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Biomedical subjects

James Thompson

Publications and source records attributed to James Thompson.

17 recordsLinked to original sources
PubMed2023

The Palestinian primary ciliary dyskinesia population: first results of the diagnostic and genetic spectrum.

BACKGROUND: Diagnostic testing for primary ciliary dyskinesia (PCD) started in 2013 in Palestine. We aimed to describe the diagnostic, genetic and clinical spectrum of the Palestinian PCD population. METHODS: Individuals with symptoms suggestive of PCD were opportunistically considered for diagnostic testing: nasal nitric oxide (nNO) measurement, transmission electron microscopy (TEM) and/or PCD genetic panel or whole-exome testing. Clinical characteristics of those with a positive diagnosis were collected close to testing including forced expiratory volume in 1 s (FEV1) Global Lung Index z-scores and body mass index z-scores. RESULTS: 68 individuals had a definite positive PCD diagnosis, 31 confirmed by genetic and TEM results, 23 by TEM results alone, and 14 by genetic variants alone. 45 individuals from 40 families had 17 clinically actionable variants and four had variants of unknown significance in 14 PCD genes. CCDC39, DNAH11 and DNAAF11 were the most commonly mutated genes. 100% of variants were homozygous. Patients had a median age of 10.0 years at diagnosis, were highly consanguineous (93%) and 100% were of Arabic descent. Clinical features included persistent wet cough (99%), neonatal respiratory distress (84%) and situs inversus (43%). Lung function at diagnosis was already impaired (FEV1 z-score median -1.90 (-5.0-1.32)) and growth was mostly within the normal range (z-score mean -0.36 (-3.03-2.57). 19% individuals had finger clubbing. CONCLUSIONS: Despite limited local resources in Palestine, detailed geno- and phenotyping forms the basis of one of the largest national PCD populations globally. There was notable familial homozygosity within the context of significant population heterogeneity.

Journal Article↗
PubMed2005

Dermatofibrosarcoma protuberans of the face: surgical management.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive, rarely metastatic, spindle cell tumor. It is most commonly found on the trunk and rarely on the head and neck. Recurrence has been found to be more common in the head and neck region, which may be attributable to delayed patient presentation or a reluctance for wide excision in that region. The authors report a rare case of DFSP presenting as a large mass of the face. Surgical treatment required aggressive local resection of the tumor, including the underlying maxillary antrum. The soft tissue was cleared by Mohs technique. More than one procedure was required to obtain clear bone margins. Adjuvant radiation therapy was used to gain local control. Reconstruction was performed using a cheek advancement flap, as well as a forehead flap and split-thickness graft to the donor site.

Dermatofibrosarcoma↗
PubMed2005

Lifetime prevalence of pathological gambling among american Indian and Hispanic American Veterans.

OBJECTIVES: We examined the prevalence and clinical correlates of pathological gambling among 1228 American Indian and Hispanic American veterans in the southwest and north central regions of the United States. METHODS: We surveyed a community sample of American Indian and Hispanic American veterans to obtain data on psychiatric disorder and treatment. RESULTS: American Indian veterans had a 10% lifetime prevalence of pathological gambling. The Hispanic American lifetime prevalence was less than that of the American Indian veterans but higher than the prevalence found for Hispanic American veterans in other surveys. Comorbid conditions associated with pathological gambling included substance, mood, and antisocial personality disorders. Ready access to casino gambling may encourage, support, or contribute to high rates of pathological gambling in both men and women. CONCLUSIONS: A 70% lifetime comorbidity of psychiatric disorders suggests that early interventions for pathological gambling should consider common psychiatric conditions rather than focusing on pathological gambling alone.

Adolescent↗
PubMed2004

EEG and postural correlates of mild traumatic brain injury in athletes.

