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1.
Sci Adv ; 5(2): eaat5096, 2019 02.
Article in English | MEDLINE | ID: mdl-30801004

ABSTRACT

Fear of predation may influence food webs more than actual predation. However, the mechanisms and magnitude of nonconsumptive predator effects are largely unknown in unicellular-dominated food webs such as marine plankton. We report a general mechanism of chemically induced predator effects in marine plankton. Copepods, the most abundant zooplankton in the oceans, imprint seawater with unique polar lipids-copepodamides-which trigger toxin production and bioluminescence in harmful dinoflagellates. We show that copepodamides also elicit defensive traits in other phytoplankton, inducing the harmful algal bloom-forming diatom Pseudo-nitzschia seriata to produce 10 times more toxins, and colony-forming diatoms to decrease colony size by half. A 1-year study in the northeast Atlantic revealed that natural copepodamide concentrations are high enough to induce harmful algal toxins and size reduction in dominant primary producers when copepods are abundant. We conclude that copepodamides will structure marine plankton toward smaller, more defended life forms on basin-wide scales.


Subject(s)
Copepoda/physiology , Diatoms/physiology , Food Chain , Phytoplankton/physiology , Zooplankton/physiology , Animals , Oceans and Seas , Seawater
2.
J Labelled Comp Radiopharm ; 59(4): 175-86, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26991121

ABSTRACT

The 24th annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK on Friday 6th November 2015. The meeting was attended by 77 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral presentations, short 'flash' presentations in association with particular posters and poster presentations. The scientific areas covered included isotopic synthesis, regulatory issues, applications of labelled compounds in imaging, isotopic separation and novel chemistry with potential implications for isotopic synthesis. Both short-lived and long-lived isotopes were represented, as were stable isotopes. The symposium was divided into a morning session chaired by Dr Rebekka Hueting (University of Oxford, UK) and afternoon sessions chaired by Dr Sofia Pascu (University of Bath, UK) and by Dr Alan Dowling (Syngenta, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK).

3.
J Oral Rehabil ; 43(1): 31-8, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26332936

ABSTRACT

It has earlier been reported that individuals with poorly controlled diabetes have severe periodontal disease (PD) compared to well-controlled diabetes. This longitudinal interventional study compared periodontal treatment outcomes with HbA1c level changes in four groups of diabetic and non-diabetic patients with or without PD, respectively. HbA1c, bleeding on probing (BOP), plaque index and periodontal pocket depth (PPD) 4 < 6 mm and ≥6 mm were recorded at baseline to 3 months after non-surgical treatment and 3-6 months for surgical treatment in subjects with or without T2D, and with or without PD. A total of 129 patients were followed from baseline to 6 months. Diabetics with PD and without PD showed reductions in HbA1c levels with a mean value of 0·3% after 3 months and mean values of 1% and 0·8%, respectively, after 6 months. Diabetics with PD showed higher levels of BOP versus non-diabetics without PD (P < 0·01) and versus diabetics without PD (P < 0·05) at baseline. After 6 months, diabetics with PD showed higher number of PPD 4 < 6 mm versus diabetics without PD (P < 0·01) and non-diabetics with PD (P < 0·01). Diabetics without PD showed higher levels of PPD 4 < 6 mm versus non-diabetics without PD (P < 0·01). Surgical and non-surgical periodontal treatment in all groups improved periodontal inflammatory conditions with a decrease in HbA1c levels in a period of three and 6 months. No change was seen in the number of pockets PPD 4 < 6 mm in diabetic subjects with PD after non-surgical and surgical treatment.


Subject(s)
Chronic Periodontitis/etiology , Diabetes Mellitus, Type 2/complications , Glycated Hemoglobin/metabolism , Periodontal Attachment Loss/etiology , Periodontal Pocket/physiopathology , Chronic Periodontitis/metabolism , Chronic Periodontitis/physiopathology , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Pakistan/epidemiology , Periodontal Attachment Loss/metabolism , Periodontal Attachment Loss/physiopathology , Periodontal Index , Periodontal Pocket/metabolism , Self Care , Treatment Outcome
4.
Cancer Chemother Pharmacol ; 69(4): 977-82, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22119758

