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1.
Epidemiol Psychiatr Sci ; 31: e19, 2022 Mar 30.
Article in English | MEDLINE | ID: mdl-35352676

ABSTRACT

AIMS: Lower parental education has been linked to adverse youth mental health outcomes. However, the relationship between parental education and youth suicidal behaviours remains unclear. We explored the association between parental education and youth suicidal ideation and attempts, and examined whether sociocultural contexts moderate such associations. METHODS: We conducted a systematic review and meta-analysis with a systematic literature search in PubMed, PsycINFO, Medline and Embase from 1900 to December 2020 for studies with participants aged 0-18, and provided quantitative data on the association between parental education and youth suicidal ideation and attempts (death included). Only articles published in English in peer-reviewed journals were considered. Two authors independently assessed eligibility of the articles. One author extracted data [e.g. number of cases and non-cases in each parental education level, effect sizes in forms of odds ratios (ORs) or beta coefficients]. We then calculated pooled ORs using a random-effects model and used moderator analysis to investigate heterogeneity. RESULTS: We included a total of 59 articles (63 study samples, totalling 2 738 374 subjects) in the meta-analysis. Lower parental education was associated with youth suicidal attempts [OR = 1.12, 95% Confidence Interval (CI) = 1.04-1.21] but not with suicidal ideation (OR = 1.05, 95% CI = 0.98-1.12). Geographical region and country income level moderated the associations. Lower parental education was associated with an increased risk of youth suicidal attempts in Northern America (OR = 1.26, 95% CI = 1.10-1.45), but with a decreased risk in Eastern and South-Eastern Asia (OR = 0.72, 95% CI = 0.54-0.96). An association of lower parental education and increased risk of youth suicidal ideation was present in high- income countries (HICs) (OR = 1.14, 95% CI = 1.05-1.25), and absent in low- and middle-income countries (LMICs) (OR = 0.91, 95% CI = 0.77-1.08). CONCLUSIONS: The association between youth suicidal behaviours and parental education seems to differ across geographical and economical contexts, suggesting that cultural, psychosocial or biological factors may play a role in explaining this association. Although there was high heterogeneity in the studies reviewed, this evidence suggests that the role of familial sociodemographic characteristics in youth suicidality may not be universal. This highlights the need to consider cultural, as well as familial factors in the clinical assessment and management of youth's suicidal behaviours in our increasingly multicultural societies, as well as in developing prevention and intervention strategies for youth suicide.


Subject(s)
Suicidal Ideation , Suicide , Adolescent , Child , Child, Preschool , Educational Status , Humans , Infant , Infant, Newborn , Parents , Poverty
2.
Sci Total Environ ; 750: 142283, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-33182218

ABSTRACT

The deterioration of monument or building stone materials is mostly due to the growth of black crusts that cause blackening and disaggregation of the exposed surface. This study reports on new oxygen (δ17O, δ18O and Δ17O) and sulphur (δ33S, δ34S, δ36S, Δ33S and Δ36S) isotopic analyses of black crust sulphates formed on building stones in Sicily (Southern Italy). The measurements are used to identify the possible influence of volcanic emissions on black crust formation. Black crusts were mostly sampled on carbonate stone substrate in different locations subject to various sulphur emission sources (marine, anthropogenic and volcanic). Unlike atmospheric sulphate aerosols that mostly exhibit Δ33S > 0‰, here most of the analysed black crust sulphates show negative Δ33S. This confirms that black crust sulphates do not result from deposition of sulphate aerosols or of rainwater but mostly from the oxidation of dry deposited SO2 onto the stone substrate. The δ34S and δ18O values indicate that most of black crust sulphate originates from anthropogenic activities. Δ17O values are found to be related to the sampling location. The largest 17O-anomalies (up to ~4‰) are measured in black crust from areas highly influenced by volcanic emissions, which demonstrates the strong involvement of ozone in the formation of black crusts in volcanically influenced environments.

