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Biomedical subjects

D Olson

Publications and source records attributed to D Olson.

At least 55 records · Page 3Linked to original sources
PubMed1992

Inhibition of HIV infection by a novel CD4 domain 2-specific monoclonal antibody. Dissecting the basis for its inhibitory effect on HIV-induced cell fusion.

HIV use the CD4 molecule as their primary cellular receptor. Residues in the N-terminal domain (D1) of CD4 are crucial to HIV attachment through the gp120 envelope component. However, other regions of CD4 appear to be required subsequently for virus- and cell-cell fusion. Little is understood of the post-binding steps which may differ between HIV variants. We report a novel anti-CD4 mAb that does not block CD4/gp120 binding, but that does efficiently block both viral infection and cell-cell syncytia formation, and define its contact site as residues in CD4 D2 using both mouse/human CD4 chimeras and CD4 substitution mutants. We also investigated the basis for its antiviral effect. Using the CD4 D2 specific mAb, we identify another conserved step in HIV infection, as evidenced by its ability to neutralize a broad range of primary isolates and T cell-line passaged strains. Monovalent forms of the mAb were used to determine if its activity was due to masking of the D2 epitope, to steric inhibition, or bivalency. Our data indicate that both binding site and bivalency of the mAb underlie its potency. The need for bivalency is not simply explained by affinity, because monovalent forms can displace the intact mAb and reverse its protective effect. These results provide evidence that binding of the D2-specific mAb prevents structural alterations necessary for membrane fusion.

Animals↗
PubMed1992

Internalization of the urokinase-plasminogen activator inhibitor type-1 complex is mediated by the urokinase receptor.

The role of the urokinase receptor (uPAR) in the internalization of the urokinase-plasminogen activator inhibitor type-1 (uPA.PAI-1) complex has been investigated. First, exploiting the species specificity of uPA binding, we show that mouse LB6 cells (that express a mouse uPAR) were unable to bind or degrade the human uPA.PAI-1 complex. On the other hand, LB6 clone 19 cells, which express a transfected human uPAR, degraded uPA.PAI-1 complexes with kinetics identical to the human monocytic U937 cells. We also show by immunofluorescence experiments with anti-uPA antibodies that in LB6 clone 19 cells, the uPA.PAI-1 complex is indeed internalized. While at 4 degrees C uPA fluorescence was visible at the cell surface, shift of the temperature to 37 degrees C caused a displacement of the immunoreactivity to the cytoplasmic compartment, with a pattern indicating lysosomal localization. If uPA.PAI-1 internalization/degradation is mediated by uPAR, inhibition of uPA.PAI-1 binding to uPAR should block degradation. Three different treatments, competition with the agonist amino-terminal fragment of uPA, treatment with a monoclonal antibody directed toward the binding domain of uPAR or release of uPAR from the cell surface with phosphatidylinositol-specific phospholipase C completely prevented uPA.PAI-1 degradation. The possibility that a serpin-enzyme complex receptor might be primarily or secondarily involved in the internalization process was excluded since a serpin-enzyme complex peptide failed to inhibit uPA.PAI-1 binding and degradation. Similarly, complexes of PAI-1 with low molecular mass uPA (33 kDa uPA), which lacks the uPAR binding domain, were neither bound nor degraded. Finally we also show that treatment of cells with uPA.PAI-1 complex caused a specific but partial down-regulation of uPAR. A similar result was obtained when PAI-1 was allowed to complex to uPA that had been previously bound to the receptor. The possibility therefore exists that the entire complex uPA.PAI-1-uPAR is internalized. All these data allow us to conclude that internalization of the uPA.PAI-1 complex is mediated by uPAR.

Amino Acid Sequence↗
PubMed1992

A mutant p53 protein is required for maintenance of the transformed phenotype in cells transformed with p53 plus ras cDNAs.