ABSTRACT

PURPOSE: Patients with advanced GIST following standard imatinib and sunitinib often have good performance status and need additional therapy. This study tested nilotinib, a second-generation tyrosine kinase inhibitor, in patients with advanced GIST refractory to standard therapies. METHODS: This single-center open-label phase II study has a primary objective to determine progression-free survival at 6 months. Using a novel statistical design, 17 patients were to be enrolled; if ≥ 10 were progression free (PF) at 2 months, 19 additional patients would be enrolled. The therapy was considered of benefit if ≥ 13 of 36 patients were PF at 6 months. All patients signed informed consent and entry criteria included normal cardiac function. Exploratory analyses correlating genotype with response were also performed. RESULTS: Thirteen patients were treated; 2 had received agents after imatinib and sunitinib. Treatment was well tolerated with one grade 4 anemia attributed to nilotinib. No measurable responses were observed; median time to progression was 2 months. One patient remained on study with stable disease for 12 months. Mutation testing is available from 10 primary tumors with 7 exon 11 mutations, 1 exon 9 mutation, and 2 without KIT/PDGFR mutations. Two samples from recurrent disease had 2 mutations, both primary exon 11 mutations with an additional exon 17 mutation, including the patient with prolonged stable disease. CONCLUSIONS: Nilotinib was well tolerated in these patients with advanced GIST. Accrual was halted due to insufficient clinical benefit. However, nilotinib may provide benefit to specific subsets of advanced GIST with exon 17 mutations.


Subject(s)
Gastrointestinal Stromal Tumors/drug therapy , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Aged , Benzamides , Disease-Free Survival , Drug Resistance, Neoplasm , Exons , Female , Gastrointestinal Stromal Tumors/enzymology , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/pathology , Humans , Imatinib Mesylate , Indoles/pharmacology , Male , Middle Aged , Mutation , Piperazines/pharmacology , Protein Kinase Inhibitors/adverse effects , Protein-Tyrosine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins c-kit/genetics , Pyrimidines/adverse effects , Pyrimidines/pharmacology , Pyrroles/pharmacology , Sunitinib
5.
Phys Med Biol ; 54(12): 3649-57, 2009 Jun 21.
Article in English | MEDLINE | ID: mdl-19458406

ABSTRACT

Complex intensity-modulated radiation therapy (IMRT) treatment plans require rigorous quality assurance tests. The aim of this study was to independently verify the delivered dose inside the patient in the region of the treatment site. A flexible naso-gastric tube containing thermoluminescent dosimeters (TLDs) was inserted into the oesophagus via the sinus cavity before the patient's first treatment. Lead markers were also inserted into the tube in order that the TLD positions could be accurately determined from the lateral and anterior-posterior electronic portal images taken prior to treatment. The measured dose was corrected for both daily linac output variations and the estimated dose received from the portal images. The predicted dose for each TLD was determined from the treatment planning system and compared to the measured TLD doses. The results comprise 431 TLD measurements on 43 patients. The mean measured-to-predicted dose ratio was 0.988 +/- 0.011 (95% confidence interval) for measured doses above 0.2 Gy. There was a variation in this ratio when the measurements were separated into low dose (0.2-1.0 Gy), medium dose (1.0-1.8 Gy) and high dose (>1.8 Gy) measurements. The TLD-loaded, naso-oesophageal tube for in vivo dose verification is straightforward to implement, and well tolerated by patients. It provides independent reassurance of the delivered dose for head and neck IMRT.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Intubation/instrumentation , Radiotherapy, Conformal/instrumentation , Thermoluminescent Dosimetry/instrumentation , Equipment Design , Equipment Failure Analysis , Humans
6.
J Oral Rehabil ; 36(1): 39-44, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18976260

ABSTRACT

The aim was to validate self-perceived oral health with salivary IgG as an inflammatory parameter in children with type 1 diabetes. Unstimulated whole saliva samples were collected from 36 children with well controlled and 12 with poorly controlled type 1 diabetes and 40 non-diabetic children (Controls). Salivary flow rate, random blood glucose level, salivary protein concentration and immunoglobulin A and G levels were recorded using standard techniques. Data concerning oral health and diabetes status were collected. Self-perceived gingival bleeding (bleeding gums), bad breath and dry mouth were higher in diabetic children when compared with those in controls (P < 0.05). Gingival bleeding was frequently perceived by children with poorly controlled compared to well-controlled type 1 diabetes (P < 0.05) and controls (P < 0.001). Bad breath was common perceived by children with poorly controlled compared to well-controlled type 1 diabetes (P < 0.05) and controls (P < 0.0001). Salivary flow rate was lower in the diabetic children compared to controls (P < 0.01) with no difference between children with poorly controlled and well-controlled type 1 diabetes. Salivary IgG per mg protein concentration was higher in the diabetics when compared with the control group (P < 0.0001). IgG per mg protein levels were also higher in children with poorly controlled when compared with well-controlled type 1 diabetes (P < 0.05). There was no difference in IgA per mg protein and total protein concentrations between children with poorly controlled and well-controlled type 1 diabetes. Self-perceived gingival bleeding and salivary IgG per mg protein concentration were increased in children with type 1 diabetes compared with controls. These variables were also increased in children with poorly controlled compared with well-controlled type 1 diabetes.


