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At least 505 records · Page 28Linked to original sources
PubMed2005

The local expression and abundance of insulin-like growth factor (IGF) binding proteins in skeletal muscle are regulated by age and gender but not local IGF-I in vivo.

We wished to determine whether sustained IGF-I production in skeletal muscle increases local IGF binding protein (IGFBP) abundance, thereby mitigating the long-term stimulation of muscle growth by IGF-I. Muscle growth of transgenic mice that overexpress IGF-I in muscle (SIS2) and of wild-type (Wt) mice was compared. At 3, 5, 10, and 20 wk of age, hind-limb muscle weights and IGFBP-3, -4, -5, and -6 mRNA and protein abundances were quantified. Additional mice were injected with IGF-I or LR3-IGF-I, and phosphorylation of the type 1 IGF receptor (IGF-1R) was compared. Muscle mass was 20% greater in SIS2 compared with Wt mice by 10 wk of age (P < 0.01), and this difference was maintained to 20 wk. IGFBP mRNA and protein abundances were unaffected by genotype. IGFBP-4 and -5 protein abundances increased with age, whereas for IGFBP-3 and -6, there was a sexual dimorphic response (P < 0.01); after 5 wk of age, IGFBP-3 decreased in males but increased in females, whereas IGFBP-6 decreased in females and remained unchanged in males. These protein expression patterns resulted from differences at both the transcriptional and posttranscriptional levels. LR3-IGF-I stimulated IGF-1R phosphorylation to a greater extent than IGF-I at both 5 and 10 wk of age (P < 0.01), regardless of gender or genotype (P > 0.21). Thus, variations in local IGF-I levels do not appear to regulate muscle IGFBP expression. The age- and gender-specific differences in muscle IGFBP expression are not sufficient to alter the response of the muscle to the IGFs but may impact the IGF-independent effects of these IGFBPs.

Aging↗
PubMed2004

Drosophila klarsicht has distinct subcellular localization domains for nuclear envelope and microtubule localization in the eye.

The Drosophila klarsicht (klar) gene is required for developmentally regulated migrations of photoreceptor cell nuclei in the eye. klar encodes a large ( approximately 250 kD) protein with only one recognizable amino acid sequence motif, a KASH (Klar, Anc-1, Syne-1 homology) domain, at its C terminus. It has been proposed that Klar facilitates nuclear migration by linking the nucleus to the microtubule organizing center (MTOC). Here we perform genetic and immunohistochemical experiments that provide a critical test of this model. We analyze mutants in the endogenous klar gene and also flies that express deleted forms of Klar protein from transgenes. We find that the KASH domain of Klar is critical for perinuclear localization and for function. In addition, we find that the N-terminal portion of Klar is also important for function and contains a domain that localizes the protein to microtubules apical to the nucleus. These results provide strong support for a model in which Klar links the nucleus to the MTOC.

Amino Acid Sequence↗
PubMed2006

Management of prostate cancer. Part 2: localized and locally advanced disease.

Prostate cancer is the most prevalent nondermatological malignancy affecting men in the Western world. An increase in public awareness has led to earlier detection. Accepted treatments for localized prostate cancer include active surveillance, radical prostatectomy, interstitial brachytherapy, external beam radiotherapy and watchful waiting. The authors discuss the rationale for the different approaches together with outcomes including toxicity. Novel approaches are also explored. The management of locally advanced disease has long been a challenge and the evolving evidence is reviewed.

Humans↗
PubMed1991

Immunohistochemical localization of carcinoembryonic antigen (CEA) in squamous cell carcinoma of the uterine cervix: prognostic significance of localization pattern of CEA.

