Impact of foliar spray with Se, nano-Se and sodium sulfate on growth, yield and metabolic activities of red kidney bean.

Sulfur (S) is an essential microelement for plants. Based on the chemical similarity between Se and S, selenium may affects sulphur uptake by plants. This work aimed at investigating the effect of foliar spray with sodium selenate, gum arabic coated selenium nanoparticles (GA-SeNPs ≈ 48.22 nm) and sodium sulfate on red kidney bean (Phaseolus vulgaris L.) plants. Each treatment was used at 0.0, 1, 5, 10 and 50 µM, alone or combination of sodium sulfate with either Se or nano-Se, each at 0.5, 2.5 and 5 µM concentrations. The effect of foliar spray on vegetative growth, seed quality, and some metabolic constituents of red kidney bean (Phaseolus vulgaris L.) plants were investigated. Selenium nanoparticles have been synthesized through the green route using gum arabic (as a stabilizing and coating agent. Foliar application of different concentrations of Se, nano-Se, Na2SO4 up to 10 µM and their interaction were effective in increasing the growth criteria (i.e. shoot and root lengths, plant fresh and dry weights, number of leaves and photosynthetic area (cm2 plant-1).There was also a significant increase in photosynthetic pigment contents, yield (i.e., 100-seed weight), total carbohydrate, crude proteins and mineral contents in both leaf as compared to their untreated control plants. Furthermore, interaction between sodium sulfate with nano-Se or Se, each at 5 µM significantly increased the vegetative growth, 100-seed weight, and pigment contents in leaves and improved the nutritional value and quality of red kidney bean seeds.

Oncological outcome of contralateral submental artery island flap versus primary closure in tongue squamous cell carcinoma: randomized non-inferiority clinical trial.

The aim of this study was to test the non-inferiority of the contralateral submental island flap (CSIF) compared with primary closure (PC) regarding local recurrence after partial glossectomy in patients with oral tongue squamous cell carcinoma (OTSCC). This open-label, non-inferiority randomized controlled trial enrolled patients with cT1-2 lateralized OTSCC. The primary outcome was local recurrence by 12 months postoperative. Non-inferiority would be declared if the upper limit of the two-sided 95% confidence interval (CI) for the proportion difference in local recurrence between the two groups did not exceed a non-inferiority margin of 15.0%. The functional outcome was assessed for superiority through secondary outcomes. In the intention-to-treat analysis, the local recurrence rate was 3.1% (1/32) in the CSIF group versus 9.4% (3/32) in the PC group; the proportion difference was - 6.3% (95% CI -18.0% to 5.5%). In the per-protocol analysis, the local recurrence rate was 3.1% (1/32) versus 3.3% (1/30); the proportion difference was - 0.2% (95% CI -9% to 8.6%). Speech was significantly superior in the CSIF group (P = 0.001). In conclusion, the CSIF was found to be non-inferior to PC regarding local recurrence at 1 year. A limitation of this study is the relatively large non-inferiority margin and consequently relatively small sample size. Further studies with a smaller non-inferiority margin and therefore larger sample size are needed to validate these findings.

Comparison Between Ultrasound-guided Caudal Analgesia versus Peripheral Nerve Blocks for Lower Limb Surgeries in Pediatrics: A Randomized Controlled Prospective Study.