Subject(s)
Diabetes Mellitus, Type 1/immunology , Gingival Hemorrhage/complications , Health Knowledge, Attitudes, Practice , Immunoglobulin G/metabolism , Oral Health , Saliva/metabolism , Adolescent , Blood Glucose/metabolism , Case-Control Studies , Child , Dental Health Surveys , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/psychology , Gingival Hemorrhage/immunology , Gingival Hemorrhage/metabolism , Gingival Hemorrhage/psychology , Glycated Hemoglobin/metabolism , Health Status , Humans , Immunoglobulin A/metabolism , Reference Values , Saliva/immunology , Salivary Proteins and Peptides/immunology , Salivary Proteins and Peptides/metabolism , Self Concept , Self-Assessment , Xerostomia/complications , Xerostomia/immunology , Xerostomia/metabolism , Xerostomia/psychology , Young Adult
7.
Dentomaxillofac Radiol ; 36(1): 7-11, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17329581

ABSTRACT

OBJECTIVE: To compare the accuracy and precision of measurements on marginal bone levels in differently processed digital radiographs and in film-based radiographs. METHODS: Twenty-one patients with a diagnosis of chronic periodontitis were included in this study. Periapical radiographs were exposed with the Dixi digital intraoral radiographic system (Planmeca Oy, Helsinki, Finland) and the F-speed Film (Insight, Eastman-Kodak Co., Rochester, NY), respectively. Digital radiographs were subsequently processed into two sets: (a) correction for attenuation and visual response and (b) the same correction but with an additional shift in grey levels. Patients had periodontal surgery immediately after the radiographs were exposed. The vertical distance from cementoenamel junction to the most apical part of the marginal bone was assessed. The measurements were then employed as reference standard and subtracted by the vertical distance from radiographs accordingly. Altogether, 47 sites were evaluated. Seven observers were employed for evaluation under the same viewing conditions. ANOVA was employed for statistical analysis. RESULTS: No significant differences were found between the absolute differences of the vertical distance obtained from radiographs to their corresponding reference standards when comparing differently processed digital radiographs, but the absolute differences were significantly smaller in digital radiographs than in films. Interobserver variances were not significant. CONCLUSION: Digital radiographs have a favourable measurement accuracy compared with film radiographs when assessing marginal bone levels.


Subject(s)
Alveolar Process/diagnostic imaging , Radiographic Image Enhancement/methods , Radiography, Dental, Digital , X-Ray Film , Adult , Aged , Aged, 80 and over , Alveolar Bone Loss/diagnostic imaging , Alveolar Bone Loss/pathology , Alveolar Process/pathology , Cephalometry/standards , Cephalometry/statistics & numerical data , Humans , Image Processing, Computer-Assisted , Middle Aged , Observer Variation , Periodontitis/diagnostic imaging , Radiography, Dental, Digital/statistics & numerical data , Reference Standards , Tooth Cervix/diagnostic imaging , Tooth Cervix/pathology , X-Ray Film/statistics & numerical data
8.
Science ; 309(5740): 1564-6, 2005 Sep 02.
Article in English | MEDLINE | ID: mdl-16141073

ABSTRACT

Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.


Subject(s)
Genome , Mice/genetics , RNA, Antisense/biosynthesis , Transcription, Genetic , Animals , Gene Expression Regulation , Humans , RNA Interference , RNA, Messenger/biosynthesis
9.
Science ; 309(5740): 1559-63, 2005 Sep 02.
Article in English | MEDLINE | ID: mdl-16141072

ABSTRACT

This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.


