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J Grunewald

Publications and source records attributed to J Grunewald.

108 records · Page 6Linked to original sources

Predominant T cell receptor V gene usage in patients with abnormal clones of B cells.

We have examined alpha/beta V gene segment usage of peripheral blood CD4+ and CD8+ T cells, respectively, from patients with multiple myeloma and monoclonal gammopathy of undetermined significance, by using T cell receptor (TCR) for antigen monoclonal antibodies (MoAbs). In 7 of 16 patients we found an increase in the usage of various TCR V gene segments. The expansion was confined to either the CD4+ or the CD8+ T-cell subset, except for one patient where an abnormal pattern was observed both within the CD4+ and CD8+ T-cell subsets. In one patient 47%, and in another patient 30% of the CD8+ lymphocytes reacted with alpha V12.1 and beta V6.7 antibodies, respectively. In two other patients 29% and 40% of the CD4+ lymphocytes reacted with beta V6.7 and beta V8.1 antibodies, respectively. We conclude that T cells with a predominant V gene usage is a frequent feature in patients with abnormal clonal B cells of malignant or benign types. T- and B-cell populations are normally clonally linked in regulatory circuits. An abnormal proliferation of B cells might therefore induce, or be regulated by, an expansion of clonal T cells, as suggested by the present results.

Antibodies, Monoclonal↗

Biased expression of individual T cell receptor V gene segments in CD4+ and CD8+ human peripheral blood T lymphocytes.

The expression of seven different alpha and beta gene segments of the T cell receptor on normal human CD4+ and CD8+ T lymphocytes, respectively, was examined using V gene-specific monoclonal antibodies. We found a statistically significant (p less than 0.001) bias of the expression of four V gene products towards the CD4+ subpopulation. In every individual analyzed, the V beta 5.1 gene segment was expressed to a higher degree among CD4+ compared to CD8+ cells, with a median value of 4.8% among CD4+ cells and 1.5% among CD8+ cells. There was also a statistically significant skewness in the usage of the V beta 6.7, V beta 8 and V beta 12 gene segments towards the CD4+ T cell population, but not as dominating as for the V beta 5.1. Lymphocytes from umbilical cord blood showed similar skewed reactivities for the V beta 5.1, V beta 6.7 and V beta 12-specific monoclonal antibodies. Aspects of positive and negative selection, as possible explanations for these findings, are discussed.

Antibodies, Monoclonal↗

An analysis of alpha/beta TCR V gene expression in the human thymus.

We have previously analysed alpha/beta T cell receptor (TCR) V gene usage in CD4+ and CD8+ subpopulations from human peripheral blood lymphocytes (PBL) and umbilical cord blood, and described a biased usage of some of the TCR V beta genes towards the CD4+ subpopulation. In this report, the TCR V gene usage in single positive (SP) CD4+ or CD8+ human thymocytes was analysed. Three previously described mAb with a biased usage in PBL and umbilical cord blood also had a skewed reactivity towards the CD4+ subpopulation in SP human thymocytes. Thus, in all 12 cases V beta 5.1 and V beta 6.7, and in 11/12 cases V beta 12 were preferentially used in the CD4+CD8-, compared to the CD4-CD8+ thymic subpopulation. Altogether, these results suggest a selection process in the thymus, supposedly through the positive influence of MHC class II determinants, to be responsible for this non-random, skewed TCR V gene usage.

Antibodies, Monoclonal↗

Abnormal T-cell expansion and V-gene usage in myasthenia gravis patients.

To determine the extent of V-gene heterogeneity of blood T lymphocytes in patients suffering from Myasthenia Gravis (MG), we used eight recently available monoclonal antibodies (MoAb), directed against different V alpha and V beta gene products of the variable part of the T-cell receptor (TCR), covering approximately 25% of the alpha/beta T cells in normal peripheral blood (PBL) of healthy individuals. Using a two-colour immunofluorescence method, we could calculate the expression of alpha/beta V segments within the two major T-cell subsets, CD4-/CD8+ and CD4+/CD8- lymphocytes. Twenty-seven per cent (4/15) of the MG patients had T cells showing signs of abnormal expansion. Furthermore, among these expanded T cells, a restricted V beta 12 gene expansion could be seen, in three out of four patients. No correlation between TCR V-gene usage and HLA haplotypes (HLA-A, -B, -DR and -DQ) could be seen. Our data suggest that the majority of MG patients have abnormally expanded T-cell clones. The relevance of these findings is discussed.

Antibodies, Monoclonal↗

The WHO Onchocerciasis Control Programme: retrospect and prospects.

The history of onchocerciasis control in Africa and the genesis of the WHO Onchocerciasis Control Programme in West Africa (OCP) are briefly reviewed. The importance of experience gained in anti-locust campaigns in helping to plan the OCP is stressed. Members of the Simulium damnosum species complex are the vectors of onchocerciasis, which OCP is controlling with insecticide treatments on the stretches of rivers where the Simulium breed. Migrations of flies have been responsible for reinfestations of controlled areas and the spread of insecticide resistance. The management of these problems and related research are described, but it is emphasized that despite setbacks OCP is achieving its aims. A strategy for the future is outlined: vector control supplemented by chemotherapy is expected to continue until the year 2004.

