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Biomedical subjects

S D Russell

Publications and source records attributed to S D Russell.

At least 19 recordsLinked to original sources

The benefit of implementing a heart failure disease management program.

BACKGROUND: To handle the increasing complexity of congestive heart failure (CHF) care, several new models for the care of patients with CHF have been developed to replace traditional strategies. We undertook this study to evaluate the potential benefit of implementing a CHF disease management program at a tertiary care center, particularly in terms of beta-blocker use and cost to the health care system. METHODS: After reviewing the literature regarding therapies and management strategies for patients with CHF, we developed the Duke Heart Failure Program. All enrolled patients had 1 of the following: recent CHF hospitalization, ejection fraction less than 20%, or symptoms consistent with New York Heart Association class III or IV. We compared preenrollment and postenrollment medication use and resource utilization. RESULTS: We enrolled 117 patients from July 1998 to April 1999. Mean enrollment time was 4.7 months. beta-Blocker use and dose significantly increased (52% vs 76% for beta-blocker, P<.01; 6% vs 13% of target dose, P<.01). The hospitalization rate decreased (1.5 vs 0 hospitalizations per patient-year, P<.01), while the number of clinic visits increased (4.3 vs 9.8 clinic visits per patient-year, P<.01). The Duke University Health System saved a median of $8571 per patient-year. CONCLUSIONS: Implementing a CHF disease management program was associated with improved CHF medication dosing and with decreased hospitalization for patients with CHF. A CHF disease management program is an effective method for a health care system to care for patients with CHF.

Adrenergic beta-Antagonists↗

Evaluation of early postoperative results after bicaval versus standard cardiac transplantation and review of the literature.

OBJECTIVE: Previous studies have been inconsistent in defining a clinical benefit to the bicaval cardiac transplantation technique relative to the standard technique, and many major centers have not adopted this newer approach. The purpose of this study was to determine whether clinically significant benefits support utilization of the bicaval technique. METHODS: Sixty-eight consecutive adult patients undergoing a standard cardiac transplant were compared with 75 consecutive patients who underwent the bicaval technique during the period from 1991 to 1999. Etiology, recipient sex, recipient age, donor age, and pulmonary vascular resistance were similar between the two groups. RESULTS: Cardiac index at 24 hours after operation was increased for the bicaval group relative to the standard group (3.15 +/- 0.7 vs 2.7 +/- 0.5 L/min/m(2), P <. 05). Inotropic requirements were significantly less, and there was significantly less tricuspid regurgitation in the bicaval group relative to the standard group. In addition, the bicaval group more frequently had a nonpaced normal sinus rhythm at 24 hours after operation (73.9% vs 50.7% [standard group], P =.025) and had fewer postoperative arrhythmias (29.3% vs 47.7% [standard group], P <.01). Finally, although mortality was similar for the two groups, length of postoperative hospitalization was longer for the standard group relative to the bicaval group (12.1 +/- 11 vs 20.4 +/- 12 days, P <. 001). Review of the literature identified reduced tricuspid regurgitation and improved rhythm as consistent benefits of the bicaval technique. CONCLUSION: This review demonstrates a clinical benefit during the early postoperative period with bicaval cardiac transplantation (relative to standard) and encourages further utilization of this technique.

Adult↗

Lack of effect of increased inspired oxygen concentrations on maximal exercise capacity or ventilation in stable heart failure.

Recent uncontrolled studies have suggested improved maximal exercise capacity and decreased exercise ventilation in heart failure after administration of increased inspired oxygen concentrations. To study the responses further, 16 patients performed staged, symptom-limited cycle ergometry with humidified 21% and 60% inspired oxygen concentrations using a randomized, double-blind, crossover study design. Serial measurements of minute ventilation, heart rate, blood pressure, leg blood flow, and arterial and venous lactate and oxygen content were obtained. Exercise time did not change between the 2 tests (595 +/- 179 seconds and 602 +/- 181 seconds for 21% and 60% oxygen concentrations, respectively). Similarly, measurements of the ventilatory response to exercise and of leg blood flow were not different between the 2 oxygen concentrations. Although hemoglobin oxygen saturation increased from 96.7 +/- 2.1% to 97.9 +/- 1.5% at rest, at both rest and maximal exercise there was no statistically significant difference in arterial or venous oxygen content. This study failed to demonstrate any physiologic or functional benefit from the administration of increased oxygen concentrations to patients with stable heart failure.

