Notes: Mastocytosis is a rare disease characterized by a primary pathological increase in mast cells in different tissues, which may present in a variety of clinical patterns. Major advances have been made in recent years in the understanding of the pathogenesis of mastocytosis. This review is aimed at familiarizing dermatologists with these recent findings, and at exploring their possible implications for the diagnosis and treatment of the condition. The heterogeneous clinical presentation of mastocytosis is detailed with respect to the type of skin lesions, age at onset, family history, organ systems involved, associated haematological disorders and prognosis. Recent genetic findings also indicate different pathogenetic forms of mastocytosis, as adult patients and those with associated haematological diseases usually express activating mutations of the stem cell factor receptor c-kit, whereas most cases of childhood-onset and familial mastocytosis seem to lack these mutations. Despite the presence of c-kit mutations, patients with cutaneous lesions generally have a good prognosis, even when there is involvement of other organs. Some patients, particularly those with childhood-onset disease, experience spontaneous remission, mostly by puberty. c-kit mutations do not explain the initial cause of mastocytosis, and their prognostic significance is as yet unclarified, as is the pathogenesis in patients without the mutations. Furthermore, these novel findings have as yet not resulted in a more effective treatment of the cause of the disease, so that counselling, prevention of exposure to mast cell secretory stimuli, and symptomatic treatment remain the mainstays of current patient management.

Notes: Background  Mastocytosis presents as a focal or generalized increase of mast cells, particularly in the skin, but also in other organs. Activating mutations of KIT (formerly c-kit), the receptor of the mast cell growth factor stem cell factor (SCF), appear to play a key role in the pathogenesis of sporadic adult onset mastocytosis. However, these mutations are not present in childhood-onset and familial mastocytosis and also fail to explain the heterogeneity of adult-onset disease. Other factors such as prolonged survival of mast cells may therefore participate in causing and modulating the pathological increase of mast cells in mastocytosis.Objectives  To examine the expression of proliferation and apoptosis markers in the mast cells of cutaneous mastocytosis lesions in order to gain further insight into the pathogenesis of mastocytosis.Methods  Lesional cutaneous biopsies from eight infants with solitary mastocytomas, five children with multiple mastocytomas, 11 children with generalized urticaria pigmentosa, 12 adults with urticaria pigmentosa, and skin from seven normal controls were used in this study. Serial sections were stained with toluidine blue to quantify mast cell numbers and with antibodies against the proliferation marker Ki67 protein, the tumour suppressor protein p53, and the inhibitor of cyclins and cyclin-dependent kinases p21WAF1/CIP1, using the alkaline phosphatase antialkaline phosphatase technique. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) method was used to assess apoptosis.Results  Cutaneous mast cell counts were significantly increased in all patient sections, particularly in childhood lesions, and similarly, a small but significant increase of proliferation was found in the lesional mast cells of all patients. Enhanced mast cell numbers and proliferation was associated with a significant decrease of TUNEL staining, particularly in mastocytomas. p53 expression was highly variable, with an overall significant increase in all patient skin mast cells, whereas p21 expression was barely observed at all.Conclusions  These findings further support the concept that an imbalance of mast cell proliferation and apoptosis is prevalent in mastocytosis lesions that may account in part for the increased focal mast cell accumulation in this condition.

Notes: In order to clarify the pathogenetic role of basophils and mast cells in chronic urticaria, histamine and leukotriene (LT)C4 release was examined in washed mixed leukocytes (n= 8) and skin mast cells (n= 5) from patients with chronic urticaria and compared with the same cells from normal controls (n= 9). Anti-IgE-stimulated basophil histamine release was significantly reduced in urticaria patients (median 2.9%vs 15.1% in normal controls), whereas histamine release to A23187. FMLP, and PAF, as well as anti-IgE-induced LTC4 release, showed no differences in both groups. In contrast, anti-IgE-stimulated skin mast cells from urticaria patients reacted similarly to those of controls (median histamine release 11.4%vs 14.2% in normal controls). Pretreatment of the cells with interleukin (IL)-3 upregulated responsiveness of basophil histamine release to anti-IgE in urticaria patients (median histamine release 14.3%), but pretreatment with the H2-antagonist cimetidine showed no effect. These data show that reduced basophil histamine releasability in chronic urticaria is not H2 mediated. It is a stimulus, mediator-, and cell type-restricted phenomenon that can, at least partially, be reversed in the presence of the cytokine IL-3.

Notes: Abstract In rats implanted with chronic hypothalamic thermodes and immunized with sheep erythrocytes, body temperature was increased, 4h per day for 2 weeks, either by exposing the animal to external heat or by cooling the preoptic area. The titre of antibodies against sheep erythrocytes was nearly tripled by preoptic cooling but was drastically decreased by heat exposure. These opposing effects of active and passive increases in body temperature indicate that factors other than the change in body temperature must also have played a significant role in modifying the humoral immune response.

