The volume of the carotid bodies and blood pressure variability and pulse pressure in patients with essential hypertension.

AIM: To assess the relationship between the volume of the carotid bodies (VrCB+lCB) examined by means of computed tomography angiography (CTA) and blood pressure variability and pulse pressure (PP) in 24-hour ambulatory blood pressure monitoring (ABPM) in patients with essential hypertension. MATERIALS AND METHODS: A group of 52 patients with essential hypertension was examined (mean age: 68.32±12.31 years), the sizes of carotid bodies were measured by means of carotid artery CTA, and 24-hour ABPM was carried out. The 24-hour ABPM established systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), PP, SBP variability (SBPV), and DBP variability (DBPV). RESULTS: SBP, MAP, and SBPV were significantly higher in the group of hypertension patients with VrCB+lCB equal to or above the median than in the group of hypertension patients with VrCB+lCB less than the median, as well as in the group of hypertension patients with oversized carotid bodies, than in the group of hypertension patients with normal VrCB+lCB. Moreover, the PP was statistically significantly higher in the group of hypertension patients with VrCB+lCB equal to or above the median than in the group of hypertension patients with VrCB+lCB less than the median. The existence of statistically significant positive linear relationships was revealed between VrCB+lCB and SBP, PP, and SBPV. A higher body mass index, older age, smoking, and higher VrCB+lCB are independent risk factors increasing SBPV in the research group. CONCLUSION: A positive relationship between the size of the carotid bodies and variability of the SBP and PP is observed in patients with essential hypertension.

Insulin Resistance and Endothelial Dysfunction Constitute a Common Therapeutic Target in Cardiometabolic Disorders.

Insulin resistance and other risk factors for atherosclerosis, such as hypertension and hypercholesterolemia, promote endothelial dysfunction and lead to development of metabolic syndrome which constitutes an introduction to cardiovascular disease. The insulin resistance and endothelial dysfunction cross talk between each other by numerous metabolic pathways. Hence, targeting one of these pathologies with pleiotropic treatment exerts beneficial effect on another one. Combined and expletive treatment of hypertension, lipid disorders, and insulin resistance with nonpharmacological interventions and conventional pharmacotherapy may inhibit the transformation of metabolic disturbances to fully developed cardiovascular disease. This paper summarises the common therapeutic targets for insulin resistance, endothelial dysfunction, and vascular inflammatory reaction at molecular level and analyses the potential pleiotropic effects of drugs used currently in management of cardiovascular disease, metabolic syndrome, and diabetes.

Nocturnal Blood Pressure Variability in Patients with Obstructive Sleep Apnea Syndrome.

Obstructive sleep apnea (OSA) is a common respiratory disorder associated with hypertension and cardiovascular complications. Blood pressure variability may be a sign of risk of cardiovascular events. The aim of this study was to investigate the hypothesis that severe OSA syndrome is associated with increased blood pressure variability. Based on respiratory polygraphy, 58 patients were categorized into two groups: severe OSA with apnea/hypopnea index (AHI) greater than 29 episodes per hour (mean 52.2 ± 19.0/h) and mild-to-moderate OSA with AHI between 5 and 30 episodes per hour (mean 20.2 ± 7.8/h). A 24-h noninvasive blood pressure monitoring was performed. The standard deviation of mean blood pressure was used as the indicator of blood pressure variability. In patients with severe, compared with mild-to-moderate OSA, a higher mean nocturnal systolic blood pressure (133.2 ± 17.4 mmHg vs. 117.7 ± 31.2 mmHg, p < 0.05) and diastolic blood pressure (80.9 ± 13.1 mmHg vs. 73.8 ± 9.2, p < 0.01), nocturnal systolic blood pressure variability (12.1 ± 6.0 vs. 7.6 ± 4.3, p < 0.01) and diastolic blood pressure variability (10.5 ± 6.1 vs. 7.3 ± 4.0 p < 0.05), nocturnal mean blood pressure variability (9.1 ± 4.9 mmHg vs. 6.8 ± 3.5 mmHg) were detected. The findings of the study point to increased nocturnal systolic and diastolic arterial blood pressure and blood pressure variability as risk factors of cardiovascular complications in patients with severe OSA.

