Treatment of accidental intakes of plutonium and americium: guidance notes.

The scientific basis for the treatment of the contamination of the human body by plutonium, americium and other actinides is reviewed. Guidance Notes are presented for the assistance of physicians and others who may be called upon to treat workers or members of the public who may become contaminated internally with inhaled plutonium nitrate, plutonium tributyl phosphate, americium nitrate or americium oxide.

Cloning and expression of a novel type (III) of human gamma-glutamyltransferase truncated mRNA.

We report the characterization of a novel human gamma-glutamyltransferase mRNA type. This type III mRNA differs from type I and type II mRNAs previously described by several point mutations and the presence of an unspliced 81 bp intron in the open reading frame. Further, type III mRNAs are truncated ones and are tissue and pathology specifically expressed. In fact, type III mRNAs are present in human placenta, sigmoid, lung and in 50% of acute lymphoblastic leukemia blood cells but they are never found in healthy lymphocytes.

Gamma-glutamyltransferase: nucleotide sequence of the human pancreatic cDNA. Evidence for a ubiquitous gamma-glutamyltransferase polypeptide in human tissues.

gamma-Glutamyltransferase (GGT, EC 2.3.2.2) is an enzyme involved in glutathione metabolism and drug and xenobiotic detoxification. Using human hepatoma Hep G2 GGT cDNA as probe, we isolated a cDNA from a human pancreatic cDNA library. Analysis of the nucleotide sequences revealed a 2244-bp insert that includes an open reading frame of 1710 bp, encoding a protein identical to the Hep G2 and human placenta GGTs. Similarly, the 5' untranslated region, though shorter, is highly homologous to that of Hep G2 cDNA. These data suggest strongly that the same gene encodes human GGT in the placenta, Hep G2 and the pancreas. We further studied the distribution of the corresponding mRNA, called type I mRNA, in different human tissues. Using a highly sensitive method associating reverse transcription with specific amplification by polymerase chain reaction, cDNA was synthesized from total RNA isolated from the tissues and GGT specific fragments were amplified. We observed the presence of a specific cDNA fragment corresponding to the type I mRNA in the human tissues and cells tested, providing the evidence for a ubiquitous expression of this GGT mRNA in human tissues.

Expression of multiple gamma-glutamyltransferase genes in man.

In clinical and pharmacological laboratories, the assay for gamma-glutamyltransferase (GGT) activity is an important diagnostic test, but one with high biological variability. Although the human genome contains multiple GGT genomic sequences, the diagnostic tests generally assume that only a single GGT gene is active. In the current study, segments encompassing parts of seven different potential human GGT genes have been molecularly cloned. Based on sequence determination of exons within these distinct genomic clones, oligonucleotide primers were designed which would prime and PCR-amplify putative mRNA of all seven potential GGT genes, if expressed. Gene-specific oligonucleotide probes were then utilized to assay the transcriptional status of the seven possible GGT genes in a wide variety of human RNAs. Our results show that a single GGT gene exhibits ubiquitous expression in all RNAs tested, including those from fetal and adult liver. A surprisingly large number of four additional GGT genes is expressed in man. Interestingly, these novel GGT genes are expressed in a tissue-restricted manner, which suggests that their corresponding gene products exhibit distinct functions in these specific tissues.

Localization of a gamma-glutamyl-transferase-related gene family on chromosome 22.

A gene family encompassing a minimum of four genes or pseudogenes for gamma-glutamyl transferase (GGT; EC 2.3.2.2) is present on chromosome 22q11. We have previously isolated a cDNA related to GGT but clearly not belonging to its gene family. The chromosomal location of this related gene, GGTLA1, has been determined by both isotopic and fluorescence in situ hybridization to metaphase cells and by Southern blot analysis of somatic cell hybrid DNAs. We show that GGTLA1 is part of a distinct gene family, which has at least four members (GGTLA1, GGTLA2, GGTLA3, GGTLA4). At least two loci are located on chromosome 22 within band q11 and proximal to the chronic myelogenous leukemia (CML) breakpoint in BCR (breakpoint cluster region gene). At least one other member is located more distally between the breakpoints found in Ewings sarcoma and CML. Some of the GGT and GGTLA family members are located on NotI restriction enzyme fragments of a similar size. Combined results indicate that a segment of human chromosome 22q11 has undergone large-scale amplification events relatively recently in evolution.

Prolactin levels in patients with systemic lupus erythematosus: a case controlled study.

Recent accumulated evidence suggests that prolactin (PRL) is an important immunomodulator and might have a role in the pathogenesis of systemic lupus erythematosus (SLE). Our aim was to assess the frequency of hyperprolactinemia in women with SLE and to evaluate its correlation with disease activity. PRL plasma levels were measured in 36 women with SLE and 20 age-matched healthy controls. We excluded patients with renal and/or hepatic failure, pregnant patients and patients taking drugs which could increase PRL levels. Disease activity was assessed using the SLE disease activity index (SLEDAI). Patients with a score > 10 were considered active. In patients and controls, PRL levels were determined by radioimmunoassay (RIA) during the first part of the menstrual cycle (between the 5th and 8th day) (normal value < 20 ng/ml). Ten of 36 (27.7%) SLE patients had high PRL levels (> 20 ng/ml). The mean PRL level was higher in SLE than in the control group (17.1+/-12.9 s.d. vs 9.9+/-3.5, P < 0.01). Patients with active disease had a trend to higher mean PRL levels than inactive patients although this difference was not statistically significant (21.1+/-4.8 vs 14.8+/-6.9, P = 0.09). No correlation was found between PRL levels and SLEDAI score. Furthermore, no significant correlation was found between PRL levels and any clinical or serological finding.