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Biomedical subjects

T G Lee

Publications and source records attributed to T G Lee.

At least 55 records · Page 3Linked to original sources

Characterization and regulation of the 58,000-dalton cellular inhibitor of the interferon-induced, dsRNA-activated protein kinase.

The P68 protein kinase is a serine/threonine kinase induced by interferon treatment and activated by double-stranded RNAs (dsRNAs). Once activated, the kinase phosphorylates its natural substrate, the alpha subunit of eukaryotic initiation factor 2 (eIF-2) leading to potential limitations in functional eIF-2 and decreases in protein synthesis initiation. We have recently purified from influenza virus-infected cells a P68 kinase inhibitor, found to be a 58-kDa cellular protein. We have now investigated the mechanisms by which the 58-kDa inhibitor regulates P68 kinase activity and how the inhibitor itself is controlled. The 58-kDa inhibitor did not function by degrading or sequestering the dsRNA activator of P68 but could repress phosphorylation of eIF-2 alpha by an already activated protein kinase. Utilizing antibody prepared against a 58-kDa-specific peptide, we showed that the 58-kDa proteins from infected and uninfected cells were present in equivalent amounts. Although kinase inhibitory activity could not be detected in crude uninfected cell extracts, ammonium sulfate treatment unmasked this activity and allowed purification of the cellular inhibitor with identical chromatographic properties as that from influenza virus-infected cells. Finally, we have identified and partially purified a specific inhibitor of the 58-kDa protein which we refer to as an "anti-inhibitor." Based on these data, we present a model depicting the complex regulation of the interferon-induced protein kinase in eukaryotic cells.

Amino Acid Sequence↗

Purification and partial characterization of a cellular inhibitor of the interferon-induced protein kinase of Mr 68,000 from influenza virus-infected cells.

A number of eukaryotic viruses have evolved mechanisms to downregulate activity of the interferon-induced, double-stranded RNA-activated protein kinase (referred to as P68 based on its Mr of 68,000 in human cells). This control is essential because once activated, the P68 kinase phosphorylates its natural substrate, the alpha subunit of the eukaryotic protein synthesis initiation factor 2 (eIF-2), limiting functional eukaryotic protein synthesis initiation factor 2 available for protein synthesis initiation. We have previously shown that influenza virus encoded a specific mechanism to repress the autophosphorylation and activity of P68. Using in vitro assays for P68 inhibition, we now have purified, to near homogeneity, the P68 repressor from influenza virus-infected cells. The purified product inhibited both the autophosphorylation of P68 as well as phosphorylation of the alpha subunit of eukaryotic protein synthesis initiation factor 2 by the kinase. We tested for both protease and phosphatase activity but found neither activity associated with the purified inhibitor. Surprisingly we found the purified repressor, which had an apparent Mr of approximately 58,000, was a cellular and not a viral-encoded protein. Possible mechanisms by which influenza virus activates this cellular regulator of the protein kinase, thereby minimizing potential antiviral effects of interferon, are discussed.

Animals↗

Antinuclear antibodies as indicators for the procainamide-induced systemic lupus erythematosus-like syndrome and its clinical presentations.

Fifty patients on a regimen of procainamide were studied in regard to the association between antinuclear antibodies (ANA) and the development of drug-induced systemic lupus erythematosus (SLE)-like syndrome. Four groups were identified: Group 1 was ANA-positive, with clinical manifestations (serologic and clinical findings); Group 2 was ANA-positive, without clinical manifestations (serologic findings only); Group 3 was ANA negative (no patients with clinical manifestations); and Group 4 had SLE persisting after discontinuance of procainamide. The leukocyte-specific ANA (LSANA) patterns were predominant, with peripheral LSANA confined to Groups 1 and 4. Furthermore, the titer of the homogeneous LSANA, to which peripheral LSANA converts on dilution, was clinically significant. A homogeneous LSANA titer of 160 or greater was seen essentially only in patients with clinical manifestations of the SLE-like syndrome. Serial ANA determinations are therefore necessary to monitor patients receiving procainamide.

Antibodies, Antinuclear↗

An algorithm for prenatal ultrasound diagnosis of congenital CNS abnormalities.

The variable expression of congenital CNS abnormalities makes their antenatal ultrasound diagnosis extremely difficult. Clinical decisions depend on ultrasound diagnosis; therefore, accurate antenatal diagnosis is imperative. A diagnostic algorithm based on ultrasonic demonstration of fetal cranial structures altered in congenital CNS abnormalities was constructed and applied retrospectively to 40 patients with clinicopathologic follow-up adequate to define the cranial abnormality. Using the algorithm our diagnosis was correct in 37/40 (92 per cent) compared with 30/40 (75 per cent) without its use. The algorithm was highly accurate in the diagnosis of hydrocephalus (13/14), anencephaly/amniotic band syndrome (13/13), and holoprosencephaly (8/8). A wide spectrum of CNS abnormalities can be accurately diagnosed by ultrasonography in the antenatal period by the application of our algorithm.

