Biomedical subjects
Publications and source records attributed to D Becker.
In both primary and secondary rhinoplasty, favorable illusion may be created by cartilage grafting of various nasal anatomic components, as well as rearranging components in relationship to one another. Recognizing which patients will benefit from the procedures described herein can lead the rhinoplasty surgeon to improved long-term outcomes.
We present the results of a case control study on the concentration of intracellular calcium [Ca+2]i in peripheral blood mononuclear cells (PBMC) of patients with Alzheimer's disease (AD), major affective disorder unipolar type (DEP), and elderly controls. We used the fluorescent dye Quin-2 to measure intracellular calcium concentration in PBMC both in their basal resting state [Ca+2]b and after activation [Ca+2]a with phytohemagglutinin (PHA). The [Ca+2]b and [Ca+2]a values in PBMC of AD patients were significantly higher than those of the elderly controls and of the DEP patients. In the DEP patients the [Ca+2]a values in PBMC were significantly higher than those of the elderly controls, but the [Ca+2]b values were not. [Ca+2]i levels did not correlate with age, gender, or duration and severity of the diseases investigated. These findings indicate that higher values of [Ca+2]b and [Ca+2]a may differentiate most AD patients from elderly controls or DEP patients.
Superantigens are potent modulators of the immune system, especially T cells. Therefore, we determined the influence of superantigens on the T-cell-mediated immune response, contact sensitivity. We chose the combination of staphylococcal enterotoxin B (SEB) as superantigen and 2,4-dinitrofluorbenzene (DNFB) as the contact sensitizer, because in BALB/c mice SEB reacts almost exclusively with V beta 8+ T cells, and these cells are capable of transferring contact sensitivity to DNFB from sensitized donors to naive syngeneic recipients. Pretreatment with a single intradermal injection of 50 ng SEB 24 h before DNFB exposure at the same site on the lower abdomen enhanced the induction of contact sensitivity: its intradermal injection permitted sensitization with non-sensitizing concentrations of DNFB as assessed by ear swelling responses after challenge with DNFB. In contrast, pretreatment with repeated intradermal injections of 50 ng SEB every other day over at least 1 week inhibited the induction of contact sensitivity following sensitization. The enhancing effect of SEB may be explained by the creation of a proinflammatory milieu in the skin after a single intradermal injection of the bacterial toxin, whereas the inhibitory effect may be due to tolerization of V beta 8+ T cells. The data indicate that products of skin-colonizing bacteria that can serve as superantigens are able to augment or inhibit the development of contact sensitivity.
Heat-stable antigen (HSA), expressed by various antigen-presenting cells (APC), has been described as a costimulatory molecule for CD4+ T cells. Recently, we observed that HSA also serves as an important costimulatory molecule on epidermal Langerhans cells (LC). During these studies, low levels of HSA staining were also detected on normal murine keratinocytes (KC). To investigate whether HSA also is involved in T-cell activation by KC, normal murine KC or the spontaneously transformed KC cell-line PAM 212 were treated with PDB or PMA to induce HSA-expression. FACS analyses showed induction of HSA expression on normal murine KC, as well as PAM 212 cells. In functional assays PDB or PMA-treated normal or transformed KC were far more potent inducers of primary allogeneic T-cell responses than untreated KC. Addition of anti-HSA-specific mAb 20C9 specifically inhibited the costimulatory activity of KC, an effect that was even more pronounced when CTLA-4Ig was added to the cultures. Cleavage of HSA on KC surfaces by a phosphoinositol-specific phospholipase C (PI-PLC) also significantly inhibited the costimulatory capacity of KC for naive CD4+ T cells. In aggregate, our data indicate that expression of HSA on activated KC contributes to the capacity of these cells to induce proliferation of allogeneic T cells.