Immunohistochemical localization of carcinoembryonic antigen (CEA) was investigated with 100 cases of invasive squamous cell carcinoma of the uterine cervix in order to evaluate the relationship of the positive pattern of CEA to the prognoses of patients with this neoplasm. Positive staining for CEA using peroxidase-antiperoxidase method was noticed in all tumors studied. The localization patterns of CEA were divided into the following four types depending on the location of CEA-positive areas in cancer nests: central type, surrounding type, diffuse type, and focal type. Survival curves based on calculation by the method of Kaplan-Meier showed that prognosis of patient was most excellent in the disease of central type, which was followed by surrounding type, diffuse type, and focal type, in this order. The survival curve for central type was significantly better than those for diffuse type and focal type (p less than 0.05) as assessed by Log rank test. In squamous cell carcinoma of the cervix, consequently, prognosis of patient might be favorable when CEA is demonstrated in the center part of cancer nests by an immunohistochemical technique.

Adult↗
PubMed1993

Neodymium-YAG laser treatment in localized prostatic cancer. High rate of local failure.

Clinically localized prostatic cancer, T0-2,NX,M0, was treated with extended transurethral resection and subsequent neodymium-YAG laser irradiation of the prostatic cavity in 20 patients in 1987-1990. The patients' mean age was 71 (range 64-84) years. During 12-month follow-up only three patients had negative biopsies, whereas 16 had residual cancer and one had atypical, suspectedly malignant cells. Eight of the 16 with residual cancer underwent repetition of the combined resection and laser treatment, but this led to negative biopsies in only two cases. The treatment per se was well tolerated and side effects were few, but the poor outcome concerning local tumor control is contradictory to previous reports and raises doubts as to the advisability of offering such treatment as an alternative to radical prostatectomy.

Aged↗
PubMedDate not supplied

Rationale for use of local hyperthermia with radiation therapy and selected anticancer drugs in locally advanced human malignancies.

The addition of local hyperthermia to radiation therapy has significantly improved the ability of oncologists to control superficial malignancies. Large tumours, tumours which cannot be heated adequately, and those situated in areas where surrounding normal tissues have decreased radiation tolerance, however, are difficult to eradicate even with this combination treatment. We believe that properly selected and scheduled anticancer drugs will add substantially to the efficacy of local hyperthermia and radiation. A review of the literature concerning the cytotoxic interactions of various anticancer agents with hyperthermia, with radiation and with relevant physiological parameters is presented. From this review, anticancer drugs which are good candidates for trimodality therapy are identified and a general approach to trimodality scheduling is suggested.

Animals↗
PubMed2005

Localization of phosphorylated forms of Bcl-2 in mitosis: co-localization with Ki-67 and nucleolin in nuclear structures and on mitotic chromosomes.

Bcl-2 phosphorylation is a normal physiological process occurring at mitosis or during mitotic arrest induced by microtubule damaging agents. The consequences of Bcl-2 phosphorylation on its function are still controversial. To better understand the role of Bcl-2 phosphorylation in mitosis, we studied the subcellular localization of phosphorylated forms of Bcl-2. Immunofluorescence experiments performed in synchronized HeLa cells indicate for the first time that mitotic phosphorylated forms of Bcl-2 can be detected in nuclear structures in prophase cells together with nucleolin and Ki-67. In later mitotic stages, as previously described, phosphorylated forms of Bcl-2 are localized on mitotic chromosomes. In addition, we demonstrate that Bcl-2 in these structures is at least in part phosphorylated on the T56 residue. Then, coimmunoprecipitation experiments reveal that, in cells synchronized at the onset of mitosis, Bcl-2 is present in a complex with nucleolin, cdc2 kinase and PP1 phosphatase. Taken together, these data further support the idea that Bcl-2 could have a new function at mitosis.

Cell Cycle↗
PubMed2000

Evidence that Wallerian degeneration and localized axon degeneration induced by local neurotrophin deprivation do not involve caspases.