Mild traumatic brain injury (MTBI), or concussion, is one of the least understood injuries facing the neuroscience and sports medicine community today. The notion of transient dysfunction and rapid symptom resolution is misleading since symptom resolution is not indicative of injury resolution. Our working hypothesis is that there are residual postural and EEG abnormalities in concussed individuals that could be reliably assessed using appropriate research methodology. This paper presents combined postural and electroencephalographic (EEG) findings suggesting the persistent functional deficits in athletes suffering from MTBI. Twelve concussed athletes and twelve normal controls participated in the study. There was a decrease in EEG power in all bandwidths studied in concussed subjects, especially in standing postures. This was accompanied by sustained postural instability especially under the no vision testing condition. Overall, this study demonstrated the presence of long-term functional abnormalities in individuals suffering from mild traumatic brain injury.

Adolescent↗
PubMed2004

Stop Hypertension with the Acupuncture Research Program (SHARP): clinical trial design and screening results.

Hypertension is a major public health problem with serious medical and financial consequences. Barriers to successful conventional pharmacological treatment include side effects, out-of-pocket expenses, patient noncompliance and insufficient dosages. Acupuncture has been studied as an alternative therapy for controlling blood pressure (BP) but previous studies have serious methodological limitations. This paper describes the design of the Stop Hypertension with the Acupuncture Research Program (SHARP) trial, a pilot randomized clinical trial designed to gather preliminary data regarding the efficacy of traditional Chinese medicine (TCM)-based acupuncture for control of essential hypertension. The design of the SHARP trial balanced rigorous clinical trial methodology with principles of TCM. Eligible participants had systolic BP (SBP) 140-179 mm Hg and diastolic BP (DBP) 90-109 mm Hg in the absence of antihypertensive therapy. Following screening, participants were randomized to one of three groups: individualized, standardized or control acupuncture. Treatments were designed according to principles of TCM; nonspecific effects associated with the interventions were standardized across the randomized groups. For individualized acupuncture, points were tailored to each participant. Standardized acupuncture used a prespecified set of points. The invasive sham control acupuncture regimen was designed to be non-active. Each participant received a "prescription" for individualized acupuncture from an acupuncturist who was masked to treatment assignment, and was subsequently treated by an independent acupuncturist. Patients and those assessing BP were masked to treatment group. Acupuncture was delivered twice a week for 6 weeks. Follow-up visits were every 2 weeks to week 10 and then at months 4, 6, 9 and 12. The primary endpoint will be change in SBP from baseline to 10 weeks. DBP, BP trajectories over the 12-month follow-up and antihypertensive medication requirements will also be examined. Initial contact was documented for 1442 prospective participants from March 2001 to April 2002; 424 provided informed consent and 192 were ultimately randomized.

Acupuncture Therapy↗
PubMed2004

Premalignant lesions in the contralateral ovary of women with unilateral ovarian carcinoma.

OBJECTIVES: A limited number of studies have looked at premalignant lesions of ovaries and the results are conflicting. Our goal is to identify, histologically and by immunohistochemistry, any features that may represent premalignant changes in the ovaries. METHODS: Our cases included 29 patients with unilateral ovarian cancer. These were compared to 19 controls that had unilateral benign ovarian pathology and to 39 controls with bilateral normal ovaries. Tissue sections from the contralateral normal ovary were examined. Analysis of histological features and immunohistochemical staining for the apoptosis inhibitor Bcl-2, the proliferation marker Ki-67 and the tumor suppressor gene p53 was performed. RESULTS: Epithelial stratification, nuclear atypia, and inclusion cysts were more often seen in the cases than in the two control groups. Epithelial stratification and nuclear atypia was statistically significantly more common among the cases than the normal controls. Inclusion cysts were present in more of the cases (P = 0.017) and in higher numbers than in the normal controls. Bcl-2 overexpression was statistically more commonly seen in the cases with contralateral ovarian cancer (39%) than in the normal controls (15%), while it was present in 28% of cases with contralateral benign pathology. CONCLUSIONS: Epithelial alterations and Bcl-2 overexpression was seen in all three groups studied. However, the epithelial alterations and Bcl-2 overexpression was more commonly seen in the contralateral ovary of women with unilateral ovarian cancer. This suggests an association between these changes and ovarian cancer. Although it is tempting to label the above changes premalignant, women with the above changes are at possibly higher risk of developing ovarian cancer rather than having acquired an oncogenic change that would inevitably lead to ovarian cancer.

