In investigation of effector moieties involved in the induction of experimental allergic encephal... more In investigation of effector moieties involved in the induction of experimental allergic encephalomyelitis (EAE), we have previously reported that lymph node cells (LNC) from Lewis rats developing EAE release a factor into the supernatant medium that is capable of transferring histopathologic changes of EAE to recipient animals. This factor, termed EAE supernate transfer activity (EAE-STA), has been localized to the
Dysphagia is a common problem in patients with neurologic disease and is often associated with si... more Dysphagia is a common problem in patients with neurologic disease and is often associated with significant morbidity and mortality. To evaluate primary brain tumor patients who complained of dysphagia, we adapted grading scales for severity of complaint and level of alertness (scale of 1 to 4) and bedside swallowing assessment and videofluoroscopic examination (scales of 1 to 5). Over 13 months, we prospectively screened 117 patients for dysphagia. Seventeen of these (14.5%) complained of dysphagia (mean age, 50.2 years; range, 20 to 75); an additional six control patients were studied from a group with no dysphagic complaints. Scoring for severity of complaint (mean, 2.3) and level of alertness (mean, 2.2) was mild-moderate in the majority of patients. Eleven of 17 patients scored > or = grade 3 (mean 3.2, moderate impairment, requiring supervision) on bedside testing, and six of seven scored > or = grade 3 (mean 3.8, moderate-moderately severe abnormality, trace or frequent aspiration) during videofluoroscopic evaluation. Bedside testing scores of the study group differed significantly (p < 0.001) from those of the control group. Level of alertness correlated strongly with bedside (r = 0.794) and videofluoroscopic (r = 0.780) scoring. Primary brain tumor patients with dysphagia are likely to have impairment of swallowing out of proportion to their complaints and therefore are at risk for aspiration and nutritional compromise. We recommend that these patients undergo formal swallowing assessment followed by rehabilitation or implementation of alternative feeding methods.
Using a heteroduplex approach and direct sequencing, we have completed the screening of approxima... more Using a heteroduplex approach and direct sequencing, we have completed the screening of approximately 88% of the neurofibromatosis type 2 (NF2)-coding sequence of DNA extracted from 33 schwannomas from NF2 patients and from 29 patients with sporadic schwannomas. The extensive screening has resulted in the identification of 33 unique mutations. Similarly to other human genes, we have shown that the CpG sites are more highly mutable in the NF2 gene. The frequency, distribution, and types of mutations were shown to differ between the sporadic and familial tumors. The majority of the mutations resulted in protein truncation and were consistent with more severe phenotype, however three missense mutations were identified during this study and were all associated with milder manifestations of the disease.
... References. Acker, S. & Bracken, J. (2002). Digital learning objects: The buildin... more ... References. Acker, S. & Bracken, J. (2002). Digital learning objects: The building blocks of on-line course design (Journalism and Communication 850C, a graduate course offered Autumn quarter, 2002. ... Felder, R. & Soloman, B. (1999). Learning styles inventory. ...
Oral cavity cancers represent 2.5% of the cancers that occur in the United States and are ranked ... more Oral cavity cancers represent 2.5% of the cancers that occur in the United States and are ranked sixth worldwide. Since current therapeutic protocols are relatively ineffective, alternative strategies for prevention need to be developed and tested in appropriate animal models. In the study reported herein, the hamster cheek pouch (HCP) was used to evaluate the ability of black raspberries to inhibit oral cavity tumors. Male Syrian Golden hamsters, 3-4 weeks of age, were fed 5% and 10% lyophilized black raspberries (LBR) in the diet for two weeks prior to treatment with 0.2% 7,12-dimethylbenz(a) anthracene in dimethylsulfoxide and for 10 weeks thereafter. HCPs were painted 3X/week for eight weeks. The animals were sacrificed 12-13 weeks from the beginning of DMBA treatment and the number and volume of tumors (mm3) determined. There was a significant difference (p = 0.02) in the number of tumors between the 5% LBR and control groups (27 tumors/14 animals and 48 tumors/15 animals, resp...
