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PubMed1992

Readthrough of the Bacillus subtilis stop codon produces an extended enzyme displaying a higher polymerase activity.

It has been generally accepted that the structural sacB gene of Bacillus subtilis levansucrase encodes a 50,000 Da extracellular protein. However, examination of the DNA sequence of the sacB flanking regions shows a putative open reading frame coding for a 20 amino acid peptide downstream immediately following the terminal TAA stop codon. By site-directed mutagenesis we have changed this stop codon to a glutamine codon. This stop codon readthrough leads to the synthesis and secretion by B. subtilis of a levansucrase possessing an extended polypeptide chain. The extended levansucrase has a molecular weight of 53,000 with a new carboxyl-terminus, rich in basic and hydrophobic amino acids and possessing one cysteine residue. This enzyme synthesizes fructosyl polymer levan of higher molecular weight than the shorter levansucrase. The increase in molecular weight was achieved by increasing the number of branches. These results suggest that the C-terminal part of the enzyme plays a specific role in the degree of branching of the synthesized polymer. Moreover, the extended enzyme is able to form an active dimer from two polypeptide chains linked by an S-S bridge.

Amino Acid Sequence↗

PubMed1992

Incidence of two virulence factors (aerobactin and mucoid phenotype) among 190 clinical isolates of Klebsiella pneumoniae producing extended-spectrum beta-lactamase.

Because outbreaks of multiple-resistant Klebsiella pneumoniae isolates producing extended-spectrum beta-lactamases were recently observed in French hospitals, the presence of virulence factors was examined for (i) phenotype by bioassay for aerobactin production and by culture for the mucoid phenotype, and (ii) genotype using intragenic probes of respectively 2-kb BglII and 235-bp BamHI-BglII fragments and dot-blotting among 190 unreplicated K. pneumoniae clinical isolates issued from 25 French hospitals and producing different types of extended-spectrum beta-lactamases (TEM-related enzymes: TEM-3, TEM-4, CAZ-1, CAZ-2, TEM-8, or SHV-related enzymes: SHV-2, SHV-3, SHV-4). Only 3.7% and 7% of K. pneumoniae isolates produced aerobactin and mucoid phenotypes respectively, unrelated to type of beta-lactamase. Only 2% had both factors. No discordance was reported according to the detection method tested. The low prevalence of such virulence factors seems to indicate they were not involved in dissemination of nosocomial K. pneumoniae isolates producing an extended-spectrum beta-lactamase.

Cross Infection↗

PubMed1979

The results of treatment of microinvasive carcinoma (stage iA) of the uterine cervix by means of simple and extended hysterectomy.

At the Department of Obstetrics and Gynecology of Tohoku University, radical hysterectomy with pelvic lymphadenectomy had been performed on patients with microinvasive carcinoma of the uterine cervix before 1966. Investigation of lymph nodes of 90 patients treated in this manner has shown no lymph node metastasis of tumor cells in any of them. Since 1967, microinvasive carcinoma has been treated as a matter of principle by extended hysterectomy without lymphadenectomy. From that time until 1974, 119 cases of microinvasive carcinoma have been treated by extended hysterectomy and 69 such cases by simple hysterectomy. The 5-year relative survival rate was 0.989 for extended hysterectomy patients and 1.008 for simple hysterectomy patients. Together, a 5-year relative survival rate of 0.992 was obtained.

Adult↗

PubMed1979

Complications associated with extended wear of soft contact lenses.

The major complications with extended wear lenses are due to hypoxia and lens deposits. Certain patients tend to deposit proteins and lipids on the lens surface with daily wear and at a greater frequency during prolonged wear. A build-up of these deposits can be associated with decreased vision, conjunctival irritation, and giant papillary conjunctivitis. Frequent lens cleaning and the frequent use of concomitant topical artificial tears will hopefully reduce the incidence of lens deposits and their complications. Superficial circumlimbal vascularization occurs in a large percentage of patients who have worn lenses for weeks at a time. Corneal edema, ocular irritation, and decreased vision are also the hallmarks of a decreased oxygen supply to the cornea. A thin-loose-fitting lens will increase the percentage of patients who are able to successfully use extended wear lenses by increasing the amount of oxygen available to the cornea. Cessation or reduction in duration of lens wear will decrease the frequency and severity of this complication. Conjunctival and corneal infections are real risks; lens loss, breakage, deformation, or discoloration also occur during extended wear.

