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Biomedical subjects

D Galasso

Publications and source records attributed to D Galasso.

8 recordsLinked to original sources

Down-regulation of SPARC/osteonectin/BM-40 expression in methylcholanthrene-induced fibrosarcomas and in Kirsten-MSV transformed fibroblasts.

SPARC (secreted protein acid and rich in cysteine), also known as osteonectin or BM-40, is a glycoprotein associated with the extracellular matrix of bone as well as with many soft tissues that produce extracellular matrix, including matrix-producing tumours. Northern and slot-blot analyses were used to study SPARC expression in tumours induced in vivo by methylcholanthrene (MCA) and in transformed cells induced in vitro by Kirsten-MSV and SV-40 infection. MCA-induced tumours expressed SPARC mRNA at quantitatively different levels. Fibroblasts transformed in vitro by Kirsten-MSV, and, to a lesser extent, by SV-40, showed reduced levels of SPARC mRNA expression compared with normal fibroblasts. Run-on assay indicated that transcription of SPARC was lower in the Kirsten-MSV transformed cells than in the normal parental fibroblast culture. However, SPARC mRNA in the transformed culture was as stable as that in normal culture. The difference, therefore, between levels of SPARC mRNA in transformed and normal culture was mainly due to different rates of transcription. Cloned cell lines derived from the Kirsten-MSV transformed culture also showed heterogeneous expression of SPARC: two lines had high and two had low expression of the gene. The level of mRNA correlated with that of the protein secreted. The SPARC expression might contribute to the malignant phenotype.

Animals

Effect of adrenergic and Ca2+ antagonists on increased ornithine decarboxylase expression in regenerating rat liver.

Partial hepatectomy (PH) (70% resection) causes within 4 hr an accumulation of ornithine decarboxylase (EC 4.1.1.17, ODC) mRNAs concomitant with an increase in ODC activity, maximum values being observed at 8 and 16 hr, respectively. In the early hours of hepatic regeneration, enhancement of transcriptional-rate of ODC gene, demonstrated by nuclear run-on analysis, can account for the accumulation of ODC mRNAs. The involvement of catecholamines in these processes is demonstrated by using prazosin and propranolol, specific antagonists of alpha 1 and beta adrenoceptors, respectively. Prazosin reduces almost completely the rise of ODC activity at 4 hr, without affecting mRNA levels. At 16 hr, enzyme activity and mRNAs increase, however, over the values observed in regenerating liver of prazosin-untreated animals. These findings suggest that alpha 1-receptor activation triggers positive control signals for ODC gene expression at the early time of liver regeneration and, on the contrary, negative signals at later times by mainly post-transcriptional and transcriptional mechanisms, respectively. Propranolol reduces similarly the initial 4 hr-rise of ODC activity. These results indicate that activation of both alpha 1- and beta-adrenoceptors causes the large increase in ODC activity. Pharmacological manipulation of intracellular Ca2+ levels by verapamil, a Ca2(+)-channel blocker, or neomycin, an inhibitor of Ca2+ release from endogenous stores, diminishes ODC activity at 4 and 16 hr after PH. ODC mRNA levels, which are not modified at 4 hr, increase over the values of partially hepatectomized rat liver at 16 hr. Trifluoperazine inhibits both ODC activity and mRNA accumulation at the times studied. As a working hypothesis it is proposed that Ca2(+)-mediated processes induced by catecholamines are involved in ODC gene expression during the prereplicative phase of liver regeneration.

Adrenergic alpha-Antagonists

Osteonectin transcript and metastatic behavior in v-Ki-ras transformed fibroblasts.

