PubMed Health⌕ Search

Biomedical subjects

L Davis

Publications and source records attributed to L Davis.

At least 55 records · Page 3Linked to original sources
PubMed2001

GDF-5 deficiency in mice leads to disruption of tail tendon form and function.

Although the biological factors which regulate tendon homeostasis are poorly understood, recent evidence suggests that Growth and Differentiation Factor-5 (GDF-5) may play a role in this important process. The purpose of this study was to investigate the effect of GDF-5 deficiency on mouse tail tendon using the brachypodism mouse model. We hypothesized that GDF-5 deficient tail tendon would exhibit altered composition, ultrastructure, and biomechanical behavior when compared to heterozygous control littermates. Mutant tail tendons did not display any compositional differences in sulfated glycosaminoglycans (GAG/DNA), collagen (hydroxyproline/DNA), or levels of fibromodulin, decorin, or lumican. However, GDF-5 deficiency did result in a 17% increase in the proportion of medium diameter (100-225 nm) collagen fibrils in tail tendon (at the expense of larger fibrils) when compared to controls (p < 0.05). Also, mutants exhibited a trend toward an increase in irregularly-shaped polymorphic fibrils (33% more, p > 0.05). While GDF-5 deficient tendon fascicles did not demonstrate any significant differences in quasistatic biomechanical properties, mutant fascicles relaxed 11% more slowly than control tendons during time-dependent stress-relaxation tests (p < 0.05). We hypothesize that this subtle alteration in time-dependent mechanical behavior is most-likely due to the increased prevalence of irregularly shaped type I collagen fibrils in the mutant tail tendons. These findings provide additional evidence to support the conclusion that GDF-5 may play a role in tendon homeostasis in mice.

Animals↗
PubMed2000

PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer.

A prostate-specific gene, PCGEM1, was identified by differential display analysis of paired normal and prostate cancer tissues. Multiple tissue Northern blot analysis revealed that PCGEM1 was expressed exclusively in human prostate tissue. Analysis of PCGEM1 expression in matched normal and primary tumor specimens revealed tumor-associated overexpression in 84% of patients with prostate cancer by in situ hybridization assay and in 56% of patients by reverse transcription-PCR assay. Among various prostate cancer cell lines analyzed, PCGEM1 expression was detected only in the androgen receptor-positive cell line LNCaP. Extensive DNA sequence analysis of the PCGEM1 cDNA and genomic DNA revealed that PCGEM1 lacks protein-coding capacity and suggests that it may belong to an emerging class of noncoding RNAs, also called "riboregulators." The PCGEM1 locus was mapped to chromosome 2q32. Taken together, the remarkable prostate-tissue specificity and androgen-dependent expression of PCGEM1 as well as its elevated expression in a significant percentage of tumor tissues suggest specific functions of PCGEM1 in the biology and tumorigenesis of the prostate gland.

Androgens↗
PubMed2000

Comparison of patient self-reports and urinalysis results obtained under naturalistic methadone treatment conditions.

This study examined under naturalistic assessment conditions the validity of self-reported opiate and cocaine use among 175 veterans enrolled in methadone treatment, and factors related to self-report validity, such as stage in treatment and drug of abuse. Veterans were interviewed by clinical staff about past 30-day drug use with the addiction severity index (ASI), and urinalysis results were obtained for the same 30-day interval assessed with the ASI. Analysis revealed that urinalysis generally produced higher rates of substance use than patient self-report, and with the exception of reported opiate use among new patients presenting for treatment, validity of patient self-reported drug use generally was poor with patients under-reporting both opiate and cocaine use. The findings are in marked contrast to those obtained in other studies in which participants are ensured confidentiality regarding their self-reports. Further, the results raise questions about the utility of self-report measures of substance use to assess patient progress or methadone program performance.

Adult↗
PubMed2000

Effect of Withania somnifera on cyclophosphamide-induced urotoxicity.

Administration of an extract from the plant Withania somnifera (Family: Solanaceae) (20 mg/dose/animal; i.p.) for five days along with cyclophosphamide (CTX) (1.5 mmol/kg body wt. i.p.) reduced the CTX induced urotoxicity. Morphological analysis of the bladders of the CTX-treated group showed severe inflammation and dark coloration whereas CTX along with the Withania-treated group showed normal bladder morphology. The extract was found to reduce the protein level in the serum (7.92 g/l) after 4 h of CTX treatment, which was higher in the CTX alone-administered group (11.44 g/l). Blood urea N2 level which was drastically enhanced (136.78 mg/100 ml) 2 after the CTX treatment was significantly reduced (52.08 mg/100 ml) when the animals were treated with Withania extract. Similarly the glutathione (GSH) content in both bladder (1.55 micromol/mg protein) and liver (3.76 micromol/mg protein) was enhanced significantly (P<0.001) in the Withania-treated group compared with the CTX alone-treated animals (bladder 0.5 micromol/mg protein; liver 1.2 micromol/mg protein) Histopathological analysis of the bladder of CTX alone-treated group showed severe necrotic damage where as the Withania somnifera-treated group showed normal bladder architecture.