Role of the functional MNS16A VNTR-243 variant of the human telomerase reverse transcriptase gene in progression and response to therapy of patients with non-Hodgkin's B-cell lymphomas.

MNS16A is a functional polymorphic tandem repeat within the human telomerase reverse transcriptase (hTERT) gene. To investigate whether any of the MNS16A repeats represents a genetic risk factor for NHL susceptibility, progression of or response to therapy in 75 patients with non-Hodgkin's lymphomas (NHLs) and 126 healthy individuals were genotyped using the PCR-VNTR technique. A slightly higher frequency of the MNS16A VNTR-243 variant was detected among patients who did not respond to treatment (NR) as compared to patients with complete or partial remission (0.83 vs. 0.51, P = 0.055). NR patients more frequently developed aggressive than indolent type of the disease (0.92 vs. 0.41, P = 0.001). The VNTR-243 allele was more frequently detected among patients with an intermediate-high/high International Prognostic Index (IPI 3-4) score (P = 0.063), especially in patients with advanced age and IPI 3-4 (P = 0.040). In multivariate analysis, higher IPI 3-4 score (OR = 11.364, P = 0.051) and aggressive type of the disease (OR = 18.182, P = 0.012) were found to be independent genetic markers associated with nonresponse to treatment. Presence of the MNS16A VNTR-243 variant also strongly tended to affect the risk of a less favourable response to therapy and was more frequently present among nonresponders (OR = 5.848, P = 0.059). Genetic variation within the hTERT gene may affect the progression and treatment of lymphoproliferative disorders.

Retrospective analysis of co-occurrence of congenital aortic stenosis and pulmonary artery stenosis in dogs.

The study has focused on the retrospective analysis of cases of coexisting congenital aortic stenosis (AS) and pulmonary artery stenosis (PS) in dogs. The research included 5463 dogs which were referred for cardiological examination (including clinical examination, ECG and echocardiography) between 2004 and 2014. Aortic stenosis and PS stenosis were detected in 31 dogs. This complex defect was the most commonly diagnosed in Boxers - 7 dogs, other breeds were represented by: 4 cross-breed dogs, 2 Bichon Maltais, 3 Miniature Pinschers, 2 Bernese Mountain Dogs, 2 French Bulldogs, and individuals of following breeds: Bichon Frise, Bull Terrier, Czech Wolfdog, German Shepherd, Hairless Chinese Crested Dog, Miniature Schnauzer, Pug, Rottweiler, Samoyed, West Highland White Terrier and Yorkshire Terrier. In all the dogs, the murmurs could be heard, graded from 2 to 5 (on a scale of 1-6). Besides, in 9 cases other congenital defects were diagnosed: patent ductus arteriosus, mitral valve dysplasia, pulmonary or aortic valve regurgitation, tricuspid valve dysplasia, ventricular or atrial septal defect. The majority of the dogs suffered from pulmonary valvular stenosis (1 dog had supravalvular pulmonary artery stenosis) and subvalvular aortic stenosis (2 dogs had valvular aortic stenosis). Conclusions and clinical relevance - co-occurrence of AS and PS is the most common complex congenital heart defect. Boxer breed was predisposed to this complex defect. It was found that coexisting AS and PS is more common in male dogs and the degree of PS and AS was mostly similar.

Can life satisfaction be considered a predictor of quality of life in patients with lung cancer?

