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Biomedical subjects

J E Olson

Publications and source records attributed to J E Olson.

At least 19 recordsLinked to original sources
PubMed1999

Osmolyte contents of cultured astrocytes grown in hypoosmotic medium.

Primary rat cerebral astrocyte cultures were grown for 2 weeks in isoosmotic medium (305 mosmol) and then placed in similar medium with a reduced NaCl concentration. During the first hour of growth in this moderately hypoosmotic medium (240 mosmol), the cells lose 88% of their taurine contents, 62% of their alanine contents, and 54% of their aspartate contents while regaining normal volume. Loss of these amino acids accounts for 43% of observed volume regulation. Contents of these amino acids remain decreased during 24 h of growth in hypoosmotic medium. In contrast, potassium, glutamate, glutamine, and asparagine contents are not changed, relative to cells in isoosmotic medium, at time points between 1 h and 24 h of hypoosmotic exposure. The data suggest astrocytes contribute to net loss of amino acids, but not potassium, from brains exposed to hypoosmotic conditions in situ.

Amino Acids↗
PubMed1998

Taurine efflux and intracellular pH during astrocyte volume regulation.

Cytotoxic cerebral edema is characterized by enlarged astroglial cells. In tissue culture, osmotically swollen astrocytes return toward normal volume over a period of 15-30 min in a process termed regulatory volume decrease (RVD). RVD is due, in part, to net efflux of taurine and other amino acids. Our objective in these studies was to examine changes in astrocyte intracellular pH (pHi) which may be related to taurine loss during RVD. We hypothesized net efflux of anionic taurine abandons a proton inside the cell, thus lowering pHi. Primary cultures of cerebral astrocytes were prepared from neonatal rats pups and grown on glass coverslips. Confluent cells were loaded at 37 degrees C with the fluorescent pH indicator BCECF. Fluorescence intensity ratios for excitation wavelengths of 440 nm and 494 nm (530 nm emission) were computed every 2 sec. Intensity ratios were calibrated to pHi at the end of each experiment using 140 mM KCl plus 8.6 microM nigericin at pH 7.4. pHi was measured in isoosmotic Hepes-buffered saline (290 mOsm) and then in hypoosmotic Hepes-buffered saline (200 mOsm) in the presence of 0.5 mM amiloride. Some solutions also contained 150 microM niflumic acid (NA). Cellular taurine content was determined in parallel studies using HPLC. Changes in pHi were compared between groups using Student's t-test with Bonferroni correction. Significance was assumed if p < 0.05. In isoosmotic saline, mean +/- SEM pHi was 7.58 +/- 0.04 and decreased to 7.35 +/- 0.09 after adding amiloride. Hypoosmotic exposure caused a further drop in pHi of 0.29 +/- 0.03 within 15 min. Recovery of pHi in isoosmotic saline was amiloride-sensitive. Subsequent hypoosmotic exposure after recovery in isoosmotic saline produced a change in pHi which was 81 +/- 9% of the change measured during the initial hypoosmotic exposure. Taurine content decreased from 147 +/- 6 nmol/(mg protein) to 116 +/- 7 nmol(mg protein) during the 15 min hypoosmotic exposure in 0.5 mM amiloride. NA significantly reduced the hypoosmotically induced change in pHi to 0.17 +/- 0.02 while completely blocking taurine loss. Assuming an intracellular buffering power of 13 mM, the NA-sensitive intracellular acidification of cells during hypoosmotic exposure in the presence of 0.5 mM amiloride corresponds to 1.6 mequiv/l additional intracellular H+. This increase in intracellular H+ content is equivalent to approximately 32% of the NA-sensitive loss of taurine. The association of changes in pHi with taurine efflux is supported by these data; however, efflux of other weak acids may contribute to intracellular acidification during astrocyte RVD and a significant portion of taurine must leave the cell with a proton.

Amiloride↗
PubMed1998

Diet and risk of colon cancer in a large prospective study of older women: an analysis stratified on family history (Iowa, United States).

