Showing papers by "Oregon Health & Science University published in 1977"

Mechanism of action of Pseudomonas aeruginosa exotoxin Aiadenosine diphosphate-ribosylation of mammalian elongation factor 2 in vitro and in vivo.

Abstract: Previous studies showed that Pseudomonas aeruginosa exotoxin A (PA toxin) catalyzes nicotinamide adenine dinucleotide (NAD)-dependent inhibition of protein synthesis in a rabbit reticulocyte lysate and transfer of radioactivity from [14C]adenine-labeled NAD to a protein having the same molecular weight as elongation factor 2 (EF-2) (B.H. Iglewski and D. Kabat, 1975). Such an inhibited protein-synthesizing lysate was restored to activity by addition of a protein from normal mouse liver which co-purifies with EF-2. In addition, EF-2 activity was almost totally absent in livers of mice which had been injected 24 h earlier with PA toxin. On the contrary, EF-2 concentrations were only partially reduced in other organs and were normal in brains of intoxicated mice. Studies using NAD labeled in various positions show that PA toxin, like fragment A of diphtheria toxin, catalyzes transfer of the adenosine 5'-diphosphate-ribosyl moiety of NAD. Furthermore, reversal occurred when the modified protein was incubated with excess concentrations of PA toxin and nicotinamide, and NAD was identified as a product of the reverse reaction. The protein modification catalyzed either by PA toxin or by fragment A of diphtheria toxin could be reversed by incubation with other toxin. These results support the proposal that these two toxins adenosine 5'-diphosphate-ribosylate and same amino acid of EF-2 in a stereochemically identical fashion. Furthermore, PA toxin inactivates EF-2 in intoxicated mice to an extent which would ultimately result in death.

Newer concepts of atopic dermatitis.

Abstract: Atopic dermatitis is a disease of fascination and frustration to medical practitioners and researchers. This very common disorder is confusing from several standpoints. The confusion begins with nomenclature; in discussions with American nondermatologic physicians, we might hear atopic dermatitis referred to as "eczema," allergic dermatitis, allergic eczema, or even neurodermatitis. Many Europeans continue to use the term prurigo Besnier. Diagnostic features of atopic dermatitis are another source of confusion. The skin lesions a pediatrician sees on a child's skin may be vastly different from the lesions the general practitioner sees on that same individual 15 years later. There may be no single distinguishing characteristic; diagnosis may depend on a combination of morphologic, distributional, and historical features. Histological findings provide very little aid in diagnosis, though a recent preliminary report by Mihm et al 1 raises the hope that new histologic techniques may reveal distinct histopathologic features in atopic dermatitis. With

Structure-activity relationships of an exotoxin of Pseudomonas aeruginosa.

Abstract: The relation of the structure of Pseudomonas aeruginosa exotoxin A (PA toxin) to its enzymatic activity (adenosine 59-diphosphate-ribosyl transferase) in vitro and to its toxicity in vivo was examined. PA toxin is produced as a single polypeptide chain with a molecular weight of about 71,500. PA toxin is produced by Pseudomonas as a toxic proenzyme that lacks enzymatic activity. Adenosine 59-diphosphate-ribosyl transferase activity is expressed when the molecule is denatured and reduced or when its is cleaved by Pseudomonas proteases to yield an enzymatically active 27,000-dalton fragment (fragment a). A 45,000-dalton protein is tentatively identified as the enzymatically inactive fragment b of PA toxin. Enzymatically active forms of the toxin lack toxicity for mouse L-cells or mouse lethality. Thus, it is concluded that the native toxin proenzyme is required for toxicity and that a structural rearrangement must precede its intracellular activity. Images

Staphylococcal Infections in Patients With Atopic Dermatitis

Abstract: • Cutaneous staphylococcal infections appear to be relatively infrequent in atopic dermatitis even though patients have broken skin heavily colonized with staphylococcal organisms. We found superficial staphylococcal pustules on the skin of 22 patients with atopic dermatitis. Such lesions were more commonly found with severe exacerbations of atopic dermatitis. They appeared on unbroken skin independent of hair follicles and were associated with considerable pruritis. Such lesions were rapidly removed by excoriation and frequently were overlooked by patients and physicians. Most lesions appeared when polymorphonuclear leukocyte chemotaxis was depressed. Ineffective chemotaxis combined with high-colonization density and inadequate stratum corneum barrier during exacerbations of atopic dermatitis may lead to mild staphylococcal infections. These infections appear to have no systemic effects but possibly the considerable associated pruritis could worsen the atopic dermatitis. Occasional patients may require intermittent or continuous antibiotic therapy. (Arch Dermatol113:1383-1386, 1977)

The fetal trimethadione syndrome: report of an additional family and further delineation of this syndrome.