Subject(s)
Genome , Mice/genetics , Terminator Regions, Genetic , Transcription Initiation Site , Transcription, Genetic , 3' Untranslated Regions , Animals , Base Sequence , Conserved Sequence , DNA, Complementary/chemistry , Genome, Human , Genomics , Humans , Promoter Regions, Genetic , Proteins/genetics , RNA/chemistry , RNA/classification , RNA Splicing , RNA, Untranslated/chemistry , Regulatory Sequences, Ribonucleic Acid
10.
Technol Cancer Res Treat ; 2(5): 459-70, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14529312

ABSTRACT

The aim of the present study is to develop a mathematical model for evaluating therapeutic response of combined treatment modalities. The study was performed in rats of the Fischer-344 strain with rat glioma N32 or N29 tumors implanted subcutaneously on the thigh of the hind leg. Pulsed electric fields, PEF, with 16 exponentially decaying pulses with a maximum electric field strength of 140 V/mm and t(1/e)= 1 ms were first applied to the tumors. Then within 5 min radiation therapy with (60)Co-gamma radiation, RT, was given in daily fractions of 5 Gy. The animals were arranged into one group of controls and 3 groups of different kind of treatments: PEF only, RT only or combination of PEF + RT. At about 4 weeks after inoculation, the tumors were given the treatment sessions during one week. In 2 experimental series with totally 52 rats with N32 tumors, of which 16 were controls, were given 4 sessions of PEF treatments and RT (totally 20 Gy). In a special experimental series with totally 56 rats with N32 tumors, of which 10 were controls, the different groups were given 1, 2, 3 or 4 treatment sessions respectively. Another strain of glioma tumor, N29 with 62 tumors of which 14 were controls was studied in 2 series given 4PEF + 4RT and 2PEF + 4RT respectively. Fitting the data obtained from consecutive measurements of tumor volume (TV) of each individual tumor to an exponential model TV = TV(0). exp[TGR.t] estimated the tumor growth rate (TGR % per day) after the first day of treatment (t = 0). The TGR of N32 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.0001), compared to RT alone (p < 0.0001) and compared to PEF alone (p < 0.001). The combined treatment of N32 gives significant effect on the tumor growth rate after 2, 3 and 4 treatment session while RT alone seems to be most efficient after one treatment of 5 Gy and PEF alone is most efficient after 2 treatments at 2 consecutive days. The TGR of N29 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.05) but the combination of 2PEF + 4RT was more effective (p < 0.005). The specific therapeutic effect STE is defined as the difference between the average tumor growth rates of controls and exposed tumors divided by the average tumor growth rate of the controls. With 4PEF treatments alone the average STE value was 0.32 for N32 tumors and 0 for N29; for 4RT alone the STE values were 0.29 and 0.42 respectively, and for combined treatments 4PEF + 4RT 0.67 and 0.17 respectively. For the N29 tumors treated with 2PEF + 4RT the STE value was 0.53. The therapeutic enhancement ratio, TER, value increase with the number of treatment sessions and the TER of the combined treatments is above 1 in two of the N32 series, which indicates a synergistic effect of 4PEF + 4RT. This work demonstrate the use of our model for analyzing the combination PEF + RT, but it can also be used for evaluation the therapeutic effects of combining RT with chemotherapy or immunogenetic therapy.


Subject(s)
Brain Neoplasms/radiotherapy , Brain Neoplasms/therapy , Disease Models, Animal , Electric Stimulation Therapy , Gamma Rays , Glioma/radiotherapy , Glioma/therapy , Animals , Brain Neoplasms/pathology , Cell Line, Tumor , Cobalt Radioisotopes , Disease Progression , Electricity , Glioma/pathology , Neoplasm Transplantation , Rats , Rats, Inbred F344 , Survival Rate
11.
Appl Microbiol Biotechnol ; 63(2): 107-14, 2003 Dec.
Article in English | MEDLINE | ID: mdl-12955353

ABSTRACT

Recently, two fresh water species, " Candidatus Brocadia anammoxidans" and " Candidatus Kuenenia stuttgartiensis", and one marine species, " Candidatus Scalindua sorokinii", of planctomycete anammox bacteria have been identified. " Candidatus Scalindua sorokinii" was discovered in the Black Sea, and contributed substantially to the loss of fixed nitrogen. All three species contain a unique organelle--the anammoxosome--in their cytoplasm. The anammoxosome contains the hydrazine/hydroxylamine oxidoreductase enzyme, and is thus the site of anammox catabolism. The anammoxosome is surrounded by a very dense membrane composed almost exclusively of linearly concatenated cyclobutane-containing lipids. These so-called 'ladderanes' are connected to the glycerol moiety via both ester and ether bonds. In natural and man-made ecosystems, anammox bacteria can cooperate with aerobic ammonium-oxidising bacteria, which protect them from harmful oxygen, and provide the necessary nitrite. The cooperation of these two groups of ammonium-oxidising bacteria is the microbial basis for a sustainable one reactor system, CANON (completely autotrophic nitrogen-removal over nitrite) to remove ammonia from high strength wastewater.


