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Biomedical subjects

M Wallace

Publications and source records attributed to M Wallace.

At least 55 records · Page 3Linked to original sources
PubMed2000

Service use patterns of youth with, and at high risk for, HIV: a care typology.

This paper uses confirmatory structural equation models to develop and test a theoretical model for understanding the service utilization history of 4679 youth who received services from 10 national HIV/AIDS demonstration models of youth-appropriate and youth-attractive services funded by the Special Projects of National Significance (SPNS) Program, HIV/AIDS Bureau, Health Resources and Services Administration. Although the projects differ from one another in the areas of emphasis in their service models, each is targeted to youth at high risk for HIV, or those youth who have already contracted HIV. Collectively, the projects represent a comprehensive adolescent HIV service model. This paper examines the characteristics of the services provided to young people ranging from outreach to intensive participation in medical treatment. Major typologies of service utilization are derived empirically through exploratory factor and cluster analysis methods. Confirmatory structural equation modeling methods are used to refine the exploratory results using a derivation and replication strategy and methods of statistical estimation appropriate for non-normally distributed service utilization indicators. The model hypothesizes that youth enter the service system through a general construct of connectedness to a comprehensive service model and through service-specific methods, primarily of outreach or emergency services. Estimates are made of the degree to which a comprehensive service model drives the services as opposed to specific service entry points.

Adolescent↗
PubMed2000

Modulation of major histocompatibility class II protein expression by varicella-zoster virus.

We sought to investigate the effects of varicella-zoster virus (VZV) infection on gamma interferon (IFN-gamma)-stimulated expression of cell surface major histocompatibility complex (MHC) class II molecules on human fibroblasts. IFN-gamma treatment induced cell surface MHC class II expression on 60 to 86% of uninfected cells, compared to 20 to 30% of cells which had been infected with VZV prior to the addition of IFN-gamma. In contrast, cells that were treated with IFN-gamma before VZV infection had profiles of MHC class II expression similar to those of uninfected cell populations. Neither IFN-gamma treatment nor VZV infection affected the expression of transferrin receptor (CD71). In situ and Northern blot hybridization of MHC II (MHC class II DR-alpha) RNA expression in response to IFN-gamma stimulation revealed that MHC class II DR-alpha mRNA accumulated in uninfected cells but not in cells infected with VZV. When skin biopsies of varicella lesions were analyzed by in situ hybridization, MHC class II transcripts were detected in areas around lesions but not in cells that were infected with VZV. VZV infection inhibited the expression of Stat 1alpha and Jak2 proteins but had little effect on Jak1. Analysis of regulatory events in the IFN-gamma signaling pathway showed that VZV infection inhibited transcription of interferon regulatory factor 1 and the MHC class II transactivator. This is the first report that VZV encodes an immunomodulatory function which directly interferes with the IFN-gamma signal transduction via the Jak/Stat pathway and enables the virus to inhibit IFN-gamma induction of cell surface MHC class II expression. This inhibition of MHC class II expression on VZV-infected cells in vivo may transiently protect cells from CD4(+) T-cell immune surveillance, facilitating local virus replication and transmission during the first few days of cutaneous lesion formation.

Adult↗
PubMed2000

Function and dysfunction of T cell receptor: structural studies.

The engagement of the T cell receptor (TCR) to its ligand, the major histocompatibility complex (MHC)-peptide complex, leads to T cell activation. The molecular mechanisms leading to this activation are still unknown. Dimerization or substantial conformational changes following TCR ligation have not been observed by classical biochemical methods or by X-ray crystallography of the TCR/MHC complex. However, most of these experiments have used reductionist approaches in which only MHC and TCR molecules were taken into account. In fact, the TCR is only one of many molecules forming the TCR complex (TCRC), and the interplay among the components of this larger complex have not been studied in depth. The reconstitution of a complete TCRC using recombinant molecules is our goal and will be the first step to new structural and functional studies.

Animals↗
PubMed2000

Sexuality and cancer: conversation comfort zone.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Psychosocial issues profoundly affect patients with cancer. Of the many complexities that make up the psychosocial dynamic, perhaps the medical profession is most uncomfortable with sexuality. Many elements of sexual behavior remain high-profile taboos. A number of diseases and treatments significantly affect sexual function. Male and female sexuality were discussed in two separate rounds with an emphasis on how to begin a dialogue about sexuality without jeopardizing other aspects of the relationship with patients. Three cases were presented. A patient with prostate cancer considering treatment options for early-stage disease and two patients with gynecologic malignancies; one with a colostomy following cytoreductive surgery for ovarian cancer and the other with a failed vaginal reconstruction for recurrent squamous cell carcinoma of the vagina. Staff discussed the wide diversity of response to sexual dysfunction and the difficulties that patients face. A sensitive and informed approach to discussing sexuality can provide effective support. The elements of successful dialogue are presented in the PLISSIT model.

