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Biomedical subjects

A Goldfarb

Publications and source records attributed to A Goldfarb.

At least 145 records · Page 8Linked to original sources

Nitroglycerin pharmacokinetics after intravenous infusion in normal subjects.

The purpose of this investigation was to examine the pharmacokinetics of nitroglycerin in normal volunteers after intravenous drug administration. Eight subjects (including one subject on two occasions) received a dose of approximately 0.6 mg iv of nitroglycerin at a rate of 18 micrograms/min. Plasma concentrations of intact drug during and after the infusion were determined using a GLC method. Intra- and intersubject variability in nitroglycerin plasma kinetics was substantial. Generally, however, plasma nitroglycerin disposition was characterized by: (a) a large apparent plasma clearance (0.3-1 liter/min/kg), (b) a large volume of distribution (approximately 3 liters/kg), and (c) a rapid plasma half-life (approximately 3 min). From the apparent volume of distribution obtained, plasma drug can be estimated to account for only approximately 1.3% of total drug in the body. Minor fluctuations in tissue distribution, which can be produced by a myriad of external and internal stimuli, could cause dramatic fluctuation in plasma nitroglycerin concentrations and, hence, in the calculated pharmacokinetic parameters. For example, in two subjects studied, plasma nitroglycerin concentrations oscillated to such an extent that pharmacokinetic analysis could not be performed. In some subjects, steady-state concentrations were not observed in spite of the apparent short plasma half-life, and rebound in plasma concentrations during the postinfusion phase were evident. These phenomena were also observed in other kinetic studies involving organic nitrates.

Administration, Sublingual↗

Changes in the promoter range of RNA polymerase resulting from bacteriophage T4-induced modification of core enzyme.

Primary transcripts made in vitro on bacteriophage T4 DNA by RNA polymerase isolated from normal or T4-infected Escherichia coli were compared by gel electrophoresis. Bacteriophage-modified RNA polymerase fails to initiate transcription at certain promoters recognized by unmodified enzyme. In the T4tRNA gene region, only one of the two promoters is active with the modified RNA polymerase. Reconstitution of separated RNA polymerase components demonstrates that this change in promoter site selection results from the modification of core enzyme and not sigma factor.

DNA, Viral↗

Pseudo-Pelger-Huët anomaly in chronic lymphocytic leukemia.

Anomalous cells of the Pelger-Huët type appear mainly in diseases affecting granulopoiesis such as myeloproliferative disorders, aplastic anemia and agranulocytosis [1]. The association of this anomaly with disorders of the lymphatic system is rare and had been described only in 1 patient with chronic lymphocytic leukemia [2]. Recently we have encountered another patient with chronic lymphocytic leukemia and acquired Pelger-Huët anomaly.

Humans↗

An Escherichia coli endonuclease responsible for primary cleavage of in vitro transcripts of bacteriophage T4 tRNA gene cluster.

An endonuclease activity was isolated from 100,000 g supernatant fraction of Escherichia coli using in vitro primary transcripts of T4 tRNA gene cluster as assay substrates. The endonuclease cleaves the polycistronic RNA precursors into fragments containing monomeric and dimeric stable RNA sequences. The result strongly suggest that this enzyme participates in the early steps of T4 tRNA maturation pathway preceding the action of RNase P.

Endonucleases↗

Transcriptional control of two gene subclusters in the tRNA operon of bacteriophage T4.

In bacteriophage T4 DNA, transcription units recognized in vitro by host RNA polymerase consist of promotor-proximal 'immediate early' (IE) genes and promotor-distal 'delayed early' (DE) genes separated from each other by rho-dependent transcription terminators. In vivo, the transition from IE to DE transcription requires phage-specific protein synthesis and can be prevented by chloramphenicol (CAM). Most of the information about IE/DE transition has been obtained by hybridizaton analyses of mixtures of RNA species synthesized simultaneously on several T4 transcription units (for review see ref. 3). A useful model for the study of T4 gene expression at the level of primary transcripts and individual gene products is provided by the T4 tRNA operon, a cluster of genes coding for eight T4-specific transfer RNAs and two stable RNAs (species 1 and 2) of unknown function (Fig. 1). The 10 genes of the tRNA operon are arranged in two subclusters (I and II) with a promotor located about 1 kilobase pair upstream. The primary transcripts and the final gene products of this region have been identified and isolated. Moreover, this genetic region was recently cloned and a part of it sequenced. We describe here the expression of T4 tRNA genes in vivo and in vitro in terms of the IE/DE concept and demonstrate that the two subclusters of the tRNA operon are subject to different modes of control.

Genes, Viral↗

Photoradiation in the treatment of recurrent breast carcinoma.

Photoradiation, with the use of hematoporphyrin derivative (Hpd) activated by visible light in the red region of the spectrum, was an effective treatment for controlling local and regional chest wall recurrences of breast carcinoma. With sufficient time between iv injection of the drug and local activation with red light, cutaneous and subcutaneous masses were treated effectively without undue damage to overlying and adjacent skin. This high therapeutic ratio resulted from the ability to Hpd to accumulate and/or to be retained to a higher degree in malignant tissue than in many normal tissues. This technique can be used as a primary treatment or upon tumor recurrence following conventional modalities such as surgery, chemotherapy, and radiation therapy.

Breast Neoplasms↗

Photoradiation therapy for the treatment of malignant tumors.

Administration of hematoporphyrin derivative i.v. followed by local exposure to red light has resulted in complete or partial response in 111 of 113 cutaneous or s.c. malignant lesions. Tumors treated have included carcinomas of the breast, colon, prostate, squamous cell, basal cell, and endometrium; malignant melanoma; mycosis fungoides; chondrosarcoma; and angiosarcoma. No type has been found to be unresponsive. In several cases complete clearing of chest wall metastatis has been achieved in treated areas. Deep-seated and pigmented tumors required a higher dose of drug for effective treatment than did the more superficial and nonpigmented lesions. A high therapeutic ratio between tumor and skin response has been obtained by allowing at least 3 days between drug injection and exposure to the therapeutic light for 2,5-mg/kg doses and at least a 4-day interval for 5.0-mg/kg doses.

Adult↗

Echocardiographic and hemodynamic characteristics of atrial septal defects created by percutaneous valvuloplasty.

Twenty-nine patients were studied by pulsed, continuous wave, and color Doppler before and after percutaneous transseptal valvuloplasty. New atrial septal defects were detected in 14 patients, and the patients were monitored for up to 320 days after the procedure. The diameter of the defect, best evaluated by the transesophageal approach, was 3 to 15 mm. A narrow, high velocity (1.4 to 3.1 meters per second) left-to-right shunt jet was detected in 13 of 14 patients. The shunt jet was continuous in nine of 14 patients, late systolic-holodiastolic in four patients, and bidirectional in one patient. Cardiac catheterization in nine patients confirmed the Doppler findings and demonstrated a peak pressure gradient of 10 to 32 mm Hg between the left and right atria. Oximetry revealed a calculated pulmonary to systemic flow ratio ranging from 2.3:1 in the patient with the largest atrial septal defect by echocardiography to 1:1 (no oxygen saturation step-up) in the patient with the smallest atrial septal defect. In the three patients who underwent cardiac surgery, the operative findings confirmed those of echocardiography. We concluded that atrial septal defects are common after transseptal valvuloplasty. Usually, their relatively small size and the underlying valvular disease that produces high left atrial pressure are responsible for the high pressure gradient between the left and right atria. This results in the high velocity and continuous shunt jet detected by Doppler echocardiography.

Adult↗