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Biomedical subjects

B Williamson

Publications and source records attributed to B Williamson.

At least 19 recordsLinked to original sources
PubMed1998

Characterization of human colon cancer antigens recognized by autologous antibodies.

The screening of cDNA expression libraries derived from human tumors with autologous antibody (SEREX) has proven to be a powerful method for defining the structure of tumor antigens recognized by the humoral immune system. In the present study, 48 distinct antigens (NY-CO-1-NY-CO-48) reactive with autologous IgG were identified by SEREX analysis in 4 patients with colon cancer. Sequencing analysis showed that 17 of the cDNA clones were previously uncharacterized molecules and 31 represented known gene products. The individual cDNA clones were analyzed in the following manner: a search for mutations or other structural changes; an analysis of mRNA expression in a panel of normal tissues; and a frequency analysis of the antibody response to the expressed product in the sera of colon cancer patients and normal individuals. The initial analysis showed NY-CO-13 to be a mutated version of the p53 tumor suppressor gene. Three of the 48 antigens showed a differential pattern of mRNA expression, with NY-CO-27 (galectin-4) expressed primarily in gastrointestinal tract, and NY-CO-37 and -38 showing a pattern of tissue-specific isoforms. With regard to immunogenicity, 20 of the 48 antigens were detected by allogeneic sera; 14 of these were reactive with sera from both normal donors and cancer patients, and 6 other clones (NY-CO-8, -9, -13, -16, -20 and -38) reacted exclusively with sera from colon cancer patients (ranging from 14% to 27%). Our results on colon cancer illustrate both the complexity and the potential of the SEREX approach for analysis of the humoral immune response against human cancer.

Adult↗
PubMed1997

Characterization of tumor necrosis factor-deficient mice.

Although tumor necrosis factor (TNF) initially came to prominence because of its anti-tumor activity, most attention is now focused on its proinflammatory actions. TNF appears to play a critical role in both early and late events involved in inflammation, from localizing the noxious agent and amplifying the cellular and mediator responses at the local site and systemically, to editing (e.g., apoptosis) injured cells or effete immune cells and repairing inflammatory damage. We have generated mice deficient in TNF (TNF-/- mice) and have begun to examine the multiple functions attributed to TNF. TNF-/- mice develop normally and have no gross structural or morphological abnormalities. As predicted, they are highly susceptible to challenge with an infectious agent (Candida albicans), are resistant to the lethality of minute doses of lipopolysaccharide (LPS) following D-galactosamine treatment, have a deficiency in granuloma development, and do not form germinal centers after immunization. Phagocytic activity of macrophages appears relatively normal, as do T cell functions, as measured by proliferation, cytokine release, and cytotoxicity. B cell response to thymus-independent antigens is normal, but the Ig response to thymus-dependent antigen is reduced. Surprisingly, cytokine production induced by LPS appears essentially intact, with the exception of reduced colony-stimulating factor activity. Other unexpected findings coming from our initial analysis are as follows. (i) TNF has low toxicity in TNF-/- mice. (ii) TNF-/- mice show an anomalous late response to heat-killed Corynebacterium parvum. In contrast to the prompt response (granuloma formation, hepatosplenomegaly) and subsequent resolution phase in C. parvum-injected TNF+/+ mice, similarly treated TNF-/- mice show little or no initial response, but then develop a vigorous, disorganized inflammatory response leading to death. These results suggest that TNF has an essential homeostatic role in limiting the extent and duration of an inflammatory process-i.e., an anti-inflammatory function. (iii) In contrast to the expectation that TNF+/+ mice and TNF+/- mice would have identical phenotypes, TNF+/- mice showed increased susceptibility to high-dose LPS lethality, increased susceptibility to Candida challenge, and delayed resolution of the C. parvum-induced inflammatory process, indicating a strong gene dose requirement for different actions of TNF.

Animals↗
PubMed1997

A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening.