Mutant p53 and activated ras cDNA clones cooperate to fully transform primary rat embryo fibroblasts in cell culture, whereas neither cDNA alone results in the full transformation of these cells. The mutant p53 protein may be required to initiate the transformation event with ras. Alternatively, mutant p53 gene expression may be required to maintain the properties of the transformed phenotype. To distinguish between these possibilities, primary rat embryo fibroblasts were transformed with mutant p53 plus ras cDNAs, where the expression of the p53 gene was regulated by an isopropyl beta-D-thiogalactoside-responsive promoter. When expression of the mutant p53 cDNA was inhibited and no detectable exogenous p53 protein was produced, both the growth rate and the morphology of the cells reverted to a normal phenotype. These results demonstrate that a mutant p53 protein is required for the maintenance of the transformed phenotype in cells transformed with p53 plus ras cDNAs.

Animals↗
PubMed1992

Production of the Mycotoxin Fumonisin B(1) by Alternaria alternata f. sp. lycopersici.

The mycotoxin fumonisin B(1), originally described as being produced by Fusarium moniliforme, was detected in liquid cultures of Alternaria alternata f. sp. lycopersici, a host-specific pathogen of tomato plants. The metabolite was detected by high-pressure liquid chromatography and mass spectrometry. Its identity was confirmed by fast atom bombardment and ion spray mass spectrometry, as well as parent-daughter tandem mass spectrometry. In three separate experiments, the concentrations found ranged between 5 and 140 ppm (mug/ml).

Journal Article↗
PubMed1992

Weight Cycling Practices and Long-term Health Conditions in a Sample of Former Wrestlers and Other Collegiate Athletes.

Weight cycling (repeated episodes of weight loss and regain) has been shown to reduce the resting metabolic rate in some chronic dieters. Concerns have been raised that wrestlers' repeated patterns of weight loss and gain may reduce metabolic rates and increase long-term health risks. We conducted this study to assess previous weight loss practices, current body weight, and incidence of chronic disease in a sample of male athletes who earned athletic letters in intercollegiate sports at the University of Wisconsin-Madison between 1950 and 1988. Survey questionnaires were mailed to 79 ex-wrestlers and 153 nonwrestling athletes, with responses from 60 wrestlers (76%) and 104 nonwrestlers (68%). We found no significant differences in weight gained after graduation (10.2 pounds for wrestlers and 8.6 pounds for nonwrestling athletes), current exercise practices, incidence of chronic disease, prevalence of obesity, and current dieting rates in this sample of former college athletes. Collegiate wrestlers gained an average of 16 pounds during the off-season. Most wrestlers reported that they lost between 3 and 11 pounds per match and that they used a combination of five or more weight loss techniques. Most frequently reported techniques included increasing exercise, restricting food, exercising in a hot environment, using a steam room or sauna, restricting fluids, and exercising in a rubber or plastic suit. Fewer wrestlers than nonwrestlers reported that they smoked tobacco. The health effects of changes in proportions of fat-free body mass after weight cycling were not addressed in this survey. The hypothesis that numerous cycles of weight loss and regain among wrestlers may result in long-term weight gain and/or increased risk of chronic disease was not supported by the results of this survey.

Journal Article↗
PubMed1991

Serum and follicular fluid (FF) estradiol (E2) levels in ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) conception cycles after pituitary suppression.

Initial hope that ovarian hyperstimulation syndrome (OHSS) would be less likely to occur after pituitary suppression with gonadotropin releasing-hormone agonists (GnRH-a) has not been substantiated. GnRH-a/human menopausal gonadotropin (hMG) protocols often lead to OHSS with markedly elevated circulating estradiol (E2) levels in susceptible patients. This study was undertaken to determine whether or not intrafollicular E2 secretion is increased in these cases. Fifty-two in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) conception cycles treated with GnRH-a/hMG were included in the study. GnRH-a, leuprolide, 0.5 mg, was administered subcutaneously from day 20 of the preceding cycle and the ovaries were stimulated with hMG, 75-225 IU bid intramuscularly, followed by human chorionic gonadotropin (hCG), 5000 IU. Twenty cycles (Group I) were associated with moderate or severe OHSS and 32 cycles (Group II) did not result in OHSS. E2 was measured in the serum on the day of hCG (day 0), on the day of oocyte retrieval (day 2), and at midluteal phase (days 6-8), as well as in the follicular fluid (FF) using a solid-phase direct RIA. Mean serum E2 was significantly higher at all three sampling times in Group I (OHSS) than in Group II. Both the number of follicles and the number of oocytes were also significantly higher in Group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Relationship between diabetes mellitus mortality rates and drinking water magnesium levels in Iowa.

