory system) is unchanged from 2/12 to 14 years. Geometric means values, standard deviations and normal ranges are given.

Adolescent↗
PubMed1979

[Oral pertussis immunization of the newborn infant (author's transl)].

Oral pertussis immunization of the newborn infant should be started from the second day after birth. A rapid increase in salivary antibody titres is observed after immunization, which then decreases slightly within the observation period of 4 weeks. These facts are discussed.

Administration, Oral↗
PubMed1977

[Autonomous thyroid adenoma in an 11 years old girl with childhood hyperthyroidism (author's transl)].

The thyroid gland of an eleven year old girl developed a 3 x6 cm nodule with endocrine activity and storage ability. Szintigraphic examination with TSH simulation identified it as an autonomous decompensating adenoma. Within a few months a clinically mild hyperthyreotic state developed. After surgical removal histology showed a follicular adenoma with papillary characteristics. Postoperatively thyroid hormon therapy was started.

Adenoma↗
PubMed1976

[Clinical, pathological and therapeutic aspects of cholesteatoma in children (author's transl)].

Middle ear cholesteatoma in childhood is discussed on the basis of 117 operated cases. Early diagnosis was rare, even after fetid otorrhea of long duration; occassionally they presented as acute mastoiditis. The cholesteatoma occurred mostly in older children (90%) and extended to the antrum (73%) or beyond it (54%), with destruction of the ossicles (77%); the hearing often remained normal. Tympanic membrane perforations were usually small, relatively often they were central. More than 50% of the children had normal mastoid pneumatization, usually there were no typical radiological signs of cholesteatoma. Tympanoplasty was most frequently type III (68.5%), the postoperative hearing gain in this group was 47.3%. Residual or recurrent cholesteatoma occurred in 8.5%.

Age Factors↗