Barriers to colorectal cancer screening in Ghana: a qualitative study of patients and physicians.

PURPOSE: The incidence of colorectal cancer (CRC) in Ghana has increased eightfold since the 1960s. In 2011, national guidelines were set forth recommending all patients aged 50-70 years old undergo annual CRC screening with fecal occult blood testing (FOBT), but adherence to these guidelines is poor and screening rates remain low for unclear reasons. METHODS: We performed semi-structured interviews with 28 Ghanaians including physicians (n = 14) and patients (n = 14) from the Komfo Anokye Teaching Hospital in Kumasi, Ghana, to better understand the factors driving screening adherence and perceived barriers identified in an earlier quantitative study. RESULTS: Participants reported sociocultural factors such as reliance on alternative medicine or religion, lack of education, and financial burden as community-level barriers to CRC screening. At the system level, screening was limited by insufficient access to FOBT as well as a perceived lack of national prioritization. This was described as inadequate efforts from the Ministry of Health regarding national education as well as lack of incorporation of CRC screening into the National Health Insurance Scheme. CONCLUSION: Several community- and system-level barriers exist to widespread screening of CRC in Ghana. A multi-level approach will be required to improve rates of CRC screening and ultimately reduce the burden of CRC in Ghana.

Developing a Patient-Centered Model of Prostate Cancer Care: Patient Satisfaction With a Survivorship Program Embedded in Urologic-Oncologic Care.

OBJECTIVE: To evaluate patients' and partners' satisfaction with a prostate cancer survivorship program embedded in urologic-oncologic care. As a part of quality improvement activity, we developed a patient and partner-centered, biopsychosocial support program for men and partners coping with the urinary and sexual side-effects of surgical treatment for prostate cancer. The program became a part of usual care for all prostate cancer patients. METHODS: Patients who saw both an advanced practice provider and a sex therapist between August 1, 2018 and July 31, 2019 were eligible. Surveys packets were sent to 146 patients with surveys included for partners (N = 292). We used descriptive statistics to characterize participant responses. RESULTS: Responses were received from 88 patients and 70 partners (56% response rate for the group). Patients and partners reported very high or fairly high satisfaction with the rehabilitation activities of the program (86-97% and 90%-100%, respectively); 91% of patients and 84% of partners thought having pre-operative education and post-operative rehabilitation was a good or fairly good idea; 83% of patients and 79% of partners would very much or somewhat recommend the program to a friend who was considering surgical treatment for prostate cancer. CONCLUSION: Embedding a patient and partner-centered prostate cancer survivorship support program in oncologic care can positively impact patients' and partners' engagement in and satisfaction with post-operative rehabilitation.

TrueNTH sexual recovery study protocol: a multi-institutional collaborative approach to developing and testing a web-based intervention for couples coping with the side-effects of prostate cancer treatment in a randomized controlled trial.

BACKGROUND: Over half of men who receive treatment for prostate suffer from a range of sexual problems that affect negatively their sexual health, sexual intimacy with their partners and their quality of life. In clinical practice, however, care for the sexual side effects of treatment is often suboptimal or unavailable. The goal of the current study is to test a web-based intervention to support the recovery of sexual intimacy of prostate cancer survivors and their partners after treatment. METHODS: The study team developed an interactive, web-based intervention, tailored to type of treatment received, relationship status (partnered/non-partnered) and sexual orientation. It consists of 10 modules, six follow the trajectory of the illness and four are theme based. They address sexual side effects, rehabilitation, psychological impacts and coaching for self-efficacy. Each includes a video to engage participants, psychoeducation and activities completed by participants on the web. Tailored strategies for identified concerns are sent by email after each module. Six of these modules will be tested in a randomized controlled trial and compared to usual care. Men with localized prostate cancer with partners will be recruited from five academic medical centers. These couples (N = 140) will be assessed prior to treatment, then 3 months and 6 months after treatment. The primary outcome will be the survivors' and partners' Global Satisfaction with Sex Life, assessed by a Patient Reported Outcome Measure Information Systems (PROMIS) measure. Secondary outcomes will include interest in sex, sexual activity, use of sexual aids, dyadic coping, knowledge about sexual recovery, grief about the loss of sexual function, and quality of life. The impact of the intervention on the couple will be assessed using the Actor-Partner Interaction Model, a mixed-effects linear regression model able to estimate both the association of partner characteristics with partner and patient outcomes and the association of patient characteristics with both outcomes. DISCUSSION: The web-based tool represents a novel approach to addressing the sexual health needs of prostate cancer survivors and their partners that-if found efficacious-will improve access to much needed specialty care in prostate cancer survivorship. TRIAL REGISTRATION: Clinicaltrials.gov registration # NCT02702453 , registered on March 3, 2016.