Adult↗

Aerobic exercise training can reverse age-related peripheral circulatory changes in healthy older men.

BACKGROUND: The age-related decline in maximal oxygen consumption is attenuated by habitual aerobic exercise. However, the relative effects of training on central and peripheral responses to exercise in older subjects are not known. The present study assessed the contribution of central and peripheral responses to the age-associated decline in peak oxygen consumption and compared the effect of exercise training in healthy older and younger subjects. METHODS AND RESULTS: Ten older and 13 younger men underwent invasive measurement of central and peripheral cardiovascular responses during an upright, staged cycle exercise test before and after a 3-month period of exercise training with cycle ergometry. At baseline, cardiac output and AV oxygen difference during exercise were significantly lower in older subjects. With training, the older and younger groups increased maximal oxygen consumption by 17.8% and 20.2%, respectively. Peak cardiac output was unchanged in both groups. Systemic AV oxygen difference increased 14.4% in the older group and 14.3% in the younger group and accounted for changes in peak oxygen consumption. Peak leg blood flow increased by 50% in older subjects, whereas the younger group showed no significant change. There was no change in peak leg oxygen extraction in the older group, but in the younger group, leg AV oxygen difference increased by 15.4%. CONCLUSIONS: These findings suggest that the age-related decline in maximal oxygen consumption results from a reversible deconditioning effect on the distribution of cardiac output to exercising muscle and an age-related reduction in cardiac output reserve.

Adult↗

Localization of the Ca(2+)-binding protein, Bra r 1, in anthers and pollen tubes.

Calcium plays an essential role during pollen development and pollen tube growth, and several Ca(2+)-binding proteins are expressed in anthers. We have previously reported that Brassica pollen allergens encoded by Bra r 1 and Bra r 2 show sequence similarities to Ca(2+)-binding proteins [Toriyama et al. (1995) Plant Mol. Biol. 29: 1157]. Herein, we report that both genes are expressed in the diploid tapetum and haploid microspores, as detected by in situ RNA hybridization. Immunoblot analysis revealed that Bra r 1 and Bra r 2 were accumulated in anthers during pollen development. When pollen grains were suspended in an aqueous solution, both proteins were mainly detected in the pollen extracellular fraction, indicating that Bra r 1 and Bra r 2 are released from the pollen upon hydration. Localization of Bra r 1 was further investigated in sections of anthers and pollen tubes. Bra r 1 was detected in the tapetum, microspores and pollen grains. In longitudinal sections of cross-pollinated pistils. Bra r 1 was detected throughout pollen tubes elongating in transmitting-tissue. These findings suggest that Bra r 1 may be involved in pollen-pistil interaction and pollen tube growth.

Allergens↗

Exertional dyspnea in heart failure: a symptom unrelated to pulmonary function at rest or during exercise. Duke University Clinical Cardiology Studies (DUCCS) Exercise Group.

BACKGROUND: Exertional dyspnea is a common symptom in patients with heart failure, and the mechanisms responsible for the symptom are unknown. The purpose of this study was to identify factors responsible for the symptom of exertional dyspnea in patients with heart failure. METHODS: Resting pulmonary-function tests and maximal cardiopulmonary exercise tests were performed in 71 patients with New York Heart Association functional class II-IV symptoms (mean ejection fraction 30.6%; mean age, 68 years). RESULTS: The severity of dyspnea at peak exercise, which patients rated as 3 to 10 on a 1 to 10 severity scale, did not correlate with rest or exercise hemodynamic, spirometric, or metabolic variables, including peak oxygen uptake (VO2), minute ventilation (Ve), and respiratory rate, or with derived variables including Ve/VO2, Ve/VCO2, and the dyspnea index (Ve/maximum voluntary ventilation). Additionally, these variables did not differ between patients who reported limitation of exercise by dyspnea and those who were limited by fatigue. CONCLUSIONS: The symptom of exertional dyspnea in patients with heart failure is not determined by abnormalities in ventilatory function or demand.

Aged↗

Improvement in the mechanical efficiency of walking: an explanation for the "placebo effect" seen during repeated exercise testing of patients with heart failure. Duke University Clinical Cardiology Studies (DUCCS) Exercise Group.

