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Catching up with history: treatment of Wilms' tumor in a developing country.

Despite the tremendous progress that pediatric oncology has achieved in the treatment of Wilms' tumor over the last several decades, survival rates in our institution before 1970 did not exceed 8%. In order to correct the problem standardized therapy was instituted in 1970 through a multimodal oncological team. Results using the new approach were reviewed in 1979 (50 patients) and showed an overall 34% 2-year survival rate. Although encouraging, these results were still far below the ones reported in the literature. This prompted us to use a vigorous professional and lay educational program in the city. Treatment methods were replaced by those advocated by the Second National Wilms' Tumor Study. A second evaluation period initiated in 1979 and extended through 1984 (35 patients) yielded an overall 83% survival rate. A retrospective study of the two periods by univariate and multivariate survival analysis revealed that, although much of the improvement in survival could be attributed to a shift in stage distribution towards earlier disease, the admission period itself had an important additional explanatory effect with respect to survival. This was probably due to the improvement in treatment protocols used in the latter period. Age was a prognostic variable only for patients admitted during the 1979-1984 period.

Actuarial Analysis↗

Identification of DNA-binding protein(s) in the developing heart.

An antiserum (anti-H2) directed at the second helix of the helix-loop-helix (HLH) protein MyoD1 reacts with a protein expressed during avian cardiac myocyte differentiation. Indirect immunohistochemical whole mount staining with anti-H2 detected a protein expressed in stage 11 hearts, but not in hearts of older embryos. At the cellular level, this staining is confined to the nucleus of cardiac cells suggesting that these proteins may have DNA-binding abilities. Several proteins were immunoprecipitated by anti-H2 from stage 11 heart tissue. Protein extracts from similarly staged hearts, when incubated with the muscle-specific enhancer sequence of muscle creatinine kinase (MCK), gave a stage-specific band shift in electromobility shift assays (EMSA), and these protein-DNA complexes were recognized and supershifted by anti-H2. Incubation with a MCK sequence containing a mutated E box did not produce a shift. The specific shift was present as early as stage 6, remained through stage 13, and disappeared by stage 17. These data suggest the presence of at least one protein that is transiently expressed in the differentiating cardiac myocyte, that is immunochemically reactive with an antiserum raised against the second helix of MyoD1, and that binds to a muscle-specific DNA enhancer sequence.

Amino Acid Sequence↗

Immunocytochemical demonstration of nerve growth factor receptor (NGF-R) in developing human fetal teeth.

Evidence is accumulating that nerve growth factor receptor (NGF-R or p75NGFR) can mediate cell growth and differentiation of non-neuronal cells. NGF-R expression was studied in developing teeth of human embryos and fetuses between the 6th and 18th weeks of gestation, using a monoclonal mouse-anti-human NGF-R antibody. In contrast to earlier findings in rodents, the NGF-R expression of the human dental papilla was found to be transient. NGF-R was present in the condensing ecto-mesenchymal cells of the dental papilla in the early cap stage tooth germ. In later developmental stages, a shift of the NGF-R expression from the papilla to the cytoplasmic membrane of the inner enamel epithelium (IEE) was demonstrated. As in rodent odontogenesis, the NGF-R immunoreactivity of the IEE remained until the odontoblasts started secretion of predentinal matrix in the late bell state. The mitotic activity in the IEE was detected by an antibody against proliferating cell nuclear antigen (PCNA) and showed that the NGF-R expression of the IEE decreased as the cell proliferation ceased. We propose that NGF-R may, be involved in differential and/or proliferative events of human odontogenesis.

Embryo, Mammalian↗

Buoyant density centrifugation of sea urchin embryo chromatin on sucrose-glucose gradient.

Unsheared chromatin isolated from sea urchin embryos was submitted to buoyant density centrifugation in sucrose-glucose gradients. The main peak of blastula chromatin was at a density position of 1.299 plus or minus 0.028 plus or minus 0.009 g ml -minus 1 whereas at gastrula stage a shift to a lower bouoyant density position of (1.276 plus or minus 0.021 plus or minus 0.007 g ml minus 1) was observed. Besides the main peak, a small band with a density of 1.18 g ml minus 1 was noticed. The lighter fraction differed from the heavy one in a higher histone to DNA ratio, a lower proportion of the F-1 histone, and a lower nonhistone to DNA ratio. The most pronounced developmental alterations of proteins were observed at the level of nonhistone protein patterns of the light fractions.

