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Biomedical subjects

D Mueller

Publications and source records attributed to D Mueller.

At least 19 recordsLinked to original sources

Cocaine-induced conditioned place preference: reinstatement by priming injections of cocaine after extinction.

To explore the way in which drugs act to reinstate drug-seeking behavior, we studied drug-induced reinstatement of a cocaine-induced conditioned place preference (CPP). In a series of experiments, we studied the establishment, maintenance, extinction and reinstatement of a cocaine-induced CPP in a three-chamber 'unbiased' apparatus. Groups of rats were given four 20-min pairings of one chamber with cocaine (10.0 mg/kg, i.p.) and four of the other with saline on alternate days. In 15-min tests for CPP, drug-free rats were placed in the center choice chamber with access to the entire apparatus. Experiments were designed to study the expression of the CPP, the maintenance of the CPP in tests given at 2, 4, and 6 weeks after training, and the reinstatement of the CPP by cocaine (5.0 mg/kg) after extinction by 12 repeated tests in the non-drugged state, and after extinction by pairing each chamber, on alternate days, with saline on four occasions. Robust CPPs were obtained that endured for 4 weeks and were maintained for up to 6 weeks when tests were given at 2-week intervals. Both extinction procedures led to the loss of the CPP that was in turn reinstated by priming injections of cocaine. These results indicate that a cocaine-induced CPP, once developed, endures for several weeks, and is maintained by occasional testing even in the absence of additional drug experience. The fact that the CPP is easily reinstated when testing is preceded by a priming injection of cocaine suggests that drugs may induce relapse by renewing the incentive value of drug-associated cues.

Animals↗

Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking.

The alpha-2 adrenergic receptor agonists, clonidine, lofexidine and guanabenz, blocked stress- but not cocaine-induced reinstatement of cocaine seeking at doses that suppressed footshock-induced release of noradrenaline in prefrontal cortex and amygdala. Rats were trained to self-administer cocaine (0.5 mg/kg/infusion, i.v; 10-12 days) and, after a drug-free period (7-13 days), were returned to the self-administration chambers for daily extinction and reinstatement test sessions. Both intermittent footshock (15 min, 0.6 mA) and cocaine priming (20 mg/kg, i.p.) reinstated extinguished drug seeking. Pretreatment with either clonidine (20, or 40 microg/kg, i.p.) or lofexidine (50, 100, 150, or 200 microg/kg, i.p.) attenuated footshock- but not cocaine-induced reinstatement of cocaine seeking. Guanabenz (640 microg/kg, i.p.), an alpha-2 agonist with low affinity for imidazoline type-1 receptors, also attenuated footshock- but not cocaine-induced reinstatement of cocaine seeking. The results point to an important role for NE systems in the effects of footshock on relapse to cocaine seeking.

Adrenergic alpha-2 Receptor Agonists↗

Pleural fibrosis associated with dihydroergocryptine treatment.

OBJECTIVES: This is the first report of a histologically confirmed pleuropulmonary fibrosis (PPF) associated with the dopamine agonist dihydroergocryptine. CASE REPORT: A 67-year-old male patient with Parkinson's disease developed a severe restrictive pulmonary disorder with dyspnea and nonproductive cough after a daily intake of 45 mg dihydroergocryptine for 2 years. After changing the dopamine agonist to the non-ergoline substance pramipexole, marked improvement of the clinical symptoms of PPF occurred, while radiological signs showed only a moderate decrease. CONCLUSION: PPF is a possibly fatal complication. Chest X-rays and specific pneumological diagnostics should be done if typical symptoms or nonspecific signs of PPF occur while a patient is on treatment with an ergoline dopamine agonist.

Aged↗

The second stalk of the yeast ATP synthase complex: identification of subunits showing cross-links with known positions of subunit 4 (subunit b).

