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Biomedical subjects

S Olson

Publications and source records attributed to S Olson.

At least 91 records · Page 5Linked to original sources

Three genes for enzymes of the pyruvate dehydrogenase complex map to human chromosomes 3, 7, and X.

The genes for three proteins of the pyruvate dehydrogenase (PDH) complex have been assigned to human chromosomes by Southern analysis of a panel of human-rodent somatic cell hybrid DNAs with cDNA probes for these genes. PDH-E1 alpha has been localized on human chromosome 3p13-q23. The assignments of lipoamide dehydrogenase(E3) and PDH-E1 alpha [corrected] to chromosomes 7 and Xp, respectively, have been confirmed. Restrictive-fragment-length polymorphisms have been identified with E3, which will permit further localization of this gene by genetic linkage analysis.

Animals↗

Unilateral microfibrillar abnormalities in a case of asymmetric Marfan syndrome.

The Marfan syndrome is a dominantly inherited connective-tissue disorder characterized by ocular, cardiovascular, and musculoskeletal abnormalities. Although the underlying biochemical and molecular defect(s) of this pleiotropic disease is currently unknown, we have consistently observed apparent diminished content of elastin-associated microfibrillar fibers accumulating in skin, or produced by cultured fibroblasts, from patients with the Marfan syndrome and have documented the cosegregation of these immunofluorescent abnormalities of microfibrillar fibers with the Marfan syndrome phenotype in family studies. Recently, an unusual patient has been described with unilateral phenotypic features of the Marfan syndrome, providing an unique opportunity to compare microfibrillar fibers and other connective-tissue components between the affected and nonaffected sides. In the present report, we demonstrate striking differences in apparent content of microfibrillar fibers, as determined by indirect immunofluorescence of skin and fibroblast cultures, that are revealed when multiple homologous samples derived from different sides of the patient's body are compared. In contrast, no differences in apparent content of type III collagen or in the biosynthesis and apparent structure of types I and III (pro)collagens were found. HLA types and chromosome heteromorphisms were identical in fibroblasts from both sides of the body, eliminating the formal possibility of chimerism and suggesting that a postzygotic mutation accounts for the asymmetric manifestation of the Marfan syndrome in this patient. The observation of striking decreases in microfibrillar fibers on the affected side of the body provides further evidence that abnormalities of this component of the elastic fiber system may be central to the pathogenesis and possibly the etiology of the Marfan syndrome.

Cells, Cultured↗

Clomipramine in obsessive-compulsive disorder: clinical response and plasma levels.

Two related data sets are presented that point to a specific pharmacological effect and support a predominantly serotonergic mediation of clomipramine's antiobsessional effect. A significant placebo versus clomipramine contrast from both the between- and within-group perspectives was found in 25 patients with moderate to severe obsessive-compulsive disorder of at least 2 years' duration and no evidence of depression who completed a double-blind, placebo-controlled, 10-week study. There was no significant improvement in the placebo group, six of whom subsequently improved with clomipramine. Analysis of the clinical significance of pharmacotherapy and the relationship between outcome and plasma drug concentrations in 33 obsessive-compulsive disorder patients treated with clomipramine (239.4 +/- 57.0 mg/day) revealed that 47% of the patients were rated in the subclinical range with one third of the sample being virtually symptom-free. Plasma levels of clomipramine, but not N-desmethylclomipramine, correlated significantly with posttreatment outcome measures, with responders having significantly higher clomipramine levels and a trend toward lower desmethylclomipramine ratios.

Adult↗

The relationship of plasma clomipramine and N-desmethylclomipramine to response in obsessive-compulsive disorder.

The clinical significance of the effects of pharmacotherapy and the relationship between plasma tricyclic concentrations and outcome in 33 obsessive-compulsive disorder (OCD) patients who completed 10 weeks of treatment with clomipramine (239.4 +/- 57.0 mg/day) were analyzed. Results revealed that at the end of treatment, OCD symptoms had decreased to a subclinical level in 15 (47%) patients and that nearly 33 percent of the sample was virtually symptom free. However, 1 out of 4 patients failed to improve. Analysis of plasma levels (clomipramine 169.9 +/- 102.1 ng/ml; N-desmethylclomipramine 379.0 +/- 160.6 ng/ml) revealed that responders had significantly higher clomipramine levels and a trend toward lower desmethylclomipramine/clomipramine ratios. A significant degree of correlation was also obtained between plasma levels of clomipramine, but not N-desmethylclomipramine, and post-treatment outcome measures.