Apoptosis↗
PubMed2004

Clinical classification of positional plagiocephaly.

Positional plagiocephaly deformities have increased dramatically in all craniofacial clinics in the United States. There are multiple methods for evaluating the degree of deformity, all of which are expensive, time consuming, and have poor reproducibility. We present a clinical classification of plagiocephaly deformities that we have employed since 1998. The classification allows us to quantitate the degree of deformity in these children at any given time, to reliably determine quantitative changes from evaluation to evaluation. The technique is highly reproducible, cost effective and readily understandable to the family, as well as referring physicians.

Communication↗
PubMed2003

Comparative molecular analysis of loss of heterozygosity in adenocarcinoma in bile duct brushings and corresponding surgical pathology specimens.

BACKGROUND: Bile duct brushing is the procedure of choice for the assessment of neoplasia of the biliary and pancreatic ducts. Conventional cytopathologic evaluation has been reported to have high specificity but relatively low sensitivity. Although a number of molecular studies regarding biliary tract tissue specimens have been performed, to the authors' knowledge their precise applicability to cytopathology specimens has not been critically analyzed. METHODS: Bile duct brushing specimens with the cytopathologic diagnosis of "suspicious" or "positive for malignant cells" along with corresponding surgical pathology specimens demonstrating adenocarcinoma were searched for in the files of UPMC-Presbyterian Hospital for the years 1990-1996. Tumor cells from representative cytopathology and histology slides were microdissected and analyzed for loss of heterozygosity (LOH) in a panel of microsatellite markers. The results obtained from cytopathologic and surgical pathology specimens were compared. RESULTS: Eight paired surgical and cytopathology cases of adenocarcinoma involving the biliary tract were identified. The fractional allelic loss (FAL) for the surgical specimens (FAL-S) ranged from 12.5-71.4% and the FAL for the cytopathology specimens (FAL-C) ranged from 25-71.4%. However, when evaluating the actual loci of LOH, the concordance rate of the surgical and cytopathology specimens ranged from 71.4-100% (mean, 88.6%). Only 3 of the 8 cases (37.5%) were found to have identical matching of the LOH loci. CONCLUSIONS: Although the overall concordance rate of LOH in biliary cytology and surgical specimens by molecular analysis is relatively high, the issue of molecular tumoral heterogeneity must be considered if clinical decisions are to be based exclusively on cytopathologic analysis.

Adenocarcinoma↗
PubMed2003

Surviving a disaster.

Explore the source record for details and available documents.

Adaptation, Psychological↗
PubMed2003

Attenuation of androgen receptor-dependent transcription by the serine/threonine kinase Pim-1.

Androgens play a key role in the regulation of the normal prostate as well as in the promotion and progression of prostate cancer. Recently, an oncogenic serine/threonine kinase, Pim-1, was reported to be overexpressed in prostate cancer. To elucidate whether Pim-1 is capable of modulating androgen signaling, we studied the effects of Pim-1 on androgen receptor (AR)-dependent transcription. Under transient transfection conditions, Pim-1 attenuated transcriptional activity of AR in a dose-dependent fashion in PC-3, HeLa, and COS-1 cells, whereas a kinase-negative mutant of Pim-1, Pim-1(K67M), showed no repressive activity. In contrast, ectopic expression of Pim-1 did not influence the activity of endogenous AR in LNCaP cells. This was, however, not a result of the T877A mutation present in AR of LNCaP cells, because that AR mutant was repressed by Pim-1 as efficiently as wild-type AR when expressed in PC-3 prostate cancer cells. Pim-1 inhibited AR mutants devoid of the ligand-binding domain or the core amino-terminal transactivation function but failed to influence the DNA binding of AR. Because we found no evidence for phosphorylation of AR by Pim-1 or for direct interaction between these proteins, Pim-1 is likely to influence AR activity via an indirect mechanism, possibly involving phosphorylation of a coregulator and/or a component of the transcription machinery. Overexpression of Pim-1 may thus attenuate androgen response during progression of prostate cancer in a cell context-dependent fashion.