Serological analysis of recombinant cDNA expression libraries (SEREX) using tumor mRNA and autologous patient serum provides a powerful approach to identify immunogenic tumor antigens. We have applied this methodology to a case of esophageal squamous cell carcinoma and identified several candidate tumor targets. One of these, NY-ESO-1, showed restricted mRNA expression in normal tissues, with high-level mRNA expression found only in testis and ovary tissues. Reverse transcription-PCR analysis showed NY-ESO-1 mRNA expression in a variable proportion of a wide array of human cancers, including melanoma, breast cancer, bladder cancer, prostate cancer, and hepatocellular carcinoma. NY-ESO-1 encodes a putative protein of Mr 17,995 having no homology with any known protein. The pattern of NY-ESO-1 expression indicates that it belongs to an expanding family of immunogenic testicular antigens that are aberrantly expressed in human cancers in a lineage-nonspecific fashion. These antigens, initially detected by either cytotoxic T cells (MAGE, BAGE, GAGE-1) or antibodies [HOM-MEL-40(SSX2), NY-ESO-1], represent a pool of antigenic targets for cancer vaccination.

Amino Acid Sequence↗
PubMed1997

Specificity of volumetric magnetic resonance imaging in detecting hippocampal sclerosis.

BACKGROUND: Magnetic resonance imaging (MRI)-based volumetric measurements of the hippocampal formation are useful in detecting unilateral hippocampal sclerosis (HS) in patients with temporal lobe epilepsy. In this pathologic entity, volumetric MRI analysis shows the epileptogenic structure to be atrophic when compared with the normal, nonepileptogenic side. Some authors have suggested that the radiological features of atrophy of medial temporal lobe structures are common in patients with complex partial seizures, but also are seen frequently in other seizure types and can occur even in patients without epilepsy. OBJECTIVE: To determine if seizures originating in extrahippocampal sites cause gliosis, cell loss, and atrophy of medial temporal lobe structures (i.e., HS). METHODS: We studied 110 patients with chronic epilepsy using volumetric MRI measurements of the hippocampal formation. Seventeen patients had pathologically proven HS, 27 patients had seizures due to extratemporal structural lesions, 15 patients had seizures caused by extrahippocampal temporal lobe lesions, 29 patients had primary generalized epilepsy, and 22 patients had secondary generalized epilepsy. RESULTS: All 17 patients with HS showed significantly reduced absolute hippocampal formation volumes of greater than 2 SDs below the mean of the control groups. The preoperative hippocampal formation volume measurements correlated well with the severity of HS on pathological examination. Hippocampal volumes were within the normal range in all patients with primary generalized epilepsy, secondary generalized epilepsy, extratemporal structural lesions, and extrahippocampal temporal lobe lesions. CONCLUSIONS: Seizures originating at extrahippocampal sites do not cause gliosis, cell loss, or atrophy of medial temporal structures. Significant reduction in hippocampal volumes is a specific marker for HS.

Adolescent↗
PubMed1996

Symptomatic spinal hemangiomas in association with cutaneous hemangiomas. A case report.

STUDY DESIGN: This case report describes a patient with associated vertebral and peripheral vascular malformations presenting with a painful scoliosis. OBJECTIVES: To treat the vertebral osseous lesion successfully with embolization. SUMMARY OF BACKGROUND DATA: Although vertebral vascular malformations are well described, the association with peripheral lesions is uncommon. When associated peripheral vascular malformations occur, they are usually in tissues derived from the same embryonic segment, which was not the case in this instance. METHODS: After investigation with angiography, this patient's vertebral osseous lesion was treated by embolization. RESULTS: This patient's pain has been abolished since embolization. Her scoliosis has not progressed during follow-up. CONCLUSIONS: This case illustrates the association between spinal and peripheral vascular malformations, and that this association is not always metameric. It highlights the fact that invasive procedures other than surgery are a valuable part of the therapeutic armamentarium.

Adolescent↗
PubMed1996

High field NMR microscopic imaging of cultivated strawberry fruit.

The experimental conditions required for discrimination of various types of tissue in fruits of cultivated strawberry (Fragaria x Ananassa) at high fields (ca. 7 T) have been investigated. In marked contrast to soft fruits of other species, from which informative images have been derived at high fields using a variety of pulse sequences and acquisition parameters, appreciable image intensities from parenchymal and vascular tissues in healthy strawberry fruits were obtained only with a spin-echo imaging sequence using large sweep widths (ca. 100,000 Hz), and consequently small values for TE ( < 5 ms), indicating predominantly short T2 values for these tissues. Damage caused by infection by the fungal pathogen Botrytis cinerea is readily seen as a result of a large increase in T2 in the infected tissue, whereas ripening processes appear to be characterized primarily by small variations in the T2-weighted contrast and in the relative magnitudes of T1 between vascular and parenchymal tissue. In addition, it was possible selectively to enhance the contributions to images from the achenes ("seeds") by using very short relaxation delays, thereby enhancing T1-dominated contrast mechanisms.