3.
Neuroimage ; 141: 490-501, 2016 Nov 01.
Article in English | MEDLINE | ID: mdl-27421183

ABSTRACT

Network theory provides a principled abstraction of the human brain: reducing a complex system into a simpler representation from which to investigate brain organisation. Recent advancement in the neuroimaging field is towards representing brain connectivity as a dynamic process in order to gain a deeper understanding of how the brain is organised for information transport. In this paper we propose a network modelling approach based on the heat kernel to capture the process of heat diffusion in complex networks. By applying the heat kernel to structural brain networks, we define new features which quantify change in heat propagation. Identifying suitable features which can classify networks between cohorts is useful towards understanding the effect of disease on brain architecture. We demonstrate the discriminative power of heat kernel features in both synthetic and clinical preterm data. By generating an extensive range of synthetic networks with varying density and randomisation, we investigate heat diffusion in relation to changes in network topology. We demonstrate that our proposed features provide a metric of network efficiency and may be indicative of organisational principles commonly associated with, for example, small-world architecture. In addition, we show the potential of these features to characterise and classify between network topologies. We further demonstrate our methodology in a clinical setting by applying it to a large cohort of preterm babies scanned at term equivalent age from which diffusion networks were computed. We show that our heat kernel features are able to successfully predict motor function measured at two years of age (sensitivity, specificity, F-score, accuracy = 75.0, 82.5, 78.6, and 82.3%, respectively).


Subject(s)
Brain/diagnostic imaging , Brain/pathology , Diffusion Magnetic Resonance Imaging/methods , Image Interpretation, Computer-Assisted/methods , Pattern Recognition, Automated/methods , Premature Birth/diagnostic imaging , Premature Birth/pathology , Female , Hot Temperature , Humans , Male , Nerve Net/diagnostic imaging , Nerve Net/pathology , Reproducibility of Results , Sensitivity and Specificity , Thermodynamics
4.
Cereb Cortex ; 24(9): 2324-33, 2014 Sep.
Article in English | MEDLINE | ID: mdl-23547135

ABSTRACT

Cerebral white-matter injury is common in preterm-born infants and is associated with neurocognitive impairments. Identifying the pattern of connectivity changes in the brain following premature birth may provide a more comprehensive understanding of the neurobiology underlying these impairments. Here, we characterize whole-brain, macrostructural connectivity following preterm delivery and explore the influence of age and prematurity using a data-driven, nonsubjective analysis of diffusion magnetic resonance imaging data. T1- and T2-weighted and -diffusion MRI were obtained between 11 and 31 months postconceptional age in 49 infants, born between 25 and 35 weeks postconception. An optimized processing pipeline, combining anatomical, and tissue segmentations with probabilistic diffusion tractography, was used to map mean tract anisotropy. White-matter tracts where connection strength was related to age of delivery or imaging were identified using sparse-penalized regression and stability selection. Older children had stronger connections in tracts predominantly involving frontal lobe structures. Increasing prematurity at birth was related to widespread reductions in connection strength in tracts involving all cortical lobes and several subcortical structures. This nonsubjective approach to mapping whole-brain connectivity detected hypothesized changes in the strength of intracerebral connections during development and widespread reductions in connectivity strength associated with premature birth.


Subject(s)
Brain/anatomy & histology , Brain/growth & development , Infant, Premature/growth & development , Child Development , Child, Preschool , Connectome , Diffusion Magnetic Resonance Imaging , Diffusion Tensor Imaging , Female , Humans , Image Processing, Computer-Assisted , Infant , Male , Nerve Fibers, Myelinated , Neural Pathways/anatomy & histology , Neural Pathways/growth & development , White Matter/anatomy & histology , White Matter/growth & development
5.
Clin Exp Allergy ; 42(3): 471-80, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22356145

ABSTRACT

BACKGROUND: Parietaria pollen is one of the major cause of pollinosis in the southern Europe. Specific immunotherapy is the only treatment able to modify the natural outcome of the disease restoring a normal immunity against allergens. METHODS: We designed a recombinant molecule (PjEDloop1) comprised of genetic-engineered variants of the major allergens of the Parietaria pollen (Par j 2/Par j 1). Purity and chemical-physical properties of the derivative were analysed by RP-HPLC chromatography and Photon Correlation Spectroscopy. Immunological activity was evaluated by means of Western blotting, ELISA inhibition and PBMC proliferation assay in 10 Parietaria allergic patients. Basophil activation was studied in six subjects. The immunogenicity of the hybrid was studied looking at the immune responses induced in a mouse model of sensitization. RESULTS: The PjEDloop1 hybrid was produced as a purified recombinant protein with high stability in solution. Western blot, ELISA inhibition and basophil activation test showed that the PjEDloop1 displays a remarkable reduced IgE binding and anaphylactic activity. CD3 reactivity was conserved in all patients. Mice immunization with the rPjEDloop1 induced antibodies and T cell responses comparable to that obtained by the wild type allergens. Such antibodies shared the specificities to rPar j 1 and rPar j 2 with human IgE antibodies. CONCLUSION: Our results demonstrated that a mutant hybrid expressing genetically engineered forms of the major P. judaica allergens displayed reduced allergenicity and retained T cell reactivity for the induction of protective antibodies in vaccination approaches for the treatment of Parietaria pollinosis.


