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Biomedical subjects

A L Johnson

Publications and source records attributed to A L Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Budding yeast RSI1/APC2, a novel gene necessary for initiation of anaphase, encodes an APC subunit.

SIC1 is a non-essential gene encoding a CDK inhibitor of Cdc28-Clb kinase activity. Sic1p is involved in both mitotic exit and the timing of DNA synthesis. To identify other genes involved in controlling Clb-kinase activity, we have undertaken a genetic screen for mutations which render SIC1 essential. Here we describe a gene we have identified by this means, RSI1/APC2. Temperature-sensitive rsi1/apc2 mutants arrest in metaphase and are unable to degrade Clb2p, suggesting that Rsi1p/Apc2p is associated with the anaphase promoting complex (APC). This is an E3 ubiquitin-ligase that controls anaphase initiation through degradation of Pds1p and mitotic exit via degradation of Clb cyclins. Indeed, the anaphase block in rsi1/apc2 temperature-sensitive mutants is overcome by removal of PDS1, consistent with Rsi1p/Apc2p being part of the APC. In addition, like our rsi1/apc2 mutations, cdc23-1, encoding a known APC subunit, is also lethal with sic1Delta. Thus SIC1 clearly becomes essential when APC function is compromised. Finally, we find that Rsi1p/Apc2p co-immunoprecipitates with Cdc23p. Taken together, our results suggest that RSI1/APC2 is a subunit of APC.

Amino Acid Sequence↗
PubMed1998

Randomised controlled trial to assess acceptability of phenobarbital for childhood epilepsy in rural India.

BACKGROUND: The use of phenobarbital for childhood epilepsy is controversial because of reported behavioural side-effects; however, whether this research can validly be extrapolated to developing countries is not clear. We undertook a randomised comparison of phenobarbital and phenytoin to assess the acceptability and efficacy of phenobarbital as monotherapy for childhood epilepsy in rural India. METHODS: Between August, 1995, and February, 1996, 109 unselected children aged 2-18 years with partial and generalised tonic-clonic epilepsy were identified by population screening. 15 families declined to take part. 94 children were randomly allocated treatment with phenobarbital (1.5 mg/kg daily for 2 weeks; maintenance dose 3.0 mg/kg daily; n = 47) or phenytoin (2.5 mg/kg daily then 5.0 mg/kg daily; n = 47). Children were followed up for 12 months. The primary outcome measure was the frequency of behavioural side-effects; behaviour was assessed by the Conners parent rating scale for children aged 6 years and older, and by the preschool behaviour screening questionnaire (BSQ) for those aged 2-5 years, at 12 months or at withdrawal from treatment. Analysis was by intention to treat. FINDINGS: The mean log-transformed scores on the behaviour rating scales did not differ significantly between the phenobarbital and phenytoin groups (Conners 2.64 [SD 0.71] vs 2.65 [0.89], p = 0.97; n = 32 in each group: BSQ 2.12 [1.31] vs 2.18 [1.02], p = 0.94; n = 4 vs 3). The odds ratio for behavioural problems (phenobarbital vs phenytoin) was 0.51 (95% CI 0.16-1.59). There was no excess in parental reports of side-effects for phenobarbital. We found no difference in efficacy between the study drugs (adjusted hazard ratio for time to first seizure from randomisation 0.97 [0.28-3.30]). INTERPRETATION: This evidence supports the acceptability of phenobarbital as a first-line drug for childhood epilepsy in rural settings in developing countries.

Adolescent↗
PubMed1998

Expanded profile of the SHAFT syndrome.

The SHAFT syndrome is a factitious disorder in which a patient manipulates the surgeon to perform operations to fulfill his or her psychological needs. The acronym describes patients who are sad, hostile, anxious, frustrating, and tenacious. A chart review from January 1990 to June 1996 was undertaken to provide a profile to aid in the recognition and diagnosis of the SHAFT syndrome. An analysis of 28 patients revealed characteristics supporting a definitive SHAFT profile. Patients with SHAFT syndrome seek physicians to perform invasive procedures. Their typical complaint is pain, usually without objective physical findings that would support a more definitive diagnosis. Such patients tend to be women, cry with pain, describe symptoms out of proportion to objective findings, and have a history of psychiatric care.

Adult↗
PubMed1998

Swi5 controls a novel wave of cyclin synthesis in late mitosis.

