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Biomedical subjects

C A Smith

Publications and source records attributed to C A Smith.

At least 217 records · Page 12Linked to original sources
PubMed1996

Breathing during exercise in dogs--passive or active?

The activation patterns of the costal and crural diaphragm and transversus abdominis muscle and their relationship to esophageal pressure (Pes) changes and footplant were examined in five chronically instrumented dogs which breathed at high frequencies at rest and during exercise. In two tracheostomized dogs, measurements were made of diaphragmatic length via sonomicrometry and of airflow and were related to diaphragmatic electrical activity and Pes. Dogs exhibited either a high-frequency breathing pattern, characterized by Pes changes occurring at 2-6 Hz, or a mixed-frequency breathing pattern, characterized by low-amplitude Pes oscillations (4-6 Hz) superimposed on a slower breathing rate of 0.5-1 Hz. Regardless of the type of breathing pattern elected or of the various breathing-to-stride frequency ratios observed during exercise, decreases in Pes were always associated with phasic electromyographic activity of the costal and crural diaphragm and with phasic diaphragmatic muscle shortening. The transversus abdominis electromyographic activity coincided with an increasing Pes from peak negative values in resting dogs and exhibited both an expiratory and a locomotory modulation during exercise. Although footplant may have contributed to some airflow generation when dogs utilized the mixed-frequency pattern, these data demonstrate that the movement of air into and out of the lungs in stationary or exercising dogs requires phasic neural activation of the diaphragm and other respiratory muscles.

Animals↗
PubMed1996

Preventing cardiovascular disease through community-based risk reduction: the Bootheel Heart Health Project.

OBJECTIVES: The purpose of this study was to determine whether a community-based risk reduction project affected behavioral risk factors for cardiovascular disease. METHODS: Community-based activities (e.g., exercise groups, healthy cooking demonstrations, blood pressure and cholesterol screenings, and cardiovascular disease education) were conducted in six southeastern Missouri counties. Evaluation involved population-based, cross-sectional samples of adult residents of the state and the intervention region. Weighted prevalence estimates were calculated for self-reported physical inactivity, cigarette smoking, consumption of fruits and vegetables, overweight, and cholesterol screening. RESULTS: Physical inactivity decreased within the intervention region, that is, in communities where heart health coalitions were developed and among respondents who were aware of these coalitions. In addition, the prevalence rates for reports of cholesterol screening within the past 2 years were higher for respondents in areas with coalitions and among persons who were aware of the coalitions. CONCLUSIONS: Even with modest resources, community-based interventions show promise in reducing self-reported risk for cardiovascular disease within a relatively brief period.

Adolescent↗
PubMed1996

Adoptive immunotherapy for Epstein-Barr virus-related lymphoma.

Epstein-Barr virus (EBV) causes opportunistic B cell lymphomas in patients whose cellular immunity is compromised. We have been investigating whether infusions of donor-derived, EBV-specific cytotoxic T cells can prevent and/or treat EBV-related lymphoproliferative disease in children receiving T cell-depleted bone marrow from HLA-matched, unrelated or HLA-mismatched, related donors. In this review, we discuss the rationale for this therapeutic approach, describe our experiences with the regimen thus far, and consider some future directions in immunotherapy.

Child↗
PubMed1996

Renal cell carcinoma in children: the Detroit experience.

PURPOSE: We analyzed the presentation, treatment and survival of 6 children with renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the pathological and hospital records of 6 children diagnosed with renal cell carcinoma at Children's Hospital of Michigan (5) and Henry Ford Hospital (1) from 1980 to 1995. RESULTS: The most common presenting complaints were flank pain (50%) and a palpable abdominal mass (50%), while gross hematuria was present in only 1 patient (16%). No patient had the classic triad of flank pain, hematuria and palpable mass. Only 1 patient had localized disease (stage II), while 5 of the 6 presented with stage III or IV disease. While followup is limited, all patients with stage III disease are without evidence of recurrence at a mean 38.5 months and 1 of 2 with stage IV disease is without evidence of disease at 22 months. CONCLUSIONS: Although renal cell carcinoma in childhood often presents at an advanced stage, the prognosis for those with isolated regional lymph node involvement appears to be encouraging.

