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Biomedical subjects

R Evans

Publications and source records attributed to R Evans.

At least 271 records · Page 15Linked to original sources
PubMed1991

Epidemiology of asthma in childhood.

The epidemiology of asthma in childhood is undergoing changes in many parts of the world. Prevalence, rates of hospitalization and mortality are all on the rise. In the United States, urban dwellers and minorities have experienced the greatest acceleration in rates. Elsewhere, some countries have experienced large increases in asthma morbidity and mortality, while others have not. Inconsistency in defining asthma and variations in methodology complicate epidemiologic investigation, but recent studies confirm the disturbing trend toward increased morbidity and mortality from childhood asthma and offer some insights into possible contributing factors.

Age Factors↗
PubMed1990

Differential inhibitory effects of lovastatin on protein isoprenylation and sterol synthesis.

It has been reported that when 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors are utilized for treatment of hypercholesterolemia, as much as 50% inhibition of whole body cholesterol biosynthesis is observed. As general inhibitors of isoprenoid biosynthesis, these compounds can also inhibit the synthesis of the substituents of isoprenylated proteins. For two mammalian proteins (p21ras and lamin A), it has been demonstrated that such inhibition of biosynthesis of the isoprenoid substituent blocks proteolytic maturation of these proteins. It has been argued that advantage may be taken of this phenomenon to block the synthesis of p21ras in malignancies. It is also possible that treatment of hypercholesterolemia with lovastatin might produce problematic inhibition of protein processing dependent upon isoprenylation. In this report, we compare the concentration dependence of inhibition of isoprenylation dependent protein processing and sterol biosynthesis. Effects of partial inhibition of isoprenylated protein processing on whole cells can be sensitively assessed by visualization of lamina structure through indirect immunofluorescence. Our results indicate that the degree of inhibition of p21ras and prelamin A maturation by lovastatin is identical. Thus, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors are unlikely to be useful as anti-malignancy drugs. However, the conditions of lovastatin treatment which produce 50% inhibition of sterol biosynthesis analogous to pharmacological conditions, produce no observable effects on isoprenylated protein maturation.

Animals↗
PubMed1990

Serpin inhibitors of urokinase and thrombin in normal rat brain and the 9L brain tumor: evidence for elevated expression of protease nexin I-like inhibitor and a novel sodium dodecyl sulfate-activated tumor antithrombin.

Increasing attention is being paid to alterations of the hemostatic balance in tumors, in general, and brain tumors, in particular. Apparently divergent results, showing excess fibrinolysis (i.e., increased plasminogen activator activity) or its inhibition (i.e., increased inhibitor activity), have been reported. The 9L rat brain tumor is a gliosarcoma and a model used to study treatment paradigms for human gliomas. To study the roles of fibrin and fibrinolysis in this brain tumor model, we used these features to investigate the nature of the plasminogen activator (PA) and thrombin inhibitors in normal rat brain and in the 9L rat brain tumor, growing both in vitro and in vivo in rat brain. The results indicate that cells cultured from the tumor in vitro express PA inhibitory activity which is both of the protease nexin I and PA inhibitor 1 types. However, the serpin PA inhibitory activity in extracts of both the normal brain and tumor is of the protease nexin I/PA inhibitor 3 type. This activity is higher in the tumor than in the surrounding "normal" tissue. In addition, we present evidence for a novel thrombin inhibitor which (a) is present only in the tumor growing in rat brain and undetectable either in the normal brain tissue or in vitro, (b) is in a latent, but sodium dodecyl sulfate-activatable, state, and (c) does not bind urokinase. In current studies, investigators are exploring the roles of these molecules and the target serine proteases they inhibit in the pathogenesis of gliomas.

Amyloid beta-Protein Precursor↗
PubMed1990

The epidermolytic toxins are serine proteases.

Certain strains of Staphylococcus aureus usually belonging to phage group II produce epidermolytic toxins (ETA and ETB) which cause intraepidermal splitting in mice, neonates and occasionally adults. Amino acid sequences of ETA and ETB have been reported but the mechanism of epidermolysis remains unknown. A search of the NBRF-PIR computer database showed the toxins to have significant sequence similarity with staphylococcal V8 protease and that the catalytic triad of V8 protease is present in ETA and ETB. Comparison of ETA, ETB and V8 protease with other members of the trypsin-like serine protease family revealed little homology save for the immediate vicinity of the residues constituting the catalytic triad. The toxins, therefore, exhibit a distant relationship to mammalian serine proteases. A potential Ca2(+)-binding loop was identified in ETA (but not ETB) on the basis of sequence similarity with the second calcium-binding loop of rat intestinal calcium-binding protein. Epidermolysis produced by ETA in the mouse bioassay was shown to be inhibited by the presence of EDTA consistent with a Ca2(+)-dependent mechanism.

Amino Acid Sequence↗
PubMed1990

Activity and thermal stability of genetically truncated forms of Aspergillus glucoamylase.

