Lack of detectable fetal microchimerism in psoriasis vulgaris lesions and in non-affected skin in spite of its presence in peripheral blood CD34-positive and CD34-negative cells.

BACKGROUND: Microchimerism is defined as a stable presence of low numbers of cells derived from a different individual due to cell transfer between twins or between mother and fetus during pregnancy. OBJECTIVE: Fetal cells in the organism of the mother (FMc) are postulated to play a role in autoimmune diseases. Psoriasis is a disease which has an autoimmune component, but no study on microchimerism in this disease has been reported. METHODS: The easiest way to detect microchimerism is to look for male cells in blood or other tissues of a woman who previously delivered a son. Here, we looked for the presence of male cells in mononuclear cell subpopulations from peripheral blood and in skin samples of women with psoriasis and of healthy women. RESULTS: We detected FMc in similar proportions of patients and controls in CD4+, CD8+ and CD34+ cells, whereas in CD34- cells they were present in higher fraction of controls, and similar but non-significant difference was observed in CD19+ cells. No microchimeric cells were detected in patients' skin samples, both from affected and non-affected skin, or in skin tissue from healthy control individuals. CONCLUSION: Our result does not prove the involvement of microchimerism in the aetiology of psoriasis.

A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: The interleukin-17 cytokine family plays a central role in psoriasis pathogenesis. OBJECTIVES: To evaluate the efficacy and safety of brodalumab, a human anti-interleukin-17 receptor antibody, in treating patients with moderate-to-severe plaque psoriasis. METHODS: In this phase III, double-blind, placebo-controlled study (NCT01708590; AMAGINE-1), adult patients in the U.S.A., Canada and Europe were randomized to brodalumab (140 or 210 mg) or placebo every 2 weeks (Q2W), with an additional dose at week 1, for a 12-week induction phase. At week 12, patients receiving brodalumab who achieved static Physician's Global Assessment 0 or 1 (sPGA success) were rerandomized to the placebo or induction dose. After week 16, patients with sPGA ≥ 3 were re-treated with the induction dose. After ≥ 12 weeks of retreatment, patients with sPGA 2 for ≥ 4 weeks or sPGA ≥ 3 were rescued with brodalumab 210 mg Q2W. At week 12, patients randomized to brodalumab with sPGA ≥ 2 or placebo received brodalumab 210 mg Q2W. Coprimary end points were the percentage of patients with ≥ 75% improvement in Psoriasis Area and Severity Index score (PASI 75) and sPGA success at week 12. RESULTS: There were 661 patients randomized: 220 placebo, 219 brodalumab 140 mg and 222 brodalumab 210 mg. At week 12, 60% (140 mg) and 83% (210 mg) vs. 3% (placebo) achieved PASI 75, and 54% (140 mg) and 76% (210 mg) vs. 1% (placebo) achieved sPGA success. The safety profile was considered acceptable. CONCLUSIONS: Brodalumab therapy resulted in significant clinical benefit and an acceptable safety profile in patients with moderate-to-severe plaque psoriasis.

A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of the Polish Adult Leukemia Group.

Purine nucleoside analogues, cladribine (2-chlorodeoxyadenosine, 2-CdA) and fludarabine (FAMP) are active agents in acute myeloid leukemias (AMLs). Synergistic interaction between FAMP or 2-CdA with cytarabine (cytosine arabinoside, Ara-C) has been demonstrated in preclinical and clinical studies. The current multicenter phase II study was initiated to evaluate the efficacy and toxicity of induction treatment consisting of 2-CdA (5 mg/m2), Ara-C (2 g/m2), mitoxantrone (MIT, 10 mg/m2) and granulocyte colony-stimulating factor (G-CSF) (CLAG-M) in refractory AML. In case of partial remission, a second CLAG-M was administered. Patients in complete remission (CR) received consolidation courses based on high-dose Ara-C and MIT with or without 2-CdA. Forty-three patients from five centers were registered: 25 primary resistant and 18 relapsed. CR was achieved in 21 (49%) patients, 20 (47%) were refractory and 2 (5%) died early. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS; 1 year) for the 42 patients as a whole and the 20 patients in CR were 43% and 73%, respectively. Disease-free survival (1 year) was 68.6%. None of the analyzed prognostic factors influenced the CR and OS probability significantly. We conclude that CLAG-M regimen has significant antileukemia activity in refractory AML, which seems to be better than the activity of many other regimens. The toxicity of the treatment is acceptable.

Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study.

To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m2/day, days 1-3; cytarabine (AraC) 200 mg/m2/day, days 1-7; cladribine (2-CdA) 5 mg/m2/day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n=200) or DA-7 (without 2-CdA, n=200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P=NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P=0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P=0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P=NS). There was a trend toward higher LFS rate for patients aged >40 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P=0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR+AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged >40 years.

Aortic pulse wave velocity in young normotensives with a family history of hypertension.

OBJECTIVE: To assess the effect of selected clinical and biochemical parameters, with particular consideration of familial hypertension, on the pulse wave velocity (PWV) in young normotensives. SUBJECTS AND METHODS: Seventy voluntary students were enrolled (mean age 22.3+/-2.1 years), 39 men and 31 women, with normal blood pressure. A history was obtained with respect to diabetes mellitus, ischaemic heart disease, lipid disorders and arterial hypertension in the family. The subjects were subdivided into two groups: those with (n = 33) and without (n = 37) a family history of arterial hypertension, and blood pressure and heart rate were measured three times and total cholesterol and its subfractions determined in plasma. The carotid to femoral PWV was measured using an automatic computerized recorder and analysed by the Complior program. RESULTS: The subjects with a family history of arterial hypertension had higher blood pressure levels (systolic and diastolic blood pressure, pulse pressure and mean arterial pressure), as well as mean body mass index and low-density lipoprotein (LDL) cholesterol. The PWV in this group did not differ from that in the subjects without a family history of arterial hypertension (9.69+/-2.8 versus 9.32+/-2.0). However, the PWV was significantly higher in males than females (10.62+/-2.2 versus 7.86+/-1.13, P < 0.0001) and there was a significant positive correlation between male gender and PWV. CONCLUSIONS: Familial arterial hypertension does not significantly affect aortic stiffness in terms of PWV. Male gender in this population of young healthy subjects is one of the most important factors associated with central arterial stiffness.

Quantitative ultrastructural evaluation of satellite cells in soleus muscle from rats kept in hypokinesia.

The aim of the present study is a morphometric, ultrastructural evaluation of satellite cells (SC) derived from the soleus muscle (SOL) of rats exposed to conditions of hypokinesia for a period of 7 or 21 days. Qualitative and quantitative analysis of 320 electron micrographs of SC from each group was carried out. After 7 and 21 days of immobilization, profiles of the SC, in contrast to the control group, had a lower mean surface area, had a cylindrical shape, and exhibited more folded membrane. Analysis of electron micrographs of SC showed that after immobilization, a lower number of SC contained profiles of mitochondria, rough endoplasmic reticulum (RER), and Golgi. Volume fractions of RER were twofold lower after 7 days of hypokinesia and fivefold lower after 21 days compared with the control group. The SC of SOL of rats subjected to hypokinesia differed from the control group by a markedly decreased number of ribosomes and RER profiles. After 21 days of immobilization the ultrastructural characteristics of SC were typical for cells in an inactive state showing various degrees of degeneration. The results of our study presented here permit the conclusion that 21 days of hypokinesia induce a depression of SC activity, whereas subtle changes in SC appear only after 7 days of immobilization.

Morphometric analysis of satellite cells in rat skeletal muscles: soleus and extensor digitorum longus.

Satellite cells (SC) are present in all types of skeletal muscles. They can exhibit DNA replication and mitotic divisions throughout their life. Depending on the kind of muscle, a different number of SC is present. The aim of this study was to establish whether the differences in muscle metabolism are reflected in the quantitative ultrastructural evaluation of their SC. Two skeletal muscles of rats, soleus (SOL) with predominant slow fibers and extensor digitorum longus (EDL) with predominant fast ones, were studied. Morphometric analysis was performed according to the modified method of Weibel [Stereological Methods, vol 1: Practical Methods for Biological Morphometry. London, Academic Press, 1979]. In the SC of EDL mitochondria, rough endoplasmic reticulum and Golgi apparatus were less frequent as compared with the SOL. The volume fractions of these organelles were much higher in SC of SOL than in EDL. The ribosomes and polyribosomes were more densely packed in SC of SOL than in EDL. Ultrastructural morphometric evaluation demonstrated significant differences between the SC components of two different muscles: a slow (SOL) and a fast (EDL) one.

