On the similarity of plasma-polymerized tetrafluoroethylene and RF plasma-sputtered polytetrafluoroethylene.
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Argon↗
Biomedical subjects
A L Johnson
Publications and source records attributed to A L Johnson.
Rehabilitation of dogs with surgically treated cranial cruciate ligament-deficient stifles by use of electrical stimulation of muscles.
OBJECTIVE: To determine effect of electrical muscle stimulation (EMS) on rate and degree of return to function of the limb and development of degenerative joint disease (DJD) after surgical creation and subsequent stabilization of the cranial cruciate ligament (CrCL)-deficient stifle. ANIMALS: 12 clinically normal adult large (19.5 to 31.5 kg) dogs. PROCEDURE: Dogs were anesthetized, and the right CrCL was severed via arthrotomy, destabilizing the stifle. After 3 weeks, the stifle was surgically stabilized. Three weeks later, 6 dogs were subjected to an EMS treatment protocol for the thigh muscles. At 5, 9, 13, and 19 weeks after stifle destabilization, treated (n = 6) and control (n = 6) dogs were evaluated for return of stifle function. Gross and histologic evaluations of the stifles were performed at 19 weeks after stifle destabilization. RESULTS: Treated dogs had significantly (P = 0.001) better lameness score than did control dogs. There was less palpable crepitation of the stifle in treated dogs (P = 0.06); treated dogs also had significantly (P = 0.01) fewer radiographic signs of bone changes. Thigh circumference was significantly (P = 0.02) larger in treated dogs. There was less gross cartilage damage (P = 0.07) in the EMS-treated dogs, but more medial meniscal damage (P = 0.058, cranial pole; P = 0.051, caudal pole). CONCLUSIONS: Improved lameness scores, larger thigh circumference, and decreased radiographically apparent bony changes observed for the treated group of dogs support the hypothesis that dogs treated by EMS after surgical stabilization of the CrCL-deficient stifle had improved limb function, with less DJD, than did dogs treated with the currently accepted clinical protocol of cage rest and slow return to normal activity. However, results of force plate evaluation did not support the hypothesis. Increased meniscal damage in dogs treated by EMS may be cause for concern.
Animals↗
Closed reduction and type-II external fixation of comminuted fractures of the radius and tibia in dogs: 23 cases (1990-1994).
OBJECTIVE: To describe a technique for closed reduction of and application of a type-II external fixator to comminuted fractures of the radius and tibia in dogs and to evaluate outcome of the technique in a series of client-owned dogs. DESIGN: Retrospective case series. ANIMALS: 23 dogs that underwent closed reduction of severely comminuted (> or = 5 fragments); mid-diaphyseal radial (n = 9); and tibial (n = 14) fractures and stabilization with a type-II external fixator. PROCEDURE: Radiographs were made postoperatively and every 4 to 6 weeks until the fixator was removed. The effect of type of fracture (open vs closed), type of pins (threaded vs smooth), and number of fixation pins on surgery time, time between surgery and development of bridging callus, and time between surgery and removal of the fixator was evaluated using one-sided Student's t-tests. RESULTS: 21 fractures healed after a single surgery. Two dogs with radial fractures required a second procedure because of complications. All fractures healed with the original fixation device in place. Mean time between surgery and the development of bridging callus was 11.4 weeks (range, 4 to 22 weeks), and mean time between surgery and fixator removal was 14.7 weeks (range, 4 to 27 weeks). Type of fracture, type of pins, and number of fixation pins did not have a significant effect on surgery time, time to development of bridging callus, or time to fixator removal. CLINICAL IMPLICATIONS: Closed reduction and application of a type-II external fixator was an effective method of treating severely comminuted radial and tibial fractures.
Animals↗
Coordinated regulation of gene expression by the cell cycle transcription factor Swi4 and the protein kinase C MAP kinase pathway for yeast cell integrity.