Abstract: • We describe a family in which seven pregnancies resulted in four infants who died and in three abortions. During these pregnancies the mother took trimethadione (Tridione), as well as other anticonvulsants. Two normal children were born after treatment with all medications were stopped. There have now been 53 reported pregnancies in which the fetuses were exposed to trimethadione or paramethadione; 46 (87%) resulted in fetal loss or a child born with congenital malformations. The most common defects include malformed ears, cleft palate, cardiac defects, urogenital malformations, and skeletal abnormalities. Delayed mental and physical development were also seen. These findings constitute a clinical entity termed the fetal trimethadione syndrome. The malformation rate is believed to be due to the teratogenic effects of trimethadione. Physicians need to be aware of the danger of trimethadione and related drugs during pregnancy and should withhold these medications during this period. ( Am J Dis Child 131:1389-1392, 1977)

Presystolic murmur in atrial fibrillation.

Abstract: From 1965 to 1976, 721 isolated aortic valve replacements were performed at the University of Oregon hospitals, utilizing Starr-Edwards caged-ball prostheses. Three models of aortic prostheses were introduced during this period: a non-cloth-covered model has been in continuous use since 1965; a cloth-covered model was begun in 1968 and has been supplanted by the modified composite-strut or "track" model since 1972. The 5-year actuarial survival rate for operative survivors is about 80% for both non-cloth-covered and cloth-covered valves, while the 10-year survival is 61%, based on the older model only. The actuarially-determined percentages of patients experiencing significant thromboembolic episodes (i.e., all except transient ischemic episodes) at 5 years are 7% for the cloth-covered and 9% for the non-cloth-covered model. If transient ischemic attacks are included, the cloth-covered model has only an 8% incidence at 5 years compared to a 22% incidence for the older model. However, the cloth-covered valves are subject to a higher risk of reoperation because of the possibility of cloth injury. The "track" valve, therefore, was designed with exposed metal on the inner surface of each strut to prevent ball-cloth contact. In 107 patients (mean follow-up period 1 year) receiving anticoagulation, this prosthesis has maintained the same low incidence of thromboembolism as the previous cloth-covered model, with no reoperations for valve failure.

Transfer of hydrophilic molecules by placenta and yolk sac of the guinea pig.

Abstract: Prenatal transfer of hydrophilic materials was studied in chronic guinea pig preparations of ca. 30-65 days gestation. In most preparations the vitelline (yolk sac placenta) circulation of one of the fetuses was ligated between 1 and 20 days before the experiment. Fetal and maternal serum protein concentrations were recorded as a function of the number of days after ligation. Prenatal transfer of hydrophilic materials of 60-5,500 daltons molecular wt was consistent with diffusion, with some evidence of steric restriction of the larger molecules. There was no difference between operated and sham-operated or control fetuses. However, the transfer of radiolabeled homologous gamma globulin ceased after ligation of the yolk sac vessels. The transfer in control fetuses accounted for most of the prenatal requirements of this protein, as calculated from the increases in fetal weight and serum gamma globulin concentrations as a function of gestational age. There was evidence of a nonspecific suppression of yolk sac function by surgery but no evidence of fetal catabolism of gamma globulin.

