Hyperplastic-like colon polyps that preceded microsatellite-unstable adenocarcinomas

We compared hyperplastic-like polyps that preceded microsatellite-unstable adenocarcinomas to incidental hyperplastic polyps to identify distinguishing morphologic criteria. The study group included 106 hyperplastic-like, nonadenomatous, serrated polyps, most from the ascending colon in 91 patients; the control group included 106 rectosigmoid hyperplastic polyps from 106 patients in whom adenocarcinoma did not develop. Study group polyps had an expanded crypt proliferative zone, a serrated architectural outline that became apparent in the basilar crypt regions, basilar crypt dilation, inverted crypts, and a predominance of dysmaturational crypts (crypts with minimal cell maturation). In contrast, control group polyps had a proliferative zone confined to the basal crypt region, serrated architecture that became apparent in the superficial crypt region, rare to no basilar crypt dilation, and rare or no dysmaturational crypts. Hyperplastic-like polyps that preceded microsatellite-unstable adenocarcinomas had a distinctive constellation of morphologic features related to altered and decreased cell function and control that resulted in dysmaturational crypts. Dysmaturation constitutes a range of morphologic alterations, some of which overlap with incidental-type innocuous hyperplastic polyps. The morphologic features described herein provide initial guidelines to identify this potentially important subset of premalignant serrated-like polyps.     

Monoaminergic Fluorescence in Frog Skin

The Falck-Hillarp fluorescence technique was employed in an attempt to determine the distribution of sympathetic innervation in frog skin. No evidence was found of a direct monoaminergic nerve supply to the cells of the non-glandular epithelium in the epidermis. Instead, specific fluorescence was mainly confined to the vicinity of the skin glands. Fluorescent fibers were observed surrounding the mucous type of gland. The secretory content of this gland was not fluorescent. In the granular type of gland the main source of fluorescence was the secretory granules filling the lumen. These developed a fluorescence in the spectral range of 5-hydroxytryptamine. The brightness of the fluorescence indicated a very high content of this amine. Fluorimetric analysis showed that no catecholamines were present in the secretion. In glands devoid of secretory granules there were some indications of a monoaminergic innervation of the secretory epithelium, but this was hard to determine because of the abundant nonspecific fluorescence. Sparse dots of specific fluorescence were found close to the surrounding smooth muscle cells. — These findings rule out the possibility of a direct sympathetic nervous control of the non-glandular epithelium in frog skin but indicate that this is instead confined to the skin glands.     

Immunohistochemical study about the Flt-1/VEGFR1 expression in the gastrointestinal tract of mouse, rat, dog, swine and monkey

Fms-like tyrosine kinase 1 (Flt-1) performs a subordinate effector role in mesenchymal angiogenesis and potentially serves an equally important functional role as a self-contained receptor in epithelial cells. In both endothelial cells and epithelial cells, Flt-1/vascular endothelial growth factor receptor 1 (VEGFR1) downstream signalling is involved in regulating cellular processes such as cytoskeletal changes and cellular survival protection. Cellular renewal of the gastrointestinal mucosa is based on these processes and might involve Flt-1/VEGFR1 pathway activities; the molecular mechanisms regulating these cellular dynamics remain unclear. This study was performed to investigate the presence and distribution of Flt-1/VEGFR1 in epithelial cells of the gastrointestinal tract by immunohistochemistry (IHC). Gastrointestinal tissues were taken from eight anatomical sites from mouse, rat, dog, swine and monkey. Present results revealed a cytosolic Flt-1/VEGFR1 staining pattern in mucosal epithelial cells for all investigated species. Non-epithelial structures also displayed a distinct Flt-1/VEGFR1 positivity and included vascular smooth muscle walls, enteric smooth muscle layers, the enteric nervous system and capillary endothelial cells. Diverse intensities of the Flt-1/VEGFR1 binding reaction within each species were observed in the intestinal mucosa with a strong immunoreaction in enterocytes and with a low protein expression in the ileum in most species. Crypt cells in the large intestine were mostly negative for Flt-1/VEGFR1. A peculiar and mainly intranuclear antibody binding reaction was found in Brunner's gland epithelial cells of mouse and rat whereas Brunner's glands of dog, swine and monkey remained completely negative. These results indicate a potential involvement of Flt-1/VEGFR1 in normal restitution of gastrointestinal structures in the species studied. Additionally, intranuclear Flt-1/VEGFR1 antibody binding in Brunner's glands of rodents may suggest a nuclear translocation of the transmembrane VEGFR1 which has not previously been described.     