Specific transcription in late G1, mediated by the transcription factors SBF (Swi4p-Swi6p) and MBF (Mbp1p-Swi6p), is crucial for cell cycle progression in budding yeast. In order to better understand the G1/S transition, we initiated a search for conditional mutations synthetic lethal with swi4delta. One of the isolated mutants, rsf8swi4delta, showed a growth defect due to cell lysis. rsf8 is allelic to PKC1, encoding a protein kinase C homologue which controls cell integrity. In the presence of the rsf8/(pkc1-8) mutation, a functional SBF but not MBF is required for viability. Importantly, swi4delta and swi6delta strains are hypersensitive to calcofluor white and SDS, indicating that they possess a weakened cell wall. Overexpression or ectopic expression of CLN did not suppress the pkc1-8swi4delta mutant phenotype, thus SBF must control cell integrity independently, rather than acting through CLN expression. We found that at least six genes involved in cell wall biosynthesis are periodically expressed at the G1/S phase boundary. In all six cases, cell cycle-regulated expression is due mainly to Swi4p. Finally, we found that the PKC1 MAP kinase pathway is a positive regulator of five of these cell wall genes, these genes being novel targets of regulation by this pathway. We suggest that SBF and the PKC1 MAP kinase pathway act in concert to maintain cell integrity during bud formation.
Alleles↗
Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy.
BACKGROUND: The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy. METHODS: Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission. FINDINGS: The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.
Adolescent↗
Is it possible to make an accurate diagnosis based only on a medical history? A pilot study on women's knee joints.
The purpose of this pilot study was to determine if an accurate diagnosis could be made concerning the knee joint using only the patients' medical history information. Only women were chosen for this study because of existing unpublished data on a cohort of 100 women with normal knees to act as a control (group I). From the 2,266 knee surgical procedures in the database of one surgeon, two other groups were selected. Group II was those women with only a torn medial meniscus. Group III were those women with only a torn anterior cruciate ligament (ACL). The medical history data of one half of the database were statistically analyzed to determine the questions that were the best predictors of each group. The medical history questions discovered to be best predictors were different from what might be expected from an individual surgeon's experience, expert opinion, or a medical consensus opinion panel, but the predictors did have a foundation in fact and are substantiated by statistical analyses. Using these predictors, a validation was performed on the other half of the database. When the top 142 predicting questions were used, the diagnostic accuracy was 98%; 98 of 100 of the "normal" group, 57 of 59 cases classified as having a torn meniscus, whereas 128 of 129 cases classified as having a torn ACL were correctly identified. When the only the 30 strongest predictors were used, the diagnostic accuracy was 85%: 100 of 100 cases were correctly classified as normal, 45 of 59 cases were correctly classified as having a torn meniscus, and 101 of 129 cases were correctly classified as having a torn ACL. This study demonstrated that statistical methods applied to medical historical data can make a differential clinical diagnosis of an unknown knee joint problem with high degree of accuracy and with statistical significance. In the future, computerized medical diagnostic instruments can be constructed using these statistical methods.
Anterior Cruciate Ligament↗
A mutation in a Saccharomyces cerevisiae gene (RAD3) required for nucleotide excision repair and transcription increases the efficiency of mismatch correction.
RAD3 functions in DNA repair and transcription in Saccharomyces cerevisiae and particular rad3 alleles confer a mutator phenotype, possibly as a consequence of defective mismatch correction. We assessed the potential involvement of the Rad3 protein in mismatch correction by comparing heteroduplex repair in isogenic rad3-1 and wild-type strains. The rad3-1 allele increased the spontaneous mutation rate but did not prevent heteroduplex repair or bias its directionality. Instead, the efficiency of mismatch correction was enhanced in the rad3-1 strain. This surprising result prompted us to examine expression of yeast mismatch repair genes. We determined that MSH2, but not MLH1, is transcriptionally regulated during the cell-cycle like PMS1, and that rad3-1 does not increase the transcript levels for these genes in log phase cells. These observations suggest that the rad3-1 mutation gives rise to an enhanced efficiency of mismatch correction via a process that does not involve transcriptional regulation of mismatch repair. Interestingly, mismatch repair also was more efficient when error-editing by yeast DNA polymerase delta was eliminated. We discuss our results in relation to possible mechanisms that may link the rad3-1 mutation to mismatch correction efficiency.
