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Biomedical subjects

E Smith

Publications and source records attributed to E Smith.

At least 253 records · Page 14Linked to original sources

The effects of genetic exchange on variable antigen expression in Trypanosoma brucei.

The inheritance of variant surface antigens in Trypanosoma brucei has been determined by identifying variable antigen types (VATs) in each of two cloned parental stocks and then examining the presence and abundance of these VATs in hybrid progeny produced when these stocks undergo genetic exchange during co-transmission through tsetse flies. Nine VATs have been identified from the repertoire of the parental stock STIB 247L and 5 VATs have been identified from the parental stock STIB 386AA; the identified VATs were exclusive to each stock. Their inheritance was elucidated using two assays. In the first, repertoire antisera (RAS) containing antibody specificities to many different VATs were raised in rabbits to the 2 parental stocks and 6 progeny clones. The presence of VAT-specific antibodies in these RAS was then determined by antibody-dependent complement-mediated lysis. In the second assay, the 2 parental stocks and 4 hybrid progeny clones were each independently transmitted through tsetse flies and VATs observed using VAT-specific antisera in indirect immunofluorescence of metacyclic trypanosomes and in bloodstream forms of fly-bitten mice. The results from both assays showed that (1) both metacyclic- and bloodstream-VATs were inherited into the progeny, (2) each hybrid progeny clone contained some VATs from both parents, (3) hybrids did not express all the VATs from either parent, (4) there was little apparent pattern as to which VATs had been inherited and which had not and (5) the VAT repertoires of the hybrid progeny appeared to be larger than those of the parents. In addition, two results indicated that control of VAT expression remains unaltered after genetic exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunodominant carbohydrate determinants in the multicellular stages of Dictyostelium discoideum.

Two families of glycoprotein are defined in Dictyostelium discoideum by the presence of different glycoconjugates, both of which are highly immunogenic in mice. The previously described monoclonal antibodies MUD50 and MUD62 recognize the glycoconjugates and identify the respective glycoprotein families. Both types of glycosylation occur on vegetative and developmentally regulated glycoproteins. The immunodominant components of both families are reportedly O-linked sugars, but Western blots do not identify any glycoprotein that has both O-glycans, suggesting that there are two independently processed types of O-linked glycosylation in D. discoideum. The synthesis of the two O-glycan families is affected by glycosylation-defective mutations. Strains with a mutation at the modB locus lack one of these glycosylation types (that recognized by MUD50) and this mutation alters the size of two minor glycoproteins in the second family. Two new mutants, HU2470 (mod-352) and HU2471 (mod-353), lack the epitope recognized by MUD62. The two mutations map to different chromosomes. The mod-353 mutation also affects the size of PsA, a cell surface glycoprotein carrying the modB-dependent O-glycan.

Animals↗

Cerebral toxoplasmosis in Danish AIDS patients.

We estimate the frequency of central nervous system (CNS) toxoplasmosis in Danish AIDS patients and evaluate the diagnostic accuracy using the following criteria for acceptance of the diagnosis: either (1) the demonstration of Toxoplasma gondii in brain tissue or (2) one or more hypodense or ring-enhancing lesions on computerized axial tomography (CAT) scan and a neurologic and CAT scan improvement in response to 2 weeks of treatment. From 1981 until July 1990 266 patients were diagnosed with AIDS at Hvidovre Hospital, Copenhagen and 29 (11%) were treated, suspected for CNS toxoplasmosis. 17 patients had the diagnosis confirmed but since 5 patients, who were never treated, were diagnosed at autopsy, the overall cumulated incidence was 8% (22/266 patients). The overall diagnostic accuracy was 59% (17/29 patients) showing some changes over time. Among patients diagnosed with AIDS in 1988 or later, the accuracy was 83% (10/12 patients) while among patients diagnosed in 1987 or earlier the accuracy was 41% (7/17 patients). Four patients were diagnosed with Pneumocystis carinii pneumonia (PCP) prior to the diagnosis of CNS toxoplasmosis, while among patients with toxoplasmosis as the AIDS-defining diagnosis, 3 later developed PCP. None of these 7 patients had received secondary prophylaxis with a drug containing sulfonamide.