Background and Aim: Ultrasound (US) guided regional analgesia is a safe and effective method in providing perioperative analgesia in pediatrics with a high success rate rapid onset and fewer side effects. The aim of this study was to compare the efficacy of US-guided caudal block versus US-guided peripheral nerve blocks (femoral and sciatic nerve blocks) in providing perioperative analgesia in pediatrics undergoing unilateral lower limb surgery. Methods: Children aged 1-12 years scheduled for unilateral lower limb surgery during the period from January 2020 to December 2021 were randomly allocated into two groups. Group C where pediatrics received US-guided caudal block, while in group P, pediatrics received US-guided femoral and sciatic nerve blocks after the induction of general anesthesia (GA). The primary aim was to compare the postoperative pain (evaluated by the COMFORT pain score) between the two groups. Secondary aims were to compare perioperative opioids used parents' satisfaction and occurrence of side effects. Results: Pediatrics who underwent unilateral lower limb surgeries were allocated into two groups (group C and group P). There was no significant difference between patients' baseline characteristics and the postoperative pain score at 2, 4, 16, and 20 h.' However there was a statistical significance at 6, 8, 12, and 24 h postoperatively, frequency of analgesia as well as the total postoperative dose of opiates (nalbuphine). Time to first analgesic (nalbuphine) requirement was significantly less in group C with a mean of (9.6±2.9 h) than in group P with a mean of (15.1±3.5 h). Parents of children in group P were more satisfied than those in group C with no recorded complications for both techniques. Conclusion: US-guided lower limb peripheral nerve block is a simple and safe method to provide adequate and more prolonged analgesia compared to US-guided caudal block for lower limb surgeries in pediatrics.

DNA integrity in diagnosis of premalignant lesions.

BACKGROUND: Carcinogenesis is a dynamic process which traditional biopsying can not keep up with. Saliva as fluid in the vicinity of the tumor can offer better insights to this process. This study aimed to identify the accuracy of salivary DNA integrity index in differentiating between oral premalignant lesions and oral cancer. MATERIAL AND METHODS: This phase II diagnostic test accuracy study included 93 patients divided into three groups: 30 oral cancer patients, 33 patients with oral premalignant lesions divided into 21 oral lichen planus patients and 12 patients with leukoplakia and 30 normal individuals who acted as controls. Oral rinse was collected from all participants and they all underwent conventional visual and tactile examination, and patients with oral lesions had the diagnosis confirmed by histopathological examination of tissue biopsy. DNA integrity index was determined as the ratio between ALU247 and ALU115 measured by qPCR. RESULTS: There was no statistically significant difference regarding ALU115, ALU247 and DNA integrity index between the three study groups. The index was significantly higher in the oral cancer group than the oral lichen planus patients, while no significant difference was found between the oral cancer and the leukoplakia cases. The DNA integrity index sensitivity, specificity, positive and negative predictive values were 73%, 45%, 55% and 65% respectively. CONCLUSIONS: Salivary DNA integrity index showed poor diagnostic abilities in differentiating between the oral cancer and premalignant lesions.

Role of indole-3-butyric acid or/and putrescine in improving productivity of chickpea (Cicer arientinum L.) plants.

The response of chickpea (Cicer arientinum L. cv. Giza 3) to treatment with two plant growth regulators putrescine (Put) and Indole-3-butyric acid (IBA) at 25, 50 and 100 mg L(-1) applied either alone or in combinations was studied. Spraying of Put and IBA either individually or in combination significantly increased the plant height, number and dry weight of branches, leaves and pods/plant and leaf area/plant at the two growth stages. Total photosynthetic pigments in fresh leaves were significantly promoted as a result of application of Put or IBA. Generally, application of Put and/or IBA at 100 mg L(-1) produced the highest numbers of pods which resulted in substantially the highest seed yield. Put and IBA increased the seed yield by 21.3 and 19.2%, respectively, while the combination of Put at 100 mgL(-1) and IBA at 50 mgL(-1) increased it by 27.4%. Greatest increases in straw and biological yield/fed (38.3 and 30.4%, respectively) were noted with the combination treatment of IBA 100 mg L(-1) plus Put at 100 mg L(-1). Put and IBA significantly increased the nitrogen, phosphorus, potassium, total soluble sugars and total free amino acids in chickpea seeds over control, but the effects were less marked than those of their combination. This response was greater following treatment with IBA than with Put. It could be conclude that spraying Put or/and IBA on chickpea plants have promotion effects on the seeds yield criteria which have promising potential as sources of low-cost protein and minerals for possible use as food/feed supplements.

Antimalarial drug quality in Africa.

