Zur klinischen Bedeutung der Eiweiss-Eisen-Stoffwechselbeziehungen

Zusammenfassung 1. Die Forschungsergebnisse der letzten Jahre weisen darauf hin, daß zwischen demEisen- und demEiweißstoffwechsel des Organismus sehrenge Beziehungen bestehen. Als allgemein gültiger Grundsatz gilt dabei,daß Störungen im Eiweißstoffwechsel, die wir klinisch alsDysproteinämien erfassen, so gut wie immermit Störungen im Eisenstoffwechsel einhergehen, was bei experimentellen und klinischen Untersuchungen stets zu berücksichtigen ist.2. Unterteilt man den Gesamteisengehalt des Organismus in 1.Funktionseisen (Hämoglobin, Myoglobin, Cytochrome), 2.Transporteisen (Transferrin, Siderophilin), 3.Lagereisen (Ferritin, Siderin) so ist es ratsam, auch eine entsprechende Unterteilung der zugehörigen Proteinkomponenten vorzunehmen. Man unterscheidet also zwischen 1.Funktionsproteinen, 2.Transportproteinen und 3.Lagerproteinen, die sich alle durch eine strenge Spezifizität auszeichnen.3. Die Einbeziehung der Eiweiße in den Fragenkomplex des Eisenstoffwechsels ist in praktischer Hinsicht von wesentlicher Bedeutung; so liegenden echten Infekt- bzw. Tumoranämien pathogenetisch Eiweißstoffwechselstörungen zugrunde und eine orale oder parenterale Eisentherapie muß daher nutzlos sein. Lebercirrhosen, besonders aber Hämochromatosen, weisen Störungen vor allem imGefüge der Lagerproteine auf, womit sich die Überflutung des Organismus mit Eisen erklärt. Die Störungen des Eisenstoffwechsels beimegalocytären Anämien sindsekundärer Natur, da diese als echteProteinmangelanämien anzusprechen sind, wobei es sichum einen Mangel des spezifischen Funktionsproteins handelt. Dieses Defizit geht primär auf den durch Vitamin B₁₂- bzw. Folsäuremangel bedingten, abwegigen Stoffwechsel der Nucleotide zurück.4. Einige aus diesen Feststellungen sich ergebende praktische Lehren für dieTherapie der Anämien wurden kurz besprochen.     

Ultrastructure and immunocytochemistry of the neuroepithelial bodies in the lung of the tiger salamander,Ambystoma tigrinum (Urodela,amphibia)

Light and electron microscopy of the lungs of Ambystoma tigrinum (Urodela) revealed a relatively complex pattern of the neuroendocrine (NE) cells. In the apical parts of smaller septa single NE cells not associated with nerve fibres were covered and surrounded by pneumocytes. The larger septa possessed small areas of ciliated epithelium, in which the NE cells were grouped in a form of neuroepithelial bodies (NEB) consisting of 3–5 cells and covered by goblet cells. NE cells possessed a large nucleus with patches of condensed chromatin, clear cytoplasm, and membrane-bound vesicles of variable morphology and size, of these dense core vesicles (DCV) ranged from 70–140 nm, while rarely the larger ones exhibited a diameter of 300–600 nm. In some NEB a second type of NE cells was observed for the first time in an amphibian species: these cells communicated with the air space and exhibited on their surface microvilli and a single modified cilium with a 8+1 microtubule arrangement. Their cytoplasm contained two types of DCV: dense core granules with a diameter of 140–260 nm and vesicles 320–700 nm in diameter with a moderately electron dense interior. The NEB were associated with intracorpuscular, sensory nerve terminals morphologically afferent and efferent. By immunocytochemistry, the NE cells revealed the presence of serotonin, met-en-kephalin, and leu-enkephalin. A paracrine and chemoreceptor role is proposed for NEB of Ambystoma tigrinum.© Willey-Liss, Inc.     

Recognition of apoptotic cells by human peripheral blood monocytes does not alter their ability to phagocytize and kill Staphylococcus aureus

