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L K Olson

Publications and source records attributed to L K Olson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Parenchymal scarring is associated with restrictive spirometric defects in patients with chronic thromboembolic pulmonary hypertension.

UNLABELLED: The finding of a restrictive pulmonary defect may divert clinicians from considering the diagnosis of chronic thromboembolic pulmonary hypertension because lung volumes are usually normal in this disorder. We have, however, encountered a significant number of these patients with reduced lung volumes. Furthermore, we have observed many patients who have developed parenchymal scars and/or pleural thickening. To determine whether such findings are associated with lung volume restriction, we analyzed patients evaluated at our institution for chronic thromboembolic pulmonary hypertension over a 20-month period in whom thoracic high-resolution CT scans and pulmonary function testing had been performed. Patients with obstructive or restrictive lung disease from another cause were excluded. We compared the presence of lung restriction (total lung capacity below 80% of predicted) with the extent of parenchymal scarring, pleural thickening, and pulmonary artery diameter on CT scans. Of 191 patients evaluated, 51 met criteria for entry. Eleven patients (22%) had lung restriction. Parenchymal scarring was highly associated with lung restriction (p = 0.01). Neither pleural thickening (p = 0.08) nor pulmonary artery diameter (p = 0.80) was associated with lung restriction. CONCLUSIONS: A significant number of patients with chronic thromboembolic pulmonary hypertension may have restrictive lung defects. The restriction may be due to parenchymal scarring.

Adult↗
PubMed1996

Insulin-secreting cell lines: classification, characteristics and potential applications.

The use of primary beta-cells in biochemical and molecular research is limited by the availability of pancreatic endocrine tissue. Numerous investigators have attempted to establish an insulin-secreting cell line that retains normal regulation of insulin secretion. Different approaches have been used, including induction of pancreatic tumors by irradiation or viral infection, immortalization of beta-cells in vitro, and development of transgenic mice with targeted expression of a recombinant oncogene in the beta-cell. Few of these attempts have proven successful, because cell differentiation and proliferation capacities are mutually exclusive. The most widely used insulin-secreting cell lines are RIN, HIT, beta TC, MIN6 and INS-1 cells. These cells contain mainly insulin and small amounts of glucagon and somatostatin. RIN cells, except for the subclone RIN-38, are not glucose-responsive. HIT cells and beta TC cells secrete insulin in response to glucose, but their dose-response curve is markedly shifted to the left MIN6, INS-1 and a newly available subclone of beta TC cells (beta TC-6 F7) are reported to retain normal regulation of glucose-induced insulin secretion. Although the behaviour of none of these cell lines perfectly mimics primary beta-cell physiology, they are extremely valuable tools for the study of molecular events underlying beta-cell function and dysfunction. In addition, insulin-secreting cell lines represent a potential source of transplantable tissue to overcome the limited availability of primary islets for this procedure.

Animals↗
PubMed1995

Chromium speciation by anion-exchange high-performance liquid chromatography with both inductively coupled plasma atomic emission spectroscopic and inductively coupled plasma mass spectrometric detection.

Development of a new method for the determination of Cr(III) and Cr(VI) is described. Anion-exchange high-performance liquid chromatography (HPLC) was used to separate Cr(III) and Cr(VI) with on-line detection by inductively coupled plasma atomic emission spectroscopy (ICP-AES) at 2766 A in preliminary studies, and inductively coupled plasma mass spectrometry (ICP-MS) with single-ion monitoring at m/z 52 and m/z 53 for final work. A mobile phase consisting of ammonium sulfate and ammonium hydroxide was used, and a simple chelation procedure with EDTA was followed to stabilize the Cr(III) species in standard solutions. ICP-MS results indicated the feasibility of using chromium isotope m/z 53 instead of the more abundant m/z 52 isotope due to a high mobile-phase background most significantly from the SO+ polyatomic interference. The absolute detection limits based on peak-height calculations were 40 pg for Cr(III) and 100 pg for Cr(VI) in aqueous media by HPLC-ICP-MS. The linear dynamic range extended from 5 ppb (ng/ml) to 1 ppm (micrograms/ml) for both species. By HPLC-ICP-AES, detection limits were 100 ng for Cr(III) and 200 ng for Cr(VI). Cr(III) was detected in NIST-SRM 1643c (National Institute of Standards and Technology-Standard Reference Material, Trace Elements in Water) by HPLC-ICP-MS at the 20 ppb level.