Animals↗

Different sialyltransferase activities in human colorectal carcinoma cells from surgical specimens detected by specific glycoprotein and glycolipid acceptors.

The amount and type of sialylation of tumor cell membranes depends on the activity of a number of different sialyltransferase enzymes. For the detection of specific activities in human colorectal carcinoma tissue several glycoprotein and glycolipid acceptors were used: desialylated fetuin, alpha 1-acid glycoprotein, beta 2-glycoprotein I, ovine submaxillaris mucin, and the gangliosides GM1, GM2, GM3 and GD1a. Because of their possible relevance for metastasis, precursors of Le(a) and Le(x) antigens, too, were employed, namely neoglycolipids produced by coupling LcOse4 or NeoLcOse4 oligosaccharides to L-alpha-phosphatidyl-ethanol-amine-dipalmitoyl. Our data indicate that human colorectal tumor tissue contains two highly active sialyltransferase enzymes, which are only weakly expressed in normal mucosa. These are a N-glycan-specific alpha 2,6-sialyltransferase, which was significantly increased in metastasizing tumors, and a Gal beta 1,3Gal-NAc-specific sialyltransferase, which was increased in tumors of early stages. A shift to enhanced alpha 2,6-sialylation of membrane glycoproteins during carcinogenesis was demonstrated by lectin ELISA analysis of magneto-bead separated tumor cells. Quantitative determination of specific sialyltransferase activities may be a sensitive tool for detection and monitoring of colon carcinoma.

Carcinoma↗

Stages of change in smoking during pregnancy in low-income women.

This study examined the effects of a smoking cessation intervention on stages of change in 349 low-income, pregnant women. At first prenatal visit, women were randomized into experimental or usual care condition and classified by stage of change: precontemplation, contemplation, preparation, or action. For each stage of change at the first prenatal visit, the stage distributions of the experimental and usual care groups were compared at the second and 36-week prenatal visits. Kruskal-Wallis tests revealed significant differences at the second visit in the stage distributions by condition for subjects who were initially in precontemplation or in preparation. In each case, a greater proportion of experimental than usual care subjects advanced through the stages. The shift was not maintained at the 36-week visit.

Adolescent↗

Experimental correlation-based identification of X-ray CT point spread function. Part 2: Simulation and design of input signal.

The preferred signals for non-parametric correlation-based point spread function identification are white noise or pseudo-random binary sequences (PRBSs). Given the difficulty of building a phantom based on either of these signals, a new input is devised that corresponds to pseudo-randomly located holes. The positions of the holes correspond to zeros in a 2-D PRBS. To optimise the design of the phantom and to ensure proper imaging procedure, a number of simulations are conducted. The effects of the following parameters on identification quality are investigated: the size of the holes and their minimum separation, the period of the PRBS, input-output translational and rotational mis-registration, pixel size and the presence of cupping. The factors affecting identification quality the most are rotational alignment, hole size and separation, as well as sequence length. During simulations, a point spread function offering characteristics similar to the Philips Tomoscan CX is identified. Optimal results are obtained when the signal consists of 0.6 mm holes, separated by 0.9 mm, whose position is based on a 32 x 32 PRBS generated with a ten-stage shift-register. When adequate rotational alignment is provided, it is shown that the pseudo-randomly located holes signal is a good substitute for a purely white signal when identifying the PSF of a CT scanner.

Humans↗

Two-dimensional gel analysis of the fate of oocyte nuclear proteins in the development of Xenopus laevis.

