A human monoclonal antibody to cytokeratin intermediate filament antigens derived from a tumor draining lymph node

Human lymphocytes derived from a lymph node draining a primary breast adenocarcinoma were fused with the mouse myeloma P3X63Ag8.653 to generate human-mouse hybridomas secreting human monoclonal antibodies (MAbs) to tumor associated antigens (TAAs). One of the resulting human MAbs, YBB 190 (IgM) is described. Enzyme-linked immunosorbent assays (ELISA) employing membrane and cytosol fractions of human tissues demonstrated YBB 190 reactivity against cytosol but not membrane components of malignant and normal epithelial tissues. When tested by an indirect immunoperoxidase staining method against fresh frozen human tissue sections, YBB 190 reacted with malignant cells in 26 of 28 epithelial cancers and with normal epithelia in 11 different benign tissues. Preliminary western blot antigen characterization indicated that YBB 190 recognizes cytokeratin intermediate filaments, or a protein that is closely associated with cytokeratins. These data indicate that B cells with specificity for intermediate filaments are present in tumor draining lymph nodes. Our findings provide insights into the nature of potential autoimmune responses in cancer patients and suggest that improved tumor directed sensitization procedures may be required to more effectively utilize lymphocytes from tumor draining lymph nodes to generate therapeutically useful human MAbs to TAAs.     

Regulation of chloride secretion in mammalian colon

A number of procedures or interventions which activate electrogenic ion transport in mammalian intestine are reviewed. Using in vitro models it is possible to demonstrate direct or indirect pathways to stimulate chloride secretion. Such activation, in vivo, would change the gut from a state of net water absorption to one of fluid secretion. The movement of water is driven by electrical and osmotic gradients set up as a consequence of opening regulated ion channels in epithelial cells. Secretagogues may govern epithelial intracellular second messenger pathways to regulate ion channel activity directly or by activation of membrane bound receptors on the surface of epithelial cells. In health or disease secretagogues may be derived from cells within the attendant lamina propria of the intestinal mucosa. Pharmacological techniques may be employed to determine which mediators contribute to indirect stimulation of electrogenic ion transport by activation of neurons or of immunocytes (mast cells or phagocytes). Dissection and reconstruction of models of intestinal hypersensitivity reactions show that neuro-immune networks which regulate intestinal ion transport appear to be complex, functionally integrated systems. Analysis of such interactions may identify cellular or humoral targets with which to examine novel diagnostic, preventative or therapeutic strategies with regard to intestinal diseases.     

Efficacy and Safety of Evening Administration of Controlled-Delivery Diltiazem Capsules in Chronic Stable Angina Patients

The safety and efficacy of controlled-delivery (CD) once-a-day formulation of diltiazem administered in the evening, at a dose of 240 mg, was assessed in 37 patients with stable angina pectoris. A double-blind, placebo-controlled, randomized, crossover protocol was used. Following a 4-day washout period, patients entered a 5--7-day single-blind placebo run-in period during which qualification and reproducibility exercise treadmill tests (ETTs) were performed 24 h postdose. Eligible patients were randomized in a double-blind fashion, to either CD diltiazem or to placebo for a 7--10-day treatment period. They then entered a 5--7-day single-blind washout period, after which they received the alternate treatment for another 7 to 10 days. ETTs were performed at the end of each treatment period. Compared to placebo, evening administration of CD diltiazem produced a marked improvement of the time to ETT termination, time to onset of angina, and time to 1 mm ST depression. In addition, the number of angina attacks recorded in patient diaries was reduced compared to placebo. Incidence of adverse events was comparable with CD diltiazem and placebo. We conclude that evening administration of controlled-delivery diltiazem is highly effective and safe in the treatment of stable angina pectoris.     

Relative medial and dorsal cortex volume in relation to foraging ecology in congeneric lizards

The need to locate distributed resources such as mates, food, and nests is correlated with an enlarged hippocampus in many mammalian and avian species. This correlation is believed to be a consequence of selection for spatial ability. Little is known about how such ecological needs affect non-mammalian, non-avian species. In lizards, the putative hippocampal homologues are the dorsal cortex (DC) and medial cortex (MC). We examined the relationship between foraging ecology and the size of the DC and MC in congeneric male lizards. We predicted based on the mammalian and avian literature that Acanthodactylus boskianus, an active forager that captures clumped, immobile prey would have a larger MC and DC than A. scutellatus, a sit-and-wait predator, that captures mobile prey. Our previous behavioral studies showed that A. boskianus did not differ from A. scutellatus on a spatial task but that A. boskianus was significantly better at the reversal of a visual discrimination, another task that is hippocampally dependent in mammals. In the current study, we found that, relative to telencephalon volume, the MC and DC were larger in the active forager whereas a control region, the lateral, olfactory, cortex, was similar in size between species. The current anatomical results suggest that MC and DC size is related to active foraging in lizards and, along with our previous behavioral studies, show that it is possible for this relationship to occur in the absence of evidence for species differences in spatial memory. Copyright (R) 2000 S.Karger AG, Basel     

CROHN'S DISEASE OF THE PREPUCE IN A 12-YEAR-OLD BOY: A Case Report and Review of the Literature

We report a case of Crohn's disease with involvement of the foreskin in a 12-year-old boy. One year previously, on the basis of clinical features (diarrhea with blood, perianal fissures) and histologic examination, a diagnosis of Crohn's disease was made. Subsequently, he developed phimosis and balanitis and underwent circumcision. Sections submitted from the foreskin revealed noncaseating granulomatous inflammation consistent with Crohn's disease. Crohn's disease with involvement of the genitalia is unusual. Only 26 cases including our case have been reported in the scientific literature. We have analyzed these cases with emphasis on gender, age, clinical features, duration of Crohn's disease, and probable mode of spread to the genitalia. Careful examination of sections from genital lesions, including those submitted from the foreskin, is essential to detect small isolated granulomas that may then lead to the diagnosis of inflammatory bowel disease.     

Formal retrospective case review and sudden infant death

A review of 24 consecutive sudden infant deaths was undertaken to evaluate the importance of the various stages in the postmortem assessment of such cases. Death in three cases was caused by obvious trauma. Of the remainder, 16 were attributed to sudden infant death syndrome (SIDS), 4 to accidental asphyxia (identified by death scene examination and/or formal case review) and 1 to a lingual thyroglossal duct cyst. Three (14%) of 21 deaths thought to be SIDS after postmortem examination were attributed to asphyxia following subsequent formal case review.     

Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice

We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.