The superantigen Staphylococcal enterotoxin B (SEB) and the contact allergen 2,4-dinitrofluorbenzene (DNFB) both react with V beta 8+ T-cells delivering distinct signals. Pre-treatment with DNFB painted onto the same skin site where SEB was to be injected, prevented the induction of anergy in V beta + T-cells that was otherwise induced after SEB had been injected intradermally over a period of 2 weeks. Application of the irritant sodium dodecyl sulfate (SDS) instead of DNFB did not exert this effect. Application of DNFB at a site distant from the site where SEB was injected resulted in a much weaker inhibitory influence on the induction of anergy by SEB. Established anergy of V beta 8+ T-cells (proliferative non-responsiveness to SEB in vitro that could be overcome by addition of exogenous interleukin 2 (IL-2)) could be largely reversed by repeated cutaneous exposure to DNFB painted to the site where SEB had been injected before. The moderate decrease of V beta 8+ T-cells normally induced by SEB-treatment was also partially prevented by DNFB pre-treatment. The data indicate the importance of the sequence of signals delivered to T cells and the plasticity of the responsiveness of this cell type.
In order to define the influence of contact allergens on the fluid-phase endocytosis (FPE) of soluble molecules of murine epidermal Langerhans cells (LC), we studied the internalization of FITC-labeled bovine serum albumin (FITC-BSA), TRITC-labeled dextrane (TRITC-DEX) as well as horseradish peroxidase by LC. A 3-parameter flow-cytometric technique was performed for quantification of internalized FITC-BSA in LC using quantum red-labeled reagents for detection of Ia-antigen expression by LC and propidium iodide for exclusion of dead cells from analysis. A temperature-dependent rapid accumulation of FITC-BSA was noticed in time-course studies reaching a plateau between 1 and 2 h of in vitro culture at 37 degrees C. The quantity of FPE under stimulation with phorbol 12-myristate 13-acetate (PMA), concanavalin A (Con A), staphylococcal enterotoxin B (SEB) and contact sensitizers (DNFB, Kathon CG, K2Cr2O7) as well as the irritant SLS was determined. Treatment of LC with PMA and Con A resulted in a significant increase of total FITC-BSA uptake. The contact sensitizers as well as SEB and SLS failed to mediate augmented fluid-phase endocytosis. By use of the pH-insensitive soluble marker, TRITC-DEX and a microscope photometer for evaluation these findings could be confirmed. This excluded any artificial influence of differences in pH values in endocytotic compartments which might have influenced the fluorescence intensity of the pH-sensitive fluorochrome FITC. For qualitative analysis of FPE, the intracellular distribution of internalized horseradish peroxidase in LC was studied. An aggregated pattern became apparent in untreated LC and did not change under stimulation with any of the substances used.(ABSTRACT TRUNCATED AT 250 WORDS)
The endolymphatic sac is part of the membranous labyrinth; it plays an important role in the hearing mechanism. Injury to the endolymphatic sac may, over time, severely compromise hearing. The endolymphatic sac is located in a duplication of the dura of the posterior aspect of the petrous pyramid and is, therefore, in the surgical field of many neurosurgical operations performed on the posterolateral cranial base. The endolymphatic sac was exposed bilaterally in 10 anatomic specimens; the distance from the center of the sac to the posterior lip of the internal auditory meatus and to the XIth nerve in the jugular foramen was measured with a caliper. Also measured was the distance between the center of the sac and the closest point on the petrous ridge and the distance between that point and the petro-sigmoid intersection. The petro-sigmoid intersection was defined as the point at which the medial aspect of the sigmoid sinus intersects the lateral aspect of the petrous ridge. The dimensions of the sac were also recorded. On the average, the sac was found to be 15.7 mm posterosuperior (superolateral) to the XIth nerve in the jugular foramen (range, 11.0-18.5 mm) and 13.3 mm posterior (lateral) to the internal auditory meatus (range, 10.0-18.0 mm). The center of