Subject(s)
Bacteria, Anaerobic/metabolism , Fresh Water/microbiology , Quaternary Ammonium Compounds/metabolism , Seawater/microbiology , Anaerobiosis , Bioreactors , Oxidation-Reduction
12.
J Periodontol ; 72(9): 1192-200, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11577951

ABSTRACT

BACKGROUND: The aims of this study were to investigate the anti-inflammatory effect and the effect on bone regeneration of hyaluronan in surgical and non-surgical groups. METHODS: In each of 15 individuals, 2 teeth with defects of similar character and magnitude in the upper or lower jaw were chosen. There were at least 2 teeth between the test and the control sites. In the surgical group, a bioabsorbable membrane was used for both test and control sites, and hyaluronan was placed in the intrabony pocket of the test site. In the non-surgical group, the periodontal pockets were scaled and hyaluronan was administered 3 times with an interval of 1 week in the test pockets. Alveolar bone height and bone healing patterns were analyzed using digital intraoral radiographs. Measurements of bone height were performed in the original digital black-and-white radiographs to obtain quantitative data on bone gain or loss. Bone healing patterns were studied with color-coded radiographs, using specially designed software in a personal computer with subsequent combinations of radiographs. Gingival crevicular fluid immunoglobulin (Ig)G, C3, and prostaglandin E2 (PGE2) responses; periodontal probing depth; bleeding on probing; and the presence of plaque were studied to evaluate the anti-inflammatory effect. Data were obtained at baseline before treatment, and at 2 weeks, and 1, 3, 6, and 12 months after treatment. RESULTS: For the surgical treatments, bone height was increased in the test group treated with hyaluronan (mean value 2.2%, corresponding to an average increase of approximately 0.5 mm) and reduced in the control group (mean value -1.8%, corresponding to an average decrease of approximately - 0.4 mm) (P<0.05) after 12 months. For the non-surgical treatments, bone height was reduced by a mean value of -1.1% (corresponding to an average decrease of approximately -0.25 mm) in the test group treated with hyaluronan and -3.3% (corresponding to an average decrease of approximately -0.75 mm) in the control group after 12 months (N.S.). According to the digital color-coded radiographs, the test sites in the surgical and non-surgical groups showed apposition of bone minerals. Immune responses showed no differences during the 12 months studied for the surgical and non-surgical sites. Mean periodontal probing depths were reduced between 2.5 mm and 4.1 mm in the surgical and non-surgical groups. CONCLUSIONS: The observed difference in bone height between test and control sites in the surgical group after 12 months was less than 1 mm, which was only detectable on radiographs. No statistical difference was found on radiographs in the non-surgical group, where a decrease in bone height was found for both groups after scaling. Probing depth reduction after the surgical treatment, as well as after scaling and root planing, was as expected. Hyaluronan in contact with bone and soft tissues had no influence on the immune system in this study. Further studies are needed to determine the extent to which hyaluronan can lead to clinically significant healing of periodontal lesions.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Alveolar Bone Loss/drug therapy , Bone Regeneration/drug effects , Hyaluronic Acid/therapeutic use , Periodontal Pocket/drug therapy , Wound Healing/drug effects , Absorbable Implants , Adjuvants, Immunologic/pharmacology , Adult , Aged , Aggregatibacter actinomycetemcomitans/isolation & purification , Alveolar Bone Loss/diagnostic imaging , Alveolar Bone Loss/surgery , Alveolar Bone Loss/therapy , Complement C3/analysis , Dental Plaque Index , Dental Scaling , Dinoprostone/analysis , Enzyme-Linked Immunosorbent Assay , Female , Gingival Crevicular Fluid/chemistry , Gingival Crevicular Fluid/immunology , Gingival Crevicular Fluid/microbiology , Guided Tissue Regeneration, Periodontal/methods , Humans , Hyaluronic Acid/pharmacology , Immunoglobulin G/analysis , Male , Membranes, Artificial , Middle Aged , Periodontal Index , Radiography, Dental, Digital , Statistics, Nonparametric
13.
Cancer Detect Prev ; 25(4): 352-61, 2001.
Article in English | MEDLINE | ID: mdl-11531012