Chromatography, High Pressure Liquid↗
PubMed1995

Reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to a supraphysiologic glucose concentration is associated with loss of STF-1 transcription factor expression.

Chronic exposure of HIT-T15 beta cells to elevated glucose concentrations leads to decreased insulin gene transcription. The reduction in expression is accompanied by diminished binding of a glucose-sensitive transcription factor (termed GSTF) that interacts with two (A+T)-rich elements within the 5' flanking control region of the insulin gene. In this study we examined whether GSTF corresponds to the recently cloned insulin gene transcription factor STF-1, a homeodomain protein whose expression is restricted to the nucleus of endodermal cells of the duodenum and pancreas. We found that an affinity-purified antibody recognizing STF-1 supershifted the GSTF activator complex formed from HIT-T15 extracts. In addition, we demonstrated a reduction in STF-1 mRNA and protein levels that closely correlated with the change in GSTF binding in HIT-T15 cells chronically cultured under supraphysiologic glucose concentrations. The reduction in STF-1 expression in these cells could be accounted for by a change in the rate of STF-1 gene transcription, suggesting a posttranscriptional control mechanism. In support of this hypothesis, no STF-1 mRNA accumulated in HIT-T15 cells passaged in 11.1 mM glucose. The only RNA species detected was a 6.4-kb STF-1 RNA species that hybridized with 5' and 3' STF-1-specific cDNA probes. We suggest that the 6.4-kb RNA represents an STF-1 mRNA precursor and that splicing of this RNA is defective in these cells. Overall, this study suggests that reduced expression of a key transcriptional regulatory factor, STF-1, contributes to the decrease in insulin gene transcription in HIT-T15 cells chronically cultured in supraphysiologic glucose concentration.

3T3 Cells↗
PubMed1995

Somatostatin coordinately regulates glucagon gene expression and exocytosis in HIT-T15 cells.

Somatostatin (SRIF) regulates secretion from several endocrine cell types. SRIF inhibits both insulin and glucagon secretion and reduces insulin gene expression. However, whether SRIF inhibition of glucagon secretion from the pancreatic alpha cell is mediated via pertussis toxin-sensitive G-proteins is not presently known, nor has it been determined whether SRIF can regulate glucagon gene expression. Consequently, we performed studies in the transformed islet cell line HIT-T15 to determine whether the inhibitory effect of SRIF on glucagon exocytosis is preserved in this cell line, whether this effect is mediated through a pertussis toxin-sensitive mechanism, and whether SRIF has an inhibitory effect on glucagon gene expression. Confocal microscopy with immunostaining revealed that 15-25% of HIT-T15 cells contained glucagon. In static incubations forskolin (FSK, 1 microM) increased glucagon secretion 3.6 +/- 0.9-fold (P < 0.01) and mixed amino acids (15 mM) increased glucagon secretion 2.8 +/- 0.4-fold (P < 0.01). Addition of SRIF significantly inhibited both forskolin- and amino acid-stimulated secretion. Maximal inhibition of both FSK- and amino acid-stimulated secretion occurred at SRIF concentrations > or = 10(-8) M and these inhibitory effects were completely prevented by pertussis toxin pretreatment. In addition to inhibiting glucagon secretion, SRIF significantly reduced both basal and FSK-stimulated glucagon mRNA levels and this reduction in glucagon mRNA was completely prevented by the addition of cyclic AMP analogue. Glucagon gene promoter activity, as assessed by transient transfection experiments, was stimulated 2.1 +/- 0.25-fold by forskolin (P < 0.01). This effect was significantly inhibited by SRIF (71 +/- 4% reduction from FSK alone, P < 0.04) suggesting that SRIF inhibition of the glucagon promoter may, at least in part, account for the observed decrease in glucagon mRNA levels. These studies uniquely demonstrate that glucagon secretion from the HIT-T15 cell line is inhibited by SRIF through a pertussis toxin-sensitive mechanism and that SRIF also inhibits glucagon gene expression in part by reducing glucagon promoter activity. These findings indicate that SRIF can coordinately regulate glucagon delivery by the alpha cell both at the level of gene expression and hormone exocytosis.

