Biomedical subjects

L Stevens

Publications and source records attributed to L Stevens.

At least 19 recordsLinked to original sources

PubMed2000

Upregulation of myosin heavy chain MHClalpha in rat muscles after unweighting and clenbuterol treatment.

Myosin heavy chain (MHC) mRNA isoforms were quantified in soleus (SOL) and gastrocnemius (GAS) muscles from rats exposed to 14 days of either hindlimb unweighting (HU), clenbuterol treatment (CB), or HU combined with CB treatment (HU-CB). All conditions induced in SOL a shift from slow to faster MHC mRNA isoforms and an upregulation of MHClalpha. Increases were highest with CB, lowest with HU-CB, and coincided mainly with elevations in MHClla mRNA isoforms. The changes in MHC mRNA levels in GAS muscle corresponded to fast-to-faster transitions. Elevations in MHClalpha mRNA were smaller than in SOL and seemed to occur in parallel with decreases in MHClbeta. Taken together, our results suggested that MHClalpha is expressed in transforming rat slow and fast muscles, most likely as an intermediate step between MHClbeta and MHClla.

Actins↗

PubMed2000

The mycosins of Mycobacterium tuberculosis H37Rv: a family of subtilisin-like serine proteases.

There is little information regarding the role of proteolysis in Mycobacterium tuberculosis and no studies on the potential involvement of proteases in the pathogenesis of tuberculosis. We identified five M. tuberculosis genes (mycP1-5) that encode a family of serine proteases (mycosins-1 to 5), ranging from 36 to 47% identity. Each protein contains a catalytic triad (Asp, His, Ser) within highly conserved sequences, typical of proteases of the subtilisin family. These genes are also present in M. bovis BCG and other virulent mycobacteria, but only one homologue (mycP3) was detected in M. smegmatis. The mycosins have N-terminal signal sequences and C-terminal transmembrane anchors, and the localisation of the mycosins to the membrane/cell wall was verified by Western blot analysis of heterologously expressed proteins in cellular fractions of M. smegmatis. In M. tuberculosis, all the mycosins were expressed constitutively during growth in broth. Mycosins-2 and 3 were also expressed constitutively in M. bovis BCG, but no expression of mycosin-1 was detected. Mycosin-2 was modified by cleavage in all three mycobacterial species. The multiplicity and constitutive expression of these proteins suggests that they have an important role in the biology of M. tuberculosis.

Amino Acid Sequence↗

PubMed2000

Male-killing Wolbachia in a flour beetle.

The bacteria in the genus Wolbachia are cytoplasmically inherited symbionts of arthropods. Infection often causes profound changes in host reproduction, enhancing bacterial transmission and spread in a population. The reproductive alterations known to result from Wolbachia infection include cytoplasmic incompatibility (CI), parthenogenesis, feminization of genetic males, fecundity enhancement, male killing and, perhaps, lethality Here, we report male killing in a third insect, the black flour beetle Tribolium madens, based on highly female-biased sex ratios of progeny from females infected with Wolbachia. The bias is cytoplasmic in nature as shown by repeated backcrossing of infected females with males of a naturally uninfected strain. Infection also lowers the egg hatch rates significantly to approximately half of those observed for uninfected females. Treatment of the host with antibiotics eliminated infection, reverted the sex ratio to unbiased levels and increased the percentage hatch. Typically Wolbachia infection is transmitted from mother to progeny, regardless of the sex of the progeny; however, infected T. madens males are never found. Virgin females are sterile, suggesting that the sex-ratio distortion in T. madens results from embryonic male killing rather than parthenogenesis. Based on DNA sequence data, the male-killing strain of Wolbachia in T. madens was indistinguishable from the CI-inducing Wolbachia in Tribolium confusum, a closely related beetle. Our findings suggest that host symbiont interaction effects may play an important role in the induction of Wolbachia reproductive phenotypes.

Animals↗

PubMed2000

Repeated measures in clinical trials: simple strategies for analysis using summary measures.

The summary measures approach to analysing repeated measures is described. The circumstances under which it can be advantageous to use such measures are considered. Strategies for baseline adjustment where there are multiple baselines are examined, as is the choice of appropriate summary statistic. A compromise trend/mean measure, regression through the origin, is proposed as being useful under some circumstances. An analysis using this measure is illustrated with a suitable example.

Biometry↗

PubMed2000

Effects of a clinical-practice guideline and practice-based education on detection and outcome of depression in primary care: Hampshire Depression Project randomised controlled trial.

