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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 379 records · Page 21Linked to original sources

Evidence that protein kinase C regulates allosensitized T lymphocyte function.

The role of second messengers in the response of alloactivated T cells to growth factors (e.g., interleukin-2) is unknown. We have previously found that intracellular calcium may be an important T-cell alloactivation marker. To determine whether protein kinase C (PKC) is also involved in allosensitized T cell function, we studied the effects of the PKC agonists phorbol 12-myristate 13-acetate (PMA), mezerein (MEZ), and 1-oleoyl-2-acetylglycerol (OAG) and the PKC antagonists phloretin and D-sphingosine on the in vitro proliferation and migration of allosensitized cells from a C57BL/6 anti-DBA/2J mixed leukocyte culture (MLC). At 0.01-1.0 microgram/ml, PMA, a potent stimulant of PKC, exerted profound stimulatory effects on secondary MLC supernatant (2 degrees SN)-induced proliferation of allosensitized T cells (132-200% increase, P less than 0.01). Both MEZ and OAG are less potent activators of PKC than PMA but also stimulated T cell proliferation (132-152% of control, P less than 0.01). The PKC antagonists phloretin and D-sphingosine both inhibited proliferation by greater than 50% at 1.0-10.0 microM (P less than 0.01). Further experiments showed that these agents exert similar effects on in vitro T cell locomotion in a Boyden chamber assay. These data indicate that PKC activation may be an important component of allosensitized T cell proliferation and locomotion and may constitute a pathway by which T cell function may be modified in the allograft response.

Animals↗

Role of depressive illness in the outcome of treatment of temporomandibular joint pain-dysfunction syndrome.

The aim of this study was to assess the role of a depressive illness in the outcome of the treatment of patients with temporomandibular joint pain-dysfunction syndrome. One group was considered psychiatrically normal and the other had a concurrent depressive illness. The latter group was subdivided equally to produce three treatment groups: one undergoing occlusal splint therapy, one receiving antidepressant medication, and the third having a combination of occlusal splint and antidepressant therapy. The results showed clearly that there was a significant difference in response in the nonpsychiatric and combined-therapy depressed groups in comparison with the two depressed groups treated either with occlusal splint or with antidepressant therapy. The combined therapy led to resolution of the painful problem and the depression, whereas the single therapies were only partly successful in relieving the pain-dysfunction syndrome. The preexisting duration of this painful problem did not influence the response to therapy.

Adolescent↗

Depression, hassles and somatic symptoms in mandibular dysfunction syndrome patients.

Thirty-seven patients with mandibular dysfunction syndrome (MDS) and 30 age-, sex- and education-matched dental outpatient controls were assessed using the Beck Depression Inventory, the Hassles Scale and a symptom checklist derived from the DSM-III criteria for somatization disorder. MDS patients had higher levels of depressive symptoms than control patients (P less than 0.05), though only five out of 37 (13.5 per cent) of the MDS patients had depression intensity levels suggesting clinically significant psychopathology. No significant differences were found between MDS patients and controls on the Hassles Scale, which fails to support the stress-induced muscular hyperactivity theory for the aetiology of MDS syndrome. MDS patients reported having a past history of more somatic symptoms than did controls (P less than 0.05). MDS patients were divided by a clinician into 'physical' and 'functional' groups based on their clinical history. Contrary to expectation, there were no between-group differences on any of the above-mentioned psychological variables.

Adult↗

Synthesis of 3-carbamoylecgonine methyl ester analogues as inhibitors of cocaine binding and dopamine uptake.

Five (1R-2-exo-3-exo)-3-(N-phenylcarbamoyl)ecgonine methyl ester analogues were synthesized and characterized by 1H and 13C NMR, IR, and thermospray MS. The compounds were synthesized in two or three steps as (-)-stereoisomers from (-)-ecgonine in good yield (56% overall). These cocaine derivatives were assessed for their ability to inhibit [3H]cocaine binding to rat striatal tissue and to inhibit [3H]dopamine uptake into synaptosomes prepared from the same tissue. The most potent of the analogues was (1R-2-exo-3-exo)-2-(carbomethoxy)-8-methyl-8-azabicyclo[3.2.1]octyl 3-N-(3'-nitrophenyl)carbamate. IC50 values for inhibition of cocaine binding and dopamine uptake were 37 and 178 nM, respectively. Amino derivatives were less active than the nitro and (1R-2-exo-3-exo)-2-(carbomethoxy)-8-methyl-8-azabicyclo [3.2.1]octyl 3-N-(4'-aminophenyl)carbamate had the lowest affinity for the receptor with IC50 values of 63 and greater than 100 microM in the aforementioned assays, respectively.