Calcium↗

PubMed1992

Correlation of in vitro release rate and in vivo absorption characteristics of four chlorpheniramine maleate extended-release formulations.

An in vitro/in vivo correlation was established for four formulations of chlorpheniramine maleate (histamine, H1-blocker) extended-release tablets exhibiting different in vitro release rate characteristics. In vitro release rate data were obtained for 12 individual tablets of each formulation using the USP Apparatus 2, paddle stirrer at 50 rpm in 1000 ml of distilled water at 37.0 +/- 0.5 degrees C. Inspection of the individual and mean release rate data indicated that the in vitro release rate of chlorpheniramine maleate was consistent with the intended design of the four extended-release formulations. The in vivo bioavailability and pharmacokinetics of these formulations were evaluated in 24 healthy subjects under fasting conditions. Wagner Nelson analyses of the in vivo data revealed extended release absorption profiles for all four formulations. Linear regression analyses of the mean percentage of dose absorbed versus the mean in vitro release resulted in a statistically significant correlation (r2 greater than 0.98, P less than 0.001) for each formulation. Qualitative rank-order correlations were observed among all combinations of in vitro and in vivo parameters. These data support a Level A correlation between the in vitro release rate profiles and the in vivo absorption for chlorpheniramine maleate determined under fasting conditions.

Adult↗

PubMed1992

Two mutations in the beta-globin polyadenylylation signal reveal extended transcripts and new RNA polyadenylylation sites.

Two mutations in the beta-globin poly(A) signal were identified in Israeli patients with beta +-thalassemia by sequence analysis following PCR. One is a point mutation (AATAAA----AATAAG) and the other is a 5-base-pair deletion (AATAAA----A----). The mutant genes were used to investigate the function of the poly(A) signal in vivo and to evaluate the mechanism whereby these mutations lead to a thalassemic phenotype. Analysis of RNA derived from peripheral blood demonstrated the presence of elongated RNA species in patients carrying either mutation. Other aspects of RNA processing (initiation, splicing) were unimpaired. RNA obtained from the patients carrying the point mutation contained four discrete, extended RNA species, 1500-2900 nucleotides long, which were found to be polyadenylated. Some normal cleavage-polyadenylylation was also observed. The 5-base-pair deletion completely abolished cleavage at the normal site. This deletion mutation resulted in a phenotype of beta +-thalassemia, thus providing evidence that the extended mRNAs are translatable in vivo. Furthermore, additional transcripts, greater than 5 kilobases, presumably mRNA precursors, were found in all RNA samples, including those of nonthalassemic controls. The extended transcripts of the poly(A) mutants, together with the high molecular weight precursors, suggest that the human beta-globin gene transcription unit is significantly longer than previously recognized.

Base Sequence↗

PubMed1977

Effect of extended photoperiod on the spermatogenic activity of chicken-pheasant hybrids.

1. Males of chicken-pheasant hybrids and non-breeding pheasants were exposed to photoperiods of 10 or 20 h/d to test the effect of light on spermatogenic activity. 2. Testicular weights of hybrids and pheasants exposed to 10 h/d were similar and extending the photoperiod did not increase this in hybrids, although it caused a 48-fold increase, and complete recovery of spermatogenic activity, in pheasant. 3. Extending the photoperiod caused an increase in the number of primary spermatocytes and a corresponding decrease in the number of spermatogonia in hybrids, however, stages beyond primary spermatocytes were not present. This suggests that the stimulus of extending the photoperiod, while sufficient to induce meiosis in existing germ cells, is not enough to effect proliferative bursts or to overcome the meiotic arrest in the hybrids.

Animals↗

PubMed1975

Subunit arrangement in the extended sheath of pyocin R.