Undersea & hyperbaric medicine: journal of the Undersea and Hyperbaric Medical Society, Inc
Neurological signs and symptoms are common in recreational divers with decompression illness (DCI... more Neurological signs and symptoms are common in recreational divers with decompression illness (DCI). The spectrum of neurological manifestations, temporal profile, and laboratory findings are described in a large series of 200 consecutive recreational divers treated for DCI. The Hyperbaric Medicine Unit charts of 200 recreational divers treated for DCI were reviewed and analyzed. The cohort was mainly male, with a median age of 40 years, and quite experienced, with a median of 100 prior dives. In 44 divers (22%) a rapid ascent was documented. The median time to onset of neurological symptoms was 60 minutes after surfacing. One hundred seventy-seven of 200 divers (88.5%) had at least one symptom of neurological DCI at presentation. The most common neurological manifestations were paresthesia, dysesthesia, incoordination, motor weakness, and dizziness. Paresthesias were associated with significantly younger (p = 0.003) and less experienced (p = 0.03) divers. Similar but less significan...
This paper presents an overview of modalities that can be used to make learning statistics fun. R... more This paper presents an overview of modalities that can be used to make learning statistics fun. Representative examples or points of departure in the literature are provided for no less than 20 modalities. Empirical evidence of effectiveness specific to statistics education is starting to emerge for some of these modalities – namely, humor, song, and cartoons. To reinforce their effectiveness as an intentional teaching tool, the authors offer practical implementation tips.
The generalization provided in this paper gives a bound on the intrinsic variability, η, that app... more The generalization provided in this paper gives a bound on the intrinsic variability, η, that applies to every bivariate distribution with finite second moments. Intrinsic variability is a key parameter in a variety of statistical situations as we demonstrate here by applying our bound to problems in time series, multiple regression, and the theory of rank tests. Because accurate estimation of η requires relatively large data sets, it may often be practical to examine a simple estimate of the lower bound on η. For this purpose we need only estimate a correlation rather than an entire regression function, and thus require less data.
The use of a statistical hypothesis test to check for a correlation between strength of opinion a... more The use of a statistical hypothesis test to check for a correlation between strength of opinion and issue preference in mail surveys is discussed. Under realistic assumptions, the presence of such correlation implies that there will be nonresponse bias in the survey estimates. As a choice of test statistic, Kendall’s tau has good power when the bias is of the same order of magnitude as the reported standard error of the preference estimate, which shows that statistical significance implies practical significance in this case.
Journal of Neuropathology and Experimental Neurology
Although there is much written about the molecular definitions of "primary" glioblastom... more Although there is much written about the molecular definitions of "primary" glioblastomas (GBM), there is little known about the histological features of this predominant subtype. We hypothesized that the "small cell architecture" would represent a histological feature of most primary GBMs. This was tested by comparing the presence of the small cell phenotype with the presence or absence of amplification of the epidermal growth factor receptor (EGFR), a common event in primary GBMs. After a pilot study that found a correlation between this small cell phenotype and EGFR amplification, we selected 9 pure small cell GBMs (SCGBM) and 12 non-SCGBMs to be studied for EGFR amplification by fluorescence in situ hybridization (FISH). In this set of 21 cases, 8 of 9 SCGBMs and 5 of 12 non-SCGBMs were amplified for EGFR. We then correlated the EGFR status of 79 GBMs unselected for their histological features from a set that had been previously characterized in regard to EGF...
