The 5' untranslated region of the At-P5R gene is involved in both transcriptional and post-transcriptional regulation.

The steady-state level of transcripts coding for the pyrroline-5-carboxylate reductase of Arabidopsis (At-P5R) increased under salt and heat stress, mainly because of an enhanced mRNA stability. However, the At-P5R protein level was not induced, and its translation was inhibited at initiation stage and probably also at later stages. Replacement of the 5' untranslated region (5'UTR) and beta-glucuronidase (gus) fusion analysis revealed that the first 92 bp region of the At-P5R 5'UTR was sufficient to mediate transcript stabilization and translation inhibition during salt and heat stresses. Furthermore, the first 92 bp region of the At-P5R 5'UTR was also involved in transcription efficiency in a promoter-dependent manner. The results demonstrated that the stress regulation of At-P5R is complex and involves the 5'UTR which acts at three levels, partly in opposing directions.

Microsatellite instability as a potential marker for poor prognosis in adult T cell leukemia/lymphoma.

Microsatellite instability (MSI) represents a replication error resulting from the dysfunction of mismatch repair gene products. In this study, MSI was analyzed in 18 patients with various subtypes of adult T cell leukemia/lymphoma (ATL/L). Using six different microsatellite loci, we defined MSI as positive when replication errors were observed in at least two loci. The MSI was positive in four cases (22.2%)with acute type ATL, who tended to show more prognostically unfavorable factors and shorter overall survival. These results suggest that genomic instability may be associated with tumor progression rather than the development of ATL/L itself. In addition, the presence of the MSI at initial presentation could appear to warrant consideration as an additional prognostically unfavorable factor.

Developmental regulation of pyrroline-5-carboxylate reductase gene expression in Arabidopsis.

At-P5R, a gene encoding the last enzyme of the proline (Pro) biosynthetic pathway in Arabidopsis thaliana, is developmentally regulated. To characterize the cis elements responsible for this developmental regulation, a series of 5' deletions of the At-P5R promoter were transcriptionally fused to a beta-glucuronidase (GUS)-coding region and transformed into Arabidopsis. The complete promoter of At-P5R directs strong GUS activity in root tips, the shoot meristem, guard cells, hydathodes, pollen grains, ovules, and developing seeds, all of which contain rapidly dividing cells and/or are undergoing changes in osmotic potential. This expression pattern is consistent with the function of Pro as an energy, nitrogen, and carbon source and as an osmoticum in response to dehydration. Promoters longer than 212 base pairs (bp) showed the same expression pattern, whereas those shorter than 143 bp did not direct any detectable GUS activity in any organs. This suggests that a 69-bp promoter region located between -212 and -143 bp is necessary to establish the tissue-specific expression of At-P5R during development. The Pro content measured in different organs suggests that, in addition to transcriptional control of the biosynthetic pathway, the transport of Pro may play a role in its distribution within Arabidopsis. Several aspects of the relationship between Pro metabolism and plant physiology are discussed.

Abscisic acid-independent and abscisic acid-dependent regulation of proline biosynthesis following cold and osmotic stresses in Arabidopsis thaliana.

The role of the phytohormone abscisic acid (ABA) in the regulation of proline synthesis was investigated by following the expression of the At-P5S and At-P5R proline biosynthesis genes in Arabidopsis thaliana wild type, in an ABA-deficient aba1-1 mutant as well as in ABA-insensitive abi1-1 and abi2-1 mutants after ABA, cold and osmotic stress treatments. In wild-type and in ABA mutant seedlings, 50 microM ABA or osmotic stress treatment triggered expression of At-P5S, whereas At-P5R accumulation was scarcely detectable. Expression of either gene was mediated by endogenous ABA since transcript levels were similar in wild-type and in ABA-deficient mutant plants. Proline accumulated to a greater extent after osmotic stress than upon ABA or cold treatment. Thus, ABA-treated abi1-1 mutant plants accumulated less proline than the ABA-treated wild type. Upon salt stress, proline accumulated to a lesser extent in aba1-1 and abi1-1 mutant plants, suggesting an indirect role of ABA on proline accumulation during salt adaptation of the plant. These results indicate that the expression of the genes of the proline biosynthetic pathway is ABA independent upon cold and osmotic treatments, although their expression can be triggered by exogenously applied ABA. However, the endogenous ABA content may affect proline accumulation upon salt stress, suggesting post-transcriptional control of proline biosynthesis in response to NaCl.

Environmental and developmental signals modulate proline homeostasis: evidence for a negative transcriptional regulator.

