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Biomedical subjects

L Alexander

Publications and source records attributed to L Alexander.

At least 37 records · Page 2Linked to original sources
PubMed1997

Prevalence of obesity with increased blood pressure in elementary school-aged children.

The objectives of this study were to estimate the prevalence of obesity in school-aged children in Jefferson County, Alabama; to learn when school-aged children become obese; to determine the susceptible groups; and to study the association between obesity and blood pressure. During the school year, 5,953 children, ranging in age from 5 years to 11 years, were screened for weight, height, and blood pressure, using standardized techniques. We found that obesity, defined as > or = 120% of ideal body weight for height, is prevalent in 5-year-old to 11-year-old children. The prevalence of obesity in girls at age 5 was 23% in blacks and 10% in whites, rising to 47% in blacks and 27% in whites by age 11. In boys, the prevalence of obesity at age 5 was 13% in blacks and 6% in whites, rising to 29% in blacks and 22% in whites by age 11. The prevalence of obesity is significantly greater in black than in white children and is also significantly greater in girls than boys. The systolic and diastolic blood pressures were significantly higher in obese than in non-obese children. We conclude that the significant prevalence of childhood obesity and an associated complication, increased blood pressure, emerge in school-aged children. Thus, we recommend investigations of prevention and intervention programs to be used in the school setting.

Black or African American↗
PubMed1997

A role for natural simian immunodeficiency virus and human immunodeficiency virus type 1 nef alleles in lymphocyte activation.

A T-lymphoid cell line termed 221 was derived from a rhesus monkey infected with herpesvirus saimiri. Growth of 221 cells was dependent on the addition of interleukin-2 (IL-2) to the culture medium. In the absence of IL-2, 221 cells arrested in G0-G1 but did not die. Simian immunodeficiency virus (SIV) replicated efficiently in IL-2-stimulated 221 cells whether or not the nef gene was present. In the absence of IL-2, nef-containing SIV replicated 8 to 100 times more efficiently in 221 cells than did the same virus lacking nef. nef-containing virus preferentially stimulated the production of IL-2 from 221 cells. HIV-1 nef and v-ras genes, but not the c-ras gene, were shown to substitute functionally for SIV nef when tested as recombinant viruses in this assay system. These results demonstrate a role for natural nef in causing lymphoid cell activation, and they provide a system for delineating the biochemical mechanisms responsible for this activation.

Alleles↗
PubMed1996

Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants.

Neuropathogenicity of poliovirus can be attenuated by mutations in the internal ribosomal entry site (IRES) within the 5' nontranslated region of its genome. The Sabin vaccine strains used in prevention of poliomyelitis carry such mutations in their IRES elements. In addition, mutations within the structural and nonstructural proteins of Sabin strains may equally contribute to the attenuation phenotype. Despite their effectiveness as vaccines, the Sabin strains retain a neuropathogenic potential in animal models for poliomyelitis and, at a very low rate, they can cause poliomyelitis in vaccine recipients. The elimination of the neurocytopathic phenotype was achieved through the exchange of the entire poliovirus IRES with its counterpart from human rhinovirus type 2 without affecting growth properties in nonneuronal cells. The attenuating effect of the human rhinovirus type 2 IRES within the context of a poliovirus genome has been mapped to the 3' portion of this genetic element.

Animals↗
PubMed1996

Feasibility study of the use of bilevel positive airway pressure for respiratory support in the emergency department.