An optical diffraction study has been made of electron micrographs of extended sheaths of pyocin R. It has been demonstrated that the extended sheath consists of annuli of six subunits, which are arranged in a helix of 3.57 annuli per one turn. The annulus repeat in the helix direction is 35A. The dimensions and probably the helical parameters of pyocin R sheath are different from those of T4 phage tail, but a structural correlation appears to exist between the extended sheath of pyocin R and that of the phage tail.

Bacteriocins↗

PubMed1992

A high frequency of the A30, B18, DR3, DRw52, DQw2 extended haplotype in Sardinian celiac disease patients: further evidence that disease susceptibility is conferred by DQ A10501, B10201.

This study characterizes by serological and molecular methods the HLA class I and class II alleles in a group of celiac disease children, their parents and a control group of Sardinian descent. We found the DR3-DQw2 haplotype in all patients which was, in almost all cases (84%), associated with the HLA-A30, B18, DR3, DRw52, DQw2 extended haplotype named "Sardinian haplotype" because of its frequency (12-15%) in this Caucasian population. This is the first time that this DQw2-linked haplotype has been reported with such a high frequency in CD. However, no different distribution of "Sardinian haplotype" was found comparing CD patients with 91 haplotyped DQw2-positive controls. This finding indicates that the DQw2 antigen in Sardinians is almost always associated with the A30, B18, DR3, DRw52, DQw2 extended haplotype. The DQA1 and DQB1 second exon sequence analysis of the B18,DR3 and B8,DR3 haplotypes showed the DQA1*0501 and DQB1*0201 alleles which shared the already published sequences. DPB1 subtyping showed the DPB1*0301 allele more frequently (p less than 0.005) in CD patients but this difference was no longer significant when patients and controls, both heterozygous for the DR3-DQw2 haplotype, were compared. We suggest that the divergent HLA extended haplotypes and DP allele associated with CD, described in different Caucasian populations, can be explained by the particular DQw2 linkage disequilibrium in each population.

Adult↗

PubMed1977

Time-extended family interviewing.

This paper presents a family-therapy technique--time-extended family interviewing--in which the therapist extends the traditional one-hour interview to three to seven hours, by plan, at a particular point in the life of a case and for a particular purpose. Extended sessions promote movement in a case for a variety of reasons. Furthermore, the use of such sessions highlights the dimension of time as an important element of good casework practice.

Adult↗

PubMed1992

Pharmacokinetics and organ specific metabolism of glycine-extended and amidated gastrin in sheep.

Glycine (Gly)-extended gastrin has been described as the inactive precursor form of the biologically active amidated gastrin. The ratio of Gly-extended to amidated gastrin is higher in the circulation than in tissue, suggesting either differential secretion and/or metabolism. Although the distribution of the precursor form is similar in tissue and circulation to its amidated product, the significance of measurable levels of precursor peptide in the circulation is unknown. In this study, we have examined the pharmacokinetic properties and organ-specific metabolism of both the Gly-extended and the amidated forms of gastrin-17 (G-17-Gly and G-17-amide) in the conscious sheep. The metabolic clearance rate, half disappearance time, and production rates were similar for both G-17-Gly and G-17-amide. G-17-Gly was extracted across the head, kidney, and lung but not across the gut and liver. Similarly, G-17-amide was extracted across the head, gut, lung, and kidney but not across the liver. G-17-Gly had no biological activity as evidenced by its failure to stimulate somatostatin secretion nor was there any measurable conversion to amidated gastrin in the circulation. We conclude that the presence of G-17-Gly in the circulation is not the result of a slower clearance and that circulating G-17-Gly is not a precursor for circulating gastrin-amide. The results of this study provide important baseline data for understanding the dynamics of the precursor product relationship between G-Gly and G-amide.