BACKGROUND: Depression is a major individual and public-health burden throughout the world and is managed mainly in primary care. The most effective strategy to reduce this burden has been believed to be education of primary-care practitioners. We tested this assumption by assessing the effectiveness of an educational programme based on a clinical-practice guideline in improving the recognition and outcome of primary-care depression. METHODS: We carried out a randomised controlled trial in a representative sample of 60 primary-care practices (26% of the total) in an English health district. Education was delivered to practice teams and quality tested by feedback from participants and expert raters. The primary endpoints were recognition of depression, defined by the hospital anxiety and depression (HAD) scale, and clinical improvement. Analysis was by intention to treat. FINDINGS: The education was well received by participants, 80% of whom thought it would change their management of patients with depression. 21409 patients were screened, of whom 4192 were classified as depressed by the HAD scale. The sensitivity of physicians to depressive symptoms was 39% in the intervention group and 36% in the control group after education (odds ratio 1.2 [95% CI 0.88-1.61]). The outcome of depressed patients as a whole at 6 weeks or 6 months after the assessment did not significantly improve. INTERPRETATION: Although well received, this in-practice programme, which was designed to convey the current consensus on best practice for the care of depression, did not deliver improvements in recognition of or recovery from depression.

Antidepressive Agents, Tricyclic↗

PubMed2000

Alterations in contractile properties and expression of myofibrillar proteins in wobbler mouse muscles.

The purpose of this study was to characterize the alterations in muscle contractile (tension-pCa relationship) and biochemical (myosin heavy and light chains, troponin C content) properties in a hereditary motoneuron disease. The study was performed on wobbler mouse mutants which presented a neuronal degeneration. The time course of the disease was followed at 5 and 7 weeks in sternocleidomastoid (SCM) and soleus muscles. The wobbler disease was found to induce a shift from fast to slow myosin heavy-chain isoform expression in SCM and soleus muscles. The analysis of the myosin light-chain (MLC) composition revealed, for the SCM muscles, the appearance of the slow isoforms at 5 weeks and an increase in the regulatory MLC2 content at 7 weeks. A significant increase in the slow troponin C isoform content was found in both types of wobbler muscles at 7 weeks. The wobbler soleus and SCM muscles presented an age- and fiber-type-related atrophy, characterized by a decline in absolute maximal tension and fiber diameter. A decrease in calcium sensitivity was observed at 7 weeks for the soleus fibers and at both 5 and 7 weeks for the SCM. The results indicated fast-to-slow changes in contractile and biochemical properties of the wobbler soleus and SCM muscles, which occurred during the motoneuron degeneration process previously described in the wobbler pathology.

Animals↗

PubMed2000

Robotic-assisted laparoscopic microsurgical tubal anastomosis: a human pilot study.

OBJECTIVE: To evaluate the feasibility and safety of a robotic device to perform a laparoscopic tubal anastomosis. DESIGN: Prospective pilot study. SETTING: Tertiary care medical center. PATIENT(S): Ten patients with previous tubal ligations underwent laparoscopic tubal ligation reversal using a robotic suturing device. INTERVENTION(S): Tubal surgery was performed with a robotic system. A two-layered closure was used for all tubes. Four stitches of 8-0 polygalactin sutures were used for each layer. MAIN OUTCOME MEASURE(S): Tubal patency; secondary measures were pregnancy rates, complications, and operative time. RESULT(S): The procedure was completed successfully in all 10 patients. No patient required conversion to an open procedure. The mean time (+/-SD) required to complete the anastomosis of both tubes was 159 +/- 33.8 minutes. Chromotubation at the end of the procedure showed patency in all tubes anastomosed. A postoperative hysterosalpingogram 6 weeks after surgery demonstrated patency in 17 of the 19 (89%) tubes anastomosed. There have been five pregnancies so far. There were no complications. CONCLUSION(S): Robotic technology can be used safely to create laparoscopic microsurgical anastomoses with adequate patency rates. Robotic technology has the potential to make laparoscopic microsuturing easier.

Adult↗

PubMed2000

Binaural-beat induced theta EEG activity and hypnotic susceptibility.

Six participants varying in degree of hypnotizability (2 lows, 2 mediums, and 2 highs) were exposed to 3 20-minute sessions of a binaural-beat sound stimulation protocol designed to enhance theta brainwave activity. The Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) was used for pre- and post-stimulus measures of hypnotic susceptibility. A time-series analysis was utilized to evaluate anterior theta activity in response to binaural-beat sound stimulation over baseline and stimulus sessions. The protocol designed to increase anterior theta activity resulted in a significant increase in percent theta for 5 of 6 participants. Hypnotic susceptibility levels remained stable in the high-susceptible group and increased significantly in the low and medium-susceptible groups.