Adolescent↗
PubMed1996

Fetal therapy for obstructive uropathy: diagnosis specific outcomes [corrected].

PURPOSE: Attempts to evaluate prenatal vesico-amniotic shunt therapy have been hampered by inconsistencies in patient selection, treatment and termination criteria, and outcomes measurement. Outcomes have generally been measured against those of patients with postnatally detected posterior urethral valves. The purpose of this report was to evaluate the influence of the underlying diagnosis on the clinical outcomes of fetuses undergoing evaluation for prenatal intervention for suspected obstructive uropathy. Furthermore, specific outcomes diagnosis was compared to the published natural history of these disorders to begin to establish a basis for measuring the efficacy of prenatal intervention. MATERIALS AND METHODS: We retrospectively reviewed the outcomes of 55 consecutive patients undergoing prenatal evaluation using structured outcome measures stratified by specific diagnoses to provide a comparison to the reported natural history for each underlying disorder. RESULTS: All fetuses had early onset of oligohydramnios/anhydramnios representing the worst end of the spectrum. Compared to postnatally diagnosed patients, prenatally diagnosed patients with posterior urethral valves had lower survival (60 versus 93%) but similar postnatal renal failure rates (31 versus 33%). Cases of prenatally detected but untreated posterior urethral valves had a 44% renal failure rate. In fetuses with the prune-belly syndrome survival (86 versus 72%) and renal function rates (17 versus 27% renal failure) compared favorably with the postnatal experience, although 55% of the cases had significant urethral obstruction. All patients with urethral atresia died. CONCLUSIONS: The underlying etiology of obstruction appears to have a marked influence on clinical outcome independently of treatment. When evaluated by specific diagnosis, intervention appears to provide outcomes in these high risk fetuses that are comparable to those for disease detected postnatally. Interpretation of series that do not distinguish cases by onset, severity and specific pathological process is problematic. Greater standardization of patient selection, treatment and outcome measurement, including the use of specific diagnoses, is necessary to allow an accurate assessment of the efficacy and proper role of fetal therapy.

Anastomosis, Surgical↗
PubMed1996

CD30 ligand expression in nonmalignant and Hodgkin's disease-involved lymphoid tissues.

The CD30 ligand (CD30L) is a type II transmembrane glycoprotein of the tumor necrosis factor ligand superfamily. Recent cloning of CD30L has enabled studies to explore its function and tissue distribution. For instance, recombinant CD30L has been shown to co-stimulate T cells and to act as mitogen for Hodgkin's disease (HD)-derived cell lines. The counter-receptor for CD30L, ie, CD30, is a type I cytokine receptor that is highly expressed by activated T cells, Hodgkin and Reed-Sternberg (H-RS) cells, and anaplastic large cell lymphoma cells. In the present study, recombinant membrane-bound and soluble human CD30L were instrumental to raise a monoclonal antibody (M80) recognizing membrane-bound CD30L on transfected and native cells. With this reagent, a panel of cultured lymphoma-derived cell lines as well as primary normal, reactive, and HD-involved lymphoid tissues were examined for expression of CD30L by immunostaining and flow cytometry. In reactive lymphnodes and tonsils, CD30L was expressed by a small subset of lymphoid cells, histiocytes, and granulocytes. Higher levels of CD30L expression were noted in HD lesions among bystander cells; ie, T cells and granulocytes that surrounded H-RS cells. Native CD30L displayed at the cell surface was functionally active as shown by the ability of fixed granulocytes to interact with CD30+ cell lines. Moreover, CD30L was detectable, although to a lower staining intensity, in primary H-RS cells of all HD tissues investigated regardless of the histological subtype and the phenotype of H-RS cells (ie, CD30+/CD40+ versus CD30-/CD40+). Co-expression of CD30 and CD30L that was seen on H-RS cells of all, except the CD30- nodular lymphocyte predominant, subtypes of HD may point to the use of this pair of molecules in paracrine and/or autocrine mitogenic cell interactions. Monoclonal antibody M80 may thus represent a useful tool for studying CD30L expression on cultured cell lines and primary cells from normal, reactive, and malignant tissues.