To determine the mechanism responsible for the "placebo effect" seen during serial exercise testing of patients with heart failure, we examined metabolic variables for 81 patients who underwent five baseline exercise tests as part of a multicenter drug trial. The patients were 50 men and 31 women with a mean ejection fraction of 30.1% and a mean age of 69 years. From test 1 to 2, the exercise time increased from 419 +/- 140 to 462 +/- 130 seconds before it reached a plateau over the next three tests. Metabolic measurements at test 1 and test 3 revealed no change in peak oxygen consumption ( 1119 +/- 376 to 1105 +/- 346 ml/min). Maximum heart rate, systolic blood pressure, ventilation, and respiratory exchange ratio also were unchanged. The onset of the anaerobic threshold was delayed from 211 +/- 81 to 238 +/- 93 seconds, but there was no change in oxygen consumption at the anaerobic threshold (810 +/- 222 to 795 +/- 220 ml/min). At a predetermined submaximal level, oxygen consumption, ventilation, and respiratory exchange ratio all decreased to a statistically significant degree. These results indicate that a rapid increase in the mechanical efficiency of walking contributes to the placebo effect among patients with heart failure during serial exercise testing and is independent of changes in conditioning or motivation.

Aged↗

Isolation and collection of two populations of viable sperm cells from the pollen of Plumbago zeylanica.

A protocol is described for individually collecting two populations of sperm cells, Svn and Sua, from pollen of Plumbago zeylanica. Pollen grains were burst in 10 mM MOPS buffer containing 0.8 M mannitol (pH 4.6). Paired sperm cells released from pollen were separated using a microinjector. Svn and Sua were then collected individually with a microinjector, based upon known size differences. Collected sperm cells were washed with isolation medium and transferred to liquid nitrogen until use. Fluorochromatic reaction (FCR) test of isolated sperm cells showed a positive reaction, indicating that the isolated sperm cells are viable; most of the sperm cells retain viability for at least 2 h.

Cell Separation↗

Spray-freezing freeze substitution (SFFS) of cell suspensions for improved preservation of ultrastructure.

Some unicellular organisms present challenges to chemical fixations that lead to common, yet obvious, artifacts. These can be avoided in entirety by adapting spray-freezing technology to ultrarapidly freeze specimens for freeze substitution. To freeze specimens, concentrated suspensions of cells ranging in diameter from 0.5-30 pm were sprayed with an airbrush at 140-200 kPa (1.05-1.5 torr; 20.3-29.0 psi) into a nylon mesh transfer basket submerged in liquid propane. After freezing, the mesh basket containing the frozen sample was lifted out of the chamber, drained and transferred through several anhydrous acetone rinses at 188 K (-85 degrees C). Freeze substitution was conducted in 1% tannic acid/1% anhydrous glutaraldehyde in acetone at 188 K (-85 degrees C), followed by 1% OsO4/acetone at 277 K (4 degrees C). Freeze substitution was facilitated using a shaking table to provide gentle mixing of the substitution medium on dry ice. High quality freezing was observed in 70% of spray-frozen dinoflagellate cells and in 95% of spray-frozen cyanobacterial cells. These could be infiltrated and observed directly; however, overall ultrastructural appearance and membrane contrast were improved when the freeze-substituted cells were rehydrated and post-fixed in aqueous OSO4, then dehydrated and embedded in either Spurr's or Epon resin. Ultrastructural preservation using this ultrarapid freezing method provided specimens that were consistently superior to those obtainable in even the best comparable chemical fixations.

Animals↗

Isolation of viable sperm cells from tobacco (Nicotiana tabacum).

Viable sperm cells of Nicotiana tabacum were isolated by the semi-vivo technique. After pollination, excised styles were floated, cut end immersed, in a solution of 15% sucrose with 0.01% boric acid and 0.03% Ca(NO3)2 at 27 degrees C in a growth chamber until pollen tubes emerged. After sperm cells were formed (at least 8 h after pollination) tubes were immersed in a 9% mannitol solution. In this solution, sperm cells are nearly ellipsoidal and retain viability for over 6 h.

Cell Survival↗

Pseudo-von Willebrand disease: a mutation in the platelet glycoprotein Ib alpha gene associated with a hyperactive surface receptor.