INTRODUCTION: During acute inflammation, leukocyte infiltration is mostly neutrophilic, but later monocytes prevail. The majority of inflammatory cells, particularly neutrophilic polymorphonuclear leukocytes (PMNs), become apoptotic at later stages of inflammation and are phagocytosed by neighboring cells, mostly by macrophages. Recently, it has been found that human peripheral blood monocytes also recognize apoptotic cells, which primes them to increased production of interleukin (IL)-10--a cytokine known to reduce phagocytes' ability to engulf and kill pathogens. Based on the above, we studied monocytes' ability to phagocytose and kill Staphylococcus aureus while in contact with apoptotic cells. MATERIALS AND METHODS: Monocytes isolated by elutriation were co-cultured with apoptotic PMNs or Jurkat cells and exposed to viable, human serum-opsonized S. aureus. To induce apoptosis PMNs were cultured overnight while Jurkat cells were UV-treated. Apoptosis, phagocytosis of bacteria and intracellular superoxide production were measured by flow cytometry. Production of reactive oxygen species was also followed by measurement of chemiluminescence. The bactericidal effect was determined by standard colony forming units method. RESULTS: Data presented show that contact of monocytes with apoptotic neutrophils and Jurkat cells had no influence on monocyte phagocytosis of S. aureus, the generation of reactive oxygen species, or the killing of bacteria. CONCLUSION: The data obtained suggest that monocytes attracted to the inflammatory site are not deficient in their ability to cope with pathogens after contact with apoptotic cells despite increased production of IL-10.     

Magnetic resonance imaging of brain abnormalities in patients with the Nijmegen breakage syndrome

The results of brain MRI are presented in 22 patients with documented Nijmegen breakage syndrome (NBS), aged from 1 and 9/12 to 20 years. T1-, PD or FLAIR and T2-weighted SE/TSE images in three planes were obtained. Twenty-one patients showed microcephaly. Decreased size of frontal lobes and narrow frontal horns of the lateral ventricles was observed in all cases. In 6 patients agenesis of the posterior part of the corpus callosum was found as well as colpocephaly and temporal horn dilatation. In 2 patients callosal hypoplasia was accompanied by other anomalies: abnormal cerebrospinal fluid spaces. Sinusitis was present in all patients as a result of primary immunodeficiency. As in ataxia teleangiectasia and other breakage syndromes, NBS patients show inherited malignancy susceptibility and hypersensitivity to X and gamma radiation. Because of that computed tomography is contraindicated in these patients and MRI should be the method of choice in diagnostic imaging.     

Effects of the CDC2 gene on adaptive mutation in the yeast Saccharomyces cerevisiae

We have studied the influence of a temperature-sensitive cdc2-1 mutation in DNA polymerase on the selection-induced mutation occurring at the LYS-2 locus in the yeast Saccharomyces cerevisiae. It was found that in cells plated on synthetic complete medium lacking only lysine, the numbers of Lys⁺ revertant colonies accumulated in a time-dependent manner in the absence of any detectable increase in cell number. When cdc2-1 mutant cells, after selective plating, were incubated at the restrictive temperature of 37°C for 5 h daily for 7 days, the frequency of an adaptive reversion of lys ^- Lys⁺ was significantly higher than the frequency in cells incubated only at the permissive temperature, or in wild-type cells incubated either at 23°C or 37°C. Therefore, when the proof-reading activity of DNA polymerase is impaired under restrictive conditions, the frequency of adaptive mutations is markedly enhanced.     

Cytological findings in nodular fasciitis

Nodular fasciitis, proliferative fasciitis, and proliferative myositis are tumorous proliferative soft tissue changes which on histological examination are quite often erroneously diagnosed as malignant neoplasms. Reported are cytological and histological findings recorded from nodular fasciitis in a man aged 34 years. The cytomorphology of nodular fasciitis is sufficiently characteristic, so that the lesion can be differentiated with certainty from malignant processes, since the cells have no features of malignancy, and the admixture of granulocytes and histiocytes in smears suggests a proliferative inflammatory process.     

Red blood cell glutathione peroxidase activity in multiple sclerosis

Summary Glutathione peroxidase (GSH-Px) activity of red blood cells of 23 multiple sclerosis (MS) patients (10 men and 13 women, aged 22–64 years) was examined and compared to the enzyme activity of 26 healthy persons (15 men and 11 women, aged 19–50 years). It was found that the mean GSH-Px activity was significantly higher (P<0.001) in red blood cells of MS patients (39.1±8.1 IU/g Hb) as compared to the group of healthy persons (25.9±5.2 IU/g Hb). There was no difference according to sexes in both the MS patients and the control group. The results are discussed based on the hypothesis that organic peroxides play a role in the etiology of multiple sclerosis.     