Antibodies, Monoclonal↗
PubMed1996

Sleep-induced breathing instability. University of Wisconsin-Madison Sleep and respiration Research Group.

We present a view of the neuromechanical regulation of breathing and causes of breathing instability during sleep. First, we would expect transient increases in upper airway resistance to be a major cause of transient hypopnea. This occurs in sleep because a hypotonic upper airway is more susceptible to narrowing and because the immediate excitatory increase in respiratory motor output in response to increased loads is absent in non-REM sleep. Secondly, sleep predisposes to an increased occurrence of ventilatory "overshoots", in part because abruptly changing sleep states cause transient changes in upper airway resistance and in the gain of the respiratory controller. Following these ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include: a) hypocapnia-if transient, will inhibit carotid chemoreceptors and cause hypopnea, but if prolonged will inhibit medullary chemoreceptors and cause apnea; b) a persistent inhibitory effect from lung stretch; c) baroreceptor stimulation, from a transient rise in systemic blood pressure immediately following termination of apnea or hypopnea may partially suppress the accompanying hyperpnea; d) depression of central respiratory motor output via prolonged brain hypoxia. Once apneas are initiated, reinitiation of inspiration is delayed even though excitatory stimuli have risen well above their apneic thresholds, and these prolonged apneas are commonly accompanied by tonic EMG activation of expiratory muscles of the chest wall and upper airway.

Adult↗
PubMed1996

Long-term intravesical oxybutynin chloride therapy in children with myelodysplasia.

PURPOSE: We evaluated the clinical use of long-term intravesical oxybutynin chloride in the treatment of neurogenic bladder dysfunction in children with myelodysplasia who could not tolerate oral anticholinergics. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients recommended for intravesical oxybutynin chloride therapy. A total of 12 girls and 18 boys 1 to 17 years old was recruited for study. Oxybutynin chloride (5 mg.) was instilled 2 times daily and pretreatment cystograms were compared to followup urodynamic studies. Duration of therapy was 2 to 26 months (mean 13, median 12). RESULTS: Mean total capacity plus or minus standard deviation increased from 209 +/- 103 to 282 +/- 148 ml. (p < 0.01), mean safe capacity increased from 157 +/- 105 to 234 +/- 147 ml. (p < 0.01) and mean age adjusted safe capacity increased from 76 +/- 36 to 115 +/- 62%. Of the 29 patients who were incontinent 3 (10%) achieved continence and 19 (65%) reported a decreased use of sanitary pads. None of the patients had systemic side effects related to intravesical treatment. CONCLUSIONS: We believe that intravesical oxybutynin chloride is a viable treatment option for patients with myelodysplasia in whom oral therapy fails.

Administration, Intravesical↗
PubMed1996

Contracting: an approach in a home dialysis setting.

Contracting, which has its roots in business, has many applications for use in nursing. It can be especially useful in the nursing of clients with chronic diseases. Our clients must change many behaviours to improve their health. Contracts between clients and health care professionals offer individualized care.

Home Care Services↗
PubMed1995

Aneuploidy in breast cancer: a fluorescence in situ hybridization study.