The selective degeneration of an axon, without the death of the parent neuron, can occur in response to injury, in a variety of metabolic, toxic, and inflammatory disorders, and during normal development. Recent evidence suggests that some forms of axon degeneration involve an active and regulated program of self-destruction rather than a passive "wasting away" and in this respect and others resemble apoptosis. Here we investigate whether selective axon degeneration depends on some of the molecular machinery that mediates apoptosis, namely, the caspase family of cysteine proteases. We focus on two models of selective axon degeneration: Wallerian degeneration of transected axons and localized axon degeneration induced by local deprivation of neurotrophin. We show that caspase-3 is not activated in the axon during either form of degeneration, although it is activated in the dying cell body of the same neurons. Moreover, caspase inhibitors do not inhibit or retard either form of axon degeneration, although they inhibit apoptosis of the same neurons. Finally, we cannot detect cleaved substrates of caspase-3 and its close relatives immunocytochemically or caspase activity biochemically in axons undergoing Wallerian degeneration. Our results suggest that a neuron contains at least two molecularly distinct self-destruction programs, one for caspase-dependent apoptosis and another for selective axon degeneration.

Animals↗
PubMed1975

[The association of local radiation therapy and systemic chemotherapy in the treatment of clinically localized Ewing's sarcoma].

The results obtained in 12 cases of still clinically localized Ewing's sarcoma by associating radiation therapy of the primary focus with intermittent systematic chemotherapy are reported. Two of these patients presented pulmonary and bone metastases 12 and 14 months respectively after bioptic diagnosis while the remaining ten were in good health and free from metastasis at between 6 and 28 months (average 16 months) after biopsy. Although it is considered necessary to make further observations before the association's validity is certain, it is considered that on this basis and on the basis of the few cases reported in the literature than the association of rationally conducted systematic chemotherapy with local radiation therapy will extend the onset time of metastasis and so increase average survival in Ewing's sarcoma.

Adolescent↗
PubMedDate not supplied

[Prognostic significance of local and systemic indicators of lipid peroxidation and antioxidant system in perforating wounds of the eyes and their time course during local antioxidant treatment].

Lipid peroxidation parameters malonic dialdehyde (MDA) and dienic conjugates (DC) and antioxidant defense (AOD) values superoxide dismutase (SOD), catalase, alpha-tocopherol were measured in the blood neutrophils and lacrimal fluid of 66 patients on days 1-2, 7-8, 14-15, and 21-22 after perforating wound of first, second, third, and fourth degree of severity according to P, 1. Lebekhov and in repeated injury, and the time course of these parameters during local treatment with therapeutic films with emoxipin and emoxipin + piridoxine was evaluated. A stable increase of MDA and DC levels in blood neutrophils, decrease of catalase, SOD, and alpha-tocopherol levels in blood neutrophils, and decrease of catalase enzymes and SOD activities in the lacrimal fluid of injured eye starting from days 7-8 are prognostically unfavorable signs. These data prompt the use of local and systemic treatment with antioxidants (emoxipin, tocopherol, etc.) in perforating wounds starting from the first days after the injury. Good clinical and antioxidant effect was observed after treatment with ocular therapeutic films with emoxipin and piridoxine.

Adult↗
PubMed2002

Localized juvenile periodontitis or localized aggressive periodontitis.

In general, the new term "localized aggressive periodontitis" replaces what was previously known as "localized juvenile periodontitis." Similarly, "generalized aggressive periodontitis" replaces what used to be called "generalized juvenile periodontitis." Aggressive periodontitis is a specific type of periodontitis with clearly identifiable clinical and laboratory findings, making it sufficiently different from chronic periodontitis and warranting separate classification. Not all the characteristics must be present to assign a diagnosis or classify the disease. The diagnosis may be based on clinical, radiographic, and historical data, and laboratory testing may not be essential for assigning a diagnosis.

Adolescent↗
PubMed2005

"Local Food - Nutraceuticals": an example of a multidisciplinary research project on local knowledge.

