CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma.

PURPOSE: We generated a humanized antibody, HuLuc63, which specifically targets CS1 (CCND3 subset 1, CRACC, and SLAMF7), a cell surface glycoprotein not previously associated with multiple myeloma. To explore the therapeutic potential of HuLuc63 in multiple myeloma, we examined in detail the expression profile of CS1, the binding properties of HuLuc63 to normal and malignant cells, and the antimyeloma activity of HuLuc63 in preclinical models. EXPERIMENTAL DESIGN: CS1 was analyzed by gene expression profiling and immunohistochemistry of multiple myeloma samples and numerous normal tissues. HuLuc63-mediated antimyeloma activity was tested in vitro in antibody-dependent cellular cytotoxicity (ADCC) assays and in vivo using the human OPM2 xenograft model in mice. RESULTS: CS1 mRNA was expressed in >90% of 532 multiple myeloma cases, regardless of cytogenetic abnormalities. Anti-CS1 antibody staining of tissues showed strong staining of myeloma cells in all plasmacytomas and bone marrow biopsies. Flow cytometric analysis of patient samples using HuLuc63 showed specific staining of CD138+ myeloma cells, natural killer (NK), NK-like T cells, and CD8+ T cells, with no binding detected on hematopoietic CD34+ stem cells. HuLuc63 exhibited significant in vitro ADCC using primary myeloma cells as targets and both allogeneic and autologous NK cells as effectors. HuLuc63 exerted significant in vivo antitumor activity, which depended on efficient Fc-CD16 interaction as well as the presence of NK cells in the mice. CONCLUSIONS: These results suggest that HuLuc63 eliminates myeloma cells, at least in part, via NK-mediated ADCC and shows the therapeutic potential of targeting CS1 with HuLuc63 for the treatment of multiple myeloma.     

Expression of peanut agglutinin-binding mucin-type glycoprotein in human esophageal squamous cell carcinoma as a marker

Background  

The TF (Thomson – Friedenreich) blood group antigen behaves as an onco-foetal carcinoma-associated antigen, showing increased expression in malignancies and its detection and quantification can be used in serologic diagnosis mainly in adenocarcinomas. This study was undertaken to analyze the sera and tissue level detectable mucin-type glycoprotein (TF-antigen) by Peanut agglutinin (PNA) and its diagnostic index in serum as well tissues of human esophageal squamous cell carcinoma as marker.     

Endovascular treatment of scalp arteriovenous fistulas associated with a large varix

Ten patients with scalp arteriovenous fistulas associated with a large varix (cirsoid aneurysms) were treated with a combination of interventional neuroradiologic procedures. These procedures included transarterial embolization, transarterial embolization followed by surgical excision, and two new methods of treatment of cirsoid aneurysms: transvenous embolization and direct puncture of the fistula for embolization. The embolic materials included liquid adhesive agents, particulate agents, detachable balloons, and wire coils. The embolization was performed to lodge the embolic agents in the fistula or proximal draining vein, not just the feeding vessels. Surgery was performed in two cases to remove a small residual nidus of fistula that could not be completely treated with intravascular embolization. With the use of these forms of treatment, cures were obtained in seven patients, and clinical and angiographic improvement was achieved in three patients. No major morbidity, blood loss, or mortality occurred during the treatment of these patients. The follow-up period ranged from 1 month to 8 years.     

Safety of a fat-reduced diet: the Dietary Intervention Study in Children (DISC)