Complete amino acid sequence of human cartilage link protein (CRTL1) deduced from cDNA clones and chromosomal assignment of the gene.

Little is known about the primary amino acid structure of human cartilage link protein (CRTL1). We screened a human genomic library with a cDNA encoding the 3' untranslated region and the adjoining B1 domain of chicken link protein. One clone was isolated and characterized. A 3.5-kb EcoRI-KpnI fragment from this genomic clone that contains the human B1 exon was used to map the gene to chromosome 5q13----q14.1. The same fragment was used to screen a cDNA library prepared from mRNA of Caco-2, a human colon tumor cell line. Two overlapping clones were isolated and shown to encode all of CRTL1. The deduced amino acid sequence is 354 residues long. The amino acid sequence shows a striking degree of identity to the porcine (96%), rat (96%), and chicken (85%) link protein sequences. Furthermore, there is greater than 86% homology between the 3' untranslated region of the genes encoding human and porcine link proteins. These results indicate that there has been strong evolutionary pressure against changes in the coding and 3' untranslated regions of the gene encoding cartilage link protein.

Structure and chromosomal location of the human gene encoding cartilage matrix protein.

Cartilage matrix protein (CMP) is a major component of the extracellular matrix of nonarticular cartilage. The structure and chromosomal location of the human gene encoding CMP was determined by molecular cloning analysis. We used a partial chicken CMP cDNA probe to isolate three overlapping human genomic clones. From one of these clones, a probe containing 2 human CMP exons was isolated and used to map the gene to chromosome 1p35 and to screen a human retina cDNA library. Two overlapping cDNA clones were isolated. The predicted protein sequence of 496 amino acids includes a 22-residue signal peptide and a 474-residue mature protein of Mr 51,344. The human CMP gene and polypeptide are strikingly similar to the chicken CMP gene and polypeptide. Human CMP is 79% identical to chicken CMP and contains two homologous domains separated by an epidermal growth factor-like domain. One potential N-glycosylation site is conserved between the two species. The human CMP gene spans 12 kilobase pairs with 8 exons and 7 introns which are similar in size to those of the chicken CMP gene. Both RNA splice junctions of intron G in the human and chicken CMP genes are nonconforming to the consensus splice sequences. This suggests that the CMP gene utilizes a new RNA splicing mechanism.

Conjunctival lymphoma: results and treatment with a single anterior electron field. A lens sparing approach.

Lymphoma of the conjunctiva is rare. It presents in older patients as a mass lesion and usually remains localized. Surgery is limited to biopsy, and radiation therapy is the definitive treatment of choice. The entire conjunctiva is treated. Relatively high doses (approximately 30 Gy) are required for local control, which may lead to cataract formation. Twelve patients with conjunctival lymphoma were treated at the Massachusetts General Hospital between 1979 and 1988. Ten of 12 patients presented with a unilateral lesion; 2 of 12 with bilateral lesions. Two of 12 patients were found to have systemic disease at the time of presentation. One patient developed conjunctival lymphoma 5 years after the diagnosis of generalized disease. Using electron beam, all patients were treated with a single anterior circular field to total doses ranging from 24 Gy to 30 Gy delivered in 8 to 16 fractions over 9 to 20 days. In all cases, the lens was shielded by a specially designed plastic contact lens bearing a 12 mm diameter lead shield. The lens dose was determined at varying depths beneath the shield for 6 MeV and 9 MeV electron beams and ranged from a minimum of 5% to an absolute maximum of 18% of the total dose delivered to the tumor. Local control was maintained in all patients with follow-up to 9 1/2 years. One patient relapsed distantly 3 years after treatment. One of 12 patients died of systemic disease 4 years after treatment of the ocular lesion. Two patients developed cataracts 4 and 5 years after treatment; one had bilateral cataract, although only one eye had been treated. Both patients were over 75 years old. In both cases, the cataracts were felt to be senile cataracts which are ophthalmologically and radiographically distinguishable from radiation induced lesions.

Phenotypic and functional characterization of human T cell clones.