Amniotic Band Syndrome↗

Sequential radionuclide angiographic assessment of left and right ventricular performance and quantitative thallium-201 scintigraphy following acute myocardial infarction.

Sequential changes in radionuclide angiographic measurement of left and right ventricular performance and quantitative thallium-201 scintigraphy were studied in 20 patients sustaining their first acute myocardial infarction (AMI). The studies were performed on the average 29.4 hours and 9.4 days after hospital admission. Anterior infarction had greater impairment of left ventricular (LV) performance in terms of ejection fraction and percentage of abnormal contraction area in addition to larger thallium-201 perfusion defects. At the time of the late study evidence of thallium-201 perfusion of infarcted area was seen in 14 of 20 patients, five of whom demonstrated improvement of regional wall motion. The remaining patients in the reperfused group and all of the patients in the nonperfused group failed to show evidence of LV functional improvement. This study indicates that reperfusion as measured by thallium-201 scintigraphy does occur spontaneously in 70% of patients with AMI and only in those patients with established reperfusion is there any potential for improvement in LV performance.

Coronary Circulation↗

Broad QRS tachycardia: electrocardiographic diagnosis and management.

The diagnostic difficulties between supraventricular tachyarrhythmias with intraventricular conduction delay and ventricular tachycardia have challenged the physician since the first recording of a ventricular tachycardia by Lewis in 1909. The examples selected emphasize some of the diagnostic and therapeutic dilemmas of "broad QRS tachycardias" and their major differential features from abberrancy. Multiple simultaneous surface ECG leads are valuable in showing the direction of the initial activation forces of the QRS complexes, the frontal QRS axis and the configuration of the QRS in lead V1. Vagal maneuvers and intra-atrial or esophageal leads are very useful in demonstrating the underlying atrial rhythm and atrioventricular dissociation when present. In life-threatening situations, urgent therapy or D.C. cardioversion may be required before a definitive diagnosis has been established. In recent years electrode catheter techniques for the diagnosis, for arrhythmia induction and for the selection and assessment of the effectiveness of the antiarrhythmic drug therapy have been carried out in the management of recurrent broad QRS tachycardia. In view of the inherent risks with the use of this invasive technique, it should be restricted to a carefully selected number of patients with recurrent life-threatening dysrhythmias as suggested by Scheinman.

Adult↗

Comparison of radionuclide and enzymatic estimate of infarct size in patients with acute myocardial infarction.

A comparison was made of the estimated size of the myocardial infarction occurring in 26 patients with a first infarction using creatine kinase (CK) enzyme release between radionuclide gated blood pool measurement of total and regional ventricular function and thallium-201 scintigraphic measurement of myocardial perfusion defects. Creatine kinase estimates of infarct size (enzymatic infarct size) correlated closely with the percent of abnormal contracting regions, left ventricular ejection fraction and thallium-201 estimates of percent of abnormal perfusion area (r = 0.78, 0.69 and 0.74, respectively, p less than 0.01). A close correlation also existed between percent abnormal perfusion area and percent of abnormal contracting regions (r = 0.81, p less than 0.01) and left ventricular ejection fraction (r = 0.69, p less than 0.01). Enzymatic infarct size was larger in anterior (116 +/- 37 CK-g-Eq) than inferior (52 +/- 29 CK-g-Eq) myocardial infarction (p less than 0.01) and was associated with significantly more left ventricular functional impairment as determined by left ventricular ejection fraction (33 +/- 7 versus 60 +/- 10%) (p less than 0.01) and percent abnormal perfusion area (58 +/- 14 versus 13 +/- 12) (p less than 0.01). No significant correlation was observed between enzymatic infarct size and right ventricular ejection fraction. These different methods of estimating infarct size correlated closely with each other in these patients with a first uncomplicated myocardial infarction.

Adult↗

Rapid, inexpensive real-time directed thoracentesis.

A safe, inexpensive, and expedient real-time ultrasound-directed thoracentesis technique that uses a unique closed needle-syringe assembly is described. No pneumothorax has occurred over a four-year period using this technique with 110 patients.

Humans↗

Unusual intrauterine objects: potential pitfalls in ultrasonographic identification.

Three cases of echogenic objects in the uterine cavity are reported. These objects had ultrasonographic characteristics of contraceptive intrauterine devices (IUDs) and, in the absence of patients' medical histories, would almost certainly have been wrongly identified as such. The authors demonstrate that noncontraceptive intrauterine objects can mimic IUDs.

Adult↗

Air as an ultrasound contrast marker for accurate determination of needle placement. Tumor biopsy localization and other applications.

Computed tomography (CT) and ultrasonography can be performed to localize tumors for percutaneous biopsy. With CT, the biopsy needle can be visualized within the sample volume. The needle can not be seen within the tumor on B-scan ultrasound images. The authors have devised an air contrast technique to determine the location of the needle tip and the biopsy site. This technique can also be used for organ biopsies.

Air↗