The amphibian oocyte nucleus is thought to provide a maternal store of protein required in embryogenesis. The fate of germinal vesicle proteins has been studied by comparing polypeptide patterns of oocytes, embryos, and several adult organs of Xenopus laevis on two-dimensional gels. A combination of silver staining and fluorography of radiolabeled protein on gels was used to analyze maternal and newly synthesized polypeptides in embryogenesis. Comparison of protein patterns was facilitated and corroborated by application of monoclonal antibodies against several germinal vesicle proteins. These were characterized by immunoblotting from two-dimensional gels, and polypeptides of identical structure were recognized in oocyte nuclei, embryos, and tadpoles. The following conclusions were drawn: (1) Almost all prevalent germinal vesicle proteins can be continuously traced in embryos up to swimming tadpole stages, although their patterns of new synthesis are greatly different, some are not radiolabeled in the embryo but solely provided by the maternal store. (2) Many of the polypeptides occurring in oocyte nuclei are also found in one or several organs of the adult. (3) Tissue specificities of germinal vesicle proteins, previously detected by immunocytochemistry with monoclonal antibodies, could be confirmed by independent biochemical methods. (4) As has been previously shown by immunohistological methods, oocyte nuclear antigens are shed into the cytoplasm of the maturing egg, and are reaccumulated in the nuclei of the embryonic cells, each at a characteristic developmental stage. These shifts between intracellular compartments are not accompanied by a change of the covalent structure of the antigen.

Age Factors↗

Cell movements during the initial phase of gastrulation in the sea urchin embryo.

The morphogenetic processes responsible for the initial phase of gastrulation in sea urchin embryos are not known. Here we report observations of the size and position of clones of cells derived from horseradish peroxidase (HRP)-injected mesomeres and macromeres. The displacement of these clones during the initial phase of gastrulation suggests that involution is a mechanism involved in primary invagination. Experiments with embryos marked with vital dyes indicate that movements occur only during a brief phase coincident with the invagination of the vegetal plate. Counts of cells derived from HRP-injected mesomeres and macromeres suggest it unlikely that localized growth in the vegetal plate is involved in gastrulation. An analysis of changes in cell shape during the initial phase of gastrulation indicates that there is a stage-dependent shift from cells being columnar to having their apices skewed toward the vegetal plate and an increase in the proportion of cells having basal processes during gastrulation. When embryos are grown in the presence of monoclonal antibodies to the apical lamina or monovalent fragments of these antibodies, the initial phase of gastrulation is delayed and they form partial exogastrulae. Analysis of embryos marked with HRP indicate that the antibody treatments interfere with the cellular movements observed in untreated embryos. We conclude that directed movements of cells within the blastoderm, probably employing tractoring on components of the hyaline layer, cause the buckling of the vegetal plate and displacement of presumptive endoderm cells seen during the initial phase of gastrulation.

Animals↗

Effects of a factor derived from polymorphonuclear leukocytes on the growth and collagen metabolism in normal and scleroderma skin fibroblast cultures.

Effects of a factor (15 kDa) derived from polymorphonuclear leukocytes (PMNs) on the growth and collagen metabolism of normal and scleroderma skin fibroblasts in culture were investigated. Skin fibroblasts from papillary, reticular or whole dermis of 5 patients with scleroderma and 7 normal controls were cultured in the presence or absence of PMN factor. The factor affected skin fibroblasts, (i) to stimulate cell proliferation, (ii) to stimulate collagenase production as observed by its functional activity, but (iii) to suppress collagen production with little effect on collagen types at a stage before the translational level. Scleroderma fibroblasts were less susceptible to the factor than normal fibroblasts in terms of cell proliferation and protein synthesis including collagen. Stimulation of cell proliferation by the factor was higher with reticular cells than papillary cells, while stimulation of collagenase production was inversely high in papillary cells and little stimulation was noted with reticular cells. Suppression of collagen production was also eminent in papillary cells, compared with that in reticular cells. These results suggest that PMNs function at the inflammatory stage in shifting tissue metabolism to a catabolic phase by releasing a factor which stimulates connective tissue cells, and that decreased susceptibility of scleroderma cells and reticular cells to PMN factor may provide for a positive factor in the accumulation of collagen in the reticular dermis of scleroderma skin.

Cell Division↗

Coupling the T7 A1 promoter to the runaway-replication vector as an efficient method for stringent control and high-level expression of lacZ.