OBJECTIVE: To assess the relationship between energy intake from fat and anthropometric, biochemical, and dietary measures of nutritional adequacy and safety. DESIGN: Three-year longitudinal study of children participating in a randomized controlled trial; intervention and usual care group data pooled to assess effects of self-reported fat intake; longitudinal regression analyses of measurements at baseline, year 1, and year 3. PARTICIPANTS: Six hundred sixty-three children (362 boys and 301 girls), 8 to 10 years of age at baseline, with elevated low-density lipoprotein cholesterol, who are participants of the Dietary Intervention Study in Children. MEASURES: Energy intake from fat assessed from three 24-hour recalls at each time point was the independent variable. Outcomes were anthropometric measures (height, weight, body mass index, and sum of skinfolds), nutritional biochemical determinations (serum ferritin, zinc, retinol, albumin, beta-carotene, and vitamin E, red blood cell folate, and hemoglobin), and dietary micronutrients (vitamins A, C, E, thiamin, riboflavin, niacin, vitamins B-6, B-12, folate, calcium, iron, zinc, magnesium, and phosphorus). RESULTS: Lower fat intake was not related to anthropometric measures or serum zinc, retinol, albumin, beta-carotene, or vitamin E. Lower fat intake was related to: 1) higher levels of red blood cell folate and hemoglobin, with a trend toward higher serum ferritin; 2) higher intakes of folate, vitamin C, and vitamin A, with a trend toward higher iron intake; 3) lower intakes of calcium, zinc, magnesium, phosphorus, vitamin B-12, thiamin, niacin, and riboflavin; 4) increased risk of consuming less than two-thirds of the Recommended Dietary Allowances for calcium in girls at baseline, and zinc and vitamin E in boys and girls at all visits. CONCLUSIONS: Lower fat intakes during puberty are nutritionally adequate for growth and for maintenance of normal levels of nutritional biochemical measures, and are associated with beneficial effects on blood folate and hemoglobin. Although lower fat diets were related to lower self-reported intakes of several nutrients, no adverse effects were observed on blood biochemical measures of nutritional status. Current public health recommendations for moderately lower fat intakes in children during puberty may be followed safely.     

Congenital cardiac anomalies with vein of Galen malformations in infants

Published reports and personal experience are reviewed relating to patients under 1 year of age diagnosed with a vein of Galen malformation and congenital heart disease. Including five patients from this institution, a total of 23 patients (12 neonates) with congenital heart disease and a vein of Galen malformation have been reported. Six of these had sinus venosus atrial septal defect and nine had aortic coarctation.     

Vaccination with glutamic acid decarboxylase plasmid DNA protects mice from spontaneous autoimmune diabetes and B7/CD28 costimulation circumvents that protection

The nonobese diabetic (NOD) mouse develops spontaneous T-cell-dependent autoimmune diabetes. We tested here whether vaccination of NOD mice with a plasmid DNA encoding glutamic acid decarboxylase (GAD), an initial target islet antigen of autoimmune T cell repertoire, would modulate their diabetes. Our results showed that vaccination of young or old female NOD mice with the GAD-plasmid DNA, but not control-plasmid DNA, effectively prevented their diabetes, demonstrating that GAD-plasmid DNA vaccination is quite effective in abrogating diabetes even after the development of insulitis. The prevention of diabetes did not follow the induction of immunoregulatory Th2 cells but was dependent upon CD28/B7 costimulation. Our results suggest a potential for treating spontaneous autoimmune diabetes via DNA vaccination with plasmids encoding self-Ag.     

The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: A European Alzheimer's Disease Consortium study

Introduction

Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear.

Distribution and risk factors of postoperative endophthalmitis in people with diabetes

Purpose:To evaluate (i) the distribution of postoperative endophthalmitis (POE) in patients who underwent cataract surgery, (ii) risk factors in diabetic versus nondiabetic patients, and (iii) distribution of POE in those who had undergone rapid reduction of preoperative blood sugar levels versus those with normal blood sugar levels.Methods:Medical records were reviewed from January 1995 to July 2021. In total, 391 eyes of 391 patients who developed POE after cataract surgery were studied. Patients with POE were divided into Group A, patients with diabetes (n = 128), and Group B, patients without diabetes (n = 263), and the associations of various clinical factors in the two groups were studied. Patients with diabetes with raised random blood sugars (RBS) preoperatively were subjected to a rapid reduction of blood sugar (RBS <200 mg%) to be considered eligible for surgery. Microbiological profile of patients was examined.Results:The cumulative incidence of POE over 26 years was 0.09%. Those who underwent a rapid reduction in preoperative blood sugar levels had higher rates of POE (53.1%) compared with (46.9%) those with blood sugar levels under control (P = 0.486). Men with diabetes had 1.634 times higher odds of POE (P = 0.048), and those with diabetes and hypertension had 3.961 times greater odds of having POE (P < 0.001) when adjusted for age, alcohol, smoking, and socioeconomic strata and presence of posterior capsule rupture. Positive culture results were observed in 45/128 (35%) patients with diabetes and 71/263 (27%) patients without diabetes. Staphylococcus epidermidis was the most commonly identified organism and was detected in 10/45 (22%) in those with diabetes and 21/71 (29%) in those without diabetes of all the culture-positive cases.Conclusion:In patients with POE, the odds are greater for men with diabetes, those with a history of hypertension, as well as those who undergo a rapid reduction of preoperative blood sugar.