The capacity of human peripheral blood-derived T cell clones to carry out a variety of functions was examined. T cell clones were generated by stimulating individual peripheral blood T cells with PHA by a procedure that yielded a growing clone from a mean of greater than 92% of the cultured cells. A total of 65 T cell clones (44 CD4+ and 21 CD8+) generated from two individual donors were examined for their functional capabilities. All T cell clones examined secreted IL-2, IFN-gamma, and lymphotoxin/tumor necrosis factor like activity when stimulated with immobilized mAb to the CD3 complex (64.1). When 54 additional T cell clones from a third donor were analyzed, all were found to produce IL-2. Upon activation with immobilized 64.1, all CD4+ clones and 91% of the CD8+ clones induced the generation of Ig-secreting cells from purified B cells. The CD8+ clones that did not serve as Th cells alone were able to augment the capacity of fresh CD4+ cells to generate Ig-secreting cells. Each of these clones was also found to effect MHC-unrestricted cytotoxicity upon activation with immobilized 64.1. The CD8+ clones were somewhat more effective killers than CD4+ clones, although there was considerable overlap. A total of 18 clones was analyzed for TCR beta-chain gene rearrangement. Of the clones exhibiting rearrangements of the beta-chain gene, 94% were found to have a single rearrangement pattern. Finally, the detailed phenotype of 15 (11 CD4+ and 4 CD8+) of these clones was examined. Variable numbers of cells of each of the clones expressed Ag identified by mAb 4B4 (CD29), Leu 8, Leu 15 (CD11b), and NKH1. Moreover, cells of 6 of 11 CD4+ clones and 4 of 4 CD8+ clones also expressed CD45R in addition to CD29; expression of CD45R and CD29 varied with the activation status of the clone. The current data demonstrate that nearly all of the T cell clones were able to accomplish each of the functions examined regardless of the surface phenotype. Inasmuch as the clones were generated using a technique that expanded more than 92% of the circulating T cells, the data imply that the progeny of the vast majority of T cells may have the inherent capacity to exert a wide array of functional activities.

Functional gamma chain-associated T cell receptors on cerebrospinal fluid-derived natural killer-like T cell clones.

We have derived 33 independent T cell clones from the cerebrospinal fluid (CSF) of a patient with subacute sclerosing panencephalitis using a single T cell cloning method. 6% (2 of 33) of these clones express the T cell receptor gamma (TCR-gamma) protein and are called CSF TCR-gamma clones. Phenotypic analyses of the CSF TCR-gamma clones indicate that they are WT-31-, CD3+, CD4-, and CD8-. The TCR-gamma protein exists on the cell surface as part of an 85-kD disulphide-linked dimer noncovalently associated with the CD3 polypeptides. The CSF TCR-gamma clones have NK-like activity that can be inhibited by anti-CD3 mAbs. Both CSF TCR-gamma clones proliferated in response to anti-CD3 mAbs coupled to Sepharose beads and/or IL-2. Furthermore, stimulation of one of these clones with anti-CD3 mAbs results in a rapid rise in intracellular calcium. These data suggest that T cells bearing the CD3-TCR-gamma protein complex are functional and play a role in the human immune response.

AKR murine thymic leukemias are from a distinct thymic cell lineage and do not express the beta chain of the T-cell antigen receptor.

Characterization of tumors that arise spontaneously in the AKR mouse indicates that they are derived from cells of a distinct T-cell lineage. Cells in this subclass bear surface antigens, designated Tpre, Tthy, Tind, and Tsu, which are encoded by genes in the Tsu linkage group on murine chromosome 12. We have examined the rearrangement and expression of genes encoding the T-cell alpha, beta, and gamma chains in these tumors. Although these cells contain alpha-chain mRNA, they do not produce a normal-sized beta-chain mRNA. Most of them also lack gamma-chain mRNA. Each thymic leukemia was derived from a cell arrested at a different stage of development as defined by their expression of terminal deoxynucleotidyl transferase and Thy-1 mRNA. The data presented here are consistent with a model in which thymocytes expressing Tpre, Tthy, Tind, or Tsu undergo somatic development parallel to the development of other T cells. However, these thymocytes do not appear to differentiate into cells bearing alpha-beta heterodimers of the T-cell antigen receptor.

Rearrangement and expression of T-cell antigen receptor genes in human T-lymphocyte tumor lines and normal human T-cell clones: evidence for allelic exclusion of Ti beta gene expression and preferential use of a J beta 2 gene segment.