Animals↗

Nebulin as a length regulator of thin filaments of vertebrate skeletal muscles: correlation of thin filament length, nebulin size, and epitope profile.

Nebulin, a family of giant proteins with size-variants from 600 to 900 kD in various skeletal muscles, have been proposed to constitute a set of inextensible filaments anchored at the Z line (Wang, K., and J. Wright. 1988. J. Cell Biol. 107:2199-2212). This newly discovered filament of the skeletal muscle sarcomere is an attractive candidate for a length-regulating template of thin filaments. To evaluate this hypothesis, we address the question of coextensiveness of nebulin and the thin filament by searching for a correlation between the size of nebulin variants and the length distribution of the thin filaments in several skeletal muscles. A positive linear correlation indeed exists for a group of six skeletal muscles that display narrow thin filament length distributions. To examine the molecular and architectural differences of nebulin size-variants, we carried out immunoelectron microscopic studies to map out epitope profiles of nebulin variants in these muscles. For this purpose, a panel of mAbs to distinct nebulin epitopes was produced against rabbit nebulin purified by an improved protocol. Epitope profiles of nebulin variants in three skeletal muscles revealed that (a) nebulin is inextensible since nebulin epitopes maintain a fixed distance to the Z line irrespective of the degree of sarcomere stretch; (b) a single nebulin polypeptide spans a minimal distance of 0.9 microns from the Z line; (c) nebulin contains repeating epitopes that are spaced at 40 nm or its multiples; (d) nebulin repeats coincide with thin filament periodicity; (e) nebulin variants differ mainly at either or both ends; and (f) nebulin remains in the sarcomere in actin-free sarcomeres produced by gelsolin treatment. Together, these data suggest that nebulin is an inextensible full-length molecular filament that is coextensive with thin filaments in skeletal muscles. We propose that nebulin acts as a length-regulating template that determines thin filament length by matching its large number of 40-nm repeating domains with an equal number of helical repeats of the actin filaments.

Animals↗

Effect of H2-receptor antagonist pretreatment on vecuronium- and atracurium-induced neuromuscular block.

Seventy-two patients were studied in a double-blind randomized controlled design to assess the effects of oral administration of cimetidine 400 mg, ranitidine 150 mg or placebo 90 min before anaesthesia on the neuromuscular blocking effects of atracurium 0.45 mg kg-1 or vecuronium 0.08 mg kg-1. The times to reappearance of T1 (first response in the train-of-four stimulation) and its recovery to 25% of control were 22.5 (SD) 5.2 and 30 (7.1) min, 30 (10) and 43 (15.4) min, and 25.8 (4.1) and 34 (6.2) min, respectively in the vecuronium groups pretreated with placebo, cimetidine and ranitidine, the times following cimetidine pretreatment being prolonged significantly (P less than 0.05). The respective recovery indices (times for 25-75% recovery of T1) in these three groups were 11.0 (3.5), 17.4 (6.8) and 13.0 (3.9) min. There were no significant differences in any of the variables following ranitidine pretreatment and either neuromuscular blocker or following cimetidine pretreatment and atracurium.

Administration, Oral↗

Role of epithelial cells of the male excurrent duct system of the rat in the endocytosis or secretion of sulfated glycoprotein-2 (clusterin).