A recent ecologic study has suggested a relationship between mortality from diabetes mellitus and levels of magnesium in drinking water. However, diabetes mortality rates were from aggregate data for the entire geographic area under study. The state of Iowa has data resources available to determine diabetes mortality rates for individuals on known water supplies in Iowa and magnesium levels for raw drinking water supplies. To determine the presence of this relationship in the state of Iowa, mortality rates from 1976 through 1985 for diabetes as an underlying cause of death and for major cardiovascular disease with diabetes as an ancillary cause of death were compared for individuals from towns in Iowa with populations of 1,000 to 10,000. At the stratification levels of magnesium in municipal drinking water used in this study, no significant differences were found in diabetes mortality rates.

Cardiovascular Diseases↗
PubMed1989

Should the elderly be resuscitated following out-of-hospital cardiac arrest?

PURPOSE: Elderly and younger patients who were successfully resuscitated and hospitalized following out-of-hospital cardiac arrest were studied to determine if there was a significant difference in hospital course and long-term survival between the two groups. PATIENTS AND METHODS: The study consisted of 214 consecutive patients, divided into two age groups: elderly (more than 70 years, n = 112) and younger (less than 70 years, n = 102). Hospital charts and paramedic run data were retrospectively reviewed for each patient and findings were compared between the two age groups. RESULTS: Prior to cardiac arrest, 47 of 112 (42 percent) elderly patients had a history of heart failure, compared with 19 of 102 (18 percent) younger patients, and were more commonly taking digitalis (51 percent versus 29 percent) and diuretics (47 percent versus 26 percent). Younger patients, however, more often had an acute myocardial infarction at the time of the cardiac arrest (33 percent versus 16 percent). At the time of cardiac arrest, 83 percent of younger patients demonstrated ventricular fibrillation, compared with 71 percent of the elderly. In contrast, electromechanical dissociation was five times more common in the elderly patients. Although hospital deaths were more common in the elderly (71 percent versus 53 percent), the length of hospitalization and stay in intensive care units were not significantly different between the age groups. The number of neurologic deaths was similar in both age groups, as were residual neurologic impairments. Only five elderly patients and six younger patients required placement in extended-care facilities. Calculated long-term survival curves demonstrated similar survival in both age groups, with approximately 65 percent of hospital survivors alive at 24 months after hospital discharge. CONCLUSION: Resuscitation of elderly patients in whom out-of-hospital cardiac arrest occurs is reasonable and appropriate, according to the findings of this study. Even though elderly patients are more likely than younger patients to die during hospitalization, the hospital stay of the elderly is not longer, the elderly do not have more residual neurologic impairments, and survival after hospital discharge is similar to that in younger patients.

Adult↗
PubMed1989

Electrocardiographic characteristics in EMD.