BACKGROUND AND OBJECTIVE: There are several reports of sub-standard and counterfeit antimalarial drugs circulating in the markets of developing countries; we aimed to review the literature for the African continent. METHODS: A search was conducted in PubMed in English using the medical subject headings (MeSH) terms: 'Antimalarials/analysis'[MeSH] OR 'Antimalarials/standards'[MeSH] AND 'Africa'[MeSH]' to include articles published up to and including 26 February 2007. Data were augmented with reports on the quality of antimalarial drugs in Africa obtained from colleagues in the World Health Organization. We summarized the data under the following themes: content and dissolution; relative bioavailability of antimalarial products; antimalarial stability and shelf life; general tests on pharmaceutical dosage forms; and the presence of degradation or unidentifiable impurities in formulations. RESULTS AND DISCUSSION: The search yielded 21 relevant peer-reviewed articles and three reports on the quality of antimalarial drugs in Africa. The literature was varied in the quality and breadth of data presented, with most bioavailability studies poorly designed and executed. The review highlights the common finding in drug quality studies that (i) most antimalarial products pass the basic tests for pharmaceutical dosage forms, such as the uniformity of weight for tablets, (ii) most antimalarial drugs pass the content test and (iii) in vitro product dissolution is the main problem area where most drugs fail to meet required pharmacopoeial specifications, especially with regard to sulfadoxine-pyrimethamine products. In addition, there are worryingly high quality failure rates for artemisinin monotherapies such as dihydroartemisinin (DHA); for instance all five DHA sampled products in one study in Nairobi, Kenya, were reported to have failed the requisite tests. CONCLUSIONS: There is an urgent need to strengthen pharmaceutical management systems such as post-marketing surveillance and the broader health systems in Africa to ensure populations in the continent have access to antimalarial drugs that are safe, of the highest quality standards and that retain their integrity throughout the distribution chain through adequate enforcement of existing legislation and enactment of new ones if necessary, and provision of the necessary resources for drug quality assurance.

The use of autologous chondrocyte implantation following and combined with anterior cruciate ligament reconstruction.

We report our experience of using autologous chondrocyte implantation (ACI) to treat osteochondral defects of the knee in combination with anterior cruciate ligament (ACL) reconstruction. The outcome of symptomatic osteochondral lesions treated with ACI following previous successful ACL reconstruction is also reviewed. Patients were followed for a mean of 23 months. Nine patients underwent ACL reconstruction in combination with ACI. Mean modified Cincinnati knee scores improved from 42 to 69 following surgery. Seven patients described their knee as better and two as the same. A second group of nine patients underwent ACI for symptomatic articular cartilage defects following previous ACL reconstruction. In this group, the mean modified Cincinnati knee score improved from 53 to 62 after surgery. Six patients described their knee as better and three as worse. Combined treatment using ACI with ACL reconstruction is technically feasible and resulted in sustained improvement in pain and function. The results following previous ACL reconstruction also resulted in clinical improvement, although results were not as good as following the combined procedure.

The quality of sulphadoxine-pyrimethamine and amodiaquine products in the Kenyan retail sector.

BACKGROUND AND OBJECTIVE: Malaria is a disease of major public health importance in Kenya killing 26,000 children under 5 years of age annually. This paper seeks to assess the quality of sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) products available over-the-counter to communities in Kenya as most malaria fevers are self-medicated using drugs from the informal retail sector. METHODS: A retail audit of 880 retail outlets was carried in 2002 in four districts in Kenya, in which antimalarial drug stocks and their primary wholesale sources were noted. In addition, the expiry dates on audited products and the basic storage conditions were recorded on a proforma. The most commonly stocked SP and AQ products were then sampled from the top 10 wholesalers in each district and samples subjected to standard United States Pharmacopoeia (USP) tests of content and dissolution. RESULTS AND DISCUSSION: SP and AQ were the most frequently stocked antimalarial drugs, accounting for approximately 75% of all the antimalarial drugs stocked in the four districts. Of 116 SP and AQ samples analysed, 47 (40.5%) did not meet the USP specifications for content and/or dissolution. Overall, approximately 45.3% of SP and 33.0% of AQ samples were found to be sub-standard. Of the sub-standard SP products, 55.2% were suspensions while 61.1% of the substandard AQ products were tablets. Most SP failures were because of the pyrimethamine component. CONCLUSION: There is a need to strengthen post-marketing surveillance systems to protect patients from being treated with sub-standard and counterfeit antimalarial drugs in Kenya.