Currently, dietary patterns change rapidly all over the world. Most notably, there is a fast increase in the convenience food market. Here we discuss the overall theoretical framework and strategy of an EU-funded project on local food, a common resource in many parts of the Mediterranean. Such food is often only available seasonally and is consumed either fresh (e.g. spring salads and vegetables, fruits in autumn) or in a conserved form (dried, fermented, pickled). There is an urgent need to document and analyse such local resources, which are today at the brink of disappearance. In this project, selected species were studied using a multidisciplinary approach, including strategies and methods from pharmacology, nutritional sciences and anthropology (i.e. ethnopharmacological or ethnonutritional ones). For example, all extracts were profiled using HPLC-MS, by determining their polyphenol content and using a variety of in vitro anti-oxidant assays (incl. guaiacol oxidation, xanthine oxidase inhibition, HOCl scavenging, eNOS activity). Such research also points to ways for ascertaining the intergenerational transmission of the knowledge and for sustainable development and management. Examples from field studies in southern Italy and from pharmacological studies using a variety of targets are used to illustrate the potential of such neglected resources. The wider implications of such an approach, for example, for the study of similar traditions in Central and Eastern Europe are also discussed.

Diet, Mediterranean↗
PubMed2006

[Case series of localized nasal NK/T-cell lymphoma treated with preceding intensified local radiation therapy before systemic chemotherapy].

Nasal NK/T-cell lymphoma is EB virus-associated aggressive lymphoma, which is more prevalent in Asia. Previously, this lymphoma which was recognized as lethal midline granuloma, commonly presents with midline facial destructive lesions. In early stage I/II disease, radiation therapy exerts a powerful treatment outcome, however, toxic adverse events are indispensable and the tolerability of radiation therapy with chemotherapy has not been fully studied. It is imperative to offer an appropriate treatment for cure of this disease. We report consecutive 4 cases of nasal NK/T-cell lymphoma, which was treated with 56 Gy intensified local radiation therapy followed by systemic chemotherapy. Two cases complicated with grade 3 stomatitis during the treatment course and 3 cases were hospitalized due to the decrease of oral intake. The scheduled radiation chemotherapy was completed and resulted in complete response of disease in all cases. High intensified radiation therapy followed by chemotherapy may be effective for localized nasal NK/T-cell lymphoma.

Adolescent↗
PubMed2006

Thoracoscopic localization techniques for patients with solitary pulmonary nodule: radioguided surgery versus hookwire localization.

AIM: The aim of this study is to compare 2 different methods for localization of peripheral pulmonary lesions requiring thoracoscopic resection: radioguided surgery (still considered an innovative method) and computed tomography-guided hookwire localization. METHODS: Thirty randomized patients (21 males and 9 females), ranging from 21-74 years, average age 56.3 years) with solitary pulmonary nodule (SPN) were enrolled in this prospective study. Inclusion criteria was: a maximum nodule diameter of less than 3 cm and a maximum distance from the visceral pleura of 3 cm. The patients were subdivided into 2 equal groups and one of the 2 different methods for diagnosing SPN was applied. Group A received a thoracoscopy using the scinti-probe technique and group B received a thoracoscopy aided by a hooked needle. RESULTS: The frozen section revealed a primitive pulmonary tumor in 13 cases, intestinal adenocarcinoma metastasis in 3 cases and renal cancer metastasis in 1 case. The remaining 13 cases were pathologically benign: sarcoidosis in 6 cases, hamartochondroma in 3 cases, scleroanthracosis in 2 cases and tuberculoma in 2 cases. CONCLUSION: On the basis of our experience, the conclusion is drawn that this methods has been proven efficacious in the diagnosis of SPN, and video-assisted thoracoscopy allows for the removal of pulmonary nodules without complications.

Adenocarcinoma↗
PubMedDate not supplied

[Local hyperthermia by means of ballon-type electrodes in combined therapy of patients with locally spread cancer of the mouth mucosa and lower lip].