Osmotic flow through the placental barrier of chronically prepared sheep

Abstract: An electromagnetic flow sensor was placed on the distal aorta of sheep fetuses in utero, and catheters were placed in a femoral artery and the common umbilical vein. Catheters were also placed in a carotid artery and a uterine vein of the pregnant ewe. Three days postoperatively maternal plasma was hyperosmotic with respect to fetal plasma by all methods: +5.8 +/- 1.4 SE by vapor-pressure osmometry, +2.2 +/- 0.7 SE by freezing-point depression osmometry corrected for bicarbonate loss; and +3.26 mosmol/liter by chemical measurement of plasma constituents. Maternal or fetal plasma was made hypertonic in vivo by infusion of concentrated solutions of mannitol, sucrose, or NaCl. Transplacental water flux was calculated from placental blood flows and arteriovenous differences in water content of the blood. The apparent osmotic conductivity of the placenta was 61 ml2-mosmol-1-kg-1, but this value should be divided by an unknown reflection coefficient to yield the true osmotic conductivity. Separate measurements were made of the placental diffusional permeability of Na+ and Cl- in five chronically prepared sheep fetuses: PSNa+ =0.20 +/- 0.04, PSCl- = 0.27 +/- 0.04 ml/(min-kg fetus). There was a highly significant positive regression between (total) placental permeability and fetal weight.

Regional intra-arterial infusion of adriamycin in the treatment of cancer.

Abstract: Forty patients with otherwise untreatable advanced carcinomas received arterial infusions of adriamycin. Significant responses were seen in five of nine tumors of the bladder, two of five hypernephromas, two of two islet cell tumors, three of five sarcomas and one of two metastatic tumors of the breast. One patient with advanced transitional cell carcinoma of the bladder had no tumor at the time of a subsequent resection. There were no responses seen in two oat cell tumors metastatic to the liver, one seminoma of the retroperitoneal space metastatic to the liver, one squamous cell tumor metastatic to the liver, one squamous cell of the vulva, one carcinoma of the cervix uteri and one cloacogenic carcinoma. these responses in advanced tumors are exciting. The use of this technique to reduce tumor bulk prior to operation, irradiation, adjuvant chemotherapy and immunotherapy may allow a significant breakthrough for such tumors as sarcomas, hypernephromas and transitional cell carcinomas of the bladder. Further studies will be pursued using this concept.

Pulmonary fibrosis from amorphous silica dust, a product of silica vapor.

Abstract: After prolonged occupation exposure to amorphous silica dust-a product of vaporized crystalline silica (quartz)-eleven out of forty workers showed reticular and/or nodular abnormalities in roentgenograms of the chest. From this group, we present three illustrative cases. These had widespread pulmonary disease with granulomatous nodules and fibrosis (documented histologically in two cases), but there was no demonstrable restrictive impairment of pulmonary function. We discuss the possible importance of this previously underestimated toxicity, especially in an industrial setting.

Elective irradiation of the lower cervical region in patients at high risk for recurrent cancer at the tracheal stoma.

Abstract: The results of treatment for recurrent cancer at the tracheal stoma have been poor. From 1971 to 1976, elective postoperative irradiation of the neck was given to 26 high-risk patients with carcinoma of the larynx and hypopharynx. None of the 22 patients whose stomas were irradiated developed stomal or peristomal recurrence, while 2 of the 4 patients whose stomas were shielded had stomal recurrence. Elective irradiation of the tracheal stoma was effective in preventing stomal recurrence; we recommend inclusion of the stomal area in preoperative or postoperative irradiation to the lower cervical region for high-risk patients.

The Starr-Edwards model 6000 valve. A fifteen-year follow-up of the first successful mitral prosthesis.

Abstract: The Starr-Edwards model 6000 mitral valve was the first successful mitral prosthesis. A fifteen year follow-up of 110 patients undergoing isolated mitral valve replacement with this prosthesis from 1960 to 1966 is presented. There were 22 (20%) operative and 37 (42%) late deaths at a mean of 8.6 years postoperatively. Preoperative variables leading to late death and thromboembolism are analyzed. Seventeen of 25 operative survivors had improvement in their NYHA Functional Class status and eight other remained unchanged an average of 13.1 years after surgery. There are 5000 patients world-wide currently relying on this prosthesis. Despite a high rate of thromboembolism in the past, elective replacement is not recommended except in selected patients.

Purification and characterization of human muscle pyruvate kinase

Abstract: The M1 isozyme of pyruvate kinase has been purified from human psoas muscle in a seven-step procedure. Fractionation by ammonium sulfate precipitation, heat treatment, acetone precipitation, diethy...