Acoustic Stimulation↗

PubMed2000

Case-control study of laparoscopic versus abdominal myomectomy.

PURPOSE: To compare laparoscopic with abdominal approaches to myomectomy. PATIENTS AND METHOD: Frequency matching was used to ensure similar fibroid weights among the laparoscopic and abdominal groups in this case-control study. The study group consisted of prospectively recruited patients undergoing laparoscopic (N = 5) or laparoscopically assisted (N = 20) myomectomy (lap). The control group represented both prospectively (N = 14) and retrospectively (N = 37) identified abdominal myomectomy patients (abd). Analysis of the variables was performed using a t-test, Wilcoxon rank-sum test, chi-square test, or analysis of covariance at the 0.01 significance level. RESULTS: All results are reported after matching for fibroid weight, with the median (quartiles) aggregate weight measuring 151 g (31.0, 262.0) and 170.0 g (81.0, 285.0) for the lap and abd patients, respectively (P = 0.15). Median (quartiles) length of hospital stay (30.5 hours [25.0, 52.5] v 65.0 hours [45.0, 76.0]; P < 0.001) and duration of postoperative intravenous narcotic use (14.8 hours [3.0, 18.5] v 24.0 hours [18.0, 40.0]; P = 0.001) were significantly shorter for the lap patients. The laparoscopic cases required a longer median operative time (222.5 minutes [192.5, 270.0]) than the abdominal cases (180.0 minutes [160.0, 220.0]; P = 0.001). No difference was detected in estimated blood loss from surgery (P = 0.57). CONCLUSIONS: A laparoscopic approach to myomectomy may be safely chosen for patients with fibroids and offers the benefits of less postoperative intravenous narcotic use, a shorter hospital stay, and no greater intraoperative blood loss than abdominal myomectomy.

Adult↗

PubMed2000

Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is the diagnosis used to describe children who are inattentive, impulsive, and hyperactive. ADHD is a widespread condition that is of public health concern. In most children with ADHD the cause is unknown, but is thought to be biological and multifactorial. Several previous studies indicated that some physical symptoms reported in ADHD are similar to symptoms observed in essential fatty acid (EFA) deficiency in animals and humans deprived of EFAs. We reported previously that a subgroup of ADHD subjects reporting many symptoms indicative of EFA deficiency (L-ADHD) had significantly lower proportions of plasma arachidonic acid and docosahexaenoic acid than did ADHD subjects with few such symptoms or control subjects. In another study using contrast analysis of the plasma polar lipid data, subjects with lower compositions of total n-3 fatty acids had significantly more behavioral problems, temper tantrums, and learning, health, and sleep problems than did those with high proportions of n-3 fatty acids. The reasons for the lower proportions of long-chain polyunsaturated fatty acids (LCPUFAs) in these children are not clear; however, factors involving fatty acid intake, conversion of EFAs to LCPUFA products, and enhanced metabolism are discussed. The relation between LCPUFA status and the behavior problems that the children exhibited is also unclear. We are currently testing this relation in a double-blind, placebo-controlled intervention in a population of children with clinically diagnosed ADHD who exhibit symptoms of EFA deficiency.

Animals↗

PubMed2000

Regulation of the resident chromosomal copy of c-myc by c-Myb is involved in myeloid leukemogenesis.

c-myb is a frequent target of retroviral insertional mutagenesis in murine leukemia virus-induced myeloid leukemia. Induction of the leukemogenic phenotype is generally associated with inappropriate expression of this transcriptional regulator. Despite intensive investigations, the target genes of c-myb that are specifically involved in development of these myeloid lineage neoplasms are still unknown. In vitro assays have indicated that c-myc may be a target gene of c-Myb; however, regulation of the resident chromosomal gene has not yet been demonstrated. To address this question further, we analyzed the expression of c-myc in a myeloblastic cell line, M1, expressing a conditionally active c-Myb-estrogen receptor fusion protein (MybER). Activation of MybER both prevented the growth arrest induced by interleukin-6 (IL-6) and rapidly restored c-myc expression in nearly terminal differentiated cells that had been exposed to IL-6 for 3 days. Restoration occurred in the presence of a protein synthesis inhibitor but not after a transcriptional block, indicating that c-myc is a direct, transcriptionally regulated target of c-Myb. c-myc is a major target that transduces Myb's proliferative signal, as shown by the ability of a c-Myc-estrogen receptor fusion protein alone to also reverse growth arrest in this system. To investigate the possibility that this regulatory connection contributes to Myb's oncogenicity, we expressed a dominant negative Myb in the myeloid leukemic cell line RI-4-11. In this cell line, c-myb is activated by insertional mutagenesis and cannot be effectively down regulated by cytokine. Myb's ability to regulate c-myc's expression was also demonstrated in these cells, showing a mechanism through which the proto-oncogene c-myb can exert its oncogenic potential in myeloid lineage hematopoietic cells.

