The role of CD8+ CD40L+ T cells in the formation of germinal centers in rheumatoid synovitis.

In rheumatoid synovitis, lymphocytes can be arranged in follicular structures resembling secondary lymphoid follicles. To understand the organizing principles of this ectopic lymphoid tissue, the cellular components contributing to synovial follicles were examined. In 9 of 24 synovial tissue biopsies, lymphoid aggregates were found consisting of CD4+ T cells and CD20+ B cells. In four of the nine patients, the follicular centers were occupied by CD23+ CD21+ cellular networks representing follicular dendritic cells involved in germinal center reactions. In five patients, CD23+ cells were absent from the centers of the aggregates, suggesting that fully developed germinal centers are generated in only a subset of patients. To identify factors involved in the regulation of the synovial microarchitecture, cell populations contributing to the follicles were quantified by digital image analysis of immunostained tissue and by flow cytometry of tissue-derived lymphocytes. Proportions of CD4+, CD20+, and CD68+ cell subsets were surprisingly invariant, irrespective of the presence or absence of CD23+ follicular dendritic cells. Instead, tissue biopsies with CD23+ germinal center-like regions could be distinguished from those with CD23- T cell-B cell aggregates by a fourfold increase in the frequency of tissue-infiltrating CD8+ T cells, a fraction of which expressed CD40 ligand (CD40L). The data suggest a previously unsuspected role of CD8+ lymphocytes in modulating germinal center formation and raise the possibility that CD8+ CD40L+ T cells are involved in aggravating pathologic immune responses in rheumatoid synovitis.

[Indication status of chromosome analysis in the diagnostic evaluation of recurrent abortions]. / Indikationsstellung zur Chromosomenanalyse bei der diagnostischen Abklärung wiederholter Aborte.

Parental (balanced) chromosome anomalies are one possible cause for the recurrence of miscarriages in the first three months of pregnancy. The preparation of karyotypes of the patients is thus an integral part of diagnostic clarification, yet the question of the relative importance of this examination among the range of diagnostic possibilities is the subject of controversy. This article reports on 112 couples examined cytogenetically over a period of four years as a result of recurrent miscarriages. In 6 cases (5.4%), chromosome aberrations were established that can be regarded as the cause of the recurrent miscarriages. With regard both to the examinations reported here and to the results published in recent literature, chromosome analysis of both partners is recommended after the second miscarriage as part of the first diagnostic steps taken.

[Are there genetic risk factors in the occurrence of choriocarcinoma?]. / Gibt es genetische Risikofaktoren für das Auftreten eines Chorionkarzinoms?

Now that we know about the genetic production mechanisms of diseases of the trophoblast, interest is concentrated on the question which risk factors can produce a disposition in the patient - seen from a clinico-genetic angle - towards malignancy of a complete mole. Many years before the genetic interrelations became known, there had been discussions on blood relationship as a possible aetiological factor in the production of chorionic carcinoma. Since consanguinity in preceding generations can lead to a selection of certain genotypes, this question was reexamined on a limited patients material (10 patients with chorionic carcinoma and 11 with mole). The negative result of this study contradicts - similar to other recent publications on this subject - the hitherto frequently advanced hypothesis that homozygotism is responsible, for a recessive "onko" gen, for rendering a complete mole malignant. Recent investigations, for example, point to a close correlation between the presence of a Y chromosome in a complete mole, and malignancy.

[Holoprosencephaly--clinical picture and genetic counseling in 6 cases]. / Holoprosenzephalie--Klinisches Erscheinungsbild und genetische Beratung in sechs Fällen.

Inadequate midfacial and forebrain development may result from constitutional chromosome aberrations, gene defects and, possibly, from as yet unidentified terato-genetic agents. The spectrum of clinical manifestations ranges from cyclopia with grossly incomplete organogenesis of the forebrain to apparently minor deviation from normal midface morphogenesis presenting as hypotelorism or absence of the philtrum. Such minor facial dysmorphias may, however, be likewise accompanied by severe anomaly in brain development and function. We report six cases of holoprosencephaly defects in children without demonstrable chromosomal anomalies. The presenting clinical symptoms in these cases were anomalies of cranio-facial shape, hypotelorism; nasal and ocular malformations, as well as median clefts. Some cases presented additional defects in extra craniofacial regions. Two infants who survived for several hours showed evidence of forebrain defects on CT-scans. Three of the cases suggest autosomal-recessive inheritance with 25% recurrence risk on the basis of proven or highly probable parental consanguinity. The remaining, presumably sporadic cases carry a low empirical recurrence risk. Three of the six cases received direct or indirect hormone treatments during early pregnancy.

[Genetics of hydatidiform moles]. / Zur Genetik der Blasenmolen.

Newer genetic investigations show that the complete or classical hydatidiform mole has in over 90% of the cases a diploid female set of chromosomes which is exclusively of paternal origin. The 23 X sperm genom is doubled and the nucleus of the ovocyte is degenerated. In contradistinction the nucleus of the ovocyte persists in partial moles. The normal ontogenesis is also disturbed by a preponderance of paternal genetic material. By melting of 2 instead of 1 paternal germ cell (Dispermia) the genom of partial moles is to 1/3 of maternal and to 2/3 of paternal origin. The triploid set of chromosomes shows usually 69xxy. Whereas the potential of malignancy of partial moles is low a choriocarcinoma results from 2 to 10% of the complete moles. Responsible maybe recessive hereditary mutations of growth controlling genes, which are present in complete moles in a homozygote form due to the doubling of a single paternal set of chromosomes. Total absence of the growth controlling loci of these genes maternally permits an unhibited expression of the growth controlling paternal genes.

Decreased oxygen supply enhances growth in culture of human mid-trimester amniotic fluid cells.

Human mid-trimester amniotic fluid cells were cultivated under conditions of decreased oxygen supply. Compared to control cultures the low-oxygen group showed improved growth which was quantitated by three independent assays (1) direct cell counts, (2) bromodeoxyuridine (BrdU)-Hoechst flow-cytometry, and (3) cloning efficiency. The growth promoting effects of lowered oxygen hold for all major morphologic categories of amniotic fluid cells.

The ultrastructure of oligodendrogliomas.

Seven Oligodendrogliomas (2 with uniform cell type, 4 with cellular or tissue variability, and 1 with glioblastomatous changes) were examined ultrastructurally. The tumor cells were of two principal types with morphologic transitions between the two main types. The two principal cell types were identified as type 1 (undifferentiated) and type 2 (differentiated) on the basis of the number of anaplastic cells in an individual tumor and on the observations of Mori and Leblond (21) on non-neoplastic oligodendrocytes. Most of the tumor cells in all tumor exhibited similar histologic and ultrastructural characteristics including their arrangement and their tendency to form cytoplasmic processes which sometimes formed short stacks. These features were also recognizable in the glioblastomatous example and confirmed the presence of an oligodendroglial component. In addition to these characteristics, an increase in size and number of mitochondria, abundant intracytoplasmic structures, microtubules were regularly present in virtually all tumor cells. Cells rich in cytoplasmic filaments were present. These were identified as reactive astrocytes or as oligodendroglial tumor cells. Thus neither cytoplasmic filaments nor microtubules appear to be specific morphological markers for oligodendroglia or astrocytes; only the predominance of one of these structures permits cytogenetic identifications. The cytologic characteristics are not specific morphologic markers; however, recognition of their presence provides important diagnostic information.