Adult↗

Localization of fructose 6-P,2-kinase: fructose 2,6-bisphosphatase to human chromosome X.

The gene encoding human liver fructose 6-P,2-kinase: fructose 2,6-bisphosphatase has been assigned to human chromosome X by Southern analysis of a panel of human-rodent somatic cell hybrid DNAs with a cDNA for this gene. A simple two-allele restriction fragment length polymorphism was found with the Fru-6-P,2-kinase:Fru-2,6-bisphosphatase probe; this will allow further localization of this gene by genetic linkage analysis.

Animals↗

A study of hospice administrative competencies and delegation of functions by program stage of development in Michigan.

There are definable stages in hospice program development which require significantly different administrative competencies. In many instances, as programs move from one stage to another, there may need to be significant changes in administrative functions, delegation, and perhaps even changes in personnel. This article reports a study of hospice administrators in Michigan in which they determined not only which stage of development they believed their hospice program to be in, but also what essential competencies they needed in managing the day-to-day operations of their hospice programs.

Adult↗

Functional abnormalities in isolated left bundle branch block. The effect of interventricular asynchrony.

Eighteen patients with isolated left bundle branch block (LBBB) were compared with 10 normal control subjects. Apexcardiograms, phonocardiograms, electrocardiograms, two-dimensional and dual M-mode echocardiograms, and radionuclide ventriculograms (RNV) were performed. There were no differences in the timing of right ventricular events between LBBB and normal subjects; however, striking delays in left ventricular systolic and diastolic events were apparent in the LBBB group. The delay was associated with shortening of left ventricular diastole and resultant increase in the ratio of right to left ventricular diastolic time in LBBB (1.2 +/- 0.08) compared with normal (1.0 +/- 0.06), p less than 0.0001. First heart sound (S1) amplitude, expressed as the ratio S1/S2, was decreased in LBBB compared with normal (0.67 +/- 0.2 compared with 1.34 +/- 0.25, p less than 0.01), in part due to wide separation of the valvular contributors to S1. The abnormal interventricular septal motion in LBBB corresponded to periods of asynchrony in contraction, ejection, end systole, and end diastole between right and left ventricles. Radionuclide ventriculograms revealed decreased regional ejection fraction of the septum in LBBB (40 +/- 16%) compared with 67 +/- 7% in normal subjects (p less than 0.001), while the apical and lateral regional ejection fractions were similar in the two groups. This loss of septal contribution resulted in a reduction in global ejection fraction in LBBB compared to normals (54 +/- 7% compared with 62 +/- 5%, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mitral stenosis: mitral dome excursion at M1 and the mitral opening snap--the concept of reciprocal heart sounds.

The dynamics of the delayed accentuated mitral component (M1) of the first heart sound and the MOS were studied in 11 patients with mitral stenosis of varying severity. Echophonocardiographic (M-mode and 2D) studies were performed with analysis of LA dimensions, dynamics, and mitral valve excursion at the time of M1 and MOS. LA area and length, mitral annular diameter, and mitral dome area (from anulus plane to fused valve tip) and length were measured at M1 and MOS. Significant dynamic increases in mitral dome area and length occurred from M1 to MOS, with less striking but consistent increases in LA area, LA length, and mitral annular diameter. Conversely, mitral dome area and length decreased significantly from MOS to M1, with less striking but consistent decreases in LA area, LA length, and mitral annular diameter. Frame-by-frame video tape analysis showed that dome movement was separate from anulus motion. Mitral dome descent into the left ventricle terminated at MOS and reversal of dome motion terminated at M1. The conformational and dimensional changes that terminated abruptly at MOS reversed and terminated abruptly in a reciprocal manner at the time of the delayed, accentuated M1. When considered in light of known hemodynamic, pressure pulse, and imaging correlates in mitral stenosis, these observations strengthen the hypothesis that the mechanisms involved in the production of M1 and MOS in mitral stenosis are paired or reciprocal in nature, and the delayed, accentuated M1 and the MOS of mitral stenosis are reciprocal cardiovascular sounds.