Glucoamylase (GA) from Aspergillus awamori (EC 3.2.1.3) is a secreted starch hydrolase with a large catalytic domain (aa 1-440), a starch-binding domain (aa 513-616), and a highly O-glycosylated region of 72 aa of unknown function that links the catalytic and starch-binding domains. We have genetically engineered a series of truncated forms of GA to determine how much of the highly O-glycosylated region is necessary for the activity or stability of GAII, a fully active form of the enzyme that lacks the starch-binding domain. Mutations were made by inserting stop-codon linkers into restriction sites within the coding region of the GA gene, and mutated genes were expressed in Saccharomyces cerevisiae for analysis of the truncated enzymes. Our results show that up to 30 aa from the C-terminal end of GAII can be deleted with little effect on the activity, thermal stability, or secretion of the enzyme. Further deletions resulted in diminution or loss of enzyme activity on starch plates, and loss of detectable enzyme in culture supernatants, indicating that these residues are essential for GAII function.

Amino Acid Sequence↗
PubMed1990

Curaderm--or is it?

Explore the source record for details and available documents.

Administration, Cutaneous↗
PubMed1990

Benign soft-tissue neoplasm simulating sarcoma of spermatic cord.

A large, painless, slow-growing mass arising in the scrotum of a twenty-three-year-old man, which proved to be benign myxoma, simulated a primary sarcoma of the spermatic cord. Only 1 case of myxoma involving the spermatic cord has been reported previously. It is extremely important that multiple microscopic sections of the specimen be examined carefully so that the proper tissue diagnosis can be made. A false diagnosis of malignancy may lead to treatment that is not indicated and that has a high morbidity.

Adult↗
PubMed1990

Value of screening thyroid function in acute medical admissions to hospital.

During a 4-month period an audit was performed to assess the value of thyroid function test (TFT) screening of all medical admissions, without known thyroid disease, to a single hospital. Abnormal TFTs were found in 125 of the 630 patients admitted (20%). Carbimazole or thyroxine was started in 13 patients (2.1%) discovered to have thyrotoxicosis (n = 4) or hypothyroidism (n = 9). In only four of these patients was the diagnosis of thyroid disease apparent clinically. The sick euthyroid state was found in 73 patients (11.6%), while the TSH compensated hypothyroid state was detected in 39 patients (6.2%). The low detection rate of new thyroid disease would suggest that unselective screening of all admissions is unjustified. However, the problem of diagnosing thyroid disease and the morbidity of untreated thyroid disease suggests that biochemical screening of TFTs in a selective group of medical patients admitted to hospital may be justified.

Acute Disease↗
PubMed1990

Rabbit brain contains an endogenous inhibitor of endothelium-dependent relaxation.

1. Supernatants prepared from the rabbit brain, lung and liver caused an endothelium-dependent and volume-related contraction of the phenylephrine-pretreated rabbit aorta and inhibited relaxation due to acetylcholine (ACh). 2. Perfusion in situ of the rabbit lung or liver with Krebs solution substantially reduced or removed the endothelium-dependent inhibitor. Spectrophotometric analysis revealed the presence of substantial amounts of haemoglobin (1.8-2.1 microM) in these organ supernatants. 3. Supernatants prepared from the Krebs-perfused rabbit brain retained the ability to contract the phenylephrine-pretreated rabbit aorta and to inhibit relaxation due to ACh and substance P (SP). Rabbit brain supernatant did not reduce the vasodilator effect of sodium nitroprusside (NP) or nitric oxide (NO). 4. Rabbit brain supernatant contained low (less than 0.35 microM) concentrations of haemoglobin. 5. The inhibitory effect of rabbit brain supernatant was reversed by L-arginine (500 microM) but not D-arginine (500 microM). 6. The inhibitor of endothelium-dependent vasodilatation present in rabbit brain was not removed by dialysis (24 h, 4 degrees C) but was partially precipitated by ammonium sulphate (30% w/v). 7. Rabbit brain contains an endogenous inhibitor of vascular NO biosynthesis. The identity of this inhibitor is not known although it seems likely to be a large peptide or protein.

Acetylcholine↗
PubMed1990

Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: a long-term follow-up of the First Intergroup study.

A total of 342 previously untreated eligible children were entered into the first Intergroup Ewing's Sarcoma Study (IESS) between May 1973 and November 1978. In group I institutions, patients were randomized between treatment 1 (radiotherapy to primary lesion plus cyclophosphamide, vincristine, dactinomycin, and Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] [VAC plus ADR]) or treatment 2 (same as treatment 1 without ADR), and group II institutions randomized patients between treatment 2 or treatment 3 (same as treatment 2 plus bilateral pulmonary radiotherapy [VAC plus BPR]). The percentages of patients relapse-free and surviving (RFS) at 5 years for treatments 1, 2, and 3 were 60%, 24%, and 44%, respectively. There was strong statistical evidence of a significant advantage in RFS for treatment 1 (VAC plus ADR) versus 2 (VAC alone) (P less than .001) and 3 (P less than .05) and also of treatment 3 versus 2 (P less than .001). Similar significant results were observed with respect to overall survival. Patients with disease at pelvic sites have significantly poorer survival at 5 years than those with disease at nonpelvic sites (34% v 57%; P less than .001). Among pelvic cases, there was no evidence of differing survival by treatment (P = .81), but among nonpelvic cases, there was strong evidence of differing survival by treatment (P less than .001). The overall percentage of patients developing metastatic disease was 44%; the percentages by treatments 1, 2, and 3 were 30%, 72%, and 42%, respectively. The overall incidence of local recurrence was 15%, and there was no evidence that local recurrence rate differed by treatment. Patient characteristics related to prognosis, both with respect to RFS and overall survival experience, were primary site (nonpelvic patients were most favorable) and patient age (younger patients were more favorable).