Subject(s)
Allergens/immunology , Desensitization, Immunologic/methods , Parietaria/immunology , Plant Proteins/immunology , Animals , Antigens, Plant , Blotting, Western , Chromatography, High Pressure Liquid , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Genetic Engineering/methods , Humans , Mice , Mice, Inbred BALB C , Mutagenesis, Site-Directed , Recombinant Proteins/chemical synthesis , Recombinant Proteins/immunology , Rhinitis, Allergic, Seasonal/therapy
6.
FASEB J ; 20(11): 1916-7, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16818470

ABSTRACT

A distinctive feature of Alzheimer's disease is the deposition of amyloid beta-protein (Abeta) in senile or diffuse plaques. The 42 residue beta-peptide (Abeta42) is the predominant form found in plaques. In the present work we report a high-yield expression and purification method of production of a recombinant Abeta42. The purified recombinant peptide shows characteristics similar to the synthetic human peptide. Different size aggregates, either small oligomers or larger aggregates, were obtained upon dissolving the recombinant Abeta42 peptide under different conditions at pH 7.2 or pH 3, respectively. We report a new toxicity assay on the morphogenic development of the sea urchin Paracentrotus lividus and study the toxicity of the two kinds of aggregates. Despite the difference between the ionic strength of human extracellular fluid (0.154 mol/l) and artificial sea water (0.48 mol/l), toxicity data collected in this system have an intrinsic relevance. The different ionic strength, in fact, could change the kinetics of oligomer formation, but the effect of morphogenic development reported here is related to the final oligomer sizes. Results of the toxicity assay of Abeta42 on sea urchin development also show a dose-dependent effect. After only 4 h of embryo development, one can note morphological defects in the cell membrane. Retardation of the embryo's development, along with cellular disorders visible inside the blastocoele, can be observed after 1 day of development. Cellular degeneration in two different pathological phenotypes-the occluded blastulae and the occluded prism-is present after 48 h of development. Results show that a greater effect on cell death is induced by the small oligomers stabilized under physiological conditions than at acid pH. In this case only occluded blastulae are found after 48 h of development.


Subject(s)
Amyloid beta-Peptides/toxicity , Embryo, Nonmammalian/drug effects , Paracentrotus/embryology , Peptide Fragments/toxicity , Animals , Base Sequence , Cloning, Molecular , DNA Primers , Humans , Morphogenesis/drug effects , Paracentrotus/drug effects , Recombinant Proteins/toxicity , Restriction Mapping , Reverse Transcriptase Polymerase Chain Reaction
7.
Analyst ; 127(4): 542-53, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12022656

ABSTRACT

Chemical analysis is a well-established procedure for the provenancing of archaeological ceramics. Various analytical techniques are routinely used and large amounts of data have been accumulated so far in data banks. However, in order to exchange results obtained by different laboratories, the respective analytical procedures need to be tested in terms of their inter-comparability. In this study, the schemes of analysis used in four laboratories that are involved in archaeological pottery studies on a routine basis were compared. The techniques investigated were neutron activation analysis (NAA), X-ray fluorescence analysis (XRF), inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). For this comparison series of measurements on different geological standard reference materials (SRM) were carried out and the results were statistically evaluated. An attempt was also made towards the establishment of calibration factors between pairs of analytical setups in order to smooth the systematic differences among the results.