OBJECTIVE: To evaluate the association between satisfaction with life and Quality of Life (QoL) in lung cancer patients, and to analyze the correlations of selected variables with QoL. PATIENTS AND METHODS: 250 patients with lung cancer were enrolled into the study, with a mean age of 63.2± 9.4, and who were treated at the Regional Lung Hospital in Poland between January and June 2019. 110 patients (43.9%) were moderately satisfied with their life (18-23 points from SWLS). 72 (28.8%) had a high level of satisfaction, and 68 (27.2%) had a low level of satisfaction with life. RESULTS: Patients with a high level of satisfaction with life had a better QoL (p<0.001) and experienced less severe symptoms, with the exception of constipation, haemoptoe, soreness in the mouth, dysphagia, hair loss, and pain in the arms. Patients with a high level of satisfaction with life have a significantly lower intensity of behaviors associated with anxious preoccupation (p<0.001) and helplessness/hopelessness (p<0.001). Destructive coping styles increase as satisfaction with life decreases (p<0.001). Patients with a high level of satisfaction with life were more accepting of their illness (p<0.001). CONCLUSIONS: Patients being treated for lung cancer have a moderate level of satisfaction with life. QoL is associated with satisfaction with life and increases depending on the level of satisfaction. Symptoms are less severe when patients are more satisfied with their life. Satisfaction with life was associated with acceptance of the illness and coping strategies. Not smoking, chest pain, time from diagnosis, performance status, and symptomatic treatment adversely affected satisfaction with life. Conversely, a lack of family history of cancer positively affected satisfaction with life.

The relationship between PNP, GSTO-1, AS3MT and ADRB3 gene polymorphisms and urinary arsenic concentration among copper smelter and refinery employers.

INTRODUCTION: The aim of this study was to assess the relationship between polymorphisms of genes encoding enzymes involved in arsenic metabolism and urinary arsenic concentration in people occupationally exposed to arsenic. MATERIALS AND METHODS: The data from 113 employers directly exposed to lead, cadmium, and arsenic in copper smelter in Legnica and Glogow were collected. Urinary arsenic concentration was measured. In addition, blood level of cadmium, lead, and zinc protoporphyrins was assayed. Genetic analyses included polymorphism of PNP (rs 1130650), GSTO-1 (rs 4925), AS3MT (rs 11191439), and ADRB3 (rs4994) genes. RESULTS: Individuals occupationally exposed to arsenic compounds, who have allele T in homozygous constellation in locus rs 1130650 of PNP gene, are predisposed to lower urinary arsenic concentration, while AA homozygosity in locus rs 4925 of GSTO-1 gene may result in statistically significant higher urinary arsenic concentration. Polymorphisms of AS3MT and ADRB3 genes showed no statistically significant correlation with urinary arsenic, however, there was a tendency to higher arsenic concentration in allele A carriers in locus rs4994 of ADRB3 gene and in allele T carriers in rs 11191439 of AS3MT gene. CONCLUSION: This study indicates that arsenic absorption and metabolism depend on polymorphisms of genes encoding PNP and GSTO-1. Individuals with disadvantageous constellation of polymorphisms are more susceptible to harmful effects of arsenic exposure.

Structure, antigenic determinants of some clinically important insect allergens: chironomid hemoglobins.

Determination of the molecular structure and properties of allergens that elicit severe immediate-type hypersensitivity diseases in humans and a knowledge of the structure of their antibody-binding sites should provide new insight into the pathogenetic mechanisms of allergic diseases. Monomeric and homodimeric hemoglobins (CTT I to X) have been identified as potent allergenic components of Chironomidae, a family of Diptera. Immunologic investigations of peptides of three of these hemoglobins (CTT IV, CTT VI, and CTT VIII) showed that human antibodies of the E and G classes recognize at least two different sites within each molecule. Individual hemoglobin peptides were aligned with homologous regions of chironomid hemoglobin CTT III, whose tertiary structure has been determined by x-ray analysis at a resolution of 1.4 angstroms. The antigenic site CTT IV(91 to 101) showed the following characteristics: (i) seven polar or hydroxylated amino acids, from a total of eleven, occupying predominantly superficial regions; (ii) the property of linkage to other molecules by hydrogen bonds or solvent clusters; and (iii) high thermal mobility factors. In contrast, peptide CTT IV(102 to 108), which does not bind human antibodies, contained no polar amino acids and had low thermal mobility factors. These results support the idea that the antigenicity of clinically relevant proteins is related to regions with a predominance of polar amino acids and with low energy barriers between different conformations, which allow high flexibility, including site-specific adaptation in antibody binding.