ABSTRACT

The dithiolethione oltipraz is being developed as a chemopreventive agent for many malignancies, including colorectal cancer, on the basis of its in vivo protective activity against chemically induced tumors in a variety of animal models. This protection has been associated with an enhanced capacity to detoxify reactive carcinogens and, more recently, with increased DNA repair. In a previous single-dose study, elevated detoxification gene expression was observed in the days after oltipraz dosing. Now, in this clinical study, we evaluated the effects of oltipraz when given over a 3-month period. Fourteen individuals with increased risk for colorectal cancer were randomly assigned to one of two oral doses (125 or 250 mg/m2) of oltipraz twice weekly for 12 weeks. Two of seven subjects at the 250 mg/m2 dosage required dose reductions, owing to significant fatigue. The 125 mg/m2 dose level was well tolerated by all patients. Blood or colon tissue (or both) for evaluation of glutathione, glutathione S-transferase, DT-diaphorase activity, and DT-diaphorase mRNA expression were obtained prior to treatment and at weeks 6, 12, and 16. No significant modulation of phase II detoxification enzymes was seen at either dose studied during this period. Phase II trials evaluating a tolerable regimen of oltipraz (as demonstrated in this study) and other possible mechanisms that may be responsible for the protective activity of oltipraz should be pursued.


Subject(s)
Anticarcinogenic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Pyrazines/therapeutic use , Aged , Aged, 80 and over , Anticarcinogenic Agents/administration & dosage , Biomarkers, Tumor/blood , Colorectal Neoplasms/genetics , Colorectal Neoplasms/prevention & control , Enzyme Induction/drug effects , Female , Glutathione/blood , Glutathione Transferase/biosynthesis , Humans , Male , Middle Aged , NAD(P)H Dehydrogenase (Quinone)/biosynthesis , Pyrazines/administration & dosage , Thiones , Thiophenes
14.
Anticancer Res ; 21(3B): 1817-22, 2001.
Article in English | MEDLINE | ID: mdl-11497264

ABSTRACT

BACKGROUND: In this study, electrochemotherapy (ECT), i.e. tumour treatment based on local augmentation of intracellular drug delivery from short, intense electric pulses, was evaluated in rats with an adenocarcinoma implanted into the liver. Tumour response and concentrations of macrophages and T-lymphocytes (CD4 and CD8) in and around the tumour were measured. MATERIALS AND METHODS: Rats were treated with permeabilizing electric pulses, bleomycin, or both, eight days after implantation of the tumour, while one group received sham treatment. RESULTS: Treatment with electric pulses and bleomycin resulted in a significantly reduced lesion volume and 92% cure rate (12 out of 13, p<0.0002 compared to the other treatment groups). The highest concentration of CD8 lymphocytes was found in tumours treated with electric pulses and bleomycin. Macrophages were found mainly in tumours treated with electric pulses, with or without bleomycin. CONCLUSION: Electrochemotherapy using millisecond exponential pulses and bleomycin is efficient in a rat liver tumour model and appears to stimulate the host's immune system.


Subject(s)
Adenocarcinoma/drug therapy , Drug Delivery Systems , Electric Stimulation Therapy/methods , Liver/pathology , Alanine Transaminase/blood , Animals , Antimetabolites, Antineoplastic/pharmacology , Bleomycin/pharmacology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Combined Modality Therapy , Electroporation/methods , Immunohistochemistry , Macrophages/metabolism , Male , Neoplasm Transplantation , Rats , Rats, Wistar
15.
Anticancer Res ; 21(3B): 1809-15, 2001.
Article in English | MEDLINE | ID: mdl-11497263

ABSTRACT

AIM: To investigate the antitumour effect of radiation in combination with electropermeabilization on subcutaneous rat glioma tumours. MATERIALS AND METHODS: Sub-optimal radiation treatment was administered separately or in combination with electric pulses of high voltage to subcutaneous rat brain tumours. The treatment was repeated on four consecutive days and evaluated by TGD and microscopical examination. The tumours were stained for Factor VlII/von Willebrand Factor to investigate the effects on the tumour vasculature. RESULTS: Radiation and electric pulses applied concomitantly resulted in a cure rate of 67% (tumour free >80 days after treatment). Radiation-treated animals showed progressive disease. Histological and immunohistochemical examination of electric impulse-treated tumours showed instant and severe deteriorating effects on tumour vasculature. CONCLUSION: A distinct antitumour effect of the combined treatment of electric pulses and radiation treatment was observed. We believe that the tumouricidal effect arises from destruction of the tumour vasculature but also from DNA related damage from reactive oxygen formed by the electric pulses and the radiation treatment.


