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Biomedical subjects

D Harrison

Publications and source records attributed to D Harrison.

At least 37 records · Page 2Linked to original sources

Hematopoietic effects of continuous intravenous infusion of mice with growth factors produced by the WEHI-3 cell line.

A method for continuous intravenous infusion of unanesthetized adult C3H/HeJ or Wx/Wv anemic mice was designed using cage immobilization and a tail vein catheter connected to a model 940 Harvard infusion pump. Infusates included: WEHI-3 cell line dialyzed, 5 times concentrated conditioned medium containing multi-colony-stimulating factor (C-SF) interleukin 3 (IL-3); purified murine IL-3; bacterial endotoxin; serum-free medium, or normal saline. Mice were monitored at days 5-7 after infusion for complete peripheral blood counts and production of granulocytes in vitro by explanted marrow in long-term bone marrow cultures. We observed a stimulatory effect of WEHI-3 conditioned medium infusion that was not attributable to endotoxin and produced significant increases in peripheral blood WBC count and neutrophils, colony-forming units in spleen and numbers of granulocyte/macrophage colony-forming unit culture responsive to both C-SF-1 (L cell C-SF) and multi-C-SF in vitro. This infusion method should prove valuable for test of the in vivo effects of purified growth factors and molecularly cloned hematopoietins.

Animals

Once-daily sustained-release theophylline reduces diurnal variation in spirometry and symptomatology in adult asthmatics.

In 22 adult asthmatics (mean age, 55.2 +/- 15.4 yr), we compared Uniphyl given once a day to Theo-Dur given twice a day using a randomized, double-blind, two-phase crossover trial. All patients demonstrated acute bronchodilator responsiveness (FEV1 increase greater than 15%) to inhaled salbutamol and were dependent upon both orally administered theophylline and inhaled salbutamol at time of entry. Each phase lasted 9 days, the first 2 days of which were a theophylline washout. Uniphyl was given once a day at 8 P.M. and Theo-Dur was given twice a day at 8 A.M. and at 8 P.M. For each patient, the total daily theophylline dose was the same during both phases. Asthma symptoms, drug side effects, and PEFR were recorded at 8 A.M. and at 4 and 8 P.M. each day. On Days 7, 8, and 9 of each phase, serum theophylline concentrations were measured and spirometry was performed at 8 A.M. and at 4 and 8 P.M. The results demonstrated significant differences in both pharmacokinetic and clinical efficacy between the 2 drugs. Uniphyl produced greater "peak" and lower "trough" theophylline concentrations than did Theo-Dur, although both lower "trough" theophylline concentrations than did Theo-Dur, although both drugs maintained concentrations within the accepted therapeutic range. In contrast to the pharmacokinetic findings, Uniphyl was associated with significantly less fluctuation in pulmonary function throughout the day, and the values at 8 A.M. for FEV1, PEFR, and wheeze demonstrated significant clinical efficacy in favor of Uniphyl.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Biological characterization of cloned permanent stromal cell lines from anemic Sl/Sld mice and +/+ littermates.

Permanent cloned bone marrow stromal cell lines, designated Sld1, Sld2, Sld3, were derived from long-term bone marrow cultures (LTBMC) of Sl/Sld mice and littermate WCB6F1 mice (designated +/+1, +/+2, +/+1.10, and +/+2.4). Production of extracellular matrix proteins by these cell lines was detected using specific antibodies. Fibronectin, laminin, and collagen type IV were detected in all clonal cell lines tested. Each cloned stromal cell line or parent stromal cell culture was also tested in vitro for support of engrafted hemopoietic stem cells. Engrafted hemopoietic stem cells from C57BL/6J LTBMCs forming CFU-GEMM and BFUe colonies were supported at 76% and 44% efficiency by lines +/+2.4 and +/+1.10, respectively, compared to the number recovered from parent uncloned C57BL/6J stromal cell cultures. In contrast, cell lines Sld1 and Sld3 were significantly less supportive of CFU-GEMM progenitor cells (14% and 18% efficiency, respectively) and erythroid progenitors (6% and less than 0.1% efficiency, respectively). Some Sld lines also showed reduced support compared to +/+ cell lines of a clonal multipotential erythroid cell line B6SUtA. These permanent stromal cell lines should be useful in elucidation of the specific microenvironmental factors required for support of multilineage and erythroid progenitor cells.

Anemia, Macrocytic

Relation between electrocardiographic and enzymatic methods of estimating acute myocardial infarct size.

The extent of initial acute myocardial infarction (AMI) and subsequent patient prognosis were studied using 2 independent indicators of AMI size. Two inexpensive, readily available techniques, the complete Selvester QRS score from the standard 12-lead electrocardiogram and the peak value of the isoenzyme MB of creatine kinase (CK-MB), were evaluated in 125 patients with initial AMI. The overall correlation between peak CK-MB and QRS score was fair (0.57), with marked difference according to anterior (0.72) or inferior (0.35) location. The prognostic capabilities of each measurement varied. Peak CK-MB provided significant information concerning hospital morbidity or early mortality (within 30 days) for both anterior (chi 2 = 9.83) and inferior (chi 2 = 7.68) AMI locations; however, the QRS score was significant only for anterior AMI (chi 2 = 9.50). For total 24-month mortality, the QRS score alone provided the most information (chi 2 = 10.0, p = 0.0016), which was not improved with the addition of CK-MB (chi 2 = 0.07, p = 0.79). This study shows a good relation between these 2 independent estimates of AMI size for patients with anterior AMI location. Both QRS and CK-MB results are significantly related to early morbidity and mortality; however, only the QRS score is related to total 24-month prognosis.