8.
Int J Radiat Oncol Biol Phys ; 50(4): 937-45, 2001 Jul 15.
Article in English | MEDLINE | ID: mdl-11429221

ABSTRACT

PURPOSE: To examine the acute urinary toxicity following transperineal prostate implant using a modified Quimby loading method with regard to time course, severity, and factors that may be associated with a higher incidence of morbidity. METHODS AND MATERIALS: One hundred thirty-nine patients with prostate adenocarcinoma treated with brachytherapy from 1997 through 1999 had follow-up records available for review. Patients considered for definitive brachytherapy alone included those with prostate specific antigen (PSA) < or = 6, Gleason score (GS) < or = 6, clinical stage < T2b, and prostate volumes generally less than 40 cc. Patients with larger prostate volumes were given neoadjuvant antiandrogen therapy. Those with GS > 6, PSA > 6, or Stage > T2a were treated with external beam radiation therapy followed by brachytherapy boost. Sources were loaded according to a modified Quimby method. At each follow-up, toxicity was graded based on a modified RTOG urinary toxicity scale. RESULTS: Acute urinary toxicity occurred in 88%. Grade I toxicity was reported in 23%, grade II in 45%, and grade III in 20%, with 14% requiring prolonged (greater than 1 week) intermittent or indwelling catheterization. Overall median duration of symptoms was 12 months. There was no difference in duration of symptoms between patients treated with I-125 or Pd-103 sources (p = 0.71). After adjusting for GS and PSA, multivariate logistic regression analysis showed higher incidence of grade 3 toxicity in patients with larger prostate volumes (p = 0.002), and those with more seeds implanted (p < 0.001). Higher incidence of prolonged catheterization was found in patients receiving brachytherapy alone (p = 0.01), with larger prostate volumes (p = 0.01), and those with more seeds implanted (p < 0.001). CONCLUSION: Interstitial brachytherapy for prostate cancer leads to a high incidence of acute urinary toxicity, most of which is mild to moderate in severity. A prolonged need for catheterization can occur in some patients. Patients receiving brachytherapy alone, those with prostate volumes greater than 30 cc, and those implanted with a greater number of seeds have the highest incidence of significant toxicity.


Subject(s)
Adenocarcinoma/radiotherapy , Brachytherapy/adverse effects , Prostatic Neoplasms/radiotherapy , Urination Disorders/etiology , Acute Disease , Adenocarcinoma/blood , Adult , Aged , Analysis of Variance , Brachytherapy/methods , Follow-Up Studies , Humans , Iodine Radioisotopes/therapeutic use , Logistic Models , Male , Middle Aged , Palladium/therapeutic use , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Radioisotopes/therapeutic use
9.
Dev Biol ; 234(1): 107-19, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11356023

ABSTRACT

In sea urchin embryos, the initial animal-vegetal (AV) axis is specified during oogenesis but the mechanism is largely unknown. By using chemical reagents such as lithium, it is possible to shift the principal embryonic territories toward a vegetal fate. We have investigated the possibility of obtaining the same morphological effect as with lithium by utilizing Fabs against the maternal Bep4 protein that is localized in the animal part of Paracentrotus lividus egg and embryos. Incubation of fertilized eggs with Fabs against Bep4 protein causes exogastrulation at 48 h of development of P. lividus embryos, similar to embryos treated with lithium. This vegetalizing effect was ascertained by utilizing territorial markers such as EctoV, EndoI, and Ig8. The effect of Fabs against Bep4 on gene expression was observed by monitoring spatial expression of the hatching enzyme gene. A decreased expression domain compared to its normal spatial distribution was detected and this effect was again comparable to those obtained with lithium treatment. Association of Bep4 with a cadherin was demonstrated by immunoprecipitation and immunostaining experiments, and an involvement in cell signaling is discussed. In addition, treatment of embryos with anti-Bep4 Fabs causes an enhancement in the level and an expansion in the pattern of nuclear beta-catenin. Moreover, this treatment also provokes a decrease of beta-catenin in adherens junctions. Together, these data indicate that anti-Bep4 Fabs provoke a shift of the animal-vegetal boundary toward the animal pole and suggest an active role of Bep4 protein in patterning along the AV axis.


Subject(s)
Body Patterning , Membrane Proteins/metabolism , Trans-Activators , Adherens Junctions , Animals , Antigens, Differentiation , Cadherins/isolation & purification , Cadherins/metabolism , Cell Adhesion , Cytoskeletal Proteins/isolation & purification , Cytoskeletal Proteins/metabolism , Embryo, Nonmammalian , Membrane Proteins/isolation & purification , Models, Biological , Nuclear Proteins/isolation & purification , Nuclear Proteins/metabolism , Protein Binding , Sea Urchins , Tissue Distribution , beta Catenin
10.
Int J Radiat Oncol Biol Phys ; 48(4): 1007-13, 2000 Nov 01.
Article in English | MEDLINE | ID: mdl-11072157