Animals↗

PubMed2000

Effects of beta(2)-agonist clenbuterol on biochemical and contractile properties of unloaded soleus fibers of rat.

The effects of clenbuterol beta(2)-agonist administration were investigated in normal and atrophied [15-day hindlimb-unloaded (HU)] rat soleus muscles. We showed that clenbuterol had a specific effect on muscle tissue, since it reduces soleus atrophy induced by HU. The study of Ca(2+) activation properties of single skinned fibers revealed that clenbuterol partly prevented the decrease in maximal tension after HU, with a preferential effect on fast-twitch fibers. Clenbuterol improved the Ca(2+) sensitivity in slow- and fast-twitch fibers by shifting the tension-pCa relationship toward lower Ca(2+) concentrations, but this effect was more marked after HU than in normal conditions. Whole muscle electrophoresis indicated slow-to-fast transitions of the myosin heavy chain isoforms for unloaded and for clenbuterol-treated soleus. The coupling of the two latter conditions did not, however, increase these phenotypical transformations. Our findings indicated that clenbuterol had an anabolic action and a beta(2)-adrenergic effect on muscle fibers and appeared to counteract some effects of unloading disuse conditions.

Adrenergic beta-Agonists↗

PubMed2000

Effects of unweighting and clenbuterol on myosin light and heavy chains in fast and slow muscles of rat.

To investigate the plasticity of slow and fast muscles undergoing slow-to-fast transition, rat soleus (SOL), gastrocnemius (GAS), and extensor digitorum longus (EDL) muscles were exposed for 14 days to 1) unweighting by hindlimb suspension (HU), or 2) treatment with the beta(2)-adrenergic agonist clenbuterol (CB), or 3) a combination of both (HU-CB). In general, HU elicited atrophy, CB induced hypertrophy, and HU-CB partially counteracted the HU-induced atrophy. Analyses of myosin heavy (MHC) and light chain (MLC) isoforms revealed HU- and CB-induced slow-to-fast transitions in SOL (increases of MHCIIa with small amounts of MHCIId and MHCIIb) and the upregulation of the slow MHCIa isoform. The HU- and CB-induced changes in GAS consisted of increases in MHCIId and MHCIIb ("fast-to-faster transitions"). Changes in the MLC composition of SOL and GAS consisted of slow-to-fast transitions and mainly encompassed an exchange of MLC1s with MLC1f. In addition, MLC3f was elevated whenever MHCIId and MHCIIb isoforms were increased. Because the EDL is predominantly composed of type IID and IIB fibers, HU, CB, and HU-CB had no significant effect on the MHC and MLC patterns.

Adrenergic beta-Agonists↗

PubMed2000

Gambling behavior of Louisiana students in grades 6 through 12.

OBJECTIVES: The prevalence of problem and gambling behavior, the average age of onset of gambling behavior, and the co-occurrence of gambling disorder with substance use were determined in the Louisiana student population grades 6 through 12. METHODS: A stratified randomized sample of 12,066 students in Louisiana schools during the 1996-1997 school year was surveyed about gambling behavior using the South Oaks Gambling Screen--Revised for Adolescents (SOGS-RA). RESULTS: Fourteen percent of the students never gambled, 70.1 percent gambled without problems, 10.1 percent indicated problem gambling in the past year (level 2 according to the SOGS-RA), and 5.8 percent indicated pathological gambling behavior in the past year (level 3). Weekly or more frequent lottery play was reported by 16.5 percent. The average age of onset of gambling behavior was 11.2 years. Fifty-nine percent of the students with problem and pathological gambling behavior reported frequent alcohol and illicit drug use. CONCLUSIONS: A significant minority of Louisiana students in grades 6 through 12-15.9 percent--acknowledged gambling-related symptoms and life problems. The association of problem and pathological gambling with use of alcohol, tobacco, and marijuana provides preliminary support for the inclusion of gambling among other adolescent risk behaviors.