Although ploidy is associated with the development and progression of most breast cancers, the value of flow cytometric ploidy as a clinical prognostic factor remains controversial. The technique of fluorescence in situ hybridization (FISH) can be used not only to determine overall ploidy, but also to assess the over-representation or under-representation of specific chromosomes in interphase cells. This information may be of prognostic value. We studied 84 primary breast cancers and 20 metastatic tumors by FISH, using chromosome-specific fluorescent centromeric probes. Of these, 100 cases were also studied by DNA flow cytometry. The FISH studies were concordant with DNA flow cytometry with regard to distinguishing aneuploid from diploid tumors in 78% of cases. The FISH data suggested that aneuploidy arises by a process of chromosome complement doubling with subsequent chromosome loss. In tumors that exhibited evidence of more than one round of chromosome complement doubling, the selective accumulation of multiple copies of specific chromosomes or chromosome segments was common. Multiple copies of chromosomes centromeres 1, 3, and 17 were accumulated selectively in the cells of individual tumors more frequently than chromosomes centromeres 7, 11, and 16. Multiple copies of chromosomes centromeres 10 and 20 were selectively accumulated only rarely, if at all. Aneuploidy in breast cancer can be divided into distinct stages using fluorescence in situ hybridization techniques. The stages of aneuploidy provide potential landmarks in the genetic evolution of this disease with possible links to chromosome-specific evolutionary changes.

Aged↗
PubMed1995

Origins and clinical implications of aneuploidy in early bladder cancer.

Cytogenetic and flow cytometric studies in a variety of human solid tumors have suggested that gross aneuploidy may arise by a process of abrupt chromosome complement doubling followed by gradual chromosome loss. However, this sequence has not been demonstrated directly in serial studies in individual patients in vivo. The purpose of this study was to search for evidence of chromosome complement doubling and subsequent chromosome loss in flow cytometric ploidy patterns in serial bladder washings and/or biopsies from individual patients with early bladder cancer. Fifty-two patients with noninvasive bladder cancer were followed with serial flow cytometric DNA studies for periods ranging from 5.1 to 42.7 months (median 15.1 months). Serial changes in DNA ploidy and S phase fractions were recorded and correlated with histologic and/or cytologic findings, response to treatment and clinical outcome. The data suggest a series of genetic evolutionary changes in early bladder cancer that include the initial development of peridiploid aneuploidy and repeated rounds of DNA content doubling with chromosome loss in patients with progressive disease. It is likely that gross DNA aneuploidy, and more specifically, DNA multiploidy and DNA hypertetraploidy, all arise by this mechanism. The sequence of DNA diploidy, peridiploid aneuploidy, near-tetraploidy, hypotetraploidy and hypertetraploidy is associated with a progressive increase in S phase fraction, and with increasing tumor grade; late steps in this ploidy sequence were often present in tumors that were refractory to local therapeutic measures and tumors that developed deep tumor invasion and/or distant metastases. We conclude that DNA multiploidy and hypertetraploidy are markers of advanced stages of genetic evolution in human bladder cancer.

Adult↗
PubMed1995

CD30-mediated signaling promotes the development of human T helper type 2-like T cells.

We have recently shown that CD30, a member of the tumor necrosis factor/nerve growth factor receptor superfamily, is preferentially expressed by human T cell clones producing T helper (Th) type 2 cytokines. We report here that costimulation with an agonistic anti-CD30 monoclonal antibody enhanced antigen (Ag)-induced proliferation and cytokine secretion by established human Th2 and Th0 clones. Moreover, costimulation of peripheral blood mononuclear cells with the same anti-CD30 monoclonal antibody resulted in the preferential development of Ag-specific T cell lines and clones showing a Th2-like profile of cytokine secretion. In contrast, early blockade in bulk culture of CD30 ligand-CD30 interaction shifted the development of Ag-specific T cells towards the opposite (Th1-like) phenotype. Taken together, these data suggest that CD30 triggering of activated Th cells by CD30 ligand-expressing Ag-presenting cells may represent an important costimulatory signaling for the development of Th2-type responses.

Antigen-Presenting Cells↗
PubMed1995

Preferred genetic evolutionary sequences in human breast cancer: a case study.