Aged

Chromosomal localization of genes by scanning electron microscopy using in situ hybridization with biotinylated probes: Y chromosome repetitive sequences.

The feasibility of using scanning electron microscopy (SEM) to identify the position of specific DNA sequences was examined using a Y chromosome 'specific' probe (pHY2.1). Tests were carried out on chromosome spreads hybridized in situ with biotinylated pHY2.1. Chromosomal sites of hybridization of the probe were localized by an indirect immunohistochemical procedure which resulted in a gold product which could be amplified by silver precipitation. In the SEM, the specific location of the probe was easily identified due to the enhanced signal produced by the gold-silver complex. The probe was localized both on the long arm of the Y chromosome and within interphase nuclei. It was found that SEM was more sensitive than light microscopy since the probe could be identified without silver amplification. With refinements to the technique, SEM could provide a useful method for high resolution localizing of unique DNA sequences (i.e. single copy genes).

Biotin

Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized controlled trial.

In a multicenter randomized trial, 107 children with bacterial meningitis were initially given either cefuroxime or ampicillin plus chloramphenicol. Patients were alternately assigned to 7- or 10-day courses of the designated antimicrobial regimen. CSF isolates included Haemophilus influenzae type b (89, of which 25% were beta-lactamase positive), Streptococcus pneumoniae, and Neisseria meningitidis. Although mean CSF bactericidal titers against Haemophilus isolates were 1:6 in each treatment group, H. influenzae was cultured from CSF in four of 39 patients receiving cefuroxime, 24 to 48 hours after initiation of therapy, compared with none of 40 patients given ampicillin plus chloramphenicol (P = 0.11). Clinical cure rates were similar (95%); one death occurred in each group. One child given cefuroxime had persistent meningitis after 5 days of therapy, and mastoiditis with secondary bacteremia developed in one on day 10. Three patients had relapse or reinfection. One patient who received cefuroxime for 10 days had a relapse of epiglottitis 17 days later, and of the patients given ampicillin plus chloramphenicol, one had a relapse of meningitis 1 week after 7 days of therapy, and bacteremia developed in one 42 days after completion of 10 days of therapy. No increase in either in-hospital complications or relapses occurred with a 7-day treatment course. Proof of the equivalence of the antibiotic regimens and the efficacy of 7-day courses of treatment, as well as the consequences of delayed CSF sterilization, will require additional investigation.

Adolescent

Cryptococcal pneumonia in a patient with sickle cell disease.

We present the findings in a patient having sickle cell disease who developed multilobar pneumonia. Cultures of bronchial aspirates and histologic specimens grew Cryptococcus neoformans. There was neither spontaneous clearing of the infection nor a response to bactericidal antibiotics. The patient had no underlying malignant neoplasm or immunodeficiency as indicated by history, physical examination, and specialized tests of humoral and cell-mediated immunity.

Adult

Osteogenic sarcoma--a rare primary tumour of the breast.

A case of primary osteogenic sarcoma of the breast is reported and the histological and mammographic features demonstrated. A role for technetium 99 diphosphonate bone scanning in the diagnosis of this condition and measurement of serum alkaline phosphatase activity for monitoring progress of the disease is suggested.

Alkaline Phosphatase

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Dental Technicians

Influence of congestive heart failure on prazosin kinetics.

The kinetics of oral prazosin was studied in 10 healthy normal subjects (NS) and in 9 patients with congestive heart failure (CHF). NS received a single 5-mg dose, and blood concentrations of prazosin (CB) were measured, using a specific HPLC assay, during an 8-hr period. CHF patients received a 2-mg dose after which CB was measured for 10 hr. These patients then received 2 to 5 mg prazosin every 8 hr for 48 hr. After the last dose of prazosin, CB was measured for 24 hr. After the initial dose, time to peak CB did not differ significantly between that of the NS (123 +/- 19 SEM min) and of patients with CHF (132 +/- 31.3 min). AUC/mg prazosin was greater (p less than 0.001) in patients with CHF (3,385 +/- 380 Ng x min/ml) than in NS (1,603 +/- 208 ng x min/ml). Elimination of prazosin from blood was slower in CHF patients (t1/2 = 374 +/- 33.4 min) than in NS (t1/2 = 144.5 +/- 4.3 min) (p less than 0.001). These data suggest that in patients with CHF the elimination of prazosin is substantially slower than in NS and therefore higher steady-state prazosin concentrations can be expected in CHF patients than in NS.

Administration, Oral

Interaction of Vinblastine with Calf Brain Microtubule protein.

The interaction of vinblastine with calf brain tubulin has been studied by velocity sedimentation, gel filtration, and fluorescence. It has been established that vinblastine induces the stable tubulin dimers to dimerize further to tetramers. The sedimentation patterns at low vinblastine concentration were analyzed by the ligand-induced dimerization theory of Cann and Goad ((1972) Arch. Biochem. Biophys. 153, 603-609). The association constant and stoichiometry for the binding of vinblastine to tubulin, determined by gel filtration and spectrofluorometry, were (2.3 +/- 0.1) X 10(4) liters/mol at 25 degrees and two vinblastine binding sites per tubulin dimer of molecular weight 110,000. The binding of vinblastine to tubulin is characterized by an enthalpy change of 5.8 kcal/mol and a positive unitary entropy change. Binding of vinblastine did not induce any significant conformational changes in tubulin as monitored by circular dichroism. However, the vinblastine-tubulin complex displayed an ultraviolet difference spectrum, which appears to reflect mostly the transfer of vinblastine to a less polar environment. Besides binding vinblastine, tubulin was shown to bind vincristine with identical free energy and stoichiometry and to have a single binding site for 8-anilino-1-naphthalene sulfonic acid per tubulin dimer, which is independent of those for vinblastine.

Animals