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Biomedical subjects

T Fuller

Publications and source records attributed to T Fuller.

At least 19 recordsLinked to original sources
PubMed2004

High-resolution DNA melting curve analysis to establish HLA genotypic identity.

High-resolution melting curve analysis is a closed-tube fluorescent technique that can be used for genotyping and heteroduplex detection after polymerase chain reaction. We applied this technique at the HLA-A locus and suggest that this method can be used as a rapid, inexpensive screen between siblings prior to living-related transplantation. At any locus, there are seven general cases of shared alleles among two individuals, ranging from identical homozygous genotypes (all alleles shared) to two heterozygous genotypes that share no alleles. We studied each case using previously typed cell lines to show that identity or non-identity can be determined in all cases by high-resolution melting curve analysis. HLA genotype identity is suggested when two individuals have the same melting curves. Identity is confirmed by comparing the melting curve of a 1:1 mixture with the individual melting curves. Non-identity at the amplified locus changes the heteroduplexes formed in the mixture compared with the original samples and alters the shape of the melting curve. The technique was tested on DNA from a 17-member CEPH family. High-resolution melting curve analysis revealed six different genotypes in the family. The genotype clustering was confirmed by sequence-based typing. Although this technique does not sequence or determine specific HLA alleles, it does rapidly establish identity at highly polymorphic HLA loci. The technique may also prove useful for confirmation of HLA genotypic identity between unrelated individuals prior to allogeneic hematopoietic stem-cell transplantation.

Base Sequence↗
PubMed1999

Effects of troglitazone on substrate storage and utilization in insulin-resistant rats.

Elevated serum and tissue lipid stores are associated with skeletal muscle insulin resistance and diminished glucose-stimulated insulin secretion, the hallmarks of type 2 diabetes. We studied the effects of 6-wk treatment with the insulin sensitizer troglitazone on substrate storage and utilization in lean control and Zucker diabetic fatty (ZDF) rats. Troglitazone prevented development of diabetes and lowered serum triglycerides (TG) in ZDF rats. Soleus muscle glycogen and TG content were elevated twofold in untreated ZDF rats, and both were normalized by troglitazone to lean control levels (P < 0.05). Troglitazone also normalized insulin-stimulated glucose uptake as well as basal and insulin-stimulated glycogen synthesis, implying increased skeletal muscle glycogen turnover. The proportion of active pyruvate dehydrogenase (PDH) in soleus muscle was reduced in ZDF relative to lean control rat muscle (16 +/- 2 vs. 21 +/- 2%) but was restored by troglitazone treatment (30 +/- 3%). Increased PDH activation was associated with a 70% increase in glucose oxidation. Muscle lipoprotein lipase activity was decreased by 35% in ZDF compared with lean control rats and was increased twofold by troglitazone. Palmitate oxidation and incorporation into TG were higher in ZDF relative to lean control rats but were unaffected by troglitazone treatment. Troglitazone decreased the incorporation of glucose into the acyl group of TG by 60% in ZDF rats. In summary, ZDF rats demonstrate increased skeletal muscle glycogen and TG stores, both of which were reduced by troglitazone treatment. Troglitazone appears to increase both glycogen and TG turnover in skeletal muscle. Normalization of PDH activity and decreased glucose incorporation into acyl TG may underlie the improvements in intracellular substrate utilization and energy stores, which lead to decreased serum TG and glucose.

Animals↗
PubMed1998

Laser treatment of solar elastosis with epithelial preservation.