Little has been written concerning the initial electrocardiographic (EKG) characteristics and/or changes which occur as the result of treatment in the electromechanical dissociation (EMD) patient. The purpose of this retrospective study was to determine predictive indicators of successful resuscitation in EMD by evaluating various EKG parameters. During 72 months, ending December 31st, 1985, there were 503 non-poisoned, prehospital adult cardiac arrest patients whose initial rhythm was EMD. All patients had their initial prehospital EKG rhythm strip evaluated for rhythm type, rate, the presence of P waves, QT interval and QRS interval. In successfully resuscitated patients, the prehospital initial rhythm analysis and the rhythm analysis on emergency department presentation were compared. Successfully resuscitated patients presenting with EMD had significantly faster initial rates, higher incidences of P waves and average QRS and QT intervals shorter than patients not responding to therapy. Furthermore, successfully resuscitated patients had significantly increased heart rates, developed new onset of P waves, and shortened QT intervals in response to treatment. Successfully resuscitated and save patients had average initial and final QRS complex lengths within normal limits. Organized atrial activity on the initial EKG was also correlated with successful resuscitation. No patient with an initial EKG rhythm of second or third degree AV block survived to hospital discharge. No patient who presented to the emergency department with atrial fibrillation survived to hospital discharge. Similarly, supraventricular tachycaydia following resuscitative efforts appeared to be associated with a negative outcome. Rate normalization following treatment was correlated with save rate. Wide complex rhythms without atrial activity were most highly associated with unsuccessful resuscitation. We believe these observed electrocardiographic characteristics and/or changes in response to treatment may have predictive value in evaluating patients with EMD.

Arrhythmias, Cardiac↗
PubMed1989

The effect of bystander CPR on neurologic outcome in survivors of prehospital cardiac arrests.

The efficacy of CPR has been questioned. A major criticism is that neurologic outcomes have not been adequately studied. For a 26-month period, 138 patients from six major receiving hospitals were discharged alive following prehospital cardiac arrests. For 65/138 (47.1%) patients, either the patient or a direct family member was contacted for information concerning neurologic outcome. For 63/138 (45.7%) patients, contact with patient or family was unsuccessful, consequently neurologic outcome at time of discharge was obtained from the medical record. For 10/138 (7.2%) patients, no data on neurologic outcome was obtainable. Neurologic outcome was rated by a 5-point Cerebral Performance Categories Scale (CPC); (1) Minimal Disability; (2) Moderate; (3) Severe; (4) Vegetative; and (5) Brain Dead. The bystander/first responder CPR group had 55.1% CPC-1; 24.4% CPC-2; 16.7% CPC-3; and 3.8% CPC-4 outcomes. The bystander/first responder NO CPR group had 58.0% CPC-1; 18.0% CPC-2; 16.0% CPC-3; and 8.0% CPC-4 outcomes. There was no significant difference at any CPC level (P not significant). Furthermore, there was no statistical difference between either group when compared for age, response time, resuscitation time, witnessing of arrest or distribution of presenting rhythms. In conclusion, no significant effect in neurologic outcome among saved cardiac arrest victims was found between bystander/first responder CPR and bystander/first responder NO CPR groups in the paramedic program studied.

First Aid↗
PubMed1989

Control of lymphokine expression in T helper 2 cells.

In this report we present evidence that Con A-activated T helper 2 cells transcribe the interleukin 2 (IL-2) gene when cycloheximide is added 3 hr after stimulation. This IL-2 mRNA can be translated into functional protein. However, no steady-state mRNA for gamma-interferon can be detected under the same experimental conditions. Furthermore, when cycloheximide is administered at time 0 of activation, no IL-2 mRNA is seen. Nuclear run-on experiments indicate that IL-2 transcription in T helper 2 cells depends on the presence of cycloheximide. It is likely, therefore, that activation of T helper 2 cells leads to the production of a labile regulatory protein that represses the expression of the IL-2 gene. These findings provide insight into the molecular mechanism that governs the differentiation of interleukin 4-producing T helper 2 cells from IL-2-producing precursor cells.

Animals↗
PubMed1988

Inhibition of growth of two human pancreatic adenocarcinomas in vivo by somatostatin analog SMS 201-995.