Animals↗
PubMed2000

Sources on the anterior and posterior banks of the central sulcus identified from magnetic somatosensory evoked responses using multistart spatio-temporal localization.

A Multi-Start Spatio-Temporal (MSST) multidipole localization algorithm was used to study sources on the anterior and posterior banks of the central sulcus localized from early somatosensory magnetoencephalography (MEG) responses. Electrical stimulation was applied to the right and left median nerves of 8 normal subjects. Two sources, one on the anterior and one on the posterior bank of the central sulcus, were localized from 16 data sets (8 subjects, 2 hemispheres). Compared with the more traditional practice of single-dipole fits to peak latencies, MSST provided more reliable source locations. The temporal dynamics of the anterior and posterior central sulcus sources, obtained using MSST, showed considerable temporal overlap. In some cases, the two sources appeared synchronous. On the other hand, in the traditional single-dipole peak-latency fit approach, there is no time course other than a focal dipole moment activated only at the selected peak latency. The same group of subjects also performed a motor task involving index-finger lifting; the anterior central sulcus source obtained from electrical median nerve stimulation localized to the same or similar region in the primary motor area identified from the finger-lift task. The physiological significance of the anterior central sulcus source is discussed. The findings suggest that one can test the integrity of cortical tissue in the region of primary motor cortex using electrical somatosensory stimulation.

Adult↗
PubMed2000

Enhanced expression of cyclooxygenase-2 in high grade human transitional cell bladder carcinomas.

Studies in human and animal models have shown that cyclooxygenase (COX)-2 is up-regulated in several epithelial carcinomas including colon, breast, and lung. To elucidate the possible involvement of COX-2 in human bladder cancer we examined the expression of COX isoforms in benign tissue and in bladder carcinoma specimens. Paraffin embedded tissues from 75 patients with urothelial carcinomas were immunostained with specific antibodies raised against COX-1 and COX-2. COX-1 expression was detected in smooth muscle cells in both benign and malignant bladders. COX-2 immunoreactivity was absent in benign tissue and in specimens with low-grade urothelial carcinoma (0/23). In contrast, expression of COX-2 was detected in malignant epithelial cells in 38% (17/47) of specimens with high-grade urothelial carcinomas. Expression of COX-2 in high-grade bladder cancer was confirmed by radioactive in situ hybridization using a COX-2-selective riboprobe. Both immunohistochemistry and in situ hybridization showed COX-2 expression in a small subset of malignant cells. COX-2 mRNA was also expressed in three out of seven malignant urothelial cell lines. These data demonstrate elevated expression of COX-2 in a high percentage of high-grade bladder carcinomas, suggesting a possible role of COX-2 in the progression of bladder urothelial carcinoma and supporting its potential as a therapeutic target in human bladder carcinoma.

Carcinoma, Transitional Cell↗
PubMed2000

Immunomodulatory activity of Withania somnifera.

Administration of an extract from the powdered root of the plant Withania somnifera was found to stimulate immunological activity in Babl/c mice. Treatment with five doses of Withania root extract (20 mg/dose/animal; i.p.) was found to enhance the total WBC count (17125 cells/mm(3)) on 10th day. Bone marrow cellularity (27x10(6) cells/femur) as well as alpha-esterase positive cell number (1800/4000 cells) also increased significantly (P<0.001) after the administration of Withania extract. Treatment with Withania extract along with the antigen (SRBC) produced an enhancement in the circulating antibody titre and the number of plaque forming cells (PFC) in the spleen. Maximum number of PFC (985 PFC/10(6) spleen cells) was obtained on the fourth day. Withania extract inhibited delayed type hypersentivity reaction in mice (Mantoux test). Administration of Withania extract also showed an enhancement in phagocytic activity of peritoneal macrophages (76.5 pigmented cells/200) when compared to control (31.5/200 cells) in mice. These results confirm the immunomodulatory activity of W. somnifera extract, which is a known immunomodulator in indigenous medicine.

Adjuvants, Immunologic↗
PubMed2000

Posttraumatic stress disorder in children and adolescents: a review and analysis.

