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Biomedical subjects

S L Hunt

Publications and source records attributed to S L Hunt.

15 recordsLinked to original sources
PubMed2000

Lamotrigine monotherapy in children.

The effectiveness of lamotrigine as a monotherapeutic agent for a variety of pediatric epilepsies was reviewed retrospectively. Children were categorized as having focal vs generalized epilepsy and according to whether they were antiepileptic drug naive or drug exposed. Data collected included dosages, side effects, length of follow-up, number of prior drugs, and treatment response. Treatment was considered successful if the patient was seizure free for 6 months or more. Eighty-three children were identified (average age = 8.7 years); 43 had focal epilepsy, 32 had generalized epilepsy, and eight were not classified. Twenty-nine patients were classified as having specific syndromes. Fourteen patients were drug naive. The median follow-up period was 8 months (mean = 8.5). Overall, 45% were seizure free, 44% with focal epilepsy and 36% with generalized epilepsy. All children with juvenile myoclonic epilepsy and benign rolandic epilepsy of childhood were seizure free, although not all had been treated for at least 6 months. One third of drug-naive patients were seizure free. Rash was the most common side effect and was reported in five patients (6%); two patients discontinued the drug. None had Stevens-Johnson syndrome. One quarter of children experienced nonquantifiable improvements, namely increased alertness and improved behavior regardless of seizure control. Lamotrigine is effective as a monotherapeutic agent in children for both focal and generalized epilepsies. Side effects are relatively uncommon. Lamotrigine may be an effective firstline agent.

Adolescent↗
PubMed1999

unr, a cellular cytoplasmic RNA-binding protein with five cold-shock domains, is required for internal initiation of translation of human rhinovirus RNA.

Initiation of translation of the animal picornavirus RNAs occurs via a mechanism of direct ribosome entry, which requires a segment of the 5' UTR of the RNA, known as the internal ribosome entry site (IRES). In addition, translation of the enterovirus and rhinovirus (HRV) subgroups requires cellular trans-acting factors that are absent from, or limiting in rabbit reticulocytes, but are more abundant in HeLa cell extracts. It has been shown previously that HeLa cells contain two separable activities, each of which independently stimulates HRV IRES-dependent translation when used to supplement reticulocyte lysate; one of these activities was identified as polypyrimidine tract-binding protein (PTB). Here, the purification of the second activity is achieved by use of an RNA-affinity column based on the HRV 5' UTR. It comprises two components: a 38-kD protein (p38), which is a novel member of the GH-WD repeat protein family and has no intrinsic RNA-binding activity; and a 96- to 97-kD protein doublet, which was identified as unr, an RNA-binding protein with five cold-shock domains. Coimmunoprecipitation with antibodies against either protein shows that the two proteins interact with each other, and thus p38 is named unrip (unr-interacting protein). Recombinant unr acts synergistically with recombinant PTB to stimulate translation dependent on the rhinovirus IRES. In contrast, unr did not significantly augment the PTB-dependent stimulation of poliovirus IRES activity.

5' Untranslated Regions↗
PubMed1999

Rhinovirus 2A proteinase mediated stimulation of rhinovirus RNA translation is additive to the stimulation effected by cellular RNA binding proteins.

The internal ribosome entry site (IRES) of enteroviruses, and especially human rhinoviruses (HRV), functions very inefficiently in rabbit reticulocyte lysates, but can be stimulated by addition of HeLa cell extracts. Two HeLa cell activities have been identified: the A-type activity is due to polypyrimidine tract binding protein and the B-type to unr. In addition HRV and enterovirus IRES function requires a third RNA binding protein, poly(rC) binding protein 2, but this is present in reticulocyte lysates in non-limiting amounts. IRES activity can also be stimulated by the cleavage of initiation factor eIF4G mediated by either HRV 2A protease, or foot-and-mouth disease virus (FMDV) L protease. This raises the question of whether this stimulation is independent of that effected by the three RNA binding proteins, or whether cleaved eIF4G functionally mimics one or more of these proteins. It is shown here that the stimulation of HRV IRES activity resulting from cleavage of eIF4G is additive with the stimulation effected by HeLa cell A- and B-type activities. It is proposed that the role of the RNA binding proteins is to maintain or attain the appropriate 3-dimensional structure of the IRES RNA element, whereas the function of eIF4G is to deliver the 40S ribosomal subunit to the correct site on the IRES, a function which, for reasons not yet fully understood, is fulfilled more efficiently by the C-terminal cleavage product of eIF4G than by the intact factor.

Animals↗
PubMed1999

Polypyrimidine-tract binding protein (PTB) is necessary, but not sufficient, for efficient internal initiation of translation of human rhinovirus-2 RNA.

Initiation of translation of the animal picornavirus RNAs is via a mechanism of direct internal ribosome entry, which requires a substantial segment of the viral 5'-untranslated region, generally known as the IRES (for "internal ribosome entry site"). Because, however, translation of the RNAs of members of the enterovirus, and more especially, the rhinovirus subgroups of the Picornaviridae is restricted in the reticulocyte lysate system, but is greatly stimulated by the addition of HeLa cell extracts, the implication is that, in these cases, internal initiation also requires cellular trans-acting factors that are more abundant in HeLa cell extracts than in rabbit reticulocytes. This was used as the basis of a functional assay for the purification of the HeLa cell factors required for translation dependent on the human rhinovirus-2 (HRV) IRES. There are two such HeLa cell factors separable by ion-exchange chromatography, each of which is individually active in the assay, although their combined effect is synergistic. One of these activities is shown to be polypyrimidine-tract binding protein (PTB) on the grounds that (1) the activity copurifies to homogeneity with PTB and (2) recombinant PTB expressed in Escherichia coli stimulates HRV IRES-dependent translation with a specific activity similar to that of the purified HeLa cell factor. Furthermore, it is shown that recombinant PTB also stimulates the translation of RNAs bearing the poliovirus type 1 (Mahoney) IRES.