OBJECTIVE: The purpose was to investigate whether dietary associations with risk of colon cancer in women differ by family history of the disease. METHODS: Data were analyzed from a prospective cohort study of 35,216 Iowa (United States) women aged 55 to 69 years at baseline. Through 31 December 1995, 241 colon cancers were identified through record linkage with the State Health Registry. The cohort was stratified on family history of colon cancer in first-degree relatives; nutrient intakes were divided into tertiles. RESULTS: Analyses using Cox regression revealed that the association of most dietary components with colon cancer incidence were similar for individuals with and without a family history. However, total calcium intake was associated inversely with colon cancer among women with a negative family history (relative risk [RR] = 0.50 for upper cf lower tertile, P < 0.001), but was unrelated to incidence for women with a positive family history (RR = 1.1 for upper cf lower tertile, P = 0.69). Similarly, total vitamin E intake was associated with lower risk among women with a negative family history (RR = 0.67 for upper cf lower tertile, P = 0.04), but not among women with a positive family history (RR = 0.87 for upper cf lower tertile, P = 0.67). High intakes of fiber, fruits, and vegetables were each weakly inversely associated with risk among family-history negative women, but not among family-history positive women. CONCLUSIONS: These data, if corroborated, suggest that dietary factors typically associated with lower risk may be less effective risk-reduction interventions against colon cancer for individuals with a family history of colon cancer.

Age Factors↗
PubMed1998

Antimalarial synergy of cysteine and aspartic protease inhibitors.

It has been proposed that the Plasmodium falciparum cysteine protease falcipain and aspartic proteases plasmepsin I and plasmepsin II act cooperatively to hydrolyze hemoglobin as a source of amino acids for erythrocytic parasites. Inhibitors of each of these proteases have potent antimalarial effects. We have now evaluated the antimalarial effects of combinations of cysteine and aspartic protease inhibitors. When incubated with cultured P. falciparum parasites, cysteine and aspartic protease inhibitors exhibited synergistic effects in blocking parasite metabolism and development. The inhibitors also demonstrated apparent synergistic inhibition of plasmodial hemoglobin degradation both in culture and in a murine malaria model. When evaluated for the treatment of murine malaria, a combination of cysteine and aspartic protease inhibitors was much more effective than higher concentrations of either compound used alone. These results support a model whereby plasmodial cysteine and aspartic proteases participate in the degradation of hemoglobin, and they suggest that combination antimalarial therapy with inhibitors of the two classes of proteases is worthy of further study.

Animals↗
PubMed1998

Taurine synthesis and cysteine metabolism in cultured rat astrocytes: effects of hyperosmotic exposure.

We investigated mechanisms controlling taurine synthesis in cultured rat cerebral astrocytes. The mean +/- SE rate of taurine synthesis from extracellular cysteine was 21.2 +/- 2.0 pmol.mg protein-1.min-1, whereas taurine degradation was < 1.3% of this rate. Eliminating cellular glutathione and inhibiting glutathione biosynthesis increased taurine synthesis from extracellular cysteine by 39%. In cell homogenates, cysteine dioxygenase (CDO) and cysteine-sulfinate decarboxylase activities were 2.4 +/- 0.2 and 8.3 +/- 2.8 nmol.mg protein-1.min-1, respectively. CDO activity was strongly dependent on cysteine concentration over physiological and pathophysiological ranges of intracellular cysteine concentration. Growth in hyperosmotic medium caused a greater increase in culture medium taurine content than that measured from cells in isosmotic growth medium. Hyperosmotic treatment transiently increased the rate of cysteine accumulation and cellular cysteine and glutathione contents but had no effect on the synthesis rate of taurine from extracellular cysteine. Thus cysteine is accumulated and then metabolized to taurine through CDO, whose activity depends on the intracellular cysteine concentration and appears to be rate limiting for taurine synthesis. Hyperosmotic exposure increases net taurine production yet has no effect on taurine synthesis from exogenously applied cysteine. Availability of substrate from intracellular pools must contribute to maintenance of high intracellular taurine during hyperosmotic exposure.

Animals↗
PubMed1998

Family histories of diabetes mellitus and breast cancer and incidence of postmenopausal breast cancer.

