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Biomedical subjects

M A Stanley

Publications and source records attributed to M A Stanley.

At least 55 records · Page 3Linked to original sources

Psychometric properties of the MSPSS and NOS in psychiatric outpatients.

Prior research has demonstrated the utility of the Multidimensional Scale of Perceived Social Support (MSPSS) and the Network Orientation Scale (NOS) as measures of perceived social support among nonpsychiatric samples. The primary objective of this study was to determine whether these two scales can be used reliably among psychiatric outpatients, in particular those with schizophrenia or a major affective disorder. Subjects were 144 outpatients, aged 21 to 67 years, who completed the MSPSS and NOS. Results demonstrated high internal consistency for the MSPSS and adequate internal consistency for the NOS. In addition, convergent validity was demonstrated. Scores on both scales for these psychiatric outpatients were found to be lower as compared to "normals."

Adult↗

Nonclinical hair-pulling: affective correlates and comparison with clinical samples.

The purposes of the current study were to examine the affective states associated with hair-pulling in a nonclinical sample and to compare levels of general psychopathology in nonclinical hair-pullers and clinic patients with trichotillomania (TM) or obsessive-compulsive disorder (OCD). Subjects included 66 college undergraduates who engaged in hair-pulling unrelated to grooming, 18 patients with TM and 29 patients with OCD. Dimensional (but not categorical) ratings of affective experiences in the nonclinical sample indicated that hair-pulling was associated with decreases in tension, boredom, anger and sadness. Further, the relationship between emotional experiences before and after hair-pulling was more salient than the pre-during relationship conceptualized as central in current diagnostic criteria for TM. Comparisons of psychopathology in nonclinical and clinical samples failed to support a continuum notion of increasing symptomatology in nonclinical pullers, TM patients and individuals with OCD. Some evidence of increased pathology in nonclinical pullers relative to TM patients was obtained, as was further support for a distinction between TM and OCD. Implications of this investigation for conceptualization of TM are discussed.

Adolescent↗

The ATP-binding and ATPase activities of human papillomavirus type 16 E1 are significantly weakened by the absence of prolines in its ATP-binding domain.

The E1 protein of human papillomavirus (HPV) type 16 is the only known papillomavirus E1 which does not contain any proline residues in the phosphate-loop (P-loop) of its ATP-binding site. To ascertain whether this feature influences the activities of HPV-16 E1, we generated a mutant HPV-16 E1 (E1Pro) in which prolines are inserted in place of alanines in this site, making the P-loop identical to its bovine papillomavirus type 1 counterpart. Glutathione S-transferase (GST) fusion proteins (GSTE1wt and GSTE1Pro) were produced, purified and used to assay for ATP-binding ability, ATPase activity and ability to complex with the HPV-16 E2 protein. The results show that the lack of prolines in the P-loop, which is unique to HPV-16 E1, significantly weakens its ATP-binding and ATPase activities without affecting its ability to complex with the HPV-16 E2 protein.

Adenosine Triphosphatases↗

Pupillary dilation and its effects on automated perimetry results.

BACKGROUND: The effects of miotic drugs on visual field sensitivity have been well documented, but few studies have reported the effects of active pupillary dilation on visual field sensitivity. Since visual field testing is sometimes performed when a patient is undergoing pupillary dilation for fundus examination, the effects of active pupillary dilation is of concern to today's optometrist. METHODS: The effects of active pupillary dilation on automated static threshold perimetry were studied in 23 normal subjects using the Humphrey Field Analyzer and the 30-2, StatPac, and FastPac programs. Baseline automated perimetry was performed on both eyes of each subject with the Humphrey Field Analyzer. On a separate visit, automated perimetry was performed on both eyes of all subjects while each eye was undergoing active pupillary dilation. Baseline and dilated visual field parameters were compared. RESULTS: A decrease in foveal threshold of 1.95 decibels (p = 0.0081), a mean deviation loss of 1.15 decibels (p = 0.0001), a decrease in short-term fluctuation (SF) of 0.19 decibels (p = 0.0423), and a decrease in the SF2 of 0.56 decibels (p = 0.0374) were found in the dilated fields as compared with the baseline visual fields in the first eye tested. A decrease in foveal threshold of 2.56 decibels (p = 0.0081) and a mean deviation loss of 1.43 decibels (p = 0.0001) were found in the dilated fields as compared with the baseline visual fields in the second eye tested. CONCLUSIONS: These findings indicate that active pupillary dilation in healthy subjects produces statistically significant differences, although these differences may not be clinically significant. To ensure repeatable visual fields, consistent pupil diameter should be controlled during serial visual field testing.