Inhibition of methylnitrosourea (MNU) induced oxidative stress and carcinogenesis by orally administered bee honey and Nigella grains in Sprague Dawely rats.

We studied the protective effect of bee honey and Nigella grains as nutraceuticals on the oxidative stress and carcinogenesis induced by methylnitrosourea (MNU) in Sprague Dawely rats. Four groups of animals were used and fed ad-libitum. The first group was a control (n=8), the second (n=8), the third (n=15) and the fourth groups (n=12) were injected MNU (single i.v. dose 50 mg/kg body weight). After one week the third and fourth groups were given orally 0.2 g ground Nigella grains and 0.2 g Nigella with 5 g honey/rat/day, respectively. After six months all animals were sacrificed except two from the second group (MNU-injected rats) that died one-week before the end of the experiment. We observed that MNU injected in the second group produced a variety of oxidative stresses ranging from severe inflammatory reaction in lung and skin to colon adenocarcinoma in four out of six animals. There was an associated elevation of malondialdehyde (MDA) and nitric oxide (NO) in sera obtained from animals of this group compared to the control one. Nigella sativa grains given orally protected against MNU-induced oxidative stress and carcinogenesis by 80% (12/15) and combated this effect by lowering MDA and NO. Whereas honey from bees and Nigella sativa together protected 100% (12/12) against MNU-induced oxidative stress, carcinogenesis and abolished the NO and MDA elevations shown in sera of animals who did not receive these nutrients. These results showed that supplementation of diet with honey and Nigella sativa has a protective effect against MNU-induced oxidative stress, inflammatory response and carcinogenesis.

Identification of domains of the HPV11 E1 protein required for DNA replication in vitro.

The HPV E1 and E2 proteins along with cellular factors, are required for replication of the viral genome. In this study we show that in vitro synthesized HPV11 E1 can support DNA replication in a cell-free system and is able to cooperate with E2 to recruit the host polymerase alpha primase to the HPV origin in vitro. Deletion analysis revealed that the N-terminal 166 amino acids of E1, which encompass a nuclear localization signal and a cyclin E-binding motif, are dispensable for E1-dependent DNA replication and for recruitment of pol alpha primase to the origin in vitro. A shorter E1 protein lacking the N-terminal 190 amino acids supported cell-free DNA replication at less than 25% the efficiency of wild-type E1 and was active in the pol alpha primase recruitment assay. An even shorter E1 protein lacking a functional DNA-binding domain due to a truncation of the N-terminal 352 amino acids was inactive in both assays despite the fact that it retains the ability to associate with E2 or pol alpha primase in the absence of ori DNA. We provide additional functional evidence that E1 interacts with pol alpha primase through the p70 subunit of the complex by showing that p70 can be recruited to the HPV origin by E1 and E2 in vitro, that the domain of E1 (amino acids 353-649) that binds to pol alpha primase in vitro is the same as that needed for interaction with p70 in the yeast two-hybrid system, and that exogenously added p70 competes with the interaction between E1 and pol alpha primase and inhibits E1-dependent cell-free DNA replication. On the basis of these results and the observation that pol alpha primase competes with the interaction between E1 and E2 in solution, we propose that these three proteins assemble at the origin in a stepwise process during which E1, following its interaction with E2, must bind to DNA prior to interacting with pol alpha primase.

Second free flaps in head and neck reconstruction.