We have shown previously that the Swi5 transcription factor regulates the expression of the SIC1 Cdk inhibitor in late mitosis. This suggests that Swi5 might control other genes with roles in ending mitosis. We identified a gene with a Swi5-binding site in the promoter that encoded a protein with high homology to Pcl2, a cyclin-like protein that associates with the Cdk Pho85. This gene, PCL9, is indeed regulated by Swi5 in late M phase, the only cyclin known to be expressed at this point in the cell cycle. The Pcl9 protein is associated with a Pho85-dependent protein kinase activity, and the protein is unstable with peak levels occurring in late M phase. PCL2 is already known to be expressed in late G1 and we find that, in addition, it is also regulated by Swi5 in telophase. The expression of PCL2 and PCL9 at this stage of the cell cycle implies a role for the Pho85 Cdk at the end of mitosis. Consistent with this a synthetic interaction was observed between pho85delta and strains deleted for SIC1, SWI5, and SPO12. These and other studies support the notion that the M/G1 switch is a major cell cycle transition.

Binding Sites↗
PubMed1998

The description of activities of daily living in five centres in England and Wales. Medical Research Council Cognitive Function and Ageing Study.

OBJECTIVES: the Medical Research Council Cognitive Function and Ageing Study is a longitudinal study of health and well-being of the ageing UK population. We present the screening interview which assesses how this group copes with activities of daily living (ADL), and characteristic ranges for the total score of these activities by age and DESIGN: random sampling was from Family Health Service Authority lists in three urban and two rural areas, including institutions. Participants (n = 13,009) in their 65th year and over were interviewed between 1991 and 1994. The sample was stratified to provide equal numbers in the 65-74 and 75 years and over age groups. Each participant was asked about socio-demographic variables, cognitive function, physical health, medication and ADL (based on the nine items from the self-reported Townsend's disability scale). RESULTS: the scale shows good reliability and validity in this study. There is a high frequency of disability amongst the oldest old, and relationships between ability and age and between ability and sex and other sociodemographic variables: the risk of having difficulty increases with living away from home, with poorer eyesight and speech, with lower social class and with lack of further education. Projections of the number (and percentage) of severely disabled over-65-year-olds in the UK in 2011 and 2051 are 1.4 million (2.2%) and 2.3 million (3.9%) respectively.

Activities of Daily Living↗
PubMed1998

Expression of the inhibitor of T-cell apoptosis (ita) gene in hen ovarian follicles during development.

It is now well established that within the hen ovary, preovulatory follicles rarely become atretic and that granulosa cells from preovulatory follicles are relatively resistant to undergoing apoptosis in vitro. By comparison, prehierarchal (< or = 8-mm diameter) follicles are highly susceptible to becoming atretic in vivo, and approximately 70% of granulosa cells collected from 3- to 8-mm-diameter follicles rapidly undergo apoptosis when incubated for as little as 6 h in vitro in defined medium. The present studies were conducted to characterize expression of an inhibitor of apoptosis (iap) gene, inhibitor of T-cell apoptosis (ita), within hen follicle tissues at various stages of follicle development. The ita gene product has recently been shown to share homology within both the baculovirus repeat sequences of the N-terminus and the zinc ring-finger motif from the C-terminus and was originally determined to be expressed in chicken cells of T-lymphocyte lineage. In the present studies, highest levels of ita mRNA within the granulosa cell layer were found in preovulatory (atresia-resistant) follicles, with significantly lower levels detected in prehierarchal follicles. After 24 h of primary culture, ita mRNA levels increased in granulosa cells from preovulatory follicles by 3.2-fold as compared to those in freshly collected cells and were elevated by 8.9-fold in those granulosa cells from 6- to 8-mm follicles that successfully formed a primary culture monolayer. Moreover, ita mRNA levels were significantly increased in 6- to 8-mm-follicle granulosa cells after only 2 h of suspension culture, and this increase could be prevented by actinomycin D. This spontaneous increase in ita expression may serve to protect from cell death the relatively small population of prehierarchal follicle granulosa cells that survive in vitro. It is concluded from these data, taken together, that patterns of ita mRNA expression during follicle development are consistent with a potential role for this gene in protecting granulosa cells from apoptosis and thus maintaining follicle viability.

Animals↗
PubMed1998

Towards a modified cardiopulmonary resuscitation policy.

