Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth.

Administration of active TG2 to two different in vitro angiogenesis assays resulted in the accumulation of a complex extracellular matrix (ECM) leading to the suppression of endothelial tube formation without causing cell death. Matrix accumulation was accompanied by a decreased rate of ECM turnover, with increased resistance to matrix metalloproteinase-1. Intratumor injection of TG2 into mice bearing CT26 colon carcinoma tumors demonstrated a reduction in tumor growth, and in some cases tumor regression. In TG2 knockout mice, tumor progression was increased and survival rate reduced compared to wild-type mice. In wild-type mice, an increased presence of TG2 was detectable in the host tissue around the tumor. Analysis of CT26 tumors injected with TG2 revealed fibrotic-like tissue containing increased collagen, TG2-mediated crosslink and reduced organized vasculature. TG2-mediated modulation of cell behavior via changes in the ECM may provide a new approach to solid tumor therapy.

Genetic diversity of the "Mediterranean" glucose-6-phosphate dehydrogenase deficiency phenotype.

Genetic diversity of the "Mediterranean" phenotype of G-6-PD (glucose-6-phosphate dehydrogenase) deficiency was revealed when detailed studies were performed on blood specimens from 79 Greek males with G-6-PD levels 0-10% of normal. Four different mutants were found to be responsible for the severely deficient phenotypes: two mutants. G-6-PD U-M (Union-Markham) and G-6-PD Orchomenos, were distinguishable by electrophoresis, while the other two. G-6-PD Athens-like and G-6-PD Mediterranean, were distinguishable on the basis of their kinetic characteristics. Of the kinetic tests applied, the most useful for differentiating the variants were those measuring utilization rates of the analogue substrates deamino-NADP, 2-deoxyglucose-6-phosphate, and galactose-6-phosphate. Among unrelated males with severe G-6-PD deficiency, the relative frequencies of the four variants were: G-6-PD U-M. 5%; G-6-PD Orchomenos, 7%; G-6-PD Athens-like, 16%; G-6-PD Mediterranean, 72%. Genetic, biochemical, and clinical implications of the findings are discussed.

Tissue transglutaminase in tumour progression: friend or foe?

Basic biological processes in which tissue transglutaminase (TG2, tTG) is thought to be important including apoptosis, cell adhesion and migration, ECM homeostasis and angiogenesis are key stages in the multistage tumour progression cascade. Studies undertaken with primary tumours and experimental models suggest that TG2 expression and activity in the tumour body and surrounding matrix generally decreases with tumour progression, favouring matrix destabilisation, but supporting angiogenesis and tumour invasion. In contrast, in the secondary metastatic tumour TG2 is often highly expressed whereby its potential roles in cell survival both at the intra- and extracellular level become important. In the following review the underlying molecular basis for the selection of these different phenotypes in tumour types and the anomaly for the requirement of TG2 is discussed in relation to the complex events of tumour progression.

The linkage relationships of the beta and delta hemoglobin genes.

Three new families providing information on the linkage relationships between the delta and beta hemoglobin loci are reported. One of the families contains the first reported individuals having Hb S and Hb B2 in coupling. Analysis of the information found in the literture is compatible with a recombination frequency of 3 percent between beta thalassemia and the delta structural locus. This highly improbable frequency might be explained by either diagnostic errors or paternity problems in the pedigrees containing recombinants or by the conceivable possibility that certain thalassemia genes increase the probability for recombination in the chromosomal region containing the non alpha globin genes.

A case of Opisthorchis felineus infestation in a pilot from Greece.

We describe the case of a 28-year-old man from Greece with Opistorchis felineus infestation. The patient presented with intense abdominal pain, bilious emesis and eosinophilia. He probably acquired the infection overseas, since he was a commercial airline pilot who used to fly to endemic areas and to consume raw or undercooked fish. He was successfully treated with praziquantel administered in divided doses over a single day. Opisthorchiasis is common to eastern Europe and areas of the former Soviet Union, but extremely rare in Greece. Medical personnel should be cognizant of this parasitic infection, since world travel can spread it to areas of the world unaccustomed to it.

Blood lymphocyte subpopulations studied with monoclonal antibodies in aleukaemic stages of mycosis fungoides.

Peripheral blood lymphocytes from 21 patients with aleukaemic stages of mycosis fungoides were studied with monoclonal T cell antibodies. Patients with erythematous eruptions or infiltrated plaques (group I) had a higher percentage of OKT4+ cells than patients with a tumorous stage (group II) or normal subjects (p = 0.05). OKT8+ cells were decreased in group I patients whereas in group II they were usually normal or increased (p less than 0.02). These data indicate that with advancing stage of the disease a different pattern of imbalance of T-cell subsets is being established.