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Biomedical subjects

S Dougherty

Publications and source records attributed to S Dougherty.

At least 19 recordsLinked to original sources
PubMed2000

Infantile refsum disease in four Amish sibs.

Infantile Refsum disease (IRD) appears with varying degrees of impaired vision, hearing loss, developmental delays, and neuromotor deficiencies. We report on four Amish sibs with IRD from a consanguineous marriage; biochemical testing supported the diagnosis of IRD. Of particular interest in this sibship are characteristic poorly formed yellow-orange teeth in at least three of the four affected sibs and behavior problems in the affected females.

Adolescent↗
PubMed1998

Undetectable serum prostate-specific antigen associated with metastatic prostate cancer: a case report and review of the literature.

A 63-year-old man, who had undergone prostatectomy for prostate cancer that was positive for prostate-specific antigen (PSA) was examined and found to have metastatic disease, proven radiologically and pathologically, but with an undetectable PSA and highly elevated prostatic acid phosphatase (PAP). Prostatic acid phosphatase levels fell in response to chemotherapy but his clinical status continued to deteriorate. A review of the literature is presented and several possible explanations for PSA remaining undetectable in these situations are discussed. The authors conclude that although PSA can be used to monitor the majority of patients postprostatectomy, physicians may still need to rely on clinical suspicion, serum PAP, and bone scan for the detection of recurrent disease.

Acid Phosphatase↗
PubMed1998

Effect of music on spatial performance: a test of generality.

Previous attempts by various researchers to replicate the enhancement of spatial performance following 10 min. exposure to music have been inconsistent in their findings. In the present study 16 subjects showed reliable improvement on a paper-folding-and-cutting task after listening to Mozart's Sonata for Two Pianos in D major, as employed by others. The enhanced performance was also noted for 16 other subjects after listening to a contemporary selection having similar musical characteristics. In both cases the control procedure included 10 min. of listening to a progressive relaxation tape.

Humans↗
PubMed1996

Analysis of 3p allelic loss in papillary and nonpapillary renal cell carcinomas. Correlation with tumor karyotypes.

Nonpapillary renal cell carcinomas (RCCs) are characterized by deletions of the short arm of chromosome 3 (3p) and papillary RCCs by increased numbers of selected chromosomes. Although recent molecular genetic studies have reported some papillary RCCs to show loss of heterozygosity (LOH) on 3p, a 3p deletion has not been demonstrated in a papillary RCC by karyotype analysis. To investigate this apparent discrepancy between molecular methods and chromosomal changes in the genetic evaluation of RCC, a series of 13 papillary and nonpapillary RCCs was investigated for 3p LOH by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis and for 3p and 3q LOH by microsatellite analysis. Karyotypes were obtained in six cases. Loss of 3p but not of 3q alleles was found in 8 of 10 nonpapillary RCCs. The region of overlapping deletion was 3p14--p21, and in six cases the deletion involved 3pter loci. One papillary RCC displayed 3p and 3q LOH, but the tumor had two morphologically normal chromosomes 3 and several trisomies. This indicated that nondisjunction of a chromosome from one parent compensated a whole chromosome loss from the other parent during tumor development. LOH in this papillary RCC constituted a reduction of chromosome 3 alleles to homozygosity, but the karyotype change, consisting of an increased number of whole chromosomes and an absence of a structural chromosome 3 abnormality, is regarded as being more characteristic of papillary than nonpapillary RCC.

Alleles↗
PubMed1995

DNA ploidy and proliferation heterogeneity in human prostate cancers.