PURPOSE: Oral squamous cell carcinoma (OSCC) is a significant worldwide health burden. Epidemiolo... more PURPOSE: Oral squamous cell carcinoma (OSCC) is a significant worldwide health burden. Epidemiologic studies show that diets rich in fruits and vegetables reduce cancer risk. Our laboratory has demonstrated that lyophilized black raspberries (LBR) inhibit OSCC cell growth in vitro. We hypothesize that clinical administration of topical LBR will modulate cancer-related genes towards a more normal expression profile. METHODS: A Phase I human trial was conducted to examine cancer-related genes expression before and after topical administration of LBR. OSCC patients (n=24) were administered three LBR troches q.i.d. between enrollment and surgery, and provided normal and tumor tissue biopsies. Affymetrix microarray analysis of an interim cohort (n=10) characterized global gene changes. DAVID analysis identified enriched biological themes and clustered annotation terms. Custom TaqMan Low-Density Arrays (TLDAs) were used to validate predicted LBR-responsive tumor biomarkers. Differences at...
This study examines statistics instructors' use of fun as well as their motivations, hesitati... more This study examines statistics instructors' use of fun as well as their motivations, hesitations, and awareness of resources. In 2011, a survey was administered to attendees at a national statistics education conference, and follow-up qualitative interviews were conducted with 16 of those (N = 249) surveyed to provide further context for interpreting the quantitative results. Motivations were similar for men and women, but female instructors admitted more hesitations in many areas. While many instructors are using or are open to using fun in the statistics classroom, the findings suggest that not having available resources at hand and not being aware of resources such as the CAUSEweb collection are major hesitations. Methods of alleviating hesitations are discussed.
The role of the hypothalamus-pituitary-adrenal (HPA) axis in regulating the growth of Mycobacteri... more The role of the hypothalamus-pituitary-adrenal (HPA) axis in regulating the growth of Mycobacterium avium in Mycobacterium bovis BCG-resistant and -susceptible congenic mice was evaluated. Restraint was used to activate the HPA axis, which resulted in an increase in the level of corticosterone in the plasma. Activation of the HPA axis increased the susceptibility of BALB/c.Bcgs mice to the growth of M. avium. In contrast, the growth of M. avium was not altered in BALB/c.Bcgr mice as a result of HPA activation. Adrenalectomy abolished the effect of HPA activation on mycobacterial growth, as did treatment of the mice with a glucocorticoid receptor antagonist, RU 486. Activation of the HPA axis also resulted in the increased susceptibility of splenic macrophages from Bcgs mice but not from Bcgr mice to M. avium growth in vitro. The production of tumor necrosis factor alpha and of reactive nitrogen intermediates by splenic macrophages from both strains of mice was suppressed as a result...
Duchenne and Becker muscular dystrophies (DMD and BMD) are caused by defects in the dystrophin ge... more Duchenne and Becker muscular dystrophies (DMD and BMD) are caused by defects in the dystrophin gene. About two-thirds of the affected patients have large deletions or duplications, which occur in the 5' and central portion of the gene. The nondeletion/duplication cases are most likely the result of smaller mutations that cannot be identified by current diagnostic screening strategies. We screened approximately 80% of the dystrophin coding sequence for small mutations in 158 patients without deletions or duplications and identified 29 mutations. The study indicates that many of the DMD and the majority of the BMD small mutations lie in noncoding regions of the gene. All of the mutations identified were unique to single patients, and most of the mutations resulted in protein truncation. We did not find a clustering of small mutations similar to the deletion distribution but found > 40% of the small mutations 3' of exon 55. The extent of protein truncation caused by the 3...
The macrophage plays a central role in the development of immune responses. Macrophages take up a... more The macrophage plays a central role in the development of immune responses. Macrophages take up and process antigen which is presented to antigen-responsive T lymphocytes in association with major histocompatibility complex class II (Ia) glycoproteins. We have investigated the effect of restraint stress on Ia expression by murine peritoneal macrophages. Stress resulted in a suppression of Ia expression which coincided with an increase in plasma corticosterone levels. In vitro experiments indicate that suppression of Ia expression can occur within 2 h after exposure to corticosterone. The suppression of this important aspect of macrophage function by stressors has important implications regarding the possible immunosuppressive effects of stress on the response of lymphocytes to antigens that depend on intact macrophage function.