The localization of sulfated glycoprotein-2 (clusterin; SGP-2) was investigated in the rete testis, efferent ducts, and epididymis of the rat using light (LM) and electron (EM) microscope immunocytochemistry. At the LM level, the epithelial cells of the rete testis and efferent ducts demonstrated an intense immunoperoxidase reaction over their apical and supranuclear regions, and sperm in the lumen of the efferent ducts were unreactive. In the EM, gold particles were found exclusively over the endocytic apparatus of these cells. In the proximal area of the epididymal initial segment, an insignificant immunostaining of epithelial cells and sperm was observed. However, the distal area of the initial segment showed a moderate staining over the epithelial principal cells and sperm, while in the intermediate zone of the epididymis a stronger reaction was observed over these cells. The strongest immunoperoxidase reaction was noted in the caput epididymidis, where it formed a distinct mottled pattern. Thus, while some principal cells were intensely stained, others were moderately or weakly stained; a few were completely unreactive. In the corpus and cauda epididymidis, the staining pattern was similar but not as intense. In the EM, only the secretory apparatus of these cells was found to be immunolabeled with gold particles. Sperm in the lumen of these different regions were also labeled. The epithelial clear cells were unreactive throughout the epididymis. Northern blot analysis substantiated these results and showed the presence of highest levels of SGP-2 mRNA in the caput epididymidis, especially in its proximal area, whereas increasingly lower levels were found in the corpus and cauda epididymidis. In summary, these results suggest that testicular SGP-2 dissociates from the sperm during passage through the rete testis and efferent ducts, where it is endocytosed by the epithelial cells lining these regions. In the epididymis, it is replaced by an epididymal SGP-2 that is secreted by the epithelial principal cells of the epididymis. Furthermore, in the epididymis, the principal cells appear to be in different functional states with respect to the secretion of epididymal SGP-2 within a given region of the duct as well as along the epididymal duct.

Animals↗

Counselling at the cultural interface: is getting back to roots enough?

This paper attempts to view counselling in its cultural context. The central issue addressed relates to the possibly unique position which psychiatric nurses occupy in relation to this issue. It is argued that psychiatric nurses have an opportunity to challenge some of the complexities and assumptions of traditional counselling models, and contribute towards the development of a helping approach, for those who are culturally 'different', which is both authentic and flexible. After tracing the notion of cultural identity and outlining the disempowering experience of many from the cultural minority groups, when encountering the British psychiatric system, the writer considers the relevance of the Western counselling tradition in relation to those who are thus disempowered. Viewed from the complexity of human experience and cultural variability, it is claimed that many of the assumptions and premises of this tradition are themselves disempowering. An argument is made for that kind of authentic helping whose genesis is the recognition of clients in their cultural setting and which is flexible enough to respond to the individual and not merely her/his cultural grouping. With such a framework, the writer feels that psychiatric nurses could occupy a vital role, whose goal would be to re-empower individuals with diverse cultural traditions, at both a micro and macro level.

Attitude to Health↗

Identification of two T-cell epitopes on the candidate Epstein-Barr virus vaccine glycoprotein gp340 recognized by CD4+ T-cell clones.

Current efforts to develop an Epstein-Barr virus subunit vaccine are based on the major envelope glycoprotein gp340. Given the central role of CD4+ T cells in regulating immune responses to subunit vaccine antigens, the present study has begun the work of identifying linear epitopes which are recognized by human CD4+ T cells within the 907-amino-acid sequence of gp340. A panel of gp340-specific CD4+ T-cell clones from an Epstein-Barr virus-immune donor were first assayed for their proliferative responses to a series of truncated gp340 molecules expressed from recombinant DNA vectors in rat GH3 cells, by using an autologous B lymphoblastoid cell line as a source of antigen-presenting cells. The first four T-cell clones analyzed all responded to a truncated form of gp340 which contained only the first 260 N-terminal amino acids. These clones were subsequently screened for responses to each of a panel of overlapping synthetic peptides (15-mers) corresponding to the primary amino acid sequence of the first 260 N-terminal amino acids of gp340. One clone (CG2.7) responded specifically to peptides from the region spanning amino acids 61 to 81, while three other clones (CG5.15, CG5.24, and CG5.36) responded specifically to peptides from the region spanning amino acids 163 to 183. Work with individual peptides from these regions allowed finer mapping of the T-cell epitopes and also revealed the highly dose-dependent nature of peptide-induced responses, with inhibitory effects apparent when the most antigenic peptides were present at supraoptimal concentrations. Experiments using homozygous typing B lymphoblastoid cell lines as antigen-presenting cells showed that the T-cell clones with different epitope specificities were restricted through different HLA class II antigens; clone CG2.7 recognized epitope 61-81 in the context of HLA DRw15, whereas clones CG5.15, CG5.24, and CG5.36 recognized epitope 163-183 in the context of HLA DRw11. The present protocol therefore makes a systematic analysis of CD4+ T-cell epitopes within gp340 possible; it will be necessary to screen gp340-specific T-cell clones from a variety of donors to assess the wider influence of HLA class II polymorphism upon epitope choice.

