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Biomedical subjects

T G Lee

Publications and source records attributed to T G Lee.

At least 19 recordsLinked 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

Ultrasound demonstration of wandering spleen.

The correct preoperative diagnosis of a wandering spleen is infrequently made either clinically or with conventional radiologic studies. Since ultrasound can readily identify the spleen, it may assist in making this diagnosis. We describe three patients to illustrate the advantages and usefulness of ultrasound. In one postmastectomy patient, the suspected abdominal metastasis was shown to be a displaced spleen, thus obviating the necessity for an exploratory laparotomy. In the other two patients, ultrasound diagnosis was helpful in clinical treatment by localizing the wandering spleen. Ultrasound evaluation is particularly suited for patients with obscure abdominal masses because it is safe, simple, and fast.

Abdominal Neoplasms

Ultrasonographic diagnosis of fetal hydronephrosis in utero.

Ultrasonography offers a noninvasive method to visualize antenatal or neonatal anatomy which will lead to early detection and treatment of abnormalities. In these 2 cases, ultrasound allowed prompt diagnosis of hydronephrosis despite normal physical examination and laboratory values at birth.

Adolescent

Ultrasound findings of renal angiomyolipoma.

Angiomyolipoma (AML) IS A BENIGN RENAL NEOPLASM. Preoperative diagnosis is important because of the different surgical approaches to benign and malignant tumors. Angiographic findings of AML and renal carcinoma may be similar and differentiation difficult. B-mode ultraslund examination of AML demonstrates a different image pattern which may be helpfou in differentiation.

Adolescent

Ultrasound diagnosis of intramural intestinal hematoma.

Intramural intestinal hemorrhage in hemophilia has been diagnosed by ultrasound. The sonographic pattern consists of a tubular anechoic mass containing a core of strong echoes. Recognition of intestinal hematoma is important because of its bearing on treatment and prognosis. To our knowledge, this is the first reported case.

Gastrointestinal Hemorrhage

Intravenous renal angiography revisited.

A non-catheter technique to visualize the renal arteries during conventional excretory urography is re-emphasized. By rapid injection of the contrast agent and immediate filming satisfactory visualization can be obtained in many cases. This technique is useful in the evaluation of vascular impressions and other urographic findings when intra-arterial catheter examination is not indicated.

Angiography

Ultrasonic diagnosis of the bladder as a symptomatic pelvic mass.

Diagnostic ultrasound for pelvic masses is now a well established modality. Its ability to distinguish between fluid-filled and solid lesions is important in the diagnostic study of pelvic masses. Two cases are presented of bladder distension causing clinical symptoms suggesting pathology outside the urinary tract, which when finally evaluated by ultrasound proved bladder distension as the etiology of the symptoms.

Diagnosis, Differential

Antenatal ultrasonic demonstration of fetal bowel.

Although ultrasound evaluation of the adult gastrointestinal tract is largely impossible because of bowel gas, the fetal bowel is fluid-filled and therefore not subject to this limitation. In our experience, the fetal bowel pattern can be recognized and antenatal abnormalities detected.

Adolescent

Prenatal fetal abdominal ultrasonography and diagnosis.

Despite the advent of gray scale recording, the feasibility and advantages of antenatal fetal ultrasound diagnosis have not received sufficient attention. This paper describes ultrasound fetal abdominal anatomy and illustrates prenatal diagnosis based on anatomical landmarks.

Adolescent

Ultrasound diagnosis of common bile duct dilatation.

The use of ultrasound in the differential diagnosis of obstructive jaundice has been previously reported. Although common bile duct dilatation has been demonstrated, criteria for its accurate identification have not been stressed. This report describes findings and relationships helpful in recognition of a dilated common bile duct. It is important to identify this structure, since it could otherwise be confused with surrounding vessels.

Adenocarcinoma