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Biomedical subjects

J Boyer

Publications and source records attributed to J Boyer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Characterization of a thymidylate synthase (TS)-inducible cell line: a model system for studying sensitivity to TS- and non-TS-targeted chemotherapies.

Thymidylate synthase (TS) is responsible for the de novo synthesis of thymidylate, which is required for DNA synthesis and repair and which is an important target for fluoropyrimidines such as 5-fluorouracil (5-FU), and antifolates such as Tomudex (TDX), ZD9331, and multitargeted antifolate (MTA). To study the importance of TS expression in determining resistance to these agents, we have developed an MDA435 breast cancer-derived cell line with tetracycline-regulated expression of TS termed MTS-5. We have demonstrated that inducible expression of TS increased the IC(50) dose of the TS-targeted therapeutic agents 5-FU, TDX, and ZD9331 by 2-, 9- and 24-fold respectively. An IC(50) dose for MTA was unobtainable when TS was overexpressed in these cells, which indicated that MTA toxicity is highly sensitive to increased TS expression levels. The growth inhibitory effects of the chemotherapeutic agents CPT-11, cisplatin, oxaliplatin, and Taxol were unaffected by TS up-regulation. Cell cycle analyses revealed that IC(50) doses of 5-FU, TDX and MTA caused an S-phase arrest in cells that did not overexpress TS, and this arrest was overcome when TS was up-regulated. Furthermore, the S-phase arrest was accompanied by 2- to 4-fold increased expression of the cell cycle regulatory genes cyclin E, cyclin A, and cyclin dependent kinase 2 (cdk2). These results indicate that acute increases in TS expression levels play a key role in determining cellular sensitivity to TS-directed chemotherapeutic drugs by modulating the degree of S-phase arrest caused by these agents. Moreover, CPT-11, cisplatin, oxaliplatin, and Taxol remain highly cytotoxic in cells that overexpress TS.

Blotting, Northern↗
PubMed2000

Evidence for changing of cosmic ray composition between 10(17) and 10(18) eV from multicomponent measurements

The average mass composition of cosmic rays with primary energies between 10(17) and 10(18) eV has been studied using a hybrid detector consisting of the High Resolution Fly's Eye (HiRes) prototype and the MIA muon array. Measurements have been made of the change in the depth of shower maximum and the muon density as a function of energy. The results show that the composition is changing from a heavy to lighter mix as the energy increases.

Journal Article↗
PubMed2000

Comparison of the Objective Structured Clinical Examination with the performance of third-year medical students in surgery.

BACKGROUND: The purpose of this study was to investigate the validity of the Objective Structured Clinical Examination (OSCE) as an evaluation technique by comparing medical student performance on the OSCE with traditional forms of evaluation. SUBJECTS AND METHODS: We analyzed the performance of 129 third-year medical students in the 1997-1998 academic year on clinical evaluations, oral examinations, and NBME subject examinations, and on OSCE, which was not included in the final grade. RESULTS: The OSCE showed high correlation with the final grades received for the clerkship. Seventy-one percent of students receiving High Pass or Honors had high OSCE scores whereas 67% of students with low OSCE scores received poor or Defer grades. Pearson product-moment correlations demonstrated significant bivariate correlations with the other test parameters. CONCLUSIONS: This study demonstrates that the OSCE is similar to the traditional methods in evaluating general ability and is also able to evaluate clinical ability in a standardized manner.

Analysis of Variance↗
PubMed2000

High-dose ifosfamide and etoposide with filgrastim for stem cell mobilization in patients with advanced ovarian cancer.

High-dose chemotherapy combined with autologous peripheral blood stem cell transplantation has shown promise as treatment for recurrent or persistent epithelial ovarian cancer. We evaluated the stem cell mobilization regimen of high-dose ifosfamide plus etoposide in 32 patients with epithelial ovarian cancer, who had a positive second-look laparatomy or recurrent disease. Ifosfamide was given at 10 g/m2 by continuous i.v. from days 1 to 3. Etoposide was given at 150 mg/m2 every 12 h for six doses on days 1-3. Filgrastim was given at 10 microg/kg/d s.c. from day 5 until the completion of peripheral blood stem cell harvest. Fourteen of 32 patients had measurable or evaluable disease before mobilization therapy and were assessed for response. In nine (64%) of the 14 patients, treatment response was demonstrated, and these patients received a second cycle of mobilization therapy. The target CD34+ cell dose (>8 x 106 cells/kg) was achieved with a median of one apheresis (range 1-5). A median of 25.1 (range 8.0-122.5) x 106 CD34+ cells/kg body weight was collected. Non-hematologic toxicity was limited to grade 2 renal dysfunction in one patient and grade 2 hepatic dysfunction in three patients. In this patient group, high-dose ifosfamide plus etoposide with filgrastim support was well tolerated, lead to successful stem cell harvest and had antitumor activity.

Adult↗
PubMed2000

Argon plasma coagulation for the treatment of hemorrhagic radiation proctitis.