Spread of old and new clones of epidemic methicillin-resistant Staphylococcus aureus in Poland

Objective: To study the relatedness among methicillin-resistant Staphylococcus aureus (MRSA) isolates originating from two regions of Poland using different epidemiologic typing methods.
Methods: Forty-five MRSA isolates (19 from Warsaw and 26 from the Grajewo region) were collected between 1995 and 1996. For phenotypic epidemiologic analysis, antimicrobial susceptibility testing (AST) with a panel of 19 antibiotics was performed. For genotypic epidemiologic analysis, pulsed-field gel electrophoresis (PFGE) of Smal-digested chromosomal DNA, restriction endonuclease analysis of plasmid (REAP) DNA digested by Hin dIII, random amplification of polymorphic DNA (RAPD) and binary typing (BT) of genomic DNA by hybridization with five different RAPD-generated strain-specific DNA probes, were used.
Results: Six clusters of clonally related strains were found among the MRSA isolates analyzed. Three of these, identified in both regions, were related to previously described Polish epidemic clones, designated HeEMRSA-Pol1 (heterogeneously methicillin resistant—18 isolates) and HoEMRSA-Pol1 (homogeneously resistant—two clones, six isolates each). The remaining three clones, identified in the Grajewo region only, are previously undescribed. One of these, represented by 11 isolates, appears to be new epidemic heterogeneous MRSA clone (HeEMRSA-Pol2). Results of PFGE and BT in general showed good correlation, and, in some cases, RAPD using AP1 and AP7 primers could discriminate between isolates belonging to single PFGE or BT types. Broad AST and REAP can provide useful additional information concerning relatedness.
Conclusion: Evidence for the spread of previously recognized epidemic MRSA clones in Poland and the presence of a new epidemic heterogeneously resistant clone of MRSA in hospitals outside Warsaw is documented.     

Decreased markers of atopy in children with presumed early exposure to allergens, unhygienic conditions, and infections.

BACKGROUND: Several risk factors for the development of asthma and atopic disease in children have been described. Furthermore, there is consistent evidence that the prevalence of atopy increases with higher socioeconomic status. The knowledge about risk factors and preventive factors for atopy needs to be improved. OBJECTIVE: To compare 2 child populations (foster care and reference children) with different risk and protective factors for the development of atopy. METHODS: The study group consisted of 415 children, living in all 10 community foster homes in Lodz, a large industrial city in Poland. The study was performed from April 2, 2004, to April 30, 2006. The reference group consisted of 500 children, living with their parents at home, recruited from primary care centers. The primary outcome measures were skin prick test results and specific IgE in serum. Secondary outcomes included symptoms of allergic diseases and family history, including life conditions in early childhood. RESULTS: The full analysis set included 408 study children and 402 reference children. Significant differences were observed in the prevalence of atopy between the study and reference groups (11.3% vs 25.9%). We observed more positive skin prick test results in children from the reference group than in study children. To explain this phenomenon, we selected 16 variables that differ in both groups in early life and relate these to atopy. We found that the more cumulative features characteristic of the foster home population (poor living conditions), the lower the risk of atopy. CONCLUSION: Extremely unfavorable environmental circumstances, which are characteristic of the foster home population during early childhood, might prevent from atopy.     

Assessment of selected co-stimulatory, adhesion and activatory molecules and cytokines of Th(1)/Th(2) balance in acute lymphoblastic leukemia in children

INTRODUCTION: Recent years have seen a rise in the importance of cytokine production and co-stimulatory/activatory molecule expression in the immune response in leukemia. The aim of our study was to assess the function of T lymphocytes in children with acute lymphoblastic leukemia (ALL) during remission induction based on selected cytokine and co-stimulatory/activatory molecule expression. MATERIAL/METHODS: The study group consisted of 50 children with ALL (B cell precursor). Peripheral blood samples were taken before treatment (day 0), after the prednisone prophase (day 8), and during (day 15) and after (day 33) remission induction. The percentages of T cells with interferon (IFN)-gamma (Th(1)), interleukin (IL)-4 (Th(2)) and IL-2 receptor (IL-2R), CD28, CTLA-4, CD38, ICAM-1, and HLA-DR expression were assessed by tricolor flow cytometry. RESULTS: At the time of diagnosis we noted higher percentages of T cells with adhesion molecule ICAM-1, activation molecule CD38 expression, and an increased population of Th(2 )cells (IL-4) compared with the control group. During and after remission induction we observed a decreased population of CD38(+) T cells, elevated percentages of helper T lymphocytes with IL-2R expression, and a rise in helper T lymphocytes producing IFN-gamma (Th(1)). During fever/infection, higher levels of activated T lymphocytes (CD4(+)HLA-DR(+), CD8(+)HLA-DR(+)), a rise in Th1, and no change in Th(2 )populations were observed. CONCLUSIONS: The results suggest T cell activation and Th(2 )predominance at the time of diagnosis and during remission induction in ALL in children. These results confirm the involvement of cellular immunity in the leukemic process and can be used in immune therapy in leukemia.