In investigation of effector moieties involved in the induction of experimental allergic encephal... more In investigation of effector moieties involved in the induction of experimental allergic encephalomyelitis (EAE), we have previously reported that lymph node cells (LNC) from Lewis rats developing EAE release a factor into the supernatant medium that is capable of transferring histopathologic changes of EAE to recipient animals. This factor, termed EAE supernate transfer activity (EAE-STA), has been localized to the
Dysphagia is a common problem in patients with neurologic disease and is often associated with si... more Dysphagia is a common problem in patients with neurologic disease and is often associated with significant morbidity and mortality. To evaluate primary brain tumor patients who complained of dysphagia, we adapted grading scales for severity of complaint and level of alertness (scale of 1 to 4) and bedside swallowing assessment and videofluoroscopic examination (scales of 1 to 5). Over 13 months, we prospectively screened 117 patients for dysphagia. Seventeen of these (14.5%) complained of dysphagia (mean age, 50.2 years; range, 20 to 75); an additional six control patients were studied from a group with no dysphagic complaints. Scoring for severity of complaint (mean, 2.3) and level of alertness (mean, 2.2) was mild-moderate in the majority of patients. Eleven of 17 patients scored > or = grade 3 (mean 3.2, moderate impairment, requiring supervision) on bedside testing, and six of seven scored > or = grade 3 (mean 3.8, moderate-moderately severe abnormality, trace or frequent aspiration) during videofluoroscopic evaluation. Bedside testing scores of the study group differed significantly (p < 0.001) from those of the control group. Level of alertness correlated strongly with bedside (r = 0.794) and videofluoroscopic (r = 0.780) scoring. Primary brain tumor patients with dysphagia are likely to have impairment of swallowing out of proportion to their complaints and therefore are at risk for aspiration and nutritional compromise. We recommend that these patients undergo formal swallowing assessment followed by rehabilitation or implementation of alternative feeding methods.
Using a heteroduplex approach and direct sequencing, we have completed the screening of approxima... more Using a heteroduplex approach and direct sequencing, we have completed the screening of approximately 88% of the neurofibromatosis type 2 (NF2)-coding sequence of DNA extracted from 33 schwannomas from NF2 patients and from 29 patients with sporadic schwannomas. The extensive screening has resulted in the identification of 33 unique mutations. Similarly to other human genes, we have shown that the CpG sites are more highly mutable in the NF2 gene. The frequency, distribution, and types of mutations were shown to differ between the sporadic and familial tumors. The majority of the mutations resulted in protein truncation and were consistent with more severe phenotype, however three missense mutations were identified during this study and were all associated with milder manifestations of the disease.
... References. Acker, S. & Bracken, J. (2002). Digital learning objects: The buildin... more ... References. Acker, S. & Bracken, J. (2002). Digital learning objects: The building blocks of on-line course design (Journalism and Communication 850C, a graduate course offered Autumn quarter, 2002. ... Felder, R. & Soloman, B. (1999). Learning styles inventory. ...
Oral cavity cancers represent 2.5% of the cancers that occur in the United States and are ranked ... more Oral cavity cancers represent 2.5% of the cancers that occur in the United States and are ranked sixth worldwide. Since current therapeutic protocols are relatively ineffective, alternative strategies for prevention need to be developed and tested in appropriate animal models. In the study reported herein, the hamster cheek pouch (HCP) was used to evaluate the ability of black raspberries to inhibit oral cavity tumors. Male Syrian Golden hamsters, 3-4 weeks of age, were fed 5% and 10% lyophilized black raspberries (LBR) in the diet for two weeks prior to treatment with 0.2% 7,12-dimethylbenz(a) anthracene in dimethylsulfoxide and for 10 weeks thereafter. HCPs were painted 3X/week for eight weeks. The animals were sacrificed 12-13 weeks from the beginning of DMBA treatment and the number and volume of tumors (mm3) determined. There was a significant difference (p = 0.02) in the number of tumors between the 5% LBR and control groups (27 tumors/14 animals and 48 tumors/15 animals, resp...