Subject(s)
Electric Stimulation Therapy , Electricity , Neoplasms/radiotherapy , Animals , Brain Neoplasms/blood supply , Brain Neoplasms/pathology , Brain Neoplasms/radiotherapy , Combined Modality Therapy , Factor VIII/biosynthesis , Glioma/blood supply , Glioma/pathology , Glioma/radiotherapy , Immunohistochemistry , Male , Rats , Rats, Inbred F344 , Time Factors
16.
J Behav Med ; 24(3): 247-58, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11436545

ABSTRACT

The purpose of the present study was to systematically compare the psychological and screening profiles of first-degree relatives (FDRs) of prostate cancer patients versus non-FDRs. FDRs (n = 56) and non-FDRs (n = 100), recruited through prostate cancer index cases and newspaper advertisements, completed questionnaires via mail. FDRs reported feeling at greater risk for prostate cancer, estimated that they were at higher average lifetime risk for the disease, agreed more strongly that prostate cancer is inherited, and that less can be done to prevent the development of the disease. Increased age, but not FDR status, was associated with more frequent screening behavior. Taken together, the results indicate that FDRs are characterized by greater perceived vulnerability to prostate cancer and lower expectations about disease prevention. Yet, they are no more likely to be screened than non-FDRs. These findings underscore the importance of developing, and evaluating, evidence-based health communication protocols to promote screening adherence among at-risk patients.


Subject(s)
Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/etiology , Family/psychology , Mass Screening , Prostatic Neoplasms/psychology , Adult , Attitude to Health , Depressive Disorder, Major/epidemiology , Humans , Male , Middle Aged , Risk Factors
17.
Plant Mol Biol ; 45(3): 247-62, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11292072

ABSTRACT

ATHB13 is a new member of the homeodomain leucine zipper (HDZip) transcription factor family of Arabidopsis thaliana. Constitutive high-level expression of the ATHB13 cDNA in transgenic plants results in altered development of cotyledons and leaves, specifically in plants grown on media containing metabolizable sugars. Cotyledons and leaves of sugar-grown transgenic plants are more narrow and the junction between the petiole and the leaf blade less distinct, as compared to the wild type. High-level expression of ATHB13 affects cotyledon shape by inhibiting lateral expansion of epidermal cells in sugar-treated seedlings. Experiments with non-metabolizable sugars indicate that the alteration in leaf shape in the ATHB13 transgenics is mediated by sucrose sensing. ATHB13 further affects a subset of the gene expression responses of the wild-type plant to sugars. The expression of genes encoding beta-amylase and vegetative storage protein is induced to higher levels in response to sucrose in the transgenic plants as compared to the wild type. The expression of other sugar-regulated genes examined is unaffected by ATHB13. These data suggest that ATHB13 may be a component of the sucrose-signalling pathway, active close to the targets of the signal transduction.


Subject(s)
Arabidopsis Proteins , Arabidopsis/drug effects , Carbohydrates/pharmacology , Cotyledon/drug effects , Homeodomain Proteins/genetics , Plant Leaves/drug effects , Plant Proteins/genetics , Amino Acid Sequence , Arabidopsis/genetics , Arabidopsis/growth & development , Cloning, Molecular , Cotyledon/growth & development , Cotyledon/ultrastructure , DNA, Complementary/chemistry , DNA, Complementary/genetics , Gene Expression , Gene Expression Regulation, Developmental/drug effects , Gene Expression Regulation, Plant/drug effects , Microscopy, Electron, Scanning , Molecular Sequence Data , Plant Leaves/growth & development , Plants, Genetically Modified/genetics , RNA, Plant/drug effects , RNA, Plant/genetics , RNA, Plant/metabolism , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Sucrose/pharmacology , beta-Amylase/genetics
18.
Plant Mol Biol ; 45(1): 63-73, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11247607