Osteonectin is one of the major non-collagenous proteins of bone. However, its transcript has been found in many soft, extracellular matrix-producing tissues; an osteonectin-related protein was detected in tumor basement membrane. We have investigated the expression of osteonectin gene in fresh BALB/c fibroblasts transformed by v-Ki-ras. Transformed cells exhibited lower levels of RNA as compared with normal fibroblasts. The transformed cells were cloned after in vivo tumorigenic assay, and 4 clones were analyzed for osteonectin expression by Northern blots. Two of them were selected for high or low osteonectin expression and tested in vivo in spontaneous and artificial metastasis assays. High osteonectin expression was correlated with high lung colonization. When 10(5) cells were injected i.v., median colony value was 55 and 20 in higher expressor vs. lower expressor respectively (p less than 0.005). Spontaneous metastasis indicates a possible reverse correlation. Our data align osteonectin with other matrix-components and adhesion molecules in affecting potential metastatic spreading of transformed cells.

Animals

Cardiac pacing practices in the United States in 1985.

Physicians active in pacemaker implantation and follow-up were surveyed to obtain a profile of permanent cardiac pacing practices in the United States during 1985. Questionnaires were sent to 628 physicians, mainly in New Jersey; 145 responses were received and analyzed. A separate questionnaire was sent to 9 pacemaker manufacturers to solicit information concerning the volume of pacemaker sales and their opinions on a variety of subjects. The rate of permanent pacemaker implantation declined for the first time: it dropped from 518 devices per million population in 1981 to 374 in 1985. Sinus node dysfunction was the chief indication for permanent pacing in 52% of primary implantations; conduction disorders of the atrioventricular node and His-Purkinje system accounted for 41% and ventricular tachyarrhythmias for 2%. Dual-chamber pacing modes were used less frequently than was predicted in 1981, accounting for 30% of primary and 19% of replacement pacemakers. More than 43% of programmable pulse generators were never reprogrammed after implantation. Surveys such as this continue to provide useful information despite obstacles encountered in the use of questionnaires. Important differences in practice patterns and outcomes were identified between surgeons and nonsurgeons, and between frequent and infrequent implanters. These differences reinforce the suggestion that implanters should work at a volume sufficient to maintain their expertise, and that cooperation between surgeons and nonsurgeons would lead to improvements in patient selection, surgical results and optimal pacemaker programming and follow-up care. Better results could be achieved by adopting the continent-wide system of a pacemaker registry now used in Eastern Europe and Great Britain.

Diagnosis-Related Groups

A special outpatient clinic for following patients with implanted tachyarrhythmia devices.

Implantable anti-tachycardia devices have become an additional therapeutic option for those patients afflicted with life-threatening tachyarrhythmias. Follow-up of these complex devices are time-consuming and, if mismanaged, may be dangerous to the patient. For these reasons, a special anti-tachycardia device clinic was started at Newark Beth Israel Medical Center in July 1984. From the inception of the clinic to September 1985, 24 patients were followed. Seventy-five percent had antitachycardia devices (ATDs) implanted for treatment of ventricular tachyarrhythmias (VT/VF) with the remaining 25% for supraventricular tachycardias. All patients were seen every 3 months or more often if clinically required. Of 112 clinic examinations, 102 (91%) were scheduled appointments (group I) while the remaining 10 visits (group II) were unscheduled and preceded by symptomatic episodes. The problems detected in clinic (groups I and II) ranged from sudden failure of an AICD to apprehension. Appropriate nonoperative treatment was given during clinic evaluation for 60% of the problems detected in group II, while the remaining 40% required eventual surgical intervention. Compliance throughout the 15-month follow-up period was 100%. Major benefits of the clinic cited by patients and their families were continuity of care, the time allotted to meet the individual needs, and management of most problems on an out-patient basis.

Electrocardiography

Guidelines for developing multidisciplinary treatment plans.

The formulation of a multidisciplinary treatment plan is important not only because it is required by federal and accreditation agencies but because it increases communication, consistency, and direction among members of the treatment team. Input from all disciplines is most effectively obtained through the multidisciplinary treatment planning conference. The author provides guidelines for formulating a plan in each of four major steps: assessment, problem identification, planning (including priorities, long- and short-term goals, and interventions), and evaluation.

Goals