In many plants, osmotic stress induces a rapid accumulation of proline through de novo synthesis from glutamate. This response is thought to play a pivotal role in osmotic stress tolerance [Kishor, P. B. K., Hong, Z., Miao, G.-H., Hu, C.-A. A. and Verma, D. P. S. (1995) Plant Physiol. 108, 1387-1394]. During recovery from osmotic stress, accumulated proline is rapidly oxidized to glutamate and the first step of this process is catalyzed by proline oxidase. We have isolated a full-length cDNA from Arabidopsis thaliana, At-POX, which maps to a single locus on chromosome 3 and that encodes a predicted polypeptide of 499 amino acids showing significant similarity with proline oxidase sequences from Drosophila and Saccharomyces cerevisiae (55.5% and 45.1%, respectively). The predicted location of the encoded polypeptide is the inner mitochondrial membrane. RNA gel blot analysis revealed that At-POX mRNA levels declined rapidly upon osmotic stress and this decline preceded proline accumulation. On the other hand, At-POX mRNA levels rapidly increased during recovery. Free proline, exogenously added to plants, was found to be an effective inducer of At-POX expression; indeed, At-POX was highly expressed in flowers and mature seeds where the proline level is higher relative to other organs of Arabidopsis. Our results indicate that stress- and developmentally derived signals interact to determine proline homeostasis in Arabidopsis.

Isolation, characterization, and chromosomal location of a gene encoding the delta 1-pyrroline-5-carboxylate synthetase in Arabidopsis thaliana.

A full-length cDNA and the corresponding At-P5S gene encoding the first enzyme of the proline biosynthetic pathway, the delta 1-pyrroline-5-carboxylate (P5C) synthetase, were isolated in Arabidopsis thaliana. The At-P5S cDNA encodes a protein of 717 amino acids showing high identity with the P5C synthetase of Vigna aconitifolia. Strong homology is also found at the N-terminus to bacterial and yeast gamma-glutamyl kinase and at the C-terminus to bacterial gamma-glutamyl phosphate reductase. Putative ATP- and NAD(P)H-binding sites are suggested in the At-P5S protein. The transcribed region of the At-P5S gene is 4.8 kb long and contains 20 exons. Southern analysis suggests the presence of only one At-P5S gene in the A. thaliana genome mapped at the bottom of the chromosome two. Expression analysis of At-P5S in different organs reveals abundant At-P5S transcripts in mature flowering plant. Rapid induction of the At-P5S gene followed by accumulation of proline was observed in NaCl-treated seedlings suggesting that At-P5S is osmoregulated.

Dose finding double-blind clinical trial with praziquantel in schistosomiasis japonica patients.

A double-blind clinical trial with praziquantel was carried out. A total of 400 cases was treated with four different dosages, namely, 60, 50, 40 and 30 mg/kg body weight of praziquantel. The drug was given in one day divided into two doses. Identical placebo tablets were used to make up a total of 60 mg/kg. Tolerance was good in all with the exception of one case suffering from asthmatic attack with papule rashes over large area of the body surface. 394 patients were able to be followed up parasitologically six months post-treatment. 79.8%, 71.7%, 78.8% and 70.1% of the patients were negative in the groups with the total dose of 60, 50, 40 and 30 mg/kg respectively. The cure rates as well as the side effects were similar for the four groups. The efficacy was lower than that reported by other authors and the possibility of reinfection was incriminated. In villages with few snails the negative hatching rates in aforementioned four groups were 89.1%, 91.1%, 88.9% and 81.8%, while in villages with abundant snails the rates were 68.2%, 46.5%, 66.7% and 54.8%. The difference between the two areas was statistically significant. Higher efficacy was observed in adults with an average cure rate of 80.0% than in children under 15 years of age, the average cure rate being 57.1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical trial on furapyrimidone in filariasis.

A clinical trial was carried out with furapyrimidone in treating 51 patients with B. malayi, 159 with W. bancrofti and eight with D. perstans using different dosage schedules. Two hundred and fifty-seven cases of Malayan and bancroftian filariasis were treated with hetrazan for comparison. The results based on the microfilaricidal effects suggest that furapyrimidone possesses similar therapeutic effects of hetrazan on Malayan filariasis at eight-month follow-up, and higher incidences of microfilarial disappearance of W. bancrofti infection (81.3%) at six-month follow-up. The drug was also effective against D. perstans. The side effects consisted of fever and irritation of the digestive tract. Fever may be related to allergic reaction of foreign protein from the dead or dying parasites. The side reactions are similar to those of hetrazan and usually not serious. Comparing the efficacies and side effects of furapyrimidone with different dosage schedules the authors recommend regimens of 15 to 20 mg/kg/day for six days in treating Malayan filariasis and 20 mg/kg/day for seven days in treating bancroftian filariasis.

A retrospective survey on side effects of praziquantel among 25,693 cases of schistosomiasis japonica.

A retrospective survey involving 25,693 persons was carried out in four provinces and the city of Shanghai, China between December 1981 until May 1982 to document relatively serious side effects of praziquantel used in a mass treatment programme for schistosomiasis japonica. Only 122 or 0.47% of those participating in the study had experienced relatively serious side reactions to the drug. Most had only one kind of side effects but two or more were recorded in a few patients. Neuropsychiatric reactions were seen in 39 persons (0.15%,) cardiovascular reactions in 37 (0.14%), hepatic changes in four (0.02%), dermatological reactions in 18 (0.07%) and delayed reactions resulting in fatigue and inability to work in 29 (0.11%). Praziquantel remains the drug of choice for the treatment of oriental schistosomiasis, it is highly effective and although side effects are minimal, caution should be taken in the treatment of chronic disease with heart failure, ascites, poor hepatic compensation and renal failure.