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Biomedical subjects

D E Wood

Publications and source records attributed to D E Wood.

At least 19 recordsLinked to original sources
PubMed1999

Caspase-dependent activation of calpain during drug-induced apoptosis.

We have previously demonstrated that calpain is responsible for the cleavage of Bax, a proapoptotic protein, during drug-induced apoptosis of HL-60 cells (Wood, D. E., Thomas, A., Devi, L. A., Berman, Y., Beavis, R. C., Reed, J. C., and Newcomb, E. W. (1998) Oncogene 17, 1069-1078). Here we show the sequential activation of caspases and calpain during drug-induced apoptosis of HL-60 cells. Time course experiments using the topoisomerase I inhibitor 9-amino-20(S)-camptothecin revealed that cleavage of caspase-3 substrates poly(ADP-ribose) polymerase (PARP) and the retinoblastoma protein as well as DNA fragmentation occurred several hours before calpain activation and Bax cleavage. Pretreatment with the calpain inhibitor calpeptin blocked calpain activation and Bax cleavage but did not inhibit PARP cleavage, DNA fragmentation, or 9-amino-20(S)-camptothecin-induced morphological changes and cell death. Pretreatment with the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk) inhibited PARP cleavage, DNA fragmentation, calpain activation, and Bax cleavage and increased cell survival by 40%. Interestingly, Z-VAD-fmk-treated cells died in a caspase- and calpain-independent manner that appeared morphologically distinct from apoptosis. Our results suggest that excessive or uncontrolled calpain activity may play a role downstream of and distinct from caspases in the degradation phase of apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Bax cleavage is mediated by calpain during drug-induced apoptosis.

The anti-apoptotic molecule Bcl-2 is located in the mitochondrial and endoplasmic reticulum membranes as well as the nuclear envelope. Although its location has not been as rigorously defined, the pro-apoptotic molecule Bax appears to be mainly a cytosolic protein which translocates to the mitochondria upon induction of apoptosis. Here we identify a protease activity in mitochondria-enriched membrane fractions from HL-60 cells capable of cleaving Bax which is absent from the cytosolic fraction. Bax protease activity is blocked in vitro by cysteine protease inhibitors including E-64 which distinguishes it from all known caspases and granzyme B, both of which are involved in apoptosis. Protease activity is also blocked by inhibitors against the calcium-activated neutral cysteine endopeptidase calpain. Partial purification of the Bax protease activity from HL-60 cell membrane fractions by column chromatography revealed that a calpain-like activity was the protease responsible for Bax cleavage. In addition, purified calpain enzymes cleaved Bax in a calcium-dependent manner. Pretreatment of HL-60 cells with the specific calpain inhibitor calpeptin effectively blocked both drug-induced Bax cleavage and calpain activation, but not PARP cleavage or cell death. These results suggest that calpains and caspases are activated during drug-induced apoptosis and that calpains, along with caspases, may be involved in modulating cell death by acting selectively on cellular substrates.

Alanine↗
PubMed1998

Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3.

Chemokines are essential mediators of normal leukocyte trafficking as well as of leukocyte recruitment during inflammation. We describe here a novel non-ELR CXC chemokine identified through sequence analysis of cDNAs derived from cytokine-activated primary human astrocytes. This novel chemokine, referred to as I-TAC (interferon-inducible T cell alpha chemoattractant), is regulated by interferon (IFN) and has potent chemoattractant activity for interleukin (IL)-2-activated T cells, but not for freshly isolated unstimulated T cells, neutrophils, or monocytes. I-TAC interacts selectively with CXCR3, which is the receptor for two other IFN-inducible chemokines, the IFN-gamma-inducible 10-kD protein (IP-10) and IFN-gamma- induced human monokine (HuMig), but with a significantly higher affinity. In addition, higher potency and efficacy of I-TAC over IP-10 and HuMig is demonstrated by transient mobilization of intracellular calcium as well as chemotactic migration in both activated T cells and transfected cell lines expressing CXCR3. Stimulation of astrocytes with IFN-gamma and IL-1 together results in an approximately 400,000-fold increase in I-TAC mRNA expression, whereas stimulating monocytes with either of the cytokines alone or in combination results in only a 100-fold increase in the level of I-TAC transcript. Moderate expression is also observed in pancreas, lung, thymus, and spleen. The high level of expression in IFN- and IL-1-stimulated astrocytes suggests that I-TAC could be a major chemoattractant for effector T cells involved in the pathophysiology of neuroinflammatory disorders, although I-TAC may also play a role in the migration of activated T cells during IFN-dominated immune responses.