ABSTRACT

PURPOSE: To determine if patients with carcinoma of the vulva, with N2/N3 lymph nodes, could undergo resection of the lymph nodes and primary tumor following preoperative chemo-radiation. METHODS AND MATERILAS: Fifty-two patients were entered in the study, but six patients did not meet the criteria of the protocol and were excluded. The remaining 46 patients are the subject of this report. Patients underwent a split course of radiation, 4760 cGy to the primary and lymph nodes, with concurrent chemotherapy, cisplatin/5-FU, followed by surgery. RESULTS: Four patients did not complete the chemo-radiation, because three expired and one refused to complete the treatment. Four patients who completed chemo-radiation did not undergo surgery, because two of them died of non-cancer-related causes, and in the other two patients, the nodes remained unresectable. Following chemo-radiation, the disease in the lymph nodes became resectable in 38/40 patients. Two patients who completed the course of chemo-radiation did not undergo surgery as per protocol because of pulmonary metastasis. One underwent radical vulvectomy and unilateral node dissection and the other radical vulvectomy only. The specimen of the lymph nodes was histologically negative in 15/37 patients. Nineteen patients developed recurrent and/or metastatic disease. The sites of failure were as follows: primary area only, 9; lymph node area only, 1; primary area and distant metastasis, 1; distant metastasis only, 8. Local control of the disease in the lymph nodes was achieved in 36/37 and in the primary area in 29/38 of the patients. Twenty patients are alive and disease-free, and five have expired without evidence of recurrence or metastasis. Two patients died of treatment-related complications. CONCLUSION: High resectability and local control rates of the lymph nodes were obtained in patients with carcinoma of the vulva with N2/N3 nodes treated preoperatively with chemo-radiation.


Subject(s)
Carcinoma/drug therapy , Carcinoma/radiotherapy , Lymph Node Excision , Vulvar Neoplasms/drug therapy , Vulvar Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/pathology , Carcinoma/surgery , Cisplatin/administration & dosage , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , Groin , Humans , Lymphatic Metastasis/pathology , Middle Aged , Neoplasm Staging , Treatment Failure , Vulvar Neoplasms/pathology , Vulvar Neoplasms/surgery
11.
Mech Dev ; 99(1-2): 113-21, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11091079

ABSTRACT

COLL1alpha mRNA is asymmetrically distributed in the Paracentrotus lividus egg. Here we examine the involvement of the cytoskeleton in the localization process of collagen mRNA. The use of drugs such as colchicine and cytochalasin B reveals a perturbation of localization collagen mRNA. Moreover, the presence of specific cis-and trans-acting factors involved in cytoskeleton binding and the localization process was investigated. By Northwestern experiment we found that the 3'UTR of COLL1alpha mRNA is also able to bind two proteins of 54 and 40 kDa in a cellular fraction containing the cytoskeleton. Finally, we found that the protein of 54 kDa is LP54, a protein that binds the 3'UTRs of P. lividus maternal bep messengers and is necessary for their localization.


Subject(s)
Collagen/biosynthesis , Collagen/genetics , Collagen/metabolism , Cytoskeleton/metabolism , Ovum/metabolism , RNA, Messenger/metabolism , Sea Urchins/embryology , Transcriptional Activation , 3' Untranslated Regions , Animals , Blotting, Northern , Cell Fractionation , Colchicine/pharmacology , Cytochalasin B/pharmacology , DNA, Complementary/metabolism , Electrophoresis, Agar Gel , Electrophoresis, Polyacrylamide Gel , Immunoblotting , Immunohistochemistry , In Situ Hybridization , Microtubules/metabolism , Ovum/drug effects , Protein Binding , RNA-Binding Proteins/metabolism , Reverse Transcriptase Polymerase Chain Reaction
12.
Radiother Oncol ; 56(1): 43-8, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10869754

