Rat brain glutathione-S-transferases are rich in Yb type subunits with major RNA transcripts coding for a relatively uncommon Yb3 form. The Yb-containing isoenzymes of brain cytosol bind glucocorticoids and are covalently labeled with dexamethasone 21-methanesulfonate. Certain neurotransmitters, hormones, and drugs, such as serotonin, dopamine, glucocorticoids, thyroxine, apomorphine, and benzodiazepine derivatives, are effective inhibitors of brain glutathione transferase activity. Immunocytochemical studies show that Yb forms are localized in ependymal cells, subventricular zone cells, astrocytes, tanycytes, and astrocyte foot processes on blood vessels, but Yb was not detected in oligodendrocytes or neurons. Based on their localization and binding properties, brain glutathione-S-transferases have the potential to function in intracellular binding of a variety of compounds and thereby govern their uptake and release in brain, transport to neurons, as well as in their detoxification.

Glutathione-S-transferase Yb subunits were recently identified in rat brain and localized to astrocytes, ependymal cells lining the ventricles, subventricular zone cells, and tanycytes. Another isoform, Yp (pi family), was detected in rat brain by immunoblotting, and its mRNA was detected by Northern hybridizations. Double immunofluorescence localized Yb and Yp in different glial cells. The strongly Yp-positive cells were identified as oligodendrocytes by virtue of their arrangement in rows in white-matter tracts, colocalization in strongly carbonic anhydrase-positive cells, and association with myelinated tracts in the corpus striatum. Ependymal cells in the choroid plexus and ventricular lining were also strongly Yp positive, whereas Yb was not detected in the choroid plexus. The occurrence of Yp at low levels in astrocytes was indicated after immunostaining by a sensitive peroxidase-antiperoxidase method, which revealed weak staining of those cells in the molecular layer of the cortex. The data suggest that Yb and Yp subunits are primarily localized to astrocytes and oligodendrocytes, respectively, and that both are absent from neurons. The glutathione-S-transferase in oligodendrocytes may participate in the removal of toxins from the vicinity of the myelin sheath. The finding of glutathione-S-transferases in ependymal cells and astrocytes in the brain also suggests that this enzyme could be a first line of defense against toxic substances.

Background. The authors analyzed the clinical usefulness of glutathione‐S‐transferase‐π (GST‐π) as a tumor marker in patients with oral cancer. Methods. GST‐π levels in plasma of 61 patients with oral squamous cell carcinomas, 65 patients with benign oral diseases, and 78 healthy subjects were investigated with the sandwich enzyme‐immunoassay (EIA) system. Results. Elevated GST‐π levels in plasma were observed in patients with oral cancer, but patients with benign oral diseases had normal GST‐π levels. More than 70% of patients with Stage III or IV oral cancer and more than 50% of those with Stage I and II disease had elevated levels of GST‐π in plasma. Elevated levels of GST‐π in plasma were also discovered in most patients with tumor recurring after surgery before recurrence was detected clinically. GST‐π also was found to be a useful marker for evaluating the response to chemotherapy, for monitoring postoperative tumor resectability or tumor burden, and for predicting the recurrence of tumor in patients with oral cancer. Conclusions. GST‐π is considered to be a useful aid for early diagnosis, predicting tumor extent, and determining parameters of treatment efficacy and prognosis for oral cancer.

We attempted to detect cytomegalovirus DNA (CMV-DNA) in the sera of four leukaemia patients who underwent an allogeneic bone marrow transplant (BMT), in six leukaemia patients who suffered from pneumonia and in 16 healthy subjects, using the polymerase chain reaction (PCR). Three of the four BMT patients subsequently developed CMV pneumonia. In two cases, CMV-DNA was detected in the sera at about the time the pneumonia occurred, and the amount of DNA increased with disease progression. The serum of the third patient became positive for CMV-DNA before he developed pneumonia. The fourth patient did not develop CMV pneumonia, but his urine became persistently positive for CMV-DNA soon after the BMT, whereas the serum was negative. A relationship was found between the occurrence of pneumonia and the serum level of CMV-DNA. CMV-DNA was also detected in three of six pneumonia patients whose anti-CMV IgM antibodies were elevated in the circulation. Sera from the 16 normal subjects were negative for CMV-DNA, regardless of their being seropositive or seronegative for CMV. While it had been previously thought that CMV did not exist in serum, we detected CMV-DNA in serum by PCR in the active disease stage. Our results suggest that PCR would be useful for the early diagnosis of CMV pneumonia and in monitoring its course.

Specific cDNA probes were used to determine steady-state mRNA levels for the multiple glutathione S-transferases in primary hepatocyte cultures. In the first 24 hr of culture, gene transcripts for the Ya family decreased sharply, Yb3 disappeared completely, but changes in levels of mRNA for Yb1 and Yb2 were smaller. These results suggest that the isoenzymes are regulated independently. Yp mRNA, which is present at greatly elevated levels in hyperplastic nodules and hepatocellular carcinomas but not in normal adult livers, was hardly detectable in freshly isolated hepatocytes, but Yp transcripts rapidly accumulated in the first 24 hr in culture and continued to increase for 72 hr. Decreased levels in Ya and Yc and increases in Yp were detected by immunoblotting methods, indicating that translation products changed together with mRNA levels in the cultured cells. The appearance of Yp transcripts in hepatocytes was effectively blocked by addition of dexamethasone to the culture medium. Elevations of Yp levels are characteristic of the cell culture system and factors regulating Yp transcription in nodules and carcinomas may also be operative in cultured hepatocytes.