BACKGROUND AND OBJECTIVE: Laser resurfacing has gained wide acceptance for the treatment of actinic facial skin. However, postoperative care of the face is reasonably complicated and prolonged erythema is common. To simplify the postoperative care and to possibly reduce the duration of the erythema, we investigated a laser treatment that spares the epithelium. STUDY DESIGN/MATERIALS AND METHODS: A 980 nm diode laser was used with a spherical optic handpiece to focus the light in the dermis. We treated in vitro breast and facial skin and measured the tissue shrinkage and the histological changes. We also treated two patients and harvested the tissue after 6 and 21 days of wound healing. RESULTS: The diode laser treatment does not ablate the epidermis. The tissue shows shrinkage (16% at 8W) similar to three passes of the scanned carbon dioxide laser treatment (15%). Thermal damage in the dermis is similar to the residual damage left after laser resurfacing with the scanned carbon dioxide laser. After 21 days the tissue shows new collagen and an abundance of young elastin fibers. CONCLUSIONS: These investigations indicate that solar elastosis in skin can be treated with the 980 nm diode laser while preserving the epithelial layer.

Carbon Dioxide↗
PubMed1995

The use of felbamate in patients with periodic lateralized epileptiform discharges (PLEDs).

This case report refers to a patient with PLEDs whose EEGs did not change while on steady levels of phenytoin and phenobarbital, but showed a complete disappearance of these discharges when felbamate was used. This report may serve to remind EEG'ers and epileptologists that the acute use of this drug may be effective in dealing with PLEDs that are often difficult to eliminate. However, physicians must keep in mind the significant risks of using this medication.

Anticonvulsants↗
PubMed1993

p70 lupus autoantigen binds the enhancer of the T-cell receptor beta-chain gene.

The p70 (Ku) autoantigen has been described as a nonhistone nuclear protein recognized by antibodies from lupus patients. In our studies on the regulation of T-cell receptor (TCR) beta-chain gene expression we have identified the p70 lupus autoantigen as a DNA-binding protein that binds the enhancer of the TCR beta-chain gene. This enhancer is essential for expression of the TCR beta gene. The core TCR beta enhancer contains the E3 motif, which we show here is essential for enhancer activity. The protection of the E3 motif in T cells and the marked reduction in enhancer activity when the E3 motif is mutated underline its physiological importance in regulating beta enhancer activity. The p70 lupus autoantigen gene was identified by screening T-cell lambda gt11 libraries with an E3 probe. The gene encodes a protein which binds the E3 motif in a sequence-specific manner. The identification of a 70-kDa protein as a major E3-binding protein by UV crosslinking is consistent with the conclusion that the p70 lupus autoantigen binds the beta enhancer. Finally, we have shown that T-cell nuclear proteins which bind the E3 motif bear p70 (Ku) lupus autoantigenic determinants. Together these data suggest that the p70 autoantigen binds a critical motif in the beta enhancer and probably regulates TCR beta gene expression.

Animals↗
PubMed1993

Laser hazards in research laboratories.

Laser use is expanding rapidly in laboratories, where multiple use strategies of research are not often amenable to laser engineering safeguards employed in industry. We report on five cases of laser-associated incidents requiring medical follow-up from a single research institution, and present exposure circumstances from four other incidents. Eye injuries from direct and reflected beams resulted from open alignment procedures in the absence of appropriate eye protection. Nd:YAG lasers operated with doubling crystals appear to create a considerable risk. For several reasons, we believe the importance of laser-associated injuries are underestimated and the incidence underreported in the research setting. Although knowledge personnel are shown to suffer lapses in standard operating procedures, most incidents and all injuries involved relatively inexperienced personnel. We propose that research laser users be registered and required to undergo formal training in laser safety. Student researchers are a key target population. Collaborative implementation between the equipment supplier and research user will be required to achieve this widespread implementation of effective training.

Accidents, Occupational↗
PubMed1992

Mapping of an inducible element in the T cell receptor V beta 2 promoter.