ABSTRACT

PURPOSE: To describe external, internal and common iliac dose rates estimated with 3D-computed tomography (CT) based dose calculations in tandem and ovoid brachytherapy. MATERIALS AND METHODS: Thirty patients with carcinoma of the uterine cervix received low dose rate brachytherapy with a CT-compatible Fletcher-Suit-Deldos device. A total of 36 implants were performed with axial CT images used to identify internal iliac, external iliac, and common iliac vessels. Dose rates on the surfaces of these vessels were calculated for the purpose of estimating the dose to their associated lymph nodes. RESULTS: In 22 out of 72 comparisons, point B overestimated the maximum dose with the external iliac nodes. In 21 out of 72 comparisons, point B overestimated the maximum dose with the internal iliac nodes. In all cases, Point B overestimated the minimum dose to the internal and external iliac nodal chains. CONCLUSION: It was found that Point B dose is similar to the maximum common iliac nodal dose. Patient to patient variability, of Point B dose, warrants further study of dose distributions to the nodal chains. The minimum dose to the external iliac nodal chain at the bifurcation of the nodal chains may provide a useful measure of 'pelvic side wall dose' and deserves further study to see if it can be correlated with pelvic side wall control and complications.


Subject(s)
Brachytherapy , Radiotherapy, Computer-Assisted , Tomography, X-Ray Computed , Uterine Cervical Neoplasms/radiotherapy , Female , Humans , Ilium , Lymph Nodes , Radiotherapy Dosage , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/pathology
13.
Clin Cancer Res ; 5(9): 2476-84, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10499622

ABSTRACT

In this report, we use new patient data to test three popular models developed to predict the outcome of definitive radiation therapy. The data come from 240 men with localized prostate cancer and who were treated with definitive radiation therapy at a community hospital. All three models tested were based on the three commonly available variables of pretreatment prostate-specific antigen (PSA), Gleason score, and tumor stage, and we used the Cox proportional hazards model and the logistic regression model to relate these variables to outcome. We discovered that in our data, the optimal way to use pretreatment PSA was as natural log(PSA), the optimal way to use T stage was in three categories: T1 and T2, T3, and T4, and that the optimal use of Gleason score was as <7 versus > or =7. Nevertheless, models confined to the optimal use of these three variables leave much uncertainty about important outcomes, such as the probability of relapse within 5 years.


Subject(s)
Models, Statistical , Prostate-Specific Antigen/analysis , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Treatment Outcome
14.
Clin Cancer Res ; 5(12): 4119-25, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10632349

ABSTRACT

We report the use of an exponential model for capturing the dynamics of serial measurements of prostate-specific antigen (PSA) made just before and after definitive radiation therapy of localized prostate cancer. Our study patients consisted of 164 men treated at a community hospital and without use of adjuvant hormonal therapy, and we had a mean of 5 years follow-up. We found that the model fits allowed us to condense PSA dynamic information into four parameters, including the initial pretreatment value of PSA, and three of these related significantly to subsequent outcome. The model also provided greater understanding of the prognosis of men with rising PSA after radiation therapy. Specifically, two of the model's parameters allowed us to compare the PSA status of these men to those with hormone-refractory disease, and we discovered that at the time of "biochemical relapse," there is a broad spectrum in expected probability of imminent death as well as in time to an adverse outcome. Thus, the model provides information that allows one to stratify men with rising PSA into a continuous spectrum from low to high risk for an adverse outcome. We believe these results show that exponential models have the potential for providing useful clinical information about men with rising PSA after definitive radiation therapy and that they could help us decide when further therapy is needed. Therefore, we recommend further study and development of these models as part of clinical research protocols involving radiation therapy of localized prostate cancer.


Subject(s)
Models, Biological , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Follow-Up Studies , Humans , Male , Mathematical Computing , Neoplasm Recurrence, Local , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Treatment Outcome
15.
Int J Radiat Oncol Biol Phys ; 42(1): 79-85, 1998 Aug 01.
Article in English | MEDLINE | ID: mdl-9747823