Increased monocyte chemoattractant protein 1 (MCP-1/CCL-2) serum level in acute myeloid leukemia.

Acute myeloid leukaemia (AML) is an aggressive malignancy with accumulation of blasts in bone marrow. Myeloblasts can entry into peripheral blood stream and secondary localize in extramedullary sites. The regulation of this process has not been clearly explained so far, but interactions between some chemokines and their specific receptors could be one of the mechanisms responsible for such kind of migration. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is the chemokine which could be involved in this process. The aim of the study was to evaluate plasma level of CCL2 in patients with AML. Plasma samples from 65 adult patients with AML taken before chemotherapy and in complete remission were measured by enzyme linked immunoassay to evaluate CCL2 levels. Control group consisted of 15 healthy subjects. In AML patients mean baseline CCL2 level (+/- SEM standard error of measurement) was significantly higher than in normal control: 365,26 +/- 5,62 pg/ml vs 265,56 +/- 5,48 pg/ml respectively (p<0.01). We demonstrate increased mean CCL2 plasma level in untreated patients with AML. Significantly lower plasma level of CCL2 was observed in patients with M4 and M5 AML subtypes according to FAB classification. In AML group chemotherapy did not reduce CCL2 plasma level.

Angiogenic and coagulation-fibrinolysis factors in non Hodgkin's lymphoma.

High serum VEGF and bFGF levels are independent prognostic factors of poor prognosis in NHL patients. There is growing evidence that both angiogenesis and haemostatic aberrancies are integral parts of the pathobiology of cancer growth and dissemination. The purpose of the study was: (a) to analyze relations of VEGF and bFGF serum levels, fibrinogen and D-dimer plasma levels with lymphoma Ann Arbor Staging System (AASS) and International Prognostic Index (IPI) and, (b) to evaluate correlations between serum levels of angiogenic cytokines and plasma levels of coagulation-fibrinolysis factors in 52 previously untreated NHL patients included to the study. The control group consisted of 23 healthy volunteers. Serum VEGF, bFGF and plasma D-dimer levels were measured by enzyme-linked immunosorbent assay (ELISA). Plasma levels of fibrinogen were determined on Behring Coagulation System (BCS) equipment. In lymphoma group serum VEGF and bFGF levels were significantly higher than in the control. Differences in concentrations of VEGF, bFGF between II, III and IV stage of disease acc. AASS were not statistically significant. Plasma levels of fibrinogen and D-dimer were elevated in lymphoma patients when compared with the control. Fibrinogen plasma levels were similar in all stages. The D-dimer level was significantly higher in patients with IV stage in comparison to stage II and III. Statistically significant differences of VEGF and bFGF serum levels were observed only between intermediate/high and high risk groups acc. IPI. Fibrinogen plasma levels were significantly higher in high risk group than in low risk group. D-dimer plasma levels were significantly higher in high risk group than in low risk group and low/intermediate group. We observed positive correlation between serum level of VEGF and plasma level of fibrinogen, and between serum level of bFGF and plasma level of fibrinogen. There was also negative correlation between serum level of VEGF and plasma level of D-dimer, and between serum level of bFGF and plasma level of D- dimer. Our study indicates that D-dimer level, but not VEGF, bFGF and fibrinogen correlates with AASS and IPI in NHL patients. Significant correlations between levels of VEGF/bFGF and fibrinogen/D-dimer suggest specific interactions between angiogenic and coagulation-fibrinolysis system.

Dual role of the CXCL12 polymorphism in patients with chronic lymphocytic leukemia.