STUDY OBJECTIVE: To determine the feasibility of bilevel positive airway pressure (BiPAP) support for acute respiratory distress (ARD) in the emergency department. METHODS: A convenience sample of patients in ARD as a result of any nontraumatic cause was recruited for a prospective, noncontrolled clinical trial in the ED of an urban tertiary care teaching hospital. Hemodynamically unstable patients and those requiring immediate endotracheal intubation were excluded. After an initial arterial blood gas (AGB) analysis was obtained, the patient was placed on BiPAP (Bi-PAP S/T noninvasive ventilator; Respironics, Incorporated) by nose mask or face mask to provide noninvasive pressure support at 5 cm H20. Settings were titrated to patient tolerance and satisfactory pulse oximetry. After at least 30 minutes on a stable setting, arterial blood gases were remeasured. The cause of respiratory distress, vital signs, assessment of need for intubation, arterial blood gas results, and patient disposition were recorded. Success of noninvasive support was defined as the presence of (1) improvement in ABG parameters, (2) clinical improvement and decrease in evident dyspnea, and (3) avoidance of endotracheal intubation and mechanical ventilation. RESULTS: Fifty patients were studied. Causes of ARD included acute congestive heart failure (CHF; n=16), exacerbation of chronic obstructive pulmonary disease (COPD; n=9), mixed COPD/CHF (n=3), pneumonia (n=10), status asthmaticus (n=6), and other causes of acute respiratory failure (eg, stroke, overdose; n=6). Noninvasive management was successful in 43 patients (86%), with patients in all etiologic categories being equally likely to respond favorably to therapy. All patients were admitted to the hospital, but 52.5% of those who ordinarily would have required ICU beds were admitted to lower (and less costly) levels of care. Three patients were eventually intubated, all after admission to the ICU on BiPAP. Two patients did not tolerate BiPAP, and two others were considered ED treatment failures but were not intubated because of advance directives. CONCLUSION: As has been reported from other critical care settings, use of BiPAP is feasible and has potential utility in the management of ARD in the ED.

Blood Gas Analysis↗
PubMed1996

Association between eye and hand dominance and hitting, fielding and pitching skill among players of the Southern Baseball League.

BACKGROUND: The relationship between eye dominance and batting skill in baseball has been investigated, but conflicting results have been obtained. In addition, little attention has been given to the relationship, if any, between eye dominance and fielding and pitching skill. METHODS: A vision screening of 215 professional baseball players in the Southern Baseball League was performed and the eye dominance of these players was determined by a sighting test. Handedness for batting, fielding, and pitching was determined by history. RESULTS: The screening revealed that 66 percent of players were right-eye dominant and that, of 92 players who met the criteria established to qualify for the league batting championship, 60 percent had matched dominance of eye and hand. When official league batting averages were obtained for these 92 players, it was found that there was no statistically significant difference between batters with matched dominance (.278 mean batting average). For the 149 fielders in the league, no statistically significant differences based on eye dominance were found for fielding average (.893 matched dominance, .864 crossed dominance); for the 89 pitchers, a similar result was obtained. Pitchers were also evaluated with respect to eye dominance and earned run average, but no significant difference was found (3.91 matched dominance, 4.03 crossed dominance). CONCLUSIONS: Results indicate that there is no association between eye dominance, and hitting, fielding, or pitching skill in baseball.

Baseball↗
PubMed1995

The role of venous colour flow Doppler to aid the non-diagnostic lung scintigram for pulmonary embolism.

Sixty patients admitted with a clinical diagnosis of pulmonary embolism underwent a prospective analysis of the value of lung ventilation/perfusion scintigraphy and lower limb colour flow venous Doppler. Twenty-two per cent of scintigrams gave a high probability of pulmonary embolus (PE) and 45% a low probability/normal. The remainder were classed as indeterminate scintigrams (33%) and of these, 55% showed leg thrombi on the ultrasound scan. These patients were therefore treated by anticoagulation. A small number of the low probability scintigrams also proved to have lower limb thrombi by ultrasound. As a result of these two investigations just over half of these patients with a clinical diagnosis of PE were anticoagulated (31 out of 60). In 62% of these the ultrasound suggested thrombi confined to the calf as a source of PE.

Algorithms↗
PubMed1995

Interaction between the 5'-terminal cloverleaf and 3AB/3CDpro of poliovirus is essential for RNA replication.

On the basis of sequence alignments and secondary structure comparisons of the first 100 nucleotides of enterovirus and rhinovirus RNAs, chimeric constructs in which this region of poliovirus type 1 Mahoney [PV1(M)] is replaced with that of human rhinovirus type 2 (HRV2) or HRV14 have been engineered. These chimeric constructs contain the internal ribosomal entry site of either poliovirus or encephalomyocarditis virus. Independent of the internal ribosomal entry site elements, only the constructs containing either the PV1(M) or HRV2 cloverleaf sequences yielded viable viruses. The secondary structures of all three cloverleaves are quite similar. However, highly purified polioviral proteins 3CDpro and 3AB together bound to the PV1(M) and HRV2 cloverleaves, albeit with different affinities, whereas the HRV14 homolog did not interact with these proteins to any appreciable extent. These results support a mechanism of poliovirus genomic replication in which the formation of a complex between the cloverleaf structure and the 3CDpro/3AB proteins of poliovirus plays an essential role.