Acquired Immunodeficiency Syndrome↗

Pharmacokinetics of monoamine oxidase inhibitors.

Few studies on the pharmacokinetics and plasma drug levels of monoamine oxidase (MAO) inhibitors have been performed, despite several decades of clinical use. Older MAO inhibitors such as tranylcypromine produce neuronal accumulation of neurotransmitter amines as a consequence of functionally irreversible MAO inhibition. Typically, these agents are cleared from the body rapidly, so plasma drug levels are not correlated with MAO inhibition. However, recent research has demonstrated that tranylcypromine can produce direct and reversible pharmacologic effects, as well as clinical mood effects, that appear more closely related to transient plasma tranylcypromine levels than to the degree of MAO inhibition. In addition, a new generation of reversible MAO inhibitors is now being introduced. The antidepressant actions of these latter agents will almost certainly be directly influenced by pharmacokinetic factors. This review summarizes the existing pharmacokinetic literature on tranylcypromine, phenelzine, moclobemide, and selegiline. These drugs and others like them promise to become increasingly important in modern psychopharmacologic practice.

Humans↗

[Hypertension in Borrelia infections].

A patient with severe hypertension caused by Borrelia burgdorferi-encephalitis is reported. The patient recovered from all symptoms following treatment with high dose cefuroxime. The diagnosis was not established until lumbar puncture was performed.

Adult↗

[HIV infected women in Copenhagen. Risk factors and sex behavior].

A total of 115 women were found to be HIV-antibody positive during the period January 1985 to September 1988 in the three large hospitals in Copenhagen. Thirty-five women (31%) had been infected heterosexually, 63 (55%) were intravenous drug addicts, 12 (10%) had been infected by transfusion and in five (4%) the mode of transmission was unknown. In 1988, 73% of the women who were found to be HIV-positive were infected heterosexually while only 14% were infected in this manner in 1985. Out of the heterosexually HIV-infected women, 25 (71%) had probably been infected by a man from a risk group while nine further women were infected by a known HIV-positive man with-out connection to any risk group. Eleven women (31%) stated that they practised "safe sex" prior to the HIV test while 22 (74%) did so after the positive HIV-test, which represents a considerable improvement. Out of the drug addicted women, six (10%) stated that they had always practiced "safe sex" prior to the test while 13 (28%) did so after the HIV-test. Approximately 1/3 of these women periodically shared syringes and needles with others. It is concluded that heterosexual contact among HIV-infected women in Copenhagen is a route of transmission of significance. Women infected heterosexually appear to alter their sexual behavior when they are made aware of the positive HIV-test.

Denmark↗

[Heterosexual HIV infection in Denmark. Observations from an infectious disease department].

Since January 1985, 77 women have been found to be HIV-positive in the Department for Infectious Diseases, Hvidovre Hospital. Thirty-four out of these 77 women had histories of intravenous drug abuse, 11 had probably been infected with HIV by transfusion while 32 had probably been infected heterosexually. Out of the heterosexually infected women, a total of 9 were found to be living in a regular partnership with a HIV positive partner and eight of these couples were suitable for investigation. Seven of the eight women were probably infected by their regular male partner, four of whom belonged to known risk groups. Six of the eight men were HIV tested on account of HIV related symptoms while all of the women were tested because their regular partners were found to be HIV positive. The diagnosis of AIDS was established in ten out of 16 persons. Six of the men and three of the women were found to have AIDS less than one year after the first positive HIV test while the diagnosis was established in one man 22 months after the HIV test. The six men with HIV related symptoms had sought medical help on an average eight weeks before a HIV test was carried out and the diagnosis of AIDS was established in five immediately after referral to the special department. It is emphasized that every Danish doctor should be aware of the symptoms of HIV and these should be borne in mind even in the case of patients who do not belong to the known risk groups.