The CXCL12 [chemokine (C-X-C motif) ligand 12] is a member of the CXC family of chemokines and interacts with its CXCR4 receptor. The CXCL12/CXCR4 axis is involved in regulation of proliferation, survival and trafficking of hematopoietic stem cells, including B lymphocytes and disruption within this signaling pathway has been implicated in pathogenesis of chronic lymphocytic leukemia (CLL). The aim of this study was to determine a potential association of the CXCL12 rs1801157 G > A polymorphism with susceptibility to CLL, the disease course and efficacy of therapy. Also, expression of the CD74 and CD38 proteins on B cells was analyzed in relation to clinical parameters and genotyping results. A total of 124 patients with CLL and 75 healthy controls were studied. CXCL12 genotyping was performed using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. The CD74 and CD38 surface expression was determined using flow cytometry. There was a significantly increased frequency of the A allele and AA genotype in CLL patients compared with control group (P < 0.001 in both cases). In addition, the A allele was overrepresented among patients with worse response to therapy in comparison to other genotypes (P < 0.001). On the contrary, patients carrying the A allele displayed lower grade of the disease at diagnosis more frequently than patients homozygous for the G allele (P = 0.037). Moreover, the AA homozygosity correlated with lower CD74 expression on B cells (P = 0.007). In conclusion, data from this study indicate that the CXCL12 rs1801157 G > A polymorphism may affect CLL development, disease progression as well as response to treatment.

Stretching magnetism with an electric field in a nitride semiconductor.

The significant inversion symmetry breaking specific to wurtzite semiconductors, and the associated spontaneous electrical polarization, lead to outstanding features such as high density of carriers at the GaN/(Al,Ga)N interface-exploited in high-power/high-frequency electronics-and piezoelectric capabilities serving for nanodrives, sensors and energy harvesting devices. Here we show that the multifunctionality of nitride semiconductors encompasses also a magnetoelectric effect allowing to control the magnetization by an electric field. We first demonstrate that doping of GaN by Mn results in a semi-insulating material apt to sustain electric fields as high as 5 MV cm-1. Having such a material we find experimentally that the inverse piezoelectric effect controls the magnitude of the single-ion magnetic anisotropy specific to Mn3+ ions in GaN. The corresponding changes in the magnetization can be quantitatively described by a theory developed here.

Endostatin serum level in acute myeloid leukemia.

Increased levels of tumor angiogenesis have been demonstrated in variety of solid tumors and hematological malignancies including acute myeloid leukemia (AML). The aim of the study was to evaluate serum level of endostatin in newly diagnosed patients with AML before chemotherapy and after achieving complete remission (CR). Serum samples from 68 adult patients (28 females and 40 males, median age 42 years, range 21-83 years) with AML had been taken before chemotherapy was administered. In addition 21 out of 68 patient were analyzed again after achieving CR. Endostatin levels were measured using ChemiKine sandwich ELISA kit (Chemicon International). Twelve samples from healthy volunteers (5 females and 7 males, median age 40 years; range 35-65 years) were evaluated as the control. Endostatin serum levels were significantly higher in untreated AML patients than in the normal controls. In AML patients baseline endostatin levels were significantly lower than in CR. We did not found any correlation between white cell count or percentage of blasts in the bone marrow and endostatin level. Moreover endostatin levels did not differ statistically among AML FAB subgroups. Increased endostatin plasma levels may reflect intensity of inhibition of angiogenesis and may by useful in prognosis of CR in AML. Chemotherapy can modulate the regulation of angiogenesis in AML patients.

LYVE-1 expression on high endothelial venules (HEVs) of lymph nodes.

LYVE-1 (lymphatic endothelium hyaluronan receptor) has been identified as a powerful marker for lymphatic endothelium. Apart from lymphatic endothelium, LYVE-1 is expressed in normal liver blood sinusoids, spleen endothelium and activated tissue macrophages. LYVE-1 has not been detected in blood vascular endothelium with the exception of blood vessels in the lung. High endothelial venules (HEVs) belong to the vascular compartment of lymph nodes. They are the major site of entry for circulating lymphocytes into the node. HEVs are characterized by cuboidal endothelial cells, the existence of discontinuous junctions between these endothelial cells, and the presence of large numbers of lymphocytes within their walls. 40 paraffin-embedded lymph node biopsy specimens from newly diagnosed patients with non-Hodgkin lymphoma were evaluated as well as 10 lymph node biopsy specimens from adult patients with reactive lymphadenitis, and 10 normal, non-metastatic lymph nodes obtained from adult patients during cancer surgery served as controls. Samples were fixed in 10% buffered formalin, paraffin embedded, and stained with hematoxylin and eosin for histopathological evaluation. Sections were also evaluated with mouse monoclonal antibodies against LYVE-1 and CD34, and expression of both LYVE-1 and CD34 was demonstrated in HEVs. LYVE-1 expression was also found on the endothelial cells of the lymphatic sinus and in reticular cells in the lymph nodes.