Short rib-polydactyly syndrome and pericentric inversion of chromosome 4

We report on a newborn infant with clinical and radiological manifestations of some type of short rib-polydactyly syndrome who died soon after birth. Chromosomal studies on peripheral blood lymphocytes and chondrocytes demonstrated an apparently balanced pericentric inversion of chromosome 4 (present in the mother also). This association may have occurred by chance but, if not, the chromosomal breakpoints could interrupt the gene responsible for short rib-polydactyly syndromes, or else be related to the mechanism of short rib-polydactyly syndromes. © 1994 Wiley-Liss, Inc.     

Antibiotic Use in Crohn’s Disease

On the assumption that bacteria in the gut may be a cause of symptoms and/or complications of Crohn's disease, various antibiotics are efficaciously employed in some affected patients. However, we do not know exactly why and how they are helpful. A possible explanation is that one or several bacterial species may have a primary role in the aetiology of Crohn's disease, but this is not supported by the data in our possession. Another hypothesis is that intestinal bacteria may cause flare-up of the disorder, either by inducing intestinal lesions or by an interaction with the immune system, but we know today that specific pathogens can cause flares only in a minority of cases. On the contrary, there is considerable evidence that the intestinal microflora and its products may amplify and perpetuate inflammation in Crohn's disease. Despite the fact that few controlled trials have been conducted, and have shown inconclusive results, antibiotics are widely employed for improving symptoms and for inducing remission of active phases. At present, a combination of metronidazole and ciprofloxacin, active against many enteric bacteria, has proved to be effective in the treatment of Crohn's disease complications. This therapy also seems to be effective in acute flares as an alternative to, or in combination with, corticosteroids.     

Site-directed ELISA with synthetic peptides representing the HIV transmembrane glycoprotein

Two partially overlapping 19 and 22 amino acids long peptides representing a highly immunogenic site of the transmembranous glycoprotein (gp41) of human immunodeficiency virus (HIV) were used as antigen in ELISA tests. The results of antibody determination with this assay were compared with those of three or more conventional ELISAs and Western blot (WB) tests and radioimmunoprecipitation assay. Twenty-six sera from patients with AIDS or LAS and from asymptomatic carriers of HIV infection all showed a pronounced reaction in the peptide ELISA as well as positive results with other tests. In contrast, 27 sera from laboratory workers and blood donors were negative by all tests. A group of 39 blood donor sera, which had shown false positive or ambiguous results in the ELISAs and sometimes in WB tests employed for confirmation, also were negative in all cases with the peptide ELISA. Consecutive samples collected from individuals with primary HIV infection were also analyzed. In 6 out of 9 cases, the peptide ELISA revealed an antibody response within one month after onset of clinical symptoms and sensitivity for antibody detection equaled that of other ELISA tests. Eight sera from five West African persons infected with HIV-related viruses did not react in the peptide ELISA, reflecting differences in properties of the envelope components. The peptide ELISA used in this study appears to represent a simple technique employing chemically synthesized antigen for accurate and sensitive estimation of antibodies to the HIV group of nontransforming human retroviruses.     

Axillary lymph node cellular immune response to HER-2/neu peptides in patients with carcinoma of the breast.