This article proposes a modification of a hospital cardiopulmonary resuscitation (CPR)/do not resuscitate (DNR) policy that prescribes CPR for all unless a DNR order is agreed to by patient and physician. Rather than maintaining CPR as an intervention that can be avoided only by a negative order, the proposed modified policy supports a positive order, i.e., perform CPR when beneficial unless the patient refuses. To provide a clinical basis for an ethical discussion comparing the current policy with the modified proposal, a brief review of the outcome of CPR in terms of survival to discharge is presented. Two principal observations were made. First, regarding overall survival, there is an element of harm for an important proportion of those who initially respond to CPR but fail to survive to discharge, spending time in the intensive care unit only to have a subsequent arrest and death in hospital. Second, a set of point estimates of survival to discharge in relation to 11 pre-arrest diagnostic characteristics shows their close correlation. The modified proposal should provide a more realistic framework within which to evaluate the needs and wishes of patients at this difficult and emotional time. This concept is implemented by establishing the CPR status of all patients as one component of their positive treatment regimen, rather than having CPR as an intervention to be avoided only by the DNR order. The author discusses the current and proposed policy relative to their effect on patient selection, discussion with patients about CPR, the dilemma that results when the patient insists on CPR when it is not recommended and the protection of patient autonomy.

Cardiopulmonary Resuscitation↗
PubMed1997

Open reduction and bone plate stabilization, compared with closed reduction and external fixation, for treatment of comminuted tibial fractures: 47 cases (1980-1995) in dogs.

OBJECTIVE: To compare open reduction and bone plate fixation with closed reduction and external skeletal fixation as treatment for severely comminuted fractures of the tibia. Limb alignment, fracture reduction, operating time, hospitalization time, postoperative care, time to unrestricted activity, bone healing, complications, and number of surgical procedures were considered. DESIGN: Retrospective case series. ANIMALS: 47 dogs with severely comminuted fractures of the tibia treated with open reduction and bone plate application (22 dogs) or closed reduction and external fixation (25 dogs). PROCEDURE: Medical records of all dogs included in this study were reviewed. Postoperative and follow-up radiographs were evaluated by 2 independent observers. RESULTS: Differences were not found in hospitalization time, time to unrestricted activity, or time to earliest radiographic evidence of bone healing between dogs with fractures treated with a bone plate and dogs with fractures treated with an external fixator. Fractures treated with an external fixator had more caudal malalignment, and fractures treated with a bone plate had more valgus malalignment. Malalignments were determined not to be related to clinical problems. Dogs with fractures treated with an external fixator had shorter surgery times and more recheck examinations. Dogs with fractures treated with a bone plate had more complications. CLINICAL IMPLICATIONS: Open reduction with bone plate fixation and closed reduction with external fixation were both effective for treatment of comminuted tibial fractures. External fixation was associated with shorter surgery time, but dogs required more extensive postoperative care. Bone plate fixation was associated with more complications.

Animals↗
PubMed1997

Risk factors associated with development of pelvic canal stenosis secondary to sacroiliac separation: 84 cases (1985-1995).

OBJECTIVE: To measure pelvic canal diameter in dogs from a ventrodorsal radiographic view of the pelvic region, to define a normal pelvic canal diameter, to evaluate risk factors associated with stenosis of the pelvic canal secondary to sacroiliac separation, and to determine clinical signs associated with pelvic canal stenosis. DESIGN: Retrospective case series. ANIMALS: 84 case-group and 46 control-group dogs. PROCEDURE: Medical records and radiographs of dogs with conditions unrelated to pelvic fracture (control group) and dogs with sacroiliac separation (case group) in which radiographs were obtained before surgery, after surgery, or after fracture healing were reviewed. Discriminant analysis was used to determine a normal pelvic canal diameter. An ANOVA and Dunnett's two-sided test were used to determine factors associated with pelvic canal stenosis. RESULTS: Pelvic canal diameter ratio determined from control-group dogs was > or = 1.1. Pelvic canal diameter ratios were significantly less for case-group dogs on radiographs obtained before surgery and after fracture healing than for control-group dogs, regardless of fracture type or treatment, except for dogs with ilial fractures treated conservatively. Pelvic canal diameter ratios did not differ for case-group dogs on radiographs obtained after surgery from those for control-group dogs, except when ilial fractures were surgically reduced. None of the dogs had clinical signs associated with pelvic canal stenosis. CLINICAL IMPLICATIONS: Pelvic canal diameter in dogs can be determined from a ventrodorsal radiographic view of the pelvic region. Dogs with pelvic fractures that have a normal pelvic canal diameter before surgery tend to have a normal pelvic canal diameter after fracture healing.

Animals↗
PubMed1997

Characterization of the avian Ich-1 cDNA and expression of Ich-1L mRNA in the hen ovary.