3C Viral Proteases↗
PubMed1995

Construction and genetic analysis of dicistronic polioviruses containing open reading frames for epitopes of human immunodeficiency virus type 1 gp120.

On the basis of previous studies of dicistronic (dc) polioviruses that carried two internal ribosomal entry sites (L. Alexander, H.-H. Lu, and E. Wimmer, Proc. Natl. Acad. Sci. USA 91:1406-1410, 1994; A. Molla, S. K. Jang, A. V. Paul, Q. Reuer, and E. Wimmer, Nature [London] 356:255-257, 1992), we have constructed a variety of dc polioviruses which express foreign genetic elements that were inserted either between two internal ribosomal entry site elements upstream of the poliovirus open reading frame (pPNENPO derivatives) or upstream of the open reading frame for the poliovirus proteinase 2Apro (pDI-E2A derivatives). Surprisingly, the addition of an N-terminal secretory pathway signal sequence to the open reading frame of the inserted foreign sequences (specifying either truncated versions of human immunodeficiency virus type 1 [HIV-1] gp120 or chloramphenicol acetyltransferase) resulted in a null phenotype, whereas removal of the signal sequence led to the production of viable viruses. Constructs that carried a foreign gene with a signal sequence were negative in RNA synthesis, an observation that suggested a very early block in viral replication. The insertion of transmembrane sequences downstream of the leader sequence did not reverse the replication block. Studies of dc polioviruses that encoded the truncated versions of HIV-1 gp120 showed an increase in genetic stability that correlated with a decrease in the size of the insert. A dc construct that contained a minigene encoding the principal neutralization determinant of HIV-1 produced a stable virus that retained the foreign sequence through multiple passages in cultured cells. These data indicate that dc polioviruses have potential as vaccines for the expression of small foreign epitopes.

Amino Acid Sequence↗
PubMed1994

Interaction of poliovirus polypeptide 3CDpro with the 5' and 3' termini of the poliovirus genome. Identification of viral and cellular cofactors needed for efficient binding.

Poliovirus proteinase 3CDpro by itself is not an RNA-binding protein. Two cellular proteins have been purified from HeLa cells (p50 and p36) which interact with purified 3CDpro but only p36-3CDpro bind to the 5'-terminal 110 nucleotides of polioviral RNA genome, an RNA segment whose secondary structure resembles a cloverleaf. The identity of these factors was determined by microsequencing tryptic digests of the purified proteins. Host protein p50 is the eukaryotic elongation factor EF-1 alpha, and p36 an N-terminal fragment thereof. p36, referred to as host factor, did not appear to interact with purified 3Cpro or 3Dpol. Significantly, the formation of a 3CDpro-cloverleaf complex was also observed in the presence of purified poliovirus polypeptide 3AB, the precursor of VPg. 3AB by itself does not stably bind to the cloverleaf. Competition experiments have demonstrated that the RNA-protein interactions are specific for the full-length cloverleaf. UV cross-linking studies were employed to examine the protein components of the cloverleaf ribonucleoproteins. RNA footprinting was used to determine the site on the cloverleaf where the viral and cellular factors bind. Finally, we have discovered that 3AB-3CDpro also interacts with the 3'-terminal sequence of poliovirus RNA. In contrast to the 5'-terminal cloverleaf, the 3'-terminal RNA can bind 3AB in the absence of other proteins. A model for initiation of poliovirus RNA synthesis is presented.

3C Viral Proteases↗
PubMed1994

Polioviruses containing picornavirus type 1 and/or type 2 internal ribosomal entry site elements: genetic hybrids and the expression of a foreign gene.