The murine V beta 2 promoter was analyzed for an element regulating phorbol ester inducibility of the TCR beta chain gene. In transient expression analysis of 5' nested deleted fragments of the V beta 2 promoter, the TPA-inducible element mapped between -85 and -42. The -85 to -62 oligo conferred 12-0-tetradecanoylphorbol-13-acetate (TPA) inducibility to the heterologous TPA-uninducible thymidine kinase promoter. The -85 to -62 region contained an AP-1 site (-85 to -72) and inverted repeat motif (-72 to -62). The AP-1 site required the 3' flanking inverted repeat region for conferring optimal inducibility. In vitro transcribed and translated jun/fos heterodimers bind to the V beta 2 AP-1 motif with a 16-fold lower affinity as compared to the collagenase AP-1 motif. This explains the inability of the V beta 2 AP-1 motif to confer optimal TPA inducibility by itself. The affinity of jun/fos heterodimers for the V beta 2 AP-1 motif was not increased by the presence in cis of the inverted repeat motif. The 3' flanking inverted repeat binds the ets transactivator but not jun/fos heterodimers. The demonstrated cooperativity between the AP-1 and the 3' flanking sequence to confer TPA inducibility can thus be explained by the individual contributions of jun/fos and ets transactivators.

Animals↗
PubMed1990

Transscleral contact retinal photocoagulation with an 810-nm semiconductor diode laser.

Since the 810-nm wavelength has marked transmissibility through the sclera and absorption by melanin, it would be ideal for transscleral photocoagulation. We performed experiments to determine if consistent transscleral chorioretinal lesions could be produced in Dutch belted pigmented rabbits using the 810-nm laser, and if this modality caused less blood-retinal barrier disruption than retinal cryopexy of clinically equivalent treatment areas. The laser applications produced whitish to grayish-white retinal lesions when the surgeon, under direct visualization, used low powers and long durations (5 to 10 seconds), and controlled the treatment duration. Histopathologic evaluation of a lesion demonstrated an intact sclera overlying the chorioretinal lesion. Vitreous protein concentration, which was measured to assess blood-retinal barrier disruption, was significantly less in eyes treated with transscleral photocoagulation than in eyes treated with cryopexy of clinically equivalent treatment areas. We conclude that transscleral 810-nm laser treatment may be a viable clinical alternative to retinal cryopexy.

Animals↗
PubMed1989

Distribution of sodium-lithium countertransport and blood pressure in Caucasians five to eighty-nine years of age.

Case-control studies suggest that increased erythrocyte sodium-lithium countertransport may predict increased susceptibility to the development of essential hypertension. To characterize interindividual variation in sodium-lithium countertransport and its relation to blood pressure levels in the general population, we studied 1,475 Caucasians between 5 and 89 years of age (711 males and 764 females) ascertained through 266 households with children in the schools of Rochester, Minnesota. Individuals who were taking antihypertensive agents or combinations of estrogen and progesterone were not included in the sample. A third-order polynomial regression on age accounted for only a small fraction of variability in sodium-lithium countertransport (2.8% in males, p less than 0.001; 2.1% in females, p less than 0.01), whereas a fourth-order regression on age accounted for a large proportion of variability in systolic blood pressure (45.7% in males, p less than 0.001; 52.5% in females, p less than 0.001) and diastolic blood pressure (39.8% in males, p less than 0.001; 33.0% in females, p less than 0.001). Mean sodium-lithium countertransport was higher in males than females at all ages; but the rank order of male and female means for systolic and diastolic blood pressure was age dependent. Positively skewed distributions for age-, height-, and weight-adjusted sodium-lithium countertransport in male and female cohorts between 5-19.9, 20-49.9, and 50-89.9 years of age were explained significantly better by postulating a mixture of two partially overlapping sodium-lithium countertransport distributions rather than a single normal distribution (p less than 0.01). Among men in the 20-49.9-year-old cohort, adjusted sodium-lithium countertransport values in the upper distribution were associated with higher systolic and diastolic blood pressure (mean +/- SD) than values in the lower distribution (for systolic blood pressure: 115 +/- 11 vs. 111 +/- 11 mm Hg, p less than 0.07; for diastolic blood pressure: 71.2 +/- 8.0 vs. 68.4 +/- 8.6 mm Hg, p less than 0.08). Among females in the 50-89.9-year-old cohort, adjusted sodium-lithium countertransport values in the upper distribution were associated with significantly greater diastolic blood pressure than values in the lower distribution (77 +/- 10 vs. 70 +/- 9 mm Hg, p less than 0.03).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

Current review of exercise testing: application and interpretation.