Adult↗

Radiation resistance in a multidrug resistant human T-cell leukemia line.

In clinical practice, cancers refractory to chemotherapy commonly appear to be comparatively radioresistant. One mechanism by which cancer cells become resistant to chemotherapy is pleiotropic multidrug resistance, characterized by cross resistance to a number of otherwise unrelated heterocyclic antineoplastic agents, including vinca alkaloids, anthracyclines, dactinomycin, and others. We have studied a drug sensitive human leukemia cell line, CEM; a pleiotropic multidrug resistant subline of CEM, CEM/VLB100; VLB-1, a drug sensitive revertant subline arising during in vivo passage of CEM/VLB100; and a methotrexate resistant subline of CEM, CEM-MTX. Using soft-agar colony formation after graded doses of X rays as an endpoint, we found that CEM, CEM-MTX, and CEM/VLB100 had similar terminal slopes (D0 = 0.66 Gy). However, the CEM/VLB100 survival curve had a broader initial shoulder (n = 3.0, Dq = 0.75 Gy) than did CEM (n = 1.6, Dq = 0.25 Gy) or CEM/MTX (n = 1.0, Dq = 0 Gy), suggesting that CEM/VLB100 has an increased capacity to repair radiation-induced DNA damage. This was tested by comparing the cell lines' abilities to accumulate sublethal damage. In split dose recovery experiments, CEM/VLB100 demonstrated increased ability to repair sublethal radiation damage following fractionated irradiation compared with the CEM parental line. Although it no longer demonstrated multidrug resistance, VLB-1 still displayed diminished radiation sensitivity. On the basis of these and other investigators' results, we suggest that diminished radiation sensitivity is separate from, but can be closely associated with, the multidrug-resistant phenotype.

Antineoplastic Agents↗

The immunophenotyping of extramedullary myeloid cell tumors in paraffin-embedded tissue sections.

Extramedullary tissue infiltrates of acute myeloid leukemia are rare and often difficult to recognize in routine paraffin-embedded tissue sections. Since appropriate therapy for these tumors depends on their precise identification, we have studied a series of tissues infiltrated with primitive myeloid cells using monoclonal and polyclonal antibodies capable of labeling cells of the myeloid/monocytic system in paraffin-embedded tissue sections. The current retrospective study involved tissues from 15 patients (eight men and seven women) with a mean age of 51 years (range, 23-77). A diagnosis of extramedullary myeloid cell tumors had been made on the basis of routine histology, chloroacetate esterase cytochemical stain, and--in some cases--electron microscopy. Paraffin-embedded tissue sections were cut and stained employing the alkaline phosphatase antialkaline phosphatase (APAAP) immunocytochemical procedure with monoclonal antibodies against leukocyte-common antigen (PD7/26-2B11), restricted components of the leukocyte-common antigen (UCHL1, 4KB5), granulocytes (Mac-387, Leu-M1), leukocytes (MT1, MT2, LN1, LN2), HLA-DR (LN3), and elastase (NP57), as well as polyclonal antibodies against lactoferrin, lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. Results indicate that antibodies against Mac-387, elastase, and lysozyme are most useful in the recognition of neoplastic myeloid cells. We conclude that tissues containing granulocytic tumors can be identified in paraffin-embedded tissue sections using a panel of antibodies and the APAAP procedure.

Adult↗

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Canada↗

Metatarsal head resection for rheumatoid deformities of the forefoot.

Thirty-five feet in 21 patients, who had had metatarsal head resection for painful rheumatoid forefoot deformities, were analyzed retrospectively. All patients but one were allowed to ambulate 48 hours after surgery. The follow-up period averaged 29 months. A grading system was devised to assess the clinical results based upon pain relief, capacity to ambulate, shoe wear, cosmesis, and use of walking aids. Using this system, the results were 46% excellent, 34% good, 17% fair, and 3% poor. One patient developed a superficial wound infection, which healed uneventfully. Bony impingement was observed on follow-up roentgenograms of 67% of the resectional arthroplasties. This finding was generally asymptomatic, and it did not correlate with the clinical outcome. Smooth wire fixation was used in some of the feet, but it did not improve the results either roentgenographically or clinically.

Adult↗

Hemodynamic, pharmacokinetic and clinical response to CI-930 in congestive heart failure due to ischemic or dilated cardiomyopathy.