Africa, Western↗

A new surface antigen on human lymphocytes defined by the murine monoclonal antibody IVF7.

The murine monoclonal antibody (MoAb) IVF7 was produced against tumour cells from a patient with a CD3+, CD4+, CD8- T-cell chronic lymphatic leukaemia (T-CLL). The MoAb IVF7 showed reactivity with subpopulations of normal peripheral blood lymphocytes (PBL), as well as with a few cell lines of haematopoietic origin. Thirty-six per cent of PBL were stained with IVF7. Analysing subpopulations, we found that 80% of NK cells, 25% of T cells, and 10-20% of B cells were positive. The myelomonocytic cell line KG-1 was also stained. The molecular weight of the molecule was 40 kDa under reducing conditions. The antigen was found to be trypsin-sensitive. MoAb IVF7 could modulate the antigen from the cell surface. The antibody did not stimulate PBL to DNA synthesis, nor did it significantly influence NK cell-mediated killing.

Animals↗

A monoclonal antibody, H2, defines a new surface antigen expressed on human lymphocytes.

We have previously described a monoclonal antibody (MoAb), H2, which recognized a tumour-unique antigen on a human T-cell chronic lymphatic leukaemia (T-CLL, CD3,4+). However, further characterization of H2 has revealed a reactivity with the majority of T lymphocytes and a minority of B lymphocytes, some malignant T cells and a few cell lines of leukaemia or of hematopoietic tumour origin. The molecular weight of the antigen (80,000) precipitated by the MoAb H2 from the cell lines NALM-6 and Reh corresponded to that previously found. When PBL were stimulated with PHA, IL-2, or Con A a reduced reactivity of H2 could be seen. The MoAb H2 was submitted to the Fourth International Conference on Human Leucocyte Differentiation Antigens, Vienna, 1989. H2 did not cluster in any of the 78 clusters of differentiation (CD 1-78) discussed at the conference, indicating its unique reactivity. This suggests that we have defined a new antigen on lymphocytes with a possible role along the resting-proliferating axis.

Animals↗

Studies on the immature stages of the Simulium neavei Roubaud complex and their associated crabs in the Eastern Usambara Mountains in Tanzania. IV. Observations on the crabs and their attached larvae under exceptionally dry conditions.

When exceptionally low rainfall resulted in the drying out of some 'permanent' streams containing the immature stages of Simulium neavei complex species, the fate of the larvae and their associated crabs was investigated. Both crabs and larvae survived under rocks, stones and boulders where some moisture persisted. Such situations would be out of reach to insecticides applied to running water in the normal way.

Animals↗

The hydro-chemical and physical conditions of the environment of the immature stages of some species of the simulium (Edwardsellum) damnosum complex (Diptera).

Water samples were collected from breeding sites of species of the Simulium (Edwardsellum) damnoslm complex in Upper Volta, Liberia and Cameroon during the dry season; and in Tanzania and Kenya at various seasons during a period of two years. The following 20 factors were analysed at 45 breeding sites: water temperature, current velocity, pH value, conductivity free carbon dioxide, oxygen content, calcium, magnesium, potassium, sodium, alkalinity, chloride, sulphate, nitrite, nitrate, ammonium, phosphate, silicate, total iron and organic substance (consumption of potassium permanganate). A number of notable differences in the chemical composition of the water of the breeding sites of 13 S. damnosum complex species were found, particularly with regard to the pH and conductivity. On the basis of these differences the various species can be divided into three main groups: Group I: 3 species (S. sanctipauli, S. yahense, "Menge"); breeding in sites with pH values always below 7 and conductivity values below 50 mumhos. Group II: 8 species (S. sirbanum, S. sudanense, S. damnosum s.s., S. squamosum, "Sanje", "Nkusi", "Nyamagasani", "Jovi"); breeding in watercourses with neutral, weakly acid or weakly alkaline reactions and conductivity values ranging from 50 to 150 mumhos. Group III: 2 species ("Kibwezi", "Kisiwani"); breeding in watercourses characterized by highly alkaline reactions with pH values between 7.7 and 10 and by conductivity values between 400 and 950 mumhos. The vectors of Onchocerca volvulus are included in group I and II only.

Animals↗

Present progress towards the laboratory colonization of African Simuliidae (Diptera).

