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Biomedical subjects

J Buckner

Publications and source records attributed to J Buckner.

14 recordsLinked to original sources
PubMed1998

Immunity to T cell receptor peptides in multiple sclerosis. III. Preferential immunogenicity of complementarity-determining region 2 peptides from disease-associated T cell receptor BV genes.

Vaccination with synthetic TCR peptides from the BV5S2 complementarity-determining region 2 (CDR2) can boost significantly the frequency of circulating CD4+ peptide-specific Th2 cells in multiple sclerosis (MS) patients, with an associated decrease in the frequency of myelin basic protein (MBP)-reactive Th1 cells and possible clinical benefit. To evaluate the immunogenicity of CDR2 vs other regions of the TCR, we vaccinated seven MS patients with overlapping BV5S2 peptides spanning amino acids 1-94. Six patients responded to at least one of three overlapping or substituted CDR2 peptides possessing a core epitope of residues 44-52, and one patient also responded to a CDR1 peptide. Of the CDR2 peptides, the substituted (Y49T)BV5S2-38-58 peptide was the most immunogenic but cross-reacted with the native sequence and had the strongest binding affinity for MS-associated HLA-DR2 alleles, suggesting that position 49 is an MHC rather than a TCR contact residue. Two MS patients who did not respond to BV5S2 peptides were immunized successfully with CDR2 peptides from different BV gene families overexpressed by their MBP-specific T cells. Taken together, these results suggest that a widely active vaccine for MS might well involve a limited set of slightly modified CDR2 peptides from BV genes involved in T cell recognition of MBP.

Adult↗
PubMed1998

Gene amplification as a prognostic factor in primary and secondary high-grade malignant gliomas.

The purpose of this study was to examine the incidence of gene amplification in patients with primary (de novo) and secondary high-grade gliomas (gliomas evolving from lower grade malignancies) and to assess its prognostic significance. A total of 186 prospectively collected frozen surgical specimens were analyzed. Extracted DNA was examined by Southern blot using probes corresponding to the EGFR, CDK4, MDM2, n-MYC, CYCD1, PDGFR-alpha, MET, c-MYC oncogenes. Complete clinical data regarding age, sex, tumor size, extent of surgical resection, postoperative therapy and patient survival were collected. We showed that EGFR followed by CDK4 were the most frequent oncogene amplifications. Oncogene amplification events were significantly more frequent in grade 4 than in grade 3 astrocytomas, mixed gliomas or oligodendrogliomas (P<0.001). With respect to EGFR, there was a significant difference in the frequency of amplification between primary and secondary gliomas (P=0.001); however, no difference in the amplification frequency of the other oncogenes was observed. There was no apparent correlation between the occurrence of gene amplification and patient survival, possibly because the genes amplified in human gliomas are part of larger signaling pathways.

Adolescent↗
PubMed1996

Modulation of HLA-DQ binding properties by differences in class II dimer stability and pH-dependent peptide interactions.

Intermolecular interactions between peptides and class II molecules intracellularly are likely to be influenced by different pH conditions in different endosomal compartments. We compared the pH-dependent binding of peptides to HLA-DQ alleles 3.1 and 3.2, two well-studied human class II molecules with limited structural variability but different genetic associations with autoimmune diseases. Binding of the "promiscuous" binding peptide 34P3A as well as that of several allele-specific peptides were optimal for DQ3.2 at relatively acidic pH, compared with DQ3.1, with a pH optimum for DQ3.2 at pH 5.5 and for DQ3.1 at pH 6.5. A specific polymorphism at residue 57 of the DQ molecule accounted for some, but not all, of this difference. When the intrinsic stability of the class II dimer was assessed using partially denaturing gel electrophoresis after incubation at different pH, the DQ3.2 molecule demonstrated relative instability at neutral pH compared with DQ3.1, again suggesting a preference for peptide binding at relatively acidic conditions for HLA-DQ3.2. Interestingly, this preference for binding at acidic pH was not found for a class II-associated invariant chain peptide. Intrinsic alphabeta dimer stability and the pH optima for peptide binding studied in this report are likely to be significant determinants for allelic differences in DQ binding profiles in vivo.

Alleles↗
PubMed1995

Vigilance and automobile accidents in patients with sleep apnea or narcolepsy.

Patients with obstructive sleep apnea or narcolepsy report difficulty remaining alert and attentive. To detect impaired vigilance, we designed Steer Clear, a computer program simulating a long and monotonous highway drive that presents 780 obstacles in 30 min. Sixty-two patients with sleep apnea hit a higher percentage of obstacles (4.3 +/- 0.6% [SEM]) than 12 age- and sex-matched subjects without sleep apnea (1.4 +/- 0.3%; p < 0.05) and 10 age- and sex-matched volunteers (1.2 +/- 0.3%; p < 0.05). Ten patients with untreated narcolepsy hit a higher percentage of obstacles while performing on Steer Clear (7.7 +/- 3.2%) than 10 age- and sex-matched subjects without narcolepsy (1.2 +/- 0.3%; p < 0.05). Poor performance on Steer Clear was associated with a higher auto accident rate in the patients with sleep apnea or narcolepsy (p < 0.01). Twenty-one patients who performed normally on Steer Clear had 1 accident in 5 years (0.05 accident/driver/5 yr), and in none of these accidents were they at fault as drivers. Twenty-five patients who performed poorly on Steer Clear had 5 auto accidents in 5 years (0.20 accident/driver/5 yr), and in 20% of these accidents they were at fault as drivers. Twenty-one patients who performed very poorly on Steer Clear had 8 auto accidents in 5 years (0.38 accident/driver/5 yr), and in 38% of these accidents they were at fault as drivers. These 21 patients who performed very poorly on Steer Clear (hitting > 4.5% of obstacles) had a significantly higher auto accident rate than the patients who performed normally (hitting < 1.8%). We conclude: (1) Patients with sleep apnea or narcolepsy performed more poorly on a test of vigilance, Steer Clear, than did control subjects; (2) Impaired vigilance as measured by Steer Clear is associated with a high automobile accident rate in patients with either sleep apnea or narcolepsy.