Amino Acid Sequence↗

Influence of weight on pulmonary function in the adult guinea pig.

We examined a group of 63 adult female Hartley strain guinea pigs with weight ranging from 625 to 1,200 g in order to ascertain whether pulmonary function tests including lung volumes, pressure-volume curves, and flow-volume curves were affected by the weight of the animal. We found that there was a weight effect on total lung capacity, vital capacity, residual volume, and the forced expiratory flow between 25 and 75% of total lung capacity, although there was no effect on other parameters of airflow. Flow-volume curves for each animal could be accurately fitted to a mathematical equation, and this equation did not vary with the animals' weight. Pressure-volume curves were affected by animal weight, but could be accurately fitted to a weight-corrected equation. We conclude that when pulmonary function tests are performed on adult guinea pigs, lung volumes may be altered in proportion to the weight of the animal. When pressure-volume or flow-volume curves are being considered, although weight can either be corrected for or has no bearing on the shape of the curve, there is a large between-animal variation, and it may be necessary to use large experimental groups when it is impossible to use the same animal as its own control.

Animals↗

Hepatocellular carcinoma in Richardson's ground squirrels (Spermophilus richardsonii): evidence for association with hepatitis B-like virus infection.

During studies of seasonal obesity, a high frequency of hepatic neoplasms was observed in Richardson's ground squirrels. Of 12 Richardson's ground squirrels examined thoroughly, 7 had mild or moderate degrees of chronic portal hepatitis and 6 (50%) had hepatocellular carcinoma. Serological tests for hepadnavirus surface antigen, anti-core antibody and virion DNA that recognize the ground squirrel hepatitis virus of California ground squirrels (Spermophilus beecheyi) were uniformly negative. Southern blot analyses of EcoRI digests of liver cell DNA demonstrated 3.2 kb fragments that hybridized with a ground squirrel hepatitis virus-specific probe in nontumorous liver tissue from 6 of 10 ground squirrels and in hepatocellular carcinoma specimens from 2 of 5 squirrels indicating infection with a hepadnavirus related to ground squirrel hepatitis virus. Failure, however, to detect serum antibody to ground squirrel hepatitis core antigen suggested probable antigenic differences between the ground squirrel hepatitis virus of California ground squirrels and the putative Richardson's ground squirrel agent. Further studies are required to fully characterize the hepadnavirus of Richardson's ground squirrels and to determine its relationship to hepatocarcinogenesis in this species.

Animals↗

Histochemical evidence for generation of active oxygen species on the apical surface of cigarette-smoke-exposed tracheal explants.

Cigarette smoke is known to contain many types of free radicals, and solutions of smoke tar have been shown to liberate hydrogen peroxide as well as superoxide radical. To further investigate the relationship of smoke exposure and generation of active oxygen species, the authors exposed rat tracheal explants to varying amounts of smoke for 10 minutes in a humidified chamber. After smoke exposure was completed, tracheal segments were incubated in a modification of the ultrastructural cerium chloride technique that was devised by Briggs et al. to demonstrate hydrogen peroxide production. Smoke dose-dependent deposition of cerium-containing reaction product was found on the cilia and the apical membranes; with low-dose smoke, the reaction product appeared as individual dots along the apical surface, but with greater amounts of smoke, heavy linear deposits of reaction product were found along the apical membranes. Smoke produced focal dose-related cell damage with blebbing of the apical membranes, loss of cilia, and focal cell necrosis. Catalase prevented both the positive histochemical reaction and the cell damage; if the catalase was first boiled, its protective effect was destroyed. Similarly, after smoke exposure was completed, tracheal segments were covered with a solution of nitroblue tetrazolium to demonstrate production of superoxide anion. A positive reaction was observed by light microscopy on the surface of tracheas that was exposed to smoke but not that exposed to air; the reaction could be prevented by addition of superoxide dismutase. The authors conclude that exposure of tracheal explants to cigarette smoke in vitro is associated with histochemical evidence of continuing production of both hydrogen peroxide and superoxide anion at the apical cell membrane.

