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Biomedical subjects

B K Schneider

Publications and source records attributed to B K Schneider.

11 recordsLinked to original sources
PubMed2001

Glutamine protects mitochondrial structure and function in oxygen toxicity.

Glutamine is an important mitochondrial substrate implicated in the protection of cells from oxidant injury, but the mechanisms of its action are incompletely understood. Human pulmonary epithelial-like (A549) cells were exposed to 95% O2 for 4 days in the absence and presence of glutamine. Cell proliferation in normoxia was dependent on glutamine, and glutamine deprivation markedly accelerated cell death in hyperoxia. Glutamine significantly increased cellular ATP levels in normoxia and prevented the loss of ATP in hyperoxia seen in glutamine-deprived cells. Mitochondrial membrane potential as assessed by flow cytometry with chloromethyltetramethylrosamine was increased by glutamine in hyperoxia-exposed A549 cells, and a glutamine dose-dependent increase in mitochondrial membrane potential was detected. Glutamine-supplemented, hyperoxia-exposed cells had a higher O2 consumption rate and GSH content. Electron and fluorescence microscopy revealed that, in hyperoxia, glutamine protected cellular structures, especially mitochondria, from damage. In hyperoxia, activity of the tricarboxylic acid cycle enzyme alpha-ketoglutarate dehydrogenase was partially protected by its indirect substrate, glutamine, indicating a mechanism of mitochondrial protection.

Adenosine Triphosphate↗
PubMed2001

Limitations to oxygen diffusion and equilibration in in vitro cell exposure systems in hyperoxia and hypoxia.

Exposure of cultured cells to changing gaseous environments is used as a model for understanding both the immediate and long-term effects of such exposures on lung cells in vivo. We conducted experiments with polystyrene tissue culture flasks and plates to determine the time course of changes in oxygen concentration occurring under in vitro conditions. Only a few minutes were required for the concentration of oxygen in the environmental chamber to reach equilibrium with that of the flushing gas. However, >3 h were required for the oxygen content in the medium in the tissue culture flasks and plates to achieve equilibrium. The low solubility of oxygen in aqueous solutions and the limited diffusion of oxygen through a boundary layer of gas above the medium are the major barriers to rapid oxygen transport into the culture medium. The delay in achieving the desired PO(2) within the culture medium limits the temporal precision of any assessment of the correlation of cellular events with the concentration of oxygen to which those cells are exposed.

Animals↗
PubMed2000

Hypoxia induces hexokinase II gene expression in human lung cell line A549.

During adaptation to hypoxic and hyperoxic conditions, the genes involved in glucose metabolism are upregulated. To probe involvement of the transcription factor hypoxia-induced factor-1 (HIF-1) in hexokinase (HK) II expression in human pulmonary cells, A549 cells and small-airway epithelial cells (SAECs) were exposed to stimuli such as hypoxia, deferoxamine (DFO), and metal ions. The largest increase in HK-II (20-fold for mRNA and 2.5-fold for enzymatic activity) was observed in A549 cells when exposed to DFO. All stimuli selectively increased the 5.5-kb rather than 4-kb transcript in A549 cells. Cycloheximide and actinomycin D inhibited these responses. In addition, cells were transfected with luciferase reporter constructs driven by the full-length HK-II 5'-regulatory region (4.0 kb) or various deletions of that region. A549 cells transfected with the 4.0-kb construct and exposed to hypoxia or DFO increased their luciferase activity 7- and 10-fold, respectively, indicating that HK-II induction is, at least in part, due to increased gene transcription. Sixty percent of the inducible activity of the 4.0-kb construct was shown to reside within the proximal 0.5 kb. Additionally, cotransfection with a stable HIF-1 mutant and the 4.0-kb promoter construct resulted in increased luciferase activity under normoxic conditions. These results strongly suggest that HK-II is selectively regulated in pulmonary cells by a HIF-1-dependent mechanism.

Cell Line↗
PubMed1992

Evaluation of cutaneous algogenic responses to bradykinin and inhibition by bradykinin analogs.

Bradykinin has long been postulated to have a major role in physiologic human pain production. We have developed a method to systematically quantify the algogenic response to bradykinin in human skin by the direct application of bradykinin to suction blister bases. After determination of the pain threshold to bradykinin, we examined the ability of synthetic peptide analogs of bradykinin to block bradykinin-induced pain. One of the six analogs (B4642) inhibited bradykinin-induced pain with at least one concentration in all subjects tested. This result could not be predicted on the basis of inhibition of bradykinin binding to its guinea-pig ileum receptor or to previous studies of bradykinin-induced pain production in animal models. This peptide may have an eventual role as a physiologic pain inhibitor.

Amino Acid Sequence↗
PubMed1986

Influence of testosterone on breathing during sleep.