An expression vector characterized by tight regulation and high expression of cloned genes appears to be indispensable for the engineering need. To achieve this goal, in association with lacI the T7 A1 promoter containing two synthetic lac operators was constructed into a runaway-replication vector. To further examine this vector system, lacZ was subcloned and placed under the control of the T7 A1 promoter on the plasmid. With the application of the thermal induction alone, the Escherichia coli strain harboring the recombinant plasmid was able to produce 15,000 Miller units of beta-galactosidase, while it yielded the recombinant protein with 45,000-50,000 Miller units upon both thermal and chemical induction. In sharp contrast, only 60-90 Miller units of beta-galactosidase was obtained for the cell at an uninduced state. As a result, the production yield of beta-galactosidase over the background level is amplified approximately 170-fold by thermal induction and 500-fold by thermal and chemical induction. To produce the recombinant protein on a large scale, an approach by connecting two fermenters in series was newly developed. By applying the three-stage temperature shift in this dual fermenter system, 55,000 Miller units of beta-galactosidase was obtained. Overall, it shows the potential use of the vector system developed here for its tight control and high production of recombinant proteins.

Bacteriophage T7↗

Probing the dielectric environment surrounding poly(N-isopropylacrylamide) in aqueous solution with covalently attached spirobenzopyran.

The dielectric environment surrounding poly(N-isopropylacrylamide) in aqueous solution was investigated by probing with spirobenzopyran covalently attached as a side chain to the polymer main chain. Inherent characteristics of the spirobenzopyran chromophore were analyzed, and the chromophore was confirmed to be suitable to probe the local polar condition around the polymer. Measurements for an aqueous polymer solution at various temperatures elucidated that the dielectric environment surrounding the polymer changed continuously even in the temperature range far below the lower critical solution temperature. This result suggested that the local and weak orientation of water molecules around the polymer diminished continuously in a preliminary stage of shifting to thermally induced phase separation. The dielectric environment surrounding thermoresponsive polymer in aqueous solution was investigated by probing with spirobenzopyran covalently attached as a side chain to the polymer main chain.

Acrylic Resins↗

Doing the right thing at the right time? The interaction of stages and processes of change in successful smoking cessation.

Research on the transtheoretical model has provided substantial support for both stages of change and processes of change (coping strategies influencing successful behavior change). This study examined whether timing of process use (using particular change processes during one stage and not during others) influences quit success. Hypothesized patterns of optimal process use were those marked by more use of experiential processes and less use of behavioral processes during contemplation and preparation and by the reverse pattern during action. Participants (N = 388) began in contemplation or preparation and took action during a 4-6 week period. Multivariate analyses of covariance examined the relationship between patterns of process use and success in staying quit both at 1-month follow-up and 5-6 months later. For the most part, results supported the hypothesis that successful stage transitions involve doing the right thing at the right time: engaging in experiential process activities during contemplation and preparation stages and shifting to behavioral process activities during action.

Adaptation, Psychological↗

Pamlin-induced tyrosine phosphorylation of SUp62 protein in primary mesenchyme cells during early embryogenesis in the sea urchin, Hemicentrotus pulcherrimus.

Ingression of primary mesenchyme cells (PMC) is associated with the encounter of basal lamina including pamlin. It was found that sea urchin embryos have a protein that binds antihuman focal adhesion kinase (FAK) antibodies, yet it has a 62 kDa homo-dimeric structure. Thus, this protein was distinctive from known FAK, and was named SUp62. In mesenchyme blastulae, one of the subunits increased its apparent molecular mass slightly but distinctively, then restored the original molecular mass in early gastrulae. This temporal and stage-specific shifting of the molecular mass was associated with the occurrence of tyrosine phosphorylation of a subunit that did not increase the apparent molecular mass. Herbimycin A induced the hyperphosphorylation of tyrosine residues of SUp62, and inhibited the occurrence of molecular mass shifting. Immunohistochemistry showed a strong positive signal of SUp62 and phosphotyrosine in PMC. Herbimycin A also severely but reversibly inhibited PMC dissociation, migration and gastrulation. Tyrosine phosphorylation of SUp62 was induced when PMC were incubated with pamlin in vitro, and it was initiated within 10 min after onset of the incubation. It reached its peak in 1 h, and declined gradually in the next 1 h, indicating that pamlin-induced tyrosine phosphorylation of SUp62 occurs closely associated with acquiring PMC migration activity.

Animals↗

[PSA related screening of prostate cancer. Panic or improvement?].