Modification of the standard chemo- and radiotherapy with local hyperthermia gives evident positive results in treatment of patients with local cancer of tunica mucosa of mouth and lower lip. Since this area having uneven complex surface needs to develop radiofrequency emitting special applicators. We have used catheters with ballons filled with hypertonic solution as electrodes to adapt the mouth cavity. An electric field creating between these ballons and high surface adjustability makes this system come in useful.

Adult↗
PubMed1991

[MK-507 (L-671 152): local tolerance and effectiveness of a new local carbonic anhydrase inhibitor in healthy probands].

A three-dose, randomized, double-blind parallel, placebo-controlled ocular tolerancy study was undertaken in 24 healthy, normal volunteers with two formulations of 2% MK-507 (L-671 152), a novel water-soluble, topical carbonic anhydrase inhibitor. In this study MK-507 was administered to humans for the first time. Subjects received 3 sequential drops of the test drug in one randomly selected eye (at 13:00, 14:00, and 14:10 o'clock): ten received 2% MK-507 formulated with 0.5% hydroxyethylcellulose (HEC); ten, 2% MK-507 with no HEC; two, vehicle with HEC; and two, vehicle without HEC. Local tolerance of 2% MK-507 was good with predominantly mild and transient local symptoms, somewhat fewer for the formulation without HEC. Significant lowering of intraocular pressure (IOP) by up to 7 mmHg was noted when comparing IOP 4 h and 5 h after the first dose with IOP 20 h and 19 h before the first dose in the treated eyes of subjects receiving MK-507. Slightly greater activity was noted when MK-507 was formulated with HEC.

Adult↗
PubMed1989

Specific marrow localization of an 131I-labeled anti-myeloid antibody in normal dogs: effects of a "cold" antibody pretreatment dose on marrow localization.

Tumor recurrence and regimen-related toxicity remain major obstacles in the successful use of marrow transplantation as therapy for hematologic malignancies. By attaching radionuclides to monoclonal antibodies (MoAbs) targeted at myeloid-associated antigenic determinants, a more effective and directed delivery of therapy may be possible without increasing toxicity. We investigated the biodistribution over time of an anti-myeloid antibody (DM-5) labeled with trace amounts of 131I in normal dogs. This study demonstrates the ability to target marrow with a high degree of selectivity, achieving marrow/blood ratios of 25-30:1 with the greatest concentration in any other organ being a tissue/blood ratio of 1.4:1 for stomach at 48 h. A pretreatment dose of unlabeled antibody effectively reduced early hepatic uptake by 80%, resulting in improved marrow localization with an estimated 58.6% of the injected dose localized in marrow within 2 h following infusion, compared to 32.8% without pretreatment. The marrow concentration clearance curve for the radioimmunoconjugate revealed an initial short half-life (4.75 h), suggesting rapid internalization, digestion, and release of free iodine (dehalogenation). This view was supported by a corresponding rise in trichloroacetic acid-non-precipitable activity during this period. Methods aimed at decreasing dehalogenation may result in longer residence time of the radionuclide within the marrow space, resulting in more effective tumor cell kill. This approach may provide a way to improve upon the current results obtained with marrow transplantation as treatment for patients with leukemia and other hematologic malignancies.

Animals↗
PubMed1986

[Various characteristics of gene localization in eukaryotic chromosomes. Formulation of a problem and analysis of non-random localization of mating type loci in fungi].

We have denoted two possible models of gene order evolution as the "card" and "chess" models. The first suggests random shuffling of genes during evolution, the second--non-random gene transposition, gene order being checked by natural selection. We discuss here localization of the mating type locus in fungal genomes. In 8 of 10 genetically well studied species of ascomycetous fungi, the mating type locus is linked to a centromere; in one species, it segregates regularly during the second meiotic division, and only one species does not show any regularity in the mating type locus segregation. Centromeric linkage of the mating type locus maintains heterozygosity of all centromeric genome regions during intratetrad fertilization observed in some fungi. Non-random localization of mating type locus can be considered as the means for conservation of heterozygosity.

Chromosome Mapping↗