Adult↗
PubMed2000

The influence of experience and specialisation on the reliability of a common clinical sign.

OBJECTIVES: To explore the influence of experience and specialisation on clinical judgement by comparing accuracy in diagnosing anaemia between a consultant general surgeon, a consultant ophthalmologist and their registrars. PATIENTS AND METHODS: Conjunctival inspection of 101 patients, subsequent correlation with haemoglobin concentration. MAIN OUTCOME MEASURES: Number of correct and incorrect diagnoses of anaemia. RESULTS: 54 patients were anaemic and 47 were not. Overall accuracy in diagnosing anaemia ranged from 0.61-0.69, sensitivity 0.52-0.65 and specificity 0.62-0.83. Agreements between pairs of examiners were 0.68-0.81, with kappa values of 0.36-0.60 when adjusted for chance agreement. CONCLUSIONS: Neither experience nor specialisation significantly influenced our ability to diagnose anaemia, based on conjunctival inspection. Without critical analysis of clinical signs, we are unaware of their diagnostic limitations.

Anemia↗
PubMed2000

Risk factors and characteristics of youth living with, or at high risk for, HIV.

Over 8,000 adolescents and young adults (4,111 males; 4,085 females) reported on several HIV-related risk behaviors during enrollment into 10 service demonstration projects targeted to youth living with, or at risk for, HIV. Distinct risk patterns emerged by gender when predicting HIV serostatus (versus unknown serostatus/negative serostatus). Males who had injection drug risk histories, had sex with an HIV positive partner, had sexually transmitted diseases, had sex with males, and/or were homeless had an inflated risk of being HIV positive. Females who engaged in sex with an HIV partner, had sex with an injection drug user, and/or had sexually transmitted diseases, were at the highest HIV risk. For both samples, engaging in sex with women reduced the likelihood of HIV positive status. Very basic information about risk factors obtained at service intake offers important information about HIV status of "high risk" youth presenting for care in community programs, as well as suggests clear risk factors for targeted preventive efforts.

Adolescent↗
PubMed1999

The 26S proteasome of the fission yeast Schizosaccharomyces pombe.

The 26S proteasome is the multiprotein complex that degrades proteins that have been marked for destruction by the ubiquitin pathway. It is made up of two multisubunit complexes, the 20S catalytic core and the 19S regulatory complex. We describe the isolation and characterization of conditional mutants in the regulatory complex and their use to investigate interactions between different subunits. In addition we have investigated the localization of the 26S proteasome in fission yeast, by immunofluorescence in fixed cells and live cells with the use of a GFP-tagged subunit. Surprisingly, we find that in mitotic cells the 26S proteasome occupies a discrete intracellular compartment, the nuclear periphery. Electron microscopic analysis demonstrates that the complex resides inside the nuclear envelope. During meiosis the localization showed a more dynamic distribution. In meiosis I the proteasome remained around the nuclear periphery. However, during meiosis II there was a dramatic relocalization: initially, the signal occupied the area between the dividing nuclei, but at the end of mitosis the signal dispersed, returning to the nuclear periphery on ascospore formation. This observation implies that the nuclear periphery is a major site of proteolysis in yeast during mitotic growth and raises important questions about the function of the 26S proteasome in protein degradation.

Animals↗
PubMed1999

Early expression of cyclo-oxygenase-2 during sporadic colorectal carcinogenesis.

Regular administration of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of colorectal cancer by targeting cyclo-oxygenase-2 (Cox-2), a key enzyme in arachidonic acid metabolism. To evaluate the role of Cox-2 in sporadic colorectal cancer development, Cox-2 expression was investigated by immunohistochemistry in 85 adenomas, 53 carcinomas, 34 hyperplastic lesions and 104 samples of histologically normal mucosa adjacent to adenoma or carcinoma. In addition, Cox-2 mRNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) in six adenomas and 14 carcinomas with paired grossly normal mucosa. Immunohistochemistry for the proliferation-associated antigen Ki-67 and in situ end labelling for demonstrating apoptotic bodies were also used to analyse the associations between Cox-2 expression and proliferation and apoptosis. Cox-2 protein expression was increased in 76/85 (89.4 per cent) adenomas and 44/53 (83.0 per cent) carcinomas compared with normal mucosa. Cox-2 protein expression was unrelated either to the degree of dysplasia or to the size of the adenomas (p > 0.50, p > 0.10, respectively) or to differentiation, Dukes stage or lymph node metastasis of carcinomas (all p > 0.50). Interestingly, 20/34 (58.8 per cent) hyperplastic lesions adjacent to adenomas or carcinomas displayed expression higher than in normal mucosa (18.3 per cent) (p < 0.0001) but lower than in adenomas or carcinomas (p < 10(-5), p < 0.001, respectively). There were no correlations between Cox-2 protein expression and proliferative or apoptotic index in either adenomas or carcinomas (all p > 0.25). Cox-2 mRNA expression was significantly increased in adenomas and carcinomas compared with normal mucosa (p < 0.005, p < 0.001, respectively). There were no differences between adenomas and carcinomas in either protein or mRNA levels (p > 0.25, p > 0.90, respectively). These data indicate that enhanced expression of Cox-2 occurs early during colorectal carcinogenesis and may contribute to tumour formation.

