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R Rai

Publications and source records attributed to R Rai.

At least 73 records · Page 4Linked to original sources

The level of DAL80 expression down-regulates GATA factor-mediated transcription in Saccharomyces cerevisiae.

Nitrogen-catabolic gene expression in Saccharomyces cerevisiae is regulated by the action of four GATA family transcription factors: Gln3p and Gat1p/Nil1p are transcriptional activators, and Dal80 and Deh1p/Gzf3p are repressors. In addition to the GATA sequences situated upstream of all nitrogen catabolite repression-sensitive genes that encode enzyme and transport proteins, the promoters of the GAT1, DAL80, and DEH1 genes all contain multiple GATA sequences as well. These GATA sequences are the binding sites of the GATA family transcription factors and are hypothesized to mediate their autogenous and cross regulation. Here we show, using DAL80 fused to the carbon-regulated GAL1,10 or copper-regulated CUP1 promoter, that GAT1 expression is inversely regulated by the level of DAL80 expression, i.e., as DAL80 expression increases, GAT1 expression decreases. The amount of DAL80 expression also dictates the level at which DAL3, a gene activated almost exclusively by Gln3p, is transcribed. Gat1p was found to partially substitute for Gln3p in transcription. These data support the contention that regulation of GATA-factor gene expression is tightly and dynamically coupled. Finally, we suggest that the complicated regulatory circuit in which the GATA family transcription factors participate is probably most beneficial as cells make the transition from excess to limited nitrogen availability.

Culture Media↗

What's in a name?

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Dermatology↗

A simple splint.

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Finger Injuries↗

Overlapping positive and negative GATA factor binding sites mediate inducible DAL7 gene expression in Saccharomyces cerevisiae.

Allantoin pathway gene expression in Saccharomyces cerevisiae responds to two different environmental stimuli. The expression of these genes is induced in the presence of allantoin or its degradative metabolites and repressed when a good nitrogen source (e. g. asparagine or glutamine) is provided. Three types of cis-acting sites and trans-acting factors are required for allantoin pathway gene transcription as follows: (i) UAS(NTR) element associated with the transcriptional activators Gln3p and Gat1p, (ii) URS(GATA) element associated with the repressor Dal80p, and (iii) UIS(ALL) element associated with the Dal82 and Dal81 proteins required for inducer-dependent transcription. Most of the work leading to the above conclusions has employed inducer-independent allantoin pathway genes (e.g. DAL5 and DAL3). The purpose of this work is to extend our understanding of these elements and their roles to inducible allantoin pathway genes using the DAL7 (encoding malate synthase) as a model. We show that eight distinct cis-acting sites participate in the process as follows: a newly identified GC-rich element, two UAS(NTR), two UIS(ALL), and three URS(GATA) elements. The two GATA-containing UAS(NTR) elements are coincident with two of the three GATA sequences that make up the URS(GATA) elements. The remaining URS(GATA) GATA sequence, however, is not a UAS(NTR) element but appears to function only in repression. The data provide insights into how these cis- and trans-acting factors function together to accomplish the regulated expression of the DAL7 gene that is observed in vivo.

Allantoin↗

A prospective, community-based evaluation of liver enzymes in individuals with hepatitis C after drug use.

Serum alanine transaminase (ALT) levels are used to select hepatitis C virus (HCV)-infected patients for treatment and liver biopsy. However, the natural history of these measurements is poorly understood. To examine the hypothesis that ALT levels vary over time in HCV-infected patients, serial serum ALT levels were prospectively measured in a cohort of 1,235 persons with a history of prior illicit drug use. Over 25 months of follow-up, there was a median of four evaluations per patient. ALT values were higher in 1,164 (94%) HCV-infected individuals than in 71 (6%) HCV-uninfected individuals. The remainder of the analysis focused on these HCV-infected individuals, 647 (62%) of whom had normal ALT values at their initial visit. However, 323 (49%) of these had at least one elevated ALT over the next 25 months. Of the 395 patients whose ALT was initially abnormal, 332 (84%) had at least one normal value over the next 25 months. Overall, among individuals with four or more visits, ALT values were persistently normal in 42%, persistently elevated in 15%, and intermittently elevated in 43%. Because serum ALT levels have high visit-to-visit variability, single assessments should not be used to manage HCV-infected individuals. Further investigation is needed to ascertain the correlation of serial ALT trends with important disease outcomes.

Adult↗

Prolonged lactic acidosis after extended hepatectomy under in situ hypothermic perfusion.

A 46-year-old woman underwent right extended hepatectomy under total vascular occlusion with in situ hypothermic perfusion for colorectal metastasis. Immediately after surgery, she developed severe lactic acidosis, which required correction with sodium bicarbonate solution and ventilatory support for 36 hours. After 2 days, her lactate normalized, and the acidosis was corrected. She made an uneventful recovery. Persistent lactic acidosis after major hepatic resection under in situ hypothermic perfusion is a rare but reversible problem.