We have sequenced the chicken interleukin-1beta-converting enzyme (ICE) and ced-3 homolog (Ich-1) cDNA, and evaluated Ich-1 mRNA expression in the hen ovary during follicle development. While two alternatively spliced forms of Ich-1, Ich-1L and Ich-1S, were amplified by PCR from an embryonic chicken cDNA library, only the Ich-1L form was found to be expressed in adult ovarian granulosa and theca tissues. The deduced amino acid (aa) sequence of ICH-1L is 70.8% identical to human ICH-1L and contains the conserved QACRG peptide active catalytic sequence characteristic of many ICE-related family of cysteine proteases.

Amino Acid Sequence↗
PubMed1997

Temporomandibular joint litigation: resolving issues of medical necessity and contract ambiguity.

Courts routinely award coverage for TMJ disorders under medical plans, despite exclusionary language and evidence that the insured failed to disclose preexisting treatment as required by the plan and neglected to attempt more conservative treatment first. Such decisions adversely affect both the health carrier and the plan participants. Various states have enacted legislation mandating coverage of TMJ; however, TMJ issues still exist and will remain a frequent topic for litigation until the judiciary recognizes that validating contract language ultimately benefits insureds as consumers and reinforces the integrity of the industry as a whole.

Humans↗
PubMed1997

The Swi5 transcription factor of Saccharomyces cerevisiae has a role in exit from mitosis through induction of the cdk-inhibitor Sic1 in telophase.

Deactivation of the B cyclin kinase (Cdc28/Clb) drives the telophase to G1 cell cycle transition. Here we investigate one of the control pathways than contributes to kinase deactivation, involving the cell cycle-regulated production of the cdk inhibition Sic1. We show that the cell cycle timing of SIC1 expression depends on the transcription factor Swi5, and that Swi5-dependent SIC1 expression begins during telophase. In contrast to Swi5, the related transcription factor Ace2, which can also induce SIC1 expression, is not active during telophase. The functional consequence of Swi5-regulated SIC1 expression in vivo is that both sic1 delta and swi5 delta strains have identical mitotic exit-related phenotypes. First, both are synthetically lethal with dbj2 delta, resulting in cell cycle arrest in telophase. Second, both are hypersensitive to overexpression of the B cyclin CLB2. Thus Swi5-dependent activation of the SIC1 gene contributes to the deactivation of the B cyclin kinase, and hence exit from mitosis.

CDC28 Protein Kinase, S cerevisiae↗
PubMed1997

Expression of avian urokinase and tissue-type plasminogen activator messenger ribonucleic acid during follicle development and atresia.

While several studies have documented the presence of plasminogen activator (PA) activity in hen ovarian follicle granulosa and theca tissues, to date it has not been possible to conclusively distinguish between the urokinase (u) and the tissue-type (t) form of the enzyme; this inability is due, in part, to lack of the cloned or characterized chicken tPA gene or gene product. Thus, the present studies were conducted to identify a partial cDNA for chicken tPA and subsequently to evaluate expression of uPA and tPA mRNA in granulosa and theca tissues in vivo and in vitro. Urokinase PA and mRNA levels were highest in prehierarchical-follicle granulosa (3- to 5- and 6- to 8-mm follicles) and theca (6- to 8-mm follicles) tissue compared to hierarchical (9-12 mm through largest preovulatory) follicles. In vitro treatment with a phorbol ester (phorbol 12-myristate, 13-acetate), but not a cAMP analogue (8-bromo-cAMP), significantly increased uPA mRNA levels in both granulosa and theca tissue from the largest and second-largest preovulatory follicles. Of special interest was the finding that levels of uPA mRNA were 10.9-fold higher in atretic compared to morphologically normal 3- to 5-mm follicles. Moreover, 4- to 8-mm-follicle granulosa cells, which spontaneously undergo apoptosis in vitro, demonstrated a rapid increase in uPA mRNA levels after 1 h of incubation (prior to the detection of oligonucleosome formation) while levels in preovulatory-follicle granulosa cells, which do not undergo spontaneous apoptosis, were not altered after 18 h of incubation. By contrast, while tPA mRNA can be identified in granulosa and theca tissues from prehierarchical and preovulatory follicles following polymerase chain reaction amplification, constitutively expressed levels of the transcript were too low to reliably measure by Northern blot analysis. These data indicate that while the chicken expresses a tPA gene that is homologous to the mammalian tPA, uPA is the predominant PA expressed in the hen ovary. In addition, the higher levels of uPA mRNA found in granulosa cells actively undergoing apoptosis and in follicles most susceptible to atresia (4-8 mm) suggest a role for this protease in mediating processes both during the early stages of programmed cell death and in the later stages of follicle atresia and resorption.