Adenosine Triphosphatases↗
Characterization of a chicken luteinizing hormone receptor (cLH-R) complementary deoxyribonucleic acid, and expression of cLH-R messenger ribonucleic acid in the ovary.
Studies were conducted to characterize the chicken ovarian LH receptor (cLH-R) cDNA and to evaluate expression of cLH-R mRNA in follicles at different stages of development. A total of 1.89 kb of nucleic acid sequence corresponding to the cLH-R (1.79 kb of the predicted coding region) was isolated by a combination of reverse transcription-polymerase chain reaction and cDNA library screening techniques. Also of interest was the finding that two of three positive clones isolated from the hen ovarian cDNA library contained an 86-bp insert located in the extracellular domain within 69 bp of the putative transmembrane domain. This insert contains an inframe TGA stop codon, suggesting that an alternatively spliced transcript results in translation of a truncated protein corresponding to the extracellular domain of the cLH-R. Considering all protein domains thus far characterized, the deduced amino acid sequence of the cLH-R shares 73.2% and 74.2% identity with the rat and porcine LH-R sequences, respectively, with highest homology occurring within the seven transmembrane spanning regions (86-88% identity vs. mammalian sequences). Northern blot analysis determined that cLH-R mRNA levels in the theca layer tend to increase through follicle development to the second largest (F2) preovulatory follicle (p = 0.084), and to decrease in the largest preovulatory (F1) follicle (p < 0.02 vs. F2). By comparison, cLH-R mRNA levels are nondetectable (by Northern blot analysis) in granulosa cells from prehierarchal (3-8-mm diameter) follicles. Constitutive expression of cLH-R mRNA in granulosa cells is first detectable at the 9-12-mm diameter stage of follicle development, and levels are further increased in cells from large preovulatory (F1, F2, and F3) follicles (p < 0.01 vs. 9-12-mm stage). Collectively, these results are consistent with previous observations that granulosa cells from prehierarchal follicles fail to produce cAMP or steroids in response to short-term incubation with ovine LH, in vitro, and that granulosa cells acquire LH responsiveness only subsequent to follicle selection into the rapid growth phase.
Alternative Splicing↗
Characterization of the chicken follicle-stimulating hormone receptor (cFSH-R) complementary deoxyribonucleic acid, and expression of cFSH-R messenger ribonucleic acid in the ovary.
Studies were conducted to characterize the chicken (c) FSH receptor (R) cDNA, and to evaluate expression of cFSH-R mRNA in the hen ovary at known stages during follicle development. A total of 2.5 kb of nucleic acid sequence including the complete cFSH-R coding region was isolated by a combination of the reverse-transcription polymerase chain reaction and 5'- and 3'-rapid amplification of cDNA ends techniques. Overall, the nucleic acid sequence homology of the cFSH-R cDNA coding region is 71.8% and 72.2% compared to the rat and bovine FSH-R, respectively, while the deduced amino acid sequence identity for the receptor protein (693 amino acids) is 71.9% and 72.4%, respectively. By comparison, the cFSH-R nucleic acid and amino acid sequences are 60.1% and 49.4% identical to the respective cLH-R sequences. Northern blot analysis detected a single 4.3-kb cFSH-R mRNA transcript, which was selectively expressed in ovarian (granulosa, theca, and stromal) tissues, but not the oviduct, adrenal, liver, muscle, or brain. As the follicle developed from the prehierarchical (6- to 8-mm diameter) to the largest preovulatory (F1 follicle) stage, cFSH-R mRNA levels progressively declined within both the granulosa and theca layers (p < 0.05). Moreover, cFSH-R mRNA levels were lower in whole atretic than in morphologically normal 3- to 5-mm follicles (p = 0.0015). The pattern of cFSH-R mRNA expression within the granulosa layer during follicle development was notably different from that of the recently reported cLH-R, in that cLH-R mRNA levels increase to become readily detectable coincident with dramatically increased steroidogenic capacity during the last few days before ovulation of the follicle. On the other hand, highest levels of cFSH-R mRNA in 6- to 8-mm (prehierarchical) follicles were consistent with a role for the cFSH-R in maintaining the viability of prehierarchical follicles and in initiating granulosa cell differentiation at the time when follicles are selected into the preovulatory hierarchy.