Only recently has the mental health community recognized the applicability of diagnostic criteria for posttraumatic stress disorder (PTSD) in children and adolescents, including a consideration of specific age-related features. This paper provides a current review of the literature on PTSD pertaining to children and adolescents. Following a discussion of issues on diagnostic criteria and assessment of this affective disorder in this population, there is an overview of the existing literature on prevalence, comorbidity, risk factors, parental and family factors, and issues of gender and age of onset. The remainder of the paper focuses on the range of traumatic stressors in children and adolescents that can result in PTSD, including natural or human disasters, war and violence, chronic or life-threatening medical conditions, community violence and the witnessing of traumatic events, and physical and/ or sexual abuse and other forms of interpersonal violence. Throughout the paper, there is an emphasis on the importance of considering developmental factors. Finally, implications of the existing literature for future areas of research are addressed.

Adolescent↗
PubMed2000

Targeted disruption of the endothelin-B-receptor gene attenuates inflammatory nociception and cutaneous inflammation in mice.

Endothelin-1 (ET-1) has been suggested to have a potential function as an inflammatory mediator. The study reported here assessed the putative inflammatory/nociceptive actions of the ET isopeptides using endothelin-B (ET(B))-receptor knockout (KO) mice and ET(A)- (SB 234551) and ET(B)- (A192621) selective antagonists. Phenylbenzoquinone (PBQ)-induced algesia was evident in the wild-type (WT) ET(B) (+/+) mice, attenuated by 80% in the heterozygous ET(B) (+/-) mice, and absent in the ET(B) (-/-) homozygotes. This was reproduced pharmacologically in WT ET(B) (+/+) mice where the algesic effect of PBQ was inhibited 74% by A192621, but unaffected by SB 234551 (both at 25 mg/kg p.o.). Similar observations were made in a model of cutaneous inflammation: ET(B) (+/+) mice had a marked inflammatory response to topical arachidonic acid, ET(B) (+/-) and ET(B) (-/-) mice had significantly reduced edema responses (37% and 65% inhibition). Neutrophil infiltration was reduced in the ET(B) (+/-) and ET(B) (-/-) mice (51% and 65% reduction, respectively). Topical administration of A192621 (500 microg/ear) inhibited arachidonic acid-induced swelling (39%) in WT ET(B) (+/+) mice. Collectively, these results support a role for the ET(B)-receptor in the mediation of inflammatory pain and cutaneous inflammatory responses. As such, the development of ET(B)-receptor-selective antagonists may be of therapeutic utility in the treatment of inflammatory disorders.

Animals↗
PubMed2000

Cytoplasmic sequestration of rel proteins by IkappaBalpha requires CRM1-dependent nuclear export.

Rel and IkappaB protein families form a complex cellular regulatory network. A major regulatory function of IkappaB proteins is to retain Rel proteins in the cell cytoplasm. In addition, IkappaB proteins have also been postulated to serve nuclear functions. These include the maintenance of inducible NF-kappaB-dependent gene transcription, as well as termination of inducible transcription. We show that IkappaBalpha shuttles between the nucleus and the cytoplasm, utilizing the nuclear export receptor CRM1. A CRM1-binding export sequence was identified in the N-terminal domain of IkappaBalpha but not in that of IkappaBbeta or IkappaBepsilon. By reconstituting major aspects of NF-kappaB-IkappaB sequestration in yeast, we demonstrate that cytoplasmic retention of p65 (also called RelA) by IkappaBalpha requires Crm1p-dependent nuclear export. In mammalian cells, inhibition of CRM1 by leptomycin B resulted in nuclear localization of cotransfected p65 and IkappaBalpha in COS cells and enhanced nuclear relocation of endogenous p65 in T cells. These observations suggest that the main function of IkappaBalpha is that of a nuclear export chaperone rather than a cytoplasmic tether. We propose that the nucleus is the major site of p65-IkappaBalpha association, from where these complexes must be exported in order to create the cytoplasmic pool.

Animals↗
PubMed2000

Persistent preceding focal neurologic deficits in children with chronic Epstein-Barr virus encephalitis.

Epstein-Barr virus encephalitis is a self-limiting disease with few sequelae. Persistence of neurologic deficits prior to and after the acute illness has yet to be described in children. We describe five children with persistent cognitive and focal neurologic deficits due to chronic Epstein-Barr virus encephalitis with various T2-weighted magnetic resonance imaging abnormalities. Clinical features were a 9-year-old boy with aphasia and apraxia, an 11-year-old girl with impulsivity and inappropriate behavior, a 17-year-old boy with deterioration of cognitive skills and judgment, a 5-year-old boy with complex-partial seizures, and a 6-year-old girl with obsessive-compulsive behavior. All patients had elevated serum Epstein-Barr virus titers for acute infection, with cerebrospinal fluid polymerase chain reaction positive for Epstein-Barr virus in four patients. Three children were treated with methylprednisolone with minimal improvement without changes on magnetic resonance imaging. Epstein-Barr virus encephalitis can present with chronic and insidious neurologic symptoms and should be considered in the differential diagnosis of children with acute or chronic neurologic illness of unknown etiology.