Over the past decade, free-tissue transfer has greatly improved the quality of oncology-related head and neck reconstruction. As this technique has developed, second free flaps have been performed for aesthetic improvement of the reconstructed site. This study evaluated the indications for and the success of second free flaps. Medical files for patients who underwent second free flaps for head and neck reconstruction at the University of Texas M.D. Anderson Cancer Center, from May 1, 1988 to November 30, 1996, were reviewed. The flaps were classified as being either immediate (done within 72 hr) or delayed (done within 2 years) reconstructions. Indications, risk factors, recipient vessels, outcome, and complications were analyzed. Of the 28 patients included in this study, 12 had immediate (nine as salvage after primary free flap failure, and three for reconstruction of a soft-tissue defect), and 16 had delayed second free flaps (two for reconstruction of a defect resulting from excision of recurrent tumors, and 14 for aesthetic improvement). Reconstruction sites included the oral cavity in 18 patients; the midface in six; the skull base in two; and the scalp in two. The success rate for the second free flaps was 96 percent. Five patients had significant wound complications. In a substantial number of cases, identical recipient vessels were used for both the first and second free flaps. The authors conclude that second free flaps can play an important role in salvaging or improving head and neck reconstruction in selected patients. In many cases, the same recipient vessels can be used for both the first and second flaps.

Reconstruction of complex radiation-induced injuries using free-tissue transfer.

The purpose of this study was to evaluate the use of free-tissue transfers for the reconstruction of radiation-induced complex injuries. The case files for patients who underwent reconstruction for radiation-induced injuries between May 1988 and November 1995 at The University of Texas M.D. Anderson Cancer Center were retrospectively reviewed. Thirty patients in whom 33 free flaps were done were included. Radiation-induced defects were located in the head and neck (n=23), extremities (n=4), chest wall (n=2), and inguinal area (n=1) The mean period between irradiation and injury was 78 months (range: 4 months to 38 years). Free-tissue transfer was successful in 97 percent (32/33) of patients. The overall complication rate was 40 percent (12/30). Flap donor sites included the fibula (n=12), latissimus dorsi (n=6), rectus abdominis (n=6), iliac crest (n=4), scapula (n=3), and radial forearm (n=2). Large-caliber vessels in the cervical, axillary, or inguinal regions were most commonly used to revascularize flaps. Vein grafts were used in five cases for the artery (2/5) or vein (3/5). Pedicle thrombosis occurred in three cases in recipient vessels located within the irradiated field. Two flaps were salvaged; one was lost, and the patient required a second free-flap reconstruction The mean follow-up was 40 months (range: 2.5 to 83 months). The disease-free survival rate was 67 percent (20/30), local failures occurred in 10 percent (3/30) of patients, and 23.3 percent (7/30) of patients either died or were lost to follow-up. Healing of radiation-induced wounds may be achieved using free-tissue transfers, but complications are frequent. Large-caliber irradiated vessels may be used to revascularize flaps, but there may be an increased risk of pedicle thrombosis.

Venous flap ischemia: microcirculatory changes in experimental flaps in a rabbit model.

This study was designed to investigate the simultaneous changes in blood flow and microcirculation in an island flap during venous occlusion (venous ischemia), in an ischemia/reperfusion injury model in the rabbit. An island groin flap based on the inferior epigastric vessels was harvested in 15 rabbits. The flap was rendered ischemic for 3 hr (n = 5) or 4 hr (n = 10, 5 heparinized and 5 not), by applying a microvascular clamp to the inferior epigastric vein. Transonic Doppler and laser Doppler were used to monitor blood flow in the epigastric artery and microcirculation of the flap for 1 hr after flap elevation, 1 hr after occlusion, and for 3 hr at the end of the ischemic period. Venous occlusion was followed by a rapid decrease of blood flow and microcirculation readings. After ischemia, both blood flow and microcirculation readings in the flap were significantly decreased, compared to pre-ischemic values in all groups. In the 3-hr ischemia group, blood flow readings returned to pre-stress values, while microcirculation remained significantly lower. In the 4-hr ischemia group treated with heparin, blood flow in the artery settled at levels significantly lower than pre-stress readings; however, microcirculation of the flap was ultimately fully restored to pre-ischemic values. In the 4-hr ischemia group, both blood flow and microcirculation in the flap settled at levels significantly lower than pre-stress values. The authors concluded that tolerance for venous ischemia is time-dependent in this model and that venous ischemia is more deleterious than global ischemia. Administration of heparin may alter the time frame of ischemia/reperfusion injury and may prevent the harmful effects of injury at the microcirculatory level.