CI-930, a new type III phosphodiesterase inhibitor, was evaluated for treatment of refractory congestive heart failure. The hemodynamic, pharmacokinetic and clinical response to the drug was determined in 10 patients. At the peak plasma concentration after intravenous CI-930, cardiac index increased from 2.0 to 2.7 liters/min/m2 (p less than 0.002), pulmonary artery wedge pressure decreased from 26 to 17 mm Hg (p less than 0.001) and systemic vascular resistance decreased from 1,999 to 1,471 dynes cm-5 (p less than 0.05). Heart rate and blood pressure did not change significantly. Similar changes were observed with oral CI-930. Peak CI-930 plasma concentration occurred 1.2 +/- 0.8 hours after oral administration. Beneficial hemodynamic effects were sustained 12 to 18 hours after the oral dose. The sustained hemodynamic effects observed after oral administration appear to be related to an active metabolite of CI-930 that has prolonged duration of action and slow washout. The drug was well tolerated and has potential for treatment of congestive heart failure.

Administration, Oral↗

Comparison of maternal and fetal chromosome heteromorphisms to monitor maternal cell contamination in chorionic villus samples.

Maternal cell contamination (MCC) presents a potential problem in the analysis of chorionic villus sampling (CVS) preparations for early prenatal diagnosis by chromosomal, biochemical and molecular methods. Through the comparison of fluorescent chromosome variants from CVS and maternal cells, we found three out of 50 samples to have MCC. One of these was observed on a direct preparation. Routine chromosome heteromorphism analysis is suggested as a reliable method for monitoring MCC in CVS specimens.

Chorionic Villi↗

Further cytologic evidence for Xp-Yp translocation in XX males using in situ hybridization with Y-derived probe.

Chromosome preparations from seven subjects with aberrations of sex chromosomes were utilized for in situ hybridization studies with the tritium-labeled Y-derived probe p50f. Two subjects had a pseudodicentric chromosome consisting of two copies of Yp and a portion of Y long arm; two were XX males [46,XX,t(Xp;Yp)], one was missing part of the Y short arm, and another had t(5p;Yq); in addition cells from an XYY male as well as a normal 46,XY male, and a 46,XX female, were hybridized with the same probe. The hybridization technique of Harper and Saunders (1981) was used. There was excess labeling of the Yp/paracentromeric regions in the cases with the normal Y, the XYY, the pseudodicentric Y, and the 5/Y translocation. No significant label was seen on metaphases from the normal 46,XX female or the female with the partially missing Y short arm. Excess label was present on the X short arm in the cases of the XX males; there were 8% and 9.5% of cells with label. The combined cytogenetic and hybridization data indicate that one X short arm in these XX males has undergone a translocation with Yp, and that genes for sex determination probably reside on the distal half of the Y short arm.

Chromosome Banding↗

Abnormalities of the cervical spine in Down's syndrome: diagnosis, risks, and review of the literature, with particular reference to the Special Olympics.

Over a four-month period, we did roentgenographic examinations of the cervical spine on 35 individuals with Down's syndrome, most of whom planned to participate in the Special Olympics. There were abnormalities in 40%, the most frequent being atlantoaxial subluxation. The presentations, risks, and recognition of this abnormality are discussed, as well as the pathomechanics. Many parents and some physicians may still be unaware of the possible hazards involving these spinal abnormalities, and of the recommendations and screening procedures that should be followed before individuals with Down's syndrome engage in strenuous activities.

Adolescent↗

Cytogenetic evidence for involvement of B lymphocytes in acquired idiopathic sideroblastic anemias.

We studied the cellular distribution of an unusual chromosomal abnormality, an interstitial deletion of the long arm of chromosome 13, in the peripheral blood lymphocytes of two patients with acquired idiopathic sideroblastic anemia (AISA). We found no metaphases containing the 13q- abnormality in preparations of phytohemagglutinin (PHA)-stimulated lymphocytes from either patient. In both cases, however, some metaphases from Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines contained the clonal karyotypic abnormality. These observations indicate that B lymphocytes but not T cells are expressed as members of the clonal cohort of cells. Our results strongly suggest that the initial pathogenetic events that led to expansion of the 13q- clone occurred in a progenitor cell capable of giving rise to both hematopoietic and B lymphoid cells.

Aged↗