Accidents, Traffic↗
PubMed1994

Chemotherapy for anaplastic oligodendroglioma. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To examine the rate and duration of response of anaplastic oligodendrogliomas to a dose-escalated combination chemotherapy regimen consisting of procarbazine, lomustine (CCNU), and vincristine (PCV) and to evaluate the side effects of this treatment. METHODS: In this single-arm multicentered phase II study, patients with measurable, newly diagnosed or recurrent, contrast-enhancing anaplastic oligodendrogliomas were treated with up to six cycles of PCV. Central pathology and radiology review were mandatory, and rigorous response criteria based on imaging were used. RESULTS: Thirty-three patients entered the trial; nine were excluded subsequently, seven due to ineligible pathology. Eighteen of 24 eligible patients (75%) responded, nine completely (38%), four had stable disease (SD), and two progressed during the first cycle of PCV. Responses were observed in nine of 10 patients (90%) with a preexisting low-grade oligodendroglioma and 10 of 15 (67%) with necrotic tumors, called glioblastoma multiforme by some. Previously irradiated patients were as likely to respond to PCV as those newly diagnosed (11 of 15 [73%] v seven of nine [78%]). The median time to progression will be at least 25.2 months for complete responders, and was 14.2 months for partial responders and 6.8 months for stable patients. Four ineligible patients also responded to PCV; all had gliomas with oligodendroglial differentiation. All responders, eligible or ineligible, were stable or improved neurologically, but nine of 22 (41%) experienced a decline in Eastern Cooperative Oncology Group (ECOG) performance status of one grade while on PCV. Adverse events on treatment included a death from Pneumocystis pneumonia, a severe reversible encephalopathy due to procarbazine, an intratumoral hemorrhage, and a subdural hematoma. All other acute toxicities were anticipated and manageable. CONCLUSION: Anaplastic oligodendrogliomas are chemosensitive brain cancers. Patients with these tumors respond predictably, durably, and often completely to PCV, and many tolerate a dose-escalated formulation. Cooperative group and randomized trials will be necessary to explore fully the role of chemotherapy in the treatment of aggressive oligodendrogliomas.

Adolescent↗
PubMed1992

Surgery, radiation therapy, and chemotherapy for metastatic tumors to the brain.

Recent literature has confirmed patient age, Karnofsky status, and the extent of extracerebral tumor as independent prognostic variables in patients with cerebral metastases. In a good-risk population, surgery followed by radiation therapy is superior to radiation alone for treatment of patients with solitary metastases. Stereotactic radiosurgery is feasible in the same select patient population, but questions regarding the extent of delayed toxicity, tumor response, and the impact on quality of life and longevity remain to be answered. Studies of external beam radiation therapy for patients with brain metastases have shown that 1) misonidazole does not improve the response rate, quality of life, or duration of survival, 2) 5 Gy for six fractions and 3 Gy for 10 fractions produce similar results, and 3) reirradiation at doses of 25 Gy for tumors progressing after initial radiation may be feasible in a selected population of patients. Chemotherapy can affect regression of brain metastases in patients with small cell lung and breast carcinoma, as well as melanoma, but the overall contribution to the quality and duration of the patient's life compared with radiation alone is unknown. Intracarotid chemotherapy is feasible for patients with brain metastases, but substantial toxicity precludes its use outside of an investigational setting. Brain metastases remain an important cause of morbidity and mortality for patients with cancer, but the majority of patients still succumb to widespread systemic disease. The goal of treatment of brain metastases should be palliation with minimal infringement upon the patient's quality of life.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Evaluation of the updated Vitek yeast identification data base.

Using 398 isolates of yeasts and yeastlike fungi comprising 9 genera and 26 species, as well as the hyphomycete Geotrichum candidum and the achlorophyllous alga Prototheca wickerhamii, we compared the API 20C yeast identification system with the modified Vitek yeast identification system with an expanded data base. We found 11 discrepancies between the two systems: five (1.3%) of the isolates (Blastoschizomyces capitatus, 1; Candida albicans, 1; Hansenula anomala, 1; Rhodotorula minuta, 2) had biocodes not included in the expanded Vitek data base, and six (1.5%) of the isolates (Candida lusitaniae, 1; Candida parapsilosis, 1; Cryptococcus uniguttulatus, 1; H. anomala, 1; Torulopsis candida, 2) were misidentified by the Vitek system. Overall, the efficacy of the Vitek system compares favorably with that of the API 20C in the identification of clinically important yeasts.

Databases, Bibliographic↗
PubMed1982

Aspirin blocks nicotinic acid-induced flushing.

Nicotinic acid flushing after placebo and 975-mg oral doses of aspirin was assessed in 29 normal subjects over a range of nicotinic acid doses. Intensity of flushing was assessed by the change in malar thermal circulation index (delta MTCI). Aspirin pretreatment resulted in smaller delta MTCIs at the higher doses of nicotinic acid. At the lower doses the change in the index after pretreatments with both aspirin and placebo remained low, suggesting that very little flushing was provoked by these doses. These results are compatible with the proposed mediation by prostaglandins of the nicotinic acid-induced flush. According to the delta MCTI method, flushing is quantitatively characterized as a nonquantal, dose-response reaction of variable intensity.

Adult↗
PubMedDate not supplied

The student's corner.

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Education, Medical↗