Isolation of human and fission yeast homologues of the budding yeast origin recognition complex subunit ORC5: human homologue (ORC5L) maps to 7q22.

Orc5p is a subunit of the origin recognition complex in the budding yeast Saccharomyces cerevisiae, which has been shown to play a critical role in both chromosomal DNA replication and transcriptional silencing. We have cloned cDNAs from both human and fission yeast Schizosaccharomyces pombe that encode proteins homologous to the budding yeast and Drosophila Orc5p. Human Orc5p showed 35.1, 22.3, and 19.4% identity to the Drosophila, S. pombe, and S. cerevisiae Orc5p, respectively. We have localized the human ORC5 gene (ORC5L) to chromosome 7 using Southern and PCR analysis of DNA isolated from a panel of human/rodent somatic cell hybrids and mapped the gene locus to 7q22 using fluorescence in situ hybridization. We have identified a YAC clone that contains human ORC5L and maps to chromosome band 7q22.1. We have identified the S. pombe ORC5 gene and located it in a cosmid mapped on chromosome II.

Transcription-positive cofactor 4 forms complexes with HSSB (RPA) on single-stranded DNA and influences HSSB-dependent enzymatic synthesis of simian virus 40 DNA.

The replication of simian virus 40 (SV40) DNA in vitro requires a trimeric single-stranded DNA (ssDNA)-binding protein called HSSB or RPA. HSSB supports the unwinding of DNA containing the SV40 origin in the presence of the viral-encoded T antigen and is required for the initiation of RNA primer synthesis as well as processive elongation of DNA catalyzed by the DNA polymerase delta holoenzyme. In this report we show that the transcription positive cofactor 4 (PC4), a ssDNA-binding protein, forms complexes with HSSB on ssDNA and markedly affects the replication functions of HSSB. PC4 supports T antigen-catalyzed unwinding of SV40 origins in lieu of HSSB but inhibits both RNA primer synthesis and polymerase delta-catalyzed DNA chain elongation reactions. These inhibitory effects can be reversed by the addition of excess HSSB. Depending on the concentration of HSSB, PC4 is capable of either inhibiting or activating SV40 DNA replication measured in both mono- and dipolymerase systems. The possible role of PC4 in the initiation of DNA replication is discussed.

Purification, gene cloning, and reconstitution of the heterotrimeric single-stranded DNA-binding protein from Schizosaccharomyces pombe.

We have purified a single-stranded DNA-binding protein (SSB) from Schizosaccharomyces pombe (Sp) and have shown that it is composed of three subunits of 68, 30, and 12 kDa. The SpSSB supports T antigen-dependent unwinding of SV40 ori containing DNA, but is not functional in the SV40 in vitro replication reaction. All three genes that encode the SpSSB subunit have been isolated. The cloned cDNA of the ssb1(+), encoding the p68 subunit, contains 609 amino acids (68.3 kDa), while that of the ssb2(+), encoding the p30 subunit, contains a 279 amino acids (30.3 kDa). The genomic DNA clone of the p12 subunit gene (ssb3(+)) has 2 introns and an open reading frame of 104 amino acids (11.8 kDa). Significant homology is observed among the largest and middle subunits of eukaryotic SSBs, but there is poor homology among the smallest subunits. In addition, we have reconstituted the SpSSB complex by coexpression of all three subunits in Escherichia coli. The reconstituted complex is active in single-stranded DNA binding and the T antigen-dependent unwinding of SV40 ori DNA. Finally, we observed a cell cycle-dependent phosphorylation pattern of the p30 subunit of SpSSB, which is similar to that observed for the human and Saccharomyces cerevisiae SSB.