Diabetes-associated endocrine factors may influence the growth of some breast tumors. Therefore, one might expect an association of family history of diabetes mellitus with breast cancer incidence. We analyzed data from a cohort study of 41,837 women ages 55-69 years. During 10 years of follow-up, we identified 1,013 incident cases of breast cancer. There was no consistent association between family history of diabetes mellitus and family history of breast cancer, except among sisters. Women with a family history of diabetes had a higher prevalence of breast cancer risk factors, but family history of diabetes was not associated with risk of postmenopausal breast cancer, regardless of family history of breast cancer status.

Aged↗
PubMed1997

Synthesis and antimalarial effects of phenothiazine inhibitors of a Plasmodium falciparum cysteine protease.

Acridinediones have previously been shown to have potent antimalarial activity. A series of sulfur isosteres of acridinediones have been synthesized and evaluated for their inhibition of the Plasmodium falciparum cysteine protease falcipain and for their antimalarial activity. A number of these phenothiazines inhibited falcipain and demonstrated activity against cultured P. falciparum parasites at low micromolar concentrations. We propose that the compounds exerted their antimalarial effects by two mechanisms, one of which involves the inhibition of falcipain and a consequent block in parasite degradation of hemoglobin. These compounds and related phenothiazines are worthy of further study as potential antimalarial agents.

Animals↗
PubMed1997

The role of radiotherapy in the management of operable locally advanced breast carcinoma: results of a randomized trial by the Eastern Cooperative Oncology Group.

BACKGROUND: The purpose of this study was to test the role of radiotherapy following total mastectomy, axillary dissection, and adjuvant systemic therapy in the management of operable locally advanced breast carcinoma. METHODS: After undergoing mastectomy and axillary dissection, 426 patients with locally advanced breast carcinoma were registered on study and stratified by patient characteristics and risk factors. All patients were then treated with six courses of chemohormonotherapy. After being restaged, the 332 patients remaining without recurrence were randomized to receive prophylactic radiotherapy or to undergo observation and receive radiotherapy only if and when there was locoregional recurrence. RESULTS: Three hundred twelve of 332 randomized patients were deemed eligible and analyzed for both time to relapse and survival. The median follow-up period was 9.1 years. There were no significant differences in time to relapse and overall survival between the two treatment arms. Of those assigned to radiation, 60% relapsed, with a median time to relapse of 4.7 years, and 46% were alive at last follow-up, with a median survival of 8.3 years. Of those assigned to observation, 56% relapsed, with a median time to relapse of 5.2 years, and 47% were alive at last follow-up, with a median survival of 8.1 years. The two treatment arms had significantly different patterns of sites of first recurrence. There were 9% fewer locoregional first recurrences among those assigned to radiation than among those assigned to observation (15% vs. 24%), whereas there were 15% more first relapses at distant sites (50% vs. 35%) among those assigned to radiation (P = 0.003). CONCLUSIONS: Radiotherapy for locally advanced breast carcinoma, following mastectomy, axillary dissection, and adjuvant systemic therapy, results in fewer locoregional but more distant recurrences at first relapse. No significant advantage was seen for consolidation radiotherapy over observation in terms of either time to relapse or survival, both of which were virtually identical in the two treatment arms. [See editorial counterpoint on pages 1061-6 and reply to counterpoint on pages 1067-8, this issue.]

Adult↗
PubMed1997

Medical record validation of maternally reported birth characteristics and pregnancy-related events: a report from the Children's Cancer Group.

Epidemiologic studies frequently obtain exposure information through subjects' self-report (personal interview or mailed questionnaire). The authors used data from a case-control study of infant leukemia, to assess the validity and reliability of maternally reported information on birth characteristics such as birth weight, reproductive history, and medical procedures. Cases were gathered from the Children's Cancer Group, a United States and Canadian cooperative clinical trails group with approximately 100 member and affiliate institutions, during 1983-1988. Telephone interviews were completed for 302 cases and 558 matched controls. Medical records of the index pregnancy were obtained for 287 cases and 467 controls. Correlations between medical charts and maternal interview were high for birth weight (r = 0.98, kappa = 0.9) and gestational age (r = 0.86, kappa = 0.6). Mean differences between the two sources were small, -10.5 g for birth weight and -0.36 weeks for gestational age. Reproductive history and medical procedures had high to moderate reliability. Problems after delivery and pregnancy complications generally had low validity and reliability. Little evidence of differential misclassification was found. Time between delivery and interview ranged from zero to 8 years and did not greatly affect reliability. This study suggests that validity and reliability of maternally reported pregnancy and delivery information may differ with the nature of the factor of interest, but is affected little by time from birth or case-control status.