Adult↗

Characterization and functional analysis of the expression of vascular adhesion molecules in human papillomavirus-related disease of the cervix.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is associated with changes in local immune cell populations, although the role of vascular adhesion molecules in mediating such changes by controlling the traffic of mononuclear cells to the cervix has not been investigated previously. METHODS: The authors used immunohistochemistry to examine the expression of three vascular adhesion molecules--ICAM-1, VCAM-1 and E-selectin--in the normal cervix and in biopsies of CIN Grade 1 (CIN-1) (low grade squamous intraepithelial lesions [LG-SIL]) and CIN-2/3 (high grade squamous intraepithelial lesions[HG-SIL]). In addition, the authors examined the functional role of these molecules by adapting the frozen section adhesion assay of Stamper and Woodruff to investigate in vitro the molecular basis of the interaction between cervical endothelial cells and activated T-lymphocytes. RESULTS: Whereas there was no difference in adhesion molecule expression between normal cervix and CIN-1 (LG-SIL), all three molecules investigated were significantly up-regulated in CIN-2/3 (HG-SIL), an observation that correlated with an enhanced ability of stromal endothelial cells in CIN-2/3 (HG-SIL) biopsies to bind activated peripheral blood lymphocytes in vitro. Monoclonal antibodies blocking ICAM-1 function were able to reduce such adhesion significantly in three of three experiments, and antibodies blocking VCAM-1 produced a significant reduction in one of three experiments. No inhibition was seen with antibodies against E-selectin. CONCLUSIONS: The enhanced expression of vascular adhesion molecules in CIN-2/3 (HG-SIL) appears to be functionally important in enabling the local recruitment of immunocompetent cells and supports the notion of a local antineoplastic immune response in high grade cervical intraepithelial lesions.

Carcinoma, Squamous Cell↗

Analysis of HLA-DR expression on keratinocytes in cervical neoplasia.

We have investigated the expression in vivo and in vitro of HLA-DR in pre-invasive squamous-cell neoplasia of the uterine cervix. Immunohistochemistry of cervical biopsies demonstrated HLA-DR expression by cervical keratinocytes in 50% of cases of high-grade squamous intra-epithelial neoplasia, although the molecule was rarely expressed in low-grade squamous intra-epithelial neoplasia and was absent from normal ectocervical cells. HLA-DR-positive high-grade lesions were associated with significantly greater numbers of T lymphocytes in the immediately sub-epithelial stroma than were the HLA-DR-negative high-grade lesions. In vitro HLA-DR expression was absent from normal ectocervical epithelium, and from the HPV type 16 containing cell lines W12 (representing low-grade squamous intra-epithelial neoplasia) and CaSki and SiHa (each representing high-grade squamous intra-epithelial neoplasia), both in monolayer and in organotypic raft culture. HLA-DR expression was induced in all cell types following recombinant interferon gamma treatment. Our data suggest that the expression of HLA-DR by keratinocytes in some high-grade cervical lesions in vivo may be due to local induction of the molecule by pro-inflammatory cytokines released by immunocompetent cells. The functional significance of HLA-DR positivity in enabling an effective host immune response to neoplastic cervical keratinocytes remains unclear.

Carcinoma, Squamous Cell↗

"Natural" presentation of human papillomavirus type-16 E7 protein to immunocompetent mice results in antigen-specific sensitization or sustained unresponsiveness.

