Malaria pigment crystals as magnetic micro-rotors: key for high-sensitivity diagnosis.

The need to develop new methods for the high-sensitivity diagnosis of malaria has initiated a global activity in medical and interdisciplinary sciences. Most of the diverse variety of emerging techniques are based on research-grade instruments, sophisticated reagent-based assays or rely on expertise. Here, we suggest an alternative optical methodology with an easy-to-use and cost-effective instrumentation based on unique properties of malaria pigment reported previously and determined quantitatively in the present study. Malaria pigment, also called hemozoin, is an insoluble microcrystalline form of heme. These crystallites show remarkable magnetic and optical anisotropy distinctly from any other components of blood. As a consequence, they can simultaneously act as magnetically driven micro-rotors and spinning polarizers in suspensions. These properties can gain importance not only in malaria diagnosis and therapies, where hemozoin is considered as drug target or immune modulator, but also in the magnetic manipulation of cells and tissues on the microscopic scale.

The detection of hepatitis C virus in South Hungary.

BACKGROUND: More than 100 million people are infected with hepatitis C virus (HCV) worldwide. The prevalence of HCV infection varies from country to country and the natural history of hepatitis C infection is not well understood. OBJECTIVES: The prevalence of anti-HCV positive blood donors in South Hungary was determined. Potential risk factors of HCV transmission were investigated and compared to anti-HCV-negative blood donors. Furthermore, the rate of anti-HCV positivity in children who had received one or more blood transfusions prior to the implementation of anti-HCV blood donor screening was evaluated. STUDY DESIGN: A total of 45719 blood donors and 120 children were tested for the presence of anti-HCV antibodies by second- and third-generation enzyme immunoassays. Positive results were confirmed by a recombinant immunoblot assay. Data on potential sources of HCV transmission were obtained by interviews. RESULTS: Among blood donors, the rate of confirmed HCV antibody-positives was 0.4% (195 of 45719 donors). Previous surgery, transfusion, more than three pregnancies, and tattoos were significantly correlated with confirmed anti-HCV positivity. Two of 120 children (1.7%) were confirmed anti-HCV positives. In both of them, serum HCV RNA could be detected. CONCLUSIONS: The prevalence of anti-HCV positive blood donors in South Hungary is low. Nosocomial infections and tattooing were found to be the most important risk factors for transmission of HCV. Because of the low prevalence of anti-HCV positive blood donors, only a small number of children, who received blood transfusions prior to the implementation of anti-HCV blood donor screening, are infected with HCV.

Relationship between the occurrence of anti-SSA, anti-SSB autoantibodies and HLA class II alleles from the aspect of in vitro inhibitory effect of glucocorticosteroid on the antibody-dependent cellular cytotoxicity in patients with primary Sjögren's syndrome.

Though at present there is no evidence-based algorithm for the treatment of primary Sjögren's syndrome, it is generally accepted that glucocorticosteroid (GS) therapy must be introduced in cases with severe systemic manifestations. As the side-effects of the GSs are well known, it would be useful to know in advance how the patients will respond to this type of treatment. For this reason we measured the in vitro steroid sensitivity of 29 SS patients using inhibition of antibody dependent cellular cytotoxicity (ADCC) test by methylprednisolone compared to that of 28 controls. SS patients proved to be significantly less sensitive to GSs than controls (inhibition of ADCC reaction: 42.4 vs 53.1%; p < 0.01). This was especially true in SS patients with anti-SSA and/or SSB autoantibody positivity and with HLA-DR2 and/or -DR3 alleles. Comparing the results of the in vitro GS sensitivity and the clinical effectiveness of the previously applied corticosteroid therapy it seems that steroid inhibition of ADCC reaction has a predictive value in determination of in vivo sensitivity to GSs. However, in patients with decreased in vitro GS sensitivity a more expressed in vivo steroid sensitivity cannot be excluded.

Extension of the protocol of OECD guideline 407 (28-day repeated dose oral toxicity test in the rat) to detect potential immunotoxicity of chemicals.