Fruit↗
PubMed1996

Medial temporal lobe heterotopia as a cause of increased hippocampal and amygdaloid MRI volumes.

Magnetic resonance imaging (MRI)-based volumetric measurements of the hippocampus and amygdala are useful in detecting hippocampal and amygdaloid sclerosis in patients with temporal lobe epilepsy. In these pathological entities, volumetric MRI analysis shows the epileptogenic structures to be atrophic when compared to the normal, nonepileptogenic side. Described are 2 patients with increased hippocampal and amygdaloid volumes on the side of seizure onset due to medial temporal lobe heteroto pias. Care must be taken in the interpretation of volumetric MRI data to make certain that asymmetries in hippocampal and amygdaloid measurements are due to atrophy and sclerosis of the abnormal side and not to increased tissue such as heterotopic gray matter.

Adult↗
PubMed1995

Atrial electrogram characteristics in patients with and without atrioventricular nodal reentrant tachycardia.

BACKGROUND: Multicomponent atrial electrograms and "slow pathway potentials" are helpful in identifying target sites for radiofrequency catheter ablation of the slow pathway in patients with atrioventricular (AV) nodal reentrant tachycardia. The purpose of this study was to compare the atrial electrograms recorded at various locations in the right atrium in patients with and without AV nodal reentrant tachycardia to assess the specificity of multicomponent atrial electrograms and possible slow pathway potentials both for the posteroseptal right atrium and for patients with AV nodal reentrant tachycardia. METHODS AND RESULTS: In 25 patients with AV nodal reentrant tachycardia and 23 control patients without AV nodal reentrant tachycardia or dual AV nodal physiology, atrial electrograms with an AV ratio of < or = 1:2 were recorded at the posteroseptal right atrium near the coronary sinus ostium and in the right atrium near the posterior, lateral, and anterior aspects of the tricuspid annulus. Attempts were made to identify broad, multicomponent, and double atrial electrograms. There were no significant differences between the patients with and without AV nodal reentrant tachycardia in the mean number of deflections in the atrial electrograms or in the mean duration of the atrial electrograms recorded at any of the atrial sites. In all patients, the number of atrial electrogram deflections and the atrial electrogram duration were significantly greater at the posteroseptal position than at the other three atrial sites. The prevalence of potentials with the appearance of slow pathway potentials in the posterior septum was similar in patients with and without AV nodal reentrant tachycardia (68% and 70%, respectively). The prevalence of these potentials was 6% to 25% at the other three atrial sites (P < .005 compared with the posterior septum). CONCLUSIONS: The atrial electrogram characteristics that have been found to be useful in identifying effective posteroseptal slow pathway ablation sites in patients with AV nodal reentrant tachycardia are equally prevalent in patients without AV nodal reentrant tachycardia or dual AV nodal physiology. Atrial electrograms in the posteroseptal area are broader and contain more deflections than at other areas in the right atrium, possibly because of conduction properties of the posterior transitional zone that are independent of the presence of AV nodal reentrant tachycardia.

Adult↗
PubMed1995

Analysis of sevoflurane degradation products in vapor phase samples.

Sevoflurane degradation products were measured by GC-flame ionization detection in vapor phase samples using manual and automated injection methods. Sample handling techniques allowed the transfer and storage of samples for up to 72 h. Compound A, fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether, was the major vapor phase degradation product formed in simulated clinical conditions. Recoveries of 4-32 ppm (v/v) compound A concentrations using the manual method were in the range of 88-117% (n = 12, mean = 102%, R.S.D. = 9%).

Anesthetics↗
PubMed1995

Effect of accessory pathway location on the efficiency of heating during radiofrequency catheter ablation.

