Biomedical subjects

T Burkholder

Publications and source records attributed to T Burkholder.

7 recordsLinked to original sources

PubMed2006

Conversion of the severe to the moderate disease phenotype with donor leukocyte microchimerism in canine leukocyte adhesion deficiency.

Leukocyte adhesion deficiency-1 (LAD-1), a genetic immunodeficiency disease characterized by life-threatening bacterial infections, results from the defective adherence and migration of leukocytes due to mutations in the leukocyte integrin CD18 molecule. Canine LAD (CLAD) represents the canine homologue of the severe phenotype of LAD-1 in children. In previous studies we demonstrated that non-myeloablative stem cell transplantation from matched littermates resulted in mixed donor-host chimerism and reversal of the disease phenotype in CLAD. In this study, we describe two CLAD dogs with less than 2% donor leukocyte chimerism following non-myeloablative transplant. Both dogs are alive more than 24 months after transplant with an attenuated CLAD phenotype resembling the moderate deficiency phenotype of LAD. The improvement in the CLAD phenotype with very low levels of donor CD18(+) leukocytes correlated with the preferential egress of the CD18(+) neutrophils into extravascular sites. The clinical response with very low levels of donor CD18(+) leukocytes in CLAD supports using this model for testing gene therapy strategies since the low levels of gene-corrected hematopoietic cells expected with hematopoietic gene therapy would likely have a therapeutic effect in CLAD.

Animals↗

PubMed1998

Sarcomere number adaptation after retinaculum transection in adult mice.

Skeletal muscle has been shown to adjust serial sarcomere number in response to chronic static length changes. However, the adaptive responses to alterations in the dynamic environment are less well defined. The adaptations of the adult mouse tibialis anterior (TA) muscle to altered length and excursion were investigated by surgical transection of the flexor retinaculum. TA moment arm and muscle excursion increased by 38±7 % (mean ± s.e.m.) and fully extended (plantarflexed) muscle length was decreased by 8 % after flexor retinaculum transection. In spite of the significant shortening of the muscle in full plantar- and dorsiflexion, serial sarcomere number decreased by 10±1 % after 2 weeks of recovery. Gait analysis of these transected animals revealed a 14±3 % decrease in dorsiflexion angular velocity after transection. The decrease in angular velocity was less than the increase in moment arm and, as a result, muscle velocity was calculated to increase by 20±4 %. These data suggested that the muscle adapted in response to the underlying change in length, irrespective of the altered excursion or velocity.

Journal Article↗

PubMed1996

Initial stability of a modular uncemented, porous-coated femoral stem: a mechanical study.

A versatile modular hip system was used to evaluate the initial stability of a cementless femoral stem in anatomically consistent composite bones. Four implant bone configurations of varying proximal and distal fit/fill were tested. The implanted femurs were tested on an Instron 1331 materials testing machine in neutral loading and flexion loading; both translational micromotions and rotations of the implant relative to the bone were recorded on all three axes of motion, accounting for all 6 degrees of freedom of joint motion. Implants were then sectioned, and both endosteal canal fit and intramedullary canal fill were measured. Results indicate that (1) loading the implant in flexion by out-of-plane forces significantly increases both relative translation and rotation at the interface, (2) increasing the proximal fit reduces implant rotation about its longitudinal axis in flexion loading and (3) increasing the distal canal fit and fill increases prosthesis rotation about its longitudinal axis in flexion loading. These results indicate that the femoral stem is more unstable in out-of-plane loading, such as during stair climbing, and that increasing the proximal fit may enhance the initial rotational stability of an uncemented femoral stem.

Biomechanical Phenomena↗

PubMed1993

A genetic comparison of behavioral actions of ethanol and nicotine in the mirrored chamber.

Human alcoholics are almost invariably heavy users of tobacco, perhaps because both ethanol and nicotine may have anxiolytic activity. However, studies in humans have not uniformly detected anxiolytic effects because significant individual differences in anxiolytic actions of these agents seem to exist. One factor that seems to contribute to these individual differences is tolerance to ethanol. Individuals who are more sensitive to depressant actions of alcohol seem to show anxiolytic actions more readily. Consequently, we examined the relative sensitivities of the ethanol-sensitive (to the anesthetic actions of ethanol) long-sleep (LS) and ethanol-resistant short-sleep (SS) mouse lines to diazepam, ethanol, nicotine, and ethanol-nicotine combinations in the mirrored chamber test. This test measures approach-conflict behavior. Ethanol and nicotine evoked changes in mirrored chamber activities that resembled those elicited by diazepam. These effects were seen at doses that did not markedly affect locomotor activity, thereby suggesting that these changes in behavior represent anxiolytic actions. The LS-SS mice did not differ in sensitivity to diazepam, but the SS were more uniformly responsive to the other drugs. Only the SS showed clear evidence for interactions between ethanol and nicotine. If the changes in mirrored chamber behavior elicited by ethanol, nicotine, and combinations of the two drugs occur because of anxiety reduction, it seems that the SS mouse line is more responsive to anxiolytic actions of these drugs.