DNA ploidy determinations have been shown to have clinical application in predicting disease progression, survival, or response to anti-androgen therapies in prostate carcinomas. Since intra-tumor heterogeneity may have a profound effect on DNA measurements, we determined the frequency of DNA ploidy and proliferation (here S-phase fraction) heterogeneity in early prostatic carcinomas, and estimated the potential impact of heterogeneity on predicting disease course, survival, or response to therapy. Using image and flow cytometric analysis of archival, paraffin-embedded prostate tumors, we measured DNA ploidy in individual foci of prostatic carcinoma in stage T1a, T1b and T1c disease. Image analysis studies included the use of Feulgen stained tissue sections, and a comparison of these results with flow cytometric DNA ploidy determinations on nuclei isolated from the same tumor foci. Flow cytometry was also used to measure DNA Index and tumor S-phase fraction, in some cases using multiparameter analysis of isolated nuclei to determine DNA content and the level of the proliferation-associated antigen, p105. Our results indicate that DNA aneuploid foci of prostate carcinoma are infrequently seen in stage T1a disease (13% of the individuals studied), and that the presence of both DNA diploid and aneuploid foci in the same sample is seen in less than 10% of these individuals. Stage T1b and T1c tumors containing only DNA diploid nuclei are seen, though these are likely most common in low volume, low Gleason grade tumors. By using flow cytometry to compare these results with those using image analysis of the same tumor foci, we demonstrated that the majority (> 75%) of these aneuploid tumors are DNA tetraploid. Our data on prostate tumor S-phase fractions indicate that DNA diploid tumors generally have a lower S-phase than DNA aneuploid foci (including comparisons of DNA diploid and aneuploid foci in the same prostate tumor). These results support the model that early prostate tumors are DNA diploid and have a low S-phase, and that these tumors likely evolve to DNA tetraploid tumors with a similar low S-phase fraction.

Aneuploidy↗
PubMed1994

Snow blowing and shoveling in normal and asymptomatic coronary artery diseased men.

We evaluated the oxygen uptake and heart-rate responses to self-paced snow blowing and snow shoveling in 10 men with asymptomatic coronary artery disease, 10 older normal men, and six younger normal men. Mean peak treadmill oxygen uptake in the three groups ranged from 26.4 +/- 1.1 to 47.3 +/- 3.9 ml/kg per min (P < 0.05). Oxygen uptake during snow blowing did not differ significantly among subject groups; values were 17.1 +/- 1.3, 17.7 +/- 1.1, and 17.2 +/- 0.9 ml/kg per min in the coronary artery disease, older normal, and younger normal groups, respectively. Oxygen uptake with snow shoveling was lower (P < 0.05) in those with coronary artery disease (18.4 +/- 1.0 ml/kg per min) than in the normal groups. In comparison with snow shoveling, oxygen uptake and heart rate did not differ (P = NS) from snow blowing in the coronary artery disease group but were lower (P < 0.05) with snow blowing in the two normal groups. The results indicate that men with asymptomatic coronary artery disease and relatively good functional work capacity perform snow blowing and snow shoveling at similar levels of oxygen uptake and heart rate.

Adult↗
PubMed1992

Cardiac response to combined moderate heat and exercise in men with coronary artery disease.

The effect of moderate heat stress on cardiac performance during sustained moderate physical work was evaluated in men greater than or equal to 6 weeks after a cardiac event. Subjects (n = 10) performed upright leg cycle ergometer exercise at approximately 50% of peak oxygen uptake for up to 60 minutes in warm (30.0 +/- 0.9 degrees C) and thermoneutral (21.5 +/- 0.3 degrees C) environments. Cardiac output (carbon dioxide rebreathing method), left ventricular ejection fraction and relative left ventricular end-diastolic volume (portable nuclear VEST monitor) were periodically determined. In both environments, heart rate increased (p less than 0.05), stroke volume decreased (p less than 0.05), and cardiac output remained unchanged with exercise time. In the warmer environment, heart rate was increased (p less than 0.05) and stroke volume tended to be decreased (p less than 0.08), with no difference in cardiac output. In both environments, left ventricular ejection fraction did not change from minute 6 to 60 of exercise, whereas relative left ventricular end-diastolic volume decreased (p less than 0.05) with exercise time. Arterial blood pressure was unchanged from minute 6 to 60 in the warm environment. Arrhythmias were not altered by exercise time or environment, and no subjects had evidence of myocardial ischemia. The data indicate that although heart rate increased and stroke volume and relative left ventricular end-diastolic volume decreased with exercise time, cardiac output and left ventricular ejection fraction remained unchanged in both thermoneutral and warm environments.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1990

Immunologic parameters of response in patients with rheumatoid arthritis treated with cyclosporin A.