Notes: Summary We report some observations which seem to be important for an understanding of the mechanism of the polarotropic and phototropic response of filamentous cells with tip growth. — The chloronemata, i. e. the filamentous young gametophytes of the fernStruthiopteris filicastrum All. show nearly the same polarotropic behaviour as the corresponding filaments of the fernDryopteris filix-mas (L.)Schott. In linearly polarized red light the positive phototropic chloronemata grow perpendicular to the plane of vibration (Fig. 2). — The rhizoids behave differently. In the case ofDryopteris they show negative phototropic reaction and therefore grow parallel to the plane of vibration whereas inStruthiopteris the rhizoids will grow downwards into the agar. This fact indicates a positive geotropic reaction. If the plane of vibration is turned by 90° the direction of growth of the chloronemata will change correspondingly (Fig. 3, above). A remarkable percentage of the chloronemata, however, reacts differently. There are unicellular chloronemata which show a curvature of the tip and additionally a new filament below the apex (Fig. 3; Fig. 4). Other types show no curvature of the tip at all but one or two new filaments originate at some distance below the apex, i. e. in the “subapical region” of the chloronema (Fig. 4; Fig. 5, f). The occurence of these phenomena is augmented if the intensity of the polarized red light is increased at the moment when the plane of vibration is turned. There is also some evidence that a turning of the plane of vibration by 90° leads to a transient reduced activity of growth. If we make the reasonable assumption (cf.Jaffe andEtzold 1962,Etzold 1965) that the dichroic red-absorbing photoreceptors occuring in the apex are oriented parallel to the nearby surface of the cell (Fig. 6), our observations must be interpreted under the point of view that the region of the highest activity of growth within the chloronema is determined by the zone of highest absorption of red light. If the plane of vibration is perpendicular to the longitudinal axis of the chloronema, growth is necessaryly confined to the extreme tip of the apex. If, however, the plane of vibration is parallel to the longitudinal axis the highest absorption in the apical region will take place on the flanks of the apex. Therefore the area of the highest growth activity is shifted to one or the other flank of the apex. The result is a polarotropic curvature. — Our additional observations, the formation of new centers of growth in the subapical region of the chloronema, indicate the existence of some red light sensitivity and growth potentiality also in the subapical region where normally the activity of growth had ceased. These findings support the view that the polarotropic and phototropic curvatures of the chloronema come about because new centers of growth originate in the zones of highest light absorption. Similar conclusions were reached byPage (1962) who studied the phototropic response of sporangiophores ofPilobolus. — This particular mechanism of phototropic response is fundamentally different from the mechanism of the phototropic response of stems or coleoptiles.

Notes: Summary The induction of flowering in mustard (Sinapis alba L.) was studied by means of night-breaks (“Störlicht”). The plants were cultivated under fully controlled conditions: 8000 Lux white light (mixed fluorescent and incandescent) 18°C, 80% relative humidity. Raised under our conditions in short days (8 hours of white light) mustard behaved as a quantitative long-day plant (Fig. 2). Flowering can be promoted by long-day treatment (Fig. 3). The long day (16 hours of white light) can be replaced by a short day plus a night-break. The highest effectiveness of the night-break is found near the middle of the dark period (Figs. 4, 5). —The spectral dependence of flower induction was studied with blue, green, yellow, red (Fig. 1) and far-red light using a 2-hour break near the middle of the dark period. The dose response curves (Fig. 6) and the action spectrum (Fig. 7) indicate a very strong effectiveness in the blue part of the spectrum, a small response in red and yellow light and no response at all in green and far-red light. The participation of phytochrome is indicated (Table 1), but no far-red reversibility could be detected (Table 2). Simultaneous irradiation with red and far-red light yielded significant enhancement effects (Fig. 8). In view of the strong shadowing in the leaves (Figs. 9, 10) these data are interpretable on the basis of phytochrome.

Notes: Summary The examination of the brain with ultrasound has become an indispensible diagnostic tool in all cases of intracranial pathology. Valuable information is obtained both in emergencies and in follow-up studies. Since long practice is necessary before the results of echoencephalograms can be interpreted accurately, a need was felt for a standardization of the examination which would eliminate the subjective influence of the investigator. The automatic midline computer, called Midliner, which has recently become available, makes fewer demands on the experience of the investigator although the diagnostic possibilities are not as broad. The position of the midline echo is of primary interest, although the width of the third ventricle can be successfully determined in occasional cases. This study, which presents the results of the Midliner examinations in three clinics, is grouped according to diagnosis. Through a comparison with conventional A-scan echoencephalograms, as well as with neuroradiological and operative findings in 1889 cases, the reliability of this method is clearly demonstrated. The advantages and disadvantages of the examination are discussed and the field of application indicated.