Adolescent↗

PubMed2000

Repair of the radial free flap donor site with full or partial thickness skin grafts. A prospective randomised controlled trial.

The radial forearm free flap has become the mainstay in the reconstruction of soft tissue defects following ablative resection in the oral cavity. The method of repair of the associated forearm tissue defect has been the subject of considerable debate. The options range from direct closure, to local soft tissue flaps or skin graft repair. Larger defects usually require a skin graft and we have routinely used partial thickness skin. An audit of our complication rate led to the consideration of whether a full thickness repair would reduce the morbidity. We randomly allocated successive patients to receive full or partial thickness skin graft repair of the radial donor site in a consecutive series of 68 patients over an 18-month period. Sixty-four patients completed the initial assessment period of wound healing. Thirty seven patients completed a questionnaire at one year to subjectively assess the aesthetic appearance of the forearm wound and the skin graft donor site. They were also assessed for pain at both sites. The partial thickness donor site required significantly more re-dressings. There was no significant difference between the two groups in graft take or number of re-dressings at the recipient site. There was no significant difference in patient assessment of aesthetic appearance or pain in either the forearm recipient site or the skin graft donor site. Provided that an adequate graft is taken, full thickness and partial thickness skin grafts have the same short-term and long-term outcomes in the repair of the radial free flap donor site.

Forearm↗

PubMed2000

Gambling in the south: implications for physicians.

Three historical cycles of legalized gambling have occurred in the South. Currently, every southern state has legalized some form of gaming. Adult past-year prevalence rates of problem gambling in southern states are within the national range. Higher prevalence rates occur in states with casinos and multiple forms of legalized gambling. States with lotteries have higher prevalence rates of adolescent problem gambling. Problem gambling can cause stress-induced physical diseases and psychiatric symptoms in gamblers and their families. Physicians can reduce personal, family, and social costs of problem gambling through increased awareness, strategic screening, and early intervention. Treatment approaches include inpatient treatment centers, self-help fellowship groups, and cognitive-behavioral and addiction-based psychotherapies. Although no standard pharmacologic treatments for gambling disorders exist, use of selective serotonin re-uptake inhibitors is under investigation. Referral resources are available to physicians in states with state-funded treatment programs for problem gamblers and/or state councils for problem gambling.

Adolescent↗

PubMed1999

Changes in myosin heavy chain mRNA and protein isoforms in single fibers of unloaded rat soleus muscle.

Changes in myosin heavy chain (MHC) mRNA and protein isoforms were investigated in single fibers from rat soleus muscle unloaded by hindlimb suspension for 4 and 7 days. Dramatic changes were seen after 4 days, when all fibers co-expressed slow and fast MHC mRNAs. Most fibers contained mRNAs for MHCIbeta, MHCIIa, MHCIId(x), and MHCIIb. The up-regulation of the fast isoforms was only partially transmitted to the protein level. Atypical combinations of MHC mRNA isoforms, which deviated from the 'next-neighbor rule', were frequent in fibers from unloaded soleus. These atypical combinations increased with time and were not observed in the controls. The results suggest that hindlimb suspension elicits in soleus muscle pronounced perturbations in the expression of MHC isoforms by disrupting transcriptional and translational activities.

Animals↗

PubMed1999

Differential effects of bepridil on functional properties of troponin C in slow and fast skeletal muscles.

1. Bepridil (BPD) is a pharmacological compound able to bind to the Ca2+ sensor protein troponin C (TnC), which triggers skeletal muscle contraction upon Ca2+-binding. BPD can thereby modulate the Ca2+-affinity of this protein. 2. The Ca2+-sensitizing action of bepridil was investigated on slow and fast isoforms of TnC from skinned slow and fast skeletal muscle fibres, activated by either Ca2+ or Sr2+ ions. 3. Bepridil did not modify the Ca2+ maximal tension of slow and fast fibres, suggesting that binding of the drug to TnC did not induce a change in the number of cross-bridges involved in maximal tension. 4. Sr2+ ions induced lower maximal tension than Ca2+ ions. However, in fast fibres, these lower Sr2+ maximal tensions could be reinforced by bepridil, suggesting an effect of bepridil on the function of site I of fast TnC. 5. Under submaximal tension, bepridil induced an increase in Ca2+ affinity of TnC in both slow and fast fibres. However, slow fibres were more drug reactive than fast fibres, and the increase in tension appeared to be modulated by the Ca2+ concentration. 6. Thus, bepridil exerted a differential effect on slow and fast fibres. Moreover, the results suggest that bepridil was more effective when activation conditions were unfavourable.

Animals↗