Adenoma↗
PubMed1999

CD40 expression in bladder cancer.

The CD40 receptor is expressed in many immune cell types and is known to play a central role in both humoral and T-cell-mediated immunity, being a subject of intense research interest in recent years. It is also expressed on a variety of carcinomas and may therefore be of biological significance in the development and treatment of cancer. The expression of CD40 was examined immunohistochemically in a series of 131 bladder transitional cell carcinomas and the correlation with known prognostic markers and clinical outcome assessed. Seventy-eight per cent of the tumours were CD40-positive, with a highly significant association with both lower stage and lower grade (p<0.001). Ta and T1 tumours expressed CD40 in 89 per cent of specimens compared with 62 per cent seen in T2-T4 tumours and in contrast to normal urothelium, which was mainly CD40-negative. CD40 expression was not related to any other clinicopathological variable including Bcl-2 and p53 expression, nor was it an independent prognostic marker. The lack of the relationship with Bcl-2 staining which is normally seen in basal epidermal cells may indicate alternative or abnormal CD40-mediated cell differentiation mechanisms. The diffuse expression seen in Ta bladder tumours may account for its clinically less aggressive behaviour and is likely to be an important factor in the excellent clinical response seen to BCG immunotherapy. It also raises the possibility of the future development of CD40/CD40 ligand-based immunotherapy for bladder cancer.

Adult↗
PubMed1999

Prospective determination of distal colon findings in average-risk patients with proximal colon cancer.

BACKGROUND: Recent guidelines indicate that colonoscopy and sigmoidoscopy are both acceptable options for screening average-risk patients for colorectal cancer. Retrospective studies have found that a majority of patients with cancer proximal to the splenic flexure have a normal screening flexible sigmoidoscopy. METHODS: This was a multicenter, prospective description of colonoscopic findings and family history in consecutive patients with proximal colon cancer. RESULTS: Among 116 prospectively identified average-risk patients with cancer proximal to the splenic flexure, 40 (34.5%) had neoplasia distal to the splenic flexure. The prevalence of patients with adenomas greater than or equal to 1 cm, with only one tubular adenoma less than 1 cm, and with only hyperplastic polyps were 16.4%, 8.6%, and 6.9%, respectively. CONCLUSIONS: Most average-risk patients with cancer proximal to the splenic flexure will have a normal screening flexible sigmoidoscopy. These patients have an unexpectedly high prevalence of large distal adenomas, but the prevalence of both single small tubular adenomas and hyperplastic polyps alone is similar to that expected during screening of the general population. Clinicians and payers should continue to seek methods to improve the cost-effectiveness and availability of screening colonoscopy in average-risk persons.

Adenocarcinoma↗
PubMed1999

Lymphocyte activation during acute simian/human immunodeficiency virus SHIV(89.6PD) infection in macaques.

Host-virus interactions control disease progression in human immunodeficiency virus-infected human beings and in nonhuman primates infected with simian or simian/human immunodeficiency viruses (SHIV). These interactions evolve rapidly during acute infection and are key to the mechanisms of viral persistence and AIDS. SHIV(89.6PD) infection in rhesus macaques can deplete CD4(+) T cells from the peripheral blood, spleen, and lymph nodes within 2 weeks after exposure and is a model for virulent, acute infection. Lymphocytes isolated from blood and tissues during the interval of acute SHIV(89.6PD) infection have lost the capacity to proliferate in response to phytohemagglutinin (PHA). T-cell unresponsiveness to mitogen occurred within 1 week after mucosal inoculation yet prior to massive CD4(+) T-cell depletion and extensive virus dissemination. The lack of mitogen response was due to apoptosis in vitro, and increased activation marker expression on circulating T cells in vivo coincided with the appearance of PHA-induced apoptosis in vitro. Inappropriately high immune stimulation associated with rapid loss of mature CD4(+) T cells suggested that activation-induced cell death is a mechanism for helper T-cell depletion in the brief period before widespread virus dissemination. Elevated levels of lymphocyte activation likely enhance SHIV(89.6PD) replication, thus increasing the loss of CD4(+) T cells and diminishing the levels of virus-specific immunity that remain after acute infection. The level of surviving immunity may dictate the capacity to control virus replication and disease progression. We describe this level of immune competence as the host set point to show its pivotal role in AIDS pathogenesis.

Animals↗