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Biomedical subjects

P Dube

Publications and source records attributed to P Dube.

34 records · Page 2Linked to original sources

The immune response and the eye: a role for TNF alpha in anterior chamber-associated immune deviation.

PURPOSE: Interleukin-1 and tumor necrosis factor (TNF) alpha are proinflammatory cytokines and crucial mediators in many aspects of immunity. In this study, their role in anterior chamber-associated immune deviation (ACAID) was investigated. METHODS: The role of these cytokines was examined by the use of neutralizing antibodies to TNF and interleukin (IL)-1 alpha, IL-1 beta, and IL-1 receptor. These reagents were co-injected with antigen into the anterior chamber and the effect on ACAID assessed. In addition, reverse transcriptase polymerase chain reaction (RT-PCR) was performed on eyes injected with TNP-spleen or bovine serum albumin to determine the levels of TNF alpha mRNA induced. RESULTS: Neutralizing antibody to TNF, when injected with TNP-spleen cells into the anterior chamber, blocked ACAID to the TNP hapten. Antibodies to IL-1 alpha, IL-1 beta, and IL-1 receptors either alone or in combination did not block the establishment of ACAID: Studies with reverse transcriptase polymerase chain reaction (Rt-PCR) confirmed that early (within 2 hours) after anterior chamber injection of TNP-cells, messenger RNA levels for TNF alpha were dramatically increased. The induction of ACAID to bovine serum albumin also required the production of TNF alpha. Further studies showed that the production of blood borne "ACAID-inducing" signals after anterior chamber injection of bovine serum albumin or TNP-spleen were dependent on TNF. CONCLUSIONS: TNF alpha plays a crucial role in ACAID: Induction of TNF alpha within the eye may be an important event in the complex series of events that induce ACAID and possibly maintain immunologic privilege.

Animals↗

The portal protein of bacteriophage SPP1: a DNA pump with 13-fold symmetry.

Electron microscopy in combination with image processing is a powerful method for obtaining structural information on non-crystallized biological macromolecules at the 10-50 A resolution level. The processing of noisy microscopical images requires advanced data processing methodologies in which one must carefully avoid the introduction of any form of bias into the data set. Using a novel multivariate statistical approach to the analysis of symmetry, we studied the structure of the bacteriophage SPP1 portal protein oligomer. This portal structure, ubiquitous in icosahedral bacteriophages which package dsDNA, is located at the site of symmetry mismatch between a 5-fold vertex of the icosahedral shell and the 6-fold symmetric (helical) tail. From previous studies such 'head-to-tail connector' structures were generally accepted to be homododecamers assembled in a 12-fold symmetric ring around a central channel. Using a new analysis methodology we have found that the phage SPP1 portal structure exhibits 13-fold cyclical symmetry: a new point group organization for oligomeric proteins. A model for the DNA packaging mechanism by 13-fold symmetric portal protein assemblies is presented which attributes a coherent functional meaning to their unusual symmetry.

Biological Transport↗

Radiation therapy in the treatment of early glottic carcinoma: the experience of Villejuif.

A retrospective analysis of 197 early glottic carcinoma treated with small field irradiation to a dose of 65 Gy is presented. The 5-year survival rate was 77.3%. Thirty-eight local failures have been observed, and the 5-year local control rate was 85.7%. Suspicion of extra glottic extension was the main prognostic factor. Final local control rate, taking into account the salvage treatment, was 90% at 5 years. Excellent functional results were observed.

Carcinoma, Squamous Cell↗

Direct determination of cadmium in urine using graphite furnace atomic absorption spectrometry with Zeeman-effect background correction.

A procedure is described for the direct determination of cadmium in human urine using graphite furnace atomic absorption spectrometry with Zeeman-effect background correction. Except for a straightforward 1 + 1 V/V dilution of samples with 1.5% nitric acid, no matrix modifier or sample pre-treatment was necessary, thus reducing the risk of contamination. The concentration of cadmium in urine was evaluated directly from a calibration graph prepared using a metal-spiked human urine pool. In this way the time-consuming method of standard additions was avoided, permitting an increased sample throughput (120-150 samples per day; 90 s per analysis) with minimal attention of the analyst. In routine use, the precision (both within day and day to day) and limit of detection were of the order of less than 10% and 0.05 micrograms l-1 of Cd, respectively. The method is suitable for the biological monitoring of cadmium in the general population or in occupationally exposed persons.

Cadmium↗

[Radiotherapy of cancer limited to the vocal cords].

197 patients, with an early glottic cancer, were heated with radiotherapy at the Institute Gustave Roussy, between 1970 and 1983. Radiation was delivered up to a dose of 65 Gy over 6 1/2 weeks on a small area centered on the glottic region. All patients had previously undergone direct laryngoscopy and showed T1 stage tumours (175 T1a and 22 T1b) although in 32 cases there was a suspicion of very limited involvement of the ventricle or sub-glottis. 5 year survival for the overall population was 77.5%. 38 local recurrences were observed, 1/4 of these occurring after 3 years. For the overall population, local control at 5 years was 85.7%. Suspicion of supra or sub-glottic involvement and the presence of impaired mobility of the larynx were shown to be important prognostic factors. Local control at 5 years was 90% for "true T1" cases. Few complications were observed and the functional results of irradiation were judged to be excellent.