Amino Acid Sequence↗
Induction of apoptotic cell death in hen granulosa cells by ceramide.
Recent studies have demonstrated that ovarian follicle atresia occurs extensively before follicle selection into the avian preovulatory hierarchy, and that this process is mediated via granulosa cell apoptosis. Subsequent to follicle selection, granulosa cells are inherently resistant to apoptosis, and such resistance is correlated with increased expression of death suppressor genes such as bcl-xlong. In the present studies we used this avian ovary model system to 1) identify cellular characteristics and mechanisms related to apoptotic cell death of granulosa cells in vitro, and 2) further characterize functional differences between apoptosis-susceptible (4- to 8-mm follicle) and apoptosis-resistant (preovulatory follicle) granulosa cells. Treatment of granulosa cells from the largest preovulatory follicle with N-octanoylsphingosine (C8-ceramide) results in pronounced oligonucleosome formation, a hallmark of apoptosis. That this is indicative of programmed cell death is supported by an increased incidence of pyknotic nuclei and apoptotic bodies in C8-ceramide-treated samples compared to that in control cultured cells. Tumor necrosis factor-alpha, a stimulator of ceramide production, actively promotes oligonucleosome formation in apoptosis-susceptible, but not in apoptosis-resistant, granulosa cells. Induction of apoptosis is also observed after exposure of apoptosis-resistant granulosa cells to sphingomyelinase treatment and UV irradiation, which are known to stimulate endogenous ceramide production, and to the anticancer drug, daunorubicin, which initiates de novo ceramide biosynthesis via activation of ceramide synthase. Although treatment of granulosa cells with fumonisin B1, a specific ceramide synthase inhibitor, blocks daunorubicin-stimulated oligonucleosome formation, UV-induced cell death is unaffected. Taken together, these results demonstrate that pharmacological factors known to mimic the actions of ceramide or stimulate ceramide production can induce oligonucleosome formation and programmed cell death in granulosa cells. More importantly, however, the ability of a physiologically relevant initiator of ceramide biosynthesis, tumor necrosis factor-alpha, to promote cell death is evident only in apoptosis-susceptible granulosa cells collected from atresia-prone prehierarchal follicles. These data provide support for ceramide as an important intracellular signaling mechanism, mediating granulosa cell apoptosis and follicle atresia.
8-Bromo Cyclic Adenosine Monophosphate↗
Susceptibility of avian ovarian granulosa cells to apoptosis is dependent upon stage of follicle development and is related to endogenous levels of bcl-xlong gene expression.