Adolescent↗

Randomized double-blind study of intravenous tocainide versus lidocaine for suppression of ventricular arrhythmias after cardiac surgery.

To compare the therapeutic efficacy and safety of intravenous tocainide with that of intravenous lidocaine in patients with ventricular arrhythmias after cardiac surgery, 25 patients were randomized to either agent in a double-blind manner. Tocainide was given in 16 patients as a 250 mg bolus followed by a loading infusion of 500 mg over 15 minutes and a maintenance infusion of 33.3 mg/min. Lidocaine was administered in 9 patients as a 100 mg bolus followed by a loading infusion of 60 mg over 15 minutes and a maintenance infusion of 1.4 mg/min. Therapy was continued for 24 hours in initially responding patients. With analysis of 24-h taped electrocardiograms it was found that single premature ventricular complexes (PVCs) were suppressed by tocainide by more than 80% in 94% of patients and by lidocaine in 75% of patients (p = NS). Couplets and ventricular tachycardia events were eliminated in all patients by either drug. Multiform PVCs were abolished in 94% of the patients after tocainide and in 75% after lidocaine (p = NS). Average overall success over the 24 hours with more than 80% suppression of single PVCs and simultaneous elimination of higher forms of arrhythmia was 71% with tocainide and 59% with lidocaine (p = NS). Adverse effects were negligible, with only one patient in the lidocaine group developing diaphoresis without necessitating termination of therapy. Treatment rapidly produced and then maintained blood levels of 4-10 mg/l for tocainide and 1-4 mg/l for lidocaine. We conclude that intravenous tocainide is well tolerated and has comparable efficacy to lidocaine in the acute therapy of postcardiac surgery ventricular arrhythmias.

Adult↗

Evidence that the mechanism of gene exchange in Trypanosoma brucei involves meiosis and syngamy.

All pairwise combinations of three cloned stocks of Trypanosoma brucei (STIB 247L, STIB 386AA and TREU 927/4) were co-transmitted through tsetse flies (Glossina morsitans) and screened for the production of hybrid trypanosomes. Clones of metacyclic and bloodstream trypanosomes from flies harbouring mature infections containing hybrid trypanosomes were established and screened for several isoenzyme and restriction fragment length polymorphisms. For each of the three combinations of parents, some progeny clones were observed to be of a phenotype and genotype indicating that genetic exchange had occurred during development of the trypanosomes in flies. These hybrid clones shared three salient features: (1) where the parents were homozygous variants the progeny were heterozygous, (2) where one of the parents was heterozygous, allelic segregation was observed and (3) the progeny clones were shown to be recombinant when two or more markers for which one of the parents was heterozygous were examined. These results are consistent with the progeny being an F1 in a diploid mendelian genetic system involving meiosis and syngamy. Our observations show that all possible combinations of the three stocks may undergo genetic exchange. A marker analysis of a series of clones each derived from single metacyclic trypanosomes showed that individual flies transmit a mixture of trypanosome genotypes corresponding to F1 progeny and to parental types, indicating that genetic exchange was a non-obligatory event in the life-cycle of the trypanosome. In addition, a preliminary analysis of the phenotype of procyclic stage trypanosomes derived from flies infected with two stocks, indicates that genetic exchange is unlikely to occur at this stage.

Alleles↗

Components of fitness become effectively neutral in equilibrium populations.

If, because of trade-offs or similar considerations, components of fitness are negatively correlated in equilibrium populations, they may then exhibit no correlation with total fitness. Lack of correlation with fitness is a fundamental characteristic of selective neutrality. Hence, selectively important traits become subsumed under neutral traits when the definition of neutrality is extended to include factors (genetic or phenotypic) that "behave as if they are neutral."

Mathematics↗

HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally.