ABSTRACT

PURPOSE: To determine the feasibility of using preoperative chemoradiotherapy to avert the need for more radical surgery for patients with T3 primary tumors, or the need for pelvic exenteration for patients with T4 primary tumors, not amenable to resection by standard radical vulvectomy. METHODS AND MATERIALS: Seventy-three evaluable patients with clinical Stage III-IV squamous cell vulvar carcinoma were enrolled in this prospective, multi-institutional trial. Treatment consisted of a planned split course of concurrent cisplatin/5-fluorouracil and radiation therapy followed by surgical excision of the residual primary tumor plus bilateral inguinal-femoral lymph node dissection. Radiation therapy was delivered to the primary tumor volume via anterior-posterior-posterior-anterior (AP-PA) fields in 170-cGy fractions to a dose of 4760 cGy. Patients with inoperable groin nodes received chemoradiation to the primary vulvar tumor, inguinal-femoral and lower pelvic lymph nodes. RESULTS: Seven patients did not undergo a post-treatment surgical procedure: deteriorating medical condition (2 patients); other medical condition (1 patient); unresectable residual tumor (2 patients); patient refusal (2 patients). Following chemoradiotherapy, 33/71 (46.5%) patients had no visible vulvar cancer at the time of planned surgery and 38/71 (53.5%) had gross residual cancer at the time of operation. Five of the latter 38 patients had positive resection margins and underwent: further radiation therapy to the vulva (3 patients); wide local excision and vaginectomy necessitating colostomy (1 patient); no further therapy (1 patient). Using this strategy of preoperative, split-course, twice-daily radiation combined with cisplatin plus 5-fluorouracil chemotherapy, only 2/71 (2.8%) had residual unresectable disease. In only three patients was it not possible to preserve urinary and/or gastrointestinal continence. Toxicity was acceptable, with acute cutaneous reactions to chemoradiotherapy and surgical wound complications being the most common adverse effects. CONCLUSION: Preoperative chemoradiotherapy in advanced squamous cell carcinoma of the vulva is feasible, and may reduce the need for more radical surgery including primary pelvic exenteration.


Subject(s)
Carcinoma, Squamous Cell/therapy , Vulvar Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Cisplatin/administration & dosage , Combined Modality Therapy , Feasibility Studies , Female , Fluorouracil/administration & dosage , Humans , Middle Aged , Neoplasm Staging , Prospective Studies , Radiotherapy Dosage , Treatment Outcome , Vulvar Neoplasms/drug therapy , Vulvar Neoplasms/pathology , Vulvar Neoplasms/radiotherapy , Vulvar Neoplasms/surgery
16.
FEBS Lett ; 425(1): 157-60, 1998 Mar 20.
Article in English | MEDLINE | ID: mdl-9541027

ABSTRACT

Bep mRNAs are localized at the animal pole of P. lividus eggs. In the present communication the secondary structures of the 3'UTRs of the bep1, bep3 and bep4 mRNAs are reported. The minimal lengths of these regions required to bind the 54-kDa protein, previously shown to be involved in localization and anchoring of these RNAs, is estimated. Microinjection of the bep3 3'UTR into egg shows that this RNA fragment is also able to become localized to one of the egg poles, as happens for the entire bep3 RNA.


Subject(s)
Invertebrate Hormones/metabolism , Membrane Proteins/metabolism , Protein Folding , Amino Acid Sequence , Animals , Invertebrate Hormones/chemistry , Invertebrate Hormones/genetics , Membrane Proteins/chemistry , Membrane Proteins/genetics , Microinjections , Molecular Sequence Data , Protein Biosynthesis , Protein Structure, Secondary , RNA, Messenger/genetics , Sea Urchins
17.
Exp Cell Res ; 238(1): 101-9, 1998 Jan 10.
Article in English | MEDLINE | ID: mdl-9457061

ABSTRACT

The maternal bep1 and bep4 mRNAs and their protein products are localized at the animal pole of Paracentrotus lividus eggs. We have examined the role of the cytoskeleton in localization both of bep RNAs and BEP proteins in unfertilized and fertilized eggs and in determining the polarity of P. lividus eggs. The use of drugs such as colchicine and cytochalasin B, which depolymerize microtubules and microfilaments respectively, revealed a perturbation of localization of bep1 and bep4 mRNAs. In contrast, the microfilament inhibitor cytochalasin B had no effect on localization of BEP1 and BEP4 antigens localization, which appears to be due only to microtubules. Moreover, the presence of bep mRNAs and BEP proteins in a microtubule preparation has been demonstrated. Maintenance of the asymmetric distribution of BEP proteins during cellular division of eggs and embryos, by association with mitotic spindle, is also shown.