Animals↗
PubMed2003

Androgen receptor mutations in high-grade prostate cancer before hormonal therapy.

Androgen action is mediated through androgen receptor (AR), which appears to undergo structural and functional alterations during prostate cancer (CaP) progression. AR mutations have been infrequently reported in CaP before hormonal therapy, but in untreated, advanced tumors AR mutations are suggested to be more common. To investigate the frequency of AR mutations in aggressive CaP before hormonal therapy, we have analyzed AR coding region for aberrations in 21 paraffin-embedded prostate carcinoma samples (14 primary tumors, 7 metastases) of poor histologic differentiation. Single-stranded conformational polymorphism and sequencing analyses revealed AR missense mutations in 29% (4/14) of the primary tumors and in one (14%) metastasis. Mutations resided in the transactivation domain and in the hinge region. One of the hinge region mutants, Ser646Phe, that was identified in a patient with short endocrine therapy response, exhibited a markedly increased transcriptional activity on single androgen response element-containing promoters. In conclusion, AR mutations are frequent in high-grade CaP before initiation of hormonal therapy, and these mutations may play a role in poor therapy response and emergence of hormone-refractory CaP in some cases.

Adenocarcinoma↗
PubMed2003

Effects of static electromagnetic fields on characteristics of MG-63 osteoblasts grown in culture.

The effects of static electromagnetic fields (SEFs) on MG-63, a human osteoblast cell-line, were investigated. We examined proliferation, proline uptake and gene expression in an SEF approximately 1/728th the intensity of those previously reported. Cells were placed within an SEF apparatus (average field intensity of 0.618mT) with appropriate controls. Proliferation was measured by 3H-thymidine incorporation and showed a 34% decrease in cells exposed to SEF (P = .0001; N = 3). Proline, a major component of collagen necessary for bone formation by osteoblasts, incorporation was reduced 37% (P = 0.006; N = 3). Reverse-transcription-polymerase chain reaction revealed that collagen I, alkaline phosphatase, parathyroid hormone-receptor, and osteocalcin mRNA's were down regulated with the low intensity SEF. Exposure to very low SEFs affects the MG-63 osteoblasts in a manner that may be detrimental to bone formation.

Bone Neoplasms↗
PubMed2002

Bcl-2 expression delays hepatocyte cell cycle progression during liver regeneration.

Bcl-2 is the prototype of a family of genes that prevent apoptosis. However, several reports indicate that Bcl-2 may also act as a cell cycle modulator. In several human tumors, Bcl-2 expression correlates with a more favorable prognosis and lower tumor proliferative activity. We have shown that Bcl-2 expression delays liver tumor development in transgenic mice even when the gene is turned on shortly before the time of tumor development. We hypothesized that Bcl-2 may delay liver tumorigenesis by interfering with hepatocyte proliferation. To test whether Bcl-2 expression may act on hepatocyte replication we studied liver regeneration in Bcl-2 transgenic mice and wild-type littermates. DNA replication was delayed by approximately 8 h in Bcl-2 transgenic mice compared to the timing of the response in wild-type littermates. Cyclin D expression showed no alterations in the regenerating liver of Bcl-2 transgenic mice. In contrast, there was a delay in the expression of p107, cyclin E and in the activity of cyclin E/cdk 2 activity. These results show that Bcl-2 expression delays cell cycle progression in hepatocytes and suggests that it acts at a step involving cyclin E and p107.