Birth Weight↗
PubMed1997

Increased potassium, chloride, and taurine conductances in astrocytes during hypoosmotic swelling.

Membrane conductances during hypoosmotic swelling were characterized in rat astrocytes in primary tissue culture. Using whole cell patch clamp techniques, mean +/- SEM cell conductance in isoosmotic phosphate-buffered saline (PBS) was 55.6 +/- 5.8 pS/pF. Cell conductance (mean +/- SEM) increased from this initial value to 187 +/- 46%, 561 +/- 188%, and 1216 +/- 376% within 9 min of exposure to 220 mOsm, 190 mOsm, and 145 mOsm PBS, respectively. With each of these hypoosmotic exposures, no change occurred in membrane capacitance. When CsCl replaced KCl in the microelectrode solution, a similar conductance increase was obtained at each osmolality. However, when gluconate salts were used in place of chloride salts in the electrode solution, no significant conductance increase was observed with 190 mOsm PBS. With a KCl microelectrode solution, all conductance increase which occurred in 190 mOsm PBS was inhibited by 200 microM niflumic acid, but not by 5 mM BaCl(2). Both niflumic acid and BaCl(2) inhibited 60-80% of the conductance increase of cells in 145 mOsm PBS. Using a microelectrode solution containing taurine as the major anion, membrane conductance increased 5-fold when cells were placed in 250 mOsm medium. This conductance increase was completely inhibited by 200 microM niflumic acid. Thus, independent chloride and potassium conductances are activated by hypoosmotic swelling of cultured astrocytes while plasma membrane area is unaltered. The chloride conductance pathway is activated at a significantly lower degree of hypoosmotic exposure than that which activates the potassium pathway and may be permeable to anionic taurine. These conductance pathways may mediate diffusive loss of potassium, chloride, and taurine from these cells during volume regulation following hypoosmotic swelling.

Animals↗
PubMed1997

Blood-brain barrier water permeability and brain osmolyte content during edema development.

OBJECTIVE: To determine mechanisms that limit changes in brain water content during acute edema development. METHODS: A controlled, laboratory investigation of the physiologic and biochemical correlates of osmotic edema was performed in rats. Hypoosmotic hyponatremia was induced by intraperitoneal injection of distilled water. Serum osmolality and electrolytes and regional blood-brain barrier water permeability. Surface area (P.S) product, osmolyte contents, and capillary size were determined during 120 minutes of hypoosmotic brain edema development. Cerebral water content predicted from these data using a mathematical model of brain water movements was compared with measured changes in brain water content. RESULTS: Fifteen minutes after distilled water injection, mean +/- SEM blood serum osmolality and sodium concentration decreased from 291 +/- 3 mOsm and 131 +/- 13 mmol/L to 267 +/- 3 mOsm and 102 +/- 9 mmol/L, respectively. Specific gravity of cerebral gray matter, cerebral white matter, and basal ganglia decreased throughout the hypoosmotic exposure period and, for gray and white matter, correlated with blood serum osmolality and sodium plus potassium content. Glutamate, but not glutamine, glycine, or taurine, decreased 120 minutes after water injection. The regional water P.S product decreased by 40% to 60% within 60 minutes of the water injection, while capillary diameters in gray and white matter were unchanged. Brain water movements calculated from the mathematical model correctly predicted actual brain water content only if the hydraulic conductivity of the blood-brain barrier was allowed to vary in proportion to the measured P.S product and the measured loss of brain osmolytes was incorporated into the formulation. CONCLUSIONS: During the first hours of hypoosmotic hyponatremia, changes in brain volume are limited by increased resistance to osmotic flux of water into the brain and reduction in the brain content of inorganic and, to a smaller degree, organic osmolytes.

Analysis of Variance↗
PubMed1997

Association of family history of cervical, ovarian, and uterine cancer with histological categories of lung cancer: the Iowa Women's Health Study.