Adult↗

Expression of a maize storage protein gene in petunia plants is not restricted to seeds.

Genes encoding maize seed storage proteins, zeins, are expressed in developing endosperm tissue. To determine whether the DNA sequences controlling the developmental expression of these genes are recognized in dicots, we introduced a gene encoding a M(r) 19,000 zein protein into petunia by Agrobacterium tumefaciens mediated transformation. Southern blot analysis of DNA from regenerated transgenic plants showed that between 1 and 12 copies of the zein gene were integrated at various locations in the petunia genome. S1 nuclease mapping with 5' and 3' probes for zein mRNA showed that transcription of the gene was correctly initiated and terminated in seeds of the transgenic plants. The mRNA was first detected in petunia seeds 10 days after pollination and disappeared 17 days after pollination. However, only small amounts of zein transcripts were synthesized and protein could not be detected at any stage of development. We also found low levels of zein mRNA in leaves, stems, and flowers of the transgenic plants, suggesting that DNA sequences responsible for developmental regulation are not readily recognized in petunia plants.

Journal Article↗

Esophageal reconstruction: an experimental approach to the control of reflux after esophageal resection.

A study of the properties of replacement gastric tubes and colonic segments, and their use in the prevention of reflux after esophageal resection indicates that, in order to prevent reflux, these tubes must be maintained in a subdiaphragmatic position. Gastric tubes have a higher intrinsic pressure barrier than colonic tubes--a 2.5- to 6-cm segment prevents reflux and the tube maintains a pressure barrier 10 cm H2O higher than stomach presure, whereas colonic segments require 12 cm of subdiaphragmatic length to control reflux and maintain a pressure barrier only 2 cm H2O above gastric pressure. Removal of the intrinsic pressure barrier by myotomy allows free reflux in tubes that previously had prevented reflux.

Abdomen↗

Structure of Lumbricus terrestris hemoglobin at 30 A resolution determined using angular reconstitution.

The three-dimensional (3D) structure of the giant hemoglobin of the common earthworm Lumbricus terrestris was determined from cryomicroscopical images of a vitrified molecular solution. From about 5000 molecular images, the best-fit 3D structure was calculated using recently developed analysis techniques. Multivariate statistical analysis data compression and automatic classification were used to find the characteristic projection images of the oligomer. The angular reconstitution approach was then applied to find the Euler angle orientations of these characteristic views. The Lumbricus hemoglobin molecule has an overall D6 (622) point-group symmetry and is found to have a local threefold symmetry axis within the 1/12th subunit. This additional symmetry appears to predict the presence of 36 abcd globin tetramers in the Lumbricus hemoglobin or a total of 144 heme chains for the whole oligomer. A distinct doughnut-shaped structure is elucidated in the center of the molecule. This central subunit, representing around 10% of the protein volume, may consist of non-heme-containing linker chains found generally in giant annelid hemoglobins.

Animals↗

Treatment of liver metastases with moderate peritoneal carcinomatosis by hepatectomy and cytoreductive surgery followed by immediate post-operative intraperitoneal chemotherapy: feasibility and preliminary results.

BACKGROUND/AIMS: Peritoneal carcinomatosis (PC) discovered during hepatectomy is usually a contraindication to resection. A potentially efficient treatment of PC is the resection of the macroscopic disease and the treatment of the residual microscopic disease with immediate post-operative intraperitoneal chemotherapy (IPIC) (before the entrapment of cancer cells inside the fibrin deposit which rapidly cover the injured tissues). Feasibility and survival results of this treatment, combined with major hepatectomy, have never been evaluated. The purpose of this study is to report tolerance and preliminary results in patients with liver metastases synchronous to moderate PC, treated with hepatectomy, complete cytoreductive surgery, and IPIC. METHODOLOGY: Twelve patients with liver metastases and moderate PC from miscellaneous origins, underwent: 1) hepatectomy (9 of them were major hepatectomies); 2) complete cytoreductive surgery of the PC resecting between 20 and 150 nodules; and, 3) IPIC, for 5 days, according to histology. RESULTS: There was no mortality. Morbidity was mainly due to four transient biliary leakages (33%) and there was no systemic complication due to the chemotherapy. After a median follow-up of 14.4 months, there was no detectable recurrence of the PC. Preliminary results concerning survival are promising with 7 patients without recurrent disease. CONCLUSIONS: When a minimal or moderate PC is discovered during laparotomy for liver resection of metastases, the combination of hepatectomy with complete cytoreductive surgery of the peritoneal disease, followed with IPIC is logical and feasible. This aggressive treatment is well tolerated although the frequency of biliary leakage seems to be higher than that after standard hepatectomy. No recurrence of the peritoneal disease was detected and survival results are very promising.

Adult↗