Amino Acid Sequence↗
PubMed1998

Percutaneous placement of tracheal T tube.

Tracheal T tubes provide effective palliation of unresectable benign and malignant tracheal obstruction, but placement may be difficult when previous operation, radiation, or tumor limits surgical exposure of the cervical trachea. Percutaneous placement using commercially available percutaneous tracheostomy kits may provide an alternative approach in these cases.

Female↗
PubMed1998

Lung-volume reduction surgery for diffuse emphysema: radiologic assessment of changes in thoracic dimensions.

Patients with severe, diffuse emphysema may be candidates for pneumectomy (lung-volume reduction surgery, LVRS) to improve lung and respiratory muscle function. To identify candidates who might benefit from this surgery, it is necessary to understand how lung volumes and respiratory function are effected. In this article, the authors demonstrate a significant difference in lung size on chest radiographs obtained before and after surgery. Thirty-five of 71 consecutive patients undergoing LVRS had both preoperative and postoperative chest radiographs and pulmonary function tests available for retrospective review. Preoperative and postoperative measurements of lung height, transthoracic diameters, mediastinal width, heart size, diaphragmatic arc, and intercostal spaces were compared using paired t-tests. Radiographic measurements where also correlated with changes in lung volumes as measured by pulmonary function tests. Lung heights (right, left, mean lateral) and coronal diameter at the aortic arch were reduced after surgery (all p < 0.05). Forced vital capacity, forced expiratory volume in 1 second (FEV1), and vital capacity increased, and total lung capacity and residual volume decreased after surgery (all p < 0.05). Left lung height showed a significant correlation (p = 0.025) with FEV1; all other correlations between radiographic changes and pulmonary function test changes were not significant. The explanation for improved lung function in patients after LVRS is not completely clear and is probably multifactorial. Radiologic alterations reflect anatomic changes caused by surgery and support the theory that modifications of chest wall configuration occur and are likely responsible, in part, for improved symptomatology and respiratory function.

Adult↗
PubMed1998

Lung volume reduction surgery has variable effects on blood gases in patients with emphysema.

Most studies of bilateral lung volume reduction surgery (LVRS) report increases in arterial oxygenation (PaO2). Some suggest this results from an increased alveolar ventilation, but others imply that ventilation-perfusion heterogeneity is reduced. We measured arterial blood gases (ABGs) on air before and 3 mo following LVRS in 46 patients (61% of eligible patients), estimate the difference between alveolar and arterial O2 (AaPO2), and correlated the changes observed with preoperative ABGs, and with pre-and postoperative pulmonary function. The mean +/- SD change in PaO2 and AaPO2 was +3 +/- 10 mm Hg (p = 0.058) and +1 +/- 11 mm Hg (p = NS), respectively, and the range of change was large (-17 to +29 mm Hg and -24 to +23 mm Hg, respectively). The mean change in PaCO2 was -3 +/- 5 mm Hg (p < 0.05) and ranged from -11 to +5 mm Hg. Changes in PaO2 and AaPO2 were poorly correlated with changes in PaCO2 or with pre- or postoperative pulmonary function. Although some patients had a marked improvement in ABGs following LVRS, almost as many deteriorated. On average, only minimal effects were seen. Although mean alveolar ventilation improved somewhat, the effect of LVRS on PaO2 primarily resulted from alterations in ventilation-perfusion heterogeneity.

Aged↗
PubMed1998

Randomized, placebo-controlled, multicenter trial of granulocyte-macrophage colony-stimulating factor as infection prophylaxis in oncologic surgery. Leukine Surgical Prophylaxis Research Group.