Exercise testing has changed dramatically in scope over the past 50 years. While initially used to assess functional capacity, it is now also utilized to detect the presence and severity of coronary artery disease (CAD), to evaluate postmyocardial infarction patients at risk for future cardiac events, to screen certain asymptomatic populations for CAD, and to evaluate dysrhythmias, peripheral vascular disease, and lung disease. Dynamic exercise in continuous multistage protocols is most popularly employed because of the more easily measured workload. The safety of exercise testing, its contraindications and termination end points are summarized. The sensitivity of exercise testing ranges between 60 and 70% while specificity has been reported between 85 and 90%. Both sensitivity and specificity are enhanced through use of radionuclide exercise thallium imaging and ventricular angiography.

Coronary Disease↗
PubMed1982

Some guidelines in the treatment of urethral condylomata with carbon dioxide laser.

Some guidelines for the use of carbon dioxide laser treatment of urethral condylomata are presented. Carbon dioxide laser treatment was accomplished successfully in 22 patients with distal urethral and meatal condylomata. Of the patients 86.6 per cent responded to a single laser treatment and 13.4 per cent had evidence of persistence or new growth that required repeat therapy. Meatotomy was required in 4 patients for adequate exposure. This form of therapy appears to be safe for eradication of superficial mucosal lesions and can be used either as a first choice of treatment or as an adjunct in those patients not responding to other well known conventional treatment modalities.

Adolescent↗
PubMed1981

Rapid superpulse carbon dioxide laser treatment of urethral condylomata.

Complete eradication of urethral condylomata was accomplished by rapid super-pulsed carbon dioxide laser in 4 patients. Minimal postoperative discomfort and lack of stricture formation indicate that this new modality is an advantageous, fast, and secure method of management of intraurethral condylomata, and substantiated by our previous experimental reports.

Carbon Dioxide↗
PubMed1979

Acute dendrotoxic changes in the hippocampus of kainate treated rats.

Kainic acid (KA), a potent neuroexcitatory and neurotoxic analog of glutamate (Glu), induces a widespread pattern of brain damage when administered subcutaneously to adult rats. The hippocampus is among the brain regions most consistently and severely damaged. Here we describe acute swelling of certain spines and branchlets of dendrites as the first detectable sign of KA neurotoxic changes in the hippocampus. These swellings conform to a laminar pattern suggesting selective toxic interaction of KA at specific levels of the dendritic trees of hippocampal pyramidal and dentate granule neurons. The frequency and severity of involvement of each type of hippocampal neuron at each level of its dendritic tree was roughly estimated and neuronal types were ranked from the most to least extensively involved (CA3 greater than CA4 greater than CA1 greater than CA2 greater than dentate granules). The same rank order has been described for the vulnerability of these neurons to acute destruction following intraventricular KA administration. Because the pattern of dendritic dilatations observed corresponds well with the pattern of termination of putative glutamergic inputs to the hippocampus, we interpret the findings as being consistent with the hypothesis that the toxic effects of KA are mediated through glutamergic excitatory receptors. We propose that the sensitivity of a given neuron to the neurodestructive action of KA may be determined by the percentage of its dendritic surface occupied by Glu receptors. We suspect that most, if not all, hippocampal neurons receive some glutamergic input and, therefore, are sensitive to KA. That CA3 pyramids are substantially more sensitive than dentate granules may signify that the former receive many more Glu terminals than the latter, an assumption quite consistent with our observation that focal dendritic swellings were both more densely and more widely distributed over the dendritic surfaces of the former than the latter.

Animals↗