To indicate the immunotoxic potential of chemicals the examinations prescribed by OECD Guideline 407 were extended by the following additional toxicological, haematological, histopathological, and immune function examinations: absolute and relative organ weight of spleen, thymus, popliteal lymph nodes, lung and brain; histopathology of thymus, mesenteric lymph nodes, popliteal lymph nodes, bone marrow (femur), Peyer's patches (ileum), lungs and colon; PFC assay (spleen), T cell proliferation and NK cell assay. Two well known immunosuppressants Azathioprine (AZA) and Cyclosporine A (CysA) were chosen as model compounds at a dose range which do not cause visible toxic signs on the animals during a 28 days treatment period. The results show that the applied experimental system is much more sensitive in detection of the immunotoxic potential of these two compounds in a low dose range than the examination required by OECD Guideline 407 are.

Substitution of mucAB or rumAB for umuDC alters the relative frequencies of the two classes of mutations induced by a site-specific T-T cyclobutane dimer and the efficiency of translesion DNA synthesis.

We have examined the effect of replacing umuDC with mucAB or rumAB on the mutagenic properties of a T-T cyclobutane dimer in an attempt to determine the molecular basis for the differences in UV-induced mutagenesis that are associated with these structurally and functionally related genes. A single-stranded vector carrying a site-specific T-T cis-syn cyclobutane dimer was transfected into a set of isogenic Escherichia coli delta umuDC strains harboring low-copy-number plasmids expressing UmuDC, MucAB, RumAB, or their genetically engineered and mutagenically active counterparts UmuD'C, MucA'B, and RumA'B, respectively. Although the overall mutation frequency was similar for all strains, the relative frequencies of the two classes of mutation induced by the T-T dimer varied according to the mutagenesis operon expressed. In umuDC strains, 3' T-->A mutations outnumbered 3' T-->C mutations, but the reverse was true for the mucAB and rumAB strains. We also found that the T-T dimer was bypassed with differing efficiencies in unirradiated cells expressing wild-type UmuDC, MucAB, and RumAB proteins. These differences can probably be attributed to the relative efficiency of the normal cellular posttranslational activation of UmuD, MucA, and RumA, respectively, since recombinant constructs expressing the mutagenically active UmuD'C, MucA'B, and RumA'B proteins all promoted similarly high levels of bypass in UV-irradiated cells. These results suggest that the UmuD'/UmuC complex and its homologs may differ in their relative abilities to promote elongation from T - T and T - G mismatched termini. Alternatively, they may differentially influence the efficiency with which these mismatches are edited or influence nucleotide insertion by the catalytic subunit of the DNA polymerase III.

Immunomodulating activities on cellular cytotoxicity and the blast transformation of human lymphocytes by 10-[n-(phthalimido)alkyl-2-substituted-10H-phenothiazines and 1-(2-chloroethyl)-3-(2-substituted-10 H-phenothiazin-10-yl)alkyl-1-ureas.

Phenothiazines, 10-[n-(phthalimido)alkyl-2-substituted-10H- phenothiazines, and 1-(2-chloroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alkyl-1- ureas were investigated for their effects on antibody-dependent cellular cytotoxicity (ADCC), natural killer (NK) cells and the blast transformation of human peripheral blood mononuclear cells. All of the compounds dose-dependently suppressed mitogen-stimulated T cell proliferation. In contrast, a strong enhancing effect on NK cell activity was detected mostly in the case of 1-(2-choroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alk yl-1-ureas and their related compounds. The stimulating effect directly influenced the NK cells and was demonstrated at all tested concentrations.

Molecular genetic analysis of HLA-DRB, -DQA, and -DQB polymorphisms in Hungarians and distribution of the DRB1*03 allele in adults and newborns.

We describe here the genetic variability of HLA-DRB1, -DQA, and -DQB in 140 healthy individuals from Hungary, including 95 randomly selected adults and 45 newborns. Allele and haplotype frequencies as well as linkage disequilibria were calculated. It was found that HLA-DRB1*11, -DQA1*0501, and -DQB1*0301 predominate in Hungarians. This information may be helpful in the future for HLA and disease association studies. Simultaneously, we observed that the frequency of the DRB1*03 allele differs between adults and newborns. Since it is well known that bearers of HLA-DR3 (and/or B8) antigens may display significant changes in immune parameters, the lower frequency in adults indicates that children with the DR3 antigen are predisposed to immune diseases in adulthood.

Effect of benzo[a]phenothiazines on natural killer cell activity of human peripheral blood mononuclear cells.