ABSTRACT

Homeodomain-leucine zipper (HDZip) proteins constitute a large family of transcription factors apparently unique to plants. In this report we characterize the DNA-binding and dimerization preferences in vitro of class I HDZip proteins. Using gel-exclusion chromatography and in vitro protein binding assays we demonstrate that the HDZip class I protein ATHB5 forms a homodimeric complex in solution. Consistent with this finding we have demonstrated the sequence-specific interaction of ATHB5 with a 9 bp pseudopalindromic DNA sequence, CAATNATTG, composed of two half-sites overlapping at a central position, by use of a PCR-assisted binding-site selection assay and competitive EMSA experiments. A majority of other known members of HDZip class I interacted with similar DNA sequences, but differed in their preference for A/T versus G/C in the central position of the binding site. Selective heterodimerization in vitro was demonstrated between ATHB5 and different class I HDZip proteins. Heterodimer formation between class I HDZip proteins is of potential functional significance for the integration of information from different signalling pathways in the control of plant development.


Subject(s)
Arabidopsis/genetics , DNA/metabolism , Homeodomain Proteins/metabolism , Plant Proteins/metabolism , Transcription Factors/metabolism , Amino Acid Sequence , Bacteria/genetics , Base Sequence , Binding Sites/genetics , DNA/genetics , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Dimerization , Homeodomain Proteins/chemistry , Homeodomain Proteins/genetics , Leucine Zippers , Molecular Sequence Data , Plant Proteins/chemistry , Plant Proteins/genetics , Protein Binding , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Sequence Homology, Amino Acid , Transcription Factors/chemistry , Transcription Factors/genetics
19.
Cancer Pract ; 9(5): 231-5, 2001.
Article in English | MEDLINE | ID: mdl-11879319

ABSTRACT

PURPOSE: This study was designed to test the feasibility of conducting routine quality assessment within community medical oncology practices. DESCRIPTION OF STUDY: Eleven medical oncologists practicing within the Fox Chase Network were surveyed over an 8-month period, using a standardized 10-item checklist. Eight of the items (ie, board certification, continuing education, office procedure manual for chemotherapy, chemotherapy flow sheets, body surface area calculations, adherence to guidelines for follow-up of breast cancer, adjuvant hormones in women with estrogen receptor-positive breast cancer, and patient satisfaction survey) were chosen because they measure structural and process variables particularly relevant to the high-volume clinical services seen in private practice oncology. The authors also calculated two rates (protocol accrual and neutropenic complications of chemotherapy) to test as putative indicators of quality. RESULTS: The authors found a high level of both physician interest in developing the audit measures and compliance with the survey process. Overall quality of care, as measured by structure and process variables, was excellent with negligible internal variability. Derived rates of protocol accrual (0.003-0.373; mean 0.11, SD 0.11) and neutropenic sepsis (0.004-0.014; mean 0.007, SD 0.004) show considerable variability, however, and are only minimally correlated (r= -.36). These are both potential indicators of quality that should be further evaluated. CLINICAL IMPLICATIONS: The authors have demonstrated the feasibility of conducting quality assessment within private medical oncology practices and have identified two easily calculated rates that merit further study as potential indicators of quality.


Subject(s)
Breast Neoplasms/therapy , Medical Oncology/standards , Quality Indicators, Health Care , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Feasibility Studies , Female , Guideline Adherence , Humans , Outcome Assessment, Health Care
20.
Cell Mol Biol (Noisy-le-grand) ; 46(5): 1017-24, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10976881

ABSTRACT

Synchrotron X-ray micro-diffraction studies along the follicle and the hair fibre allowed us to follow the keratinization process and the progressive organization of the keratin: i) molecular organization appeared progressively in the follicle; the formation of alpha-helices was completed inside the follicle. ii) supramolecular organization appeared only outside the follicle, far from the bulb; filament structure was observed far from the follicle. Comparisons between structures observed for in vitro and in vivo grown hair, whatever in the bulb or in the fibre, indicate there is no evidence of any structural difference. More, no variation in the transition in vivo/in vitro zone has been observed. In vitro and in vivo fibres exhibited the same structure.


Subject(s)
Hair/chemistry , Keratins/chemistry , Hair/growth & development , Hair/ultrastructure , Hair Follicle/chemistry , Hair Follicle/growth & development , Hair Follicle/ultrastructure , Humans , In Vitro Techniques , Keratins/metabolism , Protein Structure, Secondary , Scattering, Radiation , X-Ray Diffraction
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