Immunohistochemical staining of colorectal tissues with monoclonal antibodies to ras oncogene p21 product and carbohydrate determinant antigen 19-9.

Two monoclonal antibodies were applied to benign, dysplastic, and malignant human colorectal tissues using immunohistochemical techniques on formalin fixed paraffin embedded material. RAP-5 antibody is directed against a synthetic peptide, reflecting an amino acid sequence of the ras oncogene p21 protein product. Despite using several different techniques and antibody dilutions differential staining between the various epithelial populations was not obtained. RAP-5 also showed other tissue components such as plasma cells, histiocytes, fibroblasts, smooth muscle and vascular endothelium. CA19-9 antibody recognizes an epithelial surface carbohydrate antigen originally derived from a human colorectal carcinoma cell line: it did not stain normal colorectal mucosa or adenomatous polyps, but showed focal expression of variable strength in regenerative, dysplastic, and cancerous mucosa in ulcerative colitis, and in non-colitic colorectal carcinoma. Neither antibody was found to be a reliable marker of the evolution of malignant mucosal changes, although CA19-9 may be of limited use in confirming adenocarcinoma of gastrointestinal origin.     

Analysis of the targeting of the hypermutational machinery and the impact of subsequent selection on the distribution of nucleotide changes in human V rearrangements

Summary: B cells are unique in that they generate and tolerate a high rate of mutations in their antigen receptor genes and employ these mutations as a basis of avidity maturation. The precise role of the mutational machinery versus subsequent selection in determining the frequency and distribution of mutations has not been fully analyzed. To address these issues, the influence of the intrinsic mutational machinery and subsequent selection on the frequency and distribution of mutations in the expressed human immunoglobulin repertoire was analyzed. Analysis of non-productively rearranged v_H genes from individual human B cells provided an opportunity to examine the immediate impact of somatic hypermtitation without superimposed selective influences. Comparison with the frequency and distribution of mutations in the productively rearranged human V_H genes permitted an estimate of the influences of subsequent selection.     

Correlations of Monocyte Phagocytic Receptor Expressions with Serum Immune Complex Level in Systemic Lupus Erythematosus

The expression of FcγRI, FcγRII, and FcγRIII (the IgG receptors CD64, CD32, CD16) as well as CR3 (the C3bi receptor, CD11b) on monocytes in the blood of patients with systemic lupus erythematosus (SLE) was investigated. The relationship between the receptor expression and the serum immune complex (IC) concentration was analysed. The decrease in mean fluorescence intensity (FI) of the FcγRII of patients' monocytes stained by specific monoclonal antibodies (MoAb IV3) was very close to statistical significance ( P = 0.052). The expression (FI) of CR3 (using MoAb OKM1) on monocytes of patients was also decreased, but not significantly. The detected decrease of FcγRII and CR3 was inversely correlated with the high circulating immune complex level in patients' sera. At the same time, FcγRI expression on SLE monocytes (using MoAb 32) was significantly elevated and this change was in parallel with the serum IC concentration.     

Monoclonal antibodies to the human mammary gland: III. Monoclonal antibody LICR-LON-M18 identifies impaired expression and excess sialylation of the I(Ma) cell-surface antigen by primary breast carcinoma cells

Monoclonal antibody LICR -LON- M18 identifies the immunodominant oligosaccharide sequence of the I(Ma) blood-group antigen: Gal beta 1----4GlcNAc beta 1----6--. In primary breast cancers this structure is almost totally cryptic, due to "masking" by sialic acid, but can be revealed by digestion with the specific glycosidase neuraminidase. Following desialylation, light microscopic immunohistochemical examination has revealed the epitope identified by LICR -LON- M18 to be heterogeneously distributed throughout the population of breast carcinoma cells. These tumor cells express the antigen as both a cytoplasmic and a surface membrane determinant. In the normal human breast, this structure is expressed exclusively along the luminal plasma membranes of the duct and alveolar littoral epithelial cells. Desialylation of tissue sections of normal resting and lactating breast epithelium with neuraminidase virtually abolishes the heterogeneous intercellular distribution of the I(Ma) determinant. In desialylated nonneoplastic breast tissues, the expression of this antigen is observed within the cytoplasm of some myoepithelial cells, but not in the littoral epithelial cells. The expression of the I(Ma) antigen by neoplastic and normal breast epithelial cells has also been compared with that of the oligosaccharide sequence Gal beta 1----3GalNAc. This structure, recognized by peanut agglutinin, forms the dominant portion of the Thomsen-Friedenreich antigen. With respect to normal and lactating breast epithelial cells, both oligosaccharide structures are sialylated and appear to be similarly misprocessed by breast carcinomas. The masking of surface carbohydrate determinants and the faulty processing of structures usually expressed on the surface of non-neoplastic breast epithelial cells may be important phenomena in the pathobiology of breast carcinomas.     

Ex vivo expansion and prophylactic infusion of CMV-pp65 peptide-specific cytotoxic T-lymphocytes following allogeneic hematopoietic stem cell transplantation.