Amino Acid Sequence↗

PubMed2026

Extending the Treatment Window for Intravenous Thrombolysis in Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke within 4.5 hours of onset. However, imaging-based selection may extend the treatment window. This systematic review and meta-analysis evaluated the efficacy and safety of IVT administered beyond 4.5 hours after stroke onset or last known well (LKW) in patients selected based on imaging findings. METHODS: A comprehensive search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials comparing IVT with alteplase or tenecteplase (TNK) administered >4.5 hours after stroke onset/LKW vs standard care. Primary outcomes were 3-month excellent (modified Rankin Scale [mRS] 0-1) functional outcome and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included good (mRS 0-2) functional outcome, recanalization, and 3-month mortality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analysis assessed differences between alteplase and TNK. RESULTS: Fourteen studies involving 4,944 patients were included. The mean age was 69.8 years, 58.2% were male, the median National Institutes of Health Stroke Scale score was 9, and 12.3% received preplanned endovascular thrombectomy (EVT). A total of 2,492 patients received IVT in an extended time window (4.5-24 hours). Compared with standard care, extended IVT was associated with higher odds of achieving an excellent functional outcome (OR: 1.43 [95% CI 1.25-1.63]), a good functional outcome (OR: 1.25 [95% CI 1.11-1.40]), and recanalization (OR: 3.28 [95% CI 2.09-5.16]). There was no difference in 3-month mortality (OR: 1.21 [95% CI 0.95-1.53]). However, IVT increased the risk of sICH (OR: 2.51 [95% CI 1.47-4.28]). Sensitivity analysis excluding patients who received EVT showed no impact on the outcomes. TNK exhibited similar efficacy to alteplase but showed potentially lower odds of sICH (OR: 1.96, 95% CI 1.06-3.64) compared with alteplase (OR: 5.29, 95% CI 1.80-15.57); however, the subgroup difference was not significant (p = 0.11). DISCUSSION: Among patients selected based on imaging, 4.5-24 hours after stroke onset/LKW, IVT improves outcomes despite an increased risk of sICH. TNK showed similar efficacy to alteplase, with a possible lower risk of sICH; however, direct comparisons in future trials are needed.

Humans↗

PubMed1977

Treatment tolerance and early complications with extended field irradiation in gynaecological cancer.

Treatment tolerance and early complications have been analysed in patients treated with extended field irradiation and pelvic irradiation alone. At the Centre Georges-François Leclerc, 126 patients were treated for carcinoma of the uterine cervix and endometrium from May, 1972 to November, 1974. All patients received external irradiation using a 25 MV X-ray beam. Follow-up has been nearly complete in all patients with the minimum follow-up being 15 months and the average 24 months. Treatment tolerance was approximately the same for all field sizes except when the field was extended to the top of D12. In this situation the patients occasionally required a short rest during their irradiation. The age of the patient was found to contribute significantly to the tolerance, with 70% of the patients who experienced poor tolerance being older than 60 years. Complications were evenly distributed in all all catagories of field size and appeared to be affected only by age and previous surgery. Of the patients who experienced complications 68% were older than 60 years, and of the 37 patients who had previous surgery, 32% had a complication. With certain treatment modifications the treatment tolerance and early complications appear acceptable when using extended field irradiation for gynaecological cancer.

Adenocarcinoma↗

PubMed1992

Maturation of an NH2-terminally extended thermostable alpha-amylase in Bacillus subtilis: a possible mechanism examined by in vitro experiments.

An artificially inserted extra peptide (21 amino acid peptide) between the B. subtilis alpha-amylase signal peptide and the mature thermostable alpha-amylase was completely cleaved by B. subtilis alkaline protease in vitro. The cleavage to form a mature enzyme was observed between pH 7.5 and 10, but not between pH 6.0 and 6.5, although a similar protease activity toward Azocall was observed between pH 6.0 and 7.5. To analyze the effects of pH on the cleavage, CD spectra at pH 6, 8, and 11 of the NH2-terminally extended thermostable alpha-amylase were analyzed and the results were compared with those of the mature form of the alpha-amylase. It is suggested that the cleavage of the NH2-terminally extended peptide is controlled by the secondary and tertiary structure of the precursor enzyme. Similar cleavage of different NH2-terminally extended peptides by the alkaline protease was also found in other hybrid thermostable alpha-amylases obtained.

Amino Acid Sequence↗

PubMed1992

Plasma melatonin profiles of Romney Marsh sheep in natural photoperiod and in acutely extended darkness.