Pseudo (platelet-type)-von Willebrand disease is an autosomal dominant bleeding disorder caused by the hyperfunction of a receptor on the platelet surface. The abnormal receptor, glycoprotein Ib, displays increased affinity for its ligand, von Willebrand factor. Four members (normal mother/affected father/two affected daughters) of a family with pseudo-von Willebrand disease were studied to determine the molecular genetic basis for their congenital platelet defect. Segments of the platelet glycoprotein Ib alpha gene were amplified by means of the polymerase chain reaction, cloned, and sequenced. A point mutation (A to G, codon 239) was found in segments from the affected individuals but not from the normal. The mutation results in a single amino acid substitution (valine-mutant for methionine-normal) at residue 239 within the Ib alpha binding site for von Willebrand factor. Both the mutant and the normal sequence were found in affected individuals, suggesting a heterozygous state. Amplified DNA from family members and from 58 normal individuals was analyzed by allele-specific oligonucleotide hybridization. Only the normal sequence was found in the mother and the normal individuals, whereas both the normal and the mutant alleles were found in the affected family members. The described mutation is associated with the pseudo-von Willebrand disease phenotype seen in this kindred. The resultant single amino acid substitution in glycoprotein Ib alpha relates to increased receptor function and to excessive binding of von Willebrand factor to the platelet surface.

Base Sequence↗

Two types of neonatal-to-adult fast myosin heavy chain transitions in rat hindlimb muscle fibers.

Adult fast myosin heavy chain (MHC) isoforms are accumulated in fibers of rat hindlimb skeletal muscle which initially contain neonatal MHC at birth. The specific factors controlling these transitions are not known, but in rat and mouse muscle tissue the transition between the neonatal and adult fast MHC proteins does not appear to require continuous innervation. We have reinvestigated the role of innervation in the neonatal-to-adult fast MHC protein and mRNA transitions that occur in developing rat fast-twitch muscles using immunohistochemistry and S1 nuclease mapping. We find that neonatal MHC-containing developing fibers exhibit different responses after denervation at birth regarding the disappearance of neonatal MHC and the accumulation of adult fast MHC isoforms. Immunohistochemistry shows that one fiber population loses neonatal MHC and accumulates adult fast IIB (or possibly IIX) MHC over a period of 2-3 weeks, whereas in the other population neonatal MHC does not decrease nor does the adult fast IIA isoform accumulate to high levels. The results of S1 analysis of mRNAs show that the levels of neonatal MHC mRNA do not decrease in muscles denervated at birth. We also demonstrate that in young adult rats this mRNA is reexpressed in denervated or paralyzed muscles. Since the appearance of IIB mRNA has been previously shown to be nerve-independent (S.D. Russell, N. Cambon, B. Nadal-Ginard, and R.G. Whalen, 1988, J. Biol. Chem. 263, 6370-6374), these results suggest that fibers containing neonatal MHC in rat hindlimb muscles at birth are already differentiated (i.e., preprogrammed) to accumulate either the adult fast IIA or IIB MHC isoforms and that the neonatal-to-adult MHC transitions occurring in these two fiber populations are controlled by different mechanisms.

Animals↗

Cytoskeletal organisation and modification during pollen tube arrival, gamete delivery and fertilisation in Plumbago zeylanica.

The cytoskeletal organisation of the isolated embryo sac and egg cells of Plumbago zeylanica was examined before, during and after pollen tube penetration into the embryo sac to determine the potential involvement of microtubules and actin filaments in fertilisation. Material was singly and triply stained using Hoechst 33258 to localise DNA, fluorescein isothiocyanate (FITC)-labelled anti-alpha-tubulin to detect microtubules and rhodamine-phalloidin to visualise F-actin. Microtubules in the unfertilised egg cell are longitudinally aligned in the micropylar and mid-lateral areas, aggregating into bundles near the filiform apparatus. In the perinuclear cytoplasm of the egg cell, microtubules become more or less randomly aligned. F-actin bundles form a longitudinally aligned mesh in the chalazal cytoplasm of the egg cell. In the central cell, microtubules and F-actin are distributed along transvacuolar strands and are also evident in the perinuclear region and at the periphery of the cell. During pollen tube penetration, sparse microtubule bundles near the pathway of the pollen tube may form an apparent microtubular 'conduit' surrounding the male gametes at the delivery site. Actin aggregates become organised near the pathway of the pollen tube and at the delivery site of the sperm cells. Subsequently, actin aggregates form a 'corona' structure in the intercellular region between the egg and central cell where gametic fusion occurs. The corona may have a role in maintaining the close proximity of the egg and central cell and helping the two sperm cells move and bind to their target cells. The cytoskeleton may also be involved in causing the two nuclei of the egg and central cell to approach one another at the site of gametic fusion and transporting the two sperm nuclei into alignment with their respective female nucleus. The cytoskeleton is reorganised during early embryogenesis.