BACKGROUND AND STUDY AIMS: Chronic radiation proctitis is a complication of radiotherapy for malignant pelvic diseases. Rectal bleeding caused by radiation proctitis is difficult to manage. Argon plasma coagulation (APC) is an electrocoagulation technique that appears to be an effective and low-cost alternative to the use of lasers in gastrointestinal endoscopy. The aim of this study was to evaluate the efficacy of APC, as well as patients' tolerance of the procedure, in the treatment of bleeding radiation-induced proctitis. PATIENTS AND METHODS: The charts of 16 patients with chronic radiation proctitis were analyzed retrospectively. Their average age was 73.5 (range 62-80). Fifteen patients had prostate cancer, and one had uterine cancer. The average time to onset of symptoms after radiotherapy was 15 months (range 6-36 months). All patients had intermittent or daily rectal bleeding, and three patients needed blood transfusions. The severity of bleeding was graded from 0 to 4. APC treatment was administered every month; the argon gas flow was set at 0.6 l/min with an electrical power setting of 40 W. RESULTS: All patients were improved with APC treatment. A mean of 3.7 sessions was necessary to relieve symptoms. APC therapy resulted in a reduction in the mean severity score from 2.4 to 0.6. Seven patients had no recurrent rectal bleeding, and the bleeding was significantly reduced to occasional and negligible spotting (less than one bleeding episode per week) in nine patients. None of the patients required transfusions after treatment. During the follow-up period (average 10.7 months, range 8-28 months), one patient had a recurrence of rectal bleeding that required two repeat sessions. The tolerance was good, with no long-term treatment-related complications. CONCLUSIONS: APC is an effective, safe and well-tolerated treatment for rectal bleeding caused by chronic radiation proctitis. It should be considered as a first-line therapy for radiation proctitis.

Aged↗
PubMed2000

Late recurrence of a hepatic angiomyolipoma.

Angiomyolipomas are benign mesenchymal tumours, mostly of renal origin. Hepatic angiomyolipomas are rare, and radiological and pathological diagnoses may be difficult We report on the first case of hepatic angiomyolipoma recurrence known to us, 6 years after surgical treatment of the initial tumour. Moreover, this hepatic recurrence was associated with renal angiomyolipoma without any stigmata of tuberous sclerosis.

Adolescent↗
PubMed2000

[Laparoscopic cholecystectomy in the treatment of acute cholecystitis. Prospective non-randomized study].

OBJECTIVES: To evaluate the results of laparoscopic cholecystectomy in patients with acute cholecystitis and to determine the optimal timing. PATIENTS AND METHODS: From January 1993 to December 1999, 168 patients (91 women and 77 men with a mean age of 57.3 years) underwent laparoscopic cholecystectomy for acute cholecystitis confirmed by histopathological examination. Patients were divided into 2 groups (similar in age and ASA classification): group 1 (106 patients) underwent laparoscopic cholecystectomy within 3 days after the onset of symptoms of acute cholecystitis and group 2 (62 patients) underwent laparoscopic cholecystectomy after 3 days. RESULTS: There was no death. Conversion rates were 30.9%. Surgery lasted 141.3 min, postoperative morbidity was 12.5%, and the postoperative length of hospital stay was 6.9 days. The conversion rates in patients who underwent surgery before and 3 days after the onset of symptoms were respectively 21.7% and 46.7% (P=0.0007). There was no statistical difference between early and delayed surgery for time to surgery and postoperative complications. On the other hand, the total hospital stay was significantly shorter in group 1. CONCLUSION: Laparoscopic cholecystectomy for acute cholecystitis is safe and associated with a shorter postoperative stay, a lesser morbidity and a lesser mortality compared to "open" surgery. Laparoscopic cholecystectomy should be carried out soon as the diagnostic of acute cholecystitis is established and preferably before 3 days after the onset of the symptoms. Early laparoscopic cholecystectomy allows a reduction of the conversion rate and a reduction of total hospital stay that are medical and economic benefits.

Acute Disease↗
PubMed1999

Adenovirus E4 34k and E4 11k inhibit double strand break repair and are physically associated with the cellular DNA-dependent protein kinase.

The adenovirus oncoproteins E4 34k and E4 11k, the products of E4 open reading frames 6 and 3, respectively, individually prevent the formation of concatemers of the linear viral genome in infected cells. We show here that genome concatenation in E4 mutant-infected cells requires the cellular DNA-dependent protein kinase (DNA PK) and that E4 34k inhibits V(D)J recombination, a normal cellular process that is also dependent on DNA PK. We further show that both E4 34k and E4 11k coimmunoprecipitate with DNA PK. These observations indicate that E4 products block formation of concatemers of the viral genome by inhibiting DNA PK-dependent double strand break repair and suggest that they act by forming a physical complex with DNA PK. DNA PK also participates in activation of p53 DNA-binding activity by DNA damage. By inhibiting DNA PK function, E4 products may block p53 activation in response to the products of viral DNA replication and thus provide a new mechanism to prevent apoptosis of infected cells.