Cell Fractionation↗
PubMed1997

A review of the newer antiepileptic drugs and the ketogenic diet.

Since 1994, three new antiepileptic drugs, felbamate, lamotrigene, and gabapentin, have been released for the treatment of epilepsy. The present paper provides an overview of these three drugs and reviews their potential uses in pediatric epilepsy even though felbamate is the only one with an approved use in children. Topiramate and vigabatrin, which are under investigation, are briefly reviewed. In addition, a discussion of the ketogenic diet is included because of its recent publicity. Patient examples included provide clinical illustrations for the reader.

Acetates↗
PubMed1995

Direct evidence that polypyrimidine tract binding protein (PTB) is essential for internal initiation of translation of encephalomyocarditis virus RNA.

The requirement of PTB, polypyrimidine tract binding protein, for internal initiation of translation has been tested using an RNA affinity column to deplete rabbit reticulocyte lysates of PTB. The affinity column was prepared by coupling CNBr-activated Sepharose with the segment of the 5'-untranslated region of encephalomyocarditis virus (EMCV) RNA previously shown to bind PTB. Lysates passed through this column were devoid of PTB, and were incapable of internal initiation of translation dependent on the EMCV 5'-untranslated region, while retaining the capacity for translation dependent on ribosome scanning. Full activity for internal initiation was restored by the addition of recombinant PTB at the physiologically relevant concentration of about 5 micrograms/mL. When various PTB deletion mutants were tested, it was found that this activity required virtually the full-length protein. Thus, PTB is an essential protein for internal initiation promoted by the EMCV 5'-untranslated region. However, the PTB-depleted lysate retained the capacity for internal initiation promoted by the 5'-untranslated regions of another cardiovirus, Theiler's murine encephalomyelitis virus, and of the unrelated hepatitis C virus, and in neither case did addition of recombinant PTB stimulate internal initiation. Therefore, PTB is not a universal internal initiation factor that is indispensable in every case of internal ribosome entry.

Animals↗
PubMed1994

Age-cohort differences in treating symptoms of mental illness: a process approach.

This study examines age-cohort differences in conceptually organizing, observing, and responding to unclustered symptoms of mental illness. Older (M = 70.8) and younger (M = 19.9) adults sorted symptoms of depression, schizophrenia, and age-associated changes into similarity groupings. Hierarchical cluster analysis showed that both older and younger adults sorted the statements similarly, although labels given for depressive symptoms differed across groups. Participants then reported which symptoms they had observed within their families and listed what actions were taken. Age groups showed significant differences in symptom reporting, with older individuals observing depressive symptoms less frequently. There were small differences in the kinds of actions reported. These results suggest that differences in help-seeking behavior for mental illness may be explained by differences in the way symptoms are observed by younger and older cohorts.

Adolescent↗
PubMed1993

Use of a regenerable immobilized second antibody to determine azidothymidine in a flow system.

A regenerable immobilized second-antibody reactor was used to measure azidothymidine (AZT) by competitive enzyme immunoassay in a flow system. The immobilized antibody was regenerated 4 times with little loss of immunospecificity. A residual enzymatic activity of about 7% of the total response was obtained with horseradish peroxidase as label. AZT was measured below the nanomolar level by allowing competition to proceed for about 2 min. A limit of detection of 6.57 x 10(-11) +/- 1.56 x 10(-11) M AZT was obtained when the concentration of AZT-peroxidase conjugate was 0.125 ng/mL. This system was used to determined azidothymidine in Retrovir capsule with good results. In replicate measurements, RSDs of 5.51% and 2.44%, n = 6, were obtained at 7.48 x 10(-11) and 3.74 x 10(-9) M AZT, respectively.

Animals↗
PubMed1993

The influence of viral coding sequences on the efficiency of internal initiation of translation of cardiovirus RNAs.

Since internal initiation of translation of cardiovirus RNAs requires the approximately 450-nt segment of the viral genome immediately upstream of the authentic initiation codon for viral polyprotein synthesis, the question arises as to whether the immediately adjacent sequences, the start of the polyprotein coding region, also influence the efficiency of internal initiation. Therefore, a variety of constructs derived from encephalomyocarditis virus and Theiler's murine encephalomyelitis virus retaining various lengths of viral coding sequence were translated in rabbit reticulocyte lysates. Efficient internal initiation showed no requirement specifically for viral coding sequences, but on the other hand certain motifs, notably G-rich sequences, located immediately downstream of the initiation codon were highly inhibitory. These results suggest a possible explanation for the evolution of cardiovirus polyproteins lacking N-terminal myristylation signals and are also pertinent to the design of constructs in which the cardiovirus internal ribosome entry signal is used to drive the expression of a reporter cistron.

Base Sequence↗