Apneas and hypopneas during sleep occur more frequently in men than women. Disordered breathing is also reported to increase in hypogonadal men following testosterone administration. This suggests a hormonal influence on sleeping respiratory pattern. We therefore studied respiratory rhythm during sleep in 11 hypogonadal males both on and off testosterone-replacement therapy. In four subjects the anatomy (computerized tomography) and airflow resistance of the upper airway were also determined on both occasions. Sleep stage distribution and duration were unchanged following androgen administration. However, both apneas and hypopneas increased significantly during testosterone replacement so that the total number of disordered breathing events (apneas + hypopneas) per hour of sleep rose from 6.4 +/- 2.1 to 15.4 +/- 7.0 (P less than 0.05). This was a highly variable event with some subjects demonstrating large increases in apneas and hypopneas when androgen was replaced, whereas others had little change in respiration during sleep. Upper airway dimensions, on the other hand, were unaffected by testosterone. These results suggest that testosterone contributes to sleep-disordered breathing through mechanisms independent of anatomic changes in the upper airway.

Arousal↗
PubMed1985

Influence of testosterone on ventilation and chemosensitivity in male subjects.

There is increasing evidence that men have higher ventilatory responses to chemical stimuli than age-matched women and that certain disorders of respiratory rhythmicity, particularly sleep apnea, occur more commonly in men. Accordingly, we studied the influence of the male hormone, testosterone, on the control of breathing. Twelve hypogonadal males were studied at least 30 (mean +/- SE: 69.7 +/- 8.9) days after discontinuing testosterone replacement and again following hormone administration. In each subject plasma testosterone concentration, metabolic rate [O2 consumption (VO2) and CO2 production (VCO2)], minute ventilation (VE), and chemosensitivity [hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses] were determined on and off hormone replacement. With testosterone administration VO2 increased from 248 +/- 15 to 276 +/- 18 ml/min (P less than 0.05), with VCO2 showing a similar but nonsignificant trend. This was associated with an increase in VE from 8.41 +/- 0.78 to 9.91 +/- 0.75 l/min (P less than 0.05) but no change in PCO2. The HVR, expressed as A, increased 44% with hormone replacement from a value of 122 +/- 23 to 176 +/- 28 (P less than 0.01), whereas the HCVR was minimally affected by testosterone administration. These findings may in part explain the previously described differences between male and female subjects in hypoxic sensitivity.

Adult↗
PubMed1979

Childhood leukemia and lymphoma: correlation of clinical features with immunological and morphological studies.

Malignant cells from 49 children with lymphoid neoplasms other than Hodgkin disease were evaluated by surface marker and morphologic studies. We classified the patients into three groups: 36 patients (74%) with acute lymphocytic leukemia; 7 (14%) classified as convoluted lymphocytic lymphoma/leukemia; and 6 (12%) with small noncleaved follicular center cell lymphoma/leukemia. Diffuse marrow involvement was present at diagnosis in some patients in the latter two groups, but their clinical course was not characteristic of the patients with acute lymphocytic leukemia. Male predominance, poor prognosis, and high incidence of central nervous system disease characterized patients in the convoluted lymphocytic and follicular center cell lymphoma/leukemia groups. Clinical presentation in these two groups differed. Proliferations of convoluted lymphocytes were associated with mediastinal masses and proliferations of follicular center cells with intraabdominal tumors. The high incidence of CNS disease in children with neoplasms of convoluted lymphocytes and follicular center cells suggests that these processes have a predilection for the CNS and that patients with them may benefit from CNS prophylaxis.

Adolescent↗
PubMed1976

Surface immunoglobulin on leukemic, leukemoid, and normal granulocytes.

Using a new functional approach for the study of lymphomas and leukemias in which immunologic and cytochemical techniques were employed, we found a consistent surface immunoglobulin pattern of the gamma-, k-, lambda-type on cells from poorly differentiated (acute) and well-differentiated (chronic) granulocytic leukemias. This pattern was also found on nonneoplastic granulocytes from patients with leukemoid reactions as well as on granulocytes from normal individuals. These findings suggested that both leukemia cells and nonneoplastic granulocytes had IgG bound to the cell surface by an Fc receptor. This binding of IgG by granulocytes was not tumor-specific and appeared to correlate both with the degree of differentiation and possibly with the degree of activation of the granulocytes. In addition to raising the basic question of its functional significance, these findings offered an approach for distinction of poorly differentiated granulocytic leukemia from lymphomatous processes.

Adult↗
PubMedDate not supplied

Cancers arising from burn scars. A literature review and report of twenty-one cases.

A review of the literature and a combined burn center study of the University of Beijing and the University of Colorado Health Sciences Center looking at cancer arising from old burn injuries are reported. This study indicates that of the 21 patients 76% were male, with an age range from 15 to 67 years. The lag period for all cancers ranged from 8 months to 60 years. The distribution of the cancer was greatest in the extremities, with 71%, followed by the scalp, with 14%. Forty-three percent of the patients were treated by excision and skin grafting. Twenty-nine percent were treated by amputation, 24% had radiation therapy, and 5% received no treatment. Of the 76% who were followed up to 8 years, no deaths were reported.

Adolescent↗