A family history of cervical, ovarian, or uterine cancer has been shown to be associated with increased lung cancer risk among postmenopausal women. The present report examines the hypotheses that a family history of cervical cancer is positively associated with histological subtypes of lung cancer most strongly associated with smoking and that a family history of ovarian or uterine cancer are positively associated with risk of adenocarcinoma of the lung. Data are from the Iowa Women's Health Study, a prospective cohort study of 34,480 women ages 55-69 in 1986. Personal smoking histories, use of alcohol, and family history of selected cancers in first- and second-degree relatives were collected at baseline. Follow-up for cancer occurrence was achieved through the State Health Registry of Iowa. After baseline exclusions, a total of 343 incident lung cancers were identified in the cohort at risk through 1994. Women with a family history of cervical cancer in a first-degree relative had a multivariate-adjusted relative risk of lung cancer of 1.6 [95% confidence interval (CI): 0.98-2.6] compared to women without a family history. The risk was particularly high for malignancies most strongly associated with smoking (squamous, small cell, and large cell tumors; relative risk, 2.0; 95% CI, 1.1-3.7). Consistent with our hypotheses, a family history of ovarian cancer was associated with an approximately 2-fold increased risk (multivariate adjusted) of adenocarcinoma of the lung; the association with malignancies more strongly associated with smoking was inverse (relative risk, 0.6; 95% CI, 0.2-2.4). A family history of uterine cancer was not associated with adenocarcinoma, but there was a positive association observed for the most strongly smoking-associated histological types. These results suggest that a family history of cervical cancer is a modest independent risk factor for lung cancers most strongly associated with smoking, and a family history of ovarian cancer is a risk factor for adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1996

Relation of taurine transport and brain edema in rats with simple hyperammonemia or liver failure.

Taurine (Tau), an amino acid that abounds in brain, has been implicated in inhibitory neuromodulation and osmoregulation, the latter function being manifested by Tau release along with osmotically obligated water in response to brain tissue edema. A previous study (Hilgier and Olson: J. Neurochem. 62:197-204, 1994) had shown that simple hyperammonemia (HA) induced in rats by daily administration of ammonium acetate resulted in a decrease of both tissue specific gravity indicative of edema and Tau content, in basal ganglia (BG) but not in cerebral cortex (CC). By contrast, rats with hepatic encephalopathy (HE) following administration of a hepatotoxin, thioacetamide, were characterized by CC edema and an increased Tau content in both BG and CC. In the present study, we tested the following parameters that may potentially have affected Tau distribution in the two models: a) spontaneous, and stimulated (hypoosmolarity-induced) release of loaded [3H] Tau in vitro from CC and BG slices; b) blood Tau content; and c) uptake of [14C] Tau in vivo from blood to brain corrected for [3H] water passage-the so-called brain uptake index (BUI). The two edema-affected structures: BG in the HA model and CC in the HE model, showed increased spontaneous Tau release. Edema-associated spontaneous release of Tau may favor inhibitory neurotransmission contributing to the pathomechanism of HA or HE. Stimulated release, reflecting the ability of the tissue to reduce water content, was decreased in the BG from HA rats, in agreement with the postulated role of Tau in osmoregulation. Stimulated release was unchanged in CC of HE rats. Neither spontaneous nor stimulated release of Tau were affected in CC of HA rats or in BG of HE rats. HE, but not HA, was associated with elevated blood content and increased BUI for TAU, which in combination, contributed to the increase of Tau content in CC. The latter phenomenon adds to the list of metabolic changes distinguishing simple HA from toxic liver damage, reemphasizing the crucial role of factors other than ammonia in the pathomechanism of HE.

Ammonia↗
PubMed1996

Hyperosmotic exposure alters total taurine quantity and cellular transport in rat astrocyte cultures.