Animals↗
PubMed1995

The reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to high glucose concentration is associated with the loss of RIPE3b1 and STF-1 transcription factor expression.

The most important regulator of insulin gene expression in pancreatic beta- cells is glucose, which affects gene transcription, mRNA translation, and secretion. Insulin gene transcription is both positively and negatively regulated by glucose. Recently, we have shown that the inhibition of insulin gene transcription caused by passaging HIT T-15 beta-cells, in the presence of high glucose, was due, in part, to reduced expression of a key regulator of insulin enhancer-mediated expression, somatostatin transcription factor-1 (STF-1). In this study, we have examined whether the activity of the other essential transcription regulators of insulin gene expression, the RIPE3b1 and insulin control element (ICE) activators, were also influenced in these HIT T-15 cells. The results show that the binding and trans-activation functions of the RIPE3b1 activator are reduced in parallel with the loss in STF-1 and insulin gene expression. In contrast, the regulatory properties of the ICE activator are unaffected. Our studies indicate that insulin gene transcription is inhibited by glucose through a mechanism involving reduced expression of both the RIPE3b1 and STF-1 activators in HIT T-15 cells but is independent of the ICE activator.

Animals↗
PubMed1995

AIDS-related spontaneous pneumothorax. Risk factors and treatment.

OBJECTIVE: To define risk factors and optimum therapy for AIDS-related spontaneous pneumothorax (PTX). DESIGN: Case-control study. SETTING: Tertiary care center. PATIENTS: Thirty-five patients with AIDS who developed spontaneous PTX between January 1, 1988 and December 31, 1991, of whom 27 (77.1%) did so in the setting of Pneumocystis carinii pneumonia (PCP). Forty-one patients who were diagnosed as having PCP and did not develop PTX served as the control group. RESULTS: Using logistic regression, a history of cigarette smoking, aerosolized pentamidine treatment, and the observation of pneumatoceles by chest radiography were associated with an increased risk of PTX. Although not associated with an increased risk of occurrence of PTX, the use of systemic corticosteroids for PCP treatment was associated with a longer requirement for chest tube drainage. Although chest tube drainage alone was often successful, chemical and surgical pleurodesis was often effective in treating prolonged air leaks and was associated with a lower incidence of recurrent PTX, although this difference did not achieve statistical significance (p = 0.07). CONCLUSIONS: Patients at high risk of developing AIDS-related spontaneous PTX can be identified. Systemic corticosteroids may increase the risk of morbidity from AIDS-related PTX. Chemical and surgical pleurodesis may be of value in short-term treatment and in reducing the risk of recurrence.

AIDS-Related Opportunistic Infections↗
PubMed1994

Chronic pulmonary thromboembolism: detection of regional hypoperfusion with CT.