We have used a mouse model that utilizes the exclusively epithelial nature of human papillomavirus (HPV) infections to investigate the in vivo immune response to the E7 protein of human papillomavirus type-16. A keratinocyte cell line expressing E7 protein has been established and grafted onto syngeneic mice using a transplantation technique that permits the reformation of a differentiated epithelium on a granulation tissue bed. In this way viral antigens may be presented to the immune system in a way comparable to natural infection. A delayed-type hypersensitivity (DTH) response was studied post grafting by intradermal challenge with recombinant E7 protein. A significant response to E7 has been demonstrated in this way; however, priming with a low amount of HPV-16 E7 antigen induces immunological unresponsiveness, as measured by a loss of DTH reactivity to the protein, and persistence of keratinocytes expressing E7. Lymphocytes from mice exhibiting DTH reactivity have been shown to proliferate when stimulated with purified recombinant E7 protein in vitro, while immunoperoxidase staining of tissue from the sites of immunologically-induced inflammation has defined the cell infiltrate to be phenotypically characteristic of DTH. The observations reported here have important implications for vaccine strategy.

Animals↗

Expression of the myelomonocytic antigens CD36 and L1 by keratinocytes in squamous intraepithelial lesions of the cervix.

The keratinocytes in squamous intraepithelial lesions (SILs) of the cervix show altered expression of a number of molecules involved both in the control of growth and differentiation and in cell surface interactions, particularly with components of the immune system. We have used tissue biopsies and in vitro model systems to investigate the expression in SILs of the molecules CD36 and L1, which are predominantly expressed by myelomonocytic cells but which also have functional roles in keratinocyte biology. Whereas the L1 protein (defined by the monoclonal antibody Mac387) was expressed by suprabasal and superficial cells in 12 of 12 cases of normal cervix (NCx) and in 14 of 14 cases of low-grade SILs (LG-SILs), in two of 16 cases of high-grade SILs (HG-SILs) it was entirely absent and in the remainder it was restricted to the most superficial layers. When an arbitrary grading scale was applied, L1 expression in HG-SILs proved to be significantly lower than in LG-SILs (P < .01) or in cases of NCx (P < .01). CD36 was expressed by superficial cells in four of 12 cases of NCx, in six of 14 LG-SILs, and none of 16 cases of HG-SILs (when graded, LG-SILs v HG-SILs = P < .05). The mechanisms underlying the expression of both molecules were investigated by growth in organotypic tissue culture of normal ectocervical epithelium and the cervical keratinocyte cell lines W12 (a model for LG-SILs) and CaSki and SiHa (models for HG-SILs). L1 was diffusely expressed by NCx cells and the W12 cell line, although its expression in the CaSki and SiHa cell lines was much more irregular and restricted. CD36 was occasionally present on the surface of superficial NCx and W12 cells, but was absent from CaSki and SiHa cells. Neither molecule could be induced by treatment of the cells with interferon-gamma. These data suggest that the expression of CD36 and L1 by cervical keratinocytes is related to their differentiation status rather than representing an effect of exogenous factors, such as those released by the immune cell infiltrate associated with SILs. CD36 may function as an immunoregulatory molecule on cervical keratinocytes in SILs, while L1 is more likely to be involved in the intracellular regulation of cell proliferation and maturation.

Antigens, CD↗

Comparison of cognitive therapy and relaxation training for panic disorder.

Current approaches to the treatment of panic disorder (PD) include a treatment package consisting of relaxation training (RT), cognitive therapy (CT), and exposure-based components. In an examination of the separate effects of RT and CT without formally taught exposure of any form, 64 PD patients were assigned randomly to one of these treatment protocols or to a minimal-contact control (MCC) condition. Both RT and CT were superior to the MCC condition on a variety of measures pertaining to panic, global psychological functioning, agoraphobic fear, and other associated fears. A significantly greater percentage of patients were classified as treatment responders (based on a composite index) after CT (82%) and RT (68%), compared with the control group (36%). On measures of agoraphobic fear, CT patients fared slightly better than RT patients. Some support was demonstrated for specific cognitive changes after CT, although treatment specificity was not strongly supported overall. These results are discussed in light of current theories of PD and the presumed importance of exposure in its treatment.

Adolescent↗

Immunological events in regressing genital warts.