Intracranial and extracranial neurogenic hamartoma

Abstract: ✓ A case of neurogenic hamartoma involving the middle cranial fossa, nasopharynx, and left anterior cervical region and presenting at birth as an obstructive oropharyngeal mass is described. Special management included Gelfoam embolization of the vascular supply, control of airway and feeding, assessment of biological activity of the mass, and appropriate staging of the procedure with neurosurgical, head and neck surgical, and radiological support.

Rapid onset of hand ischemia of unknown etiology: clinical evaluation and follow-up of ten patients.

Abstract: Ten patients presenting with a history of the acute onset of hand ischemia have undergone detailed clinical, immunologic, and arteriographic evaluation. The disease is characterized by the acute onset of hand ischemia proceeding to fingertip ulceration, in the absence of recognized systemic disease. None of the patients had any evidence of large artery obstruction. Arteriography showed diffuse obstruction of the palmar and digital arteries. No evidence was found in any patient of any systemic disease process associated with small artery obstruction. These patients are suspected of having a previously unreported variant of hypersensitivity angiitis. Patients are left with permanent obstruction of the palmar and digital arteries. Follow-up suggests the disease in non-recurrent and is characterized by progessive clinical improvement associated with the development of collateral circulation. Conservative management of the condition is recommended.

alpha-chain sequence of newt haemoglobin (Taricha granulosa).

Abstract: The amino acid sequence of the IX-chain of the major haemoglobin of a newt, T. granulosa, has been determined. The chain is 142 residues long and has an extra methionine at its N-terminus when compared with human IX-chain. Most of the tryptic peptides were sequenced by a combination of the subtractive Edman method and by deduction from the compositions of overlapping fragments produced by various enzymic treatments. The sequence of two 'core' regions was obtained by automatic sequencing of large peptides produced by trypsin cleavage at arginine residues only after blockage of lysine residues by citraconylation; by cleavage between aspartic acid and proline residues with 70% formic acid, and by cyanogen bromide cleavage at methionine residues.

The importance of temperature in angiography of the hand.

Abstract: Angiograms of the hand of a normal volunteer taken at skin temperatures ranging from 22 to 33°C revealed that visualization of the arteries was highly dependent on the temperature. Lower temperatures produced vasospasm beginning in the smaller vessels and proportionally involving medium-sized and major arteries. Moderate warming led to optimum filling and is recommended prior to angiography of the hand. Prior injection of contrast material caused no perceptible change in the filling or appearance of the arteries.

Limitations of angiographic differential diagnosis in major hepatic processes.

Abstract: In 11 instances (6%) of 183 consecutive hepatic angiograms done for subsequently proven pathologic hepatic processes, either the diagnosis was incorrect (4 patients) or a satisfactory differential diagnosis was not established (7 patients), despite obvious angiographic abnormalities. Incorrect diagnoses were made in patients with suppurative hapatocarcinoma and liver cyst, macronodular regenerative cirrhosis, and multiple intrahepatic abscesses. Satisfactory differential diagnoses could not be established in patients with enlarged intrahepatic ducts, acute viral hepatitis, recurrent cirrhosis and acute liver necrosis. On analysis, means for minimizing diagnostic failure include the use of enhancement techniques such as infusion angiography and pharmacoangiography and an unbiased, detailed analysis of the angiographic findings. Changes secondary to the pathologic process and the coexistence of multiple processes, however, can occasionally prevent an accurate diagnosis.

Hand angiography and Raynaud's syndrome.

Abstract: Forty-eight patients with Raynaud's syndrome and seven volunteers without it were studied by magnification hand angiography which included studies of the effects of cold exposure before and after the selective intraarterial administration of reserpine. Most of the patients with Raynaud's syndrome, in addition to organic obstructive disease, exhibited both basal vasoconstriction and exaggerated, persisting cryogenic vasospasm of the hand arteries. Studies done two days after reserpine administration revealed decreases in both basal and cryogenic vasospasm in most patients and the degree of angiographic improvement correlated well with subsequently determined clinical responses to long-term vasodilator drug therapy. Hand angiography with examinations after cold exposure and its combination with the postreserpine pharmacodynamic studies is a useful technique in Raynaud's syndrome, both diagnostically and in predicting the outcome of longterm vasodilator therapy.