PURPOSE: To study the relationship of regional hypoperfusion and areas of decreased lung attenuation on computed tomographic (CT) scans of patients with chronic pulmonary thromboembolism. MATERIALS AND METHODS: Preoperative CT scans of five patients (four men and one woman, aged 29-72 years) with chronic pulmonary thromboembolism were reviewed and compared with axial single photon emission CT (SPECT) perfusion scans obtained at similar levels. Regions of varying attenuation and perfusion were scored on a three-point scale. RESULTS: In the five patients, 198 regions were identified. Of 176 abnormal regions at SPECT, 133 were abnormal at CT (sensitivity, 75.6%). Eleven of 22 regions interpreted as normal at SPECT were judged to have normal attenuation at CT (specificity, 50%). The overall accuracy of CT for detecting areas of hypoperfusion was 72.7% (P = .011). CONCLUSION: A mosaic pattern of lung attenuation at CT is a sign of variable regional perfusion and may suggest chronic pulmonary thromboembolism as a cause for pulmonary hypertension.

Chronic Disease↗
PubMed1994

Women and social security: a progressive approach.

This article explores some major assumptions underlying the Social Security system and alternative approaches to rendering the system more economically viable, meeting the income needs of the elderly and/or providing greater equity under its benefit and taxation provisions. It attempts to show that the current structure of Social Security not only reinforces but also exacerbates the underlying economic inequalities in our nation's political economy under the guise of a social insurance program. In addressing selected benefit and taxation issues, the article focuses on how working and older women are faring in the 1990s under the Social Security system. It argues that although the program theoretically is gender neutral, its impact is not. Women, particularly those who are single, are poorly served. The article concludes that a progressive restructuring of the Social Security system itself is imperative if we are to meet the needs of a large percentage of workers, older people, and the economic and social demands of the 1990s and beyond. It also offers some suggestions for such change.

Adult↗
PubMed1994

Differentiating glucose toxicity from glucose desensitization: a new message from the insulin gene.

Our perspective is that the concepts of glucose toxicity and glucose desensitization should be differentiated because they carry very different connotations. The term glucose desensitization most properly refers to a pharmacological event involving a temporary, readily induced, physiological and reversible state of cellular refractoriness because of repeated or prolonged exposure to high concentrations of glucose. The term glucose toxicity should be reserved for nonphysiological, irreversible alterations in cellular function caused by chronic exposure to high glucose concentrations. With regard to the pancreatic islet beta-cell, the mechanism of action for glucose desensitization seems most likely to be expressed at the level of the insulin exocytotic apparatus or insulin stores within the beta-cell, whereas the mechanism of action for glucose toxicity may be at the level of insulin gene transcription. This differentiation raises the possibility that exposure of patients to chronic hyperglycemia may cause glucose toxic effects on the process of insulin gene transcription and/or expression that are irreversible. If so, this may contribute to so-called secondary drug failure and, in any event, reemphasizes the need to intensify therapeutic efforts to better regulate glycemia in type II diabetes.

Animals↗
PubMed1993

Interpreting the mammogram report.

The standardization of imaging techniques, interpretation and reporting has become an important issue as the use of mammographic screening has increased. Each mammogram report should indicate whether the breast is fatty or consists of dense glandular tissue. A brief description of abnormalities should be followed by the conclusion and recommendations. Well-circumscribed lesions have a 98 percent benign rate; these lesions generally do not require biopsy but can be followed at six-month intervals for a period of time. The overall rate of malignancy for biopsies prompted by mammography is 20 to 35 percent. Lesions interpreted as highly suspicious are malignant in 75 to 90 percent of cases. Mammographically detected tumors are generally smaller than palpable tumors at the time of diagnosis. In addition, patients who have mammographically detected lesions are more often node-negative and therefore have a better prognosis than patients with palpable lesions.

Breast Diseases↗
PubMed1993

Chronic exposure of HIT cells to high glucose concentrations paradoxically decreases insulin gene transcription and alters binding of insulin gene regulatory protein.