Adolescent↗
PubMed2000

Comparison of student outcomes and preferences in a traditional vs. World Wide Web-based baccalaureate nursing research course.

The purpose of this project was to compare student outcomes in an undergraduate research course taught using both World Wide Web-based distance learning technology and traditional pedagogy. Reasons given for enrolling in the traditional classroom section included the perception of increased opportunity for interaction, decreased opportunity to procrastinate, immediate feedback, and more meaningful learning activities. Reasons for selecting the Web group section included cost, convenience, and flexibility. Overall, there was no significant difference in examination scores between the two groups on the three multiple-choice examinations or for the course grades (t = -.96, P = .343). Students who reported that they were self-directed and had the ability to maintain their own pace and avoid procrastination were most suited to Web-based courses. The Web-based classes can help provide opportunities for methods of communication that are not traditionally nurtured in traditional classroom settings. Secondary benefits of the World Wide Web-based course were to increase student confidence with the computer, and introduce them to skills and opportunities they would not have had in the classroom. Additionally, over time and with practice, student's writing skills improved.

Adult↗
PubMed2000

Effect of Withania somnifera on 20-methylcholanthrene induced fibrosarcoma.

Administration of an extract from the root of the plant Withania somnifera (20mg/dose/animal i.p) was found to inhibit the 20-methylcholanthrene induced sarcoma development in mice and increase the life span of tumour bearing animals. Administration of Withania could inhibit the lipid peroxide formation (152 nanomoles/mg protein) (P<0.01) compared with control (198 nanomoles/mg protein). Withania could increase the GSH level (7.7 micromoles/mg protein) which was lowered in control tumour bearing animals (3.96 micromoles/mg protein). GST level was also significantly increased (451 micromoles/min/mg protein) (P<0.001) in Withania treated animals compared to control animals (205 micromoles/min/mg protein). All the animals in the control group developed sarcoma by the 80th day of carcinogen administration. Only 3 animals in the Withania treated group developed sarcoma by the 105th day. In control animals the survival rate was 40% but in the Withania treated group the survival rate was 100% after 15 weeks of carcinogen treatment. These results indicate that Withania could inhibit 20-methylcholanthrene induced sarcoma development in mice.

Animals↗
PubMed1999

Ankyrin-B is required for intracellular sorting of structurally diverse Ca2+ homeostasis proteins.

This report describes a congenital myopathy and major loss of thymic lymphocytes in ankyrin-B (-/-) mice as well as dramatic alterations in intracellular localization of key components of the Ca(2+) homeostasis machinery in ankyrin-B (-/-) striated muscle and thymus. The sarcoplasmic reticulum (SR) and SR/T-tubule junctions are apparently preserved in a normal distribution in ankyrin-B (-/-) skeletal muscle based on electron microscopy and the presence of a normal pattern of triadin and dihydropyridine receptor. Therefore, the abnormal localization of SR/ER Ca ATPase (SERCA) and ryanodine receptors represents a defect in intracellular sorting of these proteins in skeletal muscle. Extrapolation of these observations suggests defective targeting as the basis for abnormal localization of ryanodine receptors, IP3 receptors and SERCA in heart, and of IP3 receptors in the thymus of ankyrin-B (-/-) mice. Mis-sorting of SERCA 2 and ryanodine receptor 2 in ankyrin-B (-/-) cardiomyocytes is rescued by expression of 220-kD ankyrin-B, demonstrating that lack of the 220-kD ankyrin-B polypeptide is the primary defect in these cells. Ankyrin-B is associated with intracellular vesicles, but is not colocalized with the bulk of SERCA 1 or ryanodine receptor type 1 in skeletal muscle. These data provide the first evidence of a physiological requirement for ankyrin-B in intracellular targeting of the calcium homeostasis machinery of striated muscle and immune system, and moreover, support a catalytic role that does not involve permanent stoichiometric complexes between ankyrin-B and targeted proteins. Ankyrin-B is a member of a family of adapter proteins implicated in restriction of diverse proteins to specialized plasma membrane domains. Similar mechanisms involving ankyrins may be essential for segregation of functionally defined proteins within specialized regions of the plasma membrane and within the Ca(2+) homeostasis compartment of the ER.

Animals↗