A common epitope on major allergens from non-biting midges (Chironomidae).

A synthetic peptide corresponding to sequence 91-101 of the Chironomus thummi thummi haemoglobins (Chi t I) components III and IV was used to investigate binding and cross-reactivity with polyclonal human IgE and rabbit IgG antibodies and murine IgG1 subclass monoclonal antibodies (MABs). The synthetic peptide reacted with antibodies from all three mammals. The specificity of the reaction, especially that with IgE antibodies was shown by dose dependent inhibition with native Chi t I component III. Epitope(s) reacting with these antibodies were also found in haemoglobins from 14 of the 15 chironomid species analyzed. The synthetic peptide III/IV 91-101 enabled the identification of an important antigenic/allergenic determinant of the broadly distributed insect family Chironomidae. The antigenic potency of this synthetic peptide as shown by testing with human IgE, rabbit IgG and mouse MABs, and the widespread occurrence of the epitope in an identical or homologous sequence and/or superficial location, qualifies the peptide for therapeutic applications in medicine.

Analysis of B-cell epitopes in the N-terminal region of Chi t I component III using monoclonal antibodies.

The hemoglobins of the midge Chironomus thummi thummi (Chi t I) are known to cause immediate-type hypersensitivity reactions in humans. Further knowledge of the antigenic sites of such allergens will provide new therapeutic approaches. The aim of our study was to identify and characterize linear B-cell epitopes of the hemoglobin component III of Chi t I (136 amino acid residues). Using the antigenic index algorithm of Jameson and Wolf (Jameson and Wolf (1988) Comput. Appl. Biosci. 4, 181-186), three linear binding sequences of this allergen molecule were predicted. Two mouse monoclonal antibodies (mAbs 3 and 6) raised against purified Chi t I component III were investigated by ELISA for their binding to nine synthetic peptides 19-21 residues in length, covering nearly the whole sequence of component III. MAb 6 recognized only one peptide (11-30) while mAb 3 bound to both N-terminal peptides (1-19 and 11-30), suggesting that the antibody binding site is located in the overlapping region. This assumption could be confirmed in ELISA with solid phase-bound recombinant peptides (RP) as well as in inhibition studies with free tryptic peptides indicating that identification of these linear B-cell epitopes is neither influenced by the method of peptide production nor by the kind of used immunoassay. To define the essential amino acid residues we investigated mAbs with solid phase-bound overlapping octamers. In the case of mAb 3, amino acids experimentally identified as essential for antibody binding (aa 13-17) are identical with those residues predicted as a B-cell epitope with the antigenic index of Jameson and Wolf.

High-dose chemotherapy with autologous stem cell transplantation is an effective treatment of primary refractory Hodgkin's disease. Retrospective study of the Polish Lymphoma Research Group.

We analysed the treatment outcome of primary refractory HD patients managed with high-dose chemotherapy and haematopoietic cell transplantation. Data of 65 adult patients who underwent HDC/ASCT in nine Polish centres for primary resistant Hodgkin's disease between June 1991 and July 2000 were collected retrospectively. Response rate to HDC/ASC: CR, 54%; PR, 20%; less than PR, 15%; early deaths, 11%. Actuarial 3-year OS and PFS were 55% and 36%, respectively. In multivariate analysis, lack of bulky lymph nodes and use of immunotherapy were favourable factors for both OS and PFS. IPF <3 at the time of transplantation was predictive for PFS. However, the prognostic impact of immunotherapy should be interpreted with caution since this group included more patients who achieved CR after HDC/ASCT. The results of HDC/ASCT are encouraging and confirm earlier findings. The role of immunotherapy should be further investigated in prospective trials.