Adenoviridae↗
PubMed1999

[Barrett's esophagus].

Barrett's oesophagus is a complication of oesophagogastric reflux. Diagnosis is made on the basis of endoscopy and histology showing glandular and intestinal metaplasia above the oeso-gastric junction. The most severe complication is adenocarcinoma. Endoscopic follow up is effective in individual patients. Other solutions would be either to protect the Barrett oesophagus from carcinogenic and cocarcinogenic agents contained in particular in the duodenal reflux fluid, or to ablate Barrett's mucosa by thermal or physicochemical processes, allowing subsequent regrowth of normal malpighian mucosa by suppression of the oesophagogastric reflux.

Adenocarcinoma↗
PubMed1999

Protective immune correlates can segregate by vaccine type in a murine herpes model system.

A central tenet of vaccine development is to identify immune correlates of protection. Both plasmid-encoded gD as well as recombinant protein gD can protect mice from lethal herpes simplex virus (HSV) challenge. It is known that different vaccine modalities should induce different immune phenotypes. Yet, paradoxically, it is also thought that the basis for protection should rely on exploitation of vulnerabilities of the pathogen and therefore that the overlapping properties of these different vaccines would reveal insight into common immune mechanisms responsible for protection. We sought to investigate this question by comparing two different vaccine modalities in the HSV-2 mouse model. We observed that gD protein was a strong inducer of T(h)2-type immune responses, and overall antibody titers of IgG, IgE and IgA were significantly higher than those induced by plasmid gD vaccines. In contrast, the plasmid gD vaccine induced a strong T(h)1 bias. Following high-dose challenge the gD protein was most effective at providing protection. However, at lower lethal dose challenge, while both vaccines were protective with regards to survival, only the plasmid-vaccinated animals were protected from HSV-2 infection-induced morbidity. These studies suggest that these different vaccine modalities induce protection through unique non-overlapping mechanisms, supporting that vaccine correlates are associated with the types of immunogen rather than solely the pathogen.

Animals↗
PubMed1999

[Endoscopic sphincteroclasy for choledocholithiasis of the principal bile duct. Short-term results and follow-up].

AIMS: The hydrostatic dilatation of the papilla of Vater, or sphincteroclasy, has been recently proposed as an alternative to endoscopic sphincterotomy. Our aim was to assess short term results and follow-up after sphincteroclasy for choledocholithiasis. METHODS: From August, 1994 to December, 1996, 52 patients were included for endoscopic therapy of choledocholithiasis (mean age 66 +/- 17 years). Patients were prospectively followed on the short term-period (24 h, 48 h and 30 days) and longer term after treatment (every 6 months) by clinical and biological controls. MAIN RESULTS: Forty-eight sphincteroclasies were performed successfully (92.3%). Thirty seven patients had a choledocolithiasis. Eleven were stone-free. Eight had undergone former gastric surgery and 8 had impaired coagulation test. Complete stone clearance was achieved in 98% of patients. Mild pancreatitis were observed in three patients (6.25%). Thirty-day mortality was nil. Long term follow-up (mean 21.4 +/- 7 months) revealed: 2 patients with cholecystitis 6 and 13 months after treatment, one of which was followed 8 months later by a fatal septic shock, and 3 patients with cholangitis, 2 of which in the same patient, 9, 12 and 24 months after sphincteroclasy. The global long term biliary complication rate was 8.4%, 4.2% of which were potentially related to the endoscopic procedure. CONCLUSION: Sphincteroclasy is an efficient procedure for the treatment of choledocholithiasis. Its short term results are similar to those of endoscopic sphincterotomy. Complications after 2 years appear to be scarce, but longer follow-up is required before routinely performing sphincteroclasy.

Adult↗
PubMed1998

Random exploration of the Kluyveromyces lactis genome and comparison with that of Saccharomyces cerevisiae.

The genome of the yeast Kluyveromyces lactis was explored by sequencing 588 short tags from two random genomic libraries (random sequenced tags, or RSTs), representing altogether 1.3% of the K. lactis genome. After systematic translation of the RSTs in all six possible frames and comparison with the complete set of proteins predicted from the Saccharomyces cerevisiae genomic sequence using an internally standardized threshold, 296 K.lactis genes were identified of which 292 are new. This corresponds to approximately 5% of the estimated genes of this organism and triples the total number of identified genes in this species. Of the novel K.lactis genes, 169 (58%) are homologous to S.cerevisiae genes of known or assigned functions, allowing tentative functional assignment, but 59 others (20%) correspond to S.cerevisiae genes of unknown function and previously without homolog among all completely sequenced genomes. Interestingly, a lower degree of sequence conservation is observed in this latter class. In nearly all instances in which the novel K.lactis genes have homologs in different species, sequence conservation is higher with their S.cerevisiae counterparts than with any of the other organisms examined. Conserved gene order relationships (synteny) between the two yeast species are also observed for half of the cases studied.

Base Sequence↗