Cytoskeleton↗

Three-dimensional ultrastructure of generative cell mitosis in the pollen tube of Nicotiana tabacum.

Generative cell mitosis was examined in stylar-grown pollen tubes of Nicotiana tabacum using serial sectioning, transmission electron microscopy and computer-assisted reconstruction. Before mitosis, the generative cell has a cage-like organization of cytoplasmic microtubules. The mitotic spindle forms when the cytoplasmic microtubules reduce in frequency and kinetochore microtubules form in an area delimited by sheets of endoplasmic reticulum; no preprophase band of microtubules is observed. At metaphase, 21 pairs of kinetochores are distributed unevenly along the length and depth of the cell without the formation of a strictly planar metaphase plate. The metaphase spindle is highly oblique, with diffuse subpoles distributed along the sides of the cell, colocalized with endoplasmic reticulum lamellae. From these dispersed subpoles the kinetochore bundles emanate, closely associated with tubular endoplasmic reticulum. Anaphase consists of three principal processes: convergence of diffused mitotic poles, shortening of the kinetochore bundles, and the elongation of the spindle by an average of nearly 50%. At mid-anaphase, a phragmoplast begins to form, mainly by the assembly of new microtubules at the equatorial area, which form as a cluster of numerous short microtubules. Cytokinesis is essentially conventional, with centrifugal cell plate formation. Cytoplasmic microtubules are restored in the newly formed "brother" sperm cells in a distribution similar to that in the generative cell but fewer in number.

Endoplasmic Reticulum↗

A possible regulatory role for conserved promoter motifs in an adult-specific muscle myosin gene from mouse.

The mouse gene encoding a myosin heavy chain (MHC) protein expressed in type IIB fibers of adult skeletal muscle has been cloned and its promoter isolated. A number of DNA sequence motifs are found within the first 2.5 kilobases of the promoter which are similar to motifs present in the promoters of other muscle-specific genes. One sequence located at approximately -940 base pairs corresponds to the motif called MEF1 which has been shown in other muscle genes to bind the myogenic regulatory factors of which MyoD is one example. The MEF1 site of this adult IIB MHC promoter does indeed bind MyoD although this factor is normally thought to be involved in early muscle cell differentiation. The IIB MHC promoter also has several motifs located in the first 200 base pairs which are strikingly conserved between this mouse gene and several chicken skeletal MHC genes. Of these evolutionarily conserved sequences, two motifs rich in A and T residues appear to be major contributors to the muscle-specific transcriptional activity of the mouse IIB MHC promoter when transfected into quail myogenic and non-myogenic cells. These observations suggest an important functional role for these AT-rich sequence motifs in the regulation of genes of the MHC family.

Animals↗

Evolutionarily conserved promoter motifs and enhancer organization in the mouse gene encoding the IIB myosin heavy chain isoform expressed in adult fast skeletal muscle.

We have isolated the mouse gene for the MHC isoform expressed in adult type IIB (fast-contracting, glycolytic) skeletal muscle fibers, and determined the DNA sequence of the promoter region. This sequence represents the first example of a promoter for a gene encoding an adult-specific isoform of a mammalian skeletal MHC. The proximal 200 bp of the promoter contains several sequence motifs which are identical or very similar to homologous motifs found in the promoters of a family of chicken skeletal MHC genes. Of these, two novel AT-rich sequences may be important for regulation of the promoter. A second feature of the mouse IIB MHC promoter sequence concerns a number of sequence motifs located at ca. -1,000 bp which are organized in a similar fashion in the IIB MHC promoter and a homologous region of promoter of the mouse muscle creatine kinase gene.

Animals↗

A method for improved resolution for fluorescence microscopy using plastic-embedded material subjected to resin extraction.

A protocol is given that uses NaOH, benzene, acetone and methanol to extract epoxy resins from semithin sections. Such sections appear superior to paraffin or unsectioned materials for fluorescence microscopic observations. Use of ultrarapid films (e.g., Kodak T-Max P3200) at ISO 3200 minimizes fading without use of antifading agents and without introducing unacceptable photographic grain size.

Epoxy Resins↗