A component of the stator of the yeast ATP synthase (subunit 4 or b) showed many cross-linked products with the homobifunctional reagent dithiobis[succinimidyl propionate], which reacts with the amino group of lysine residues. The positions in subunit 4 that were involved in the cross-linkings were determined by using cysteine-generated mutants constructed by site-directed mutagenesis of ATP4. Cross-linking experiments with the heterobifunctional reagent p-azidophenacyl bromide, which has a spacer arm of 9 A, were performed with mitochondria and crude Triton X-100 extracts containing the solubilized enzyme. Substitution of lysine residues by cysteine residues in the hydrophilic C-terminal part of subunit 4 allowed cross-links with subunit h from C98 and with subunit d from C141, C143, and C151. OSCP was cross-linked from C174 and C209. A cross-linked product, 4+beta, was also obtained from C174. It is concluded that the C-terminus of subunit 4 is distant from the membrane surface and close to F(1) and OSCP. The N-terminal part of subunit 4 is close to subunit g, as demonstrated by the identification of a cross-linked product involving subunit g and the cysteine residues 7 or 14 of subunit 4.

ATP Synthetase Complexes↗

Analysis of TCR beta chains in Lewis rats with experimental allergic encephalomyelitis. II. Vbeta8.2+ T cells with limited CDR3 N region additions derive from the adult thymus.

Immunization of Lewis (LEW) rats with guinea pig myelin basic protein (MBP) induces a population of encephalitogenic CD4 T cells having specificity for the dominant immunogenic peptide of MBP, 68-86. The TCR beta chains of these disease-causing T cells show three distinct features: they are almost exclusively Vbeta8.2, they use AspSer as the first two amino acid residues of the third complementarity-determining region (CDR3) and these junctional region sequences show few if any non-germline N-region nucleotide additions. This last feature raises the possibility that these autoimmune T cell precursors derive from TCR gene rearrangements occurring during early, perinatal ontogeny, a period when the enzyme terminal deoxynucleotidyl transferase (TdT), responsible for N region additions, is not expressed. An alternative possibility is that these features of the TCR of MBP 68-86-reactive T cells are dictated by considerations of antigen selection throughout ontogeny both in the thymus and in the periphery--ie., that such beta chains are conformationally the most appropriate for triggering by an epitope of 68-86 complexed to class II RT1.BI MHC molecules. We show here that active experimental allergic encephalomyelitis, while delayed in onset, occurs in heavily irradiated animals, but not in the absence of a thymus, a finding indicating that this autoimmune disease is caused by a T cell subpopulation derived from the post-irradiation adult thymus. These disease-causing T cells are heavily Vbeta8.2+, CDR3 AspSer+ and use few N region additions. We conclude that T cells with these TCR beta chain features can be generated in the adult thymus and most likely reflect requirements imposed by antigen selection.

Animals↗

Hybrid fiber coax networks: a viable option for telemedicine.

Cable companies have improved their networks to the degree that they are viable alternatives to currently deployed networks. A detailed look at these cable networks shows them to be superior in bandwidth (capacity), speed, flexibility, and ubiquity. The services that can be provided by these networks are ideal to numerous advanced applications, including telemedicine.

Computer Communication Networks↗

Respiratory muscle reserve in rats during heavy exercise.

The extent to which the respiratory pump muscles limit maximal aerobic capacity in quadrupeds is not entirely clear. To examine the effect of reduced respiratory muscle reserve on aerobic capacity, whole body peak oxygen consumption (VO2 peak) was measured in healthy Sprague-Dawley rats before and after Sham, unilateral, or bilateral hemidiaphragm denervation (Dnv) surgery. VO2 peak was determined by using a graded treadmill running test. Hemidiaphragm paralysis was verified after testing by recording the absence of electromyographic activity during inspiration. Before surgery, VO2 peak averaged 86, 87, and 92 ml . kg-1 . min-1 for the Sham, unilateral, and bilateral Dnv groups, respectively. Two weeks after surgery, there was no significant change in VO2 peak for either the Sham or unilateral Dnv group. However, VO2 peak decreased approximately 19% in the bilateral Dnv group 2 wk after surgery. These findings strongly suggest that the pulmonary system in rats is designed such that during heavy exercise, the remaining respiratory pump muscles are able to compensate for the loss of one hemidiaphragm, but not of both.

Animals↗

Short-term continuous infusion thrombolytic therapy for occluded central nervous venous dialysis catheters.