The early detection of prostate cancer and the aggressive treatment is the only chance for a cure. The use of PSA-related screening techniques brings forward the diagnosis of the disease by 5-10 years. While such early detection regimens shift the stage at the time of detection towards locally confined disease, and while there is no doubt that early treatment is the only way of curing prostate cancer, the application of screening in practice and healthcare policy remains controversial. This is because there are uncertainties about the degree of "over-diagnosis" which most probably results from screening, and from uncertainties about the risk-benefit balance. Randomized studies will show whether early detection of prostate cancer can reduce cancer-specific mortality. Conclusive data will not be available before 2005 respectively 2008. At that time, only the validated complied information about the risks and benefits of screening and about the possible therapeutic consequences may provide a way out of this current dilemma. A synopsis of the (European Randomized Study of Screening for Prostate Cancer) was given by F. H. Schröder in the British Journal of Urology International, December 2003.

Biomarkers, Tumor↗

Omitting axillary surgery for low-risk breast cancer patients--a Swedish prospective cohort study.

The effects of mammography screening are a decrease in the sizes of tumours and a shift in stage. Very few small breast cancers (< or = 10 mm) have lymph node metastases when screening-detected, the rate being as low as 7%. Axillary clearance is not necessary for all such small tumours. A Swedish prospective cohort study, scheduled for 1500 patients, is being launched, where axillary surgery is omitted for screening-detected breast cancers of < or = 10 mm showing Elston grade I or II/and/or S-phase < or = 10%. Axillary surgery, with the associated disadvantages, will not be performed in 970 women out of 1000 expecting an axillary recurrence rate of 3%. Nordic breast cancer centres are welcome to join the study, which has already recruited around 500 patients.

Adult↗

Periodic movements during sleep, sleep fragmentation, and sleep-wake complaints.

To better understand the relation of sleep complaint to sleep continuity and periodic movements during sleep (PMS), two groups of patients were studied retrospectively. One group of 51 patients, 26 men and 25 women, with a mean age of 56.4 years, complained of insomnia. The other group of 29 patients, 20 men and nine women, with a mean age of 55.8 years, complained of excessive daytime sleepiness. Sleepy patients differed significantly from insomnia patients in that they fell asleep faster and slept longer. They showed more frequent arousals (shifts to stage 1 sleep and number of awakenings) than insomnia patients who had longer arousals (mean duration of awakenings). Insomnia patients had more series of PMS, but sleepy patients had more PMS bursts per series.

Arousal↗

Myocardial infarction after microvascular head and neck reconstruction.

OBJECTIVE/HYPOTHESIS: Microvascular flap transfer is a popular method for immediate reconstruction of defects in the head and neck resulting after the treatment of head and neck cancer. Head and neck cancer occurs most commonly in elderly patients with a high prevalence of heavy smoking. Surgery in this patient population is frequently prolonged and is associated with significant intraoperative blood loss. The present study seeks to identify factors contributing to perioperative myocardial infarction and to determine the best course of management. STUDY DESIGN: Retrospective analysis of 193 consecutive free flap surgeries. METHODS A series of 193 microvascular free flaps performed over a 5-year period for reconstruction of defects in the head and neck was retrospectively analyzed to identify the incidence, management, and outcome of perioperative myocardial infarction in this patient population. RESULTS: Myocardial infarctions occurred in seven patients, for an overall incidence of 3.6%. Statistical analysis using logistic regression failed to demonstrate any significant relationship between age, sex, total operative time, operative blood loss, net intraoperative fluid shifts, tumor stage, American Society of Anesthesiology (ASA) preoperative classification, type of free flap, and the occurrence of perioperative myocardial infarction. Hemodynamic instability manifested by hypotension occurred in four patients who had perioperative myocardial infarction. Three of these patients underwent urgent coronary artery bypass surgery, whereas one patient underwent urgent endovascular therapy with subsequent stabilization of the hemodynamic instability. All free flaps survived despite myocardial infarction and hemodynamic instability. Two patients (29%) died after postoperative intervals of 74 and 99 days, never having left the hospital. CONCLUSIONS: Systemic hypotension is a well-recognized risk factor for free flap failure. Our experience suggests that aggressive intervention to reverse coronary ischemia associated with hemodynamic instability has a favorable outcome on free flap survival, and free flap thrombosis is not an inevitable outcome of the low-flow state associated with perioperative cardiopulmonary bypass. Although the overall incidence of perioperative myocardial infarction in patients undergoing microvascular head and neck reconstruction is low, patient mortality is high, so emphasis should be placed on preoperative identification of patients with coronary artery disease.

Aged↗