Chronically culturing HIT-T15 cells in media containing high glucose concentrations leads to decreased insulin mRNA levels, insulin content, and insulin secretion. These changes can be prevented by culturing the cells in media containing lower glucose levels (Robertson, R. P., H.-J. Zhang, K. L. Pyzdrowski, and T. F. Walseth. 1992. J. Clin. Invest. 90:320-325). The mechanism of this seemingly paradoxical phenomenon was examined by transiently transfecting HIT cells with a chloramphenicol acetyl transferase (CAT) reporter gene controlled by the 5'-regulatory domain of the human insulin gene (INSCAT). Early passages of HIT cells readily expressed INSCAT, whereas late passages of cells chronically cultured in 11.1 mM glucose expressed only 28.7 +/- 2.3% (mean +/- SEM) of the CAT activity expressed in early passages. In contrast, late passages of HIT cells chronically cultured in 0.8 mM glucose retained the ability to express the INSCAT reporter gene to 69.6 +/- 10.0% of the CAT activity observed in early passages. The decrease in INSCAT expression in late passages of cells serially cultured in 11.1 mM glucose was associated with the inability to form a specific nuclear protein-DNA complex with the CT motifs of the human insulin promoter. Formation of this specific protein-DNA complex was preserved in late passages of HIT cells when serially cultured in 0.8 mM glucose. Mutations of the CT motifs caused markedly diminished CAT activity in all passages examined. These data indicate that chronic exposure of the beta cell to high glucose concentrations can paradoxically decrease insulin gene transcription, in part, by altering the ability of a regulatory protein (GSTF) to interact with the insulin gene promoter. This provides a potential mechanism for glucotoxic effects on the beta cell at the level of the insulin gene.

Animals↗
PubMed1991

The relationship of task and ego orientation to sportsmanship attitudes and the perceived legitimacy of injurious acts.

Nicholls's theory of achievement motivation (1989) assumes one's goal orientation in an achievement activity is consistent with one's views concerning what is acceptable behavior in that setting. The purpose of this study was to determine the relationship of a task and ego goal orientation (i.e., the tendency to focus on personal mastery or beating others, respectively) to sportsmanship attitudes and perceptions of the legitimacy of aggressive acts by testing this assumption in the context of interscholastic sport. Fifty-six male and 67 female high school basketball players completed a three-part questionnaire assessing (a) individual differences in goal orientation, (b) approval of "unsportsmanlike play/cheating," "strategic play," and "sportsmanship behaviors," and (c) subjective ratings of the legitimacy of intentionally injurious behaviors. All measures were basketball-specific. Results indicated a low task orientation and high ego orientation corresponded to an endorsement of unsportsmanlike play/cheating. Ego orientation positively related to the rating of aggressive acts as more legitimate. Gender differences in goal orientation, sportsmanship attitudes, and legitimacy ratings were observed.

Achievement↗
PubMed1989

Increase in Gs and cyclic AMP generation in HIT cells. Evidence that the 45-kDa alpha-subunit of Gs has greater functional activity than the 52-kDa alpha-subunit.