the sac was 24.1 mm (mean value) (range, 20.0-28.0 mm) in front of the petro-sigmoid intersection at a point 11.5 mm (mean value) (range, 8-17 mm) below the petrous ridge. The mean width and height of the sac were 3.83 (range, 2-6 mm) and 3.80 mm (range, 2.5-8 mm), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Sonographic diagnostics has been essentially enlarged by blood flow measurements with the color Doppler technique. Nevertheless, the method has certain limitations, especially when employed to visualize extremely slow blood flow velocities, which occur e.g. in malignant tumors due to neovascularization. Recently, a new technique, the so-called angio-color procedure, has been presented, which is supposed to overcome the above-mentioned limitations. The way of coding the signal differs considerably from that in conventional color Doppler: The amplitude is color coded, not the frequency deviations. Results and first experiences with the new procedure in various domains were discussed at a 'Heidelberg Round Table' and are summarized in the present article. In the obstetrics/gynecology there are clear advantages in the representation of blood flow in the placenta. In eutrophic fetuses a blood flow over the entire placental breadth was detected, in dystrophic fetuses, however, only on the margins of the placenta. Conventional color Doppler could not visualize blood flow in the placenta at all. Blood flow assessment in the fetal organs also provided different results with the two procedures: the angio-color method showed color pixels even in the peripheral areas. In 8 malignant breast tumors the same observation was made, the angio-color procedure seemed to visualize more color pixels. In 4 of 6 benign lesions blood flow could be measured with the traditional color Doppler, but in 5 of 6 patients with the angio-color Doppler. This was also observed in ovarian tumors. Angio-color representation of renal transplants with normal function resulted in blood flow information reaching deep into the renal capsule, whereas in cases of renal transplants with impaired function a clearly reduced perfusion was visualized. These differences were not so evident with the conventional Doppler method. In lymph node diagnosis, too, marked differences between malignant and reactive lymph nodes could be visualized. In the diagnosis of arteriosclerotic plaques, blood flow in the residual lumen could also be detected more exactly with the angio-color technique. Color representation of liver tumors also showed a higher color signal density with ultrasound angiography. In summary, ultrasound angiography can provide additional information in the color representation of vessels with slow flow velocities. However, an obvious problem is the unability to quantify detected low blood flow. The new procedure will not replace but usefully complete the established sonographic techniques.
The application of the new Treatment of Mental Patients Law, 1991, has been responsible for significant changes in the work of mental health workers, in particular those involved in the often complex process of civil commitment for examination/hospitalization. The experience of implementing this new law shows that some of the clauses related to this process contain controversial concepts. These concepts will be the focus of this paper.
In a prospective study the reliability of colour-coded duplex-sonography (CCDS) and phlebography in the diagnosis of deep leg and pelvic vein thrombosis was compared. In 82 consecutive in- or out-patients (42 men, 40 women; mean age 53 [19-86] years) with clinically suspected leg or pelvic vein thrombosis the results of 275 phlebographies (reference method) and 275 CCDS were compared on admission and during follow-up. The two methods were performed less than 6 hours apart. In the diagnosis of thrombosis the sensitivity of CCDS was 99%, specificity 80%. In 88% of all tests, the different thrombosis levels, as diagnosed by phlebography, were also demonstrated by CCDS. These data indicate that, if the clinical picture of suspected deep leg or pelvic vein thrombosis is unclear, CCDS should be done first. Phlebography should be performed only if the results of the former are inconclusive.