Acidosis, Lactic↗

Prospective randomized trial of end-to-end versus side-to-side biliary reconstruction after orthotopic liver transplantation.

BACKGROUND: Biliary reconstruction is the Achilles heel of liver transplantation. Side-to-side anastomosis of donor and recipient bile duct has been claimed to be superior to end-to-end anastomosis in uncontrolled studies. METHODS: A total of 100 consecutive patients undergoing orthotopic liver transplantation were randomized after commencement of the transplant procedure to end-to-end or side-to-side anastomosis. No T tube drainage was employed. Endoscopic retrograde cholangiography was performed 2 weeks after transplantation and findings were reported by an experienced endoscopist as normal, leak or stricture. Median follow-up was 53 (range 35-63) months. RESULTS: Patient age, sex, the graft preservation time and indication for transplantation were similar in both groups. Sixty patients received end-to-end and 40 side-to-side anastomosis. Ten patients randomized to side-to-side anastomosis had an end-to-end procedure. The total number of biliary complications was similar in both groups (end-to-end 32 per cent versus side-to-side 30 per cent) as were the number of leaks (17 versus 18 per cent) and biliary strictures (15 versus 12 per cent). There was no difference in the number of biliary complications that required interventional treatment (22 per cent in both groups). CONCLUSION: Side-to-side and end-to-end biliary anastomosis at liver transplantation are equally effective.

Adolescent↗

Bone density changes in pregnant women treated with heparin: a prospective, longitudinal study.

Heparin plus aspirin significantly improves the live birth rate of women with primary antiphospholipid syndrome. Osteopenia is a major concern of long-term heparin therapy. We studied prospectively the bone mineral density (BMD) changes during pregnancy and the puerperium in 123 women with primary antiphospholipid syndrome treated with low-dose aspirin and subcutaneous low-dose heparin (46 women took unfractionated heparin and 77 took low-molecular-weight heparin). Lumbar spine, neck of femur and forearm BMD were measured, using dual energy X-ray absorptiometry, at 12 weeks gestation, immediately postpartum and 12 weeks postpartum. The mean heparin duration was 27 weeks (range 22-29). During pregnancy, BMD decreased by 3.7% (P < 0.001) at the lumbar spine and by 0.9% (P < 0.05) at the neck of femur with no significant change at the forearm. Lactation was associated with a significant decrease in the lumbar spine and neck of femur BMD. There was no significant difference in BMD changes between the two heparin preparations. No woman suffered a symptomatic fracture. Long-term heparin treatment during pregnancy is associated with a small but significant decrease in BMD at the lumbar spine and neck of femur. This decrease is similar to that previously reported to occur in untreated pregnancies.

Absorptiometry, Photon↗

Results of percutaneous plastic stents for malignant distal biliary obstruction following failed endoscopic stent insertion and comparison with current literature on expandable metallic stents.

BACKGROUND: Endoscopic stenting is an effective method of relieving biliary obstruction in patients with unresectable malignancy. If this fails, optimal management is controversial. Percutaneous insertion of plastic or mesh metal stents has been advocated. AIM: To review the outcome of percutaneous plastic stents and compare this with contemporary data from the literature on mesh metal stenting. PATIENTS AND METHODS: Over a period of six years, 400 patients had attempted endoscopic stenting for distal malignant biliary obstruction which failed in 54 (13.5%). These 54 patients were treated with percutaneously placed plastic stents. RESULTS: Percutaneous stenting was technically successful in 48 patients (89%). Early complications occurred in 13 patients (24%), the commonest being acute cholangitis in seven (12%). There was no procedure-related mortality but a 30-day mortality of 11 % (n = 6). Ten patients (18%) required re-admission after 30 days for stent block (mean period 4 months). Forty-seven patients (87%) were followed up until death. The median survival for the patients undergoing palliative stenting was 3 months (5 days to 17 months). CONCLUSIONS: These results suggest that percutaneous plastic stents can be used safely and effectively in patients who have failed endoscopic stenting.

Adult↗

Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin.