A picornavirus hybrid genome was constructed in which the internal ribosomal entry site (IRES) of encephalomyocarditis virus was inserted between the 5' non-translated region and the open reading frame of poliovirus (PV), type 1 (Mahoney). Upon transfection into HeLa cells, the hybrid RNA replicated and yielded a derivative of PV (W1-PNENPO). The PV IRES could be removed from pPNENPO, which resulted in a hybrid picornavirus (W1-P108ENPO) in which the translation of the PV open reading frame normally promoted by the type 1 IRES of PV was promoted by the type 2 IRES of encephalomyocarditis virus. This result indicates that these elements are not likely to contain cis-acting elements necessary for PV replication or encapsidation. A foreign gene (bacterial chloramphenicol acetyltransferase, CAT) was inserted into pPNENPO cDNA between the PV and encephalomyocarditis virus IRES elements. The dicistronic RNA replicated in HeLa cells and yielded a derivative of PV (W1-DICAT) with a genome 17% longer than that of wild-type PV. CAT assays and immunoblot analyses showed that the viral RNA efficiently expressed the foreign gene in cell culture. The CAT activity diminished somewhat with each passage of the dicistronic virus, an observation which suggested that the inserted gene had a deleterious effect on viral replication. However, even after five virus passages, a significant quantity of the foreign gene was still expressed. Insertion of the open reading frame of luciferase (67 kDa) resulted in an RNA species that replicated and expressed luciferase for up to 20 hr after transfection. However, this elongated RNA was not encapsidated.

Base Sequence↗
PubMed1994

Dicistronic polioviruses as expression vectors for foreign genes.

We have made use of certain novel genetic elements of picornaviruses termed internal ribosomal entry sites (IRES) to construct a viral RNA with the following genetic order: PV 5' NTR-EMCV IRES-PV ORF-3' NTR (PV, poliovirus; NTR, nontranslated region; EMCV, encephalomyocarditis virus; ORF, open reading frame). Transfection of this RNA into HeLa cells yielded a poliovirus (W1-PNENPO) that contained two heterologous IRES elements (type 1 IRES of PV; type 2 IRES of EMCV) in tandem. The insertion of foreign coding sequences into the genome of W1-PNENPO between the IRES elements yielded viable polioviruses with the gene order PV 5' NTR-foreign ORF-EMCV IRES-PV ORF-3' NTR. The foreign ORFs we have employed in this study included the coding region for chloramphenicol acetyltransferase (CAT), or segments of either luciferase or the HIV-1 envelope glycoprotein gp120. W1-PV/V3-3, a dicistronic poliovirus that contained HIV-1-specific sequences that included the V3 domain of gp120, was used to infect transgenic mice (PVR+) that were engineered to express the poliovirus receptor. The genetic stability of the dicistronic viruses and the HIV-1-specific immune response in PVR+ mice after infection with these novel agents are discussed.

AIDS Vaccines↗
PubMed1993

Colour flow mapping in the diagnosis of the calf deep vein thrombosis.

This prospective trial was organized to evaluate further the role of colour flow Doppler ultrasound techniques in the diagnosis of deep vein thrombosis (DVT) with particular reference to the isolated calf lesion. In 100 patients ultrasound was compared against the recognized gold standard of ascending venography. Fifty venograms were positive for DVT compared with 49 on ultrasound, a sensitivity of 98%. The specificity of ultrasound for DVT in the 50 patients without DVT on venography was 100%. Forty-five venograms demonstrated calf thrombus with varying proximal extent. Sixteen proved to be isolated calf lesions and these were all identified by ultrasound (100% sensitivity and specificity respectively for isolated calf DVT). In five of these isolated calf thrombus cases, results suggested that ultrasound better diagnosed the presence of thrombus. Ultrasound diagnosed significant pathology in 13 of the normal venogram patients giving an overall diagnostic yield of 62% as compared to 50% at venography.

Adolescent↗
PubMed1993

Psychological health-sickness (PHS) as a predictor of outcomes in dynamic and other psychotherapies.

This is the first dedicated review of quantitative studies on Sigmund Freud's proposition that the poorer the psychological health, the more limited are the benefits from treatment. Since observer-rated scales for psychological health-sickness were developed in 1949, many studies have applied them, and the majority show significant prediction of outcomes of psychotherapy, with correlations between .2 and .35. This article reviews (a) the main methods of measurement, (b) the record of predictive success, (c) validity studies, (d) the relation to psychiatric diagnosis, (e) prediction in forms of treatment other than psychotherapy, and (e) theories of why psychological health predicts outcomes of psychotherapy.

Humans↗