Studies were conducted to evaluate the susceptibility of avian ovarian granulosa cells to apoptosis when incubated in vitro and to relate this relative susceptibility to both the stage of follicle development from which granulosa cells were collected (atresia-prone vs. -resistant) and to the expression of a gene previously linked to the regulation of cell viability, bcl-xlong. Granulosa cells from slow growing, prehierarchal (4- to 8-mm diameter; atresia-prone) follicles were found to undergo rapid and progressively extensive apoptosis after incubation in defined medium for 6-24 h (P < 0.05 vs. unincubated controls). By contrast, cells from the largest preovulatory (F1) follicle, as well as from follicles most recently recruited into the follicle hierarchy (9- to 12-mm diameter), showed significantly less low molecular wt labeling at 6 h of incubation (P < 0.05 vs. 4- to 8-mm follicles). Furthermore, the amount of low molecular wt labeling did not significantly increase in cells from either stage of follicle development at 12 or 24 h of incubation (P < 0.05 vs. 6 h incubation). This biochemical indication of ongoing apoptosis in prehierarchal follicle granulosa cells was confirmed by an increased incidence of pyknotic nuclei detected by morphological analysis. Thus, increased susceptibility to apoptosis in incubated prehierarchal follicle granulosa cells is correlated with the high rate of follicle atresia that is known to occur at this stage of development in vivo. Recombinant human FSH (100 mIU) and transforming growth factor-alpha (3.3 nM) partially suppressed apoptosis in prehierarchal follicle granulosa cells after 6 h of incubation (by 46-57%; P < 0.05 vs. control), as did the cAMP analog, 8-Br-cAMP (1 mM; by 59%; P < 0.05). A single form of the bcl-2-related gene, bcl-x, was detected in hen ovarian tissues; this transcript corresponded to bcl-xlong, the death-suppressing form of bcl-x. The highest levels of bcl-xlong messenger RNA were found in granulosa tissue from preovulatory follicles, with significantly lower levels detected in prehierarchal follicle granulosa tissue (P < 0.05). Elevated expression of bcl-xlong in preovulatory follicles was correlated to increased resistance to the process of apoptosis, in vitro, and the virtual absence of follicle atresia at this stage of development, in vivo. We conclude that there is a direct relationship between the inherent susceptibility of avian granulosa cells to apoptosis and the high rate of follicle atresia in follicles not yet selected into the preovulatory hierarchy. Moreover, our results are consistent with the proposal that the expression of death-suppressing genes, including bcl-xlong, is capable of rendering cells resistant to the process of apoptosis. The findings reported herein provide the foundation for a novel model with which to further elucidate molecular mechanisms related not only to the initiation of follicle atresia, but also events associated with the process of follicle selection.
Alternative Splicing↗
Rme1, a negative regulator of meiosis, is also a positive activator of G1 cyclin gene expression.
Control of G1 cyclin expression in Saccharomyces cerevisiae is mediated primarily by the transcription factor SBF (Swi4/Swi6). In the absence of Swi4 and Swi6 cell viability is lost, but can be regained by ectopic expression of the G1 cyclin encoding genes, CLN1 or CLN2. Here we demonstrate that the RME1 (regulator of meiosis) gene can also bypass the normally essential requirement for SBF. RME1 encodes a zinc finger protein which is able to repress transcription of IME1 (inducer of meiosis) and thereby inhibit cells from entering meiosis. We have found that expression of RME1 from a high copy number plasmid can specifically induce CLN2 expression. Deletion of RME1 alone shows no discernible effect on vegetative growth, however, deletion of RME1 in a swi6 delta swi4ts strain results in a lowering of the non-permissive temperature for viability. This suggests that Rme1 plays a significant but ancillary role in SBF in inducing CLN2 expression. We show that Rme1 interacts directly with the CLN2 promoter and have mapped the region of the CLN2 promoter required for Rme1-dependent activation. Consistent with Rme1 having a cell cycle role in G1, we have found that RME1 mRNA is synthesized periodically in the cell cycle, with maximum accumulation occurring at the M/G1 boundary. Thus Rme1 may act both to promote mitosis, by activating CLN2 expression, and prevent meiosis, by repressing IME1 expression.
Base Sequence↗
Remission of epilepsy: results from the National General Practice Study of Epilepsy.