Adolescent↗
PubMed1990

Multimodal therapy for the management of nonpelvic, localized Ewing's sarcoma of bone: intergroup study IESS-II.

Two hundred fourteen eligible patients with previously untreated, localized Ewing's sarcoma of bone were randomized on IESS-II to receive Adriamycin (ADR; doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, vincristine, and dactinomycin by either a high-dose intermittent method (treatment [trt] 1) or a moderate-dose continuous method (trt 2) similar to the four-drug arm of IESS-I. Patient characteristics (sex, primary site, type of surgery) were stratified at the time of registration; these and other patient characteristics (age, time from symptoms to diagnosis, race) were distributed similarly between treatments. Surgical resection was encouraged, but not mandatory. Local radiation therapy was the same as for IESS-I. The median follow-up time is 5.6 years. The overall outcome was significantly better on trt 1 than on trt 2. At 5 years, the estimated percentages of patients who were disease-free, relapse-free, and surviving were 68%, 73%, and 77% for trt 1 and 48%, 56%, and 63% for trt 2 (P = .02, .03, and .05, respectively). The major reason for treatment failure for both treatment groups was the development of metastatic disease. The lung was the most common site of metastases followed by bone sites. The combined incidence of severe or worse toxicity (67%) was comparable between the treatments; however, severe or worse cardiovascular toxicity was significantly greater on trt 1. Tne only treatment-associated deaths (N = 3) were on trt 1 and were cardiac-related.

Adolescent↗
PubMed1990

Stability of RNA isolated from macrophages depends on the removal of an RNA-degrading activity early in the extraction procedure.

Ubiquitous RNases are the usual causes of RNA degradation on its isolation from mammalian cells. Using guanidine hydrochloride for the extraction of RNA from mouse peritoneal macrophages, we identify a major source of RNA-degrading activity, the stage of the extraction procedure at which this activity may be detected and show that its removal early in the extraction leads to a more dependable method for the recovery of high quality RNA.

Animals↗
PubMed1990

Testicular neoplasms: seminoma.

From 1969 to 1984, 58 patients with a diagnosis of testicular seminoma were seen and treated at the University of Kansas Medical Center. The median age was 34 years (range of 20 to 62 years). The American Joint Committee on Cancer Staging System was followed: stage I (34 patients); stage II (6); stage III (8); and stage IV (10). Forty-two patients had typical seminoma, and 16 had anaplastic histology. Nine patients had elevated B subunit of human chorionic gonadotropin, and nine had a history of cryptorchidism. Fifty-six patients received radiation treatment, and seven received chemotherapy with or without radiation. The median follow-up was 7 years (range 3 to 16 years). The overall disease-free (absolute) survival according to stage was: stage I, 91% (100%); stage II, 66% (80%); stage III, 75% (85%); and stage IV, 50% (50%). There were no late complications. The survival for patients with anaplastic histology or with elevated B subunit of human chorionic gonadotropin was not significantly different from that of typical seminoma.

Adult↗
PubMed1990

Decreased activity of the platelet Na+,K(+)-adenosine triphosphatase enzyme in allergic subjects.

A pathogenic role and abnormal function have both been ascribed to the blood platelet in allergy, but the explanation for these observations is unknown. This study compared the cation-stimulated adenosine triphosphatase enzyme (ATPase) activities of platelets from allergic (n = 18), potentially allergic (asymptomatic, positive skin test, n = 5) and normal patients (n = 10), all of whom were without symptoms at the time of the study. Platelets were separated by centrifugation, were sonicated, and were assayed for cation-dependent ATPase activity by spectrophotometry. The mean Na+,K(+)-ATPase activity (in nanomoles per microgram protein per minute) of allergic subjects (0.94 +/- 1.28) was significantly lower than that of normal subjects (3.93 +/- 1.58). No Na+,K(+)-ATPase activity was detectable in platelets from eight of the allergic subjects. The Na+,K(+)-ATPase activity of potentially allergic subjects was intermediate between those of the allergic and normal subjects. A significant negative correlation (p less than 0.01) was observed between serum IgE levels and platelet Na+,K(+)-ATPase values, thus suggesting a relationship between the reduced platelet Na+,K(+)-ATPase and IgE immunoglobulin. No such differences were observed for the Ca+(+)- and Mg+(+)-stimulated ATPases. In vivo dysfunction of the plasma membrane Na+,K(+)-ATPase enzyme in allergic subjects could have profound effects on levels of intracellular cations and thus platelet activation and function.

Adult↗