During radiofrequency catheter ablation of accessory pathways there is a poor correlation between applied power and temperature at target sites for catheter ablation. This study was designed to examine the relation between power and temperature during radiofrequency catheter ablation in patients with accessory pathways and to identify the factors that affect the efficiency of heating, defined as the ratio of applied power and temperature. Twenty-nine patients underwent radiofrequency catheter ablation of an accessory pathway. Among 257 energy applications, 108 were applied for ablation of a right-sided accessory pathway, 105 for a left-sided accessory pathway, and 44 for a posteroseptal accessory pathway. During each application of radiofrequency energy, temperature was continually monitored by use of an ablation catheter with a thermistor embedded in the tip of the distal electrode. During some applications of energy, fluctuations in temperature were observed. The average power, impedance, temperature, and efficiency of heating for all applications of radiofrequency energy was 37 +/- 11 W, 100 +/- 9 ohms, 53 +/- 9 degrees C, and 1.7 +/- 0.8 degrees C/W (range 0.9 degrees to 6.6 degrees C/W), respectively. The efficiency of heating varied by location (p < 0.0001), with the greatest efficiency of heating for posteroseptal energy applications (2.3 +/- 1.2 degrees C/W, which were significantly greater than for left-sided (1.8 +/- 0.8 degrees C/W; p < 0.01) or right-sided (1.2 +/- 0.4 degrees C/W; p < 0.0001) applications. Phasic fluctuation in temperature was observed during 127 (49%) energy applications, and the efficiency of heating was 1.5 +/- 0.7 degrees C/W.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The end of an era.

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Chromosome Mapping↗
PubMed1995

My guardian angel.

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Diabetes Mellitus, Type 1↗
PubMed1994

Randomized comparison of anatomic and electrogram mapping approaches to ablation of the slow pathway of atrioventricular node reentrant tachycardia.

OBJECTIVES: The purpose of this study was to prospectively compare in random fashion an anatomic and an electrogram mapping approach for ablation of the slow pathway of atrioventricular (AV) node reentrant tachycardia. BACKGROUND: Ablation of the slow pathway in patients with AV node reentrant tachycardia can be performed by using either an anatomic or an electrogram mapping approach to identify target sites for ablation. These two approaches have never been compared prospectively. METHODS: Fifty consecutive patients with typical AV node reentrant tachycardia were randomly assigned to undergo either an anatomic or an electrogram mapping approach for ablation of the slow AV node pathway. In 25 patients randomly assigned to the anatomic approach, sequential radiofrequency energy applications were delivered along the tricuspid annulus from the level of the coronary sinus ostium to the His bundle position. In 25 patients assigned to the electrogram mapping approach, target sites along the posteromedial tricuspid annulus near the coronary sinus ostium were sought where there was a multicomponent atrial electrogram or evidence of a possible slow pathway potential. If the initial approach was ineffective after 12 radiofrequency energy applications, the alternative approach was then used. RESULTS: The anatomic approach was effective in 21 (84%) of 25 patients, and the electrogram mapping approach was effective in all 25 patients (100%) randomly assigned to this technique (p = 0.1). The four patients with an ineffective anatomic approach had a successful outcome with the electrogram mapping approach. On the basis of intention to treat analysis, there were no significant differences between the electrogram mapping approach and the anatomic approach with respect to the time required for ablation (28 +/- 21 and 31 +/- 31 min, respectively, mean +/- SD, p = 0.7) duration of fluoroscopic exposure (27 +/- 20 and 27 +/- 18 min, respectively, p = 0.9) or mean number of radiofrequency applications delivered (6.3 +/- 3.9 vs. 7.2 +/- 8.0, p = 0.6). With both the anatomic and electrogram mapping approaches, the atrial electrogram duration and number of peaks in the atrial electrogram were significantly greater at successful target sites than at unsuccessful target sites. CONCLUSIONS: The anatomic and electrogram mapping approaches for ablation of the slow AV nodal pathway are comparable in efficacy and duration. If the anatomic approach is initially attempted and fails, the electrogram mapping approach may be successful at sites outside the areas targeted in the anatomic approach. With both the anatomic and electrogram mapping approaches, there are significant differences in the atrial electrogram configuration between successful and unsuccessful target sites.

Cardiac Pacing, Artificial↗