Phosphorylated and unphosphorylated forms of human single-stranded DNA-binding protein are equally active in simian virus 40 DNA replication and in nucleotide excision repair.

The trimeric human single-stranded DNA-binding protein (HSSB; also called RP-A) plays an essential role in DNA replication, nucleotide excision repair, and homologous DNA recombination. The p34 subunit of HSSB is phosphorylated at the G1/S boundary of the cell cycle or upon exposure of cells to DNA damage-inducing agents including ionizing and UV radiation. We have previously shown that the phosphorylation of p34 is catalyzed by both cyclin-dependent kinase-cyclin A complex and DNA-dependent protein kinase. In this study, we investigated the effect of phosphorylation of p34 by these kinases on the replication and repair function of HSSB. We observed no significant difference with the unphosphorylated and phosphorylated forms of HSSB in the simian virus 40 DNA replication or nucleotide excision repair systems reconstituted with purified proteins. The phosphorylation status of the p34 subunit of HSSB was unchanged during the reactions. We suggest that the phosphorylated HSSB has no direct effect on the basic mechanism of DNA replication and nucleotide excision repair reactions in vitro, although we cannot exclude a role of p34 phosphorylation in modulating HSSB function in vivo through a yet poorly understood control pathway in the cellular response to DNA damage and replication.

Propranolol reduces mortality in patients with portal hypertension secondary to schistosomiasis.

Although beta-adrenoceptor antagonists improve morbidity and mortality in patients with portal hypertension associated with cirrhosis, this has not been demonstrated in non-cirrhotic patients. In the present, double-blind, 24-month, prospective study of patients with endoscopically-proven varices and ultrasonographically-confirmed hepatic fibrosis, the effects of propranolol 160 mg LA and placebo on the incidence of rebleeding and mortality were compared in 82 patients with portal hypertension secondary to schistosomiasis. The results, analysed on intention-to-treat basis, indicated a reduction in rebleeding (median time to rebleeding 589 days for propanol v. 252 days for placebo; P < 0.02) and increased survival in the propranolol-treated patients (three deaths v. seven deaths on placebo; P < 0.02). Fifteen patients withdrew from the propranolol group and 18 from the placebo group. A positive prognostic indicator was a large portal vein diameter whereas a small liver size indicated a negative outcome.

Phosphorylation of the p34 subunit of human single-stranded-DNA-binding protein in cyclin A-activated G1 extracts is catalyzed by cdk-cyclin A complex and DNA-dependent protein kinase.

The human single-stranded-DNA-binding protein (HSSB, also called RP-A) is a trimeric complex (p70, p34, and p14) required for multiple functions in DNA transactions. We report here that the p34 subunit of HSSB was hyperphosphorylated by kinase activities present in G1 extract (obtained from HeLa cells in G1 phase) preincubated with human cyclin A. This hyperphosphorylated HSSB product included at least four species of p34 that migrated more slowly through denaturing polyacrylamide gels than the hypophosphorylated form. Fractionation of cyclin A-activated G1 extract identified two kinases involved in the hyperphosphorylation of HSSB p34: cdk-cyclin A complex and DNA-dependent p350 protein kinase (DNA-PK). Kinetic analysis revealed that in cyclin A-activated G1 extract, p34 was first phosphorylated by cdk-cyclin A prior to the action of DNA-PK. Addition of p21cip1, a specific inhibitor of cdk-cyclin A but not DNA-PK, nearly abolished the hyperphosphorylation of HSSB p34 in G1 extract preincubated with cyclin A. This suggests a requirement of the cdk-cyclin A activity for the phosphorylation of p34 by DNA-PK in G1 extract.