Undersea & hyperbaric medicine: journal of the Undersea and Hyperbaric Medical Society, Inc
Neurological signs and symptoms are common in recreational divers with decompression illness (DCI... more Neurological signs and symptoms are common in recreational divers with decompression illness (DCI). The spectrum of neurological manifestations, temporal profile, and laboratory findings are described in a large series of 200 consecutive recreational divers treated for DCI. The Hyperbaric Medicine Unit charts of 200 recreational divers treated for DCI were reviewed and analyzed. The cohort was mainly male, with a median age of 40 years, and quite experienced, with a median of 100 prior dives. In 44 divers (22%) a rapid ascent was documented. The median time to onset of neurological symptoms was 60 minutes after surfacing. One hundred seventy-seven of 200 divers (88.5%) had at least one symptom of neurological DCI at presentation. The most common neurological manifestations were paresthesia, dysesthesia, incoordination, motor weakness, and dizziness. Paresthesias were associated with significantly younger (p = 0.003) and less experienced (p = 0.03) divers. Similar but less significan...
This paper presents an overview of modalities that can be used to make learning statistics fun. R... more This paper presents an overview of modalities that can be used to make learning statistics fun. Representative examples or points of departure in the literature are provided for no less than 20 modalities. Empirical evidence of effectiveness specific to statistics education is starting to emerge for some of these modalities – namely, humor, song, and cartoons. To reinforce their effectiveness as an intentional teaching tool, the authors offer practical implementation tips.
The generalization provided in this paper gives a bound on the intrinsic variability, η, that app... more The generalization provided in this paper gives a bound on the intrinsic variability, η, that applies to every bivariate distribution with finite second moments. Intrinsic variability is a key parameter in a variety of statistical situations as we demonstrate here by applying our bound to problems in time series, multiple regression, and the theory of rank tests. Because accurate estimation of η requires relatively large data sets, it may often be practical to examine a simple estimate of the lower bound on η. For this purpose we need only estimate a correlation rather than an entire regression function, and thus require less data.
The use of a statistical hypothesis test to check for a correlation between strength of opinion a... more The use of a statistical hypothesis test to check for a correlation between strength of opinion and issue preference in mail surveys is discussed. Under realistic assumptions, the presence of such correlation implies that there will be nonresponse bias in the survey estimates. As a choice of test statistic, Kendall’s tau has good power when the bias is of the same order of magnitude as the reported standard error of the preference estimate, which shows that statistical significance implies practical significance in this case.
Journal of Neuropathology and Experimental Neurology
Although there is much written about the molecular definitions of "primary" glioblastom... more Although there is much written about the molecular definitions of "primary" glioblastomas (GBM), there is little known about the histological features of this predominant subtype. We hypothesized that the "small cell architecture" would represent a histological feature of most primary GBMs. This was tested by comparing the presence of the small cell phenotype with the presence or absence of amplification of the epidermal growth factor receptor (EGFR), a common event in primary GBMs. After a pilot study that found a correlation between this small cell phenotype and EGFR amplification, we selected 9 pure small cell GBMs (SCGBM) and 12 non-SCGBMs to be studied for EGFR amplification by fluorescence in situ hybridization (FISH). In this set of 21 cases, 8 of 9 SCGBMs and 5 of 12 non-SCGBMs were amplified for EGFR. We then correlated the EGFR status of 79 GBMs unselected for their histological features from a set that had been previously characterized in regard to EGF...