PURPOSE: Postoperative infections are a frequent source of preventable morbidity and mortality in the oncologic population. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent modulator of immune effector cells in vitro and in vivo. This study was conducted to determine whether GM-CSF, when administered perioperatively, could reduce the incidence of surgical infections in cancer patients. METHODS: This was a prospective, randomized, placebo-controlled, multicenter study. Cancer patients at high risk of infectious surgical morbidity were randomized to receive GM-CSF 125 microg/m2 per day or placebo subcutaneously for 8 days beginning 3 days preoperatively. Routine antibiotic prophylaxis was administered to all patients. RESULTS: Three hundred ninety-nine patients were enrolled, with 198 randomized to receive GM-CSF. Twenty-one percent of patients experienced infections during the first 2 weeks postoperatively, and there was no difference in infection rate between the study groups. The most common sites of infection were respiratory tract (53%) and surgical wound (25%). The duration of operation and American Society of Anesthesiology (ASA) physical status classification were the most significant predictors of infection in multivariate analysis. GM-CSF was well tolerated and was not associated with fever. CONCLUSION: The eligibility criteria for this study were successful at defining a patient subgroup at high risk for postoperative infections. At an immunomodulatory dose of 125 microg/m2 per day, GM-CSF was safe and well tolerated, but did not reduce the incidence of postoperative infections in this high-risk oncologic population. Infectious morbidity in surgical oncology remains an important subject for continued clinical investigation.

Adult↗
PubMed1997

Tracheobronchial resection and reconstruction.

OBJECTIVE: To assess the indications and results of airway resection and how frequently airway reconstructive options changed proposed therapy. DESIGN: A retrospective survey of patients undergoing major airway resection. SETTING: University of Washington-affiliated hospitals, Seattle, May 1992 through December 1996. PATIENTS: Fifty consecutive patients with resectable benign and malignant tracheal or main bronchial disease undergoing tracheobronchial resections. INTERVENTIONS: Patients underwent major airway resection as follows: tracheal or laryngotracheal resection, 23 patients; carinal resection, 6; and bronchial sleeve resection with or without pulmonary resection, 21. Indications for surgery were non-small cell lung cancer in 19 patients, primary airway tumor in 12, thyroid carcinoma in 1, and tracheal or bronchial stenosis in 18. MAIN OUTCOME MEASURES: Change in prereferral planned therapy from palliative to definitive or to pulmonary-sparing procedure, morbidity and mortality, relief of symptoms, and survival. RESULTS: Mortality was 0%, and morbidity, 32% (15/50). Airway reconstruction changed the proposed therapy in 42 patients (84%). Functional results were good to excellent in 17 (94%) of 18 patients with benign disease. Patients with malignant disease had a 1-year survival of 93% (27/29) and a 2-year survival of 67% (12/18). CONCLUSIONS: Airway resection and reconstruction provide reliable relief of benign and malignant tracheobronchial disease with minimal morbidity and mortality. Airway reconstruction frequently changed prereferral planned therapy and provided definitive and parenchymal-sparing procedures to patients with complex airway lesions.

Adolescent↗
PubMed1997

Internal mammary silicone lymphadenopathy mimicking recurrent breast cancer.

This case describes a unique complication of silicone breast implantation that is previously undocumented. Internal mammary silicone lymphadenopathy mimicking breast cancer recurrence represents an important new clinical entity. The diagnosis and management of this clinical enigma are challenging. In our patient, videothoracoscopy proved to be minimally invasive and allowed complete resection of the entire chain of pathologic nodes. Explantation of the silicone prostheses and complete capsulectomy are indicated. Light microscopy alone can suggest the diagnosis of silicone lymphadenopathy. Infrared spectral analysis can be a helpful adjunct to allow an unequivocal diagnosis.

Biopsy↗
PubMed1997

Changes in breathing and ventilatory muscle recruitment patterns induced by lung volume reduction surgery.

Patients with chronic obstructive pulmonary disease have abnormal breathing and ventilatory muscle recruitment patterns at rest and during exercise, and these alterations may contribute to the limited exercise capacity seen in this disease. Lung volume reduction surgery (LVRS), a recently described treatment for emphysema, is reported to improve exercise performance. We studied the breathing and ventilatory muscle recruitment (VMR) patterns in eight patients with severe chronic obstructive lung disease (median FEV1 = 0.79 L, range 0.46 to 1.13 L) by measuring esophageal and gastric pressure measurements as well as tidal volumes (VT), respiratory rates (f), inspiratory (TI) and expiratory (TE) times, and watts at rest and during maximal exercise, before and 3 mo after lung volume reduction surgery. Maximal exercise capacity increased a median of 49% (median increase 17 watts, range 6 to 44 watts, p < 0.05) and maximal minute ventilation (VEmax) increased by a median of 22% (median increase 6.5 L/min, range 3 to 25 L/min, p < 0.05). At isowatt exercise after surgery, VT increased 0.31 L (range 0.07 to 0.69 L) and f decreased four breaths/min (range +0.5 to -15 breaths/min). Dyspnea scores as measured by a visual analog scale (VAS) decreased significantly at rest and at peak exercise after surgery. End-expiratory esophageal (Pes) and gastric (Pga) pressures at rest and at isowatt exercise decreased. A rightward shift in the slope of the Pes versus Pga plot was also observed suggesting increased use of the diaphragm after surgery. Our data indicate that LVRS improves the mechanics of breathing both at rest and during exercise.