Interleukin 10 (IL-10) is released during the induction phase of contact sensitivity and was shown in prior functional studies to convert epidermal Langerhans cells (LC) from potent inducers of primary immune responses to specifically tolerizing cells in vitro. To investigate whether IL-10 also subserves the function of a tolerizing agent in vivo ears of BALB/c or C3H mice were injected intradermally with 1-2 micrograms of recombinant mouse (rm)IL-10 8 h before epicutaneous application of 3% trinitrochlorobenzene (TNCB; a contact allergen). As a control, mice were injected with phosphate-buffered saline or IL-10 plus neutralizing amounts of anti-IL-10 mAb. 5 d later, mice were challenged with 1% TNCB on contralateral ears and ear swelling response was measured 24 h later. Whereas control-treated mice showed a normal ear swelling response to epicutaneous challenge (delta mm-2 = 25 +/- 5), ear swelling response of IL-10-treated animals was significantly inhibited (delta mm-2 = 3 +/- 2). Coinjection of IL-10-specific mAb together with rmIL-10 completely abrogated this effect. To differentiate between a state of nonresponsiveness and induction of tolerance by IL-10, mice initially treated with IL-10 and TNCB were resensitized with 3% TNCB in the absence of any treatment after 14 d of rest (group 1). Again mice were challenged 5 d later and ear swelling responses were tested. Whereas control mice treated with allergen alone (group 2) showed a good swelling response (delta mm-2 = 28 +/- 6), IL-10-treated mice (group 1) showed a minimal response towards application of allergen (delta mm-2 = 4 +/- 2). To show that anergy induction by IL-10 was antigen-specific, mice initially treated with IL-10 plus TNCB were exposed to 0.5% dinitrofluorobenzene (DNFB) 14 d later (group 1). After challenge with 0.1% DNFB, IL-10-treated mice showed an ear swelling response (delta mm-2 = 13 +/- 3; group 1) similar to that of control mice only sensitized with DNFB (delta mm-2 = 14 +/- 3; group 3). In an attempt to show the induction of antigen-specific tolerance in these mice in vitro, regional lymph nodes of mice initially treated with TNCB plus IL-10 (group 1) and control-treated mice (groups 2 and 3) were prepared and cultured in the presence of TNBS, dinitrobenzene sulfonate (DNBS), or medium to measure antigen-specific proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)
Several in vivo and in vitro studies have shown that contact sensitizing agents induce enhanced internalization of cell membrane constituents by epidermal Langerhans cells (LC). However the intracellular distribution of the internalized material has not yet been clearly defined. For this reason we investigated the uptake of gold-labeled antibodies against MHC class II molecules by cultured murine LC under the influence of various contact sensitizing agents, non-sensitizing analogues, and irritants. Antigen-antibody complexes were visualized by light microscopy using the silver enhancement technique and by pre-embedding electron microscopy. Viability was monitored by staining dead cells with propidium iodide. For light-microscopic evaluation of the intracellular distribution pattern of gold particles, a stimulation index was defined and used for the assessment of endocytotic activation. Untreated and solvent treated (control) cells exhibited an accumulation of internalized gold complexes into large aggregates composed of few intracellular vesicles. Cytoplasmic staining was absent and few gold particles were detectable in the endocytotic organelles under these conditions. In contrast to the non-sensitizing compounds DCNB and DNBSO3, which had no effect at all, treatment with subtoxic concentrations of the contact sensitizing agents DNFB, DNCB, TNCB, K2Cr2O7, NISO4 and p-phenylenediamine resulted in diffuse intracellular staining which was most pronounced in the submembraneous region. This was due to the numerous endocytotic vesicles which were closely associated with the cell membrane. Consequently a significant increase in the stimulation index was noted for these compounds. An irritant such as sodium lauryl sulphate used in subtoxic concentrations did not influence the intracellular distribution of internalized gold particles whereas toxic amounts of this compound induced a diffuse intracellular staining pattern indicative of membrane destruction. This approach represents a practical and reliable test for endocytotic activation of murine LC and may be useful for in vitro tests of the activating and possibly sensitizing properties of new chemical compounds.
Intracellular pH was measured in normal 8-cell stage mouse embryos and in embryos from a cross between DDK females and C3H males. DDK/C3H embryos display the DDK syndrome and spontaneously begin to decompact toward the late 16-cell stage. Ultimately, 90% fail to form blastocysts. Normal embryos have a resting intracellular pH close to neutrality. In DDK/C3H embryos a substantial proportion (46%) has an intracellular pH below 6.7. An equivalent proportion of DDK/C3H embryos was found previously to show slow communication through gap junctions at the 8-cell stage. This is probably a consequence of low intracellular pH. In normal embryos the weak acid, butyric acid, decreased intracellular pH and slowed the transfer of Lucifer Yellow through gap junctions. Normal embryos treated with butyrate for between 1 and 6 hr beginning at the 8-cell stage and cultured for 24 hr, reproduced the DDK/C3H phenotype. After 48 hr some butyrate treated embryos recovered, while others remained as decompacted morulae. Treatment of control and DDK/C3H 8-cell stage embryos with dibutyryl cyclic AMP or forskolin, which will increase intracellular cyclic AMP, speeded gap junctional communication. Forskolin treatment prevented expression of the DDK syndrome in DDK/C3H embryos, although the rescue was transient and the syndrome returned when forskolin was removed. The finding that the DDK syndrome is manifested as low intracellular pH may provide clues to the molecular basis of the defect.