HER-2/neu peptides have recently been shown to induce a proliferative response by peripheral CD4(+) T cells in breast cancer patients. To investigate potential differences in the local cellular immune response between breast cancer patients with and without nodal metastases, lymphocytes were isolated from axillary lymph nodes from patients with breast cancer, and proliferative and cytokine responses to HER-2/neu peptides were determined. Freshly isolated lymphocytes from lymph nodes of 7 women undergoing surgery for invasive breast cancer were plated at 20 x 10(5) cells per well in triplicate. Cells were stimulated with HER-2/neu peptides at 50 microg/ml and with control antigens. Incorporation of tritium-labeled thymidine was determined 4 days later. The levels of the cytokines interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-10 were determined at priming and at restimulation with HER-2/neu peptides using a cytokine-specific, double-sandwich, enzyme-linked immunosorbent assay (ELISA). Lymphocytes isolated from the axillary lymph nodes of the patients mounted significant cellular immune response to HER-2/neu peptides, manifested by proliferation and specific cytokine elaboration. Proliferative responses to HER-2/neu peptides were seen in lymphocytes of patients with and without overexpression of HER-2/neu in the primary tumor. In some patients, the proliferative response to HER-2/neu peptides in lymphocytes from lymph nodes with metastases was absent or blunted compared with the response in lymphocytes from lymph nodes without metastases from the same patient (p < 0.05). HER-2/neu peptides induced a predominantly T helper type 1 (Th1) pattern of cytokine response in nodal lymphocytes isolated from breast cancer patients. A Th1-specific cytokine production pattern was maintained at priming and restimulation with HER-2/neu peptides and was amplified with IL-12 costimulation. These results indicate that HER-2/neu peptides can activate T cells in draining lymph nodes from women with invasive breast cancer. This activation is associated with a predominantly Th1 cytokine response, which suggests that conditioning with HER-2/neu peptides may be of value in the development of breast cancer vaccines.     

Muscle spindles in rheumatoid arthritis

Summary Ultrastructural features of muscle spindles were studied in biopsy material from 100 patients suffering from classical rheumatoid arthritis. Thickening of the outer capsule, increased amount of extracellular ground substance within the inner capsule, and marked thickening of the basement membrane of capillary blood vessels supplying the muscle spindles were observed. Chronic inflammatory cells and macrophages were present within the spindles. Changes affecting the intrafusal muscle fibres were also seen. They were manifest as atrophy and degeneration of the intrafusal muscle fibres, absence of the specialised junctional complexes, and of the intercellular bridges, microladders and satellite cells. It is suggested that the changes affecting the intrafusal muscle fibres are probably secondary. Damage to the myelinated nerves was present, while the sensory and motor nerve endings were well preserved.Temporary Research Fellow the Rotterdam Centre for Rheumatic Disease Present address: Division of Pathology, Department of Obstetrics and Gynaecology, University of Chicago, Chicago, Illinois 60637, USA     

Direct screening of clinical specimens for multiple respiratory pathogens using the Genaco Respiratory Panels 1 and 2.

We report here on the results of a pilot study comparing our clinical diagnostic virology laboratory's current methods of respiratory pathogen detection against the Genaco Respiratory Infections Panels 1 and 2. These assays employ xMap (Luminex) liquid phase bead conjugated array technology to facilitate automated detection of PCR and RT-PCR products, which provides potential for levels of assay multiplexing above those currently practical with either conventional gel-resolved or real-time methods. In the study presented here we used the Genaco panels to simultaneously screen previously analyzed clinical specimens (nasopharyngeal washings) for twenty-one important pathogens. Our results indicate the Genaco panels met or exceeded our current methods' sensitivity and specificity although allowing for detection of a wider range of infectious agents than practical by current diagnostic laboratory practices. In addition, the Genaco panels provided data on the presence of multiple respiratory pathogens in single specimens, which would otherwise be missed in most instances. To our knowledge, this study represents the first trial of these panels on standard clinical specimens in a routine diagnostic setting.