Hepatocyte-specific gene expression requires the interaction of many proteins with multiple binding sites in the regulatory regions. HNF-3 is a site found to be important in the maximal hepatocyte-specific expression of several genes. We find that liver nuclear extracts contain three major binding activities for this site, which we call HNF-3A, HNF-3B, and HNF-3C. Purification from rat liver nuclear extracts of HNF-3A and HNF-3C reveals that each activity corresponds to a distinct polypeptide, as determined by SDS-PAGE. Peptide sequence derived from the most abundant species, HNF-3A, was used for synthesizing probes with which to isolate a cDNA clone of this protein. The encoded protein contains 466 amino acids (48.7 kD) and has binding properties identical to those of the purified protein. A 160-amino-acid region that does not resemble the binding domain of any known transcription factor is essential for DNA binding. The mRNA for HNF-3A is present in the rat liver but not in brain, kidney, intestine, or spleen, and the basis for this difference is cell-specific regulation of HNF-3A gene transcription.

Amino Acid Sequence↗

Clinical competencies for community health nursing.

Cost-containment strategies initiated in the early 1980s caused a major shift in site of care delivery for persons needing nursing care. Where once the majority of clients were cared for in the acute-care setting until they were self-sufficient, now most are discharged to the home environment still requiring acute-care nursing interventions as well as community health nursing skills. This rapid shift in practice sites has placed severe strain on community health nursing agencies. Not only are more nurses required to fill the increased demand for services, but the demand comes at a time when we are experiencing a severe nursing shortage. This has forced many agencies to hire acute care nurses who have little or no community health nursing experience. These nurses come to community health nursing expecting to use the same set of skills and knowledge base used in their acute-care practice; however, the skill levels and concepts required for community health nursing are quite different from the acute care setting. Educational preparation has not kept pace with this shift in practice. Consequently, many nurses are not adequately prepared to enter community health nursing. Preparation must include theoretical and experiential components that focus on assessment skills (of the community and individual), decision making, case management, health systems management, teaching, and leadership. Collaborative efforts between community health organizations and educational institutions would seem to be one solution that would ensure adequately prepared nurses for community health nursing. The establishment and maintenance of strong staff-development programs within community health nursing agencies are also required.

Clinical Competence↗

Surecut 0.6 mm liver biopsy in the diagnosis of cirrhosis.

Liver biopsy with the 0.6 mm (23 gauge) Surecut needle was compared to conventional Menghini biopsy in the diagnosis of cirrhosis. Seventy-seven consecutive patients (mainly alcoholics) with a clinical indication for liver biopsy had both biopsies performed simultaneously. In 71 patients sufficient material for a morphological diagnosis concerning liver architecture was obtained with both biopsy techniques (Surecut insufficient in 5 cases and Menghini insufficient in 2 cases). The biopsies were classified as cirrhosis or non-cirrhosis. There was agreement in 69 cases (97%, confidence limits 90-100%). Using the result of the Menghini biopsy as the final diagnosis, the predictive values for a positive and negative diagnosis for the Surecut needle were 96% and 98%, respectively. There were no complications to either of the biopsies. It is suggested that the 0.6 mm Surecut biopsy may be used in the diagnosis of cirrhosis in cases where conventional Menghini needle biopsy is contraindicated.

Biopsy, Needle↗

Heterosexually acquired human immunodeficiency virus infection in women in Copenhagen: sexual behavior and other risk factors.

In order to describe the risk pattern including sexual behaviour among HIV-infected women in Copenhagen we studied the charts of all women tested seropositive between January 1985 and August 1988 in the three main hospitals handling HIV/AIDS. One hundred and fifteen women were positive for HIV antibodies: 35 (31%) were infected by heterosexual contact and 63 (55%) were intravenous drug users. Among the heterosexually transmitted cases 25 (71%) had intercourse with a man from a high risk group and nine women had intercourse with a known HIV antibody positive man without known risk factors. Use of condoms was claimed by 31% of the heterosexually-transmitted women before the HIV test, and by 74% (P = 0.002) after the test. In 1988 73% of the women tested HIV positive were infected by heterosexual contact, in 1985 only 14%. We conclude that among HIV infected women in Copenhagen heterosexual transmission is a problem. These women seem to change sexual behaviour when informed about HIV positivity.

Contraceptive Devices, Male↗