Thirty-one patients with seropositive rheumatoid arthritis treated with cyclosporin A (CsA) were evaluated for immune function prior to, during, and after 1 year of therapy. Patients whose pretreatment peripheral blood mononuclear cells were hypoproliferative in vitro to soluble recall antigens responded better clinically to CsA treatment than did the other patients. During therapy, proliferative responses became normal and remained so until 1-2 months after CsA was discontinued. At that time, the lymphocyte proliferation defect reappeared. In addition, patients who responded clinically to CsA had a higher percentage of Leu-7+ natural killer cells in their peripheral blood prior to therapy. All patients exhibited greater frequencies of cells that expressed interleukin-2 receptors, which decreased with CsA treatment. The clinical response to CsA appears to be associated with distinct immunologic parameters in rheumatoid arthritis.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation.

Transforming growth factor-beta (TGF-beta), a product of neoplastic and hemopoietic cells, is a bifunctional regulator of the immune response. At femtomolar concentrations, TGF-beta stimulates monocyte migration, and picomolar quantities induce synthesis of monocyte growth factors, including IL-1, that may promote tissue repair by regulating fibrosis and angiogenesis. Paradoxically, TGF-beta at picomolar concentrations also blocks the ability of IL-1 to stimulate lymphocyte proliferation. At 0.01 to 1.0 ng/ml, TGF-beta 1 and its homologue, TGF-beta 2, suppress the IL-1-dependent murine thymocyte proliferation assay. TGF-beta also inhibits human peripheral blood T lymphocyte mitogenesis. Inhibition of cell division appears to occur after activation of the lymphocytes inasmuch as neither gene expression nor translation of IL-2R is suppressed. Furthermore, TGF-beta does not block synthesis of IL-2. Therefore, TGF-beta 1 and TGF-beta 2 likely act at a site distal to IL-1 to block lymphocyte DNA synthesis. These findings suggest that TGF-beta secreted in an inflammatory site may be beneficial in diminishing lymphocyte function while promoting fibrosis and tissue repair. However, TGF-beta generated by neoplastic tissues may provide a mechanism for unrestricted tumor cell growth through its selective immunosuppressive effects.

Humans↗
PubMed1986

T lymphocyte-dependent evolution of bacterial cell wall-induced hepatic granulomas.

Injection of streptococcal cell walls (SCW) i.p. into susceptible rats results in dissemination of SCW primarily to the liver, spleen, bone marrow, and peripheral joints. Within the liver, the SCW are phagocytized by the Kupffer cells, initiating a sequence of events leading to the formation of hepatic granulomas. The granulomas are characterized by large numbers of W3/13+, W3/25+ T lymphocytes and Ia+, esterase-positive macrophages. The generation of inflammatory mediators by these mononuclear cells appears to be central to the evolution of the granulomas and the subsequent fibrotic sequelae evoked by the SCW. In the absence of functional T lymphocytes (athymic rats), injection of SCW does not trigger lymphokine production, and organized granulomas do not develop in the livers. Furthermore, inhibition of T lymphocyte proliferation and lymphokine synthesis pharmacologically by cyclosporin A administration in euthymic animals inhibits SCW-induced hepatic granuloma development. Although macrophage function is apparently not impaired as evidenced by IL 1 and PGE2 production, a chronic inflammatory response to SCW cannot be sustained in the absence of T lymphocyte participation. These studies provide insight into the cellular and molecular mechanisms leading to formation and maintenance of chronic granulomatous lesions.

Animals↗