Cholecystokinin CCK(B) receptor mRNA isoforms: expression in schizophrenic brains.

In the light of earlier findings of reduced cholecystokinin (CCK) peptide and CCK mRNA levels in the cerebral cortex, we have used in situ hybridization to examine possible regulation of mRNAs coding for two isoforms of the CCK(B) receptor in frontal cortex (Brodmann's area 10) of schizophrenic patients. The hybridizations revealed a 51% decrease of the full length CCK(B) receptor mRNA in the outer layers (II-III) of the frontal cortex. The corresponding alterations for the truncated isoform were a 65% reduction in the outer layers and a 62% reduction in the inner layers (IV-VI) of the frontal cortex. This strengthens the hypothesis that CCKergic transmission in this part of the brain is involved in the pathophysiology of schizophrenia.

Multilayers of cells growing on a permeable support. An in vitro tumour model.

A system for growing three-dimensional cell culture has been developed which exhibits many features of solid tumours. This system comprises cells growing as a thick mat on a semipermeable membrane suspended in stirred media. SiHa cells grown as these multilayered cell cultures (MCCs) have produced cultures up to ca. 20 cell diameters in thickness. The MCCs, like solid tumours growing in vivo. develop diffusion-dependent necrosis and hypoxia and the cell packing acts as a barrier to the diffusion of drugs. These cultures can, therefore, be used to study aspects of cancer biology and drug transport that are difficult to study using other techniques.

The effect of thalidomide on experimental tumors and metastases.

Thalidomide has recently been shown to antagonize basic fibroblast growth factor-induced angiogenesis in the rat corneal micropocket assay. We have investigated the effect of thalidomide on growth, radiosensitivity and metastasis in murine SCCVII and Lewis Lung tumors. We found that daily thalidomide administration (0.77 mmol/kg/day, i.p.) does not alter primary tumor growth of SCCVII or Lewis Lung tumors. However, thalidomide administration does reduce radiosensitivity of the Lewis Lung tumor, and increases its sensitivity to combined treatment with radiation and the bioreductive cytotoxin tirapazamine. These findings suggest that thalidomide is elevating tumor hypoxia in the Lewis Lung tumor, presumably via an anti-angiogenic mechanism. We also found that thalidomide administration reduces the incidence of lung metastases from primary Lewis Lung tumors. Thalidomide may therefore have utility in the management of solid tumors, especially when combined with drugs that are selectively toxic to cells at reduced oxygen tension (e.g. bioreductive cytotoxins).

Separation of Three Species of Ditylenchus and Some Host Races of D. dipsaci by Restriction Fragment Length Polymorphism.

This study examined the ribosomal cistron of Ditylenchus destructor, D. myceliophagus and seven host races of D. dipsaci from different geographic locations. The three species showed restriction fragment length polymorphisms (RFLPs) in the ribosomal cistron, the 18S rDNA gene, and the ribosomal internal transcribed spacer (ITS). Southern blot analysis with a 7.5-kb ribosomal cistron probe differentiated the five host races of D. dipsaci examined. Polymerase chain reaction (PCR) amplification of the ITS, followed by digestion with some restriction endonucleases (but not others), produced restriction fragments diagnostic of the giant race. Because the PCR product from D. myceliophagus and the host races of D. dipsaci was about 900 base pairs and the ITS size in D. destructor populations was 1,200 base pairs, mixtures of populations could be detected by PCR amplification. ITS fragments differentiated between D. dipsaci and Aphelenchoides rhyntium in mixed populations. This study establishes the feasibility of differentiation of the host races of D. dipsaci by probing Southern blots with the whole ribosomal cistron.