Somatostatin inhibits hormone secretion from gastrointestinal endocrine tumors. The purpose of this study was to determine whether SMS 201-995, a long-acting analog, would inhibit the growth of pancreatic adenocarcinomas. Two human pancreatic cancers grown in nude mice were studied: SKI, which has cholecystokinin receptors, and CAV, which does not. Tumors were implanted in groups of six mice each. Treatment groups received SMS 201-995 (100 micrograms/kg three times daily) by intraperitoneal injections and control animals received saline solution. Tumor area was measured twice weekly. After 7 weeks, the tumors and mouse pancreases were excised, weighed, and analyzed for protein and RNA and DNA content. In a second set of experiments, treatment was begun 21 days after transplantation. Mean body weights between groups were not different in any experiment. With treatment beginning on the day of transplantation, the tumor areas of SKI and CAV cancers were reduced by the third and fifth weeks of treatment, respectively. Tumor doubling times were prolonged with treatment in both SKI tumors (5 days) and CAV tumors (6 days). In the SKI treatment groups, tumor weight (52 percent), RNA content (72 percent), and DNA content (60 percent) were decreased at sacrifice compared with those of the control groups. In the CAV treatment group, the mean tumor weight (55 percent) and protein (48 percent), RNA (67 percent) and DNA contents (60 percent) were decreased compared with the CAV control group. Tumor growth of SKI and CAV cancers was also inhibited when treatment was delayed 21 days after transplantation. We conclude that these effects are not mediated by inhibition of cholecystokinin, as seen by similar inhibitory effects on both tumors. Treatment with SMS 201-995 may be an effective hormonal therapy in patients with pancreatic cancers.

Adenocarcinoma↗
PubMed1988

Prehospital external cardiac pacing: a prospective, controlled clinical trial.

This prehospital prospective, controlled study was conducted to determine if prehospital cardiac pacing affects survival. The study involved 239 patients, 226 pulseless, nonbreathing patients (rhythms of asystole and electromechanical dissociation with heart rates less than 70) and 13 patients with hemodynamically significant bradycardia (heart rate less than 60; blood pressure less than 90 mm Hg; not responding to atropine). Patients were assigned to treatment or control groups on an every-other-day basis. One hundred three patients were treated with an external cardiac pacing device; 22 (21.4%) were resuscitated (arrival at admitting hospital with pulse and blood pressure) and seven (6.8%) were saved (survival to hospital discharge). One hundred thirty-six patients were not paced and served as controls; 28 (20.6%) were resuscitated (P = .90) and six (4.4%) were saved (P = .71). Analysis of pacing times showed increased resuscitation in patients paced early. All surviving paced patients were paced in 17 minutes or less. Analysis of rhythm subgroups showed no significant difference in the resuscitation or survival rates of paced and control groups for primary asystole, primary electromechanical dissociation, and secondary asystole and electromechanical dissociation occurring after countershock treatment of ventricular fibrillation when compared respectively. However, among patients with hypotensive bradycardia, six of six paced patients were resuscitated and five were saved, while only two of seven controls were resuscitated (P = .01) and one was saved (P = .01). Interpretation of the bradycardic patient data is limited by inequalities noted between control and treatment groups with regard to the administration of isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)

Bradycardia↗
PubMed1987

The epidemiology of nosocomial Pseudomonas cepacia infections: endemic infections.

Pseudomonas cepacia has recently emerged as an important nosocomial pathogen. We analyzed a national nosocomial infections database, the National Nosocomial Infections Surveillance (NNIS) system, to describe the epidemiology of endemic nosocomial P. cepacia infections. Between 1980 and 1985, the P. cepacia nosocomial infection rate was 2.4 per 100,000 patient discharges. During this period, there was a significant increase in the P. cepacia infection rate. The highest infection rate was reported from large medical school-affiliated hospitals. Over 90% of the infections were reported from medicine and surgery services. The most frequently reported site of infection was the lower respiratory tract (31%), followed by blood (20%) and the urinary tract (20%). Nosocomial P. cepacia infections are often associated with mortality, particularly when they involve the lung. These data confirm the hypothesis that P. cepacia is an emerging nosocomial pathogen and suggest that the epidemiology of endemic infections differs from that reported for epidemic infections.

Cross Infection↗