Adult↗
PubMed1997

Lung volume reduction surgery improves maximal O2 consumption, maximal minute ventilation, O2 pulse, and dead space-to-tidal volume ratio during leg cycle ergometry.

Early experience suggests that lung volume reduction surgery improves exercise tolerance as measured by the 6-min walk distance in patients with emphysema. To identify the physiologic mechanism(s) by which lung volume reduction surgery improved exercise, we performed progressive cardiopulmonary exercise testing, including rest and peak exercise blood gas determinations, on 21 consecutive patients before and 3 mo after lung volume reduction surgery. Maximal work (median, range, % change) increased 17.5 watts (-13 to +44 watts, 46%, p < 0.05), maximal oxygen consumption increased 0.16 L/min (-0.17 to +0.48, 25%, p < 0.05), maximal ventilation increased 6.6 L/min (-7 to +26 L/min, 27%, p < 0.05), and the dead space/tidal volume ratio at peak exercise decreased 0.07 (-0.22 to +0.09, 12%, p < 0.05), exclusively as a result of an increase in the tidal volume. After lung volume reduction surgery heart rate decreased at the point of isowatt exercise, from 115 to 111 beats/min (p < 0.05). No difference was observed in the other physiologic variables measured at isowatt exercise. In 13 patients exercised while breathing room air, the alveolar-to-arterial O2 difference increased, and the arterial O2 tension decreased from rest to peak exercise both before and after the operation, but significant changes in this response were not observed after surgery. The primary problem limiting exercise performance in these patients was the limited ventilatory capacity as 16 and 13 of the 21 subjects developed acute respiratory acidemia at peak exercise before and after surgery, respectively. Lung volume reduction surgery in patients with severe emphysema improved maximal ventilation, thereby improving maximal exercise performance.

Exercise Test↗
PubMed1997

The effects of common peroneal stimulation on the effort and speed of walking: a randomized controlled trial with chronic hemiplegic patients.

OBJECTIVE: To measure the effect of the Odstock Dropped Foot Stimulator (ODFS), a common peroneal stimulator, on the effort and speed of walking. DESIGN: A randomized controlled trial. SUBJECTS: Hemiplegic patients who had suffered a single stroke at least six months prior to the start of the trial whose walking was impaired by a drop-foot. INTERVENTIONS: The treatment, functional electrical stimulation (FES) group, used the stimulator and received a course of physiotherapy; the control group received physiotherapy alone. MAIN OUTCOME MEASURES: Changes in walking speed measured over 10 m and the effort of walking measured by physiological cost index (PCI). RESULTS: Thirty-two subjects completed the trial, 16 in the FES group and 16 in the control group. Mean increase in walking speed between the beginning and end of the trial was 20.5% in the FES group (when the stimulator was used), and 5.2% in the control group. Improvement was also measured in PCI with a reduction of 24.9% in the FES group (when the stimulator was used) and 1% in the control group. No improvement in these parameters was measured in the FES group when the stimulator was not used. CONCLUSION: Walking was statistically significantly improved when the ODFS was worn but no 'carry-over' was measured. Physiotherapy alone, in this group of subjects with established stroke, did not improve walking.

Aged↗
PubMed1997

Lung transplantation. Part II. Postoperative management and results.

In part I of this 2-part article on lung transplantation (Western Journal of Medicine 1996; 165:355-363), we reviewed the current indications and operative techniques of the procedure. In part II, we describe the postoperative management and results of lung transplantation. We also discuss current controversies, such as the use of marginal donors, living-related transplants, marginal recipients, and single-versus double-lung transplantation for emphysema or pulmonary hypertension.

Bronchial Diseases↗
PubMed1997

Successful lung transplantation in spite of cystic fibrosis-associated liver disease: a case series.