Little is known of the in vivo role of the immune system in controlling human papillomavirus infection in the genital tract. The authors have studied 125 closely monitored patients with genital warts. Of these 125 patients, wart regression was seen in 28 patients. This study provides evidence that clearance of human papillomavirus from the genital tract is characterized by an active cell-mediated immune response. Regressing warts (n = 14) contained significantly more T lymphocytes (P < .05, Wilcoxon rank sum test) and macrophages (P < .01) than did nonregressing controls (n = 14). CD4-positive lymphocytes predominated in regression, both within the wart stroma and the surface epithelium, where there was a significant change in the ratio of CD4+ to CD8+ cells (P < .01). Lymphocytes in regression also showed greater expression of activation markers, and the majority were of the "antigen-experienced" phenotype. There was no difference in Langerhans cell numbers, although there was significant induction of the immune accessory molecules HLA-DR and ICAM1 (P < .05) on keratinocytes, and E-selectin and VCAM1 (P < .05) on endothelial cells in regressing warts. The changes in regression are consistent with a delayed-type hypersensitivity reaction to foreign antigen, and the ability to induce and mount such a response may be a critical determinant of effective natural immunity to the genital HPVs. Specific targeting of delayed-type hypersensitivity responsiveness may increase the efficacy of strategies for immuno-intervention against HPV infection in the genital tract.

Adult↗

Delayed-type hypersensitivity response to human papillomavirus type 16 E6 protein in a mouse model.

A mouse model incorporating the epitheliotropic nature of human papillomavirus (HPV) infections has been used to study an immune response to HPV type 16 (HPV-16) E6 protein in vivo. Using a transplantation technique, a novel immortal keratinocyte cell line expressing the E6 protein has been grafted onto syngeneic mice to re-form a differentiated epithelium overlying a granulation tissue bed. By this approach the presentation of viral antigens to the immune system can be modelled in a way analogous to the natural infection. Here we report a delayed-type hypersensitivity (DTH) reaction in grafted mice challenged intradermally with a recombinant vaccinia virus expressing the HPV-16 E6 protein. The specificity of the response was confirmed by the absence of a DTH reaction to challenge with virus expressing either HPV-16 E7 or L1 protein.

Animals↗

Can the Yale-Brown Obsessive Compulsive Scale be used to assess trichotillomania? A preliminary report.

Given recent conceptualizations of trichotillomania (TM) as a variant of obsessive compulsive disorder (OCD), clinician-rated measures of obsessive compulsive symptoms have been adapted for use in the assessment of TM. Although the reliability and validity of these instruments have been well-documented in patients with OCD, psychometric properties have not been examined systematically in patients with TM. Here, we evaluate the reliability and validity of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) in a sample of 11 patients with a primary diagnosis of TM. Data addressed the utility of the Y-BOCS for evaluating symptoms of TM, and provided information regarding the proposed overlap between OCD and TM. Initial analyses suggested that interrater reliability, internal consistency, and test-retest reliability for the total score were adequate. However, the range of scores was somewhat restricted, and suggested in particular that interference in daily functioning from TM symptoms is quite low. Both internal consistency and test-retest reliability for the Target Behaviors subscale were inadequate, suggesting that this combined score is inappropriate for use with TM patients. Concurrent validity data using the total score were mixed, although the Y-BOCS did appear to be sensitive to change in TM symptoms over treatment. Implications for the use of the Y-BOCS with TM patients and hypothesized phenomenological differences between TM and OCD are discussed.

Adult↗

Delayed-type hypersensitivity response to the human papillomavirus type 16 E7 protein in a mouse model.

To study the immune response to human papillomavirus type 16, a mouse model was developed using a mouse keratinocyte cell line expressing the E7 protein. This line was grafted onto syngeneic mice to form a differentiated epithelium, thus closely mimicking the natural infection. A delayed-type hypersensitivity response could be demonstrated after intradermal challenge with a vaccinia virus recombinant expressing the E7 protein. This response appeared to be specific for the E7 polypeptide and was mediated by CD4+ cells.