OBJECTIVE: To study the obstetric course of women with a history of recurrent miscarriage associated with antiphospholipid antibodies, lupus anticoagulant and anticardiolipin antibodies, treated with low dose aspirin and low dose heparin. DESIGN: Prospective observational study. SETTING: University based tertiary referral clinic. POPULATION: One hundred and fifty pregnant women with a history of recurrent miscarriage associated with persistently positive tests for antiphospholipid antibodies. METHODS: Lupus anticoagulant was detected using the dilute Russell's viper venom time together with a platelet neutralisation procedure. IgG and IgM anticardiolipin antibodies were detected using a standardised enzyme linked immunosorbent assay. An IgG anticardiolipin level > or = 5 per litre units and an IgM anticardiolipin level > or = 3 per litre units was considered positive. Aspirin (75 mg daily) was commenced at the time of a positive pregnancy test and heparin (5000 units subcutaneously 12 hourly, or enoxaparin 20 mg daily) was started when fetal heart activity was demonstrated on ultrasound. Treatment was stopped at the time of miscarriage or at 34 weeks of gestation. RESULTS: One hundred and seven pregnancies (71%) resulted in a live birth. Forty-one pregnancies (27%) miscarried, the majority in the first trimester. One woman had a stillbirth, and one a premature baby who died in the neonatal period. One pregnancy was terminated for a fetal anomaly. Gestational hypertension complicated 17% (18/108) of ongoing pregnancies and antepartum haemorrhage 7% (8/108). Twenty-six babies (24%) were delivered before 37 weeks of gestation. Fifty women (46%) were delivered by caesarean section. The median birthweight of all live born infants was 3069 g (range 531-4300); however 15% (16/108) of the infants were small for gestational age. CONCLUSION: Combination treatment with aspirin and heparin leads to a high live birth rate among women with recurrent miscarriage and antiphospholipid antibodies. However, successful pregnancies are prone to a high risk of complications during all trimesters. Close antenatal surveillance and planned delivery of these pregnancies in a unit with specialist obstetric and neonatal intensive care facilities are indicated.

Abortion, Habitual↗

Synergistic operation of the CAR2 (Ornithine transaminase) promoter elements in Saccharomyces cerevisiae.

Dal82p binds to the UIS(ALL) sites of allophanate-induced genes of the allantoin-degradative pathway and functions synergistically with the GATA family Gln3p and Gat1p transcriptional activators that are responsible for nitrogen catabolite repression-sensitive gene expression. CAR2, which encodes the arginine-degradative enzyme ornithine transaminase, is not nitrogen catabolite repression sensitive, but its expression can be modestly induced by the allantoin pathway inducer. The dominant activators of CAR2 transcription have been thought to be the ArgR and Mcm1 factors, which mediate arginine-dependent induction. These observations prompted us to investigate the structure of the CAR2 promoter with the objectives of determining whether other transcription factors were required for CAR2 expression and, if so, of ascertaining their relative contributions to CAR2's expression and control. We show that Rap1p binds upstream of CAR2 and plays a central role in its induced expression irrespective of whether the inducer is arginine or the allantoin pathway inducer analogue oxalurate (OXLU). Our data also explain the early report that ornithine transaminase production is induced when cells are grown with urea. OXLU induction derives from the Dal82p binding site, which is immediately downstream of the Rap1p site, and Dal82p functions synergistically with Rap1p. This synergism is unlike all other known instances of Dal82p synergism, namely, that with the GATA family transcription activators Gln3p and Gat1p, which occurs only in the presence of an inducer. The observations reported suggest that CAR2 gene expression results from strong constitutive transcriptional activation mediated by Rap1p and Dal82p being balanced by the down regulation of an equally strong transcriptional repressor, Ume6p. This balance is then tipped in the direction of expression by the presence of the inducer. The formal structure of the CAR2 promoter and its operation closely follow the model proposed for CAR1.

5' Untranslated Regions↗

Papain catalysed hydantoin hydrolysis in the synthesis of amino acids.

Papain has been shown, for the first time, to exhibit hydantoinase activity. It hydrolyzes the 5-mono and 5,5'-disubstituted hydantoins with linear and cyclic substituents, with a higher activity for the latter, to the corresponding N-carbamoyl amino acids, which on chemical hydrolysis yield the corresponding amino acids. The up-scaling of this simple procedure could be a major break-through for amino acid synthesis in chemical and pharmaceutical industries.

Amidohydrolases↗

Leopard syndrome: a tropical rarity.

This is a case report of a classical presentation of the Leopard syndrome from the Indian subcontinent. The male patient had progressively increasing generalised multiple lentiginosis, ocular hypertelorism, pulmonary stenosis, short stature, cryptorchidism, and pectus excavatum. The case is documented for its rarity in this part of the world and typical clinical presentation.

Abnormalities, Multiple↗

Antiphospholipid syndrome and pregnancy loss.

Antiphospholipid antibodies (aPL) are associated with recurrent miscarriage. Pregnancies that survive the first trimester risk developing pre-eclampsia, intrauterine growth retardation and fetal distress during labour. Pregnancy loss is initially caused by defective embryonic implantation and later by thrombosis of the placental vasculature. In women with aPL, thromboprophylaxis during pregnancy improves the live birth rate.

Abortion, Habitual↗