PURPOSE: Oral squamous cell carcinoma (OSCC) is a significant worldwide health burden. Epidemiolo... more PURPOSE: Oral squamous cell carcinoma (OSCC) is a significant worldwide health burden. Epidemiologic studies show that diets rich in fruits and vegetables reduce cancer risk. Our laboratory has demonstrated that lyophilized black raspberries (LBR) inhibit OSCC cell growth in vitro. We hypothesize that clinical administration of topical LBR will modulate cancer-related genes towards a more normal expression profile. METHODS: A Phase I human trial was conducted to examine cancer-related genes expression before and after topical administration of LBR. OSCC patients (n=24) were administered three LBR troches q.i.d. between enrollment and surgery, and provided normal and tumor tissue biopsies. Affymetrix microarray analysis of an interim cohort (n=10) characterized global gene changes. DAVID analysis identified enriched biological themes and clustered annotation terms. Custom TaqMan Low-Density Arrays (TLDAs) were used to validate predicted LBR-responsive tumor biomarkers. Differences at...
This study examines statistics instructors' use of fun as well as their motivations, hesitati... more This study examines statistics instructors' use of fun as well as their motivations, hesitations, and awareness of resources. In 2011, a survey was administered to attendees at a national statistics education conference, and follow-up qualitative interviews were conducted with 16 of those (N = 249) surveyed to provide further context for interpreting the quantitative results. Motivations were similar for men and women, but female instructors admitted more hesitations in many areas. While many instructors are using or are open to using fun in the statistics classroom, the findings suggest that not having available resources at hand and not being aware of resources such as the CAUSEweb collection are major hesitations. Methods of alleviating hesitations are discussed.
The role of the hypothalamus-pituitary-adrenal (HPA) axis in regulating the growth of Mycobacteri... more The role of the hypothalamus-pituitary-adrenal (HPA) axis in regulating the growth of Mycobacterium avium in Mycobacterium bovis BCG-resistant and -susceptible congenic mice was evaluated. Restraint was used to activate the HPA axis, which resulted in an increase in the level of corticosterone in the plasma. Activation of the HPA axis increased the susceptibility of BALB/c.Bcgs mice to the growth of M. avium. In contrast, the growth of M. avium was not altered in BALB/c.Bcgr mice as a result of HPA activation. Adrenalectomy abolished the effect of HPA activation on mycobacterial growth, as did treatment of the mice with a glucocorticoid receptor antagonist, RU 486. Activation of the HPA axis also resulted in the increased susceptibility of splenic macrophages from Bcgs mice but not from Bcgr mice to M. avium growth in vitro. The production of tumor necrosis factor alpha and of reactive nitrogen intermediates by splenic macrophages from both strains of mice was suppressed as a result...
Duchenne and Becker muscular dystrophies (DMD and BMD) are caused by defects in the dystrophin ge... more Duchenne and Becker muscular dystrophies (DMD and BMD) are caused by defects in the dystrophin gene. About two-thirds of the affected patients have large deletions or duplications, which occur in the 5' and central portion of the gene. The nondeletion/duplication cases are most likely the result of smaller mutations that cannot be identified by current diagnostic screening strategies. We screened approximately 80% of the dystrophin coding sequence for small mutations in 158 patients without deletions or duplications and identified 29 mutations. The study indicates that many of the DMD and the majority of the BMD small mutations lie in noncoding regions of the gene. All of the mutations identified were unique to single patients, and most of the mutations resulted in protein truncation. We did not find a clustering of small mutations similar to the deletion distribution but found > 40% of the small mutations 3' of exon 55. The extent of protein truncation caused by the 3...
The macrophage plays a central role in the development of immune responses. Macrophages take up a... more The macrophage plays a central role in the development of immune responses. Macrophages take up and process antigen which is presented to antigen-responsive T lymphocytes in association with major histocompatibility complex class II (Ia) glycoproteins. We have investigated the effect of restraint stress on Ia expression by murine peritoneal macrophages. Stress resulted in a suppression of Ia expression which coincided with an increase in plasma corticosterone levels. In vitro experiments indicate that suppression of Ia expression can occur within 2 h after exposure to corticosterone. The suppression of this important aspect of macrophage function by stressors has important implications regarding the possible immunosuppressive effects of stress on the response of lymphocytes to antigens that depend on intact macrophage function.
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Papers by Dennis Pearl