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Finland and Sweden have the highest incidence of insulin-dependent diabetes in children in the world, about 3-4 times that of countries in the Mediterranean area, with the exception of Sardinia. We have collected information from several European clinics and from Pittsburgh, USA, in order to find out whether this difference incidence is associated with corresponding differences of the disease pattern. Patients in Finland or Sweden ('North') and Pittsburgh were younger (< 10 years old) at diagnosis compared with those in the other clinics in Europe (P < 0.05 versus P < 0.02). In the North, boys were in excess (58%) in contrast to France (40%) and Pittsburgh (46%). Patients in the North had a shorter duration of symptoms (< 8 days; P < 0.001) and higher blood glucose (> 20 mmol/l; P < 0.05) than those attending the other European clinics. Irrespective of age, there were more ICA-positive patients in the North (94%) than in Berlin-Vienna (67%; P < 0.01) or in France (70%; P < 0.01). There was a tendency for non-diabetic parents and siblings in the North to have lower C-peptide values (< 0.26 pmol/ml) at the time of diagnosis of the proband and to be ICA-positive more often than relatives in the other European clinics. The seasonal variation of diagnosis showed no obvious geographical differences, with recorded diagnosis always lowest during the summer. We conclude that certain factors seem to cause not only a high incidence of diabetes in children in Finland and Sweden but perhaps also a more aggressive early disease process.
The temporal branch of the facial nerve may be saved in a pterional-transzygomatic craniotomy if the dissection is carried beneath the superficial temporal fascia. The anatomical and technical aspects of this exposure are described in this report.
Taking into account the increase in worldwide human migration, leprosy is of growing importance in the differential diagnosis of dermatological diseases encountered in Central Europe. We report on the case of a young man from Ghana who developed hypopigmented maculae and plaques on his trunk and proximal limbs. The diagnosis of lepromatous leprosy could be made in consideration of the histological pattern of infiltrating leucocytes and detection of numerous acid-fast mycobacteria on skin biopsy. The results of the physical examination as well as routine laboratory and immunological parameters were consistent with this form of leprosy. Due to glucose-6-phosphate-dehydrogenase deficiency, treatment with dapsone was contraindicated. With high-dose rifampicin and clofazimine therapy, the skin changes cleared over the course of 11 months following a leprosy reaction type II (erythema nodosum leprosum) that developed during a phase of discontinued therapy due to low patient compliance.
A reproducible transformation system for hexaploid wheat was developed based on particle bombardment of scutellar tissue of immature embryos. Particle bombardment was carried out using a PDS 1000/He gun. Plant material was bombarded with the plasmid pDB1 containing the beta-glucuronidase gene (uidA) under the control of the actin-1 promoter of rice, and the selectable marker gene bar (phosphinothricin acetyltransferase) under the control of the CaMV 35S promoter. Selection was carried out using the herbicide Basta (Glufosinate-ammonium). From a total number of 1050 bombarded immature embryos, in seven independent transformation experiments, 59 plants could be regenerated. Putative transformants were screened for enzyme activity by the histochemical GUS assay using cut leaf material and by spraying the whole plants with an aqueous solution of the herbicide Basta. Twelve regenerants survived Basta spraying and showed GUS-activity. Southern-blot analysis indicated the presence of introduced foreign genes in the genomic DNA of the transformants and both marker genes were present in all plants analysed. To date, four plants have been grown to maturity and set seed. Histochemically stained pollen grains showed a 1:1 segregation of the uidA gene in all plants tested. A 3:1 segregation of the introduced genes was demonstrated by enzyme activity tests and Southern blot analysis of R1 plants.