Animals↗
PubMed2002

Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia.

Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electrophysiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia-hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included. Under basal conditions, the authors found the metabolic milieu in the brain to be strikingly different from that in the circulation. In contrast to plasma, lactate levels in brain ECF were threefold higher than glucose. Results from complementary studies in rats were consistent with the human data. During the hyperglycemia-hypoglycemia clamp study the relationship between plasma and brain ECF levels of glucose remained similar, but changes in brain ECF glucose lagged approximately 30 minutes behind changes in plasma. The data demonstrate that the brain is exposed to substantially lower levels of glucose and higher levels of lactate than those in plasma; moreover, the brain appears to be a site of significant anaerobic glycolysis, raising the possibility that glucose-derived lactate is an important fuel for the brain.

Adolescent↗
PubMed2002

Perceived barriers to VA mental health care among Upper Midwest American Indian veterans: description and associations.

OBJECTIVES: This community-based study was undertaken to understand why Native-American veterans in the Upper Midwest choose not to use VA mental health services despite high rates of certain psychiatric disorders. RESEARCH DESIGN: A sample consisting of 543 Native-American veterans was obtained using a focused-intensive nonprobability sampling method, structured to over-sample urban and female veterans. Data sources included (1) interview (ie, an open-ended query regarding barriers to VA mental health care), (2) questionnaire (demography, psychiatric rating scales), and (3) computer-based diagnostic questionnaire, the Quick Diagnostic Interview Schedule, and a treatment questionnaire. RESULTS: These data confirmed that Native-American veterans were less apt to employ VA mental health services as compared with other professional and nonprofessional mental health services. Perceived barriers to VA mental health care were coded using a schema developed among Native American and Hispanic VA workers. Types of perceived barriers were qualitatively similar to those obtained from the VA workers, ie, barriers in the VA system, among Native-American veterans themselves, in VA staff members, and among Native American families and communities. Demographic and clinical characteristics among these 543 veterans were not associated with presence-versus-absence of barrier reporting. Among those who did report any barriers, veterans who used more traditional-alternative-complementary (TAC) care reported more barriers than did other veterans. Secondary analysis of those who reported barriers and used TAC revealed that this group had high current rates of Mood Disorder and PTSD symptoms, and high lifetime rates of PTSD and Mood Disorder. Although this latter group had tended to use VA mental health services in the past, they had generally not used them in the last year.

Adult↗
PubMed2002

Pattern of somatic androgen receptor gene mutations in patients with hormone-refractory prostate cancer.

Progression to hormone-refractory growth of prostate cancer has been suggested to be mediated by androgen receptor (AR) gene alterations. We analyzed AR for mutations and amplifications in 21 locally recurrent prostate carcinomas treated with orchiectomy, estrogens, or a combination of orchiectomy and estramustine phosphate using fluorescence in situ hybridization, single-strand conformation polymorphism, and DNA sequence analyses. Amplification was observed in 4 of 16 (25%) and amino acid changing mutations was observed in 7 of 21 (33%) of the tumors, respectively. Two (50%) tumors with AR amplification also had missense mutation of the gene. Four of five (80%) cancers that were treated with a combination of orchiectomy and estramustine phosphate had a mutation clustered at codons 514 to 533 in the N-terminal domain of AR. In functional studies, these mutations did not render AR more sensitive to testosterone, dihydrotestosterone, androstenedione, or beta-estradiol. Tumors treated by orchiectomy had mutations predominantly in the ligand-binding domain. In summary, we found molecular alterations of AR in more than half of the prostate carcinomas that recurred locally. Some tumors developed both aberrations, possibly enhancing the cancer cell to respond efficiently to low levels of androgens. Furthermore, localization of point mutations in AR seems to be influenced by the type of treatment.

Estramustine↗