Amino Acid Sequence↗
PubMed1997

Expression of bcl-2 and nr-13 in hen ovarian follicles during development.

Follicle atresia is initiated within the granulosa cell layer of ovarian follicles and is mediated via the process of apoptosis. In the hen, at least two populations of granulosa cells can be distinguished during follicle development on the basis of their inherent susceptibility or resistance to apoptosis, in vitro. Given the previously established correlation between expression of bcl-xLong and hen granulosa cell resistance to apoptosis, the present studies were conducted to characterize expression of bcl-2 and an avian bcl-2 homologue, nr-13, in follicles at various stages of development. Levels of nr-13 mRNA were significantly higher only in granulosa cells from the largest (F1) preovulatory follicle compared to 3- to 5-mm prehierarchal follicles. By comparison, bcl-2 mRNA levels were 5- to 9-fold higher in granulosa cells from the three largest preovulatory follicles compared to those from follicles 9 to 12 mm in diameter and prehierarchal follicles. The increase in neither nr-13 nor bcl-2 was correlated with the stage of follicle development associated with the acquisition of resistance to apoptosis in granulosa cells (e.g., at the 9- to 12-mm stage). Results from the present studies do not support a close correlation between constitutive expression of nr-13 or bcl-2 mRNA and the transition from a state of apoptosis susceptibility to apoptosis resistance in hen granulosa cells. Thus, it is proposed that nr-13 and bcl-2 play more of a supportive role in regulating additional aspects of ovarian cell function such as cell proliferation and/or differentiation.

Animals↗
PubMed1997

Prognosis of epilepsy: a review and further analysis of the first nine years of the British National General Practice Study of Epilepsy, a prospective population-based study.

PURPOSE: To understand the prognosis of newly diagnosed epilepsy to provide rational therapy and advice for patients and their physicians. METHODS: The National General Practice Study of Epilepsy (NGPSE) is the first large population-based study that has assessed the prognosis of patients with newly diagnosed epilepsy prospectively over a prolonged period. We review the previously published data on the prognosis of epilepsy after 9 years of follow-up. One thousand ninety-one patients with newly diagnosed or suspected epilepsy who were attending 1 of 275 general practices throughout the United Kingdom between 1984 and 1987 were ascertained. Cases in this study were defined as the occurrence of one or more seizures, including provoked seizures. Prognosis in terms of remission of seizures, and mortality, was analyzed in the patients who were classified 6 months after recruitment as having definite epilepsy (n = 564) or possible/probable epilepsy (n = 228). RESULTS: Only 33 patients were completely lost to follow-up. After 9 years, 86% [95% confidence interval (CI) 81, 90] of patients with definite epilepsy had achieved a remission of 3 years, and 68% (CI 61, 75), had achieved a remission of 5 years. For the complete cohort, with possible/probable epilepsy included, the rates increased to 87% (CI 83, 91) for 3-year remission and 71% (CI 65, 77) for 5-year remission. The proportion of patients with definite epilepsy who were still in remission at 9-year follow-up (terminal remission) was 68% (CI 62, 74) for 3-year remission and 54% (CI 48, 60) for 5-year remission. When stratified by etiology, the proportions achieving 5-year remission by 9 years was 69% (CI 60, 77) for idiopathic seizures, and 61% (CI 46, 75) for remote symptomatic epilepsy. Age and seizure type had small effects on the chances of achieving remission, with children experiencing slightly lower rates than older patients, and partial seizures having lower remission rates than generalized seizures. The overall standardized mortality ratio (SMR) for patients with definite or possible/probable epilepsy was 2.5 (CI 2.1, 2.9), and 3.0 (CI 2.5, 3.7) for patients who were classified as having definite epilepsy. The SMR for patients with idiopathic epilepsy was 1.6 (CI 1.0, 2.4), for those with remote symptomatic epilepsy it was 4.3 (CI 3.3, 5.5), and for those with acute symptomatic epilepsy it was 2.9 (CI 1.7, 4.5). CONCLUSIONS: Overall, most patients with epilepsy will enter remission; however, there is a higher than expected risk of death, especially in those with symptomatic epilepsy.

Actuarial Analysis↗