Animals↗

PubMed1992

Gross and microscopic anatomy of the vagal innervation of the rat heart.

Intrinsic cardiac ganglia and their vagal innervation are described from gross and microscopic dissections and functional studies in the anesthetized, open-chest, adult rat. Dissecting microscope sketches of the ventral and dorsal aspects of the rat heart provide gross descriptions of the anatomical course of the vagal cardiac nerves. Histological sectioning of adipose tissue packets surrounding the terminal endings of vagal branches distributed to the roots of the great cardiac vessels (aorta, pulmonary artery, precaval veins) revealed clusters of autonomic ganglia. These packets or "fat pads" were located: (1) along the dorsal surface of the right precava and extending medially toward the aortic root, (2) deep to the aortic arch, (3) in the angle between the root of the left precava and the pulmonary artery on the superior-dorsal surface of the left atrium, and (4) in the rostro-dorsal interatrial septum. Vagal distributions of small terminal branches were traced to each of these pads, which contained numerous autonomic ganglia. Electrical excitation of right or left cervical vagus elicited varying degrees of sinus slowing, slowing of A-V conduction, and suppression in atrial contractile force. Very small quantities (0.5 mg in 10 microliters saline) of the ganglionic blocking agent, hexamethonium (C6) were injected selectively into a single fat pad, followed by repetition of right or left vagal stimulation, with careful analysis of changes in heart rate (paced and unpaced), A-V conduction, and contractile force.

Adipose Tissue↗

PubMed1990

Hands-on laboratory experience in teaching-learning physiology.

Reactivation of several model 5 (vacuum tube) Grass polygraphs for active hands-on laboratory experiments by small student groups, in contrast to demonstrations and pretaped illustrations of physiological principles, resulted in remarkable rejuvenation of interest and excitement for learning in premed and introductory science classes at Taylor University. Accurate and perceptive observations were performed on the students themselves, each recording his own electrocardiogram, for example, as well as direct recordings from the pithed frog, the turtle heart, the anesthetized rabbit, and noninvasive recordings from students subjects during exercise. In the latter experiment, sweat recruitment patterns were recorded initially on the lower extremities, followed by successive appearances on thigh and abdomen and with final occurrence on the upper extremities and face. To our knowledge, this is the first report of such recruitment patterns during exercise. Results of actual student participation, with organized group discussions, convince us that laboratory teaching remains the premiere mechanism for teaching and learning organ-system physiology.

Animals↗

PubMedDate not supplied

Baroreflex responses to the stress of severe hemorrhage in the rat.

In two groups of anesthetized (sodium pentobarbital), mature Sprague-Dawley rats, 1) aged 2 years and weighing 300-400 grams, 2) aged 6 months weighing 200-300 grams, baroreflex-induced circulatory responses to pressor (graded doses phenylephrine) and depressor (graded doses nitroglycerine) agents were compared to those occurring during progressive hemorrhage in the same animals. Graded withdrawals of blood from the femoral artery elicited progressive hypotension accompanied by bradycardia rather than expected tachycardia. Graded doses of phenylephrine (2.5 ug to 40 ug bolus, via femoral vein) regularly induced elevations in arterial blood pressure with associated reflex bradycardia. Similarly graded doses of nitroglycerine induced a marked decline in arterial blood pressure, without expected tachycardia. As hypotension became more severe (during hemorrhage), atrioventricular conduction slowed and A-V block developed, resulting in statistically greater slowing in ventricular than in atrial excitation and contractile cycles. Heart failure during hemorrhage in the rat is characterized sequentially by severe bradycardia, depressed atrial contractile force, impaired conduction and A-V block, terminating in ventricular, atrial, and finally, in pacemaker failure. Baroreceptor reflexes were blunted or even absent in both young and old animals during induced hypotension.

Animals↗