Animals↗

Immunoelectron microscopical localization of human papillomavirus type 16 L1 and E4 proteins in cervical keratinocytes cultured in vivo.

The human papillomavirus (HPV) causes warts, but is also associated with the development of squamous cell dysplasia and carcinoma. The virus is host and tissue specific and the numerous HPV types show predilection for different body sites. Experimental production of HPV 16 particles is at present only possible using in vivo culture of keratinocytes containing episomal viral DNA. Using immunoelectron microscopy, we have investigated the localization of HPV 16 E4 and L1 proteins in a keratinized epithelium formed by grafting HPV 16-containing cervical keratinocytes onto the athymic mouse. New viral progeny are produced in this system, as confirmed by labeling of intranuclear particles with a mouse monoclonal antibody against the HPV 16 major capsid (L1) protein. The role of the E4 protein is not yet clear, although it is believed to be important for the later stages of the virus life cycle. Here we confirm its cytoplasmic localization in the cells of the spinous and granular layers and demonstrate co-localization with keratin tonofilaments.

Animals↗

Characterization and functional analysis of the expression of intercellular adhesion molecule-1 in human papillomavirus-related disease of cervical keratinocytes.

We have investigated the expression of intercellular adhesion molecule-1 (ICAM-1) in squamous neoplasia of the cervix and have noted a significant induction of the molecule in high-grade intra-epithelial lesions. Using monolayer and organotypic in vitro tissue culture systems, we have shown that there is no constitutive ICAM-1 expression on cervical keratinocytes immortalized but not transformed by human papillomavirus type 16, whereas two human papillomaviruses type 16 containing and fully transformed cervical keratinocyte lines do constitutively express the molecule. All cell types, including human papillomavirus-negative normal cervical keratinocytes, can be induced to up-regulate their expression of ICAM-1 by pro-inflammatory cytokines such as interferon-gamma. In addition, we have used an in vitro adhesion assay to show that ICAM-1:lymphocyte function antigen-1 interaction is functionally important in lymphocyte binding to cervical keratinocytes, suggesting a role for ICAM-1 in retaining and enabling functional activity of lymphocytes in the cervix in intraepithelial neoplasia.

Carcinoma in Situ↗

Attention and memory for threat in panic disorder.

Recently, information processing paradigms have been utilized to explore the role of attentional and memory processes in the maintenance of clinical anxiety disorders. The present study extended these data using a dual-task paradigm to assess attentional vigilance and a cued recognition task to evaluate short-term memory effects in Panic Disorder (PD). Twenty PD patients and 20 normal controls completed a computerized task wherein they read aloud one of a pair of rapidly presented words (primary task) while simultaneously attempting to detect a small probe that appeared adjacent to one of the words (secondary task). Eighty stimulus words were chosen to represent four categories: physical panic-related threat, social threat, positive-emotional, and neutral. Reaction time and accuracy in detecting the probe were assessed, as well as psychophysiological responding (heart rate, skin conductance, EMG). Following task completion, a cued recognition task was administered to examine short-term memory of task stimuli. Results indicated that PD patients exhibited slower reaction times relative to normal controls during presentation of physical panic-related threat and positive-emotional stimuli. A similar trend emerged for social threat stimuli, although the PD and control samples responded similarly to neutral stimuli. No group differences were found on the cued recognition measure or psychophysiological responding during task performance. The data are discussed in terms of possible implications for cognitive models of PD.

Adult↗

A comparison of clinical features in trichotillomania and obsessive-compulsive disorder.

Trichotillomania (TM) recently has been conceptualized as a variant of obsessive-compulsive disorder (OCD). However, no systematic data have compared the clinical features of these two disorders. Here we report data from 8 TM and 13 OCD patients which suggest important clinical differences between groups. First, TM patients reported a significantly greater degree of pleasure during hair-pulling than OCD patients reported during performance of ritualistic behaviors. Second, TM was accompanied by significantly fewer associated obsessive-compulsive symptoms. Third, the groups differed with regard to other clinical features including anxiety, depression, and personality characteristics. We conclude that TM is not conceptualized best as a variant of OCD.

Adult↗