Taurine content and cellular taurine transport were characterized in astrocytes from rat cerebral cortex after growth in isoosmotic or hyperosmotic culture conditions to investigate mechanisms of taurine accumulation during conditions of increased osmolality. Total taurine content of the culture dishes was significantly (P < 0.05) elevated after 8, 24, and 48 h of hyperosmotic exposure compared to cultures grown for the same period in isoosmotic (300 mOsm, control) conditions. Hyperosmotic medium elevated intracellular taurine (nmol/mg protein) levels by 29-108% over control cultures. Significant (P < 0.02) increases in carrier-mediated taurine uptake rates were observed in astrocytes exposed to 350, 400, and 450 mOsm culture medium for 24 h compared to control cultures at the same time point. The increase in uptake rate decreased to control values by 48 h in 450 mOsm treated cultures. The carrier-mediated transport binding constant for taurine uptake, Km, was not altered at any time after hyperosmotic treatment. Maximal velocity of uptake, V(max), increased by 70% and 36% after 24 h growth in 400 and 450 mOsm culture medium, respectively, compared to control cells at the same time. After 48 h of hyperosmotic exposure, V(max) returned to control values. The diffusional transport rate for taurine efflux, Kdiff, was not affected by hyperosmotic exposure at any time point. Taurine release rates were increased by over two-fold during the first 8 h of exposure to 450 mOsm medium compared with cells grown in control conditions. After 24 and 48 h hyperosmotic exposure, release rates decreased to 44-72% of the release from control cultures. These data indicate at least three mechanisms contribute to taurine accumulation in cultured cerebral astrocytes exposed to hyperosmotic conditions. These mechanisms are (i) an increased rate of taurine uptake from the extracellular space within 24 h, (ii) a decrease in net taurine efflux by 48 h, and (iii) an enhanced rate of taurine synthesis.

Animals↗
PubMed1996

Optimal positioning for cervical immobilization.

STUDY OBJECTIVE: We hypothesized that optimal positioning of the head and neck to protect the spinal cord during cervical spine immobilization can be determined with reference to external landmarks. In this study we sought to determine the optimal position for cervical spine immobilization using magnetic resonance imaging (MRI) and to define this optimal position in a clinically reproducible fashion. METHODS: Our subjects were 19 healthy adult volunteers (11 women, 8 men). In each, we positioned the head to produce various degrees of neck flexion and extension. This positioning was followed by quantitative MRI of the cervical spine. RESULTS: The mean ratio of spinal canal and spinal cord cross-sectional areas was smallest at C6 but exceeded 2.0 at all levels from C2 to T1 (P < .05). At the C5 and C6 levels, the maximal area ratio was most consistently obtained with slight flexion (cervical-thoracic angle of 14 degrees) (P < .05). For a patient lying flat on a backboard, this corresponds to raising the occiput 2 cm. More extreme flexion or extension produced variable results. CONCLUSION: In healthy adults, a slight degree of flexion equivalent to 2 cm of occiput elevation produces a favorable increase in spinal canal/spinal cord ration at levels C5 and C6, a region of frequent unstable spine injuries.

Adult↗
PubMed1996

Antimalarial effects of vinyl sulfone cysteine proteinase inhibitors.

We evaluated the antimalarial effects of vinyl sulfone cysteine proteinase inhibitors. A number of vinyl sulfones strongly inhibited falcipain, a Plasmodium falciparum cysteine proteinase that is a critical hemoglobinase. In studies of cultured parasites, nanomolar concentrations of three vinyl sulfones inhibited parasite hemoglobin degradation, metabolic activity, and development. The antimalarial effects correlated with the inhibition of falcipain. Our results suggest that vinyl sulfones or related cysteine proteinase inhibitors may have promise as antimalarial agents.

Animals↗
PubMed1995

Hypoosmotic volume regulation and osmolyte transport in astrocytes is blocked by an anion transport inhibitor, L-644,711.

Cell volume, potassium content, and potassium influx were measured in rat cerebral astrocytes grown in primary culture following exposure to hypoosmotic medium containing either 3.2 mM or 50 mM potassium. Some solutions also contained 1 mM L-644,711, an anion transport inhibitor. L-644,711 inhibited volume regulation and taurine efflux induced by hypoosmotic exposure in medium containing either potassium concentration. L-644,711 also inhibited potassium uptake associated and not associated with the sodium/potassium pump. The correlation of reduced taurine efflux and volume decrease produced by L-644,711 exposure indicates the important role for this amino acid in hypoosmotic astrocyte volume regulation. However, the effects of L-644,711 on potassium transport indicate that multiple actions of this drug may be important factors in its effect on astrocyte volume regulatory mechanisms.

Amino Acids↗