Morphometric ultrastructural evaluation of satellite cells in musculus soleus and musculus extensor digitorum longus of rats subjected to hypokinesia.

NASA: Soleus and extensor digitorum longus muscles were studied in rats confined to cages which restricted their movement. Ultrastructural study by electron microscopy of satellite cells did not reveal major differences between the cytoplasmic organelles of confined animals and those of controls. Some changes in mitochondria were noted. Results of the ultrastructural analysis are discussed.^ieng

Morphometric ultrastructural evaluation of satellite cells in musculus gastrocnemius and musculus latissimus dorsi anterior of rats subjected to 7 day hypokinesia.

The investigations were undertaken to evaluate morphometrically the satellite cells (SC) of two muscles: the slow, musclus latissimus dorsi and the fast, musculus gastrocnemius from rats kept in hypokinetic conditions for seven days. The changes in both muscle were of similar character, they concerned a decrease in the Golgi apparatus, rough endoplasmic reticulum fractions and the number of ribosomes, and an increase in the relative volume of heterochromatin content. These findings seem to indicate a reduced activity of the SC. Differences were also demonstrated between the satellite cells in both examined muscles in the control group. They also suggest that the SC are not a homogeneous population as regards parameters evaluated in the present study.

Morphometric ultrastructural study of satellite cells of rats during postnatal development (1st and 30th day of life).

Ultrastructural morphometric analysis of satellite cells of the diaphragm from one and 30-day-old rats was performed. The nuclear and cytoplasmic components of the cells were evaluated. The results obtained indicate that the satellite cells of one-day-old female rats are in a state of low activity. In 30-day-old animals, on the contrary, the cells are excited and active. This may be connected with their intensive participation in the process of development of the diaphragm muscle.

Interleukin 2- and interferon alpha induced natural killer cell activity as a marker of progression in hairy cell leukemia.

Hairy cell leukemia (HCL), a rare B-cell chronic lymphoproliferative disorder, is often accompanied by immune abnormalities. A marked impairment of the natural killer cell-mediated cytotoxicity (NK activity) has been reported in most patients at diagnosis. In the present report a long-term follow-up study of NK activity of splenectomized HCL patients is recorded. Among patients who persisted with stable disease two groups, one with normal NK activity, and another with low NK activity, could be recognized. Patients with progressive stage were characterized by a low NK cytotoxic activity. In vitro tests showed that interferon alpha (IFN-alpha) and interleukin 2 (IL2) could increase the NK activity to normal levels only in HCL patients with stable disease, while in progressive HCL these cytokines showed a significantly decreased effect. These results indicate that cytokine-induced NK cytotoxicity appears to be a valuable parameter in assessing the stage of HCL.

[Relation between the duration of the chronic phase of chronic myeloid leukemia and total dose of busulfan in the first year of the treatment]. / Zaleznosc czasu trwania fazy przewleklej przewleklej bialaczki szpikowej od rocznej dawki busulfanu w pierwszym roku leczenia.

The analysis was based on 31 patients with chronic granulocytic leukaemia (CGL) treated during the period 1975-1986 and the correlation between the total dose of busulphan administered during the first year of treatment and the duration of chronic phase of the disease was investigated. We found such correlation and also we found that the duration of the chronic phase was more significantly correlated with one year maintenance dose of busulphan. This suggests that the prognosis in CGL is more connected with the proliferation activity of leukaemic cells than with the extent of disease at the time of diagnosis.

Trisomy 13 in a case of myelodysplastic syndrome.

The clinical and cytogenetic findings of a patient with refractory anemia with excess of blasts are presented. Trisomy 13 was present as the sole numerical aberration in all analyzed bone marrow metaphases; this finding has not been reported previously in myelodysblastic syndrome.