Lung transplantation has recently offered hope for prolonged survival in patients with cystic fibrosis. Patients with cystic fibrosis have a 7% prevalence of associated liver disease and portal hypertension. These patients have been previously excluded from consideration for lung transplantation. The natural history of cystic fibrosis-associated liver disease suggests a benign and protracted course in most cases. At the University of Washington, 14 of 53 patients (26%) have undergone lung transplantation for cystic fibrosis-related respiratory failure. We report the outcome of double lung transplantation in four of these 14 patients who also had cystic fibrosis-associated liver disease and portal hypertension, all of whom were symptom free from their liver disease. All four patients are alive and well without complications 4 to 31 months after transplantation. We conclude that the presence of cystic fibrosis-associated liver disease with portal hypertension, in the setting of good synthetic function (albumin > 3.0 gm/L and normal prothrombin time), normal serum bilirubin, minimal varices, without ascites or encephalopathy, should not be an absolute contraindication to lung transplantation. We recommend that other transplantation centers also include this patient population in consideration for lung transplantation.

Adult↗
PubMed1996

Proctolinlike immunoreactivity and identified neurosecretory cells as putative substrates for modulation of courtship display behavior in the blue crab, Callinectes sapidus.

Pheromonally stimulated courtship display (CD) behavior in male blue crabs (Callinectes sapidus) is characterized by rhythmic waving of the fifth legs. The waving of the fifth legs is modulated by proctolin in freely moving crabs and in reduced preparations. To begin to identify an anatomical substrate for CD behavior we have localized putative proctolinergic cells and described the morphology of neurosecretory neurons known to oscillate during pheromonal stimulation of reduced preparations. Proctolin-induced CD occurs with developmental and seasonal dependence. Male crabs altered hormonally by eyestalk ligation spontaneously produce CD behavior. We have localized proctolinlike immunoreactivity (PIR) in the central nervous system (CNS) and compared this immunoreactivity across sexes, developmental stage, eyestalk ligation, and seasonal conditions to determine whether or not expression of PIR is correlated with CD behavior. PIR was found in most areas of the CNS. Clusters of PIR-positive cells were found in the sinus gland and eyestalk ganglia, olfactory neuropil with associated cell bodies, and in a large cell cluster in the subesophageal region of the ventral nerve cord. Three pairs of cell bodies in different cell body groups in the brains of adult crabs stained positively for PIR but did not stain in the youngest juvenile animals. Comparison of PIR distribution with toluidine blue studies of the ventral nerve cord indicated a high likelihood that cells in the PIR-positive cluster of the subesophageal ganglia were also members of the cluster of neurons identified as oscillatory neurosecretory neurons.

Animals↗
PubMed1996

Distribution of dopamine-like immunoreactivity suggests a role for dopamine in the courtship display behavior of the blue crab, Callinectes sapidus.

Injection of dopamine initiates a posture in the blue crab, Callinectes sapidus, identical to courtship display behavior of the male crab. The threshold for proctolin-induced rhythmic components of courtship display is lowered in preparations when dopamine is co-applied with proctolin. To elucidate the anatomical substrate of this behavior, immunocytochemistry was used to map dopamine-immunoreactive neurons. Courtship display is sex-specific, and dependent on the hormonal, developmental, and seasonal state of the animal. We compared the distribution of dopamine-like immunoreactivity between adults and juveniles of both sexes across seasons, with hormonal alteration, and with the distribution of proctolin-like immunoreactivity. Dopamine-like immunoreactivity was found throughout the nervous system in identical patterns between the sexes and hormonal states. Differences were found between juveniles and adults that are not obviously correlated with the development of behavior. Two areas of staining were of interest: neurites that longitudinally traverse and terminate in the posterior ventral nerve cord, and a neuron in the esophageal ganglion that has projections to the pericardial organ. The results do not suggest that proctolin-like and dopamine-like immunoreactivity co-localize, but in the subesophageal ganglion there was a region of close proximity.

Animals↗
PubMed1996

Tracheostomy.

Tracheostomy is a common procedure used by a wide variety of surgeons. Complications after tracheostomy have been used as a rationale for prolonging a translaryngeal intubation. Understanding the pathogenesis of tracheostomy complications combined with meticulous surgical and perioperative management avoids the majority of complications. The remaining complications are readily managed and should not provide a rationale for denying intubated patients the benefits of tracheostomy.

Humans↗