The laboratory colonization of African simuliids would facilitate critical work on many aspects of their biology and onchocerciasis vectors could be studied away from natural breeding-sites. In addition to a review of the literature of past achievements in this field, the authors' own studies are described: these centred on the Simulium damnosum and S. neavei complexes because they include vectors of human onchocerciasis. Other species studied included vectors of Onchocerca gutturosa and avian Haematozoa. Techniques for collecting the various developmental stages of African simuliids are discussed. Adult simuliids may be kept singly in small containers, or together in larger vessels, and fed on sugar-solutions, fruits or flowers. Only two members of the S. damnosum complex (one not yet identified) and one S. bovis complex species are so far known to mate in captivity. Many African simuliids have been blood-fed in captivity from sources including blood-soaked filter paper, birds, rabbits, man and the McMahon feeding apparatus, but results have been inconsistent and a few species have rarely taken blood. Blood/sugar mixtures have given better results, but in most cases normal oogenesis has not subsequently occurred. Some African simuliids lay eggs when kept in tubes, while others do so if placed in water and/or after decapitation. Although some females either fail to oviposit or retain many eggs, others lay a large number, but usually not all develop. The eggs of one species have been temporarily stored at low temperatures, but required protection from fungal attack. Larval development requires adequate water-flow and correct hydro-chemical conditions. Various rearing techniques are described. An apparatus in which the conditions of the water may be regulated has recently been modified for use with the S. damnosum complex and three members of the complex have been reared successfully so far. The Kibwezi form of the S. damnosum complex has been successfully induced to complete every stage of its life-cycle in the laboratory. The reduction of wastage throughout the life-cycle is now being attempted.

Africa↗

Development of Rhodnius prolixus (Hemiptera: Reduviidae) under constant and cyclic conditions of temperature and humidity.

Development of Rhodnius prolixus after eclosion until the adult stage was studied at constant temperatures (T), 15, 20, 25, 28, 35 C, and relative humidities (RH), 75, 86 and 97%, and fluctuating (16/8 hr) temperatures, T I/II, 15/28 C, 20/25 C, 25/28 C and 25/35 C, and relative humidities, RH I/II, 86/75% and 97/75%. Eclosion or molting were not observed at 15 C and 86 or 97% RH, respectively. At 35 C and 75% RH only few insects molted. By alternating T I/II, 15/28 C and 25/35 C, insects developed at high frequency. Cumulating the average lengths of the interphases within independent groups for each instar, R. prolixus reached the adult stage most rapidly (86.7 days) and at highest frequency per instar (mean: 91.8%) at 28 C and 75% RH. Under fluctuating T I/II, development was completed within 100 days or less at 25/28 C and 25/35 C with high rates of hatch and molting. Development was slowest at fluctuating TI/II, 15/28 C and 20/25 C (>185 days), and at constant 20 C (>300 days). Mortality was higher at constant 97% RH or fluctuating RH I, 97%, than at constant or fluctuating 86% RH. Refeeding was minimal at optimal conditions of T and RH for development. The most refeeding was observed at a constant 35 C.

Animals↗

Contribution to the sand fly fauna (Diptera: Phlebotominae) of Rio Grande do Sul, Brazil and Leishmania (Viannia) infections.

American cutaneous leishmaniasis (ACL) is endemic in the State of Rio Grande do Sul, Brazil. As reports of nearby hospitals suggest, the Parque Estadual do Turvo seems to serve as a source for the disease. During three months from November 1996 to February 1997 we collected, in this park, 2,228 sandflies (10 Lutzomyia species and 2 6species). We applied the polymerase chain reaction to 920 females which belong to the following species: Lutzomyia migonei, Lu. pessoai, Lu. fischeri, Lu. misionensis, Lu. lanei, Lu. neivai, Lu. shannoni, and Lu. monticola, in an attempt to verify natural infection by Leishmania (Viannia), the causative agent of ACL. Le. (Viannia) infections were demonstrated by DNA amplification from two Lu. pessoai and one Lu. misionensis female. Lu. pessoai have been found with leptomonas in the gut believed to be Le. (V.) braziliensis in other endemic areas of northeastern and southeastern Brazil. However, Lu. misionensis has never been found carrying a natural infection of Le. (Viannia).

Animals↗

Expression of matrix metalloproteinases in a series of 12 meningiomas.

The expression of metalloproteinases was evaluated in a series of 12 meningiomas of various histological subtypes including 3 meningotheliomatous, 3 fibroblastic, 4 transitional and one psammomatous meningioma (WHO grade I) as well as one anaplastic meningioma (WHO grade III). No gelatinolytic activity could be detected in all tumor samples pointing towards no or very low activity of both MMP-2 and MMP-9. At least MMP-2 mRNA could be found in 10 out of 12 tumor samples by the reverse transcription PCR method (RT-PCR) followed by electrophoresis on silver-stained polyacrylamide gels, which allows the detection even of small traces of a specific mRNA. The PCR products were identified as MMP-2 sequences without introns (mRNA-derived) by direct sequencing, thereby demonstrating a low transcriptional activity of the gene. The translation of these mRNAs, however, did not result in amounts of protein detectable by immunohistochemistry or Western blotting. Therefore, neither MMP-2 nor MMP-9 should play a major role for tumor growth within dura mater or bone structures or for brain infiltration in our tumor series. Therefore, other mechanisms must be responsible for extracellular matrix degradation at least in a fraction of meningiomas.

Gene Expression Regulation, Enzymologic↗