Animals↗

Are consumers of modern fertility treatments satisfied?

OBJECTIVE: To determine the extent of patients satisfaction with fertility treatments, its antecedents, and its correlates. DESIGN: This is a two-wave correlational panel study in which consumer satisfaction was assessed 6 and 12 months after admission to the clinic. PATIENTS: The sample consisted of 385 couples who consulted the fertility clinic of a large metropolitan hospital. MEASURES: After their admission, patients completed scales measuring psychosocial disturbances. These variables were reassessed 6 and 12 months later along with a consumer satisfaction questionnaire. RESULTS: Patients were generally satisfied with modern fertility treatments. Approximately 10% of the sample expressed dissatisfaction with received services. Analyses revealed that consumer satisfaction was significantly related to poor psychosocial functioning at intake and after 6 months. CONCLUSIONS: Our results suggest that consumers of fertility treatments are generally satisfied with the quality and quantity of service they received at the clinic. The more patients exhibited personal, marital, and social symptoms of distress when they were admitted to the clinic, the more they were likely to be later dissatisfied with fertility treatments.

Adaptation, Psychological↗

Sustained increases in cytosolic calcium during T lymphocyte allosensitization, proliferation, and acquisition of locomotor function.

Activation of resting T cells is accompanied by an increase in cytosolic calcium ([Ca2+]i). However, the role of [Ca2+]i in the effector function of allosensitized cells, and how this may affect the evolution of the allograft response is unknown. To evaluate this more directly, we determined [Ca2+]i in both unsensitized T cells (C57BL/6 murine thymocytes) and in allosensitized T cells derived from different days of a C57BL/6 anti-DBA/2J mixed leukocyte culture. To correlate potential changes in [Ca2+]i with concomitant development of T cell effector function, the [Ca2+]i, proliferation (3HTdR uptake), and random locomotion (in vitro modified Boyden chamber assay) of the same cells was assayed simultaneously. Allosensitized T cells exhibited higher (P less than 0.05) [Ca2+]i than unsensitized thymocytes on all days of culture tested. Further, there was a progressive rise in [Ca2+]i during the course of allosensitization. Con A stimulated an increase in [Ca2+]i over basal levels (P less than .05) for all cell types. A rise in [Ca2+]i preceded the onset of maximal allosensitized T cell proliferation (which peaked at day 7) and this continued to increase even after completion of DNA synthesis. In contrast, optimal T cell locomotion coincided with maximal [Ca2+]i, well after cell division had occurred. Prostaglandin E2, a known inhibitor of lymphocyte function, did not alter either basal or Con A-stimulated [Ca2+]i in thymocytes or MLC cells. These results indicate that [Ca2+]i signaling persists long after initial T lymphocyte alloactivation, and is maintained during DNA synthesis and acquisition of locomotor capacity. Furthermore, the inhibitory effects of PGE2 on allosensitized T lymphocyte function may be mediated by a calcium-independent mechanism.

Animals↗

The histomorphologic and morphometric study of asymptomatic hip arthroplasty. A postmortem study.

The purpose of this study was to determine the histologic findings at the bone-cement interface in successful asymptomatic total hip replacements (THR) retrieved from patients at autopsy. The criteria for a successful hip arthroplasty were clinical, radiologic, and direct examination of the prosthesis at the time of harvesting. Twelve patients with a total of 14 cemented hip arthroplasties came to autopsy at a mean of 4.7 years after implantation. A detailed histomorphometric objective means of assessing the tissue response was applied to the membrane. The density of histiocytes correlated with the thickness of the membrane, the density of polyethylene particles, and the time after implantation. The fibrohistiocytic membrane in this group of patients was similar to that described in the literature in cases of loose THRs. These findings advance current understanding of transcellular particle transportation (directional exocytosis) in tissue reactions to endoprostheses of THR.

Acetabulum↗