Cytomegalovirus reactivation and infection post-allogeneic hematopoietic stem cell transplant continue to cause morbidity and mortality. Current pharmacologic therapies are limited by side effects. Adoptive transfer of ex vivo generated cytomegalovirus-specific T cells has the potential to restore immunity, prevent cytomegalovirus, and circumvent the need for pharmacologic therapies. We have generated donor-derived cytomegalovirus-specific cytotoxic T cells using dendritic cells pulsed with the HLA-A2 restricted nonapeptide NLVPMVATV (NLV) derived from the cytomegalovirus-pp65 protein. These cytotoxic T cells have been given prophylactically to 9 recipients aged 4 to 65 years on or after day 28 post-allogeneic hematopoietic stem cell transplant. Only 2 of 9 recipients received T cell depletion in vivo or in vitro. There were no immediate adverse reactions to the infusions. During 97-798 days of follow-up, 2 recipients developed cytomegalovirus reactivation; neither developed cytomegalovirus disease or required pharmacotherapy. Three recipients developed acute graft versus host disease after infusion. Two recipients died, 1 from thrombotic thrombocytopenia purpura secondary to cyclosporine, 1 from complications of graft versus host disease. A transient increase in numbers of cytomegalovirus-specific T cells demonstrated by NLV-tetramer binding was seen in 6 recipients. Prophylactic adoptive transfer of NLV-specific T cells is safe and may be effective in preventing cytomegalovirus reactivation.     

Expression of breast epithelial differentiation antigens in human primary breast cancer

Monoclonal antibody LICR-LON-M18 is a marker of normal human breast epithelial cell differentiation. The epitope recognized by LICR-LON-M18 is a prominent component of luminal plasma membranes of nonneoplastic resting and lactating human breast epithelial cells but is rarely expressed by human breast carcinomas. With the use of competitive binding-inhibition studies, the immunodominant portion of the LICR-LON-M18 epitope was shown to be the following oligosaccharide sequence [with galactose (Gal) and N-acetylglucosamine (GlcNAc)]: Gal beta 1----4GlcNAc beta 1----. This structure was distinct from Gal beta 1----3GalNac, which was bound by peanut agglutinin (PNA) and was not recognized by LICR-LON-M18 [corrected]. With the use of biochemical techniques, the present data not only confirmed sialylation and consequent "masking" of the LICR-LON-M18 epitope and PNA determinants in human breast carcinomas but also identified the particular groups of glycoproteins involved in this process. These studies provided additional support for the thesis that sialylation of human breast carcinoma glycoproteins represented an enhancement of specific differentiation events normally regulated in the morphogenesis of nonneoplastic human breast epithelium and that specific glycoproteins became masked during the genesis of primary human breast cancer.     

Osteopetrosis: MR characteristics at 1.5 T

Four patients with proved osteopetrosis (three with the infantile malignant form and one with the benign form) were examined with magnetic resonance imaging at 1.5 T. All patients were studied in the coronal and sagittal planes using both short and long repetition time/echo time sequences. The infantile malignant form was characterized by a complete lack of signal from the marrow alternating with a signal intensity equivalent to that of the intervertebral disks, resulting in a "stepladder" appearance. In the benign form or after successful marrow transplantation in the infantile malignant form, intermediate or high signal intensity in the vertebrae was noted, suggesting the presence of some marrow elements.     

Antegrade Colonic Lavage in Acute Colonic Obstruction

Conventional management of acute left sided colonic obstruction employs some form of proximal colostomy. Intraoperative antegrade colonic irrigation relieves proximal faecal loading and may permit safer primary resection and anastomosis. The results of a pilot study are presented, and are shown to be favourable.

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Development and Validation of the Sexual and Reproductive Empowerment Scale for Adolescents and Young Adults

PurposeWe developed and validated a measure that assesses the latent construct of sexual and reproductive empowerment among adolescents and young adults. A specific measure for this group is critical because of their unique life stage and circumstances, which often includes frequent changes in sexual partners and involvement from parents in decision-making.MethodsAfter formative qualitative research, a review of the literature, and cognitive interviews, we developed 95 items representing nine dimensions of sexual and reproductive empowerment. Items were then fielded among a national sample of young people aged 15–24 years, and those who identified as sexually active completed a 3-month follow-up survey. We conducted psychometric analysis and scale validation.ResultsExploratory factor analysis on responses from 1,117 participants resulted in the Sexual and Reproductive Empowerment Scale for Adolescents and Young Adults, containing 23 items captured by seven subscales: comfort talking with partner; choice of partners, marriage, and children; parental support; sexual safety; self-love; sense of future; and sexual pleasure. Validation using logistic regression demonstrated that the subscales were consistently associated with sexual and reproductive health information and access to sexual and reproductive health services measured at baseline and moderately associated with the use of desired contraceptive methods at 3-month follow-up.ConclusionsThe Sexual and Reproductive Empowerment Scale for Adolescents and Young Adults is a new measure that assesses young people’s empowerment regarding sexual and reproductive health. It can be used by researchers, public health practitioners, and clinicians to measure sexual and reproductive empowerment among young people.