Plasma melatonin was measured at the summer and winter solstices and the autumn and spring equinoxes in Romney Marsh sheep held under natural conditions in South Australia (35 degrees S). The amount of melatonin detected was generally related to the extent of natural darkness, though the melatonin onset was particularly delayed after dusk in winter compared with other seasons. The duration of detectable melatonin was shorter in summer than at any other season. After each initial 24 h sampling, the sheep were resampled for a further 24 h in acutely extended darkness to mark the phase and duration of suprachiasmatic nuclei activity which is believed to be the source of the melatonin signal. The onset of high plasma melatonin was earlier than the time of natural sunset in spring and summer, but not different from the time of natural sunset in autumn and winter. The offset of high plasma melatonin was later than the time of natural sunrise at all times of year and particularly so in summer. Under the extended dark conditions, the duration of detectable melatonin was longer than that under natural photoperiod at all seasons of the year and the duration of melatonin was again shorter in summer than winter. If melatonin measurements under the conditions of extended darkness do reflect the phase and duration of suprachiasmatic nuclei function then the natural light of the photoperiod can, particularly during long photoperiod conditions, mask the expression of the pacemaker. The findings may have implications for the timing of the breeding season in Romney Marsh sheep.

Animals↗

PubMed1977

Effects of package, extender, and light on stored frozen bull spermatozoa.

Spermatozoa were analyzed when fresh, freshly frozen, and stored at --196 C for 6 and 18 mo after processing in egg yolk-citrate and Promine-D extender with varying exposure to light and packaging in straws or glass ampules. Over all treatments there were decreases with time in spermatozoal motility, oxygen uptake, and cellular glutamic oxaloacetic transaminase due to freezing-thawing. Percent progressive motility decreased from spermatozoa freshly frozen (36.5%) to those stored for 6 mo (33.6%). Oxygen uptake in freshly frozen samples was 8.4 microliter per 10(8) cells per h. In frozen semen stored for 6 and 18 mo corresponding values were 12.2 and 8.3 microliter. Packaging methods did not have a significant effect on oxygen uptake, but package interacted with storage. Egg yolk-citrate extender supported greater progressive spermatoal motility than did promine-D. Extender interacted with storage for all criteria. Visible light radiation reduced progressive spermatozoal motility from 40.2 to 38.0% and oxygen uptake from 11.8 to 10.8 microliter per 10(8) cells per h. Light interacted with storage time. Correlations between all criteria and storage times were not important practically.

Animals↗

PubMedDate not supplied

Annulo-aortic ectasia extending to the arch: composite graft repair with circulatory arrest.

OBJECTIVE: To examine the results of surgery performed in patients with annulo-aortic ectasia extending to the arch. DESIGN: Retrospective hospital record review. SETTING: A Canadian teaching hospital. PATIENTS: Five patients (mean age 57 years) had annulo-aortic ectasia with severe aortic insufficiency, a maximum aneurysmal diameter ranging from 6.5 to 13 cm at the root or ascending aortic level, and extending into the arch with a diameter of at least 5 cm at the innominate artery level. They all had reconstruction with a composite prosthetic valve and Dacron tube graft employing standard techniques of aortic root replacement as well as aortic arch reconstruction with a single bevelled anastomosis in a state of profound hypothermia and circulatory arrest. MAIN RESULTS: No perioperative deaths, neurological complications nor significant cardiac complications. At a median follow-up period of 46 months all patients are alive, free from cardiovascular symptoms and show no evidence of aortic aneurysmal disease. CONCLUSIONS: This safe, effective and durable repair should be applied to selected patients with annulo-aortic ectasia which extends to the arch.

Adult↗

PubMed1977

A physician extender training program based on clinical algorithms.

The ability of physician extenders to provide patient care in a variety of settings has been reported widely. Less attention has been paid to training programs, especially those of short duration, for physician extenders. A three-month training program for physician extenders at a large teaching hospital was based on teaching the skills needed to run 39 clinical algorithms. The course content and the methods used to test the students during the three months may prove of value to those preparing similar programs.

California↗