The gene encoding the beta chain of the human T-cell receptor for antigen is composed of variable (V), diversity (D), joining (J), and constant (C) gene segments which undergo specific rearrangements during T-lymphocyte ontogeny. Southern blot analyses of seven human T-cell tumor lines and normal human T-lymphocyte clones revealed that most of these T-cell lines rearrange their Ti beta genes differently. The T-cell tumor line HPB-MLT rearranges and transcribes both of its Ti beta genes. Cloning and sequencing of the Ti beta cDNAs corresponding to these rearrangements revealed that one of the rearranged Ti beta genes is defective, while the other is functional and corresponds to the Ti beta protein expressed on the surface of these cells. Thus, this cell line displays a pattern of allelic exclusion of Ti beta gene expression. A comparison of four C beta 2-containing Ti beta cDNAs from three different cell lines revealed that three of the four utilize the same J beta 2.5 gene segment joined to different D beta and V beta genes, suggesting that there may be preferential use of this J gene during J beta 2 rearrangements. Hybridization analyses with probes for the alpha and beta genes of the T-cell receptor and the T-cell-specific T gamma gene revealed that HPB-MLT cells appear to express approximately equivalent amounts of RNA corresponding to each of the rearranged Ti alpha and Ti beta genes. However, they express a much lower level of T gamma RNA.

Abnormal recombination products result from aberrant DNA rearrangement of the human T-cell antigen receptor beta-chain gene.

Two unusual rearrangements of the T-cell antigen receptor beta-chain gene have occurred in the human T-cell tumor line CEM. The beta chain of the T-cell antigen receptor is encoded in germ-line DNA by immunoglobulin-like gene segments that rearrange during the somatic development of T cells to form active genes. Structural analysis of rearranged immunoglobulin genes has already revealed a great deal about the mechanisms by which these genes rearrange. To further characterize the mechanism by which beta-chain genes rearrange, we have determined the organization of the rearranged beta-chain gene segments in the human T-cell tumor line CEM. Three rearranged joining (J) or diversity (D) segments of the beta-chain gene are found in CEM. One of these segments rearranged during the formation of a normal rearranged beta-chain gene that comprises a variable (V beta), D beta, and J beta gene segment associated with a constant region gene segment. Two abnormal recombination products are found at the other rearranged beta-chain locus. One product has the structure, J beta-D beta-J beta, with the J beta gene segments joined in a head-to-head fashion, while the other one consists of a V beta-D beta recombined segment not associated with a J beta gene segment. We propose that the J beta-D beta-J beta structure was formed by an inversion of 6 kilobases of DNA and subsequently, a V beta-D beta rearrangement occurred. The presence of these products in CEM has important implications for our understanding of the mechanism by which somatic rearrangements of beta-chain gene segments occur.

T cell receptor gene rearrangements define a monoclonal T cell proliferation in patients with T cell lymphocytosis and cytopenia.

We have used probes from the T cell receptor beta and gamma chain loci to investigate the clonality of T lymphocytes in eight patients with T cell lymphocytosis and cytopenia (TCLC). This syndrome, which is strongly associated with rheumatoid arthritis, is characterized by peripheral blood and bone marrow lymphocytosis and neutropenia, red cell aplasia, or both. By means of T cell monoclonal antibodies and flow cytometry, T lymphocytes from patients with this syndrome have been shown to have characteristic immunologic features. Investigators have disagreed as to whether the syndrome represents a T cell malignancy or a more benign immunologic disorder. DNA from five of five patients with symptomatic "classic" T cell lymphocytosis with cytopenia demonstrated unique rearrangements of the T cell receptor beta chain locus, whereas neither of two patients with atypical features showed rearrangement. In addition, we found evidence for gamma chain rearrangement in those DNAs with clonal beta chain rearrangement. We thus postulate that the classic form of this syndrome is associated with a monoclonal proliferation of T cells. Its potential relationship to T cell chronic lymphocytic leukemia is discussed.

Human T-cell gamma chain genes: organization, diversity, and rearrangement.

The human T-cell gamma chain genes have been characterized in an attempt to better understand their role in immune response. These immunoglobulin-like genes are encoded in the genome in variable, joining, and constant segments. The human gamma genes include at least six variable region genes, two joining segments, and two constant-region genes in germline DNA. Variable and joining segments recombine during the development of T cells to form rearranged genes. The diversity of human gamma genes produced by this recombinational mechanism is greater than that produced by the murine genome but is more limited than that of other immunoglobulin-like genes.

A novel mechanism of somatic rearrangement predicted by a human T-cell antigen receptor beta-chain complementary DNA.

The T-cell antigen receptor is a cell surface molecule vital in mediating the cellular immune response. The arrangement and rearrangement of the gene segments encoding the beta-chain polypeptide of the receptor are similar to those of immunoglobulin gene segments. The two constant region genes of the human T-cell antigen receptor are 8 kilobases apart with a cluster of joining segments located 5' of each constant region gene. Although most beta-chain gene rearrangements involve the variable, diversity, and joining segments, analysis of a beta-chain complementary DNA clone suggests the occasional occurrence of another type of rearrangement.