The necessity of maintaining a strict schedule of dialysis treatments in patients with chronic renal failure dictates that occluded access catheters be restored to full function in a timely and cost-effective manner. The records of 22 consecutive patients receiving outpatient treatment for occluded hemodialysis catheters at Osteopathic Medical Center of Texas were reviewed by the authors. Each patient had 100,000 units of urokinase in 50 ml normal saline instilled over 30 minutes through the occluded catheter. In most instances the dose was divided to allow 35 ml to the proximal port and 15 ml to the distal port. The maximum sustained blood flow rate on dialysis was recorded for each patient. The mean maximum sustained blood flow rate improved from 150 ml/min +/- 79 ml to 261 ml/min +/- 62 ml. Following infusion, improvement was obtained in 19 of 22 patients, with 14 catheters delivering blood flow greater than 250 ml/min. The total cost per treatment was $316. No adverse events were experienced. Thrombotic occlusion of extended use hemodialysis catheters can be rapidly and safely relieved in a cost-effective manner with little delay in scheduled dialysis treatments.

Catheterization, Central Venous↗

T cells from BB-DP rats show a unique cytokine mRNA profile associated with the IDDM1 susceptibility gene, Lyp.

Diabetes prone biobreeding rats display several abnormalities in T cell numbers, T cell function and T cell surface phenotype which are associated with the onset of spontaneous disease. One of the most pronounced abnormalities in these animals is a marked T cell lymphopenia which is evident in both CD4+ and CD8+ peripheral T cell subsets. To gain a better understanding as to the nature of T cell responses in these animals, we have utilized RT-PCR to analyze the cytokine mRNA profiles of mitogen activated peripheral T cells derived from lymphopenic and non-lymphopenic animals. Our results suggest that inheritance of the lymphopenia gene, Lyp, is associated with a unique cytokine profile most similar to that previously described for mouse medullary thymocytes. In addition, cell surface staining of peripheral T cells from diabetes prone animals revealed a high frequency of Thyl+ cells, which is characteristic of both thymocytes and recent thymic emigrants. Following thymectomy, T cell responsiveness to a number of different stimuli is greatly reduced on a cell for cell basis as is the absolute number of surviving T cells. Taken collectively, our results suggest that the majority of the peripheral T cell pool in these diabetic prone rats consists of short lived, recent thymic emigrants which most likely also contain the effector cells required for initiation of diabetes.

Animals↗

Mesenteric defects as a cause of intestinal volvulus without malrotation and as the possible primary etiology of intestinal atresia.

Mesenteric defects can lead to intestinal volvulus even when the midgut is normally rotated. There are two types of mesenteric defects: basilar, in which the entire base of the mesentery is involved, and segmental, in which only an isolated portion of the mesentery is affected. These defects can present at any age, and the clinical symptoms depend on the extent of the disease and the amount of intestine involved in the volvulus. In the newborn, the basilar defects have clinical signs and symptoms similar to those of midgut volvulus secondary to malrotation. Similar to midgut volvulus secondary to malrotation, this is a surgical emergency. In older patients, basilar defects can be misdiagnosed because of the normal placement of the ligament of Treitz and because of failure to consider mesenteric defects as a possible cause. The treatment for basilar mesenteric defects is intestinal fixation. Intestinal volvulus secondary to segmental defects always presents as intestinal obstruction. In the newborn, these lesions may be indistinguishable from intestinal atresia. Older children present with intestinal obstruction of an unknown cause. Resection of the affected intestine is the treatment for segmental mesenteric defects. Intestinal mesenteric abnormalities as a cause of intestinal atresia unifies under one etiology all the lesions observed in intestinal atresia. Although this theory does not rule out other causes of intestinal atresia, intestinal mesenteric defects may be the primary condition under which intestinal atresia occurs.

Child↗

Nutrition interventions for intensive therapy in the Diabetes Control and Complications Trial. The DCCT Research Group.

As part of an intensive treatment regimen that had as its goal achieving and maintaining blood glucose levels in the normal range in individuals with insulin-dependent diabetes mellitus, dietitians in the Diabetes Control and Complications Trial implemented varying nutrition intervention strategies to counsel patients to attain normoglycemia. Dietary management encompassed recommendations on altering insulin dosages for varying food intake. Nutrition intervention was tailored to best meet a participant's life-style, motivation, ability to grasp information, diet history, and specific intensive insulin therapy. Dietitians were integral participants in the team management of individuals in the intensive treatment group. Selected nutrition interventions--Healthy Food Choices, exchange systems, carbohydrate counting, and total available glucose--and behavior management approaches were coupled with intensive insulin therapy. Case presentations illustrate each nutrition intervention in the attainment of normoglycemia.

Adult↗