Multiparameter flow cytometry studies were performed on the cells of an aggressive human breast cancer at the time of diagnosis and at relapse. The aneuploid cells that overexpressed large amounts of both HER-2/neu and ras survived intensive chemotherapy and were responsible for tumor relapse. At relapse, these cells were shown to overexpress simultaneously at least five oncogenes: HER-2/neu, ras, EGF receptor, p53 and c-myc. A partial reconstruction of the genetic evolutionary sequence in this tumor indicated that HER-2/neu overexpression was an early step in the sequence. Subsequent HER-2/neu overexpression, EGF receptor overexpression and p53 protein overexpression were each associated with ras overexpression. The data suggest that ploidy and oncogene overexpression cannot be used as independent clinical prognostic factors. The ability to characterize tumors according to the degree of advancement in the genetic evolutionary might serve as a basis for genetic staging for adjuvant therapy.

Adult↗
PubMed1995

Assessing sequential oncogene amplification in human breast cancer.

Studies of amplification and/or overexpression of c-myc, HER-2/neu, and H-ras in breast cancer have shown that each is associated with a poor prognosis. The purpose of this study was to explore the possibility that there is a preferred sequence of amplification of these oncogenes in breast cancer. The frequencies of amplification and patterns of co-amplification of c-myc, HER-2/neu, and H-ras were studied in a group of 84 breast cancers. The data suggested a preferred sequence of amplification that consisted of c-myc amplification-HER-2/neu amplification-H-ras amplification. This model was supported by loglinear analysis. In addition, the levels of amplification of JC-A, a DNA fragment newly isolated from a patient with advanced breast cancer, were studied in 61 of these cases. The data suggested that JC-A amplification occurred early. Loglinear analysis supported a model in which JC-A amplification occurred either before or after c-myc amplification but was unrelated to Her-2/neu or ras amplification.

Adenocarcinoma↗
PubMed1995

Crystallization and preliminary X-ray diffraction studies of arginase from a thermophilic organism Bacillus caldevelox.

A thermostable hexameric arginase purified from the extreme thermophile Bacillus caldevelox has been crystallized from Hepes buffer at pH 7.5 in the presence of 12% polyethylene glycol 4000 and 10% 2-propanol, and from cacodylate buffer at pH 7.2 in the presence of 15% 2-propanol and sodium citrate. The latter crystals are more suitable for X-ray diffraction analysis. The crystals are in the orthorhombic space group P2(1)2(1)2(1) with unit-cell dimensions a = 156.3, b = 148.0 and c = 85.4 A. The asymmetric unit contains one hexamer (approximate molecular mass 183 kDa) and has a solvent content of approximately 54%. The crystals diffract to 2.8 A resolution.

Journal Article↗
PubMed1995

X-ray structures of the myosin motor domain of Dictyostelium discoideum complexed with MgADP.BeFx and MgADP.AlF4-.

The three-dimensional structures of the truncated myosin head from Dictyostelium discoideum myosin II complexed with beryllium and aluminum fluoride and magnesium ADP are reported at 2.0 and 2.6 A resolution, respectively. Crystals of the beryllium fluoride-MgADP complex belong to space group P2(1)2(1)2 with unit cell parameters of a = 105.3 A, b = 182.6 A, and c = 54.7 A, whereas the crystals of the aluminum fluoride complex belong to the orthorhombic space group C222(1) with unit cell dimensions of a = 87.9 A, b = 149.0 A, and c = 153.8 A. Chemical modification was not necessary to obtain these crystals. These structures reveal the location of the nucleotide complexes and define the amino acid residues that form the active site. The tertiary structure of the protein complexed with MgADP.BeFx is essentially identical to that observed previously in the three-dimensional model of chicken skeletal muscle myosin subfragment-1 in which no nucleotide was present. By contrast, the complex with MgADP.AlF4- exhibits significant domain movements. The structures suggest that the MgADP.BeFx complex mimics the ATP bound state and the MgADP.AlF4- complex is an analog of the transition state for hydrolysis. The domain movements observed in the MgADP.AlF4- complex indicate that myosin undergoes a conformational change during hydrolysis that is not associated with the nucleotide binding pocket but rather occurs in the COOH-terminal segment of the myosin motor domain.

Adenine↗