Intermittent 2-hour intravenous infusions of 2-chlorodeoxyadenosine in the treatment of 110 patients with refractory or previously untreated B-cell chronic lymphocytic leukemia.

The purpose of our study was to determine the effectiveness of 2-CdA in 2-hour intravenous infusions in the treatment of B-CLL. One hundred and ten patients with B-CLL received 1 to 10 courses of 2-CdA (median 2.5) at a dosage of 0.12 mg/kg daily for 5 consecutive days. Eighteen of them were untreated and 92 relapsed or became refractory to previous therapeutic modalities. Complete remission (CR) was achieved in 8 (7.3%) and partial remission (PR) in 35 patients (31.8%) giving an overall response rate of 39.1%. In 3 patients, cross-resistance to fludarabine was noticed. Toxic effects of 2-CdA were more frequently observed in previously treated patients. Hemorrhagic complications due to drug-induced thrombocytopenia were noticed in 25 (22.7%) and severe infections including sepsis in 14 (12.7%) patients.

Impaired CD25 expression and soluble CD25-IL-2R alpha receptor release by anti-CD3 stimulated peripheral blood mononuclear cells in Hodgkin's disease patients.

We examined 22 patients in active phase of Hodgkin's disease (HD), 12 patients in complete clinical remission and 16 healthy subjects for their responsiveness to anti-CD3 stimulation as measured by CD25 antigen expression on peripheral blood mononuclear cells (PBMC) and production of CD25-IL-2R alpha. Simultaneously, the serum levels of soluble interleukin 2 receptor alpha (sIL-2R alpha) were estimated. Our studies indicate that PBMC in patients in active phase and in clinical remission have impaired ability to express CD25 antigen after stimulation with anti-CD3 monoclonal antibody. Similarly, the levels of sIL-2R alpha in culture supernatants were significantly lower in both groups of patients: in active phase and clinical remission compared with the controls. In contrast, the mean serum level of sIL-2R alpha was significantly higher in active phase of the disease compared to that found in patients in clinical remission and controls. Our studies suggest that sIL-2R alpha, derived from PBMC, is not the source of increased levels of sIL-2R alpha found in the sera of patients in active phase of HD. Their synthesis and secretion/shedding most probably takes place in the involved tissues.

Contribution of flow cytometric immunophenotyping and bone marrow trephine biopsy in the detection of lymphoid bone marrow infiltration in non-Hodgkin's lymphomas.

The bone marrow (BM) is a frequent site of involvement in non-Hodgkins lymphomas (NHL) and evidence of an infiltrated BM may implicate different therapeutical regimens. Flow cytometric immunophenotyping of bone marrow aspirates now is included in the assessment of patients with NHL and used as an adjunct to morphologic evaluation in the staging of lymphoma. The aim of the study was to compare flow cytometric immunophenotyping of BM and paraffin section staining of BM biopsies in the marrow involvement of NHL. Cytometric immunophenotyping of bone marrow and immunohistochemical paraffin section staining of bone marrow biopsies in 53 B- and T-cell lymphoma patients were performed. We used the following fluorochrom conjugated monoclonal antibodies specific for: CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD20, CD22, CD23, CD79B, FMC7 and Ig kappagamma light chain. Unilateral BM trephine biopsies were obtained in all cases, fixed, decalcified and paraffin-embedded. Morphologic marrow involvement by lymphoma was found in 24 cases; flow immunophenotyping identified 26 cases with NHL: morphology-positive/flow-positive (n=21), morphology positive/flow-negative (n=3), morphology-negative/flow-positive (n=4), and morphology-negative/flow-negative (n=23). The concurrence rate of BM trephine biopsy and flow cytometric immunophenotyping in evaluation of NHL bone marrow infiltration was 88.7%. Immunophenotyping of the bone marrow of NHL patients by flow cytometry is helpful for assessment of bone marrow infiltration, especially in B-cell disorders. Both trephine biopsies and flow cytometry are better than single investigation for detection of infiltration in NHL.