Four benzo[a]phenothiazines were investigated for their effects on antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) cell and blast transformation of human peripheral blood mononuclear cells (PBM). Benzo[a]phenothiazines dose-dependently suppressed the nitrogen-stimulated T cell proliferation. The suppressive effect of non differentiation-inducing benzo[a]phenothiazines was higher than that of differentiation-inducing benzo[a]phenothiazines. The stimulation effect of differentiation-inducing compounds on the NK activity was reduced by removal of monocytes from the PBM. The results suggest the direct activation of monocytes (Mo) by differentiation-inducing benzo[a]phenothiazines.

Detection of Fc gamma-receptor blocking antibodies in the serum following vaccination.

In the current series of experiments the Fc gamma-receptor blocking serum activity (EAI) was studied before and after vaccination with tetanus toxoid and rDNA HBsAg vaccines in two groups of 6 healthy persons. The analysis of the individual serum samples (on three different allogeneic and on autologous B lymphocytes) suggests that two types of EAI antibodies were produced: allo- and autoantibodies. In all cases an increase of EAI activity was noticed after immunization (in the cases of tetanus toxoid vaccination from 17.7 +/- 9.7 to 39.3 +/- 16.0 and in the cases of virus vaccination from 67.4 +/- 16.5 to 80.2 +/- 4.5).

[Hyperpigmentation of the face]. / Hyperpigmentierung des Gesichts.

A 49-year-old male patient is presented, who developed hyperpigmented macules on the face. An exact classification of the disorder was not possible on the basis of anamnestic data, histology and electron microscopy. An attempt was made to differentiate it from other known dyschromias of the face.

Efficient cell mediated lysis of human erythrocyte target cells is mediated by a human glycophorine A specific murine monoclonal antibody.

A human glycophorine A specific murine monoclonal antibody mediates the antibody dependent killing of antibody sensitized human erythrocytes by human K cells (monocyte-free mononuclear cells). The overall level of killing is lower than that mediated by conventional, human anti-D antibodies but it is significant on each target cell.

Clinical characteristics of cutaneous melanoma in southeastern Hungary.

Clinical and histopathologic characteristics and data on the incidence of primary cutaneous melanoma are presented from an area of Hungary with 1.9 million inhabitants. Experiences with delayed elective node dissection on survival are also documented.

Xanthoma disseminatum: a rare condition with non-X, non-lipid cutaneous histiocytopathy.

We describe a 35-year-old man with cutaneous, mucosal, pulmonary, and bone involvement of xanthoma disseminatum. The 7-year course of the disease and the results of light and electron microscopic and immunocytochemical examinations are presented.

[Segmental pigment anomaly with neurologic disorders]. / Segmentale Pigmentanomalie mit neurologischen Störungen.

A 28-year-old female patient who developed an asymmetrically localized depigmentation on the right arm and on the right side of the trunk shortly after birth is presented. The depigmented areas with hyperpigmented macules within them had not changed in shape or extent since their development. At the age of 18 years, neurological alterations (hyporeflexy, sensory deficiencies, muscle atrophy and paralysis) were also observed. Ultrastructural investigations revealing the lack of melanocytes in the depigmented areas and the presence of atypical melanosomes in the hyperpigmented macules indicate a rare pigmentation disorder.

Repigmentation of vitiligo macules treated topically with Efudix cream.

Repigmentation has been observed under the influence of topically administered Efudix cream in 3 patients with vitiligo of symmetrical acral type. No response has been received in 2 patients with segmental vitiligo treated in the same way. Recurrence of vitiligo was seen in 1 patient. Histologic and electron microscopic characterization of recolonized melanocytes is described. The significance of topical 5-fluorouracil treatment in vitiligo is discussed.

[Appearance of disseminated hyperpigmented lesions during PUVA therapy]. / Auftreten disseminierter hyperpigmentierter Flecke unter PUVA-Behandlung.

Disseminated, hyperpigmented lesions were observed in two patients with psoriasis under PUVA treatment independently from psoriatic lesions. Light microscopic examination revealed besides hypertrophy of melanocytes no considerable changes. Additionally to the formation of large melanosomes (Longitudinal diameter over 8,8 micrometers) and the pronounced melanin-storage in the melanophages, electron microscopic results referred to degenerative processes of melanocytes and the epidermal basal lamina.