Remission of seizures is a crucial measure of outcome in epilepsy. The National General Practice Study of Epilepsy (NGPSE) aimed to investigate the remission of patients with epilepsy and the effect of various factors on the likelihood of remission. The NGPSE is a prospective population-based study free from major selection bias. We enrolled 1091 patients with newly diagnosed or suspected epilepsy who attended one of 275 general practices throughout the UK between 1984 and 1987. Remission was analysed in those patients who were classified after 6 months as having definite epilepsy (n = 564) or possible epilepsy (n = 228). After 9 years from the index seizure, 86% (95% CI 81-90) of patients with definite epilepsy had achieved a remission of 3 years and 68% (61-75) a remission of 5 years. For the complete cohort, including those with possible epilepsy, the remission rates at 9 years were 87% (83-91) for 3-year remission and 71% (65-77) for 5-year remission. The proportion of patients with definite epilepsy who were still in remission at 9 years' follow-up (terminal remission) was 68% (62-74) for 3-year and 54% (48-60) for 5-year remission. 61% (56-68) of patients with idiopathic seizures and 61% (46-75) of those with remote symptomatic epilepsy had achieved 5-year remission by 9 years. Overall, age and seizure type had little effect on the chances of achieving remission. This study confirms the good outcome for seizure control in the majority of patients.
Anticonvulsants↗
The DNA repair genes RAD54 and UNG1 are cell cycle regulated in budding yeast but MCB promoter elements have no essential role in the DNA damage response.
The DNA repair genes RAD54 and UNG1 have MCB elements in their promoters and are shown to be cell cycle regulated. Their transcripts are coordinately expressed with RNR1, ribonucleotide reductase, a MCB-regulated gene known to be expressed in late G1. However, no evidence was obtained for a direct role of MCB elements in DNA repair. Of the proteins that bind and activate MCB elements, only mutations in SWI6 have a defect in DNA repair, showing significant sensitivity to methyl methane sulphonate. Furthermore, analysis of the CDC9 promoter indicates that MCB elements are not required for the induction of the gene by ultraviolet light irradiation. These promoter elements may not respond directly to DNA damage but may have a role in enhancing the induction response.
Cell Cycle↗
Comparison of surgical skills of veterinary students trained using models or live animals.
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Animals↗
Design, synthesis, and structure--activity relationship studies for a new imidazole series of J774 macrophage specific acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors.
Acyl-CoA:cholesterol acyltransferase (ACAT) is the primary enzyme involved in intracellular cholesterol esterification. Arterial wall infiltration by macrophages and subsequent uncontrolled esterification of cholesterol leading to foam cell formation is believed to be an important process which leads to the development of fatty streaks. Inhibitors of the ACAT enzyme may retard this atherogenic process. We have recently discovered a series of imidazoles which are potent in vitro ACAT inhibitors in the J774 macrophage cell culture assay. This paper will describe the design, synthesis, and structure--activity relationship for this very potent series of compounds.
Animals↗
Veterinary student expectations and outcomes assessment of a small animal surgical curriculum.
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Animals↗
Randomized, controlled trial of the efficacy of carprofen, a nonsteroidal anti-inflammatory drug, in the treatment of osteoarthritis in dogs.
Seventy dogs were included in a randomized, controlled, multicenter trial to test the efficacy of carprofen (2.2 mg/kg of body weight, PO, q 12 h) for relief of clinical signs associated with osteoarthritis. Thirty-six dogs received carprofen, and 34 received a placebo. Response of the dogs was evaluated by comparing results of force plate examination and a graded lameness examination performed before and immediately after 2 weeks of treatment, and by obtaining a subjective assessment of the dog's posttreatment condition from owners and participating veterinarians. A physical examination, CBC, serum biochemical analyses, urinalysis, and fecal occult blood test were performed before and after treatment to monitor safety. For force plate evaluation, the odds ratio was 3.3, meaning that a dog treated with carprofen was 3.3 times more likely to have a positive response than was a dog treated with the placebo. For evaluation by a veterinarian, the odds ratio was 3.5, and for owner evaluation, the odds ratio was 4.2. Institution where dogs were treated did not have a significant effect on results. A variety of reactions that may have been related to the medication (placebo or carprofen) were recorded; however, none were considered serious. Serum alanine aminotransferase activity was high in 3 dogs (2 that received placebo and 1 that received carprofen) at the conclusion of treatment; none of the 3 dogs were clinically ill. Ten dogs (5 that received placebo and 5 that received caprofen) had negative pretreatment and positive posttreatment fecal occult blood test results.
Animals↗