Subject(s)
Cytoskeleton/physiology , Membrane Proteins/biosynthesis , Ovum/physiology , Ovum/ultrastructure , Sea Urchins , Zygote/physiology , Zygote/ultrastructure , Animals , Cell Polarity , Cytoskeleton/ultrastructure , Female , In Situ Hybridization , Invertebrate Hormones/biosynthesis , Membrane Proteins/analysis , Microtubules/physiology , RNA, Messenger/metabolism , Transcription, Genetic
18.
Radiat Oncol Investig ; 6(6): 268-75, 1998.
Article in English | MEDLINE | ID: mdl-9885943

ABSTRACT

The purpose of this work is to compare bladder and rectal dose rates in brachytherapy for carcinoma of the cervix using two different dosimetry systems: traditional orthogonal radiograph-based dosimetry vs. computed axial tomography tandem and ovoids (CATTO) dosimetry. Twenty-two patients with carcinoma of the uterine cervix received the brachytherapy component of their radiotherapy with a computed-tomography compatible Fletcher-Suit-Delclos device. A total of 27 implants were performed. The average maximum bladder dose (Bmax) for the implants was 85.8 cGy/hr using the CATTO system as compared to 42.6 cGy/hr using traditional dosimetry, (P < 0.005). The average maximum rectal dose (R.) using the CATTO system was 59.2 cGy/hr as compared with 46.3 cGy/hr using the traditional system (P < 0.05). The traditional methods for choosing points to determine bladder and rectal dose rates underestimated the true Bmax in all cases and the R. in most. Based on the complication rates published in the literature, it is likely that the maximum tolerance dose of both the rectum and bladder, but especially the bladder, is higher than previously thought.


Subject(s)
Brachytherapy , Radiotherapy Planning, Computer-Assisted , Rectum/radiation effects , Urinary Bladder/radiation effects , Uterine Cervical Neoplasms/radiotherapy , Female , Humans , Radiation Dosage , Tomography, X-Ray Computed
19.
Prostate Cancer Prostatic Dis ; 1(4): 216-222, 1998 Jun.
Article in English | MEDLINE | ID: mdl-12496898

ABSTRACT

Objective: To compare results of treatment of adenocardinoma of the prostate using Standard (2D) vs Conformal (3D) treatment planning. Methods: The records of all patients with adenocarcinoma of the prostate treated curatively with radiation therapy alone from July 1991 to June 1994 were reviewed. Acute and late complications were scored by the RTOG criteria. Biochemical failure was defined as a rising PSA of at least 10% on two measurements separated >/=1 month or either a PSA nadir >4 ng/ml or >1 ng/ml. Disease free survival (DFS) was defined as no evidence of local, distant, or biochemical failure. 2D planning included standard simulation with target volume drawn from the treatment planning or diagnostic CT. 3D planning included a CT in the treatment position with computer simulation using beam's-eye-view for field design. Results: Two-hundred and seventeen 2D and 45 3D patients had similar median age and pre-treatment PSA, T-stage, and dose to the prostate. The median follow-up periods for the 2D and 3D groups were 32.0 and 21.5 months, respectively. The two-year actuarial survival, local or biochemical control, and DFS were not different. The 3D group had a significantly higher incidence of acute bladder side effects of all grades and acute grade 1/2 rectal complications. There were no differences in the incidence of late bladder or rectal complications. Conclusions: Careful 2D planning for the treatment of localized adenocarcinoma of the prostate is an acceptable means of treatment. Within the dose range of 64-70 Gy, this preliminary analysis demonstrated no reduction in complications nor improvement in local or biochemical control, or DFS was seen with the the use of 3D treatment planning.

20.
Cell Biol Int ; 22(4): 305-11, 1998.
Article in English | MEDLINE | ID: mdl-10101047

ABSTRACT

The temporal expression of two cell surface proteins, called BEP1 and BEP4, during Paracentrosus lividus embryonic development was studied. These proteins are found in both monomeric and dimeric forms in egg and embryos and we have established that their specific form is related to their being in the cytoplasm or on the cell surface. The spatial distribution of BEP1 and BEP4 proteins in eggs and embryos was established by whole mount immunohistochemistry. These proteins are located in the animal part of unfertilized and fertilized eggs; thereafter they are much less represented in structures derived from the vegetal cells of the embryo such as the micromeres of the 16 cell stage, the primary mesenchyme of blastula and the gut of gastrula. At the prism stage BEP1 and BEP4 proteins are present to some ectodermal parts and thereafter, at the pluteus stage, to the oral region.


Subject(s)
Membrane Proteins/metabolism , Sea Urchins/embryology , Sea Urchins/metabolism , Animals , Blotting, Western , Immunoblotting , Immunohistochemistry , Precipitin Tests , Recombinant Fusion Proteins , Time Factors , Tissue Distribution
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