Cyclic AMP accumulation in response to forskolin, cholera toxin, or isoproterenol is dramatically increased in HIT T-15 cells, a clonal cell line of Syrian hamster pancreatic islet beta cells, as a function of passage number. Forskolin and cholera toxin elevate cyclic AMP levels 5- to 10-fold higher in later passages (87-100) than in earlier passages (70-80). A similar phenomenon is observed with isoproterenol (10 microM) which increases cyclic AMP levels 56-fold in older HIT cells (passage 94), whereas only marginally stimulating cyclic AMP production in younger cells (passage 70-82). To determine whether a change in the stimulatory or inhibitory guanine nucleotide regulatory proteins, Gs or Gi, was responsible for these observations, ADP-ribosylation of HIT cell membranes with cholera toxin and pertussis toxin was examined. All passages contained two cholera toxin substrates at 52 and 45 kDa. The amount of 52 kDa did not appear to change with passage number, but the amount of 45 kDa increased in the later passages (89 and 94). The ratio of 45 to 52 kDa cholera toxin substrate, as determined by densitometric analysis, increased from 0.1 in passages 70, 75, and 82 to 0.45 at passage 89. No passage related changes in a 40-kDa pertussis toxin substrate were observed. An increase in the amount of the 45-kDa alpha-subunit of Gs was confirmed on immunoblots using antisera specific for the alpha-subunits of Gs. The amount of functional Gs present in various HIT cell passages was examined by determining the extent to which extracts from HIT cell membranes reconstituted guanine nucleotide-sensitive adenylyl cyclase in S49 cyc- membranes. Extracts derived from passage 94 reconstituted three to four times more adenylyl cyclase activity in cyc- membranes than extracts from passages 70, 75, and 82. These data indicate that an increase in functional Gs in later passages may be the underlying cause for the increased responsiveness to isoproterenol and forskolin in later passages. These data also suggest that functional differences exist between the Gs alpha-subunits, with the smaller 45-kDa subunit being more efficacious in coupling to cyclic AMP synthesis than the larger 52-kDa subunit. This is a departure from the commonly held view that the two subunits have similar efficacies in stimulating adenylyl cyclase.

Adenylate Cyclase Toxin↗
PubMed1989

Computed tomography of the chest in the trauma patient.

Thirty-six (1.5%) of 2340 patients admitted to the Trauma Unit at UCSD Medical Center over a 26-month period had 46 chest CT scans. A retrospective review of these cases showed that CT was useful in the diagnosis and management of suspected post-traumatic infective complications, assessment of suspected sternoclavicular joint dislocation, and localisation of bullet fragments. Other unsuspected abnormalities (pneumothoraces, misplaced endotracheal tube, intraperitoneal air, and axillary vein disruption) were also well demonstrated. However, CT failed to demonstrate some skeletal injuries, in particular, manubriosternal joint dislocation and vertebral fracture. Our experience supports a role for chest CT in certain limited clinical situations following trauma.

Humans↗
PubMed1989

Computed tomography in the diagnosis of traumatic rupture of the thoracic aorta.

Over a 26-month period, 25 patients admitted to the Trauma Unit at UCSD Medical Center following blunt trauma were investigated for suspected traumatic rupture of the thoracic aorta by computed tomography (CT) of the chest. A retrospective review of these patients was performed. Twenty-one (84%) also had CT of other body areas, most commonly the head or abdomen. Nine of the 25 patients subsequently had aortography; in 15 patients the CT findings were felt at the time to exclude rupture, and one patient was not investigated further because of severe head injuries. In general, if CT failed to show a mediastinal haematoma, aortography was not performed. However, five patients with CT evidence of a haematoma, including two with vertebral fractures, were not investigated by aortography. Two of the 25 patients (8%) had angiographically proven aortic ruptures; in both CT had shown not only a haematoma but also an abnormal outline of the aorta on contrast-enhanced scans. The haematoma was large in one patient and small in the other. Although 10 of the 25 patients had unenhanced scans, no case of aortic rupture is known to have been missed. During the same study period, 47 patients were investigated for suspected aortic rupture solely by aortography. Four patients (8% of this group) had aortic rupture, and two had subclavian or innominate artery ruptures. Only a minority (approximately one-quarter) also had CT of the head or abdomen. The role of CT in the diagnosis of traumatic rupture of the aorta is critically assessed in the light of our experience and a review of the literature.

Aorta, Thoracic↗
PubMed1989

Chronic thromboembolic occlusion in the adult can mimic pulmonary artery agenesis.

In the first 100 patients operated on for C T-E PH, three were referred with the diagnosis of UPAA having been made elsewhere. We found that many features of these two conditions are so similar that differential diagnosis is very difficult. Shared features may include findings on chest x-ray film, pulmonary angiography, CT scan and MRI studies. Since the two conditions vary substantially with respect to the methods of potential surgical correction, recognition of this possible differential diagnostic dilemma is important.

Adult↗